Dynamics in population heterogeneity during batch and continuous fermentation of Saccharomyces cerevisiae

DEFF Research Database (Denmark)

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

2012-01-01

Traditionally, microbial populations in optimization studies of fermentation processes have been considered homogeneous. However, research has shown that a typical microbial population in fermentation is heterogeneous. There are indications that this heterogeneity may be both beneficial...... (facilitates quick adaptation to new conditions) and harmful (reduces yields and productivities)[1,2]. Typically, gradients of e.g. dissolved oxygen, substrates, and pH are observed in industrial scale fermentation processes. Consequently, microbial cells circulating throughout a bioreactor experience rapid...... distribution during different growth stages. To further simulate which effect gradients have on population heterogeneity, glucose and ethanol perturbations during continuous cultivation were performed. Physiological changes were analyzed on single cell level by using flow cytometry followed by cell sorting...

Heterogeneity within the spleen colony-forming cell population in rat bone marrow

International Nuclear Information System (INIS)

Martens, A.C.; van Bekkum, D.W.; Hagenbeek, A.

1986-01-01

The pluripotent hemopoietic stem cell (HSC) of the rat can be enumerated in a spleen colony assay (SCA) in rats as well as mice. After injection of rat bone marrow into lethally irradiated mice, macroscopically visible spleen colonies (CFU-S) are found from day 6 through 14, but the number varies on consecutive days. In normal bone marrow a constant ratio of day-8 to day-12 colony numbers is observed. However, this ratio is changed after in vivo treatment of rats with cyclophosphamide, as well as after in vitro treatment of rat bone marrow with cyclophosphamide derivatives. This indicates that the CFU-S that form colonies on day 8 react differently to this treatment than the CFU-S that form colonies on day 12, and suggests heterogeneity among the CFU-S population. Posttreatment regrowth of day-8 and day-12 CFU-S is characterized by differences in population-doubling times (Td = 0.85 days vs 1.65 days). Another argument in support of the postulate of heterogeneity within the rat CFU-S population is derived from the fact that (in contrast to normal rat spleen) the spleen of leukemic rats contains high numbers of CFU-S that show a ratio of day-8 to day-12 CFU-S of 4.5, which is different than that observed for a CFU-S population in normal bone marrow (a ratio of 2.4). It is concluded that, in rat hemopoiesis, two populations of spleen colony-forming cells can be distinguished using the rat-to-mouse SCA. This indicates that mouse and rat hemopoiesis are comparable in this respect and that heterogeneity in the stem cell compartment is a general phenomenon

Programming strategy for efficient modeling of dynamics in a population of heterogeneous cells

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Hald, Bjørn Olav; Hendriksen, Morten; Sørensen, Preben Graae

2013-01-01

Heterogeneity is a ubiquitous property of biological systems. Even in a genetically identical population of a single cell type, cell-to-cell differences are observed. Although the functional behavior of a given population is generally robust, the consequences of heterogeneity are fairly unpredict...

SIR dynamics in structured populations with heterogeneous connectivity

OpenAIRE

Volz, Erik

2005-01-01

Most epidemic models assume equal mixing among members of a population. An alternative approach is to model a population as random network in which individuals may have heterogeneous connectivity. This paper builds on previous research by describing the exact dynamical behavior of epidemics as they occur in random networks. A system of nonlinear differential equations is presented which describes the behavior of epidemics spreading through random networks with arbitrary degree distributions. ...

Evolutionary mixed games in structured populations: Cooperation and the benefits of heterogeneity

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Amaral, Marco A.; Wardil, Lucas; Perc, Matjaž; da Silva, Jafferson K. L.

2016-04-01

Evolutionary games on networks traditionally involve the same game at each interaction. Here we depart from this assumption by considering mixed games, where the game played at each interaction is drawn uniformly at random from a set of two different games. While in well-mixed populations the random mixture of the two games is always equivalent to the average single game, in structured populations this is not always the case. We show that the outcome is, in fact, strongly dependent on the distance of separation of the two games in the parameter space. Effectively, this distance introduces payoff heterogeneity, and the average game is returned only if the heterogeneity is small. For higher levels of heterogeneity the distance to the average game grows, which often involves the promotion of cooperation. The presented results support preceding research that highlights the favorable role of heterogeneity regardless of its origin, and they also emphasize the importance of the population structure in amplifying facilitators of cooperation.

To leave from social scenario: on heterogeneity and specifity of populism

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Sebastián Barros

2009-12-01

Full Text Available This paper is part of a discussion on the specificity of populism. Taking Laclau’s theorerical framework as a starting point, we analise the importance of the concept of heterogeneity in his argument. Later on, we analise Rancière’s understanding of politics as conflict and conclude that the idea of heterogeneity is central to a definition of populism. In this sense, we argue that heterogenity is something which is moved from its natural place in the order of domination, and starts to be taken as a part in the definition of the commonness of the community. This would have three specific effects over the subsequent political articulations. The inclusion of a heterogeneity would demonstrate the inexistance of the community of equals, forcing the need for a new representation of that community, now incarnated in a subject that, in the name of the past tort, claims to represent the universal plenitude of the community. Finally, we analise interventions by Gramsci and Ortega y Gasset in relation to the irruption of heterogeneity.

Heterogeneity in isogenic populations of microorganisms

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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...

Programming strategy for efficient modeling of dynamics in a population of heterogeneous cells.

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Hald, Bjørn Olav; Garkier Hendriksen, Morten; Sørensen, Preben Graae

2013-05-15

Heterogeneity is a ubiquitous property of biological systems. Even in a genetically identical population of a single cell type, cell-to-cell differences are observed. Although the functional behavior of a given population is generally robust, the consequences of heterogeneity are fairly unpredictable. In heterogeneous populations, synchronization of events becomes a cardinal problem-particularly for phase coherence in oscillating systems. The present article presents a novel strategy for construction of large-scale simulation programs of heterogeneous biological entities. The strategy is designed to be tractable, to handle heterogeneity and to handle computational cost issues simultaneously, primarily by writing a generator of the 'model to be simulated'. We apply the strategy to model glycolytic oscillations among thousands of yeast cells coupled through the extracellular medium. The usefulness is illustrated through (i) benchmarking, showing an almost linear relationship between model size and run time, and (ii) analysis of the resulting simulations, showing that contrary to the experimental situation, synchronous oscillations are surprisingly hard to achieve, underpinning the need for tools to study heterogeneity. Thus, we present an efficient strategy to model the biological heterogeneity, neglected by ordinary mean-field models. This tool is well posed to facilitate the elucidation of the physiologically vital problem of synchronization. The complete python code is available as Supplementary Information. bjornhald@gmail.com or pgs@kiku.dk Supplementary data are available at Bioinformatics online.

Metabolic heterogeneity in clonal microbial populations.

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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.

Modeling heterogeneous populations of thermostatically controlled loads using diffusion-advection PDEs

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Moura, Scott; Ruiz, Victor; Bendtsen, Jan Dimon

2013-01-01

This paper focuses on developing a partial differential equation (PDE)-based model and parameter identification scheme for heterogeneous populations of thermostatically controlled loads (TCLs). First, a coupled two-state hyperbolic PDE model for homogenous TCL populations is derived. This model i...

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

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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.

An alternative covariance estimator to investigate genetic heterogeneity in populations.

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Heslot, Nicolas; Jannink, Jean-Luc

2015-11-26

For genomic prediction and genome-wide association studies (GWAS) using mixed models, covariance between individuals is estimated using molecular markers. Based on the properties of mixed models, using available molecular data for prediction is optimal if this covariance is known. Under this assumption, adding individuals to the analysis should never be detrimental. However, some empirical studies showed that increasing training population size decreased prediction accuracy. Recently, results from theoretical models indicated that even if marker density is high and the genetic architecture of traits is controlled by many loci with small additive effects, the covariance between individuals, which depends on relationships at causal loci, is not always well estimated by the whole-genome kinship. We propose an alternative covariance estimator named K-kernel, to account for potential genetic heterogeneity between populations that is characterized by a lack of genetic correlation, and to limit the information flow between a priori unknown populations in a trait-specific manner. This is similar to a multi-trait model and parameters are estimated by REML and, in extreme cases, it can allow for an independent genetic architecture between populations. As such, K-kernel is useful to study the problem of the design of training populations. K-kernel was compared to other covariance estimators or kernels to examine its fit to the data, cross-validated accuracy and suitability for GWAS on several datasets. It provides a significantly better fit to the data than the genomic best linear unbiased prediction model and, in some cases it performs better than other kernels such as the Gaussian kernel, as shown by an empirical null distribution. In GWAS simulations, alternative kernels control type I errors as well as or better than the classical whole-genome kinship and increase statistical power. No or small gains were observed in cross-validated prediction accuracy. This alternative

Identifying and Assessing Interesting Subgroups in a Heterogeneous Population.

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Lee, Woojoo; Alexeyenko, Andrey; Pernemalm, Maria; Guegan, Justine; Dessen, Philippe; Lazar, Vladimir; Lehtiö, Janne; Pawitan, Yudi

2015-01-01

Biological heterogeneity is common in many diseases and it is often the reason for therapeutic failures. Thus, there is great interest in classifying a disease into subtypes that have clinical significance in terms of prognosis or therapy response. One of the most popular methods to uncover unrecognized subtypes is cluster analysis. However, classical clustering methods such as k-means clustering or hierarchical clustering are not guaranteed to produce clinically interesting subtypes. This could be because the main statistical variability--the basis of cluster generation--is dominated by genes not associated with the clinical phenotype of interest. Furthermore, a strong prognostic factor might be relevant for a certain subgroup but not for the whole population; thus an analysis of the whole sample may not reveal this prognostic factor. To address these problems we investigate methods to identify and assess clinically interesting subgroups in a heterogeneous population. The identification step uses a clustering algorithm and to assess significance we use a false discovery rate- (FDR-) based measure. Under the heterogeneity condition the standard FDR estimate is shown to overestimate the true FDR value, but this is remedied by an improved FDR estimation procedure. As illustrations, two real data examples from gene expression studies of lung cancer are provided.

Discovery of Power-Law Growth in the Self-Renewal of Heterogeneous Glioma Stem Cell Populations.

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Michiya Sugimori

Full Text Available Accumulating evidence indicates that cancer stem cells (CSCs drive tumorigenesis. This suggests that CSCs should make ideal therapeutic targets. However, because CSC populations in tumors appear heterogeneous, it remains unclear how CSCs might be effectively targeted. To investigate the mechanisms by which CSC populations maintain heterogeneity during self-renewal, we established a glioma sphere (GS forming model, to generate a population in which glioma stem cells (GSCs become enriched. We hypothesized, based on the clonal evolution concept, that with each passage in culture, heterogeneous clonal sublines of GSs are generated that progressively show increased proliferative ability.To test this hypothesis, we determined whether, with each passage, glioma neurosphere culture generated from four different glioma cell lines become progressively proliferative (i.e., enriched in large spheres. Rather than monitoring self-renewal, we measured heterogeneity based on neurosphere clone sizes (#cells/clone. Log-log plots of distributions of clone sizes yielded a good fit (r>0.90 to a straight line (log(% total clones = k*log(#cells/clone indicating that the system follows a power-law (y = xk with a specific degree exponent (k = -1.42. Repeated passaging of the total GS population showed that the same power-law was maintained over six passages (CV = -1.01 to -1.17. Surprisingly, passage of either isolated small or large subclones generated fully heterogeneous populations that retained the original power-law-dependent heterogeneity. The anti-GSC agent Temozolomide, which is well known as a standard therapy for glioblastoma multiforme (GBM, suppressed the self-renewal of clones, but it never disrupted the power-law behavior of a GS population.Although the data above did not support the stated hypothesis, they did strongly suggest a novel mechanism that underlies CSC heterogeneity. They indicate that power-law growth governs the self-renewal of heterogeneous

Spatial and temporal heterogeneity in high-grade serous ovarian cancer: a phylogenetic analysis.

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Roland F Schwarz

2015-02-01

Full Text Available The major clinical challenge in the treatment of high-grade serous ovarian cancer (HGSOC is the development of progressive resistance to platinum-based chemotherapy. The objective of this study was to determine whether intra-tumour genetic heterogeneity resulting from clonal evolution and the emergence of subclonal tumour populations in HGSOC was associated with the development of resistant disease.Evolutionary inference and phylogenetic quantification of heterogeneity was performed using the MEDICC algorithm on high-resolution whole genome copy number profiles and selected genome-wide sequencing of 135 spatially and temporally separated samples from 14 patients with HGSOC who received platinum-based chemotherapy. Samples were obtained from the clinical CTCR-OV03/04 studies, and patients were enrolled between 20 July 2007 and 22 October 2009. Median follow-up of the cohort was 31 mo (interquartile range 22-46 mo, censored after 26 October 2013. Outcome measures were overall survival (OS and progression-free survival (PFS. There were marked differences in the degree of clonal expansion (CE between patients (median 0.74, interquartile range 0.66-1.15, and dichotimization by median CE showed worse survival in CE-high cases (PFS 12.7 versus 10.1 mo, p = 0.009; OS 42.6 versus 23.5 mo, p = 0.003. Bootstrap analysis with resampling showed that the 95% confidence intervals for the hazard ratios for PFS and OS in the CE-high group were greater than 1.0. These data support a relationship between heterogeneity and survival but do not precisely determine its effect size. Relapsed tissue was available for two patients in the CE-high group, and phylogenetic analysis showed that the prevalent clonal population at clinical recurrence arose from early divergence events. A subclonal population marked by a NF1 deletion showed a progressive increase in tumour allele fraction during chemotherapy.This study demonstrates that quantitative measures of intra

Assessment of Genetic Heterogeneity in Structured Plant Populations Using Multivariate Whole-Genome Regression Models.

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Lehermeier, Christina; Schön, Chris-Carolin; de Los Campos, Gustavo

2015-09-01

Plant breeding populations exhibit varying levels of structure and admixture; these features are likely to induce heterogeneity of marker effects across subpopulations. Traditionally, structure has been dealt with as a potential confounder, and various methods exist to "correct" for population stratification. However, these methods induce a mean correction that does not account for heterogeneity of marker effects. The animal breeding literature offers a few recent studies that consider modeling genetic heterogeneity in multibreed data, using multivariate models. However, these methods have received little attention in plant breeding where population structure can have different forms. In this article we address the problem of analyzing data from heterogeneous plant breeding populations, using three approaches: (a) a model that ignores population structure [A-genome-based best linear unbiased prediction (A-GBLUP)], (b) a stratified (i.e., within-group) analysis (W-GBLUP), and (c) a multivariate approach that uses multigroup data and accounts for heterogeneity (MG-GBLUP). The performance of the three models was assessed on three different data sets: a diversity panel of rice (Oryza sativa), a maize (Zea mays L.) half-sib panel, and a wheat (Triticum aestivum L.) data set that originated from plant breeding programs. The estimated genomic correlations between subpopulations varied from null to moderate, depending on the genetic distance between subpopulations and traits. Our assessment of prediction accuracy features cases where ignoring population structure leads to a parsimonious more powerful model as well as others where the multivariate and stratified approaches have higher predictive power. In general, the multivariate approach appeared slightly more robust than either the A- or the W-GBLUP. Copyright © 2015 by the Genetics Society of America.

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

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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.

Analytic Investigation Into Effect of Population Heterogeneity on Parameter Ratio Estimates

International Nuclear Information System (INIS)

Schinkel, Colleen; Carlone, Marco; Warkentin, Brad; Fallone, B. Gino

2007-01-01

Purpose: A homogeneous tumor control probability (TCP) model has previously been used to estimate the α/β ratio for prostate cancer from clinical dose-response data. For the ratio to be meaningful, it must be assumed that parameter ratios are not sensitive to the type of tumor control model used. We investigated the validity of this assumption by deriving analytic relationships between the α/β estimates from a homogeneous TCP model, ignoring interpatient heterogeneity, and those of the corresponding heterogeneous (population-averaged) model that incorporated heterogeneity. Methods and Materials: The homogeneous and heterogeneous TCP models can both be written in terms of the geometric parameters D 50 and γ 50 . We show that the functional forms of these models are similar. This similarity was used to develop an expression relating the homogeneous and heterogeneous estimates for the α/β ratio. The expression was verified numerically by generating pseudo-data from a TCP curve with known parameters and then using the homogeneous and heterogeneous TCP models to estimate the α/β ratio for the pseudo-data. Results: When the dominant form of interpatient heterogeneity is that of radiosensitivity, the homogeneous and heterogeneous α/β estimates differ. This indicates that the presence of this heterogeneity affects the value of the α/β ratio derived from analysis of TCP curves. Conclusions: The α/β ratio estimated from clinical dose-response data is model dependent-a heterogeneous TCP model that accounts for heterogeneity in radiosensitivity will produce a greater α/β estimate than that resulting from a homogeneous TCP model

De novo assembly of highly diverse viral populations

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Yang Xiao

2012-09-01

Full Text Available Abstract Background Extensive genetic diversity in viral populations within infected hosts and the divergence of variants from existing reference genomes impede the analysis of deep viral sequencing data. A de novo population consensus assembly is valuable both as a single linear representation of the population and as a backbone on which intra-host variants can be accurately mapped. The availability of consensus assemblies and robustly mapped variants are crucial to the genetic study of viral disease progression, transmission dynamics, and viral evolution. Existing de novo assembly techniques fail to robustly assemble ultra-deep sequence data from genetically heterogeneous populations such as viruses into full-length genomes due to the presence of extensive genetic variability, contaminants, and variable sequence coverage. Results We present VICUNA, a de novo assembly algorithm suitable for generating consensus assemblies from genetically heterogeneous populations. We demonstrate its effectiveness on Dengue, Human Immunodeficiency and West Nile viral populations, representing a range of intra-host diversity. Compared to state-of-the-art assemblers designed for haploid or diploid systems, VICUNA recovers full-length consensus and captures insertion/deletion polymorphisms in diverse samples. Final assemblies maintain a high base calling accuracy. VICUNA program is publicly available at: http://www.broadinstitute.org/scientific-community/science/projects/viral-genomics/ viral-genomics-analysis-software. Conclusions We developed VICUNA, a publicly available software tool, that enables consensus assembly of ultra-deep sequence derived from diverse viral populations. While VICUNA was developed for the analysis of viral populations, its application to other heterogeneous sequence data sets such as metagenomic or tumor cell population samples may prove beneficial in these fields of research.

A novel staining protocol for multiparameter assessment of cell heterogeneity in Phormidium populations (cyanobacteria employing fluorescent dyes.

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Daria Tashyreva

Full Text Available Bacterial populations display high heterogeneity in viability and physiological activity at the single-cell level, especially under stressful conditions. We demonstrate a novel staining protocol for multiparameter assessment of individual cells in physiologically heterogeneous populations of cyanobacteria. The protocol employs fluorescent probes, i.e., redox dye 5-cyano-2,3-ditolyl tetrazolium chloride, 'dead cell' nucleic acid stain SYTOX Green, and DNA-specific fluorochrome 4',6-diamidino-2-phenylindole, combined with microscopy image analysis. Our method allows simultaneous estimates of cellular respiration activity, membrane and nucleoid integrity, and allows the detection of photosynthetic pigments fluorescence along with morphological observations. The staining protocol has been adjusted for, both, laboratory and natural populations of the genus Phormidium (Oscillatoriales, and tested on 4 field-collected samples and 12 laboratory strains of cyanobacteria. Based on the mentioned cellular functions we suggest classification of cells in cyanobacterial populations into four categories: (i active and intact; (ii injured but active; (iii metabolically inactive but intact; (iv inactive and injured, or dead.

Addressing population heterogeneity and distribution in epidemics models using a cellular automata approach.

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López, Leonardo; Burguerner, Germán; Giovanini, Leonardo

2014-04-12

The spread of an infectious disease is determined by biological and social factors. Models based on cellular automata are adequate to describe such natural systems consisting of a massive collection of simple interacting objects. They characterize the time evolution of the global system as the emergent behaviour resulting from the interaction of the objects, whose behaviour is defined through a set of simple rules that encode the individual behaviour and the transmission dynamic. An epidemic is characterized trough an individual-based-model built upon cellular automata. In the proposed model, each individual of the population is represented by a cell of the automata. This way of modeling an epidemic situation allows to individually define the characteristic of each individual, establish different scenarios and implement control strategies. A cellular automata model to study the time evolution of a heterogeneous populations through the various stages of disease was proposed, allowing the inclusion of individual heterogeneity, geographical characteristics and social factors that determine the dynamic of the desease. Different assumptions made to built the classical model were evaluated, leading to following results: i) for low contact rate (like in quarantine process or low density population areas) the number of infective individuals is lower than other areas where the contact rate is higher, and ii) for different initial spacial distributions of infected individuals different epidemic dynamics are obtained due to its influence on the transition rate and the reproductive ratio of disease. The contact rate and spatial distributions have a central role in the spread of a disease. For low density populations the spread is very low and the number of infected individuals is lower than in highly populated areas. The spacial distribution of the population and the disease focus as well as the geographical characteristic of the area play a central role in the dynamics of the

Heterogeneous responses of temperate-zone amphibian populations to climate change complicates conservation planning

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Muths, Erin L.; Chambert, Thierry A.; Schmidt, B. R.; Miller, D. A. W.; Hossack, Blake R.; Joly, P.; Grolet, O.; Green, D. M.; Pilliod, David S.; Cheylan, M.; Fisher, Robert N.; McCaffery, R. M.; Adams, M. J.; Palen, W. J.; Arntzen, J. W.; Garwood, J.; Fellers, Gary M.; Thirion, J. M.; Grant, Evan H. Campbell; Besnard, A.

2017-01-01

The pervasive and unabated nature of global amphibian declines suggests common demographic responses to a given driver, and quantification of major drivers and responses could inform broad-scale conservation actions. We explored the influence of climate on demographic parameters (i.e., changes in the probabilities of survival and recruitment) using 31 datasets from temperate zone amphibian populations (North America and Europe) with more than a decade of observations each. There was evidence for an influence of climate on population demographic rates, but the direction and magnitude of responses to climate drivers was highly variable among taxa and among populations within taxa. These results reveal that climate drivers interact with variation in life-history traits and population-specific attributes resulting in a diversity of responses. This heterogeneity complicates the identification of conservation ‘rules of thumb’ for these taxa, and supports the notion of local focus as the most effective approach to overcome global-scale conservation challenges.

The Hawk-Dove game in phenotypically homogeneous and heterogeneous populations of finite dimension

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Laruelle, Annick; da Silva Rocha, André Barreira; Escobedo, Ramón

2018-02-01

The Hawk-Dove game played between individuals in populations of finite dimension is analyzed by means of a stochastic model. We take into account both cases when all individuals in the population are either phenotypically homogeneous or heterogeneous. A strategy in the model is a gene representing the probability of playing the Hawk strategy. Individual interactions at the microscopic level are described by a genetic algorithm where evolution results from the interplay among selection, mutation, drift and cross-over of genes. We show that the behavioral patterns observed at the macroscopic level can be reproduced as the emergent result of individual interactions governed by the rules of the Hawk-Dove game at the microscopic level. We study how the results of the genetic algorithm compare with those obtained in evolutionary game theory, finding that, although genes continuously change both their presence and frequency in the population over time, the population average behavior always achieves stationarity and, when this happens, the final average strategy played in the population oscillates around the evolutionarily stable strategy in the homogeneous population case or the neutrally stable set in the heterogeneous population case.

Dynamics of epidemics outbreaks in heterogeneous populations

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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.

Environmental heterogeneity explains the genetic structure of Continental and Mediterranean populations of Fraxinus angustifolia Vahl.

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Martina Temunović

Full Text Available Tree species with wide distributions often exhibit different levels of genetic structuring correlated to their environment. However, understanding how environmental heterogeneity influences genetic variation is difficult because the effects of gene flow, drift and selection are confounded. We investigated the genetic variation and its ecological correlates in a wind-pollinated Mediterranean tree species, Fraxinus angustifolia Vahl, within a recognised glacial refugium in Croatia. We sampled 11 populations from environmentally divergent habitats within the Continental and Mediterranean biogeographical regions. We combined genetic data analyses based on nuclear microsatellite loci, multivariate statistics on environmental data and ecological niche modelling (ENM. We identified a geographic structure with a high genetic diversity and low differentiation in the Continental region, which contrasted with the significantly lower genetic diversity and higher population divergence in the Mediterranean region. The positive and significant correlation between environmental and genetic distances after controlling for geographic distance suggests an important influence of ecological divergence of the sites in shaping genetic variation. The ENM provided support for niche differentiation between the populations from the Continental and Mediterranean regions, suggesting that contemporary populations may represent two divergent ecotypes. Ecotype differentiation was also supported by multivariate environmental and genetic distance analyses. Our results suggest that despite extensive gene flow in continental areas, long-term stability of heterogeneous environments have likely promoted genetic divergence of ashes in this region and can explain the present-day genetic variation patterns of these ancient populations.

Novel microchip-based tools facilitating live cell imaging and assessment of functional heterogeneity within NK cell populations

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Elin eForslund

2012-10-01

Full Text Available Each individual has a heterogeneous pool of NK cells consisting of cells that may be specialized towards specific functional responses such as secretion of cytokines or killing of tumor cells. Many conventional methods are not fit to characterize heterogeneous populations as they measure the average response of all cells. Thus, there is a need for experimental platforms that provide single cell resolution. In addition, there are also transient and stochastic variations in functional responses at the single cell level, calling for methods that allow studies of many events over extended times. This paper presents a versatile microchip platform enabling long-term microscopic studies of individual NK cells interacting with target cells. Each microchip contains an array of microwells, optimized for medium or high-resolution time-lapse imaging of single or multiple NK and target cells, or for screening of thousands of isolated NK-target cell interactions. Individual NK cells confined with target cells in small microwells is a suitable setup for high-content screening and rapid assessment of heterogeneity within populations, while microwells of larger dimensions are appropriate for studies of NK cell migration and sequential interactions with multiple target cells. By combining the chip technology with ultrasonic manipulation, NK and target cells can be forced to interact and positioned with high spatial accuracy within individual microwells. This setup effectively and synchronously creates NK-target conjugates at hundreds of parallel positions in the microchip. Thus, this facilitates assessment of temporal aspects of NK-target cell interactions, e.g. conjugation, immune synapse formation and cytotoxic events. The microchip platform presented here can be used to effectively address questions related to fundamental functions of NK cells that can lead to better understanding of how the behavior of individual cells add up to give a functional response at

Spatial heterogeneity as a genetic mixing mechanism in highly philopatric colonial seabirds.

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Cristofari, Robin; Trucchi, Emiliano; Whittington, Jason D; Vigetta, Stéphanie; Gachot-Neveu, Hélène; Stenseth, Nils Christian; Le Maho, Yvon; Le Bohec, Céline

2015-01-01

How genetic diversity is maintained in philopatric colonial systems remains unclear, and understanding the dynamic balance of philopatry and dispersal at all spatial scales is essential to the study of the evolution of coloniality. In the King penguin, Aptenodytes patagonicus, return rates of post-fledging chicks to their natal sub-colony are remarkably high. Empirical studies have shown that adults return year after year to their previous breeding territories within a radius of a few meters. Yet, little reliable data are available on intra- and inter-colonial dispersal in this species. Here, we present the first fine-scale study of the genetic structure in a king penguin colony in the Crozet Archipelago. Samples were collected from individual chicks and analysed at 8 microsatellite loci. Precise geolocation data of hatching sites and selective pressures associated with habitat features were recorded for all sampling locations. We found that despite strong natal and breeding site fidelity, king penguins retain a high degree of panmixia and genetic diversity. Yet, genetic structure appears markedly heterogeneous across the colony, with higher-than-expected inbreeding levels, and local inbreeding and relatedness hotspots that overlap predicted higher-quality nesting locations. This points towards heterogeneous population structure at the sub-colony level, in which fine-scale environmental features drive local philopatric behaviour, while lower-quality patches may act as genetic mixing mechanisms at the colony level. These findings show how a lack of global genetic structuring can emerge from small-scale heterogeneity in ecological parameters, as opposed to the classical model of homogeneous dispersal. Our results also emphasize the importance of sampling design for estimation of population parameters in colonial seabirds, as at high spatial resolution, basic genetic features are shown to be location-dependent. Finally, this study stresses the importance of

Spatial heterogeneity as a genetic mixing mechanism in highly philopatric colonial seabirds.

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Robin Cristofari

Full Text Available How genetic diversity is maintained in philopatric colonial systems remains unclear, and understanding the dynamic balance of philopatry and dispersal at all spatial scales is essential to the study of the evolution of coloniality. In the King penguin, Aptenodytes patagonicus, return rates of post-fledging chicks to their natal sub-colony are remarkably high. Empirical studies have shown that adults return year after year to their previous breeding territories within a radius of a few meters. Yet, little reliable data are available on intra- and inter-colonial dispersal in this species. Here, we present the first fine-scale study of the genetic structure in a king penguin colony in the Crozet Archipelago. Samples were collected from individual chicks and analysed at 8 microsatellite loci. Precise geolocation data of hatching sites and selective pressures associated with habitat features were recorded for all sampling locations. We found that despite strong natal and breeding site fidelity, king penguins retain a high degree of panmixia and genetic diversity. Yet, genetic structure appears markedly heterogeneous across the colony, with higher-than-expected inbreeding levels, and local inbreeding and relatedness hotspots that overlap predicted higher-quality nesting locations. This points towards heterogeneous population structure at the sub-colony level, in which fine-scale environmental features drive local philopatric behaviour, while lower-quality patches may act as genetic mixing mechanisms at the colony level. These findings show how a lack of global genetic structuring can emerge from small-scale heterogeneity in ecological parameters, as opposed to the classical model of homogeneous dispersal. Our results also emphasize the importance of sampling design for estimation of population parameters in colonial seabirds, as at high spatial resolution, basic genetic features are shown to be location-dependent. Finally, this study stresses the

Phenotypic heterogeneity in a bacteriophage population only appears as stress-induced mutagenesis.

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Yosef, Ido; Edgar, Rotem; Qimron, Udi

2016-11-01

Stress-induced mutagenesis has been studied in cancer cells, yeast, bacteria, and archaea, but not in viruses. In a recent publication, we present a bacteriophage model showing an apparent stress-induced mutagenesis. We show that the stress does not drive the mutagenesis, but only selects the fittest mutants. The mechanism underlying the observed phenomenon is a phenotypic heterogeneity that resembles persistence of the viral population. The new findings, the background for the ongoing debate on stress-induced mutagenesis, and the phenotypic heterogeneity underlying a novel phage infection strategy are discussed in this short manuscript.

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

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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

Policy options for alcohol price regulation: the importance of modelling population heterogeneity.

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Meier, Petra Sylvia; Purshouse, Robin; Brennan, Alan

2010-03-01

Context and aims Internationally, the repertoire of alcohol pricing policies has expanded to include targeted taxation, inflation-linked taxation, taxation based on alcohol-by-volume (ABV), minimum pricing policies (general or targeted), bans of below-cost selling and restricting price-based promotions. Policy makers clearly need to consider how options compare in reducing harms at the population level, but are also required to demonstrate proportionality of their actions, which necessitates a detailed understanding of policy effects on different population subgroups. This paper presents selected findings from a policy appraisal for the UK government and discusses the importance of accounting for population heterogeneity in such analyses. Method We have built a causal, deterministic, epidemiological model which takes account of differential preferences by population subgroups defined by age, gender and level of drinking (moderate, hazardous, harmful). We consider purchasing preferences in terms of the types and volumes of alcoholic beverages, prices paid and the balance between bars, clubs and restaurants as opposed to supermarkets and off-licenses. Results Age, sex and level of drinking fundamentally affect beverage preferences, drinking location, prices paid, price sensitivity and tendency to substitute for other beverage types. Pricing policies vary in their impact on different product types, price points and venues, thus having distinctly different effects on subgroups. Because population subgroups also have substantially different risk profiles for harms, policies are differentially effective in reducing health, crime, work-place absence and unemployment harms. Conclusion Policy appraisals must account for population heterogeneity and complexity if resulting interventions are to be well considered, proportionate, effective and cost-effective.

Socioeconomic Heterogeneity in the Effect of Health Shocks on Earnings: Evidence from Population-Wide Data on Swedish Workers

OpenAIRE

Lundborg, Petter; Nilsson, Martin; Vikström, Johan

2011-01-01

In this paper, we estimate socioeconomic heterogeneity in the effect of unexpected health shocks on labor market outcomes, using register-based data on the entire population of Swedish workers. We effectively exploit a Difference-in-Difference-in-Differences design, in which we compare the change in labor earnings across treated and control groups with high and low education levels. If the anticipation effects are similar for individuals with high and low education, any difference in the esti...

The effect of correlated neuronal firing and neuronal heterogeneity on population coding accuracy in guinea pig inferior colliculus.

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Oran Zohar

Full Text Available It has been suggested that the considerable noise in single-cell responses to a stimulus can be overcome by pooling information from a large population. Theoretical studies indicated that correlations in trial-to-trial fluctuations in the responses of different neurons may limit the improvement due to pooling. Subsequent theoretical studies have suggested that inherent neuronal diversity, i.e., the heterogeneity of tuning curves and other response properties of neurons preferentially tuned to the same stimulus, can provide a means to overcome this limit. Here we study the effect of spike-count correlations and the inherent neuronal heterogeneity on the ability to extract information from large neural populations. We use electrophysiological data from the guinea pig Inferior-Colliculus to capture inherent neuronal heterogeneity and single cell statistics, and introduce response correlations artificially. To this end, we generate pseudo-population responses, based on single-cell recording of neurons responding to auditory stimuli with varying binaural correlations. Typically, when pseudo-populations are generated from single cell data, the responses within the population are statistically independent. As a result, the information content of the population will increase indefinitely with its size. In contrast, here we apply a simple algorithm that enables us to generate pseudo-population responses with variable spike-count correlations. This enables us to study the effect of neuronal correlations on the accuracy of conventional rate codes. We show that in a homogenous population, in the presence of even low-level correlations, information content is bounded. In contrast, utilizing a simple linear readout, that takes into account the natural heterogeneity, even of neurons preferentially tuned to the same stimulus, within the neural population, one can overcome the correlated noise and obtain a readout whose accuracy grows linearly with the size of

Deconstructing stem cell population heterogeneity: Single-cell analysis and modeling approaches

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Wu, Jincheng; Tzanakakis, Emmanuel S.

2014-01-01

Isogenic stem cell populations display cell-to-cell variations in a multitude of attributes including gene or protein expression, epigenetic state, morphology, proliferation and proclivity for differentiation. The origins of the observed heterogeneity and its roles in the maintenance of pluripotency and the lineage specification of stem cells remain unclear. Addressing pertinent questions will require the employment of single-cell analysis methods as traditional cell biochemical and biomolecular assays yield mostly population-average data. In addition to time-lapse microscopy and flow cytometry, recent advances in single-cell genomic, transcriptomic and proteomic profiling are reviewed. The application of multiple displacement amplification, next generation sequencing, mass cytometry and spectrometry to stem cell systems is expected to provide a wealth of information affording unprecedented levels of multiparametric characterization of cell ensembles under defined conditions promoting pluripotency or commitment. Establishing connections between single-cell analysis information and the observed phenotypes will also require suitable mathematical models. Stem cell self-renewal and differentiation are orchestrated by the coordinated regulation of subcellular, intercellular and niche-wide processes spanning multiple time scales. Here, we discuss different modeling approaches and challenges arising from their application to stem cell populations. Integrating single-cell analysis with computational methods will fill gaps in our knowledge about the functions of heterogeneity in stem cell physiology. This combination will also aid the rational design of efficient differentiation and reprogramming strategies as well as bioprocesses for the production of clinically valuable stem cell derivatives. PMID:24035899

HSM: Heterogeneous Subspace Mining in High Dimensional Data

DEFF Research Database (Denmark)

Müller, Emmanuel; Assent, Ira; Seidl, Thomas

2009-01-01

Heterogeneous data, i.e. data with both categorical and continuous values, is common in many databases. However, most data mining algorithms assume either continuous or categorical attributes, but not both. In high dimensional data, phenomena due to the "curse of dimensionality" pose additional...... challenges. Usually, due to locally varying relevance of attributes, patterns do not show across the full set of attributes. In this paper we propose HSM, which defines a new pattern model for heterogeneous high dimensional data. It allows data mining in arbitrary subsets of the attributes that are relevant...... for the respective patterns. Based on this model we propose an efficient algorithm, which is aware of the heterogeneity of the attributes. We extend an indexing structure for continuous attributes such that HSM indexing adapts to different attribute types. In our experiments we show that HSM efficiently mines...

Noise-Driven Phenotypic Heterogeneity with Finite Correlation Time in Clonal Populations.

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UnJin Lee

Full Text Available There has been increasing awareness in the wider biological community of the role of clonal phenotypic heterogeneity in playing key roles in phenomena such as cellular bet-hedging and decision making, as in the case of the phage-λ lysis/lysogeny and B. Subtilis competence/vegetative pathways. Here, we report on the effect of stochasticity in growth rate, cellular memory/intermittency, and its relation to phenotypic heterogeneity. We first present a linear stochastic differential model with finite auto-correlation time, where a randomly fluctuating growth rate with a negative average is shown to result in exponential growth for sufficiently large fluctuations in growth rate. We then present a non-linear stochastic self-regulation model where the loss of coherent self-regulation and an increase in noise can induce a shift from bounded to unbounded growth. An important consequence of these models is that while the average change in phenotype may not differ for various parameter sets, the variance of the resulting distributions may considerably change. This demonstrates the necessity of understanding the influence of variance and heterogeneity within seemingly identical clonal populations, while providing a mechanism for varying functional consequences of such heterogeneity. Our results highlight the importance of a paradigm shift from a deterministic to a probabilistic view of clonality in understanding selection as an optimization problem on noise-driven processes, resulting in a wide range of biological implications, from robustness to environmental stress to the development of drug resistance.

Friendship-based partner switching promotes cooperation in heterogeneous populations

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Chen, Wei; Wu, Te; Li, Zhiwu; Wang, Long

2016-02-01

The forming of human social ties tends to be with similar individuals. This study concentrates on the emergence of cooperation among heterogeneous populations. A simple model is proposed by considering the impact of interplay between the evolution of strategies and that of social partnerships on cooperation dynamics. Whenever two individuals acquire the rewards by playing prisoner's dilemma game with each other, the friendship (friendship is quantified as the weight of a link) between the two individuals deepens. Individuals can switch off the social ties with the partners who are unfriendly and rewire to similar new ones. Under this partner switching mechanism, population structure is divided into several groups and cooperation can prevail. It is observed that the frequent tendency of partner switching can lead to the enhancement of cooperative behavior under the enormous temptation to defect. Moreover, the influence of discounting the relationship between different individuals is also investigated. Meanwhile, the cooperation prevails when the adjustment of friendships mainly depends on the incomes of selected individuals rather than that of their partners. Finally, it is found that too similar population fail to maximize the cooperation and there exists a moderate similarity that can optimize cooperation.

Heterogeneity revealed through meta-analysis might link geographical differences with nasopharyngeal carcinoma incidence in Han Chinese populations

International Nuclear Information System (INIS)

Su, Wen-Hui; Chiu, Chi-Cking; Yao Shugart, Yin

2015-01-01

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy highly prevalent in southern China, and incidence rates among Han Chinese people vary according to geographic region. Recently, three independent genome-wide association studies (GWASs) confirmed that HLA-A is the main risk gene for NPC. However, the results of studies conducted in regions with dissimilar incidence rates contradicted the claims that HLA-A is the sole risk gene and that the association of rs29232 is independent of the HLA-A effect in the chromosome 6p21.3 region. We performed a meta-analysis, selecting five single-nucleotide polymorphisms (SNPs) in chromosome 6p21.3 mapped in three published GWASs and four case–control studies. The studies involved 8994 patients with NPC and 11,157 healthy controls, all of whom were Han Chinese. The rs2517713 SNP located downstream of HLA-A was significantly associated with NPC (P = 1.08 × 10 −91 , odds ratio [OR] = 0.58, 95 % confidence interval [CI] = 0.55–0.61). The rs29232 SNP exhibited a moderate level of heterogeneity (I 2 = 47 %) that disappeared (I 2 = 0 %) after stratification by moderate- and high-incidence NPC regions. Our results suggested that the HLA-A gene is strongly associated with NPC risk. In addition, the heterogeneity revealed by the meta-analysis of rs29232 might be associated with regional differences in NPC incidence among Han Chinese people. The higher OR of rs29232 and the fact that rs29232 was independent of the HLA-A effect in the moderate-incidence population suggested that rs29232 might have greater relevance to NPC incidence in a moderate-incidence population than in a high-incidence population. The online version of this article (doi:10.1186/s12885-015-1607-0) contains supplementary material, which is available to authorized users

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

NARCIS (Netherlands)

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

Environmental heterogeneity generates opposite gene-by-environment interactions for two fitness-related traits within a population.

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Culumber, Zachary W; Schumer, Molly; Monks, Scott; Tobler, Michael

2015-02-01

Theory predicts that environmental heterogeneity offers a potential solution to the maintenance of genetic variation within populations, but empirical evidence remains sparse. The live-bearing fish Xiphophorus variatus exhibits polymorphism at a single locus, with different alleles resulting in up to five distinct melanistic "tailspot" patterns within populations. We investigated the effects of heterogeneity in two ubiquitous environmental variables (temperature and food availability) on two fitness-related traits (upper thermal limits and body condition) in two different tailspot types (wild-type and upper cut crescent). We found gene-by-environment (G × E) interactions between tailspot type and food level affecting upper thermal limits (UTL), as well as between tailspot type and thermal environment affecting body condition. Exploring mechanistic bases underlying these G × E patterns, we found no differences between tailspot types in hsp70 gene expression despite significant overall increases in expression under both thermal and food stress. Similarly, there was no difference in routine metabolic rates between the tailspot types. The reversal of relative performance of the two tailspot types under different environmental conditions revealed a mechanism by which environmental heterogeneity can balance polymorphism within populations through selection on different fitness-related traits. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Proteomic Markers of Functional Sperm Population in Bovines: Comparison of Low- and High-Density Spermatozoa Following Cryopreservation.

Science.gov (United States)

D'Amours, Olivier; Frenette, Gilles; Bourassa, Sylvie; Calvo, Ézéchiel; Blondin, Patrick; Sullivan, Robert

2018-01-05

Mammalian semen contains a heterogeneous population of sperm cells. This heterogeneity results from variability in the complex processes of cell differentiation in the testis, biochemical modifications undergone by spermatozoa during transit along the male reproductive tract, interactions with secretions from accessory sex glands at ejaculation, and, in the context of reproductive technologies, in the ability of ejaculated spermatozoa to resist damage associated with freeze-thaw procedures. When submitted to density gradient centrifugation, ejaculated spermatozoa distribute themselves into two distinct populations: a low-density population characterized by low motility parameters, and a high-density population with high motility characteristics. To understand the origin of ejaculated spermatozoa heterogeneity, cryopreserved semen samples from bulls used by the artificial insemination (A.I.) industry were submitted to Percoll gradient centrifugation. Proteins from low and high density spermatozoa were then extracted with sodium deoxycholate and submitted to proteomic analysis using iTRAQ (isobaric tag for relative and absolute quantitation) methodologies. Quantification of selected sperm proteins was confirmed by multiple reaction monitoring (MRM). Overall, 31 different proteins were more abundant in low-density spermatozoa, while 80 different proteins were more abundant in the high-density subpopulation. Proteins enriched in high-density spermatozoa were markers of sperm functionality such as the glycolytic process, binding to the egg zona pellucida, and motility. Low-density spermatozoa were not solely characterized by loss of proteins and their associated functions. Chaperonin-containing TCP1s and chaperones are hallmarks of the low-density subpopulation. iTRAQ analysis revealed that other proteins such as binder of sperm proteins, histone, GPX5, ELSPBP1, and clusterin are overexpressed in low-density spermatozoa suggesting that these proteins represent defects

The effects of spatial and temporal heterogeneity on the population dynamics of four animal species in a Danish landscape

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Forchhammer Mads C

2009-06-01

Full Text Available Abstract Background Variation in carrying capacity and population return rates is generally ignored in traditional studies of population dynamics. Variation is hard to study in the field because of difficulties controlling the environment in order to obtain statistical replicates, and because of the scale and expense of experimenting on populations. There may also be ethical issues. To circumvent these problems we used detailed simulations of the simultaneous behaviours of interacting animals in an accurate facsimile of a real Danish landscape. The models incorporate as much as possible of the behaviour and ecology of skylarks Alauda arvensis, voles Microtus agrestis, a ground beetle Bembidion lampros and a linyphiid spider Erigone atra. This allows us to quantify and evaluate the importance of spatial and temporal heterogeneity on the population dynamics of the four species. Results Both spatial and temporal heterogeneity affected the relationship between population growth rate and population density in all four species. Spatial heterogeneity accounted for 23–30% of the variance in population growth rate after accounting for the effects of density, reflecting big differences in local carrying capacity associated with the landscape features important to individual species. Temporal heterogeneity accounted for 3–13% of the variance in vole, skylark and spider, but 43% in beetles. The associated temporal variation in carrying capacity would be problematic in traditional analyses of density dependence. Return rates were less than one in all species and essentially invariant in skylarks, spiders and beetles. Return rates varied over the landscape in voles, being slower where there were larger fluctuations in local population sizes. Conclusion Our analyses estimated the traditional parameters of carrying capacities and return rates, but these are now seen as varying continuously over the landscape depending on habitat quality and the mechanisms

TCP isoeffect analysis using a heterogeneous distribution of radiosensitivity

International Nuclear Information System (INIS)

Carlone, Marco; Wilkins, David; Nyiri, Balazs; Raaphorst, Peter

2004-01-01

A formula for the α/β ratio is derived using the heterogeneous (population averaged) tumor control model. This formula is nearly identical to the formula obtained using the homogeneous (individual) tumor control model, but the new formula includes extra terms showing that the α/β ratio, the ratio of the mean value of α divided by the mean value of β that would be observed in a patient population, explicitly depends on the survival level and heterogeneity. The magnitude of this correction is estimated for prostate cancer, and this appears to raise the mean value of the ratio estimate by about 20%. The method also allows investigation of confidence limits for α/β based on a population distribution of radiosensitivity. For a widely heterogeneous population, the upper 95% confidence interval for the α/β ratio can be as high as 7.3 Gy, even though the population mean is between 2.3 and 2.6 Gy

Comparisons of Adherence to Antiretroviral Therapy in a High-Risk Population in China: A Systematic Review and Meta-Analysis.

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Zhou Huan

Full Text Available Reports on antiretroviral therapy (ART adherence are scare in China; we performed this meta-analysis to estimate ART adherence rates in different populations at high risk for HIV transmission in China.We searched PubMed, Chinese Biomedical Literature Database (Chinese, China National Knowledge Infrastructure (Chinese, and Wanfang (Chinese to identify studies published from January 1985 to May 2015. We used random-effects meta-analysis to calculate weighted mean estimates across studies and 95% CIs. Data were pooled with proportions transformed prior to pooling using the Freeman-Tukey double arcsine transformation and then back transformed to the original scale. We calculated the I2 (and its 95% confidence intervals and tau2 to assess between-study heterogeneity.We identified 36 eligible articles, including 6885 HIV-positive individuals, reporting ART adherence. Pooled analysis produced an estimate of 77.61% (95% CI = 71.63-83.08 of patients with HIV with adequate adherence; however, high heterogeneity was observed between studies (I2 = 96.60%, 95%CI = 96.00%-97.20%; tau2 = 0.16. Three studies, which included 149 old HIV-infected patients, reported the highest ART adequate adherence rate (89.39%, 95% CI = 72.01-99.26 with high heterogeneity between the studies (I2 = 86.20%, 95%CI = 60.00-95.20%; tau2 = 0.13. While, only two studies, which included 143 heterosexual transmission group (HTG patients, reported the lowest ART adequate adherence rate (51.55%, 95% CI = 41.33-61.71 with low heterogeneity between the studies (I2 = 31.3%, tau2 = 0.007. In the multivariable meta-regression model, high-risk populations was the main factor explaining heterogeneity (variance explained 28.14%.ART adherence in some high-risk populations (e.g., heterosexual transmission group is below the recommended levels for maintaining virologic suppression. It is crucial to develop comprehensive intervention strategies to promote ART adherence in high-risk populations and

Higher rates of sex evolve in spatially heterogeneous environments.

Science.gov (United States)

Becks, Lutz; Agrawal, Aneil F

2010-11-04

The evolution and maintenance of sexual reproduction has puzzled biologists for decades. Although this field is rich in hypotheses, experimental evidence is scarce. Some important experiments have demonstrated differences in evolutionary rates between sexual and asexual populations; other experiments have documented evolutionary changes in phenomena related to genetic mixing, such as recombination and selfing. However, direct experiments of the evolution of sex within populations are extremely rare (but see ref. 12). Here we use the rotifer, Brachionus calyciflorus, which is capable of both sexual and asexual reproduction, to test recent theory predicting that there is more opportunity for sex to evolve in spatially heterogeneous environments. Replicated experimental populations of rotifers were maintained in homogeneous environments, composed of either high- or low-quality food habitats, or in heterogeneous environments that consisted of a mix of the two habitats. For populations maintained in either type of homogeneous environment, the rate of sex evolves rapidly towards zero. In contrast, higher rates of sex evolve in populations experiencing spatially heterogeneous environments. The data indicate that the higher level of sex observed under heterogeneity is not due to sex being less costly or selection against sex being less efficient; rather sex is sufficiently advantageous in heterogeneous environments to overwhelm its inherent costs. Counter to some alternative theories for the evolution of sex, there is no evidence that genetic drift plays any part in the evolution of sex in these populations.

Quorum Sensing in Populations of Spatially Extended Chaotic Oscillators Coupled Indirectly via a Heterogeneous Environment

Science.gov (United States)

Li, Bing-Wei; Cao, Xiao-Zhi; Fu, Chenbo

2017-12-01

Many biological and chemical systems could be modeled by a population of oscillators coupled indirectly via a dynamical environment. Essentially, the environment by which the individual element communicates with each other is heterogeneous. Nevertheless, most of previous works considered the homogeneous case only. Here we investigated the dynamical behaviors in a population of spatially distributed chaotic oscillators immersed in a heterogeneous environment. Various dynamical synchronization states (such as oscillation death, phase synchronization, and complete synchronized oscillation) as well as their transitions were explored. In particular, we uncovered a non-traditional quorum sensing transition: increasing the population density leaded to a transition from oscillation death to synchronized oscillation at first, but further increasing the density resulted in degeneration from complete synchronization to phase synchronization or even from phase synchronization to desynchronization. The underlying mechanism of this finding was attributed to the dual roles played by the population density. What's more, by treating the environment as another component of the oscillator, the full system was then effectively equivalent to a locally coupled system. This fact allowed us to utilize the master stability functions approach to predict the occurrence of complete synchronization oscillation, which agreed with that from the direct numerical integration of the system. The potential candidates for the experimental realization of our model were also discussed.

Landscape heterogeneity drives intra-population niche variation and reproduction in an arctic top predator.

Science.gov (United States)

L'hérault, Vincent; Franke, Alastair; Lecomte, Nicolas; Alogut, Adam; Bêty, Joël

2013-09-01

While intra-population variability in resource use is ubiquitous, little is known of how this measure of niche diversity varies in space and its role in population dynamics. Here we examined how heterogeneous breeding environments can structure intra-population niche variation in both resource use and reproductive output. We investigated intra-population niche variation in the Arctic tundra ecosystem, studying peregrine falcon (Falco peregrinus tundrius, White) breeding within a terrestrial-marine gradient near Rankin Inlet, Nunavut, Canada. Using stable isotope analysis, we found that intra-population niches varied at the individual level; we examined within-nest and among-nest variation, though only the latter varied along the terrestrial-marine gradient (i.e., increased among-nest variability among birds nesting within the marine environment, indicating higher degree of specialization). Terrestrial prey species (small herbivores and insectivores) were consumed by virtually all falcons. Falcons nesting within the marine environment made use of marine prey (sea birds), but depended heavily on terrestrial prey (up to 90% of the diet). Using 28-years of peregrine falcon nesting data, we found a positive relationship between the proportion of terrestrial habitat surrounding nest sites and annual nestling production, but no relationship with the likelihood of successfully rearing at least one nestling reaching 25 days old. Annually, successful inland breeders raised 0.47 more young on average compared to offshore breeders, which yields potential fitness consequences for this long-living species. The analyses of niche and reproductive success suggest a potential breeding cost for accessing distant terrestrial prey, perhaps due to additional traveling costs, for those individuals with marine nest site locations. Our study indicates how landscape heterogeneity can generate proximate (niche variation) and ultimate (reproduction) consequences on a population of generalist

Differing effects of attention in single-units and populations are well predicted by heterogeneous tuning and the normalization model of attention.

Science.gov (United States)

Hara, Yuko; Pestilli, Franco; Gardner, Justin L

2014-01-01

Single-unit measurements have reported many different effects of attention on contrast-response (e.g., contrast-gain, response-gain, additive-offset dependent on visibility), while functional imaging measurements have more uniformly reported increases in response across all contrasts (additive-offset). The normalization model of attention elegantly predicts the diversity of effects of attention reported in single-units well-tuned to the stimulus, but what predictions does it make for more realistic populations of neurons with heterogeneous tuning? Are predictions in accordance with population-scale measurements? We used functional imaging data from humans to determine a realistic ratio of attention-field to stimulus-drive size (a key parameter for the model) and predicted effects of attention in a population of model neurons with heterogeneous tuning. We found that within the population, neurons well-tuned to the stimulus showed a response-gain effect, while less-well-tuned neurons showed a contrast-gain effect. Averaged across the population, these disparate effects of attention gave rise to additive-offsets in contrast-response, similar to reports in human functional imaging as well as population averages of single-units. Differences in predictions for single-units and populations were observed across a wide range of model parameters (ratios of attention-field to stimulus-drive size and the amount of baseline response modifiable by attention), offering an explanation for disparity in physiological reports. Thus, by accounting for heterogeneity in tuning of realistic neuronal populations, the normalization model of attention can not only predict responses of well-tuned neurons, but also the activity of large populations of neurons. More generally, computational models can unify physiological findings across different scales of measurement, and make links to behavior, but only if factors such as heterogeneous tuning within a population are properly accounted for.

Imperfect repair and lifesaving in heterogeneous populations

Energy Technology Data Exchange (ETDEWEB)

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.

Population heterogeneity in Saccharomyces cerevisiae and Escherichia coli lab scale cultivations simulating industrial scale bioprocesses

DEFF Research Database (Denmark)

Heins, Anna-Lena

Today it is well known that a population of cells in a bioreactor is heterogeneous, opposite to traditional belief, and thus exhibiting distributions of single cell properties e.g. cell size, viability and metabolic activity rather than having a set of characteristics that can be described...

Emergence of cooperation in phenotypically heterogeneous populations: a replicator dynamics analysis

International Nuclear Information System (INIS)

Barreira da Silva Rocha, A; Escobedo, R; Laruelle, A

2015-01-01

The emergence of cooperation is analyzed in heterogeneous populations where two kinds of individuals exist according to their phenotypic appearance. Phenotype recognition is assumed for all individuals: individuals are able to identify the type of every other individual, but fail to recognize their own type. Individuals thus behave under partial information conditions. The interactions between individuals are described by the snowdrift game, where individuals can either cooperate or defect. The evolution of such populations is studied in the framework of evolutionary game theory by means of the replicator dynamics. Overlapping generations are considered, so the replicator equations are formulated in discrete-time form. The stability analysis of the dynamical system is carried out and a detailed description of the behavior of trajectories starting from the interior of the state-space is given. We find that the four monomorphic states are unstable and that a polymorphic state exists which is a global attractor for non-degenerate initial states of the population. The result for the discrete-time replicator coincides with the one of the continuous case. (paper)

Population Heterogeneity of Lactobacillus plantarum WCFS1 Microcolonies in Response to and Recovery from Acid Stress

NARCIS (Netherlands)

Ingham, C.J.; Beerthuyzen, M.; Vlieg, J.E.T.V.H.

2008-01-01

Within an isogenic microbial population in a homogenous environment, individual bacteria can still exhibit differences in phenotype. Phenotypic heterogeneity can facilitate the survival of subpopulations under stress. As the gram-positive bacterium Lactobacillus plantarum grows, it acidifies the

High throughput screening method for assessing heterogeneity of microorganisms

NARCIS (Netherlands)

Ingham, C.J.; Sprenkels, A.J.; van Hylckama Vlieg, J.E.T.; Bomer, Johan G.; de Vos, W.M.; van den Berg, Albert

2006-01-01

The invention relates to the field of microbiology. Provided is a method which is particularly powerful for High Throughput Screening (HTS) purposes. More specific a high throughput method for determining heterogeneity or interactions of microorganisms is provided.

Direct-Imaging-Based Quantification of Bacillus cereus ATCC 14579 Population Heterogeneity at a Low Incubation Temperature

NARCIS (Netherlands)

Besten, den H.M.W.; Garcia, D.; Moezelaar, R.; Zwietering, M.H.; Abee, T.

2010-01-01

Bacillus cereus ATCC 14579 was cultured in microcolonies on Anopore strips near its minimum growth temperature to directly image and quantify its population heterogeneity at an abusive refrigeration temperature. Eleven percent of the microcolonies failed to grow during low-temperature incubation,

Population specific genetic heterogeneity of familial hypercholesterolemia in South Africa.

Science.gov (United States)

Smyth, Natalie; Ramsay, Michèle; Raal, Frederick J

2018-04-01

To describe the prevalence and population-specific genetic heterogeneity of familial hypercholesterolemia in South Africa. This review highlights the paucity of data on familial hypercholesterolemia in South Africa, and the urgent need to uncover the mutation profiles in lipid-associated genes, causing an increase in LDL-cholesterol in the different ethnic groups. Case reports and small studies have shown that familial hypercholesterolemia, although apparently uncommon, is present in black Africans. Local founder effects have led to an increased prevalence of familial hypercholesterolemia in several South African populations: Afrikaner founder mutations (c.681 C>G, c.1285 G>A, c.523 G>A), Ashkenazi founder mutation (c.654_656del) and possible Indian founder mutation (c.2054 C>T). Preliminary data in black Africans with elevated LDL-cholesterol identified a possible common mutation, c.137_142del. The South African multiethnic society and well described founder effects emphasize the need for differential approaches to diagnosis and management of familial hypercholesterolemia. Studies involving larger cohorts and inclusive of different ethnicities are paramount to establishing an accurate prevalence of familial hypercholesterolemia in black Africans, not only in South Africa but in the Sub-Saharan African region. It is clear that the estimated world prevalence of one in 250 cannot be generally applied across African populations.

Dynamic single-cell analysis of Saccharomyces cerevisiae under process perturbation: Comparison of different methods for monitoring the intensity of population heterogeneity

DEFF Research Database (Denmark)

Delvigne, Frank; Baert, Jonathan; Gofflot, Sébastien

2015-01-01

BACKGROUND: Single cell biology has attracted a lot of attention in recent years and has led to numerous fundamental results pointing out the heterogeneity of clonal cell populations. In this context, microbial phenotypic heterogeneity under bioprocessing conditions needs to be further investigat...

Selective adaptation in networks of heterogeneous populations: model, simulation, and experiment.

Directory of Open Access Journals (Sweden)

Avner Wallach

2008-02-01

Full Text Available Biological systems often change their responsiveness when subject to persistent stimulation, a phenomenon termed adaptation. In neural systems, this process is often selective, allowing the system to adapt to one stimulus while preserving its sensitivity to another. In some studies, it has been shown that adaptation to a frequent stimulus increases the system's sensitivity to rare stimuli. These phenomena were explained in previous work as a result of complex interactions between the various subpopulations of the network. A formal description and analysis of neuronal systems, however, is hindered by the network's heterogeneity and by the multitude of processes taking place at different time-scales. Viewing neural networks as populations of interacting elements, we develop a framework that facilitates a formal analysis of complex, structured, heterogeneous networks. The formulation developed is based on an analysis of the availability of activity dependent resources, and their effects on network responsiveness. This approach offers a simple mechanistic explanation for selective adaptation, and leads to several predictions that were corroborated in both computer simulations and in cultures of cortical neurons developing in vitro. The framework is sufficiently general to apply to different biological systems, and was demonstrated in two different cases.

Projection specificity in heterogeneous locus coeruleus cell populations: implications for learning and memory

Science.gov (United States)

Uematsu, Akira; Tan, Bao Zhen

2015-01-01

Noradrenergic neurons in the locus coeruleus (LC) play a critical role in many functions including learning and memory. This relatively small population of cells sends widespread projections throughout the brain including to a number of regions such as the amygdala which is involved in emotional associative learning and the medial prefrontal cortex which is important for facilitating flexibility when learning rules change. LC noradrenergic cells participate in both of these functions, but it is not clear how this small population of neurons modulates these partially distinct processes. Here we review anatomical, behavioral, and electrophysiological studies to assess how LC noradrenergic neurons regulate these different aspects of learning and memory. Previous work has demonstrated that subpopulations of LC noradrenergic cells innervate specific brain regions suggesting heterogeneity of function in LC neurons. Furthermore, noradrenaline in mPFC and amygdala has distinct effects on emotional learning and cognitive flexibility. Finally, neural recording data show that LC neurons respond during associative learning and when previously learned task contingencies change. Together, these studies suggest a working model in which distinct and potentially opposing subsets of LC neurons modulate particular learning functions through restricted efferent connectivity with amygdala or mPFC. This type of model may provide a general framework for understanding other neuromodulatory systems, which also exhibit cell type heterogeneity and projection specificity. PMID:26330494

High-resolution charge carrier mobility mapping of heterogeneous organic semiconductors

Science.gov (United States)

Button, Steven W.; Mativetsky, Jeffrey M.

2017-08-01

Organic electronic device performance is contingent on charge transport across a heterogeneous landscape of structural features. Methods are therefore needed to unravel the effects of local structure on overall electrical performance. Using conductive atomic force microscopy, we construct high-resolution out-of-plane hole mobility maps from arrays of 5000 to 16 000 current-voltage curves. To demonstrate the efficacy of this non-invasive approach for quantifying and mapping local differences in electrical performance due to structural heterogeneities, we investigate two thin film test systems, one bearing a heterogeneous crystal structure [solvent vapor annealed 5,11-Bis(triethylsilylethynyl)anthradithiophene (TES-ADT)—a small molecule organic semiconductor] and one bearing a heterogeneous chemical composition [p-DTS(FBTTh2)2:PC71BM—a high-performance organic photovoltaic active layer]. TES-ADT shows nearly an order of magnitude difference in hole mobility between semicrystalline and crystalline areas, along with a distinct boundary between the two regions, while p-DTS(FBTTh2)2:PC71BM exhibits subtle local variations in hole mobility and a nanoscale domain structure with features below 10 nm in size. We also demonstrate mapping of the built-in potential, which plays a significant role in organic light emitting diode and organic solar cell operation.

High-throughput heterogeneous catalyst research

Science.gov (United States)

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

Functional heterogeneity of side population cells in skeletal muscle

International Nuclear Information System (INIS)

Uezumi, Akiyoshi; Ojima, Koichi; Fukada, So-ichiro; Ikemoto, Madoka; Masuda, Satoru; Miyagoe-Suzuki, Yuko; Takeda, Shin'ichi

2006-01-01

Skeletal muscle regeneration has been exclusively attributed to myogenic precursors, satellite cells. A stem cell-rich fraction referred to as side population (SP) cells also resides in skeletal muscle, but its roles in muscle regeneration remain unclear. We found that muscle SP cells could be subdivided into three sub-fractions using CD31 and CD45 markers. The majority of SP cells in normal non-regenerating muscle expressed CD31 and had endothelial characteristics. However, CD31 - CD45 - SP cells, which are a minor subpopulation in normal muscle, actively proliferated upon muscle injury and expressed not only several regulatory genes for muscle regeneration but also some mesenchymal lineage markers. CD31 - CD45 - SP cells showed the greatest myogenic potential among three SP sub-fractions, but indeed revealed mesenchymal potentials in vitro. These SP cells preferentially differentiated into myofibers after intramuscular transplantation in vivo. Our results revealed the heterogeneity of muscle SP cells and suggest that CD31 - CD45 - SP cells participate in muscle regeneration

Nanoscale high-content analysis using compositional heterogeneities of single proteoliposomes

DEFF Research Database (Denmark)

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....

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

DEFF Research Database (Denmark)

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...

Morphological heterogeneity and population differentiation in the green chromid Etroplus suratensis (Pisces: Cichlidae in Sri Lanka

Directory of Open Access Journals (Sweden)

K. B. Suneetha Gunawickrama

2007-09-01

Full Text Available Morphological variation of the euryhaline cichlid fish Etroplus suratensis (Bloch from six geographically apart estuarine localities along the southern and western coasts of Sri Lanka was studied. Significant heterogeneity in morphology of the cichlid were found with respect to nine morphometric characters (n=218. Fish of Nilwala estuary and Garanduwa lagoon were not significantly different in morphology, yet they show discernible differences from the other four samples (Kahanda lagoon, Chilaw lagoon, Walawe estuary and Koggala lagoon with respect to the most of the studied characters. Concordant results were found by multivariate analysis of the sizecorrected morphological data as well. Three functions were significant in discriminating the populations of which the first two functions accounted for 95% of the covariance (CV1 85.4 % and CV2 9.7%. The function with the greatest discriminatory power (CV1 can clearly separate samples of Nilwala estuary (L5 and Garanduwa lagoon (L6 from the rest of the samples, while the magnitude of the discrimination between the latter samples is much smaller. Classification functions could correctly classify an average of 65.7% of the individuals into their respective a priori population units. No evidence was found for isolation-by-distance model. The results suggest that E. suratensis populations in some of the studied estuarine localities maintain significant morphological heterogeneity, and the morphological variation can be used to differentiate some of these populations.

Fluctuating Asymmetry of Craniological Features of Small Mammals as a Reflection of Heterogeneity of Natural Populations

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Elena Shadrina

2016-11-01

Full Text Available Fluctuating asymmetry (FA in nine species of small mammals (Insectivora and Rodentia was estimated using 10 cranial features (foramina for nerves and blood vessels. The main criterion was the occurrence of the fluctuating asymmetry manifestations (OFAM. A total of 2300 skulls collected in the taiga and forest-tundra of Yakutia (Northeast Asia were examined. The examined species are characterized by comparable OFAM values in the vast territories of the taiga zone; on the ecological periphery of the range an increased FA level is registered. Asymmetric manifestations in analyzed features are equally likely to occur in males and females. OFAM values in juveniles are higher than in adults; this difference is more pronounced on the periphery of the geographic range. Among juveniles, lower FA levels are observed in individuals that have bred. It can be surmised that the risk of elimination of individuals with high FA levels increases in stressful periods (active reproduction and winter. In conditions that are close to optimal, populations demonstrate relatively homogeneous FA levels, while on the periphery of the area an increase in occurrence of disturbances in developmental stability is observed, which leads, on one hand, to higher average FA for the population and, on the other hand, to heterogeneity of the population in this parameter.

A millifluidic study of cell-to-cell heterogeneity in growth-rate and cell-division capability in populations of isogenic cells of Chlamydomonas reinhardtii.

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Shima P Damodaran

Full Text Available To address possible cell-to-cell heterogeneity in growth dynamics of isogenic cell populations of Chlamydomonas reinhardtii, we developed a millifluidic drop-based device that not only allows the analysis of populations grown from single cells over periods of a week, but is also able to sort and collect drops of interest, containing viable and healthy cells, which can be used for further experimentation. In this study, we used isogenic algal cells that were first synchronized in mixotrophic growth conditions. We show that these synchronized cells, when placed in droplets and kept in mixotrophic growth conditions, exhibit mostly homogeneous growth statistics, but with two distinct subpopulations: a major population with a short doubling-time (fast-growers and a significant subpopulation of slowly dividing cells (slow-growers. These observations suggest that algal cells from an isogenic population may be present in either of two states, a state of restricted division and a state of active division. When isogenic cells were allowed to propagate for about 1000 generations on solid agar plates, they displayed an increased heterogeneity in their growth dynamics. Although we could still identify the original populations of slow- and fast-growers, drops inoculated with a single progenitor cell now displayed a wider diversity of doubling-times. Moreover, populations dividing with the same growth-rate often reached different cell numbers in stationary phase, suggesting that the progenitor cells differed in the number of cell divisions they could undertake. We discuss possible explanations for these cell-to-cell heterogeneities in growth dynamics, such as mutations, differential aging or stochastic variations in metabolites and macromolecules yielding molecular switches, in the light of single-cell heterogeneities that have been reported among isogenic populations of other eu- and prokaryotes.

Clonal heterogeneity and chromosomal instability at disease presentation in high hyperdiploid acute lymphoblastic leukemia.

Science.gov (United States)

Talamo, Anna; Chalandon, Yves; Marazzi, Alfio; Jotterand, Martine

2010-12-01

Although aneuploidy has many possible causes, it often results from underlying chromosomal instability (CIN) leading to an unstable karyotype with cell-to-cell variation and multiple subclones. To test for the presence of CIN in high hyperdiploid acute lymphoblastic leukemia (HeH ALL) at diagnosis, we investigated 20 patients (10 HeH ALL and 10 non-HeH ALL), using automated four-color interphase fluorescence in situ hybridization (I-FISH) with centromeric probes for chromosomes 4, 6, 10, and 17. In HeH ALL, the proportion of abnormal cells ranged from 36.3% to 92.4%, and a variety of aneuploid populations were identified. Compared with conventional cytogenetics, I-FISH revealed numerous additional clones, some of them very small. To investigate the nature and origin of this clonal heterogeneity, we determined average numerical CIN values for all four chromosomes together and for each chromosome and patient group. The CIN values in HeH ALL were relatively high (range, 22.2-44.7%), compared with those in non-HeH ALL (3.2-6.4%), thus accounting for the presence of numerical CIN in HeH ALL at diagnosis. We conclude that numerical CIN may be at the origin of the high level of clonal heterogeneity revealed by I-FISH in HeH ALL at presentation, which would corroborate the potential role of CIN in tumor pathogenesis. Copyright © 2010 Elsevier Inc. All rights reserved.

Characterizing heterogeneous cellular responses to perturbations.

Science.gov (United States)

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.

Stable Regulation of Cell Cycle Events in Mycobacteria: Insights From Inherently Heterogeneous Bacterial Populations.

Science.gov (United States)

Logsdon, Michelle M; Aldridge, Bree B

2018-01-01

Model bacteria, such as E. coli and B. subtilis , tightly regulate cell cycle progression to achieve consistent cell size distributions and replication dynamics. Many of the hallmark features of these model bacteria, including lateral cell wall elongation and symmetric growth and division, do not occur in mycobacteria. Instead, mycobacterial growth is characterized by asymmetric polar growth and division. This innate asymmetry creates unequal birth sizes and growth rates for daughter cells with each division, generating a phenotypically heterogeneous population. Although the asymmetric growth patterns of mycobacteria lead to a larger variation in birth size than typically seen in model bacterial populations, the cell size distribution is stable over time. Here, we review the cellular mechanisms of growth, division, and cell cycle progression in mycobacteria in the face of asymmetry and inherent heterogeneity. These processes coalesce to control cell size. Although Mycobacterium smegmatis and Mycobacterium bovis Bacillus Calmette-Guérin (BCG) utilize a novel model of cell size control, they are similar to previously studied bacteria in that initiation of DNA replication is a key checkpoint for cell division. We compare the regulation of DNA replication initiation and strategies used for cell size homeostasis in mycobacteria and model bacteria. Finally, we review the importance of cellular organization and chromosome segregation relating to the physiology of mycobacteria and consider how new frameworks could be applied across the wide spectrum of bacterial diversity.

High variability of the heterogeneous ice nucleation potential of oxalic acid dihydrate and sodium oxalate

Directory of Open Access Journals (Sweden)

R. Wagner

2010-08-01

Full Text Available The heterogeneous ice nucleation potential of airborne oxalic acid dihydrate and sodium oxalate particles in the deposition and condensation mode has been investigated by controlled expansion cooling cycles in the AIDA aerosol and cloud chamber of the Karlsruhe Institute of Technology at temperatures between 244 and 228 K. Previous laboratory studies have highlighted the particular role of oxalic acid dihydrate as the only species amongst a variety of other investigated dicarboxylic acids to be capable of acting as a heterogeneous ice nucleus in both the deposition and immersion mode. We could confirm a high deposition mode ice activity for 0.03 to 0.8 μm sized oxalic acid dihydrate particles that were either formed by nucleation from a gaseous oxalic acid/air mixture or by rapid crystallisation of highly supersaturated aqueous oxalic acid solution droplets. The critical saturation ratio with respect to ice required for deposition nucleation was found to be less than 1.1 and the size-dependent ice-active fraction of the aerosol population was in the range from 0.1 to 22%. In contrast, oxalic acid dihydrate particles that had crystallised from less supersaturated solution droplets and had been allowed to slowly grow in a supersaturated environment from still unfrozen oxalic acid solution droplets over a time period of several hours were found to be much poorer heterogeneous ice nuclei. We speculate that under these conditions a crystal surface structure with less-active sites for the initiation of ice nucleation was generated. Such particles partially proved to be almost ice-inactive in both the deposition and condensation mode. At times, the heterogeneous ice nucleation ability of oxalic acid dihydrate significantly changed when the particles had been processed in preceding cloud droplet activation steps. Such behaviour was also observed for the second investigated species, namely sodium oxalate. Our experiments address the atmospheric scenario

High variability of the heterogeneous ice nucleation potential of oxalic acid dihydrate and sodium oxalate

Science.gov (United States)

Wagner, R.; Möhler, O.; Saathoff, H.; Schnaiter, M.; Leisner, T.

2010-08-01

The heterogeneous ice nucleation potential of airborne oxalic acid dihydrate and sodium oxalate particles in the deposition and condensation mode has been investigated by controlled expansion cooling cycles in the AIDA aerosol and cloud chamber of the Karlsruhe Institute of Technology at temperatures between 244 and 228 K. Previous laboratory studies have highlighted the particular role of oxalic acid dihydrate as the only species amongst a variety of other investigated dicarboxylic acids to be capable of acting as a heterogeneous ice nucleus in both the deposition and immersion mode. We could confirm a high deposition mode ice activity for 0.03 to 0.8 μm sized oxalic acid dihydrate particles that were either formed by nucleation from a gaseous oxalic acid/air mixture or by rapid crystallisation of highly supersaturated aqueous oxalic acid solution droplets. The critical saturation ratio with respect to ice required for deposition nucleation was found to be less than 1.1 and the size-dependent ice-active fraction of the aerosol population was in the range from 0.1 to 22%. In contrast, oxalic acid dihydrate particles that had crystallised from less supersaturated solution droplets and had been allowed to slowly grow in a supersaturated environment from still unfrozen oxalic acid solution droplets over a time period of several hours were found to be much poorer heterogeneous ice nuclei. We speculate that under these conditions a crystal surface structure with less-active sites for the initiation of ice nucleation was generated. Such particles partially proved to be almost ice-inactive in both the deposition and condensation mode. At times, the heterogeneous ice nucleation ability of oxalic acid dihydrate significantly changed when the particles had been processed in preceding cloud droplet activation steps. Such behaviour was also observed for the second investigated species, namely sodium oxalate. Our experiments address the atmospheric scenario that coating layers

Theory of Pulsed Neutron Experiments in Highly Heterogeneous Multiplying Media

International Nuclear Information System (INIS)

Corno, S.E.

1965-01-01

In this work we investigate the time and space dependence of the neutron flux within a highly heterogeneous assembly, in which pulsed or sinusoidally modulated neutrons are injected. We consider, for the sake of simplicity, a device consisting of a cylindrical block of heavy moderator, along the axis of which a line-shaped region of fissionable material is located. The driving neutron source is assumed to be located on one of the end faces of the cylinder. The extent of the fissionable region allows us to deal with it as with an absorbing and multiplying singularity of the neutron field. As our attention is mostly concentrated on space and time variation of the neutron flux, rather crude approximations are assumed as far as the energy dependence of the neutron population is concerned. Within the limits of the age-diffusion theory, the response of the device to any neutron excitation may be found in closed form. For a sinusoidally modulated source of given frequency, it may easily be shown that, if the axial singularity were a purely absorbing one, the neutron waves being propagated along the device would possess a phase shift; a wavelength and an attenuation constant depending on the absorbing properties of the singularity. This picture becomes more and more complicated when neutron multiplication occurs. For this general case the solution derived in our paper obviously turns out to be dependent on both absorption and multiplication properties of the singularity. This circumstance suggests, among others, the idea of using a device of the type described above for testing fuel elements of heterogeneous reactors. (author) [fr

Heterogeneity in quorum sensing-regulated bioluminescence of Vibrio harveyi.

Science.gov (United States)

Anetzberger, Claudia; Pirch, Torsten; Jung, Kirsten

2009-07-01

Quorum sensing (QS) refers to the ability of bacterial populations to read out the local environment for cell density and to collectively activate gene expression. Vibrio harveyi, one of the best characterized model organisms in QS, was used to address the question how single cells behave within a QS-activated community in a homogeneous environment. Analysis of the QS-regulated bioluminescence of a wild type strain revealed that even at high cell densities only 69% of the cells of the population produced bioluminescence, 25% remained dark and 6% were dead. Moreover, light intensities greatly varied from cell to cell at high population density. Addition of autoinducer to a bright liquid culture of V. harveyi increased the percentage of luminescent cells up to 98%, suggesting that V. harveyi produces and/or keeps the autoinducers at non-saturating concentrations. In contrast, all living cells of a constitutive QS-active mutant (DeltaluxO) produced light. We also found that QS affects biofilm formation in V. harveyi. Our data provide first evidence that a heterogeneous population produces more biofilm than a homogeneous one. It is suggested that even a QS-committed population of V. harveyi takes advantage of heterogeneity, which extends the current view of QS-regulated uniformity.

Local Climate Heterogeneity Shapes Population Genetic Structure of Two Undifferentiated Insular Scutellaria Species.

Science.gov (United States)

Hsiung, Huan-Yi; Huang, Bing-Hong; Chang, Jui-Tse; Huang, Yao-Moan; Huang, Chih-Wei; Liao, Pei-Chun

2017-01-01

Spatial climate heterogeneity may not only affect adaptive gene frequencies but could also indirectly shape the genetic structure of neutral loci by impacting demographic dynamics. In this study, the effect of local climate on population genetic variation was tested in two phylogenetically close Scutellaria species in Taiwan. Scutellaria taipeiensis , which was originally assumed to be an endemic species of Taiwan Island, is shown to be part of the widespread species S. barbata based on the overlapping ranges of genetic variation and climatic niches as well as their morphological similarity. Rejection of the scenario of "early divergence with secondary contact" and the support for multiple origins of populations of S. taipeiensis from S. barbata provide strong evolutionary evidence for a taxonomic revision of the species combination. Further tests of a climatic effect on genetic variation were conducted. Regression analyses show nonlinear correlations among any pair of geographic, climatic, and genetic distances. However, significantly, the bioclimatic variables that represent the precipitation from late summer to early autumn explain roughly 13% of the genetic variation of our sampled populations. These results indicate that spatial differences of precipitation in the typhoon season may influence the regeneration rate and colonization rate of local populations. The periodic typhoon episodes explain the significant but nonlinear influence of climatic variables on population genetic differentiation. Although, the climatic difference does not lead to species divergence, the local climate variability indeed impacts the spatial genetic distribution at the population level.

Collective Motion in Behaviorally Heterogeneous Systems

Science.gov (United States)

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

Stable Regulation of Cell Cycle Events in Mycobacteria: Insights From Inherently Heterogeneous Bacterial Populations

Directory of Open Access Journals (Sweden)

Michelle M. Logsdon

2018-03-01

Full Text Available Model bacteria, such as E. coli and B. subtilis, tightly regulate cell cycle progression to achieve consistent cell size distributions and replication dynamics. Many of the hallmark features of these model bacteria, including lateral cell wall elongation and symmetric growth and division, do not occur in mycobacteria. Instead, mycobacterial growth is characterized by asymmetric polar growth and division. This innate asymmetry creates unequal birth sizes and growth rates for daughter cells with each division, generating a phenotypically heterogeneous population. Although the asymmetric growth patterns of mycobacteria lead to a larger variation in birth size than typically seen in model bacterial populations, the cell size distribution is stable over time. Here, we review the cellular mechanisms of growth, division, and cell cycle progression in mycobacteria in the face of asymmetry and inherent heterogeneity. These processes coalesce to control cell size. Although Mycobacterium smegmatis and Mycobacterium bovis Bacillus Calmette-Guérin (BCG utilize a novel model of cell size control, they are similar to previously studied bacteria in that initiation of DNA replication is a key checkpoint for cell division. We compare the regulation of DNA replication initiation and strategies used for cell size homeostasis in mycobacteria and model bacteria. Finally, we review the importance of cellular organization and chromosome segregation relating to the physiology of mycobacteria and consider how new frameworks could be applied across the wide spectrum of bacterial diversity.

Population genomics of Pacific lamprey: adaptive variation in a highly dispersive species.

Science.gov (United States)

Hess, Jon E; Campbell, Nathan R; Close, David A; Docker, Margaret F; Narum, Shawn R

2013-06-01

Unlike most anadromous fishes that have evolved strict homing behaviour, Pacific lamprey (Entosphenus tridentatus) seem to lack philopatry as evidenced by minimal population structure across the species range. Yet unexplained findings of within-region population genetic heterogeneity coupled with the morphological and behavioural diversity described for the species suggest that adaptive genetic variation underlying fitness traits may be responsible. We employed restriction site-associated DNA sequencing to genotype 4439 quality filtered single nucleotide polymorphism (SNP) loci for 518 individuals collected across a broad geographical area including British Columbia, Washington, Oregon and California. A subset of putatively neutral markers (N = 4068) identified a significant amount of variation among three broad populations: northern British Columbia, Columbia River/southern coast and 'dwarf' adults (F(CT) = 0.02, P ≪ 0.001). Additionally, 162 SNPs were identified as adaptive through outlier tests, and inclusion of these markers revealed a signal of adaptive variation related to geography and life history. The majority of the 162 adaptive SNPs were not independent and formed four groups of linked loci. Analyses with matsam software found that 42 of these outlier SNPs were significantly associated with geography, run timing and dwarf life history, and 27 of these 42 SNPs aligned with known genes or highly conserved genomic regions using the genome browser available for sea lamprey. This study provides both neutral and adaptive context for observed genetic divergence among collections and thus reconciles previous findings of population genetic heterogeneity within a species that displays extensive gene flow. © 2012 John Wiley & Sons Ltd.

Modelling the collective response of heterogeneous cell populations to stationary gradients and chemical signal relay

Science.gov (United States)

Pineda, M.; Eftimie, R.

2017-12-01

The directed motion of cell aggregates toward a chemical source occurs in many relevant biological processes. Understanding the mechanisms that control this complex behavior is of great relevance for our understanding of developmental biological processes and many diseases. In this paper, we consider a self-propelled particle model for the movement of heterogeneous subpopulations of chemically interacting cells towards an imposed stable chemical gradient. Our simulations show explicitly how self-organisation of cell populations (which could lead to engulfment or complete cell segregation) can arise from the heterogeneity of chemotactic responses alone. This new result complements current theoretical and experimental studies that emphasise the role of differential cell-cell adhesion on self-organisation and spatial structure of cellular aggregates. We also investigate how the speed of individual cell aggregations increases with the chemotactic sensitivity of the cells, and decreases with the number of cells inside the aggregates

Temperature dependent heterogeneous rotational correlation in lipids.

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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.

Recent advances and opportunities in proteomic analyses of tumour heterogeneity.

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Bateman, Nicholas W; Conrads, Thomas P

2018-04-01

Solid tumour malignancies comprise a highly variable admixture of tumour and non-tumour cellular populations, forming a complex cellular ecosystem and tumour microenvironment. This tumour heterogeneity is not incidental, and is known to correlate with poor patient prognosis for many cancer types. Indeed, non-malignant cell populations, such as vascular endothelial and immune cells, are known to play key roles supporting and, in some cases, driving aggressive tumour biology, and represent targets of emerging therapeutics, such as antiangiogenesis and immune checkpoint inhibitors. The biochemical interplay between these cellular populations and how they contribute to molecular tumour heterogeneity remains enigmatic, particularly from the perspective of the tumour proteome. This review focuses on recent advances in proteomic methods, namely imaging mass spectrometry, single-cell proteomic techniques, and preanalytical sample processing, that are uniquely positioned to enable detailed analysis of discrete cellular populations within tumours to improve our understanding of tumour proteomic heterogeneity. This review further emphasizes the opportunity afforded by the application of these techniques to the analysis of tumour heterogeneity in formalin-fixed paraffin-embedded archival tumour tissues, as these represent an invaluable resource for retrospective analyses that is now routinely accessible, owing to recent technological and methodological advances in tumour tissue proteomics. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

High Shedding Potential and Significant Individual Heterogeneity in Naturally-Infected Alpine ibex (Capra ibex With Brucella melitensis

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Sébastien Lambert

2018-05-01

Full Text Available Wildlife reservoirs of infectious diseases raise major management issues. In Europe, brucellosis has been eradicated in domestic ruminants from most countries and wild ruminants have not been considered important reservoirs so far. However, a high prevalence of Brucella melitensis infection has been recently identified in a French population of Alpine ibex (Capra ibex, after the emergence of brucellosis was confirmed in a dairy cattle farm and two human cases. This situation raised the need to identify the factors driving the persistence of Brucella infection at high prevalence levels in this ibex population. In the present paper, we studied the shedding pattern of B. melitensis in ibex from Bargy Massif, French Alps. Bacteriological examinations (1–15 tissues/samples per individual were performed on 88 seropositive, supposedly infected and euthanized individuals. Among them, 51 (58% showed at least one positive culture, including 45 ibex with at least one Brucella isolation from a urogenital sample or a lymph node in the pelvic area (active infection in organs in the pelvic area. Among these 45 ibex, 26 (30% of the total number of necropsied animals showed at least one positive culture for a urogenital organ and were considered as being at risk of shedding the bacteria at the time of capture. We observed significant heterogeneity between sex-and-age classes: seropositive females were most at risk to excrete Brucella before the age of 5 years, possibly corresponding to abortion during the first pregnancy following infection such as reported in the domestic ruminants. The high shedding potential observed in young females may have contributed to the self-sustained maintenance of infection in this population, whereas males are supposed to play a role of transmission between spatial units through venereal transmission during mating. This heterogeneity in the shedding potential of seropositive individuals should be considered in the future to

Individual-Based Modeling of Tuberculosis in a User-Friendly Interface: Understanding the Epidemiological Role of Population Heterogeneity in a City.

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Prats, Clara; Montañola-Sales, Cristina; Gilabert-Navarro, Joan F; Valls, Joaquim; Casanovas-Garcia, Josep; Vilaplana, Cristina; Cardona, Pere-Joan; López, Daniel

2015-01-01

For millennia tuberculosis (TB) has shown a successful strategy to survive, making it one of the world's deadliest infectious diseases. This resilient behavior is based not only on remaining hidden in most of the infected population, but also by showing slow evolution in most sick people. The course of the disease within a population is highly related to its heterogeneity. Thus, classic epidemiological approaches with a top-down perspective have not succeeded in understanding its dynamics. In the past decade a few individual-based models were built, but most of them preserved a top-down view that makes it difficult to study a heterogeneous population. We propose an individual-based model developed with a bottom-up approach to studying the dynamics of pulmonary TB in a certain population, considered constant. Individuals may belong to the following classes: healthy, infected, sick, under treatment, and treated with a probability of relapse. Several variables and parameters account for their age, origin (native or immigrant), immunodeficiency, diabetes, and other risk factors (smoking and alcoholism). The time within each infection state is controlled, and sick individuals may show a cavitated disease or not that conditions infectiousness. It was implemented in NetLogo because it allows non-modelers to perform virtual experiments with a user-friendly interface. The simulation was conducted with data from Ciutat Vella, a district of Barcelona with an incidence of 67 TB cases per 100,000 inhabitants in 2013. Several virtual experiments were performed to relate the disease dynamics with the structure of the infected subpopulation (e.g., the distribution of infected times). Moreover, the short-term effect of health control policies on modifying that structure was studied. Results show that the characteristics of the population are crucial for the local epidemiology of TB. The developed user-friendly tool is ready to test control strategies of disease in any city in the

Three-dimensional imaging of aquifer and aquitard heterogeneity via transient hydraulic tomography at a highly heterogeneous field site

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Zhao, Zhanfeng; Illman, Walter A.

2018-04-01

Previous studies have shown that geostatistics-based transient hydraulic tomography (THT) is robust for subsurface heterogeneity characterization through the joint inverse modeling of multiple pumping tests. However, the hydraulic conductivity (K) and specific storage (Ss) estimates can be smooth or even erroneous for areas where pumping/observation densities are low. This renders the imaging of interlayer and intralayer heterogeneity of highly contrasting materials including their unit boundaries difficult. In this study, we further test the performance of THT by utilizing existing and newly collected pumping test data of longer durations that showed drawdown responses in both aquifer and aquitard units at a field site underlain by a highly heterogeneous glaciofluvial deposit. The robust performance of the THT is highlighted through the comparison of different degrees of model parameterization including: (1) the effective parameter approach; (2) the geological zonation approach relying on borehole logs; and (3) the geostatistical inversion approach considering different prior information (with/without geological data). Results reveal that the simultaneous analysis of eight pumping tests with the geostatistical inverse model yields the best results in terms of model calibration and validation. We also find that the joint interpretation of long-term drawdown data from aquifer and aquitard units is necessary in mapping their full heterogeneous patterns including intralayer variabilities. Moreover, as geological data are included as prior information in the geostatistics-based THT analysis, the estimated K values increasingly reflect the vertical distribution patterns of permeameter-estimated K in both aquifer and aquitard units. Finally, the comparison of various THT approaches reveals that differences in the estimated K and Ss tomograms result in significantly different transient drawdown predictions at observation ports.

Mitochondrial DNA from El Mirador cave (Atapuerca, Spain reveals the heterogeneity of Chalcolithic populations.

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Daniel Gómez-Sánchez

Full Text Available Previous mitochondrial DNA analyses on ancient European remains have suggested that the current distribution of haplogroup H was modeled by the expansion of the Bell Beaker culture (ca 4,500-4,050 years BP out of Iberia during the Chalcolithic period. However, little is known on the genetic composition of contemporaneous Iberian populations that do not carry the archaeological tool kit defining this culture. Here we have retrieved mitochondrial DNA (mtDNA sequences from 19 individuals from a Chalcolithic sample from El Mirador cave in Spain, dated to 4,760-4,200 years BP and we have analyzed the haplogroup composition in the context of modern and ancient populations. Regarding extant African, Asian and European populations, El Mirador shows affinities with Near Eastern groups. In different analyses with other ancient samples, El Mirador clusters with Middle and Late Neolithic populations from Germany, belonging to the Rössen, the Salzmünde and the Baalberge archaeological cultures but not with contemporaneous Bell Beakers. Our analyses support the existence of a common genetic signal between Western and Central Europe during the Middle and Late Neolithic and points to a heterogeneous genetic landscape among Chalcolithic groups.

Cell surface profiling using high-throughput flow cytometry: a platform for biomarker discovery and analysis of cellular heterogeneity.

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Craig A Gedye

Full Text Available Cell surface proteins have a wide range of biological functions, and are often used as lineage-specific markers. Antibodies that recognize cell surface antigens are widely used as research tools, diagnostic markers, and even therapeutic agents. The ability to obtain broad cell surface protein profiles would thus be of great value in a wide range of fields. There are however currently few available methods for high-throughput analysis of large numbers of cell surface proteins. We describe here a high-throughput flow cytometry (HT-FC platform for rapid analysis of 363 cell surface antigens. Here we demonstrate that HT-FC provides reproducible results, and use the platform to identify cell surface antigens that are influenced by common cell preparation methods. We show that multiple populations within complex samples such as primary tumors can be simultaneously analyzed by co-staining of cells with lineage-specific antibodies, allowing unprecedented depth of analysis of heterogeneous cell populations. Furthermore, standard informatics methods can be used to visualize, cluster and downsample HT-FC data to reveal novel signatures and biomarkers. We show that the cell surface profile provides sufficient molecular information to classify samples from different cancers and tissue types into biologically relevant clusters using unsupervised hierarchical clustering. Finally, we describe the identification of a candidate lineage marker and its subsequent validation. In summary, HT-FC combines the advantages of a high-throughput screen with a detection method that is sensitive, quantitative, highly reproducible, and allows in-depth analysis of heterogeneous samples. The use of commercially available antibodies means that high quality reagents are immediately available for follow-up studies. HT-FC has a wide range of applications, including biomarker discovery, molecular classification of cancers, or identification of novel lineage specific or stem cell

Cell surface profiling using high-throughput flow cytometry: a platform for biomarker discovery and analysis of cellular heterogeneity.

Science.gov (United States)

Gedye, Craig A; Hussain, Ali; Paterson, Joshua; Smrke, Alannah; Saini, Harleen; Sirskyj, Danylo; Pereira, Keira; Lobo, Nazleen; Stewart, Jocelyn; Go, Christopher; Ho, Jenny; Medrano, Mauricio; Hyatt, Elzbieta; Yuan, Julie; Lauriault, Stevan; Meyer, Mona; Kondratyev, Maria; van den Beucken, Twan; Jewett, Michael; Dirks, Peter; Guidos, Cynthia J; Danska, Jayne; Wang, Jean; Wouters, Bradly; Neel, Benjamin; Rottapel, Robert; Ailles, Laurie E

2014-01-01

Cell surface proteins have a wide range of biological functions, and are often used as lineage-specific markers. Antibodies that recognize cell surface antigens are widely used as research tools, diagnostic markers, and even therapeutic agents. The ability to obtain broad cell surface protein profiles would thus be of great value in a wide range of fields. There are however currently few available methods for high-throughput analysis of large numbers of cell surface proteins. We describe here a high-throughput flow cytometry (HT-FC) platform for rapid analysis of 363 cell surface antigens. Here we demonstrate that HT-FC provides reproducible results, and use the platform to identify cell surface antigens that are influenced by common cell preparation methods. We show that multiple populations within complex samples such as primary tumors can be simultaneously analyzed by co-staining of cells with lineage-specific antibodies, allowing unprecedented depth of analysis of heterogeneous cell populations. Furthermore, standard informatics methods can be used to visualize, cluster and downsample HT-FC data to reveal novel signatures and biomarkers. We show that the cell surface profile provides sufficient molecular information to classify samples from different cancers and tissue types into biologically relevant clusters using unsupervised hierarchical clustering. Finally, we describe the identification of a candidate lineage marker and its subsequent validation. In summary, HT-FC combines the advantages of a high-throughput screen with a detection method that is sensitive, quantitative, highly reproducible, and allows in-depth analysis of heterogeneous samples. The use of commercially available antibodies means that high quality reagents are immediately available for follow-up studies. HT-FC has a wide range of applications, including biomarker discovery, molecular classification of cancers, or identification of novel lineage specific or stem cell markers.

Mechanisms of population heterogeneity among molting common mergansers on Kodiak Island, Alaska: Implications for genetic assessments of migratory connectivity

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Pearce, John M.; Zwiefelhofer, Denny; Maryanski, Nate

2009-01-01

Quantifying population genetic heterogeneity within nonbreeding aggregations can inform our understanding of patterns of site fidelity, migratory connectivity, and gene flow between breeding and nonbreeding areas. However, characterizing mechanisms that contribute to heterogeneity, such as migration and dispersal, is required before site fidelity and migratory connectivity can be assessed accurately. We studied nonbreeding groups of Common Mergansers (Mergus merganser) molting on Kodiak Island, Alaska, from 2005 to 2007, using banding data to assess rates of recapture, mitochondrial (mt) DNA to determine natal area, and nuclear microsatellite genotypes to assess dispersal. Using baseline information from differentiated mtDNA haplogroups across North America, we were able to assign individuals to natal regions and document population genetic heterogeneity within and among molting groups. Band-recovery and DNA data suggest that both migration from and dispersal among natal areas contribute to admixed groups of males molting on Kodiak Island. A lack of differentiation in the Common Merganser's nuclear, bi-parentally inherited DNA, observed across North America, implies that dispersal can mislead genetic assessments of migratory connectivity and assignments of nonbreeding individuals to breeding areas. Thus multiple and independent data types are required to account for such behaviors before accurate assessments of migratory connectivity can be made.

Mouse V1 population correlates of visual detection rely on heterogeneity within neuronal response patterns

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Montijn, Jorrit S; Goltstein, Pieter M; Pennartz, Cyriel MA

2015-01-01

Previous studies have demonstrated the importance of the primary sensory cortex for the detection, discrimination, and awareness of visual stimuli, but it is unknown how neuronal populations in this area process detected and undetected stimuli differently. Critical differences may reside in the mean strength of responses to visual stimuli, as reflected in bulk signals detectable in functional magnetic resonance imaging, electro-encephalogram, or magnetoencephalography studies, or may be more subtly composed of differentiated activity of individual sensory neurons. Quantifying single-cell Ca2+ responses to visual stimuli recorded with in vivo two-photon imaging, we found that visual detection correlates more strongly with population response heterogeneity rather than overall response strength. Moreover, neuronal populations showed consistencies in activation patterns across temporally spaced trials in association with hit responses, but not during nondetections. Contrary to models relying on temporally stable networks or bulk signaling, these results suggest that detection depends on transient differentiation in neuronal activity within cortical populations. DOI: http://dx.doi.org/10.7554/eLife.10163.001 PMID:26646184

Family Structure Transitions and Child Development: Instability, Selection, and Population Heterogeneity.

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Lee, Dohoon; McLanahan, Sara

2015-08-01

A growing literature documents the importance of family instability for child wellbeing. In this article, we use longitudinal data from the Fragile Families and Child Wellbeing Study to examine the impacts of family instability on children's cognitive and socioemotional development in early and middle childhood. We extend existing research in several ways: (1) by distinguishing between the number and types of family structure changes; (2) by accounting for time-varying as well as time-constant confounding; and (3) by assessing racial/ethnic and gender differences in family instability effects. Our results indicate that family instability has a causal effect on children's development, but the effect depends on the type of change, the outcome assessed, and the population examined. Generally speaking, transitions out of a two-parent family are more negative for children's development than transitions into a two-parent family. The effect of family instability is stronger for children's socioemotional development than for their cognitive achievement. For socioemotional development, transitions out of a two-parent family are more negative for white children, whereas transitions into a two-parent family are more negative for Hispanic children. These findings suggest that future research should pay more attention to the type of family structure transition and to population heterogeneity.

Stage-dependent responses to emergent habitat heterogeneity: consequences for a predatory insect population in a coffee agroecosystem.

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Liere, Heidi; Perfecto, Ivette; Vandermeer, John

2014-08-01

Interactions among members of biological communities can create spatial patterns that effectively generate habitat heterogeneity for other members in the community, and this heterogeneity might be crucial for their persistence. For example, stage-dependent vulnerability of a predatory lady beetle to aggression of the ant, Azteca instabilis, creates two habitat types that are utilized differently by the immature and adult life stages of the beetle. Due to a mutualistic association between A. instabilis and the hemipteran Coccus viridis - which is A. orbigera main prey in the area - only plants around ant nests have high C. viridis populations. Here, we report on a series of surveys at three different scales aimed at detecting how the presence and clustered distribution of ant nests affect the distribution of the different life stages of this predatory lady beetle in a coffee farm in Chiapas, Mexico. Both beetle adults and larvae were more abundant in areas with ant nests, but adults were restricted to the peripheries of highest ant activity and outside the reach of coffee bushes containing the highest densities of lady beetle larvae. The abundance of adult beetles located around trees with ants increased with the size of the ant nest clusters but the relationship is not significant for larvae. Thus, we suggest that A. orbigera undergoes an ontogenetic niche shift, not through shifting prey species, but through stage-specific vulnerability differences against a competitor that renders areas of abundant prey populations inaccessible for adults but not for larvae. Together with evidence presented elsewhere, this study shows how an important predator is not only dependent on the existence of two qualitatively distinct habitat types, but also on the spatial distribution of these habitats. We suggest that this dependency arises due to the different responses that the predator's life stages have to this emergent spatial pattern.

Global importation and population risk factors for measles in New Zealand: a case study for highly immunized populations.

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Hayman, D T S; Marshall, J C; French, N P; Carpenter, T E; Roberts, M G; Kiedrzynski, T

2017-07-01

As endemic measles is eliminated through immunization, countries must determine the risk factors for the importation of measles into highly immunized populations to target control measures. Despite eliminating endemic measles, New Zealand suffers from outbreaks after introductions from abroad, enabling us to use it as a model for measles introduction risk. We used a generalized linear model to analyze risk factors for 1137 measles cases from 2007 to June 2014, provide estimates of national immunity levels, and model measles importation risk. People of European ethnicity made up the majority of measles cases. Age is a positive risk factor, particularly 0-2-year-olds and 5-17-year-old Europeans, along with increased wealth. Pacific islanders were also at greater risk, but due to 0-2-year-old cases. Despite recent high measles, mumps, and rubella vaccine immunization coverage, overall population immunity against measles remains ~90% and is lower in people born between 1982 and 2005. Greatest measles importation risk is during December, and countries predicted to be sources have historical connections and highest travel rates (Australia and UK), followed by Asian countries with high travel rates and higher measles incidences. Our results suggest measles importation due to travel is seeding measles outbreaks, and immunization levels are insufficient to continue to prevent outbreaks because of heterogeneous immunity in the population, leaving particular age groups at risk.

Effects of diffusion on total biomass in heterogeneous continuous and discrete-patch systems

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DeAngelis, Donald L.; Ming Ni, Wei; Zhang, Bo

2016-01-01

Theoretical models of populations on a system of two connected patches previously have shown that when the two patches differ in maximum growth rate and carrying capacity, and in the limit of high diffusion, conditions exist for which the total population size at equilibrium exceeds that of the ideal free distribution, which predicts that the total population would equal the total carrying capacity of the two patches. However, this result has only been shown for the Pearl-Verhulst growth function on two patches and for a single-parameter growth function in continuous space. Here, we provide a general criterion for total population size to exceed total carrying capacity for three commonly used population growth rates for both heterogeneous continuous and multi-patch heterogeneous landscapes with high population diffusion. We show that a sufficient condition for this situation is that there is a convex positive relationship between the maximum growth rate and the parameter that, by itself or together with the maximum growth rate, determines the carrying capacity, as both vary across a spatial region. This relationship occurs in some biological populations, though not in others, so the result has ecological implications.

Homogenizing bacterial cell factories: Analysis and engineering of phenotypic heterogeneity.

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Binder, Dennis; Drepper, Thomas; Jaeger, Karl-Erich; Delvigne, Frank; Wiechert, Wolfgang; Kohlheyer, Dietrich; Grünberger, Alexander

2017-07-01

In natural habitats, microbes form multispecies communities that commonly face rapidly changing and highly competitive environments. Thus, phenotypic heterogeneity has evolved as an innate and important survival strategy to gain an overall fitness advantage over cohabiting competitors. However, in defined artificial environments such as monocultures in small- to large-scale bioreactors, cell-to-cell variations are presumed to cause reduced production yields as well as process instability. Hence, engineering microbial production toward phenotypic homogeneity is a highly promising approach for synthetic biology and bioprocess optimization. In this review, we discuss recent studies that have unraveled the cell-to-cell heterogeneity observed during bacterial gene expression and metabolite production as well as the molecular mechanisms involved. In addition, current single-cell technologies are briefly reviewed with respect to their applicability in exploring cell-to-cell variations. We highlight emerging strategies and tools to reduce phenotypic heterogeneity in biotechnological expression setups. Here, strain or inducer modifications are combined with cell physiology manipulations to achieve the ultimate goal of equalizing bacterial populations. In this way, the majority of cells can be forced into high productivity, thus reducing less productive subpopulations that tend to consume valuable resources during production. Modifications in uptake systems, inducer molecules or nutrients represent valuable tools for diminishing heterogeneity. Finally, we address the challenge of transferring homogeneously responding cells into large-scale bioprocesses. Environmental heterogeneity originating from extrinsic factors such as stirring speed and pH, oxygen, temperature or nutrient distribution can significantly influence cellular physiology. We conclude that engineering microbial populations toward phenotypic homogeneity is an increasingly important task to take biotechnological

Vaccination Games with Peer Effects in a Heterogeneous Hospital Worker Population

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Troy Tassier

2015-01-01

Full Text Available We develop a game theoretic model to analyze the Nash equilibrium of vaccine decisions in a hospital population with heterogeneous contacts. We use the model in conjunction with person-to-person contact data within a large university hospital. We simulate, using agent-based models, the probability of infection for various worker types in the data and use these probabilities to identify the Nash equilibrium vaccine choices of hospital workers. The analysis suggests that there may be large differences in vaccination rates among hospital worker groups. We extend the model to include peer effects within the game. The peer effects may create additional equilibria or may further cement existing equilibria depending on parameter values. Further, depending on the magnitude of the peer effects and the costs of infection and vaccination, peer effects may increase or decrease differences in worker group vaccination rates within the hospital.

Deconstructing transcriptional heterogeneity in pluripotent stem cells

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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

Carrying capacity in a heterogeneous environment with habitat connectivity.

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Zhang, Bo; Kula, Alex; Mack, Keenan M L; Zhai, Lu; Ryce, Arrix L; Ni, Wei-Ming; DeAngelis, Donald L; Van Dyken, J David

2017-09-01

A large body of theory predicts that populations diffusing in heterogeneous environments reach higher total size than if non-diffusing, and, paradoxically, higher size than in a corresponding homogeneous environment. However, this theory and its assumptions have not been rigorously tested. Here, we extended previous theory to include exploitable resources, proving qualitatively novel results, which we tested experimentally using spatially diffusing laboratory populations of yeast. Consistent with previous theory, we predicted and experimentally observed that spatial diffusion increased total equilibrium population abundance in heterogeneous environments, with the effect size depending on the relationship between r and K. Refuting previous theory, however, we discovered that homogeneously distributed resources support higher total carrying capacity than heterogeneously distributed resources, even with species diffusion. Our results provide rigorous experimental tests of new and old theory, demonstrating how the traditional notion of carrying capacity is ambiguous for populations diffusing in spatially heterogeneous environments. © 2017 John Wiley & Sons Ltd/CNRS.

A Metric and Workflow for Quality Control in the Analysis of Heterogeneity in Phenotypic Profiles and Screens

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Gough, Albert; Shun, Tongying; Taylor, D. Lansing; Schurdak, Mark

2016-01-01

Heterogeneity is well recognized as a common property of cellular systems that impacts biomedical research and the development of therapeutics and diagnostics. Several studies have shown that analysis of heterogeneity: gives insight into mechanisms of action of perturbagens; can be used to predict optimal combination therapies; and to quantify heterogeneity in tumors where heterogeneity is believed to be associated with adaptation and resistance. Cytometry methods including high content screening (HCS), high throughput microscopy, flow cytometry, mass spec imaging and digital pathology capture cell level data for populations of cells. However it is often assumed that the population response is normally distributed and therefore that the average adequately describes the results. A deeper understanding of the results of the measurements and more effective comparison of perturbagen effects requires analysis that takes into account the distribution of the measurements, i.e. the heterogeneity. However, the reproducibility of heterogeneous data collected on different days, and in different plates/slides has not previously been evaluated. Here we show that conventional assay quality metrics alone are not adequate for quality control of the heterogeneity in the data. To address this need, we demonstrate the use of the Kolmogorov-Smirnov statistic as a metric for monitoring the reproducibility of heterogeneity in an SAR screen, describe a workflow for quality control in heterogeneity analysis. One major challenge in high throughput biology is the evaluation and interpretation of heterogeneity in thousands of samples, such as compounds in a cell-based screen. In this study we also demonstrate that three heterogeneity indices previously reported, capture the shapes of the distributions and provide a means to filter and browse big data sets of cellular distributions in order to compare and identify distributions of interest. These metrics and methods are presented as a

Population equations for degree-heterogenous neural networks

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Kähne, M.; Sokolov, I. M.; Rüdiger, S.

2017-11-01

We develop a statistical framework for studying recurrent networks with broad distributions of the number of synaptic links per neuron. We treat each group of neurons with equal input degree as one population and derive a system of equations determining the population-averaged firing rates. The derivation rests on an assumption of a large number of neurons and, additionally, an assumption of a large number of synapses per neuron. For the case of binary neurons, analytical solutions can be constructed, which correspond to steps in the activity versus degree space. We apply this theory to networks with degree-correlated topology and show that complex, multi-stable regimes can result for increasing correlations. Our work is motivated by the recent finding of subnetworks of highly active neurons and the fact that these neurons tend to be connected to each other with higher probability.

High mass resolution time of flight mass spectrometer for measuring products in heterogeneous catalysis in highly sensitive microreactors

DEFF Research Database (Denmark)

Andersen, Thomas; Jensen, Robert; Christensen, M. K.

2012-01-01

We demonstrate a combined microreactor and time of flight system for testing and characterization of heterogeneous catalysts with high resolution mass spectrometry and high sensitivity. Catalyst testing is performed in silicon-based microreactors which have high sensitivity and fast thermal...

Heterogeneity of functional properties of Clone 66 murine breast cancer cells expressing various stem cell phenotypes.

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Mukhopadhyay, Partha; Farrell, Tracy; Sharma, Gayatri; McGuire, Timothy R; O'Kane, Barbara; Sharp, J Graham

2013-01-01

Breast cancer grows, metastasizes and relapses from rare, therapy resistant cells with a stem cell phenotype (cancer stem cells/CSCs). However, there is a lack of studies comparing the functions of CSCs isolated using different phenotypes in order to determine if CSCs are homogeneous or heterogeneous. Cells with various stem cell phenotypes were isolated by sorting from Clone 66 murine breast cancer cells that grow orthotopically in immune intact syngeneic mice. These populations were compared by in vitro functional assays for proliferation, growth, sphere and colony formation; and in vivo limiting dilution analysis of tumorigenesis. The proportion of cells expressing CD44(high)CD24(low/neg), side population (SP) cells, ALDH1(+), CD49f(high), CD133(high), and CD34(high) differed, suggesting heterogeneity. Differences in frequency and size of tumor spheres from these populations were observed. Higher rates of proliferation of non-SP, ALDH1(+), CD34(low), and CD49f(high) suggested properties of transit amplifying cells. Colony formation was higher from ALDH1(-) and non-SP cells than ALDH1(+) and SP cells suggesting a progenitor phenotype. The frequency of clonal colonies that grew in agar varied and was differentially altered by the presence of Matrigel™. In vivo, fewer cells with a stem cell phenotype were needed for tumor formation than "non-stem" cells. Fewer SP cells were needed to form tumors than ALDH1(+) cells suggesting further heterogeneities of cells with stem phenotypes. Different levels of cytokines/chemokines were produced by Clone 66 with RANTES being the highest. Whether the heterogeneity reflects soluble factor production remains to be determined. These data demonstrate that Clone 66 murine breast cancer cells that express stem cell phenotypes are heterogeneous and exhibit different functional properties, and this may also be the case for human breast cancer stem cells.

Ih equalizes membrane input resistance in a heterogeneous population of fusiform neurons in the dorsal cochlear nucleus.

Directory of Open Access Journals (Sweden)

Cesar Celis Ceballos

2016-10-01

Full Text Available In a neuronal population, several combinations of its ionic conductances are used to attain a specific firing phenotype. Some neurons present heterogeneity in their firing, generally produced by expression of a specific conductance, but how additional conductances vary along in order to homeostatically regulate membrane excitability is less known. Dorsal cochlear nucleus principal neurons, fusiform neurons, display heterogeneous spontaneous action potential activity and thus represent an appropriate model to study the role of different conductances in establishing firing heterogeneity. Particularly, fusiform neurons are divided into quiet, with no spontaneous firing, or active neurons, presenting spontaneous, regular firing. These modes are determined by the expression levels of an intrinsic membrane conductance, an inwardly rectifying potassium current (IKir. In this work, we tested whether other subthreshold conductances vary homeostatically to maintain membrane excitability constant across the two subtypes. We found that Ih expression covaries specifically with IKir in order to maintain membrane resistance constant. The impact of Ih on membrane resistance is dependent on the level of IKir expression, being much smaller in quiet neurons with bigger IKir, but Ih variations are not relevant for creating the quiet and active phenotypes. Finally, we demonstrate that the individual proportion of each conductance, and not their absolute conductance, is relevant for determining the neuronal firing mode. We conclude that in fusiform neurons the variations of their different subthreshold conductances are limited to specific conductances in order to create firing heterogeneity and maintain membrane homeostasis.

Heterogeneity of the jealousy phenomenon in the general population: an Italian study.

Science.gov (United States)

Marazziti, Donatella; Sbrana, Alfredo; Rucci, Paola; Cherici, Luca; Mungai, Francesco; Gonnelli, Chiara; Massimetti, Enrico; Raimondi, Francesca; Doria, Maria Rosaria; Spagnolli, Sabrina; Ravani, Laura; Consoli, Giorgio; Catena Dell Osso, Mario

2010-01-01

Despite the general agreement that normal jealousy is heterogenous, little is known about this specific topic. In the present study, we explored the possibility of distinguishing between four subtypes of "normal" jealousy (depressive, anxious, obsessive, and paranoid) amongst a cohort of 500 healthy university students by means of a specifically designed questionnaire, "Ouestionario della gelosia" (QUEGE). QUEGE is a self-report instrument of 30 items which explores the presence, frequency, and duration of feelings and behaviors related to jealousy. It was devised to investigate four hypothetical psychopathological profiles: depressive, paranoid, obsessive, and anxious. The factor analysis identified five rather than four clear-cut factors: self-esteem, paranoia, interpersonal Sensitivity, fear of being abandoned, and obsessionality. Women showed statistically significant lower levels of self-esteem and higher levels of obsessionality than men. Younger age (jealousy phenomenon in the general population.

Spatial Heterogeneity of Water Quality in a Highly Degraded Tropical Freshwater Ecosystem

Science.gov (United States)

Zambrano, Luis; Contreras, Victoria; Mazari-Hiriart, Marisa; Zarco-Arista, Alba E.

2009-02-01

Awareness of environmental heterogeneity in ecosystems is critical for management and conservation. We used the Xochimilco freshwater system to describe the relationship between heterogeneity and human activities. This tropical aquatic ecosystem south of Mexico City is comprised of a network of interconnected canals and lakes that are influenced by agricultural and urban activities. Environmental heterogeneity was characterized by spatially extensive surveys within four regions of Xochimilco during rainy and dry seasons over 2 years. These surveys revealed a heterogeneous system that was shallow (1.1 m, SD = 0.4 ), warm (17°C, SD = 2.9), well oxygenated (5.0 mg l-1, SD = 3), turbid (45.7 NTU SD = 26.96), and extremely nutrient-rich (NO3-N = 15.9 mg l-1, SD=13.7; NH4-N = 2.88 mg l-1, SD = 4.24; and PO4-P = 8.3 mg l-1, SD = 2.4). Most of the variables were not significantly different between years, but did differ between seasons, suggesting a dynamic system within a span of a year but with a high resilience over longer periods of time. Maps were produced using interpolations to describe distributions of all variables. There was no correlation between individual variables and land use. Consequently, we searched for relationships using all variables together by generating a combined water quality index. Significant differences in the index were apparent among the four regions. Index values also differed within individual region and individual water bodies (e.g., within canals), indicating that Xochimilco has high local heterogeneity. Using this index on a map helped to relate water quality to human activities and provides a simple and clear tool for managers and policymakers.

The effect of heterogeneity on invasion in spatial epidemics

DEFF Research Database (Denmark)

Neri, Franco M; Bates, Anne; Füchtbauer, Winnie Sophie

2011-01-01

Heterogeneity in host populations is an important factor affecting the ability of a pathogen to invade, yet the quantitative investigation of its effects on epidemic spread is still an open problem. In this paper, we test recent theoretical results, which extend the established “percolation...... paradigm” to the spread of a pathogen in discrete heterogeneous host populations. In particular, we test the hypothesis that the probability of epidemic invasion decreases when host heterogeneity is increased. We use replicated experimental microcosms, in which the ubiquitous pathogenic fungus Rhizoctonia...

Confabulation Based Real-time Anomaly Detection for Wide-area Surveillance Using Heterogeneous High Performance Computing Architecture

Science.gov (United States)

2015-06-01

CONFABULATION BASED REAL-TIME ANOMALY DETECTION FOR WIDE-AREA SURVEILLANCE USING HETEROGENEOUS HIGH PERFORMANCE COMPUTING ARCHITECTURE SYRACUSE...DETECTION FOR WIDE-AREA SURVEILLANCE USING HETEROGENEOUS HIGH PERFORMANCE COMPUTING ARCHITECTURE 5a. CONTRACT NUMBER FA8750-12-1-0251 5b. GRANT...processors including graphic processor units (GPUs) and Intel Xeon Phi processors. Experimental results showed significant speedups, which can enable

Heterogeneous mobile phone ownership and usage patterns in Kenya.

Science.gov (United States)

Wesolowski, Amy; Eagle, Nathan; Noor, Abdisalan M; Snow, Robert W; Buckee, Caroline O

2012-01-01

The rapid adoption of mobile phone technologies in Africa is offering exciting opportunities for engaging with high-risk populations through mHealth programs, and the vast volumes of behavioral data being generated as people use their phones provide valuable data about human behavioral dynamics in these regions. Taking advantage of these opportunities requires an understanding of the penetration of mobile phones and phone usage patterns across the continent, but very little is known about the social and geographical heterogeneities in mobile phone ownership among African populations. Here, we analyze a survey of mobile phone ownership and usage across Kenya in 2009 and show that distinct regional, gender-related, and socioeconomic variations exist, with particularly low ownership among rural communities and poor people. We also examine patterns of phone sharing and highlight the contrasting relationships between ownership and sharing in different parts of the country. This heterogeneous penetration of mobile phones has important implications for the use of mobile technologies as a source of population data and as a public health tool in sub-Saharan Africa.

Inhibitory coherence in a heterogeneous population of subthreshold and suprathreshold type-I neurons

International Nuclear Information System (INIS)

Kim, Sang-Yoon; Hong, Duk-Geun; Kim, Jean; Lim, Woochang

2012-01-01

We study inhibitory coherence (i.e. collective coherence by synaptic inhibition) in a population of globally coupled type-I neurons, which can fire at arbitrarily low frequency. No inhibitory coherence is observed in a homogeneous population composed of only subthreshold neurons, which exhibit noise-induced firings. In addition to subthreshold neurons, there exist spontaneously firing suprathreshold neurons in a noisy environment of a real brain. To take into consideration the effect of suprathreshold neurons on inhibitory coherence, we consider a heterogeneous population of subthreshold and suprathreshold neurons and investigate the inhibitory coherence by increasing the fraction of suprathreshold neurons P supra . As P supra passes a threshold P* supra , suprathreshold neurons begin to synchronize and play the role of coherent inhibitors for the emergence of inhibitory coherence. Thus, regularly oscillating population-averaged global potential appears for P supra > P* supra . For this coherent case, suprathreshold neurons exhibit sparse spike synchronization (i.e. individual potentials of suprathreshold neurons consist of coherent sparse spikings and coherent subthreshold small-amplitude hoppings). By virtue of their coherent inhibition, sparsely synchronized suprathreshold neurons suppress the noisy activity of subthreshold neurons. Thus, subthreshold neurons exhibit hopping synchronization (i.e. only coherent subthreshold hopping oscillations without spikings appear in the individual potentials of subthreshold neurons). We also characterize the inhibitory coherence in terms of the ‘statistical-mechanical’ spike-based and correlation-based measures, which quantify the average contributions of the microscopic individual spikes and individual potentials to the macroscopic global potential. Finally, the effect of sparse randomness of synaptic connectivity on the inhibitory coherence is briefly discussed. (paper)

Sampling strategies to capture single-cell heterogeneity

OpenAIRE

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. ...

Heterogeneity in time and energy use of watching television

International Nuclear Information System (INIS)

Sekar, Ashok; Williams, Eric; Chen, Roger

2016-01-01

There is substantial variability in residential energy use, partly driven by heterogeneous behavioral patterns. Time-use is relevant to energy when consumption tracks the time a device is used. Cluster analysis is a promising approach to identify time-use patterns. If clusters with particularly long time use and thus high energy consumption emerge, these groups could merit targeted policy intervention. We investigate these ideas via an empirical study of time use for television watching in the U.S. Three clusters were identified. In 2013, the average time spent watching television by Clusters 1, 2 and 3 are dramatically different: 1.1, 3.5 and 7.7 h per day respectively. While members of Cluster 3 are only 14% of the total population they represent 34% of TV energy consumption. The population of Cluster 3 tends to be older, less employed and less educated. Energy savings per adopter is much larger for Cluster 3, suggesting much higher benefits from efficient devices. These results are relevant to the design of efficiency programs, indicating potential for variable rebates and/or tiered communication. With variable rebates, utilities would offer higher incentives to high-use customers. In tiered communication, utilities would devote more resources to engage customers with larger savings potential. - Highlights: •Utility and other efficiency programs often treat consumers as homogenous groups. •Heterogeneity in consumer behavior affects benefits/costs of efficiency upgrade. •Significant heterogeneity is found in U.S. television watching patterns. •Heavy watchers (7.7 h/day) are 14% of population but consume 34% of energy. •Energy savings of efficient television for heavy watcher is 3 times the average.

Range expansion of heterogeneous populations.

Science.gov (United States)

Reiter, Matthias; Rulands, Steffen; Frey, Erwin

2014-04-11

Risk spreading in bacterial populations is generally regarded as a strategy to maximize survival. Here, we study its role during range expansion of a genetically diverse population where growth and motility are two alternative traits. We find that during the initial expansion phase fast-growing cells do have a selective advantage. By contrast, asymptotically, generalists balancing motility and reproduction are evolutionarily most successful. These findings are rationalized by a set of coupled Fisher equations complemented by stochastic simulations.

High-Resolution Genome-Wide Linkage Mapping Identifies Susceptibility Loci for BMI in the Chinese Population

DEFF Research Database (Denmark)

Zhang, Dong Feng; Pang, Zengchang; Li, Shuxia

2012-01-01

The genetic loci affecting the commonly used BMI have been intensively investigated using linkage approaches in multiple populations. This study aims at performing the first genome-wide linkage scan on BMI in the Chinese population in mainland China with hypothesis that heterogeneity in genetic...... linkage could exist in different ethnic populations. BMI was measured from 126 dizygotic twins in Qingdao municipality who were genotyped using high-resolution Affymetrix Genome-Wide Human SNP arrays containing about 1 million single-nucleotide polymorphisms (SNPs). Nonparametric linkage analysis...... in western countries. Multiple loci showing suggestive linkage were found on chromosome 1 (lod score 2.38 at 242 cM), chromosome 8 (2.48 at 95 cM), and chromosome 14 (2.2 at 89.4 cM). The strong linkage identified in the Chinese subjects that is consistent with that found in populations of European origin...

Demographic variability and heterogeneity among individuals within and among clonal bacteria strains

DEFF Research Database (Denmark)

Jouvet, Lionel; Rodriguez-Rojas, Alexandro; Steiner, Ulrich

2018-01-01

to accurately decompose the drivers of heterogeneity among individuals as genetically fixed or selectively neutral. Rather than working on wild populations we present here data from a simple bacterial system in the lab, Escherichia coli. Our system, based on cutting-edge microfluidic techniques, provides high...... control over the genotype and the environment. It therefore allows to unambiguously decompose and quantify fixed genetic variability and dynamic stochastic variability among individuals. We show that within clonal individual variability (dynamic heterogeneity) in lifespan and lifetime reproduction...

Rethinking the evolution of specialization: A model for the evolution of phenotypic heterogeneity.

Science.gov (United States)

Rubin, Ilan N; Doebeli, Michael

2017-12-21

Phenotypic heterogeneity refers to genetically identical individuals that express different phenotypes, even when in the same environment. Traditionally, "bet-hedging" in fluctuating environments is offered as the explanation for the evolution of phenotypic heterogeneity. However, there are an increasing number of examples of microbial populations that display phenotypic heterogeneity in stable environments. Here we present an evolutionary model of phenotypic heterogeneity of microbial metabolism and a resultant theory for the evolution of phenotypic versus genetic specialization. We use two-dimensional adaptive dynamics to track the evolution of the population phenotype distribution of the expression of two metabolic processes with a concave trade-off. Rather than assume a Gaussian phenotype distribution, we use a Beta distribution that is capable of describing genotypes that manifest as individuals with two distinct phenotypes. Doing so, we find that environmental variation is not a necessary condition for the evolution of phenotypic heterogeneity, which can evolve as a form of specialization in a stable environment. There are two competing pressures driving the evolution of specialization: directional selection toward the evolution of phenotypic heterogeneity and disruptive selection toward genetically determined specialists. Because of the lack of a singular point in the two-dimensional adaptive dynamics and the fact that directional selection is a first order process, while disruptive selection is of second order, the evolution of phenotypic heterogeneity dominates and often precludes speciation. We find that branching, and therefore genetic specialization, occurs mainly under two conditions: the presence of a cost to maintaining a high phenotypic variance or when the effect of mutations is large. A cost to high phenotypic variance dampens the strength of selection toward phenotypic heterogeneity and, when sufficiently large, introduces a singular point into

Local introduction and heterogeneous spatial spread of dengue-suppressing Wolbachia through an urban population of Aedes aegypti.

Directory of Open Access Journals (Sweden)

Tom L Schmidt

2017-05-01

Full Text Available Dengue-suppressing Wolbachia strains are promising tools for arbovirus control, particularly as they have the potential to self-spread following local introductions. To test this, we followed the frequency of the transinfected Wolbachia strain wMel through Ae. aegypti in Cairns, Australia, following releases at 3 nonisolated locations within the city in early 2013. Spatial spread was analysed graphically using interpolation and by fitting a statistical model describing the position and width of the wave. For the larger 2 of the 3 releases (covering 0.97 km2 and 0.52 km2, we observed slow but steady spatial spread, at about 100-200 m per year, roughly consistent with theoretical predictions. In contrast, the smallest release (0.11 km2 produced erratic temporal and spatial dynamics, with little evidence of spread after 2 years. This is consistent with the prediction concerning fitness-decreasing Wolbachia transinfections that a minimum release area is needed to achieve stable local establishment and spread in continuous habitats. Our graphical and likelihood analyses produced broadly consistent estimates of wave speed and wave width. Spread at all sites was spatially heterogeneous, suggesting that environmental heterogeneity will affect large-scale Wolbachia transformations of urban mosquito populations. The persistence and spread of Wolbachia in release areas meeting minimum area requirements indicates the promise of successful large-scale population transformation.

Is high-resolution inverse characterization of heterogeneous river bed hydraulic conductivities needed and possible?

Directory of Open Access Journals (Sweden)

W. Kurtz

2013-10-01

Full Text Available River–aquifer exchange fluxes influence local and regional water balances and affect groundwater and river water quality and quantity. Unfortunately, river–aquifer exchange fluxes tend to be strongly spatially variable, and it is an open research question to which degree river bed heterogeneity has to be represented in a model in order to achieve reliable estimates of river–aquifer exchange fluxes. This research question is addressed in this paper with the help of synthetic simulation experiments, which mimic the Limmat aquifer in Zurich (Switzerland, where river–aquifer exchange fluxes and groundwater management activities play an important role. The solution of the unsaturated–saturated subsurface hydrological flow problem including river–aquifer interaction is calculated for ten different synthetic realities where the strongly heterogeneous river bed hydraulic conductivities (L are perfectly known. Hydraulic head data (100 in the default scenario are sampled from the synthetic realities. In subsequent data assimilation experiments, where L is unknown now, the hydraulic head data are used as conditioning information, with the help of the ensemble Kalman filter (EnKF. For each of the ten synthetic realities, four different ensembles of L are tested in the experiments with EnKF; one ensemble estimates high-resolution L fields with different L values for each element, and the other three ensembles estimate effective L values for 5, 3 or 2 zones. The calibration of higher-resolution L fields (i.e. fully heterogeneous or 5 zones gives better results than the calibration of L for only 3 or 2 zones in terms of reproduction of states, stream–aquifer exchange fluxes and parameters. Effective L for a limited number of zones cannot always reproduce the true states and fluxes well and results in biased estimates of net exchange fluxes between aquifer and stream. Also in case only 10 head data are used for conditioning, the high

Phenotypic heterogeneity in modeling cancer evolution.

Directory of Open Access Journals (Sweden)

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.

Conceptualizing a tool to optimize therapy based on dynamic heterogeneity

International Nuclear Information System (INIS)

Liao, David; Estévez-Salmerón, Luis; Tlsty, Thea D

2012-01-01

Complex biological systems often display a randomness paralleled in processes studied in fundamental physics. This simple stochasticity emerges owing to the complexity of the system and underlies a fundamental aspect of biology called phenotypic stochasticity. Ongoing stochastic fluctuations in phenotype at the single-unit level can contribute to two emergent population phenotypes. Phenotypic stochasticity not only generates heterogeneity within a cell population, but also allows reversible transitions back and forth between multiple states. This phenotypic interconversion tends to restore a population to a previous composition after that population has been depleted of specific members. We call this tendency homeostatic heterogeneity. These concepts of dynamic heterogeneity can be applied to populations composed of molecules, cells, individuals, etc. Here we discuss the concept that phenotypic stochasticity both underlies the generation of heterogeneity within a cell population and can be used to control population composition, contributing, in particular, to both the ongoing emergence of drug resistance and an opportunity for depleting drug-resistant cells. Using notions of both ‘large’ and ‘small’ numbers of biomolecular components, we rationalize our use of Markov processes to model the generation and eradication of drug-resistant cells. Using these insights, we have developed a graphical tool, called a metronomogram, that we propose will allow us to optimize dosing frequencies and total course durations for clinical benefit. (paper)

Epidemics spread in heterogeneous populations

Science.gov (United States)

Capała, Karol; Dybiec, Bartłomiej

2017-05-01

Individuals building populations are subject to variability. This variability affects progress of epidemic outbreaks, because individuals tend to be more or less resistant. Individuals also differ with respect to their recovery rate. Here, properties of the SIR model in inhomogeneous populations are studied. It is shown that a small change in model's parameters, e.g. recovery or infection rate, can substantially change properties of final states which is especially well-visible in distributions of the epidemic size. In addition to the epidemic size and radii distributions, the paper explores first passage time properties of epidemic outbreaks.

Evolution of Cooperation in Evolutionary Games for Heterogeneous Interactions

International Nuclear Information System (INIS)

Qian Xiaolan; Yang Junzhong

2012-01-01

When a population structure is modelled as a square lattice, the cooperation may be improved for an evolutionary prisoner dilemma game or be inhibited for an evolutionary snowdrift game. In this work, we investigate cooperation in a population on a square lattice where the interaction among players contains both prisoner dilemma game and snowdrift game. The heterogeneity in interaction is introduced to the population in two different ways: the heterogenous character of interaction assigned to every player (HCP) or the heterogenous character of interaction assigned to every link between any two players (HCL). The resonant enhancement of cooperation in the case of HCP is observed while the resonant inhibition of cooperation in the case of HCL is prominent. The explanations on the enhancement or inhibition of cooperation are presented for these two cases. (general)

Impact of Pathogen Population Heterogeneity and Stress-Resistant Variants on Food Safety.

Science.gov (United States)

Abee, T; Koomen, J; Metselaar, K I; Zwietering, M H; den Besten, H M W

2016-01-01

This review elucidates the state-of-the-art knowledge about pathogen population heterogeneity and describes the genotypic and phenotypic analyses of persister subpopulations and stress-resistant variants. The molecular mechanisms underlying the generation of persister phenotypes and genetic variants are identified. Zooming in on Listeria monocytogenes, a comparative whole-genome sequence analysis of wild types and variants that enabled the identification of mutations in variants obtained after a single exposure to lethal food-relevant stresses is described. Genotypic and phenotypic features are compared to those for persistent strains isolated from food processing environments. Inactivation kinetics, models used for fitting, and the concept of kinetic modeling-based schemes for detection of variants are presented. Furthermore, robustness and fitness parameters of L. monocytogenes wild type and variants are used to model their performance in food chains. Finally, the impact of stress-resistant variants and persistence in food processing environments on food safety is discussed.

Team Heterogeneity in Startups and its Development over Time

DEFF Research Database (Denmark)

Kaiser, Ulrich; Müller, Bettina

We investigate the workforce heterogeneity of startups with respect to education, age and wages. Our explorative study uses data on the population of 1,614 Danish firms founded in 1998. We track these firms until 2001 which enables us to analyze changes in workforce composition over time. Such a ......We investigate the workforce heterogeneity of startups with respect to education, age and wages. Our explorative study uses data on the population of 1,614 Danish firms founded in 1998. We track these firms until 2001 which enables us to analyze changes in workforce composition over time....... Our result holds both for non-knowledge-based and, to a lesser extent, knowledge-based startups. This seems surprising since a vast management literature advocates heterogeneous teams. The difficulties associated with workforce heterogeneity (like affective conflict or coordination cost) as well...... as “homophily” (people’s inclination to bound with others with similar characteristics) hence appear to generally overweigh the benefits of heterogeneity (like greater variety in perspectives or more creativity). We also document that workforces become more heterogeneous over time startups add workers...

Rapidly reconfigurable high-fidelity optical arbitrary waveform generation in heterogeneous photonic integrated circuits.

Science.gov (United States)

Feng, Shaoqi; Qin, Chuan; Shang, Kuanping; Pathak, Shibnath; Lai, Weicheng; Guan, Binbin; Clements, Matthew; Su, Tiehui; Liu, Guangyao; Lu, Hongbo; Scott, Ryan P; Ben Yoo, S J

2017-04-17

This paper demonstrates rapidly reconfigurable, high-fidelity optical arbitrary waveform generation (OAWG) in a heterogeneous photonic integrated circuit (PIC). The heterogeneous PIC combines advantages of high-speed indium phosphide (InP) modulators and low-loss, high-contrast silicon nitride (Si3N4) arrayed waveguide gratings (AWGs) so that high-fidelity optical waveform syntheses with rapid waveform updates are possible. The generated optical waveforms spanned a 160 GHz spectral bandwidth starting from an optical frequency comb consisting of eight comb lines separated by 20 GHz channel spacing. The Error Vector Magnitude (EVM) values of the generated waveforms were approximately 16.4%. The OAWG module can rapidly and arbitrarily reconfigure waveforms upon every pulse arriving at 2 ns repetition time. The result of this work indicates the feasibility of truly dynamic optical arbitrary waveform generation where the reconfiguration rate or the modulator bandwidth must exceed the channel spacing of the AWG and the optical frequency comb.

Rate response of neurons subject to fast or frozen noise: from stochastic and homogeneous to deterministic and heterogeneous populations.

Science.gov (United States)

Alijani, Azadeh Khajeh; Richardson, Magnus J E

2011-07-01

The response of a neuronal population to afferent drive can be expected to be sensitive to both the distribution and dynamics of membrane voltages within the population. Voltage fluctuations can be driven by synaptic noise, neuromodulators, or cellular inhomogeneities: processes ranging from millisecond autocorrelation times to effectively static or "frozen" noise. Here we extend previous studies of filtered fluctuations to the experimentally verified exponential integrate-and-fire model. How fast or frozen fluctuations affect the steady-state rate and firing-rate response are both examined using perturbative solutions and limits of a 1 + 2 dimensional Fokker-Planck equation. The central finding is that, under conditions of a more-or-less constant population voltage variance, the firing-rate response is only weakly dependent on the fluctuation filter constant: The voltage distribution is the principal determinant of the population response. This result is unexpected given the nature of the systems underlying the extreme limits of fast and frozen fluctuations; the first limit represents a homogeneous population of neurons firing stochastically, whereas the second limit is equivalent to a heterogeneous population of neurons firing deterministically.

Long-term spatial heterogeneity in mallard distribution in the Prairie pothole region

Science.gov (United States)

Janke, Adam K.; Anteau, Michael J.; Stafford, Joshua D.

2017-01-01

The Prairie Pothole Region (PPR) of north-central United States and south-central Canada supports greater than half of all breeding mallards (Anas platyrhynchos) annually counted in North America and is the focus of widespread conservation and research efforts. Allocation of conservation resources for this socioeconomically important population would benefit from an understanding of the nature of spatiotemporal variation in distribution of breeding mallards throughout the 850,000 km2 landscape. We used mallard counts from the Waterfowl Breeding Population and Habitat Survey to test for spatial heterogeneity and identify high- and low-abundance regions of breeding mallards over a 50-year time series. We found strong annual spatial heterogeneity in all years: 90% of mallards counted annually were on an average of only 15% of surveyed segments. Using a local indicator of spatial autocorrelation, we found a relatively static distribution of low-count clusters in northern Montana, USA, and southern Alberta, Canada, and a dynamic distribution of high-count clusters throughout the study period. Distribution of high-count clusters shifted southeast from northwestern portions of the PPR in Alberta and western Saskatchewan, Canada, to North and South Dakota, USA, during the latter half of the study period. This spatial redistribution of core mallard breeding populations was likely driven by interactions between environmental variation that created favorable hydrological conditions for wetlands in the eastern PPR and dynamic land-use patterns related to upland cropping practices and government land-retirement programs. Our results highlight an opportunity for prioritizing relatively small regions within the PPR for allocation of wetland and grassland conservation for mallard populations. However, the extensive spatial heterogeneity in core distributions over our study period suggests such spatial prioritization will have to overcome challenges presented by dynamic land

Connexin-based intercellular communication and astrocyte heterogeneity.

Science.gov (United States)

Theis, Martin; Giaume, Christian

2012-12-03

This review gives an overview of the current knowledge on connexin-mediated communication in astrocytes, covering gap junction and hemichannel functions mediated by connexins. Astroglia is the main brain cell type that expresses the largest amount of connexin and exhibits high level of gap junctional communication compared to neurons and oligodendrocytes. However, in certain developmental and regional situations, astrocytes are also coupled with oligodendrocytes and neurons. This heterotypic coupling is infrequent and minor in terms of extent of the coupling area, which does not mean that it is not important in terms of cell interaction. Here, we present an update on heterogeneity of connexin expression and function at the molecular, subcellular, cellular and networking levels. Interestingly, while astrocytes were initially considered as a homogenous population, there is now increasing evidence for morphological, developmental, molecular and physiological heterogeneity of astrocytes. Consequently, the specificity of gap junction channel- and hemichannel-mediated communication, which tends to synchronize cell populations, is also a parameter to take into account when neuroglial interactions are investigated. This article is part of a Special Issue entitled Electrical Synapses. Copyright © 2012 Elsevier B.V. All rights reserved.

Heterogeneity and plasticity of epidermal stem cells

DEFF Research Database (Denmark)

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....

Experimental methods and modeling techniques for description of cell population heterogeneity

DEFF Research Database (Denmark)

Lencastre Fernandes, Rita; Nierychlo, M.; Lundin, L.

2011-01-01

With the continuous development, in the last decades, of analytical techniques providing complex information at single cell level, the study of cell heterogeneity has been the focus of several research projects within analytical biotechnology. Nonetheless, the complex interplay between environmen......With the continuous development, in the last decades, of analytical techniques providing complex information at single cell level, the study of cell heterogeneity has been the focus of several research projects within analytical biotechnology. Nonetheless, the complex interplay between...

Laser-Induced Fluorescence Detection in High-Throughput Screening of Heterogeneous Catalysts and Single Cells Analysis

Energy Technology Data Exchange (ETDEWEB)

Su, Hui [Iowa State Univ., Ames, IA (United States)

2001-01-01

Laser-induced fluorescence detection is one of the most sensitive detection techniques and it has found enormous applications in various areas. The purpose of this research was to develop detection approaches based on laser-induced fluorescence detection in two different areas, heterogeneous catalysts screening and single cell study. First, we introduced laser-induced imaging (LIFI) as a high-throughput screening technique for heterogeneous catalysts to explore the use of this high-throughput screening technique in discovery and study of various heterogeneous catalyst systems. This scheme is based on the fact that the creation or the destruction of chemical bonds alters the fluorescence properties of suitably designed molecules. By irradiating the region immediately above the catalytic surface with a laser, the fluorescence intensity of a selected product or reactant can be imaged by a charge-coupled device (CCD) camera to follow the catalytic activity as a function of time and space. By screening the catalytic activity of vanadium pentoxide catalysts in oxidation of naphthalene, we demonstrated LIFI has good detection performance and the spatial and temporal resolution needed for high-throughput screening of heterogeneous catalysts. The sample packing density can reach up to 250 x 250 subunits/cm₂ for 40-μm wells. This experimental set-up also can screen solid catalysts via near infrared thermography detection.

Laser-Induced Fluorescence Detection in High-Throughput Screening of Heterogeneous Catalysts and Single Cells Analysis

International Nuclear Information System (INIS)

Hui Su

2001-01-01

Laser-induced fluorescence detection is one of the most sensitive detection techniques and it has found enormous applications in various areas. The purpose of this research was to develop detection approaches based on laser-induced fluorescence detection in two different areas, heterogeneous catalysts screening and single cell study. First, we introduced laser-induced imaging (LIFI) as a high-throughput screening technique for heterogeneous catalysts to explore the use of this high-throughput screening technique in discovery and study of various heterogeneous catalyst systems. This scheme is based on the fact that the creation or the destruction of chemical bonds alters the fluorescence properties of suitably designed molecules. By irradiating the region immediately above the catalytic surface with a laser, the fluorescence intensity of a selected product or reactant can be imaged by a charge-coupled device (CCD) camera to follow the catalytic activity as a function of time and space. By screening the catalytic activity of vanadium pentoxide catalysts in oxidation of naphthalene, we demonstrated LIFI has good detection performance and the spatial and temporal resolution needed for high-throughput screening of heterogeneous catalysts. The sample packing density can reach up to 250 x 250 subunits/cm(sub 2) for 40-(micro)m wells. This experimental set-up also can screen solid catalysts via near infrared thermography detection

Sparse covariance estimation in heterogeneous samples.

Science.gov (United States)

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.

High-density multicore fiber with heterogeneous core arrangement

DEFF Research Database (Denmark)

Amma, Y.; Sasaki, Y.; Takenaga, K.

2015-01-01

A 30-core fiber with heterogeneous cores that achieved large spatial multiplicity and low crosstalk of less than −40 dB at 100 km was demonstrated. The correlation lengths were estimated to be more than 1 m.......A 30-core fiber with heterogeneous cores that achieved large spatial multiplicity and low crosstalk of less than −40 dB at 100 km was demonstrated. The correlation lengths were estimated to be more than 1 m....

Methodological approach for substantiating disease freedom in a heterogeneous small population. Application to ovine scrapie, a disease with a strong genetic susceptibility.

Science.gov (United States)

Martinez, Marie-José; Durand, Benoit; Calavas, Didier; Ducrot, Christian

2010-06-01

Demonstrating disease freedom is becoming important in different fields including animal disease control. Most methods consider sampling only from a homogeneous population in which each animal has the same probability of becoming infected. In this paper, we propose a new methodology to calculate the probability of detecting the disease if it is present in a heterogeneous population of small size with potentially different risk groups, differences in risk being defined using relative risks. To calculate this probability, for each possible arrangement of the infected animals in the different groups, the probability that all the animals tested are test-negative given this arrangement is multiplied by the probability that this arrangement occurs. The probability formula is developed using the assumption of a perfect test and hypergeometric sampling for finite small size populations. The methodology is applied to scrapie, a disease affecting small ruminants and characterized in sheep by a strong genetic susceptibility defining different risk groups. It illustrates that the genotypes of the tested animals influence heavily the confidence level of detecting scrapie. The results present the statistical power for substantiating disease freedom in a small heterogeneous population as a function of the design prevalence, the structure of the sample tested, the structure of the herd and the associated relative risks. (c) 2010 Elsevier B.V. All rights reserved.

High-Efficient Parallel CAVLC Encoders on Heterogeneous Multicore Architectures

Directory of Open Access Journals (Sweden)

H. Y. Su

2012-04-01

Full Text Available This article presents two high-efficient parallel realizations of the context-based adaptive variable length coding (CAVLC based on heterogeneous multicore processors. By optimizing the architecture of the CAVLC encoder, three kinds of dependences are eliminated or weaken, including the context-based data dependence, the memory accessing dependence and the control dependence. The CAVLC pipeline is divided into three stages: two scans, coding, and lag packing, and be implemented on two typical heterogeneous multicore architectures. One is a block-based SIMD parallel CAVLC encoder on multicore stream processor STORM. The other is a component-oriented SIMT parallel encoder on massively parallel architecture GPU. Both of them exploited rich data-level parallelism. Experiments results show that compared with the CPU version, more than 70 times of speedup can be obtained for STORM and over 50 times for GPU. The implementation of encoder on STORM can make a real-time processing for 1080p @30fps and GPU-based version can satisfy the requirements for 720p real-time encoding. The throughput of the presented CAVLC encoders is more than 10 times higher than that of published software encoders on DSP and multicore platforms.

Dynamic phase microscopy, a new method to detect viable and killed spores and to estimate the heterogeneity of spore populations

Science.gov (United States)

Tychinsky, Vladimir P.; Mulyukin, Andrey L.; Lisovskii, Vitalii V.; Nikolaev, Yury A.; Kretushev, Aleksander V.; Vyshenskaya, Tatyana V.; Suzina, Nataliya E.; Duda, Vitalii I.; El-Registan, Galina I.

reversible: after cessation of heating, PT values became similar to dormant spores. So, DPM allowed us to track the first, reversible stage of activation, when a spore maintains the attributes of the dormant state. Under the conditions that favor germination (in the presence of nutrients), irreversible changes in the PT and spore diameter, d, were detectable in a single germinating spore and spore population. In addition, DPM allowed an easy estimation of the heterogeneity of spore populations. It is a great advantage of DPM that it makes possible to reveal the ability of spores to respond to various stimuli with or without further germination and outgrowth - the salient feature of a living cell. DPM may have a high potential in general microbiology and astrobiology, enabling to: (1) estimate the heterogeneity of spore populations either under standard conditions and subjected to solar radiation and simulated extraterrestrial factors; (2) to track a response of spores to changing conditions at the early germination stage, even if they do not enter further outgrowth; (3) to develop some approaches for monitoring studies and appraisal of the physiological state of dormant cells in situ, in samples of dry soils, permafrost, etc. regarded as models for searching life beyond the Earth.

Heterogeneity of breast cancer stem cells as evidenced with Notch-dependent and Notch-independent populations

International Nuclear Information System (INIS)

Wong, Nelson K Y; Fuller, Megan; Sung, Sandy; Wong, Fred; Karsan, Aly

2012-01-01

Studies have suggested the potential importance of Notch signaling to the cancer stem cell population in some tumors, but it is not known whether all cells in the cancer stem cell fraction require Notch activity. To address this issue, we blocked Notch activity in MCF-7 cells by expressing a dominant-negative MAML-GFP (dnMAML) construct, which inhibits signaling through all Notch receptors, and quantified the effect on tumor-initiating activity. Inhibition of Notch signaling reduced primary tumor sphere formation and side population. Functional quantification of tumor-initiating cell numbers in vivo showed a significant decrease, but not a complete abrogation, of these cells in dnMAML-expressing cells. Interestingly, when assessed in secondary assays in vitro or in vivo, there was no difference in tumor-initiating activity between the dnMAML-expressing cells and control cells. The fact that a subpopulation of dnMAML-expressing cells was capable of forming primary and secondary tumors indicates that there are Notch-independent tumor-initiating cells in the breast cancer cell line MCF-7. Our findings thus provide direct evidence for a heterogeneous cancer stem cell pool, which will require combination therapies against multiple oncogenic pathways to eliminate the tumor-initiating cell population

Genomic analysis of a heterogeneous Mendelian phenotype: multiple novel alleles for inherited hearing loss in the Palestinian population

Directory of Open Access Journals (Sweden)

Walsh Tom

2006-01-01

Full Text Available Abstract Recessively inherited phenotypes are frequent in the Palestinian population, as the result of a historical tradition of marriages within extended kindreds, particularly in isolated villages. In order to characterise the genetics of inherited hearing loss in this population, we worked with West Bank schools for the deaf to identify children with prelingual, bilateral, severe to profound hearing loss not attributable to infection, trauma or other known environmental exposure. Of 156 families enrolled, hearing loss in 17 families (11 per cent was due to mutations in GJB2 (connexin 26, a smaller fraction of GJB2-associated deafness than in other populations. In order to estimate how many different genes might be responsible for hearing loss in this population, we evaluated ten families for linkage to all 36 known human autosomal deafness-related genes, fully sequencing hearing-related genes at any linked sites in informative relatives. Four families harboured four novel alleles of TMPRSS3 (988ΔA = 352stop, otoancorin (1067A >T = D356V and pendrin (716T > A = V239D and 1001G > T = 346stop. In each family, all affected individuals were homozygous for the critical mutation. Each allele was specific to one or a few families in the cohort; none were widespread. Since epidemiological tests of association of mutations with deafness were not feasible for such rare alleles, we used functional and bioinformatics approaches to evaluate their consequences. In six other families, hearing loss was not linked to any known gene, suggesting that these families harbour novel genes responsible for this phenotype. We conclude that inherited hearing loss is highly heterogeneous in this population, with most extended families acting as genetic isolates in this context. We also conclude that the same genes are responsible for hearing loss in this population as elsewhere, so that gene discovery in these families informs the genetics of hearing loss worldwide.

Effects of soil nutrient heterogeneity on intraspecific competition in the invasive, clonal plant Alternanthera philoxeroides.

Science.gov (United States)

Zhou, Jian; Dong, Bi-Cheng; Alpert, Peter; Li, Hong-Li; Zhang, Ming-Xiang; Lei, Guang-Chun; Yu, Fei-Hai

2012-03-01

Fine-scale, spatial heterogeneity in soil nutrient availability can increase the growth of individual plants, the productivity of plant communities and interspecific competition. If this is due to the ability of plants to concentrate their roots where nutrient levels are high, then nutrient heterogeneity should have little effect on intraspecific competition, especially when there are no genotypic differences between individuals in root plasticity. We tested this hypothesis in a widespread, clonal species in which individual plants are known to respond to nutrient heterogeneity. Plants derived from a single clone of Alternanthera philoxeroides were grown in the greenhouse at low or high density (four or 16 plants per 27·5 × 27·5-cm container) with homogeneous or heterogeneous availability of soil nutrients, keeping total nutrient availability per container constant. After 9 weeks, measurements of size, dry mass and morphology were taken. Plants grew more in the heterogeneous than in the homogeneous treatment, showing that heterogeneity promoted performance; they grew less in the high- than in the low-density treatment, showing that plants competed. There was no interactive effect of nutrient heterogeneity and plant density, supporting the hypothesis that heterogeneity does not affect intraspecific competition in the absence of genotypic differences in plasticity. Treatments did not affect morphological characteristics such as specific leaf area or root/shoot ratio. Results indicate that fine-scale, spatial heterogeneity in the availability of soil nutrients does not increase competition when plants are genetically identical, consistent with the suggestion that effects of heterogeneity on competition depend upon differences in plasticity between individuals. Heterogeneity is only likely to increase the spread of monoclonal, invasive populations such as that of A. philoxeroides in China.

Heterogeneity in Models of Electoral Choice

OpenAIRE

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...

Heterogeneity in preferences and behavior in threshold models

Directory of Open Access Journals (Sweden)

Philip R Neary

2017-12-01

Full Text Available A coordination game is repeatedly played on a graph by players (vertices who have heterogeneous cardinal preferences and whose strategy choice is governed by the individualistic asynchronous logit dynamic. The idea of potential driven autonomy of sets of players is used to derive results on the possibility of heterogeneous preferences leading to heterogeneous behavior. In particular, a class of graphs is identified such that for large enough graphs in this class, diversity in ordinal preferences will nearly always lead to heterogeneity in behavior, regardless of the cardinal strength of the preferences. These results have implications for network design problems, such as when a social planner wishes to induce homogeneous/heterogeneous behavior in a population.

Individual heterogeneity generating explosive system network dynamics.

Science.gov (United States)

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.

Individual heterogeneity generating explosive system network dynamics

Science.gov (United States)

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.

[Diagnostic imaging of high-grade astrocytoma: heterogeneity of clinical manifestation, image characteristics, and histopathological findings].

Science.gov (United States)

Okajima, Kaoru; Ohta, Yoshio

2012-10-01

Recent developments in diagnostic radiology, which have enabled accurate differential diagnoses of brain tumors, have been well described in the last three decades. MR and PET imaging can also provide information to predict histological grades and prognoses that might influence treatment strategies. However, high-grade astrocytomas consist of many different subtypes that are associated with different imaging and histological characteristics. Hemorrhage and necrosis results in a variety of imaging features, and infiltrative tumor growth entrapping normal neurons may cause different clinical manifestations. We reviewed patients with high-grade astrocytomas that showed various imaging characteristics, with special emphasis on initial symptoms and histological features. Clinicopathological characteristics of astrocytomas were also compared with other malignant tumors. Neurological deficits were not notable in patients with grade 3-4 astrocytomas when they showed infiltrative tumor growth, while brain metastases with compact cellular proliferation caused more neurological symptoms. Infiltrative tumors did not show any enhancing masses on MR imaging, but these tumors may show intratumor heterogeneity. Seizures were reported to be more frequent in low-grade glioma and in secondary glioblastoma. Tumor heterogeneity was also reported in molecular genetic profile, and investigators identified some subsets of astrocytomas. They investigated IHD1/2 mutation, EGFR amplification, TP53 mutation, Ki-67 index, etc. In summary, high-grade astrocytomas are not homogenous groups of tumors, and this is associated with the heterogeneity of clinical manifestation, image characteristics, and histopathological findings. Molecular studies may explain the tumor heterogeneity in the near future.

Stochastic variation in telomere shortening rate causes heterogeneity of human fibroblast replicative life span.

Science.gov (United States)

Martin-Ruiz, Carmen; Saretzki, Gabriele; Petrie, Joanne; Ladhoff, Juliane; Jeyapalan, Jessie; Wei, Wenyi; Sedivy, John; von Zglinicki, Thomas

2004-04-23

The replicative life span of human fibroblasts is heterogeneous, with a fraction of cells senescing at every population doubling. To find out whether this heterogeneity is due to premature senescence, i.e. driven by a nontelomeric mechanism, fibroblasts with a senescent phenotype were isolated from growing cultures and clones by flow cytometry. These senescent cells had shorter telomeres than their cycling counterparts at all population doubling levels and both in mass cultures and in individual subclones, indicating heterogeneity in the rate of telomere shortening. Ectopic expression of telomerase stabilized telomere length in the majority of cells and rescued them from early senescence, suggesting a causal role of telomere shortening. Under standard cell culture conditions, there was a minor fraction of cells that showed a senescent phenotype and short telomeres despite active telomerase. This fraction increased under chronic mild oxidative stress, which is known to accelerate telomere shortening. It is possible that even high telomerase activity cannot fully compensate for telomere shortening in all cells. The data show that heterogeneity of the human fibroblast replicative life span can be caused by significant stochastic cell-to-cell variation in telomere shortening.

Synthesis of carbonate esters by carboxymethylation using NaAlO2 as a highly active heterogeneous catalyst

OpenAIRE

Ramesh, Sreerangappa; Indukuri, Kiran; Riant, Olivier; Debecker, Damien

2018-01-01

Sodium aluminate is presented as a highly active heterogeneous catalyst able to convert a range of alcohols into the corresponding mixed carbonate esters, in high yield and under green conditions. The reaction is carried out using dimethyl carbonate both as a reactant and solvent, at 90°C. Allylic, aliphatic and aromatic alcohols are converted in good yields. The solid catalyst is shown to be truly heterogeneous, resistant to leaching, and recyclable.

High-density biosynthetic fuels: the intersection of heterogeneous catalysis and metabolic engineering.

Science.gov (United States)

Harvey, Benjamin G; Meylemans, Heather A; Gough, Raina V; Quintana, Roxanne L; Garrison, Michael D; Bruno, Thomas J

2014-05-28

Biosynthetic valencene, premnaspirodiene, and natural caryophyllene were hydrogenated and evaluated as high performance fuels. The parent sesquiterpenes were then isomerized to complex mixtures of hydrocarbons with the heterogeneous acid catalyst Nafion SAC-13. High density fuels with net heats of combustion ranging from 133-141 000 Btu gal(-1), or up to 13% higher than commercial jet fuel could be generated by this approach. The products of caryophyllene isomerization were primarily tricyclic hydrocarbons which after hydrogenation increased the fuel density by 6%. The isomerization of valencene and premnaspirodiene also generated a variety of sesquiterpenes, but in both cases the dominant product was δ-selinene. Ab initio calculations were conducted to determine the total electronic energies for the reactants and products. In all cases the results were in excellent agreement with the experimental distribution of isomers. The cetane numbers for the sesquiterpane fuels ranged from 20-32 and were highly dependent on the isomer distribution. Specific distillation cuts may have the potential to act as high density diesel fuels, while use of these hydrocarbons as additives to jet fuel will increase the range and/or time of flight of aircraft. In addition to the ability to generate high performance renewable fuels, the powerful combination of metabolic engineering and heterogeneous catalysis will allow for the preparation of a variety of sesquiterpenes with potential for pharmaceutical, flavor, and fragrance applications.

Murine bone marrow Lin⁻Sca⁻1⁺CD45⁻ very small embryonic-like (VSEL cells are heterogeneous population lacking Oct-4A expression.

Directory of Open Access Journals (Sweden)

Krzysztof Szade

Full Text Available Murine very small embryonic-like (VSEL cells, defined by the Lin(-Sca-1(+CD45(- phenotype and small size, were described as pluripotent cells and proposed to be the most primitive hematopoietic precursors in adult bone marrow. Although their isolation and potential application rely entirely on flow cytometry, the immunophenotype of VSELs has not been extensively characterized. Our aim was to analyze the possible heterogeneity of Lin(-Sca(+CD45(- population and investigate the extent to which VSELs characteristics may overlap with that of hematopoietic stem cells (HSCs or endothelial progenitor cells (EPCs. The study evidenced that murine Lin(-Sca-1(+CD45(- population was heterogeneous in terms of c-Kit and KDR expression. Accordingly, the c-Kit(+KDR(-, c-Kit(-KDR(+, and c-Kit(-KDR(- subpopulations could be distinguished, while c-Kit(+KDR(+ events were very rare. The c-Kit(+KDR(- subset contained almost solely small cells, meeting the size criterion of VSELs, in contrast to relatively bigger c-Kit(-KDR(+ cells. The c-Kit(-KDR(-FSC(low subset was highly enriched in Annexin V-positive, apoptotic cells, hence omitted from further analysis. Importantly, using qRT-PCR, we evidenced lack of Oct-4A and Oct-4B mRNA expression either in whole adult murine bone marrow or in the sorted of Lin(-Sca-1(+CD45(-FSC(low population, even by single-cell qRT-PCR. We also found that the Lin(-Sca-1(+CD45(-c-Kit(+ subset did not exhibit hematopoietic potential in a single cell-derived colony in vitro assay, although it comprised the Sca-1(+c-Kit(+Lin(- (SKL CD34(-CD45(-CD105(+ cells, expressing particular HSC markers. Co-culture of Lin(-Sca-1(+CD45(-FSC(low with OP9 cells did not induce hematopoietic potential. Further investigation revealed that SKL CD45(-CD105(+ subset consisted of early apoptotic cells with fragmented chromatin, and could be contaminated with nuclei expelled from erythroblasts. Concluding, murine bone marrow Lin(-Sca-1(+CD45(-FSC(low cells are

Spatial heterogeneity study of vegetation coverage at Heihe River Basin

Science.gov (United States)

Wu, Lijuan; Zhong, Bo; Guo, Liyu; Zhao, Xiangwei

2014-11-01

Spatial heterogeneity of the animal-landscape system has three major components: heterogeneity of resource distributions in the physical environment, heterogeneity of plant tissue chemistry, heterogeneity of movement modes by the animal. Furthermore, all three different types of heterogeneity interact each other and can either reinforce or offset one another, thereby affecting system stability and dynamics. In previous studies, the study areas are investigated by field sampling, which costs a large amount of manpower. In addition, uncertain in sampling affects the quality of field data, which leads to unsatisfactory results during the entire study. In this study, remote sensing data is used to guide the sampling for research on heterogeneity of vegetation coverage to avoid errors caused by randomness of field sampling. Semi-variance and fractal dimension analysis are used to analyze the spatial heterogeneity of vegetation coverage at Heihe River Basin. The spherical model with nugget is used to fit the semivariogram of vegetation coverage. Based on the experiment above, it is found, (1)there is a strong correlation between vegetation coverage and distance of vegetation populations within the range of 0-28051.3188m at Heihe River Basin, but the correlation loses suddenly when the distance greater than 28051.3188m. (2)The degree of spatial heterogeneity of vegetation coverage at Heihe River Basin is medium. (3)Spatial distribution variability of vegetation occurs mainly on small scales. (4)The degree of spatial autocorrelation is 72.29% between 25% and 75%, which means that spatial correlation of vegetation coverage at Heihe River Basin is medium high.

HIGH TEMPERATURE, HIGH POWER HETEROGENEOUS NUCLEAR REACTOR

Science.gov (United States)

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.

Coordination Frictions and Job Heterogeneity

DEFF Research Database (Denmark)

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...

Etiologic heterogeneity of the psychoses: is there a dopamine psychosis?

Science.gov (United States)

Garver, D L; Steinberg, J L; McDermott, B E; Yao, J K; Ramberg, J E; Lewis, S; Kingsbury, S J

1997-03-01

The distribution of drug-free plasma homovanillic acid (pHVA) concentrations was studied in a sample of psychotic patients, some of whom were selected for good prognostic features. Baseline pHVA was bimodally distributed, suggesting two different patient populations. The high-pHVA patients showed periods of better functioning and/or fewer symptoms 5 years before admission (p pHVA psychotics. High-pHVA psychotics did not differ in other aspects of demographics or clinical presentation from lower-pHVA psychotics. Compared to the general population, there were more psychotics in the families of high-pHVA patients (p pHVA psychotics is consistent with blockade of the effects of excess synaptic dopamine at D2 receptors for these patients. Results are discussed in the context of the syndromic heterogeneity of the psychoses.

Heterogeneity and convergence of olfactory first-order neurons account for the high speed and sensitivity of second-order neurons.

Directory of Open Access Journals (Sweden)

Jean-Pierre Rospars

2014-12-01

Full Text Available In the olfactory system of male moths, a specialized subset of neurons detects and processes the main component of the sex pheromone emitted by females. It is composed of several thousand first-order olfactory receptor neurons (ORNs, all expressing the same pheromone receptor, that contact synaptically a few tens of second-order projection neurons (PNs within a single restricted brain area. The functional simplicity of this system makes it a favorable model for studying the factors that contribute to its exquisite sensitivity and speed. Sensory information--primarily the identity and intensity of the stimulus--is encoded as the firing rate of the action potentials, and possibly as the latency of the neuron response. We found that over all their dynamic range, PNs respond with a shorter latency and a higher firing rate than most ORNs. Modelling showed that the increased sensitivity of PNs can be explained by the ORN-to-PN convergent architecture alone, whereas their faster response also requires cell-to-cell heterogeneity of the ORN population. So, far from being detrimental to signal detection, the ORN heterogeneity is exploited by PNs, and results in two different schemes of population coding based either on the response of a few extreme neurons (latency or on the average response of many (firing rate. Moreover, ORN-to-PN transformations are linear for latency and nonlinear for firing rate, suggesting that latency could be involved in concentration-invariant coding of the pheromone blend and that sensitivity at low concentrations is achieved at the expense of precise encoding at high concentrations.

Engineering Microbial Metabolite Dynamics and Heterogeneity.

Science.gov (United States)

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.

Supervised learning methods in modeling of CD4+ T cell heterogeneity

OpenAIRE

Lu, Pinyi; Abedi, Vida; Mei, Yongguo; Hontecillas, Raquel; Hoops, Stefan; Carbo, Adria; Bassaganya-Riera, Josep

2015-01-01

Background Modeling of the immune system – a highly non-linear and complex system – requires practical and efficient data analytic approaches. The immune system is composed of heterogeneous cell populations and hundreds of cell types, such as neutrophils, eosinophils, macrophages, dendritic cells, T cells, and B cells. Each cell type is highly diverse and can be further differentiated into subsets with unique and overlapping functions. For example, CD4+ T cells can be differentiated into T...

TGIF1 is a potential candidate gene for high myopia in ethnic Kashmiri population.

Science.gov (United States)

Ahmed, Ishfaq; Rasool, Shabhat; Jan, Tariq; Qureshi, Tariq; Naykoo, Niyaz A; Andrabi, Khurshid I

2014-03-01

High myopia is a complex disorder that imposes serious consequences on ocular health. Linkage analysis has identified several genetic loci with a series of potential candidate genes that reveal an ambiguous pattern of association with high myopia due to population heterogeneity. We have accordingly chosen to examine the prospect of association of one such gene [transforming growth β-induced factor 1 (TGIF1)] in population that is purely ethnic (Kashmiri) and represents a homogeneous cohort from Northern India. Cases with high myopia with a spherical equivalent of ≥-6 diopters (D) and emmetropic controls with spherical equivalent within ±0.5 D in one or both eyes represented by a sample size of 212 ethnic Kashmiri subjects and 239 matched controls. Genomic DNA was genotyped for sequence variations in TGIF1 gene and allele frequencies tested for Hardy-Weinberg disequilibrium. Potential association was evaluated using χ(2) or Fisher's exact test. Two previously reported missense variations C > T, rs4468717 (first base of codon 143) changing proline to serine and rs2229333 (second base of codon 143) changing proline to leucine were identified in exon 10 of TGIF1. Both variations exhibited possibly significant (p population. In silico predictions show that substitutions are likely to have an impact on the structure and functional properties of the protein, making it imperative to understand their functional consequences in relation to high myopia. TGIF1 is a relevant candidate gene with potential to contribute in the genesis of high myopia.

Heterogeneity reduces sensitivity of cell death for TNF-Stimuli

Directory of Open Access Journals (Sweden)

Schliemann Monica

2011-12-01

Full Text Available Abstract Background Apoptosis is a form of programmed cell death essential for the maintenance of homeostasis and the removal of potentially damaged cells in multicellular organisms. By binding its cognate membrane receptor, TNF receptor type 1 (TNF-R1, the proinflammatory cytokine Tumor Necrosis Factor (TNF activates pro-apoptotic signaling via caspase activation, but at the same time also stimulates nuclear factor κB (NF-κB-mediated survival pathways. Differential dose-response relationships of these two major TNF signaling pathways have been described experimentally and using mathematical modeling. However, the quantitative analysis of the complex interplay between pro- and anti-apoptotic signaling pathways is an open question as it is challenging for several reasons: the overall signaling network is complex, various time scales are present, and cells respond quantitatively and qualitatively in a heterogeneous manner. Results This study analyzes the complex interplay of the crosstalk of TNF-R1 induced pro- and anti-apoptotic signaling pathways based on an experimentally validated mathematical model. The mathematical model describes the temporal responses on both the single cell level as well as the level of a heterogeneous cell population, as observed in the respective quantitative experiments using TNF-R1 stimuli of different strengths and durations. Global sensitivity of the heterogeneous population was quantified by measuring the average gradient of time of death versus each population parameter. This global sensitivity analysis uncovers the concentrations of Caspase-8 and Caspase-3, and their respective inhibitors BAR and XIAP, as key elements for deciding the cell's fate. A simulated knockout of the NF-κB-mediated anti-apoptotic signaling reveals the importance of this pathway for delaying the time of death, reducing the death rate in the case of pulse stimulation and significantly increasing cell-to-cell variability. Conclusions Cell

A note on variational multiscale methods for high-contrast heterogeneous porous media flows with rough source terms

KAUST Repository

Calo, Victor M.

2011-09-01

In this short note, we discuss variational multiscale methods for solving porous media flows in high-contrast heterogeneous media with rough source terms. Our objective is to separate, as much as possible, subgrid effects induced by the media properties from those due to heterogeneous source terms. For this reason, enriched coarse spaces designed for high-contrast multiscale problems are used to represent the effects of heterogeneities of the media. Furthermore, rough source terms are captured via auxiliary correction equations that appear in the formulation of variational multiscale methods [23]. These auxiliary equations are localized and one can use additive or multiplicative constructions for the subgrid corrections as discussed in the current paper. Our preliminary numerical results show that one can capture the effects due to both spatial heterogeneities in the coefficients (such as permeability field) and source terms (e.g., due to singular well terms) in one iteration. We test the cases for both smooth source terms and rough source terms and show that with the multiplicative correction, the numerical approximations are more accurate compared to the additive correction. © 2010 Elsevier Ltd.

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

Science.gov (United States)

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

Spatially correlated heterogeneous aspirations to enhance network reciprocity

Science.gov (United States)

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.

A Generalized Estimating Equations Approach to Model Heterogeneity and Time Dependence in Capture-Recapture Studies

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Akanda Md. Abdus Salam

2017-03-01

Full Text Available Individual heterogeneity in capture probabilities and time dependence are fundamentally important for estimating the closed animal population parameters in capture-recapture studies. A generalized estimating equations (GEE approach accounts for linear correlation among capture-recapture occasions, and individual heterogeneity in capture probabilities in a closed population capture-recapture individual heterogeneity and time variation model. The estimated capture probabilities are used to estimate animal population parameters. Two real data sets are used for illustrative purposes. A simulation study is carried out to assess the performance of the GEE estimator. A Quasi-Likelihood Information Criterion (QIC is applied for the selection of the best fitting model. This approach performs well when the estimated population parameters depend on the individual heterogeneity and the nature of linear correlation among capture-recapture occasions.

Assessing submarine groundwater discharge (SGD) and nitrate fluxes in highly heterogeneous coastal karst aquifers: Challenges and solutions

Science.gov (United States)

Montiel, Daniel; Dimova, Natasha; Andreo, Bartolomé; Prieto, Jorge; García-Orellana, Jordi; Rodellas, Valentí

2018-02-01

Groundwater discharge in coastal karst aquifers worldwide represents a substantial part of the water budget and is a main pathway for nutrient transport to the sea. Groundwater discharge to the sea manifests under different forms, making its assessment very challenging particularly in highly heterogeneous coastal systems karst systems. In this study, we present a methodology approach to identify and quantify four forms of groundwater discharge in a mixed lithology system in southern Spain (Maro-Cerro Gordo) that includes an ecologically protected coastal area comprised of karstic marble. We found that groundwater discharge to the sea occurs via: (1) groundwater-fed creeks, (2) coastal springs, (3) diffuse groundwater seepage through seabed sediments, and (4) submarine springs. We used a multi-method approach combining tracer techniques (salinity, 224Ra, and 222Rn) and direct measurements (seepage meters and flowmeters) to evaluate the discharge. Groundwater discharge via submarine springs was the most difficult to assess due to their depth (up to 15 m) and extensive development of the springs conduits. We determined that the total groundwater discharge over the 16 km of shoreline of the study area was at least 11 ± 3 × 103 m3 d-1 for the four types of discharge assessed. Groundwater-derived nitrate (NO3-) fluxes to coastal waters over ∼3 km (or 20%) in a highly populated and farmed section of Maro-Cerro Gordo was 641 ± 166 mol d-1, or ∼75% of the total NO3- loading in the study area. We demonstrate in this study that a multi-method approach must be applied to assess all forms of SGD and derived nutrient fluxes to the sea in highly heterogeneous karst aquifer systems.

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

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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...

A further analysis of the role of heterogeneity in coevolutionary spatial games

Science.gov (United States)

Cardinot, Marcos; Griffith, Josephine; O'Riordan, Colm

2018-03-01

Heterogeneity has been studied as one of the most common explanations of the puzzle of cooperation in social dilemmas. A large number of papers have been published discussing the effects of increasing heterogeneity in structured populations of agents, where it has been established that heterogeneity may favour cooperative behaviour if it supports agents to locally coordinate their strategies. In this paper, assuming an existing model of a heterogeneous weighted network, we aim to further this analysis by exploring the relationship (if any) between heterogeneity and cooperation. We adopt a weighted network which is fully populated by agents playing both the Prisoner's Dilemma or the Optional Prisoner's Dilemma games with coevolutionary rules, i.e., not only the strategies but also the link weights evolve over time. Surprisingly, results show that the heterogeneity of link weights (states) on their own does not always promote cooperation; rather cooperation is actually favoured by the increase in the number of overlapping states and not by the heterogeneity itself. We believe that these results can guide further research towards a more accurate analysis of the role of heterogeneity in social dilemmas.

The impact of individual-level heterogeneity on estimated infectious disease burden: a simulation study.

Science.gov (United States)

McDonald, Scott A; Devleesschauwer, Brecht; Wallinga, Jacco

2016-12-08

Disease burden is not evenly distributed within a population; this uneven distribution can be due to individual heterogeneity in progression rates between disease stages. Composite measures of disease burden that are based on disease progression models, such as the disability-adjusted life year (DALY), are widely used to quantify the current and future burden of infectious diseases. Our goal was to investigate to what extent ignoring the presence of heterogeneity could bias DALY computation. Simulations using individual-based models for hypothetical infectious diseases with short and long natural histories were run assuming either "population-averaged" progression probabilities between disease stages, or progression probabilities that were influenced by an a priori defined individual-level frailty (i.e., heterogeneity in disease risk) distribution, and DALYs were calculated. Under the assumption of heterogeneity in transition rates and increasing frailty with age, the short natural history disease model predicted 14% fewer DALYs compared with the homogenous population assumption. Simulations of a long natural history disease indicated that assuming homogeneity in transition rates when heterogeneity was present could overestimate total DALYs, in the present case by 4% (95% quantile interval: 1-8%). The consequences of ignoring population heterogeneity should be considered when defining transition parameters for natural history models and when interpreting the resulting disease burden estimates.

Controlling the diversity of cell populations in a stem cell culture

NARCIS (Netherlands)

Heo, Inha; Clevers, Hans

2015-01-01

Culturing intestinal stem cells into 3D organoids results in heterogeneous cell populations, reflecting the in vivo cell type diversity. In a recent paper published in Nature, Wang et al. established a culture condition for a highly homogeneous population of intestinal stem cells.

High Intra- and Inter-Tumoral Heterogeneity of RAS Mutations in Colorectal Cancer

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Marion Jeantet

2016-12-01

Full Text Available Approximately 30% of patients with wild type RAS metastatic colorectal cancer are non-responders to anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR mAbs, possibly due to undetected tumoral subclones harboring RAS mutations. The aim of this study was to analyze the distribution of RAS mutations in different areas of the primary tumor, metastatic lymph nodes and distant metastasis. A retrospective cohort of 18 patients with a colorectal cancer (CRC was included in the study. Multiregion analysis was performed in 60 spatially separated tumor areas according to the pathological tumor node metastasis (pTNM staging and KRAS, NRAS and BRAF mutations were tested using pyrosequencing. In primary tumors, intra-tumoral heterogeneity for RAS mutation was found in 33% of cases. Inter-tumoral heterogeneity for RAS mutation between primary tumors and metastatic lymph nodes or distant metastasis was found in 36% of cases. Moreover, 28% of tumors had multiple RAS mutated subclones in the same tumor. A high proportion of CRCs presented intra- and/or inter-tumoral heterogeneity, which has relevant clinical implications for anti-EGFR mAbs prescription. These results suggest the need for multiple RAS testing in different parts of the same tumor and/or more sensitive techniques.

Parallel Gene Expression Differences between Low and High Latitude Populations of Drosophila melanogaster and D. simulans.

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Zhao, Li; Wit, Janneke; Svetec, Nicolas; Begun, David J

2015-05-01

Gene expression variation within species is relatively common, however, the role of natural selection in the maintenance of this variation is poorly understood. Here we investigate low and high latitude populations of Drosophila melanogaster and its sister species, D. simulans, to determine whether the two species show similar patterns of population differentiation, consistent with a role for spatially varying selection in maintaining gene expression variation. We compared at two temperatures the whole male transcriptome of D. melanogaster and D. simulans sampled from Panama City (Panama) and Maine (USA). We observed a significant excess of genes exhibiting differential expression in both species, consistent with parallel adaptation to heterogeneous environments. Moreover, the majority of genes showing parallel expression differentiation showed the same direction of differential expression in the two species and the magnitudes of expression differences between high and low latitude populations were correlated across species, further bolstering the conclusion that parallelism for expression phenotypes results from spatially varying selection. However, the species also exhibited important differences in expression phenotypes. For example, the genomic extent of genotype × environment interaction was much more common in D. melanogaster. Highly differentiated SNPs between low and high latitudes were enriched in the 3' UTRs and CDS of the geographically differently expressed genes in both species, consistent with an important role for cis-acting variants in driving local adaptation for expression-related phenotypes.

Heterogeneity maintenance in glioblastoma: a social network.

Science.gov (United States)

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.

Field heritability of a plant adaptation to fire in heterogeneous landscapes.

Science.gov (United States)

Castellanos, M C; González-Martínez, S C; Pausas, J G

2015-11-01

The strong association observed between fire regimes and variation in plant adaptations to fire suggests a rapid response to fire as an agent of selection. It also suggests that fire-related traits are heritable, a precondition for evolutionary change. One example is serotiny, the accumulation of seeds in unopened fruits or cones until the next fire, an important strategy for plant population persistence in fire-prone ecosystems. Here, we evaluate the potential of this trait to respond to natural selection in its natural setting. For this, we use a SNP marker approach to estimate genetic variance and heritability of serotiny directly in the field for two Mediterranean pine species. Study populations were large and heterogeneous in climatic conditions and fire regime. We first estimated the realized relatedness among trees from genotypes, and then partitioned the phenotypic variance in serotiny using Bayesian animal models that incorporated environmental predictors. As expected, field heritability was smaller (around 0.10 for both species) than previous estimates under common garden conditions (0.20). An estimate on a subset of stands with more homogeneous environmental conditions was not different from that in the complete set of stands, suggesting that our models correctly captured the environmental variation at the spatial scale of the study. Our results highlight the importance of measuring quantitative genetic parameters in natural populations, where environmental heterogeneity is a critical aspect. The heritability of serotiny, although not high, combined with high phenotypic variance within populations, confirms the potential of this fire-related trait for evolutionary change in the wild. © 2015 John Wiley & Sons Ltd.

Structural Optimization of a High-Speed Press Considering Multi-Source Uncertainties Based on a New Heterogeneous TOPSIS

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Jin Cheng

2018-01-01

Full Text Available In order to achieve high punching precision, good operational reliability and low manufacturing cost, the structural optimization of a high-speed press in the presence of a set of available alternatives comprises a heterogeneous multiple-attribute decision-making (HMADM problem involving deviation, fixation, cost and benefit attributes that can be described in various mathematical forms due to the existence of multi-source uncertainties. Such a HMADM problem cannot be easily resolved by existing methods. To overcome this difficulty, a new heterogeneous technique for order preference by similarity to an ideal solution (HTOPSIS is proposed. A new approach to normalization of heterogeneous attributes is proposed by integrating the possibility degree method, relative preference relation and the attribute transformation technique. Expressions for determining positive and negative ideal solutions corresponding to heterogeneous attributes are also developed. Finally, alternative structural configurations are ranked according to their relative closeness coefficients, and the optimal structural configuration can be determined. The validity and effectiveness of the proposed HTOPSIS are demonstrated by a numerical example. The proposed HTOPSIS can also be applied to structural optimization of other complex equipment, because there is no prerequisite of independency among various attributes for its application.

GenHtr: a tool for comparative assessment of genetic heterogeneity in microbial genomes generated by massive short-read sequencing

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Yu GongXin

2010-10-01

Full Text Available Abstract Background Microevolution is the study of short-term changes of alleles within a population and their effects on the phenotype of organisms. The result of the below-species-level evolution is heterogeneity, where populations consist of subpopulations with a large number of structural variations. Heterogeneity analysis is thus essential to our understanding of how selective and neutral forces shape bacterial populations over a short period of time. The Solexa Genome Analyzer, a next-generation sequencing platform, allows millions of short sequencing reads to be obtained with great accuracy, allowing for the ability to study the dynamics of the bacterial population at the whole genome level. The tool referred to as GenHtr was developed for genome-wide heterogeneity analysis. Results For particular bacterial strains, GenHtr relies on a set of Solexa short reads on given bacteria pathogens and their isogenic reference genome to identify heterogeneity sites, the chromosomal positions with multiple variants of genes in the bacterial population, and variations that occur in large gene families. GenHtr accomplishes this by building and comparatively analyzing genome-wide heterogeneity genotypes for both the newly sequenced genomes (using massive short-read sequencing and their isogenic reference (using simulated data. As proof of the concept, this approach was applied to SRX007711, the Solexa sequencing data for a newly sequenced Staphylococcus aureus subsp. USA300 cell line, and demonstrated that it could predict such multiple variants. They include multiple variants of genes critical in pathogenesis, e.g. genes encoding a LysR family transcriptional regulator, 23 S ribosomal RNA, and DNA mismatch repair protein MutS. The heterogeneity results in non-synonymous and nonsense mutations, leading to truncated proteins for both LysR and MutS. Conclusion GenHtr was developed for genome-wide heterogeneity analysis. Although it is much more time

Single-cell RNA sequencing reveals metallothionein heterogeneity during hESC differentiation to definitive endoderm

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Junjie Lu

2018-04-01

Full Text Available Differentiation of human pluripotent stem cells towards definitive endoderm (DE is the critical first step for generating cells comprising organs such as the gut, liver, pancreas and lung. This in-vitro differentiation process generates a heterogeneous population with a proportion of cells failing to differentiate properly and maintaining expression of pluripotency factors such as Oct4. RNA sequencing of single cells collected at four time points during a 4-day DE differentiation identified high expression of metallothionein genes in the residual Oct4-positive cells that failed to differentiate to DE. Using X-ray fluorescence microscopy and multi-isotope mass spectrometry, we discovered that high intracellular zinc level corresponds with persistent Oct4 expression and failure to differentiate. This study improves our understanding of the cellular heterogeneity during in-vitro directed differentiation and provides a valuable resource to improve DE differentiation efficiency. Keywords: hPSC, Differentiation, Definitive endoderm, Heterogeneity, Single cell, RNA sequencing

High-Dimensional Adaptive Particle Swarm Optimization on Heterogeneous Systems

International Nuclear Information System (INIS)

Wachowiak, M P; Sarlo, B B; Foster, A E Lambe

2014-01-01

Much work has recently been reported in parallel GPU-based particle swarm optimization (PSO). Motivated by the encouraging results of these investigations, while also recognizing the limitations of GPU-based methods for big problems using a large amount of data, this paper explores the efficacy of employing other types of parallel hardware for PSO. Most commodity systems feature a variety of architectures whose high-performance capabilities can be exploited. In this paper, high-dimensional problems and those that employ a large amount of external data are explored within the context of heterogeneous systems. Large problems are decomposed into constituent components, and analyses are undertaken of which components would benefit from multi-core or GPU parallelism. The current study therefore provides another demonstration that ''supercomputing on a budget'' is possible when subtasks of large problems are run on hardware most suited to these tasks. Experimental results show that large speedups can be achieved on high dimensional, data-intensive problems. Cost functions must first be analysed for parallelization opportunities, and assigned hardware based on the particular task

Heterogeneity in risk of prostate cancer: A Swedish population-based cohort study of competing risks and type 2 diabetes mellitus.

Science.gov (United States)

Häggström, Christel; Van Hemelrijck, Mieke; Garmo, Hans; Robinson, David; Stattin, Pär; Rowley, Mark; Coolen, Anthony C C; Holmberg, Lars

2018-05-09

Most previous studies of prostate cancer have not taken into account that men in the studied populations are also at risk of competing event, and that these men may have different susceptibility to prostate cancer risk. The aim of this study was to investigate heterogeneity in risk of prostate cancer, using a recently developed latent class regression method for competing risks. We further aimed to elucidate the association between type 2 diabetes mellitus (T2DM) and prostate cancer risk, and to compare the results with conventional methods for survival analysis. We analysed the risk of prostate cancer in 126,482 men from the comparison cohort of the Prostate Cancer Data base Sweden (PCBaSe) 3.0. During a mean follow-up of 6 years 6,036 men were diagnosed with prostate cancer and 22,393 men died. We detected heterogeneity in risk of prostate cancer with two distinct latent classes in the study population. The smaller class included 9% of the study population in which men had a higher risk of prostate cancer and the risk was stronger associated with class membership than any of the covariates included in the study. Moreover, we found no association between T2DM and risk of prostate cancer after removal of the effect of informative censoring due to competing risks. The recently developed latent class for competing risks method could be used to provide new insights in precision medicine with the target to classify individuals regarding different susceptibility to a particular disease, reaction to a risk factor or response to treatment. This article is protected by copyright. All rights reserved. © 2018 UICC.

Laser-Induced Fluorescence Detection in High-Throughput Screening of Heterogeneous Catalysts and Single Cells Analysis

Energy Technology Data Exchange (ETDEWEB)

Su, Hui [Iowa State Univ., Ames, IA (United States)

2001-01-01

Laser-induced fluorescence detection is one of the most sensitive detection techniques and it has found enormous applications in various areas. The purpose of this research was to develop detection approaches based on laser-induced fluorescence detection in two different areas, heterogeneous catalysts screening and single cell study. First, the author introduced laser-induced imaging (LIFI) as a high-throughput screening technique for heterogeneous catalysts to explore the use of this high-throughput screening technique in discovery and study of various heterogeneous catalyst systems. This scheme is based on the fact that the creation or the destruction of chemical bonds alters the fluorescence properties of suitably designed molecules. By irradiating the region immediately above the catalytic surface with a laser, the fluorescence intensity of a selected product or reactant can be imaged by a charge-coupled device (CCD) camera to follow the catalytic activity as a function of time and space. By screening the catalytic activity of vanadium pentoxide catalysts in oxidation of naphthalene, they demonstrated LIFI has good detection performance and the spatial and temporal resolution needed for high-throughput screening of heterogeneous catalysts. The sample packing density can reach up to 250 x 250 subunits/cm² for 40-μm wells. This experimental set-up also can screen solid catalysts via near infrared thermography detection. In the second part of this dissertation, the author used laser-induced native fluorescence coupled with capillary electrophoresis (LINF-CE) and microscope imaging to study the single cell degranulation. On the basis of good temporal correlation with events observed through an optical microscope, they have identified individual peaks in the fluorescence electropherograms as serotonin released from the granular core on contact with the surrounding fluid.

Clinical and pathological heterogeneity of cervical intraepithelial neoplasia grade 3.

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Hannah P Yang

Full Text Available Cervical intraepithelial neoplasia grade 3 (CIN3, the immediate cervical cancer precursor, is a target of cervical cancer prevention. However, less than half of CIN3s will progress to cancer. Routine treatment of all CIN3s and the majority of CIN2s may lead to overtreatment of many lesions that would not progress. To improve our understanding of CIN3 natural history, we performed a detailed characterization of CIN3 heterogeneity in a large referral population in the US.We examined 309 CIN3 cases in the SUCCEED, a large population-based study of women with abnormal cervical cancer screening results. Histology information for 12 individual loop electrosurgical excision procedure (LEEP segments was evaluated for each woman. We performed case-case comparisons of CIN3s to analyze determinants of heterogeneity and screening test performance.CIN3 cases varied substantially by size (1-10 LEEP segments and by presentation with concomitant CIN2 and CIN1. All grades of CINs were equally distributed over the cervical surface. In half of the women, CIN3 lesions were found as multiple distinct lesions on the cervix. Women with large and solitary CIN3 lesions were more likely to be older, have longer sexual activity span, and have fewer multiple high risk HPV infections. Screening frequency, but not HPV16 positivity, was an important predictor of CIN3 size. Large CIN3 lesions were also characterized by high-grade clinical test results.We demonstrate substantial heterogeneity in clinical and pathological presentation of CIN3 in a US population. Time since sexual debut and participation in screening were predictors of CIN3 size. We did not observe a preferential site of CIN3 on the cervical surface that could serve as a target for cervical biopsy. Cervical cancer screening procedures were more likely to detect larger CIN3s, suggesting that CIN3s detected by multiple independent diagnostic tests may represent cases with increased risk of invasion.

in Heterogeneous Media

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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.

Heterogeneous gas core reactor

International Nuclear Information System (INIS)

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

Catalysts and conditions for the highly efficient, selective and stable heterogeneous oligomerisation of ethylene

CSIR Research Space (South Africa)

Heveling, J

1998-10-11

Full Text Available The oligomerisation of ethylene into products in the C-4-C-20 range over heterogeneous nickel catalysts in a fixed-bed reactor at low temperature and high pressure (LT-HP) is reported. The catalysts were obtained by Ni (II) exchange or impregnation...

Numerical Simulation of Hydraulic Fracturing in Low-/High-Permeability, Quasi-Brittle and Heterogeneous Rocks

Science.gov (United States)

Pakzad, R.; Wang, S. Y.; Sloan, S. W.

2018-04-01

In this study, an elastic-brittle-damage constitutive model was incorporated into the coupled fluid/solid analysis of ABAQUS to iteratively calculate the equilibrium effective stress of Biot's theory of consolidation. The Young's modulus, strength and permeability parameter of the material were randomly assigned to the representative volume elements of finite element models following the Weibull distribution function. The hydraulic conductivity of elements was associated with their hydrostatic effective stress and damage level. The steady-state permeability test results for sandstone specimens under different triaxial loading conditions were reproduced by employing the same set of material parameters in coupled transient flow/stress analyses of plane-strain models, thereby indicating the reliability of the numerical model. The influence of heterogeneity on the failure response and the absolute permeability was investigated, and the post-peak permeability was found to decrease with the heterogeneity level in the coupled analysis with transient flow. The proposed model was applied to the plane-strain simulation of the fluid pressurization of a cavity within a large-scale block under different conditions. Regardless of the heterogeneity level, the hydraulically driven fractures propagated perpendicular to the minimum principal far-field stress direction for high-permeability models under anisotropic far-field stress conditions. Scattered damage elements appeared in the models with higher degrees of heterogeneity. The partially saturated areas around propagating fractures were simulated by relating the saturation degree to the negative pore pressure in low-permeability blocks under high pressure. By replicating previously reported trends in the fracture initiation and breakdown pressure for different pressurization rates and hydraulic conductivities, the results showed that the proposed model for hydraulic fracture problems is reliable for a wide range of

Pricing strategies under heterogeneous service requirements

NARCIS (Netherlands)

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

Intratumor and Intertumor Heterogeneity in Melanoma

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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.

Effect of temperature and density fluctuations on the spatially heterogeneous dynamics of glass-forming Van der Waals liquids under high pressure.

Science.gov (United States)

Koperwas, K; Grzybowski, A; Grzybowska, K; Wojnarowska, Z; Sokolov, A P; Paluch, M

2013-09-20

In this Letter, we show how temperature and density fluctuations affect the spatially heterogeneous dynamics at ambient and elevated pressures. By using high-pressure experimental data for van der Waals liquids, we examine contributions of the temperature and density fluctuations to the dynamics heterogeneity. We show that the dynamic heterogeneity decreases significantly with increasing pressure at a constant structural relaxation time (isochronal condition), while the broadening of the relaxation spectrum remains constant. This observation questions the relationship between spectral broadening and dynamic heterogeneity.

Population heterogeneity in the surface expression of Ulex europaeus I-lectin (UEA I)-binding sites in cultured malignant and transformed cells

Energy Technology Data Exchange (ETDEWEB)

Virtanen, I.; Lehtonen, E.; Naervaenen, O.; Leivo, I.; Lehto, V.P.

1985-11-01

We studied the binding of fluorochrome-coupled Ulex europaeus I-lectin (UEA-I) to cultured malignant cells: all human malignant and transformed cells and also mouse teratocarcinoma cells examined gave a homogeneous cell membrane-type of surface staining only in some of the cells. Such a population heterogeneity appeared to be independent of the cell cycle. Instead, other lectin conjugates used bound homogeneously to all cell. In permeabilized cells, a juxtanuclear reticular staining of the Golgi apparatus was seen in the UEA-I-positive cells. No staining of the pericellular matrix components, produced by malignant cells grown in serum-free culture medium, could be obtained with TRITC-UEA-I. UEA-I-lectin recognized most polypeptides from A8387 fibrosarcoma cells and HeLa cells, metabolically labelled with (/sup 3/H)fucose. Furthermore, surface labelling of these cells with the neuraminidase-galactose oxidase/sodium borohydride method disclosed that both UEA-I and Ricinus communis agglutinin I revealed the same major surface glycoproteins. Results with metabolically labelled cells showed, in addition, that UEA-I-lectin did not bind to secreted glycoproteins produced by A8387 cells and recognized by other lectins. The results indicate that transformed and malignant cells show a distinct population heterogeneity in their expression of some cell surface-associated fucosyl glycoconjugates. The results also suggest that malignant cells can glycosylate their membrane and secreted glycoproteins in a different manner.

How heterogeneous susceptibility and recovery rates affect the spread of epidemics on networks

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Wei Gou

2017-08-01

Full Text Available In this paper, an extended heterogeneous SIR model is proposed, which generalizes the heterogeneous mean-field theory. Different from the traditional heterogeneous mean-field model only taking into account the heterogeneity of degree, our model considers not only the heterogeneity of degree but also the heterogeneity of susceptibility and recovery rates. Then, we analytically study the basic reproductive number and the final epidemic size. Combining with numerical simulations, it is found that the basic reproductive number depends on the mean of distributions of susceptibility and disease course when both of them are independent. If the mean of these two distributions is identical, increasing the variance of susceptibility may block the spread of epidemics, while the corresponding increase in the variance of disease course has little effect on the final epidemic size. It is also shown that positive correlations between individual susceptibility, course of disease and the square of degree make the population more vulnerable to epidemic and avail to the epidemic prevalence, whereas the negative correlations make the population less vulnerable and impede the epidemic prevalence. Keywords: Networks, Heterogeneity, Susceptibility, Recovery rates, Correlation, The basic reproductive number, The final epidemic size

High population increase rates.

Science.gov (United States)

1991-09-01

In addition to its economic and ethnic difficulties, the USSR faces several pressing demographic problems, including high population increase rates in several of its constituent republics. It has now become clear that although the country's rigid centralized planning succeeded in covering the basic needs of people, it did not lead to welfare growth. Since the 1970s, the Soviet economy has remained sluggish, which as led to increase in the death and birth rates. Furthermore, the ideology that held that demography could be entirely controlled by the country's political and economic system is contradicted by current Soviet reality, which shows that religion and ethnicity also play a significant role in demographic dynamics. Currently, Soviet republics fall under 2 categories--areas with high or low natural population increase rates. Republics with low rates consist of Christian populations (Armenia, Moldavia, Georgia, Byelorussia, Russia, Lithuania, Estonia, Latvia, Ukraine), while republics with high rates are Muslim (Tadzhikistan, Uzbekistan, Turkmenistan, Kirgizia, Azerbaijan Kazakhstan). The later group has natural increase rates as high as 3.3%. Although the USSR as a whole is not considered a developing country, the later group of republics fit the description of the UNFPA's priority list. Another serious demographic issue facing the USSR is its extremely high rate of abortion. This is especially true in the republics of low birth rates, where up to 60% of all pregnancies are terminated by induced abortions. Up to 1/5 of the USSR's annual health care budget is spent on clinical abortions -- money which could be better spent on the production of contraceptives. Along with the recent political and economic changes, the USSR is now eager to deal with its demographic problems.

Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms.

Science.gov (United States)

Kravchenko, Julia; Akushevich, Igor; Seewaldt, Victoria L; Abernethy, Amy P; Lyerly, H Kim

2011-07-01

The observed bimodal patterns of breast cancer incidence in the U.S. suggested that breast cancer may be viewed as more than one biological entity. We studied the factors potentially contributing to this phenomenon, specifically focusing on how disease heterogeneity could be linked to breast carcinogenesis mechanisms. Using empirical analyses and population-based biologically motivated modeling, age-specific patterns of incidence of ductal and lobular breast carcinomas from the SEER registry (1990-2003) were analyzed for heterogeneity and characteristics of carcinogenesis, stratified by race, stage, grade, and estrogen (ER)/progesterone (PR) receptor status. The heterogeneity of breast carcinoma age patterns decreased after stratification by grade, especially for grade I and III tumors. Stratification by ER/PR status further reduced the heterogeneity, especially for ER(+)/PR(-) and ER(-)/(-) tumors; however, the residual heterogeneity was still observed. The number of rate-limiting events of carcinogenesis and the latency of ductal and lobular carcinomas differed, decreasing from grade I to III, with poorly differentiated tumors associated with the least number of carcinogenesis stages and the shortest latency. Tumor grades play important role in bimodal incidence of breast carcinoma and have distinct mechanisms of carcinogenesis. Race and cancer subtype could play modifying role. ER/PR status contributes to the observed heterogeneity, but is subdominant to tumor grade. Further studies on sources of "remaining" heterogeneity of population with breast cancer (such as genetic/epigenetic characteristics) are necessary. The results of this study could suggest stratification rather than unification of breast cancer prevention strategies, risk assessment, and treatment.

Green heterogeneous wireless networks

CERN Document Server

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...

Determining the drivers of population structure in a highly urbanized landscape to inform conservation planning.

Science.gov (United States)

Thomassen, Henri A; Harrigan, Ryan J; Semple Delaney, Kathleen; Riley, Seth P D; Serieys, Laurel E K; Pease, Katherine; Wayne, Robert K; Smith, Thomas B

2018-02-01

Understanding the environmental contributors to population structure is of paramount importance for conservation in urbanized environments. We used spatially explicit models to determine genetic population structure under current and future environmental conditions across a highly fragmented, human-dominated environment in Southern California to assess the effects of natural ecological variation and urbanization. We focused on 7 common species with diverse habitat requirements, home-range sizes, and dispersal abilities. We quantified the relative roles of potential barriers, including natural environmental characteristics and an anthropogenic barrier created by a major highway, in shaping genetic variation. The ability to predict genetic variation in our models differed among species: 11-81% of intraspecific genetic variation was explained by environmental variables. Although an anthropogenically induced barrier (a major highway) severely restricted gene flow and movement at broad scales for some species, genetic variation seemed to be primarily driven by natural environmental heterogeneity at a local level. Our results show how assessing environmentally associated variation for multiple species under current and future climate conditions can help identify priority regions for maximizing population persistence under environmental change in urbanized regions. © 2017 Society for Conservation Biology.

Intratumor and Intertumor Heterogeneity in Melanoma.

Science.gov (United States)

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.

Heterogeneous Monolithic Integration of Single-Crystal Organic Materials.

Science.gov (United States)

Park, Kyung Sun; Baek, Jangmi; Park, Yoonkyung; Lee, Lynn; Hyon, Jinho; Koo Lee, Yong-Eun; Shrestha, Nabeen K; Kang, Youngjong; Sung, Myung Mo

2017-02-01

Manufacturing high-performance organic electronic circuits requires the effective heterogeneous integration of different nanoscale organic materials with uniform morphology and high crystallinity in a desired arrangement. In particular, the development of high-performance organic electronic and optoelectronic devices relies on high-quality single crystals that show optimal intrinsic charge-transport properties and electrical performance. Moreover, the heterogeneous integration of organic materials on a single substrate in a monolithic way is highly demanded for the production of fundamental organic electronic components as well as complex integrated circuits. Many of the various methods that have been designed to pattern multiple heterogeneous organic materials on a substrate and the heterogeneous integration of organic single crystals with their crystal growth are described here. Critical issues that have been encountered in the development of high-performance organic integrated electronics are also addressed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dynamics of Tumor Heterogeneity Derived from Clonal Karyotypic Evolution

Directory of Open Access Journals (Sweden)

Ashley M. Laughney

2015-08-01

Full Text Available Numerical chromosomal instability is a ubiquitous feature of human neoplasms. Due to experimental limitations, fundamental characteristics of karyotypic changes in cancer are poorly understood. Using an experimentally inspired stochastic model, based on the potency and chromosomal distribution of oncogenes and tumor suppressor genes, we show that cancer cells have evolved to exist within a narrow range of chromosome missegregation rates that optimizes phenotypic heterogeneity and clonal survival. Departure from this range reduces clonal fitness and limits subclonal diversity. Mapping of the aneuploid fitness landscape reveals a highly favorable, commonly observed, near-triploid state onto which evolving diploid- and tetraploid-derived populations spontaneously converge, albeit at a much lower fitness cost for the latter. Finally, by analyzing 1,368 chromosomal translocation events in five human cancers, we find that karyotypic evolution also shapes chromosomal translocation patterns by selecting for more oncogenic derivative chromosomes. Thus, chromosomal instability can generate the heterogeneity required for Darwinian tumor evolution.

Host heterogeneity influences the impact of a non-native disease invasion on populations of a foundation tree species

Science.gov (United States)

Jules, Erik S.; Carroll, Allyson L.; Garcia, Andrea M.; Steenbock, Christopher M.; Kauffman, Matthew J.

2014-01-01

 P. lateralis causes profound impacts to population structure and the invasion outcome will be governed by the heterogeneity found in host size and location. Models of disease invasion will require an understanding of how heterogeneity influences spread dynamics to adequately predict the outcome for host populations.

Heterogeneous Single-Atom Catalyst for Visible-Light-Driven High-Turnover CO2 Reduction: The Role of Electron Transfer.

Science.gov (United States)

Gao, Chao; Chen, Shuangming; Wang, Ying; Wang, Jiawen; Zheng, Xusheng; Zhu, Junfa; Song, Li; Zhang, Wenkai; Xiong, Yujie

2018-03-01

Visible-light-driven conversion of CO 2 into chemical fuels is an intriguing approach to address the energy and environmental challenges. In principle, light harvesting and catalytic reactions can be both optimized by combining the merits of homogeneous and heterogeneous photocatalysts; however, the efficiency of charge transfer between light absorbers and catalytic sites is often too low to limit the overall photocatalytic performance. In this communication, it is reported that the single-atom Co sites coordinated on the partially oxidized graphene nanosheets can serve as a highly active and durable heterogeneous catalyst for CO 2 conversion, wherein the graphene bridges homogeneous light absorbers with single-atom catalytic sites for the efficient transfer of photoexcited electrons. As a result, the turnover number for CO production reaches a high value of 678 with an unprecedented turnover frequency of 3.77 min -1 , superior to those obtained with the state-of-the-art heterogeneous photocatalysts. This work provides fresh insights into the design of catalytic sites toward photocatalytic CO 2 conversion from the angle of single-atom catalysis and highlights the role of charge kinetics in bridging the gap between heterogeneous and homogeneous photocatalysts. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Association of IRS1, CAPN10, and PPARG gene polymorphisms with type 2 diabetes mellitus in the high-risk population of Hyderabad, India.

Science.gov (United States)

Kommoju, Uma Jyothi; Maruda, Jayaraj; Kadarkarai Samy, Subburaj; Irgam, Kumuda; Kotla, Jaya Prasad; Reddy, Battini Mohan

2014-11-01

We attempted to validate earlier findings on the nature of the association of the IRS1, CAPN10, and PPARG genes with type 2 diabetes mellitus (T2DM) in the high-risk population of Hyderabad, India. A sample of 1379 subjects (758 T2DM patients, 621 controls) was genotyped for single nucleotide polymorphisms (SNPs) of the IRS1 (rs1801278), CAPN10 (rs3792267, rs5030952), and PPARG (rs1801282) genes. The allele and genotype frequencies of IRS1 (rs1801278) and CAPN10 (rs3792267) SNPs differed significantly between the patient and control groups. Logistic regression analysis suggested a significant association of these two SNPs (P ≤ 0.007) with T2DM and the strength of association did not alter when adjusted for age, gender, body mass index, and the waist : hip ratio as covariates. The same two SNPs showed significant association in multivariate logistic regression analyses, even after Bonferroni correction for multiple testing, suggesting an independent nature of the role of these genes in the manifestation of T2DM in our population. We replicated the significant association of rs1801278 and rs3792267 SNPs of the IRS1 and CAPN10 genes with T2DM in the population of Hyderabad. Despite the known biological significance of the PPARG gene and a sufficient statistical power of the present study, we could not replicate the association of PPARG with T2DM in our high-risk population. Given the vast ethnic, geographic, and genetic heterogeneity of the Indian population, many more studies are needed covering the ethnic and geographic heterogeneity of India to enable identification of an Indian-specific profile of genes associated with T2DM. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

The evolution of strong reciprocity: cooperation in heterogeneous populations.

Science.gov (United States)

Bowles, Samuel; Gintis, Herbert

2004-02-01

How do human groups maintain a high level of cooperation despite a low level of genetic relatedness among group members? We suggest that many humans have a predisposition to punish those who violate group-beneficial norms, even when this imposes a fitness cost on the punisher. Such altruistic punishment is widely observed to sustain high levels of cooperation in behavioral experiments and in natural settings. We offer a model of cooperation and punishment that we call STRONG RECIPROCITY: where members of a group benefit from mutual adherence to a social norm, strong reciprocators obey the norm and punish its violators, even though as a result they receive lower payoffs than other group members, such as selfish agents who violate the norm and do not punish, and pure cooperators who adhere to the norm but free-ride by never punishing. Our agent-based simulations show that, under assumptions approximating likely human environments over the 100000 years prior to the domestication of animals and plants, the proliferation of strong reciprocators when initially rare is highly likely, and that substantial frequencies of all three behavioral types can be sustained in a population. As a result, high levels of cooperation are sustained. Our results do not require that group members be related or that group extinctions occur.

Recharge heterogeneity and high intensity rainfall events increase contamination risk for Mediterranean groundwater resources

Science.gov (United States)

Hartmann, Andreas; Jasechko, Scott; Gleeson, Tom; Wada, Yoshihide; Andreo, Bartolomé; Barberá, Juan Antonio; Brielmann, Heike; Charlier, Jean-Baptiste; Darling, George; Filippini, Maria; Garvelmann, Jakob; Goldscheider, Nico; Kralik, Martin; Kunstmann, Harald; Ladouche, Bernard; Lange, Jens; Mudarra, Matías; Francisco Martín, José; Rimmer, Alon; Sanchez, Damián; Stumpp, Christine; Wagener, Thorsten

2017-04-01

Karst develops through the dissolution of carbonate rock and results in pronounced spatiotemporal heterogeneity of hydrological processes. Karst groundwater in Europe is a major source of fresh water contributing up to half of the total drinking water supply in some countries like Austria or Slovenia. Previous work showed that karstic recharge processes enhance and alter the sensitivity of recharge to climate variability. The enhanced preferential flow from the surface to the aquifer may be followed by enhanced risk of groundwater contamination. In this study we assess the contamination risk of karst aquifers over Europe and the Mediterranean using simulated transit time distributions. Using a new type of semi-distributed model that considers the spatial heterogeneity of karst hydraulic properties, we were able to simulate karstic groundwater recharge including its heterogeneous spatiotemporal dynamics. The model is driven by gridded daily climate data from the Global Land Data Assimilation System (GLDAS). Transit time distributions are calculated using virtual tracer experiments. We evaluated our simulations by independent information on transit times derived from observed time series of water isotopes of >70 karst springs over Europe. The simulations indicate that, compared to humid, mountain and desert regions, the Mediterranean region shows a stronger risk of contamination in Europe because preferential flow processes are most pronounced given thin soil layers and the seasonal abundance of high intensity rainfall events in autumn and winter. Our modelling approach includes strong simplifications and its results cannot easily be generalized but it still highlights that the combined effects of variable climate and heterogeneous catchment properties constitute a strong risk on water quality.

[Genetic differentiation of Isaria farinosa populations in Anhui Province of East China].

Science.gov (United States)

Sun, Zhao-Hong; Luan, Feng-Gang; Zhang, Da-Min; Chen, Ming-Jun; Wang, Bin; Li, Zeng-Zhi

2011-11-01

Isaria farinosa is an important entomopathogenic fungus. By using ISSR, this paper studied the genetic heterogeneity of six I. farinosa populations at different localities of Anhui Province, East China. A total of 98.5% polymorphic loci were amplified with ten polymorphic primers, but the polymorphism at population level varied greatly, within the range of 59.6%-93.2%. The genetic differentiation index (G(st)) between the populations based on Nei's genetic heterogenesis analysis was 0.3365, and the gene flow (N(m)) was 0.4931. The genetic differentiation between the populations was lower than that within the populations, suggesting that the genetic variation of I. farinosa mainly come from the interior of the populations. The UPGMA clustering based on the genetic similarities between the isolates revealed that the Xishan population was monophylectic, while the other five populations were polyphylectic, with the Yaoluoping population being the most heterogenic and the Langyashan population being the least heterogenic. No correlations were observed between the geographic distance and the genetic distance of the populations. According to the UPGMA clustering based on the genetic distance between the populations, the six populations were classified into three groups, and this classification was accorded with the clustering based on geographic environment, suggesting the effects of environmental heterogeneity on the population heterogeneity.

Acculturation, Dietary Practices and Risk for Childhood Obesity in an Ethnically Heterogeneous Population of Latino School Children in the San Francisco Bay Area

OpenAIRE

Wojcicki, Janet M.; Schwartz, Norah; Jiménez-Cruz, Arturo; Bacardi-Gascon, Montserrat; Heyman, Melvin B.

2012-01-01

Previous studies have found increased acculturation to the US lifestyle increases risk for obesity in Latinos. However, methodologies differ, and results in children are inconsistent. Moreover, previous studies have not evaluated risk factors within the heterogeneous US population. We recruited 144 self-identified Latino school children and their mother or father in grades 4–6 in San Francisco parochial schools and South San Francisco public schools using an information letter distributed to ...

Spatial heterogeneity in liquid–liquid phase transition

International Nuclear Information System (INIS)

Duan Yun-Rui; Li Tao; Wu Wei-Kang; Li Jie; Zhou Xu-Yan; Liu Si-Da; Li Hui

2017-01-01

Molecular dynamics simulations are performed to investigate the liquid–liquid phase transition (LLPT) and the spatial heterogeneity in Al–Pb monotectic alloys. The results reveal that homogeneous liquid Al–Pb alloy undergoes an LLPT, separating into Al-rich and Pb-rich domains, which is quite different from the isocompositional liquid water with a transition between low-density liquid (LDL) and high-density liquid (HDL). With spatial heterogeneity becoming large, LLPT takes place correspondingly. The relationship between the cooling rate, relaxation temperature and percentage of Al and the spatial heterogeneity is also reported. This study may throw light on the relationship between the structure heterogeneity and LLPT, which provides novel strategies to control the microstructures in the fabrication of the material with high performance. (paper)

Synergistic rate boosting of collagen fibrillogenesis in heterogeneous mixtures of crowding agents.

Science.gov (United States)

Dewavrin, Jean-Yves; Abdurrahiem, Muhammed; Blocki, Anna; Musib, Mrinal; Piazza, Francesco; Raghunath, Michael

2015-03-26

The competition for access to space that arises between macromolecules is the basis of the macromolecular crowding phenomenon, known to modulate biochemical reactions in subtle ways. Crowding is a highly conserved physiological condition in and around cells in metazoans, and originates from a mixture of heterogeneous biomolecules. Here, using collagen fibrillogenesis as an experimental test platform and ideas from the theory of nonideal solutions, we show that an entropy-based synergy is created by a mixture of two different populations of artificial crowders, providing small crowders with extra volume occupancy when in the vicinity of bigger crowders. We present the physiological mechanism by which synergistic effects maximize volume exclusion with the minimum amount of heterogeneous crowders, demonstrating how the evolutionarily optimized crowded conditions found in vivo can be reproduced effectively in vitro.

Trans-ethnic fine-mapping of lipid loci identifies population-specific signals and allelic heterogeneity that increases the trait variance explained.

Directory of Open Access Journals (Sweden)

Ying Wu

2013-03-01

Full Text Available Genome-wide association studies (GWAS have identified ~100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG, high-density lipoprotein cholesterol (HDL-C, and low-density lipoprotein cholesterol (LDL-C, respectively, in individuals of African American (n = 6,832, East Asian (n = 9,449, and European (n = 10,829 ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at P<1 × 10(-4 in at least one ancestry group. Sequential conditional analyses revealed that ten, nine, and four loci in African Americans, Europeans, and East Asians, respectively, exhibited two or more signals. At these loci, accounting for all signals led to a 1.3- to 1.8-fold increase in the explained phenotypic variance compared to the strongest signals. Distinct signals across ancestry groups were identified at PCSK9 and APOA5. Trans-ethnic analyses narrowed the signals to smaller sets of variants at GCKR, PPP1R3B, ABO, LCAT, and ABCA1. Of 27 variants reported previously to have functional effects, 74% exhibited the strongest association at the respective signal. In conclusion, trans-ethnic high-density genotyping and analysis confirm the presence of allelic heterogeneity, allow the identification of population-specific variants, and limit the number of candidate SNPs for functional studies.

Population genetic structure in natural and reintroduced beaver (Castor fiber populations in Central Europe

Directory of Open Access Journals (Sweden)

Kautenburger, R.

2008-12-01

Full Text Available Castor fiber Linnaeus, 1758 is the only indigenous species of the genus Castor in Europe and Asia. Due to extensive hunting until the beginning of the 20th century, the distribution of the formerly widespread Eurasian beaver was dramatically reduced. Only a few populations remained and these were in isolated locations, such as the region of the German Elbe River. The loss of genetic diversity in small or captive populations throughgenetic drift and inbreeding is a severe conservation problem. However, the reintroduction of beaver populations from several regions in Europe has shown high viability and populations today are growing fast. In the present study we analysed the population genetic structure of a natural and two reintroduced beaver populations in Germany and Austria. Furthermore, we studied the genetic differentiation between two beaver species, C. fiber and the American beaver (C. canadensis, using RAPD (Random Amplified Polymorphic DNA as a genetic marker. The reintroduced beaver populations of different origins and the autochthonous population of the Elbe River showed a similar low genetic heterogeneity. There was an overall high genetic similarity in the species C. fiber, and no evidence was found for a clear subspecific structure in the populations studied.

Skill Heterogeneity in Startups and its Development over Time

DEFF Research Database (Denmark)

Kaiser, Ulrich; Müller, Bettina

2015-01-01

We study how startup teams are assembled in terms of team member human capital characteristics. To this end, we derive a statistically motivated benchmark for new venture team heterogeneity in terms of observed team member characteristics to generate stylized facts about team member diversity...... at startup and how it evolves as the new venture matures. We use the population of Danish startups that were established in 1998 and track them until 2001. Main findings are that teams are relatively more homogeneous at startup compared to our benchmark, indicating that difficulties associated with workforce...... heterogeneity (like affective conflict or coordination cost) as well as “homophily” (people’s inclination to bound with others with similar characteristics) may overweigh the benefits of heterogeneity. While workforce heterogeneity does increase over time, the increase is smaller compared to our benchmark...

Dynamic heterogeneity and life history variability in the kittiwake

DEFF Research Database (Denmark)

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

2010-01-01

1. Understanding the evolution of life histories requires an assessment of the process that generates variation in life histories. Within-population heterogeneity of life histories can be dynamically generated by stochastic variation of reproduction and survival or be generated by individual...... differences that are fixed at birth. 2. We show for the kittiwake that dynamic heterogeneity is a sufficient explanation of observed variation of life histories. 3. The total heterogeneity in life histories has a small contribution from reproductive stage dynamics and a large contribution from survival...... differences. We quantify the diversity in life histories by metrics computed from the generating stochastic process. 4. We show how dynamic heterogeneity can be used as a null model and also how it can lead to positive associations between reproduction and survival across the life span. 5. We believe our...

High resolution of heterogeneity among human neutrophil granules: physical, biochemical, and ultrastructural properties of isolated fractions.

Science.gov (United States)

Rice, W G; Kinkade, J M; Parmley, R T

1986-08-01

Previous studies on the fractionation of human neutrophil granules have identified two major populations: myeloperoxidase (MPO)-containing azurophil, or primary, granules and MPO-deficient specific, or secondary, granules. Peripheral blood neutrophils from individual donors were lysed in sucrose-free media by either hypotonic shock or nitrogen cavitation. Using a novel two-gradient Percoll density centrifugation system, the granule-rich postnuclear supernatant was rapidly (ten minutes) and reproducibly resolved into 13 granule fractions (L1 through L8 and H1 through H5). Granule flotation and recentrifugation experiments on both continuous, self-generated and multiple-step gradients using individual and mixed isolated fractions demonstrated that the banding patterns were isopycnic and nonartifactual. Isolated granules were intact based on the findings that biochemical latency of several granule enzymes was greater than 95%, and thin-sectioned electron micrographs demonstrated intact granule profiles. Biochemical analyses of the granule marker proteins MPO, beta-glucuronidase, lysozyme, and lactoferrin indicated that a number of the fractions were related to the major azurophil and specific granule populations. Lactoferrin was found in ten of 13 fractions (L1 through L8, H1 to H2), whereas MPO was found in every fraction. Consistent with these biochemical data, all fractions exhibited varying degrees of heterogeneity based on ultrastructural morphology and cytochemistry, including diaminobenzidine (DAB) reactivity for peroxidase and periodate-thiocarbohydrazide-silver proteinate (PA-TCH-SP) staining for complex glycoconjugates. A variable but significant percentage (23% to 70%) of the granules in fractions L1 through L8 and H1 and H2 showed DAB reactivity, while about 90% of the granules in fractions H3 through H5 were peroxidase positive. These results demonstrated that DAB-reactive granules spanned the entire range of granule size and density. Ultrastructural PA

Population-averaged macaque brain atlas with high-resolution ex vivo DTI integrated into in vivo space.

Science.gov (United States)

Feng, Lei; Jeon, Tina; Yu, Qiaowen; Ouyang, Minhui; Peng, Qinmu; Mishra, Virendra; Pletikos, Mihovil; Sestan, Nenad; Miller, Michael I; Mori, Susumu; Hsiao, Steven; Liu, Shuwei; Huang, Hao

2017-12-01

Animal models of the rhesus macaque (Macaca mulatta), the most widely used nonhuman primate, have been irreplaceable in neurobiological studies. However, a population-averaged macaque brain diffusion tensor imaging (DTI) atlas, including comprehensive gray and white matter labeling as well as bony and facial landmarks guiding invasive experimental procedures, is not available. The macaque white matter tract pathways and microstructures have been rarely recorded. Here, we established a population-averaged macaque brain atlas with high-resolution ex vivo DTI integrated into in vivo space incorporating bony and facial landmarks, and delineated microstructures and three-dimensional pathways of major white matter tracts in vivo MRI/DTI and ex vivo (postmortem) DTI of ten rhesus macaque brains were acquired. Single-subject macaque brain DTI template was obtained by transforming the postmortem high-resolution DTI data into in vivo space. Ex vivo DTI of ten macaque brains was then averaged in the in vivo single-subject template space to generate population-averaged macaque brain DTI atlas. The white matter tracts were traced with DTI-based tractography. One hundred and eighteen neural structures including all cortical gyri, white matter tracts and subcortical nuclei, were labeled manually on population-averaged DTI-derived maps. The in vivo microstructural metrics of fractional anisotropy, axial, radial and mean diffusivity of the traced white matter tracts were measured. Population-averaged digital atlas integrated into in vivo space can be used to label the experimental macaque brain automatically. Bony and facial landmarks will be available for guiding invasive procedures. The DTI metric measurements offer unique insights into heterogeneous microstructural profiles of different white matter tracts.

Dynamic heterogeneity of DNA methylation and hydroxymethylation in embryonic stem cell populations captured by single-cell 3D high-content analysis

Energy Technology Data Exchange (ETDEWEB)

Tajbakhsh, Jian, E-mail: tajbakhshj@cshs.org [Chromatin Biology Laboratory, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Translational Cytomics Group, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Stefanovski, Darko [Translational Cytomics Group, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19348 (United States); Tang, George [Chromatin Biology Laboratory, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Translational Cytomics Group, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Wawrowsky, Kolja [Translational Cytomics Group, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048 (United States); Liu, Naiyou; Fair, Jeffrey H. [Department of Surgery and UF Health Comprehensive Transplant Center, University of Florida College of Medicine, Gainesville, FL 32608 (United States)

2015-03-15

Cell-surface markers and transcription factors are being used in the assessment of stem cell fate and therapeutic safety, but display significant variability in stem cell cultures. We assessed nuclear patterns of 5-hydroxymethylcytosine (5hmC, associated with pluripotency), a second important epigenetic mark, and its combination with 5-methylcytosine (5mC, associated with differentiation), also in comparison to more established markers of pluripotency (Oct-4) and endodermal differentiation (FoxA2, Sox17) in mouse embryonic stem cells (mESC) over a 10-day differentiation course in vitro: by means of confocal and super-resolution imaging together with 3D high-content analysis, an essential tool in single-cell screening. In summary: 1) We did not measure any significant correlation of putative markers with global 5mC or 5hmC. 2) While average Oct-4 levels stagnated on a cell-population base (0.015 lnIU/day), Sox17 and FoxA2 increased 22-fold and 3-fold faster, respectively (Sox17: 0.343 lnIU/day; FoxA2: 0.046 lnIU/day). In comparison, global DNA methylation levels increased 4-fold faster (0.068 lnIU/day), and global hydroxymethylation declined at 0.046 lnIU/day, both with a better explanation of the temporal profile. 3) This progression was concomitant with the occurrence of distinct nuclear codistribution patterns that represented a heterogeneous spectrum of states in differentiation; converging to three major coexisting 5mC/5hmC phenotypes by day 10: 5hmC{sup +}/5mC{sup −}, 5hmC{sup +}/5mC{sup +}, and 5hmC{sup −}/5mC{sup +} cells. 4) Using optical nanoscopy we could delineate the respective topologies of 5mC/5hmC colocalization in subregions of nuclear DNA: in the majority of 5hmC{sup +}/5mC{sup +} cells 5hmC and 5mC predominantly occupied mutually exclusive territories resembling euchromatic and heterochromatic regions, respectively. Simultaneously, in a smaller subset of cells we observed a tighter colocalization of the two cytosine variants, presumably

Biofouling patterns in spacer filled channels: High resolution imaging for characterization of heterogeneous biofilms

KAUST Repository

Staal, Marc

2017-08-15

Biofilms develop in heterogeneous patterns at a µm scale up to a cm scale, and patterns become more pronounced when biofilms develop under complex hydrodynamic flow regimes. Spatially heterogeneous biofilms are especially known in spiral wound reverse osmosis (RO) and nanofiltration (NF) membrane filtration systems used for desalination and wastewater reuse to produce high quality (drinking) water. These spiral wound membrane modules contain mesh-like spacer structures used to create an intermembrane space and improve water mixing. Spacers create inhomogeneous water flow patterns resulting in zones favouring biofilm growth, possibly leading to biofouling thus hampering water production. Oxygen sensing planar optodes were used to visualize variations in oxygen decrease rates (ODR). ODR is an indication of biofilm activity. In this study, ODR images of multiple repetitive spacer areas in a membrane fouling simulator were averaged to produce high resolution, low noise ODR images. Averaging 40 individual spacer areas improved the ODR distribution image significantly and allowed comparison of biofilm patterning over a spacer structure at different positions in an RO filter. This method clearly showed that most active biofilm accumulated on and in direct vicinity of the spacer. The averaging method was also used to calculate the deviation of ODR patterning from individual spacer areas to the average ODR pattern, proposing a new approach to determine biofilm spatial heterogeneity. This study showed that the averaging method can be applied and that the improved, averaged ODR images can be used as an analytical, in-situ, non-destructive method to assess and quantify the effect of membrane installation operational parameters or different spacer geometries on biofilm development in spiral wound membrane systems characterized by complex hydrodynamic conditions.

Sexual harassment in heterogeneous landscapes can mediate population regulation in a grasshopper

NARCIS (Netherlands)

Bauer, S.; Samietz, J.; Berger, U.

2005-01-01

Population regulation has been related to differences in the quality among habitats, which mediate differences in vital rates such that in poor habitats reproductive rates are lower than those in high-quality habitats. The spatial distribution of animals in such habitats depends on their preferences

K-means cluster analysis of rehabilitation service users in the Home Health Care System of Ontario: examining the heterogeneity of a complex geriatric population.

Science.gov (United States)

Armstrong, Joshua J; Zhu, Mu; Hirdes, John P; Stolee, Paul

2012-12-01

To examine the heterogeneity of home care clients who use rehabilitation services by using the K-means algorithm to identify previously unknown patterns of clinical characteristics. Observational study of secondary data. Home care system. Assessment information was collected on 150,253 home care clients using the provincially mandated Resident Assessment Instrument-Home Care (RAI-HC) data system. Not applicable. Assessment information from every long-stay (>60 d) home care client that entered the home care system between 2005 and 2008 and used rehabilitation services within 3 months of their initial assessment was analyzed. The K-means clustering algorithm was applied using 37 variables from the RAI-HC assessment. The K-means cluster analysis resulted in the identification of 7 relatively homogeneous subgroups that differed on characteristics such as age, sex, cognition, and functional impairment. Client profiles were created to illustrate the diversity of this geriatric population. The K-means algorithm provided a useful way to segment a heterogeneous rehabilitation client population into more homogeneous subgroups. This analysis provides an enhanced understanding of client characteristics and needs, and could enable more appropriate targeting of rehabilitation services for home care clients. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Explaining the heterogeneous scrapie surveillance figures across Europe: a meta-regression approach

Directory of Open Access Journals (Sweden)

Ru Giuseppe

2007-06-01

Full Text Available Abstract Background Two annual surveys, the abattoir and the fallen stock, monitor the presence of scrapie across Europe. A simple comparison between the prevalence estimates in different countries reveals that, in 2003, the abattoir survey appears to detect more scrapie in some countries. This is contrary to evidence suggesting the greater ability of the fallen stock survey to detect the disease. We applied meta-analysis techniques to study this apparent heterogeneity in the behaviour of the surveys across Europe. Furthermore, we conducted a meta-regression analysis to assess the effect of country-specific characteristics on the variability. We have chosen the odds ratios between the two surveys to inform the underlying relationship between them and to allow comparisons between the countries under the meta-regression framework. Baseline risks, those of the slaughtered populations across Europe, and country-specific covariates, available from the European Commission Report, were inputted in the model to explain the heterogeneity. Results Our results show the presence of significant heterogeneity in the odds ratios between countries and no reduction in the variability after adjustment for the different risks in the baseline populations. Three countries contributed the most to the overall heterogeneity: Germany, Ireland and The Netherlands. The inclusion of country-specific covariates did not, in general, reduce the variability except for one variable: the proportion of the total adult sheep population sampled as fallen stock by each country. A large residual heterogeneity remained in the model indicating the presence of substantial effect variability between countries. Conclusion The meta-analysis approach was useful to assess the level of heterogeneity in the implementation of the surveys and to explore the reasons for the variation between countries.

Sources of heterogeneity in studies of the BMI-mortality association.

Science.gov (United States)

Peter, Raphael Simon; Nagel, Gabriele

2017-06-01

To date, the amount of heterogeneity among studies of the body mass index-mortality association attributable to differences in the age distribution and length of follow-up has not been quantified. Therefore, we wanted to quantify the amount of heterogeneity attributable to age and follow-up in results of studies on the body mass index-mortality relation. We used optima of the body mass index mortality association reported for 30 populations and performed meta-regression to estimate the amount of heterogeneity attributable to sex, ethnicity, mean age at baseline, percentage smokers, and length of follow-up. Ethnicity as single factor accounted for 36% (95% CI, 11-56%) of heterogeneity. Mean age and length of follow-up had an interactive effect and together accounted for 56% (95% CI, 24-74%) of the remaining heterogeneity. Sex did not significantly contribute to the heterogeneity, after controlling for ethnicity, age, and length of follow-up. A considerable amount of heterogeneity in studies of the body mass index-mortality association is attributable to ethnicity, age, and length of follow-up. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Identification, Attribution, and Quantification of Highly Heterogeneous Methane Sources Using a Mobile Stable Isotope Analyzer

Science.gov (United States)

Crosson, E.; Rella, C.; Cunningham, K.

2012-04-01

Despite methane's importance as a potent greenhouse gas second only to carbon dioxide in the magnitude of its contribution to global warming, natural contributions to the overall methane budget are only poorly understood. A big contributor to this gap in knowledge is the highly spatially and temporally heterogeneous nature of most natural (and for that matter anthropogenic) methane sources. This high degree of heterogeneity, where the methane emission rates can vary over many orders of magnitude on a spatial scale of meters or even centimeters, and over a temporal scale of minutes or even seconds, means that traditional methods of emissions flux estimation, such as flux chambers or eddy-covariance, are difficult or impossible to apply. In this paper we present new measurement methods that are capable of detecting, attributing, and quantifying emissions from highly heterogeneous sources. These methods take full advantage of the new class of methane concentration and stable isotope analyzers that are capable of laboratory-quality analysis from a mobile field platform in real time. In this paper we present field measurements demonstrating the real-time detection of methane 'hot spots,' attribution of the methane to a source process via real-time stable isotope analysis, and quantification of the emissions flux using mobile concentration measurements of the horizontal and vertical atmospheric dispersion, combined with atmospheric transport calculations. Although these techniques are applicable to both anthropogenic and natural methane sources, in this initial work we focus primarily on landfills and fugitive emissions from natural gas distribution, as these sources are better characterized, and because they provide a more reliable and stable source of methane for quantifying the measurement uncertainty inherent in the different methods. Implications of these new technologies and techniques are explored for the quantification of natural methane sources in a variety of

Quasi-linear score for capturing heterogeneous structure in biomarkers.

Science.gov (United States)

Omae, Katsuhiro; Komori, Osamu; Eguchi, Shinto

2017-06-19

Linear scores are widely used to predict dichotomous outcomes in biomedical studies because of their learnability and understandability. Such approaches, however, cannot be used to elucidate biodiversity when there is heterogeneous structure in target population. Our study was focused on describing intrinsic heterogeneity in predictions. Because heterogeneity can be captured by a clustering method, integrating different information from different clusters should yield better predictions. Accordingly, we developed a quasi-linear score, which effectively combines the linear scores of clustered markers. We extended the linear score to the quasi-linear score by a generalized average form, the Kolmogorov-Nagumo average. We observed that two shrinkage methods worked well: ridge shrinkage for estimating the quasi-linear score, and lasso shrinkage for selecting markers within each cluster. Simulation studies and applications to real data show that the proposed method has good predictive performance compared with existing methods. Heterogeneous structure is captured by a clustering method. Quasi-linear scores combine such heterogeneity and have a better predictive ability compared with linear scores.

Systematic heterogenization for better reproducibility in animal experimentation.

Science.gov (United States)

Richter, S Helene

2017-08-31

The scientific literature is full of articles discussing poor reproducibility of findings from animal experiments as well as failures to translate results from preclinical animal studies to clinical trials in humans. Critics even go so far as to talk about a "reproducibility crisis" in the life sciences, a novel headword that increasingly finds its way into numerous high-impact journals. Viewed from a cynical perspective, Fett's law of the lab "Never replicate a successful experiment" has thus taken on a completely new meaning. So far, poor reproducibility and translational failures in animal experimentation have mostly been attributed to biased animal data, methodological pitfalls, current publication ethics and animal welfare constraints. More recently, the concept of standardization has also been identified as a potential source of these problems. By reducing within-experiment variation, rigorous standardization regimes limit the inference to the specific experimental conditions. In this way, however, individual phenotypic plasticity is largely neglected, resulting in statistically significant but possibly irrelevant findings that are not reproducible under slightly different conditions. By contrast, systematic heterogenization has been proposed as a concept to improve representativeness of study populations, contributing to improved external validity and hence improved reproducibility. While some first heterogenization studies are indeed very promising, it is still not clear how this approach can be transferred into practice in a logistically feasible and effective way. Thus, further research is needed to explore different heterogenization strategies as well as alternative routes toward better reproducibility in animal experimentation.

The Simple, Effective Synthesis of Highly Dispersed Pd/C and CoPd/C Heterogeneous Catalysts via Charge-Enhanced Dry Impregnation

Directory of Open Access Journals (Sweden)

Lawrence D’Souza

2016-05-01

Full Text Available Pd/C and CoPd/C heterogeneous catalysts have been synthesized by adopting Charge Enhanced Dry Impregnation (CEDI. The particles size distribution, their high metal surface-to-bulk ratios, and synthesis feasibility are unmatchable to any known noble metal bimetallic heterogeneous catalyst preparation techniques. Next generation Fuel Cells and Fischer-Tropsch catalytic processes economy will be benefited from the proposed methodology.

Evaluation of C-ErbB-2 Overexpression and Her-2/neu Gene Copy Number Heterogeneity in Barrett’s Adenocarcinoma

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Axel Walch

2000-01-01

Full Text Available Amplifiction of the Her-2/neu gene is accompanied by overexpression of its cell surface receptor product, c‐erbB‐2 protein. To investigate the degree of intratumoural heterogeneity we applied immunohistochemistry in primary Barrett’s adenocarcinoma (BCA (n = 6 and dysplasia adjacent to the carcinoma (n = 4. In addition, fluorescence in situ hybridisation (FISH was performed in primary BCA (n=5 and dysplastic areas (n=4. For an objective evaluation digital image analysis and laser scanning microscopy were used. Five of six BCA showed a marked intratumoural heterogeneous staining pattern ranging from areas in which the tumour cells were negative or faintly positive to tumour areas with a strong staining of the entire membrane. Among the two dysplastic areas also a heterogenous staining pattern was observed. FISH analysis revealed marked heterogeneity of intratumoural gene copy number changes in all BCA showing populations with different fractions of cells with polysomy, low level amplification and high level amplification. One dysplasia showed a minor population with Her‐2/neu signal clusters. In conclusion, we observed marked intratumoural heterogeneity of c‐erbB‐2 protein overexpression and Her‐2/neu gene copy number in the majority of the primary BCA analyzed. Digital image analysis and laser scanning microscopy were helpful in quantifying the variations in protein expression and DNA copy number in individual tumour cells. The observed heterogeneity could hamper the exact diagnostic determination of the c‐erbB‐2 status in small biopsies and possibly influence the effectiveness of a potential c‐erbB‐2 targeting therapy.

Intensive evaporation and boiling of a heterogeneous liquid droplet with an explosive disintegration in high-temperature gas area

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Piskunov Maxim V.

2016-01-01

Full Text Available The using of the high-speed (not less than 105 frames per second video recording tools (“Phantom” and the software package ("TEMA Automotive" allowed carrying out an experimental research of laws of intensive vaporization with an explosive disintegration of heterogeneous (with a single solid nontransparent inclusion liquid droplet (by the example of water in high-temperature (500-800 K gases (combustion products. Times of the processes under consideration and stages (liquid heat-up, evaporation from an external surface, bubble boiling at internal interfaces, growth of bubble sizes, explosive droplet breakup were established. Necessary conditions of an explosive vaporization of a heterogeneous droplet were found out. Mechanisms of this process and an influence of properties of liquid and inclusion material on them were determined.

Clonal Heterogeneity in the Neuronal and Glial Differentiation of Dental Pulp Stem/Progenitor Cells

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Fraser I. Young

2016-01-01

Full Text Available Cellular heterogeneity presents an important challenge to the development of cell-based therapies where there is a fundamental requirement for predictable and reproducible outcomes. Transplanted Dental Pulp Stem/Progenitor Cells (DPSCs have demonstrated early promise in experimental models of spinal cord injury and stroke, despite limited evidence of neuronal and glial-like differentiation after transplantation. Here, we report, for the first time, on the ability of single cell-derived clonal cultures of murine DPSCs to differentiate in vitro into immature neuronal-like and oligodendrocyte-like cells. Importantly, only DPSC clones with high nestin mRNA expression levels were found to successfully differentiate into Map2 and NF-positive neuronal-like cells. Neuronally differentiated DPSCs possessed a membrane capacitance comparable with primary cultured striatal neurons and small inward voltage-activated K+ but not outward Na+ currents were recorded suggesting a functionally immature phenotype. Similarly, only high nestin-expressing clones demonstrated the ability to adopt Olig1, Olig2, and MBP-positive immature oligodendrocyte-like phenotype. Together, these results demonstrate that appropriate markers may be used to provide an early indication of the suitability of a cell population for purposes where differentiation into a specific lineage may be beneficial and highlight that further understanding of heterogeneity within mixed cellular populations is required.

Interntional Migration with Heterogeneous Agents: Theory and Evidence

DEFF Research Database (Denmark)

Schröder, Philipp J.H.; Brücker, Herbert

Two puzzling facts of international migration are that only a small share of a sending country's population emigrates and that net migration rates tend to cease over time. This paper addresses these issues in a migration model with heterogeneous agents that features temporary migration...

Understanding heterogeneity of social preferences for fire prevention management

DEFF Research Database (Denmark)

Varela, Elsa; Jacobsen, Jette Bredahl; Soliño, Mario

2014-01-01

The forest area burnt annually in the European Mediterranean region has more than doubled since the 1970s. In these forests, the main preventive action consists of forest compartmentalization by fuel break networks, which entail high costs and sometimes significant negative impacts. While many...... studies look at public preferences for fire suppression, this study analyses the heterogeneity of social preferences for fire prevention. The visual characteristics of fire prevention structures are very familiar to respondents, but their management is unfamiliar, which raises specific attention in terms...... for the density of fuel breaks. These results are important for designing fire prevention policies that are efficient and acceptable by the population....

A least-effort principle based model for heterogeneous pedestrian flow considering overtaking behavior

Science.gov (United States)

Liu, Chi; Ye, Rui; Lian, Liping; Song, Weiguo; Zhang, Jun; Lo, Siuming

2018-05-01

In the context of global aging, how to design traffic facilities for a population with a different age composition is of high importance. For this purpose, we propose a model based on the least effort principle to simulate heterogeneous pedestrian flow. In the model, the pedestrian is represented by a three-disc shaped agent. We add a new parameter to realize pedestrians' preference to avoid changing their direction of movement too quickly. The model is validated with numerous experimental data on unidirectional pedestrian flow. In addition, we investigate the influence of corridor width and velocity distribution of crowds on unidirectional heterogeneous pedestrian flow. The simulation results reflect that widening corridors could increase the specific flow for the crowd composed of two kinds of pedestrians with significantly different free velocities. Moreover, compared with a unified crowd, the crowd composed of pedestrians with great mobility differences requires a wider corridor to attain the same traffic efficiency. This study could be beneficial in providing a better understanding of heterogeneous pedestrian flow, and quantified outcomes could be applied in traffic facility design.

Heterogeneous Gpu&Cpu Cluster For High Performance Computing In Cryptography

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Michał Marks

2012-01-01

Full Text Available This paper addresses issues associated with distributed computing systems andthe application of mixed GPU&CPU technology to data encryption and decryptionalgorithms. We describe a heterogenous cluster HGCC formed by twotypes of nodes: Intel processor with NVIDIA graphics processing unit and AMDprocessor with AMD graphics processing unit (formerly ATI, and a novel softwareframework that hides the heterogeneity of our cluster and provides toolsfor solving complex scientific and engineering problems. Finally, we present theresults of numerical experiments. The considered case study is concerned withparallel implementations of selected cryptanalysis algorithms. The main goal ofthe paper is to show the wide applicability of the GPU&CPU technology tolarge scale computation and data processing.

Reliability of different mark-recapture methods for population size estimation tested against reference population sizes constructed from field data.

Directory of Open Access Journals (Sweden)

Annegret Grimm

Full Text Available Reliable estimates of population size are fundamental in many ecological studies and biodiversity conservation. Selecting appropriate methods to estimate abundance is often very difficult, especially if data are scarce. Most studies concerning the reliability of different estimators used simulation data based on assumptions about capture variability that do not necessarily reflect conditions in natural populations. Here, we used data from an intensively studied closed population of the arboreal gecko Gehyra variegata to construct reference population sizes for assessing twelve different population size estimators in terms of bias, precision, accuracy, and their 95%-confidence intervals. Two of the reference populations reflect natural biological entities, whereas the other reference populations reflect artificial subsets of the population. Since individual heterogeneity was assumed, we tested modifications of the Lincoln-Petersen estimator, a set of models in programs MARK and CARE-2, and a truncated geometric distribution. Ranking of methods was similar across criteria. Models accounting for individual heterogeneity performed best in all assessment criteria. For populations from heterogeneous habitats without obvious covariates explaining individual heterogeneity, we recommend using the moment estimator or the interpolated jackknife estimator (both implemented in CAPTURE/MARK. If data for capture frequencies are substantial, we recommend the sample coverage or the estimating equation (both models implemented in CARE-2. Depending on the distribution of catchabilities, our proposed multiple Lincoln-Petersen and a truncated geometric distribution obtained comparably good results. The former usually resulted in a minimum population size and the latter can be recommended when there is a long tail of low capture probabilities. Models with covariates and mixture models performed poorly. Our approach identified suitable methods and extended options to

Assessment of heterogeneity between European Populations: a Baltic and Danish replication case-control study of SNPs from a recent European ulcerative colitis genome wide association study.

Science.gov (United States)

Andersen, Vibeke; Ernst, Anja; Sventoraityte, Jurgita; Kupcinskas, Limas; Jacobsen, Bent A; Krarup, Henrik B; Vogel, Ulla; Jonaitis, Laimas; Denapiene, Goda; Kiudelis, Gediminas; Balschun, Tobias; Franke, Andre

2011-10-13

Differences in the genetic architecture of inflammatory bowel disease between different European countries and ethnicities have previously been reported. In the present study, we wanted to assess the role of 11 newly identified UC risk variants, derived from a recent European UC genome wide association study (GWAS) (Franke et al., 2010), for 1) association with UC in the Nordic countries, 2) for population heterogeneity between the Nordic countries and the rest of Europe, and, 3) eventually, to drive some of the previous findings towards overall genome-wide significance. Eleven SNPs were replicated in a Danish sample consisting of 560 UC patients and 796 controls and nine missing SNPs of the German GWAS study were successfully genotyped in the Baltic sample comprising 441 UC cases and 1156 controls. The independent replication data was then jointly analysed with the original data and systematic comparisons of the findings between ethnicities were made. Pearson's χ2, Breslow-Day (BD) and Cochran-Mantel-Haenszel (CMH) tests were used for association analyses and heterogeneity testing. The rs5771069 (IL17REL) SNP was not associated with UC in the Danish panel. The rs5771069 (IL17REL) SNP was significantly associated with UC in the combined Baltic, Danish and Norwegian UC study sample driven by the Norwegian panel (OR = 0.89, 95% CI: 0.79-0.98, P = 0.02). No association was found between rs7809799 (SMURF1/KPNA7) and UC (OR = 1.20, 95% CI: 0.95-1.52, P = 0.10) or between UC and all other remaining SNPs. We had 94% chance of detecting an association for rs7809799 (SMURF1/KPNA7) in the combined replication sample, whereas the power were 55% or lower for the remaining SNPs.Statistically significant PBD was found for OR heterogeneity between the combined Baltic, Danish, and Norwegian panel versus the combined German, British, Belgian, and Greek panel (rs7520292 (P = 0.001), rs12518307 (P = 0.007), and rs2395609 (TCP11) (P = 0.01), respectively).No SNP reached genome

Heterogeneous inflation expectations, learning, and market outcomes

OpenAIRE

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...

Evolution of altruistic punishment in heterogeneous populations

NARCIS (Netherlands)

de Weerd, Harmen; Verbrugge, Rineke

2011-01-01

Evolutionary models for altruistic behavior typically make the assumption of homogeneity: each individual has the same costs and benefits associated with cooperating with each other and punishing for selfish behavior. In this paper, we relax this assumption by separating the population into

High coffee consumption and different brewing methods in relation to postmenopausal endometrial cancer risk in the Norwegian women and cancer study: a population-based prospective study.

Science.gov (United States)

Gavrilyuk, Oxana; Braaten, Tonje; Skeie, Guri; Weiderpass, Elisabete; Dumeaux, Vanessa; Lund, Eiliv

2014-03-25

Coffee and its compounds have been proposed to inhibit endometrial carcinogenesis. Studies in the Norwegian population can be especially interesting due to the high coffee consumption and increasing incidence of endometrial cancer in the country. A total of 97 926 postmenopausal Norwegian women from the population-based prospective Norwegian Women and Cancer (NOWAC) Study, were included in the present analysis. We evaluated the general association between total coffee consumption and endometrial cancer risk as well as the possible impact of brewing method. Multivariate Cox regression analysis was used to estimate risks, and heterogeneity tests were performed to compare brewing methods. During an average of 10.9 years of follow-up, 462 incident endometrial cancer cases were identified. After multivariate adjustment, significant risk reduction was found among participants who drank ≥8 cups/day of coffee with a hazard ratio of 0.52 (95% confidence interval, CI 0.34-0.79). However, we did not observe a significant dose-response relationship. No significant heterogeneity in risk was found when comparing filtered and boiled coffee brewing methods. A reduction in endometrial cancer risk was observed in subgroup analyses among participants who drank ≥8 cups/day and had a body mass index ≥25 kg/m2, and in current smokers. These data suggest that in this population with high coffee consumption, endometrial cancer risk decreases in women consuming ≥8 cups/day, independent of brewing method.

Heterogeneous architecture to process swarm optimization algorithms

Directory of Open Access Journals (Sweden)

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.

A heterogeneous lattice gas model for simulating pedestrian evacuation

Science.gov (United States)

Guo, Xiwei; Chen, Jianqiao; Zheng, Yaochen; Wei, Junhong

2012-02-01

Based on the cellular automata method (CA model) and the mobile lattice gas model (MLG model), we have developed a heterogeneous lattice gas model for simulating pedestrian evacuation processes in an emergency. A local population density concept is introduced first. The update rule in the new model depends on the local population density and the exit crowded degree factor. The drift D, which is one of the key parameters influencing the evacuation process, is allowed to change according to the local population density of the pedestrians. Interactions including attraction, repulsion, and friction between every two pedestrians and those between a pedestrian and the building wall are described by a nonlinear function of the corresponding distance, and the repulsion forces increase sharply as the distances get small. A critical force of injury is introduced into the model, and its effects on the evacuation process are investigated. The model proposed has heterogeneous features as compared to the MLG model or the basic CA model. Numerical examples show that the model proposed can capture the basic features of pedestrian evacuation, such as clogging and arching phenomena.

Heterogeneity of long-history migration predicts emotion recognition accuracy.

Science.gov (United States)

Wood, Adrienne; Rychlowska, Magdalena; Niedenthal, Paula M

2016-06-01

Recent work (Rychlowska et al., 2015) demonstrated the power of a relatively new cultural dimension, historical heterogeneity, in predicting cultural differences in the endorsement of emotion expression norms. Historical heterogeneity describes the number of source countries that have contributed to a country's present-day population over the last 500 years. People in cultures originating from a large number of source countries may have historically benefited from greater and clearer emotional expressivity, because they lacked a common language and well-established social norms. We therefore hypothesized that in addition to endorsing more expressive display rules, individuals from heterogeneous cultures will also produce facial expressions that are easier to recognize by people from other cultures. By reanalyzing cross-cultural emotion recognition data from 92 papers and 82 cultures, we show that emotion expressions of people from heterogeneous cultures are more easily recognized by observers from other cultures than are the expressions produced in homogeneous cultures. Heterogeneity influences expression recognition rates alongside the individualism-collectivism of the perceivers' culture, as more individualistic cultures were more accurate in emotion judgments than collectivistic cultures. This work reveals the present-day behavioral consequences of long-term historical migration patterns and demonstrates the predictive power of historical heterogeneity. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

High resolution SPECT imaging for visualization of intratumoral heterogeneity using a SPECT/CT scanner dedicated for small animal imaging

International Nuclear Information System (INIS)

Umeda, Izumi O.; Tani, Kotaro; Tsuda, Keisuke

2012-01-01

Tumor interiors are never homogeneous and in vivo visualization of intratumoral heterogeneity would be an innovation that contributes to improved cancer therapy. But, conventional nuclear medicine tests have failed to visualize heterogeneity in vivo because of limited spatial resolution. Recently developed single photon emission computed tomographic (SPECT) scanners dedicated for small animal imaging are of interest due to their excellent spatial resolution of 111 In and simulations of actual small animal imaging. The optimal conditions obtained were validated by in vivo imaging of sarcoma 180-bearing mice. Larger number of counts must be obtained within limited acquisition time to visualize tumor heterogeneity in vivo in animal imaging, compared to cases that simply detect tumors. At an acquisition time of 30 min, better image quality was obtained with pinhole apertures diameter of 1.4 mm than of 1.0 mm. The obtained best spatial resolution was 1.3 mm, it was acceptable for our purpose, though a little worse than the best possible performance of the scanner (1.0 mm). Additionally, the reconstruction parameters, such as noise suppression, voxel size, and iteration/subset number, needed to be optimized under the limited conditions and were different from those found under the ideal condition. The minimal radioactivity concentration for visualization of heterogeneous tumor interiors was estimated to be as high as 0.2-0.5 MBq/mL. Liposomes containing 111 In met this requirement and were administered to tumor-bearing mice. SPECT imaging successfully showed heterogeneous 111 In distribution within the tumors in vivo with good spatial resolution. A threshold of 0.2 MBq/g for clear visualization of tumor heterogeneity was validated. Autoradiograms obtained ex vivo of excised tumors confirmed that the in vivo SPECT images accurately depicted the heterogeneous intratumoral accumulation of liposomes. Intratumoral heterogeneity was successfully visualized under the optimized

Heterochromatin heterogeneity in Hypostomus prope unae (Steindachner, 1878 (Siluriformes, Loricariidae from Northeastern Brazil

Directory of Open Access Journals (Sweden)

Jamille Bitencourt

2011-11-01

Full Text Available Cytogenetic analyses using C-banding and chromosomal digestion by several restriction enzymes were carried out in four populations (named A, B, C and D of Hypostomus prope unae (Loricariidae, Hypostominae from Contas river basin, northeastern Brazil. These populations share 2n=76 and single NORs on the second metacentric pair but exclusive karyotype forms for each locality. Populations A and B presented conspicuous terminal and interstitial heterochromatic blocks on most of acrocentric chromosomes and equivalent to NORs with differences in both position and bearing pair. Population D showed evident marks at interstitial regions and interspersed with nucleolar region while population C presented interstitial and terminal heterochromatin segments, non-coincident with NORs. The banding pattern after digestion with the endonucleases Alu I, Bam HI, Hae III and Dde I revealed a remarkable heterogeneity within heterochromatin, allowing the identification of distinctive clusters of repeated DNA in the studied populations, besides specific patterns along euchromatic regions. The analysis using restriction enzymes has proved to be highly informative, characterizing population differences and peculiarities in the genome organization of H. prope unae.

The effect of spatial heterogeneity on the extinction transition in stochastic population dynamics

International Nuclear Information System (INIS)

Kessler, David A; Shnerb, Nadav M

2009-01-01

Stochastic logistic-type growth on a static heterogeneous substrate is studied both above and below the drift-induced delocalization transition. Using agent-based simulations, the delocalization of the highest eigenfunction of the deterministic operator is connected with the large N limit of the stochastic theory. It is seen that the localization length of the deterministic theory controls the divergence of the spatial correlation length with N at the transition. It is argued that, in the presence of a strong wind, the extinction transition belongs to the directed percolation universality class, as any finite colony made of discrete agents is washed away from a heterogeneity with compact support. Some of the difficulties in the analysis of the extinction transition in the presence of a weak wind, where there is a localized active state, are discussed.

Heterogeneous High Throughput Scientific Computing with APM X-Gene and Intel Xeon Phi

CERN Document Server

Abdurachmanov, David; Elmer, Peter; Eulisse, Giulio; Knight, Robert; Muzaffar, Shahzad

2014-01-01

Electrical power requirements will be a constraint on the future growth of Distributed High Throughput Computing (DHTC) as used by High Energy Physics. Performance-per-watt is a critical metric for the evaluation of computer architectures for cost- efficient computing. Additionally, future performance growth will come from heterogeneous, many-core, and high computing density platforms with specialized processors. In this paper, we examine the Intel Xeon Phi Many Integrated Cores (MIC) co-processor and Applied Micro X-Gene ARMv8 64-bit low-power server system-on-a-chip (SoC) solutions for scientific computing applications. We report our experience on software porting, performance and energy efficiency and evaluate the potential for use of such technologies in the context of distributed computing systems such as the Worldwide LHC Computing Grid (WLCG).

Heterogeneous High Throughput Scientific Computing with APM X-Gene and Intel Xeon Phi

Science.gov (United States)

Abdurachmanov, David; Bockelman, Brian; Elmer, Peter; Eulisse, Giulio; Knight, Robert; Muzaffar, Shahzad

2015-05-01

Electrical power requirements will be a constraint on the future growth of Distributed High Throughput Computing (DHTC) as used by High Energy Physics. Performance-per-watt is a critical metric for the evaluation of computer architectures for cost- efficient computing. Additionally, future performance growth will come from heterogeneous, many-core, and high computing density platforms with specialized processors. In this paper, we examine the Intel Xeon Phi Many Integrated Cores (MIC) co-processor and Applied Micro X-Gene ARMv8 64-bit low-power server system-on-a-chip (SoC) solutions for scientific computing applications. We report our experience on software porting, performance and energy efficiency and evaluate the potential for use of such technologies in the context of distributed computing systems such as the Worldwide LHC Computing Grid (WLCG).

Heterogeneous High Throughput Scientific Computing with APM X-Gene and Intel Xeon Phi

International Nuclear Information System (INIS)

Abdurachmanov, David; Bockelman, Brian; Elmer, Peter; Eulisse, Giulio; Muzaffar, Shahzad; Knight, Robert

2015-01-01

Electrical power requirements will be a constraint on the future growth of Distributed High Throughput Computing (DHTC) as used by High Energy Physics. Performance-per-watt is a critical metric for the evaluation of computer architectures for cost- efficient computing. Additionally, future performance growth will come from heterogeneous, many-core, and high computing density platforms with specialized processors. In this paper, we examine the Intel Xeon Phi Many Integrated Cores (MIC) co-processor and Applied Micro X-Gene ARMv8 64-bit low-power server system-on-a-chip (SoC) solutions for scientific computing applications. We report our experience on software porting, performance and energy efficiency and evaluate the potential for use of such technologies in the context of distributed computing systems such as the Worldwide LHC Computing Grid (WLCG). (paper)

When high achievers and low achievers work in the same group: the roles of group heterogeneity and processes in project-based learning.

Science.gov (United States)

Cheng, Rebecca Wing-yi; Lam, Shui-fong; Chan, Joanne Chung-yan

2008-06-01

There has been an ongoing debate about the inconsistent effects of heterogeneous ability grouping on students in small group work such as project-based learning. The present research investigated the roles of group heterogeneity and processes in project-based learning. At the student level, we examined the interaction effect between students' within-group achievement and group processes on their self- and collective efficacy. At the group level, we examined how group heterogeneity was associated with the average self- and collective efficacy reported by the groups. The participants were 1,921 Hong Kong secondary students in 367 project-based learning groups. Student achievement was determined by school examination marks. Group processes, self-efficacy and collective efficacy were measured by a student-report questionnaire. Hierarchical linear modelling was used to analyse the nested data. When individual students in each group were taken as the unit of analysis, results indicated an interaction effect of group processes and students' within-group achievement on the discrepancy between collective- and self-efficacy. When compared with low achievers, high achievers reported lower collective efficacy than self-efficacy when group processes were of low quality. However, both low and high achievers reported higher collective efficacy than self-efficacy when group processes were of high quality. With 367 groups taken as the unit of analysis, the results showed that group heterogeneity, group gender composition and group size were not related to the discrepancy between collective- and self-efficacy reported by the students. Group heterogeneity was not a determinant factor in students' learning efficacy. Instead, the quality of group processes played a pivotal role because both high and low achievers were able to benefit when group processes were of high quality.

Large epidemic thresholds emerge in heterogeneous networks of heterogeneous nodes

Science.gov (United States)

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.

Large epidemic thresholds emerge in heterogeneous networks of heterogeneous nodes.

Science.gov (United States)

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.

The human endurance athlete: heterogeneity and adaptability of ...

African Journals Online (AJOL)

In human subjects, large variations between individuals (up to 3-fold) exist in the capacity for endurance exercise performance. In a heterogeneous population, endurance performance is strongly related to whole body maximal oxygen uptake (VO2 max). This is in part genotype dependent (~25%) but is adaptable with ...

Single cell analysis of Vibrio harveyi uncovers functional heterogeneity in response to quorum sensing signals

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Anetzberger Claudia

2012-09-01

Full Text Available Abstract Background Vibrio harveyi and closely related species are important pathogens in aquaculture. A complex quorum sensing cascade involving three autoinducers controls bioluminescence and several genes encoding virulence factors. Single cell analysis of a V. harveyi population has already indicated intercellular heterogeneity in the production of bioluminescence. This study was undertaken to analyze the expression of various autoinducer-dependent genes in individual cells. Results Here we used reporter strains bearing promoter::gfp fusions to monitor the induction/repression of three autoinducer-regulated genes in wild type conjugates at the single cell level. Two genes involved in pathogenesis - vhp and vscP, which code for an exoprotease and a component of the type III secretion system, respectively, and luxC (the first gene in the lux operon were chosen for analysis. The lux operon and the exoprotease gene are induced, while vscP is repressed at high cell density. As controls luxS and recA, whose expression is not dependent on autoinducers, were examined. The responses of the promoter::gfp fusions in individual cells from the same culture ranged from no to high induction. Importantly, simultaneous analysis of two autoinducer induced phenotypes, bioluminescence (light detection and exoproteolytic activity (fluorescence of a promoter::gfp fusion, in single cells provided evidence for functional heterogeneity within a V. harveyi population. Conclusions Autoinducers are not only an indicator for cell density, but play a pivotal role in the coordination of physiological activities within the population.

Single cell analysis of Vibrio harveyi uncovers functional heterogeneity in response to quorum sensing signals.

Science.gov (United States)

Anetzberger, Claudia; Schell, Ursula; Jung, Kirsten

2012-09-18

Vibrio harveyi and closely related species are important pathogens in aquaculture. A complex quorum sensing cascade involving three autoinducers controls bioluminescence and several genes encoding virulence factors. Single cell analysis of a V. harveyi population has already indicated intercellular heterogeneity in the production of bioluminescence. This study was undertaken to analyze the expression of various autoinducer-dependent genes in individual cells. Here we used reporter strains bearing promoter::gfp fusions to monitor the induction/repression of three autoinducer-regulated genes in wild type conjugates at the single cell level. Two genes involved in pathogenesis - vhp and vscP, which code for an exoprotease and a component of the type III secretion system, respectively, and luxC (the first gene in the lux operon) were chosen for analysis. The lux operon and the exoprotease gene are induced, while vscP is repressed at high cell density. As controls luxS and recA, whose expression is not dependent on autoinducers, were examined. The responses of the promoter::gfp fusions in individual cells from the same culture ranged from no to high induction. Importantly, simultaneous analysis of two autoinducer induced phenotypes, bioluminescence (light detection) and exoproteolytic activity (fluorescence of a promoter::gfp fusion), in single cells provided evidence for functional heterogeneity within a V. harveyi population. Autoinducers are not only an indicator for cell density, but play a pivotal role in the coordination of physiological activities within the population.

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

Science.gov (United States)

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.

Evidence of heterogeneity within bovine satellite cells isolated from young and adult animals.

Science.gov (United States)

Li, J; Gonzalez, J M; Walker, D K; Hersom, M J; Ealy, A D; Johnson, S E

2011-06-01

Satellite cells are a heterogeneous population of myogenic precursors responsible for muscle growth and repair in mammals. The objectives of the experiment were to examine the growth rates and degree of heterogeneity within bovine satellite cells (BSC) isolated from young and adult animals. The BSC were harvested from the semimembranosus of young (4.3 ± 0.5 d) and adult (estimated 24 to 27 mo) cattle and cultured en masse. Young animal BSC re-enter the cell cycle sooner and reach maximal 5-ethynyl-2'-deoxyuridine (EdU) incorporation earlier (P animals after 3, 4, and 5 d in culture. These results indicate that BSC from young animals activate, proliferate, and differentiate sooner than isolates from adult animals. Lineage heterogeneity within BSC was examined using antibodies specific for Pax7 and Myf5, lineage markers of satellite cells, and myoblasts. Immunocytochemistry revealed the majority of Pax7-expressing BSC also express Myf5; a minor population (~5%) fails to exhibit Myf5 immunoreactivity. The percentage of Pax7:Myf5 BSC from young animals decreases sooner (P cell clones were established and analyzed after 10 d. Colonies segregated into 2 groups based upon population doubling time. Immunostaining of the slow-growing colonies (population doubling time ≥ 3 d) revealed that a portion exhibited asymmetric distribution of the lineage markers Pax7 and Myf5, similar to self-renewable mouse muscle stem cells. In summary, these results offer insight into the heterogeneity of BSC and provide evidence for subtle differences between rodent and bovine myogenic precursors.

Rapid analysis of heterogeneously methylated DNA using digital methylation-sensitive high resolution melting: application to the CDKN2B (p15) gene

DEFF Research Database (Denmark)

Candiloro, Ida Lm; Mikeska, Thomas; Hokland, Peter

2008-01-01

ABSTRACT: BACKGROUND: Methylation-sensitive high resolution melting (MS-HRM) methodology is able to recognise heterogeneously methylated sequences by their characteristic melting profiles. To further analyse heterogeneously methylated sequences, we adopted a digital approach to MS-HRM (dMS-HRM) t......ABSTRACT: BACKGROUND: Methylation-sensitive high resolution melting (MS-HRM) methodology is able to recognise heterogeneously methylated sequences by their characteristic melting profiles. To further analyse heterogeneously methylated sequences, we adopted a digital approach to MS-HRM (d......MS-HRM) that involves the amplification of single templates after limiting dilution to quantify and to determine the degree of methylation. We used this approach to study methylation of the CDKN2B (p15) cell cycle progression inhibitor gene which is inactivated by DNA methylation in haematological malignancies...... the methylated alleles and assess the degree of methylation. Direct sequencing of selected dMS-HRM products was used to determine the exact DNA methylation pattern and confirmed the degree of methylation estimated by dMS-HRM. CONCLUSION: dMS-HRM is a powerful technique for the analysis of methylation in CDKN2B...

Population expanding with the phalanx model and lineages split by environmental heterogeneity: a case study of Primula obconica in subtropical China.

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Hai-Fei Yan

Full Text Available Current and historical events have both affected the current distribution patterns and intraspecific divergence of plants. While numerous studies have focused on the Qinghai-Tibetan Plateau (QTP, the impacts of such events on the flora of subtropical China remain poorly understood. Subtropical China is famous for its highly complex topography and the limited impact from glaciation during the Pleistocene; this may have resulted in a different genetic legacy for species in this region compared to fully glaciated areas.We used plastid and nuclear DNA sequence data and distribution modeling to analyze the divergence patterns and demographic history of Primula obconica Hance, a widespread herbaceous montane species in subtropical China. The phylogenetic analysis revealed two major lineages (lineage A and lineage B, representing a west-east split into the Yunnan and Eastern groups, and the Sichuan and Central groups, respectively. The Eastern and Central groups comprised relatively new derived haplotypes. Nested Clade Analysis and Bayesian Skyline Plot analyses both indicated that P. obconica mainly experienced a gradual expansion of populations. In addition, the simulated distribution of P. obconica during the Last Glacial Maximum was slightly larger than its present-day distribution.Our results are the first to identify a west-east migration of P. obconica. The gradual expansion pattern and a larger potential distribution range in cold periods detected for P. obconica indicate that the population expansion of this species is consistent with the phalanx model. In addition, the current patterns of genetic differentiation have persisted as a result of the extensive environmental heterogeneity that exists in subtropical China.

The heterogeneity of wooded-agricultural landscape mosaics influences woodland bird community assemblages

OpenAIRE

Neumann, Jessica L.; Griffiths, Geoffrey H.; Foster, Christopher W.; Holloway, Graham J.

2016-01-01

Context\\ud Landscape heterogeneity (the composition and configuration of different landcover types) plays a key role in shaping woodland bird assemblages in wooded-agricultural mosaics. Understanding how species respond to landscape factors could contribute to preventing further decline of woodland bird populations.\\ud Objective\\ud To investigate how woodland birds with different species traits respond to landscape heterogeneity, and to identify whether specific landcover types are important ...

Renewable energy adoption in an ageing population: Heterogeneity in preferences for micro-generation technology adoption

Energy Technology Data Exchange (ETDEWEB)

Willis, Ken, E-mail: Ken.Willis@ncl.ac.uk [School of Architecture, Planning and Landscape, University of Newcastle, Newcastle upon Tyne NE1 7RU (United Kingdom); Scarpa, Riccardo [Department of Economics, Waikato School of Management, University of Waikato, Hamilton (New Zealand); Gilroy, Rose; Hamza, Neveen [School of Architecture, Planning and Landscape, University of Newcastle, Newcastle upon Tyne NE1 7RU (United Kingdom)

2011-10-15

Many countries are endeavouring to supply more of their energy from renewable resources. Such countries are also experiencing an aging population with a greater proportion of people aged {>=}65 years. This demographic shift may reduce the uptake of renewable energy, if older person households are less inclined to accept change and adopt new technologies. This paper assesses whether such households have different behavioural responses to energy efficiency compared to the rest of society and investigates whether micro-generation renewable energy technologies are less likely to be adopted by these households. It uses conditional logit and mixed logit models to investigate the impact of age of household on primary heating adoption, and also to assess the impact of older households on the installation of discretionary micro-generation technologies (solar thermal, solar voltaic, and wind power) to supplement existing heating and lighting systems. Results indicate that primary heating choice is not affected but that older person households are less inclined to adopt micro-generation technologies. - Highlights: > Heterogeneity exists in decisions on micro-generation technology installation. > Older person households are less inclined to adopt micro-generation technologies. > Micro-generation technologies fail a social cost-benefit analysis test.

Renewable energy adoption in an ageing population: Heterogeneity in preferences for micro-generation technology adoption

International Nuclear Information System (INIS)

Willis, Ken; Scarpa, Riccardo; Gilroy, Rose; Hamza, Neveen

2011-01-01

Many countries are endeavouring to supply more of their energy from renewable resources. Such countries are also experiencing an aging population with a greater proportion of people aged ≥65 years. This demographic shift may reduce the uptake of renewable energy, if older person households are less inclined to accept change and adopt new technologies. This paper assesses whether such households have different behavioural responses to energy efficiency compared to the rest of society and investigates whether micro-generation renewable energy technologies are less likely to be adopted by these households. It uses conditional logit and mixed logit models to investigate the impact of age of household on primary heating adoption, and also to assess the impact of older households on the installation of discretionary micro-generation technologies (solar thermal, solar voltaic, and wind power) to supplement existing heating and lighting systems. Results indicate that primary heating choice is not affected but that older person households are less inclined to adopt micro-generation technologies. - Highlights: → Heterogeneity exists in decisions on micro-generation technology installation. → Older person households are less inclined to adopt micro-generation technologies. → Micro-generation technologies fail a social cost-benefit analysis test.

Epigenetic and conventional regulation is distributed among activators of FLO11 allowing tuning of population-level heterogeneity in its expression.

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Leah M Octavio

2009-10-01

Full Text Available Epigenetic switches encode their state information either locally, often via covalent modification of DNA or histones, or globally, usually in the level of a trans-regulatory factor. Here we examine how the regulation of cis-encoded epigenetic switches controls the extent of heterogeneity in gene expression, which is ultimately tied to phenotypic diversity in a population. We show that two copies of the FLO11 locus in Saccharomyces cerevisiae switch between a silenced and competent promoter state in a random and independent fashion, implying that the molecular event leading to the transition occurs locally at the promoter, in cis. We further quantify the effect of trans regulators both on the slow epigenetic transitions between a silenced and competent promoter state and on the fast promoter transitions associated with conventional regulation of FLO11. We find different classes of regulators affect epigenetic, conventional, or both forms of regulation. Distributing kinetic control of epigenetic silencing and conventional gene activation offers cells flexibility in shaping the distribution of gene expression and phenotype within a population.

Unraveling Macrophage Heterogeneity in Erythroblastic Islands

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Katie Giger Seu

2017-09-01

Full Text Available Mammalian erythropoiesis occurs within erythroblastic islands (EBIs, niches where maturing erythroblasts interact closely with a central macrophage. While it is generally accepted that EBI macrophages play an important role in erythropoiesis, thorough investigation of the mechanisms by which they support erythropoiesis is limited largely by inability to identify and isolate the specific macrophage sub-population that constitute the EBI. Early studies utilized immunohistochemistry or immunofluorescence to study EBI morphology and structure, while more recent efforts have used flow cytometry for high-throughput quantitative characterization of EBIs and their central macrophages. However, these approaches based on the expectation that EBI macrophages are a homogeneous population (F4/80+/CD169+/VCAM-1+ for example provide an incomplete picture and potentially overlook critical information about the nature and biology of the islands and their central macrophages. Here, we present a novel method for analysis of EBI macrophages from hematopoietic tissues of mice and rats using multispectral imaging flow cytometry (IFC, which combines the high-throughput advantage of flow cytometry with the morphological and fluorescence features derived from microscopy. This method provides both quantitative analysis of EBIs, as well as structural and morphological details of the central macrophages and associated cells. Importantly, the images, combined with quantitative software features, can be used to evaluate co-expression of phenotypic markers which is crucial since some antigens used to identify macrophages (e.g., F4/80 and CD11b can be expressed on non-erythroid cells associated with the islands instead of, or in addition to the central macrophage itself. We have used this method to analyze native EBIs from different hematopoietic tissues and evaluated the expression of several markers that have been previously reported to be expressed on EBI macrophages. We

Homogenization techniques for population dynamics in strongly heterogeneous landscapes.

Science.gov (United States)

Yurk, Brian P; Cobbold, Christina A

2018-12-01

An important problem in spatial ecology is to understand how population-scale patterns emerge from individual-level birth, death, and movement processes. These processes, which depend on local landscape characteristics, vary spatially and may exhibit sharp transitions through behavioural responses to habitat edges, leading to discontinuous population densities. Such systems can be modelled using reaction-diffusion equations with interface conditions that capture local behaviour at patch boundaries. In this work we develop a novel homogenization technique to approximate the large-scale dynamics of the system. We illustrate our approach, which also generalizes to multiple species, with an example of logistic growth within a periodic environment. We find that population persistence and the large-scale population carrying capacity is influenced by patch residence times that depend on patch preference, as well as movement rates in adjacent patches. The forms of the homogenized coefficients yield key theoretical insights into how large-scale dynamics arise from the small-scale features.

Highly Dispersed Pseudo-Homogeneous and Heterogeneous Catalysts Synthesized via Inverse Micelle Solutions for the Liquefaction of Coal

Energy Technology Data Exchange (ETDEWEB)

Hampden-Smith, M.; Kawola, J.S.; Martino, A.; Sault, A.G.; Yamanaka, S.A.

1999-01-05

The mission of this project was to use inverse micelle solutions to synthesize nanometer sized metal particles and test the particles as catalysts in the liquefaction of coal and other related reactions. The initial focus of the project was the synthesis of iron based materials in pseudo-homogeneous form. The frost three chapters discuss the synthesis, characterization, and catalyst testing in coal liquefaction and model coal liquefaction reactions of iron based pseudo-homogeneous materials. Later, we became interested in highly dispersed catalysts for coprocessing of coal and plastic waste. Bifunctional catalysts . to hydrogenate the coal and depolymerize the plastic waste are ideal. We began studying, based on our previously devised synthesis strategies, the synthesis of heterogeneous catalysts with a bifunctional nature. In chapter 4, we discuss the fundamental principles in heterogeneous catalysis synthesis with inverse micelle solutions. In chapter 5, we extend the synthesis of chapter 4 to practical systems and use the materials in catalyst testing. Finally in chapter 6, we return to iron and coal liquefaction now studied with the heterogeneous catalysts.

Functional Heterogeneity and Senior Management Team Effectiveness

Science.gov (United States)

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…

Detection of admittivity anomaly on high-contrast heterogeneous backgrounds using frequency difference EIT.

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Jang, J; Seo, J K

2015-06-01

This paper describes a multiple background subtraction method in frequency difference electrical impedance tomography (fdEIT) to detect an admittivity anomaly from a high-contrast background conductivity distribution. The proposed method expands the use of the conventional weighted frequency difference EIT method, which has been used limitedly to detect admittivity anomalies in a roughly homogeneous background. The proposed method can be viewed as multiple weighted difference imaging in fdEIT. Although the spatial resolutions of the output images by fdEIT are very low due to the inherent ill-posedness, numerical simulations and phantom experiments of the proposed method demonstrate its feasibility to detect anomalies. It has potential application in stroke detection in a head model, which is highly heterogeneous due to the skull.

Exploring heterogeneous market hypothesis using realized volatility

Science.gov (United States)

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.

Neurobiological heterogeneity in ADHD

NARCIS (Netherlands)

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

Influence of Nutrient Availability and Quorum Sensing on the Formation of Metabolically Inactive Microcolonies Within Structurally Heterogeneous Bacterial Biofilms: An Individual-Based 3D Cellular Automata Model.

Science.gov (United States)

Machineni, Lakshmi; Rajapantul, Anil; Nandamuri, Vandana; Pawar, Parag D

2017-03-01

The resistance of bacterial biofilms to antibiotic treatment has been attributed to the emergence of structurally heterogeneous microenvironments containing metabolically inactive cell populations. In this study, we use a three-dimensional individual-based cellular automata model to investigate the influence of nutrient availability and quorum sensing on microbial heterogeneity in growing biofilms. Mature biofilms exhibited at least three structurally distinct strata: a high-volume, homogeneous region sandwiched between two compact sections of high heterogeneity. Cell death occurred preferentially in layers in close proximity to the substratum, resulting in increased heterogeneity in this section of the biofilm; the thickness and heterogeneity of this lowermost layer increased with time, ultimately leading to sloughing. The model predicted the formation of metabolically dormant cellular microniches embedded within faster-growing cell clusters. Biofilms utilizing quorum sensing were more heterogeneous compared to their non-quorum sensing counterparts, and resisted sloughing, featuring a cell-devoid layer of EPS atop the substratum upon which the remainder of the biofilm developed. Overall, our study provides a computational framework to analyze metabolic diversity and heterogeneity of biofilm-associated microorganisms and may pave the way toward gaining further insights into the biophysical mechanisms of antibiotic resistance.

Measuring the effects of heterogeneity on distributed systems

Science.gov (United States)

El-Toweissy, Mohamed; Zeineldine, Osman; Mukkamala, Ravi

1991-01-01

Distributed computer systems in daily use are becoming more and more heterogeneous. Currently, much of the design and analysis studies of such systems assume homogeneity. This assumption of homogeneity has been mainly driven by the resulting simplicity in modeling and analysis. A simulation study is presented which investigated the effects of heterogeneity on scheduling algorithms for hard real time distributed systems. In contrast to previous results which indicate that random scheduling may be as good as a more complex scheduler, this algorithm is shown to be consistently better than a random scheduler. This conclusion is more prevalent at high workloads as well as at high levels of heterogeneity.

Agent-Based Modeling of Mitochondria Links Sub-Cellular Dynamics to Cellular Homeostasis and Heterogeneity.

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Giovanni Dalmasso

Full Text Available Mitochondria are semi-autonomous organelles that supply energy for cellular biochemistry through oxidative phosphorylation. Within a cell, hundreds of mobile mitochondria undergo fusion and fission events to form a dynamic network. These morphological and mobility dynamics are essential for maintaining mitochondrial functional homeostasis, and alterations both impact and reflect cellular stress states. Mitochondrial homeostasis is further dependent on production (biogenesis and the removal of damaged mitochondria by selective autophagy (mitophagy. While mitochondrial function, dynamics, biogenesis and mitophagy are highly-integrated processes, it is not fully understood how systemic control in the cell is established to maintain homeostasis, or respond to bioenergetic demands. Here we used agent-based modeling (ABM to integrate molecular and imaging knowledge sets, and simulate population dynamics of mitochondria and their response to environmental energy demand. Using high-dimensional parameter searches we integrated experimentally-measured rates of mitochondrial biogenesis and mitophagy, and using sensitivity analysis we identified parameter influences on population homeostasis. By studying the dynamics of cellular subpopulations with distinct mitochondrial masses, our approach uncovered system properties of mitochondrial populations: (1 mitochondrial fusion and fission activities rapidly establish mitochondrial sub-population homeostasis, and total cellular levels of mitochondria alter fusion and fission activities and subpopulation distributions; (2 restricting the directionality of mitochondrial mobility does not alter morphology subpopulation distributions, but increases network transmission dynamics; and (3 maintaining mitochondrial mass homeostasis and responding to bioenergetic stress requires the integration of mitochondrial dynamics with the cellular bioenergetic state. Finally, (4 our model suggests sources of, and stress conditions

High-resolution observations of combustion in heterogeneous surface fuels

Science.gov (United States)

E. Louise Loudermilk; Gary L. Achtemeier; Joseph J. O' Brien; J. Kevin Hiers; Benjamin S. Hornsby

2014-01-01

In ecosystems with frequent surface fires, fire and fuel heterogeneity at relevant scales have been largely ignored. This could be because complete burns give an impression of homogeneity, or due to the difficulty in capturing fine-scale variation in fuel characteristics and fire behaviour. Fire movement between patches of fuel can have implications for modelling fire...

Homogeneous Combinations of ASD-ADHD Traits and Their Cognitive and Behavioral Correlates in a Population-Based Sample.

Science.gov (United States)

van der Meer, Jolanda M J; Lappenschaar, Martijn G A; Hartman, Catharina A; Greven, Corina U; Buitelaar, Jan K; Rommelse, Nanda N J

2017-07-01

Autism Spectrum Disorders (ASD) and ADHD are assumed to be the extreme manifestations of continuous heterogeneous traits that frequently co-occur. This study aims to identify subgroups of children with distinct ASD-ADHD trait profiles in the general population, using measures sensitive across both trait continua, and show how these subgroups differ in cognitive functioning. We examined 378 children (6-13 years) from a population-based sample. Latent class analyses (LCA) detected three concordant classes with low (10.1%), medium (54.2%), or high (13.2%) scores on both traits, and two discordant classes with more ADHD than ASD characteristics (ADHD > ASD, 18.3%) and vice versa (ASD > ADHD, 4.2%). Findings suggest that ASD and ADHD traits usually are strongly related in the unaffected population, and that a minority of children displays atypical discordant trait profiles characterized by differential visual-spatial functioning. This dissociation suggests that heterogeneity in ASD and ADHD is rooted in heterogeneity in the lower unaffected end of the distribution.

Organizational heterogeneity of vertebrate genomes.

Science.gov (United States)

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.

Organizational heterogeneity of vertebrate genomes.

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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.

Dynamics of spatial heterogeneity of stomatal closure in Tradescantia virginiana altered by growth at high relative air humidity

NARCIS (Netherlands)

Rezaei Nejad, A.; Harbinson, J.; Meeteren, van U.

2006-01-01

The spatial heterogeneity of stomatal closure in response to rapid desiccation of excised well-watered Tradescantia virginiana leaves grown at moderate (55%) or high (90%) relative air humidity (RH) was studied using a chlorophyll fluorescence imaging system under non-photorespiratory conditions.

Design and Performance Analysis of Multi-tier Heterogeneous Network through Coverage, Throughput and Energy Efficiency

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A. Shabbir,

2017-12-01

Full Text Available The unprecedented acceleration in wireless industry strongly compels wireless operators to increase their data network throughput, capacity and coverage on emergent basis. In upcoming 5G heterogeneous networks inclusion of low power nodes (LPNs like pico cells and femto cells for increasing network’s throughput, capacity and coverage are getting momentum. Addition of LPNs in such a massive level will eventually make a network populated in terms of base stations (BSs.The dense deployments of BSs will leads towards high operating expenditures (Op-Ex, capital expenditure (Cap-Ex and most importantly high energy consumption in future generation networks. Recognizing theses networks issues this research work investigates data throughput and energy efficiency of 5G multi-tier heterogeneous network. The network is modeled using tools from stochastic geometry. Monte Carlo results confirmed that rational deployment of LPNs can contribute towards increased throughput along with better energy efficiency of overall network.

Heterogeneity of anatomic regions by MR volumetry in juvenile myoclonic epilepsy.

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Swartz, B E; Spitz, J; Vu, A L; Mandelkern, M; Su, M L

2016-10-01

To investigate brain volumes in patients with well-characterized juvenile myoclonic epilepsy (JME). We studied the MRI images of seventeen subjects with EEG and clinically defined JME and seventeen age- and sex-matched controls using voxel-based morphometry (VBM) and automated and manual volumetry. We found no significant group differences in the cortical volumes by automated techniques for all regions or for the whole brain. However, we found a larger pulvinar nucleus in JME using VBM with small volume correction and a larger thalamus with manual volumetry (P = 0.001; corrected two-tailed t-test). By analysing the individual subjects, we determined that considerable heterogeneity exists even in this highly selected group. Histograms of all JME and matched control regions' volumes showed more subjects with JME had smaller hippocampi and larger thalami (P < 0.05; chi-square). Subjects in whom the first seizure was absence were more likely to have smaller hippocampi than their matched control, while those without absences showed no differences (P < 0.05, chi-square). There is ample evidence for frontal cortical thalamic network changes in JME, but subcortical structural differences were more distinct in this group. Given the heterogeneity of brain volumes in the clinical population, further advancement in the field will require the examination of stringent genetically controlled populations. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High heterogeneity of malaria transmission and a large sub-patent and diverse reservoir of infection in Wusab As Safil district, Republic of Yemen.

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Cook, Jackie; Grignard, Lynn; Al-Eryani, Samira; Al-Selwei, Mustafa; Mnzava, Abraham; Al-Yarie, Hafed; Rand, Alison; Kleinschmidt, Immo; Drakeley, Chris

2016-04-08

Yemen remains the country with the highest malaria transmission within the Arabian Peninsula and a source of imported cases to neighbouring countries. This study collected samples from individuals resident in a valley in Western Yemen as a baseline to examine infection prevalence for a future trial. As well as rapid diagnostic test (RDT) and microscopy, a filter paper blood spot was collected for molecular and serological analyses. Samples were collected from 2261 individuals from 12 clusters across a study area of approximately 100 km(2). Plasmodium falciparum infection prevalence was 12.4, 11.1 and 19.6% by RDT, microscopy and polymerase chain reaction (PCR), respectively. RDT and microscopy did not detect 45% of infections present, suggesting many infections were low-density. Infection prevalence and seroprevalence were highly heterogeneous between clusters, with evidence of higher exposure in clusters close to the wadi. The mean multiplicity of infection (MOI) was 2.3 and high heterozygosity and allelic richness were detected. This highly diverse parasite population suggests a high degree of transmissibility and coupled with the substantial proportion of low-density infections, may pose challenges for malaria control and elimination efforts.

Analysis of heterogeneity and epistasis in physiological mixed populations by combined structural equation modelling and latent class analysis

DEFF Research Database (Denmark)

Fenger, Mogens; Linneberg, A.; Werge, Thomas Mears

2008-01-01

and genetic variations of such networks. METHODS: In this study on type 2 diabetes mellitus, heterogeneity was resolved in a latent class framework combined with structural equation modelling using phenotypic indicators of distinct physiological processes. We modelled the clinical condition "the metabolic......BACKGROUND: Biological systems are interacting, molecular networks in which genetic variation contributes to phenotypic heterogeneity. This heterogeneity is traditionally modelled as a dichotomous trait (e.g. affected vs. non-affected). This is far too simplistic considering the complexity...

Inference of Cell Mechanics in Heterogeneous Epithelial Tissue Based on Multivariate Clone Shape Quantification

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Tsuboi, Alice; Umetsu, Daiki; Kuranaga, Erina; Fujimoto, Koichi

2017-01-01

Cell populations in multicellular organisms show genetic and non-genetic heterogeneity, even in undifferentiated tissues of multipotent cells during development and tumorigenesis. The heterogeneity causes difference of mechanical properties, such as, cell bond tension or adhesion, at the cell–cell interface, which determine the shape of clonal population boundaries via cell sorting or mixing. The boundary shape could alter the degree of cell–cell contacts and thus influence the physiological consequences of sorting or mixing at the boundary (e.g., tumor suppression or progression), suggesting that the cell mechanics could help clarify the physiology of heterogeneous tissues. While precise inference of mechanical tension loaded at each cell–cell contacts has been extensively developed, there has been little progress on how to distinguish the population-boundary geometry and identify the cause of geometry in heterogeneous tissues. We developed a pipeline by combining multivariate analysis of clone shape with tissue mechanical simulations. We examined clones with four different genotypes within Drosophila wing imaginal discs: wild-type, tartan (trn) overexpression, hibris (hbs) overexpression, and Eph RNAi. Although the clones were previously known to exhibit smoothed or convoluted morphologies, their mechanical properties were unknown. By applying a multivariate analysis to multiple criteria used to quantify the clone shapes based on individual cell shapes, we found the optimal criteria to distinguish not only among the four genotypes, but also non-genetic heterogeneity from genetic one. The efficient segregation of clone shape enabled us to quantitatively compare experimental data with tissue mechanical simulations. As a result, we identified the mechanical basis contributed to clone shape of distinct genotypes. The present pipeline will promote the understanding of the functions of mechanical interactions in heterogeneous tissue in a non-invasive manner. PMID

Differential tolerance to nickel between Dreissena polymorpha and Dreissena rostriformis bugensis populations.

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Potet, Marine; Giambérini, Laure; Pain-Devin, Sandrine; Louis, Fanny; Bertrand, Carole; Devin, Simon

2018-01-15

Differential tolerance to stress is partly responsible for the heterogeneity of biomarker responses between populations of a sentinel species. Although currently used for freshwater biomonitoring, studies concerning inter-populational variability in tolerance to contaminants for the zebra mussel (Dreissena polymorpha) are scarce. Moreover, this well-known invader is currently replaced by another, the quagga mussel (Dreissena rostriformis bugensis). To evaluate the differential tolerance between dreissenids, several populations of both species were exposed to a high concentration of nickel. A LT 50 (time when 50% of individuals were dead) was established for each population. Biomarker responses and internal nickel concentration were also measured, to link tolerance with physiological status. Results evidenced that D. polymorpha populations are more heterogeneous and more tolerant than D. r. bugensis ones. For D. polymorpha populations only, LT 50 values were positively correlated with the nickel contamination in situ, with higher anti-oxidative defences and a higher Integrated Biomarker Response value in the field. Such findings may be explained by local adaptation and invasion dynamic within each species. The significance of this differential tolerance when using biomarker responses for biomonitoring purposes is thus discussed.

Assessment of heterogeneity between European Populations: a Baltic and Danish replication case-control study of SNPs from a recent European ulcerative colitis genome wide association study

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Jonaitis Laimas

2011-10-01

Full Text Available Abstract Background Differences in the genetic architecture of inflammatory bowel disease between different European countries and ethnicities have previously been reported. In the present study, we wanted to assess the role of 11 newly identified UC risk variants, derived from a recent European UC genome wide association study (GWAS (Franke et al., 2010, for 1 association with UC in the Nordic countries, 2 for population heterogeneity between the Nordic countries and the rest of Europe, and, 3 eventually, to drive some of the previous findings towards overall genome-wide significance. Methods Eleven SNPs were replicated in a Danish sample consisting of 560 UC patients and 796 controls and nine missing SNPs of the German GWAS study were successfully genotyped in the Baltic sample comprising 441 UC cases and 1156 controls. The independent replication data was then jointly analysed with the original data and systematic comparisons of the findings between ethnicities were made. Pearson's χ2, Breslow-Day (BD and Cochran-Mantel-Haenszel (CMH tests were used for association analyses and heterogeneity testing. Results The rs5771069 (IL17REL SNP was not associated with UC in the Danish panel. The rs5771069 (IL17REL SNP was significantly associated with UC in the combined Baltic, Danish and Norwegian UC study sample driven by the Norwegian panel (OR = 0.89, 95% CI: 0.79-0.98, P = 0.02. No association was found between rs7809799 (SMURF1/KPNA7 and UC (OR = 1.20, 95% CI: 0.95-1.52, P = 0.10 or between UC and all other remaining SNPs. We had 94% chance of detecting an association for rs7809799 (SMURF1/KPNA7 in the combined replication sample, whereas the power were 55% or lower for the remaining SNPs. Statistically significant PBD was found for OR heterogeneity between the combined Baltic, Danish, and Norwegian panel versus the combined German, British, Belgian, and Greek panel (rs7520292 (P = 0.001, rs12518307 (P = 0.007, and rs2395609 (TCP11 (P = 0

New insights into the Lake Chad Basin population structure revealed by high-throughput genotyping of mitochondrial DNA coding SNPs.

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María Cerezo

Full Text Available BACKGROUND: Located in the Sudan belt, the Chad Basin forms a remarkable ecosystem, where several unique agricultural and pastoral techniques have been developed. Both from an archaeological and a genetic point of view, this region has been interpreted to be the center of a bidirectional corridor connecting West and East Africa, as well as a meeting point for populations coming from North Africa through the Saharan desert. METHODOLOGY/PRINCIPAL FINDINGS: Samples from twelve ethnic groups from the Chad Basin (n = 542 have been high-throughput genotyped for 230 coding region mitochondrial DNA (mtDNA Single Nucleotide Polymorphisms (mtSNPs using Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight (MALDI-TOF mass spectrometry. This set of mtSNPs allowed for much better phylogenetic resolution than previous studies of this geographic region, enabling new insights into its population history. Notable haplogroup (hg heterogeneity has been observed in the Chad Basin mirroring the different demographic histories of these ethnic groups. As estimated using a Bayesian framework, nomadic populations showed negative growth which was not always correlated to their estimated effective population sizes. Nomads also showed lower diversity values than sedentary groups. CONCLUSIONS/SIGNIFICANCE: Compared to sedentary population, nomads showed signals of stronger genetic drift occurring in their ancestral populations. These populations, however, retained more haplotype diversity in their hypervariable segments I (HVS-I, but not their mtSNPs, suggesting a more ancestral ethnogenesis. Whereas the nomadic population showed a higher Mediterranean influence signaled mainly by sub-lineages of M1, R0, U6, and U5, the other populations showed a more consistent sub-Saharan pattern. Although lifestyle may have an influence on diversity patterns and hg composition, analysis of molecular variance has not identified these differences. The present study indicates that

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

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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

A system for tumor heterogeneity evaluation and diagnosis based on tumor markers measured routinely in the laboratory.

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Hui, Liu; Rixv, Liu; Xiuying, Zhou

2015-12-01

To develop an efficient and reliable approach to estimate tumor heterogeneity and improve tumor diagnosis using multiple tumor markers measured routinely in the clinical laboratory. A total of 161 patients with different cancers were recruited as the cancer group, and 91 patients with non-oncological conditions were required as the non-oncological disease group. The control group comprised 90 randomly selected healthy subjects. AFP, CEA, CYFRA, CA125, CA153, CA199, CA724, and NSE levels were measured in all these subjects with a chemiluminescent microparticle immunoassay. The tumor marker with the maximum S/CO value (sample test value:cutoff value for discriminating individuals with and without tumors) was considered as a specific tumor marker (STM) for an individual. Tumor heterogeneity index (THI)=N/P (N: number of STMs; P: percentage of individuals with STMs in a certain tumor population) was used to quantify tumor heterogeneity: high THI indicated high tumor heterogeneity. The tumor marker index (TMI), TMI = STM×(number of positive tumor markers+1), was used for diagnosis. The THIs of lung, gastric, and liver cancers were 8.33, 9.63, and 5.2, respectively, while the ROC-areas under the curve for TMI were 0.862, 0.809, and 0.966. In this study, we developed a novel index for tumor heterogeneity based on the expression of various routinely evaluated serum tumor markers. Development of an evaluation system for tumor heterogeneity on the basis of this index could provide an effective diagnostic tool for some cancers. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Adoption of a High-Impact Innovation in a Homogeneous Population

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Weiss, Curtis H.; Poncela-Casasnovas, Julia; Glaser, Joshua I.; Pah, Adam R.; Persell, Stephen D.; Baker, David W.; Wunderink, Richard G.; Nunes Amaral, Luís A.

2014-10-01

Adoption of innovations, whether new ideas, technologies, or products, is crucially important to knowledge societies. The landmark studies of adoption dealt with innovations having great societal impact (such as antibiotics or hybrid crops) but where determining the utility of the innovation was straightforward (such as fewer side effects or greater yield). Recent large-scale studies of adoption were conducted within heterogeneous populations and focused on products with little societal impact. Here, we focus on a case with great practical significance: adoption by small groups of highly trained individuals of innovations with large societal impact but for which it is impractical to determine the true utility of the innovation. Specifically, we study experimentally the adoption by critical care physicians of a diagnostic assay that complements current protocols for the diagnosis of life-threatening bacterial infections and for which a physician cannot estimate the true accuracy of the assay based on personal experience. We show through computational modeling of the experiment that infection-spreading models—which have been formalized as generalized contagion processes—are not consistent with the experimental data, while a model inspired by opinion models is able to reproduce the empirical data. Our modeling approach enables us to investigate the efficacy of different intervention schemes on the rate and robustness of innovation adoption in the real world. While our study is focused on critical care physicians, our findings have implications for other settings in education, research, and business, where small groups of highly qualified peers make decisions about the adoption of innovations whose utility is difficult if not impossible to gauge.

Robust Synchronization in an E/I Network with Medium Synaptic Delay and High Level of Heterogeneity

International Nuclear Information System (INIS)

Han Fang; Wang Zhi-Jie; Gong Tao; Fan Hong

2015-01-01

It is known that both excitatory and inhibitory neuronal networks can achieve robust synchronization only under certain conditions, such as long synaptic delay or low level of heterogeneity. In this work, robust synchronization can be found in an excitatory/inhibitory (E/I) neuronal network with medium synaptic delay and high level of heterogeneity, which often occurs in real neuronal networks. Two effects of post-synaptic potentials (PSP) to network synchronization are presented, and the synaptic contribution of excitatory and inhibitory neurons to robust synchronization in this E/I network is investigated. It is found that both excitatory and inhibitory neurons may contribute to robust synchronization in E/I networks, especially the excitatory PSP has a more positive effect on synchronization in E/I networks than that in excitatory networks. This may explain the strong robustness of synchronization in E/I neuronal networks. (paper)

Multiscale Lattice Boltzmann method for flow simulations in highly heterogenous porous media

KAUST Repository

Li, Jun

2013-01-01

A lattice Boltzmann method (LBM) for flow simulations in highly heterogeneous porous media at both pore and Darcy scales is proposed in the paper. In the pore scale simulations, flow of two phases (e.g., oil and gas) or two immiscible fluids (e.g., water and oil) are modeled using cohesive or repulsive forces, respectively. The relative permeability can be computed using pore-scale simulations and seamlessly applied for intermediate and Darcy-scale simulations. A multiscale LBM that can reduce the computational complexity of existing LBM and transfer the information between different scales is implemented. The results of coarse-grid, reduced-order, simulations agree very well with the averaged results obtained using fine grid.

The nature and nurture of cell heterogeneity: accounting for macrophage gene-environment interactions with single-cell RNA-Seq.

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Wills, Quin F; Mellado-Gomez, Esther; Nolan, Rory; Warner, Damien; Sharma, Eshita; Broxholme, John; Wright, Benjamin; Lockstone, Helen; James, William; Lynch, Mark; Gonzales, Michael; West, Jay; Leyrat, Anne; Padilla-Parra, Sergi; Filippi, Sarah; Holmes, Chris; Moore, Michael D; Bowden, Rory

2017-01-07

Single-cell RNA-Seq can be a valuable and unbiased tool to dissect cellular heterogeneity, despite the transcriptome's limitations in describing higher functional phenotypes and protein events. Perhaps the most important shortfall with transcriptomic 'snapshots' of cell populations is that they risk being descriptive, only cataloging heterogeneity at one point in time, and without microenvironmental context. Studying the genetic ('nature') and environmental ('nurture') modifiers of heterogeneity, and how cell population dynamics unfold over time in response to these modifiers is key when studying highly plastic cells such as macrophages. We introduce the programmable Polaris™ microfluidic lab-on-chip for single-cell sequencing, which performs live-cell imaging while controlling for the culture microenvironment of each cell. Using gene-edited macrophages we demonstrate how previously unappreciated knockout effects of SAMHD1, such as an altered oxidative stress response, have a large paracrine signaling component. Furthermore, we demonstrate single-cell pathway enrichments for cell cycle arrest and APOBEC3G degradation, both associated with the oxidative stress response and altered proteostasis. Interestingly, SAMHD1 and APOBEC3G are both HIV-1 inhibitors ('restriction factors'), with no known co-regulation. As single-cell methods continue to mature, so will the ability to move beyond simple 'snapshots' of cell populations towards studying the determinants of population dynamics. By combining single-cell culture, live-cell imaging, and single-cell sequencing, we have demonstrated the ability to study cell phenotypes and microenvironmental influences. It's these microenvironmental components - ignored by standard single-cell workflows - that likely determine how macrophages, for example, react to inflammation and form treatment resistant HIV reservoirs.

High Content Analysis of Compositional Heterogeneities to Study GPCR Oligomerization

DEFF Research Database (Denmark)

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...

Overview of medium heterogeneity and transport processes

International Nuclear Information System (INIS)

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

Bidirectional interconversion of stem and non-stem cancer cell populations: A reassessment of theoretical models for tumor heterogeneity

NARCIS (Netherlands)

van Neerven, Sanne M.; Tieken, Mathijs; Vermeulen, Louis; Bijlsma, Maarten F.

2016-01-01

Resolving the origin of intratumor heterogeneity has proven to be one of the central challenges in cancer research during recent years. Two theoretical models explaining the emergence of intratumor heterogeneity have come to dominate cancer biology literature: the clonal evolution model and the

State-of-the-art in Heterogeneous Computing

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Andre R. Brodtkorb

2010-01-01

Full Text Available Node level heterogeneous architectures have become attractive during the last decade for several reasons: compared to traditional symmetric CPUs, they offer high peak performance and are energy and/or cost efficient. With the increase of fine-grained parallelism in high-performance computing, as well as the introduction of parallelism in workstations, there is an acute need for a good overview and understanding of these architectures. We give an overview of the state-of-the-art in heterogeneous computing, focusing on three commonly found architectures: the Cell Broadband Engine Architecture, graphics processing units (GPUs, and field programmable gate arrays (FPGAs. We present a review of hardware, available software tools, and an overview of state-of-the-art techniques and algorithms. Furthermore, we present a qualitative and quantitative comparison of the architectures, and give our view on the future of heterogeneous computing.

Interactive macroeconomics stochastic aggregate dynamics with heterogeneous and interacting agents

CERN Document Server

Di Guilmi, Corrado

2017-01-01

One of the major problems of macroeconomic theory is the way in which the people exchange goods in decentralized market economies. There are major disagreements among macroeconomists regarding tools to influence required outcomes. Since the mainstream efficient market theory fails to provide an internal coherent framework, there is a need for an alternative theory. The book provides an innovative approach for the analysis of agent based models, populated by the heterogeneous and interacting agents in the field of financial fragility. The text is divided in two parts; the first presents analytical developments of stochastic aggregation and macro-dynamics inference methods. The second part introduces macroeconomic models of financial fragility for complex systems populated by heterogeneous and interacting agents. The concepts of financial fragility and macroeconomic dynamics are explained in detail in separate chapters. The statistical physics approach is applied to explain theories of macroeconomic modelling a...

Acculturation, Dietary Practices and Risk for Childhood Obesity in an Ethnically Heterogeneous Population of Latino School Children in the San Francisco Bay Area

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Schwartz, Norah; Jiménez-Cruz, Arturo; Bacardi-Gascon, Montserrat; Heyman, Melvin B.

2015-01-01

Previous studies have found increased acculturation to the US lifestyle increases risk for obesity in Latinos. However, methodologies differ, and results in children are inconsistent. Moreover, previous studies have not evaluated risk factors within the heterogeneous US population. We recruited 144 self-identified Latino school children and their mother or father in grades 4–6 in San Francisco parochial schools and South San Francisco public schools using an information letter distributed to all students. Children and parents had weights, heights, demographic information, dietary patterns and lifestyle variables collected in English or Spanish through an interview format. A high percentage of our children were overweight [≥85th percentile body mass index (BMI)] (62.5%) and obese (≥95th percentile BMI) (45.2%). Correspondingly parents also had a high percentage of overweight (BMI ≥ 25 & obesity (BMI ≥ 30) (45.3%). Mexico was the country of origin for 62.2% of parents, and 26.6% were from Central or South America. In multivariate logistic analysis, speaking Spanish at home was an independent risk factor for obesity [odds ratio (OR) 2.97, 95% confidence interval (CI) 1.28–6.86]. Eating breakfast daily (OR 0.34, 95% CI 0.15–0.78) and consumption of tortas (a Mexican fast food sandwich) (OR 0.45, 95% CI 0.21–1.00) were associated with decreased risk. In stratified analysis, significant differences in risk factors existed between Mexican origin versus Central/South American Latino children. The processes of acculturation likely impact eating and lifestyle practices differentially among Latino groups. Interventions should focus on ensuring that all children eat a nutritious breakfast and take into consideration ethnicity when working with Latino populations. PMID:22101726

Generalizing Evidence From Randomized Clinical Trials to Target Populations

Science.gov (United States)

Cole, Stephen R.; Stuart, Elizabeth A.

2010-01-01

Properly planned and conducted randomized clinical trials remain susceptible to a lack of external validity. The authors illustrate a model-based method to standardize observed trial results to a specified target population using a seminal human immunodeficiency virus (HIV) treatment trial, and they provide Monte Carlo simulation evidence supporting the method. The example trial enrolled 1,156 HIV-infected adult men and women in the United States in 1996, randomly assigned 577 to a highly active antiretroviral therapy and 579 to a largely ineffective combination therapy, and followed participants for 52 weeks. The target population was US people infected with HIV in 2006, as estimated by the Centers for Disease Control and Prevention. Results from the trial apply, albeit muted by 12%, to the target population, under the assumption that the authors have measured and correctly modeled the determinants of selection that reflect heterogeneity in the treatment effect. In simulations with a heterogeneous treatment effect, a conventional intent-to-treat estimate was biased with poor confidence limit coverage, but the proposed estimate was largely unbiased with appropriate confidence limit coverage. The proposed method standardizes observed trial results to a specified target population and thereby provides information regarding the generalizability of trial results. PMID:20547574

Extracellular Vesicle Heterogeneity: Subpopulations, Isolation Techniques, and Diverse Functions in Cancer Progression

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Eduard Willms

2018-04-01

Full Text Available Cells release membrane enclosed nano-sized vesicles termed extracellular vesicles (EVs that function as mediators of intercellular communication by transferring biological information between cells. Tumor-derived EVs have emerged as important mediators in cancer development and progression, mainly through transfer of their bioactive content which can include oncoproteins, oncogenes, chemokine receptors, as well as soluble factors, transcripts of proteins and miRNAs involved in angiogenesis or inflammation. This transfer has been shown to influence the metastatic behavior of primary tumors. Moreover, tumor-derived EVs have been shown to influence distant cellular niches, establishing favorable microenvironments that support growth of disseminated cancer cells upon their arrival at these pre-metastatic niches. It is generally accepted that cells release a number of major EV populations with distinct biophysical properties and biological functions. Exosomes, microvesicles, and apoptotic bodies are EV populations most widely studied and characterized. They are discriminated based primarily on their intracellular origin. However, increasing evidence suggests that even within these EV populations various subpopulations may exist. This heterogeneity introduces an extra level of complexity in the study of EV biology and function. For example, EV subpopulations could have unique roles in the intricate biological processes underlying cancer biology. Here, we discuss current knowledge regarding the role of subpopulations of EVs in cancer development and progression and highlight the relevance of EV heterogeneity. The position of tetraspanins and integrins therein will be highlighted. Since addressing EV heterogeneity has become essential for the EV field, current and novel techniques for isolating EV subpopulations will also be discussed. Further dissection of EV heterogeneity will advance our understanding of the critical roles of EVs in health and

Extracellular Vesicle Heterogeneity: Subpopulations, Isolation Techniques, and Diverse Functions in Cancer Progression.

Science.gov (United States)

Willms, Eduard; Cabañas, Carlos; Mäger, Imre; Wood, Matthew J A; Vader, Pieter

2018-01-01

Cells release membrane enclosed nano-sized vesicles termed extracellular vesicles (EVs) that function as mediators of intercellular communication by transferring biological information between cells. Tumor-derived EVs have emerged as important mediators in cancer development and progression, mainly through transfer of their bioactive content which can include oncoproteins, oncogenes, chemokine receptors, as well as soluble factors, transcripts of proteins and miRNAs involved in angiogenesis or inflammation. This transfer has been shown to influence the metastatic behavior of primary tumors. Moreover, tumor-derived EVs have been shown to influence distant cellular niches, establishing favorable microenvironments that support growth of disseminated cancer cells upon their arrival at these pre-metastatic niches. It is generally accepted that cells release a number of major EV populations with distinct biophysical properties and biological functions. Exosomes, microvesicles, and apoptotic bodies are EV populations most widely studied and characterized. They are discriminated based primarily on their intracellular origin. However, increasing evidence suggests that even within these EV populations various subpopulations may exist. This heterogeneity introduces an extra level of complexity in the study of EV biology and function. For example, EV subpopulations could have unique roles in the intricate biological processes underlying cancer biology. Here, we discuss current knowledge regarding the role of subpopulations of EVs in cancer development and progression and highlight the relevance of EV heterogeneity. The position of tetraspanins and integrins therein will be highlighted. Since addressing EV heterogeneity has become essential for the EV field, current and novel techniques for isolating EV subpopulations will also be discussed. Further dissection of EV heterogeneity will advance our understanding of the critical roles of EVs in health and disease.

Multiple data sources improve DNA-based mark-recapture population estimates of grizzly bears.

Science.gov (United States)

Boulanger, John; Kendall, Katherine C; Stetz, Jeffrey B; Roon, David A; Waits, Lisette P; Paetkau, David

2008-04-01

A fundamental challenge to estimating population size with mark-recapture methods is heterogeneous capture probabilities and subsequent bias of population estimates. Confronting this problem usually requires substantial sampling effort that can be difficult to achieve for some species, such as carnivores. We developed a methodology that uses two data sources to deal with heterogeneity and applied this to DNA mark-recapture data from grizzly bears (Ursus arctos). We improved population estimates by incorporating additional DNA "captures" of grizzly bears obtained by collecting hair from unbaited bear rub trees concurrently with baited, grid-based, hair snag sampling. We consider a Lincoln-Petersen estimator with hair snag captures as the initial session and rub tree captures as the recapture session and develop an estimator in program MARK that treats hair snag and rub tree samples as successive sessions. Using empirical data from a large-scale project in the greater Glacier National Park, Montana, USA, area and simulation modeling we evaluate these methods and compare the results to hair-snag-only estimates. Empirical results indicate that, compared with hair-snag-only data, the joint hair-snag-rub-tree methods produce similar but more precise estimates if capture and recapture rates are reasonably high for both methods. Simulation results suggest that estimators are potentially affected by correlation of capture probabilities between sample types in the presence of heterogeneity. Overall, closed population Huggins-Pledger estimators showed the highest precision and were most robust to sparse data, heterogeneity, and capture probability correlation among sampling types. Results also indicate that these estimators can be used when a segment of the population has zero capture probability for one of the methods. We propose that this general methodology may be useful for other species in which mark-recapture data are available from multiple sources.

PHOTOINHIBITION AND RECOVERY IN RELATION TO HETEROGENEITY OF PHOTOSYSTEM-II

NARCIS (Netherlands)

VANWIJK, KJ; SCHNETTGER, B; GRAF, M; KRAUSE, GH

1993-01-01

Photosystem II (PS II) heterogeneity during photoinhibition at 4-degrees-C and subsequent recovery at 20-degrees-C was investigated in spinach leaves and chloroplasts. The population of inactive, Q(B)-nonreducing centers was estimated by means of fluorescence induction in the presence of

Homogenization analysis of invasion dynamics in heterogeneous landscapes with differential bias and motility.

Science.gov (United States)

Yurk, Brian P

2018-07-01

Animal movement behaviors vary spatially in response to environmental heterogeneity. An important problem in spatial ecology is to determine how large-scale population growth and dispersal patterns emerge within highly variable landscapes. We apply the method of homogenization to study the large-scale behavior of a reaction-diffusion-advection model of population growth and dispersal. Our model includes small-scale variation in the directed and random components of movement and growth rates, as well as large-scale drift. Using the homogenized model we derive simple approximate formulas for persistence conditions and asymptotic invasion speeds, which are interpreted in terms of residence index. The homogenization results show good agreement with numerical solutions for environments with a high degree of fragmentation, both with and without periodicity at the fast scale. The simplicity of the formulas, and their connection to residence index make them appealing for studying the large-scale effects of a variety of small-scale movement behaviors.

Spatial Heterogeneity and Population Mobility in India

OpenAIRE

Jajati Keshari Parida; S Madheswaran

2010-01-01

Mobility is one of the important aspects of human nature, which is often guided by socio-economic, political as well as environmental factors. The nature, pattern and direction of population mobility may vary across the space. The dynamics of internal migration in India plays an important role in the process of economic development and social transformation and shows an increasing trend of rural to urban flow over the years. At the same time, it shows falling trends in all other streams of mi...

Investigating the Relationship between Test-Taker Background Characteristics and Test Performance in a Heterogeneous English-as-a-Second-Language (ESL) Test Population: A Factor Analytic Approach. Research Report. ETS RR-15-25

Science.gov (United States)

Manna, Venessa F.; Yoo, Hanwook

2015-01-01

This study examined the heterogeneity in the English-as-a-second-language (ESL) test population by modeling the relationship between test-taker background characteristics and test performance as measured by the "TOEFL iBT"® using a confirmatory factor analysis (CFA) with covariate approach. The background characteristics studied…

Pharmacogenetics in the Brazilian population

Directory of Open Access Journals (Sweden)

Guilherme eSuarez-Kurtz

2010-10-01

Full Text Available Brazil is the 5th largest country in the world and its present population, in excess of 190 million, is highly heterogeneous, as a result of centuries of admixture between Amerindians, Europeans and Sub-Saharan Africans. The estimated individual proportions of biogeographical ancestry vary widely and continuously among Brazilians, most individuals - irrespective of self-identification as White, Brown or Black, the major categories of the Brazilian Census race/color system - having significant degrees of European and African ancestry, while a sizeable number display also Amerindian ancestry. These features have important pharmacogenetic (PGx implications: first, extrapolation of PGx data from relatively well-defined ethnic groups is clearly not applicable to the majority of Brazilians; second, the frequency distribution of polymorphisms in pharmacogenes (e.g. CYP3A5, CYP2C9, GSTM1, ABCB1, GSTM3, VKORC, etc varies continuously among Brazilians and is not captured by race/color self-identification; third, the intrinsic heterogeneity of the Brazilian population must be acknowledged in the design and interpretation of PGx studies in order to avoid spurious conclusions based on improper matching of study cohorts. The peculiarities of PGx in Brazilians are illustrated with data for different therapeutic groups, such as anticoagulants, HIV-protease inhibitors and nonsteroidal antinflammatory drugs, and the challenges and advantages created by population admixture for the study and implementation of PGx are discussed. PGx data for Amerindian groups and Brazilian-born, first generation Japanese are presented to illustrate the rich diversity of the Brazilian population. Finally, I introduce the reader to the Brazilian Pharmacogenetic Network or Refargen (www.refargen.org.br, a nationwide consortium of research groups, with the mission to provide leadership in PGx research and education in Brazil, with a population health impact.

Natriuretic peptides: prediction of cardiovascular disease in the general population and high risk populations

DEFF Research Database (Denmark)

Hildebrandt, Per

2009-01-01

(General Practitioner) setting as in the acute setting. Supporting this use is a very strong prognostic value of the natriuretic peptides. This has been shown in as well heart failure as acute coronary syndromes, but also in the general population and in high-risk groups as patients with diabetes......, hypertension and coronary artery disease. This has of course raised interest for the use of the natriuretic peptides as a risk marker and for screening for heart failure with reduced systolic function in these populations. In symptomatic persons and in high risk populations, the natriuretic peptides have...... demonstrated a high sensitivity for ruling out the disease, if the right decision limits are choosen. Thus the number of normal echocardiographies can be reduced. More recently, the use in screening asymptomatic persons for left ventricular systolic dysfunction has gained more interest. In the unselected...

'Pragmatic randomized controlled trial of individually prescribed exercise versus usual care in a heterogeneous cancer survivor population': a feasibility study PEACH trial: prescribed exercise after chemotherapy.

LENUS (Irish Health Repository)

Walsh, Julie M

2010-01-01

BACKGROUND: Many cancer survivors suffer a range of physical and psychological symptoms which may persist for months or years after cessation of treatment. Despite the known benefits of exercise and its potential to address many of the adverse effects of treatment, the role of exercise as well as optimum duration, frequency, and intensity in this population has yet to be fully elucidated. Many cancer rehabilitation programmes presented in the literature are very long and have tight eligibility criteria which make them non-applicable to the majority of cancer survivors. This paper presents the protocol of a novel 8-week intervention which aims to increase fitness, and address other physical symptoms in a heterogeneous cancer survivor population. METHODS\\/DESIGN: The aim is to recruit 64 cancer survivors 2-6 months after completion of chemotherapy, usually adjuvant, with curative intent. Subjects will be recruited through oncology clinics in a single institution and randomised to usual care or an exercise intervention. The exercise intervention consists of two specifically tailored supervised moderate intensity aerobic exercise sessions weekly over 8-weeks. All participants will be assessed at baseline (0 weeks), at the end of the intervention (8 weeks), and at 3-month follow-up. The primary outcome measure is fitness, and secondary patient-related outcome measures include fatigue, quality of life, and morphological outcomes. A further secondary outcome is process evaluation including adherence to and compliance with the exercise program. DISCUSSION: This study will provide valuable information about the physical outcomes of this 8-week supervised aerobic programme. Additionally, process information and economic evaluation will inform the feasibility of implementing this program in a heterogeneous population post cessation of chemotherapy.

Global gene expression profiling of individual human oocytes and embryos demonstrates heterogeneity in early development.

Directory of Open Access Journals (Sweden)

Lisa Shaw

Full Text Available Early development in humans is characterised by low and variable embryonic viability, reflected in low fecundity and high rates of miscarriage, relative to other mammals. Data from assisted reproduction programmes provides additional evidence that this is largely mediated at the level of embryonic competence and is highly heterogeneous among embryos. Understanding the basis of this heterogeneity has important implications in a number of areas including: the regulation of early human development, disorders of pregnancy, assisted reproduction programmes, the long term health of children which may be programmed in early development, and the molecular basis of pluripotency in human stem cell populations. We have therefore investigated global gene expression profiles using polyAPCR amplification and microarray technology applied to individual human oocytes and 4-cell and blastocyst stage embryos. In order to explore the basis of any variability in detail, each developmental stage is replicated in triplicate. Our data show that although transcript profiles are highly stage-specific, within each stage they are relatively variable. We describe expression of a number of gene families and pathways including apoptosis, cell cycle and amino acid metabolism, which are variably expressed and may be reflective of embryonic developmental competence. Overall, our data suggest that heterogeneity in human embryo developmental competence is reflected in global transcript profiles, and that the vast majority of existing human embryo gene expression data based on pooled oocytes and embryos need to be reinterpreted.

Going deeper into phosphorus adsorbents for lake restoration: Combined effects of magnetic particles, intraspecific competition and habitat heterogeneity pressure on Daphnia magna.

Science.gov (United States)

Del Arco, Ana; Parra, Gema; de Vicente, Inmaculada

2018-02-01

Aquatic population responses to chemical exposure may be exacerbated by intraspecific competition pressures, being also shaped by habitat heterogeneity. Magnetic particles (MPs) have been recently proposed as promising phosphorus (P) adsorbents for lake restoration. This study focuses on assessing the effects of MPs on the abundance of the crustacean Daphnia magna under different levels of both intraspecific competition pressure and habitat heterogeneity. The experimental design consisted of two experiments (in homogeneous and heterogeneous habitats) done in glass jars with four concentrations of MPs: controls of 0g MPsL -1 , and treatments of 1, 1.5 and 2g MPsL -1 . In addition, competition treatments were established by using different population densities, and hence, no competition (C), low (L) and high (H) competition pressures were simulated. The experiments lasted for 7 days, with a 4-day pre-exposure period, in which competition was all allowed to take place, and a 3-day post-exposure period. Twenty-four hours after adding MPs, the MPs were removed by applying a magnetic separation technique. The results showed that competition pressures occurred and significantly reduced population abundances during the pre-exposure period. During the post-exposure period, the combined effects of competition and MPs were detected in both homogeneous (Ho-) and heterogeneous (He-) habitat experiments, showing a significantly drastic reduction in abundances. In fact, the lethal concentration for 50% of the population (LC 50 - 24h) was 0 and 0.16g MPsL -1 in the Ho- and He-experiments respectively, indicating that the addition and especially the removal of MPs cause extreme mortality. These results indicated that even though competition plays a role in shaping populations, its influence was down-weighted by the stronger pressures of MPs. In addition, as no significant differences between homogeneous and heterogeneous habitats were found, we may state that the refuge offered was

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

Science.gov (United States)

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.

Male emergence schedule and dispersal behaviour are modified by mate availability in heterogeneous landscapes: evidence from the orange-tip butterfly

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W James Davies

2015-01-01

Full Text Available Protandry (prior emergence of males in insect populations is usually considered to be the result of natural selection acting directly on eclosion timing. When females are monandrous (mate once, males in high density populations benefit from early emergence in the intense scramble competition for mates. In low density populations, however, scramble competition is reduced or absent, and theoretical models predict that protandry will be less favoured. This raises the question of how males behave in heterogeneous landscapes characterized by high density core populations in a low density continuum. We hypothesized that disadvantaged late emerging males in a core population would disperse to the continuum to find mates. We tested this idea using the protandrous, monandrous, pierid butterfly Anthocharis cardamines (the orange-tip in a core population in Cheshire, northwest England. Over a six-year period, predicted male fitness (the number of matings a male can expect during his residence time, determined by the daily ratio of virgin females to competing males consistently declined to <1 in late season. This decline affected a large proportion (∼44% of males in the population and was strongly associated with decreased male recapture-rates, which we attribute to dispersal to the surrounding continuum. In contrast, reanalysis of mark-release-recapture data from an isolated population in Durham, northeast England, showed that in the absence of a continuum very few males (∼3% emerged when fitness declined to <1 in late season. Hence the existence of a low density continuum may lead to the evolution of plastic dispersal behaviour in high density core populations, maintaining late emerging males which would otherwise be eliminated by selection. This has important theoretical consequences, since a truncated male emergence curve is a key prediction in game theoretic models of emergence timing which has so far received limited support. Our results have

SinCHet: a MATLAB toolbox for single cell heterogeneity analysis in cancer.

Science.gov (United States)

Li, Jiannong; Smalley, Inna; Schell, Michael J; Smalley, Keiran S M; Chen, Y Ann

2017-09-15

Single-cell technologies allow characterization of transcriptomes and epigenomes for individual cells under different conditions and provide unprecedented resolution for researchers to investigate cellular heterogeneity in cancer. The SinCHet ( gle ell erogeneity) toolbox is developed in MATLAB and has a graphical user interface (GUI) for visualization and user interaction. It analyzes both continuous (e.g. mRNA expression) and binary omics data (e.g. discretized methylation data). The toolbox does not only quantify cellular heterogeneity using S hannon P rofile (SP) at different clonal resolutions but also detects heterogeneity differences using a D statistic between two populations. It is defined as the area under the P rofile of S hannon D ifference (PSD). This flexible tool provides a default clonal resolution using the change point of PSD detected by multivariate adaptive regression splines model; it also allows user-defined clonal resolutions for further investigation. This tool provides insights into emerging or disappearing clones between conditions, and enables the prioritization of biomarkers for follow-up experiments based on heterogeneity or marker differences between and/or within cell populations. The SinCHet software is freely available for non-profit academic use. The source code, example datasets, and the compiled package are available at http://labpages2.moffitt.org/chen/software/ . ann.chen@moffitt.org. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

IDENTIFIABILITY VERSUS HETEROGENEITY IN GROUNDWATER MODELING SYSTEMS

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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.

Titanium Dioxide as a Catalyst Support in Heterogeneous Catalysis

Science.gov (United States)

Bagheri, Samira; Muhd Julkapli, Nurhidayatullaili; Bee Abd Hamid, Sharifah

2014-01-01

The lack of stability is a challenge for most heterogeneous catalysts. During operations, the agglomeration of particles may block the active sites of the catalyst, which is believed to contribute to its instability. Recently, titanium oxide (TiO2) was introduced as an alternative support material for heterogeneous catalyst due to the effect of its high surface area stabilizing the catalysts in its mesoporous structure. TiO2 supported metal catalysts have attracted interest due to TiO2 nanoparticles high activity for various reduction and oxidation reactions at low pressures and temperatures. Furthermore, TiO2 was found to be a good metal oxide catalyst support due to the strong metal support interaction, chemical stability, and acid-base property. The aforementioned properties make heterogeneous TiO2 supported catalysts show a high potential in photocatalyst-related applications, electrodes for wet solar cells, synthesis of fine chemicals, and others. This review focuses on TiO2 as a support material for heterogeneous catalysts and its potential applications. PMID:25383380

Evaluation on island ecological vulnerability and its spatial heterogeneity.

Science.gov (United States)

Chi, Yuan; Shi, Honghua; Wang, Yuanyuan; Guo, Zhen; Wang, Enkang

2017-12-15

The evaluation on island ecological vulnerability (IEV) can help reveal the comprehensive characteristics of the island ecosystem and provide reference for controlling human activities on islands. An IEV evaluation model which reflects the land-sea dual features, natural and anthropogenic attributes, and spatial heterogeneity of the island ecosystem was established, and the southern islands of Miaodao Archipelago in North China were taken as the study area. The IEV, its spatial heterogeneity, and its sensitivities to the evaluation elements were analyzed. Results indicated that the IEV was in status of mild vulnerability in the archipelago scale, and population pressure, ecosystem productivity, environmental quality, landscape pattern, and economic development were the sensitive elements. The IEV showed significant spatial heterogeneities both in land and surrounding waters sub-ecosystems. Construction scale control, optimization of development allocation, improvement of exploitation methods, and reasonable ecological construction are important measures to control the IEV. Copyright © 2017 Elsevier Ltd. All rights reserved.

Adoption of a High-Impact Innovation in a Homogeneous Population

Directory of Open Access Journals (Sweden)

Curtis H. Weiss

2014-10-01

Full Text Available Adoption of innovations, whether new ideas, technologies, or products, is crucially important to knowledge societies. The landmark studies of adoption dealt with innovations having great societal impact (such as antibiotics or hybrid crops but where determining the utility of the innovation was straightforward (such as fewer side effects or greater yield. Recent large-scale studies of adoption were conducted within heterogeneous populations and focused on products with little societal impact. Here, we focus on a case with great practical significance: adoption by small groups of highly trained individuals of innovations with large societal impact but for which it is impractical to determine the true utility of the innovation. Specifically, we study experimentally the adoption by critical care physicians of a diagnostic assay that complements current protocols for the diagnosis of life-threatening bacterial infections and for which a physician cannot estimate the true accuracy of the assay based on personal experience. We show through computational modeling of the experiment that infection-spreading models—which have been formalized as generalized contagion processes—are not consistent with the experimental data, while a model inspired by opinion models is able to reproduce the empirical data. Our modeling approach enables us to investigate the efficacy of different intervention schemes on the rate and robustness of innovation adoption in the real world. While our study is focused on critical care physicians, our findings have implications for other settings in education, research, and business, where small groups of highly qualified peers make decisions about the adoption of innovations whose utility is difficult if not impossible to gauge.

Solving radiative transfer problems in highly heterogeneous media via domain decomposition and convergence acceleration techniques

International Nuclear Information System (INIS)

Previti, Alberto; Furfaro, Roberto; Picca, Paolo; Ganapol, Barry D.; Mostacci, Domiziano

2011-01-01

This paper deals with finding accurate solutions for photon transport problems in highly heterogeneous media fastly, efficiently and with modest memory resources. We propose an extended version of the analytical discrete ordinates method, coupled with domain decomposition-derived algorithms and non-linear convergence acceleration techniques. Numerical performances are evaluated using a challenging case study available in the literature. A study of accuracy versus computational time and memory requirements is reported for transport calculations that are relevant for remote sensing applications.

Temperature-associated population diversity in salmon confers benefits to mobile consumers

Science.gov (United States)

Ruff, Casey P.; Schindle, Daniel E.; Armstrong, Jonathan B.; Bentle, Kale T.; Brooks, Gabriel T.; Holtgrieve, Gordon W.; McGlauflin, Molly T.; Torgersen, Christian E.; Seeb, James E.

2011-01-01

Habitat heterogeneity can generate intraspecific diversity through local adaptation of populations. While it is becoming increasingly clear that population diversity can increase stability in species abundance, less is known about how population diversity can benefit consumers that can integrate across population diversity in their prey. Here we demonstrate cascading effects of thermal heterogeneity on trout–salmon interactions in streams where rainbow trout rely heavily on the seasonal availability of anadromous salmon eggs. Water temperature in an Alaskan stream varied spatially from 5°C to 17.5°C, and spawning sockeye salmon showed population differentiation associated with this thermal heterogeneity. Individuals that spawned early in cool regions of the 5 km long stream were genetically differentiated from those spawning in warmer regions later in the season. Sockeye salmon spawning generates a pulsed resource subsidy that supports the majority of seasonal growth in stream-dwelling rainbow trout. The spatial and temporal structuring of sockeye salmon spawn timing in our focal stream extended the duration of the pulsed subsidy compared to a thermally homogeneous stream with a single population of salmon. Further, rainbow trout adopted movement strategies that exploited the multiple pulses of egg subsidies in the thermally heterogeneous stream. Fish that moved to track the resource pulse grew at rates about 2.5 times higher than those that remained stationary or trout in the reference stream with a single seasonal pulse of eggs. Our results demonstrate that habitat heterogeneity can have important effects on the population diversity of dominant species, and in turn, influence their value to species that prey upon them. Therefore, habitat homogenization may have farther-reaching ecological effects than previously considered.

A high performance image processing platform based on CPU-GPU heterogeneous cluster with parallel image reconstroctions for micro-CT

International Nuclear Information System (INIS)

Ding Yu; Qi Yujin; Zhang Xuezhu; Zhao Cuilan

2011-01-01

In this paper, we report the development of a high-performance image processing platform, which is based on CPU-GPU heterogeneous cluster. Currently, it consists of a Dell Precision T7500 and HP XW8600 workstations with parallel programming and runtime environment, using the message-passing interface (MPI) and CUDA (Compute Unified Device Architecture). We succeeded in developing parallel image processing techniques for 3D image reconstruction of X-ray micro-CT imaging. The results show that a GPU provides a computing efficiency of about 194 times faster than a single CPU, and the CPU-GPU clusters provides a computing efficiency of about 46 times faster than the CPU clusters. These meet the requirements of rapid 3D image reconstruction and real time image display. In conclusion, the use of CPU-GPU heterogeneous cluster is an effective way to build high-performance image processing platform. (authors)

Numerical calculations on heterogeneity of groundwater flow

International Nuclear Information System (INIS)

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.)

Declines in low-elevation subalpine tree populations outpace growth in high-elevation populations with warming

Science.gov (United States)

Conlisk, Erin; Castanha, Cristina; Germino, Matthew J.; Veblen, Thomas T; Smith, Jeremy M.; Kueppers, Lara M.

2017-01-01

Species distribution shifts in response to climate change require that recruitment increase beyond current range boundaries. For trees with long life spans, the importance of climate-sensitive seedling establishment to the pace of range shifts has not been demonstrated quantitatively.Using spatially explicit, stochastic population models combined with data from long-term forest surveys, we explored whether the climate-sensitivity of recruitment observed in climate manipulation experiments was sufficient to alter populations and elevation ranges of two widely distributed, high-elevation North American conifers.Empirically observed, warming-driven declines in recruitment led to rapid modelled population declines at the low-elevation, ‘warm edge’ of subalpine forest and slow emergence of populations beyond the high-elevation, ‘cool edge’. Because population declines in the forest occurred much faster than population emergence in the alpine, we observed range contraction for both species. For Engelmann spruce, this contraction was permanent over the modelled time horizon, even in the presence of increased moisture. For limber pine, lower sensitivity to warming may facilitate persistence at low elevations – especially in the presence of increased moisture – and rapid establishment above tree line, and, ultimately, expansion into the alpine.Synthesis. Assuming 21st century warming and no additional moisture, population dynamics in high-elevation forests led to transient range contractions for limber pine and potentially permanent range contractions for Engelmann spruce. Thus, limitations to seedling recruitment with warming can constrain the pace of subalpine tree range shifts.

Whole genome sequencing reveals genomic heterogeneity and antibiotic purification in Mycobacterium tuberculosis isolates

KAUST Repository

Black, PA

2015-10-24

Background Whole genome sequencing has revolutionised the interrogation of mycobacterial genomes. Recent studies have reported conflicting findings on the genomic stability of Mycobacterium tuberculosis during the evolution of drug resistance. In an age where whole genome sequencing is increasingly relied upon for defining the structure of bacterial genomes, it is important to investigate the reliability of next generation sequencing to identify clonal variants present in a minor percentage of the population. This study aimed to define a reliable cut-off for identification of low frequency sequence variants and to subsequently investigate genetic heterogeneity and the evolution of drug resistance in M. tuberculosis. Methods Genomic DNA was isolated from single colonies from 14 rifampicin mono-resistant M. tuberculosis isolates, as well as the primary cultures and follow up MDR cultures from two of these patients. The whole genomes of the M. tuberculosis isolates were sequenced using either the Illumina MiSeq or Illumina HiSeq platforms. Sequences were analysed with an in-house pipeline. Results Using next-generation sequencing in combination with Sanger sequencing and statistical analysis we defined a read frequency cut-off of 30 % to identify low frequency M. tuberculosis variants with high confidence. Using this cut-off we demonstrated a high rate of genetic diversity between single colonies isolated from one population, showing that by using the current sequencing technology, single colonies are not a true reflection of the genetic diversity within a whole population and vice versa. We further showed that numerous heterogeneous variants emerge and then disappear during the evolution of isoniazid resistance within individual patients. Our findings allowed us to formulate a model for the selective bottleneck which occurs during the course of infection, acting as a genomic purification event. Conclusions Our study demonstrated true levels of genetic diversity

Research on the Effects of Heterogeneity on Pedestrian Dynamics in Walkway of Subway Station

Directory of Open Access Journals (Sweden)

Haoling Wu

2016-01-01

Full Text Available The major objective of this paper is to study the effects of heterogeneity on pedestrian dynamics in walkway of subway station. We analyze the observed data of the selected facility and find that walking speed and occupied space were varied in the population. In reality, pedestrians are heterogeneous individuals with different attributes. However, the research on how the heterogeneity affects the pedestrian dynamics in facilities of subway stations is insufficient. The improved floor field model is therefore presented to explore the effects of heterogeneity. Pedestrians are classified into pedestrians walking in pairs, fast pedestrians, and ordinary pedestrians. For convenience, they are denoted as P-pedestrians, F-pedestrians, and O-pedestrians, respectively. The proposed model is validated under homogeneous and heterogeneous conditions. Three pedestrian compositions are simulated to analyze the effects of heterogeneity on pedestrian dynamics. The results show that P-pedestrians have negative effect and F-pedestrians have positive effect. All of the results in this paper indicate that the capacity of walkway is not a constant value. It changes with different component proportions of heterogeneous pedestrians. The heterogeneity of pedestrian has an important influence on the pedestrian dynamics in the walkway of the subway station.

Homogeneous, heterogeneous and enzymatic catalysis for transesterification of high free fatty acid oil (waste cooking oil) to biodiesel: a review.

Science.gov (United States)

Lam, Man Kee; Lee, Keat Teong; Mohamed, Abdul Rahman

2010-01-01

In the last few years, biodiesel has emerged as one of the most potential renewable energy to replace current petrol-derived diesel. It is a renewable, biodegradable and non-toxic fuel which can be easily produced through transesterification reaction. However, current commercial usage of refined vegetable oils for biodiesel production is impractical and uneconomical due to high feedstock cost and priority as food resources. Low-grade oil, typically waste cooking oil can be a better alternative; however, the high free fatty acids (FFA) content in waste cooking oil has become the main drawback for this potential feedstock. Therefore, this review paper is aimed to give an overview on the current status of biodiesel production and the potential of waste cooking oil as an alternative feedstock. Advantages and limitations of using homogeneous, heterogeneous and enzymatic transesterification on oil with high FFA (mostly waste cooking oil) are discussed in detail. It was found that using heterogeneous acid catalyst and enzyme are the best option to produce biodiesel from oil with high FFA as compared to the current commercial homogeneous base-catalyzed process. However, these heterogeneous acid and enzyme catalyze system still suffers from serious mass transfer limitation problems and therefore are not favorable for industrial application. Nevertheless, towards the end of this review paper, a few latest technological developments that have the potential to overcome the mass transfer limitation problem such as oscillatory flow reactor (OFR), ultrasonication, microwave reactor and co-solvent are reviewed. With proper research focus and development, waste cooking oil can indeed become the next ideal feedstock for biodiesel.

Evaluation of trap capture in a geographically closed population of brown treesnakes on Guam

Science.gov (United States)

Tyrrell, C.L.; Christy, M.T.; Rodda, G.H.; Yackel Adams, A.A.; Ellingson, A.R.; Savidge, J.A.; Dean-Bradley, K.; Bischof, R.

2009-01-01

1. Open population mark-recapture analysis of unbounded populations accommodates some types of closure violations (e.g. emigration, immigration). In contrast, closed population analysis of such populations readily allows estimation of capture heterogeneity and behavioural response, but requires crucial assumptions about closure (e.g. no permanent emigration) that are suspect and rarely tested empirically. 2. In 2003, we erected a double-sided barrier to prevent movement of snakes in or out of a 5-ha semi-forested study site in northern Guam. This geographically closed population of >100 snakes was monitored using a series of transects for visual searches and a 13 ?? 13 trapping array, with the aim of marking all snakes within the site. Forty-five marked snakes were also supplemented into the resident population to quantify the efficacy of our sampling methods. We used the program mark to analyse trap captures (101 occasions), referenced to census data from visual surveys, and quantified heterogeneity, behavioural response, and size bias in trappability. Analytical inclusion of untrapped individuals greatly improved precision in the estimation of some covariate effects. 3. A novel discovery was that trap captures for individual snakes consisted of asynchronous bouts of high capture probability lasting about 7 days (ephemeral behavioural effect). There was modest behavioural response (trap happiness) and significant latent (unexplained) heterogeneity, with small influences on capture success of date, gender, residency status (translocated or not), and body condition. 4. Trapping was shown to be an effective tool for eradicating large brown treesnakes Boiga irregularis (>900 mm snout-vent length, SVL). 5. Synthesis and applications. Mark-recapture modelling is commonly used by ecological managers to estimate populations. However, existing models involve making assumptions about either closure violations or response to capture. Physical closure of our population on a

The population program shifts to 'high-scenario' targets.

Science.gov (United States)

Aragon-choudury, P

1986-01-01

The Philippine Population Program would like to achieve a replacement level of 1 daughter per childbearing woman by the year 2000 to reduce the population growth rate to 2% by 1992. Laing projected that high performance by the National Population Program would mean continued increase of sterilization prevalence at an average 1978-1983 rate. Strategies have been adopted to strengthen information-education-communication efforts, to attain higher contraceptive prevalence rates and use-effectiveness, to develop manpower, to achieve self-reliance, and to effect better program coordination, monitoring, research use. Effective service delivery will be a key to achieving the high-scenario targets. Effective use of natural family planning (NFP), will help in achieving the high-scenario goals. Apart from the heavy demand on NFP follow-up, need for prompt delivery of supplies, and lack of doctors and nurses, other factors may impede the high-scenario targets. Saniel believes that program workers should be allowed to insert IUDs and to dispense pills. Under the cost-recovery and cost-sharing schemes of the high-scenario targets, only sterilization will be done for free. It might affect the campaign for increased acceptors, but the start for self-reliance must happen now.

Numerical Study of Critical Role of Rock Heterogeneity in Hydraulic Fracture Propagation

Energy Technology Data Exchange (ETDEWEB)

J. Zhou; H. Huang; M. Deo

2016-03-01

Log and seismic data indicate that most shale formations have strong heterogeneity. Conventional analytical and semi-analytical fracture models are not enough to simulate the complex fracture propagation in these highly heterogeneous formation. Without considering the intrinsic heterogeneity, predicted morphology of hydraulic fracture may be biased and misleading in optimizing the completion strategy. In this paper, a fully coupling fluid flow and geomechanics hydraulic fracture simulator based on dual-lattice Discrete Element Method (DEM) is used to predict the hydraulic fracture propagation in heterogeneous reservoir. The heterogeneity of rock is simulated by assigning different material force constant and critical strain to different particles and is adjusted by conditioning to the measured data and observed geological features. Based on proposed model, the effects of heterogeneity at different scale on micromechanical behavior and induced macroscopic fractures are examined. From the numerical results, the microcrack will be more inclined to form at the grain weaker interface. The conventional simulator with homogeneous assumption is not applicable for highly heterogeneous shale formation.

Evaluation of Segmentation Bases for the Heterogeneous Elderly Consumer Population: the Functional Food Market

NARCIS (Netherlands)

Zanden, van der L.D.T.; Kleef, van E.; Wijk, de R.A.; Trijp, van J.C.M.

2014-01-01

It is beneficial for both the public health community and the food industry to meet nutritional needs of elderly consumers through product formats that they want. The heterogeneity of the elderly market poses a challenge, however, and calls for market segmentation. Although many researchers have

Heterogeneous all-solid multicore fiber based multipath Michelson interferometer for high temperature sensing.

Science.gov (United States)

Duan, Li; Zhang, Peng; Tang, Ming; Wang, Ruoxu; Zhao, Zhiyong; Fu, Songnian; Gan, Lin; Zhu, Benpeng; Tong, Weijun; Liu, Deming; Shum, Perry Ping

2016-09-05

A compact high temperature sensor utilizing a multipath Michelson interferometer (MI) structure based on weak coupling multicore fiber (MCF) is proposed and experimentally demonstrated. The device is fabricated by program-controlled tapering the spliced region between single mode fiber (SMF) and a segment of MCF. After that, a spherical reflective structure is formed by arc-fusion splicing the end face of MCF. Theoretical analysis has been implemented for this specific multipath MI structure; beam propagation method based simulation and corresponding experiments were performed to investigate the effect of taper and spherical end face on system's performance. Benefiting from the multipath interferences and heterogeneous structure between the center core and surrounding cores of the all-solid MCF, an enhanced temperature sensitivity of 165 pm/°C up to 900°C and a high-quality interference spectrum with 25 dB fringe visibility were achieved.

Nano-catalysts: Bridging the gap between homogeneous and heterogeneous catalysis

Science.gov (United States)

Functionalized nanoparticles have emerged as sustainable alternatives to conventional materials, as robust, high-surface-area heterogeneous catalyst supports. We envisioned a catalyst system, which can bridge the homogenous and heterogeneous system. Postsynthetic surface modifica...

High temporal resolution mapping of seismic noise sources using heterogeneous supercomputers

Science.gov (United States)

Gokhberg, Alexey; Ermert, Laura; Paitz, Patrick; Fichtner, Andreas

2017-04-01

Time- and space-dependent distribution of seismic noise sources is becoming a key ingredient of modern real-time monitoring of various geo-systems. Significant interest in seismic noise source maps with high temporal resolution (days) is expected to come from a number of domains, including natural resources exploration, analysis of active earthquake fault zones and volcanoes, as well as geothermal and hydrocarbon reservoir monitoring. Currently, knowledge of noise sources is insufficient for high-resolution subsurface monitoring applications. Near-real-time seismic data, as well as advanced imaging methods to constrain seismic noise sources have recently become available. These methods are based on the massive cross-correlation of seismic noise records from all available seismic stations in the region of interest and are therefore very computationally intensive. Heterogeneous massively parallel supercomputing systems introduced in the recent years combine conventional multi-core CPU with GPU accelerators and provide an opportunity for manifold increase and computing performance. Therefore, these systems represent an efficient platform for implementation of a noise source mapping solution. We present the first results of an ongoing research project conducted in collaboration with the Swiss National Supercomputing Centre (CSCS). The project aims at building a service that provides seismic noise source maps for Central Europe with high temporal resolution (days to few weeks depending on frequency and data availability). The service is hosted on the CSCS computing infrastructure; all computationally intensive processing is performed on the massively parallel heterogeneous supercomputer "Piz Daint". The solution architecture is based on the Application-as-a-Service concept in order to provide the interested external researchers the regular access to the noise source maps. The solution architecture includes the following sub-systems: (1) data acquisition responsible for

Image-based computational quantification and visualization of genetic alterations and tumour heterogeneity.

Science.gov (United States)

Zhong, Qing; Rüschoff, Jan H; Guo, Tiannan; Gabrani, Maria; Schüffler, Peter J; Rechsteiner, Markus; Liu, Yansheng; Fuchs, Thomas J; Rupp, Niels J; Fankhauser, Christian; Buhmann, Joachim M; Perner, Sven; Poyet, Cédric; Blattner, Miriam; Soldini, Davide; Moch, Holger; Rubin, Mark A; Noske, Aurelia; Rüschoff, Josef; Haffner, Michael C; Jochum, Wolfram; Wild, Peter J

2016-04-07

Recent large-scale genome analyses of human tissue samples have uncovered a high degree of genetic alterations and tumour heterogeneity in most tumour entities, independent of morphological phenotypes and histopathological characteristics. Assessment of genetic copy-number variation (CNV) and tumour heterogeneity by fluorescence in situ hybridization (ISH) provides additional tissue morphology at single-cell resolution, but it is labour intensive with limited throughput and high inter-observer variability. We present an integrative method combining bright-field dual-colour chromogenic and silver ISH assays with an image-based computational workflow (ISHProfiler), for accurate detection of molecular signals, high-throughput evaluation of CNV, expressive visualization of multi-level heterogeneity (cellular, inter- and intra-tumour heterogeneity), and objective quantification of heterogeneous genetic deletions (PTEN) and amplifications (19q12, HER2) in diverse human tumours (prostate, endometrial, ovarian and gastric), using various tissue sizes and different scanners, with unprecedented throughput and reproducibility.

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

Science.gov (United States)

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

Chloride Transport in Heterogeneous Formation

Science.gov (United States)

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.

Scale-dependent effects of a heterogeneous landscape on genetic differentiation in the Central American squirrel monkey (Saimiri oerstedii.

Directory of Open Access Journals (Sweden)

Mary E Blair

Full Text Available Landscape genetic studies offer a fine-scale understanding of how habitat heterogeneity influences population genetic structure. We examined population genetic structure and conducted a landscape genetic analysis for the endangered Central American Squirrel Monkey (Saimiri oerstedii that lives in the fragmented, human-modified habitats of the Central Pacific region of Costa Rica. We analyzed non-invasively collected fecal samples from 244 individuals from 14 groups for 16 microsatellite markers. We found two geographically separate genetic clusters in the Central Pacific region with evidence of recent gene flow among them. We also found significant differentiation among groups of S. o. citrinellus using pairwise F(ST comparisons. These groups are in fragments of secondary forest separated by unsuitable "matrix" habitats such as cattle pasture, commercial African oil palm plantations, and human residential areas. We used an individual-based landscape genetic approach to measure spatial patterns of genetic variance while taking into account landscape heterogeneity. We found that large, commercial oil palm plantations represent moderate barriers to gene flow between populations, but cattle pastures, rivers, and residential areas do not. However, the influence of oil palm plantations on genetic variance was diminished when we restricted analyses to within population pairs, suggesting that their effect is scale-dependent and manifests during longer dispersal events among populations. We show that when landscape genetic methods are applied rigorously and at the right scale, they are sensitive enough to track population processes even in species with long, overlapping generations such as primates. Thus landscape genetic approaches are extremely valuable for the conservation management of a diverse array of endangered species in heterogeneous, human-modified habitats. Our results also stress the importance of explicitly considering the heterogeneity of

Impact of Heterogeneity in Sexual Behavior on Effectiveness in Reducing HIV Transmission with Test-and-Treat Strategy.

Directory of Open Access Journals (Sweden)

Ganna Rozhnova

2016-08-01

Full Text Available The WHO's early-release guideline for antiretroviral treatment (ART of HIV infection based on a recent trial conducted in 34 countries recommends starting treatment immediately upon an HIV diagnosis. Therefore, the test-and-treat strategy may become more widely used in an effort to scale up HIV treatment and curb further transmission. Here we examine behavioural determinants of HIV transmission and how heterogeneity in sexual behaviour influences the outcomes of this strategy. Using a deterministic model, we perform a systematic investigation into the effects of various mixing patterns in a population of men who have sex with men (MSM, stratified by partner change rates, on the elimination threshold and endemic HIV prevalence. We find that both the level of overdispersion in the distribution of the number of sexual partners and mixing between population subgroups have a large influence on endemic prevalence before introduction of ART and on possible long term effectiveness of ART. Increasing heterogeneity in risk behavior may lead to lower endemic prevalence levels, but requires higher coverage levels of ART for elimination. Elimination is only feasible for populations with a rather low degree of assortativeness of mixing and requires treatment coverage of almost 80% if rates of testing and treatment uptake by all population subgroups are equal. In this case, for fully assortative mixing and 80% coverage endemic prevalence is reduced by 57%. In the presence of heterogeneity in ART uptake, elimination is easier to achieve when the subpopulation with highest risk behavior is tested and treated more often than the rest of the population, and vice versa when it is less. The developed framework can be used to extract information on behavioral heterogeneity from existing data which is otherwise hard to determine from population surveys.

Visual Analytics for Heterogeneous Geoscience Data

Science.gov (United States)

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

Screening of Chlamydomonas reinhardtii Populations with Single-Cell Resolution by Using a High-Throughput Microscale Sample Preparation for Matrix-Assisted Laser Desorption Ionization Mass Spectrometry.

Science.gov (United States)

Krismer, Jasmin; Sobek, Jens; Steinhoff, Robert F; Fagerer, Stephan R; Pabst, Martin; Zenobi, Renato

2015-08-15

The consequences of cellular heterogeneity, such as biocide persistence, can only be tackled by studying each individual in a cell population. Fluorescent tags provide tools for the high-throughput analysis of genomes, RNA transcripts, or proteins on the single-cell level. However, the analysis of lower-molecular-weight compounds that elude tagging is still a great challenge. Here, we describe a novel high-throughput microscale sample preparation technique for single cells that allows a mass spectrum to be obtained for each individual cell within a microbial population. The approach presented includes spotting Chlamydomonas reinhardtii cells, using a noncontact microarrayer, onto a specialized slide and controlled lysis of cells separated on the slide. Throughout the sample preparation, analytes were traced and individual steps optimized using autofluorescence detection of chlorophyll. The lysates of isolated cells are subjected to a direct, label-free analysis using matrix-assisted laser desorption ionization mass spectrometry. Thus, we were able to differentiate individual cells of two Chlamydomonas reinhardtii strains based on single-cell mass spectra. Furthermore, we showed that only population profiles with real single-cell resolution render a nondistorted picture of the phenotypes contained in a population. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Functional heterogeneity and heritability in CHO cell populations.

Science.gov (United States)

Davies, Sarah L; Lovelady, Clare S; Grainger, Rhian K; Racher, Andrew J; Young, Robert J; James, David C

2013-01-01

In this study, we address the hypothesis that it is possible to exploit genetic/functional variation in parental Chinese hamster ovary (CHO) cell populations to isolate clonal derivatives that exhibit superior, heritable attributes for biomanufacturing--new parental cell lines which are inherently more "fit for purpose." One-hundred and ninety-nine CHOK1SV clones were isolated from a donor CHOK1SV parental population by limiting dilution cloning and microplate image analysis, followed by primary analysis of variation in cell-specific proliferation rate during extended deep-well microplate suspension culture of individual clones to accelerate genetic drift in isolated cultures. A subset of 100 clones were comparatively evaluated for transient production of a recombinant monoclonal antibody (Mab) and green fluorescent protein following transfection of a plasmid vector encoding both genes. The heritability of both cell-specific proliferation rate and Mab production was further assessed using a subset of 23 clones varying in functional capability that were subjected to cell culture regimes involving both cryopreservation and extended sub-culture. These data showed that whilst differences in transient Mab production capability were not heritable per se, clones exhibiting heritable variation in specific proliferation rate, endocytotic transfectability and N-glycan processing were identified. Finally, for clonal populations most "evolved" by extended sub-culture in vitro we investigated the relationship between cellular protein biomass content, specific proliferation rate and cell surface N-glycosylation. Rapid-specific proliferation rate was inversely correlated to CHO cell size and protein content, and positively correlated to cell surface glycan content, although substantial clone-specific variation in ability to accumulate cell biomass was evident. Taken together, our data reveal the dynamic nature of the CHO cell functional genome and the potential to evolve and

Skeeter Buster: a stochastic, spatially explicit modeling tool for studying Aedes aegypti population replacement and population suppression strategies.

Directory of Open Access Journals (Sweden)

Krisztian Magori

2009-09-01

Full Text Available Dengue is the most important mosquito-borne viral disease affecting humans. The only prevention measure currently available is the control of its vectors, primarily Aedes aegypti. Recent advances in genetic engineering have opened the possibility for a new range of control strategies based on genetically modified mosquitoes. Assessing the potential efficacy of genetic (and conventional strategies requires the availability of modeling tools that accurately describe the dynamics and genetics of Ae. aegypti populations.We describe in this paper a new modeling tool of Ae. aegypti population dynamics and genetics named Skeeter Buster. This model operates at the scale of individual water-filled containers for immature stages and individual properties (houses for adults. The biology of cohorts of mosquitoes is modeled based on the algorithms used in the non-spatial Container Inhabiting Mosquitoes Simulation Model (CIMSiM. Additional features incorporated into Skeeter Buster include stochasticity, spatial structure and detailed population genetics. We observe that the stochastic modeling of individual containers in Skeeter Buster is associated with a strongly reduced temporal variation in stage-specific population densities. We show that heterogeneity in container composition of individual properties has a major impact on spatial heterogeneity in population density between properties. We detail how adult dispersal reduces this spatial heterogeneity. Finally, we present the predicted genetic structure of the population by calculating F(ST values and isolation by distance patterns, and examine the effects of adult dispersal and container movement between properties.We demonstrate that the incorporated stochasticity and level of spatial detail have major impacts on the simulated population dynamics, which could potentially impact predictions in terms of control measures. The capacity to describe population genetics confers the ability to model the outcome

Heterogeneous network architectures

DEFF Research Database (Denmark)

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...

Effects of heterogeneous wealth distribution on public cooperation with collective risk

Science.gov (United States)

Wang, Jing; Fu, Feng; Wang, Long

2010-07-01

The distribution of wealth among individuals in real society can be well described by the Pareto principle or “80-20 rule.” How does such heterogeneity in initial wealth distribution affect the emergence of public cooperation, when individuals, the rich and the poor, engage in a collective-risk enterprise, not to gain a profit but to avoid a potential loss? Here we address this issue by studying a simple but effective model based on threshold public goods games. We analyze the evolutionary dynamics for two distinct scenarios, respectively: one with fair sharers versus defectors and the other with altruists versus defectors. For both scenarios, particularly, we in detail study the dynamics of the population with dichotomic initial wealth—the rich versus the poor. Moreover, we demonstrate the possible steady compositions of the population and provide the conditions for stability of these steady states. We prove that in a population with heterogeneous wealth distribution, richer individuals are more likely to cooperate than poorer ones. Participants with lower initial wealth may choose to cooperate only if all players richer than them are cooperators. The emergence of pubic cooperation largely relies on rich individuals. Furthermore, whenever the wealth gap between the rich and the poor is sufficiently large, cooperation of a few rich individuals can substantially elevate the overall level of social cooperation, which is in line with the well-known Pareto principle. Our work may offer an insight into the emergence of cooperative behavior in real social situations where heterogeneous distribution of wealth among individual is omnipresent.

Neuroanatomical heterogeneity of schizophrenia revealed by semi-supervised machine learning methods.

Science.gov (United States)

Honnorat, Nicolas; Dong, Aoyan; Meisenzahl-Lechner, Eva; Koutsouleris, Nikolaos; Davatzikos, Christos

2017-12-20

Schizophrenia is associated with heterogeneous clinical symptoms and neuroanatomical alterations. In this work, we aim to disentangle the patterns of neuroanatomical alterations underlying a heterogeneous population of patients using a semi-supervised clustering method. We apply this strategy to a cohort of patients with schizophrenia of varying extends of disease duration, and we describe the neuroanatomical, demographic and clinical characteristics of the subtypes discovered. We analyze the neuroanatomical heterogeneity of 157 patients diagnosed with Schizophrenia, relative to a control population of 169 subjects, using a machine learning method called CHIMERA. CHIMERA clusters the differences between patients and a demographically-matched population of healthy subjects, rather than clustering patients themselves, thereby specifically assessing disease-related neuroanatomical alterations. Voxel-Based Morphometry was conducted to visualize the neuroanatomical patterns associated with each group. The clinical presentation and the demographics of the groups were then investigated. Three subgroups were identified. The first two differed substantially, in that one involved predominantly temporal-thalamic-peri-Sylvian regions, whereas the other involved predominantly frontal regions and the thalamus. Both subtypes included primarily male patients. The third pattern was a mix of these two and presented milder neuroanatomic alterations and comprised a comparable number of men and women. VBM and statistical analyses suggest that these groups could correspond to different neuroanatomical dimensions of schizophrenia. Our analysis suggests that schizophrenia presents distinct neuroanatomical variants. This variability points to the need for a dimensional neuroanatomical approach using data-driven, mathematically principled multivariate pattern analysis methods, and should be taken into account in clinical studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of heterogeneous wealth distribution on public cooperation with collective risk.

Science.gov (United States)

Wang, Jing; Fu, Feng; Wang, Long

2010-07-01

The distribution of wealth among individuals in real society can be well described by the Pareto principle or "80-20 rule." How does such heterogeneity in initial wealth distribution affect the emergence of public cooperation, when individuals, the rich and the poor, engage in a collective-risk enterprise, not to gain a profit but to avoid a potential loss? Here we address this issue by studying a simple but effective model based on threshold public goods games. We analyze the evolutionary dynamics for two distinct scenarios, respectively: one with fair sharers versus defectors and the other with altruists versus defectors. For both scenarios, particularly, we in detail study the dynamics of the population with dichotomic initial wealth-the rich versus the poor. Moreover, we demonstrate the possible steady compositions of the population and provide the conditions for stability of these steady states. We prove that in a population with heterogeneous wealth distribution, richer individuals are more likely to cooperate than poorer ones. Participants with lower initial wealth may choose to cooperate only if all players richer than them are cooperators. The emergence of pubic cooperation largely relies on rich individuals. Furthermore, whenever the wealth gap between the rich and the poor is sufficiently large, cooperation of a few rich individuals can substantially elevate the overall level of social cooperation, which is in line with the well-known Pareto principle. Our work may offer an insight into the emergence of cooperative behavior in real social situations where heterogeneous distribution of wealth among individual is omnipresent.

Heterogeneity of the HIV epidemic in the general population of Karnataka state, south India

Directory of Open Access Journals (Sweden)

Banandur Pradeep

2011-12-01

Full Text Available Abstract Background In the context of AVAHAN, the India AIDS Initiative of the Bill & Melinda Gates Foundation, general population surveys (GPS were carried out between 2006 and 2008 in Belgaum (northern, Bellary (mid-state and Mysore (southern districts of Karnataka state, south India. Data from these three surveys were analysed to understand heterogeneity in HIV risk. Methods Outcome variables were the prevalence of HIV and sexually transmitted infections (STIs. Independent variables included age, district, place of residence, along with socio-demographic, medical and behavioural characteristics. Multivariate logistic regression was undertaken to identify characteristics associated with HIV and differences between districts, incorporating survey statistics to consider weights and cluster effects. Results The participation rate was 79.0% for the interview and 72.5% for providing a blood or urine sample that was tested for HIV. Belgaum had the highest overall HIV (1.43% and Herpes simplex type-2 (HSV-2 (16.93% prevalence, and the lowest prevalence of curable STIs. In Belgaum, the HIV epidemic is predominantly rural, and among women. In Bellary, the epidemic is predominantly in urban areas and among men, and HIV prevalence was 1.18%. Mysore had the lowest prevalence of HIV (0.80% and HSV-2 (10.89% and the highest prevalence of curable STIs. Higher HIV prevalence among men was associated with increasing age (p25-29years=11.22,95%CI:1.42-88.74, AOR30-34years=13.13,95%CI:1.67-103.19 and AOR35-39years=11.33,95%CI:1.32-96.83, having more than one lifetime sexual partner (AOR=4.61,95%CI:1.26-16.91 and having ever used a condom (AOR=3.32,95%CI:1.38-7.99. Having a dissolved marriage (being widowed/divorced/separated was the strongest predictor (AOR=10.98,95%CI: 5.35-22.57 of HIV among women. Being a muslim woman was associated with lower HIV prevalence (AOR=0.27,95%CI:0.08-0.87. Conclusion The HIV epidemic in Karnataka shows considerable heterogeneity

Interfacial mechanisms of heterogeneous Fenton reactions catalyzed by iron-based materials: A review.

Science.gov (United States)

He, Jie; Yang, Xiaofang; Men, Bin; Wang, Dongsheng

2016-01-01

The heterogeneous Fenton reaction can generate highly reactive hydroxyl radicals (OH) from reactions between recyclable solid catalysts and H2O2 at acidic or even circumneutral pH. Hence, it can effectively oxidize refractory organics in water or soils and has become a promising environmentally friendly treatment technology. Due to the complex reaction system, the mechanism behind heterogeneous Fenton reactions remains unresolved but fascinating, and is crucial for understanding Fenton chemistry and the development and application of efficient heterogeneous Fenton technologies. Iron-based materials usually possess high catalytic activity, low cost, negligible toxicity and easy recovery, and are a superior type of heterogeneous Fenton catalysts. Therefore, this article reviews the fundamental but important interfacial mechanisms of heterogeneous Fenton reactions catalyzed by iron-based materials. OH, hydroperoxyl radicals/superoxide anions (HO2/O2(-)) and high-valent iron are the three main types of reactive oxygen species (ROS), with different oxidation reactivity and selectivity. Based on the mechanisms of ROS generation, the interfacial mechanisms of heterogeneous Fenton systems can be classified as the homogeneous Fenton mechanism induced by surface-leached iron, the heterogeneous catalysis mechanism, and the heterogeneous reaction-induced homogeneous mechanism. Different heterogeneous Fenton systems catalyzed by characteristic iron-based materials are comprehensively reviewed. Finally, related future research directions are also suggested. Copyright © 2015. Published by Elsevier B.V.

Genetic heterogeneity in Pakistani microcephaly families

DEFF Research Database (Denmark)

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....

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

DEFF Research Database (Denmark)

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....

Mechanical heterogeneity in ionic liquids

Science.gov (United States)

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.

High Productivity Programming of Dense Linear Algebra on Heterogeneous NUMA Architectures

KAUST Repository

Alomairy, Rabab M.

2013-07-01

High-end multicore systems with GPU-based accelerators are now ubiquitous in the hardware landscape. Besides dealing with the nontrivial heterogeneous environ- ment, end users should often take into consideration the underlying memory architec- ture to decrease the overhead of data motion, especially when running on non-uniform memory access (NUMA) platforms. We propose the OmpSs parallel programming model approach using its Nanos++ dynamic runtime system to solve the two challeng- ing problems aforementioned, through 1) an innovative NUMA node-aware scheduling policy to reduce data movement between NUMA nodes and 2) a nested parallelism feature to concurrently exploit the resources available from the GPU devices as well as the CPU host, without compromising the overall performance. Our approach fea- tures separation of concerns by abstracting the complexity of the hardware from the end users so that high productivity can be achieved. The Cholesky factorization is used as a benchmark representative of dense numerical linear algebra algorithms. Superior performance is also demonstrated on the symmetric matrix inversion based on Cholesky factorization, commonly used in co-variance computations in statistics. Performance on a NUMA system with Kepler-based GPUs exceeds that of existing implementations, while the OmpSs-enabled code remains very similar to its original sequential version.

Nanoscale-Agglomerate-Mediated Heterogeneous Nucleation.

Science.gov (United States)

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.

Tumor heterogeneity and progression: conceptual foundations for modeling.

Science.gov (United States)

Greller, L D; Tobin, F L; Poste, G

1996-01-01

A conceptual foundation for modeling tumor progression, growth, and heterogeneity is presented. The purpose of such models is to aid understanding, test ideas, formulate experiments, and to model cancer 'in machina' to address the dynamic features of tumor cell heterogeneity, progression, and growth. The descriptive capabilities of such an approach provides a consistent language for qualitatively reasoning about tumor behavior. This approach provides a schema for building conceptual models that combine three key phenomenological driving elements: growth, progression, and genetic instability. The growth element encompasses processes contributing to changes in tumor bulk and is distinct from progression per se. The progression element subsumes a broad collection of processes underlying phenotypic progression. The genetics elements represents heritable changes which potentially affect tumor character and behavior. Models, conceptual and mathematical, can be built for different tumor situations by drawing upon the interaction of these three distinct driving elements. These models can be used as tools to explore a diversity of hypotheses concerning dynamic changes in cellular populations during tumor progression, including the generation of intratumor heterogeneity. Such models can also serve to guide experimentation and to gain insight into dynamic aspects of complex tumor behavior.

Single-cell MALDI-MS as an analytical tool for studying intrapopulation metabolic heterogeneity of unicellular organisms.

Science.gov (United States)

Amantonico, Andrea; Urban, Pawel L; Fagerer, Stephan R; Balabin, Roman M; Zenobi, Renato

2010-09-01

Heterogeneity is a characteristic feature of all populations of living organisms. Here we make an attempt to validate a single-cell mass spectrometric method for detection of changes in metabolite levels occurring in populations of unicellular organisms. Selected metabolites involved in central metabolism (ADP, ATP, GTP, and UDP-Glucose) could readily be detected in single cells of Closterium acerosum by means of negative-mode matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS). The analytical capabilities of this approach were characterized using standard compounds. The method was then used to study populations of individual cells with different levels of the chosen metabolites. With principal component analysis and support vector machine algorithms, it was possible to achieve a clear separation of individual C. acerosum cells in different metabolic states. This study demonstrates the suitability of mass spectrometric analysis of metabolites in single cells to measure cell-population heterogeneity.

Not All Smokers Die Young: A Model for Hidden Heterogeneity within the Human Population

Science.gov (United States)

Levine, Morgan; Crimmins, Eileen

2014-01-01

The ability of some individuals to reach extreme old age in the presence of clearly high exposure to damaging factors may signal an innate biological advantage. For this study we used data on 4,655 current and never smokers, ages 50 and above, from NHANES III to examine whether long-lived smokers represent a biologically resilient phenotype that could facilitate our understanding of heterogeneity in the aging process. Using a proportional hazards model, our results showed that while smoking significantly increased mortality in most age groups, it did not increase the mortality risk for those who were age 80 and over at baseline. Additionally when comparing the adjusted means of biomarkers between never and current smokers, we found that long-lived smokers (80+) had similar inflammation, HDL, and lung function levels to never smokers. Given that factors which allow some individuals to withstand smoking may also enable others to cope with everyday biological stressors, the investigation of long-lived smokers may eventually allow us to identify molecular and genetic mechanisms which enable longevity extension. PMID:24520332

Landscape structure mediates the effects of a stressor on field vole populations

DEFF Research Database (Denmark)

Dalkvist, Trine; Sibly, Richard M.; Topping, Christopher John

2013-01-01

Spatio-temporal landscape heterogeneity has rarely been considered in population-level impact assessments. Here we test whether landscape heterogeneity is important by examining the case of a pesticide applied seasonally to orchards which may affect non-target vole populations, using a validated ...... results show that accurate prediction of population impact cannot be achieved without taking account of landscape structure. The specifics of landscape structure and habitat connectivity are likely always important in mediating the effects of stressors....

Automated analysis of heterogeneous carbon nanostructures by high-resolution electron microscopy and on-line image processing

International Nuclear Information System (INIS)

Toth, P.; Farrer, J.K.; Palotas, A.B.; Lighty, J.S.; Eddings, E.G.

2013-01-01

High-resolution electron microscopy is an efficient tool for characterizing heterogeneous nanostructures; however, currently the analysis is a laborious and time-consuming manual process. In order to be able to accurately and robustly quantify heterostructures, one must obtain a statistically high number of micrographs showing images of the appropriate sub-structures. The second step of analysis is usually the application of digital image processing techniques in order to extract meaningful structural descriptors from the acquired images. In this paper it will be shown that by applying on-line image processing and basic machine vision algorithms, it is possible to fully automate the image acquisition step; therefore, the number of acquired images in a given time can be increased drastically without the need for additional human labor. The proposed automation technique works by computing fields of structural descriptors in situ and thus outputs sets of the desired structural descriptors in real-time. The merits of the method are demonstrated by using combustion-generated black carbon samples. - Highlights: ► The HRTEM analysis of heterogeneous nanostructures is a tedious manual process. ► Automatic HRTEM image acquisition and analysis can improve data quantity and quality. ► We propose a method based on on-line image analysis for the automation of HRTEM image acquisition. ► The proposed method is demonstrated using HRTEM images of soot particles

Ethnic heterogeneity, social capital and psychological distress in Sweden.

Science.gov (United States)

Johnson-Singh, Charisse M; Rostila, Mikael; Ponce de Leon, Antonio; Forsell, Yvonne; Engström, Karin

2018-05-25

Ethnic heterogeneity has been linked to both protective and detrimental effects on mental health. Few studies have investigated the role of social capital in this relationship and none have found that it has an explanatory role. The aim of this study is to investigate the relationship between two measures of ethnic heterogeneity and psychological distress in Stockholm County, as well as the explanatory role of social capital for individuals with Swedish-background, foreign-background and those who are foreign-born. This study used data collected from respondents aged 18-64 to the 2002, 2006, 2010 baseline questionnaires of the Stockholm Public Health Cohort and was linked with individual and area-level register information. Ethnic heterogeneity was the main exposure, measured by: 1) ethnic density, defined as the proportion of first and second generation immigrants with 2 foreign-born parents; and 2) ethnic diversity, using the fragmentation index. Social capital measures of individual and contextual-level social support and horizontal trust were the main explanatory factors of interest. The outcome, psychological distress, was assessed using the General Health Questionnaire-12 with a 2/3 cut-off. Prevalence ratios with 95% confidence intervals were estimated using multi-level poisson regression with robust variances. Age and sex adjusted analyses for the whole study population demonstrated that a 10% increase in ethnic density or diversity was associated with a 1.06 (1.05-1.07) times higher prevalence of psychological distress. In the stratified analyses, both foreign-born respondents and those with Swedish-background showed increasing prevalence of psychological distress with increasing ethnic heterogeneity. However, this trend was entirely explained by socioeconomic factors in the Swedish-background respondents and by additional adjustments for individual and contextual social support and horizontal trust for the foreign-born. Further adjustment for contextual

Dynamic heterogeneity in life histories

DEFF Research Database (Denmark)

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...

Mapping High-Resolution Soil Moisture over Heterogeneous Cropland Using Multi-Resource Remote Sensing and Ground Observations

Directory of Open Access Journals (Sweden)

Lei Fan

2015-10-01

Full Text Available High spatial resolution soil moisture (SM data are crucial in agricultural applications, river-basin management, and understanding hydrological processes. Merging multi-resource observations is one of the ways to improve the accuracy of high spatial resolution SM data in the heterogeneous cropland. In this paper, the Bayesian Maximum Entropy (BME methodology is implemented to merge the following four types of observed data to obtain the spatial distribution of SM at 100 m scale: soil moisture observed by wireless sensor network (WSN, Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER-derived soil evaporative efficiency (SEE, irrigation statistics, and Polarimetric L-band Multi-beam Radiometer (PLMR-derived SM products (~700 m. From the poor BME predictions obtained by merging only WSN and SEE data, we observed that the SM heterogeneity caused by irrigation and the attenuating sensitivity of the SEE data to SM caused by the canopies result in BME prediction errors. By adding irrigation statistics to the merged datasets, the overall RMSD of the BME predictions during the low-vegetated periods can be successively reduced from 0.052 m3·m−3 to 0.033 m3·m−3. The coefficient of determination (R2 and slope between the predicted and in situ measured SM data increased from 0.32 to 0.64 and from 0.38 to 0.82, respectively, but large estimation errors occurred during the moderately vegetated periods (RMSD = 0.041 m3·m−3, R = 0.43 and the slope = 0.41. Further adding the downscaled SM information from PLMR SM products to the merged datasets, the predictions were satisfactorily accurate with an RMSD of 0.034 m3·m−3, R2 of 0.4 and a slope of 0.69 during moderately vegetated periods. Overall, the results demonstrated that merging multi-resource observations into SM estimations can yield improved accuracy in heterogeneous cropland.

A Knockin Reporter Allows Purification and Characterization of mDA Neurons from Heterogeneous Populations

Directory of Open Access Journals (Sweden)

Ninuo Xia

2017-03-01

Full Text Available Generation of midbrain dopaminergic (mDA neurons from human pluripotent stem cells provides a platform for inquiry into basic and translational studies of Parkinson’s disease (PD. However, heterogeneity in differentiation in vitro makes it difficult to identify mDA neurons in culture or in vivo following transplantation. Here, we report the generation of a human embryonic stem cell (hESC line with a tyrosine hydroxylase (TH-RFP (red fluorescent protein reporter. We validated that RFP faithfully mimicked TH expression during differentiation. Use of this TH-RFP reporter cell line enabled purification of mDA-like neurons from heterogeneous cultures with subsequent characterization of neuron transcriptional and epigenetic programs (global binding profiles of H3K27ac, H3K4me1, and 5-hydroxymethylcytosine [5hmC] at four different stages of development. We anticipate that the tools and data described here will contribute to the development of mDA neurons for applications in disease modeling and/or drug screening and cell replacement therapies for PD.

A Knockin Reporter Allows Purification and Characterization of mDA Neurons from Heterogeneous Populations.

Science.gov (United States)

Xia, Ninuo; Fang, Fang; Zhang, Pengbo; Cui, Jun; Tep-Cullison, Chhavy; Hamerley, Tim; Lee, Hyun Joo; Palmer, Theo; Bothner, Brian; Lee, Jin Hyung; Pera, Renee Reijo

2017-03-07

Generation of midbrain dopaminergic (mDA) neurons from human pluripotent stem cells provides a platform for inquiry into basic and translational studies of Parkinson's disease (PD). However, heterogeneity in differentiation in vitro makes it difficult to identify mDA neurons in culture or in vivo following transplantation. Here, we report the generation of a human embryonic stem cell (hESC) line with a tyrosine hydroxylase (TH)-RFP (red fluorescent protein) reporter. We validated that RFP faithfully mimicked TH expression during differentiation. Use of this TH-RFP reporter cell line enabled purification of mDA-like neurons from heterogeneous cultures with subsequent characterization of neuron transcriptional and epigenetic programs (global binding profiles of H3K27ac, H3K4me1, and 5-hydroxymethylcytosine [5hmC]) at four different stages of development. We anticipate that the tools and data described here will contribute to the development of mDA neurons for applications in disease modeling and/or drug screening and cell replacement therapies for PD. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Sub-Tg enthalpy relaxation in an unstable oxide glass former: insights into the structural heterogeneity

DEFF Research Database (Denmark)

Yue, Yuanzheng; Zhang, Yanfei

Structural heterogeneity plays a crucial role in determining functionality of glasses. In this work we have found that the sub-Tg enthalpy relaxation pattern in a hyperquenched glass is highly sensitive to structural heterogeneity. As a consequence, the former can be used as an effective approach...... to detect and quantify the structural heterogeneity in glass-forming liquids. However, the chemical nature of structural heterogeneity should be revealed by other means such as high resolution microscopic and spectroscopic methods. To study the impact of the structural heterogeneity on the sub-Tg relaxation...... chemical features and degrees of structural heterogeneity in glass-forming liquids. This finding contributes to the microscopic origin of both the primary and secondary relaxation in terms of structural heterogeneity. Finally the results provide insights into the relation between structural heterogeneity...

Heterotypic mouse models of canine osteosarcoma recapitulate tumor heterogeneity and biological behavior

Directory of Open Access Journals (Sweden)

Milcah C. Scott

2016-12-01

Full Text Available Osteosarcoma (OS is a heterogeneous and rare disease with a disproportionate impact because it mainly affects children and adolescents. Lamentably, more than half of patients with OS succumb to metastatic disease. Clarification of the etiology of the disease, development of better strategies to manage progression, and methods to guide personalized treatments are among the unmet health needs for OS patients. Progress in managing the disease has been hindered by the extreme heterogeneity of OS; thus, better models that accurately recapitulate the natural heterogeneity of the disease are needed. For this study, we used cell lines derived from two spontaneous canine OS tumors with distinctly different biological behavior (OS-1 and OS-2 for heterotypic in vivo modeling that recapitulates the heterogeneous biology and behavior of this disease. Both cell lines demonstrated stability of the transcriptome when grown as orthotopic xenografts in athymic nude mice. Consistent with the behavior of the original tumors, OS-2 xenografts grew more rapidly at the primary site and had greater propensity to disseminate to lung and establish microscopic metastasis. Moreover, OS-2 promoted formation of a different tumor-associated stromal environment than OS-1 xenografts. OS-2-derived tumors comprised a larger percentage of the xenograft tumors than OS-1-derived tumors. In addition, a robust pro-inflammatory population dominated the stromal cell infiltrates in OS-2 xenografts, whereas a mesenchymal population with a gene signature reflecting myogenic signaling dominated those in the OS-1 xenografts. Our studies show that canine OS cell lines maintain intrinsic features of the tumors from which they were derived and recapitulate the heterogeneous biology and behavior of bone cancer in mouse models. This system provides a resource to understand essential interactions between tumor cells and the stromal environment that drive the progression and metastatic propensity of

Heterotypic mouse models of canine osteosarcoma recapitulate tumor heterogeneity and biological behavior.

Science.gov (United States)

Scott, Milcah C; Tomiyasu, Hirotaka; Garbe, John R; Cornax, Ingrid; Amaya, Clarissa; O'Sullivan, M Gerard; Subramanian, Subbaya; Bryan, Brad A; Modiano, Jaime F

2016-12-01

Osteosarcoma (OS) is a heterogeneous and rare disease with a disproportionate impact because it mainly affects children and adolescents. Lamentably, more than half of patients with OS succumb to metastatic disease. Clarification of the etiology of the disease, development of better strategies to manage progression, and methods to guide personalized treatments are among the unmet health needs for OS patients. Progress in managing the disease has been hindered by the extreme heterogeneity of OS; thus, better models that accurately recapitulate the natural heterogeneity of the disease are needed. For this study, we used cell lines derived from two spontaneous canine OS tumors with distinctly different biological behavior (OS-1 and OS-2) for heterotypic in vivo modeling that recapitulates the heterogeneous biology and behavior of this disease. Both cell lines demonstrated stability of the transcriptome when grown as orthotopic xenografts in athymic nude mice. Consistent with the behavior of the original tumors, OS-2 xenografts grew more rapidly at the primary site and had greater propensity to disseminate to lung and establish microscopic metastasis. Moreover, OS-2 promoted formation of a different tumor-associated stromal environment than OS-1 xenografts. OS-2-derived tumors comprised a larger percentage of the xenograft tumors than OS-1-derived tumors. In addition, a robust pro-inflammatory population dominated the stromal cell infiltrates in OS-2 xenografts, whereas a mesenchymal population with a gene signature reflecting myogenic signaling dominated those in the OS-1 xenografts. Our studies show that canine OS cell lines maintain intrinsic features of the tumors from which they were derived and recapitulate the heterogeneous biology and behavior of bone cancer in mouse models. This system provides a resource to understand essential interactions between tumor cells and the stromal environment that drive the progression and metastatic propensity of OS. © 2016

FDG uptake heterogeneity in FIGO IIb cervical carcinoma does not predict pelvic lymph node involvement.

Science.gov (United States)

Brooks, Frank J; Grigsby, Perry W

2013-12-23

Many types of cancer are located and assessed via positron emission tomography (PET) using the 18F-fluorodeoxyglucose (FDG) radiotracer of glucose uptake. There is rapidly increasing interest in exploiting the intra-tumor heterogeneity observed in these FDG-PET images as an indicator of disease outcome. If this image heterogeneity is of genuine prognostic value, then it either correlates to known prognostic factors, such as tumor stage, or it indicates some as yet unknown tumor quality. Therefore, the first step in demonstrating the clinical usefulness of image heterogeneity is to explore the dependence of image heterogeneity metrics upon established prognostic indicators and other clinically interesting factors. If it is shown that image heterogeneity is merely a surrogate for other important tumor properties or variations in patient populations, then the theoretical value of quantified biological heterogeneity may not yet translate into the clinic given current imaging technology. We explore the relation between pelvic lymph node status at diagnosis and the visually evident uptake heterogeneity often observed in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) images of cervical carcinomas. We retrospectively studied the FDG-PET images of 47 node negative and 38 node positive patients, each having FIGO stage IIb tumors with squamous cell histology. Imaged tumors were segmented using 40% of the maximum tumor uptake as the tumor-defining threshold and then converted into sets of three-dimensional coordinates. We employed the sphericity, extent, Shannon entropy (S) and the accrued deviation from smoothest gradients (ζ) as image heterogeneity metrics. We analyze these metrics within tumor volume strata via: the Kolmogorov-Smirnov test, principal component analysis and contingency tables. We found no statistically significant difference between the positive and negative lymph node groups for any one metric or plausible combinations thereof. Additionally

FDG uptake heterogeneity in FIGO IIb cervical carcinoma does not predict pelvic lymph node involvement

International Nuclear Information System (INIS)

Brooks, Frank J; Grigsby, Perry W

2013-01-01

Many types of cancer are located and assessed via positron emission tomography (PET) using the 18F-fluorodeoxyglucose (FDG) radiotracer of glucose uptake. There is rapidly increasing interest in exploiting the intra-tumor heterogeneity observed in these FDG-PET images as an indicator of disease outcome. If this image heterogeneity is of genuine prognostic value, then it either correlates to known prognostic factors, such as tumor stage, or it indicates some as yet unknown tumor quality. Therefore, the first step in demonstrating the clinical usefulness of image heterogeneity is to explore the dependence of image heterogeneity metrics upon established prognostic indicators and other clinically interesting factors. If it is shown that image heterogeneity is merely a surrogate for other important tumor properties or variations in patient populations, then the theoretical value of quantified biological heterogeneity may not yet translate into the clinic given current imaging technology. We explore the relation between pelvic lymph node status at diagnosis and the visually evident uptake heterogeneity often observed in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) images of cervical carcinomas. We retrospectively studied the FDG-PET images of 47 node negative and 38 node positive patients, each having FIGO stage IIb tumors with squamous cell histology. Imaged tumors were segmented using 40% of the maximum tumor uptake as the tumor-defining threshold and then converted into sets of three-dimensional coordinates. We employed the sphericity, extent, Shannon entropy (S) and the accrued deviation from smoothest gradients (ζ) as image heterogeneity metrics. We analyze these metrics within tumor volume strata via: the Kolmogorov-Smirnov test, principal component analysis and contingency tables. We found no statistically significant difference between the positive and negative lymph node groups for any one metric or plausible combinations thereof. Additionally

A new, highly selective CCK-B receptor radioligand ([3H][N-methyl-Nle28,31]CCK26-33): Evidence for CCK-B receptor heterogeneity

International Nuclear Information System (INIS)

Knapp, R.J.; Vaughn, L.K.; Fang, S.N.; Bogert, C.L.; Yamamura, M.S.; Hruby, V.J.; Yamamura, H.I.

1990-01-01

[N-methyl-Nle28,31]CCK26-33 (SNF 8702) is a nonsulfated cholecystokinin octapeptide analog that is highly selective for cholecystokinin-B (CCK-B) receptors. Inhibition studies using [125I] Bolton-Hunter-labeled CCK-8 show that SNF 8702 has over 4,000-fold greater affinity for CCK receptors in guinea pig cortex relative to those in guinea pig pancreas. SNF 8702 was tritium-labeled to a specific activity of 23.7 Ci/mmol and its binding properties characterized for guinea pig brain membrane preparations. [3H]SNF 8702 binds to a single site with high affinity (Kd = 0.69-0.90 nM) in guinea pig cortex, cerebellum, hippocampus and pons-medulla. Of these four tissues, the highest receptor density was measured in the cortex (86 fmol/mg of protein) and the lowest in the pons-medulla (22 fmol/mg of protein). In contrast to findings of single-site binding in some brain regions, evidence for CCK-B receptor heterogeneity is observed under other conditions. [3H]SNF 8702 binding to membranes prepared from whole guinea pig brain shows biphasic association kinetics at a concentration of 2.0 nM consistent with the presence of binding site heterogeneity. Binding site heterogeneity is consistently observed for [3H]SNF 8702 binding to guinea pig whole brain membranes in saturation studies where a high-affinity site (Kd = 0.31 nM) is distinguished from a low-affinity site (Kd = 3.3 nM). Binding site heterogeneity is also observed for the midbrain-thalamic region. CCK-B receptor heterogeneity is suggested by the effect of the guanyl nucleotide analogue, guanylyl-imidodiphosphate (Gpp(NH)p), on [3H]SNF 8702 binding to CCK-B receptors in the cerebellum

Transfer Printed Nanomembranes for Heterogeneously Integrated Membrane Photonics

Directory of Open Access Journals (Sweden)

Hongjun Yang

2015-11-01

Full Text Available Heterogeneous crystalline semiconductor nanomembrane (NM integration is investigated for single-layer and double-layer Silicon (Si NM photonics, III-V/Si NM lasers, and graphene/Si NM total absorption devices. Both homogeneous and heterogeneous integration are realized by the versatile transfer printing technique. The performance of these integrated membrane devices shows, not only intact optical and electrical characteristics as their bulk counterparts, but also the unique light and matter interactions, such as Fano resonance, slow light, and critical coupling in photonic crystal cavities. Such a heterogeneous integration approach offers tremendous practical application potentials on unconventional, Si CMOS compatible, and high performance optoelectronic systems.

Population III Stars and Remnants in High-redshift Galaxies

Science.gov (United States)

Xu, Hao; Wise, John H.; Norman, Michael L.

2013-08-01

Recent simulations of Population III star formation have suggested that some fraction form in binary systems, in addition to having a characteristic mass of tens of solar masses. The deaths of metal-free stars result in the initial chemical enrichment of the universe and the production of the first stellar-mass black holes. Here we present a cosmological adaptive mesh refinement simulation of an overdense region that forms a few 109 M ⊙ dark matter halos and over 13,000 Population III stars by redshift 15. We find that most halos do not form Population III stars until they reach M vir ~ 107 M ⊙ because this biased region is quickly enriched from both Population III and galaxies, which also produce high levels of ultraviolet radiation that suppress H2 formation. Nevertheless, Population III stars continue to form, albeit in more massive halos, at a rate of ~10-4 M ⊙ yr-1 Mpc-3 at redshift 15. The most massive starless halo has a mass of 7 × 107 M ⊙, which could host massive black hole formation through the direct gaseous collapse scenario. We show that the multiplicity of the Population III remnants grows with halo mass above 108 M ⊙, culminating in 50 remnants located in 109 M ⊙ halos on average. This has implications that high-mass X-ray binaries and intermediate-mass black holes that originate from metal-free stars may be abundant in high-redshift galaxies.

An Improved STARFM with Help of an Unmixing-Based Method to Generate High Spatial and Temporal Resolution Remote Sensing Data in Complex Heterogeneous Regions.

Science.gov (United States)

Xie, Dengfeng; Zhang, Jinshui; Zhu, Xiufang; Pan, Yaozhong; Liu, Hongli; Yuan, Zhoumiqi; Yun, Ya

2016-02-05

Remote sensing technology plays an important role in monitoring rapid changes of the Earth's surface. However, sensors that can simultaneously provide satellite images with both high temporal and spatial resolution haven't been designed yet. This paper proposes an improved spatial and temporal adaptive reflectance fusion model (STARFM) with the help of an Unmixing-based method (USTARFM) to generate the high spatial and temporal data needed for the study of heterogeneous areas. The results showed that the USTARFM had higher accuracy than STARFM methods in two aspects of analysis: individual bands and of heterogeneity analysis. Taking the predicted NIR band as an example, the correlation coefficients (r) for the USTARFM, STARFM and unmixing methods were 0.96, 0.95, 0.90, respectively (p-value data fusion problems faced when using STARFM. Additionally, the USTARFM method could help researchers achieve better performance than STARFM at a smaller window size from its heterogeneous land surface quantitative representation.

Heterogeneity and Developmental Connections between Cell Types Inhabiting Teeth

Directory of Open Access Journals (Sweden)

Jan Krivanek

2017-06-01

Full Text Available Every tissue is composed of multiple cell types that are developmentally, evolutionary and functionally integrated into the unit we call an organ. Teeth, our organs for biting and mastication, are complex and made of many different cell types connected or disconnected in terms of their ontogeny. In general, epithelial and mesenchymal compartments represent the major framework of tooth formation. Thus, they give rise to the two most important matrix–producing populations: ameloblasts generating enamel and odontoblasts producing dentin. However, the real picture is far from this quite simplified view. Diverse pulp cells, the immune system, the vascular system, the innervation and cells organizing the dental follicle all interact, and jointly participate in transforming lifeless matrix into a functional organ that can sense and protect itself. Here we outline the heterogeneity of cell types that inhabit the tooth, and also provide a life history of the major populations. The mouse model system has been indispensable not only for the studies of cell lineages and heterogeneity, but also for the investigation of dental stem cells and tooth patterning during development. Finally, we briefly discuss the evolutionary aspects of cell type diversity and dental tissue integration.

Addressing Longevity’ Heterogeneity in Pension Scheme Design

OpenAIRE

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...

Bet hedging in yeast by heterogeneous, age-correlated expression of a stress protectant.

Directory of Open Access Journals (Sweden)

Sasha F Levy

Full Text Available Genetically identical cells grown in the same culture display striking cell-to-cell heterogeneity in gene expression and other traits. A crucial challenge is to understand how much of this heterogeneity reflects the noise tolerance of a robust system and how much serves a biological function. In bacteria, stochastic gene expression results in cell-to-cell heterogeneity that might serve as a bet-hedging mechanism, allowing a few cells to survive through an antimicrobial treatment while others perish. Despite its clinical importance, the molecular mechanisms underlying bet hedging remain unclear. Here, we investigate the mechanisms of bet hedging in Saccharomyces cerevisiae using a new high-throughput microscopy assay that monitors variable protein expression, morphology, growth rate, and survival outcomes of tens of thousands of yeast microcolonies simultaneously. We find that clonal populations display broad distributions of growth rates and that slow growth predicts resistance to heat killing in a probabalistic manner. We identify several gene products that are likely to play a role in bet hedging and confirm that Tsl1, a trehalose-synthesis regulator, is an important component of this resistance. Tsl1 abundance correlates with growth rate and replicative age and predicts survival. Our results suggest that yeast bet hedging results from multiple epigenetic growth states determined by a combination of stochastic and deterministic factors.

Analysis of heterogeneities in strain and microstructure in aluminum alloy and magnesium processed by high-pressure torsion

Energy Technology Data Exchange (ETDEWEB)

Panda, Subrata, E-mail: subrata.panda@univ-lorraine.fr [Université de Lorraine, Laboratory of Excellence on Design of Alloy Metals for low-mass Structures (DAMAS), Ile du Saulcy, Metz F-57045 (France); Université de Lorraine, Laboratoire d' Etude des Microstructures et de Mécanique des Matériaux (LEM3 UMR 7239), Ile du Saulcy, Metz F-57045 (France); Toth, Laszlo S., E-mail: laszlo.toth@univ-lorraine.fr [Université de Lorraine, Laboratory of Excellence on Design of Alloy Metals for low-mass Structures (DAMAS), Ile du Saulcy, Metz F-57045 (France); Université de Lorraine, Laboratoire d' Etude des Microstructures et de Mécanique des Matériaux (LEM3 UMR 7239), Ile du Saulcy, Metz F-57045 (France); Fundenberger, Jean-Jacques, E-mail: jean-jacques.fundenberger@univ-lorraine.fr [Université de Lorraine, Laboratory of Excellence on Design of Alloy Metals for low-mass Structures (DAMAS), Ile du Saulcy, Metz F-57045 (France); Université de Lorraine, Laboratoire d' Etude des Microstructures et de Mécanique des Matériaux (LEM3 UMR 7239), Ile du Saulcy, Metz F-57045 (France); Perroud, Olivier, E-mail: olivier.perroud@univ-lorraine.fr [Université de Lorraine, Laboratory of Excellence on Design of Alloy Metals for low-mass Structures (DAMAS), Ile du Saulcy, Metz F-57045 (France); Université de Lorraine, Laboratoire d' Etude des Microstructures et de Mécanique des Matériaux (LEM3 UMR 7239), Ile du Saulcy, Metz F-57045 (France); and others

2017-01-15

Two distinct bulk light metals were opted to study the shear strain evolution and associated heterogeneities in texture/microstructure development during torsional straining by high pressure torsion (HPT): a face centered cubic Al alloy (A5086) and a hexagonal commercial purity Mg. Relatively thick disk samples - four times thicker than usually employed in HPT process - were processed to 180° and 270° rotations. With the help of X-ray tomography, the shear strain gradients were examined in the axial direction. The results showed strongly localized shear deformation in the middle plane of the disks in both materials. These gradients involved strong heterogeneities in texture, microstructure and associated hardness, in particular through the thickness direction at the periphery of the disk where the interplay between significant strain hardening and possible dynamic recrystallization could occur. - Highlights: •HPT processing was conducted on bulk specimens thicker than the usual thin-disks. •The Al alloy (A5086) and commercial purity magnesium samples were compared. •Distributions of strain and microhardness were evaluated in the radial and axial direction. •Plastic deformation is highly localized in the middle plane at outer edge in both materials. •Different DRX rates governed the differences in microstructure and hardening behavior.

Population-genetic analysis of seven qualitative traits in the population of the municipality Maglaj (Bosnia and Herzegovina

Directory of Open Access Journals (Sweden)

Mrehić Elma

2015-01-01

Full Text Available On the basis of the complex seven monogenic qualitative characteristics (shape of the earlobes, hairiness of middle phalange, flexibility of lateral tongue edges, the extensiveness of the distal and proximal joint of the thumb and the flexibility of the distal phalanx of the little finger and one sexually conditioned property (digital index we analyzed the genetic structure of four populations of rural municipality Maglaj: Kosova, Novi Šeher, Jablanica, Moševac, then one isolated local population Ravna and one urban population area called Maglaj. The survey covered a total of 440 students (213 girls and 227 boys aged 11-18 years. According to the degree of genetic heterogeneity, values of Wahlund variance that are obtained for each trait belong in the category of low genetic differentiation. The maximum value of Wahlund variance was identified for the property shape of the earlobes (by Cavalli - Sforza, Bodmer = 0.0452, and the lowest for phenotypic system flexibility of lateral tongue edges (by Cavalli - Sforza, Bodmer = 0.0000. Studied set of population is the most heterogeneous according to the frequency of recessive allelogene for phenotypic characteristic shape of the earlobes, and the most homogeneous for the phenotypic trait flexibility of lateral tongue edge. Based on the analysis of genetic distance for seven phenotypic traits in populations of municipality Maglaj we established the minimum genetic distance between populations of Kosova and Maglaj (fθ = 0.0007, and the largest genetic distance between populations of Jablanica and Moševac (fθ = 0.0144. It was noted that the lowest average coefficient of kinship has a local population of Kosova (fθ = 0.0028, while the highest average coefficient of kinship has a population Moševac (fθ = 0.0081. The greatest characteristic has a population of Moševac (fθs = 0.7556, and the lowest characteristic has a population of Novi Šeher (fθs = -0.0795. Based on the obtained values of

Investigation on generalized Variational Nodal Methods for heterogeneous nodes

International Nuclear Information System (INIS)

Wang, Yongping; Wu, Hongchun; Li, Yunzhao; Cao, Liangzhi; Shen, Wei

2017-01-01

Highlights: • We developed two heterogeneous nodal methods based on the Variational Nodal Method. • Four problems were solved to evaluate the two heterogeneous nodal methods. • The function expansion method is good at treating continuous-changing heterogeneity. • The finite sub-element method is good at treating discontinuous-changing heterogeneity. - Abstract: The Variational Nodal Method (VNM) is generalized for heterogeneous nodes and applied to four kinds of problems including Molten Salt Reactor (MSR) core problem with continuous cross section profile, Pressurized Water Reactor (PWR) control rod cusping effect problem, PWR whole-core pin-by-pin problem, and heterogeneous PWR core problem without fuel-coolant homogenization in each pin cell. Two approaches have been investigated for the treatment of the nodal heterogeneity in this paper. To concentrate on spatial heterogeneity, diffusion approximation was adopted for the angular variable in neutron transport equation. To provide demonstrative numerical results, the codes in this paper were developed in slab geometry. The first method, named as function expansion (FE) method, expands nodal flux by orthogonal polynomials and the nodal cross sections are also expressed as spatial depended functions. The second path, named as finite sub-element (FS) method, takes advantage of the finite-element method by dividing each node into numbers of homogeneous sub-elements and expanding nodal flux into the combination of linear sub-element trial functions. Numerical tests have been carried out to evaluate the ability of the two nodal (coarse-mesh) heterogeneous VNMs by comparing with the fine-mesh homogeneous VNM. It has been demonstrated that both heterogeneous approaches can handle heterogeneous nodes. The FE method is good at continuous-changing heterogeneity as in the MSR core problem, while the FS method is good at discontinuous-changing heterogeneity such as the PWR pin-by-pin problem and heterogeneous PWR core

A Heterogeneous Quantum Computer Architecture

NARCIS (Netherlands)

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

Morphology stabilization of heterogeneous blends

International Nuclear Information System (INIS)

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)

Heterogeneous skills and homogeneous land: segmentation and agglomeration

OpenAIRE

Matthias Wrede

2013-01-01

This paper analyzes the impact of skill heterogeneity on regional patterns of production and housing in the presence of pecuniary externalities within a general-equilibrium framework assuming monopolistic competition at intermediate good markets. It shows that the interplay of heterogeneous skills and relatively homogeneous land demand triggers skill segmentation and agglomeration. The core region, being more attractive to high skilled workers, has a disproportionately large share of producti...

High-resolution simulation of link-level vehicle emissions and concentrations for air pollutants in a traffic-populated eastern Asian city

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S. Zhang

2016-08-01

Full Text Available Vehicle emissions containing air pollutants created substantial environmental impacts on air quality for many traffic-populated cities in eastern Asia. A high-resolution emission inventory is a useful tool compared with traditional tools (e.g. registration data-based approach to accurately evaluate real-world traffic dynamics and their environmental burden. In this study, Macau, one of the most populated cities in the world, is selected to demonstrate a high-resolution simulation of vehicular emissions and their contribution to air pollutant concentrations by coupling multimodels. First, traffic volumes by vehicle category on 47 typical roads were investigated during weekdays in 2010 and further applied in a networking demand simulation with the TransCAD model to establish hourly profiles of link-level vehicle counts. Local vehicle driving speed and vehicle age distribution data were also collected in Macau. Second, based on a localized vehicle emission model (e.g. the emission factor model for the Beijing vehicle fleet – Macau, EMBEV–Macau, this study established a link-based vehicle emission inventory in Macau with high resolution meshed in a temporal and spatial framework. Furthermore, we employed the AERMOD (AMS/EPA Regulatory Model model to map concentrations of CO and primary PM2.5 contributed by local vehicle emissions during weekdays in November 2010. This study has discerned the strong impact of traffic flow dynamics on the temporal and spatial patterns of vehicle emissions, such as a geographic discrepancy of spatial allocation up to 26 % between THC and PM2.5 emissions owing to spatially heterogeneous vehicle-use intensity between motorcycles and diesel fleets. We also identified that the estimated CO2 emissions from gasoline vehicles agreed well with the statistical fuel consumption in Macau. Therefore, this paper provides a case study and a solid framework for developing high-resolution environment assessment tools for other

Negative binomial models for abundance estimation of multiple closed populations

Science.gov (United States)

Boyce, Mark S.; MacKenzie, Darry I.; Manly, Bryan F.J.; Haroldson, Mark A.; Moody, David W.

2001-01-01

Counts of uniquely identified individuals in a population offer opportunities to estimate abundance. However, for various reasons such counts may be burdened by heterogeneity in the probability of being detected. Theoretical arguments and empirical evidence demonstrate that the negative binomial distribution (NBD) is a useful characterization for counts from biological populations with heterogeneity. We propose a method that focuses on estimating multiple populations by simultaneously using a suite of models derived from the NBD. We used this approach to estimate the number of female grizzly bears (Ursus arctos) with cubs-of-the-year in the Yellowstone ecosystem, for each year, 1986-1998. Akaike's Information Criteria (AIC) indicated that a negative binomial model with a constant level of heterogeneity across all years was best for characterizing the sighting frequencies of female grizzly bears. A lack-of-fit test indicated the model adequately described the collected data. Bootstrap techniques were used to estimate standard errors and 95% confidence intervals. We provide a Monte Carlo technique, which confirms that the Yellowstone ecosystem grizzly bear population increased during the period 1986-1998.

Discontinuous Galerkin Subgrid Finite Element Method for Heterogeneous Brinkman’s Equations

KAUST Repository

Iliev, Oleg P.; Lazarov, Raytcho D.; Willems, Joerg

2010-01-01

We present a two-scale finite element method for solving Brinkman's equations with piece-wise constant coefficients. This system of equations model fluid flows in highly porous, heterogeneous media with complex topology of the heterogeneities. We

Epidemiology of human leukocyte antigens among omani population.

Science.gov (United States)

Al Salmi, Issa; Metry, Abdul Massiah; Al Ismaili, Faisal; Hola, Alan; Shaheen, Faissal; Fakhoury, Hana; Hannawi, Suad

2017-01-01

Oman is located on the Southeastern coast of the Arabian Peninsula, and its population has high levels of consanguinity. Human leukocytic antigen (HLA) typing analysis in human population holds unexploited potential for elucidating the genetic causes of human disease and possibly leads to personalized medicine. This is a retrospective, descriptive study evaluating HLA frequencies of Omani individuals who underwent workup for kidney transplantation at the Royal Hospital (RH) from 2005 to 2016. Data on 870 subjects were collected from the Oman kidney transplant registry at RH as well from electronic medical record system. The mean age (standard deviation) years for the cohort were 33.2 (13.0). Males constituted 56.3% (490) while females constituted 43.7% (380). Seven HLA-A alleles accounted for more than 70% of the total alleles. Of which, HLA-A2 contributed the highest frequency (24%), followed by HLA A11 (9.4%), and A32 (8.1%). Ten alleles accounted for 70% of HLA-B alleles. Of which, HLA-B51 was the most common (18.9%), followed by HLA-B-35 (13.6%), and HLA-B8 (7.9%). Seven HLA-DRB1 alleles accounted for more than 70% of the total HLA DRB1 alleles, of which HLA- DRB1*16 contributed the highest frequency (29.56%). This was followed by HLA-DRB1*03 (14.57%) and HLA-DRB1*11 (9.48%). While three alleles accounted for more than 75% of the total HLA DQB1alleles. Of which, HLA-DQB1*05 contributed the highest frequency (37.56%). This was followed by allele HLA-DQB1*02 (26.48%) and HLA-DQB1*03 (17.18%). This study showed considerable heterogeneity in both HLA Class I and Class II antigens, which reflects admixture of our population with rest of old world countries. Despite the high levels of consanguinity, this population is genetically highly heterogeneous. These findings may be useful for transplantation programs, noncommunicable diseases, epidemiology of HLA linked diseases, pharmacogenomics, and anthropology.

Epidemiology of human leukocyte antigens among omani population

Directory of Open Access Journals (Sweden)

Issa Al Salmi

2017-01-01

Full Text Available Oman is located on the Southeastern coast of the Arabian Peninsula, and its population has high levels of consanguinity. Human leukocytic antigen (HLA typing analysis in human population holds unexploited potential for elucidating the genetic causes of human disease and possibly leads to personalized medicine. This is a retrospective, descriptive study evaluating HLA frequencies of Omani individuals who underwent workup for kidney transplantation at the Royal Hospital (RH from 2005 to 2016. Data on 870 subjects were collected from the Oman kidney transplant registry at RH as well from electronic medical record system. The mean age (standard deviation years for the cohort were 33.2 (13.0. Males constituted 56.3% (490 while females constituted 43.7% (380. Seven HLA-A alleles accounted for more than 70% of the total alleles. Of which, HLA-A2 contributed the highest frequency (24%, followed by HLA A11 (9.4%, and A32 (8.1%. Ten alleles accounted for 70% of HLA-B alleles. Of which, HLA-B51 was the most common (18.9%, followed by HLA-B-35 (13.6%, and HLA-B8 (7.9%. Seven HLA-DRB1 alleles accounted for more than 70% of the total HLA DRB1 alleles, of which HLA- DRB1*16 contributed the highest frequency (29.56%. This was followed by HLA-DRB1*03 (14.57% and HLA-DRB1*11 (9.48%. While three alleles accounted for more than 75% of the total HLA DQB1alleles. Of which, HLA-DQB1*05 contributed the highest frequency (37.56%. This was followed by allele HLA-DQB1*02 (26.48% and HLA-DQB1*03 (17.18%. This study showed considerable heterogeneity in both HLA Class I and Class II antigens, which reflects admixture of our population with rest of old world countries. Despite the high levels of consanguinity, this population is genetically highly heterogeneous. These findings may be useful for transplantation programs, noncommunicable diseases, epidemiology of HLA linked diseases, pharmacogenomics, and anthropology.

Direct Breakthrough Curve Prediction From Statistics of Heterogeneous Conductivity Fields

Science.gov (United States)

Hansen, Scott K.; Haslauer, Claus P.; Cirpka, Olaf A.; Vesselinov, Velimir V.

2018-01-01

This paper presents a methodology to predict the shape of solute breakthrough curves in heterogeneous aquifers at early times and/or under high degrees of heterogeneity, both cases in which the classical macrodispersion theory may not be applicable. The methodology relies on the observation that breakthrough curves in heterogeneous media are generally well described by lognormal distributions, and mean breakthrough times can be predicted analytically. The log-variance of solute arrival is thus sufficient to completely specify the breakthrough curves, and this is calibrated as a function of aquifer heterogeneity and dimensionless distance from a source plane by means of Monte Carlo analysis and statistical regression. Using the ensemble of simulated groundwater flow and solute transport realizations employed to calibrate the predictive regression, reliability estimates for the prediction are also developed. Additional theoretical contributions include heuristics for the time until an effective macrodispersion coefficient becomes applicable, and also an expression for its magnitude that applies in highly heterogeneous systems. It is seen that the results here represent a way to derive continuous time random walk transition distributions from physical considerations rather than from empirical field calibration.

Evolutionary conservation advice for despotic populations: habitat heterogeneity favours conflict and reduces productivity in Seychelles magpie robins.

Science.gov (United States)

López-Sepulcre, Andrés; Kokko, Hanna; Norris, Ken

2010-11-22

Individual preferences for good habitat are often thought to have a beneficial stabilizing effect for populations. However, if individuals preferentially compete for better-quality territories, these may become hotspots of conflict. We show that, in an endangered species, this process decreases the productivity of favoured territories to the extent that differences in productivity between territories disappear. Unlike predictions from current demographic theory on site-dependent population regulation (ideal despotic distribution), we show that population productivity is reduced if resources are distributed unevenly in space. Competition for high-quality habitat can thus have detrimental consequences for populations even though it benefits individuals. Manipulating conflict (e.g. by reducing variation in habitat quality) can therefore prove an effective conservation measure in species with strong social or territorial conflict.

The Effect of High Ambient Temperature on the Elderly Population in Three Regions of Sweden

Directory of Open Access Journals (Sweden)

Joacim Rocklöv

2010-06-01

Full Text Available The short-term effects of high temperatures are a serious concern in the context of climate change. In areas that today have mild climates the research activity has been rather limited, despite the fact that differences in temperature susceptibility will play a fundamental role in understanding the exposure, acclimatization, adaptation and health risks of a changing climate. In addition, many studies employ biometeorological indexes without careful investigation of the regional heterogeneity in the impact of relative humidity. We aimed to investigate the effects of summer temperature and relative humidity and regional differences in three regions of Sweden allowing for heterogeneity of the effect over the scale of summer temperature. To do so, we collected mortality data for ages 65+ from Stockholm, Göteborg and Skåne from the Swedish National Board of Health and Welfare and the Swedish Meteorological and Hydrological Institute for the years 1998 through 2005. In Stockholm and Skåne on average 22 deaths per day occurred, while in Göteborg the mean frequency of daily deaths was 10. We fitted time-series regression models to estimate relative risks of high ambient temperatures on daily mortality using smooth functions to control for confounders, and estimated non-linear effects of exposure while allowing for auto-regressive correlation of observations within summers. The effect of temperature on mortality was found distributed over the same or following day, with statistically significant cumulative combined relative risk of about 5.1% (CI = 0.3, 10.1 per °C above the 90th percentile of summer temperature. The effect of high relative humidity was statistically significant in only one of the regions, as was the effect of relative humidity (above 80th percentile and temperature (above 90th percentile. In the southernmost region studied there appeared to be a significant increase in mortality with decreasing low summer temperatures that was not

Heterogeneous cellular networks

CERN Document Server

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

Modeling the effects of space structure and combination therapies on phenotypic heterogeneity and drug resistance in solid tumors.

Science.gov (United States)

Lorz, Alexander; Lorenzi, Tommaso; Clairambault, Jean; Escargueil, Alexandre; Perthame, Benoît

2015-01-01

Histopathological evidence supports the idea that the emergence of phenotypic heterogeneity and resistance to cytotoxic drugs can be considered as a process of selection in tumor cell populations. In this framework, can we explain intra-tumor heterogeneity in terms of selection driven by the local cell environment? Can we overcome the emergence of resistance and favor the eradication of cancer cells by using combination therapies? Bearing these questions in mind, we develop a model describing cell dynamics inside a tumor spheroid under the effects of cytotoxic and cytostatic drugs. Cancer cells are assumed to be structured as a population by two real variables standing for space position and the expression level of a phenotype of resistance to cytotoxic drugs. The model takes explicitly into account the dynamics of resources and anticancer drugs as well as their interactions with the cell population under treatment. We analyze the effects of space structure and combination therapies on phenotypic heterogeneity and chemotherapeutic resistance. Furthermore, we study the efficacy of combined therapy protocols based on constant infusion and bang-bang delivery of cytotoxic and cytostatic drugs.

Robust mechanobiological behavior emerges in heterogeneous myosin systems

Science.gov (United States)

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.

POPULATION III STARS AND REMNANTS IN HIGH-REDSHIFT GALAXIES

International Nuclear Information System (INIS)

Xu Hao; Norman, Michael L.; Wise, John H.

2013-01-01

Recent simulations of Population III star formation have suggested that some fraction form in binary systems, in addition to having a characteristic mass of tens of solar masses. The deaths of metal-free stars result in the initial chemical enrichment of the universe and the production of the first stellar-mass black holes. Here we present a cosmological adaptive mesh refinement simulation of an overdense region that forms a few 10 9 M ☉ dark matter halos and over 13,000 Population III stars by redshift 15. We find that most halos do not form Population III stars until they reach M vir ∼ 10 7 M ☉ because this biased region is quickly enriched from both Population III and galaxies, which also produce high levels of ultraviolet radiation that suppress H 2 formation. Nevertheless, Population III stars continue to form, albeit in more massive halos, at a rate of ∼10 –4 M ☉ yr –1 Mpc –3 at redshift 15. The most massive starless halo has a mass of 7 × 10 7 M ☉ , which could host massive black hole formation through the direct gaseous collapse scenario. We show that the multiplicity of the Population III remnants grows with halo mass above 10 8 M ☉ , culminating in 50 remnants located in 10 9 M ☉ halos on average. This has implications that high-mass X-ray binaries and intermediate-mass black holes that originate from metal-free stars may be abundant in high-redshift galaxies

Coordinated Energy Management in Heterogeneous Processors

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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.

Quantification of the heterogeneity of prognostic cellular biomarkers in ewing sarcoma using automated image and random survival forest analysis.

Directory of Open Access Journals (Sweden)

Claudia Bühnemann

Full Text Available Driven by genomic somatic variation, tumour tissues are typically heterogeneous, yet unbiased quantitative methods are rarely used to analyse heterogeneity at the protein level. Motivated by this problem, we developed automated image segmentation of images of multiple biomarkers in Ewing sarcoma to generate distributions of biomarkers between and within tumour cells. We further integrate high dimensional data with patient clinical outcomes utilising random survival forest (RSF machine learning. Using material from cohorts of genetically diagnosed Ewing sarcoma with EWSR1 chromosomal translocations, confocal images of tissue microarrays were segmented with level sets and watershed algorithms. Each cell nucleus and cytoplasm were identified in relation to DAPI and CD99, respectively, and protein biomarkers (e.g. Ki67, pS6, Foxo3a, EGR1, MAPK localised relative to nuclear and cytoplasmic regions of each cell in order to generate image feature distributions. The image distribution features were analysed with RSF in relation to known overall patient survival from three separate cohorts (185 informative cases. Variation in pre-analytical processing resulted in elimination of a high number of non-informative images that had poor DAPI localisation or biomarker preservation (67 cases, 36%. The distribution of image features for biomarkers in the remaining high quality material (118 cases, 104 features per case were analysed by RSF with feature selection, and performance assessed using internal cross-validation, rather than a separate validation cohort. A prognostic classifier for Ewing sarcoma with low cross-validation error rates (0.36 was comprised of multiple features, including the Ki67 proliferative marker and a sub-population of cells with low cytoplasmic/nuclear ratio of CD99. Through elimination of bias, the evaluation of high-dimensionality biomarker distribution within cell populations of a tumour using random forest analysis in quality

Quantification of the heterogeneity of prognostic cellular biomarkers in ewing sarcoma using automated image and random survival forest analysis.

Science.gov (United States)

Bühnemann, Claudia; Li, Simon; Yu, Haiyue; Branford White, Harriet; Schäfer, Karl L; Llombart-Bosch, Antonio; Machado, Isidro; Picci, Piero; Hogendoorn, Pancras C W; Athanasou, Nicholas A; Noble, J Alison; Hassan, A Bassim

2014-01-01

Driven by genomic somatic variation, tumour tissues are typically heterogeneous, yet unbiased quantitative methods are rarely used to analyse heterogeneity at the protein level. Motivated by this problem, we developed automated image segmentation of images of multiple biomarkers in Ewing sarcoma to generate distributions of biomarkers between and within tumour cells. We further integrate high dimensional data with patient clinical outcomes utilising random survival forest (RSF) machine learning. Using material from cohorts of genetically diagnosed Ewing sarcoma with EWSR1 chromosomal translocations, confocal images of tissue microarrays were segmented with level sets and watershed algorithms. Each cell nucleus and cytoplasm were identified in relation to DAPI and CD99, respectively, and protein biomarkers (e.g. Ki67, pS6, Foxo3a, EGR1, MAPK) localised relative to nuclear and cytoplasmic regions of each cell in order to generate image feature distributions. The image distribution features were analysed with RSF in relation to known overall patient survival from three separate cohorts (185 informative cases). Variation in pre-analytical processing resulted in elimination of a high number of non-informative images that had poor DAPI localisation or biomarker preservation (67 cases, 36%). The distribution of image features for biomarkers in the remaining high quality material (118 cases, 104 features per case) were analysed by RSF with feature selection, and performance assessed using internal cross-validation, rather than a separate validation cohort. A prognostic classifier for Ewing sarcoma with low cross-validation error rates (0.36) was comprised of multiple features, including the Ki67 proliferative marker and a sub-population of cells with low cytoplasmic/nuclear ratio of CD99. Through elimination of bias, the evaluation of high-dimensionality biomarker distribution within cell populations of a tumour using random forest analysis in quality controlled tumour

Decoding a Decision Process in the Neuronal Population of Dorsal Premotor Cortex.

Science.gov (United States)

Rossi-Pool, Román; Zainos, Antonio; Alvarez, Manuel; Zizumbo, Jerónimo; Vergara, José; Romo, Ranulfo

2017-12-20

When trained monkeys discriminate the temporal structure of two sequential vibrotactile stimuli, dorsal premotor cortex (DPC) showed high heterogeneity among its neuronal responses. Notably, DPC neurons coded stimulus patterns as broader categories and signaled them during working memory, comparison, and postponed decision periods. Here, we show that such population activity can be condensed into two major coding components: one that persistently represented in working memory both the first stimulus identity and the postponed informed choice and another that transiently coded the initial sensory information and the result of the comparison between the two stimuli. Additionally, we identified relevant signals that coded the timing of task events. These temporal and task-parameter readouts were shown to be strongly linked to the monkeys' behavior when contrasted to those obtained in a non-demanding cognitive control task and during error trials. These signals, hidden in the heterogeneity, were prominently represented by the DPC population response. Copyright © 2017 Elsevier Inc. All rights reserved.

Pronounced zonal heterogeneity in Eocene southern high-latitude sea surface temperatures.

Science.gov (United States)

Douglas, Peter M J; Affek, Hagit P; Ivany, Linda C; Houben, Alexander J P; Sijp, Willem P; Sluijs, Appy; Schouten, Stefan; Pagani, Mark

2014-05-06

Paleoclimate studies suggest that increased global warmth during the Eocene epoch was greatly amplified at high latitudes, a state that climate models cannot fully reproduce. However, proxy estimates of Eocene near-Antarctic sea surface temperatures (SSTs) have produced widely divergent results at similar latitudes, with SSTs above 20 °C in the southwest Pacific contrasting with SSTs between 5 and 15 °C in the South Atlantic. Validation of this zonal temperature difference has been impeded by uncertainties inherent to the individual paleotemperature proxies applied at these sites. Here, we present multiproxy data from Seymour Island, near the Antarctic Peninsula, that provides well-constrained evidence for annual SSTs of 10-17 °C (1σ SD) during the middle and late Eocene. Comparison of the same paleotemperature proxy at Seymour Island and at the East Tasman Plateau indicate the presence of a large and consistent middle-to-late Eocene SST gradient of ∼7 °C between these two sites located at similar paleolatitudes. Intermediate-complexity climate model simulations suggest that enhanced oceanic heat transport in the South Pacific, driven by deep-water formation in the Ross Sea, was largely responsible for the observed SST gradient. These results indicate that very warm SSTs, in excess of 18 °C, did not extend uniformly across the Eocene southern high latitudes, and suggest that thermohaline circulation may partially control the distribution of high-latitude ocean temperatures in greenhouse climates. The pronounced zonal SST heterogeneity evident in the Eocene cautions against inferring past meridional temperature gradients using spatially limited data within given latitudinal bands.

Population-level consequences of spatially heterogeneous exposure to heavy metals in soil: An individual-based model of springtails

DEFF Research Database (Denmark)

Meli, Mattia; Auclerc, Apolline; Palmqvist, Annemette

2013-01-01

Contamination of soil with toxic heavy metals poses a major threat to the environment and human health. Anthropogenic sources include smelting of ores, municipal wastes, fertilizers, and pesticides. In assessing soil quality and the environmental and ecological risk of contamination with heavy...... metals, often homogeneous contamination of the soil is assumed. However, soils are very heterogeneous environments. Consequently, both contamination and the response of soil organisms can be assumed to be heterogeneous. This might have consequences for the exposure of soil organisms...

Rupture Dynamics and Ground Motion from Earthquakes in Heterogeneous Media

Science.gov (United States)

Bydlon, S.; Dunham, E. M.; Kozdon, J. E.

2012-12-01

Heterogeneities in the material properties of Earth's crust scatter propagating seismic waves. The effects of scattered waves are reflected in the seismic coda and depend on the relative strength of the heterogeneities, spatial arrangement, and distance from source to receiver. In the vicinity of the fault, scattered waves influence the rupture process by introducing fluctuations in the stresses driving propagating ruptures. Further variability in the rupture process is introduced by naturally occurring geometric complexity of fault surfaces, and the stress changes that accompany slip on rough surfaces. We have begun a modeling effort to better understand the origin of complexity in the earthquake source process, and to quantify the relative importance of source complexity and scattering along the propagation path in causing incoherence of high frequency ground motion. To do this we extended our two-dimensional high order finite difference rupture dynamics code to accommodate material heterogeneities. We generate synthetic heterogeneous media using Von Karman correlation functions and their associated power spectral density functions. We then nucleate ruptures on either flat or rough faults, which obey strongly rate-weakening friction laws. Preliminary results for flat faults with uniform frictional properties and initial stresses indicate that off-fault material heterogeneity alone can lead to a complex rupture process. Our simulations reveal the excitation of high frequency bursts of waves, which radiate energy away from the propagating rupture. The average rupture velocity is thus reduced relative to its value in simulations employing homogeneous material properties. In the coming months, we aim to more fully explore parameter space by varying the correlation length, Hurst exponent, and amplitude of medium heterogeneities, as well as the statistical properties characterizing fault roughness.

Interpretable Categorization of Heterogeneous Time Series Data

Science.gov (United States)

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.

Graphene: a promising two-dimensional support for heterogeneous catalysts

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Xiaobin eFan

2015-01-01

Full Text Available Graphene has many advantages that make it an attractive two-dimensional (2D support for heterogeneous catalysts. It not only allows the high loading of targeted catalytic species, but also facilitates the mass transfer during the reaction processes. These advantages, along with its unique physical and chemical properties, endow graphene great potential as catalyst support in heterogeneous catalysis.

Mitochondrial cytopathies, phenotypic heterogeneity and a high incidence.

LENUS (Irish Health Repository)

Ryan, E

2006-10-01

Mitochondrial respiratory chain disorders account for significant and varied presentations in paediatric practice. The true prevalence of these disorders in the paediatric population is still not well documented with predicted geographic variation. We report a retrospective analysis over a seven year period of cases presenting to a tertiary care centre and associated clinical features. The overall prevalence of mitochondrial disorders in our population is higher than expected (1\\/9,000 births), explained in part by multiple presentations in a consanguineous subgroup of the population (Irish travellers).

High effective heterogeneous plasma vortex reactor for production of heat energy and hydrogen

Science.gov (United States)

Belov, N. K.; Zavershinskii, I. P.; Klimov, A. I.; Molevich, N. E.; Porfiriev, D. P.; Tolkunov, B. N.

2018-03-01

This work is a continuation of our previous studies [1-10] of physical parameters and properties of a long-lived heterogeneous plasmoid (plasma formation with erosive nanoclusters) created by combined discharge in a high-speed swirl flow. Here interaction of metal nanoclusters with hydrogen atoms is studied in a plasma vortex reactor (PVR) with argon-water steam mixture. Metal nanoclusters were created by nickel cathode’s erosion at combined discharge on. Dissociated hydrogen atoms and ions were obtained in water steam by electric discharge. These hydrogen atoms and ions interacted with metal nanoclusters, which resulted in the creation of a stable plasmoid in a swirl gas flow. This plasmoid has been found to create intensive soft X-ray radiation. Plasma parameters of this plasmoid were measured by optical spectroscopy method. It has been obtained that there is a high non-equilibrium plasmoid: Te > TV >> TR. The measured coefficient of energy performance of this plasmoid is about COP = 2÷10. This extra power release in plasmoid is supposed to be connected with internal excited electrons. The obtained experimental results have proved our suggestion.

Heterogeneous policies, heterogeneous technologies: The case of renewable energy

International Nuclear Information System (INIS)

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.

Derivation of Batho's correction factor for heterogeneities

International Nuclear Information System (INIS)

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

Heterogeneity of life histories in a nonhuman primate population

DEFF Research Database (Denmark)

Hernández Pacheco, Raisa; Steiner, Uli

2014-01-01

histories within a primate population is generated by density-dependent dynamics, the demographic data of Cayo Santiago rhesus macaques over 40 years and 7000 individuals was used. A multi-stage model using a first-order Markov process describing reproductive dynamics was constructed and annual entropy...

High-resolution 2-D Bragg diffraction reveal heterogeneous domain transformation behavior in a bulk relaxor ferroelectric

Energy Technology Data Exchange (ETDEWEB)

Pramanick, Abhijit, E-mail: apramani@cityu.edu.hk [Department of Physics and Materials Science, City University of Hong Kong, Kowloon (Hong Kong); Stoica, Alexandru D.; An, Ke [Chemical and Engineering Materials Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831 (United States)

2016-08-29

In-situ measurement of fine-structure of neutron Bragg diffraction peaks from a relaxor single-crystal using a time-of-flight instrument reveals highly heterogeneous mesoscale domain transformation behavior under applied electric fields. It is observed that only ∼25% of domains undergo reorientation or phase transition contributing to large average strains, while at least 40% remain invariant and exhibit microstrains. Such insights could be central for designing new relaxor materials with better performance and longevity. The current experimental technique can also be applied to resolve complex mesoscale phenomena in other functional materials.

Mechanical Design of Odin, an Extendable Heterogeneous Deformable Modular Robot

DEFF Research Database (Denmark)

Lyder, Andreas; Garcia, Ricardo Franco Mendoza; Støy, Kasper

2008-01-01

Highly sophisticated animals consist of a set of heterogenous modules decided by nature so that they can survive in a complex environment. In this paper we present a new modular robot inspired by biology called Odin. The Odin robot is based on a deformable lattice and consists of an extendable se...... of heterogeneous modules. We present the design and implementation of a cubic closed-packed (CCP) joint module, a telescoping link, and a flexible connection mechanism. The developed robot is highly versatile and opens up for a wide range of new research in modular robotics.......Highly sophisticated animals consist of a set of heterogenous modules decided by nature so that they can survive in a complex environment. In this paper we present a new modular robot inspired by biology called Odin. The Odin robot is based on a deformable lattice and consists of an extendable set...

Geographic stratification of linkage disequilibrium: a worldwide population study in a region of chromosome 22

Directory of Open Access Journals (Sweden)

González-Neira Anna

2004-11-01

Full Text Available Abstract Recent studies of haplotype diversity in a number of genomic regions have suggested that long stretches of DNA are preserved in the same chromosome, with little evidence of recombination events. The knowledge of the extent and strength of these haplotypes could become a powerful tool for future genetic analysis of complex traits. Different patterns of linkage disequilibrium (LD have been found when comparing individuals of African and European descent, but there is scarce knowledge about the worldwide population stratification. Thus, the study of haplotype composition and the pattern of LD from a global perspective are relevant for elucidating their geographical stratification, as it may have implications in the future analysis of complex traits. We have typed 12 single nucleotide polymorphisms in a chromosome 22 region--previously described as having high LD levels in European populations -- in 39 different world populations. Haplotype structure has a clear continental structure with marked heterogeneity within some continents (Africa, America. The pattern of LD among neighbouring markers exhibits a strong clustering of all East Asian populations on the one hand and of Western Eurasian populations (including Europe on the other, revealing only two major LD patterns, but with some very specific outliers due to specific demographic histories. Moreover, it should be taken into account that African populations are highly heterogeneous. The present results support the existence of a wide (but not total communality in LD patterns in human populations from different continental regions, despite differences in their demographic histories, as population factors seem to be less relevant compared with genomic forces in shaping the patterns of LD.

A New Advanced Backcross Tomato Population Enables High Resolution Leaf QTL Mapping and Gene Identification

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Daniel Fulop

2016-10-01

Full Text Available Quantitative Trait Loci (QTL mapping is a powerful technique for dissecting the genetic basis of traits and species differences. Established tomato mapping populations between domesticated tomato (Solanum lycopersicum and its more distant interfertile relatives typically follow a near isogenic line (NIL design, such as the S. pennellii Introgression Line (IL population, with a single wild introgression per line in an otherwise domesticated genetic background. Here, we report on a new advanced backcross QTL mapping resource for tomato, derived from a cross between the M82 tomato cultivar and S. pennellii. This so-called Backcrossed Inbred Line (BIL population is comprised of a mix of BC2 and BC3 lines, with domesticated tomato as the recurrent parent. The BIL population is complementary to the existing S. pennellii IL population, with which it shares parents. Using the BILs, we mapped traits for leaf complexity, leaflet shape, and flowering time. We demonstrate the utility of the BILs for fine-mapping QTL, particularly QTL initially mapped in the ILs, by fine-mapping several QTL to single or few candidate genes. Moreover, we confirm the value of a backcrossed population with multiple introgressions per line, such as the BILs, for epistatic QTL mapping. Our work was further enabled by the development of our own statistical inference and visualization tools, namely a heterogeneous hidden Markov model for genotyping the lines, and by using state-of-the-art sparse regression techniques for QTL mapping.

Surface current double-heterogeneous multilayer multicell methodology

International Nuclear Information System (INIS)

Stepanek, J.; Segev, M.

1991-01-01

A surface current methodology is developed to respond to the need for treating the various levels of material heterogeneity in a double-heterogeneous multilayer multicell in processing neutron multigroup cross sections in the resonance as well as thermal energy range. First, the basic surface cosine current transport equations to calculate the energy-dependent neutron flux spatial distribution in the multilayered multicell are formulated. Slab, spherical and cylindrical geometries, as well as square and hexagonal lattices and pebble-bed configurations with white or reflective cell boundary conditions, are considered. Second, starting from the surface cosine-current formulation, a two-zone three-layer multicell formalism for reduction of heterogeneous flux expressions to equivalent homogeneous flux expression for table method was developed. This formalism allows an infinite, as well as a limited, number of second-heterogeneity cells within a partial first-heterogeneity cell layer to be considered. Also, the number of the first-and second-heterogeneity cell types is quite general. The 'outer' (right side) as well as 'inner' (left side) Dancoff probabilities can be calculated for any particular layer. An accurate, efficient, and compact interpolation procedure is developed to calculate the basic collision probabilities. These are transmission and escape probabilities for shells in slab, cylindrical, and spherical geometries, as well as Dancoff probabilities for cylinders in square and hexagonal lattices. The use of the interpolation procedure is exemplified in a multilayer multicell approximation for the Dancoff probability, enabling a routine evaluation of the equivalence-based shielded resonance integral in highly complex lattices of slab, cylindrical, or spherical cells. (author) 1 fig., 2 tabs., 10 refs

Heterogeneity in Multiple Sclerosis: Scratching the Surface of a Complex Disease

Science.gov (United States)

Disanto, Giulio; Berlanga, Antonio J.; Handel, Adam E.; Para, Andrea E.; Burrell, Amy M.; Fries, Anastasia; Handunnetthi, Lahiru; De Luca, Gabriele C.; Morahan, Julia M.

2011-01-01

Multiple Sclerosis (MS) is the most common demyelinating disease of the central nervous system. Although the etiology and the pathogenesis of MS has been extensively investigated, no single pathway, reliable biomarker, diagnostic test, or specific treatment have yet been identified for all MS patients. One of the reasons behind this failure is likely to be the wide heterogeneity observed within the MS population. The clinical course of MS is highly variable and includes several subcategories and variants. Moreover, apart from the well-established association with the HLA-class II DRB1*15:01 allele, other genetic variants have been shown to vary significantly across different populations and individuals. Finally both pathological and immunological studies suggest that different pathways may be active in different MS patients. We conclude that these “MS subtypes” should still be considered as part of the same disease but hypothesize that spatiotemporal effects of genetic and environmental agents differentially influence MS course. These considerations are extremely relevant, as outcome prediction and personalised medicine represent the central aim of modern research. PMID:21197462

Heterogeneous sharpness for cross-spectral face recognition

Science.gov (United States)

Cao, Zhicheng; Schmid, Natalia A.

2017-05-01

Matching images acquired in different electromagnetic bands remains a challenging problem. An example of this type of comparison is matching active or passive infrared (IR) against a gallery of visible face images, known as cross-spectral face recognition. Among many unsolved issues is the one of quality disparity of the heterogeneous images. Images acquired in different spectral bands are of unequal image quality due to distinct imaging mechanism, standoff distances, or imaging environment, etc. To reduce the effect of quality disparity on the recognition performance, one can manipulate images to either improve the quality of poor-quality images or to degrade the high-quality images to the level of the quality of their heterogeneous counterparts. To estimate the level of discrepancy in quality of two heterogeneous images a quality metric such as image sharpness is needed. It provides a guidance in how much quality improvement or degradation is appropriate. In this work we consider sharpness as a relative measure of heterogeneous image quality. We propose a generalized definition of sharpness by first achieving image quality parity and then finding and building a relationship between the image quality of two heterogeneous images. Therefore, the new sharpness metric is named heterogeneous sharpness. Image quality parity is achieved by experimentally finding the optimal cross-spectral face recognition performance where quality of the heterogeneous images is varied using a Gaussian smoothing function with different standard deviation. This relationship is established using two models; one of them involves a regression model and the other involves a neural network. To train, test and validate the model, we use composite operators developed in our lab to extract features from heterogeneous face images and use the sharpness metric to evaluate the face image quality within each band. Images from three different spectral bands visible light, near infrared, and short

An Overview of Autism Spectrum Disorder, Heterogeneity and Treatment Options

Institute of Scientific and Technical Information of China (English)

Anne Masi; Marilena M.DeMayo; Nicholas Glozier; Adam J.Guastella

2017-01-01

Since the documented observations of Kanner in 1943,there has been great debate about the diagnoses,the sub-types,and the diagnostic threshold that relates to what is now known as autism spectrum disorder (ASD).Reflecting this complicated history,there has been continual refinement from DSM-Ⅲ with ‘Infantile Autism’ to the current DSM-Ⅴ diagnosis.The disorder is now widely accepted as a complex,pervasive,heterogeneous condition with multiple etiologies,sub-types,and developmental trajectories.Diagnosis remains based on observation of atypical behaviors,with criteria of persistent deficits in social communication and restricted and repetitive patterns of behavior.This review provides a broad overview of the history,prevalence,etiology,clinical presentation,and heterogeneity of ASD.Factors contributing to heterogeneity,including genetic variability,comorbidity,and gender are reviewed.We then explore current evidencebased pharmacological and behavioral treatments for ASD and highlight the complexities of conducting clinical trials that evaluate therapeutic efficacy in ASD populations.Finally,we discuss the potential of a new wave of research examining objective biomarkers to facilitate the evaluation of sub-typing,diagnosis,and treatment response in ASD.

Indoor Location Fingerprinting with Heterogeneous Clients

DEFF Research Database (Denmark)

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...

Green Product Development with Consumer Heterogeneity under Horizontal Competition

Directory of Open Access Journals (Sweden)

Bing Xu

2018-06-01

Full Text Available In this paper, we explore the pricing and greenness issues of two competitive firms without and with consumer heterogeneity. We derive and compare the optimal solutions and profits employed by firms under different scenarios. Then, we identify the effects of consumer heterogeneity under different competition intensities. The analytical results reveal that if market competition is at a relatively low level, we find that: (i when the greenness sensitivity of consumers with no preference is sufficiently small, more consumers have high environmental awareness, and companies easily achieve their environmental goals as well as economic goals; (ii when the greenness sensitivity of consumers with no preference is at a medium level, as the fraction of consumers with high environmental awareness increases, and the firm might achieve economic goals at the cost of reducing environmental goals; and (iii when the greenness sensitivity of consumers with no preference is at a high level, the fraction of consumers with high environmental awareness increases, but firms might have more difficulty achieving their environmental and economic goals. On the other hand, if the market competition is at a relatively high level, the presence of consumer heterogeneity can help improve environmental goals, but make achievement of economic goals difficult.

Data Driven Approach for High Resolution Population Distribution and Dynamics Models

Energy Technology Data Exchange (ETDEWEB)

Bhaduri, Budhendra L [ORNL; Bright, Eddie A [ORNL; Rose, Amy N [ORNL; Liu, Cheng [ORNL; Urban, Marie L [ORNL; Stewart, Robert N [ORNL

2014-01-01

High resolution population distribution data are vital for successfully addressing critical issues ranging from energy and socio-environmental research to public health to human security. Commonly available population data from Census is constrained both in space and time and does not capture population dynamics as functions of space and time. This imposes a significant limitation on the fidelity of event-based simulation models with sensitive space-time resolution. This paper describes ongoing development of high-resolution population distribution and dynamics models, at Oak Ridge National Laboratory, through spatial data integration and modeling with behavioral or activity-based mobility datasets for representing temporal dynamics of population. The model is resolved at 1 km resolution globally and describes the U.S. population for nighttime and daytime at 90m. Integration of such population data provides the opportunity to develop simulations and applications in critical infrastructure management from local to global scales.

Genetic heterogeneity of L-Zagreb mumps virus vaccine strain.

Science.gov (United States)

Kosutic-Gulija, Tanja; Forcic, Dubravko; Santak, Maja; Ramljak, Ana; Mateljak-Lukacevic, Sanja; Mazuran, Renata

2008-07-10

The most often used mumps vaccine strains Jeryl Lynn (JL), RIT4385, Urabe-AM9, L-Zagreb and L-3 differ in immunogenicity and reactogenicity. Previous analyses showed that JL, Urabe-AM9 and L-3 are genetically heterogeneous. We identified the heterogeneity of L-Zagreb throughout the entire genome. Two major variants were defined: variant A being identical to the consensus sequence of viral seeds and vaccine(s) and variant B which differs from variant A in three nucleotide positions. The difference between viral variants in L-Zagreb strain is insufficient for distinct viral strains to be defined. We demonstrated that proportion of variants in L-Zagreb viral population depends on cell substrate used for viral replication in vitro and in vivo. L-Zagreb strain should be considered as a single strain composed of at least two variant viral genomes.

Blasting methods for heterogeneous rocks in hillside open-pit mines with high and steep slopes

Science.gov (United States)

Chen, Y. J.; Chang, Z. G.; Chao, X. H.; Zhao, J. F.

2017-06-01

In the arid desert areas in Xinjiang, most limestone quarries are hillside open-pit mines (OPMs) where the limestone is hard, heterogeneous, and fractured, and can be easily broken into large blocks by blasting. This study tried to find effective technical methods for blasting heterogeneous rocks in such quarries based on an investigation into existing problems encountered in actual mining at Hongshun Limestone Quarry in Xinjiang. This study provided blasting schemes for hillside OPMs with different heights and slopes. These schemes involve the use of vertical deep holes, oblique shallow holes, and downslope hole-by-hole sublevel or simultaneous detonation techniques. In each bench, the detonations of holes in a detonation unit occur at intervals of 25-50 milliseconds. The research findings can offer technical guidance on how to blast heterogeneous rocks in hillside limestone quarries.

The population genetics of Pseudomonas aeruginosa isolates from different patient populations exhibits high-level host specificity.

Directory of Open Access Journals (Sweden)