Sample records for double heterogeneity effect

  1. Rock anelasticity due to patchy saturation and fabric heterogeneity: A double double-porosity model of wave propagation

    NASA Astrophysics Data System (ADS)

    Ba, Jing; Xu, Wenhao; Fu, Li-Yun; Carcione, José M.; Zhang, Lin

    2017-03-01

    Heterogeneity of rock's fabric can induce heterogeneous distribution of immiscible fluids in natural reservoirs, since the lithological variations (mainly permeability) may affect fluid migration in geological time scales, resulting in patchy saturation of fluids. Therefore, fabric and saturation inhomogeneities both affect wave propagation. To model the wave effects (attenuation and velocity dispersion), we introduce a double double-porosity model, where pores saturated with two different fluids overlap with pores having dissimilar compressibilities. The governing equations are derived by using Hamilton's principle based on the potential energy, kinetic energy, and dissipation functions, and the stiffness coefficients are determined by gedanken experiments, yielding one fast P wave and four slow Biot waves. Three examples are given, namely, muddy siltstones, clean dolomites, and tight sandstones, where fabric heterogeneities at three different spatial scales are analyzed in comparison with experimental data. In muddy siltstones, where intrapore clay and intergranular pores constitute a submicroscopic double-porosity structure, wave anelasticity mainly occurs in the frequency range (104-107 Hz), while in pure dolomites with microscopic heterogeneity of grain contacts and tight sandstones with mesoscopic heterogeneity of less consolidated sands, it occurs at 103-107 Hz and 101-103 Hz (seismic band), respectively. The predicted maximum quality factor of the fast compressional wave for the sandstone is the lowest (approximately 8), and that of the dolomite is the highest. The results of the diffusive slow waves are affected by the strong friction effects between solids and fluids. The model describes wave propagation in patchy-saturated rocks with fabric heterogeneity at different scales, and the relevant theoretical predictions agree well with the experimental data in fully and partially saturated rocks.

  2. Not simply more of the same: distinguishing between patient heterogeneity and parameter uncertainty.

    PubMed

    Vemer, Pepijn; Goossens, Lucas M A; Rutten-van Mölken, Maureen P M H

    2014-11-01

    In cost-effectiveness (CE) Markov models, heterogeneity in the patient population is not automatically taken into account. We aimed to compare methods of dealing with heterogeneity on estimates of CE, using a case study in chronic obstructive pulmonary disease (COPD). We first present a probabilistic sensitivity analysis (PSA) in which we sampled only from distributions representing parameter uncertainty. This ignores any heterogeneity. Next, we explored heterogeneity by presenting results for subgroups, using a method that samples parameter uncertainty simultaneously with heterogeneity in a single-loop PSA. Finally, we distinguished parameter uncertainty from heterogeneity in a double-loop PSA by performing a nested simulation within each PSA iteration. Point estimates and uncertainty differed substantially between methods. The incremental CE ratio (ICER) ranged from € 4900 to € 13,800. The single-loop PSA led to a substantially different shape of the CE plane and an overestimation of the uncertainty compared with the other 3 methods. The CE plane for the double-loop PSA showed substantially less uncertainty and a stronger negative correlation between the difference in costs and the difference in effects compared with the other methods. This came at the cost of higher calculation times. Not accounting for heterogeneity, subgroup analysis and the double-loop PSA can be viable options, depending on the decision makers' information needs. The single-loop PSA should not be used in CE research. It disregards the fundamental differences between heterogeneity and sampling uncertainty and overestimates uncertainty as a result. © The Author(s) 2014.

  3. Association between hepatitis B virus/hepatitis C virus infection and primary hepatocellular carcinoma risk: A meta-analysis based on Chinese population.

    PubMed

    Li, Libo; Lan, Xiaolin

    2016-12-01

    To assess the relationship between hepatitis B virus (HBV), hepatitis C virus (HCV), and HBV/HCV double infection and hepatocellular carcinoma risk in Chinese population. The databases of PubMed and CNKI were electronic searched by reviewers according to the searching words of HBV, HCV, and hepatocellular carcinoma. The related case-control studies or cohort studies were included. The association between virus infection and hepatocellular carcinoma risk was demonstrated by odds ratio (OR) and 95% confidence interval (95% CI). The data were pooled by fixed or random effects model according to the statistical heterogeneity. The publication bias was assessed by Begg's funnel plot and Egger's linear regression test. Finally, 13 publications were included in this meta-analysis. For significant statistical heterogeneity (I2 = 99.8%,P = 0.00), the OR was pooled by random effects model. The pooled results showed that HBV infection can significantly increase the risk of developing hepatocellular carcinoma (OR = 58.01, 95% CI: 44.27-71.75); statistical heterogeneity analysis showed that significant heterogeneity existed in evaluation of HCV infection and hepatocellular carcinoma risk across the included 13 studies I2 = 77.78%, P = 0.00). The OR was pooled by random effects model. The pooled results showed that HCV infection can significantly increase the risk of developing hepatocellular carcinoma (OR = 2.34, 95% CI: 1.20-3.47); significant heterogeneity did not exist in evaluation HBV/HCV double infection and hepatocellular carcinoma risk for the included 13 studies (I2 = 0.00%,P = 0.80). The OR was pooled by fixed effects model. The pooled results showed that HBV/HCV double infection can significantly increase the risk of developing hepatocellular carcinoma (OR = 11.39, 95% CI: 4.58-18.20). No publication bias was found in the aspects of HBV, HCV, and HBV/HCV double infection and hepatocellular carcinoma. For Chinese population, HBV, HCV or HBV/HCV double infection can significantly increase the risk of developing hepatocellular carcinoma.

  4. Coarse-Grained Clustering Dynamics of Heterogeneously Coupled Neurons.

    PubMed

    Moon, Sung Joon; Cook, Katherine A; Rajendran, Karthikeyan; Kevrekidis, Ioannis G; Cisternas, Jaime; Laing, Carlo R

    2015-12-01

    The formation of oscillating phase clusters in a network of identical Hodgkin-Huxley neurons is studied, along with their dynamic behavior. The neurons are synaptically coupled in an all-to-all manner, yet the synaptic coupling characteristic time is heterogeneous across the connections. In a network of N neurons where this heterogeneity is characterized by a prescribed random variable, the oscillatory single-cluster state can transition-through [Formula: see text] (possibly perturbed) period-doubling and subsequent bifurcations-to a variety of multiple-cluster states. The clustering dynamic behavior is computationally studied both at the detailed and the coarse-grained levels, and a numerical approach that can enable studying the coarse-grained dynamics in a network of arbitrarily large size is suggested. Among a number of cluster states formed, double clusters, composed of nearly equal sub-network sizes are seen to be stable; interestingly, the heterogeneity parameter in each of the double-cluster components tends to be consistent with the random variable over the entire network: Given a double-cluster state, permuting the dynamical variables of the neurons can lead to a combinatorially large number of different, yet similar "fine" states that appear practically identical at the coarse-grained level. For weak heterogeneity we find that correlations rapidly develop, within each cluster, between the neuron's "identity" (its own value of the heterogeneity parameter) and its dynamical state. For single- and double-cluster states we demonstrate an effective coarse-graining approach that uses the Polynomial Chaos expansion to succinctly describe the dynamics by these quickly established "identity-state" correlations. This coarse-graining approach is utilized, within the equation-free framework, to perform efficient computations of the neuron ensemble dynamics.

  5. Estimating crustal heterogeneity from double-difference tomography

    USGS Publications Warehouse

    Got, J.-L.; Monteiller, V.; Virieux, J.; Okubo, P.

    2006-01-01

    Seismic velocity parameters in limited, but heterogeneous volumes can be inferred using a double-difference tomographic algorithm, but to obtain meaningful results accuracy must be maintained at every step of the computation. MONTEILLER et al. (2005) have devised a double-difference tomographic algorithm that takes full advantage of the accuracy of cross-spectral time-delays of large correlated event sets. This algorithm performs an accurate computation of theoretical travel-time delays in heterogeneous media and applies a suitable inversion scheme based on optimization theory. When applied to Kilauea Volcano, in Hawaii, the double-difference tomography approach shows significant and coherent changes to the velocity model in the well-resolved volumes beneath the Kilauea caldera and the upper east rift. In this paper, we first compare the results obtained using MONTEILLER et al.'s algorithm with those obtained using the classic travel-time tomographic approach. Then, we evaluated the effect of using data series of different accuracies, such as handpicked arrival-time differences ("picking differences"), on the results produced by double-difference tomographic algorithms. We show that picking differences have a non-Gaussian probability density function (pdf). Using a hyperbolic secant pdf instead of a Gaussian pdf allows improvement of the double-difference tomographic result when using picking difference data. We completed our study by investigating the use of spatially discontinuous time-delay data. ?? Birkha??user Verlag, Basel, 2006.

  6. A New Equivalence Theory Method for Treating Doubly Heterogeneous Fuel - I. Theory

    DOE PAGES

    Williams, Mark L.; Lee, Deokjung; Choi, Sooyoung

    2015-03-04

    A new methodology has been developed to treat resonance self-shielding in doubly heterogeneous very high temperature gas-cooled reactor systems in which the fuel compact region of a reactor lattice consists of small fuel grains dispersed in a graphite matrix. This new method first homogenizes the fuel grain and matrix materials using an analytically derived disadvantage factor from a two-region problem with equivalence theory and intermediate resonance method. This disadvantage factor accounts for spatial self-shielding effects inside each grain within the framework of an infinite array of grains. Then the homogenized fuel compact is self-shielded using a Bondarenko method to accountmore » for interactions between the fuel compact regions in the fuel lattice. In the final form of the equations for actual implementations, the double-heterogeneity effects are accounted for by simply using a modified definition of a background cross section, which includes geometry parameters and cross sections for both the grain and fuel compact regions. With the new method, the doubly heterogeneous resonance self-shielding effect can be treated easily even with legacy codes programmed only for a singly heterogeneous system by simple modifications in the background cross section for resonance integral interpolations. This paper presents a detailed derivation of the new method and a sensitivity study of double-heterogeneity parameters introduced during the derivation. The implementation of the method and verification results for various test cases are presented in the companion paper.« less

  7. Ozone response to a CO2 doubling - Results from a stratospheric circulation model with heterogeneous chemistry

    NASA Technical Reports Server (NTRS)

    Pitari, G.; Palermi, S.; Visconti, G.; Prinn, R. G.

    1992-01-01

    A spectral 3D model of the stratosphere has been used to study the sensitivity of polar ozone with respect to a carbon dioxide increase. The lower stratospheric cooling associated with an imposed CO2 doubling may increase the probability of polar stratospheric cloud (PSC) formation and this affect ozone. The ozone perturbation obtained with the inclusion of a simple parameterization for heterogeneous chemistry on PSCs is compared to that relative to a pure homogeneous chemistry. In both cases the temperature perturbation is determined by a CO2 doubling, while the total chlorine content is kept at the present level. It is shown that the lower temperature may increase the depth and the extension of the ozone hole by extending the area amenable to PSC formation. It may be argued that this effect, coupled with an increasing amount of chlorine, may produce a positive feedback on the ozone destruction.

  8. Influence of initial stress, irregularity and heterogeneity on Love-type wave propagation in double pre-stressed irregular layers lying over a pre-stressed half-space

    NASA Astrophysics Data System (ADS)

    Singh, Abhishek Kumar; Das, Amrita; Parween, Zeenat; Chattopadhyay, Amares

    2015-10-01

    The present paper deals with the propagation of Love-type wave in an initially stressed irregular vertically heterogeneous layer lying over an initially stressed isotropic layer and an initially stressed isotropic half-space. Two different types of irregularities, viz., rectangular and parabolic, are considered at the interface of uppermost initially stressed heterogeneous layer and intermediate initially stressed isotropic layer. Dispersion equations are obtained in closed form for both cases of irregularities, distinctly. The effect of size and shape of irregularity, horizontal compressive initial stress, horizontal tensile initial stress, heterogeneity of the uppermost layer and width ratio of the layers on phase velocity of Love-type wave are the major highlights of the study. Comparative study has been made to identify the effects of different shapes of irregularity, presence of heterogeneity and initial stresses. Numerical computations have been carried out and depicted by means of graphs for the present study.

  9. No evidence for intervention-dependent influence of methodological features on treatment effect.

    PubMed

    Jacobs, Wilco C H; Kruyt, Moyo C; Moojen, Wouter A; Verbout, Ab J; Oner, F Cumhur

    2013-12-01

    The goal of this systematic review was to evaluate if the influence of methodological features on treatment effect differs between types of intervention. MEDLINE, Embase, Web of Science, Cochrane methodology register, and reference lists were searched for meta-epidemiologic studies on the influence of methodological features on treatment effect. Studies analyzing influence of methodological features related to internal validity were included. We made a distinction among surgical, pharmaceutical, and therapeutical as separate types of intervention. Heterogeneity was calculated to identify differences among these types. Fourteen meta-epidemiologic studies were found with 51 estimates of influence of methodological features on treatment effect. Heterogeneity was observed among the intervention types for randomization. Surgical intervention studies showed a larger treatment effect when randomized; this was in contrast to pharmaceutical studies that found the opposite. For allocation concealment and double blinding, the influence of methodological features on the treatment effect was comparable across different types of intervention. For the remaining methodological features, there were insufficient observations. The influence of allocation concealment and double blinding on the treatment effect is consistent across studies of different interventional types. The influence of randomization although, may be different between surgical and nonsurgical studies. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Effective electromagnetic properties of microheterogeneous materials with surface phenomena

    NASA Astrophysics Data System (ADS)

    Levin, Valery; Markov, Mikhail; Mousatov, Aleksandr; Kazatchenko, Elena; Pervago, Evgeny

    2017-10-01

    In this paper, we present an approach to calculate the complex dielectric permittivity of a micro-heterogeneous medium composed of non-conductive solid inclusions embedded into the conductive liquid continuous host. To take into account the surface effects, we approximate the inclusion by a layered ellipsoid consisting of a dielectric core and an infinitesimally thin outer shell corresponding to an electrical double layer (EDL). To predict the effective complex dielectric permittivity of materials with a high concentration of inclusions, we have modified the Effective Field Method (EFM) for the layered ellipsoidal particles with complex electrical properties. We present the results of complex permittivity calculations for the composites with randomly and parallel oriented ellipsoidal inclusions. To analyze the influence of surface polarization, we have accomplished modeling in a wide frequency range for different existing physic-chemical models of double electrical layer. The results obtained show that the tensor of effective complex permittivity of a micro-heterogeneous medium with surface effects has complicate dependences on the component electrical properties, spatial material texture, and the inclusion shape (ellipsoid aspect ratio) and size. The dispersion of dielectric permittivity corresponds to the frequency dependence for individual inclusion of given size, and does not depend on the inclusion concentration.

  11. Cohesive fracture of elastically heterogeneous materials: An integrative modeling and experimental study

    NASA Astrophysics Data System (ADS)

    Wang, Neng; Xia, Shuman

    2017-01-01

    A combined modeling and experimental effort is made in this work to examine the cohesive fracture mechanisms of heterogeneous elastic solids. A two-phase laminated composite, which mimics the key microstructural features of many tough engineering and biological materials, is selected as a model material system. Theoretical and finite element analyses with cohesive zone modeling are performed to study the effective fracture resistance of the heterogeneous material associated with unstable crack propagation and arrest. A crack-tip-position controlled algorithm is implemented in the finite element analysis to overcome the inherent instability issues resulting from crack pinning and depinning at local heterogeneities. Systematic parametric studies are carried out to investigate the effects of various material and geometrical parameters, including the modulus mismatch ratio, phase volume fraction, cohesive zone size, and cohesive law shape. Concurrently, a novel stereolithography-based three-dimensional (3D) printing system is developed and used for fabricating heterogeneous test specimens with well-controlled structural and material properties. Fracture testing of the specimens is performed using the tapered double-cantilever beam (TDCB) test method. With optimal material and geometrical parameters, heterogeneous TDCB specimens are shown to exhibit enhanced effective fracture energy and effective fracture toughness than their homogeneous counterparts, which is in good agreement with the modeling predictions. The integrative computational and experimental study presented here provides a fundamental mechanistic understanding of the fracture mechanisms in brittle heterogeneous materials and sheds light on the rational design of tough materials through patterned heterogeneities.

  12. Chaotic dynamics in nonlinear duopoly Stackelberg game with heterogeneous players

    NASA Astrophysics Data System (ADS)

    Xiao, Yue; Peng, Yu; Lu, Qian; Wu, Xue

    2018-02-01

    In this paper, a nonlinear duopoly Stackelberg game of competition on output is concerned. In consideration of the effects of difference between plan products and actual products, the two heterogeneous players always adopt suitable strategies which can improve their benefits most. In general, status of each firm is unequal. As the firms take strategies sequentially and produce simultaneously, complex behaviors are brought about. Numerical simulation presents period doubling bifurcation, maximal Lyapunov exponent and chaos. Moreover, an appropriate method of chaos controlling is applied and fractal dimension is analyzed as well.

  13. DNA forms of the geminivirus African cassava mosaic virus consistent with a rolling circle mechanism of replication.

    PubMed Central

    Saunders, K; Lucy, A; Stanley, J

    1991-01-01

    We have analysed DNA from African cassava mosaic virus (ACMV)-infected Nicotiana benthamiana by two-dimensional agarose gel electrophoresis and detected ACMV-specific DNAs by blot-hybridisation. ACMV DNA forms including the previously characterised single-stranded, open-circular, linear and supercoiled DNAs along with five previously uncharacterised heterogeneous DNAs (H1-H5) were resolved. The heterogeneous DNAs were characterised by their chromatographic properties on BND-cellulose and their ability to hybridise to strand-specific and double-stranded probes. The data suggest a rolling circle mechanism of DNA replication, based on the sizes and strand specificity of the heterogeneous single-stranded DNA forms and their electrophoretic properties in relation to genome length single-stranded DNAs. Second-strand synthesis on a single-stranded virus-sense template is evident from the position of heterogeneous subgenomic complementary-sense DNA (H3) associated with genome-length virus-sense template (VT) DNA. The position of heterogeneous virus-sense DNA (H5), ranging in size from one to two genome lengths, is consistent with its association with genome-length complementary-sense template (CT) DNA, reflecting virus-sense strand displacement during replication from a double-stranded intermediate. The absence of subgenomic complementary-sense DNA associated with the displaced virus-sense strand suggests that replication proceeds via an obligate single-stranded intermediate. The other species of heterogeneous DNAs comprised concatemeric single-stranded virus-sense DNA (H4), and double-stranded or partially single-stranded DNA (H1 and H2). Images PMID:2041773

  14. DCE: A Distributed Energy-Efficient Clustering Protocol for Wireless Sensor Network Based on Double-Phase Cluster-Head Election.

    PubMed

    Han, Ruisong; Yang, Wei; Wang, Yipeng; You, Kaiming

    2017-05-01

    Clustering is an effective technique used to reduce energy consumption and extend the lifetime of wireless sensor network (WSN). The characteristic of energy heterogeneity of WSNs should be considered when designing clustering protocols. We propose and evaluate a novel distributed energy-efficient clustering protocol called DCE for heterogeneous wireless sensor networks, based on a Double-phase Cluster-head Election scheme. In DCE, the procedure of cluster head election is divided into two phases. In the first phase, tentative cluster heads are elected with the probabilities which are decided by the relative levels of initial and residual energy. Then, in the second phase, the tentative cluster heads are replaced by their cluster members to form the final set of cluster heads if any member in their cluster has more residual energy. Employing two phases for cluster-head election ensures that the nodes with more energy have a higher chance to be cluster heads. Energy consumption is well-distributed in the proposed protocol, and the simulation results show that DCE achieves longer stability periods than other typical clustering protocols in heterogeneous scenarios.

  15. Wave propagation in a strongly heterogeneous elastic porous medium: Homogenization of Biot medium with double porosities

    NASA Astrophysics Data System (ADS)

    Rohan, Eduard; Naili, Salah; Nguyen, Vu-Hieu

    2016-08-01

    We study wave propagation in an elastic porous medium saturated with a compressible Newtonian fluid. The porous network is interconnected whereby the pores are characterized by two very different characteristic sizes. At the mesoscopic scale, the medium is described using the Biot model, characterized by a high contrast in the hydraulic permeability and anisotropic elasticity, whereas the contrast in the Biot coupling coefficient is only moderate. Fluid motion is governed by the Darcy flow model extended by inertia terms and by the mass conservation equation. The homogenization method based on the asymptotic analysis is used to obtain a macroscopic model. To respect the high contrast in the material properties, they are scaled by the small parameter, which is involved in the asymptotic analysis and characterized by the size of the heterogeneities. Using the estimates of wavelengths in the double-porosity networks, it is shown that the macroscopic descriptions depend on the contrast in the static permeability associated with pores and micropores and on the frequency. Moreover, the microflow in the double porosity is responsible for fading memory effects via the macroscopic poroviscoelastic constitutive law. xml:lang="fr"

  16. Doubled heterogeneous crystal nucleation in sediments of hard sphere binary-mass mixtures

    NASA Astrophysics Data System (ADS)

    Löwen, Hartmut; Allahyarov, Elshad

    2011-10-01

    Crystallization during the sedimentation process of a binary colloidal hard spheres mixture is explored by Brownian dynamics computer simulations. The two species are different in buoyant mass but have the same interaction diameter. Starting from a completely mixed system in a finite container, gravity is suddenly turned on, and the crystallization process in the sample is monitored. If the Peclet numbers of the two species are both not too large, crystalline layers are formed at the bottom of the cell. The composition of lighter particles in the sedimented crystal is non-monotonic in the altitude: it is first increasing, then decreasing, and then increasing again. If one Peclet number is large and the other is small, we observe the occurrence of a doubled heterogeneous crystal nucleation process. First, crystalline layers are formed at the bottom container wall which are separated from an amorphous sediment. At the amorphous-fluid interface, a secondary crystal nucleation of layers is identified. This doubled heterogeneous nucleation can be verified in real-space experiments on colloidal mixtures.

  17. Performance characteristics of a nanoscale double-gate reconfigurable array

    NASA Astrophysics Data System (ADS)

    Beckett, Paul

    2008-12-01

    The double gate transistor is a promising device applicable to deep sub-micron design due to its inherent resistance to short-channel effects and superior subthreshold performance. Using both TCAD and SPICE circuit simulation, it is shown that the characteristics of fully depleted dual-gate thin-body Schottky barrier silicon transistors will not only uncouple the conflicting requirements of high performance and low standby power in digital logic, but will also allow the development of a locally-connected reconfigurable computing mesh. The magnitude of the threshold shift effect will scale with device dimensions and will remain compatible with oxide reliability constraints. A field-programmable architecture based on the double gate transistor is described in which the operating point of the circuit is biased via one gate while the other gate is used to form the logic array, such that complex heterogeneous computing functions may be developed from this homogeneous, mesh-connected organization.

  18. Molecular dynamic heterogeneity of confined lipid films by 1H magnetization-exchange nuclear magnetic resonance

    NASA Astrophysics Data System (ADS)

    Buda, A.; Demco, D. E.; Jagadeesh, B.; Blümich, B.

    2005-01-01

    The molecular dynamic heterogeneity of monolayer to submonolayer thin lecithin films confined to submicron cylindrical pores were investigated by 1H magnetization exchange nuclear magnetic resonance. In this experiment a z-magnetization gradient was generated by a double-quantum dipolar filter. The magnetization-exchange decay and buildup curves were interpreted with the help of a theoretical model based on the approximation of a one-dimensional spin-diffusion process in a three-domain morphology. The dynamic heterogeneity of the fatty acid chains and the effects of the surface area per molecule, the diameter of the pores, and the temperature were characterized with the help of local spin-diffusion coefficients. The effect of various parameters on the molecular dynamics of the mobile region of the fatty acid chains was quantified by introducing an ad hoc Gaussian distribution function of the 1H residual dipolar couplings. For the lipid films investigated in this study, the surface induced order and the geometrical confinement affect the chain dynamics of the entire molecule. Therefore, each part of the chain independently reflects the effect of surface coverage, pore size, and temperature.

  19. Cascade of chromosomal rearrangements caused by a heterogeneous T-DNA integration supports the double-stranded break repair model for T-DNA integration.

    PubMed

    Hu, Yufei; Chen, Zhiyu; Zhuang, Chuxiong; Huang, Jilei

    2017-06-01

    Transferred DNA (T-DNA) from Agrobacterium tumefaciens can be integrated into the plant genome. The double-stranded break repair (DSBR) pathway is a major model for T-DNA integration. From this model, we expect that two ends of a T-DNA molecule would invade into a single DNA double-stranded break (DSB) or independent DSBs in the plant genome. We call the later phenomenon a heterogeneous T-DNA integration, which has never been observed. In this work, we demonstrated it in an Arabidopsis T-DNA insertion mutant seb19. To resolve the chromosomal structural changes caused by T-DNA integration at both the nucleotide and chromosome levels, we performed inverse PCR, genome resequencing, fluorescence in situ hybridization and linkage analysis. We found, in seb19, a single T-DNA connected two different chromosomal loci and caused complex chromosomal rearrangements. The specific break-junction pattern in seb19 is consistent with the result of heterogeneous T-DNA integration but not of recombination between two T-DNA insertions. We demonstrated that, in seb19, heterogeneous T-DNA integration evoked a cascade of incorrect repair of seven DSBs on chromosomes 4 and 5, and then produced translocation, inversion, duplication and deletion. Heterogeneous T-DNA integration supports the DSBR model and suggests that two ends of a T-DNA molecule could be integrated into the plant genome independently. Our results also show a new origin of chromosomal abnormalities. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

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

    PubMed

    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.

  1. "If you have the flu symptoms, your asymptomatic spouse may better answer the willingness-to-pay question". Evidence from a double-bounded dichotomous choice model with heterogeneous anchoring.

    PubMed

    Schwarzinger, Michaël; Carrat, Fabrice; Luchini, Stéphane

    2009-07-01

    The small sample size of contingent valuation (CV) surveys conducted in patients may have limited the use of the single-bounded (SB) dichotomous choice format which is recommended in environmental economics. In this paper, we explore two ways to increase the statistical efficiency of the SB format: (1) by the inclusion of proxies in addition to patients; (2) by the addition of a follow-up dichotomous question, i.e. the double-bounded (DB) dichotomous choice format. We found that patients (n=223) and spouses (n=64) answering on behalf of the patient had on average a similar willingness-to-pay for earlier alleviation of flu symptoms. However, a patient was significantly more likely to anchor his/her answer on the first bid as compared to a spouse. Finally, our original DB model with shift effect and heterogeneous anchoring reconciled the discrepancies found in willingness-to-pay statistics between SB and DB models in keeping with increased statistical efficiency.

  2. EFFECTS OF PLATING DENSITY AND CULTURE TIME ON BONE MARROW STROMAL CELL CHARACTERISTICS

    PubMed Central

    Neuhuber, Birgit; Swanger, Sharon A.; Howard, Linda; Mackay, Alastair; Fischer, Itzhak

    2008-01-01

    Objective Bone marrow stromal cells (MSC) are multipotent adult stem cells that have emerged as promising candidates for cell therapy in disorders including cardiac infarction, stroke and spinal cord injury. While harvesting methods used by different laboratories are relatively standard, MSC culturing protocols vary widely. This study is aimed at evaluating the effects of initial plating density and total time in culture on proliferation, cell morphology, and differentiation potential of heterogeneous MSC cultures and more homogeneous cloned subpopulations. Methods Rat MSC were plated at 20, 200 and 2000 cells/cm2 and grown to 50% confluency. The numbers of population doublings and doubling times were determined within and across multiple passages. Changes in cell morphology and differentiation potential to adipogenic, chondrogenic, and osteogenic lineages were evaluated and compared among early, intermediate and late passages, as well as between heterogeneous and cloned MSC populations. Results We found optimal cell growth at a plating density of 200 cells/cm2. Cultures derived from all plating densities developed increased proportions of flat cells over time. Assays for chondrogenesis, osteogenesis and adipogenesis showed that heterogeneous MSC plated at all densities sustained the potential for all three mesenchymal phenotypes through at least passage 5; the flat subpopulation lost adipogenic and chondrogenic potential. Conclusion Our findings suggest that the initial plating density is not critical for maintaining a well-defined, multipotent MSC population. Time in culture, however, affects cell characteristics, suggesting that cell expansion should be limited, especially until the specific characteristics of different MSC subpopulations are better understood. PMID:18495329

  3. Effectiveness and cost-effectiveness of double reading in digital mammography screening: A systematic review and meta-analysis.

    PubMed

    Posso, Margarita; Puig, Teresa; Carles, Misericòrdia; Rué, Montserrat; Canelo-Aybar, Carlos; Bonfill, Xavier

    2017-11-01

    Double reading is the strategy of choice for mammogram interpretation in screening programmes. It remains, however, unknown whether double reading is still the strategy of choice in the context of digital mammography. Our aim was to determine the effectiveness and cost-effectiveness of double reading versus single reading of digital mammograms in screening programmes. We performed a systematic review by searching the PubMed, Embase, and Cochrane Library databases up to April 2017. We used the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool and CHEERS (Consolidated Health Economic Evaluation Reporting Standards) checklist to assess the methodological quality of the diagnostic studies and economic evaluations, respectively. A proportion's meta-analysis approach, 95% Confidence Intervals (95% CI) and test of heterogeneity (P values) were used for pooled results. Costs are expressed US$ PPP (United States Dollar purchasing power parities). The PROSPERO ID of this Systematic Review's protocol is CRD42014013804. Of 1473 potentially relevant hits, four high-quality studies were included. The pooled cancer detection rate of double reading was 6.01 per 1000 screens (CI: 4.47‰-7.77‰), and it was 5.65 per 1000 screens (CI: 3.95‰-7.65‰) for single reading (P=0.76). The pooled proportion of false-positives of double reading was 47.03 per 1000 screens (CI: 39.13‰-55.62‰) and it was 40.60 per 1000 screens (CI: 38.58‰-42.67‰) for single reading (P=0.12). One study reported, for double reading, an ICER (Incremental Cost-Effectiveness Ratio) of 16,684 Euros (24,717 US$ PPP; 2015 value) per detected cancer. Single reading+CAD (computer-aided-detection) was cost-effective in Japan. The evidence of benefit for double reading compared to single reading for digital mammography interpretation is scarce. Double reading seems to increase operational costs, have a not significantly higher false-positive rate, and a similar cancer detection rate. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Double-moment Cloud Microphysics Scheme for the Deep Convection Parameterization in the GFDL AM3

    NASA Astrophysics Data System (ADS)

    Belochitski, A.; Donner, L.

    2013-12-01

    A double-moment cloud microphysical scheme originally developed by Morrision and Gettelman (2008) for the stratiform clouds and later adopted for the deep convection by Song and Zhang (2011) is being implemented in to the deep convection parameterization of Geophysical Fluid Dynamics Laboratory's atmospheric general circulation model AM3. The scheme treats cloud drop, cloud ice, rain, and snow number concentrations and mixing ratios as diagnostic variables and incorporates processes of autoconversion, self-collection, collection between hydrometeor species, sedimentation, ice nucleation, drop activation, homogeneous and heterogeneous freezing, and the Bergeron-Findeisen process. Detailed representation of microphysical processes makes the scheme suitable for studying the interactions between aerosols and convection, as well as aerosols' indirect effects on clouds and the roles of these effects in climate change. The scheme is implemented into the single column version of the GFDL AM3 and evaluated using large scale forcing data obtained at the U.S. Department of Energy Atmospheric Radiation Measurment project's Southern Great Planes and Tropical West Pacific sites. Sensitivity of the scheme to formulations for autoconversion of cloud water and its accretion by rain, self-collection of rain and self-collection of snow, as well as the formulation for heterogenous ice nucleation is investigated. In the future, tests with the full atmospheric GCM will be conducted.

  5. Increase in transmission loss of a double panel system by addition of mass inclusions to a poro-elastic layer: A comparison between theory and experiment

    NASA Astrophysics Data System (ADS)

    Idrisi, Kamal; Johnson, Marty E.; Toso, Alessandro; Carneal, James P.

    2009-06-01

    This paper is concerned with the modeling and optimization of heterogeneous (HG) blankets, which are used in this investigation to reduce the sound transmission through double panel systems. HG blankets consist of poro-elastic media with small embedded masses, which act similarly to a distributed mass-spring-damper-system. HG blankets have shown significant potential to reduce low frequency radiated sound from structures, where traditional poro-elastic materials have little effect. A mathematical model of a double panel system with an acoustic cavity and HG blanket was developed using impedance and mobility methods. The predicted responses of the source and the receiving panel due to a point force are validated with experimental measurements. The presented results indicate that proper tuning of the HG blankets can result in broadband noise reduction below 500 Hz with less than 10% added mass.

  6. The Kinetics of Heterogeneous Electron Transfer Reactions in Polar Solvents

    DTIC Science & Technology

    1994-04-20

    focussed on systems for which rate constants and activation parameters are available as a function of the solvent, and as a function of temperature . The... temperature . The role of reactant structure in determining the kinetic parameters is also considered. Double layer effects both at unmodified and...that the Gibbs activation energy to form a monovalent cation from a neutral molecule via electrooxidation is different from that to form a monovalent

  7. Effectiveness of Sealed Double-Ring Infiltrometers{trademark} and effects of changes in atmospheric pressure on hydraulic conductivity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    McMullin, S.R.

    The Savannah River Site is currently evaluating some 40 hazardous and radioactive-waste sites for remediation. Among the remedial alternatives considered is closure using a kaolin clay cap. The hydraulic conductivity suggested by the US Environmental Protection Agency is 1.0 {times} 10{sup {minus}7} cm/sec. One instrument to measure this value is the Sealed Double-Ring Infiltrometer{trademark} (SDRI). Six SDRI were recently installed on a kaolin test cap. Test results demonstrated uniform performance of these instruments. However, the test data showed as much as an order of magnitude of variation over time. This variation is attributed to both internal structural heterogeneity and variablemore » external boundary conditions. The internal heterogeneity is caused by construction variability within a specified range of moisture and density. The external influences considered are temperature and barometric pressure. Temperature was discharged as a source of heterogeneity because of a lack of correlation with test data and a negligible impact from the range of variability. However, a direct correlation was found between changes in barometric pressure and hydraulic conductivity. This correlation is most pronounced when pressure changes occur over a short period of time. Additionally, this correlation is related to a single soil layer. When the wetting front passes into a more porous foundation layer, the correlation with pressure changes disappears. Conclusions are that the SDRI performs adequately, with good repeatability of results. The duration of test is critical to assure a statistically valid data set. Data spikes resulting from pressure changes should be identified, and professional judgment used to determine the representative hydraulic conductivity. Further evaluation is recommended to determine the impact of pressure change on the actual hydraulic conductivity.« less

  8. Diet and ADHD, Reviewing the Evidence: A Systematic Review of Meta-Analyses of Double-Blind Placebo-Controlled Trials Evaluating the Efficacy of Diet Interventions on the Behavior of Children with ADHD.

    PubMed

    Pelsser, Lidy M; Frankena, Klaas; Toorman, Jan; Rodrigues Pereira, Rob

    2017-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a debilitating mental health problem hampering the child's development. The underlying causes include both genetic and environmental factors and may differ between individuals. The efficacy of diet treatments in ADHD was recently evaluated in three reviews, reporting divergent and confusing conclusions based on heterogeneous studies and subjects. To address this inconsistency we conducted a systematic review of meta-analyses of double-blind placebo-controlled trials evaluating the effect of diet interventions (elimination and supplementation) on ADHD. Our literature search resulted in 14 meta-analyses, six of which confined to double-blind placebo-controlled trials applying homogeneous diet interventions, i.e. artificial food color (AFC) elimination, a few-foods diet (FFD) and poly-unsaturated fatty acid (PUFA) supplementation. Effect sizes (ES) and Confidence intervals (CI) of study outcomes were depicted in a forest plot. I2 was calculated to assess heterogeneity if necessary and additional random effects subgroup meta-regression was conducted if substantial heterogeneity was present. The AFC ESs were 0.44 (95% CI: 0.16-0.72, I2 = 11%) and 0.21 (95% CI: -0.02-0.43, I2 = 68%) [parent ratings], 0.08 (95% CI: -0.07-0.24, I2 = 0%) [teacher ratings] and 0.11 (95% CI: -0.13-0.34, I2 = 12%) [observer ratings]. The FFD ESs were 0.80 (95% CI: 0.41-1.19, I2 = 61%) [parent ratings] and 0.51 (95% CI: -0.02-1.04, I2 = 72%) [other ratings], while the PUFA ESs were 0.17 (95% CI: -0.03-0.38, I2 = 38%) [parent ratings], -0.05 (95% CI: -0.27-0.18, I2 = 0%) [teacher ratings] and 0.16 (95% CI: 0.01-0.31, I2 = 0%) [parent and teacher ratings]. Three meta-analyses (two FFD and one AFC) resulted in high I2 without presenting subgroup results. The FFD meta-analyses provided sufficient data to perform subgroup analyses on intervention type, resulting in a decrease of heterogeneity to 0% (diet design) and 37.8% (challenge design). Considering the small average ESs PUFA supplementation is unlikely to provide a tangible contribution to ADHD treatment, while further research is required for AFC elimination before advising this intervention as ADHD treatment. The average FFD ES is substantial, offering treatment opportunities in subgroups of children with ADHD not responding to or too young for medication. Further FFD research should focus on establishing the underlying mechanisms of food (e.g. incrimination of gut microbiota) to simplify the FFD approach in children with ADHD.

  9. Does double-row rotator cuff repair improve functional outcome of patients compared with single-row technique? A systematic review.

    PubMed

    DeHaan, Alexander M; Axelrad, Thomas W; Kaye, Elizabeth; Silvestri, Lorenzo; Puskas, Brian; Foster, Timothy E

    2012-05-01

    The advantage of single-row versus double-row arthroscopic rotator cuff repair techniques has been a controversial issue in sports medicine and shoulder surgery. There is biomechanical evidence that double-row techniques are superior to single-row techniques; however, there is no clinical evidence that the double-row technique provides an improved functional outcome. When compared with single-row rotator cuff repair, double-row fixation, although biomechanically superior, has no clinical benefit with respect to retear rate or improved functional outcome. Systematic review. The authors reviewed prospective studies of level I or II clinical evidence that compared the efficacy of single- and double-row rotator cuff repairs. Functional outcome scores included the American Shoulder and Elbow Surgeons (ASES) shoulder scale, the Constant shoulder score, and the University of California, Los Angeles (UCLA) shoulder rating scale. Radiographic failures and complications were also analyzed. A test of heterogeneity for patient demographics was also performed to determine if there were differences in the patient profiles across the included studies. Seven studies fulfilled our inclusion criteria. The test of heterogeneity across these studies showed no differences. The functional ASES, Constant, and UCLA outcome scores revealed no difference between single- and double-row rotator cuff repairs. The total retear rate, which included both complete and partial retears, was 43.1% for the single-row repair and 27.2% for the double-row repair (P = .057), representing a trend toward higher failures in the single-row group. Through a comprehensive literature search and meta-analysis of current arthroscopic rotator cuff repairs, we found that the single-row repairs did not differ from the double-row repairs in functional outcome scores. The double-row repairs revealed a trend toward a lower radiographic proven retear rate, although the data did not reach statistical significance. There may be a concerning trend toward higher retear rates in patients undergoing a single-row repair, but further studies are required.

  10. Noniterative Multireference Coupled Cluster Methods on Heterogeneous CPU-GPU Systems

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bhaskaran-Nair, Kiran; Ma, Wenjing; Krishnamoorthy, Sriram

    2013-04-09

    A novel parallel algorithm for non-iterative multireference coupled cluster (MRCC) theories, which merges recently introduced reference-level parallelism (RLP) [K. Bhaskaran-Nair, J.Brabec, E. Aprà, H.J.J. van Dam, J. Pittner, K. Kowalski, J. Chem. Phys. 137, 094112 (2012)] with the possibility of accelerating numerical calculations using graphics processing unit (GPU) is presented. We discuss the performance of this algorithm on the example of the MRCCSD(T) method (iterative singles and doubles and perturbative triples), where the corrections due to triples are added to the diagonal elements of the MRCCSD (iterative singles and doubles) effective Hamiltonian matrix. The performance of the combined RLP/GPU algorithmmore » is illustrated on the example of the Brillouin-Wigner (BW) and Mukherjee (Mk) state-specific MRCCSD(T) formulations.« less

  11. An efficient algorithm for double-difference tomography and location in heterogeneous media, with an application to the Kilauea volcano

    USGS Publications Warehouse

    Monteiller, V.; Got, J.-L.; Virieux, J.; Okubo, P.

    2005-01-01

    Improving our understanding of crustal processes requires a better knowledge of the geometry and the position of geological bodies. In this study we have designed a method based upon double-difference relocation and tomography to image, as accurately as possible, a heterogeneous medium containing seismogenic objects. Our approach consisted not only of incorporating double difference in tomography but also partly in revisiting tomographic schemes for choosing accurate and stable numerical strategies, adapted to the use of cross-spectral time delays. We used a finite difference solution to the eikonal equation for travel time computation and a Tarantola-Valette approach for both the classical and double-difference three-dimensional tomographic inversion to find accurate earthquake locations and seismic velocity estimates. We estimated efficiently the square root of the inverse model's covariance matrix in the case of a Gaussian correlation function. It allows the use of correlation length and a priori model variance criteria to determine the optimal solution. Double-difference relocation of similar earthquakes is performed in the optimal velocity model, making absolute and relative locations less biased by the velocity model. Double-difference tomography is achieved by using high-accuracy time delay measurements. These algorithms have been applied to earthquake data recorded in the vicinity of Kilauea and Mauna Loa volcanoes for imaging the volcanic structures. Stable and detailed velocity models are obtained: the regional tomography unambiguously highlights the structure of the island of Hawaii and the double-difference tomography shows a detailed image of the southern Kilauea caldera-upper east rift zone magmatic complex. Copyright 2005 by the American Geophysical Union.

  12. The effect of gas double-dynamic on mass distribution in solid-state fermentation.

    PubMed

    Chen, Hong-Zhang; Zhao, Zhi-Min; Li, Hong-Qiang

    2014-05-10

    The mass distribution regularity in substrate of solid-state fermentation (SSF) has rarely been reported due to the heterogeneity of solid medium and the lack of suitable instrument and method, which limited the comprehensive analysis and enhancement of the SSF performance. In this work, the distributions of water, biomass, and fermentation product in different medium depths of SSF were determined using near-infrared spectroscopy (NIRS) and the developed models. Based on the mass distribution regularity, the effects of gas double-dynamic on heat transfer, microbial growth and metabolism, and product distribution gradient were systematically investigated. Results indicated that the maximum temperature of substrate and the maximum carbon dioxide evolution rate (CER) were 39.5°C and 2.48mg/(hg) under static aeration solid-state fermentation (SASSF) and 33.9°C and 5.38mg/(hg) under gas double-dynamic solid-state fermentation (GDSSF), respectively, with the environmental temperature for fermentation of 30±1°C. The fermentation production (cellulase activity) ratios of the upper, middle, and lower levels were 1:0.90:0.78 at seventh day under SASSF and 1:0.95:0.89 at fifth day under GDSSF. Therefore, combined with NIRS analysis, gas double-dynamic could effectively strengthen the solid-state fermentation performance due to the enhancement of heat transfer, the stimulation of microbial metabolism and the increase of the homogeneity of fermentation products. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Charge heterogeneity of surfaces: mapping and effects on surface forces.

    PubMed

    Drelich, Jaroslaw; Wang, Yu U

    2011-07-11

    The DLVO theory treats the total interaction force between two surfaces in a liquid medium as an arithmetic sum of two components: Lifshitz-van der Waals and electric double layer forces. Despite the success of the DLVO model developed for homogeneous surfaces, a vast majority of surfaces of particles and materials in technological systems are of a heterogeneous nature with a mosaic structure composed of microscopic and sub-microscopic domains of different surface characteristics. In such systems, the heterogeneity of the surface can be more important than the average surface character. Attractions can be stronger, by orders of magnitude, than would be expected from the classical mean-field DLVO model when area-averaged surface charge or potential is employed. Heterogeneity also introduces anisotropy of interactions into colloidal systems, vastly ignored in the past. To detect surface heterogeneities, analytical tools which provide accurate and spatially resolved information about material surface chemistry and potential - particularly at microscopic and sub-microscopic resolutions - are needed. Atomic force microscopy (AFM) offers the opportunity to locally probe not only changes in material surface characteristic but also charges of heterogeneous surfaces through measurements of force-distance curves in electrolyte solutions. Both diffuse-layer charge densities and potentials can be calculated by fitting the experimental data with a DLVO theoretical model. The surface charge characteristics of the heterogeneous substrate as recorded by AFM allow the charge variation to be mapped. Based on the obtained information, computer modeling and simulation can be performed to study the interactions among an ensemble of heterogeneous particles and their collective motions. In this paper, the diffuse-layer charge mapping by the AFM technique is briefly reviewed, and a new Diffuse Interface Field Approach to colloid modeling and simulation is briefly discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Frustration by competing interactions in the highly-distorted double perovskites La2NaRuO6 and La2NaOsO6

    NASA Astrophysics Data System (ADS)

    Aczel, A. A.; Bugaris, D. E.; Li, L.; Yan, J.-Q.; de La Cruz, C.; Zur Loye, H.-C.; Nagler, S. E.

    2013-03-01

    The usual classical behavior of S = 3/2, B-site ordered double perovskites results in simple, commensurate magnetic ground states. In contrast, heat capacity and neutron powder diffraction measurements for the S = 3/2 systems La2NaB'O6 (B' = Ru, Os) reveal an incommensurate magnetic ground state for La2NaRuO6 and a drastically suppressed ordered moment for La2NaOsO6. This behavior is attributed to the large monoclinic structural distortions of these double perovskites. The distortions have the effect of weakening the nearest neighbor superexchange interactions, presumably to an energy scale that is comparable to the next nearest neighbor superexchange. The exotic ground states in these materials can then arise from a competition between these two types of antiferromagnetic interactions, providing a novel mechanism for achieving frustration in the double perovskite family. Work at ORNL is supported by the Division of Scientific User Facilities and the Materials Science and Engineering Division, DOE Basic Energy Sciences. Work at the University of South Carolina is supported by the Heterogeneous Functional Materials Research Center, funded by DOE under award number de-sc0001061.

  15. Facile fabrication of high-efficiency near-infrared absorption film with tungsten bronze nanoparticle dense layer

    NASA Astrophysics Data System (ADS)

    Lee, Seong Yun; Kim, Jae Young; Lee, Jun Young; Song, Ho Jun; Lee, Sangkug; Choi, Kyung Ho; Shin, Gyojic

    2014-06-01

    An excellent transparent film with effective absorption property in near-infrared (NIR) region based on cesium-doped tungsten oxide nanoparticles was fabricated using a facile double layer coating method via the theoretical considerations. The optical performance was evaluated; the double layer-coated film exhibited 10% transmittance at 1,000 nm in the NIR region and over 80% transmittance at 550 nm in the visible region. To optimize the selectivity, the optical spectrum of this film was correlated with a theoretical model by combining the contributions of the Mie-Gans absorption-based localized surface plasmon resonance and reflections by the interfaces of the heterogeneous layers and the nanoparticles in the film. Through comparison of the composite and double layer coating method, the difference of the nanoscale distances between nanoparticles in each layer was significantly revealed. It is worth noting that the nanodistance between the nanoparticles decreased in the double layer film, which enhanced the optical properties of the film, yielding a haze value of 1% or less without any additional process. These results are very attractive for the nanocomposite coating process, which would lead to industrial fields of NIR shielding and thermo-medical applications.

  16. The effectiveness of dopamine agonists for treatment of neuropsychiatric symptoms post brain injury and stroke.

    PubMed

    Sami, Musa Basseer; Faruqui, Rafey

    2015-12-01

    Traumatic brain injury and stroke are among the leading causes of neurological disability worldwide. Although dopaminergic agents have long been associated with improvement of neuropsychiatric outcomes, to date much of the evidence to date has been in case reports and case series or open label trials. We undertook a systematic review of double-blinded randomised controlled trials (RCT) to determine the effect of dopaminergic agents on pre-defined outcomes of (a) apathy; (b) psychomotor retardation; (c) behavioural management and (d) cognitive function. Databases searched were: Medline, EMBASE, and PsychInfo for human studies. The Cochrane Clinical Trials Database and the TRIP Medical database were also searched. All identified studies, were further hand-searched. We identified six studies providing data on 227 participants, 150 of whom received dopaminergic therapy. Trials were compromised by cross-over design, inadequate wash out period, small numbers and heterogeneous outcome measures. However one good quality RCT demonstrates the efficacy of amantadine in behavioural management. One further RCT shows methylphenidate-levodopa is efficacious for mood post-stroke. One study shows rotigotine to improve hemi-inattention caused by prefrontal damage. Our systematic review demonstrates an evolving evidence base to suggest some benefits in agitation and aggression, mood and attentional deficits. However, there are key limitations of the studies undertaken to date involving small numbers of participants, heterogeneous outcome measures, and variable study designs. There is a need for on-going large prospective double-blind RCTs in these medications using standardised criteria and outcomes to fully understand their effectiveness in this patient group.

  17. Cancer treatment scheduling and dynamic heterogeneity in social dilemmas of tumour acidity and vasculature.

    PubMed

    Kaznatcheev, Artem; Vander Velde, Robert; Scott, Jacob G; Basanta, David

    2017-03-14

    Tumours are diverse ecosystems with persistent heterogeneity in various cancer hallmarks like self-sufficiency of growth factor production for angiogenesis and reprogramming of energy metabolism for aerobic glycolysis. This heterogeneity has consequences for diagnosis, treatment and disease progression. We introduce the double goods game to study the dynamics of these traits using evolutionary game theory. We model glycolytic acid production as a public good for all tumour cells and oxygen from vascularisation via vascular endothelial growth factor production as a club good benefiting non-glycolytic tumour cells. This results in three viable phenotypic strategies: glycolytic, angiogenic and aerobic non-angiogenic. We classify the dynamics into three qualitatively distinct regimes: (1) fully glycolytic; (2) fully angiogenic; or (3) polyclonal in all three cell types. The third regime allows for dynamic heterogeneity even with linear goods, something that was not possible in prior public good models that considered glycolysis or growth factor production in isolation. The cyclic dynamics of the polyclonal regime stress the importance of timing for anti-glycolysis treatments like lonidamine. The existence of qualitatively different dynamic regimes highlights the order effects of treatments. In particular, we consider the potential of vascular normalisation as a neoadjuvant therapy before follow-up with interventions like buffer therapy.

  18. Hydroxide catalysts for lignin depolymerization

    DOEpatents

    Beckham, Gregg T; Biddy, Mary J.; Kruger, Jacob S.; Chmely, Stephen C.; Sturgeon, Matthew

    2017-10-17

    Solid base catalysts and their use for the base-catalyzed depolymerization (BCD) of lignin to compounds such as aromatics are presented herein. Exemplary catalysts include layered double hydroxides (LDHs) as recyclable, heterogeneous catalysts for BCD of lignin.

  19. Hydroxide catalysts for lignin depolymerization

    DOEpatents

    Beckham, Gregg T.; Biddy, Mary J.; Chmely, Stephen C.; Sturgeon, Matthew

    2017-04-25

    Solid base catalysts and their use for the base-catalyzed depolymerization (BCD) of lignin to compounds such as aromatics are presented herein. Exemplary catalysts include layered double hydroxides (LDHs) as recyclable, heterogeneous catalysts for BCD of lignin.

  20. Single- versus double-row repair for full-thickness rotator cuff tears using suture anchors. A systematic review and meta-analysis of basic biomechanical studies.

    PubMed

    Hohmann, Erik; König, Anya; Kat, Cor-Jacques; Glatt, Vaida; Tetsworth, Kevin; Keough, Natalie

    2018-07-01

    The purpose of this study was to perform a systematic review and meta-analysis comparing single- and double-row biomechanical studies to evaluate load to failure, mode of failure and gap formation. A systematic review of MEDLINE, Embase, Scopus and Google Scholar was performed from 1990 through 2016. The inclusion criteria were: documentation of ultimate load to failure, failure modes and documentation of elongation or gap formation. Studies were excluded if the study protocol did not use human specimens. Publication bias was assessed by funnel plot and Egger's test. The risk of bias was established using the Cochrane Collaboration's risk of bias tool. Heterogeneity was assessed using χ 2 and I 2 statistic. Eight studies were included. The funnel plot was asymmetric suggesting publication bias, which was confirmed by Egger's test (p = 0.04). The pooled estimate for load to failure demonstrated significant differences (SMD 1.228, 95% CI: 0.55-5.226, p = 0.006, I 2  = 60.47%), favouring double-row repair. There were no differences for failure modes. The pooled estimate for elongation/gap formation demonstrated significant differences (SMD 0.783, 95% CI: 0.169-1.398, p = 0.012, I 2  = 58.8%), favouring double-row repair. The results of this systematic review and meta-analysis suggest that double-row repair is able to tolerate a significantly greater load to failure. Gap formation was also significantly lower in the double-row repair group, but both of these findings should be interpreted with caution because of the inherent interstudy heterogeneity. Systematic review and meta-analysis.

  1. Spatial heterogeneities and variability of karst hydro-system : insights from geophysics

    NASA Astrophysics Data System (ADS)

    Champollion, C.; Fores, B.; Lesparre, N.; Frederic, N.

    2017-12-01

    Heterogeneous systems such as karsts or fractured hydro-systems are challenging for both scientist and groundwater resources management. Karsts heterogeneities prevent the comparison and moreover the combination of data representative of different scales: borehole water level can generally not be used directly to interpret spring flow dynamic for example. The spatial heterogeneity has also an impact on the temporal variability of groundwater transfer and storage. Karst hydro-systems have characteristic non linear relation between precipitation amount and discharge at the outlets with threshold effects and a large variability of groundwater transit times In the presentation, geophysical field experiments conducted in karst hydro-system in the south of France are used to investigate groundwater transfer and storage variability at a scale of a few hundred meters. We focus on the added value of both geophysical time-lapse gravity experiments and 2D ERT imaging of the subsurface heterogeneities. Both gravity and ERT results can only be interpreted with large ambiguity or some strong a priori: the relation between resistivity and water content is not unique; almost no information about the processes can be inferred from the groundwater stock variations. The present study demonstrate how the ERT and gravity field experiments can be interpreted together in a coherent scheme with less ambiguity. First the geological and hydro-meteorological context is presented. Then the ERT field experiment including the processing and the results are detailed in the section about geophysical imaging of the heterogeneities. The gravity double difference (S2D) time-lapse experiment is described in the section about geophysical monitoring of the temporal variability. The following discussion demonstrate the impact of both experiments on the interpretation in terms of processes and heterogeneities.

  2. The effectiveness and cost-effectiveness of intraoperative imaging in high-grade glioma resection; a comparative review of intraoperative ALA, fluorescein, ultrasound and MRI.

    PubMed

    Eljamel, M Sam; Mahboob, Syed Osama

    2016-12-01

    Surgical resection of high-grade gliomas (HGG) is standard therapy because it imparts significant progression free (PFS) and overall survival (OS). However, HGG-tumor margins are indistinguishable from normal brain during surgery. Hence intraoperative technology such as fluorescence (ALA, fluorescein) and intraoperative ultrasound (IoUS) and MRI (IoMRI) has been deployed. This study compares the effectiveness and cost-effectiveness of these technologies. Critical literature review and meta-analyses, using MEDLINE/PubMed service. The list of references in each article was double-checked for any missing references. We included all studies that reported the use of ALA, fluorescein (FLCN), IoUS or IoMRI to guide HGG-surgery. The meta-analyses were conducted according to statistical heterogeneity between studies. If there was no heterogeneity, fixed effects model was used; otherwise, a random effects model was used. Statistical heterogeneity was explored by χ 2 and inconsistency (I 2 ) statistics. To assess cost-effectiveness, we calculated the incremental cost per quality-adjusted life-year (QALY). Gross total resection (GTR) after ALA, FLCN, IoUS and IoMRI was 69.1%, 84.4%, 73.4% and 70% respectively. The differences were not statistically significant. All four techniques led to significant prolongation of PFS and tended to prolong OS. However none of these technologies led to significant prolongation of OS compared to controls. The cost/QALY was $16,218, $3181, $6049 and $32,954 for ALA, FLCN, IoUS and IoMRI respectively. ALA, FLCN, IoUS and IoMRI significantly improve GTR and PFS of HGG. Their incremental cost was below the threshold for cost-effectiveness of HGG-therapy, denoting that each intraoperative technology was cost-effective on its own. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Ionic Attachment as a Feasible Approach to Heterogenizing Anionic Solution Catalysts. The Carbonylation of Methanol,

    DTIC Science & Technology

    1980-08-01

    carbonylation of methanol to acetic acid reaction is well suited for a demonstration of the feasibility and value of ionically binding a catalyst to a...approximate doubling of the reaction rate. This result suggests that a liquid flow system design in which there is a large catalyst to methanol ratio could...Heterogenizing Anionic Solution Catalysts . The Carbonylation of Methanol by Russell S. Drago, Eric D. Nyberg, Anton El A’mma and Alan Zombeck ABSTRACT -’Few

  4. Double-shell Fe2O3 hollow box-like structure for enhanced photo-Fenton degradation of malachite green dye

    NASA Astrophysics Data System (ADS)

    Jiang, De Bin; Liu, Xiaoying; Xu, Xuan; Zhang, Yu Xin

    2018-01-01

    In this work we demonstrate the synthesis of novel Fe2O3 nanosheets with double-shell hollow morphology by replica molding from diatomite framework. The nanostructures of Fe2O3 nanosheets were examined by focused-ion-beam scanning electron microscopy (FIB/SEM), X-ray diffraction spectroscopy (XRD), Brunauer-Emmett-Teller (BET) specific surface area measurements and Fourier transform infrared (FT-IR) spectroscopy. The results reveal that (1) Pure Fe2O3 nanosheets were successfully obtained; (2) The double-shell Fe2O3 hollow structure achieved via the NaOH etching silica method was observed; (3) Fe2O3 nanosheets possessed uniformly distributed porous nanosheets. Such structural features enlarged the specific surface area of Fe2O3 nanosheets and led to more catalytic active sites. In the heterogeneous photo-Fenton reaction, the double-shell Fe2O3 hollow morphology exhibited excellent catalytic capability for the degradation of malachite green (MG) at circumneutral pH condition. Under optimum condition, MG solution was almost completely decolorized in 60 min (99.9%). The Fe2O3 nanosheets also showed good stability and recyclability, demonstrating great potential as a promising photo-Fenton catalyst for the effective degradation of MG dye in wastewater.

  5. Testing for qualitative heterogeneity: An application to composite endpoints in survival analysis.

    PubMed

    Oulhaj, Abderrahim; El Ghouch, Anouar; Holman, Rury R

    2017-01-01

    Composite endpoints are frequently used in clinical outcome trials to provide more endpoints, thereby increasing statistical power. A key requirement for a composite endpoint to be meaningful is the absence of the so-called qualitative heterogeneity to ensure a valid overall interpretation of any treatment effect identified. Qualitative heterogeneity occurs when individual components of a composite endpoint exhibit differences in the direction of a treatment effect. In this paper, we develop a general statistical method to test for qualitative heterogeneity, that is to test whether a given set of parameters share the same sign. This method is based on the intersection-union principle and, provided that the sample size is large, is valid whatever the model used for parameters estimation. We propose two versions of our testing procedure, one based on a random sampling from a Gaussian distribution and another version based on bootstrapping. Our work covers both the case of completely observed data and the case where some observations are censored which is an important issue in many clinical trials. We evaluated the size and power of our proposed tests by carrying out some extensive Monte Carlo simulations in the case of multivariate time to event data. The simulations were designed under a variety of conditions on dimensionality, censoring rate, sample size and correlation structure. Our testing procedure showed very good performances in terms of statistical power and type I error. The proposed test was applied to a data set from a single-center, randomized, double-blind controlled trial in the area of Alzheimer's disease.

  6. Effect of distance-related heterogeneity on population size estimates from point counts

    USGS Publications Warehouse

    Efford, Murray G.; Dawson, Deanna K.

    2009-01-01

    Point counts are used widely to index bird populations. Variation in the proportion of birds counted is a known source of error, and for robust inference it has been advocated that counts be converted to estimates of absolute population size. We used simulation to assess nine methods for the conduct and analysis of point counts when the data included distance-related heterogeneity of individual detection probability. Distance from the observer is a ubiquitous source of heterogeneity, because nearby birds are more easily detected than distant ones. Several recent methods (dependent double-observer, time of first detection, time of detection, independent multiple-observer, and repeated counts) do not account for distance-related heterogeneity, at least in their simpler forms. We assessed bias in estimates of population size by simulating counts with fixed radius w over four time intervals (occasions). Detection probability per occasion was modeled as a half-normal function of distance with scale parameter sigma and intercept g(0) = 1.0. Bias varied with sigma/w; values of sigma inferred from published studies were often 50% for a 100-m fixed-radius count. More critically, the bias of adjusted counts sometimes varied more than that of unadjusted counts, and inference from adjusted counts would be less robust. The problem was not solved by using mixture models or including distance as a covariate. Conventional distance sampling performed well in simulations, but its assumptions are difficult to meet in the field. We conclude that no existing method allows effective estimation of population size from point counts.

  7. The effect of e-cigarette indoor vaping restrictions on adult prenatal smoking and birth outcomes.

    PubMed

    Cooper, Michael T; Pesko, Michael F

    2017-12-01

    We estimate the effect of county-level e-cigarette indoor vaping restrictions on adult prenatal smoking and birth outcomes using United States birth record data for 7 million pregnant women living in places already comprehensively banning the indoor use of traditional cigarettes. We use both cross-sectional and panel data to estimate our difference-in-difference models. Our panel model results suggest that adoption of a comprehensive indoor vaping restriction increased prenatal smoking by 2.0 percentage points, which is double the estimate obtained from a cross-sectional model. We also document heterogeneity in effect sizes along lines of age, education, and type of insurance. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    PubMed

    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 < 0.05) than adult contemporaries. Adult BSC contain fewer (P < 0.05) MyoD and myogenin immunopositive nuclei than BSC isolated from young 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 < 0.05) in culture than adult BSC, indicating a more rapid rate of muscle fiber formation. A subpopulation immunopositive for Myf5 only was identified in both ages of BSC isolates. The growth kinetics and heterogeneity of young BSC was further evaluated by clonal analysis. Single 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.

  9. [Study of fusion of bacteriophage f2 double-stranded RNA, poly(A).poly(U), and poly(G).poly(C) in the presence of tetraethylammonium bromide].

    PubMed

    Permogorov, V I; Tiaglov, B V; Minaev, V E

    1980-01-01

    The data on the dependence of the melting curve parameters of double-stranded RNA (replicative form of RNA of f2 bacteriophage) poly(A) times poly(U) and poly(G) times poly(C) on the concentration of (C2H5)4NBr were obtained. The RNA melting range width is shown to pass through the minimum value T =2.1+/-0.1degrees at the point of inversion of relative stability of GC and AU pairs that corresponds to 4.0+/-0.1 M concentration of (C2H5)4NBr. Using the melting temperatures of poly(A) times poly(U) and poly(G) times poly(C) the rependence of Tgc-Tau parameter on (C2H5)4NBr concentration was shown. It was concluded from these data that the effect of the double-stranded RNA stacking heterogeneity was negligible in the 0-3 M range of (C2H5)4NBr concentration. Melting curves of RNA were obtained at various values of Tgc-Tau parameter. It was shown that the profile of fine structure of melting curves depends on the value of Tgc-Tau parameter.

  10. Assessement of angiogenesis reveals blood vessel heterogeneity in lung carcinoma

    PubMed Central

    BIRAU, AMALIA; CEAUSU, RALUCA AMALIA; CIMPEAN, ANCA MARIA; GAJE, PUSA; RAICA, MARIUS; OLARIU, TEODORA

    2012-01-01

    Despite advances in treatment, the prognosis for lung cancer patients remains poor. Angiogenesis appears to be a promising target for lung cancer therapy; however, the clinical significance of vascular changes are not completely understood. The aim of this study was to evaluate the types and morphology of blood vessels in various lung carcinomas. Using double immunostaining, we investigated 39 biopsies from patients admitted with various histological types of lung carcinoma. Tumor blood vessels were quantified separately for CD34/smooth muscle actin and described as either immature, intermediate or mature. Double immunostaining evaluation of the type of blood vessels in lung carcinomas revealed a marked heterogeneity. The immature and intermediate type of vessels were more common in adenocarcinomas (ADCs) and squamous cell carcinomas (SCCs) of the lung. Small cell lung carcinomas revealed a significant correlation between pathological and immature types of blood vessels. Therefore, quantifying the types of tumor vessels in lung carcinomas may be an important element to improve the results of anti-vascular therapy. PMID:23205116

  11. Double-aberration corrected TEM/STEM of solid acid nanocatalysts in the development of pharmaceutical NSAIDS

    NASA Astrophysics Data System (ADS)

    Yoshida, K.; Shiju, N.; Brown, R.; Wright, I.; Boyes, E. D.; Gai, P. L.

    2012-07-01

    We report nanostructural and physico-chemical studies in the development of an efficient low temperature heterogeneous catalytic process for nonsteroidal anti-inflammatory drugs (NSAIDS) such as N-acetyl-p-aminophenol (paracetamol or acetaminophen) on tungstated zirconia nanocatalysts. Using a double-aberration corrected TEM/STEM, modified in-house for in-situ studies at the sub-Angstrom level, we directly observed in real-time, the dynamic precursor transformation to the active catalyst. We quantified the observations with catalytic activity studies for the NSAIDS. The studies have provided the direct evidence for single tungsten promoter atoms and surface WOx species of <= 0.35 nm, with nanoclusters of WOx (0.6 to 1nm), located at grain boundaries on the surface of the zirconia nanoparticles. The correlation between the nanostructure and catalytic activity indicates that the species create Brønsted acid sites highly active for the low temperature process. The results open up opportunities for developing green heterogeneous methods for pharmaceuticals.

  12. [Critical of the additive model of the randomized controlled trial].

    PubMed

    Boussageon, Rémy; Gueyffier, François; Bejan-Angoulvant, Theodora; Felden-Dominiak, Géraldine

    2008-01-01

    Randomized, double-blind, placebo-controlled clinical trials are currently the best way to demonstrate the clinical effectiveness of drugs. Its methodology relies on the method of difference (John Stuart Mill), through which the observed difference between two groups (drug vs placebo) can be attributed to the pharmacological effect of the drug being tested. However, this additive model can be questioned in the event of statistical interactions between the pharmacological and the placebo effects. Evidence in different domains has shown that the placebo effect can influence the effect of the active principle. This article evaluates the methodological, clinical and epistemological consequences of this phenomenon. Topics treated include extrapolating results, accounting for heterogeneous results, demonstrating the existence of several factors in the placebo effect, the necessity to take these factors into account for given symptoms or pathologies, as well as the problem of the "specific" effect.

  13. Micromechanics Based Failure Analysis of Heterogeneous Materials

    NASA Astrophysics Data System (ADS)

    Sertse, Hamsasew M.

    In recent decades, heterogeneous materials are extensively used in various industries such as aerospace, defense, automotive and others due to their desirable specific properties and excellent capability of accumulating damage. Despite their wide use, there are numerous challenges associated with the application of these materials. One of the main challenges is lack of accurate tools to predict the initiation, progression and final failure of these materials under various thermomechanical loading conditions. Although failure is usually treated at the macro and meso-scale level, the initiation and growth of failure is a complex phenomena across multiple scales. The objective of this work is to enable the mechanics of structure genome (MSG) and its companion code SwiftComp to analyze the initial failure (also called static failure), progressive failure, and fatigue failure of heterogeneous materials using micromechanics approach. The initial failure is evaluated at each numerical integration point using pointwise and nonlocal approach for each constituent of the heterogeneous materials. The effects of imperfect interfaces among constituents of heterogeneous materials are also investigated using a linear traction-displacement model. Moreover, the progressive and fatigue damage analyses are conducted using continuum damage mechanics (CDM) approach. The various failure criteria are also applied at a material point to analyze progressive damage in each constituent. The constitutive equation of a damaged material is formulated based on a consistent irreversible thermodynamics approach. The overall tangent modulus of uncoupled elastoplastic damage for negligible back stress effect is derived. The initiation of plasticity and damage in each constituent is evaluated at each numerical integration point using a nonlocal approach. The accumulated plastic strain and anisotropic damage evolution variables are iteratively solved using an incremental algorithm. The damage analyses are performed for both brittle failure/high cycle fatigue (HCF) for negligible plastic strain and ductile failure/low cycle fatigue (LCF) for large plastic strain. The proposed approach is incorporated in SwiftComp and used to predict the initial failure envelope, stress-strain curve for various loading conditions, and fatigue life of heterogeneous materials. The combined effects of strain hardening and progressive fatigue damage on the effective properties of heterogeneous materials are also studied. The capability of the current approach is validated using several representative examples of heterogeneous materials including binary composites, continuous fiber-reinforced composites, particle-reinforced composites, discontinuous fiber-reinforced composites, and woven composites. The predictions of MSG are also compared with the predictions obtained using various micromechanics approaches such as Generalized Methods of Cells (GMC), Mori-Tanaka (MT), and Double Inclusions (DI) and Representative Volume Element (RVE) Analysis (called as 3-dimensional finite element analysis (3D FEA) in this document). This study demonstrates that a micromechanics based failure analysis has a great potential to rigorously and more accurately analyze initiation and progression of damage in heterogeneous materials. However, this approach requires material properties specific to damage analysis, which are needed to be independently calibrated for each constituent.

  14. Olefin metathesis for effective polymer healing via dynamic exchange of strong carbon-carbon bonds

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Guan, Zhibin; Lu, Yixuan

    A method of preparing a malleable and/or self-healing polymeric or composite material is provided. The method includes providing a polymeric or composite material comprising at least one alkene-containing polymer, combining the polymer with at least one homogeneous or heterogeneous transition metal olefin metathesis catalyst to form a polymeric or composite material, and performing an olefin metathesis reaction on the polymer so as to form reversible carbon-carbon double bonds in the polymer. Also provided is a method of healing a fractured surface of a polymeric material. The method includes bringing a fractured surface of a first polymeric material into contact withmore » a second polymeric material, and performing an olefin metathesis reaction in the presence of a transition metal olefin metathesis catalyst such that the first polymeric material forms reversible carbon-carbon double bonds with the second polymeric material. Compositions comprising malleable and/or self-healing polymeric or composite material are also provided.« less

  15. Dynamic transverse shear modulus for a heterogeneous fluid-filled porous solid containing cylindrical inclusions

    NASA Astrophysics Data System (ADS)

    Song, Yongjia; Hu, Hengshan; Rudnicki, John W.; Duan, Yunda

    2016-09-01

    An exact analytical solution is presented for the effective dynamic transverse shear modulus in a heterogeneous fluid-filled porous solid containing cylindrical inclusions. The complex and frequency-dependent properties of the dynamic shear modulus are caused by the physical mechanism of mesoscopic-scale wave-induced fluid flow whose scale is smaller than wavelength but larger than the size of pores. Our model consists of three phases: a long cylindrical inclusion, a cylindrical shell of poroelastic matrix material with different mechanical and/or hydraulic properties than the inclusion and an outer region of effective homogeneous medium of laterally infinite extent. The behavior of both the inclusion and the matrix is described by Biot's consolidation equations, whereas the surrounding effective medium which is used to describe the effective transverse shear properties of the inner poroelastic composite is assumed to be a viscoelastic solid whose complex transverse shear modulus needs to be determined. The determined effective transverse shear modulus is used to quantify the S-wave attenuation and velocity dispersion in heterogeneous fluid-filled poroelastic rocks. The calculation shows the relaxation frequency and relative position of various fluid saturation dispersion curves predicted by this study exhibit very good agreement with those of a previous 2-D finite-element simulation. For the double-porosity model (inclusions having a different solid frame than the matrix but the same pore fluid as the matrix) the effective shear modulus also exhibits a size-dependent characteristic that the relaxation frequency moves to lower frequencies by two orders of magnitude if the radius of the cylindrical poroelastic composite increases by one order of magnitude. For the patchy-saturation model (inclusions having the same solid frame as the matrix but with a different pore fluid from the matrix), the heterogeneity in pore fluid cannot cause any attenuation in the transverse shear modulus at all. A comparison with the case of spherical inclusions illustrates that the transverse shear modulus for the cylindrical inclusion exhibits more S-wave attenuation than spherical inclusions.

  16. Coupled thermo-chemical boundary conditions in double-diffusive geodynamo models at arbitrary Lewis numbers.

    NASA Astrophysics Data System (ADS)

    Bouffard, M.

    2016-12-01

    Convection in the Earth's outer core is driven by the combination of two buoyancy sources: a thermal source directly related to the Earth's secular cooling, the release of latent heat and possibly the heat generated by radioactive decay, and a compositional source due to the crystallization of the growing inner core which releases light elements into the liquid outer core. The dynamics of fusion/crystallization being dependent on the heat flux distribution, the thermochemical boundary conditions are coupled at the inner core boundary which may affect the dynamo in various ways, particularly if heterogeneous conditions are imposed at one boundary. In addition, the thermal and compositional molecular diffusivities differ by three orders of magnitude. This can produce significant differences in the convective dynamics compared to pure thermal or compositional convection due to the potential occurence of double-diffusive phenomena. Traditionally, temperature and composition have been combined into one single variable called codensity under the assumption that turbulence mixes all physical properties at an "eddy-diffusion" rate. This description does not allow for a proper treatment of the thermochemical coupling and is certainly incorrect within stratified layers in which double-diffusive phenomena can be expected. For a more general and rigorous approach, two distinct transport equations should therefore be solved for temperature and composition. However, the weak compositional diffusivity is technically difficult to handle in current geodynamo codes and requires the use of a semi-Lagrangian description to minimize numerical diffusion. We implemented a "particle-in-cell" method into a geodynamo code to properly describe the compositional field. The code is suitable for High Parallel Computing architectures and was successfully tested on two benchmarks. Following the work by Aubert et al. (2008) we use this new tool to perform dynamo simulations including thermochemical coupling at the inner core boundary as well as exploration of the infinite Lewis number limit to study the effect of a heterogeneous core mantle boundary heat flow on the inner core growth.

  17. Food allergy--fact or fiction: a review.

    PubMed Central

    Finn, R

    1992-01-01

    Food sensitivity is a common condition presenting with various clinical syndromes including migraine, urticaria, gluten enteropathy, Crohn's disease and irritable bowel syndrome. It is a heterogeneous condition affecting different organ systems and is also aetiologically diverse with subgroups due to allergy, pharmacological reactions, enzyme deficiencies and psychological causes. Clinical acceptance of food sensitivity has been delayed by the use of dubious diagnostic techniques by a minority of practitioners and the lack of laboratory diagnostic tests, but several double blind studies have now fully validated the existence of food sensitivity syndromes. More widespread recognition of food sensitivity would be cost effective for the National Health Service. PMID:1433127

  18. Ion Structure Near a Core-Shell Dielectric Nanoparticle

    NASA Astrophysics Data System (ADS)

    Ma, Manman; Gan, Zecheng; Xu, Zhenli

    2017-02-01

    A generalized image charge formulation is proposed for the Green's function of a core-shell dielectric nanoparticle for which theoretical and simulation investigations are rarely reported due to the difficulty of resolving the dielectric heterogeneity. Based on the formulation, an efficient and accurate algorithm is developed for calculating electrostatic polarization charges of mobile ions, allowing us to study related physical systems using the Monte Carlo algorithm. The computer simulations show that a fine-tuning of the shell thickness or the ion-interface correlation strength can greatly alter electric double-layer structures and capacitances, owing to the complicated interplay between dielectric boundary effects and ion-interface correlations.

  19. Verification of statistical method CORN for modeling of microfuel in the case of high grain concentration

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chukbar, B. K., E-mail: bchukbar@mail.ru

    Two methods of modeling a double-heterogeneity fuel are studied: the deterministic positioning and the statistical method CORN of the MCU software package. The effect of distribution of microfuel in a pebble bed on the calculation results is studied. The results of verification of the statistical method CORN for the cases of the microfuel concentration up to 170 cm{sup –3} in a pebble bed are presented. The admissibility of homogenization of the microfuel coating with the graphite matrix is studied. The dependence of the reactivity on the relative location of fuel and graphite spheres in a pebble bed is found.

  20. Factors influencing heterogeneity of radiation-induced DNA-damage measured by the alkaline comet assay.

    PubMed

    Seidel, Clemens; Lautenschläger, Christine; Dunst, Jürgen; Müller, Arndt-Christian

    2012-04-20

    To investigate whether different conditions of DNA structure and radiation treatment could modify heterogeneity of response. Additionally to study variance as a potential parameter of heterogeneity for radiosensitivity testing. Two-hundred leukocytes per sample of healthy donors were split into four groups. I: Intact chromatin structure; II: Nucleoids of histone-depleted DNA; III: Nucleoids of histone-depleted DNA with 90 mM DMSO as antioxidant. Response to single (I-III) and twice (IV) irradiation with 4 Gy and repair kinetics were evaluated using %Tail-DNA. Heterogeneity of DNA damage was determined by calculation of variance of DNA-damage (V) and mean variance (Mvar), mutual comparisons were done by one-way analysis of variance (ANOVA). Heterogeneity of initial DNA-damage (I, 0 min repair) increased without histones (II). Absence of histones was balanced by addition of antioxidants (III). Repair reduced heterogeneity of all samples (with and without irradiation). However double irradiation plus repair led to a higher level of heterogeneity distinguishable from single irradiation and repair in intact cells. Increase of mean DNA damage was associated with a similarly elevated variance of DNA damage (r = +0.88). Heterogeneity of DNA-damage can be modified by histone level, antioxidant concentration, repair and radiation dose and was positively correlated with DNA damage. Experimental conditions might be optimized by reducing scatter of comet assay data by repair and antioxidants, potentially allowing better discrimination of small differences. Amount of heterogeneity measured by variance might be an additional useful parameter to characterize radiosensitivity.

  1. The double nucleation model for sickle cell haemoglobin polymerization: full integration and comparison with experimental data.

    PubMed

    Medkour, Terkia; Ferrone, Frank; Galactéros, Frédéric; Hannaert, Patrick

    2008-06-01

    Sickle cell haemoglobin (HbS) polymerization reduces erythrocyte deformability, causing deleterous vaso-occlusions. The double-nucleation model states that polymers grow from HbS aggregates, the nuclei, (i) in solution (homogeneous nucleation), (ii) onto existing polymers (heterogeneous nucleation). When linearized at initial HbS concentration, this model predicts early polymerization and its characteristic delay-time (Ferrone et al. J Mol Biol 183(4):591-610, 611-631, 1985). Addressing its relevance for describing complete polymerization, we constructed the full, non-linearized model (Simulink), The MathWorks). Here, we compare the simulated outputs to experimental progress curves (n = 6-8 different [HbS], 3-6 mM range, from Ferrone's group). Within 10% from start, average root mean square (rms) deviation between simulated and experimental curves is 0.04 +/- 0.01 (25 degrees C, n = 8; mean +/- standard error). Conversely, for complete progress curves, averaged rms is 0.48 +/- 0.04. This figure is improved to 0.13 +/- 0.01 by adjusting heterogeneous pathway parameters (p < 0.01): the nucleus stability (sigma(2) micro( cc ): + 40%), and the fraction of polymer surface available for nucleation (phi), from 5e(-7), (3 mM) to 13 (6 mM). Similar results are obtained at 37 degrees C. We conclude that the physico-chemical description of heterogeneous nucleation warrants refinements in order to capture the whole HbS polymerization process.

  2. Suspected Nonceliac Gluten Sensitivity Confirmed in Few Patients After Gluten Challenge in Double-Blind, Placebo-Controlled Trials.

    PubMed

    Molina-Infante, Javier; Carroccio, Antonio

    2017-03-01

    A double-blind, placebo-controlled, gluten challenge has been proposed to confirm a diagnosis of nonceliac gluten sensitivity (NCGS) in patients without celiac disease who respond to a gluten-free diet. To determine the accuracy of this approach, we analyzed data from 10 double-blind, placebo-controlled, gluten-challenge trials, comprising 1312 adults. The studies varied in the duration of the challenge (range, 1 d to 6 wk), daily doses for the gluten challenge (range, 2-52 g; 3 studies administered <8 g/d), and composition of the placebo (gluten-free products, xylose, whey protein, rice, or corn starch containing fermentable carbohydrates). Most of the studies found gluten challenge to significantly increase symptom scores compared with placebo. However, only 38 of 231 NCGS patients (16%) showed gluten-specific symptoms. Furthermore, 40% of these subjects had a nocebo response (similar or increased symptoms in response to placebo). These findings reveal heterogeneity and potential methodology flaws among studies of gluten challenge, cast doubt on gluten as the culprit food component in most patients with presumptive NCGS, and highlight the importance of the nocebo effect in these types of studies. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  3. The role of mineral elements and other chemical compounds used in balneology: data from double-blind randomized clinical trials.

    PubMed

    Morer, Carla; Roques, Christian-François; Françon, Alain; Forestier, Romain; Maraver, Francisco

    2017-12-01

    The aims of this study were to conduct a systematic literature review on balneotherapy about the specific therapeutic role of mineral elements and other chemical compounds of mineral waters and derivate peloids/muds and to discuss the study methods used to evaluate it (in musculoskeletal conditions). We searched Medline by PubMed using the following key words: "spa therapy" "balneotherapy" "mud" "peloid" "mud pack Therapy" in combination with "randomized controlled trial" "double blind trial." We also reviewed the reference list of articles retrieved by the Medline search. We selected the double-blind randomized clinical trials that assessed the effects of mineral water or mud treatments compared to tap water, attenuated peloid/mud therapy or similar treatments without the specific minerals or chemical compounds of the treatment group ("non-mineral"). We evaluated the internal validity and the quality of the statistical analysis of these trials. The final selection comprised 27 double-blind randomized clinical trials, 20 related to rheumatology. A total of 1118 patients with rheumatological and other musculoskeletal diseases were evaluated in these studies: 552 of knee osteoarthritis, 47 of hand osteoarthritis, 147 chronic low back pain, 308 of reumathoid arthritis, and 64 of osteoporosis; 293 of these participants were assigned to the experimental groups of knee osteoarthritis, 24 in hand osteoarthritis, 82 of low back pain, 152 with reumathoid arthritis, and 32 with osteoporosis. They were treated with mineral water baths and/or mud/peloid (with or without other forms of treatment, like physical therapy, exercise…). The rest were allocated to the control groups; they received mainly tap water and/or "non-mineral" mud/peloid treatments. Mineral water or mud treatments had better and longer improvements in pain, function, quality of life, clinical parameters, and others in some rheumatologic diseases (knee and hand osteoarthritis, chronic low back pain, rheumatoid arthritis, and osteoporosis) compared to baseline and non-mineral similar treatments. Internal validity and other limitations of the study's methodology impede causal relation of spa therapy on these improvements. Randomized clinical trials are very heterogeneous. Double-blind randomized clinical trials seem to be the key for studying the role of mineral elements and other chemical compounds, observing enough consistency to demonstrate better and longer improvements for mineral waters or derivate compared to tap water; but due to heterogeneity and gaps on study protocol and methodology, existing research is not sufficiently strong to draw firm conclusions. Well-designed studies in larger patients' population are needed to establish the role of minerals and other chemical compounds in spa therapy.

  4. The role of mineral elements and other chemical compounds used in balneology: data from double-blind randomized clinical trials

    NASA Astrophysics Data System (ADS)

    Morer, Carla; Roques, Christian-François; Françon, Alain; Forestier, Romain; Maraver, Francisco

    2017-12-01

    The aims of this study were to conduct a systematic literature review on balneotherapy about the specific therapeutic role of mineral elements and other chemical compounds of mineral waters and derivate peloids/muds and to discuss the study methods used to evaluate it (in musculoskeletal conditions). We searched Medline by PubMed using the following key words: "spa therapy" "balneotherapy" "mud" "peloid" "mud pack Therapy" in combination with "randomized controlled trial" "double blind trial." We also reviewed the reference list of articles retrieved by the Medline search. We selected the double-blind randomized clinical trials that assessed the effects of mineral water or mud treatments compared to tap water, attenuated peloid/mud therapy or similar treatments without the specific minerals or chemical compounds of the treatment group ("non-mineral"). We evaluated the internal validity and the quality of the statistical analysis of these trials. The final selection comprised 27 double-blind randomized clinical trials, 20 related to rheumatology. A total of 1118 patients with rheumatological and other musculoskeletal diseases were evaluated in these studies: 552 of knee osteoarthritis, 47 of hand osteoarthritis, 147 chronic low back pain, 308 of reumathoid arthritis, and 64 of osteoporosis; 293 of these participants were assigned to the experimental groups of knee osteoarthritis, 24 in hand osteoarthritis, 82 of low back pain, 152 with reumathoid arthritis, and 32 with osteoporosis. They were treated with mineral water baths and/or mud/peloid (with or without other forms of treatment, like physical therapy, exercise…). The rest were allocated to the control groups; they received mainly tap water and/or "non-mineral" mud/peloid treatments. Mineral water or mud treatments had better and longer improvements in pain, function, quality of life, clinical parameters, and others in some rheumatologic diseases (knee and hand osteoarthritis, chronic low back pain, rheumatoid arthritis, and osteoporosis) compared to baseline and non-mineral similar treatments. Internal validity and other limitations of the study's methodology impede causal relation of spa therapy on these improvements. Randomized clinical trials are very heterogeneous. Double-blind randomized clinical trials seem to be the key for studying the role of mineral elements and other chemical compounds, observing enough consistency to demonstrate better and longer improvements for mineral waters or derivate compared to tap water; but due to heterogeneity and gaps on study protocol and methodology, existing research is not sufficiently strong to draw firm conclusions. Well-designed studies in larger patients' population are needed to establish the role of minerals and other chemical compounds in spa therapy.

  5. Evaluating the assumption of power-law late time scaling of breakthrough curves in highly heterogeneous media

    NASA Astrophysics Data System (ADS)

    Pedretti, Daniele

    2017-04-01

    Power-law (PL) distributions are widely adopted to define the late-time scaling of solute breakthrough curves (BTCs) during transport experiments in highly heterogeneous media. However, from a statistical perspective, distinguishing between a PL distribution and another tailed distribution is difficult, particularly when a qualitative assessment based on visual analysis of double-logarithmic plotting is used. This presentation aims to discuss the results from a recent analysis where a suite of statistical tools was applied to evaluate rigorously the scaling of BTCs from experiments that generate tailed distributions typically described as PL at late time. To this end, a set of BTCs from numerical simulations in highly heterogeneous media were generated using a transition probability approach (T-PROGS) coupled to a finite different numerical solver of the flow equation (MODFLOW) and a random walk particle tracking approach for Lagrangian transport (RW3D). The T-PROGS fields assumed randomly distributed hydraulic heterogeneities with long correlation scales creating solute channeling and anomalous transport. For simplicity, transport was simulated as purely advective. This combination of tools generates strongly non-symmetric BTCs visually resembling PL distributions at late time when plotted in double log scales. Unlike other combination of modeling parameters and boundary conditions (e.g. matrix diffusion in fractures), at late time no direct link exists between the mathematical functions describing scaling of these curves and physical parameters controlling transport. The results suggest that the statistical tests fail to describe the majority of curves as PL distributed. Moreover, they suggest that PL or lognormal distributions have the same likelihood to represent parametrically the shape of the tails. It is noticeable that forcing a model to reproduce the tail as PL functions results in a distribution of PL slopes comprised between 1.2 and 4, which are the typical values observed during field experiments. We conclude that care must be taken when defining a BTC late time distribution as a power law function. Even though the estimated scaling factors are found to fall in traditional ranges, the actual distribution controlling the scaling of concentration may different from a power-law function, with direct consequences for instance for the selection of effective parameters in upscaling modeling solutions.

  6. A double mutation in AGXT gene in families with primary hyperoxaluria type 1.

    PubMed

    Kanoun, Houda; Jarraya, Faiçal; Hadj Salem, Ikhlass; Mahfoudh, Hichem; Chaabouni, Yosr; Makni, Fatma; Hachicha, Jamil; Fakhfakh, Faiza

    2013-12-01

    Primary hyperoxaluria type 1 (PH1) is a severe autosomal recessive inherited disorder of glyoxylate metabolism caused by mutations in the AGXT gene on chromosome 2q37.3 that encodes the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase. These mutations are found throughout the entire gene and cause a wide spectrum of clinical severity. Rare in Europe, PH1 is responsible for 13% of the end stage renal failure in the Tunisian child. In the present work, we identified the double mutation c.32C>T (Pro11Leu) and c.731T>C (p.Ile244Thr) in AGXT gene in five unrelated Tunisian families with PH1 disease. Our results provide evidence regarding the potential involvement of c.32C>T, originally described as common polymorphism, on the resulting phenotype. We also reported an extreme intrafamilial heterogeneity in clinical presentation of PH1. Despite the same genetic background, the outcome of the affected members differs widely. The significant phenotypic heterogeneity observed within a same family, with a same genotype, suggests the existence of relevant modifier factors. © 2013.

  7. A novel mutation of the beta myosin heavy chain gene responsible for familial hypertrophic cardiomyopathy.

    PubMed

    Wang, Juan; Xu, Shi-Jie; Zhou, Hua; Wang, Li-Jie; Hu, Bo; Fang, Fang; Zhang, Xu-Min; Luo, Yi-Wei; He, Xiao-Yan; Zhuang, Shao-Wei; Li, Xin-Ming; Liu, Zhong-Ming; Hu, Da-Yi

    2009-09-01

    Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder and shows high variability in genetic heterogeneity and phenotypic characteristics. The genetic etiology responsible for HCM in many individuals remains unclear. This instigation was sought to identify novel genetic determinants for familial hypertrophic cardiomyopathy. Six unrelated Chinese families with HCM were studied. For each of the 13 established HCM-susceptibility genes, 3 to 5 microsatellite markers were selected to perform genotyping and haplotype analysis. The linked genes were sequenced. Haplotype analyses on candidate genetic loci revealed cosegregation of the gene beta-myosin heavy chain (MYH7) with HCM in a single family. A novel double heterozygous missense mutation of Ala26Val plus Arg719Trp in MYH7 was subsequently identified by sequencing in this family and was associated with a severe phenotype of HCM. The novel double mutation of Ala26Val plus Arg719Trp in MYH7 identified in a Chinese family highlights the remarkable genetic heterogeneity of HCM, which provides important information for genetic counseling, accurate diagnosis, prognostic evaluation, and appropriate clinical management. Copyright 2009 Wiley Periodicals, Inc.

  8. Peri-Urban, but Not Urban, Residence in Bolivia Is Associated with Higher Odds of Co-Occurrence of Overweight and Anemia among Young Children, and of Households with an Overweight Woman and Stunted Child.

    PubMed

    Jones, Andrew D; Hoey, Lesli; Blesh, Jennifer; Janda, Kathryn; Llanque, Ramiro; Aguilar, Ana María

    2018-04-01

    Urban populations have grown globally alongside emerging simultaneous burdens of undernutrition and obesity. Yet, how heterogeneous urban environments are associated with this nutritional double burden is poorly understood. We aimed to determine: 1) the prevalence of the nutritional double burden and its components in urban, peri-urban, and rural areas of Bolivia; and 2) the association of residence in these areas with the nutritional double burden and its components. We surveyed 3946 randomly selected households from 2 metropolitan regions of Bolivia. Census data and remotely sensed imagery were used to define urban, peri-urban, and rural districts along a transect in each region. We defined 5 nutritional double burdens: concurrent overweight and anemia among women of reproductive age (15-49 y), and children (6-59 mo), respectively; concurrent overweight and stunting among children; and households with an overweight woman and, respectively, an anemic or stunted child. Capillary hemoglobin concentrations were measured to assess anemia (women: hemoglobin <120 g/L; children: hemoglobin <110 g/L), and overweight and stunting were calculated from height, weight, and age data. In multiple logistic regression models, peri-urban, but not urban residence, was associated with higher odds of concurrent overweight and anemia among children (OR: 1.8; 95% CI; 1.0, 3.2) and of households with an overweight woman and stunted child (1.8; 1.2, 2.7). Examining the components of the double burden, peri-urban women and children, respectively, had higher odds of overweight than rural residents [women (1.5; 1.2, 1.8); children (1.5; 1.0, 2.4)], and children from peri-urban regions had higher odds of stunting (1.5; 1.1, 2.2). Peri-urban, but not urban, residence in Bolivia is associated with a higher risk of the nutritional double burden than rural areas. Understanding how heterogeneous urban environments influence nutrition outcomes could inform integrated policies that simultaneously address both undernutrition and obesity.

  9. Theory of wave propagation in partially saturated double-porosity rocks: a triple-layer patchy model

    NASA Astrophysics Data System (ADS)

    Sun, Weitao; Ba, Jing; Carcione, José M.

    2016-04-01

    Wave-induced local fluid flow is known as a key mechanism to explain the intrinsic wave dissipation in fluid-saturated rocks. Understanding the relationship between the acoustic properties of rocks and fluid patch distributions is important to interpret the observed seismic wave phenomena. A triple-layer patchy (TLP) model is proposed to describe the P-wave dissipation process in a double-porosity media saturated with two immiscible fluids. The double-porosity rock consists of a solid matrix with unique host porosity and inclusions which contain the second type of pores. Two immiscible fluids are considered in concentric spherical patches, where the inner pocket and the outer sphere are saturated with different fluids. The kinetic and dissipation energy functions of local fluid flow (LFF) in the inner pocket are formulated through oscillations in spherical coordinates. The wave propagation equations of the TLP model are based on Biot's theory and the corresponding Lagrangian equations. The P-wave dispersion and attenuation caused by the Biot friction mechanism and the local fluid flow (related to the pore structure and the fluid distribution) are obtained by a plane-wave analysis from the Christoffel equations. Numerical examples and laboratory measurements indicate that P-wave dispersion and attenuation are significantly influenced by the spatial distributions of both, the solid heterogeneity and the fluid saturation distribution. The TLP model is in reasonably good agreement with White's and Johnson's models. However, differences in phase velocity suggest that the heterogeneities associated with double-porosity and dual-fluid distribution should be taken into account when describing the P-wave dispersion and attenuation in partially saturated rocks.

  10. The varied clinical presentations of major depressive disorder.

    PubMed

    Rush, A John

    2007-01-01

    DSM-IV major depressive disorder (MDD) is a clinical syndrome notable for heterogeneity of its clinical presentation, genetics, neurobiology, clinical course, and treatment responsiveness. In an attempt to make sense of this heterogeneity, clinicians and researchers have proposed a number of MDD "subtypes" based on differences in characteristic symptoms (e.g., atypical, melancholic, psychotic), onset (e.g., early vs. late, post-partum, seasonal), course of illness (e.g., single vs. recurrent, chronic, double), and severity. This article provides a brief review of the status of several of the most common subtypes in terms of their clinical features, biological correlates, course of illness, and treatment implications.

  11. Factors influencing heterogeneity of radiation-induced DNA-damage measured by the alkaline comet assay

    PubMed Central

    2012-01-01

    Background To investigate whether different conditions of DNA structure and radiation treatment could modify heterogeneity of response. Additionally to study variance as a potential parameter of heterogeneity for radiosensitivity testing. Methods Two-hundred leukocytes per sample of healthy donors were split into four groups. I: Intact chromatin structure; II: Nucleoids of histone-depleted DNA; III: Nucleoids of histone-depleted DNA with 90 mM DMSO as antioxidant. Response to single (I-III) and twice (IV) irradiation with 4 Gy and repair kinetics were evaluated using %Tail-DNA. Heterogeneity of DNA damage was determined by calculation of variance of DNA-damage (V) and mean variance (Mvar), mutual comparisons were done by one-way analysis of variance (ANOVA). Results Heterogeneity of initial DNA-damage (I, 0 min repair) increased without histones (II). Absence of histones was balanced by addition of antioxidants (III). Repair reduced heterogeneity of all samples (with and without irradiation). However double irradiation plus repair led to a higher level of heterogeneity distinguishable from single irradiation and repair in intact cells. Increase of mean DNA damage was associated with a similarly elevated variance of DNA damage (r = +0.88). Conclusions Heterogeneity of DNA-damage can be modified by histone level, antioxidant concentration, repair and radiation dose and was positively correlated with DNA damage. Experimental conditions might be optimized by reducing scatter of comet assay data by repair and antioxidants, potentially allowing better discrimination of small differences. Amount of heterogeneity measured by variance might be an additional useful parameter to characterize radiosensitivity. PMID:22520045

  12. Double-scattering/reflection in a Single Nanoparticle for Intensified Ultrasound Imaging

    PubMed Central

    Zhang, Kun; Chen, Hangrong; Guo, Xiasheng; Zhang, Dong; Zheng, Yuanyi; Zheng, Hairong; Shi, Jianlin

    2015-01-01

    Ultrasound contrast agents (UCAs) designed by the conventional composition-based strategy, often suffer from relatively low ultrasound utilization efficiency. In this report, a structure-based design concept of double-scattering/reflection in a single nanoparticle for enhancing ultrasound imaging has been proposed. To exemplify this concept, a rattle-type mesoporous silica nanostructure (MSN) with two contributing interfaces has been employed as the ideal model. Contributed by double-scattering/reflection interfaces, the rattle-type MSN, as expected, performs much better in in vitro and in vivo ultrasound imaging than the other two nanostructures (solid and hollow) containing only one scattering/reflection interface. More convincingly, related acoustic measurements and simulation calculations also confirm this design concept. Noticeably, the rattle-type MSN has also been demonstrated capable of improving intracellular ultrasound molecular imaging. As a universal method, the structure-design concept can extend to guide the design of new generation UCAs with many other compositions and similar structures (e.g., heterogeneous rattle-type, double-shelled). PMID:25739832

  13. Double-scattering/reflection in a single nanoparticle for intensified ultrasound imaging.

    PubMed

    Zhang, Kun; Chen, Hangrong; Guo, Xiasheng; Zhang, Dong; Zheng, Yuanyi; Zheng, Hairong; Shi, Jianlin

    2015-03-05

    Ultrasound contrast agents (UCAs) designed by the conventional composition-based strategy, often suffer from relatively low ultrasound utilization efficiency. In this report, a structure-based design concept of double-scattering/reflection in a single nanoparticle for enhancing ultrasound imaging has been proposed. To exemplify this concept, a rattle-type mesoporous silica nanostructure (MSN) with two contributing interfaces has been employed as the ideal model. Contributed by double-scattering/reflection interfaces, the rattle-type MSN, as expected, performs much better in in vitro and in vivo ultrasound imaging than the other two nanostructures (solid and hollow) containing only one scattering/reflection interface. More convincingly, related acoustic measurements and simulation calculations also confirm this design concept. Noticeably, the rattle-type MSN has also been demonstrated capable of improving intracellular ultrasound molecular imaging. As a universal method, the structure-design concept can extend to guide the design of new generation UCAs with many other compositions and similar structures (e.g., heterogeneous rattle-type, double-shelled).

  14. Genetic polymorphisms of molecules involved in host immune response to dengue virus infection.

    PubMed

    Fang, Xin; Hu, Zhen; Shang, Weilong; Zhu, Junmin; Xu, Chuanshan; Rao, Xiancai

    2012-11-01

    The dengue virus (DENV) belongs to the flavivirus family. Each of the four distinct serotypes of this virus is capable of causing human disease, especially in tropical and subtropical areas. The majority of people infected with DENV manifest asymptomatic or dengue fever with flu-like self-limited symptoms. However, a small portion of patients emerge with severe manifestations referred to as dengue hemorrhagic fever, which has a high mortality rate if not treated promptly. The host immune system, which plays important roles throughout the whole process of DENV infection, has been confirmed to have double-edged effects on DENV infection. Recently, much attention has been paid to the genetic heterogeneity of molecules involved in the host immune response to DENV infection. This heterogeneity has been proved to be the determining factor for DENV disease orientation. The present review discusses the primary functions and single nucleotide polymorphisms of some critical molecules in the human DENV immunological defense, especially the polymorphism locus associated with the DENV pathogenesis and disease susceptibility. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  15. A 1D radiative transfer benchmark with polarization via doubling and adding

    NASA Astrophysics Data System (ADS)

    Ganapol, B. D.

    2017-11-01

    Highly precise numerical solutions to the radiative transfer equation with polarization present a special challenge. Here, we establish a precise numerical solution to the radiative transfer equation with combined Rayleigh and isotropic scattering in a 1D-slab medium with simple polarization. The 2-Stokes vector solution for the fully discretized radiative transfer equation in space and direction derives from the method of doubling and adding enhanced through convergence acceleration. Updates to benchmark solutions found in the literature to seven places for reflectance and transmittance as well as for angular flux follow. Finally, we conclude with the numerical solution in a partially randomly absorbing heterogeneous medium.

  16. Prevalence of asymptomatic Zika virus infection: a systematic review.

    PubMed

    Haby, Michelle M; Pinart, Mariona; Elias, Vanessa; Reveiz, Ludovic

    2018-06-01

    To conduct a systematic review to estimate the prevalence of asymptomatic Zika virus infection in the general population and in specific population groups. We searched PubMed®, Embase® and LILACS online databases from inception to 26 January 2018. We included observational epidemiological studies where laboratory testing was used to confirm positive exposure of participants to Zika virus and in which Zika virus symptom status was also recorded. We excluded studies in which having symptoms of Zika virus was a criterion for inclusion. The main outcome assessed was percentage of all Zika virus-positive participants who were asymptomatic. We used a quality-effects approach and the double arcsine transformation for the meta-analysis. We assessed 753 studies for inclusion, of which 23 were included in the meta-analysis, totalling 11 305 Zika virus-positive participants. The high degree of heterogeneity in the studies ( I 2  = 99%) suggests that the pooled prevalence of asymptomatic Zika virus-positive participants was probably not a robust estimate. Analysis based on subgroups of the population (general population, returned travellers, blood donors, adults with Guillain-Barré syndrome, pregnant women and babies with microcephaly) was not able to explain the heterogeneity. Funnel and Doi plots showed major asymmetry, suggesting selection bias or true heterogeneity. Better-quality research is needed, using standardized methods, to determine the true prevalence of asymptomatic Zika virus and whether it varies between populations or over time.

  17. Subtyping of Children with Developmental Dyslexia via Bootstrap Aggregated Clustering and the Gap Statistic: Comparison with the Double-Deficit Hypothesis

    ERIC Educational Resources Information Center

    King, Wayne M.; Giess, Sally A.; Lombardino, Linda J.

    2007-01-01

    Background: The marked degree of heterogeneity in persons with developmental dyslexia has motivated the investigation of possible subtypes. Attempts have proceeded both from theoretical models of reading and the application of unsupervised learning (clustering) methods. Previous cluster analyses of data obtained from persons with reading…

  18. Double layer zinc-UDP coordination polymers: structure and properties.

    PubMed

    Qiu, Qi-Ming; Gu, Leilei; Ma, Hongwei; Yan, Li; Liu, Minghua; Li, Hui

    2018-05-17

    A homochiral Zn-UDP coordination polymer with an alternating parallel ABAB sequence was constructed and studied by X-ray single crystal diffraction analysis. Its crystal structure shows that there are potentially open sites in the 2D layers. The activation of the sites makes the coordination polymer a fluorescent sensor for novel heterogeneous detection of amino acids.

  19. A systematic review of integrated use of disease-management interventions in asthma and COPD.

    PubMed

    Lemmens, Karin M M; Nieboer, Anna P; Huijsman, Robbert

    2009-05-01

    The effectiveness of multiple interventions in asthma and chronic obstructive pulmonary disease (COPD) is unclear. To examine the effectiveness of multiple interventions as compared to single interventions or usual care on health outcomes and health care utilisation within the context of integrated disease management in asthma and COPD. MEDLINE and the Cochrane Library (1995-May 2008) were searched for controlled trials. Two reviewers independently extracted data and assessed study quality. Meta-analyses were performed on quality of life and health care utilisation data. Furthermore, the effects of multiple interventions versus single interventions and usual care were assessed qualitatively. Of the 36 studies included, 17 targeted double interventions (patient-related and organisational interventions); 19 studies performed triple interventions (patient-related, professional-directed and organisational interventions). They were heterogeneous in terms of (combinations of) interventions, outcomes measured, study design and setting. Pooled data showed that studied disease management programmes significantly improved quality of life on several domains. Patients within triple intervention programmes had less chance of at least one hospital admission compared with usual care. No significant effects were found in number of emergency department visits. Qualitative analyses revealed positive trends on process improvements and satisfaction. Inconclusive results were reported on symptoms; no effects were found in lung function. In spite of the heterogeneity of disease management studies in asthma and COPD care, this review showed promising improvements in quality of life and reductions in hospitalisations, especially for triple intervention programmes.

  20. CNOT sequences for heterogeneous spin qubit architectures in a noisy environment

    NASA Astrophysics Data System (ADS)

    Ferraro, Elena; Fanciulli, Marco; de Michielis, Marco

    Explicit CNOT gate sequences for two-qubits mixed architectures are presented in view of applications for large-scale quantum computation. Different kinds of coded spin qubits are combined allowing indeed the favorable physical properties of each to be employed. The building blocks for such composite systems are qubit architectures based on the electronic spin in electrostatically defined semiconductor quantum dots. They are the single quantum dot spin qubit, the double quantum dot singlet-triplet qubit and the double quantum dot hybrid qubit. The effective Hamiltonian models expressed by only exchange interactions between pair of electrons are exploited in different geometrical configurations. A numerical genetic algorithm that takes into account the realistic physical parameters involved is adopted. Gate operations are addressed by modulating the tunneling barriers and the energy offsets between different couple of quantum dots. Gate infidelities are calculated considering limitations due to unideal control of gate sequence pulses, hyperfine interaction and unwanted charge coupling. Second affiliation: Dipartimento di Scienza dei Materiali, University of Milano Bicocca, Via R. Cozzi, 55, 20126 Milano, Italy.

  1. Sleep, performance, and plasma levels in chronic insomniacs during 14-day use of flurazepam and midazolam: an introduction.

    PubMed

    Johnson, L C; Chernik, D A; Sateia, M J

    1990-08-01

    A review of the published literature reveals many unanswered questions regarding the effects of sedative-hypnotics on sleep, performance, and mood. The relationship between plasma half-life and hypnotic efficacy is also not clear. A randomized, double-blind, parallel-groups, multicenter study was designed to examine sleep, performance, and mood in patients with insomnia. A large, heterogeneous sample of patients with a history of benzodiazepine use for chronic insomnia was chosen to reflect the adult population for which sedative-hypnotics are often prescribed and to ensure statistical reliability. Although the major focus of the current study was on the effects of two benzodiazepine hypnotics on performance, this study also provided information on the following important issues: (1) effect of dose level; (2) short-versus long-term administration; and (3) significance of plasma half-life as it relates to hypnotic efficacy.

  2. The effect of obsessive-compulsive symptomatology on executive functions in schizophrenia: a systematic review and meta-analysis.

    PubMed

    Cunill, Ruth; Huerta-Ramos, Elena; Castells, Xavier

    2013-11-30

    The presence of obsessive-compulsive symptoms (OCS) and obsessive-compulsive disorder (OCD) is frequent in patients with schizophrenia and has been associated with greater functional impairment. The impact of these features on cognitive function is unclear. In this article, we performed a systematic review and meta-analysis to assess the effect of OCS/OCD on executive functions in schizophrenia patients. Results indicate that schizophrenia patients with OCS/OCD were more impaired in abstract thinking than schizophrenia patients without OCS/OCD. This finding provides support to the double jeopardy hypothesis and may partially explain the greater functional impairment shown in schizo-obsessive patients compared to those with schizophrenia. Inconsistent results were found for set-shifting, cognitive flexibility, cognitive inhibition and verbal fluency, as indicated by the high statistical heterogeneity found. Potential sources of heterogeneity such as definition of OCS/OCD, age of onset, severity of negative symptoms and premorbid intelligence were planned to be explored but there was an insufficient number of studies to perform these analyses. Our findings highlight the complexity of the relationship between OCS/OCD and schizophrenia and warrant further investigation of the cognitive function of schizo-obsessive patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  3. The Effects of Void Geometry and Contact Angle on the Absorption of Liquids into Porous Calcium Carbonate Structures.

    PubMed

    Ridgway, Cathy J.; Schoelkopf, Joachim; Matthews, G. Peter; Gane, Patrick A. C.; James, Philip W.

    2001-07-15

    The absorption (permeation) of alcohols into porous blocks of calcium carbonate has been studied experimentally and with a computer model. The experimental measurement was of change in apparent weight of a block with time after contact with liquid. The modeling used the previously developed 'Pore-Cor' model, based on unit cells of 1000 cubic pores connected by cylindrical throats. To gain some insight into absorption into voids of complex geometry, and to provide a representation of heterogeneities in surface interaction energy, the cylindrical throats were converted to double cones. Relative to cylinders, such geometries caused hold-ups of the percolation of nonwetting fluids with respect to increasing applied pressure, and a change in the rate of absorption of wetting fluids. Both the measured absorption of the alcohols and the simulated absorption of the alcohols and of water showed significant deviations from that predicted by an effective hydraulic radius approximation. The simulation demonstrated the development of a highly heterogeneous wetting front, and of preferred wetting pathways that were perturbed by inertial retardation. The findings are useful in the design of high-performance, low-waste pigments for paper coatings, and environmentally friendly printing inks, as well as in wider industrial, environmental, and geological contexts. Copyright 2001 Academic Press.

  4. Effects of Simple Leaching of Crushed and Powdered Materials on High-precision Pb Isotope Analyses

    NASA Astrophysics Data System (ADS)

    Todd, E.; Stracke, A.

    2013-12-01

    We present new results of simple leaching experiments on the Pb isotope composition of USGS standard reference material powders and on ocean island basalt whole rock splits and powders. Rock samples were leached with 6N HCl in two steps, first hot and then in an ultrasonic bath, and washed with ultrapure H2O before conventional sample digestion and chromatographic purification of Pb. Pb isotope analyses were determined with Tl-doped MC-ICP-MS. Intra- and inter-session analytical reproducibility of repeated analyses of both synthetic Pb solutions and Pb from single digests of chemically processed natural samples were generally < 100 ppm (2 S.D.). The comparison of leached and unleached samples shows that leaching reliably removes variable amounts of different contaminants for different starting materials. For repeated digests of a single sample, the leached samples reproduce better than the unleached ones, showing that leaching effectively removes heterogeneously distributed extraneous Pb. However, the reproducibility of repeated digests of variably contaminated natural samples is up to an order of magnitude worse than the analytical reproducibility of ca. 100 ppm. More complex leaching methods (e.g., Nobre Silva et al., 2009) yield Pb isotope ratios within error of and with similar reproducibility to our method, showing that the simple leaching method is reliable. The remaining Pb isotope heterogeneity of natural samples, which typically exceeds 100 ppm, is thus attributed to inherent isotopic sample heterogeneity. Tl-doped MC-ICP-MS Pb ratio determination is therefore a sufficiently precise method for Pb isotope analyses in natural rocks. More precise Pb double- or triple-spike methods (e.g., Galer, 1999; Thirlwall, 2000), may exploit their full potential only in cases where natural isotopic sample heterogeneity is demonstrably negligible. References: Galer, S., 1999, Chem. Geol. 157, 255-274. Nobre Silva, et al. 2009, Geochemistry Geophysics Geosystems 10, Q08012. Thirlwall, M.F., 2000, Chem. Geol. 163, 299-322.

  5. SU-F-T-160: Commissioning of a Single-Room Double-Scattering Proton Therapy System

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jin, H; Ahmad, S; Chen, Y

    2016-06-15

    Purpose: To report the detailed commissioning experience for a compact double-scattering Mevion S250 proton therapy system at a University Cancer Center site. Methods: The commissioning of the proton therapy system mainly consisted of ensuring integrity of mechanical and imaging system, beam data collection, and commissioning of a treatment planning system (TPS). First, mechanical alignment and imaging were tested including safety, interlocks, positional accuracy of couch and gantry, image quality, mechanical and imaging isocenter and so on. Second, extensive beam data (outputs, PDDs, and profiles) were collected and analyzed through effective sampling of range (R) and modulation width (M) from 24more » beam options. Three different output (cGy/MU) prediction models were also commissioned as primary and secondary MU calculation tool. Third, the Varian Eclipse TPS was commissioned through five sets of data collections (in-water Bragg peak scans, in-air longitudinal fluence scans, in-air lateral profiles, in-air half-beam profiles, and an HU-to-stopping-power conversion curve) and accuracy of TPS calculation was tested using in-water scans and dose measurements with a 2D array detector with block and range compensator. Finally, an anthropomorphic phantom was scanned and heterogeneity effects were tested by inserting radiochromic films in the phantom and PET activation scans for range verification in conjunction with end-to-end test. Results: Beam characteristics agreed well with the vendor specifications; however, minor mismatches in R and M were found in some measurements during the beam data collection. These were reflected into the TPS commissioning such that the TPS could accurately predict the R and M within tolerance levels. The output models had a good agreement with measured outputs (<3% error). The end-to-end test using the film and PET showed reasonably the TPS predicted dose, R and M in heterogeneous medium. Conclusion: The proton therapy system was successfully commissioned and was released for clinical use.« less

  6. Layered transition metal carboxylates: efficient reusable heterogeneous catalyst for epoxidation of olefins.

    PubMed

    Sen, Rupam; Bhunia, Susmita; Mal, Dasarath; Koner, Subratanath; Miyashita, Yoshitaro; Okamoto, Ken-Ichi

    2009-12-01

    Layered metal carboxylates [M(malonato)(H(2)O)(2)](n) (M = Ni(II) and Mn(II)) that have a claylike structure have been synthesized hydrothermally and characterized. The interlayer separation in these layered carboxylates is comparable to that of the intercalation distance of the naturally occurring clay materials or layered double hydroxides (LDHs). In this study, we have demonstrated that, instead of intercalating the metal complex into layers of the clay or LDH, layered transition metal carboxylates, [M(malonato)(H(2)O)(2)](n), as such can be used as a recyclable heterogeneous catalyst in olefin epoxidation reaction. Metal carboxylates [M(malonato)(H(2)O)(2)](n) exhibit excellent catalytic performance in olefin epoxidation reaction.

  7. A collision probability analysis of the double-heterogeneity problem

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hebert, A.

    1993-10-01

    A practical collision probability model is presented for the description of geometries with many levels of heterogeneity. Regular regions of the macrogeometry are assumed to contain a stochastic mixture of spherical grains or cylindrical tubes. Simple expressions for the collision probabilities in the global geometry are obtained as a function of the collision probabilities in the macro- and microgeometries. This model was successfully implemented in the collision probability kernel of the APOLLO-1, APOLLO-2, and DRAGON lattice codes for the description of a broad range of reactor physics problems. Resonance self-shielding and depletion calculations in the microgeometries are possible because eachmore » microregion is explicitly represented.« less

  8. Nanohole optical tweezers in heterogeneous mixture analysis

    NASA Astrophysics Data System (ADS)

    Hacohen, Noa; Ip, Candice J. X.; Laxminarayana, Gurunatha K.; DeWolf, Timothy S.; Gordon, Reuven

    2017-08-01

    Nanohole optical trapping is a tool that has been shown to analyze proteins at the single molecule level using pure samples. The next step is to detect and study single molecules with dirty samples. We demonstrate that using our double nanohole optical tweezing configuration, single particles in an egg white solution can be classified when trapped. Different sized molecules provide different signal variations in their trapped state, allowing the proteins to be statistically characterized. Root mean squared variation and trap stiffness are methods used on trapped signals to distinguish between the different proteins. This method to isolate and determine single molecules in heterogeneous samples provides huge potential to become a reliable tool for use within biomedical and scientific communities.

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

    USGS Publications Warehouse

    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 landscape scale allowed us to determine the relative importance of covariates influencing capture probability (body size, trappability periods, and latent heterogeneity). This information was used to develop models in which different segments of the population could be assigned different probabilities of capture, and suggests that modelling of open populations should incorporate easily measured, but potentially overlooked, parameters such as body size or condition. ?? 2008 The Authors.

  10. [Study on transformation of P-dissolving Penicillium oxalicum P8 with double-marker vector expressing green fluorescent protein and hygromycin B resistance].

    PubMed

    Zhang, Lei; Fan, Bing-Quan; Huang, Wei-Yi

    2005-12-01

    P-dissolving Penicillium oxalicum P8 was isolated previously in this lab which has a considerable ability to dissolve many kinds of inorganic phosphorus and improve crop growth. In order to study rhizosphere colonization of plants by Penicillium oxalicum P8, protoplasts were transformed with a double-marker expression vector of green fluorescent protein and hygromycin B resistance. Some transformants were selected which expressed both the GFP and hygromycin B phosphotransferase and did not show significant morphological or physiological differences as compared to wild-type strain. Southern blot analysis confirmed the heterogeneous genomic integration of the vector DNA into the transformants.

  11. Concentration analysis of breast tissue phantoms with terahertz spectroscopy

    PubMed Central

    Truong, Bao C. Q.; Fitzgerald, Anthony J.; Fan, Shuting; Wallace, Vincent P.

    2018-01-01

    Terahertz imaging has been previously shown to be capable of distinguishing normal breast tissue from its cancerous form, indicating its applicability to breast conserving surgery. The heterogeneous composition of breast tissue is among the main challenges to progressing this potential research towards a practical application. In this paper, two concentration analysis methods are proposed for analyzing phantoms mimicking breast tissue. The dielectric properties and the double Debye parameters were used to determine the phantom composition. The first method is wholly based on the conventional effective medium theory while the second one combines this theoretical model with empirical polynomial models. Through assessing the accuracy of these methods, their potential for application to quantifying breast tissue pathology was confirmed. PMID:29541525

  12. Ordered macro-microporous metal-organic framework single crystals

    NASA Astrophysics Data System (ADS)

    Shen, Kui; Zhang, Lei; Chen, Xiaodong; Liu, Lingmei; Zhang, Daliang; Han, Yu; Chen, Junying; Long, Jilan; Luque, Rafael; Li, Yingwei; Chen, Banglin

    2018-01-01

    We constructed highly oriented and ordered macropores within metal-organic framework (MOF) single crystals, opening up the area of three-dimensional–ordered macro-microporous materials (that is, materials containing both macro- and micropores) in single-crystalline form. Our methodology relies on the strong shaping effects of a polystyrene nanosphere monolith template and a double-solvent–induced heterogeneous nucleation approach. This process synergistically enabled the in situ growth of MOFs within ordered voids, rendering a single crystal with oriented and ordered macro-microporous structure. The improved mass diffusion properties of such hierarchical frameworks, together with their robust single-crystalline nature, endow them with superior catalytic activity and recyclability for bulky-molecule reactions, as compared with conventional, polycrystalline hollow, and disordered macroporous ZIF-8.

  13. Tracking the Evolution of Non-Small-Cell Lung Cancer.

    PubMed

    Jamal-Hanjani, Mariam; Wilson, Gareth A; McGranahan, Nicholas; Birkbak, Nicolai J; Watkins, Thomas B K; Veeriah, Selvaraju; Shafi, Seema; Johnson, Diana H; Mitter, Richard; Rosenthal, Rachel; Salm, Max; Horswell, Stuart; Escudero, Mickael; Matthews, Nik; Rowan, Andrew; Chambers, Tim; Moore, David A; Turajlic, Samra; Xu, Hang; Lee, Siow-Ming; Forster, Martin D; Ahmad, Tanya; Hiley, Crispin T; Abbosh, Christopher; Falzon, Mary; Borg, Elaine; Marafioti, Teresa; Lawrence, David; Hayward, Martin; Kolvekar, Shyam; Panagiotopoulos, Nikolaos; Janes, Sam M; Thakrar, Ricky; Ahmed, Asia; Blackhall, Fiona; Summers, Yvonne; Shah, Rajesh; Joseph, Leena; Quinn, Anne M; Crosbie, Phil A; Naidu, Babu; Middleton, Gary; Langman, Gerald; Trotter, Simon; Nicolson, Marianne; Remmen, Hardy; Kerr, Keith; Chetty, Mahendran; Gomersall, Lesley; Fennell, Dean A; Nakas, Apostolos; Rathinam, Sridhar; Anand, Girija; Khan, Sajid; Russell, Peter; Ezhil, Veni; Ismail, Babikir; Irvin-Sellers, Melanie; Prakash, Vineet; Lester, Jason F; Kornaszewska, Malgorzata; Attanoos, Richard; Adams, Haydn; Davies, Helen; Dentro, Stefan; Taniere, Philippe; O'Sullivan, Brendan; Lowe, Helen L; Hartley, John A; Iles, Natasha; Bell, Harriet; Ngai, Yenting; Shaw, Jacqui A; Herrero, Javier; Szallasi, Zoltan; Schwarz, Roland F; Stewart, Aengus; Quezada, Sergio A; Le Quesne, John; Van Loo, Peter; Dive, Caroline; Hackshaw, Allan; Swanton, Charles

    2017-06-01

    Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC. In this prospective cohort study, we performed multiregion whole-exome sequencing on 100 early-stage NSCLC tumors that had been resected before systemic therapy. We sequenced and analyzed 327 tumor regions to define evolutionary histories, obtain a census of clonal and subclonal events, and assess the relationship between intratumor heterogeneity and recurrence-free survival. We observed widespread intratumor heterogeneity for both somatic copy-number alterations and mutations. Driver mutations in EGFR, MET, BRAF, and TP53 were almost always clonal. However, heterogeneous driver alterations that occurred later in evolution were found in more than 75% of the tumors and were common in PIK3CA and NF1 and in genes that are involved in chromatin modification and DNA damage response and repair. Genome doubling and ongoing dynamic chromosomal instability were associated with intratumor heterogeneity and resulted in parallel evolution of driver somatic copy-number alterations, including amplifications in CDK4, FOXA1, and BCL11A. Elevated copy-number heterogeneity was associated with an increased risk of recurrence or death (hazard ratio, 4.9; P=4.4×10 -4 ), which remained significant in multivariate analysis. Intratumor heterogeneity mediated through chromosome instability was associated with an increased risk of recurrence or death, a finding that supports the potential value of chromosome instability as a prognostic predictor. (Funded by Cancer Research UK and others; TRACERx ClinicalTrials.gov number, NCT01888601 .).

  14. Replication of tobacco mosaic virus. VII. Further characterization of single- and double-stranded virus-related RNAs from TMV-infected plants.

    PubMed

    Palukaitis, P; García-Arenal, F; Sulzinski, M A; Zaitlin, M

    1983-12-01

    The single-stranded (ss) and double-stranded (ds) RNAs produced in tobacco tissue as a result of infection by tobacco mosaic virus (TMV) have been reinvestigated. 32P-labeled probes consisting of either cDNA or viral RNA, complementary to specific regions of either the viral RNA or its negative strand, respectively, were used in "Northern" hybridization experiments. Of the 10 ssRNA bands observed, all but four appeared to be artifacts of electrophoresis. These four RNAs were found on polyribosomes and are presumed to be true mRNAs; three were identified as the well-known genomic RNA, the I2-mRNA and the coat protein mRNA, or LMC. The fourth RNA species of MW approximately 1.2 x 10(6) had not previously been specifically identified as a subgenomic RNA of TMV. The viral RNA which gave rise to the six artifactual ssRNA bands was heterogeneous in size and was shown to be encapsidated in vivo. Upon electrophoresis, these heterogeneous RNA fragments comigrated approximately with plant rRNAs also present in the extracts, generating the observed artifactual bands. Four dsRNAs were also identified. From molecular weight and hybridization analyses, they appeared to be double-stranded forms of the above four polyribosome-associated ssRNAs. Attempts to translate proteins from the denatured dsRNAs in vitro were unsuccessful. A population of low-molecular-weight, TMV-specific ssRNAs, (+) and (-) in sequence, was generated during infection; however these RNAs were believed to be breakdown products.

  15. Prevalence of asymptomatic Zika virus infection: a systematic review

    PubMed Central

    Pinart, Mariona; Elias, Vanessa; Reveiz, Ludovic

    2018-01-01

    Abstract Objective To conduct a systematic review to estimate the prevalence of asymptomatic Zika virus infection in the general population and in specific population groups. Methods We searched PubMed®, Embase® and LILACS online databases from inception to 26 January 2018. We included observational epidemiological studies where laboratory testing was used to confirm positive exposure of participants to Zika virus and in which Zika virus symptom status was also recorded. We excluded studies in which having symptoms of Zika virus was a criterion for inclusion. The main outcome assessed was percentage of all Zika virus-positive participants who were asymptomatic. We used a quality-effects approach and the double arcsine transformation for the meta-analysis. Findings We assessed 753 studies for inclusion, of which 23 were included in the meta-analysis, totalling 11 305 Zika virus-positive participants. The high degree of heterogeneity in the studies (I2 = 99%) suggests that the pooled prevalence of asymptomatic Zika virus-positive participants was probably not a robust estimate. Analysis based on subgroups of the population (general population, returned travellers, blood donors, adults with Guillain–Barré syndrome, pregnant women and babies with microcephaly) was not able to explain the heterogeneity. Funnel and Doi plots showed major asymmetry, suggesting selection bias or true heterogeneity. Conclusion Better-quality research is needed, using standardized methods, to determine the true prevalence of asymptomatic Zika virus and whether it varies between populations or over time. PMID:29904223

  16. Species richness alters spatial nutrient heterogeneity effects on above-ground plant biomass.

    PubMed

    Xi, Nianxun; Zhang, Chunhui; Bloor, Juliette M G

    2017-12-01

    Previous studies have suggested that spatial nutrient heterogeneity promotes plant nutrient capture and growth. However, little is known about how spatial nutrient heterogeneity interacts with key community attributes to affect plant community production. We conducted a meta-analysis to investigate how nitrogen heterogeneity effects vary with species richness and plant density. Effect size was calculated using the natural log of the ratio in plant biomass between heterogeneous and homogeneous conditions. Effect sizes were significantly above zero, reflecting positive effects of spatial nutrient heterogeneity on community production. However, species richness decreased the magnitude of heterogeneity effects on above-ground biomass. The magnitude of heterogeneity effects on below-ground biomass did not vary with species richness. Moreover, we detected no modification in heterogeneity effects with plant density. Our results highlight the importance of species richness for ecosystem function. Asynchrony between above- and below-ground responses to spatial nutrient heterogeneity and species richness could have significant implications for biotic interactions and biogeochemical cycling in the long term. © 2017 The Author(s).

  17. The 2005 Tarapaca, Chile, Intermediate-depth Earthquake: Evidence of Heterogeneous Fluid Distribution Across the Plate?

    NASA Astrophysics Data System (ADS)

    Kuge, K.; Kase, Y.; Urata, Y.; Campos, J.; Perez, A.

    2008-12-01

    The physical mechanism of intermediate-depth earthquakes remains unsolved, and dehydration embrittlement in subducting plates is a candidate. An earthquake of Mw7.8 occurred at a depth of 115 km beneath Tarapaca, Chile. In this study, we suggest that the earthquake rupture can be attributed to heterogeneous fluid distribution across the subducting plate. The distribution of aftershocks suggests that the earthquake occurred on the subhorizontal fault plane. By modeling regional waveforms, we determined the spatiotemporal distribution of moment release on the fault plane, testing a different suite of velocity models and hypocenters. Two patches of high slip were robustly obtained, although their geometry tends to vary. We tested the results separately by computing the synthetic teleseismic P and pP waveforms. Observed P waveforms are generally modeled, whereas two pulses of observed pP require that the two patches are in the WNW-ESE direction. From the selected moment-release evolution, the dynamic rupture model was constructed by means of Mikumo et al. (1998). The model shows two patches of high dynamic stress drop. Notable is a region of negative stress drop between the two patches. This was required so that the region could lack wave radiation but propagate rupture from the first to the second patches. We found from teleseismic P that the radiation efficiency of the earthquake is relatively small, which can support the existence of negative stress drop during the rupture. The heterogeneous distribution of stress drop that we found can be caused by fluid. The T-P condition of dehydration explains the locations of double seismic zones (e.g. Hacker et al., 2003). The distance between the two patches of high stress drop agrees with the distance between the upper and lower layers of the double seismic zone observed in the south (Rietbrock and Waldhauser, 2004). The two patches can be parts of the double seismic zone, indicating the existence of fluid from dehydration, whereas the region of negative stress drop is in the absence of fluid. In the background environment of negative stress drop, fluid can change the negative stress drop to positive, due to pore pressure variation (e.g. thermal pressurization).

  18. Recent Advances in the Synthesis, Characterization and Application of Zn+-containing Heterogeneous Catalysts.

    PubMed

    Chen, Guangbo; Zhao, Yufei; Shang, Lu; Waterhouse, Geoffrey I N; Kang, Xiaofeng; Wu, Li-Zhu; Tung, Chen-Ho; Zhang, Tierui

    2016-07-01

    Monovalent Zn + (3d 10 4s 1 ) systems possess a special electronic structure that can be exploited in heterogeneous catalysis and photocatalysis, though it remains challenge to synthesize Zn + -containing materials. By careful design, Zn + -related species can be synthesized in zeolite and layered double hydroxide systems, which in turn exhibit excellent catalytic potential in methane, CO and CO 2 activation. Furthermore, by utilizing advanced characterization tools, including electron spin resonance, X-ray absorption fine structure and density functional theory calculations, the formation mechanism of the Zn + species and their structure-performance relationships can be understood. Such advanced characterization tools guide the rational design of high-performance Zn + -containing catalysts for efficient energy conversion.

  19. Recent Advances in the Synthesis, Characterization and Application of Zn+‐containing Heterogeneous Catalysts

    PubMed Central

    Chen, Guangbo; Zhao, Yufei; Shang, Lu; Waterhouse, Geoffrey I. N.; Kang, Xiaofeng; Wu, Li‐Zhu; Tung, Chen‐Ho

    2016-01-01

    Monovalent Zn+ (3d104s1) systems possess a special electronic structure that can be exploited in heterogeneous catalysis and photocatalysis, though it remains challenge to synthesize Zn+‐containing materials. By careful design, Zn+‐related species can be synthesized in zeolite and layered double hydroxide systems, which in turn exhibit excellent catalytic potential in methane, CO and CO2 activation. Furthermore, by utilizing advanced characterization tools, including electron spin resonance, X‐ray absorption fine structure and density functional theory calculations, the formation mechanism of the Zn+ species and their structure‐performance relationships can be understood. Such advanced characterization tools guide the rational design of high‐performance Zn+‐containing catalysts for efficient energy conversion. PMID:27818902

  20. A scalable approach to solving dense linear algebra problems on hybrid CPU-GPU systems

    DOE PAGES

    Song, Fengguang; Dongarra, Jack

    2014-10-01

    Aiming to fully exploit the computing power of all CPUs and all graphics processing units (GPUs) on hybrid CPU-GPU systems to solve dense linear algebra problems, in this paper we design a class of heterogeneous tile algorithms to maximize the degree of parallelism, to minimize the communication volume, and to accommodate the heterogeneity between CPUs and GPUs. The new heterogeneous tile algorithms are executed upon our decentralized dynamic scheduling runtime system, which schedules a task graph dynamically and transfers data between compute nodes automatically. The runtime system uses a new distributed task assignment protocol to solve data dependencies between tasksmore » without any coordination between processing units. By overlapping computation and communication through dynamic scheduling, we are able to attain scalable performance for the double-precision Cholesky factorization and QR factorization. Finally, our approach demonstrates a performance comparable to Intel MKL on shared-memory multicore systems and better performance than both vendor (e.g., Intel MKL) and open source libraries (e.g., StarPU) in the following three environments: heterogeneous clusters with GPUs, conventional clusters without GPUs, and shared-memory systems with multiple GPUs.« less

  1. Single-cell analyses of transcriptional heterogeneity during drug tolerance transition in cancer cells by RNA sequencing.

    PubMed

    Lee, Mei-Chong Wendy; Lopez-Diaz, Fernando J; Khan, Shahid Yar; Tariq, Muhammad Akram; Dayn, Yelena; Vaske, Charles Joseph; Radenbaugh, Amie J; Kim, Hyunsung John; Emerson, Beverly M; Pourmand, Nader

    2014-11-04

    The acute cellular response to stress generates a subpopulation of reversibly stress-tolerant cells under conditions that are lethal to the majority of the population. Stress tolerance is attributed to heterogeneity of gene expression within the population to ensure survival of a minority. We performed whole transcriptome sequencing analyses of metastatic human breast cancer cells subjected to the chemotherapeutic agent paclitaxel at the single-cell and population levels. Here we show that specific transcriptional programs are enacted within untreated, stressed, and drug-tolerant cell groups while generating high heterogeneity between single cells within and between groups. We further demonstrate that drug-tolerant cells contain specific RNA variants residing in genes involved in microtubule organization and stabilization, as well as cell adhesion and cell surface signaling. In addition, the gene expression profile of drug-tolerant cells is similar to that of untreated cells within a few doublings. Thus, single-cell analyses reveal the dynamics of the stress response in terms of cell-specific RNA variants driving heterogeneity, the survival of a minority population through generation of specific RNA variants, and the efficient reconversion of stress-tolerant cells back to normalcy.

  2. Single-cell analyses of transcriptional heterogeneity during drug tolerance transition in cancer cells by RNA sequencing

    PubMed Central

    Lee, Mei-Chong Wendy; Lopez-Diaz, Fernando J.; Khan, Shahid Yar; Tariq, Muhammad Akram; Dayn, Yelena; Vaske, Charles Joseph; Radenbaugh, Amie J.; Kim, Hyunsung John; Emerson, Beverly M.; Pourmand, Nader

    2014-01-01

    The acute cellular response to stress generates a subpopulation of reversibly stress-tolerant cells under conditions that are lethal to the majority of the population. Stress tolerance is attributed to heterogeneity of gene expression within the population to ensure survival of a minority. We performed whole transcriptome sequencing analyses of metastatic human breast cancer cells subjected to the chemotherapeutic agent paclitaxel at the single-cell and population levels. Here we show that specific transcriptional programs are enacted within untreated, stressed, and drug-tolerant cell groups while generating high heterogeneity between single cells within and between groups. We further demonstrate that drug-tolerant cells contain specific RNA variants residing in genes involved in microtubule organization and stabilization, as well as cell adhesion and cell surface signaling. In addition, the gene expression profile of drug-tolerant cells is similar to that of untreated cells within a few doublings. Thus, single-cell analyses reveal the dynamics of the stress response in terms of cell-specific RNA variants driving heterogeneity, the survival of a minority population through generation of specific RNA variants, and the efficient reconversion of stress-tolerant cells back to normalcy. PMID:25339441

  3. A scalable approach to solving dense linear algebra problems on hybrid CPU-GPU systems

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Song, Fengguang; Dongarra, Jack

    Aiming to fully exploit the computing power of all CPUs and all graphics processing units (GPUs) on hybrid CPU-GPU systems to solve dense linear algebra problems, in this paper we design a class of heterogeneous tile algorithms to maximize the degree of parallelism, to minimize the communication volume, and to accommodate the heterogeneity between CPUs and GPUs. The new heterogeneous tile algorithms are executed upon our decentralized dynamic scheduling runtime system, which schedules a task graph dynamically and transfers data between compute nodes automatically. The runtime system uses a new distributed task assignment protocol to solve data dependencies between tasksmore » without any coordination between processing units. By overlapping computation and communication through dynamic scheduling, we are able to attain scalable performance for the double-precision Cholesky factorization and QR factorization. Finally, our approach demonstrates a performance comparable to Intel MKL on shared-memory multicore systems and better performance than both vendor (e.g., Intel MKL) and open source libraries (e.g., StarPU) in the following three environments: heterogeneous clusters with GPUs, conventional clusters without GPUs, and shared-memory systems with multiple GPUs.« less

  4. Genetic variance in micro-environmental sensitivity for milk and milk quality in Walloon Holstein cattle.

    PubMed

    Vandenplas, J; Bastin, C; Gengler, N; Mulder, H A

    2013-09-01

    Animals that are robust to environmental changes are desirable in the current dairy industry. Genetic differences in micro-environmental sensitivity can be studied through heterogeneity of residual variance between animals. However, residual variance between animals is usually assumed to be homogeneous in traditional genetic evaluations. The aim of this study was to investigate genetic heterogeneity of residual variance by estimating variance components in residual variance for milk yield, somatic cell score, contents in milk (g/dL) of 2 groups of milk fatty acids (i.e., saturated and unsaturated fatty acids), and the content in milk of one individual fatty acid (i.e., oleic acid, C18:1 cis-9), for first-parity Holstein cows in the Walloon Region of Belgium. A total of 146,027 test-day records from 26,887 cows in 747 herds were available. All cows had at least 3 records and a known sire. These sires had at least 10 cows with records and each herd × test-day had at least 5 cows. The 5 traits were analyzed separately based on fixed lactation curve and random regression test-day models for the mean. Estimation of variance components was performed by running iteratively expectation maximization-REML algorithm by the implementation of double hierarchical generalized linear models. Based on fixed lactation curve test-day mean models, heritability for residual variances ranged between 1.01×10(-3) and 4.17×10(-3) for all traits. The genetic standard deviation in residual variance (i.e., approximately the genetic coefficient of variation of residual variance) ranged between 0.12 and 0.17. Therefore, some genetic variance in micro-environmental sensitivity existed in the Walloon Holstein dairy cattle for the 5 studied traits. The standard deviations due to herd × test-day and permanent environment in residual variance ranged between 0.36 and 0.45 for herd × test-day effect and between 0.55 and 0.97 for permanent environmental effect. Therefore, nongenetic effects also contributed substantially to micro-environmental sensitivity. Addition of random regressions to the mean model did not reduce heterogeneity in residual variance and that genetic heterogeneity of residual variance was not simply an effect of an incomplete mean model. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  5. World distribution of the T833C/844INS68 CBS in cis double mutation: a reliable anthropological marker.

    PubMed

    Pepe, G; Vanegas, O C; Rickards, O; Giusti, B; Comeglio, P; Brunelli, T; Marcucci, R; Prisco, D; Gensini, G F; Abbate, R

    1999-02-01

    Mild hyperhomocysteinemia is associated to mutations either in cystathionine beta-synthase (CBS) or in 5,10-methylenetetrahydrofolate reductase (MTHFR) genes. In 1995, Sebastio et al. characterized a 68 bp insertion in cis with the most common CBS mutation (T833C) detected in homocystinuric patients. Recently, this double mutation has been detected in Italian and North-American controls. Compared to a group of patients affected by coronary artery disease, North-American controls showed not statistically significant difference. Moreover, Italian controls displayed a microheterogeneity in the mutant allele frequency distribution depending on their geographical origin (North or South of Italy). Aim of our study was to evaluate the prevalence of the double in cis mutation in different populations. We studied 377 healthy subjects belonging to various human groups. Genomic DNA, extracted from peripheral blood samples, was amplified using specific primers; PCR fragments were digested with Bsr I restriction enzyme to detect the double mutation. Our data show a significant heterogeneity among the populations studied, therefore this mutation turned out to be a reliable anthropogenetic marker. The distribution of the double mutation will contribute, with other DNA polymorphisms, to evaluate the genetic admixture of mixed populations such as Afro-Americans.

  6. Does centralisation of acute obstetric care reduce intrapartum and first-week mortality? An empirical study of over 1 million births in the Netherlands.

    PubMed

    Poeran, Jashvant; Borsboom, Gerard J J M; de Graaf, Johanna P; Birnie, Erwin; Steegers, Eric A P; Mackenbach, Johan P; Bonsel, Gouke J

    2014-07-01

    In this hypothetical analysis with retrospective cohort data (1,160,708 hospital births) we estimated outcome of centralisation of acute obstetric care, i.e., closure of 10 hospitals (out of 99) in The Netherlands. The main outcome was predicted intrapartum and first-week mortality (further referred to as neonatal mortality) for several subgroups of patients affected by two centralisation scenarios: (1) closure of the 10 smallest hospitals; (2) closure of the 10 smallest hospitals, but avoiding adjacent closures. Predictions followed from regression coefficients from a multilevel logistic regression model. Scenario 1 resulted in doubled travel time, and 10% increased mortality (210 [0.34%] to 231 [0.38%] cases). Scenario 2 showed less effect on mortality (268 [0.33%] to 259 [0.32%] cases) and travel time. Heterogeneity in hospital organisational features caused simultaneous improvement and deterioration of predicted neonatal mortality. Consequences vary for subgroups. We demonstrate that (in The Netherlands) centralisation of acute obstetric care according to the 'closure-of-the-smallest-rule' yields suboptimal outcomes. In order to develop an optimal strategy one would need to consider all positive and negative effects, e.g., organisational heterogeneity of closing and surviving hospitals, differential effects for patient subgroups, increased travel time, and financial aspects. The provided framework may be beneficial for other countries considering centralisation of acute obstetric care. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. The Prefrontal Model Revisited: Double Dissociations Between Young Sleep Deprived and Elderly Subjects on Cognitive Components of Performance

    PubMed Central

    Tucker, Adrienne M.; Stern, Yaakov; Basner, Robert C.; Rakitin, Brian C.

    2011-01-01

    Study Objectives: The prefrontal model suggests that total sleep deprivation (TSD) and healthy aging produce parallel cognitive deficits. Here we decompose global performance on two common tasks into component measures of specific cognitive processes to pinpoint the source of impairments in elderly and young TSD participants relative to young controls and to each other. Setting: The delayed letter recognition task (DLR) was performed in 3 studies. The psychomotor vigilance task (PVT) was performed in 1 of the DLR studies and 2 additional studies. Subjects: For DLR, young TSD (n = 20, age = 24.60 ± 0.62 years) and young control (n = 17, age = 24.00 ± 2.42); elderly (n = 26, age = 69.92 ± 1.06). For the PVT, young TSD (n = 18, age = 26.65 ± 4.57) and young control (n = 16, age = 25.19 ± 2.90); elderly (n = 21, age = 71.1 ± 4.92). Measurements and Results: Both elderly and young TSD subjects displayed impaired reaction time (RT), our measure of global performance, on both tasks relative to young controls. After decomposing global performance on the DLR, however, a double dissociation was observed as working memory scanning speed was impaired only in elderly subjects while other components of performance were impaired only by TSD. Similarly, for the PVT a second double dissociation was observed as vigilance impairments were present only in TSD while short-term response preparation effects were altered only in the elderly. Conclusions: The similarity between TSD and the elderly in impaired performance was evident only when examining global RT. In contrast, when specific cognitive components were examined double dissociations were observed between TSD and elderly subjects. This demonstrates the heterogeneity in those cognitive processes impaired in TSD versus the elderly. Citation: Tucker AM; Stern Y; Basner RC; Rakitin BC. The prefrontal model revisited: double dissociations between young sleep deprived and elderly subjects on cognitive components of performance. SLEEP 2011;34(8):1039-1050. PMID:21804666

  8. A geometric model of mortality and crop protection for insects feeding on discrete toxicant deposits.

    PubMed

    Ebert, Timothy; Derksen, Richard

    2004-04-01

    Current theory governing the biological effectiveness of toxicants stresses the dose-response relationship and focuses on uniform toxicant distributions in the insect's environment. However, toxicants are seldom uniformly dispersed under field conditions. Toxicant distribution affects bioavailability, but the mechanics of such interactions is not well documented. We present a geometric model of the interactions between insects and heterogeneously distributed toxicants. From the model, we conclude the following: 1) There is an optimal droplet size, and droplets both smaller and larger than this optimum will decrease efficacy. 2) There is an ideal droplet distribution. Droplets should be spaced based on two criteria: calculate the allowable damage, double this quantity, and one lethal deposit should be placed in this area; and define the quantity of leaf the larva could eat before the toxicant decays below the lethal level and place one lethal deposit within this area. 3) Distributions of toxicant where deposits are sublethal will often be ineffective, but the application is wasteful if deposits contain more than a lethal dose. 4) Insect behavior both as individuals and collectively influences the level of crop production provided by an application. This conclusion has implications for both crop protection and natural plant-insect interactions. The effective utilization of new more environmentally sensitive toxicants may depend on how well we understand how heterogeneous toxicant distributions interact with insect behavior to determine the biological outcome.

  9. Evidence for a remodelling of DNA-PK upon autophosphorylation from electron microscopy studies

    PubMed Central

    Morris, Edward P.; Rivera-Calzada, Angel; da Fonseca, Paula C. A.; Llorca, Oscar; Pearl, Laurence H.; Spagnolo, Laura

    2011-01-01

    The multi-subunit DNA-dependent protein kinase (DNA-PK), a crucial player in DNA repair by non-homologous end-joining in higher eukaryotes, consists of a catalytic subunit (DNA-PKcs) and the Ku heterodimer. Ku recruits DNA-PKcs to double-strand breaks, where DNA-PK assembles prior to DNA repair. The interaction of DNA-PK with DNA is regulated via autophosphorylation. Recent SAXS data addressed the conformational changes occurring in the purified catalytic subunit upon autophosphorylation. Here, we present the first structural analysis of the effects of autophosphorylation on the trimeric DNA-PK enzyme, performed by electron microscopy and single particle analysis. We observe a considerable degree of heterogeneity in the autophosphorylated material, which we resolved into subpopulations of intact complex, and separate DNA-PKcs and Ku, by using multivariate statistical analysis and multi-reference alignment on a partitioned particle image data set. The proportion of dimeric oligomers was reduced compared to non-phosphorylated complex, and those dimers remaining showed a substantial variation in mutual monomer orientation. Together, our data indicate a substantial remodelling of DNA-PK holo-enzyme upon autophosphorylation, which is crucial to the release of protein factors from a repaired DNA double-strand break. PMID:21450809

  10. Earthquake mechanisms from linear-programming inversion of seismic-wave amplitude ratios

    USGS Publications Warehouse

    Julian, B.R.; Foulger, G.R.

    1996-01-01

    The amplitudes of radiated seismic waves contain far more information about earthquake source mechanisms than do first-motion polarities, but amplitudes are severely distorted by the effects of heterogeneity in the Earth. This distortion can be reduced greatly by using the ratios of amplitudes of appropriately chosen seismic phases, rather than simple amplitudes, but existing methods for inverting amplitude ratios are severely nonlinear and require computationally intensive searching methods to ensure that solutions are globally optimal. Searching methods are particularly costly if general (moment tensor) mechanisms are allowed. Efficient linear-programming methods, which do not suffer from these problems, have previously been applied to inverting polarities and wave amplitudes. We extend these methods to amplitude ratios, in which formulation on inequality constraint for an amplitude ratio takes the same mathematical form as a polarity observation. Three-component digital data for an earthquake at the Hengill-Grensdalur geothermal area in southwestern Iceland illustrate the power of the method. Polarities of P, SH, and SV waves, unusually well distributed on the focal sphere, cannot distinguish between diverse mechanisms, including a double couple. Amplitude ratios, on the other hand, clearly rule out the double-couple solution and require a large explosive isotropic component.

  11. Methane Emissions From Western Siberian Wetlands: Heterogeneity and Sensitivity to Climate Change

    NASA Astrophysics Data System (ADS)

    Bohn, T. J.; Lettenmaier, D. P.; Podest, E.; McDonald, K. C.; Sathulur, K.; Bowling, L. C.; Friborg, T.

    2007-12-01

    Prediction of methane emissions from high-latitude wetlands is important given concerns about their sensitivity to a warming climate. As a basis for prediction of wetland methane emissions at regional scales, we have coupled the Variable Infiltration Capacity macroscale hydrological model (VIC) with the Biosphere-Energy-Transfer- Hydrology terrestrial ecosystem model (BETHY) and a wetland methane emissions model to make large-scale estimates of methane emissions as a function of soil temperature, water table depth, and net primary productivity (NPP), with a parameterization of the sub-grid heterogeneity of the water table depth based on topographic wetness index. Using landcover classifications derived from L-band satellite synthetic aperture radar imagery, we simulated methane emissions for the Chaya River basin in western Siberia, an area that includes the Bakchar Bog, for a retrospective baseline period of 1980-1999, and evaluated their sensitivity to increases in temperature of 0-5 °C and increases in precipitation of 0-15%. The interactions of temperature and precipitation, through their effects on the water table depth, play an important role in determining methane emissions from these wetlands. The balance between these effects varies spatially, and their net effect depends in part on sub- grid topographic heterogeneity. Higher temperatures alone increase methane production in saturated areas, but cause those saturated areas to shrink in extent, resulting in a net reduction in methane emissions. Higher precipitation alone raises water tables and expands the saturated area, resulting in a net increase in methane emissions. Combining a temperature increase of 3 °C and an increase of 10% in precipitation, to represent the climate conditions likely in western Siberia at the end of this century, results in roughly a doubling of annual methane emissions. This work was carried out at the University of Washington, at Purdue University, and at the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration.

  12. Characterization of Microstructure and Texture of 13Cr4Ni Martensitic Stainless Steel Weld Before and After Tempering =

    NASA Astrophysics Data System (ADS)

    Mokhtabad Amrei, Mohsen

    13Cr4Ni martensitic stainless steels are known for their outstanding performances in the hydroelectric industry, where they are mainly used in the construction of turbine components. Considering the size and geometry of turbine runners and blades, multi-pass welding procedures are commonly used in the fabrication and repair of such turbines. The final microstructure and mechanical properties of the weld are sensitive to the welding process parameters and thermal history. In the case of 13Cr4Ni steel, the thermal cycles imposed by the multi-pass welding operation have significant effects on the complex weld microstructure. Additionally, post-weld heat treatments are commonly used to reduce weld heterogeneity and improve the material's mechanical properties by tempering the microstructure and by forming a "room-temperature-stable austenite." In the first phase of this research, the microstructures and crystallographic textures of aswelded single-pass and double-pass welds were studied as a basis to studying the more complex multi-pass weld microstructure. This study found that the maximum hardness is obtained in high temperature heat affected zone inside the base metal. In particular, the results showed that the heat cycle exposed by the second pass increases the hardness of the previous pass because it produces a finer martensite microstructure. In areas of heat affected zone, a tempering effect is reported from 3 up to 6 millimeters far from the fusion line. Finding austenite phase in these areas are matter of interest and it can be indicative of the microstructure complexity of multi-pass welds. In the second phase of research, the microstructure of multi-pass welds was found to be more heterogeneous than that of single- and double-pass welds. Any individual pass in a multi-pass weld consists of several regions formed by adjacent weld passes heat cycle. Results showed that former austenite grains modification occurred in areas close to the subsequent weld passes. Furthermore, low angle interface laths were observed inside martensite sub-blocks over different regions. The hardness profile of a multi-pass weld was explained by the overlaying heat effects of surrounding passes. In some regions, a tempered matrix was observed, while in other regions a double-quenched microstructure was found. The final aspect of this study focused on the effects of post-weld heat treatments on reformed austenite and carbide formations, and evolution of hardness. The effects of tempering duration and temperature on microstructure were investigated. The study found that nanometer-sized carbides form at martensite lath interfaces and sub-block boundaries. Additionally, it was determined that for any holding duration, the maximum austenite percentage is achievable by tempering at 610 °C. Similarly, the maximum softening was reported for tempering at 610 °C, for any given holding period.

  13. One-Cell Doubling Evaluation by Living Arrays of Yeast, ODELAY!

    DOE PAGES

    Herricks, Thurston; Dilworth, David J.; Mast, Fred D.; ...

    2016-11-16

    Cell growth is a complex phenotype widely used in systems biology to gauge the impact of genetic and environmental perturbations. Due to the magnitude of genome-wide studies, resolution is often sacrificed in favor of throughput, creating a demand for scalable, time-resolved, quantitative methods of growth assessment. We present ODELAY (One-cell Doubling Evaluation by Living Arrays of Yeast), an automated and scalable growth analysis platform. High measurement density and single-cell resolution provide a powerful tool for large-scale multiparameter growth analysis based on the modeling of microcolony expansion on solid media. Pioneered in yeast but applicable to other colony forming organisms, ODELAYmore » extracts the three key growth parameters (lag time, doubling time, and carrying capacity) that define microcolony expansion from single cells, simultaneously permitting the assessment of population heterogeneity. The utility of ODELAY is illustrated using yeast mutants, revealing a spectrum of phenotypes arising from single and combinatorial growth parameter perturbations.« less

  14. One-Cell Doubling Evaluation by Living Arrays of Yeast, ODELAY!

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Herricks, Thurston; Dilworth, David J.; Mast, Fred D.

    Cell growth is a complex phenotype widely used in systems biology to gauge the impact of genetic and environmental perturbations. Due to the magnitude of genome-wide studies, resolution is often sacrificed in favor of throughput, creating a demand for scalable, time-resolved, quantitative methods of growth assessment. We present ODELAY (One-cell Doubling Evaluation by Living Arrays of Yeast), an automated and scalable growth analysis platform. High measurement density and single-cell resolution provide a powerful tool for large-scale multiparameter growth analysis based on the modeling of microcolony expansion on solid media. Pioneered in yeast but applicable to other colony forming organisms, ODELAYmore » extracts the three key growth parameters (lag time, doubling time, and carrying capacity) that define microcolony expansion from single cells, simultaneously permitting the assessment of population heterogeneity. The utility of ODELAY is illustrated using yeast mutants, revealing a spectrum of phenotypes arising from single and combinatorial growth parameter perturbations.« less

  15. Wormlike Chain Theory and Bending of Short DNA

    NASA Astrophysics Data System (ADS)

    Mazur, Alexey K.

    2007-05-01

    The probability distributions for bending angles in double helical DNA obtained in all-atom molecular dynamics simulations are compared with theoretical predictions. The computed distributions remarkably agree with the wormlike chain theory and qualitatively differ from predictions of the subelastic chain model. The computed data exhibit only small anomalies in the apparent flexibility of short DNA and cannot account for the recently reported AFM data. It is possible that the current atomistic DNA models miss some essential mechanisms of DNA bending on intermediate length scales. Analysis of bent DNA structures reveal, however, that the bending motion is structurally heterogeneous and directionally anisotropic on the length scales where the experimental anomalies were detected. These effects are essential for interpretation of the experimental data and they also can be responsible for the apparent discrepancy.

  16. ChAMP: updated methylation analysis pipeline for Illumina BeadChips.

    PubMed

    Tian, Yuan; Morris, Tiffany J; Webster, Amy P; Yang, Zhen; Beck, Stephan; Feber, Andrew; Teschendorff, Andrew E

    2017-12-15

    The Illumina Infinium HumanMethylationEPIC BeadChip is the new platform for high-throughput DNA methylation analysis, effectively doubling the coverage compared to the older 450 K array. Here we present a significantly updated and improved version of the Bioconductor package ChAMP, which can be used to analyze EPIC and 450k data. Many enhanced functionalities have been added, including correction for cell-type heterogeneity, network analysis and a series of interactive graphical user interfaces. ChAMP is a BioC package available from https://bioconductor.org/packages/release/bioc/html/ChAMP.html. a.teschendorff@ucl.ac.uk or s.beck@ucl.ac.uk or a.feber@ucl.ac.uk. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

  17. Direct synthesis and application of bridged diamino-functionalized periodic mesoporous organosilicas with high nitrogen contents

    NASA Astrophysics Data System (ADS)

    Zhu, Feng-Xia; Zhao, Pu-Su; Sun, Xiao-Jun; An, Li-Tao; Deng, Yong; Wu, Jia-Min

    2017-11-01

    Bridged diamino-functionalized periodic mesoporous organosilicas [BD-PMO(Et), Et = ethyl] materials were synthesized directly by co-condensation of 2-bis (triethoxysilyl)ethane (BTEE) and 1,4-bis[3-(tirmethoxysilyl)-propyl]ethylenediamino (BTMSEN) under acidic conditions with pluronic triblock copolymer P123 as a template. The nitrogen content in BD-PMO(Et) could be adjusted up to 40% without disturbing the ordered mesoporous structure. These materials were proved to be effective heterogeneous catalysts for the liquid-phase reactions such as Knoevenagel and Henry condensations as well as in the intermolecular cross-double-Michael addition reaction between α-methyl-β-nitrostyrene and α, β-unsaturated ketone. They exhibited comparable catalytic activities with homogeneous catalyst piperazine and can be reused for several times without any negative environmental impact.

  18. Removal of heavy metals from polluted soil using the citric acid fermentation broth: a promising washing agent.

    PubMed

    Zhang, Hongjiao; Gao, Yuntao; Xiong, Huabin

    2017-04-01

    The citric acid fermentation broth was prepared and it was employed to washing remediation of heavy metal-polluted soil. A well-defined washing effect was obtained, the removal percentages using citric acid fermentation broth are that 48.2% for Pb, 30.6% for Cu, 43.7% for Cr, and 58.4% for Cd and higher than that using citric acid solution. The kinetics of heavy metals desorption can be described by the double constant equation and Elovich equation and is a heterogeneous diffusion process. The speciation analysis shows that the citric acid fermentation broth can effectively reduce bioavailability and environmental risk of heavy metals. Spectroscopy characteristics analysis suggests that the washing method has only a small effect on the mineral composition and does not destroy the framework of soil system. Therefore, the citric acid fermentation broth is a promising washing agent and possesses a potential practical application value in the field of remediation of soils with a good washing performance.

  19. Tough composite materials: Recent developments

    NASA Technical Reports Server (NTRS)

    Vosteen, L. F. (Editor); Johnston, N. J. (Editor); Teichman, L. A. (Editor); Blankenship, C. P. (Editor)

    1985-01-01

    The present volume broadly considers topics in composite fracture toughness and impact behavior characterization, composite system constituent properties and their interrelationships, and matrix systems' synthesis and characterization. Attention is given to the characterization of interlaminar crack growth in composites by means of the double cantilever beam specimen, the characterization of delamination resistance in toughened resin composites, the effect of impact damage and open holes on the compressive strength of tough resin/high strain fiber laminates, the effect of matrix and fiber properties on compression failure mechanisms and impact resistance, the relation of toughened neat resin properties to advanced composite mechanical properties, and constituent and composite properties' relationships in thermosetting matrices. Also treated are the effect of cross-link density on the toughening mechanism of elastomer-modified epoxies, the chemistry of fiber/resin interfaces, novel carbon fibers and their properties, the development of a heterogeneous laminating resin, solvent-resistant thermoplastics, NASA Lewis research in advanced composites, and opportunities for the application of composites in commercial aircraft transport structures.

  20. Incidence of retear with double-row versus single-row rotator cuff repair.

    PubMed

    Shen, Chong; Tang, Zhi-Hong; Hu, Jun-Zu; Zou, Guo-Yao; Xiao, Rong-Chi

    2014-11-01

    Rotator cuff tears have a high recurrence rate, even after arthroscopic rotator cuff repair. Although some biomechanical evidence suggests the superiority of the double-row vs the single-row technique, clinical findings regarding these methods have been controversial. The purpose of this study was to determine whether the double-row repair method results in a lower incidence of recurrent tearing compared with the single-row method. Electronic databases were systematically searched to identify reports of randomized, controlled trials (RCTs) comparing single-row with double-row rotator cuff repair. The primary outcome assessed was retear of the repaired cuff. Secondary outcome measures were the American Shoulder and Elbow Surgeons (ASES) shoulder score, the Constant shoulder score, and the University of California, Los Angeles (UCLA) score. Heterogeneity between the included studies was assessed. Six studies involving 428 patients were included in the review. Compared with single-row repair, double-row repair demonstrated a lower retear incidence (risk ratio [RR]=1.71 [95% confidence interval (CI), 1.18-2.49]; P=.005; I(2)=0%) and a reduced incidence of partial-thickness retears (RR=2.16 [95% CI, 1.26-3.71]; P=.005; I(2)=26%). Functional ASES, Constant, and UCLA scores showed no difference between single- and double-row cuff repairs. Use of the double-row technique decreased the incidence of retears, especially partial-thickness retears, compared with the single-row technique. The functional outcome was not significantly different between the 2 techniques. To improve the structural outcome of the repaired rotator cuff, surgeons should use the double-row technique. However, further long-term RCTs on this topic are needed. Copyright 2014, SLACK Incorporated.

  1. Spatial distribution of the electron component parameters in the nitrogen plasma of a low-pressure electrode microwave Discharge

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lebedev, Yu. A., E-mail: lebedev@ips.ac.ru; Krashevskaya, G. V., E-mail: krashevskaya-gv@mail.ru; Gogoleva, M. A., E-mail: masha-g@list.ru

    2016-01-15

    Spatial distributions of charged particle concentration, electron temperature, and DC potential in an electrode microwave discharge in nitrogen at a pressure of 1 Torr have been measured using the double electric probe method. It has been shown that, near the electrode/antenna, the charged particle concentration exceeds a critical value. The concentration and heterogeneity of the discharge increase with increasing microwave power.

  2. Gold Nanoparticles Supported on a Layered Double Hydroxide as Efficient Catalysts for the One-Pot Synthesis of Flavones.

    PubMed

    Yatabe, Takafumi; Jin, Xiongjie; Yamaguchi, Kazuya; Mizuno, Noritaka

    2015-11-02

    Flavones are a class of natural products with diverse biological activities and have frequently been synthesized by step-by-step procedures using stoichiometric amounts of reagents. Herein, a catalytic one-pot procedure for the synthesis of flavone and its derivatives is developed. In the presence of gold nanoparticles supported on a Mg-Al layered double hydroxide (Au/LDH), various kinds of flavones can be synthesized starting from 2'-hydroxyacetophenones and benzaldehydes (or benzyl alcohols). The present one-pot procedure consists of a sequence of several reactions, and Au/LDH can catalyze all these different types of reactions. The catalysis is shown to be truly heterogeneous, and Au/LDH can be readily recovered and reused. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Computed tomography characteristics of fibrosarcoma -- a histological subtype of feline injection-site sarcoma.

    PubMed

    Travetti, Olga; di Giancamillo, Mauro; Stefanello, Damiano; Ferrari, Roberta; Giudice, Chiara; Grieco, Valeria; Saunders, Jimmy H

    2013-06-01

    Feline injection-site sarcoma (FISS) may be a consequence of subcutaneous injection. In the present study, the medical records and the computed tomography (CT) features of 22 cats with a FISS, histopathological subtype fibrosarcoma, were used. The majority of the fibrosarcomas (45%) were located in the interscapular region. All fibrosarcomas, except one with mild enhancement, showed strong contrast uptake, characterised as ring (42%), heterogeneous (36%), homogeneous (9%), heterogeneous/ring (6.5%) or mixed heterogeneous/homogeneous enhancement (6.5%). The longest axis of the mass was in a cranio-caudal (68%) or dorso-ventral (32%) direction. The median volume calculated on CT was 7.57 cm(3). Common features were a marked local invasiveness of the musculature and heterogeneity of the tissue in the periphery of the neoplasia. When the fibrosarcoma was interscapular, performing an additional post-contrast scan with the forelimbs positioned caudally along the body, in addition to the standard protocol with the forelimbs extended cranially, allowed better evaluation of the actual relationship between the tumour and the surrounding tissues. The mean number of muscles involved with the tumour was 2.09 with extended and 1.95 with flexed forelimbs. When a lower number of structures was considered infiltrated through the double positioning, a less invasive surgical approach to underlying muscles and scapula was performed.

  4. The concept, reality and utility of single-site heterogeneous catalysts (SSHCs).

    PubMed

    Thomas, John Meurig

    2014-05-07

    Very substantial advances have recently been made in the design and construction of solid catalysts and in elucidating both their mode of operation and the factors that determine their selectivity and longevity. This Perspective explains how and why such progress has been made. One important factor, the deployment of single-site heterogeneous and enzymatic catalysts, used either alone or in conjunction with other strategies, including metabolic engineering, enables a multitude of new products (for example, environmentally clean jet fuel) to be readily manufactured. In a practical sense SSHCs enable the advantages of homogeneous and to a lesser degree enzymatic catalysts to be united with those of heterogeneous ones. With the aid of the vastly increasing families of nanoporous solids, desired catalytically active sites may be engineered in atomic detail on their inner, accessible surfaces, thereby opening up new possibilities in synthetic organic chemistry - as in the smooth formation of C-C and C[double bond, length as m-dash]N bonds in a number of intermolecular reactions - as well as in photocatalysts and in fluidized catalytic cracking of hydrocarbons.

  5. Products and kinetics of the heterogeneous reaction of suspended vinclozolin particles with ozone.

    PubMed

    Gan, Jie; Yang, Bo; Zhang, Yang; Shu, Xi; Liu, Changgeng; Shu, Jinian

    2010-11-25

    Vinclozolin is a widely used fungicide that can be released into the atmosphere via application and volatilization. This paper reports an experimental investigation on the heterogeneous ozonation of vinclozolin particles. The ozonation of vinclozolin adsorbed on azelaic acid particles under pseudo-first-order conditions is investigated online with a vacuum ultraviolet photoionization aerosol time-of-flight mass spectrometer (VUV-ATOFMS). The ozonation products are analyzed with a combination of VUV-ATOFMS and GC/MS. Two main ozonation products are observed. The formation of the ozonation products results from addition of O(3) on the C-C double bond of the vinyl group. The heterogeneous reactive rate constant of vinclozolin particles under room temperature is (2.4 ± 0.4) × 10(-17) cm(3) molecules(-1) s(-1), with a corresponding lifetime at 100 ppbv O(3) of 4.3 ± 0.7 h, which is almost comparable with the estimated lifetime due to the reaction with atmospheric OH radicals (∼1.7 h). The reactive uptake coefficient for O(3) on vinclozolin particles is (6.1 ± 1.0) × 10(-4).

  6. Porous Metal Organic Polyhedral Framework Containing Cuboctahedron Cages as SBUs with High Affinity for H2 and CO2 Sorptions: A Heterogeneous Catalyst for Chemical Fixation of CO2.

    PubMed

    Biradha, Kumar; Maity, Kartik; Karan, Chandan Kumar

    2018-06-11

    Development of active porous materials that can efficiently adsorb H2 and CO2 are in need due to their practical utilities. Here we present the design and synthesis of an interpenetrated Cu(II)-MOF that is thermally stable, highly porous and can act as a heterogeneous catalyst. The Cu(II)-MOF contains highly symmetric polyhedral metal cluster (Cu24) with cuboctahedron geometry as SBU. The double interpenetration of such huge cluster containing nets provides high density of open metal sites due to which it exhibits remarkable H2 storage capacity (313 cm3g-1 at 1bar and 77K) as well as high CO2 capture ability (159 cm3g-1 at 1bar and 273K). Further, its propensity towards the CO2 sorption utilized for the heterogeneous catalysis of chemical conversion of CO2 into the corresponding cyclic carbonates upon reaction with epoxides with high TON and TOF values. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Dissecting hematopoietic and renal cell heterogeneity in adult zebrafish at single-cell resolution using RNA sequencing.

    PubMed

    Tang, Qin; Iyer, Sowmya; Lobbardi, Riadh; Moore, John C; Chen, Huidong; Lareau, Caleb; Hebert, Christine; Shaw, McKenzie L; Neftel, Cyril; Suva, Mario L; Ceol, Craig J; Bernards, Andre; Aryee, Martin; Pinello, Luca; Drummond, Iain A; Langenau, David M

    2017-10-02

    Recent advances in single-cell, transcriptomic profiling have provided unprecedented access to investigate cell heterogeneity during tissue and organ development. In this study, we used massively parallel, single-cell RNA sequencing to define cell heterogeneity within the zebrafish kidney marrow, constructing a comprehensive molecular atlas of definitive hematopoiesis and functionally distinct renal cells found in adult zebrafish. Because our method analyzed blood and kidney cells in an unbiased manner, our approach was useful in characterizing immune-cell deficiencies within DNA-protein kinase catalytic subunit ( prkdc ), interleukin-2 receptor γ a ( il2rga ), and double-homozygous-mutant fish, identifying blood cell losses in T, B, and natural killer cells within specific genetic mutants. Our analysis also uncovered novel cell types, including two classes of natural killer immune cells, classically defined and erythroid-primed hematopoietic stem and progenitor cells, mucin-secreting kidney cells, and kidney stem/progenitor cells. In total, our work provides the first, comprehensive, single-cell, transcriptomic analysis of kidney and marrow cells in the adult zebrafish. © 2017 Tang et al.

  8. Dissecting hematopoietic and renal cell heterogeneity in adult zebrafish at single-cell resolution using RNA sequencing

    PubMed Central

    Iyer, Sowmya; Lobbardi, Riadh; Chen, Huidong; Hebert, Christine; Shaw, McKenzie L.; Neftel, Cyril; Suva, Mario L.; Bernards, Andre; Aryee, Martin; Drummond, Iain A.

    2017-01-01

    Recent advances in single-cell, transcriptomic profiling have provided unprecedented access to investigate cell heterogeneity during tissue and organ development. In this study, we used massively parallel, single-cell RNA sequencing to define cell heterogeneity within the zebrafish kidney marrow, constructing a comprehensive molecular atlas of definitive hematopoiesis and functionally distinct renal cells found in adult zebrafish. Because our method analyzed blood and kidney cells in an unbiased manner, our approach was useful in characterizing immune-cell deficiencies within DNA–protein kinase catalytic subunit (prkdc), interleukin-2 receptor γ a (il2rga), and double-homozygous–mutant fish, identifying blood cell losses in T, B, and natural killer cells within specific genetic mutants. Our analysis also uncovered novel cell types, including two classes of natural killer immune cells, classically defined and erythroid-primed hematopoietic stem and progenitor cells, mucin-secreting kidney cells, and kidney stem/progenitor cells. In total, our work provides the first, comprehensive, single-cell, transcriptomic analysis of kidney and marrow cells in the adult zebrafish. PMID:28878000

  9. Promotion of cooperation induced by heterogeneity of both investment and payoff allocation in spatial public goods game

    NASA Astrophysics Data System (ADS)

    Fan, Ruguo; Zhang, Yingqing; Luo, Ming; Zhang, Hongjuan

    2017-01-01

    Heterogeneity has attracted mounting attention across multiple disciplines and is confirmed to be a greater promoter of cooperation. It is often the case that the heterogeneity always exists in investment and payoff allocation concurrently instead of separately. In addition, the factors that affect heterogeneous investment and payoff allocation are various. Inspired by this, this paper extends the previous models by incorporating heterogeneous investment and payoff allocation into the typical PGG model to further investigate the incentive mechanisms of cooperative behavior. In order to better understand the model, three different feedback mechanisms, namely the wealth-preference mechanism, the social-self-preference mechanism, and the mixed-preference mechanism, are addressed. The former two mechanisms correspond to the case of single factor and the latter corresponds to the case of double factors. The numerical simulations indicate that feedback mechanism by bridging the connections between the investment and the payoff allocation can reduce the free-rider problem. Furthermore, it is found that the cooperative frequency and average payoff perform better in the case of the mixed-preference mechanism where players will not only take previous payoff feedback as well as current investment but also their social status into their game decision-making process. In addition, full cooperation and profitability over all players can be promoted by means of increasing r or reducing α. At last, compared with another two classic networks, the extent of cooperation is promoted under the structures of the BA scale free networks.

  10. Theoretical and experimental specific capacitance of polyaniline in sulfuric acid

    NASA Astrophysics Data System (ADS)

    Li, Hanlu; Wang, Jixiao; Chu, Qingxian; Wang, Zhi; Zhang, Fengbao; Wang, Shichang

    The theoretical mass specific capacitance (C s) of polyaniline (PANI) is firstly estimated by combining electrical double-layer capacitance and pseudocapacitance. The maximum C s is 2.0 × 10 3 F g -1 for one single PANI electrode. In present work, the PANI nanofiber modified stainless-steel (SS) electrode (PANI/SS) was used to assemble supercapacitors. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images indicate that the PANI nanofiber has a coarse surface arising from the heterogeneous structure which likes an aggregation of nanoparticles. The performance of the assembled PANI/SS supercapacitors was investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and galvanostatic charge/discharge methods in 1.0 M H 2SO 4. The maximum C s obtained from these methods in present work is 608, 445.0, and 524.9 F g -1, respectively, which is only 30%, 22%, and 26% of the theoretical one. The significant difference between the experimental and the theoretical value indicates that only a low percentage of PANI (effective) has contribution to capacitance. The percentage of effective PANI depends on both the diffusion of dopants (counter-anions) and the conductivity of PANI. Under practical conditions, the former factor makes PANI nanofiber behave like a concentric cable with only the shell part involved in the charge/discharge process. The latter one which determines the electron transfer rate in PANI has an influence on the degree of redox reaction. In present work, the heterogeneous structure of the PANI nanofiber has a negative effect on the conductivity.

  11. Long-term effective population size dynamics of an intensively monitored vertebrate population

    PubMed Central

    Mueller, A-K; Chakarov, N; Krüger, O; Hoffman, J I

    2016-01-01

    Long-term genetic data from intensively monitored natural populations are important for understanding how effective population sizes (Ne) can vary over time. We therefore genotyped 1622 common buzzard (Buteo buteo) chicks sampled over 12 consecutive years (2002–2013 inclusive) at 15 microsatellite loci. This data set allowed us to both compare single-sample with temporal approaches and explore temporal patterns in the effective number of parents that produced each cohort in relation to the observed population dynamics. We found reasonable consistency between linkage disequilibrium-based single-sample and temporal estimators, particularly during the latter half of the study, but no clear relationship between annual Ne estimates () and census sizes. We also documented a 14-fold increase in between 2008 and 2011, a period during which the census size doubled, probably reflecting a combination of higher adult survival and immigration from further afield. Our study thus reveals appreciable temporal heterogeneity in the effective population size of a natural vertebrate population, confirms the need for long-term studies and cautions against drawing conclusions from a single sample. PMID:27553455

  12. Stretching chimeric DNA: A test for the putative S-form

    NASA Astrophysics Data System (ADS)

    Whitelam, Stephen; Pronk, Sander; Geissler, Phillip L.

    2008-11-01

    Double-stranded DNA "overstretches" at a pulling force of about 65 pN, increasing in length by a factor of 1.7. The nature of the overstretched state is unknown, despite its considerable importance for DNA's biological function and technological application. Overstretching is thought by some to be a force-induced denaturation and by others to consist of a transition to an elongated, hybridized state called S-DNA. Within a statistical mechanical model, we consider the effect upon overstretching of extreme sequence heterogeneity. "Chimeric" sequences possessing halves of markedly different AT composition elongate under fixed external conditions via distinct, spatially segregated transitions. The corresponding force-extension data vary with pulling rate in a manner that depends qualitatively and strikingly upon whether the hybridized S-form is accessible. This observation implies a test for S-DNA that could be performed in experiment.

  13. Variation of HPV Subtypes with Focus on HPV-Infection and Cancer in the Head and Neck Region.

    PubMed

    Wichmann, Gunnar

    The human papillomavirus (HPV) comprises a heterogeneous group of double-strand DNA viruses with variable potential to infect human epithelial cells and trigger neoplastic transformation. Its 8 kb genome encodes proteins required for virus replication and self-organized formation of infectious particles but also for early proteins E6 and E7 able to trigger neoplastic transformation. E6 and E7 of high-risk (HR) HPV subtypes can bind to p53 or release E2F and abrogate replication control. Due to variable amino acid sequence (AAS) in the binding sites of E6 and E7 particular HR-HPV variants within subtypes are essentially heterogeneous in efficacy triggering neoplastic transformation and cancer development. This could explain differences in the clinical course of HPV-driven head and neck cancer.

  14. Micro CT-based multiscale elasticity of double-porous (pre-cracked) hydroxyapatite granules for regenerative medicine.

    PubMed

    Dejaco, Alexander; Komlev, Vladimir S; Jaroszewicz, Jakub; Swieszkowski, Wojciech; Hellmich, Christian

    2012-04-05

    Hundred micrometers-sized porous hydroxyapatite globules have proved as a successful tissue engineering strategy for bone defects in vivo, as was shown in studies on human mandibles. These granules need to provide enough porous space for bone ingrowth, while maintaining sufficient mechanical competence (stiffness and strength) in this highly load-bearing organ. This double challenge motivates us to scrutinize more deeply the micro- and nanomechanical characteristics of such globules, as to identify possible optimization routes. Therefore, we imaged such a (pre-cracked) granule in a microCT scanner, transformed the attenuation coefficients into voxel-specific nanoporosities, from which we determined, via polycrystal micromechanics, voxel-specific (heterogeneous) elastic properties. The importance of the latter and of the presence of one to several hundred micrometers-sized cracks for realistically estimating the load-carrying behavior of the globule under a typical two-point compressive loading (as in a "splitting" test) is shown through results of large-scale Finite Element analyses, in comparison to analytical results for a sphere loaded at its poles: Use of homogeneous instead of heterogeneous elastic properties would overestimate the structure's stiffness by 5% (when employing a micromechanics-based process as to attain homogeneous properties)-the cracks, in comparison, weaken the structure by one to two orders of magnitudes. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    Treesearch

    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...

  16. Double-moment cloud microphysics scheme for the deep convection parameterization in the GFDL AM3

    NASA Astrophysics Data System (ADS)

    Belochitski, A.; Donner, L.

    2014-12-01

    A double-moment cloud microphysical scheme originally developed by Morrision and Gettelman (2008) for the stratiform clouds and later adopted for the deep convection by Song and Zhang (2011) has been implemented in to the Geophysical Fluid Dynamics Laboratory's atmospheric general circulation model AM3. The scheme treats cloud drop, cloud ice, rain, and snow number concentrations and mixing ratios as diagnostic variables and incorporates processes of autoconversion, self-collection, collection between hydrometeor species, sedimentation, ice nucleation, drop activation, homogeneous and heterogeneous freezing, and the Bergeron-Findeisen process. Such detailed representation of microphysical processes makes the scheme suitable for studying the interactions between aerosols and convection, as well as aerosols' indirect effects on clouds and their roles in climate change. The scheme is first tested in the single column version of the GFDL AM3 using forcing data obtained at the U.S. Department of Energy Atmospheric Radiation Measurment project's Southern Great Planes site. Scheme's impact on SCM simulations is discussed. As the next step, runs of the full atmospheric GCM incorporating the new parameterization are compared to the unmodified version of GFDL AM3. Global climatological fields and their variability are contrasted with those of the original version of the GCM. Impact on cloud radiative forcing and climate sensitivity is investigated.

  17. Enhanced lysis by bispecific oncolytic measles viruses simultaneously using HER2/neu or EpCAM as target receptors

    PubMed Central

    Hanauer, Jan RH; Gottschlich, Lisa; Riehl, Dennis; Rusch, Tillmann; Koch, Vivian; Friedrich, Katrin; Hutzler, Stefan; Prüfer, Steffen; Friedel, Thorsten; Hanschmann, Kay-Martin; Münch, Robert C; Jost, Christian; Plückthun, Andreas; Cichutek, Klaus; Buchholz, Christian J; Mühlebach, Michael D

    2016-01-01

    To target oncolytic measles viruses (MV) to tumors, we exploit the binding specificity of designed ankyrin repeat proteins (DARPins). These DARPin-MVs have high tumor selectivity while maintaining excellent oncolytic potency. Stability, small size, and efficacy of DARPins allowed the generation of MVs simultaneously targeted to tumor marker HER2/neu and cancer stem cell (CSC) marker EpCAM. For optimization, the linker connecting both DARPins was varied in flexibility and length. Flexibility had no impact on fusion helper activity whereas length had. MVs with bispecific MV-H are genetically stable and revealed the desired double-target specificity. In vitro, the cytolytic activity of bispecific MVs was superior or comparable to mono-targeted viruses depending on the target cells. In vivo, therapeutic efficacy of the bispecific viruses was validated in an orthotopic ovarian carcinoma model revealing an effective reduction of tumor mass. Finally, the power of bispecific targeting was demonstrated on cocultures of different tumor cells thereby mimicking tumor heterogeneity in vitro, more closely reflecting real tumors. Here, bispecific excelled monospecific viruses in efficacy. DARPin-based targeting domains thus allow the generation of efficacious oncolytic viruses with double specificity, with the potential to handle intratumoral variation of antigen expression and to simultaneously target CSCs and the bulk tumor mass. PMID:27119117

  18. Who is entitled to double effect?

    PubMed

    Boyle, J

    1991-10-01

    The doctrine of double effect continues to be an important tool in bioethical casuistry. Its role within the Catholic moral tradition continues, and there is considerable interest in it by contemporary moral philosophers. But problems of justification and correct application remain. I argue that if the traditional Catholic conviction that there are exceptionless norms prohibiting inflicting some kinds of harms on people is correct, then double effect is justified and necessary. The objection that double effect is superfluous is a rejection of that normative conviction, not a refutation of double effect itself. This justification suggests the correct way of applying double effect to controversial cases. But versions of double effect which dispense with the absolutism of the Catholic tradition lack justification and fall to the objection that double effect is an unnecessary complication.

  19. A randomized, double-blind, placebo-controlled trial of polyethylene glycol effects on fasting and postprandial rectal sensitivity and symptoms in hypersensitive constipation-predominant irritable bowel syndrome.

    PubMed

    Awad, R A; Camacho, S

    2010-11-01

    To assess the effect of polyethylene glycol 3350 (PEG) on fasting and postprandial (PP) perception of rectal distension and symptoms in hypersensitive constipation-predominant irritable bowel syndrome (IBS-C). Forty-two patients meeting Rome II criteria for IBS-C and with a pain threshold of < 32 mmHg were included in a randomized, double-blind, placebo-controlled trial. Patients received either oral PEG, 3.45 g t.i.d. orally for 30 days or placebo. Rectal sensitivity was assessed before and after treatment with a barostat using the ascending method of limits, during basal and PP periods. No changes in fasting and PP rectal tone and thresholds for first sensation, gas sensation, urge to defecate, and pain was observed with PEG in relation to placebo. In both groups, pressure at which patients crossed the thresholds for noxious (PEG: from 28 ± 8.8 to 22 ± 6.9 mmHg) and non noxious (PEG: from 16 ± 4.9 to 12 ± 3.6 mmHg) stimuli decreased compared with pretreatment values. PEG improved consistency of faeces and showed a trend to diminish blood in faeces. PEG and placebo increased bowel movements per week (P < 0.001), and relieved symptoms without significant side-effects. Both PEG 3350 and placebo were clinically useful in patients with IBS-C, an effect that cannot be explained by changes in rectal tone and sensation. The results support the concept that visceral sensitivity is not stable and has a heterogeneous response to drugs, and suggest the existence of a post healing hypersensitivity state. © 2010 The Authors. Colorectal Disease © 2010 The Association of Coloproctology of Great Britain and Ireland.

  20. Dynamics of propagation of premature impulses in structurally remodeled infarcted myocardium: a computational analysis

    PubMed Central

    Cabo, Candido

    2014-01-01

    Initiation of cardiac arrhythmias typically follows one or more premature impulses either occurring spontaneously or applied externally. In this study, we characterize the dynamics of propagation of single (S2) and double premature impulses (S3), and the mechanisms of block of premature impulses at structural heterogeneities caused by remodeling of gap junctional conductance (Gj) in infarcted myocardium. Using a sub-cellular computer model of infarcted tissue, we found that |INa,max|, prematurity (coupling interval with the previous impulse), and conduction velocity (CV) of premature impulses change dynamically as they propagate away from the site of initiation. There are fundamental differences between the dynamics of propagation of S2 and S3 premature impulses: for S2 impulses |INa,max| recovers fast, prematurity decreases and CV increases as propagation proceeds; for S3 impulses low values of |INa,max| persist, prematurity could increase, and CV could decrease as impulses propagate away from the site of initiation. As a consequence it is more likely that S3 impulses block at sites of structural heterogeneities causing source/sink mismatch than S2 impulses block. Whether premature impulses block at Gj heterogeneities or not is also determined by the values of Gj (and the space constant λ) in the regions proximal and distal to the heterogeneity: when λ in the direction of propagation increases >40%, premature impulses could block. The maximum slope of CV restitution curves for S2 impulses is larger than for S3 impulses. In conclusion: (1) The dynamics of propagation of premature impulses make more likely that S3 impulses block at sites of structural heterogeneities than S2 impulses block; (2) Structural heterogeneities causing an increase in λ (or CV) of >40% could result in block of premature impulses; (3) A decrease in the maximum slope of CV restitution curves of propagating premature impulses is indicative of an increased potential for block at structural heterogeneities. PMID:25566085

  1. Dynamics of propagation of premature impulses in structurally remodeled infarcted myocardium: a computational analysis.

    PubMed

    Cabo, Candido

    2014-01-01

    Initiation of cardiac arrhythmias typically follows one or more premature impulses either occurring spontaneously or applied externally. In this study, we characterize the dynamics of propagation of single (S2) and double premature impulses (S3), and the mechanisms of block of premature impulses at structural heterogeneities caused by remodeling of gap junctional conductance (Gj) in infarcted myocardium. Using a sub-cellular computer model of infarcted tissue, we found that |INa,max|, prematurity (coupling interval with the previous impulse), and conduction velocity (CV) of premature impulses change dynamically as they propagate away from the site of initiation. There are fundamental differences between the dynamics of propagation of S2 and S3 premature impulses: for S2 impulses |INa,max| recovers fast, prematurity decreases and CV increases as propagation proceeds; for S3 impulses low values of |INa,max| persist, prematurity could increase, and CV could decrease as impulses propagate away from the site of initiation. As a consequence it is more likely that S3 impulses block at sites of structural heterogeneities causing source/sink mismatch than S2 impulses block. Whether premature impulses block at Gj heterogeneities or not is also determined by the values of Gj (and the space constant λ) in the regions proximal and distal to the heterogeneity: when λ in the direction of propagation increases >40%, premature impulses could block. The maximum slope of CV restitution curves for S2 impulses is larger than for S3 impulses. (1) The dynamics of propagation of premature impulses make more likely that S3 impulses block at sites of structural heterogeneities than S2 impulses block; (2) Structural heterogeneities causing an increase in λ (or CV) of >40% could result in block of premature impulses; (3) A decrease in the maximum slope of CV restitution curves of propagating premature impulses is indicative of an increased potential for block at structural heterogeneities.

  2. Reproducibility of tumor uptake heterogeneity characterization through textural feature analysis in 18F-FDG PET.

    PubMed

    Tixier, Florent; Hatt, Mathieu; Le Rest, Catherine Cheze; Le Pogam, Adrien; Corcos, Laurent; Visvikis, Dimitris

    2012-05-01

    (18)F-FDG PET measurement of standardized uptake value (SUV) is increasingly used for monitoring therapy response and predicting outcome. Alternative parameters computed through textural analysis were recently proposed to quantify the heterogeneity of tracer uptake by tumors as a significant predictor of response. The primary objective of this study was to evaluate the reproducibility of these heterogeneity measurements. Double baseline (18)F-FDG PET scans were acquired within 4 d of each other for 16 patients before any treatment was considered. A Bland-Altman analysis was performed on 8 parameters based on histogram measurements and 17 parameters based on textural heterogeneity features after discretization with values between 8 and 128. The reproducibility of maximum and mean SUV was similar to that in previously reported studies, with a mean percentage difference of 4.7% ± 19.5% and 5.5% ± 21.2%, respectively. By comparison, better reproducibility was measured for some textural features describing local heterogeneity of tracer uptake, such as entropy and homogeneity, with a mean percentage difference of -2% ± 5.4% and 1.8% ± 11.5%, respectively. Several regional heterogeneity parameters such as variability in the intensity and size of regions of homogeneous activity distribution had reproducibility similar to that of SUV measurements, with 95% confidence intervals of -22.5% to 3.1% and -1.1% to 23.5%, respectively. These parameters were largely insensitive to the discretization range. Several parameters derived from textural analysis describing heterogeneity of tracer uptake by tumors on local and regional scales had reproducibility similar to or better than that of simple SUV measurements. These reproducibility results suggest that these (18)F-FDG PET-derived parameters, which have already been shown to have predictive and prognostic value in certain cancer models, may be used to monitor therapy response and predict patient outcome.

  3. Reproducibility of tumor uptake heterogeneity characterization through textural feature analysis in 18F-FDG PET

    PubMed Central

    Tixier, Florent; Hatt, Mathieu; Le Rest, Catherine Cheze; Le Pogam, Adrien; Corcos, Laurent; Visvikis, Dimitris

    2012-01-01

    18F-FDG PET measurement of standardized uptake values (SUV) is increasingly used for monitoring therapy response or predicting outcome. Alternative parameters computed through textural analysis were recently proposed to quantify the tumor tracer uptake heterogeneity as significant predictors of response. The primary objective of this study was the evaluation of the reproducibility of these heterogeneity measurements. Methods Double-baseline 18F-FDG PET scans of 16 patients acquired within a period of 4 days prior to any treatment were considered. A Bland-Altman analysis was carried out on six parameters based on histogram measurements and 17 heterogeneity parameters based on textural features obtained after discretization with values between 8 and 128. Results SUVmax and SUVmean reproducibility were similar to previously reported studies with a mean percentage difference of 4.7±19.5% and 5.5±21.2% respectively. By comparison better reproducibility was measured for some of the textural features describing tumor tracer local heterogeneity, such as entropy and homogeneity with a mean percentage difference of −2±5.4% and 1.8±11.5% respectively. Several of the tumor regional heterogeneity parameters such as the variability in the intensity and size of homogeneous tumor activity distribution regions had similar reproducibility to the SUV measurements with 95% confidence intervals of −22.5% to 3.1% and −1.1% to 23.5% respectively. These parameters were largely insensitive to the discretization range values. Conclusion Several of the parameters derived from textural analysis describing tumor tracer heterogeneity at local and regional scales had similar or better reproducibility as simple SUV measurements. These reproducibility results suggest that these FDG PET image derived parameters which have already been shown to have a predictive and prognostic value in certain cancer models, may be used within the context of therapy response monitoring or predicting patient outcome. PMID:22454484

  4. 2.5-D poroelastic wave modelling in double porosity media

    NASA Astrophysics Data System (ADS)

    Liu, Xu; Greenhalgh, Stewart; Wang, Yanghua

    2011-09-01

    To approximate seismic wave propagation in double porosity media, the 2.5-D governing equations of poroelastic waves are developed and numerically solved. The equations are obtained by taking a Fourier transform in the strike or medium-invariant direction over all of the field quantities in the 3-D governing equations. The new memory variables from the Zener model are suggested as a way to represent the sum of the convolution integrals for both the solid particle velocity and the macroscopic fluid flux in the governing equations. By application of the memory equations, the field quantities at every time step need not be stored. However, this approximation allows just two Zener relaxation times to represent the very complex double porosity and dual permeability attenuation mechanism, and thus reduce the difficulty. The 2.5-D governing equations are numerically solved by a time-splitting method for the non-stiff parts and an explicit fourth-order Runge-Kutta method for the time integration and a Fourier pseudospectral staggered-grid for handling the spatial derivative terms. The 2.5-D solution has the advantage of producing a 3-D wavefield (point source) for a 2-D model but is much more computationally efficient than the full 3-D solution. As an illustrative example, we firstly show the computed 2.5-D wavefields in a homogeneous single porosity model for which we reformulated an analytic solution. Results for a two-layer, water-saturated double porosity model and a laterally heterogeneous double porosity structure are also presented.

  5. Double-diffusive convection in geothermal systems: the salton sea, California, geothermal system as a likely candidate

    USGS Publications Warehouse

    Fournier, R.O.

    1990-01-01

    Much has been published about double-diffusive convection as a mechanism for explaining variations in composition and temperature within all-liquid natural systems. However, relatively little is known about the applicability of this phenomenon within the heterogeneous rocks of currently active geothermal systems where primary porosity may control fluid flow in some places and fractures may control it in others. The main appeal of double-diffusive convection within hydrothermal systems is-that it is a mechanism that may allow efficient transfer of heat mainly by convection, while at the same time maintaining vertical and lateral salinity gradients. The Salton Sea geothermal system exhibits the following reservoir characteristics: (1) decreasing salinity and temperature from bottom to top and center toward the sides, (2) a very high heat flow from the top of the system that seems to require a major component of convective transfer of heat within the chemically stratified main reservoir, and (3) a relatively uniform density of the reservoir fluid throughout the system at all combinations of subsurface temperature, pressure, and salinity. Double-diffusive convection can account for these characteristics very nicely whereas other previously suggested models appear to account either for the thermal structure or for the salinity variations, but not both. Hydrologists, reservoir engineers, and particularly geochemists should consider the possibility and consequences of double-diffusive convection when formulating models of hydrothermal processes, and of the response of reservoirs to testing and production. ?? 1990.

  6. Cpu/gpu Computing for AN Implicit Multi-Block Compressible Navier-Stokes Solver on Heterogeneous Platform

    NASA Astrophysics Data System (ADS)

    Deng, Liang; Bai, Hanli; Wang, Fang; Xu, Qingxin

    2016-06-01

    CPU/GPU computing allows scientists to tremendously accelerate their numerical codes. In this paper, we port and optimize a double precision alternating direction implicit (ADI) solver for three-dimensional compressible Navier-Stokes equations from our in-house Computational Fluid Dynamics (CFD) software on heterogeneous platform. First, we implement a full GPU version of the ADI solver to remove a lot of redundant data transfers between CPU and GPU, and then design two fine-grain schemes, namely “one-thread-one-point” and “one-thread-one-line”, to maximize the performance. Second, we present a dual-level parallelization scheme using the CPU/GPU collaborative model to exploit the computational resources of both multi-core CPUs and many-core GPUs within the heterogeneous platform. Finally, considering the fact that memory on a single node becomes inadequate when the simulation size grows, we present a tri-level hybrid programming pattern MPI-OpenMP-CUDA that merges fine-grain parallelism using OpenMP and CUDA threads with coarse-grain parallelism using MPI for inter-node communication. We also propose a strategy to overlap the computation with communication using the advanced features of CUDA and MPI programming. We obtain speedups of 6.0 for the ADI solver on one Tesla M2050 GPU in contrast to two Xeon X5670 CPUs. Scalability tests show that our implementation can offer significant performance improvement on heterogeneous platform.

  7. An overview of the treatment of Tourette's disorder and tics.

    PubMed

    Párraga, Humberto C; Harris, Kara M; Párraga, Karen L; Balen, George M; Cruz, Cristina

    2010-08-01

    The aim of this study was to review the efficacy of various treatments for Tourette's disorder (TD) and tics. This study is a historical review of the treatment modalities prior to the advent of neuroleptics. A review of double-blind and placebo-controlled clinical trials and open studies on the use of neuroleptics and selected reports was also carried out. The literature review reveals that the treatment of TD and tics has evolved from an early history of marginally effective approaches to the advent of neuroleptics, which started a new era in TD and tic treatment, with a significantly broader range of effectiveness. Although progress has been made, the literature review nevertheless reveals a great deal of confusion as related to the clinical heterogeneity of TD and tics, differences in populations, medication-dose combinations, and outcomes. However, a role for a limited number of pharmacologic agents, combined with psychosocial approaches, has been identified. There is a need for studies in larger, diagnostically homogenous samples and for the use of more sophisticated methodology, to identify intelligible models that would allow the development of more effective treatment approaches.

  8. Coupled Electro-Hydrodynamic Effects of Electro-Osmosis from Pore Scale to Darcy Scale

    NASA Astrophysics Data System (ADS)

    Schotting, R.; Joekar-Niasar, V.; Leijnse, A.

    2011-12-01

    Electro-osmosis is "movement of a fluid under the effect of an electric field in a porous medium". This phenomenon has many applications in civil engineering (slope stabilization, dewatering), environmental engineering (soil remediation, sludge dewatering), chemical engineering (micro- or nano- mixers), medical engineering (drug delivery), etc. The key factor in electro-osmosis is the competition between the electrochemical and hydrodynamic forces as well as the coupling between the solid surface and the electrolyte properties. The objective of this research is to understand the influence of pore-scale heterogeneities of surface properties on the Darcy-scale behavior. We develop novel analytical solutions for the flow and transport of electrolyte including electro-hydrodynamic forces in a single micro-channel. We propose the complete analytical solution for monovalent electrolyte at full range overlapping double layers, and nonlinear electric field, including the Donan effect in transport of ions. These pore-scale formulations are numerically upscaled to obtain the Darcy-scale behavior. Our results show the contribution of electro-osmotic, chemical-osmotic and hydrodynamic components of the flow equation on pressure field evolution and multi-directional flow field at Darcy scale.

  9. Reductive alkylation of active methylene compounds with carbonyl derivatives, calcium hydride and a heterogeneous catalyst.

    PubMed

    Guyon, Carole; Duclos, Marie-Christine; Sutter, Marc; Métay, Estelle; Lemaire, Marc

    2015-07-07

    A one-pot two-step reaction (Knoevenagel condensation - reduction of the double bond) has been developed using calcium hydride as a reductant in the presence of a supported noble metal catalyst. The reaction between carbonyl compounds and active methylene compounds such as methylcyanoacetate, 1,3-dimethylbarbituric acid, dimedone and the more challenging dimethylmalonate, affords the corresponding monoalkylated products in moderate to good yields (up to 83%) with minimal reduction of the starting carbonyl compounds.

  10. Dual-circuit, multiple-effect refrigeration system and method

    DOEpatents

    DeVault, Robert C.

    1995-01-01

    A dual circuit absorption refrigeration system comprising a high temperature single-effect refrigeration loop and a lower temperature double-effect refrigeration loop separate from one another and provided with a double-condenser coupling therebetween. The high temperature condenser of the single-effect refrigeration loop is double coupled to both of the generators in the double-effect refrigeration loop to improve internal heat recovery and a heat and mass transfer additive such as 2-ethyl-1-hexanol is used in the lower temperature double-effect refrigeration loop to improve the performance of the absorber in the double-effect refrigeration loop.

  11. Theoretical analysis of optical poling and frequency doubling effect based on classical model

    NASA Astrophysics Data System (ADS)

    Feng, Xi; Li, Fuquan; Lin, Aoxiang; Wang, Fang; Chai, Xiangxu; Wang, Zhengping; Zhu, Qihua; Sun, Xun; Zhang, Sen; Sun, Xibo

    2018-03-01

    Optical poling and frequency doubling effect is one of the effective manners to induce second order nonlinearity and realize frequency doubling in glass materials. The classical model believes that an internal electric field is built in glass when it's exposed by fundamental and frequency-doubled light at the same time, and second order nonlinearity appears as a result of the electric field and the orientation of poles. The process of frequency doubling in glass is quasi phase matched. In this letter, the physical process of poling and doubling process in optical poling and frequency doubling effect is deeply discussed in detail. The magnitude and direction of internal electric field, second order nonlinear coefficient and its components, strength and direction of frequency doubled output signal, quasi phase matched coupled wave equations are given in analytic expression. Model of optical poling and frequency doubling effect which can be quantitatively analyzed are constructed in theory, which set a foundation for intensive study of optical poling and frequency doubling effect.

  12. Spatial resolution of the electrical conductance of ionic fluids using a Green-Kubo method.

    PubMed

    Jones, R E; Ward, D K; Templeton, J A

    2014-11-14

    We present a Green-Kubo method to spatially resolve transport coefficients in compositionally heterogeneous mixtures. We develop the underlying theory based on well-known results from mixture theory, Irving-Kirkwood field estimation, and linear response theory. Then, using standard molecular dynamics techniques, we apply the methodology to representative systems. With a homogeneous salt water system, where the expectation of the distribution of conductivity is clear, we demonstrate the sensitivities of the method to system size, and other physical and algorithmic parameters. Then we present a simple model of an electrochemical double layer where we explore the resolution limit of the method. In this system, we observe significant anisotropy in the wall-normal vs. transverse ionic conductances, as well as near wall effects. Finally, we discuss extensions and applications to more realistic systems such as batteries where detailed understanding of the transport properties in the vicinity of the electrodes is of technological importance.

  13. Amniotic-Fluid Stem Cells: Growth Dynamics and Differentiation Potential after a CD-117-Based Selection Procedure

    PubMed Central

    Arnhold, S.; Glüer, S.; Hartmann, K.; Raabe, O.; Addicks, K.; Wenisch, S.; Hoopmann, M.

    2011-01-01

    Amniotic fluid (AF) has become an interesting source of fetal stem cells. However, AF contains heterogeneous and multiple, partially differentiated cell types. After isolation from the amniotic fluid, cells were characterized regarding their morphology and growth dynamics. They were sorted by magnetic associated cell sorting using the surface marker CD 117. In order to show stem cell characteristics such as pluripotency and to evaluate a possible therapeutic application of these cells, AF fluid-derived stem cells were differentiated along the adipogenic, osteogenic, and chondrogenic as well as the neuronal lineage under hypoxic conditions. Our findings reveal that magnetic associated cell sorting (MACS) does not markedly influence growth characteristics as demonstrated by the generation doubling time. There was, however, an effect regarding an altered adipogenic, osteogenic, and chondrogenic differentiation capacity in the selected cell fraction. In contrast, in the unselected cell population neuronal differentiation is enhanced. PMID:21437196

  14. Introduction to fatty acids and lipids.

    PubMed

    Burdge, Graham C; Calder, Philip C

    2015-01-01

    The purpose of this article is to describe the structure, function and metabolism of fatty acids and lipids that are of particular importance in the context of parenteral nutrition. Lipids are a heterogeneous group of molecules that share the common property of hydrophobicity. Lipids range in structure from simple short hydrocarbon chains to more complex molecules, including triacylglycerols, phospholipids and sterols and their esters. Lipids within each class may differ structurally. Fatty acids are common components of complex lipids, and these differ according to chain length and the presence, number and position of double bonds in the hydrocarbon chain. Structural variation among complex lipids and among fatty acids gives rise to functional differences that result in different impacts upon metabolism and upon cell and tissue responses. Fatty acids and complex lipids exhibit a variety of structural variations that influence their metabolism and their functional effects. © 2015 S. Karger AG, Basel.

  15. Charge reversal at a planar boundary between two dielectrics.

    PubMed

    Wang, Zhi-Yong

    2016-01-01

    Despite the ubiquitous character and relevance of the electric double layer in the entire realm of interface and colloid science, very little is known of the effect that surface heterogeneity exerts on the underlying mechanisms of ion adsorption. Herein, computer simulations offer a perspective that, in sharp contrast to the homogeneously charged surface, discrete groups promote multivalent counterion binding, leading to charge reversal but possibly having not a sign change of the electrophoretic mobility. Counterintuitively, the introduction of dielectric images yields a significantly greater accumulation of counterions, which further facilitates the magnitude of charge reversal. The reported results are very sensitive to both the degree of ion hydration and the representation of surface charges. Our findings shed light on the mechanism for charge reversal over a broad range of coupling regimes operating the adsorption of counterions through surface group bridging attraction with their own images and provide opportunities for experimental studies and theoretical development.

  16. Charge reversal at a planar boundary between two dielectrics

    NASA Astrophysics Data System (ADS)

    Wang, Zhi-Yong

    2016-01-01

    Despite the ubiquitous character and relevance of the electric double layer in the entire realm of interface and colloid science, very little is known of the effect that surface heterogeneity exerts on the underlying mechanisms of ion adsorption. Herein, computer simulations offer a perspective that, in sharp contrast to the homogeneously charged surface, discrete groups promote multivalent counterion binding, leading to charge reversal but possibly having not a sign change of the electrophoretic mobility. Counterintuitively, the introduction of dielectric images yields a significantly greater accumulation of counterions, which further facilitates the magnitude of charge reversal. The reported results are very sensitive to both the degree of ion hydration and the representation of surface charges. Our findings shed light on the mechanism for charge reversal over a broad range of coupling regimes operating the adsorption of counterions through surface group bridging attraction with their own images and provide opportunities for experimental studies and theoretical development.

  17. Timelapse ultrasonic tomography for measuring damage localization in geomechanics laboratory tests.

    PubMed

    Tudisco, Erika; Roux, Philippe; Hall, Stephen A; Viggiani, Giulia M B; Viggiani, Gioacchino

    2015-03-01

    Variation of mechanical properties in materials can be detected non-destructively using ultrasonic measurements. In particular, changes in elastic wave velocity can occur due to damage, i.e., micro-cracking and particles debonding. Here the challenge of characterizing damage in geomaterials, i.e., rocks and soils, is addressed. Geomaterials are naturally heterogeneous media in which the deformation can localize, so that few measurements of acoustic velocity across the sample are not sufficient to capture the heterogeneities. Therefore, an ultrasonic tomography procedure has been implemented to map the spatial and temporal variations in propagation velocity, which provides information on the damage process. Moreover, double beamforming has been successfully applied to identify and isolate multiple arrivals that are caused by strong heterogeneities (natural or induced by the deformation process). The applicability of the developed experimental technique to laboratory geomechanics testing is illustrated using data acquired on a sample of natural rock before and after being deformed under triaxial compression. The approach is then validated and extended to time-lapse monitoring using data acquired during plane strain compression of a sample including a well defined layer with different mechanical properties than the matrix.

  18. Heterogeneous structure and its effect on properties and electrochemical behavior of ion-exchange membrane

    NASA Astrophysics Data System (ADS)

    Ariono, D.; Khoiruddin; Subagjo; Wenten, I. G.

    2017-02-01

    Generally, commercially available ion-exchange membrane (IEM) can be classified into homogeneous and heterogeneous membranes. The classification is based on degree of heterogeneity in membrane structure. It is well known that the heterogeneity greatly affects the properties of IEM, such as conductivity, permselectivity, chemical and mechanical stability. The heterogeneity also influences ionic and electrical current transfer behavior of IEM-based processes during their operation. Therefore, understanding the role of heterogeneity in IEM properties is important to provide preliminary information on their operability and applicability. In this paper, the heterogeneity and its effect on IEM properties are reviewed. Some models for describing the heterogeneity of IEM and methods for characterizing the degree of heterogeneity are discussed. In addition, the influence of heterogeneity on the performance of IEM-based processes and their electrochemical behavior are described.

  19. NSC30049 inhibits Chk1 pathway in 5-FU-resistant CRC bulk and stem cell populations.

    PubMed

    Narayan, Satya; Jaiswal, Aruna S; Sharma, Ritika; Nawab, Akbar; Duckworth, Lizette Vila; Law, Brian K; Zajac-Kaye, Maria; George, Thomas J; Sharma, Jay; Sharma, Arun K; Hromas, Robert A

    2017-08-22

    The 5-fluorouracil (5-FU) treatment induces DNA damage and stalling of DNA replication forks. These stalled replication forks then collapse to form one sided double-strand breaks, leading to apoptosis. However, colorectal cancer (CRC) stem cells rapidly repair the stalled/collapsed replication forks and overcome treatment effects. Recent evidence suggests a critical role of checkpoint kinase 1 (Chk1) in preventing the replicative stress. Therefore, Chk1 kinase has been a target for developing mono or combination therapeutic agents. In the present study, we have identified a novel orphan molecule NSC30049 (NSC49L) that is effective alone, and in combination potentiates 5-FU-mediated growth inhibition of CRC heterogeneous bulk and FOLFOX-resistant cell lines in culture with minimal effect on normal colonic epithelial cells. It also inhibits the sphere forming activity of CRC stem cells, and decreases the expression levels of mRNAs of CRC stem cell marker genes. Results showed that NSC49L induces 5-FU-mediated S-phase cell cycle arrest due to increased load of DNA damage and increased γ-H2AX staining as a mechanism of cytotoxicity. The pharmacokinetic analysis showed a higher bioavailability of this compound, however, with a short plasma half-life. The drug is highly tolerated by animals with no pathological aberrations. Furthermore, NSC49L showed very potent activity in a HDTX model of CRC stem cell tumors either alone or in combination with 5-FU. Thus, NSC49L as a single agent or combined with 5-FU can be developed as a therapeutic agent by targeting the Chk1 pathway in 5-FU-resistant CRC heterogeneous bulk and CRC stem cell populations.

  20. Citicoline for Acute Ischemic Stroke: A Systematic Review and Formal Meta-analysis of Randomized, Double-Blind, and Placebo-Controlled Trials.

    PubMed

    Secades, Julio J; Alvarez-Sabín, José; Castillo, José; Díez-Tejedor, Exuperio; Martínez-Vila, Eduardo; Ríos, José; Oudovenko, Natalia

    2016-08-01

    Citicoline is a drug approved for the treatment of acute ischemic stroke. Although evidence of its efficacy has been reported, recently published results of a large placebo-controlled clinical trial did not show differences. This study aims to assess whether starting citicoline treatment within 14 days after stroke onset improves the outcome in patients with acute ischemic stroke, as compared with placebo. A systematic search was performed to identify all published, unconfounded, randomized, double-blind, and placebo-controlled clinical trials of citicoline in acute ischemic stroke. Ten randomized clinical trials met our inclusion criteria. The administration of citicoline was associated with a significant higher rate of independence, independently of the method of evaluation used (odds ratio [OR] 1.56, 95% confidence interval [CI] = 1.12-2.16 under random effects; OR 1.20, 95% CI = 1.06-1.36 under fixed effects). After studying the cumulative meta-analysis, and with the results obtained with the subgroup of patients who were not treated with recombinant tissue plasminogen activator (rtPA) (OR 1.63, 95% CI = 1.18-2.24 under random effects; OR 1.42, 95% CI = 1.22-1.66 under fixed effects), our hypothesis of dilution of the effect of citicoline was confirmed. When we analyzed the effect of citicoline in patients who were not treated with rtPA and were receiving the highest dose of citicoline started in the first 24 hours after onset, based on more recent trials, there was no heterogeneity, and the size of the effect has an OR of 1.27 (95% CI = 1.05-1.53). This systematic review supports some benefits of citicoline in the treatment of acute ischemic stroke. But, on top of the best treatment available (rtPA), citicoline offers a limited benefit. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  1. 3D Printing in Surgical Management of Double Outlet Right Ventricle.

    PubMed

    Yoo, Shi-Joon; van Arsdell, Glen S

    2017-01-01

    Double outlet right ventricle (DORV) is a heterogeneous group of congenital heart diseases that require individualized surgical approach based on precise understanding of the complex cardiovascular anatomy. Physical 3-dimensional (3D) print models not only allow fast and unequivocal perception of the complex anatomy but also eliminate misunderstanding or miscommunication among imagers and surgeons. Except for those cases showing well-recognized classic surgical anatomy of DORV such as in cases with a typical subaortic or subpulmonary ventricular septal defect, 3D print models are of enormous value in surgical decision and planning. Furthermore, 3D print models can also be used for rehearsal of the intended procedure before the actual surgery on the patient so that the outcome of the procedure is precisely predicted and the procedure can be optimally tailored for the patient's specific anatomy. 3D print models are invaluable resource for hands-on surgical training of congenital heart surgeons.

  2. Numerical calculation on a two-step subdiffusion behavior of lateral protein movement in plasma membranes

    NASA Astrophysics Data System (ADS)

    Sumi, Tomonari; Okumoto, Atsushi; Goto, Hitoshi; Sekino, Hideo

    2017-10-01

    A two-step subdiffusion behavior of lateral movement of transmembrane proteins in plasma membranes has been observed by using single-molecule experiments. A nested double-compartment model where large compartments are divided into several smaller ones has been proposed in order to explain this observation. These compartments are considered to be delimited by membrane-skeleton "fences" and membrane-protein "pickets" bound to the fences. We perform numerical simulations of a master equation using a simple two-dimensional lattice model to investigate the heterogeneous diffusion dynamics behavior of transmembrane proteins within plasma membranes. We show that the experimentally observed two-step subdiffusion process can be described using fence and picket models combined with decreased local diffusivity of transmembrane proteins in the vicinity of the pickets. This allows us to explain the two-step subdiffusion behavior without explicitly introducing nested double compartments.

  3. RNA circularization reveals terminal sequence heterogeneity in a double-stranded RNA virus.

    PubMed

    Widmer, G

    1993-03-01

    Double-stranded RNA viruses (dsRNA), termed LRV1, have been found in several strains of the protozoan parasite Leishmania. With the aim of constructing a full-length cDNA copy of the viral genome, including its terminal sequences, a protocol based on PCR amplification across the 3'-5' junction of circularized RNA was developed. This method proved to be applicable to dsRNA. It provided a relatively simple alternative to one-sided PCR, without loss of specificity inherent in the use of generic primers. LRV1 terminal nucleotide sequences obtained by this method showed a considerable variation in length, particularly at the 5' end of the positive strand, as well as the potential for forming 3' overhangs. The opposite genomic end terminates in 0, 1, or 2 TCA trinucleotide repeats. These results are compared with terminal sequences derived from one-sided PCR experiments.

  4. Design and construction of porous metal-organic frameworks based on flexible BPH pillars

    NASA Astrophysics Data System (ADS)

    Hao, Xiang-Rong; Yang, Guang-sheng; Shao, Kui-Zhan; Su, Zhong-Min; Yuan, Gang; Wang, Xin-Long

    2013-02-01

    Three metal-organic frameworks (MOFs), [Co2(BPDC)2(4-BPH)·3DMF]n (1), [Cd2(BPDC)2(4-BPH)2·2DMF]n (2) and [Ni2(BDC)2(3-BPH)2 (H2O)·4DMF]n (3) (H2BPDC=biphenyl-4,4'-dicarboxylic acid, H2BDC=terephthalic acid, BPH=bis(pyridinylethylidene)hydrazine and DMF=N,N'-dimethylformamide), have been solvothermally synthesized based on the insertion of heterogeneous BPH pillars. Framework 1 has "single-pillared" MOF-5-like motif with inner cage diameters of up to 18.6 Å. Framework 2 has "double pillared" MOF-5-like motif with cage diameters of 19.2 Å while 3 has "double pillared" 8-connected framework with channel diameters of 11.0 Å. Powder X-ray diffraction (PXRD) shows that 3 is a dynamic porous framework.

  5. Large field of view quantitative phase imaging of induced pluripotent stem cells and optical pathlength reference materials

    NASA Astrophysics Data System (ADS)

    Kwee, Edward; Peterson, Alexander; Stinson, Jeffrey; Halter, Michael; Yu, Liya; Majurski, Michael; Chalfoun, Joe; Bajcsy, Peter; Elliott, John

    2018-02-01

    Induced pluripotent stem cells (iPSCs) are reprogrammed cells that can have heterogeneous biological potential. Quality assurance metrics of reprogrammed iPSCs will be critical to ensure reliable use in cell therapies and personalized diagnostic tests. We present a quantitative phase imaging (QPI) workflow which includes acquisition, processing, and stitching multiple adjacent image tiles across a large field of view (LFOV) of a culture vessel. Low magnification image tiles (10x) were acquired with a Phasics SID4BIO camera on a Zeiss microscope. iPSC cultures were maintained using a custom stage incubator on an automated stage. We implement an image acquisition strategy that compensates for non-flat illumination wavefronts to enable imaging of an entire well plate, including the meniscus region normally obscured in Zernike phase contrast imaging. Polynomial fitting and background mode correction was implemented to enable comparability and stitching between multiple tiles. LFOV imaging of reference materials indicated that image acquisition and processing strategies did not affect quantitative phase measurements across the LFOV. Analysis of iPSC colony images demonstrated mass doubling time was significantly different than area doubling time. These measurements were benchmarked with prototype microsphere beads and etched-glass gratings with specified spatial dimensions designed to be QPI reference materials with optical pathlength shifts suitable for cell microscopy. This QPI workflow and the use of reference materials can provide non-destructive traceable imaging method for novel iPSC heterogeneity characterization.

  6. Agpat4/Lpaatδ deficiency highlights the molecular heterogeneity of epididymal and perirenal white adipose depots.

    PubMed

    Mardian, Emily B; Bradley, Ryan M; Aristizabal Henao, Juan J; Marvyn, Phillip M; Moes, Katherine A; Bombardier, Eric; Tupling, A Russell; Stark, Ken D; Duncan, Robin E

    2017-10-01

    Acylglycerophosphate acyltransferase 4 (AGPAT4)/lysophosphatidic acid acyltransferase delta catalyzes the formation of phosphatidic acid (PA), a precursor of triacyl-glycerol (TAG). We investigated the effect of Agpat4 gene ablation on white adipose tissue (WAT) after finding consistent expression across depots. Epididymal WAT mass was 40% larger in male Agpat4 -/- mice than wild-type littermates, but unchanged in perirenal, retroperitoneal, and inguinal WAT and subscapular brown adipose tissue. Metabolic changes were identified in epididymal WAT that were not evident in perirenal WAT, which was analyzed for comparison. The total epididymal TAG content doubled, increasing adipocyte cell size without changing markers of differentiation. Enzymes involved in de novo lipogenesis and complex lipid synthesis downstream of phosphatidic acid production were also unchanged. However, total epididymal TAG hydrolase activity was reduced, and there were significant decreases in total ATGL and reduced phosphorylation of hormone-sensitive lipase at the S563 and S660 PKA-activation sites. Analysis of Agpats 1, 2, 3 , and 5 , as well as Gpats 1, 2, 3, and 4, demonstrated compensatory upregulation in perirenal WAT that did not occur in epididymal WAT. Our findings therefore indicate depot-specific differences in the redundancy of Agpat4 and highlight the molecular and metabolic heterogeneity of individual visceral depots. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  7. Predicting Intra-Urban Population Densities in Africa using SAR and Optical Remote Sensing Data

    NASA Astrophysics Data System (ADS)

    Linard, C.; Steele, J.; Forget, Y.; Lopez, J.; Shimoni, M.

    2017-12-01

    The population of Africa is predicted to double over the next 40 years, driving profound social, environmental and epidemiological changes within rapidly growing cities. Estimations of within-city variations in population density must be improved in order to take urban heterogeneities into account and better help urban research and decision making, especially for vulnerability and health assessments. Satellite remote sensing offers an effective solution for mapping settlements and monitoring urbanization at different spatial and temporal scales. In Africa, the urban landscape is covered by slums and small houses, where the heterogeneity is high and where the man-made materials are natural. Innovative methods that combine optical and SAR data are therefore necessary for improving settlement mapping and population density predictions. An automatic method was developed to estimate built-up densities using recent and archived optical and SAR data and a multi-temporal database of built-up densities was produced for 48 African cities. Geo-statistical methods were then used to study the relationships between census-derived population densities and satellite-derived built-up attributes. Best predictors were combined in a Random Forest framework in order to predict intra-urban variations in population density in any large African city. Models show significant improvement of our spatial understanding of urbanization and urban population distribution in Africa in comparison to the state of the art.

  8. A sampling design and model for estimating abundance of Nile crocodiles while accounting for heterogeneity of detectability of multiple observers

    USGS Publications Warehouse

    Shirley, Matthew H.; Dorazio, Robert M.; Abassery, Ekramy; Elhady, Amr A.; Mekki, Mohammed S.; Asran, Hosni H.

    2012-01-01

    As part of the development of a management program for Nile crocodiles in Lake Nasser, Egypt, we used a dependent double-observer sampling protocol with multiple observers to compute estimates of population size. To analyze the data, we developed a hierarchical model that allowed us to assess variation in detection probabilities among observers and survey dates, as well as account for variation in crocodile abundance among sites and habitats. We conducted surveys from July 2008-June 2009 in 15 areas of Lake Nasser that were representative of 3 main habitat categories. During these surveys, we sampled 1,086 km of lake shore wherein we detected 386 crocodiles. Analysis of the data revealed significant variability in both inter- and intra-observer detection probabilities. Our raw encounter rate was 0.355 crocodiles/km. When we accounted for observer effects and habitat, we estimated a surface population abundance of 2,581 (2,239-2,987, 95% credible intervals) crocodiles in Lake Nasser. Our results underscore the importance of well-trained, experienced monitoring personnel in order to decrease heterogeneity in intra-observer detection probability and to better detect changes in the population based on survey indices. This study will assist the Egyptian government establish a monitoring program as an integral part of future crocodile harvest activities in Lake Nasser

  9. Flow-Induced Dispersion Analysis for Probing Anti-dsDNA Antibody Binding Heterogeneity in Systemic Lupus Erythematosus Patients: Toward a New Approach for Diagnosis and Patient Stratification.

    PubMed

    Poulsen, Nicklas N; Pedersen, Morten E; Østergaard, Jesper; Petersen, Nickolaj J; Nielsen, Christoffer T; Heegaard, Niels H H; Jensen, Henrik

    2016-09-20

    Detection of immune responses is important in the diagnosis of many diseases. For example, the detection of circulating autoantibodies against double-stranded DNA (dsDNA) is used in the diagnosis of Systemic Lupus Erythematosus (SLE). It is, however, difficult to reach satisfactory sensitivity, specificity, and accuracy with established assays. Also, existing methodologies for quantification of autoantibodies are challenging to transfer to a point-of-care setting. Here we present the use of flow-induced dispersion analysis (FIDA) for rapid (minutes) measurement of autoantibodies against dsDNA. The assay is based on Taylor dispersion analysis (TDA) and is fully automated with the use of standard capillary electrophoresis (CE) based equipment employing fluorescence detection. It is robust toward matrix effects as demonstrated by the direct analysis of samples composed of up to 85% plasma derived from human blood samples, and it allows for flexible exchange of the DNA sequences used to probe for the autoantibodies. Plasma samples from SLE positive patients were analyzed using the new FIDA methodology as well as by standard indirect immunofluorescence and solid-phase immunoassays. Interestingly, the patient antibodies bound DNA sequences with different affinities, suggesting pronounced heterogeneity among autoantibodies produced in SLE. The FIDA based methodology is a new approach for autoantibody detection and holds promise for being used for patient stratification and monitoring of disease activity.

  10. An efficient implementation of 3D high-resolution imaging for large-scale seismic data with GPU/CPU heterogeneous parallel computing

    NASA Astrophysics Data System (ADS)

    Xu, Jincheng; Liu, Wei; Wang, Jin; Liu, Linong; Zhang, Jianfeng

    2018-02-01

    De-absorption pre-stack time migration (QPSTM) compensates for the absorption and dispersion of seismic waves by introducing an effective Q parameter, thereby making it an effective tool for 3D, high-resolution imaging of seismic data. Although the optimal aperture obtained via stationary-phase migration reduces the computational cost of 3D QPSTM and yields 3D stationary-phase QPSTM, the associated computational efficiency is still the main problem in the processing of 3D, high-resolution images for real large-scale seismic data. In the current paper, we proposed a division method for large-scale, 3D seismic data to optimize the performance of stationary-phase QPSTM on clusters of graphics processing units (GPU). Then, we designed an imaging point parallel strategy to achieve an optimal parallel computing performance. Afterward, we adopted an asynchronous double buffering scheme for multi-stream to perform the GPU/CPU parallel computing. Moreover, several key optimization strategies of computation and storage based on the compute unified device architecture (CUDA) were adopted to accelerate the 3D stationary-phase QPSTM algorithm. Compared with the initial GPU code, the implementation of the key optimization steps, including thread optimization, shared memory optimization, register optimization and special function units (SFU), greatly improved the efficiency. A numerical example employing real large-scale, 3D seismic data showed that our scheme is nearly 80 times faster than the CPU-QPSTM algorithm. Our GPU/CPU heterogeneous parallel computing framework significant reduces the computational cost and facilitates 3D high-resolution imaging for large-scale seismic data.

  11. Strain induced grain boundary migration effects on grain growth of an austenitic stainless steel during static and metadynamic recrystallization

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Paggi, A., E-mail: alpaggi@tenaris.com; Angella, G.; Donnini, R.

    Static and metadynamic recrystallization of an AISI 304L austenitic stainless steel was investigated at 1100 °C and 10{sup −} {sup 2} s{sup −} {sup 1} strain rate. The kinetics of recrystallization was determined through double hit compression tests. Two strain levels were selected for the first compression hit: ε{sub f} = 0.15 for static recrystallization (SRX) and 0.25 for metadynamic recrystallization (MDRX). Both the as-deformed and the recrystallized microstructures were investigated through optical microscopy and electron back-scattered diffraction (EBSD) technique. During deformation, strain induced grain boundary migration appeared to be significant, producing a square-like grain boundary structure aligned along themore » directions of the maximum shear stresses in compression. EBSD analysis revealed to be as a fundamental technique that the dislocation density was distributed heterogeneously in the deformed grains. Grain growth driven by surface energy reduction was also investigated, finding that it was too slow to explain the experimental data. Based on microstructural results, it was concluded that saturation of the nucleation sites occurred in the first stages of recrystallization, while grain growth driven by strain induced grain boundary migration (SIGBM) dominated the subsequent stages. - Highlights: • Recrystallization behavior of a stainless steel was investigated at 1100 °C. • EBSD revealed that the dislocation density distribution was heterogeneous during deformation. • Saturation of nucleation sites occurred in the first stages of recrystallization. • Strain induced grain boundary migration (SIGBM) effects were significant. • Grain growth driven by SIGBM dominated the subsequent stages.« less

  12. Diapycnal Transport and Pattern Formation in Double-Diffusive Convection

    DTIC Science & Technology

    2015-12-01

    of knowledge. The effects of turbulent-dominated and purely double-diffusive regimes are compared to dual turbulent/double-diffusive systems and...is presented to remedy this dearth of knowledge. The effects of turbulent-dominated and purely double-diffusive regimes are compared to dual...8 2. Double-Diffusion: The Constant Flux Ratio Model ..........................9 3. The Combined Effects of

  13. The dominant role of side chains in supramolecular double helical organisation in synthetic tripeptides

    NASA Astrophysics Data System (ADS)

    Sharma, Ankita; Tiwari, Priyanka; Dutt Konar, Anita

    2018-06-01

    Peptide self-assembled nanostructures have attracted attention recently owing to their promising applications in diversified avenues. To validate the importance of sidechains in supramolecular architectural stabilization, herein this report describes the self-assembly propensities involving weak interactions in a series of model tripeptides Boc-Xaa-Aib-Yaa-OMe I-IV, (where Xaa = 4-F-Phe/NMeSer/Ile & Yaa = Tyr in peptide I-III respectively and Xaa = 4-F-Phe & Yaa = Ile in peptide IV) differing in terminal side chains. The solid state structural analysis reveals that tripeptide (I) displays supramolecular preference for double helical architecture. However, when slight modification has been introduced in the N-terminal side chains disfavour the double helical organisation (Peptide II and III). Indeed the peptides display sheet like ensemble within the framework. Besides replacement of C-terminal Tyr by Ile in peptide I even do not promote the architecture, emphasizing the dominant role of balance of side chains in stabilizing double helical organisation. The CD measurements, concentration dependant studies, NMR titrations and ROESY spectra are well in agreement with the solid state conformational investigation. Moreover the morphological experiments utilizing FE-SEM, support the heterogeneity present in the peptides. Thus this work may not only hold future promise in understanding the structure and function of neurodegenerative diseases but also assist in rational design of protein modification in biologically active peptides.

  14. Magnetic field homogeneity of a conical coaxial coil pair.

    PubMed

    Salazar, F J; Nieves, F J; Bayón, A; Gascón, F

    2017-09-01

    An analytical study of the magnetic field created by a double-conical conducting sheet is presented. The analysis is based on the expansion of the magnetic field in terms of Legendre polynomials. It is demonstrated analytically that the angle of the conical surface that produces a nearly homogeneous magnetic field coincides with that of a pair of loops that fulfills the Helmholtz condition. From the results obtained, we propose an electric circuit formed by pairs of isolated conducting loops tightly wound around a pair of conical surfaces, calculating numerically the magnetic field produced by this system and its heterogeneity. An experimental setup of the proposed circuit was constructed and its magnetic field was measured. The results were compared with those obtained by numerical calculation, finding a good agreement. The numerical results demonstrate a significant improvement in homogeneity in the field of the proposed pair of conical coils compared with that achieved with a simple pair of Helmholtz loops or with a double solenoid. Moreover, a new design of a double pair of conical coils based on Braunbek's four loops is also proposed to achieve greater homogeneity. Regarding homogeneity, the rating of the analyzed configurations from best to worst is as follows: (1) double pair of conical coils, (2) pair of conical coils, (3) Braunbek's four loops, (4) Helmholtz pair, and (5) solenoid pair.

  15. Magnetic field homogeneity of a conical coaxial coil pair

    NASA Astrophysics Data System (ADS)

    Salazar, F. J.; Nieves, F. J.; Bayón, A.; Gascón, F.

    2017-09-01

    An analytical study of the magnetic field created by a double-conical conducting sheet is presented. The analysis is based on the expansion of the magnetic field in terms of Legendre polynomials. It is demonstrated analytically that the angle of the conical surface that produces a nearly homogeneous magnetic field coincides with that of a pair of loops that fulfills the Helmholtz condition. From the results obtained, we propose an electric circuit formed by pairs of isolated conducting loops tightly wound around a pair of conical surfaces, calculating numerically the magnetic field produced by this system and its heterogeneity. An experimental setup of the proposed circuit was constructed and its magnetic field was measured. The results were compared with those obtained by numerical calculation, finding a good agreement. The numerical results demonstrate a significant improvement in homogeneity in the field of the proposed pair of conical coils compared with that achieved with a simple pair of Helmholtz loops or with a double solenoid. Moreover, a new design of a double pair of conical coils based on Braunbek's four loops is also proposed to achieve greater homogeneity. Regarding homogeneity, the rating of the analyzed configurations from best to worst is as follows: (1) double pair of conical coils, (2) pair of conical coils, (3) Braunbek's four loops, (4) Helmholtz pair, and (5) solenoid pair.

  16. Effect of subsurface heterogeneity on free-product recovery from unconfined aquifers

    NASA Astrophysics Data System (ADS)

    Kaluarachchi, Jagath J.

    1996-03-01

    Free-product record system designs for light-hydrocarbon-contaminated sites were investigated to evaluate the effects of subsurface heterogeneity using a vertically integrated three-phase flow model. The input stochastic variable of the areal flow analysis was the log-intrinsic permeability and it was generated using the Turning Band method. The results of a series of hypothetical field-scale simulations showed that subsurface heterogeneity has a substantial effect on free-product recovery predictions. As the heterogeneity increased, the recoverable oil volume decreased and the residual trapped oil volume increased. As the subsurface anisotropy increased, these effects together with free- and total-oil contaminated areas were further enhanced. The use of multiple-stage water pumping was found to be insignificant compared to steady uniform pumping due to reduced recovery efficiency and increased residual oil volume. This observation was opposite to that produced under homogeneous scenarios. The effect of subsurface heterogeneity was enhanced at relatively low water pumping rates. The difference in results produced by homogeneous and heterogeneous simulations was substantial, indicating greater attention should be paid in modeling free-product recovery systems with appropriate subsurface heterogeneity.

  17. The effects of vortioxetine on cognitive dysfunction in patients with inadequate response to current antidepressants in major depressive disorder: A short-term, randomized, double-blind, exploratory study versus escitalopram.

    PubMed

    Vieta, Eduard; Sluth, Lasse B; Olsen, Christina K

    2018-02-01

    Major Depressive Disorder (MDD) is a heterogeneous disease characterized by emotional, physical and cognitive symptoms. This study explored the effects of vortioxetine versus escitalopram on outcomes of cognition, functioning and mood symptoms in depressed patients with inadequate response to current antidepressant treatment. In this parallel-group, active-comparator study, adult patients (18-65 years, N = 101) with MDD, with inadequate response to current antidepressant monotherapy, were randomized 1:1 to 8 weeks' double-blind treatment with flexible doses (10-20mg/day) of either vortioxetine or escitalopram. Primary and key secondary efficacy measures were the Digit Symbol Substitution Test (DSST), analyzed using a mixed model for repeated measurements, and the University of San Diego Performance-based Skills Assessment - Brief (UPSA-B), analyzed using analysis of covariance (last observation carried forward method). At week 8, DSST and UPSA-B performance had improved in both treatment groups, with no statistically significant treatment differences. Numerical improvements across measures of cognition, functioning and mood symptoms generally favored vortioxetine. Most adverse events were mild or moderate, with nausea being the most common adverse event. This was an exploratory study with small sample sizes implying limited statistical power. Although this explorative study did not meet primary endpoints, the results confirm vortioxetine in doses of 10-20mg/day as an efficacious and well-tolerated antidepressant switch treatment. The overall direction of numerical effect sizes across cognition endpoints support previous findings that vortioxetine specifically benefits cognitive function in MDD. Copyright © 2017 H Lundbeck A/S. Published by Elsevier B.V. All rights reserved.

  18. Ultrastructural instability of paired helical filaments from corticobasal degeneration as examined by scanning transmission electron microscopy.

    PubMed Central

    Ksiezak-Reding, H.; Tracz, E.; Yang, L. S.; Dickson, D. W.; Simon, M.; Wall, J. S.

    1996-01-01

    Paired helical filaments (PHFs) accumulate in the brains of subjects affected with Alzheimer's disease (AD) and certain other neurodegenerative disorders, including corticobasal degeneration (CBD). Electron microscope studies have shown that PHFs from CBD differ from those of AD by being wider and having a longer periodicity of the helical twist. Moreover, PHFs from CBD have been shown to be primarily composed of two rather than three highly phosphorylated polypeptides of tau (PHF-tau), with these polypeptides expressing no exons 3 and 10. To further explore the relationship between the heterogeneity of PHF-tau and the appearance of abnormal filaments, the ultrastructure and physical parameters such as mass per unit length and dimensions were compared in filaments from CBD and AD using high resolution scanning transmission electron microscopy (STEM). Filament-enriched fractions were isolated as Sarcosyl-insoluble pellets and for STEM studies, samples were freeze-dried without prior fixation or staining. Ultrastructurally, PHFs from CBD were shown to be a heterogeneous population as double- and single-stranded filaments could be identified based on their width and physical mass per unit length expressed in kilodaltons (kd) per nanometer (nm). Less abundant, double-stranded filaments had a maximal width of 29 nm and a mass per unit length of 133 kd/nm, whereas three times more abundant single-stranded filaments were 15 nm wide and bad a mass per unit length of 62 kd/nm. Double-stranded filaments also displayed a distinct axial region of less dense mass, which appeared to divide the PHFs into two protofilament-like strands. Furthermore, these filaments were frequently observed to physically separate along the long axis into two single strands or to break longitudinally. In contrast, PHFs from AD were ultrastructurally stable and uniform both in their width (22 nm) and physical mass per unit length (104 kd/nm). The ultrastructural features indicate that filaments of CBD and AD differ both in stability and packing of tau and that CBD filaments, composed of two distinct protofilaments, are more labile under STEM conditions. As fixed and stained filaments from CBD have been shown to be stable and uniform in size by conventional transmission electron microscopy, STEM studies may be particularly suitable for detecting instability of unstained and unfixed filaments. The results also suggest that molecular heterogeneity and/or post-translational modifications of tau may strongly influence the morphology and stability of abnormal filaments. Images Figure 1 Figure 2 Figure 3 PMID:8702002

  19. Quantifying, displaying and accounting for heterogeneity in the meta-analysis of RCTs using standard and generalised Q statistics

    PubMed Central

    2011-01-01

    Background Clinical researchers have often preferred to use a fixed effects model for the primary interpretation of a meta-analysis. Heterogeneity is usually assessed via the well known Q and I2 statistics, along with the random effects estimate they imply. In recent years, alternative methods for quantifying heterogeneity have been proposed, that are based on a 'generalised' Q statistic. Methods We review 18 IPD meta-analyses of RCTs into treatments for cancer, in order to quantify the amount of heterogeneity present and also to discuss practical methods for explaining heterogeneity. Results Differing results were obtained when the standard Q and I2 statistics were used to test for the presence of heterogeneity. The two meta-analyses with the largest amount of heterogeneity were investigated further, and on inspection the straightforward application of a random effects model was not deemed appropriate. Compared to the standard Q statistic, the generalised Q statistic provided a more accurate platform for estimating the amount of heterogeneity in the 18 meta-analyses. Conclusions Explaining heterogeneity via the pre-specification of trial subgroups, graphical diagnostic tools and sensitivity analyses produced a more desirable outcome than an automatic application of the random effects model. Generalised Q statistic methods for quantifying and adjusting for heterogeneity should be incorporated as standard into statistical software. Software is provided to help achieve this aim. PMID:21473747

  20. Alternative Measures of Between-Study Heterogeneity in Meta-Analysis: Reducing the Impact of Outlying Studies

    PubMed Central

    Lin, Lifeng; Chu, Haitao; Hodges, James S.

    2016-01-01

    Summary Meta-analysis has become a widely used tool to combine results from independent studies. The collected studies are homogeneous if they share a common underlying true effect size; otherwise, they are heterogeneous. A fixed-effect model is customarily used when the studies are deemed homogeneous, while a random-effects model is used for heterogeneous studies. Assessing heterogeneity in meta-analysis is critical for model selection and decision making. Ideally, if heterogeneity is present, it should permeate the entire collection of studies, instead of being limited to a small number of outlying studies. Outliers can have great impact on conventional measures of heterogeneity and the conclusions of a meta-analysis. However, no widely accepted guidelines exist for handling outliers. This article proposes several new heterogeneity measures. In the presence of outliers, the proposed measures are less affected than the conventional ones. The performance of the proposed and conventional heterogeneity measures are compared theoretically, by studying their asymptotic properties, and empirically, using simulations and case studies. PMID:27167143

  1. Effect of concentration boundary layers on passive solute flows in a system of two polymeric membranes positioned in vertical planes.

    PubMed

    Slezak, Andrzej; Jasik-Slezak, Jolanta; Dworecki, Kazimierz

    2003-01-01

    The results of studies of influence of concentration boundary layers on passive diffusive transport in a double-membrane osmo-diffusive cell, containing a series of two (Ml and M(r)) vertically positioned, flat, microporous and symmetric polymer membranes (Nephrophane and Cellulose IMP-1) are presented in this paper. The membranes separated three compartments (l, m, r) containing binary, heterogeneous and non-ionic solutions (aqueous solutions of glucose or ethanol) or ternary non-electrolyte solutions (glucose solutions in 0.75 mol.l-1 solution of ethanol or ethanol solutions in 0.1 mol.l-1 aqueous solution of glucose). Solution concentrations fulfilled the condition C(k)l > C(k)m > C(k)r. The intermembrane compartment (m) was an infinitesimal solution layer. The volume of the m compartment and the volumes of the external (l and r) compartments fulfilled the condition Vl = Vr approximately 170 Vm. The tests were performed for configurations A and B of a double-membrane osmo-diffusive cell. In configuration A, the solution was located behind the M(r) membrane, and water was placed behind the Ml membrane, while in configuration B this sequence was reversed. The results obtained during experiment were interpreted in the categories of convective instability, which increased the value of diffusive permeability coefficient of the system: concentration boundary layer/membrane/concentration boundary layer.

  2. Cardiovascular diseases in mega-countries: the challenges of the nutrition, physical activity and epidemiologic transitions, and the double burden of disease

    PubMed Central

    Barquera, Simon; Pedroza-Tobias, Andrea; Medina, Catalina

    2016-01-01

    Purpose of review There are today 11 mega-countries with more than 100 million inhabitants. Together these countries represent more than 60% of the world's population. All are facing noncommunicable chronic disease (NCD) epidemic where high cholesterol, obesity, diabetes, and cardiovascular diseases are becoming the main public health concerns. Most of these countries are facing the double burden of malnutrition where undernutrition and obesity coexist, increasing the complexity for policy design and implementation. The purpose of this study is to describe diverse sociodemographic characteristics of these countries and the challenges for prevention and control in the context of the nutrition transition. Recent findings Mega-countries are mostly low or middle-income and are facing important epidemiologic, nutrition, and physical activity transitions because of changes in food systems and unhealthy lifestyles. NCDs are responsible of two-thirds of the 57 million global deaths annually. Approximately, 80% of these are in low and middle-income countries. Only developed countries have been able to reduce mortality rates attributable to recognized risk factors for NCDs, in particular high cholesterol and blood pressure. Summary Mega-countries share common characteristics such as complex bureaucracies, internal ethnic, cultural and socioeconomic heterogeneity, and complexities to implement effective health promotion and education policies across population. Priorities for action must be identified and successful lessons and experiences should be carefully analyzed and replicated. PMID:27389629

  3. Person Heterogeneity of the BDI-II-C and Its Effects on Dimensionality and Construct Validity: Using Mixture Item Response Models

    ERIC Educational Resources Information Center

    Wu, Pei-Chen; Huang, Tsai-Wei

    2010-01-01

    This study was to apply the mixed Rasch model to investigate person heterogeneity of Beck Depression Inventory-II-Chinese version (BDI-II-C) and its effects on dimensionality and construct validity. Person heterogeneity was reflected by two latent classes that differ qualitatively. Additionally, person heterogeneity adversely affected the…

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

    PubMed

    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.

  5. Predictive uncertainty analysis of a saltwater intrusion model using null-space Monte Carlo

    USGS Publications Warehouse

    Herckenrath, Daan; Langevin, Christian D.; Doherty, John

    2011-01-01

    Because of the extensive computational burden and perhaps a lack of awareness of existing methods, rigorous uncertainty analyses are rarely conducted for variable-density flow and transport models. For this reason, a recently developed null-space Monte Carlo (NSMC) method for quantifying prediction uncertainty was tested for a synthetic saltwater intrusion model patterned after the Henry problem. Saltwater intrusion caused by a reduction in fresh groundwater discharge was simulated for 1000 randomly generated hydraulic conductivity distributions, representing a mildly heterogeneous aquifer. From these 1000 simulations, the hydraulic conductivity distribution giving rise to the most extreme case of saltwater intrusion was selected and was assumed to represent the "true" system. Head and salinity values from this true model were then extracted and used as observations for subsequent model calibration. Random noise was added to the observations to approximate realistic field conditions. The NSMC method was used to calculate 1000 calibration-constrained parameter fields. If the dimensionality of the solution space was set appropriately, the estimated uncertainty range from the NSMC analysis encompassed the truth. Several variants of the method were implemented to investigate their effect on the efficiency of the NSMC method. Reducing the dimensionality of the null-space for the processing of the random parameter sets did not result in any significant gains in efficiency and compromised the ability of the NSMC method to encompass the true prediction value. The addition of intrapilot point heterogeneity to the NSMC process was also tested. According to a variogram comparison, this provided the same scale of heterogeneity that was used to generate the truth. However, incorporation of intrapilot point variability did not make a noticeable difference to the uncertainty of the prediction. With this higher level of heterogeneity, however, the computational burden of generating calibration-constrained parameter fields approximately doubled. Predictive uncertainty variance computed through the NSMC method was compared with that computed through linear analysis. The results were in good agreement, with the NSMC method estimate showing a slightly smaller range of prediction uncertainty than was calculated by the linear method. Copyright 2011 by the American Geophysical Union.

  6. Habitat size modulates the influence of heterogeneity on species richness patterns in a model zooplankton community.

    PubMed

    Schuler, Matthew S; Chase, Jonathan M; Knight, Tiffany M

    2017-06-01

    Habitat heterogeneity is a primary mechanism influencing species richness. Despite the general expectation that increased heterogeneity should increase species richness, there is considerable variation in the observed relationship, including many studies that show negative effects of heterogeneity on species richness. One mechanism that can create such disparate results is the predicted trade-off between habitat area and heterogeneity, sometimes called the area-heterogeneity-trade-off (AHTO) hypothesis. The AHTO hypothesis predicts positive effects of heterogeneity on species richness in large habitats, but negative effects in small habitats. We examined the interplay between habitat size and habitat heterogeneity in experimental mesocosms that mimic freshwater ponds, and measured responses in a species-rich zooplankton community. We used the AHTO hypothesis and related mechanisms to make predictions about how heterogeneity would affect species richness and diversity in large compared to small habitats. We found that heterogeneity had a positive influence on species richness in large, but not small habitats, and that this likely resulted because habitat specialists were able to persist only when habitat size was sufficiently large, consistent with the predictions of the AHTO hypothesis. Our results emphasize the importance of considering context (e.g., habitat size in this case) when investigating the relative importance of ecological drivers of diversity, like heterogeneity. © 2017 by the Ecological Society of America.

  7. Modeling and analyzing malware propagation in social networks with heterogeneous infection rates

    NASA Astrophysics Data System (ADS)

    Jia, Peng; Liu, Jiayong; Fang, Yong; Liu, Liang; Liu, Luping

    2018-10-01

    With the rapid development of social networks, hackers begin to try to spread malware more widely by utilizing various kinds of social networks. Thus, studying malware epidemic dynamics in these networks is becoming a popular subject in the literature. Most of the previous works focus on the effects of factors, such as network topology and user behavior, on malware propagation. Some researchers try to analyze the heterogeneity of infection rates, but the common problem of their works is the factors they mentioned that could affect the heterogeneity are not comprehensive enough. In this paper, focusing on the effects of heterogeneous infection rates, we propose a novel model called HSID (heterogeneous-susceptible-infectious-dormant model) to characterize virus propagation in social networks, in which a connection factor is presented to evaluate the heterogeneous relationships between nodes, and a resistance factor is introduced to represent node's mutable resistant ability. We analyzed how key parameters in the two factors affect the heterogeneity and then performed simulations to explore the effects in three real-world social networks. The results indicate: heterogeneous relationship could lead to wider diffusion in directed network, and heterogeneous security awareness could lead to wider diffusion in both directed and undirected networks; heterogeneous relationship could restrain the outbreak of malware but heterogeneous initial security awareness would increase the probability; furthermore, the increasing resistibility along with infected times would lead to malware's disappearance in social networks.

  8. Effects of pore-scale dispersion, degree of heterogeneity, sampling size, and source volume on the concentration moments of conservative solutes in heterogeneous formations

    Treesearch

    Daniele Tonina; Alberto Bellin

    2008-01-01

    Pore-scale dispersion (PSD), aquifer heterogeneity, sampling volume, and source size influence solute concentrations of conservative tracers transported in heterogeneous porous formations. In this work, we developed a new set of analytical solutions for the concentration ensemble mean, variance, and coefficient of variation (CV), which consider the effects of all these...

  9. Effect of lithological heterogeneity of bitumen sandstones on SAGD reservoir development

    NASA Astrophysics Data System (ADS)

    Korolev, E. A.; Usmanov, S. A.; Nikolaev, D. S.; Gabdelvaliyeva, R. R.

    2018-05-01

    The article describes the heavy oil field developed by the SAGD method. While development planning all the heterogeneity of the reservoir is must be taken into account. The objective of this work is to identify the distribution of lithological heterogeneities and their influence on oil production. For this reason, the studies of core samples were conducted and the heterogeneity was identified. Then properties and approximate geometry of lithological objects were studied. Also the effect of the heterogeneity on the heat propagation and production of fluid were analyzed. In the end, recommendations were made for the study of such heterogeneities on other deposits with similar geology

  10. Nonlinear effects of locally heterogeneous hydraulic conductivity fields on regional stream-aquifer exchanges

    NASA Astrophysics Data System (ADS)

    Zhu, J.; Winter, C. L.; Wang, Z.

    2015-08-01

    Computational experiments are performed to evaluate the effects of locally heterogeneous conductivity fields on regional exchanges of water between stream and aquifer systems in the Middle Heihe River Basin (MHRB) of northwestern China. The effects are found to be nonlinear in the sense that simulated discharges from aquifers to streams are systematically lower than discharges produced by a base model parameterized with relatively coarse effective conductivity. A similar, but weaker, effect is observed for stream leakage. The study is organized around three hypotheses: (H1) small-scale spatial variations of conductivity significantly affect regional exchanges of water between streams and aquifers in river basins, (H2) aggregating small-scale heterogeneities into regional effective parameters systematically biases estimates of stream-aquifer exchanges, and (H3) the biases result from slow-paths in groundwater flow that emerge due to small-scale heterogeneities. The hypotheses are evaluated by comparing stream-aquifer fluxes produced by the base model to fluxes simulated using realizations of the MHRB characterized by local (grid-scale) heterogeneity. Levels of local heterogeneity are manipulated as control variables by adjusting coefficients of variation. All models are implemented using the MODFLOW simulation environment, and the PEST tool is used to calibrate effective conductivities defined over 16 zones within the MHRB. The effective parameters are also used as expected values to develop log-normally distributed conductivity (K) fields on local grid scales. Stream-aquifer exchanges are simulated with K fields at both scales and then compared. Results show that the effects of small-scale heterogeneities significantly influence exchanges with simulations based on local-scale heterogeneities always producing discharges that are less than those produced by the base model. Although aquifer heterogeneities are uncorrelated at local scales, they appear to induce coherent slow-paths in groundwater fluxes that in turn reduce aquifer-stream exchanges. Since surface water-groundwater exchanges are critical hydrologic processes in basin-scale water budgets, these results also have implications for water resources management.

  11. Cancer: fundamentals behind pH targeting and the double-edged approach

    PubMed Central

    Koltai, Tomas

    2016-01-01

    The highly regulated pH of cells and the less-regulated pH of the surrounding extracellular matrix (ECM) is the result of a delicate balance between metabolic processes and proton production, proton transportation, chemical buffering, and vascular removal of waste products. Malignant cells show a pronounced increase in metabolic processes where the 10- to 15-fold rise in glucose consumption is only the tip of the iceberg. Aerobic glycolysis (Warburg effect) is one of the hallmarks of cancer metabolism that implies excessive production of protons, which if stayed inside the cells would result in fatal intracellular acidosis (maintaining a strict acid–base balance is essential for the survival of eukaryotic cells). Malignant cells solve this problem by increasing mechanisms of proton transportation which expel the excess acidity. This allows cancer cells to keep a normal intracellular pH, or even overshooting this mechanism permits a slightly alkaline intracellular tendency. The proton excess expelled from malignant cells accumulates in the ECM, where chronic hypoxia and relative lack of enough blood vessels impede adequate proton clearance, thus creating an acidic microenvironment. This microenvironment is quite heterogeneous due to the tumor’s metabolic heterogeneity and variable degrees of hypoxia inside the tumor mass. The acidic environment (plus other necessary cellular modifications) stimulates migration and invasion and finally intravasation of malignant cells which eventually may result in metastasis. Targeting tumor pH may go in two directions: 1) increasing extracellular pH which should result in less migration, invasion, and metastasis; and 2) decreasing intracellular pH which may result in acidic stress and apoptosis. Both objectives seem achievable at the present state of the art with repurposed drugs. This hypothesis analyzes the altered pH of tumors and its implications for progression and metastasis and also possible repurposed drug combinations targeting this vulnerable side of cancer development. It also analyzes the double-edged approach, which consists in pharmacologically increasing intracellular proton production and simultaneously decreasing proton extrusion creating intracellular acidity, acid stress, and eventual apoptosis. PMID:27799782

  12. Balloon enteroscopy versus spiral enteroscopy for small-bowel disorders: a systematic review and meta-analysis.

    PubMed

    Baniya, Ramkaji; Upadhaya, Sunil; Subedi, Subash Chandra; Khan, Jahangir; Sharma, Prabin; Mohammed, Tabrez Shaik; Bachuwa, Ghassan; Jamil, Laith H

    2017-12-01

    Two novel enteroscopic procedures, balloon enteroscopy and spiral enteroscopy, have revolutionized the diagnostic and therapeutic approach to small-bowel disorders. These disorders that historically required surgical interventions are now investigated and managed nonsurgically. Only a few weakly powered studies have compared the outcomes of spiral enteroscopy and balloon enteroscopy. We conducted a systematic review and meta-analysis to compare the efficacy and safety of these 2 procedures. PubMed, Cochrane Library, Scopus, and clinicaltrials.gov databases were searched for all studies published up to January 12, 2017 comparing the efficacy and safety of balloon enteroscopy (single or double) and spiral enteroscopy. Primary outcomes of interest were diagnostic and therapeutic success rates. Other outcomes included procedure length, depth of maximal insertion (DMI), rate of complete enteroscopy, and adverse events. We calculated Odds ratios (ORs) for categorical variables and mean difference (MD) for continuous variables. The Mantel-Haenszel method was used to analyze the data. Fixed and random effect models were used for <50% heterogeneity and >50% heterogeneity, respectively. Eight studies met the inclusion criteria for this meta-analysis. A total of 615 procedures were analyzed, which included 394 balloon enteroscopy and 221 spiral enteroscopy procedures. There were no significant differences in diagnostic and therapeutic success rates (OR, 1.27; 95% confidence interval [CI], .86-1.88; P = .22; and OR, 1.23; 95% CI, .82-1.84; P = .32, respectively) between the 2 procedures. Similarly, DMI was not significantly different between the 2 groups (MD, 26.29; 95% CI, 20.92-73.49; P = .28). However, the procedure time was significantly shorter for the spiral enteroscopy group compared with the balloon enteroscopy group (MD, 11.26; 95% CI, 2.72-19.79; P = .010). A subgroup analysis comparing double balloon enteroscopy with spiral enteroscopy yielded similar results. Both procedures achieved similar diagnostic and therapeutic outcomes and with similar depth of insertion. Spiral enteroscopy has the benefit of shorter procedural time. Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

  13. Effects of Spatial Patch Arrangement and Scale of Covarying Resources on Growth and Intraspecific Competition of a Clonal Plant

    PubMed Central

    Wang, Yong-Jian; Shi, Xue-Ping; Meng, Xue-Feng; Wu, Xiao-Jing; Luo, Fang-Li; Yu, Fei-Hai

    2016-01-01

    Spatial heterogeneity in two co-variable resources such as light and water availability is common and can affect the growth of clonal plants. Several studies have tested effects of spatial heterogeneity in the supply of a single resource on competitive interactions of plants, but none has examined those of heterogeneous distribution of two co-variable resources. In a greenhouse experiment, we grew one (without intraspecific competition) or nine isolated ramets (with competition) of a rhizomatous herb Iris japonica under a homogeneous environment and four heterogeneous environments differing in patch arrangement (reciprocal and parallel patchiness of light and soil water) and patch scale (large and small patches of light and water). Intraspecific competition significantly decreased the growth of I. japonica, but at the whole container level there were no significant interaction effects of competition by spatial heterogeneity or significant effect of heterogeneity on competitive intensity. Irrespective of competition, the growth of I. japonica in the high and the low water patches did not differ significantly in the homogeneous treatments, but it was significantly larger in the high than in the low water patches in the heterogeneous treatments with large patches. For the heterogeneous treatments with small patches, the growth of I. japonica was significantly larger in the high than in the low water patches in the presence of competition, but such an effect was not significant in the absence of competition. Furthermore, patch arrangement and patch scale significantly affected competitive intensity at the patch level. Therefore, spatial heterogeneity in light and water supply can alter intraspecific competition at the patch level and such effects depend on patch arrangement and patch scale. PMID:27375630

  14. Effects of Spatial Patch Arrangement and Scale of Covarying Resources on Growth and Intraspecific Competition of a Clonal Plant.

    PubMed

    Wang, Yong-Jian; Shi, Xue-Ping; Meng, Xue-Feng; Wu, Xiao-Jing; Luo, Fang-Li; Yu, Fei-Hai

    2016-01-01

    Spatial heterogeneity in two co-variable resources such as light and water availability is common and can affect the growth of clonal plants. Several studies have tested effects of spatial heterogeneity in the supply of a single resource on competitive interactions of plants, but none has examined those of heterogeneous distribution of two co-variable resources. In a greenhouse experiment, we grew one (without intraspecific competition) or nine isolated ramets (with competition) of a rhizomatous herb Iris japonica under a homogeneous environment and four heterogeneous environments differing in patch arrangement (reciprocal and parallel patchiness of light and soil water) and patch scale (large and small patches of light and water). Intraspecific competition significantly decreased the growth of I. japonica, but at the whole container level there were no significant interaction effects of competition by spatial heterogeneity or significant effect of heterogeneity on competitive intensity. Irrespective of competition, the growth of I. japonica in the high and the low water patches did not differ significantly in the homogeneous treatments, but it was significantly larger in the high than in the low water patches in the heterogeneous treatments with large patches. For the heterogeneous treatments with small patches, the growth of I. japonica was significantly larger in the high than in the low water patches in the presence of competition, but such an effect was not significant in the absence of competition. Furthermore, patch arrangement and patch scale significantly affected competitive intensity at the patch level. Therefore, spatial heterogeneity in light and water supply can alter intraspecific competition at the patch level and such effects depend on patch arrangement and patch scale.

  15. Analysis of dose-incidence relationships for marrow failure in different species, in terms of radiosensitivity of tissue-rescuing units

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hendry, J.H.; Roberts, S.A.

    1990-05-01

    The analysis of 68 published sets of dose-incidence data for marrow failure in different species, using a double-log mortality function, indicates: (a) There is more heterogeneity, i.e. greater sums-of-squares per degree of freedom, within the data sets for mouse than for larger species (monkey, dog, sheep, goat, pig). (b) For mice the curves for acute doses are characterized by a D0 of about 100 cGy for tissue-rescuing units (or target cells), which are depleted at most to about 3 x 10(-4) at LD50. (c) Larger species are much less tolerant to target-cell depletion, the corresponding level being consistently in themore » range of 10(-2)-10(-3) at LD50. Also, the D0 is often lower (approximately 55 cGy), which is compatible in the dog with such a value for hemopoietic progenitor cells. (d) With larger species there is an unexpected reduction in heterogeneity when the dose rate is lower, which gives a D0 lower than expected and a higher extrapolate. It is concluded that the position and slope of the dose-incidence curves are compatible with interpretations based primarily on target-cell number and survival characteristics, modified by additional heterogeneity factors.« less

  16. Spiking network simulation code for petascale computers.

    PubMed

    Kunkel, Susanne; Schmidt, Maximilian; Eppler, Jochen M; Plesser, Hans E; Masumoto, Gen; Igarashi, Jun; Ishii, Shin; Fukai, Tomoki; Morrison, Abigail; Diesmann, Markus; Helias, Moritz

    2014-01-01

    Brain-scale networks exhibit a breathtaking heterogeneity in the dynamical properties and parameters of their constituents. At cellular resolution, the entities of theory are neurons and synapses and over the past decade researchers have learned to manage the heterogeneity of neurons and synapses with efficient data structures. Already early parallel simulation codes stored synapses in a distributed fashion such that a synapse solely consumes memory on the compute node harboring the target neuron. As petaflop computers with some 100,000 nodes become increasingly available for neuroscience, new challenges arise for neuronal network simulation software: Each neuron contacts on the order of 10,000 other neurons and thus has targets only on a fraction of all compute nodes; furthermore, for any given source neuron, at most a single synapse is typically created on any compute node. From the viewpoint of an individual compute node, the heterogeneity in the synaptic target lists thus collapses along two dimensions: the dimension of the types of synapses and the dimension of the number of synapses of a given type. Here we present a data structure taking advantage of this double collapse using metaprogramming techniques. After introducing the relevant scaling scenario for brain-scale simulations, we quantitatively discuss the performance on two supercomputers. We show that the novel architecture scales to the largest petascale supercomputers available today.

  17. Spiking network simulation code for petascale computers

    PubMed Central

    Kunkel, Susanne; Schmidt, Maximilian; Eppler, Jochen M.; Plesser, Hans E.; Masumoto, Gen; Igarashi, Jun; Ishii, Shin; Fukai, Tomoki; Morrison, Abigail; Diesmann, Markus; Helias, Moritz

    2014-01-01

    Brain-scale networks exhibit a breathtaking heterogeneity in the dynamical properties and parameters of their constituents. At cellular resolution, the entities of theory are neurons and synapses and over the past decade researchers have learned to manage the heterogeneity of neurons and synapses with efficient data structures. Already early parallel simulation codes stored synapses in a distributed fashion such that a synapse solely consumes memory on the compute node harboring the target neuron. As petaflop computers with some 100,000 nodes become increasingly available for neuroscience, new challenges arise for neuronal network simulation software: Each neuron contacts on the order of 10,000 other neurons and thus has targets only on a fraction of all compute nodes; furthermore, for any given source neuron, at most a single synapse is typically created on any compute node. From the viewpoint of an individual compute node, the heterogeneity in the synaptic target lists thus collapses along two dimensions: the dimension of the types of synapses and the dimension of the number of synapses of a given type. Here we present a data structure taking advantage of this double collapse using metaprogramming techniques. After introducing the relevant scaling scenario for brain-scale simulations, we quantitatively discuss the performance on two supercomputers. We show that the novel architecture scales to the largest petascale supercomputers available today. PMID:25346682

  18. Genetic control of residual variance of yearling weight in Nellore beef cattle.

    PubMed

    Iung, L H S; Neves, H H R; Mulder, H A; Carvalheiro, R

    2017-04-01

    There is evidence for genetic variability in residual variance of livestock traits, which offers the potential for selection for increased uniformity of production. Different statistical approaches have been employed to study this topic; however, little is known about the concordance between them. The aim of our study was to investigate the genetic heterogeneity of residual variance on yearling weight (YW; 291.15 ± 46.67) in a Nellore beef cattle population; to compare the results of the statistical approaches, the two-step approach and the double hierarchical generalized linear model (DHGLM); and to evaluate the effectiveness of power transformation to accommodate scale differences. The comparison was based on genetic parameters, accuracy of EBV for residual variance, and cross-validation to assess predictive performance of both approaches. A total of 194,628 yearling weight records from 625 sires were used in the analysis. The results supported the hypothesis of genetic heterogeneity of residual variance on YW in Nellore beef cattle and the opportunity of selection, measured through the genetic coefficient of variation of residual variance (0.10 to 0.12 for the two-step approach and 0.17 for DHGLM, using an untransformed data set). However, low estimates of genetic variance associated with positive genetic correlations between mean and residual variance (about 0.20 for two-step and 0.76 for DHGLM for an untransformed data set) limit the genetic response to selection for uniformity of production while simultaneously increasing YW itself. Moreover, large sire families are needed to obtain accurate estimates of genetic merit for residual variance, as indicated by the low heritability estimates (<0.007). Box-Cox transformation was able to decrease the dependence of the variance on the mean and decreased the estimates of genetic parameters for residual variance. The transformation reduced but did not eliminate all the genetic heterogeneity of residual variance, highlighting its presence beyond the scale effect. The DHGLM showed higher predictive ability of EBV for residual variance and therefore should be preferred over the two-step approach.

  19. The incidence of post-traumatic stress disorder among survivors after earthquakes:a systematic review and meta-analysis.

    PubMed

    Dai, Wenjie; Chen, Long; Lai, Zhiwei; Li, Yan; Wang, Jieru; Liu, Aizhong

    2016-06-07

    Post-traumatic stress disorder (PTSD) is a common psychological disorder caused by unusual threats or catastrophic events. Little is known about the combined incidence of PTSD after earthquakes. This study aimed at evaluating the combined incidence of PTSD among survivors after earthquakes using systematic review and meta-analysis. The electronic databases of PubMed, Embase, Web of Science and PsycARTICLES were searched for relevant articles in this study. Loney criteria were used to assess the quality of eligible articles. The combined incidence of PTSD was estimated by using the Freeman-Tukey double arcsine transformation method. Subgroup analyses were conducted using the following variables: the time of PTSD assessment, gender, educational level, marital status, damage to one's house, bereavement, injury of body and witnessing death. Forty-six eligible articles containing 76,101 earthquake survivors met the inclusion criteria, of which 17,706 were diagnosed as having PTSD. Using a random effects model, the combined incidence of PTSD after earthquakes was 23.66 %. Moreover, the combined incidence of PTSD among survivors who were diagnosed at not more than 9 months after earthquake was 28.76 %, while for survivors who were diagnosed at over nine months after earthquake the combined incidence was 19.48 %. A high degree of heterogeneity (I(2) = 99.5 %, p<0.001) was observed in the results, with incidence ranging from 1.20 to 82.64 %. The subgroup analyses showed that the incidence of PTSD after earthquake varied significantly across studies in relation to the time of PTSD assessment, gender, educational level, damage to one's house, bereavement, injury of body and witnessing death. However, stratified analyses could not entirely explain the heterogeneity in the results. Given the high heterogeneity observed in this study, future studies should aim at exploring more possible risk factors for PTSD after earthquakes, especially genetic factors. In spite of that, the results of this study suggest that nearly 1 in 4 earthquake survivors are diagnosed as having PTSD. Therefore, the local government should plan effective psychological interventions for earthquake survivors.

  20. Geometric heterogeneity of the lattice and its effect on the kinetics phase transitions of surface reactions

    NASA Astrophysics Data System (ADS)

    Cortés, Joaquín.; Valencia, Eliana

    1999-04-01

    Two novel phenomena are discussed in this paper. The first one refers to the effect of the catalyst's surface heterogeneity on the smoothing of the first-order transition observed in the ( A+ B2) reaction (ZGB model). The second effect corresponds to obtaining information on the surface heterogeneity from the shape of the transition curve. Two types of heterogeneity were considered: the structure obtained by the random blocking of reactive sites, and the existence of a distribution in independent strips or terraces on the catalyst's surface.

  1. The effects of habitat connectivity and regional heterogeneity on artificial pond metacommunities.

    PubMed

    Pedruski, Michael T; Arnott, Shelley E

    2011-05-01

    Habitat connectivity and regional heterogeneity represent two factors likely to affect biodiversity across different spatial scales. We performed a 3 × 2 factorial design experiment to investigate the effects of connectivity, heterogeneity, and their interaction on artificial pond communities of freshwater invertebrates at the local (α), among-community (β), and regional (γ) scales. Despite expectations that the effects of connectivity would depend on levels of regional heterogeneity, no significant interactions were found for any diversity index investigated at any spatial scale. While observed responses of biodiversity to connectivity and heterogeneity depended to some extent on the diversity index and spatial partitioning formula used, the general pattern shows that these factors largely act at the β scale, as opposed to the α or γ scales. We conclude that the major role of connectivity in aquatic invertebrate communities is to act as a homogenizing force with relatively little effect on diversity at the α or γ levels. Conversely, heterogeneity acts as a force maintaining differences between communities.

  2. Experimental protocol for manipulating plant-induced soil heterogeneity.

    PubMed

    Brandt, Angela J; del Pino, Gaston A; Burns, Jean H

    2014-03-13

    Coexistence theory has often treated environmental heterogeneity as being independent of the community composition; however biotic feedbacks such as plant-soil feedbacks (PSF) have large effects on plant performance, and create environmental heterogeneity that depends on the community composition. Understanding the importance of PSF for plant community assembly necessitates understanding of the role of heterogeneity in PSF, in addition to mean PSF effects. Here, we describe a protocol for manipulating plant-induced soil heterogeneity. Two example experiments are presented: (1) a field experiment with a 6-patch grid of soils to measure plant population responses and (2) a greenhouse experiment with 2-patch soils to measure individual plant responses. Soils can be collected from the zone of root influence (soils from the rhizosphere and directly adjacent to the rhizosphere) of plants in the field from conspecific and heterospecific plant species. Replicate collections are used to avoid pseudoreplicating soil samples. These soils are then placed into separate patches for heterogeneous treatments or mixed for a homogenized treatment. Care should be taken to ensure that heterogeneous and homogenized treatments experience the same degree of soil disturbance. Plants can then be placed in these soil treatments to determine the effect of plant-induced soil heterogeneity on plant performance. We demonstrate that plant-induced heterogeneity results in different outcomes than predicted by traditional coexistence models, perhaps because of the dynamic nature of these feedbacks. Theory that incorporates environmental heterogeneity influenced by the assembling community and additional empirical work is needed to determine when heterogeneity intrinsic to the assembling community will result in different assembly outcomes compared with heterogeneity extrinsic to the community composition.

  3. Breaking the limits of structural and mechanical imaging of the heterogeneous structure of coal macerals

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Collins, L.; Tselev, A.; Jesse, S.

    The correlation between local mechanical (elasto-plastic) and structural (composition) properties of coal presents significant fundamental and practical interest for coal processing and the development of rheological models of coal to coke transformations and for advancing novel approaches. Here, we explore the relationship between the local structural, chemical composition and mechanical properties of coal using a combination of confocal micro-Raman imaging and band excitation atomic force acoustic microscopy (BE-AFAM) for a bituminous coal. This allows high resolution imaging (10s of nm) of mechanical properties of the heterogeneous (banded) architecture of coal and correlating them to the optical gap, average crystallite size,more » the bond-bending disorder of sp2 aromatic double bonds and the defect density. This methodology hence allows the structural and mechanical properties of coal components (lithotypes, microlithotypes, and macerals) to be understood, and related to local chemical structure, potentially allowing for knowledge-based modelling and optimization of coal utilization processes.« less

  4. Modeling Strain Rate Effect of Heterogeneous Materials Using SPH Method

    NASA Astrophysics Data System (ADS)

    Ma, G. W.; Wang, X. J.; Li, Q. M.

    2010-11-01

    The strain rate effect on the dynamic compressive failure of heterogeneous material based on the smoothed particle hydrodynamics (SPH) method is studied. The SPH method employs a rate-insensitive elasto-plastic damage model incorporated with a Weibull distribution law to reflect the mechanical behavior of heterogeneous rock-like materials. A series of simulations are performed for heterogeneous specimens by applying axial velocity conditions, which induce different strain-rate loadings to the specimen. A detailed failure process of the specimens in terms of microscopic crack-activities and the macro-mechanical response are discussed. Failure mechanisms between the low and high strain rate cases are compared. The result shows that the strain-rate effects on the rock strength are mainly caused by the changing internal pressure due to the inertial effects as well as the material heterogeneity. It also demonstrates that the inertial effect becomes significant only when the induced strain rate exceeds a threshold, below which, the dynamic strength enhancement can be explained due to the heterogeneities in the material. It also shows that the dynamic strength is affected more significantly for a relatively more heterogeneous specimen, which coincides with the experimental results showing that the poor quality specimen had a relatively larger increase in the dynamic strength.

  5. Bayesian random-effect model for predicting outcome fraught with heterogeneity--an illustration with episodes of 44 patients with intractable epilepsy.

    PubMed

    Yen, A M-F; Liou, H-H; Lin, H-L; Chen, T H-H

    2006-01-01

    The study aimed to develop a predictive model to deal with data fraught with heterogeneity that cannot be explained by sampling variation or measured covariates. The random-effect Poisson regression model was first proposed to deal with over-dispersion for data fraught with heterogeneity after making allowance for measured covariates. Bayesian acyclic graphic model in conjunction with Markov Chain Monte Carlo (MCMC) technique was then applied to estimate the parameters of both relevant covariates and random effect. Predictive distribution was then generated to compare the predicted with the observed for the Bayesian model with and without random effect. Data from repeated measurement of episodes among 44 patients with intractable epilepsy were used as an illustration. The application of Poisson regression without taking heterogeneity into account to epilepsy data yielded a large value of heterogeneity (heterogeneity factor = 17.90, deviance = 1485, degree of freedom (df) = 83). After taking the random effect into account, the value of heterogeneity factor was greatly reduced (heterogeneity factor = 0.52, deviance = 42.5, df = 81). The Pearson chi2 for the comparison between the expected seizure frequencies and the observed ones at two and three months of the model with and without random effect were 34.27 (p = 1.00) and 1799.90 (p < 0.0001), respectively. The Bayesian acyclic model using the MCMC method was demonstrated to have great potential for disease prediction while data show over-dispersion attributed either to correlated property or to subject-to-subject variability.

  6. Solute transport with time-variable flow paths during upward and downward flux in a heterogeneous unsaturated porous medium

    NASA Astrophysics Data System (ADS)

    Cremer, Clemens; Neuweiler, Insa; Bechtold, Michel; Vanderborght, Jan

    2014-05-01

    To acquire knowledge of solute transport through the unsaturated zone in the shallow subsurface is decisive to assess groundwater quality, nutrient cycling or to plan remediation strategies. The shallow subsurface is characterized by structural heterogeneity and strongly influenced by atmospheric conditions. This leads to changing flow directions, strong temporal changes in saturation and heterogeneous water fluxes during infiltration and evaporation events. Recent studies (e.g. Lehmann and Or, 2009; Bechtold et al.,2011) demonstrated the importance of lateral flow and solute transport during evaporation conditions (upward flux). The heterogeneous structure in these studies was constructed using two types of sand with strong material contrasts and arranged in parallel with a vertical orientation. Lateral transport and redistribution of solute from coarse to fine media was observed deeper in the soil column and from fine to coarse close to the soil surface. However, if boundary conditions are reversed due to precipitation, the flow field is not necessarily reversed in the same manner, resulting in entirely different transport patterns for downward and upward flow. Therefore, considering net-flow rates alone is misleading when describing transport under those conditions. In this contribution we analyze transport of a solute in the shallow subsurface to assess effects resulting from the temporal change of heterogeneous soil structures due to dynamic flow conditions. Two-dimensional numerical simulations of unsaturated flow and transport are conducted using a coupled finite volume and random walk particle tracking algorithm to quantify solute transport and leaching rates. Following previous studies (Lehmann and Or, 2009; Bechtold et al., 2011), the chosen domain is composed of two materials, coarse and fine sand, arranged in parallel with a vertical orientation. Hence, one sharp interface of strong material heterogeneity is induced. During evaporation both sands are assumed to stay under liquid-flow dominated evaporation conditions ("stage 1"). Simulations considering dynamic (infiltration-evaporation) and steady (solely infiltration) boundary conditions are carried out. The influence of dynamic boundary conditions (intensity and duration of precipitation and evaporation events) is examined in a multitude of simulations. If flow rates smaller than the saturated hydraulic conductivity of both materials are chosen to be applied as boundary condition, simulation results indicate that the flow field within the domain is exactly reversed. However, if applied flow rates exceed the saturated hydraulic conductivity of one material, the flow field is not just reversed, but different flow paths during downward and upward flow are observed. Results show the tendency of faster solute leaching under dynamic boundary conditions compared to steady infiltration conditions with the same net-infiltration rate. We use a double domain transport method as an upscaled model to reproduce vertically averaged concentration profiles with net flux only and compare the model parameters for information about flow dynamics and soil heterogeneity.

  7. Catalase-Modulated Heterogeneous Fenton Reaction for Selective Cancer Cell Eradication: SnFe2O4 Nanocrystals as an Effective Reagent for Treating Lung Cancer Cells.

    PubMed

    Lee, Kuan-Ting; Lu, Yu-Jen; Mi, Fwu-Long; Burnouf, Thierry; Wei, Yi-Ting; Chiu, Shao-Chieh; Chuang, Er-Yuan; Lu, Shih-Yuan

    2017-01-18

    Heterogeneous Fenton reactions have been proven to be an effective and promising selective cancer cell treatment method. The key working mechanism for this method to achieve the critical therapeutic selectivity however remains unclear. In this study, we proposed and demonstrated for the first time the critical role played by catalase in realizing the therapeutic selectivity for the heterogeneous Fenton reaction-driven cancer cell treatment. The heterogeneous Fenton reaction, with the lattice ferric ions of the solid catalyst capable of converting H 2 O 2 to highly reactive hydroxyl radicals, can effectively eradicate cancer cells. In this study, SnFe 2 O 4 nanocrystals, a recently discovered outstanding heterogeneous Fenton catalyst, were applied for selective killing of lung cancer cells. The SnFe 2 O 4 nanocrystals, internalized into the cancer cells, can effectively convert endogenous H 2 O 2 into highly reactive hydroxyl radicals to invoke an intensive cytotoxic effect on the cancer cells. On the other hand, catalase, present at a significantly higher concentration in normal cells than in cancer cells, remarkably can impede the apoptotic cell death induced by the internalized SnFe 2 O 4 nanocrystals. According to the results obtained from the in vitro cytotoxicity study, the relevant oxidative attacks were effectively suppressed by the presence of normal physiological levels of catalase. The SnFe 2 O 4 nanocrystals were thus proved to effect apoptotic cancer cell death through the heterogeneous Fenton reaction and were benign to cells possessing normal physiological levels of catalase. The catalase modulation of the involved heterogeneous Fenton reaction plays the key role in achieving selective cancer cell eradication for the heterogeneous Fenton reaction-driven cancer cell treatment.

  8. HiRISE observations of new impact craters exposing Martian ground ice

    USGS Publications Warehouse

    Dundas, Colin M.; Byrne, Shane; McEwen, Alfred S.; Mellon, Michael T.; Kennedy, Megan R.; Daubar, Ingrid J.; Saper, Lee

    2014-01-01

    Twenty small new impact craters or clusters have been observed to excavate bright material inferred to be ice at mid and high latitudes on Mars. In the northern hemisphere, the craters are widely distributed geographically and occur at latitudes as low as 39°N. Stability modeling suggests that this ice distribution requires a long-term average atmospheric water vapor content around 25 precipitable microns, more than double the present value, which is consistent with the expected effect of recent orbital variations. Alternatively, near-surface humidity could be higher than expected for current column abundances if water vapor is not well-mixed with atmospheric CO2, or the vapor pressure at the ice table could be lower due to salts. Ice in and around the craters remains visibly bright for months to years, indicating that it is clean ice rather than ice-cemented regolith. Although some clean ice may be produced by the impact process, it is likely that the original ground ice was excess ice (exceeding dry soil pore space) in many cases. Observations of the craters suggest small-scale heterogeneities in this excess ice. The origin of such ice is uncertain. Ice lens formation by migration of thin films of liquid is most consistent with local heterogeneity in ice content and common surface boulders, but in some cases nearby thermokarst landforms suggest large amounts of excess ice that may be best explained by a degraded ice sheet.

  9. Genetic heterogeneity underlying variation in a locally adaptive clinal trait in Pinus sylvestris revealed by a Bayesian multipopulation analysis.

    PubMed

    Kujala, S T; Knürr, T; Kärkkäinen, K; Neale, D B; Sillanpää, M J; Savolainen, O

    2017-05-01

    Local adaptation is a common feature of plant and animal populations. Adaptive phenotypic traits are genetically differentiated along environmental gradients, but the genetic basis of such adaptation is still poorly known. Genetic association studies of local adaptation combine data over populations. Correcting for population structure in these studies can be problematic since both selection and neutral demographic events can create similar allele frequency differences between populations. Correcting for demography with traditional methods may lead to eliminating some true associations. We developed a new Bayesian approach for identifying the loci underlying an adaptive trait in a multipopulation situation in the presence of possible double confounding due to population stratification and adaptation. With this method we studied the genetic basis of timing of bud set, a surrogate trait for timing of yearly growth cessation that confers local adaptation to the populations of Scots pine (Pinus sylvestris). Population means of timing of bud set were highly correlated with latitude. Most effects at individual loci were small. Interestingly, we found genetic heterogeneity (that is, different sets of loci associated with the trait) between the northern and central European parts of the cline. We also found indications of stronger stabilizing selection toward the northern part of the range. The harsh northern conditions may impose greater selective pressure on timing of growth cessation, and the relative importance of different environmental cues used for tracking the seasons might differ depending on latitude of origin.

  10. Evaluation of Clove Oil, Icaridin, and Transfluthrin for Spatial Repellent Effects in Three Tests Systems Against the Aedes aegypti (Diptera: Culicidae).

    PubMed

    Nentwig, G; Frohberger, S; Sonneck, R

    2017-01-01

    One essential oil (clove oil), one skin repellent (icaridin), and one insecticide (transfluthrin) were tested for spatial repellent effects against non-blood-fed female Aedes aegypti (L.) mosquitoes. The compounds were tested in acetone dilution series using a Y-olfactometer, a double cage system, and a double room system. All compounds exhibited spatial repellent effects at certain concentrations. Clove oil required relative high dosages to cause high effects (Y-olfactometer 6 mg, double cage 60 mg, and double room 1,200 mg). The dosages to achieve comparable results with icaridin were lower (Y-olfactometer and double cage 1 mg, and double room 150 mg). For transfluthrin, the equivalent dosages were lower again (Y-olfactometer 0.003 mg, double cage 0.03 mg, and double room 0.1 mg). Furthermore, these results reveal a correlation between the size of the test system and the effective dosage. Averaged for the three compounds, the quantity for the double room was 21-fold higher than for the double cage, which required again a 9-fold higher dosage than the Y-olfactometer. An establishment of a screening cascade is discussed starting with the Y-olfactometer (high throughput rate), followed by the double cage system and ending with the double room system as the most nearest to practical conditions. Furthermore, the testing of existing repellent products to validate the double room test, the role of sublethal dosages concerning insecticides including possible upcoming of resistance after exposure, the delayed action and impact on blood feeding and oviposition are exemplified. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. CryoEM and image sorting for flexible protein/DNA complexes.

    PubMed

    Villarreal, Seth A; Stewart, Phoebe L

    2014-07-01

    Intrinsically disordered regions of proteins and conformational flexibility within complexes can be critical for biological function. However, disorder, flexibility, and heterogeneity often hinder structural analyses. CryoEM and single particle image processing techniques offer the possibility of imaging samples with significant flexibility. Division of particle images into more homogenous subsets after data acquisition can help compensate for heterogeneity within the sample. We present the utility of an eigenimage sorting analysis for examining two protein/DNA complexes with significant conformational flexibility and heterogeneity. These complexes are integral to the non-homologous end joining pathway, and are involved in the repair of double strand breaks of DNA. Both complexes include the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and biotinylated DNA with bound streptavidin, with one complex containing the Ku heterodimer. Initial 3D reconstructions of the two DNA-PKcs complexes resembled a cryoEM structure of uncomplexed DNA-PKcs without additional density clearly attributable to the remaining components. Application of eigenimage sorting allowed division of the DNA-PKcs complex datasets into more homogeneous subsets. This led to visualization of density near the base of the DNA-PKcs that can be attributed to DNA, streptavidin, and Ku. However, comparison of projections of the subset structures with 2D class averages indicated that a significant level of heterogeneity remained within each subset. In summary, image sorting methods allowed visualization of extra density near the base of DNA-PKcs, suggesting that DNA binds in the vicinity of the base of the molecule and potentially to a flexible region of DNA-PKcs. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. The heterogeneity of antipsychotic response in the treatment of schizophrenia

    PubMed Central

    Case, M.; Stauffer, V. L.; Ascher-Svanum, H.; Conley, R.; Kapur, S.; Kane, J. M.; Kollack-Walker, S.; Jacob, J.; Kinon, B. J.

    2011-01-01

    Background Schizophrenia is a heterogeneous disorder in terms of patient response to antipsychotic treatment. Understanding the heterogeneity of treatment response may help to guide treatment decisions. This study was undertaken to capture inherent patterns of response to antipsychotic treatment in patients with schizophrenia, characterize the subgroups of patients with similar courses of response, and examine illness characteristics at baseline as possible predictors of response. Method Growth mixture modeling (GMM) was applied to data from a randomized, double-blind, 12-week study of 628 patients with schizophrenia or schizo-affective disorder treated with risperidone or olanzapine. Results Four distinct response trajectories based on Positive and Negative Syndrome Scale (PANSS) total score over 12 weeks were identified: Class 1 (420 patients, 80.6%) with moderate average baseline PANSS total score showing gradual symptom improvement; Class 2 (65 patients, 12.5%) showing rapid symptom improvement; Class 3 (24 patients, 4.6%) with high average baseline PANSS total score showing gradual symptom improvement; and Class 4 (12 patients, 2.3%) showing unsustained symptom improvement. Latent class membership of early responders (ER) and early non-responders (ENR) was determined based on 20% symptom improvement criteria at 2 weeks and ultimate responders (UR) and ultimate non-responders (UNR) based on 40% symptom improvement criteria at 12 weeks. Baseline factors with potential influence on latent class membership were identified. Conclusions This study identified four distinct treatment response patterns with predominant representation of responders or non-responders to treatment in these classes. This heterogeneity may represent discrete endophenotypes of response to treatment with different etiologic underpinnings. PMID:20925971

  13. Van Der Waals heterogeneous layer-layer carbon nanostructures involving π···H-C-C-H···π···H-C-C-H stacking based on graphene and graphane sheets.

    PubMed

    Yuan, Kun; Zhao, Rui-Sheng; Zheng, Jia-Jia; Zheng, Hong; Nagase, Shigeru; Zhao, Sheng-Dun; Liu, Yan-Zhi; Zhao, Xiang

    2017-04-15

    Noncovalent interactions involving aromatic rings, such as π···π stacking, CH···π are very essential for supramolecular carbon nanostructures. Graphite is a typical homogenous carbon matter based on π···π stacking of graphene sheets. Even in systems not involving aromatic groups, the stability of diamondoid dimer and layer-layer graphane dimer originates from C - H···H - C noncovalent interaction. In this article, the structures and properties of novel heterogeneous layer-layer carbon-nanostructures involving π···H-C-C-H···π···H-C-C-H stacking based on [n]-graphane and [n]-graphene and their derivatives are theoretically investigated for n = 16-54 using dispersion corrected density functional theory B3LYP-D3 method. Energy decomposition analysis shows that dispersion interaction is the most important for the stabilization of both double- and multi-layer-layer [n]-graphane@graphene. Binding energy between graphane and graphene sheets shows that there is a distinct additive nature of CH···π interaction. For comparison and simplicity, the concept of H-H bond energy equivalent number of carbon atoms (noted as NHEQ), is used to describe the strength of these noncovalent interactions. The NHEQ of the graphene dimers, graphane dimers, and double-layered graphane@graphene are 103, 143, and 110, indicating that the strength of C-H···π interaction is close to that of π···π and much stronger than that of C-H···H-C in large size systems. Additionally, frontier molecular orbital, electron density difference and visualized noncovalent interaction regions are discussed for deeply understanding the nature of the C-H···π stacking interaction in construction of heterogeneous layer-layer graphane@graphene structures. We hope that the present study would be helpful for creations of new functional supramolecular materials based on graphane and graphene carbon nano-structures. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  14. Effect of heterogeneous investments on the evolution of cooperation in spatial public goods game.

    PubMed

    Huang, Keke; Wang, Tao; Cheng, Yuan; Zheng, Xiaoping

    2015-01-01

    Understanding the emergence of cooperation in spatial public goods game remains a grand challenge across disciplines. In most previous studies, it is assumed that the investments of all the cooperators are identical, and often equal to 1. However, it is worth mentioning that players are diverse and heterogeneous when choosing actions in the rapidly developing modern society and researchers have shown more interest to the heterogeneity of players recently. For modeling the heterogeneous players without loss of generality, it is assumed in this work that the investment of a cooperator is a random variable with uniform distribution, the mean value of which is equal to 1. The results of extensive numerical simulations convincingly indicate that heterogeneous investments can promote cooperation. Specifically, a large value of the variance of the random variable can decrease the two critical values for the result of behavioral evolution effectively. Moreover, the larger the variance is, the better the promotion effect will be. In addition, this article has discussed the impact of heterogeneous investments when the coevolution of both strategy and investment is taken into account. Comparing the promotion effect of coevolution of strategy and investment with that of strategy imitation only, we can conclude that the coevolution of strategy and investment decreases the asymptotic fraction of cooperators by weakening the heterogeneity of investments, which further demonstrates that heterogeneous investments can promote cooperation in spatial public goods game.

  15. Effects of reservoir heterogeneity on scaling of effective mass transfer coefficient for solute transport

    NASA Astrophysics Data System (ADS)

    Leung, Juliana Y.; Srinivasan, Sanjay

    2016-09-01

    Modeling transport process at large scale requires proper scale-up of subsurface heterogeneity and an understanding of its interaction with the underlying transport mechanisms. A technique based on volume averaging is applied to quantitatively assess the scaling characteristics of effective mass transfer coefficient in heterogeneous reservoir models. The effective mass transfer coefficient represents the combined contribution from diffusion and dispersion to the transport of non-reactive solute particles within a fluid phase. Although treatment of transport problems with the volume averaging technique has been published in the past, application to geological systems exhibiting realistic spatial variability remains a challenge. Previously, the authors developed a new procedure where results from a fine-scale numerical flow simulation reflecting the full physics of the transport process albeit over a sub-volume of the reservoir are integrated with the volume averaging technique to provide effective description of transport properties. The procedure is extended such that spatial averaging is performed at the local-heterogeneity scale. In this paper, the transport of a passive (non-reactive) solute is simulated on multiple reservoir models exhibiting different patterns of heterogeneities, and the scaling behavior of effective mass transfer coefficient (Keff) is examined and compared. One such set of models exhibit power-law (fractal) characteristics, and the variability of dispersion and Keff with scale is in good agreement with analytical expressions described in the literature. This work offers an insight into the impacts of heterogeneity on the scaling of effective transport parameters. A key finding is that spatial heterogeneity models with similar univariate and bivariate statistics may exhibit different scaling characteristics because of the influence of higher order statistics. More mixing is observed in the channelized models with higher-order continuity. It reinforces the notion that the flow response is influenced by the higher-order statistical description of heterogeneity. An important implication is that when scaling-up transport response from lab-scale results to the field scale, it is necessary to account for the scale-up of heterogeneity. Since the characteristics of higher-order multivariate distributions and large-scale heterogeneity are typically not captured in small-scale experiments, a reservoir modeling framework that captures the uncertainty in heterogeneity description should be adopted.

  16. Nonlinear effects of locally heterogeneous hydraulic conductivity fields on regional stream-aquifer exchanges

    NASA Astrophysics Data System (ADS)

    Zhu, J.; Winter, C. L.; Wang, Z.

    2015-11-01

    Computational experiments are performed to evaluate the effects of locally heterogeneous conductivity fields on regional exchanges of water between stream and aquifer systems in the Middle Heihe River basin (MHRB) of northwestern China. The effects are found to be nonlinear in the sense that simulated discharges from aquifers to streams are systematically lower than discharges produced by a base model parameterized with relatively coarse effective conductivity. A similar, but weaker, effect is observed for stream leakage. The study is organized around three hypotheses: (H1) small-scale spatial variations of conductivity significantly affect regional exchanges of water between streams and aquifers in river basins, (H2) aggregating small-scale heterogeneities into regional effective parameters systematically biases estimates of stream-aquifer exchanges, and (H3) the biases result from slow paths in groundwater flow that emerge due to small-scale heterogeneities. The hypotheses are evaluated by comparing stream-aquifer fluxes produced by the base model to fluxes simulated using realizations of the MHRB characterized by local (grid-scale) heterogeneity. Levels of local heterogeneity are manipulated as control variables by adjusting coefficients of variation. All models are implemented using the MODFLOW (Modular Three-dimensional Finite-difference Groundwater Flow Model) simulation environment, and the PEST (parameter estimation) tool is used to calibrate effective conductivities defined over 16 zones within the MHRB. The effective parameters are also used as expected values to develop lognormally distributed conductivity (K) fields on local grid scales. Stream-aquifer exchanges are simulated with K fields at both scales and then compared. Results show that the effects of small-scale heterogeneities significantly influence exchanges with simulations based on local-scale heterogeneities always producing discharges that are less than those produced by the base model. Although aquifer heterogeneities are uncorrelated at local scales, they appear to induce coherent slow paths in groundwater fluxes that in turn reduce aquifer-stream exchanges. Since surface water-groundwater exchanges are critical hydrologic processes in basin-scale water budgets, these results also have implications for water resources management.

  17. Chronic care management for patients with COPD: a critical review of available evidence.

    PubMed

    Lemmens, Karin M M; Lemmens, Lidwien C; Boom, José H C; Drewes, Hanneke W; Meeuwissen, Jolanda A C; Steuten, Lotte M G; Vrijhoef, Hubertus J M; Baan, Caroline A

    2013-10-01

    Clinical diversity and methodological heterogeneity exists between studies on chronic care management. This study aimed to examine the effectiveness of chronic care management in chronic obstructive pulmonary disease (COPD) while taking heterogeneity into account, enabling the understanding of and the decision making about such programmes. Three investigated sources of heterogeneity were study quality, length of follow-up, and number of intervention components. We performed a review of previously published reviews and meta-analyses on COPD chronic care management. Their primary studies that were analyzed as statistical, clinical and methodological heterogeneity were present. Meta-regression analyses were performed to explain the variances among the primary studies. Generally, the included reviews showed positive results on quality of life and hospitalizations. Inconclusive effects were found on emergency department visits and no effects on mortality. Pooled effects on hospitalizations, emergency department visits and quality of life of primary studies did not reach significant improvement. No effects were found on mortality. Meta-regression showed that the number of components of chronic care management programmes explained present heterogeneity for hospitalizations and emergency department visits. Four components showed significant effects on hospitalizations, whereas two components had significant effects on emergency department visits. Methodological study quality and length of follow-up did not significantly explain heterogeneity. This study demonstrated that COPD chronic care management has the potential to improve outcomes of care; heterogeneity in outcomes was explained. Further research is needed to elucidate the diversity between COPD chronic care management studies in terms of the effects measured and strengthen the support for chronic care management. © 2011 John Wiley & Sons Ltd.

  18. Nano-targeted induction of dual ferroptotic mechanisms eradicates high-risk neuroblastoma.

    PubMed

    Hassannia, Behrouz; Wiernicki, Bartosz; Ingold, Irina; Qu, Feng; Van Herck, Simon; Tyurina, Yulia Y; Bayır, Hülya; Abhari, Behnaz A; Angeli, Jose Pedro Friedmann; Choi, Sze Men; Meul, Eline; Heyninck, Karen; Declerck, Ken; Chirumamilla, Chandra Sekhar; Lahtela-Kakkonen, Maija; Van Camp, Guy; Krysko, Dmitri V; Ekert, Paul G; Fulda, Simone; De Geest, Bruno G; Conrad, Marcus; Kagan, Valerian E; Berghe, Wim Vanden; Vandenabeele, Peter; Berghe, Tom Vanden

    2018-06-25

    High-risk neuroblastoma is a devastating malignancy with very limited therapeutic options. Here, we identify withaferin A (WA) as a natural ferroptosis-inducing agent in neuroblastoma, which acts through a novel double-edged mechanism. WA dose-dependently either activates the nuclear factor-like 2 pathway through targeting of Kelch-like ECH-associated protein 1 (noncanonical ferroptosis induction) or inactivates glutathione peroxidase 4 (canonical ferroptosis induction). Noncanonical ferroptosis induction is characterized by an increase in intracellular labile Fe(II) upon excessive activation of heme oxygenase-1, which is sufficient to induce ferroptosis. This double-edged mechanism might explain the superior efficacy of WA as compared with etoposide or cisplatin in killing a heterogeneous panel of high-risk neuroblastoma cells, and in suppressing the growth and relapse rate of neuroblastoma xenografts. Nano-targeting of WA allows systemic application and suppressed tumor growth due to an enhanced accumulation at the tumor site. Collectively, our data propose a novel therapeutic strategy to efficiently kill cancer cells by ferroptosis.

  19. Aging and failure mode of electrochemical double layer capacitors during accelerated constant load tests

    NASA Astrophysics Data System (ADS)

    Kötz, R.; Ruch, P. W.; Cericola, D.

    Electrochemical double layer capacitors of the BCAP0350 type (Maxwell Technologies) were tested under constant load conditions at different voltages and temperatures. The aging of the capacitors was monitored during the test in terms of capacitance, internal resistance and leakage current. Aging was significantly accelerated by elevated temperature or increased voltage. Only for extreme conditions at voltages of 3.5 V or temperatures above 70 °C the capacitors failed due to internal pressure build-up. No other failure events such as open circuit or short circuit were detected. Impedance measurements after the tests showed increased high frequency resistance, an increased distributed resistance and most likely an increase in contact resistance between electrode and current collector together with a loss of capacitance. Capacitors aged at elevated voltages (3.3 V) exhibited a tilting of the low frequency component, which implies an increase in the heterogeneity of the electrode surface. This feature was not observed upon aging at elevated temperatures (70 °C).

  20. Transesterification of edible, non-edible and used cooking oils for biodiesel production using calcined layered double hydroxides as reusable base catalysts.

    PubMed

    Sankaranarayanan, Sivashunmugam; Antonyraj, Churchil A; Kannan, S

    2012-04-01

    Fatty acid methyl esters (FAME) were produced from edible, non-edible and used cooking oils with different fatty acid contents by transesterification with methanol using calcined layered double hydroxides (LDHs) as solid base catalysts. Among the catalysts, calcined CaAl2-LDH (hydrocalumite) showed the highest activity with >90% yield of FAME using low methanol:oil molar ratio (<6:1) at 65 °C in 5 h. The activity of the catalyst was attributed to its high basicity as supported by Hammett studies and CO(2)-TPD measurements. The catalyst was successfully reused in up to four cycles. Some of the properties such as density, viscosity, neutralization number and glycerol content of the obtained biodiesel matched well with the standard DIN values. It is concluded that a scalable heterogeneously catalyzed process for production of biodiesel in high yields from a wide variety of triglyceride oils including used oils is possible using optimized conditions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Layered double hydroxide-based nanomaterials as highly efficient catalysts and adsorbents.

    PubMed

    Li, Changming; Wei, Min; Evans, David G; Duan, Xue

    2014-11-01

    Layered double hydroxides (LDHs) are a class of anion clays consisting of brucite-like host layers and interlayer anions, which have attracted increasing interest in the fields of catalysis/adsorption. By virtue of the versatility in composition, morphology, and architecture of LDH materials, as well as their unique structural properties (intercalation, topological transformation, and self-assembly with other functional materials), LDHs display great potential in the design and fabrication of nanomaterials applied in photocatalysis, heterogeneous catalysis, and adsorption/separation processes. Taking advantage of the structural merits and various control synthesis strategies of LDHs, the active center structure (e.g., crystal facets, defects, geometric and electronic states, etc.) and macro-nano morphology can be facilely manipulated for specific catalytic/adsorbent processes with largely enhanced performances. In this review, the latest advancements in the design and preparation of LDH-based functional nanomaterials for sustainable development in catalysis and adsorption are summarized. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. High-pressure, high-temperature equations of state using nanofabricated controlled-geometry Ni/SiO 2/Ni double hot-plate samples

    DOE PAGES

    Pigott, Jeffrey S.; Ditmer, Derek A.; Fischer, Rebecca A.; ...

    2015-11-24

    We have fabricated novel controlled-geometry samples for the laser-heated diamond anvil cell (LHDAC) in which a transparent oxide layer (SiO 2) is sandwiched between two laser-absorbing layers (Ni) in a single, cohesive sample. The samples were mass manufactured (>10 4 samples) using a combination of physical vapor deposition, photolithography, and wet and plasma etching. The double hot-plate arrangement of the samples, coupled with the chemical and spatial homogeneity of the laser-absorbing layers, addresses problems of spatial temperature heterogeneities encountered in previous studies where simple mechanical mixtures of transparent and opaque materials were used. Here we report thermal equations of statemore » (EOS) for nickel to 100 GPa and 3000 K and stishovite to 50 GPa and 2400 K obtained using the LHDAC and in situ synchrotron x-ray micro-diffraction. Lastly, we discuss the inner core composition and the stagnation of subducted slabs in the mantle based on our refined thermal EOS.« less

  3. Plant responses to soil heterogeneity and global environmental change

    PubMed Central

    García-Palacios, Pablo; Maestre, Fernando T.; Bardgett, Richard D.; de Kroon, Hans

    2015-01-01

    Summary Recent evidence suggests that soil nutrient heterogeneity, a ubiquitous feature of terrestrial ecosystems, modulates plant responses to ongoing global change (GC). However, we know little about the overall trends of such responses, the GC drivers involved, and the plant attributes affected. We synthesized literature to answer the question: Does soil heterogeneity significantly affect plant responses to main GC drivers, such as elevated atmospheric carbon dioxide concentration (CO2), nitrogen (N) enrichment and changes in rainfall regime? Overall, most studies have addressed short-term effects of N enrichment on the performance of model plant communities using experiments conducted under controlled conditions. The role of soil heterogeneity as a modulator of plant responses to elevated CO2 may depend on the plasticity in nutrient uptake patterns. Soil heterogeneity does interact with N enrichment to determine plant growth and nutrient status, but the outcome of this interaction has been found to be both synergistic and inhibitory. The very few studies published on interactive effects of soil heterogeneity and changes in rainfall regime prevented us from identifying any general pattern. We identify the long-term consequences of soil heterogeneity on plant community dynamics in the field, and the ecosystem level responses of the soil heterogeneity × GC driver interaction, as the main knowledge gaps in this area of research. In order to fill these gaps and take soil heterogeneity and GC research a step forward, we propose the following research guidelines: 1) combining morphological and physiological plant responses to soil heterogeneity with field observations of community composition and predictions from simulation models; and 2) incorporating soil heterogeneity into a trait-based response-effect framework, where plant resource-use traits are used as both response variables to this heterogeneity and GC, and predictors of ecosystem functioning. Synthesis. There is enough evidence to affirm that soil heterogeneity modulates plant responses to elevated atmospheric CO2 and N enrichment. Our synthesis indicates that we must explicitly consider soil heterogeneity to accurately predict plant responses to GC drivers. PMID:25914423

  4. Influence of patchy saturation on seismic dispersion and attenuation in fractured porous media

    NASA Astrophysics Data System (ADS)

    Jinwei, Zhang; Handong, Huang; Chunhua, Wu; Sheng, Zhang; Gang, Wu; Fang, Chen

    2018-04-01

    Wave induced fluid flow due to mesoscopic heterogeneity can explain seismic dispersion and attenuation in the seismic frequency band. The mesoscopic heterogeneity mainly contains lithological variations, patchy saturation and mesoscopic fractures. The patchy saturation models which are locally based on Biot theory for porous media have been deeply studied, but the patchy saturation model for fractured porous media is rarely studied. In this paper, we develop a model to describe the poroelastic characteristics in fractured porous media where the background and fractures are filled with different fluids based on two scales of squirt flow. The seismic dispersion and attenuation in fractured porous media occur in two scales, the microscale due to fluid flow between pores and micro-cracks and mesoscale due to fluid flow between background and heterogeneities. We derive the complex stiffness tensor through the solution of stress equivalence and fluid conservation. Two new parameters embodying the fluid effects are introduced into the model compared with the single fluid phase model. The model is consistent with Gassmann-Wood equation at low frequency limit and consistent with the isolated fracture model at high frequency limit. After the frequency dependent stiffness tensor is obtained, the variations of velocities and inverse quality factors with frequency are analyzed through several numerical examples. We investigated three poroelastic cases: medium including pores and micro-cracks, media including pores, micro-cracks and fractures, media including pores and fractures. The frequency dependent characteristics of patchy saturation model are different with those of single fluid model not only in characteristic frequency but also in the magnitude of the attenuation. Finally, we discuss the results obtained and the special case where the fractures are saturated with gas or dry and the background is filled with water. We also compare our results with those of patchy saturation model and double porosity model. The results will contribute to the actual exploration work to a certain extent, such as the fluid identification in fractured reservoirs.

  5. Influence of patchy saturation on seismic dispersion and attenuation in fractured porous media

    NASA Astrophysics Data System (ADS)

    Zhang, Jinwei; Huang, Handong; Wu, Chunhua; Zhang, Sheng; Wu, Gang; Chen, Fang

    2018-07-01

    Wave-induced fluid flow due to mesoscopic heterogeneity can explain seismic dispersion and attenuation in the seismic frequency band. The mesoscopic heterogeneity mainly contains lithological variations, patchy saturation and mesoscopic fractures. The patchy saturation models which are locally based on Biot theory for porous media have been deeply studied, but the patchy saturation model for fractured porous media is rarely studied. In this paper, we develop a model to describe the poroelastic characteristics in fractured porous media where the background and fractures are filled with different fluids based on two scales of squirt flow. The seismic dispersion and attenuation in fractured porous media occur in two scales, the microscale due to fluid flow between pores and microcracks and mesoscale due to fluid flow between background and heterogeneities. We derive the complex stiffness tensor through the solution of stress equivalence and fluid conservation. Two new parameters embodying the fluid effects are introduced into the model compared with the single fluid phase model. The model is consistent with Gassmann-Wood equation at low-frequency limit and consistent with the isolated fracture model at high-frequency limit. After the frequency-dependent stiffness tensor is obtained, the variations of velocities and inverse quality factors with frequency are analysed through several numerical examples. We investigated three poroelastic cases: medium including pores and microcracks; media including pores, microcracks and fractures; media including pores and fractures. The frequency-dependent characteristics of patchy saturation model are different with those of single fluid model not only in characteristic frequency but also in the magnitude of the attenuation. Finally, we discuss the results obtained and the special case where the fractures are saturated with gas or dry and the background is filled with water. We also compare our results with those of patchy saturation model and double porosity model. The results will contribute to the actual exploration work to a certain extent, such as the fluid identification in fractured reservoirs.

  6. Runtime and Architecture Support for Efficient Data Exchange in Multi-Accelerator Applications.

    PubMed

    Cabezas, Javier; Gelado, Isaac; Stone, John E; Navarro, Nacho; Kirk, David B; Hwu, Wen-Mei

    2015-05-01

    Heterogeneous parallel computing applications often process large data sets that require multiple GPUs to jointly meet their needs for physical memory capacity and compute throughput. However, the lack of high-level abstractions in previous heterogeneous parallel programming models force programmers to resort to multiple code versions, complex data copy steps and synchronization schemes when exchanging data between multiple GPU devices, which results in high software development cost, poor maintainability, and even poor performance. This paper describes the HPE runtime system, and the associated architecture support, which enables a simple, efficient programming interface for exchanging data between multiple GPUs through either interconnects or cross-node network interfaces. The runtime and architecture support presented in this paper can also be used to support other types of accelerators. We show that the simplified programming interface reduces programming complexity. The research presented in this paper started in 2009. It has been implemented and tested extensively in several generations of HPE runtime systems as well as adopted into the NVIDIA GPU hardware and drivers for CUDA 4.0 and beyond since 2011. The availability of real hardware that support key HPE features gives rise to a rare opportunity for studying the effectiveness of the hardware support by running important benchmarks on real runtime and hardware. Experimental results show that in a exemplar heterogeneous system, peer DMA and double-buffering, pinned buffers, and software techniques can improve the inter-accelerator data communication bandwidth by 2×. They can also improve the execution speed by 1.6× for a 3D finite difference, 2.5× for 1D FFT, and 1.6× for merge sort, all measured on real hardware. The proposed architecture support enables the HPE runtime to transparently deploy these optimizations under simple portable user code, allowing system designers to freely employ devices of different capabilities. We further argue that simple interfaces such as HPE are needed for most applications to benefit from advanced hardware features in practice.

  7. Runtime and Architecture Support for Efficient Data Exchange in Multi-Accelerator Applications

    PubMed Central

    Cabezas, Javier; Gelado, Isaac; Stone, John E.; Navarro, Nacho; Kirk, David B.; Hwu, Wen-mei

    2014-01-01

    Heterogeneous parallel computing applications often process large data sets that require multiple GPUs to jointly meet their needs for physical memory capacity and compute throughput. However, the lack of high-level abstractions in previous heterogeneous parallel programming models force programmers to resort to multiple code versions, complex data copy steps and synchronization schemes when exchanging data between multiple GPU devices, which results in high software development cost, poor maintainability, and even poor performance. This paper describes the HPE runtime system, and the associated architecture support, which enables a simple, efficient programming interface for exchanging data between multiple GPUs through either interconnects or cross-node network interfaces. The runtime and architecture support presented in this paper can also be used to support other types of accelerators. We show that the simplified programming interface reduces programming complexity. The research presented in this paper started in 2009. It has been implemented and tested extensively in several generations of HPE runtime systems as well as adopted into the NVIDIA GPU hardware and drivers for CUDA 4.0 and beyond since 2011. The availability of real hardware that support key HPE features gives rise to a rare opportunity for studying the effectiveness of the hardware support by running important benchmarks on real runtime and hardware. Experimental results show that in a exemplar heterogeneous system, peer DMA and double-buffering, pinned buffers, and software techniques can improve the inter-accelerator data communication bandwidth by 2×. They can also improve the execution speed by 1.6× for a 3D finite difference, 2.5× for 1D FFT, and 1.6× for merge sort, all measured on real hardware. The proposed architecture support enables the HPE runtime to transparently deploy these optimizations under simple portable user code, allowing system designers to freely employ devices of different capabilities. We further argue that simple interfaces such as HPE are needed for most applications to benefit from advanced hardware features in practice. PMID:26180487

  8. Association of Intensive Blood Pressure Control and Kidney Disease Progression in Nondiabetic Patients With Chronic Kidney Disease: A Systematic Review and Meta-analysis.

    PubMed

    Tsai, Wan-Chuan; Wu, Hon-Yen; Peng, Yu-Sen; Yang, Ju-Yeh; Chen, Hung-Yuan; Chiu, Yen-Ling; Hsu, Shih-Ping; Ko, Mei-Ju; Pai, Mei-Fen; Tu, Yu-Kang; Hung, Kuan-Yu; Chien, Kuo-Liong

    2017-06-01

    The optimal blood pressure (BP) target remains debated in nondiabetic patients with chronic kidney disease (CKD). To compare intensive BP control (<130/80 mm Hg) with standard BP control (<140/90 mm Hg) on major renal outcomes in patients with CKD without diabetes. Searches of PubMed, MEDLINE, Embase, and Cochrane Library for publications up to March 24, 2016. Randomized clinical trials that compared an intensive vs a standard BP target in nondiabetic adults with CKD, reporting changes in glomerular filtration rate (GFR), doubling of serum creatinine level, 50% reduction in GFR, end-stage renal disease (ESRD), or all-cause mortality. Random-effects meta-analyses for pooling effect measures. Meta-regression and subgroup analyses for exploring heterogeneity. Differences in annual rate of change in GFR were expressed as mean differences with 95% CIs. Differences in doubling of serum creatinine or 50% reduction in GFR, ESRD, composite renal outcome, and all-cause mortality were expressed as risk ratios (RRs) with 95% CIs. We identified 9 trials with 8127 patients and a median follow-up of 3.3 years. Compared with standard BP control, intensive BP control did not show a significant difference on the annual rate of change in GFR (mean difference, 0.07; 95% CI, -0.16 to 0.29 mL/min/1.73 m2/y), doubling of serum creatinine level or 50% reduction in GFR (RR, 0.99; 95% CI, 0.76-1.29), ESRD (RR, 0.96; 95% CI, 0.78-1.18), composite renal outcome (RR, 0.99; 95% CI, 0.81-1.21), or all-cause mortality (RR, 0.95; 95% CI, 0.66-1.37). Nonblacks and patients with higher levels of proteinuria showed a trend of lower risk of kidney disease progression with intensive BP control. Targeting BP below the current standard did not provide additional benefit for renal outcomes compared with standard treatment during a follow-up of 3.3 years in patients with CKD without diabetes. However, nonblack patients or those with higher levels of proteinuria might benefit from the intensive BP-lowering treatments.

  9. Performance related issues in distributed database systems

    NASA Technical Reports Server (NTRS)

    Mukkamala, Ravi

    1991-01-01

    The key elements of research performed during the year long effort of this project are: Investigate the effects of heterogeneity in distributed real time systems; Study the requirements to TRAC towards building a heterogeneous database system; Study the effects of performance modeling on distributed database performance; and Experiment with an ORACLE based heterogeneous system.

  10. Mutagenic consequences of a single G-quadruplex demonstrate mitotic inheritance of DNA replication fork barriers

    PubMed Central

    Lemmens, Bennie; van Schendel, Robin; Tijsterman, Marcel

    2015-01-01

    Faithful DNA replication is vital to prevent disease-causing mutations, chromosomal aberrations and malignant transformation. However, accuracy conflicts with pace and flexibility and cells rely on specialized polymerases and helicases to ensure effective and timely replication of genomes that contain DNA lesions or secondary structures. If and how cells can tolerate a permanent barrier to replication is, however, unknown. Here we show that a single unresolved G-quadruplexed DNA structure can persist through multiple mitotic divisions without changing conformation. Failed replication across a G-quadruplex causes single-strand DNA gaps that give rise to DNA double-strand breaks in subsequent cell divisions, which are processed by polymerase theta (POLQ)-mediated alternative end joining. Lineage tracing experiments further reveal that persistent G-quadruplexes cause genetic heterogeneity during organ development. Our data demonstrate that a single lesion can cause multiple unique genomic rearrangements, and that alternative end joining enables cells to proliferate in the presence of mitotically inherited replication blocks. PMID:26563448

  11. Mutagenic consequences of a single G-quadruplex demonstrate mitotic inheritance of DNA replication fork barriers.

    PubMed

    Lemmens, Bennie; van Schendel, Robin; Tijsterman, Marcel

    2015-11-13

    Faithful DNA replication is vital to prevent disease-causing mutations, chromosomal aberrations and malignant transformation. However, accuracy conflicts with pace and flexibility and cells rely on specialized polymerases and helicases to ensure effective and timely replication of genomes that contain DNA lesions or secondary structures. If and how cells can tolerate a permanent barrier to replication is, however, unknown. Here we show that a single unresolved G-quadruplexed DNA structure can persist through multiple mitotic divisions without changing conformation. Failed replication across a G-quadruplex causes single-strand DNA gaps that give rise to DNA double-strand breaks in subsequent cell divisions, which are processed by polymerase theta (POLQ)-mediated alternative end joining. Lineage tracing experiments further reveal that persistent G-quadruplexes cause genetic heterogeneity during organ development. Our data demonstrate that a single lesion can cause multiple unique genomic rearrangements, and that alternative end joining enables cells to proliferate in the presence of mitotically inherited replication blocks.

  12. 3D printing of tissue-simulating phantoms for calibration of biomedical optical devices

    NASA Astrophysics Data System (ADS)

    Zhao, Zuhua; Zhou, Ximing; Shen, Shuwei; Liu, Guangli; Yuan, Li; Meng, Yuquan; Lv, Xiang; Shao, Pengfei; Dong, Erbao; Xu, Ronald X.

    2016-10-01

    Clinical utility of many biomedical optical devices is limited by the lack of effective and traceable calibration methods. Optical phantoms that simulate biological tissues used for optical device calibration have been explored. However, these phantoms can hardly simulate both structural and optical properties of multi-layered biological tissue. To address this limitation, we develop a 3D printing production line that integrates spin coating, light-cured 3D printing and Fused Deposition Modeling (FDM) for freeform fabrication of optical phantoms with mechanical and optical heterogeneities. With the gel wax Polydimethylsiloxane (PDMS), and colorless light-curable ink as matrix materials, titanium dioxide (TiO2) powder as the scattering ingredient, graphite powder and black carbon as the absorption ingredient, a multilayer phantom with high-precision is fabricated. The absorption and scattering coefficients of each layer are measured by a double integrating sphere system. The results demonstrate that the system has the potential to fabricate reliable tissue-simulating phantoms to calibrate optical imaging devices.

  13. Preferences for lamb meat: a choice experiment for Spanish consumers.

    PubMed

    Gracia, Azucena; de-Magistris, Tiziana

    2013-10-01

    This paper analyzes consumers' preferences for different lamb meat attributes using a choice experiment. In particular, preferences for the type of commercial lamb meat ("Ternasco" and "Suckling") and the origin of production (locally produced "Ojinegra from Teruel") were evaluated. Moreover, we endogenously identify consumers' segments based on consumers' preferences for the analyzed attributes. Data come from a survey administrated in Spain during 2009. A latent class model was used to estimate the effect of the attributes on consumer utility, derive the willingness to pay and determine consumers' segments. Results suggest that consumers' preferences for both attributes are heterogeneous and two homogenous consumers' segments were detected. The largest segment (79%) did not value any of the analyzed attributes while the smaller one (21%) valued both of them positively. In particular, consumers in this second segment are willing to pay an extra premium for the "Ternasco" lamb meat, around double the premium they are willing to pay for the locally produced lamb meat "Ojinegra from Teruel". Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Temperature effect on radiation induced reactions in ethylene and tetrafluoroethylene copolymer (ETFE)

    NASA Astrophysics Data System (ADS)

    Oshima, Akihiro; Ikeda, Shigetoshi; Seguchi, Tadao; Tabata, Yoneho

    1997-11-01

    Ethylene and tetrafluoroethylene copolymer (ETFE) was irradiated by γ-rays or electron beam (EB) under oxygen-free atmosphere at various temperatures ranging from 77 to 573 K. Mechanical and thermal properties, and absorption spectra of the irradiated ETFEs were measured. The mechanical properties of the film have been observed to change by irradiation. The modulus and yield strength increase with increasing dose, and these phenomena are clearly distinguished above the melting temperature of ETFE (533 K). Heat of crystallization changes drastically as a function of irradiation dose around the melting temperature, compared with other temperatures. The absorption band around 250 nm of irradiated ETFE shifts to a longer wavelength region with increase of irradiation temperature. Therefore, it was concluded from those experimental results mentioned above that crosslinking takes place and conjugated double bonds formation proceeds in a wide range of irradiation temperatures. Those reactions are enhanced by increasing temperature. The homogeneous crosslinking takes place in the molten state, while the heterogeneous crosslinking does in the crystalline solid state.

  15. Modeling the Capacitive Deionization Process in Dual-Porosity Electrodes

    DOE PAGES

    Gabitto, Jorge; Tsouris, Costas

    2016-04-28

    In many areas of the world, there is a need to increase water availability. Capacitive deionization (CDI) is an electrochemical water treatment process that can be a viable alternative for treating water and for saving energy. A model is presented to simulate the CDI process in heterogeneous porous media comprising two different pore sizes. It is based on a theory for capacitive charging by ideally polarizable porous electrodes without Faradaic reactions or specific adsorption of ions. A two steps volume averaging technique is used to derive the averaged transport equations in the limit of thin electrical double layers. A one-equationmore » model based on the principle of local equilibrium is derived. The constraints determining the range of application of the one-equation model are presented. The effective transport parameters for isotropic porous media are calculated solving the corresponding closure problems. The source terms that appear in the average equations are calculated using theoretical derivations. The global diffusivity is calculated by solving the closure problem.« less

  16. Ginkgo biloba for prevention of dementia: a systematic review and meta-analysis.

    PubMed

    Charemboon, Thammanard; Jaisin, Kankamol

    2015-05-01

    To determine the efficacy of Ginkgo biloba for the prevention of dementia in individuals without dementia. English databases including Medline, Embase, Cochrane Library and PsycINFO, were searched, and randomized double-blind controlled studies comparing Ginkgo biloba with placebo in prevention of dementia were considered. Two trials met inclusion criteria. Methodological quality was assessed using the Jadad criteria. Meta-analysis of the two trials involving 5,889 participants indicated no significant difference in dementia rate between Ginkgo biloba and the placebo (347/2,951 vs. 330/2,938, odds ratio = 1.05, 95% CI 0.89-1.23) and there was no considerable heterogeneity between the trials. The two studies revealed no statistically significant differences in the rate of serious adverse effect between Ginko biloba and the placebo. There is no convincing evidence from this review that demonstrated Ginkgo biloba in late-life can prevent the development of dementia. Using it for this indication is not suggested at present.

  17. Scattering of plane transverse waves by spherical inclusions in a poroelastic medium

    NASA Astrophysics Data System (ADS)

    Liu, Xu; Greenhalgh, Stewart; Zhou, Bing

    2009-03-01

    The scattering of plane transverse waves by a spherical inclusion embedded in an infinite poroelastic medium is treated for the first time in this paper. The vector displacement wave equations of Biot's theory are solved as an infinite series of vector spherical harmonics for the case of a plane S-wave impinging from a porous medium onto a spherical inclusion which itself is assumed to be another porous medium. Based on the single spherical scattering theory and dynamic composite elastic medium theory, the non-self-consistent shear wavenumber is derived for a porous rock having numerous spherical inclusions of another medium. The frequency dependences of the shear wave velocity and the shear wave attenuation have been calculated for both the patchy saturation model (inclusions having the same solid frame as the host but with a different pore fluid from the host medium) and the double porosity model (inclusions having a different solid frame than the host but the same pore fluid as the host medium) with dilute concentrations of identical inclusions. Unlike the case of incident P-wave scattering, we show that although the fluid and the heterogeneity of the rock determine the shear wave velocity of the composite, the attenuation of the shear wave caused by scattering is actually contributed by the heterogeneity of the rock for spherical inclusions. The scattering of incident shear waves in the patchy saturation model is quite different from that of the double porosity model. For the patchy saturation model, the gas inclusions do not significantly affect the shear wave dispersion characteristic of the water-filled host medium. However, the softer inclusion with higher porosity in the double porosity model can cause significant shear wave scattering attenuation which occurs at a frequency at which the wavelength of the shear wave is approximately equal to the characteristic size of the inclusion and depends on the volume fraction. Compared with analytic formulae for the low frequency limit of the shear velocity, our scattering model yields discrepancies within 4.0 per cent. All calculated shear velocities of the composite medium with dilute inclusion concentrations approach the high frequency limit of the host material.

  18. Treatment of fatigue with methylphenidate, modafinil and amantadine in multiple sclerosis (TRIUMPHANT-MS): Study design for a pragmatic, randomized, double-blind, crossover clinical trial.

    PubMed

    Nourbakhsh, Bardia; Revirajan, Nisha; Waubant, Emmanuelle

    2018-01-01

    Fatigue is the most common symptom of multiple sclerosis (MS). Amantadine, modafinil and amphetamine-like stimulants are commonly used in clinical practice for treatment of fatigue; however, the evidence supporting their effectiveness is sparse and conflicting. To describe the design of a trial study funded by Patient-Centered Outcome Research Institute (PCORI) that will compare the efficacy of commonly used fatigue medications in patients with MS. The study is a randomized, placebo-controlled, crossover, four-sequence, four-period, double-blind, multicenter trial of three commonly used medications for the treatment of MS-related fatigue (amantadine, modafinil, methylphenidate) versus placebo in fatigued subjects with MS. Adult patients with MS, with an Expanded Disability Status Scale of <7.0 are eligible to participate. Participants will be randomized to one of four predefined sequences of medication administration. Each sequence comprises four 6-week periods of treatment with one of the 3 study drugs or placebo, and three 2-week washout periods between medication periods. 136 participants will be randomized over two years in two academic centers in the United States starting in the Summer 2017. Complete enrollment is expected by early 2019. The primary outcome of the study is the modified fatigue impact scale (MFIS) score while participants receive the maximally tolerated dose of each study medication (or placebo). Safety and tolerability of the medications and heterogeneity of treatment effect will also be assessed. Results of the proposed study will provide evidence-based and personalized treatment options for patients affected by MS-related fatigue. Clinicaltrials.gov registration number: NCT03185065. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. The cardiovascular safety trials of DPP-4 inhibitors, GLP-1 agonists, and SGLT2 inhibitors.

    PubMed

    Secrest, Matthew H; Udell, Jacob A; Filion, Kristian B

    2017-04-01

    In this paper, we review the results of large, double-blind, placebo-controlled randomized trials mandated by the US Food and Drug Administration to examine the cardiovascular safety of newly-approved antihyperglycemic agents in patients with type 2 diabetes. The cardiovascular effects of dipeptidyl peptidase-4 (DPP-4) inhibitors remain controversial: while these drugs did not reduce or increase the risk of primary, pre-specified composite cardiovascular outcomes, one DPP-4 inhibitor (saxagliptin) increased the risk of hospitalization for heart failure in the overall population; another (alogliptin) demonstrated inconsistent effects on heart failure hospitalization across subgroups of patients, and a third (sitagliptin) demonstrated no effect on heart failure. Evidence for cardiovascular benefits of glucagon-like peptide-1 (GLP-1) agonists has been similarly heterogeneous, with liraglutide and semaglutide reducing the risk of composite cardiovascular outcomes, but lixisenatide having no reduction or increase in cardiovascular risk. The effect of GLP-1 agonists on retinopathy remains a potential concern. In the only completed trial to date to assess a sodium-glucose cotransporter-2 (SGLT2) inhibitor, empagliflozin reduced the risk of composite cardiovascular endpoints, predominantly through its impact on cardiovascular mortality and heart failure hospitalization. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Heterogeneous reactions in aircraft gas turbine engines

    NASA Astrophysics Data System (ADS)

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

    2002-05-01

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

  1. Membrane formation in liquids by adding an antagonistic salt

    NASA Astrophysics Data System (ADS)

    Sadakane, Koichiro; Seto, Hideki

    2018-03-01

    Antagonistic salts are composed of hydrophilic and hydrophobic ions. In a binary mixture, such as water and organic solvent, these ion pairs preferentially dissolve to those phases, respectively, and there is a coupling between the charge density and the composition. The heterogeneous distribution of ions forms a large electric double layer at the interface between these solvents. This reduces the interfacial tension between water and organic solvent, and stabilizes an ordered structure, such as a membrane. These phenomena have been extensively studied from both theoretical and experimental point of view. In addition, the numerical simulations can reproduce such ordered structures.

  2. Non-preconditioned conjugate gradient on cell and FPGA based hybrid supercomputer nodes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dubois, David H; Dubois, Andrew J; Boorman, Thomas M

    2009-01-01

    This work presents a detailed implementation of a double precision, non-preconditioned, Conjugate Gradient algorithm on a Roadrunner heterogeneous supercomputer node. These nodes utilize the Cell Broadband Engine Architecture{sup TM} in conjunction with x86 Opteron{sup TM} processors from AMD. We implement a common Conjugate Gradient algorithm, on a variety of systems, to compare and contrast performance. Implementation results are presented for the Roadrunner hybrid supercomputer, SRC Computers, Inc. MAPStation SRC-6 FPGA enhanced hybrid supercomputer, and AMD Opteron only. In all hybrid implementations wall clock time is measured, including all transfer overhead and compute timings.

  3. Non-preconditioned conjugate gradient on cell and FPCA-based hybrid supercomputer nodes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dubois, David H; Dubois, Andrew J; Boorman, Thomas M

    2009-03-10

    This work presents a detailed implementation of a double precision, Non-Preconditioned, Conjugate Gradient algorithm on a Roadrunner heterogeneous supercomputer node. These nodes utilize the Cell Broadband Engine Architecture{trademark} in conjunction with x86 Opteron{trademark} processors from AMD. We implement a common Conjugate Gradient algorithm, on a variety of systems, to compare and contrast performance. Implementation results are presented for the Roadrunner hybrid supercomputer, SRC Computers, Inc. MAPStation SRC-6 FPGA enhanced hybrid supercomputer, and AMD Opteron only. In all hybrid implementations wall clock time is measured, including all transfer overhead and compute timings.

  4. Efficient Double Auction Mechanisms in the Energy Grid with Connected and Islanded Microgrids

    NASA Astrophysics Data System (ADS)

    Faqiry, Mohammad Nazif

    The future energy grid is expected to operate in a decentralized fashion as a network of autonomous microgrids that are coordinated by a Distribution System Operator (DSO), which should allocate energy to them in an efficient manner. Each microgrid operating in either islanded or grid-connected mode may be considered to manage its own resources. This can take place through auctions with individual units of the microgrid as the agents. This research proposes efficient auction mechanisms for the energy grid, with is-landed and connected microgrids. The microgrid level auction is carried out by means of an intermediate agent called an aggregator. The individual consumer and producer units are modeled as selfish agents. With the microgrid in islanded mode, two aggregator-level auction classes are analyzed: (i) price-heterogeneous, and (ii) price homogeneous. Under the price heterogeneity paradigm, this research extends earlier work on the well-known, single-sided Kelly mechanism to double auctions. As in Kelly auctions, the proposed algorithm implements the bidding without using any agent level private infor-mation (i.e. generation capacity and utility functions). The proposed auction is shown to be an efficient mechanism that maximizes the social welfare, i.e. the sum of the utilities of all the agents. Furthermore, the research considers the situation where a subset of agents act as a coalition to redistribute the allocated energy and price using any other specific fairness criterion. The price homogeneous double auction algorithm proposed in this research ad-dresses the problem of price-anticipation, where each agent tries to influence the equilibri-um price of energy by placing strategic bids. As a result of this behavior, the auction's efficiency is lowered. This research proposes a novel approach that is implemented by the aggregator, called virtual bidding, where the efficiency can be asymptotically maximized, even in the presence of price anticipatory bidders. Next, an auction mechanism for the energy grid, with multiple connected mi-crogrids is considered. A globally efficient bi-level auction algorithm is proposed. At the upper-level, the algorithm takes into account physical grid constraints in allocating energy to the microgrids. It is implemented by the DSO as a linear objective quadratic constraint problem that allows price heterogeneity across the aggregators. In parallel, each aggrega-tor implements its own lower-level price homogeneous auction with virtual bidding. The research concludes with a preliminary study on extending the DSO level auc-tion to multi-period day-ahead scheduling. It takes into account storage units and conven-tional generators that are present in the grid by formulating the auction as a mixed inte-ger linear programming problem.

  5. Ionic Structure at Dielectric Interfaces

    NASA Astrophysics Data System (ADS)

    Jing, Yufei

    The behavior of ions in liquids confined between macromolecules determines the outcome of many nanoscale assembly processes in synthetic and biological materials such as colloidal dispersions, emulsions, hydrogels, DNA, cell membranes, and proteins. Theoretically, the macromolecule-liquid boundary is often modeled as a dielectric interface and an important quantity of interest is the ionic structure in a liquid confined between two such interfaces. The knowledge gleaned from the study of ionic structure in such models can be useful in several industrial applications, such as biosensors, lithium-ion batteries double-layer supercapacitors for energy storage and seawater desalination. Electrostatics plays a critical role in the development of such functional materials. Many of the functions of these materials, result from charge and composition heterogeneities. There are great challenges in solving electrostatics problems in heterogeneous media with arbitrary shapes because electrostatic interactions remains unknown but depend on the particular density of charge distributions. Charged molecules in heterogeneous media affect the media's dielectric response and hence the interaction between the charges is unknown since it depends on the media and on the geometrical properties of the interfaces. To determine the properties of heterogeneous systems including crucial effects neglected in classical mean field models such as the hard core of the ions, the dielectric mismatch and interfaces with arbitrary shapes. The effect of hard core interactions accounts properly for short range interactions and the effect of local dielectric heterogeneities in the presence of ions and/or charged molecules for long-range interactions are both analyzed via an energy variational principle that enables to update charges and the medium's response in the same simulation time step. In particular, we compute the ionic structure in a model system of electrolyte confined by two planar dielectric interfaces using molecular dynamics(MD) simulations and compared it with liquid state theory result. We explore the effects of high electrolyte concentrations, multivalent ions, and dielectric contrasts on the ionic distributions. We observe the presence of non-monotonous ionic density profiles leading to structure deformation in the fluid which is attributed to the competition between electrostatic and steric (entropic) interactions. We find that thermal forces that arise from symmetry breaking at the interfaces can have a profound effect on the ionic structure and can oftentimes overwhelm the influence of dielectric discontinuity. The combined effect of ionic correlations and inhomogeneous dielectric permittivity significantly changes the character of effective interaction between two interfaces. We show that, in concentrated electrolytes with confinement, it is imperative to take into account the finite-size of the ions as well as proper description of electrostatic interactions in heterogeneous media, which is not fully fulfilled by Poisson-Boltzmann based approaches. The effect of electric field at interface between two immiscible electrolyte solutions is studied as well. The classical Poisson-Boltzmann theory has been widely used to describe the corresponding ionic distribution, even though it neglects the polarization and ion correlations typical of these charged systems. Using Monte Carlo simulations, we provide an enhanced description of an oil-water interface in the presence of an electric field without needing any adjustable parameter, including realistic ionic sizes, ion correlations, and image charges. Our data agree with experimental measurements of excess surface tension for a wide range of electrolyte concentrations of LiCl and TBATPB (tetrabutylammonium-tetraphenylborate), contrasting with the result of the classical non-linear Poisson-Boltzmann theory. More importantly, we show that the size-asymmetry between small Li+ and large Cl- ions can significantly increase the electric field near the liquid interface, or can even reverse it locally, at high salt concentrations in the aqueous phase. These observations suggest a novel trapping/release mechanism of charged nanoparticles at oil-water interfaces in the vicinity of the point of zero charge. In addition, we study the effects of size asymmetry and charge asymmetry on ion distribution at a dielectric interface using coarse-grained MD based on an energy variational principle. The goal is to explore charge amplification with exact consideration of surface polarization. We find that both size asymmetry and charge asymmetry lead to charge separation at the interfaces. In addition, charge separation is enhanced by interface polarization. We are currently extending the research to charged interfaces that has broad applications such as batteries and supercapacitors for energy storage.

  6. Interconnecting heterogeneous database management systems

    NASA Technical Reports Server (NTRS)

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

    1984-01-01

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

  7. Accounting for heterogeneity among treatment sites and time trends in developing crash modification functions.

    PubMed

    Sacchi, Emanuele; Sayed, Tarek

    2014-11-01

    Collision modification factors (CMFs) are commonly used to quantify the impact of safety countermeasures. The CMFs obtained from observational before-after (BA) studies are usually estimated by averaging the safety impact (i.e., index of effectiveness) for a group of treatment sites. The heterogeneity among the treatment locations, in terms of their characteristics, and the effect of this heterogeneity on safety treatment effectiveness are usually ignored. This is in contrast to treatment evaluations in other fields like medical statistics where variations in the magnitude (or in the direction) of response to the same treatment given to different patients are considered. This paper introduces an approach for estimating a CMFunction from BA safety studies that account for variable treatment location characteristics (heterogeneity). The treatment sites heterogeneity was incorporated into the CMFunction using fixed-effects and random-effects regression models. In addition to heterogeneity, the paper also advocates the use of CMFunctions with a time variable to acknowledge that the safety treatment (intervention) effects do not occur instantaneously but are spread over future time. This is achieved using non-linear intervention (Koyck) models, developed within a hierarchical full Bayes (FB) context. To demonstrate the approach, a case study is presented to evaluate the safety effectiveness of the "Signal Head Upgrade Program" recently implemented in the city of Surrey (British Columbia, Canada), where signal visibility was improved at several urban signalized intersections. The results demonstrated the importance of considering treatment sites heterogeneity and time trends when developing CMFunctions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. E1B and E4 oncoproteins of adenovirus antagonize the effect of apoptosis inducing factor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Turner, Roberta L.; Wilkinson, John C., E-mail: john.wilkinson@ndsu.edu; Ornelles, David A., E-mail: ornelles@wakehealth.edu

    2014-05-15

    Adenovirus inundates the productively infected cell with linear, double-stranded DNA and an abundance of single-stranded DNA. The cellular response to this stimulus is antagonized by the adenoviral E1B and E4 early genes. A mutant group C adenovirus that fails to express the E1B-55K and E4ORF3 genes is unable to suppress the DNA-damage response. Cells infected with this double-mutant virus display significant morphological heterogeneity at late times of infection and frequently contain fragmented nuclei. Nuclear fragmentation was due to the translocation of apoptosis inducing factor (AIF) from the mitochondria into the nucleus. The release of AIF was dependent on active poly(ADP-ribose)more » polymerase-1 (PARP-1), which appeared to be activated by viral DNA replication. Nuclear fragmentation did not occur in AIF-deficient cells or in cells treated with a PARP-1 inhibitor. The E1B-55K or E4ORF3 proteins independently prevented nuclear fragmentation subsequent to PARP-1 activation, possibly by altering the intracellular distribution of PAR-modified proteins. - Highlights: • E1B-55K or E4orf3 prevents nuclear fragmentation. • Nuclear fragmentation requires AIF and PARP-1 activity. • Adenovirus DNA replication activates PARP-1. • E1B-55K or E4orf3 proteins alter the distribution of PAR.« less

  9. A hybrid double-observer sightability model for aerial surveys

    USGS Publications Warehouse

    Griffin, Paul C.; Lubow, Bruce C.; Jenkins, Kurt J.; Vales, David J.; Moeller, Barbara J.; Reid, Mason; Happe, Patricia J.; Mccorquodale, Scott M.; Tirhi, Michelle J.; Schaberi, Jim P.; Beirne, Katherine

    2013-01-01

    Raw counts from aerial surveys make no correction for undetected animals and provide no estimate of precision with which to judge the utility of the counts. Sightability modeling and double-observer (DO) modeling are 2 commonly used approaches to account for detection bias and to estimate precision in aerial surveys. We developed a hybrid DO sightability model (model MH) that uses the strength of each approach to overcome the weakness in the other, for aerial surveys of elk (Cervus elaphus). The hybrid approach uses detection patterns of 2 independent observer pairs in a helicopter and telemetry-based detections of collared elk groups. Candidate MH models reflected hypotheses about effects of recorded covariates and unmodeled heterogeneity on the separate front-seat observer pair and back-seat observer pair detection probabilities. Group size and concealing vegetation cover strongly influenced detection probabilities. The pilot's previous experience participating in aerial surveys influenced detection by the front pair of observers if the elk group was on the pilot's side of the helicopter flight path. In 9 surveys in Mount Rainier National Park, the raw number of elk counted was approximately 80–93% of the abundance estimated by model MH. Uncorrected ratios of bulls per 100 cows generally were low compared to estimates adjusted for detection bias, but ratios of calves per 100 cows were comparable whether based on raw survey counts or adjusted estimates. The hybrid method was an improvement over commonly used alternatives, with improved precision compared to sightability modeling and reduced bias compared to DO modeling.

  10. Combined effects between temporal heterogeneity of water supply, nutrient level, and population density on biomass of four broadly distributed herbaceous species.

    PubMed

    Hagiwara, Yousuke; Kachi, Naoki; Suzuki, Jun-Ichirou

    2012-01-01

    Temporal heterogeneity of water supply affects grassland community productivity and it can interact with nutrient level and intraspecific competition. To understand community responses, the responses of individual species to water heterogeneity must be evaluated while considering the interactions of this heterogeneity with nutrient levels and population density. We compared responses of four herbaceous species grown in monocultures to various combinations of water heterogeneity, nutrient level, and population density: two grasses (Cynodon dactylon and Lolium perenne), a forb (Artemisia princeps), and a legume (Trifolium repens). Treatment effects on shoot and root biomass were analyzed. In all four species, shoot biomass was larger under homogeneous than under heterogeneous water supply. Shoot responses of L. perenne tended to be greater at high nutrient levels. Although root biomass was also larger under homogeneous water supply, effects of water heterogeneity on root biomass were not significant in the grasses. Trifolium repens showed marked root responses, particularly at high population density. Although greater shoot and root growth under homogeneous water supply appears to be a general trend among herbaceous species, our results suggested differences among species could be found in the degree of response to water heterogeneity and its interactions with nutrient level and intraspecific competition.

  11. Meta-Analysis of Rare Binary Adverse Event Data

    PubMed Central

    Bhaumik, Dulal K.; Amatya, Anup; Normand, Sharon-Lise; Greenhouse, Joel; Kaizar, Eloise; Neelon, Brian; Gibbons, Robert D.

    2013-01-01

    We examine the use of fixed-effects and random-effects moment-based meta-analytic methods for analysis of binary adverse event data. Special attention is paid to the case of rare adverse events which are commonly encountered in routine practice. We study estimation of model parameters and between-study heterogeneity. In addition, we examine traditional approaches to hypothesis testing of the average treatment effect and detection of the heterogeneity of treatment effect across studies. We derive three new methods, simple (unweighted) average treatment effect estimator, a new heterogeneity estimator, and a parametric bootstrapping test for heterogeneity. We then study the statistical properties of both the traditional and new methods via simulation. We find that in general, moment-based estimators of combined treatment effects and heterogeneity are biased and the degree of bias is proportional to the rarity of the event under study. The new methods eliminate much, but not all of this bias. The various estimators and hypothesis testing methods are then compared and contrasted using an example dataset on treatment of stable coronary artery disease. PMID:23734068

  12. Effect of Heterogeneous Investments on the Evolution of Cooperation in Spatial Public Goods Game

    PubMed Central

    Huang, Keke; Wang, Tao; Cheng, Yuan; Zheng, Xiaoping

    2015-01-01

    Understanding the emergence of cooperation in spatial public goods game remains a grand challenge across disciplines. In most previous studies, it is assumed that the investments of all the cooperators are identical, and often equal to 1. However, it is worth mentioning that players are diverse and heterogeneous when choosing actions in the rapidly developing modern society and researchers have shown more interest to the heterogeneity of players recently. For modeling the heterogeneous players without loss of generality, it is assumed in this work that the investment of a cooperator is a random variable with uniform distribution, the mean value of which is equal to 1. The results of extensive numerical simulations convincingly indicate that heterogeneous investments can promote cooperation. Specifically, a large value of the variance of the random variable can decrease the two critical values for the result of behavioral evolution effectively. Moreover, the larger the variance is, the better the promotion effect will be. In addition, this article has discussed the impact of heterogeneous investments when the coevolution of both strategy and investment is taken into account. Comparing the promotion effect of coevolution of strategy and investment with that of strategy imitation only, we can conclude that the coevolution of strategy and investment decreases the asymptotic fraction of cooperators by weakening the heterogeneity of investments, which further demonstrates that heterogeneous investments can promote cooperation in spatial public goods game. PMID:25781345

  13. Combined effects of waggle dance communication and landscape heterogeneity on nectar and pollen uptake in honey bee colonies.

    PubMed

    Nürnberger, Fabian; Steffan-Dewenter, Ingolf; Härtel, Stephan

    2017-01-01

    The instructive component of waggle dance communication has been shown to increase resource uptake of Apis mellifera colonies in highly heterogeneous resource environments, but an assessment of its relevance in temperate landscapes with different levels of resource heterogeneity is currently lacking. We hypothesized that the advertisement of resource locations via dance communication would be most relevant in highly heterogeneous landscapes with large spatial variation of floral resources. To test our hypothesis, we placed 24 Apis mellifera colonies with either disrupted or unimpaired instructive component of dance communication in eight Central European agricultural landscapes that differed in heterogeneity and resource availability. We monitored colony weight change and pollen harvest as measure of foraging success. Dance disruption did not significantly alter colony weight change, but decreased pollen harvest compared to the communicating colonies by 40%. There was no general effect of resource availability on nectar or pollen foraging success, but the effect of landscape heterogeneity on nectar uptake was stronger when resource availability was high. In contrast to our hypothesis, the effects of disrupted bee communication on nectar and pollen foraging success were not stronger in landscapes with heterogeneous compared to homogenous resource environments. Our results indicate that in temperate regions intra-colonial communication of resource locations benefits pollen foraging more than nectar foraging, irrespective of landscape heterogeneity. We conclude that the so far largely unexplored role of dance communication in pollen foraging requires further consideration as pollen is a crucial resource for colony development and health.

  14. Evaluation of an educational program on deciphering heterogeneity for medical coverage decisions.

    PubMed

    Warholak, Terri L; Hilgaertner, Jianhua W; Dean, Joni L; Taylor, Ann M; Hines, Lisa E; Hurwitz, Jason; Brown, Mary; Malone, Daniel C

    2014-06-01

    It is increasingly important for decision makers, such as medical and pharmacy managers (or pharmacy therapeutics committee members and staff), to understand the variation and diversity in treatment response as decisions shift from an individual patient perspective to optimizing care for populations of patients. To assess the effectiveness of an instructional program on heterogeneity designed for medical and pharmacy managers. A live educational program was offered to members of the Academy of Managed Care Pharmacy at the fall 2012 educational meeting and also to medical directors and managers attending a national payer roundtable meeting in October 2012. Participants completed a retrospective pretest-posttest assessment of their knowledge, attitudes, and self-efficacy immediately following the program. Participants were offered the opportunity to participate in a follow-up assessment 6 months later. Willing participants for the follow-up assessment were contacted via e-mail and telephone. Rasch rating scale models were used to compare pre- and postscores measuring participants' knowledge about and attitude towards heterogeneity. A total of 49 individuals completed the retrospective pretest-posttest assessment and agreed to be a part of the program evaluation. Fifty percent (n = 25) of participants had heard of the phrase "heterogeneity of treatment effect," and 36 (72%) were familiar with the phrase "individualized treatment effect" prior to the live program. Participants reported a significant improvement in knowledge of heterogeneity (P  less than  0.01) and attitudes about heterogeneity (P  less than  0.01) immediately after attending the program. At the time of the educational program, participants had either never considered heterogeneity (26%) or reported not knowing (28%) whether their organizations considered it when determining basic coverage. Participants were more likely to report "sometimes" considering heterogeneity for determining necessity for individual appeals, prior authorization, tier placement for pharmaceutical therapies, and other types of medical management. At the 6-month follow-up, 21 of the 49 willing participants (43% response rate) completed the evaluation; participants continued to have a good understanding of heterogeneity, but there was no significant difference in attitudes towards heterogeneity between pre- and 6-month follow-up. A live educational program was effective in improving participants' immediate knowledge and attitudes regarding the topic of heterogeneity. Participating managed care pharmacists and medical managers indicated that heterogeneity of treatment effect was likely to be used in determining prior authorizations and determining necessity.

  15. Computational Assessment of Blood Flow Heterogeneity in Peritoneal Dialysis Patients' Cardiac Ventricles

    PubMed Central

    Kharche, Sanjay R.; So, Aaron; Salerno, Fabio; Lee, Ting-Yim; Ellis, Chris; Goldman, Daniel; McIntyre, Christopher W.

    2018-01-01

    Dialysis prolongs life but augments cardiovascular mortality. Imaging data suggests that dialysis increases myocardial blood flow (BF) heterogeneity, but its causes remain poorly understood. A biophysical model of human coronary vasculature was used to explain the imaging observations, and highlight causes of coronary BF heterogeneity. Post-dialysis CT images from patients under control, pharmacological stress (adenosine), therapy (cooled dialysate), and adenosine and cooled dialysate conditions were obtained. The data presented disparate phenotypes. To dissect vascular mechanisms, a 3D human vasculature model based on known experimental coronary morphometry and a space filling algorithm was implemented. Steady state simulations were performed to investigate the effects of altered aortic pressure and blood vessel diameters on myocardial BF heterogeneity. Imaging showed that stress and therapy potentially increased mean and total BF, while reducing heterogeneity. BF histograms of one patient showed multi-modality. Using the model, it was found that total coronary BF increased as coronary perfusion pressure was increased. BF heterogeneity was differentially affected by large or small vessel blocking. BF heterogeneity was found to be inversely related to small blood vessel diameters. Simulation of large artery stenosis indicates that BF became heterogeneous (increase relative dispersion) and gave multi-modal histograms. The total transmural BF as well as transmural BF heterogeneity reduced due to large artery stenosis, generating large patches of very low BF regions downstream. Blocking of arteries at various orders showed that blocking larger arteries results in multi-modal BF histograms and large patches of low BF, whereas smaller artery blocking results in augmented relative dispersion and fractal dimension. Transmural heterogeneity was also affected. Finally, the effects of augmented aortic pressure in the presence of blood vessel blocking shows differential effects on BF heterogeneity as well as transmural BF. Improved aortic blood pressure may improve total BF. Stress and therapy may be effective if they dilate small vessels. A potential cause for the observed complex BF distributions (multi-modal BF histograms) may indicate existing large vessel stenosis. The intuitive BF heterogeneity methods used can be readily used in clinical studies. Further development of the model and methods will permit personalized assessment of patient BF status. PMID:29867555

  16. An upscaled rate law for magnesite dissolution in heterogeneous porous media

    NASA Astrophysics Data System (ADS)

    Wen, Hang; Li, Li

    2017-08-01

    Spatial heterogeneity in natural subsurface systems governs water fluxes and residence time in reactive zones and therefore determines effective rates of mineral dissolution. Extensive studies have documented mineral dissolution rates in natural systems, although a general rate law has remain elusive. Here we fill this gap by answering two questions: (1) how and to what extent does spatial heterogeneity affect water residence time and effectively-dissolving surface area? (2) what is the upscaled rate law that quantifies effective dissolution rates in natural, heterogeneous media? With data constraints from experimental work, 240 Monte-Carlo numerical experiments of magnesite dissolution within quartz matrix were run with spatial distributions characterized by a range of permeability variance σ2lnκ (0.5-6.0) and correlation length (2-50 cm). Although the total surface area and global residence time (τa) are the same in all experiments, the water fluxes through reactive magnesite zones varies between 0.7 and 72.8% of the total water fluxes. Highly heterogeneous media with large σ2lnκ and long λ divert water mostly into non-reactive preferential flow paths, therefore bypassing and minimizing flow in low permeability magnesite zones. As a result, the water residence time in magnesite zones (i.e., reactive residence time τa,r) is long and magnesite dissolution quickly reaches local equilibrium, which leads to small effective surface area and low dissolution rates. Magnesite dissolution rates in heterogeneous media vary from 2.7 to 100% of the rates in the equivalent homogeneous media, with effectively-dissolving surface area varying from 0.18 to 6.83 m2 (out of 51.71 m2 total magnesite surface area). Based on 240 numerical experiments and 45 column experiments, a general upscaled rate law in heterogeneous media, RMgCO3,ht =kAe,hm(1 - exp(-τa/τa,r))α, was derived to quantify effective dissolution rates. The dissolution rates in heterogeneous media are a function of the rate constants k being those measured under well-mixed conditions, effective surface area in equivalent homogeneous media Ae,hm, and the heterogeneity factor (1 - exp(-τa/τa,r))α. The heterogeneity factor quantify heterogeneity effects and depends on the relative magnitude of global residence time (τa) and reactive residence time (τa,r), as well as the shape factor α(= 5 σlnκ2) of the gamma distribution for reactive residence times. Exponential forms of rate laws have been used at the micro-scale describing direct interactions among water and mineral surface, and at the catchment scale describing weathering rates and concentration-discharge relationships. These observations highlight the key role of mineral-water contact time in determining dissolution rates at different scales. This work also emphasizes the importance of critical interfaces between reactive and non-reactive zones as determined by the details of spatial patterns and effective surface area as a scaling factor that quantifies dissolution rates in heterogeneous media across scales.

  17. Factor Xa inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in patients with atrial fibrillation.

    PubMed

    Bruins Slot, Karsten M H; Berge, Eivind

    2013-08-08

    Anticoagulant treatment with vitamin K antagonists (VKAs) is aimed at preventing thromboembolic complications and has been the therapy of choice for most people with non-valvular atrial fibrillation (AF) for many decades. A new class of anticoagulants, the factor Xa inhibitors, appear to have several pharmacological and practical advantages over VKAs. To assess the effectiveness and safety of treatment with factor Xa inhibitors versus VKAs for the prevention of cerebral or systemic embolic events in people with AF. We searched the trials registers of the Cochrane Stroke Group and the Cochrane Heart Group (June 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 10), MEDLINE (1950 to April 2013) and EMBASE (1980 to April 2013). In an effort to identify further published, unpublished and ongoing trials we searched trials registers and Google Scholar (July 2012). We also screened reference lists and contacted pharmaceutical companies, authors and sponsors of relevant published trials. Randomised controlled trials that directly compared the effects of long-term treatment (more than four weeks) with factor Xa inhibitors and VKAs for the prevention of cerebral and systemic embolism in patients with AF. We included patients with and without a previous stroke or TIA. The primary efficacy outcome was the composite endpoint of all strokes and other systemic embolic events. Two authors independently assessed trial quality and the risk of bias, and extracted data. We calculated a weighted estimate of the typical treatment effect across trials using the odds ratio (OR) with 95% confidence interval (CI) by means of a fixed-effect model. However, in the case of moderate or high heterogeneity of treatment effects, we used a random-effects model to compare the overall treatment effects and performed a pre-specified sensitivity analysis excluding any fully open-label studies. We included data from 42,084 participants randomised into 10 trials. All participants had a confirmed diagnosis of AF (or atrial flutter) and were deemed by the randomising physician to be eligible for long-term anticoagulant treatment with a VKA (warfarin) with a target International Normalised Ratio (INR) of 2.0 to 3.0 in most patients. The included trials directly compared dose-adjusted warfarin with either apixaban, betrixaban, darexaban, edoxaban, idraparinux or rivaroxaban. Four trials were double-masked, five partially-masked (that is different doses of factor Xa inhibitor administered double-masked and warfarin administered open-label) and one was open-label. Median duration of follow-up ranged from 12 weeks to 1.9 years.The composite primary efficacy endpoint of all strokes (both ischaemic and haemorrhagic) and non-central nervous systemic embolic events was reported in nine of the included studies (40,777 participants). Treatment with a factor Xa inhibitor significantly decreased the number of strokes and systemic embolic events compared with dose-adjusted warfarin (OR 0.81, 95% CI 0.72 to 0.91). We also analysed both components of this composite endpoint separately: treatment with a factor Xa inhibitor significantly decreased both the number of ischaemic and haemorrhagic strokes (OR 0.78, 95% CI 0.69 to 0.89) and the number of systemic embolic events (OR 0.53, 95% CI 0.32 to 0.87).All of the included studies (42,078 participants) reported the number of major bleedings. Treatment with a factor Xa inhibitor significantly reduced the number of major bleedings compared with warfarin (OR 0.89, 95% CI 0.81 to 0.98). There was, however, statistically significant and high heterogeneity (I² = 81%) and an analysis using a random-effects model did not show a statistically significant decrease in the number of major bleedings (OR 0.92, 95% CI 0.63 to 1.34). The pre-specified sensitivity analysis excluding open-label studies showed that treatment with a factor Xa inhibitor significantly reduced the number of major bleedings compared with warfarin (OR 0.84, 95% CI 0.76 to 0.92) but moderate heterogeneity was still observed (I² = 65%). A similar sensitivity analysis using a random-effects model did not show a statistically significant decrease in the number of major bleedings in patients treated with factor Xa inhibitors (OR 0.78, 95% CI 0.57 to 1.05). Part of the observed heterogeneity can thus be explained by the increased risk of major bleedings in the factor Xa treatment arm in the single included open-label study, which studied idraparinux. Other heterogeneity might be explained by differences in baseline bleeding risks in the two largest trials of apixaban and rivaroxaban that we included in this review.Data on intracranial haemorrhages (ICHs) were reported in eight studies (39,638 participants). Treatment with a factor Xa inhibitor significantly reduced the risk of ICH compared with warfarin (OR 0.56, 95% CI 0.45 to 0.70). Again, we observed statistically significant heterogeneity (I² = 60%). The pre-specified sensitivity analysis excluding the open-label study showed that treatment with a factor Xa inhibitor significantly reduced the number of ICHs compared with warfarin (OR 0.51, 95% CI 0.41 to 0.64), without any sign of statistical heterogeneity (I² = 0%).The number of patients who died from any cause was reported in six studies (38,924 participants). Treatment with a factor Xa inhibitor significantly reduced the number of all-cause deaths compared with warfarin (OR 0.88, 95% 0.81 to 0.97). Factor Xa inhibitors significantly reduced the number of strokes and systemic embolic events compared with warfarin in patients with AF. Factor Xa inhibitors also seem to reduce the number of major bleedings and ICHs compared with warfarin, though the evidence for a reduction of major bleedings is somewhat less robust. There is currently no conclusive evidence to determine which factor Xa inhibitor is more effective and safer for long-term anticoagulant treatment of patients with AF as head-to-head studies of the different factor Xa inhibitors have not yet been performed.

  18. Uneven-aged silviculture can enhance within stand heterogeneity and beetle diversity.

    PubMed

    Joelsson, Klara; Hjältén, Joakim; Work, Timothy

    2018-01-01

    Uneven-aged silviculture may better maintain species assemblages associated with old-growth forests than clear felling in part due to habitat heterogeneity created by maintaining standing retention strips adjacent to harvest trails. Retention strips and harvest trails created at the time of tree removal will likely have different microclimate and may harbor different assemblages. In some cases, the resultant stand heterogeneity associated with uneven-aged silviculture may be similar to natural small-scale disturbances. For beetles, increased light and temperature as well as potential access to young vegetation and deadwood substrates present in harvset trails may harbor beetle assemblages similar to those found in natural gaps. We sampled saproxylic beetles using flight intercept traps placed in harvest corridors and retention strips in 9 replicated uneven-aged spruce stands in central Sweden. We compared abundance, species richness and composition between harvest corridors and retention strips using generalized linear models, rarefaction, permutational multivariate analysis of variance and indicator species analysis. Canopy openness doubled, mean temperature and variability in daily temperature increased and humidity decreased on harvest trails. Beetle richness and abundance were greater in harvests trails than in retention strips and the beetle species composition differed significantly between habitats. Twenty-five species were associated with harvest trails, including three old-growth specialists such as Agathidium discoideum (Erichson), currently red-listed. We observed only one species, Xylechinus pilosus (Ratzeburg) that strongly favored retention strips. Harvest trails foster both open habitat species and old-growth species while retention strips harbored forest interior specialists. The combination of closed canopy, stratified forest in the retention strips and gap-like conditions on the harvest trails thus increases overall species richness and maintains more diverse assemblages at the stand level than would otherwise be seen in less heterogeneous stand types. This suggests that uneven-aged silviculture may provide added conservation benefits for both open habitat and old-growth specialists than silvicultural approaches that reduce stand heterogeneity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Incorporating heterogeneity into the transmission dynamics of a waterborne disease model.

    PubMed

    Collins, O C; Govinder, K S

    2014-09-07

    We formulate a mathematical model that captures the essential dynamics of waterborne disease transmission to study the effects of heterogeneity on the spread of the disease. The effects of heterogeneity on some important mathematical features of the model such as the basic reproduction number, type reproduction number and final outbreak size are analysed accordingly. We conduct a real-world application of this model by using it to investigate the heterogeneity in transmission in the recent cholera outbreak in Haiti. By evaluating the measure of heterogeneity between the administrative departments in Haiti, we discover a significant difference in the dynamics of the cholera outbreak between the departments. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Cell-Surface Expression of Neuron-Glial Antigen 2 (NG2) and Melanoma Cell Adhesion Molecule (CD146) in Heterogeneous Cultures of Marrow-Derived Mesenchymal Stem Cells

    PubMed Central

    Russell, Katie C.; Tucker, H. Alan; Bunnell, Bruce A.; Andreeff, Michael; Schober, Wendy; Gaynor, Andrew S.; Strickler, Karen L.; Lin, Shuwen; Lacey, Michelle R.

    2013-01-01

    Cellular heterogeneity of mesenchymal stem cells (MSCs) impedes their use in regenerative medicine. The objective of this research is to identify potential biomarkers for the enrichment of progenitors from heterogeneous MSC cultures. To this end, the present study examines variation in expression of neuron-glial antigen 2 (NG2) and melanoma cell adhesion molecule (CD146) on the surface of MSCs derived from human bone marrow in response to culture conditions and among cell populations. Multipotent cells isolated from heterogeneous MSC cultures exhibit a greater than three-fold increase in surface expression for NG2 and greater than two-fold increase for CD146 as compared with parental and lineage-committed MSCs. For both antigens, surface expression is downregulated by greater than or equal to six-fold when MSCs become confluent. During serial passage, maximum surface expression of NG2 and CD146 is associated with minimum doubling time. Upregulation of NG2 and CD146 during loss of adipogenic potential at early passage suggests some limits to their utility as potency markers. A potential relationship between proliferation and antigen expression was explored by sorting heterogeneous MSCs into rapidly and slowly dividing groups. Fluorescence-activated cell sorting revealed that rapidly dividing MSCs display lower scatter and 50% higher NG2 surface expression than slowly dividing cells, but CD146 expression is comparable in both groups. Heterogeneous MSCs were sorted based on scatter properties and surface expression of NG2 and CD146 into high (HI) and low (LO) groups. ScLONG2HI and ScLONG2HICD146HI MSCs have the highest proliferative potential of the sorted groups, with colony-forming efficiencies that are 1.5–2.2 times the value for the parental controls. The ScLO gate enriches for rapidly dividing cells. Addition of the NG2HI gate increases cell survival to 1.5 times the parental control. Further addition of the CD146HI gate does not significantly improve cell division or survival. The combination of low scatter and high NG2 surface expression is a promising selection criterion to enrich a proliferative phenotype from heterogeneous MSCs during ex vivo expansion, with potentially numerous applications. PMID:23611563

  1. Spatial environmental heterogeneity affects plant growth and thermal performance on a green roof.

    PubMed

    Buckland-Nicks, Michael; Heim, Amy; Lundholm, Jeremy

    2016-05-15

    Green roofs provide ecosystem services, including stormwater retention and reductions in heat transfer through the roof. Microclimates, as well as designed features of green roofs, such as substrate and vegetation, affect the magnitude of these services. Many green roofs are partially shaded by surrounding buildings, but the effects of this within-roof spatial environmental heterogeneity on thermal performance and other ecosystem services have not been examined. We quantified the effects of spatial heterogeneity in solar radiation, substrate depth and other variables affected by these drivers on vegetation and ecosystem services in an extensive green roof. Spatial heterogeneity in substrate depth and insolation were correlated with differential growth, survival and flowering in two focal plant species. These effects were likely driven by the resulting spatial heterogeneity in substrate temperature and moisture content. Thermal performance (indicated by heat flux and substrate temperature) was influenced by spatial heterogeneity in vegetation cover and substrate depth. Areas with less insolation were cooler in summer and had greater substrate moisture, leading to more favorable conditions for plant growth and survival. Spatial variation in substrate moisture (7%-26% volumetric moisture content) and temperature (21°C-36°C) during hot sunny conditions in summer could cause large differences in stormwater retention and heat flux within a single green roof. Shaded areas promote smaller heat fluxes through the roof, leading to energy savings, but lower evapotranspiration in these areas should reduce stormwater retention capacity. Spatial heterogeneity can thus result in trade-offs between different ecosystem services. The effects of these spatial heterogeneities are likely widespread in green roofs. Structures that provide shelter from sun and wind may be productively utilized to design higher functioning green roofs and increase biodiversity by providing habitat heterogeneity. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Triple-effect absorption chiller cycle: A step beyond double-effect cycles

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    DeVault, R.C.

    1990-01-01

    Many advanced'' absorption cycles have been proposed during the current century. Of the hundreds of absorption cycles which have been patented throughout the world, all commercially manufactured products for air conditioning buildings have been variations of just two basic absorption cycles: single-effect and condenser-coupled double-effect cycles. The relatively low cooling coefficients of performance (COPs) inherent in single-effect and double-effect cycles limits the economic applicability of absorption air conditioners (chillers) in the United States. A triple-effect absorption chiller cycle is discussed. This cycle uses two condensers and two absorbers to achieve the triple effect.'' Depending on the absorption fluids selected, thismore » triple-effect cycle is predicted to improve cooling COPs by 18% to 60% compared with the equivalent double-effect cycle. This performance improvement is obtained without increasing the total amount of heat-transfer surface area needed for the heat exchangers. A comparison between the calculated performances of a double-effect cycle and a triple-effect cycle (both using ammonia-water (NH{sub 3}/H{sub 2}O) as the absorption fluid pair) is presented. The triple-effect cycle is predicted to have an 18% higher cooling COP (1.41 compared with 1.2 for a double-effect), lower pressure (47.70 atm (701 psi) instead of 68.05 atm (1000 psi)), significantly reduced pumping power (less than one-half that of the double-effect cycle), and potentially lower construction cost (33% less total heat exchange needed). Practical implications for this triple-effect cycle are discussed. 16 refs., 5 figs., 1 tab.« less

  3. Early double J stent removal in renal transplant patients to prevent urinary tract infection - systematic review and meta-analysis of randomized controlled trials.

    PubMed

    Yahav, Dafna; Green, Hefziba; Eliakim-Raz, Noa; Mor, Eytan; Husain, Shahid

    2018-04-01

    Ureteral stents are routinely used in renal transplant and are associated with reduced urological complications but increased urinary tract infections (UTIs). There is no agreement on the preferred time to removal of stents after transplantation. We performed a systematic review and meta-analysis of all randomized controlled trials (RCTs) comparing stent duration of <14 days vs > =14 days. Electronic databases were searched to identify RCTs that compared early vs late stent removal. Primary outcome was urinary tract infections. Secondary outcomes included various urological complications. No significant difference in UTI rates was demonstrated between short and long stent duration (relative risk (RR) 0.85, 95% confidence interval (CI) 0.44-1.64), with significant heterogeneity (I 2  = 86%). Sensitivity analysis evaluating studies with low risk of bias for allocation concealment demonstrated statistically significant lower rates of UTI with short stent duration (RR 0.48, 95% CI 0.32-0.71) with no heterogeneity. No significant difference was demonstrated for the outcome of major urological complications (RR 0.72, 95% CI 0.50-1.05), without heterogeneity. Ureteral stenosis rates were significantly lower in the short duration arm (RR 0.42, 95% CI 0.18-0.98). Early removal of ureteral stents after renal transplant may be associated with reduced rates of UTI and ureteral stenosis. Additional RCTs are needed.

  4. Evolution of cooperation on complex networks with synergistic and discounted group interactions

    NASA Astrophysics Data System (ADS)

    Zhou, Lei; Li, Aming; Wang, Long

    2015-06-01

    In the real world individuals often engage in group interactions and their payoffs are determined by many factors, including the typical nonlinear interactions, i.e., synergy and discounting. Previous literatures assume that individual payoffs are either synergistically enhanced or discounted with the additional cooperators. Such settings ignore the interplay of these two factors, which is in sharp contrast with the fact that they ubiquitously coexist. Here we investigate how the coexistence and periodical switching of synergistic and discounted group interactions affect the evolution of cooperation on various complex networks. We show that scale-free networks facilitate the emergence of cooperation in terms of fixation probability for group interactions. With nonlinear interactions the heterogeneity of the degree acts as a double-edged sword: below the neutral drift it is the best for cooperation while above the neutral drift it instead provides the least opportunity for cooperators to be fixed. The advantages of the heterogeneity fade as interactive attributes switch between synergy and discounting, which suggests that the heterogeneity of population structures cannot favor cooperators in group interactions even with simple nonlinear interactions. Nonetheless, scale-free networks always guarantee cooperators the fastest rate of fixation. Our work implies that even very simple nonlinear group interactions could greatly shape the fixation probability and fixation time of cooperators in structured populations indicated by complex networks.

  5. The role of spatial and temporal heterogeneity and competition in structuring trematode communities in the great pond snail, Lymnaea stagnalis (L.)

    USGS Publications Warehouse

    Soldánová, Miroslava; Kuris, Armand M.; Scholz, Tomáš; Lafferty, Kevin D.

    2012-01-01

    We assessed how spatial and temporal heterogeneity and competition structure larval trematode communities in the pulmonate snail Lymnaea stagnalis. To postulate a dominance hierarchy, mark-release-recapture was used to monitor replacements of trematode species within snails over time. In addition, we sampled the trematode community in snails in different ponds in 3 consecutive years. A total of 7,623 snails (10,382 capture events) was sampled in 7 fishponds in the Jindřichův Hradec and Třeboň areas in South Bohemia (Czech Republic) from August 2006 to October 2008. Overall, 39% of snails were infected by a community of 14 trematode species; 7% of snails were infected with more than 1 trematode species (constituting 16 double- and 4 triple-species combinations). Results of the null-model analyses suggested that spatial heterogeneity in recruitment among ponds isolated trematode species from each other, whereas seasonal pulses in recruitment increased species interactions in some ponds. Competitive exclusion among trematodes led to a rarity of multiple infections compared to null-model expectations. Competitive relationships among trematode species were hypothesized as a dominance hierarchy based on direct evidence of replacement and invasion and on indirect evidence. Seven top dominant species with putatively similar competitive abilities (6 rediae and 1 sporocyst species) reduced the prevalence of the other trematode species developing in sporocysts only.

  6. Hybrid motion sensing and experimental modal analysis using collocated smartphone camera and accelerometers

    NASA Astrophysics Data System (ADS)

    Ozer, Ekin; Feng, Dongming; Feng, Maria Q.

    2017-10-01

    State-of-the-art multisensory technologies and heterogeneous sensor networks propose a wide range of response measurement opportunities for structural health monitoring (SHM). Measuring and fusing different physical quantities in terms of structural vibrations can provide alternative acquisition methods and improve the quality of the modal testing results. In this study, a recently introduced SHM concept, SHM with smartphones, is focused to utilize multisensory smartphone features for a hybridized structural vibration response measurement framework. Based on vibration testing of a small-scale multistory laboratory model, displacement and acceleration responses are monitored using two different smartphone sensors, an embedded camera and accelerometer, respectively. Double-integration or differentiation among different measurement types is performed to combine multisensory measurements on a comparative basis. In addition, distributed sensor signals from collocated devices are processed for modal identification, and performance of smartphone-based sensing platforms are tested under different configuration scenarios and heterogeneity levels. The results of these tests show a novel and successful implementation of a hybrid motion sensing platform through multiple sensor type and device integration. Despite the heterogeneity of motion data obtained from different smartphone devices and technologies, it is shown that multisensory response measurements can be blended for experimental modal analysis. Getting benefit from the accessibility of smartphone technology, similar smartphone-based dynamic testing methodologies can provide innovative SHM solutions with mobile, programmable, and cost-free interfaces.

  7. Flexibility Matters: Cooperative Active Sites in Covalent Organic Framework and Threaded Ionic Polymer.

    PubMed

    Sun, Qi; Aguila, Briana; Perman, Jason; Nguyen, Nicholas; Ma, Shengqian

    2016-12-07

    The combination of two or more reactive centers working in concert on a substrate to facilitate the reaction is now considered state of the art in catalysis, yet there still remains a tremendous challenge. Few heterogeneous systems of this sort have been exploited, as the active sites spatially separated within the rigid framework are usually difficult to cooperate. It is now shown that this roadblock can be surpassed. The underlying principle of the strategy presented here is the integration of catalytic components with excellent flexibility and porous heterogeneous catalysts, as demonstrated by the placement of linear ionic polymers in close proximity to surface Lewis acid active sites anchored on the walls of a covalent organic framework (COF). Using the cycloaddition of the epoxides and CO 2 as a model reaction, dramatic activity improvements have been achieved for the composite catalysts in relation to the individual catalytic component. Furthermore, they also clearly outperform the benchmark catalytic systems formed by the combination of the molecular organocatalysts and heterogeneous Lewis acid catalysts, while affording additional recyclability. The extraordinary flexibility and enriched concentration of the catalytically active moieties on linear polymers facilitate the concerted catalysis, thus leading to superior catalytic performance. This work therefore uncovers an entirely new strategy for designing bifunctional catalysts with double-activation behavior and opens a new avenue in the design of multicapable systems that mimic biocatalysis.

  8. Fine structure of the retinal photoreceptors of the great horned owl (Bubo virginianus).

    PubMed

    Braekevelt, C R

    1993-01-01

    The retinal photoreceptors of the great horned owl (Bubo virginianus) consist of rods, single cones and unequal double cones present in a ratio of about 30:1.2. In the light-adapted state the rods are stout cells which are not felt to undergo retinomotor movements. The rod outer segment consists of a stack of scalloped membranous discs enclosed by the cell membrane. The rod inner segment shows an ellipsoid of mitochondria and a wealth of rough endoplasmic reticulum (RER) and polysomes, Golgi zones and autophagic vacuoles but not hyperboloid of glycogen. Single cones show a slightly tapered outer segment, a heterogenous oil droplet and an ellipsoid of mitochondria at the apex of the inner segment. Double cones consist of a larger chief member which also displays an oil droplet and a slightly smaller accessory member which does not. Both members of the double cone as well as the single cone show a prominent ellipsoid, plentiful polysomes and RER and Golgi zones in the inner segment. Neither single nor double cones possess a condensed paraboloid of glycogen but instead show plentiful scattered glycogen particles. Along the contiguous membranes between accessory and chief cones a few presumed junctional complexes are seen near the external limiting membrane. Judging by their morphology in light-adaptation the cones of this species do not undergo photomechanical movements. Rods and cones (both types) have both invaginated (ribbon) and numerous superficial (conventional) synaptic sites. Rods are more numerous in this nocturnally active bird than is usually noted in avian species.

  9. Variable synaptic strengths controls the firing rate distribution in feedforward neural networks.

    PubMed

    Ly, Cheng; Marsat, Gary

    2018-02-01

    Heterogeneity of firing rate statistics is known to have severe consequences on neural coding. Recent experimental recordings in weakly electric fish indicate that the distribution-width of superficial pyramidal cell firing rates (trial- and time-averaged) in the electrosensory lateral line lobe (ELL) depends on the stimulus, and also that network inputs can mediate changes in the firing rate distribution across the population. We previously developed theoretical methods to understand how two attributes (synaptic and intrinsic heterogeneity) interact and alter the firing rate distribution in a population of integrate-and-fire neurons with random recurrent coupling. Inspired by our experimental data, we extend these theoretical results to a delayed feedforward spiking network that qualitatively capture the changes of firing rate heterogeneity observed in in-vivo recordings. We demonstrate how heterogeneous neural attributes alter firing rate heterogeneity, accounting for the effect with various sensory stimuli. The model predicts how the strength of the effective network connectivity is related to intrinsic heterogeneity in such delayed feedforward networks: the strength of the feedforward input is positively correlated with excitability (threshold value for spiking) when firing rate heterogeneity is low and is negatively correlated with excitability with high firing rate heterogeneity. We also show how our theory can be used to predict effective neural architecture. We demonstrate that neural attributes do not interact in a simple manner but rather in a complex stimulus-dependent fashion to control neural heterogeneity and discuss how it can ultimately shape population codes.

  10. Landscape heterogeneity-biodiversity relationship: effect of range size.

    PubMed

    Katayama, Naoki; Amano, Tatsuya; Naoe, Shoji; Yamakita, Takehisa; Komatsu, Isamu; Takagawa, Shin-ichi; Sato, Naoto; Ueta, Mutsuyuki; Miyashita, Tadashi

    2014-01-01

    The importance of landscape heterogeneity to biodiversity may depend on the size of the geographic range of species, which in turn can reflect species traits (such as habitat generalization) and the effects of historical and contemporary land covers. We used nationwide bird survey data from Japan, where heterogeneous landscapes predominate, to test the hypothesis that wide-ranging species are positively associated with landscape heterogeneity in terms of species richness and abundance, whereas narrow-ranging species are positively associated with landscape homogeneity in the form of either open or forest habitats. We used simultaneous autoregressive models to explore the effects of climate, evapotranspiration, and landscape heterogeneity on the richness and abundance of breeding land-bird species. The richness of wide-ranging species and the total species richness were highest in heterogeneous landscapes, where many wide-ranging species showed the highest abundance. In contrast, the richness of narrow-ranging species was not highest in heterogeneous landscapes; most of those species were abundant in either open or forest landscapes. Moreover, in open landscapes, narrow-ranging species increased their species richness with decreasing temperature. These results indicate that heterogeneous landscapes are associated with rich bird diversity but that most narrow-ranging species prefer homogeneous landscapes--particularly open habitats in colder regions, where grasslands have historically predominated. There is a need to reassess the generality of the heterogeneity-biodiversity relationship, with attention to the characteristics of species assemblages determined by environments at large spatiotemporal scales.

  11. Firing rate dynamics in recurrent spiking neural networks with intrinsic and network heterogeneity.

    PubMed

    Ly, Cheng

    2015-12-01

    Heterogeneity of neural attributes has recently gained a lot of attention and is increasing recognized as a crucial feature in neural processing. Despite its importance, this physiological feature has traditionally been neglected in theoretical studies of cortical neural networks. Thus, there is still a lot unknown about the consequences of cellular and circuit heterogeneity in spiking neural networks. In particular, combining network or synaptic heterogeneity and intrinsic heterogeneity has yet to be considered systematically despite the fact that both are known to exist and likely have significant roles in neural network dynamics. In a canonical recurrent spiking neural network model, we study how these two forms of heterogeneity lead to different distributions of excitatory firing rates. To analytically characterize how these types of heterogeneities affect the network, we employ a dimension reduction method that relies on a combination of Monte Carlo simulations and probability density function equations. We find that the relationship between intrinsic and network heterogeneity has a strong effect on the overall level of heterogeneity of the firing rates. Specifically, this relationship can lead to amplification or attenuation of firing rate heterogeneity, and these effects depend on whether the recurrent network is firing asynchronously or rhythmically firing. These observations are captured with the aforementioned reduction method, and furthermore simpler analytic descriptions based on this dimension reduction method are developed. The final analytic descriptions provide compact and descriptive formulas for how the relationship between intrinsic and network heterogeneity determines the firing rate heterogeneity dynamics in various settings.

  12. Persistent rupture terminations at a restraining bend from slip rates on the eastern Altyn Tagh fault

    NASA Astrophysics Data System (ADS)

    Elliott, A. J.; Oskin, M. E.; Liu-zeng, J.; Shao, Y.-X.

    2018-05-01

    Restraining double-bends along strike-slip faults inhibit or permit throughgoing ruptures depending on bend angle, length, and prior rupture history. Modeling predicts that for mature strike-slip faults in a regional stress regime characterized by simple shear, a restraining bend of >18° and >4 km length impedes propagating rupture. Indeed, natural evidence shows that the most recent rupture(s) of the Xorkoli section (90°-93°E) of the eastern Altyn Tagh fault (ATF) ended at large restraining bends. However, when multiple seismic cycles are considered in numerical dynamic rupture modeling, heterogeneous residual stresses enable some ruptures to propagate further, modulating whether the bends persistently serve as barriers. These models remain to be tested using observations of the cumulative effects of multiple earthquake ruptures. Here we investigate whether a large restraining double-bend on the ATF serves consistently as a barrier to rupture by measuring long-term slip rates around the terminus of its most recent surface rupture at the Aksay bend. Our results show a W-E decline in slip as the SATF enters the bend, as would be predicted from repeated rupture terminations there. Prior work demonstrated no Holocene slip on the central, most misoriented portion of the bend, while 19-79 m offsets suggest that multiple ruptures have occurred on the west side of the bend during the Holocene. Thus we conclude the gradient in the SATF's slip rate results from the repeated termination of earthquake ruptures there. However, a finite slip rate east of the bend represents the transmission of some slip, suggesting that a small fraction of ruptures may fully traverse or jump the double-bend. This agreement between natural observations of slip accumulation and multi-cycle models of fault rupture enables us to translate observed slip rates into insight about the dynamic rupture process of individual earthquakes as they encounter geometric complexities along faults.

  13. Systematic oxidation of polystyrene by ultraviolet-ozone, characterized by near-edge X-ray absorption fine structure and contact angle.

    PubMed

    Klein, Robert J; Fischer, Daniel A; Lenhart, Joseph L

    2008-08-05

    The process of implanting oxygen in polystyrene (PS) via exposure to ultraviolet-ozone (UV-O) was systematically investigated using the characterization technique of near-edge X-ray absorption fine structure (NEXAFS). Samples of PS exposed to UV-O for 10-300 s and washed with isopropanol were analyzed using the carbon and oxygen K-edge NEXAFS partial electron yields, using various retarding bias voltages to depth-profile the oxygen penetration into the surface. Evaluation of reference polymers provided a scale to quantify the oxygen concentration implanted by UV-O treatment. We find that ozone initially reacts with the double bonds on the phenyl rings, forming carbonyl groups, but within 1 min of exposure, the ratio of double to single oxygen bonds stabilizes at a lower value. Oxygen penetrates the film with relative ease, creating a fairly uniform distribution of oxygen within at least the first 4 nm (the effective depth probed by NEXAFS here). Before oxygen accumulates in large concentrations, however, it preferentially degrades the uppermost layer of the film by removing oxygenated low-molecular-weight oligomers. The failure to accumulate high concentrations of oxygen is seen in the nearly constant carbon edge jump, the low concentration of oxygen even at 5 min exposure (58% of that in poly(4-acetoxystyrene), the polymer with the most similarities to UV-O-treated PS), and the relatively high contact angles. At 5 min exposure the oxygen concentration contains ca. 7 atomic % oxygen. The oxygen species that are implanted consist predominantly of single O-C bonds and double O=C bonds but also include a small fraction of O-H. UV-O treatment leads a plateau after 2 min exposure in the water contact angle hysteresis, at a value of 67 +/- 2 degrees , due primarily to chemical heterogeneity. Annealing above T(g) allows oxygenated species to move short distances away from the surface but not diffuse further than 1-2 nm.

  14. Cost-Effectiveness of Double Reading versus Single Reading of Mammograms in a Breast Cancer Screening Programme

    PubMed Central

    Posso, Margarita; Carles, Misericòrdia; Rué, Montserrat; Puig, Teresa; Bonfill, Xavier

    2016-01-01

    Objectives The usual practice in breast cancer screening programmes for mammogram interpretation is to perform double reading. However, little is known about its cost-effectiveness in the context of digital mammography. Our purpose was to evaluate the cost-effectiveness of double reading versus single reading of digital mammograms in a population-based breast cancer screening programme. Methods Data from 28,636 screened women was used to establish a decision-tree model and to compare three strategies: 1) double reading; 2) double reading for women in their first participation and single reading for women in their subsequent participations; and 3) single reading. We calculated the incremental cost-effectiveness ratio (ICER), which was defined as the expected cost per one additionally detected cancer. We performed a deterministic sensitivity analysis to test the robustness of the ICER. Results The detection rate of double reading (5.17‰) was similar to that of single reading (4.78‰; P = .768). The mean cost of each detected cancer was €8,912 for double reading and €8,287 for single reading. The ICER of double reading versus single reading was €16,684. The sensitivity analysis showed variations in the ICER according to the sensitivity of reading strategies. The strategy that combines double reading in first participation with single reading in subsequent participations was ruled out due to extended dominance. Conclusions From our results, double reading appears not to be a cost-effective strategy in the context of digital mammography. Double reading would eventually be challenged in screening programmes, as single reading might entail important net savings without significantly changing the cancer detection rate. These results are not conclusive and should be confirmed in prospective studies that investigate long-term outcomes like quality adjusted life years (QALYs). PMID:27459663

  15. Meta-analysis of the effectiveness of chronic care management for diabetes: investigating heterogeneity in outcomes.

    PubMed

    Elissen, Arianne M J; Steuten, Lotte M G; Lemmens, Lidwien C; Drewes, Hanneke W; Lemmens, Karin M M; Meeuwissen, Jolanda A C; Baan, Caroline A; Vrijhoef, Hubertus J M

    2013-10-01

    The study aims to support decision making on how best to redesign diabetes care by investigating three potential sources of heterogeneity in effectiveness across trials of diabetes care management. Medline, CINAHL and PsycInfo were searched for systematic reviews and empirical studies focusing on: (1) diabetes mellitus; (2) adult patients; and (3) interventions consisting of at least two components of the chronic care model (CCM). Systematic reviews were analysed descriptively; empirical studies were meta-analysed. Pooled effect measures were estimated using a meta-regression model that incorporated study quality, length of follow-up and number of intervention components as potential predictors of heterogeneity in effects. Overall, reviews (n = 15) of diabetes care programmes report modest improvements in glycaemic control. Empirical studies (n = 61) show wide-ranging results on HbA1c, systolic blood pressure and guideline adherence. Differences between studies in methodological quality cannot explain this heterogeneity in effects. Variety in length of follow-up can explain (part of) the variability, yet not across all outcomes. Diversity in the number of included intervention components can explain 8-12% of the heterogeneity in effects on HbA1c and systolic blood pressure. The outcomes of chronic care management for diabetes are generally positive, yet differ considerably across trials. The most promising results are attained in studies with limited follow-up (<1 year) and by programmes including more than two CCM components. These factors can, however, explain only part of the heterogeneity in effectiveness between studies. Other potential sources of heterogeneity should be investigated to ensure implementation of evidence-based improvements in diabetes care. © 2012 John Wiley & Sons Ltd.

  16. Composite catalyst surfaces: Effect of inert and active heterogeneities on pattern formation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Baer, M.; Bangia, A.K.; Kevrekidis, I.G.

    1996-12-05

    Spatiotemporal dynamics in reaction-diffusion systems can be altered through the properties (reactivity, diffusivity) of the medium in which they occur. We construct active heterogeneous media (composite catalytic surfaces with inert as well as active illusions) using microelectronics fabrication techniques and study the spatiotemporal dynamics of heterogeneous catalytic reactions on these catalysts. In parallel, we perform simulations as well as numerical stability and bifurcation analysis of these patterns using mechanistic models. At the limit of large heterogeneity `grain size` (compared to the wavelength of spontaneously arising structures) the interaction patterns with inert or active boundaries dominates (e.g., pinning, transmission, and boundarymore » breakup of spirals, interaction of pulses with corners, `pacemaker` effects). At the opposite limit of very small or very finely distributed heterogeneity, effective behavior is observed (slight modulation of pulses, nearly uniform oscillations, effective spirals). Some representative studies of transitions between the two limits are presented. 48 refs., 11 figs.« less

  17. Cirrus Heterogeneity Effects on Cloud Optical Properties Retrieved with an Optimal Estimation Method from MODIS VIS to TIR Channels.

    NASA Technical Reports Server (NTRS)

    Fauchez, T.; Platnick, S.; Meyer, K.; Sourdeval, O.; Cornet, C.; Zhang, Z.; Szczap, F.

    2016-01-01

    This study presents preliminary results on the effect of cirrus heterogeneities on top-of-atmosphere (TOA) simulated radiances or reflectances for MODIS channels centered at 0.86, 2.21, 8.56, 11.01 and 12.03 micrometers , and on cloud optical properties retrieved with a research-level optimal estimation method (OEM). Synthetic cirrus cloud fields are generated using a 3D cloud generator (3DCLOUD) and radiances/reflectances are simulated using a 3D radiative transfer code (3DMCPOL). We find significant differences between the heterogeneity effects on either visible and near-infrared (VNIR) or thermal infrared (TIR) radiances. However, when both wavelength ranges are combined, heterogeneity effects are dominated by the VNIR horizontal radiative transport effect. As a result, small optical thicknesses are overestimated and large ones are underestimated. Retrieved effective diameter are found to be slightly affected, contrarily to retrievals using TIR channels only.

  18. Effect of Population Heterogenization on the Reproducibility of Mouse Behavior: A Multi-Laboratory Study

    PubMed Central

    Richter, S. Helene; Garner, Joseph P.; Zipser, Benjamin; Lewejohann, Lars; Sachser, Norbert; Touma, Chadi; Schindler, Britta; Chourbaji, Sabine; Brandwein, Christiane; Gass, Peter; van Stipdonk, Niek; van der Harst, Johanneke; Spruijt, Berry; Võikar, Vootele; Wolfer, David P.; Würbel, Hanno

    2011-01-01

    In animal experiments, animals, husbandry and test procedures are traditionally standardized to maximize test sensitivity and minimize animal use, assuming that this will also guarantee reproducibility. However, by reducing within-experiment variation, standardization may limit inference to the specific experimental conditions. Indeed, we have recently shown in mice that standardization may generate spurious results in behavioral tests, accounting for poor reproducibility, and that this can be avoided by population heterogenization through systematic variation of experimental conditions. Here, we examined whether a simple form of heterogenization effectively improves reproducibility of test results in a multi-laboratory situation. Each of six laboratories independently ordered 64 female mice of two inbred strains (C57BL/6NCrl, DBA/2NCrl) and examined them for strain differences in five commonly used behavioral tests under two different experimental designs. In the standardized design, experimental conditions were standardized as much as possible in each laboratory, while they were systematically varied with respect to the animals' test age and cage enrichment in the heterogenized design. Although heterogenization tended to improve reproducibility by increasing within-experiment variation relative to between-experiment variation, the effect was too weak to account for the large variation between laboratories. However, our findings confirm the potential of systematic heterogenization for improving reproducibility of animal experiments and highlight the need for effective and practicable heterogenization strategies. PMID:21305027

  19. Fine-Scale Habitat Heterogeneity Influences Occupancy in Terrestrial Mammals in a Temperate Region of Australia

    PubMed Central

    Stirnemann, Ingrid; Mortelliti, Alessio; Gibbons, Philip; Lindenmayer, David B.

    2015-01-01

    Vegetation heterogeneity is an inherent feature of most ecosystems, characterises the structure of habitat, and is considered an important driver of species distribution patterns. However, quantifying fine-scale heterogeneity of vegetation cover can be time consuming, and therefore it is seldom measured. Here, we determine if heterogeneity is worthwhile measuring, in addition to the amount of cover, when examining species distribution patterns. Further, we investigated the effect of the surrounding landscape heterogeneity on species occupancy. We tested the effect of cover and heterogeneity of trees and shrubs, and the context of the surrounding landscape (number of habitats and distance to an ecotone) on site occupancy of three mammal species (the black wallaby [Wallabia bicolor], the long-nosed bandicoot [Perameles nasuta], and the bush rat [Rattus fuscipes]) within a naturally heterogeneous landscape in a temperate region of Australia. We found that fine-scale heterogeneity of vegetation attributes is an important driver of mammal occurrence of two of these species. Further, we found that, although all three species responded positively to vegetation heterogeneity, different mammals vary in their response to different types of vegetation heterogeneity measurement. For example, the black wallaby responded to the proximity of an ecotone, and the bush rat and the long-nosed bandicoot responded to fine-scale heterogeneity of small tree cover, whereas none of the mammals responded to broad scale heterogeneity (i.e., the number of habitat types). Our results highlight the influence of methodological decisions, such as how heterogeneity vegetation is measured, in quantifying species responses to habitat structures. The findings confirm the importance of choosing meaningful heterogeneity measures when modelling the factors influencing occupancy of the species of interest. PMID:26394327

  20. Contagion on complex networks with persuasion

    NASA Astrophysics Data System (ADS)

    Huang, Wei-Min; Zhang, Li-Jie; Xu, Xin-Jian; Fu, Xinchu

    2016-03-01

    The threshold model has been widely adopted as a classic model for studying contagion processes on social networks. We consider asymmetric individual interactions in social networks and introduce a persuasion mechanism into the threshold model. Specifically, we study a combination of adoption and persuasion in cascading processes on complex networks. It is found that with the introduction of the persuasion mechanism, the system may become more vulnerable to global cascades, and the effects of persuasion tend to be more significant in heterogeneous networks than those in homogeneous networks: a comparison between heterogeneous and homogeneous networks shows that under weak persuasion, heterogeneous networks tend to be more robust against random shocks than homogeneous networks; whereas under strong persuasion, homogeneous networks are more stable. Finally, we study the effects of adoption and persuasion threshold heterogeneity on systemic stability. Though both heterogeneities give rise to global cascades, the adoption heterogeneity has an overwhelmingly stronger impact than the persuasion heterogeneity when the network connectivity is sufficiently dense.

  1. Contagion on complex networks with persuasion

    PubMed Central

    Huang, Wei-Min; Zhang, Li-Jie; Xu, Xin-Jian; Fu, Xinchu

    2016-01-01

    The threshold model has been widely adopted as a classic model for studying contagion processes on social networks. We consider asymmetric individual interactions in social networks and introduce a persuasion mechanism into the threshold model. Specifically, we study a combination of adoption and persuasion in cascading processes on complex networks. It is found that with the introduction of the persuasion mechanism, the system may become more vulnerable to global cascades, and the effects of persuasion tend to be more significant in heterogeneous networks than those in homogeneous networks: a comparison between heterogeneous and homogeneous networks shows that under weak persuasion, heterogeneous networks tend to be more robust against random shocks than homogeneous networks; whereas under strong persuasion, homogeneous networks are more stable. Finally, we study the effects of adoption and persuasion threshold heterogeneity on systemic stability. Though both heterogeneities give rise to global cascades, the adoption heterogeneity has an overwhelmingly stronger impact than the persuasion heterogeneity when the network connectivity is sufficiently dense. PMID:27029498

  2. Contagion on complex networks with persuasion.

    PubMed

    Huang, Wei-Min; Zhang, Li-Jie; Xu, Xin-Jian; Fu, Xinchu

    2016-03-31

    The threshold model has been widely adopted as a classic model for studying contagion processes on social networks. We consider asymmetric individual interactions in social networks and introduce a persuasion mechanism into the threshold model. Specifically, we study a combination of adoption and persuasion in cascading processes on complex networks. It is found that with the introduction of the persuasion mechanism, the system may become more vulnerable to global cascades, and the effects of persuasion tend to be more significant in heterogeneous networks than those in homogeneous networks: a comparison between heterogeneous and homogeneous networks shows that under weak persuasion, heterogeneous networks tend to be more robust against random shocks than homogeneous networks; whereas under strong persuasion, homogeneous networks are more stable. Finally, we study the effects of adoption and persuasion threshold heterogeneity on systemic stability. Though both heterogeneities give rise to global cascades, the adoption heterogeneity has an overwhelmingly stronger impact than the persuasion heterogeneity when the network connectivity is sufficiently dense.

  3. Effects of capillary heterogeneity on vapor-liquid counterflow in porous media

    NASA Astrophysics Data System (ADS)

    Stubos, A. K.; Satik, C.; Yortsos, Y. C.

    1992-06-01

    Based on a continuum description, the effect of capillary heterogeneity, induced by variation in permeability, on the steady state, countercurrent, vapor-liquid flow in porous media is analyzed. It is shown that the heterogeneity acts as a body force that may enhance or diminish gravity effects on heat pipes. Selection rules that determine the steady states reached in homogeneous, gravity-driven heat pipes are also formulated. It is shown that the 'infinite' two-phase zone may terminate by a substantial change in the permeability somewhere in the medium. The two possible sequences, liquid-liquid dominated-dry, or liquid-vapor dominated-dry find applications in geothermal systems. Finally, it is shown that although weak heterogeneity affects only gravity controlled flows, stronger variations in permeability can give rise to significant capillary effects.

  4. Solving global shallow water equations on heterogeneous supercomputers

    PubMed Central

    Fu, Haohuan; Gan, Lin; Yang, Chao; Xue, Wei; Wang, Lanning; Wang, Xinliang; Huang, Xiaomeng; Yang, Guangwen

    2017-01-01

    The scientific demand for more accurate modeling of the climate system calls for more computing power to support higher resolutions, inclusion of more component models, more complicated physics schemes, and larger ensembles. As the recent improvements in computing power mostly come from the increasing number of nodes in a system and the integration of heterogeneous accelerators, how to scale the computing problems onto more nodes and various kinds of accelerators has become a challenge for the model development. This paper describes our efforts on developing a highly scalable framework for performing global atmospheric modeling on heterogeneous supercomputers equipped with various accelerators, such as GPU (Graphic Processing Unit), MIC (Many Integrated Core), and FPGA (Field Programmable Gate Arrays) cards. We propose a generalized partition scheme of the problem domain, so as to keep a balanced utilization of both CPU resources and accelerator resources. With optimizations on both computing and memory access patterns, we manage to achieve around 8 to 20 times speedup when comparing one hybrid GPU or MIC node with one CPU node with 12 cores. Using a customized FPGA-based data-flow engines, we see the potential to gain another 5 to 8 times improvement on performance. On heterogeneous supercomputers, such as Tianhe-1A and Tianhe-2, our framework is capable of achieving ideally linear scaling efficiency, and sustained double-precision performances of 581 Tflops on Tianhe-1A (using 3750 nodes) and 3.74 Pflops on Tianhe-2 (using 8644 nodes). Our study also provides an evaluation on the programming paradigm of various accelerator architectures (GPU, MIC, FPGA) for performing global atmospheric simulation, to form a picture about both the potential performance benefits and the programming efforts involved. PMID:28282428

  5. Combined effects of waggle dance communication and landscape heterogeneity on nectar and pollen uptake in honey bee colonies

    PubMed Central

    Steffan-Dewenter, Ingolf; Härtel, Stephan

    2017-01-01

    The instructive component of waggle dance communication has been shown to increase resource uptake of Apis mellifera colonies in highly heterogeneous resource environments, but an assessment of its relevance in temperate landscapes with different levels of resource heterogeneity is currently lacking. We hypothesized that the advertisement of resource locations via dance communication would be most relevant in highly heterogeneous landscapes with large spatial variation of floral resources. To test our hypothesis, we placed 24 Apis mellifera colonies with either disrupted or unimpaired instructive component of dance communication in eight Central European agricultural landscapes that differed in heterogeneity and resource availability. We monitored colony weight change and pollen harvest as measure of foraging success. Dance disruption did not significantly alter colony weight change, but decreased pollen harvest compared to the communicating colonies by 40%. There was no general effect of resource availability on nectar or pollen foraging success, but the effect of landscape heterogeneity on nectar uptake was stronger when resource availability was high. In contrast to our hypothesis, the effects of disrupted bee communication on nectar and pollen foraging success were not stronger in landscapes with heterogeneous compared to homogenous resource environments. Our results indicate that in temperate regions intra-colonial communication of resource locations benefits pollen foraging more than nectar foraging, irrespective of landscape heterogeneity. We conclude that the so far largely unexplored role of dance communication in pollen foraging requires further consideration as pollen is a crucial resource for colony development and health. PMID:28603677

  6. Effect of shoulder abduction angle on biomechanical properties of the repaired rotator cuff tendons with 3 types of double-row technique.

    PubMed

    Mihata, Teruhisa; Fukuhara, Tetsutaro; Jun, Bong Jae; Watanabe, Chisato; Kinoshita, Mitsuo

    2011-03-01

    After rotator cuff repair, the shoulder is immobilized in various abduction positions. However, there is no consensus on the proper abduction angle. To assess the effect of shoulder abduction angle on the biomechanical properties of the repaired rotator cuff tendons among 3 types of double-row techniques. Controlled laboratory study. Thirty-two fresh-frozen porcine shoulders were used. A simulated rotator cuff tear was repaired by 1 of 3 double-row techniques: conventional double-row repair, transosseous-equivalent repair, and a combination of conventional double-row and bridging sutures (compression double-row repair). Each specimen underwent cyclic testing followed by tensile testing to failure at a simulated shoulder abduction angle of 0° or 40° on a material testing machine. Gap formation and failure loads were measured. Gap formation in conventional double-row repair at 0° (1.2 ± 0.5 mm) was significantly greater than that at 40° (0.5 ± 0.3mm, P = .01). The yield and ultimate failure loads for conventional double-row repair at 40° were significantly larger than those at 0° (P < .01), whereas those for transosseous-equivalent repair (P < .01) and compression double-row repair (P < .0001) at 0° were significantly larger than those at 40°. The failure load for compression double-row repair was the greatest among the 3 double-row techniques at both 0° and 40° of abduction. Bridging sutures have a greater effect on the biomechanical properties of the repaired rotator cuff tendon at a low abduction angle, and the conventional double-row technique has a greater effect at a high abduction angle. Proper abduction position after rotator cuff repair differs between conventional double-row repair and transosseous-equivalent repair. The authors recommend the use of the combined technique of conventional double-row and bridging sutures to obtain better biomechanical properties at both low and high abduction angles.

  7. Dissecting cancer evolution at the macro-heterogeneity and micro-heterogeneity scale.

    PubMed

    Barber, Louise J; Davies, Matthew N; Gerlinger, Marco

    2015-02-01

    Intratumour heterogeneity complicates biomarker discovery and treatment personalization, and pervasive cancer evolution is a key mechanism leading to therapy failure and patient death. Thus, understanding subclonal heterogeneity architectures and cancer evolution processes is critical for the development of effective therapeutic approaches which can control or thwart cancer evolutionary plasticity. Current insights into heterogeneity are mainly limited to the macroheterogeneity level, established by cancer subclones that have undergone significant clonal expansion. Novel single cell sequencing and blood-based subclonal tracking technologies are enabling detailed insights into microheterogeneity and the dynamics of clonal evolution. We assess how this starts to delineate the rules governing cancer evolution and novel angles for more effective therapeutic intervention. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Methodologies and systems for heterogeneous concurrent computing

    NASA Technical Reports Server (NTRS)

    Sunderam, V. S.

    1994-01-01

    Heterogeneous concurrent computing is gaining increasing acceptance as an alternative or complementary paradigm to multiprocessor-based parallel processing as well as to conventional supercomputing. While algorithmic and programming aspects of heterogeneous concurrent computing are similar to their parallel processing counterparts, system issues, partitioning and scheduling, and performance aspects are significantly different. In this paper, we discuss critical design and implementation issues in heterogeneous concurrent computing, and describe techniques for enhancing its effectiveness. In particular, we highlight the system level infrastructures that are required, aspects of parallel algorithm development that most affect performance, system capabilities and limitations, and tools and methodologies for effective computing in heterogeneous networked environments. We also present recent developments and experiences in the context of the PVM system and comment on ongoing and future work.

  9. Pharmacological interventions for self-injurious behaviour in adults with intellectual disabilities: Abridged republication of a Cochrane systematic review.

    PubMed

    Gormez, A; Rana, F; Varghese, S

    2014-07-01

    We aimed to determine clinical effectiveness of pharmacological interventions for self-injurious behaviour in adults with intellectual disability. We searched the following databases: CENTRAL; MEDLINE; EMBASE; PsycINFO; CINAHL; SCI; SSCI; Conference Proceedings Citation Index - Science; Conference Proceedings Citation Index - Social Science and Humanities; ZETOC; World Cat .We also searched ClinicalTrials.gov,ICTRP and the reference lists of included trials. We included randomised controlled trials that examined drug interventions versus placebo for self-injurious behaviour. We found five double-blind, placebo-controlled trials, which included a total of 50 people. Four trials compared the effects of naltrexone versus placebo and one trial clomipramine versus placebo. We did not identify any relevant placebo-controlled trials for other drugs. We presented a narrative summary, as meta-analysis was not appropriate due to differences in study designs, differences between interventions and heterogeneous outcome measures. There was weak evidence in included trials that any active drug was more effective than placebo for people with intellectual disability demonstrating self-injurious behaviour. Due to sparse data, an absence of power and statistical significance, and high risk of bias for four of the included trials, we are unable to reach any definite conclusions about the relative benefits of naltrexone or clomipramine compared to placebo. © The Author(s) 2014.

  10. Elaborate Manipulation for Sub-10 nm Hollow Catalyst Sensitized Heterogeneous Oxide Nanofibers for Room Temperature Chemical Sensors.

    PubMed

    Jang, Ji-Soo; Choi, Seon-Jin; Koo, Won-Tae; Kim, Sang-Joon; Cheong, Jun Young; Kim, Il-Doo

    2017-07-26

    Room-temperature (RT) operation sensors are constantly in increasing demand because of their low power consumption, simple operation, and long lifetime. However, critical challenges such as low sensing performance, vulnerability under highly humid state, and poor recyclability hinder their commercialization. In this work, sub-10 nm hollow, bimetallic Pt-Ag nanoparticles (NPs) were successfully formed by galvanic replacement reaction in bioinspired hollow protein templates and sensitized on the multidimensional SnO 2 -WO 3 heterojunction nanofibers (HNFs). Formation of hollow, bimetallic NPs resulted in the double-side catalytic effect, rendering both surface and inner side chemical reactions. Subsequently, SnO 2 -WO 3 HNFs were synthesized by incorporating 2D WO 3 nanosheets (NSs) with 0D SnO 2 sphere by c-axis growth inhibition effect and fluid dynamics of liquid Sn during calcination. Hierarchically assembled HNFs effectively modulate surface depletion layer of 2D WO 3 NSs by electron transfers from WO 3 to SnO 2 stemming from creation of heterojunction. Careful combination of bimetallic catalyst NPs with HNFs provided an extreme recyclability under exhaled breath (95 RH%) with outstanding H 2 S sensitivity. Such sensing platform clearly distinguished between the breath of healthy people and simulated halitosis patients.

  11. Predicting the extent of heterogeneity in meta-analysis, using empirical data from the Cochrane Database of Systematic Reviews

    PubMed Central

    Turner, Rebecca M; Davey, Jonathan; Clarke, Mike J; Thompson, Simon G; Higgins, Julian PT

    2012-01-01

    Background Many meta-analyses contain only a small number of studies, which makes it difficult to estimate the extent of between-study heterogeneity. Bayesian meta-analysis allows incorporation of external evidence on heterogeneity, and offers advantages over conventional random-effects meta-analysis. To assist in this, we provide empirical evidence on the likely extent of heterogeneity in particular areas of health care. Methods Our analyses included 14 886 meta-analyses from the Cochrane Database of Systematic Reviews. We classified each meta-analysis according to the type of outcome, type of intervention comparison and medical specialty. By modelling the study data from all meta-analyses simultaneously, using the log odds ratio scale, we investigated the impact of meta-analysis characteristics on the underlying between-study heterogeneity variance. Predictive distributions were obtained for the heterogeneity expected in future meta-analyses. Results Between-study heterogeneity variances for meta-analyses in which the outcome was all-cause mortality were found to be on average 17% (95% CI 10–26) of variances for other outcomes. In meta-analyses comparing two active pharmacological interventions, heterogeneity was on average 75% (95% CI 58–95) of variances for non-pharmacological interventions. Meta-analysis size was found to have only a small effect on heterogeneity. Predictive distributions are presented for nine different settings, defined by type of outcome and type of intervention comparison. For example, for a planned meta-analysis comparing a pharmacological intervention against placebo or control with a subjectively measured outcome, the predictive distribution for heterogeneity is a log-normal (−2.13, 1.582) distribution, which has a median value of 0.12. In an example of meta-analysis of six studies, incorporating external evidence led to a smaller heterogeneity estimate and a narrower confidence interval for the combined intervention effect. Conclusions Meta-analysis characteristics were strongly associated with the degree of between-study heterogeneity, and predictive distributions for heterogeneity differed substantially across settings. The informative priors provided will be very beneficial in future meta-analyses including few studies. PMID:22461129

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

    NASA Astrophysics Data System (ADS)

    Negi, Vineet

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

  13. Effect of chemical and physical heterogeneities on colloid-facilitated cesium transport

    NASA Astrophysics Data System (ADS)

    Rod, Kenton; Um, Wooyong; Chun, Jaehun; Wu, Ning; Yin, Xialong; Wang, Guohui; Neeves, Keith

    2018-06-01

    A set of column experiments was conducted to investigate the chemical and physical heterogeneity effect on colloid facilitated transport under slow pore velocity conditions. Pore velocities were kept below 100 cm d-1 for all experiments. Glass beads were packed into columns establishing four different conditions: 1) homogeneous, 2) mixed physical heterogeneity, 3) sequentially layered physical heterogeneity, and 4) chemical heterogeneity. The homogeneous column was packed with glass beads (diameter 500-600 μm), and physical heterogeneities were created by sequential layering or mixing two sizes of glass bead (500-600 μm and 300-400 μm). A chemical heterogeneity was created using 25% of the glass beads coated with hydrophobic molecules (1H-1H-2H-2H-perfluorooctyltrichlorosilane) mixed with 75% pristine glass beads (all 500-600 μm). Input solution with 0.5 mM CsI and 50 mg L-1 colloids (1-μm diameter SiO2) was pulsed into columns under saturated conditions. The physical heterogeneity in the packed glass beads retarded the transport of colloids compared to homogeneous (R = 25.0), but showed only slight differences between sequentially layered (R = 60.7) and mixed heterogeneity(R = 62.4). The column with the chemical, hydrophobic/hydrophilic, heterogeneity removed most of the colloids from the input solution. All column conditions stripped Cs from colloids onto the column matrix of packed glass beads.

  14. 369 TFlop/s molecular dynamics simulations on the Roadrunner general-purpose heterogeneous supercomputer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Swaminarayan, Sriram; Germann, Timothy C; Kadau, Kai

    2008-01-01

    The authors present timing and performance numbers for a short-range parallel molecular dynamics (MD) code, SPaSM, that has been rewritten for the heterogeneous Roadrunner supercomputer. Each Roadrunner compute node consists of two AMD Opteron dual-core microprocessors and four PowerXCell 8i enhanced Cell microprocessors, so that there are four MPI ranks per node, each with one Opteron and one Cell. The interatomic forces are computed on the Cells (each with one PPU and eight SPU cores), while the Opterons are used to direct inter-rank communication and perform I/O-heavy periodic analysis, visualization, and checkpointing tasks. The performance measured for our initial implementationmore » of a standard Lennard-Jones pair potential benchmark reached a peak of 369 Tflop/s double-precision floating-point performance on the full Roadrunner system (27.7% of peak), corresponding to 124 MFlop/Watt/s at a price of approximately 3.69 MFlops/dollar. They demonstrate an initial target application, the jetting and ejection of material from a shocked surface.« less

  15. Heterogeneous Coordination Environments in Lithium-Neutralized Ionomers Identified Using 1H and 7Li MAS NMR

    PubMed Central

    Alam, Todd M.; Jenkins, Janelle E.; Bolintineanu, Dan S.; Stevens, Mark J.; Frischknecht, Amalie L.; Buitrago, C. Francisco; Winey, Karen I.; Opper, Kathleen L.; Wagener, Kenneth B.

    2012-01-01

    The carboxylic acid proton and the lithium coordination environments for precise and random Li-neutralized polyethylene acrylic acid P(E-AA) ionomers were explored using high speed solid-state 1H and 7Li MAS NMR. While the 7Li NMR revealed only a single Li coordination environment, the chemical shift temperature variation was dependent on the precise or random nature of the P(E-AA) ionomer. The 1H MAS NMR revealed two different carboxylic acid proton environments in these materials. By utilizing 1H-7Li rotational echo double resonance (REDOR) MAS NMR experiments, it was demonstrated that the proton environments correspond to different average 1H-7Li distances, with the majority of the protonated carboxylic acids having a close through space contact with the Li. Molecular dynamics simulations suggest that the shortest 1H-7Li distance corresponds to un-neutralized carboxylic acids directly involved in the coordination environment of Li clusters. These solid-state NMR results show that heterogeneous structural motifs need to be included when developing descriptions of these ionomer materials.

  16. Nontoxic chemical process for in situ permeability enhancement and accelerated decontamination of fine-grain subsurface sediments

    DOEpatents

    Kansa, E.J.; Wijesinghe, A.M.; Viani, B.E.

    1997-01-14

    The remediation of heterogeneous subsurfaces is extremely time consuming and expensive with current and developing technologies. Although such technologies can adequately remove contaminants in the high hydraulic conductivity, coarse-grained sediments, they cannot access the contaminated low hydraulic conductivity fine-grained sediments. The slow bleed of contaminants from the fine-grained sediments is the primary reason why subsurface remediation is so time-consuming and expensive. This invention addresses the problem of remediating contaminated fine-grained sediments. It is intended that, in the future, a heterogeneous site be treated by a hybrid process that first remediates the high hydraulic conductivity, coarse-grained sediments, to be followed by the process, described in this invention, to treat the contaminated low hydraulic conductivity fine-grained sediments. The invention uses cationic flocculants and organic solvents to collapse the swelling negative double layer surrounding water saturated clay particles, causing a flocculated, cracked clay structure. The modification of the clay fabric in fine-grained sediments dramatically increases the hydraulic conductivity of previously very tight clays many orders of magnitude. 8 figs.

  17. Nontoxic chemical process for in situ permeability enhancement and accelerated decontamination of fine-grain subsurface sediments

    DOEpatents

    Kansa, Edward J.; Wijesinghe, Ananda M.; Viani, Brian E.

    1997-01-01

    The remediation of heterogeneous subsurfaces is extremely time consuming and expensive with current and developing technologies. Although such technologies can adequately remove contaminants in the high hydraulic conductivity, coarse-grained sediments, they cannot access the contaminated low hydraulic conductivity fine-grained sediments. The slow bleed of contaminants from the fine-grained sediments is the primary reason why subsurface remediation is so time-consuming and expensive. This invention addresses the problem of remediating contaminated fine-grained sediments. It is intended that, in the future, a heterogeneous site be treated by a hybrid process that first remediates the high hydraulic conductivity, coarse-grained sediments, to be followed by the process, described in this invention, to treat the contaminated low hydraulic conductivity fine-grained sediments. The invention uses cationic flocculents and organic solvents to collapse the swelling negative double layer surrounding water saturated clay particles, causing a flocculated, cracked clay structure. The modification of the clay fabric in fine-grained sediments dramatically increases the hydraulic conductivity of previously very tight clays many orders of magnitude.

  18. Effects of Fiber Type and Size on the Heterogeneity of Oxygen Distribution in Exercising Skeletal Muscle

    PubMed Central

    Liu, Gang; Mac Gabhann, Feilim; Popel, Aleksander S.

    2012-01-01

    The process of oxygen delivery from capillary to muscle fiber is essential for a tissue with variable oxygen demand, such as skeletal muscle. Oxygen distribution in exercising skeletal muscle is regulated by convective oxygen transport in the blood vessels, oxygen diffusion and consumption in the tissue. Spatial heterogeneities in oxygen supply, such as microvascular architecture and hemodynamic variables, had been observed experimentally and their marked effects on oxygen exchange had been confirmed using mathematical models. In this study, we investigate the effects of heterogeneities in oxygen demand on tissue oxygenation distribution using a multiscale oxygen transport model. Muscles are composed of different ratios of the various fiber types. Each fiber type has characteristic values of several parameters, including fiber size, oxygen consumption, myoglobin concentration, and oxygen diffusivity. Using experimentally measured parameters for different fiber types and applying them to the rat extensor digitorum longus muscle, we evaluated the effects of heterogeneous fiber size and fiber type properties on the oxygen distribution profile. Our simulation results suggest a marked increase in spatial heterogeneity of oxygen due to fiber size distribution in a mixed muscle. Our simulations also suggest that the combined effects of fiber type properties, except size, do not contribute significantly to the tissue oxygen spatial heterogeneity. However, the incorporation of the difference in oxygen consumption rates of different fiber types alone causes higher oxygen heterogeneity compared to control cases with uniform fiber properties. In contrast, incorporating variation in other fiber type-specific properties, such as myoglobin concentration, causes little change in spatial tissue oxygenation profiles. PMID:23028531

  19. Uranium (VI) transport in saturated heterogeneous media: Influence of kaolinite and humic acid.

    PubMed

    Chen, Chong; Zhao, Kang; Shang, Jianying; Liu, Chongxuan; Wang, Jin; Yan, Zhifeng; Liu, Kesi; Wu, Wenliang

    2018-05-07

    Natural aquifers typically exhibit a variety of structural heterogeneities. However, the effect of mineral colloids and natural organic matter on the transport behavior of uranium (U) in saturated heterogeneous media are not totally understood. In this study, heterogeneous column experiments were conducted, and the constructed columns contained a fast-flow domain (FFD) and a slow-flow domain (SFD). The effect of kaolinite, humic acid (HA), and kaolinite/HA mixture on U(VI) retention and release in saturated heterogeneous media was examined. Media heterogeneity significantly influenced U fate and transport behavior in saturated subsurface environment. The presence of kaolinite, HA, and kaolinite/HA enhanced the mobility of U in heterogeneous media, and the mobility of U was the highest in the presence of kaolinite/HA and the lowest in the presence of kaolinite. In the presence of kaolinite, there was no difference in the amount of U released from the FFD and SFD. However, in the presence of HA and kaolinite/HA, a higher amount of U was released from the FFD. The findings in this study showed that medium structure and mineral colloids, as well as natural organic matter in the aqueous phase had significant effects on U transport and fate in subsurface environment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Habitat heterogeneity hypothesis and edge effects in model metacommunities.

    PubMed

    Hamm, Michaela; Drossel, Barbara

    2017-08-07

    Spatial heterogeneity is an inherent property of any living environment and is expected to favour biodiversity due to a broader niche space. Furthermore, edges between different habitats can provide additional possibilities for species coexistence. Using computer simulations, this study examines metacommunities consisting of several trophic levels in heterogeneous environments in order to explore the above hypotheses on a community level. We model heterogeneous landscapes by using two different sized resource pools and evaluate the combined effect of dispersal and heterogeneity on local and regional species diversity. This diversity is obtained by running population dynamics and evaluating the robustness (i.e., the fraction of surviving species). The main results for regional robustness are in agreement with the habitat heterogeneity hypothesis, as the largest robustness is found in heterogeneous systems with intermediate dispersal rates. This robustness is larger than in homogeneous systems with the same total amount of resources. We study the edge effect by arranging the two types of resources in two homogeneous blocks. Different edge responses in diversity are observed, depending on dispersal strength. Local robustness is highest for edge habitats that contain the smaller amount of resource in combination with intermediate dispersal. The results show that dispersal is relevant to correctly identify edge responses on community level. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Cosmic Microwave Background Observations with a Compact Heterogeneous 150 GHz Interferometer in Chile

    NASA Astrophysics Data System (ADS)

    Fowler, J. W.; Doriese, W. B.; Marriage, T. A.; Tran, H. T.; Aboobaker, A. M.; Dumont, C.; Halpern, M.; Kermish, Z. D.; Loh, Y.-S.; Page, L. A.; Staggs, S. T.; Wesley, D. H.

    2005-01-01

    We report on the design, first observing season, and analysis of data from a new prototype millimeter-wave interferometer, MINT. MINT consists of four 145 GHz SIS mixers operating in double-sideband mode in a compact heterogeneous configuration. The signal band is subdivided by a monolithic channelizer, after which the correlations between antennas are performed digitally. The typical receiver sensitivity in a 2 GHz band is 1.4 mK s1/2. The primary beams are 0.45d and 0.30d FWHM, with fringe spacing as small as 0.1d. MINT observed the cosmic microwave background (CMB) from Cerro Toco, in the Chilean Altiplano. The site quality at 145 GHz is good, with median nighttime atmospheric temperature of 9 K at zenith (exclusive of the CMB). Repeated observations of Mars, Jupiter, and a telescope-mounted calibration source establish the phase and magnitude stability of the system. MINT is the first interferometer dedicated to CMB studies to operate above 50 GHz. The same type of system can be used to probe the Sunyaev-Zel'dovich effect in galaxy clusters near the SZ null at 217 GHz. We give the essential features of MINT and present an analysis of sideband-separated, digitally sampled data recorded by the array. Based on 215 hours of data taken in late 2001, we set an upper limit on the CMB anisotropy in a band of width Δl=700 around l=1540 of δT<105 μK (95% confidence). Increased sensitivity can be achieved with more integration time, greater bandwidth, and more elements.

  2. Digenic retinitis pigmentosa due to mutations at the unlinked peripherin/RDS and ROM1 loci

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kajiwara, K.; Berson, E.L.; Dryja, T.P.

    1994-06-10

    In spite of recent advances in identifying genes causing monogenic human disease, very little is known about the genes involved in polygenic disease. Three families were identified with mutations in the unlinked photoreceptor-specific genes ROM 1 and peripherin/RDS, in which only double heterozygotes develop retinitis pigmentosa (RP). These findings indicate that the allelic and nonallelic heterogeneity known to be a feature of monogenic RP is complicated further by interactions between unlinked mutations causing digenic RP. Recognition of the inheritance pattern exemplified by these three families might facilitate the identification of other examples of digenic inheritance in human disease.

  3. Dynamics of the DNA damage response: insights from live-cell imaging

    PubMed Central

    Karanam, Ketki; Loewer, Alexander

    2013-01-01

    All organisms have to safeguard the integrity of their genome to prevent malfunctioning and oncogenic transformation. Sophisticated DNA damage response mechanisms have evolved to detect and repair genomic lesions. With the emergence of live-cell microscopy of individual cells, we now begin to appreciate the complex spatiotemporal kinetics of the DNA damage response and can address the causes and consequences of the heterogeneity in the responses of genetically identical cells. Here, we highlight key discoveries where live-cell imaging has provided unprecedented insights into how cells respond to DNA double-strand breaks and discuss the main challenges and promises in using this technique. PMID:23292635

  4. Label-free hyperspectral dark-field microscopy for quantitative scatter imaging

    NASA Astrophysics Data System (ADS)

    Cheney, Philip; McClatchy, David; Kanick, Stephen; Lemaillet, Paul; Allen, David; Samarov, Daniel; Pogue, Brian; Hwang, Jeeseong

    2017-03-01

    A hyperspectral dark-field microscope has been developed for imaging spatially distributed diffuse reflectance spectra from light-scattering samples. In this report, quantitative scatter spectroscopy is demonstrated with a uniform scattering phantom, namely a solution of polystyrene microspheres. A Monte Carlo-based inverse model was used to calculate the reduced scattering coefficients of samples of different microsphere concentrations from wavelength-dependent backscattered signal measured by the dark-field microscope. The results are compared to the measurement results from a NIST double-integrating sphere system for validation. Ongoing efforts involve quantitative mapping of scattering and absorption coefficients in samples with spatially heterogeneous optical properties.

  5. Quantifying the impact of between-study heterogeneity in multivariate meta-analyses

    PubMed Central

    Jackson, Dan; White, Ian R; Riley, Richard D

    2012-01-01

    Measures that quantify the impact of heterogeneity in univariate meta-analysis, including the very popular I2 statistic, are now well established. Multivariate meta-analysis, where studies provide multiple outcomes that are pooled in a single analysis, is also becoming more commonly used. The question of how to quantify heterogeneity in the multivariate setting is therefore raised. It is the univariate R2 statistic, the ratio of the variance of the estimated treatment effect under the random and fixed effects models, that generalises most naturally, so this statistic provides our basis. This statistic is then used to derive a multivariate analogue of I2, which we call . We also provide a multivariate H2 statistic, the ratio of a generalisation of Cochran's heterogeneity statistic and its associated degrees of freedom, with an accompanying generalisation of the usual I2 statistic, . Our proposed heterogeneity statistics can be used alongside all the usual estimates and inferential procedures used in multivariate meta-analysis. We apply our methods to some real datasets and show how our statistics are equally appropriate in the context of multivariate meta-regression, where study level covariate effects are included in the model. Our heterogeneity statistics may be used when applying any procedure for fitting the multivariate random effects model. Copyright © 2012 John Wiley & Sons, Ltd. PMID:22763950

  6. Heterogeneity of link weight and the evolution of cooperation

    NASA Astrophysics Data System (ADS)

    Iwata, Manabu; Akiyama, Eizo

    2016-04-01

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

  7. Pluridirectional High-Energy Agile Scanning Electron Radiotherapy (PHASER): Extremely Rapid Treatment for Early Lung Cancer

    DTIC Science & Technology

    2015-09-01

    used to simulate 50- 150MeV VHEE beam dose deposition and its effects on steel and titanium (Ti) heterogeneities in a water phantom. Heterogeneities of...and water with segmented prostheses ( steel and Ti) geometries with 100MeV and 150MeV beams. Results: 100MeV PDD 5cm behind steel /Ti heterogeneity...in steel and 18% in Ti heterogeneities. The dose immediately behind steel heterogeneity decreased by an average of 6%, although for 150MeV, the

  8. Modeling electrical double-layer effects for microfluidic impedance spectroscopy from 100 kHz to 110 GHz.

    PubMed

    Little, Charles A E; Orloff, Nathan D; Hanemann, Isaac E; Long, Christian J; Bright, Victor M; Booth, James C

    2017-07-25

    Broadband microfluidic-based impedance spectroscopy can be used to characterize complex fluids, with applications in medical diagnostics and in chemical and pharmacological manufacturing. Many relevant fluids are ionic; during impedance measurements ions migrate to the electrodes, forming an electrical double-layer. Effects from the electrical double-layer dominate over, and reduce sensitivity to, the intrinsic impedance of the fluid below a characteristic frequency. Here we use calibrated measurements of saline solution in microfluidic coplanar waveguide devices at frequencies between 100 kHz and 110 GHz to directly measure the double-layer admittance for solutions of varying ionic conductivity. We successfully model the double-layer admittance using a combination of a Cole-Cole response with a constant phase element contribution. Our analysis yields a double-layer relaxation time that decreases linearly with solution conductivity, and allows for double-layer effects to be separated from the intrinsic fluid response and quantified for a wide range of conducting fluids.

  9. Landscape Heterogeneity–Biodiversity Relationship: Effect of Range Size

    PubMed Central

    Katayama, Naoki; Amano, Tatsuya; Naoe, Shoji; Yamakita, Takehisa; Komatsu, Isamu; Takagawa, Shin-ichi; Sato, Naoto; Ueta, Mutsuyuki; Miyashita, Tadashi

    2014-01-01

    The importance of landscape heterogeneity to biodiversity may depend on the size of the geographic range of species, which in turn can reflect species traits (such as habitat generalization) and the effects of historical and contemporary land covers. We used nationwide bird survey data from Japan, where heterogeneous landscapes predominate, to test the hypothesis that wide-ranging species are positively associated with landscape heterogeneity in terms of species richness and abundance, whereas narrow-ranging species are positively associated with landscape homogeneity in the form of either open or forest habitats. We used simultaneous autoregressive models to explore the effects of climate, evapotranspiration, and landscape heterogeneity on the richness and abundance of breeding land-bird species. The richness of wide-ranging species and the total species richness were highest in heterogeneous landscapes, where many wide-ranging species showed the highest abundance. In contrast, the richness of narrow-ranging species was not highest in heterogeneous landscapes; most of those species were abundant in either open or forest landscapes. Moreover, in open landscapes, narrow-ranging species increased their species richness with decreasing temperature. These results indicate that heterogeneous landscapes are associated with rich bird diversity but that most narrow-ranging species prefer homogeneous landscapes—particularly open habitats in colder regions, where grasslands have historically predominated. There is a need to reassess the generality of the heterogeneity-biodiversity relationship, with attention to the characteristics of species assemblages determined by environments at large spatiotemporal scales. PMID:24675969

  10. Effectiveness evaluation of double-layered satellite network with laser and microwave hybrid links based on fuzzy analytic hierarchy process

    NASA Astrophysics Data System (ADS)

    Zhang, Wei; Rao, Qiaomeng

    2018-01-01

    In order to solve the problem of high speed, large capacity and limited spectrum resources of satellite communication network, a double-layered satellite network with global seamless coverage based on laser and microwave hybrid links is proposed in this paper. By analyzing the characteristics of the double-layered satellite network with laser and microwave hybrid links, an effectiveness evaluation index system for the network is established. And then, the fuzzy analytic hierarchy process, which combines the analytic hierarchy process and the fuzzy comprehensive evaluation theory, is used to evaluate the effectiveness of the double-layered satellite network with laser and microwave hybrid links. Furthermore, the evaluation result of the proposed hybrid link network is obtained by simulation. The effectiveness evaluation process of the proposed double-layered satellite network with laser and microwave hybrid links can help to optimize the design of hybrid link double-layered satellite network and improve the operating efficiency of the satellite system.

  11. Characteristic Features of Double Layers in Rotating, Magnetized Plasma Contaminated with Dust Grains with Varying Charges

    NASA Astrophysics Data System (ADS)

    Paul, Jaydeep; Nag, Apratim; Devi, Karabi; Das, Himadri Sekhar

    2018-03-01

    The evolution and the characteristic features of double layers in a plasma under slow rotation and contaminated with dust grains with varying charges under the effect of an external magnetic field are studied. The Coriolis force resulting from the slow rotation is responsible for the generation of an equivalent magnetic field. A comparatively new pseudopotential approach has been used to derive the small amplitude double layers. The effect of the relative electron-ion concentration, as well as the temperature ratio, on the formation of the double layers has also been investigated. The study reveals that compressive, as well as rarefactive, double layers can be made to co-exist in plasma by controlling the dust charge fluctuation effect supplemented by variations of the plasma constituents. The effectiveness of slow rotation in causing double layers to exist has also emanated from the study. The results obtained could be of interest because of their possible applications in both laboratories and space.

  12. Synergistic oxygen atom transfer by ruthenium complexes with non-redox metal ions.

    PubMed

    Lv, Zhanao; Zheng, Wenrui; Chen, Zhuqi; Tang, Zhiming; Mo, Wanling; Yin, Guochuan

    2016-07-28

    Non-redox metal ions can affect the reactivity of active redox metal ions in versatile biological and heterogeneous oxidation processes; however, the intrinsic roles of these non-redox ions still remain elusive. This work demonstrates the first example of the use of non-redox metal ions as Lewis acids to sharply improve the catalytic oxygen atom transfer efficiency of a ruthenium complex bearing the classic 2,2'-bipyridine ligand. In the absence of Lewis acid, the oxidation of ruthenium(ii) complex by PhI(OAc)2 generates the Ru(iv)[double bond, length as m-dash]O species, which is very sluggish for olefin epoxidation. When Ru(bpy)2Cl2 was tested as a catalyst alone, only 21.2% of cyclooctene was converted, and the yield of 1,2-epoxycyclooctane was only 6.7%. As evidenced by electronic absorption spectra and EPR studies, both the oxidation of Ru(ii) by PhI(OAc)2 and the reduction of Ru(iv)[double bond, length as m-dash]O by olefin are kinetically slow. However, adding non-redox metal ions such as Al(iii) can sharply improve the oxygen transfer efficiency of the catalyst to 100% conversion with 89.9% yield of epoxide under identical conditions. Through various spectroscopic characterizations, an adduct of Ru(iv)[double bond, length as m-dash]O with Al(iii), Ru(iv)[double bond, length as m-dash]O/Al(iii), was proposed to serve as the active species for epoxidation, which in turn generated a Ru(iii)-O-Ru(iii) dimer as the reduced form. In particular, both the oxygen transfer from Ru(iv)[double bond, length as m-dash]O/Al(iii) to olefin and the oxidation of Ru(iii)-O-Ru(iii) back to the active Ru(iv)[double bond, length as m-dash]O/Al(iii) species in the catalytic cycle can be remarkably accelerated by adding a non-redox metal, such as Al(iii). These results have important implications for the role played by non-redox metal ions in catalytic oxidation at redox metal centers as well as for the understanding of the redox mechanism of ruthenium catalysts in the oxygen atom transfer reaction.

  13. Memantine for Alzheimer's Disease: An Updated Systematic Review and Meta-analysis.

    PubMed

    Kishi, Taro; Matsunaga, Shinji; Oya, Kazuto; Nomura, Ikuo; Ikuta, Toshikazu; Iwata, Nakao

    2017-01-01

    The clinical benefit of memantine for Alzheimer's disease (AD) remains inconclusive. We performed an updated systematic review and meta-analysis of the efficacy/safety of memantine in AD. We included randomized trials of memantine for AD patients. Cognitive function scores (CF), behavioral disturbances scores (BD), and all-cause discontinuation were used as primary measures. Effect size based on a random-effects model was evaluated in the meta-analyses. Thirty studies (n = 7,567; memantine versus placebo: N = 11, n = 3,298; memantine + cholinesterase inhibitors (M+ChEIs) versus ChEIs: N = 17, n = 4,175) were identified. Memantine showed a significant improvement in CF [standardized mean difference (SMD) = -0.24, 95% confidence intervals (95% CIs) = -0.34, -0.15, p < 0.00001, I2 = 35% ] and BD (SMD = -0.16, 95% CIs = -0.29, -0.04, p = 0.01, I2 = 52%) compared with placebo. In the sensitivity analysis including only patients with moderate-severe AD, memantine was superior to the placebo in reducing BD without considerable heterogeneity (SMD = -0.20, 95% CIs = -0.34, -0.07, p = 0.003, I2 = 36%). Compared with ChEIs, M+ChEIs showed a greater reduction in BD (SMD = -0.20, 95% CIs = -0.36, -0.03, p = 0.02, I2 = 77%) and a trend of CF improvement (SMD = -0.11, 95% CIs = -0.22, 0.01, p = 0.06, I2 = 56%). However, in the sensitivity analysis of double-blind, placebo-controlled studies only, M+ChEIs showed a significant reduction in BD compared with ChEIs without considerable heterogeneity (SMD = -0.11, 95% CIs = -0.21, -0.01, p = 0.04, I2 = 40%). When performing the sensitivity analysis of donepezil studies only, M+ChEIs was superior to ChEIs in improving CF without considerable heterogeneity (SMD = -0.18, 95% CIs = -0.31, -0.05, p = 0.006, I2 = 49%). No differences were detected in all-cause discontinuation between the groups. The meta-analyses suggest the credible efficacy and safety of memantine in treating AD when used alone or in combination with ChEIs.

  14. Characterizations of double pulsing in neutron multiplicity and coincidence counting systems

    DOE PAGES

    Koehler, Katrina E.; Henzl, Vladimir; Croft, Stephen; ...

    2016-06-29

    Passive neutron coincidence/multiplicity counters are subject to non-ideal behavior, such as double pulsing and dead time. It has been shown in the past that double-pulsing exhibits a distinct signature in a Rossi-alpha distribution, which is not readily noticed using traditional Multiplicity Shift Register analysis. But, it has been assumed that the use of a pre-delay in shift register analysis removes any effects of double pulsing. Here, we use high-fidelity simulations accompanied by experimental measurements to study the effects of double pulsing on multiplicity rates. By exploiting the information from the double pulsing signature peak observable in the Rossi-alpha distribution, themore » double pulsing fraction can be determined. Algebraic correction factors for the multiplicity rates in terms of the double pulsing fraction have been developed. We also discuss the role of these corrections across a range of scenarios.« less

  15. An abnormal bone marrow microenvironment contributes to hematopoietic dysfunction in Fanconi anemia.

    PubMed

    Zhou, Yuan; He, Yongzheng; Xing, Wen; Zhang, Peng; Shi, Hui; Chen, Shi; Shi, Jun; Bai, Jie; Rhodes, Steven D; Zhang, Fengqui; Yuan, Jin; Yang, Xianlin; Zhu, Xiaofan; Li, Yan; Hanenberg, Helmut; Xu, Mingjiang; Robertson, Kent A; Yuan, Weiping; Nalepa, Grzegorz; Cheng, Tao; Clapp, D Wade; Yang, Feng-Chun

    2017-06-01

    Fanconi anemia is a complex heterogeneous genetic disorder with a high incidence of bone marrow failure, clonal evolution to acute myeloid leukemia and mesenchymal-derived congenital anomalies. Increasing evidence in Fanconi anemia and other genetic disorders points towards an interdependence of skeletal and hematopoietic development, yet the impact of the marrow microenvironment in the pathogenesis of the bone marrow failure in Fanconi anemia remains unclear. Here we demonstrated that mice with double knockout of both Fancc and Fancg genes had decreased bone formation at least partially due to impaired osteoblast differentiation from mesenchymal stem/progenitor cells. Mesenchymal stem/progenitor cells from the double knockout mice showed impaired hematopoietic supportive activity. Mesenchymal stem/progenitor cells of patients with Fanconi anemia exhibited similar cellular deficits, including increased senescence, reduced proliferation, impaired osteoblast differentiation and defective hematopoietic stem/progenitor cell supportive activity. Collectively, these studies provide unique insights into the physiological significance of mesenchymal stem/progenitor cells in supporting the marrow microenvironment, which is potentially of broad relevance in hematopoietic stem cell transplantation. Copyright© Ferrata Storti Foundation.

  16. An abnormal bone marrow microenvironment contributes to hematopoietic dysfunction in Fanconi anemia

    PubMed Central

    Zhou, Yuan; He, Yongzheng; Xing, Wen; Zhang, Peng; Shi, Hui; Chen, Shi; Shi, Jun; Bai, Jie; Rhodes, Steven D.; Zhang, Fengqui; Yuan, Jin; Yang, Xianlin; Zhu, Xiaofan; Li, Yan; Hanenberg, Helmut; Xu, Mingjiang; Robertson, Kent A.; Yuan, Weiping; Nalepa, Grzegorz; Cheng, Tao; Clapp, D. Wade; Yang, Feng-Chun

    2017-01-01

    Fanconi anemia is a complex heterogeneous genetic disorder with a high incidence of bone marrow failure, clonal evolution to acute myeloid leukemia and mesenchymal-derived congenital anomalies. Increasing evidence in Fanconi anemia and other genetic disorders points towards an interdependence of skeletal and hematopoietic development, yet the impact of the marrow microenvironment in the pathogenesis of the bone marrow failure in Fanconi anemia remains unclear. Here we demonstrated that mice with double knockout of both Fancc and Fancg genes had decreased bone formation at least partially due to impaired osteoblast differentiation from mesenchymal stem/progenitor cells. Mesenchymal stem/progenitor cells from the double knockout mice showed impaired hematopoietic supportive activity. Mesenchymal stem/progenitor cells of patients with Fanconi anemia exhibited similar cellular deficits, including increased senescence, reduced proliferation, impaired osteoblast differentiation and defective hematopoietic stem/progenitor cell supportive activity. Collectively, these studies provide unique insights into the physiological significance of mesenchymal stem/progenitor cells in supporting the marrow microenvironment, which is potentially of broad relevance in hematopoietic stem cell transplantation. PMID:28341737

  17. Studying dielectric mechanism and magnetization of double perovskite Gd2NiMnO6 ceramic

    NASA Astrophysics Data System (ADS)

    Mohapatra, S. R.; Sahu, B.; Kaushik, S. D.; Singh, A. K.

    2016-05-01

    In the present work, the structure, dielectric and magnetic properties of Gd2NiMnO6 double perovskite have been studied. X-Ray diffraction study reveals the phase pure formation of the material that crystallizes into monoclinic phase (space group 'P21/n'). Surface morphology depicts heterogeneous grain distribution with average grain size of ~1 µm. Temperature dependent (50 - 330 K) dielectric measurements at different frequencies (0.5 - 50 kHz) relate to Maxwell-Wagner interfacial polarization model. Giant dielectric constant at 1 kHz for 300 K (ɛ' ~1900) is noticed as compared to that of 50 K (ɛ' ~10) coupled with a peak shift in tan loss towards higher temperature with frequency. The activation energy (0.24 eV) obtained using Arrhenius relation for thermally activated relaxor behavior of the material signifies an electron hopping mechanism between Ni2+ and Mn4+ cations. Lastly, M-H study shows `S' shape hysteresis loop at 50 K with remnant magnetization (Mr) of 0.72 µB/f.u. along with a linear plot for 300 K which reveals paramagnetic nature of the material.

  18. Highly Conductive Ionic-Liquid Gels Prepared with Orthogonal Double Networks of a Low-Molecular-Weight Gelator and Cross-Linked Polymer.

    PubMed

    Kataoka, Toshikazu; Ishioka, Yumi; Mizuhata, Minoru; Minami, Hideto; Maruyama, Tatsuo

    2015-10-21

    We prepared a heterogeneous double-network (DN) ionogel containing a low-molecular-weight gelator network and a polymer network that can exhibit high ionic conductivity and high mechanical strength. An imidazolium-based ionic liquid was first gelated by the molecular self-assembly of a low-molecular-weight gelator (benzenetricarboxamide derivative), and methyl methacrylate was polymerized with a cross-linker to form a cross-linked poly(methyl methacrylate) (PMMA) network within the ionogel. Microscopic observation and calorimetric measurement revealed that the fibrous network of the low-molecular-weight gelator was maintained in the DN ionogel. The PMMA network strengthened the ionogel of the low-molecular-weight gelator and allowed us to handle the ionogel using tweezers. The orthogonal DNs produced ionogels with a broad range of storage elastic moduli. DN ionogels with low PMMA concentrations exhibited high ionic conductivity that was comparable to that of a neat ionic liquid. The present study demonstrates that the ionic conductivities of the DN and single-network, low-molecular-weight gelator or polymer ionogels strongly depended on their storage elastic moduli.

  19. Heterogeneous belief and asset returns

    NASA Astrophysics Data System (ADS)

    Lei-Sun, Wen-Zou, Hui

    2014-10-01

    Based on DSSW model, this paper introduces the noise traders with heterogeneous belief. With an equilibrium analysis, this paper examines the return of risky asset. The results show that the belief biases, the probability of economy state, the degree of the heterogeneous noise trader's aversion risk, the coefficient between heterogeneous noise traders are all the factors that have effects on the risky asset pricing and the return of risky asset.

  20. Meta-analysis of two studies in the presence of heterogeneity with applications in rare diseases.

    PubMed

    Friede, Tim; Röver, Christian; Wandel, Simon; Neuenschwander, Beat

    2017-07-01

    Random-effects meta-analyses are used to combine evidence of treatment effects from multiple studies. Since treatment effects may vary across trials due to differences in study characteristics, heterogeneity in treatment effects between studies must be accounted for to achieve valid inference. The standard model for random-effects meta-analysis assumes approximately normal effect estimates and a normal random-effects model. However, standard methods based on this model ignore the uncertainty in estimating the between-trial heterogeneity. In the special setting of only two studies and in the presence of heterogeneity, we investigate here alternatives such as the Hartung-Knapp-Sidik-Jonkman method (HKSJ), the modified Knapp-Hartung method (mKH, a variation of the HKSJ method) and Bayesian random-effects meta-analyses with priors covering plausible heterogeneity values; R code to reproduce the examples is presented in an appendix. The properties of these methods are assessed by applying them to five examples from various rare diseases and by a simulation study. Whereas the standard method based on normal quantiles has poor coverage, the HKSJ and mKH generally lead to very long, and therefore inconclusive, confidence intervals. The Bayesian intervals on the whole show satisfying properties and offer a reasonable compromise between these two extremes. © 2016 The Authors. Biometrical Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Limited Benefits of Heterogeneous Dual-Task Training on Transfer Effects in Older Adults.

    PubMed

    Lussier, Maxime; Brouillard, Philippe; Bherer, Louis

    2017-09-01

    It has often been reported that cognitive training has limited transfer effects. The present study addresses training context variability as a factor that could increase transfer effects, as well as the manifestation through time of transfer effects. Fifty-eight older adults were assigned to an active placebo or two dual-task training conditions, one in which the training context varies between sessions (heterogeneous training) and the other in a fixed training context (homogeneous training). Transfer was assessed with near and far-modality transfer tasks. Results show that heterogeneous and homogeneous training led to larger near-modality transfer effects than an active placebo (computer lessons). Transfer effects were roughly comparable in both training groups, but heterogeneous training led to a steeper improvement of the dual-task coordination learning curve within training sessions. Also, results indicated that dual-task cost did not improve in the active placebo group from the pre- to the post-training sessions. Heterogeneous training showed modest advantages over homogeneous training. Results also suggest that transfer effects on dual-task cost induced by training take place early on in the post-training session. These findings provide valuable insights on benefits arising from variability in the training protocol for maximizing transfer effects. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. The cost-effectiveness of single-row compared with double-row arthroscopic rotator cuff repair.

    PubMed

    Genuario, James W; Donegan, Ryan P; Hamman, Daniel; Bell, John-Erik; Boublik, Martin; Schlegel, Theodore; Tosteson, Anna N A

    2012-08-01

    Interest in double-row techniques for arthroscopic rotator cuff repair has increased over the last several years, presumably because of a combination of literature demonstrating superior biomechanical characteristics and recent improvements in instrumentation and technique. As a result of the increasing focus on value-based health-care delivery, orthopaedic surgeons must understand the cost implications of this practice. The purpose of this study was to examine the cost-effectiveness of double-row arthroscopic rotator cuff repair compared with traditional single-row repair. A decision-analytic model was constructed to assess the cost-effectiveness of double-row arthroscopic rotator cuff repair compared with single-row repair on the basis of the cost per quality-adjusted life year gained. Two cohorts of patients (one with a tear of <3 cm and the other with a tear of ≥3 cm) were evaluated. Probabilities for retear and persistent symptoms, health utilities for the particular health states, and the direct costs for rotator cuff repair were derived from the orthopaedic literature and institutional data. The incremental cost-effectiveness ratio for double-row compared with single-row arthroscopic rotator cuff repair was $571,500 for rotator cuff tears of <3 cm and $460,200 for rotator cuff tears of ≥3 cm. The rate of radiographic or symptomatic retear alone did not influence cost-effectiveness results. If the increase in the cost of double-row repair was less than $287 for small or moderate tears and less than $352 for large or massive tears compared with the cost of single-row repair, then double-row repair would represent a cost-effective surgical alternative. On the basis of currently available data, double-row rotator cuff repair is not cost-effective for any size rotator cuff tears. However, variability in the values for costs and probability of retear can have a profound effect on the results of the model and may create an environment in which double-row repair becomes the more cost-effective surgical option. The identification of the threshold values in this study may help surgeons to determine the most cost-effective treatment.

  3. Effect of chemical and physical heterogeneities on colloid-facilitated cesium transport

    DOE PAGES

    Rod, Kenton; Um, Wooyong; Chun, Jaehun; ...

    2018-03-31

    A set of column experiments was conducted to investigate the chemical and physical heterogeneity effect on colloid facilitated transport under slow pore velocity conditions. Pore velocities were kept below 100 cm d -1 for all experiments. Glass beads were packed into columns establishing four different conditions: 1) homogeneous, 2) mixed physical heterogeneity, 3) sequentially layered physical heterogeneity, and 4) chemical heterogeneity. The homogeneous column was packed with glass beads (diameter 500–600 μm), and physical heterogeneities were created by sequential layering or mixing two sizes of glass bead (500–600 μm and 300–400 μm). A chemical heterogeneity was created using 25% ofmore » the glass beads coated with hydrophobic molecules (1H-1H-2H-2H-perfluorooctyltrichlorosilane) mixed with 75% pristine glass beads (all 500–600 μm). Input solution with 0.5 mM CsI and 50 mg L -1 colloids (1-μm diameter SiO 2) was pulsed into columns under saturated conditions. The physical heterogeneity in the packed glass beads retarded the transport of colloids compared to homogeneous (R = 25.0), but showed only slight differences between sequentially layered (R = 60.7) and mixed heterogeneity(R = 62.4). The column with the chemical, hydrophobic/hydrophilic, heterogeneity removed most of the colloids from the input solution. All column conditions stripped Cs from colloids onto the column matrix of packed glass beads.« less

  4. Effect of chemical and physical heterogeneities on colloid-facilitated cesium transport

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rod, Kenton; Um, Wooyong; Chun, Jaehun

    A set of column experiments was conducted to investigate the chemical and physical heterogeneity effect on colloid facilitated transport under slow pore velocity conditions. Pore velocities were kept below 100 cm d -1 for all experiments. Glass beads were packed into columns establishing four different conditions: 1) homogeneous, 2) mixed physical heterogeneity, 3) sequentially layered physical heterogeneity, and 4) chemical heterogeneity. The homogeneous column was packed with glass beads (diameter 500–600 μm), and physical heterogeneities were created by sequential layering or mixing two sizes of glass bead (500–600 μm and 300–400 μm). A chemical heterogeneity was created using 25% ofmore » the glass beads coated with hydrophobic molecules (1H-1H-2H-2H-perfluorooctyltrichlorosilane) mixed with 75% pristine glass beads (all 500–600 μm). Input solution with 0.5 mM CsI and 50 mg L -1 colloids (1-μm diameter SiO 2) was pulsed into columns under saturated conditions. The physical heterogeneity in the packed glass beads retarded the transport of colloids compared to homogeneous (R = 25.0), but showed only slight differences between sequentially layered (R = 60.7) and mixed heterogeneity(R = 62.4). The column with the chemical, hydrophobic/hydrophilic, heterogeneity removed most of the colloids from the input solution. All column conditions stripped Cs from colloids onto the column matrix of packed glass beads.« less

  5. Estimating finite-population reproductive numbers in heterogeneous populations.

    PubMed

    Keegan, Lindsay T; Dushoff, Jonathan

    2016-05-21

    The basic reproductive number, R0, is one of the most important epidemiological quantities. R0 provides a threshold for elimination and determines when a disease can spread or when a disease will die out. Classically, R0 is calculated assuming an infinite population of identical hosts. Previous work has shown that heterogeneity in the host mixing rate increases R0 in an infinite population. However, it has been suggested that in a finite population, heterogeneity in the mixing rate may actually decrease the finite-population reproductive numbers. Here, we outline a framework for discussing different types of heterogeneity in disease parameters, and how these affect disease spread and control. We calculate "finite-population reproductive numbers" with different types of heterogeneity, and show that in a finite population, heterogeneity has complicated effects on the reproductive number. We find that simple heterogeneity decreases the finite-population reproductive number, whereas heterogeneity in the intrinsic mixing rate (which affects both infectiousness and susceptibility) increases the finite-population reproductive number when R0 is small relative to the size of the population and decreases the finite-population reproductive number when R0 is large relative to the size of the population. Although heterogeneity has complicated effects on the finite-population reproductive numbers, its implications for control are straightforward: when R0 is large relative to the size of the population, heterogeneity decreases the finite-population reproductive numbers, making disease control or elimination easier than predicted by R0. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Zero-inflated count models for longitudinal measurements with heterogeneous random effects.

    PubMed

    Zhu, Huirong; Luo, Sheng; DeSantis, Stacia M

    2017-08-01

    Longitudinal zero-inflated count data arise frequently in substance use research when assessing the effects of behavioral and pharmacological interventions. Zero-inflated count models (e.g. zero-inflated Poisson or zero-inflated negative binomial) with random effects have been developed to analyze this type of data. In random effects zero-inflated count models, the random effects covariance matrix is typically assumed to be homogeneous (constant across subjects). However, in many situations this matrix may be heterogeneous (differ by measured covariates). In this paper, we extend zero-inflated count models to account for random effects heterogeneity by modeling their variance as a function of covariates. We show via simulation that ignoring intervention and covariate-specific heterogeneity can produce biased estimates of covariate and random effect estimates. Moreover, those biased estimates can be rectified by correctly modeling the random effects covariance structure. The methodological development is motivated by and applied to the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study, the largest clinical trial of alcohol dependence performed in United States with 1383 individuals.

  7. The occurrence of double strand DNA breaks is not the sole condition for meiotic crossing over in Drosophila melanogaster.

    PubMed

    Portin, P; Rantanen, M

    2000-01-01

    Analysis of the interchromosomal effects of In(2L + 2R)Cy, In(3L + 3R)LVM and their joint effect on the frequencies of single and double crossovers in the cv-v-f region of the X chromosome as well as interference showed that both inversions, occurring separately, increased the frequency of single as well as double crossovers and the coefficient of coincidence. However, when the inversions occurred together the frequencies of single crossovers no longer increased, but the frequency of double crossovers, as well as the coefficient of coincidence did increase. These results indicate firstly that the interchromosomal effects influence some precondition of exchange, but that this precondition is not an occurrence of double strand DNA breaks. Thus, the occurrence of double strand DNA breaks is not the sole condition for crossing over in Drosophila melanogaster.

  8. A common oxytocin receptor gene (OXTR) polymorphism modulates intranasal oxytocin effects on the neural response to social cooperation in humans.

    PubMed

    Feng, C; Lori, A; Waldman, I D; Binder, E B; Haroon, E; Rilling, J K

    2015-09-01

    Intranasal oxytocin (OT) can modulate social-emotional functioning and related brain activity in humans. Consequently, OT has been discussed as a potential treatment for psychiatric disorders involving social behavioral deficits. However, OT effects are often heterogeneous across individuals. Here we explore individual differences in OT effects on the neural response to social cooperation as a function of the rs53576 polymorphism of the oxytocin receptor gene (OXTR). Previously, we conducted a double-blind, placebo-controlled study in which healthy men and women were randomized to treatment with intranasal OT or placebo. Afterwards, they were imaged with functional magnetic resonance imaging while playing an iterated Prisoner's Dilemma Game with same-sex partners. Within the left ventral caudate nucleus, intranasal OT treatment increased activation to reciprocated cooperation in men, but tended to decrease activation in women. Here, we show that these sex differences in OT effects are specific to individuals with the rs53576 GG genotype, and are not found for other genotypes (rs53576 AA/AG). Thus, OT may increase the reward or salience of positive social interactions for male GG homozygotes, while decreasing those processes for female GG homozygotes. These results suggest that rs53576 genotype is an important variable to consider in future investigations of the clinical efficacy of intranasal OT treatment. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  9. Women’s Preferences for Treatment of Perinatal Depression and Anxiety: A Discrete Choice Experiment

    PubMed Central

    Ride, Jemimah; Lancsar, Emily

    2016-01-01

    Perinatal depression and anxiety (PNDA) are an international healthcare priority, associated with significant short- and long-term problems for women, their children and families. Effective treatment is available but uptake is suboptimal: some women go untreated whilst others choose treatments without strong evidence of efficacy. Better understanding of women’s preferences for treatment is needed to facilitate uptake of effective treatment. To address this issue, a discrete choice experiment (DCE) was administered to 217 pregnant or postnatal women in Australia, who were recruited through an online research company and had similar sociodemographic characteristics to Australian data for perinatal women. The DCE investigated preferences regarding cost, treatment type, availability of childcare, modality and efficacy. Data were analysed using logit-based models accounting for preference and scale heterogeneity. Predicted probability analysis was used to explore relative attribute importance and policy change scenarios, including how these differed by women’s sociodemographic characteristics. Cost and treatment type had the greatest impact on choice, such that a policy of subsidising effective treatments was predicted to double their uptake compared with the base case. There were differences in predicted uptake associated with certain sociodemographic characteristics: for example, women with higher educational attainment were more likely to choose effective treatment. The findings suggest policy directions for decision makers whose goal is to reduce the burden of PNDA on women, their children and families. PMID:27258096

  10. Women's Preferences for Treatment of Perinatal Depression and Anxiety: A Discrete Choice Experiment.

    PubMed

    Ride, Jemimah; Lancsar, Emily

    2016-01-01

    Perinatal depression and anxiety (PNDA) are an international healthcare priority, associated with significant short- and long-term problems for women, their children and families. Effective treatment is available but uptake is suboptimal: some women go untreated whilst others choose treatments without strong evidence of efficacy. Better understanding of women's preferences for treatment is needed to facilitate uptake of effective treatment. To address this issue, a discrete choice experiment (DCE) was administered to 217 pregnant or postnatal women in Australia, who were recruited through an online research company and had similar sociodemographic characteristics to Australian data for perinatal women. The DCE investigated preferences regarding cost, treatment type, availability of childcare, modality and efficacy. Data were analysed using logit-based models accounting for preference and scale heterogeneity. Predicted probability analysis was used to explore relative attribute importance and policy change scenarios, including how these differed by women's sociodemographic characteristics. Cost and treatment type had the greatest impact on choice, such that a policy of subsidising effective treatments was predicted to double their uptake compared with the base case. There were differences in predicted uptake associated with certain sociodemographic characteristics: for example, women with higher educational attainment were more likely to choose effective treatment. The findings suggest policy directions for decision makers whose goal is to reduce the burden of PNDA on women, their children and families.

  11. [Euthanasia and the doctrine of double effect].

    PubMed

    Klein, Martin

    2005-01-01

    Direct active euthanasia is prohibited in most countries while passive and indirect is not. However, many arguments against the legalization of voluntary active euthanasia are flawed. Ethical differences between active and passive or indirect euthanasia are difficult to maintain especially when the passivity of the actor causes death. The crucial point is not activity or passivity but respect for the autonomy of individual human beings. In particular there appears to be little ethical difference between active and indirect euthanasia. Indirect euthanasia has often been justified by the principle of double effect, which traces back to Thomas Aquinas. But resorting to this rule contains a logical fallacy. The principle of double effect does not allow foreseen and unwanted adverse effects of an action to occur when they are avoidable. In terminal sedation, an example for indirect euthanasia, hypoxemia and dehydration can easily be prevented by respirator therapy and fluid administration. Therefore the rule of double effect is not applicable. Indirect and direct active euthanasia cannot be ethically distinguished by resorting to the principle of double effect.

  12. Finding missing heritability in less significant Loci and allelic heterogeneity: genetic variation in human height.

    PubMed

    Zhang, Ge; Karns, Rebekah; Sun, Guangyun; Indugula, Subba Rao; Cheng, Hong; Havas-Augustin, Dubravka; Novokmet, Natalija; Durakovic, Zijad; Missoni, Sasa; Chakraborty, Ranajit; Rudan, Pavao; Deka, Ranjan

    2012-01-01

    Genome-wide association studies (GWAS) have identified many common variants associated with complex traits in human populations. Thus far, most reported variants have relatively small effects and explain only a small proportion of phenotypic variance, leading to the issues of 'missing' heritability and its explanation. Using height as an example, we examined two possible sources of missing heritability: first, variants with smaller effects whose associations with height failed to reach genome-wide significance and second, allelic heterogeneity due to the effects of multiple variants at a single locus. Using a novel analytical approach we examined allelic heterogeneity of height-associated loci selected from SNPs of different significance levels based on the summary data of the GIANT (stage 1) studies. In a sample of 1,304 individuals collected from an island population of the Adriatic coast of Croatia, we assessed the extent of height variance explained by incorporating the effects of less significant height loci and multiple effective SNPs at the same loci. Our results indicate that approximately half of the 118 loci that achieved stringent genome-wide significance (p-value<5×10(-8)) showed evidence of allelic heterogeneity. Additionally, including less significant loci (i.e., p-value<5×10(-4)) and accounting for effects of allelic heterogeneity substantially improved the variance explained in height.

  13. A distributed scheduling algorithm for heterogeneous real-time systems

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

    Much of the previous work on load balancing and scheduling in distributed environments was concerned with homogeneous systems and homogeneous loads. Several of the results indicated that random policies are as effective as other more complex load allocation policies. The effects of heterogeneity on scheduling algorithms for hard real time systems is examined. A distributed scheduler specifically to handle heterogeneities in both nodes and node traffic is proposed. The performance of the algorithm is measured in terms of the percentage of jobs discarded. While a random task allocation is very sensitive to heterogeneities, the algorithm is shown to be robust to such non-uniformities in system components and load.

  14. Measuring the effects of heterogeneity on distributed systems

    NASA Technical Reports Server (NTRS)

    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.

  15. Effects of lung ventilation–perfusion and muscle metabolism–perfusion heterogeneities on maximal O2 transport and utilization

    PubMed Central

    Cano, I; Roca, J; Wagner, P D

    2015-01-01

    Previous models of O2 transport and utilization in health considered diffusive exchange of O2 in lung and muscle, but, reasonably, neglected functional heterogeneities in these tissues. However, in disease, disregarding such heterogeneities would not be justified. Here, pulmonary ventilation–perfusion and skeletal muscle metabolism–perfusion mismatching were added to a prior model of only diffusive exchange. Previously ignored O2 exchange in non-exercising tissues was also included. We simulated maximal exercise in (a) healthy subjects at sea level and altitude, and (b) COPD patients at sea level, to assess the separate and combined effects of pulmonary and peripheral functional heterogeneities on overall muscle O2 uptake ( and on mitochondrial (). In healthy subjects at maximal exercise, the combined effects of pulmonary and peripheral heterogeneities reduced arterial () at sea level by 32 mmHg, but muscle by only 122 ml min−1 (–3.5%). At the altitude of Mt Everest, lung and tissue heterogeneity together reduced by less than 1 mmHg and by 32 ml min−1 (–2.4%). Skeletal muscle heterogeneity led to a wide range of potential among muscle regions, a range that becomes narrower as increases, and in regions with a low ratio of metabolic capacity to blood flow, can exceed that of mixed muscle venous blood. For patients with severe COPD, peak was insensitive to substantial changes in the mitochondrial characteristics for O2 consumption or the extent of muscle heterogeneity. This integrative computational model of O2 transport and utilization offers the potential for estimating profiles of both in health and in diseases such as COPD if the extent for both lung ventilation–perfusion and tissue metabolism–perfusion heterogeneity is known. PMID:25640017

  16. The role of the bi-compartmental stem cell niche in delaying cancer

    NASA Astrophysics Data System (ADS)

    Shahriyari, Leili; Komarova, Natalia L.

    2015-10-01

    In recent years, by using modern imaging techniques, scientists have found evidence of collaboration between different types of stem cells (SCs), and proposed a bi-compartmental organization of the SC niche. Here we create a class of stochastic models to simulate the dynamics of such a heterogeneous SC niche. We consider two SC groups: the border compartment, S1, is in direct contact with transit-amplifying (TA) cells, and the central compartment, S2, is hierarchically upstream from S1. The S1 SCs differentiate or divide asymmetrically when the tissue needs TA cells. Both groups proliferate when the tissue requires SCs (thus maintaining homeostasis). There is an influx of S2 cells into the border compartment, either by migration, or by proliferation. We examine this model in the context of double-hit mutant generation, which is a rate-limiting step in the development of many cancers. We discover that this type of a cooperative pattern in the stem niche with two compartments leads to a significantly smaller rate of double-hit mutant production compared with a homogeneous, one-compartmental SC niche. Furthermore, the minimum probability of double-hit mutant generation corresponds to purely symmetric division of SCs, consistent with the literature. Finally, the optimal architecture (which minimizes the rate of double-hit mutant production) requires a large proliferation rate of S1 cells along with a small, but non-zero, proliferation rate of S2 cells. This result is remarkably similar to the niche structure described recently by several authors, where one of the two SC compartments was found more actively engaged in tissue homeostasis and turnover, while the other was characterized by higher levels of quiescence (but contributed strongly to injury recovery). Both numerical and analytical results are presented.

  17. Histochemical and cellular changes accompanying the appearance of lung fibrosis in an experimental mouse model for Hermansky Pudlak syndrome

    PubMed Central

    Lyerla, Timothy

    2010-01-01

    Hermansky Pudlak syndrome (HPS) is a heterogeneous recessive genetic disease with a tendency to develop lung fibrosis with aging. A mouse strain with two mutant HPS genes affecting separate vesicle trafficking pathways, C57BL/6-Hps1ep-Ap3b1pe, exhibits severe lung abnormalities at young ages, including enlarged alveolar type II (ATII) cells with giant lamellar bodies and foamy alveolar macrophages (AMs), which are readily identified histologically. In this study, the appearance of lung fibrosis in older animals was studied using classical histological and biochemical methods. The HPS double mutant mice, but not Chediak Higashi syndrome (C57BL/6-Lystbg-J-J, CHS) or C57BL/6J black control (WT) mice, were found to develop lung fibrosis at about 17 months of age using Masson trichrome staining, which was confirmed by hydroxyproline analysis. TGF β1 levels were elevated in bronchial alveolar lavage samples at all ages tested in the double mutant, but not WT or CHS mice, indicative of a prefibrotic condition in this experimental strain; and AMs were highly positive for this cytokine using immunohistochemistry staining. Prosurfactant protein C staining for ATII cells showed redistribution and dysmorphism of these cells with aging, but there was no evidence for epithelial-mesenchymal transition of ATII cells by dual staining for prosurfactant C protein and α-smooth muscle actin. This investigation showed that the HPS double mutant mouse strain develops interstitial pneumonia (HPSIP) past 1 year of age, which may be initiated by abnormal ATII cells and exacerbated by AM activation. With prominent prefibrotic abnormalities, this double mutant may serve as a model for interventive therapy in HPS. PMID:20603711

  18. Combined Use of Gene Expression Modeling and siRNA Screening Identifies Genes and Pathways Which Enhance the Activity of Cisplatin When Added at No Effect Levels to Non-Small Cell Lung Cancer Cells In Vitro

    PubMed Central

    Leung, Ada W. Y.; Hung, Stacy S.; Backstrom, Ian; Ricaurte, Daniel; Kwok, Brian; Poon, Steven; McKinney, Steven; Segovia, Romulo; Rawji, Jenna; Qadir, Mohammed A.; Aparicio, Samuel; Stirling, Peter C.; Steidl, Christian; Bally, Marcel B.

    2016-01-01

    Platinum-based combination chemotherapy is the standard treatment for advanced non-small cell lung cancer (NSCLC). While cisplatin is effective, its use is not curative and resistance often emerges. As a consequence of microenvironmental heterogeneity, many tumour cells are exposed to sub-lethal doses of cisplatin. Further, genomic heterogeneity and unique tumor cell sub-populations with reduced sensitivities to cisplatin play a role in its effectiveness within a site of tumor growth. Being exposed to sub-lethal doses will induce changes in gene expression that contribute to the tumour cell’s ability to survive and eventually contribute to the selective pressures leading to cisplatin resistance. Such changes in gene expression, therefore, may contribute to cytoprotective mechanisms. Here, we report on studies designed to uncover how tumour cells respond to sub-lethal doses of cisplatin. A microarray study revealed changes in gene expressions that occurred when A549 cells were exposed to a no-observed-effect level (NOEL) of cisplatin (e.g. the IC10). These data were integrated with results from a genome-wide siRNA screen looking for novel therapeutic targets that when inhibited transformed a NOEL of cisplatin into one that induced significant increases in lethality. Pathway analyses were performed to identify pathways that could be targeted to enhance cisplatin activity. We found that over 100 genes were differentially expressed when A549 cells were exposed to a NOEL of cisplatin. Pathways associated with apoptosis and DNA repair were activated. The siRNA screen revealed the importance of the hedgehog, cell cycle regulation, and insulin action pathways in A549 cell survival and response to cisplatin treatment. Results from both datasets suggest that RRM2B, CABYR, ALDH3A1, and FHL2 could be further explored as cisplatin-enhancing gene targets. Finally, pathways involved in repairing double-strand DNA breaks and INO80 chromatin remodeling were enriched in both datasets, warranting further research into combinations of cisplatin and therapeutics targeting these pathways. PMID:26938915

  19. Combined Use of Gene Expression Modeling and siRNA Screening Identifies Genes and Pathways Which Enhance the Activity of Cisplatin When Added at No Effect Levels to Non-Small Cell Lung Cancer Cells In Vitro.

    PubMed

    Leung, Ada W Y; Hung, Stacy S; Backstrom, Ian; Ricaurte, Daniel; Kwok, Brian; Poon, Steven; McKinney, Steven; Segovia, Romulo; Rawji, Jenna; Qadir, Mohammed A; Aparicio, Samuel; Stirling, Peter C; Steidl, Christian; Bally, Marcel B

    2016-01-01

    Platinum-based combination chemotherapy is the standard treatment for advanced non-small cell lung cancer (NSCLC). While cisplatin is effective, its use is not curative and resistance often emerges. As a consequence of microenvironmental heterogeneity, many tumour cells are exposed to sub-lethal doses of cisplatin. Further, genomic heterogeneity and unique tumor cell sub-populations with reduced sensitivities to cisplatin play a role in its effectiveness within a site of tumor growth. Being exposed to sub-lethal doses will induce changes in gene expression that contribute to the tumour cell's ability to survive and eventually contribute to the selective pressures leading to cisplatin resistance. Such changes in gene expression, therefore, may contribute to cytoprotective mechanisms. Here, we report on studies designed to uncover how tumour cells respond to sub-lethal doses of cisplatin. A microarray study revealed changes in gene expressions that occurred when A549 cells were exposed to a no-observed-effect level (NOEL) of cisplatin (e.g. the IC10). These data were integrated with results from a genome-wide siRNA screen looking for novel therapeutic targets that when inhibited transformed a NOEL of cisplatin into one that induced significant increases in lethality. Pathway analyses were performed to identify pathways that could be targeted to enhance cisplatin activity. We found that over 100 genes were differentially expressed when A549 cells were exposed to a NOEL of cisplatin. Pathways associated with apoptosis and DNA repair were activated. The siRNA screen revealed the importance of the hedgehog, cell cycle regulation, and insulin action pathways in A549 cell survival and response to cisplatin treatment. Results from both datasets suggest that RRM2B, CABYR, ALDH3A1, and FHL2 could be further explored as cisplatin-enhancing gene targets. Finally, pathways involved in repairing double-strand DNA breaks and INO80 chromatin remodeling were enriched in both datasets, warranting further research into combinations of cisplatin and therapeutics targeting these pathways.

  20. Emergent dynamics of spatio-temporal chaos in a heterogeneous excitable medium.

    PubMed

    Bittihn, Philip; Berg, Sebastian; Parlitz, Ulrich; Luther, Stefan

    2017-09-01

    Self-organized activation patterns in excitable media such as spiral waves and spatio-temporal chaos underlie dangerous cardiac arrhythmias. While the interaction of single spiral waves with different types of heterogeneity has been studied extensively, the effect of heterogeneity on fully developed spatio-temporal chaos remains poorly understood. We investigate how the complexity and stability properties of spatio-temporal chaos in the Bär-Eiswirth model of excitable media depend on the heterogeneity of the underlying medium. We employ different measures characterizing the chaoticity of the system and find that the spatial arrangement of multiple discrete lower excitability regions has a strong impact on the complexity of the dynamics. Varying the number, shape, and spatial arrangement of the heterogeneities, we observe strong emergent effects ranging from increases in chaoticity to the complete cessation of chaos, contrasting the expectation from the homogeneous behavior. The implications of our findings for the development and treatment of arrhythmias in the heterogeneous cardiac muscle are discussed.

  1. Emergent dynamics of spatio-temporal chaos in a heterogeneous excitable medium

    NASA Astrophysics Data System (ADS)

    Bittihn, Philip; Berg, Sebastian; Parlitz, Ulrich; Luther, Stefan

    2017-09-01

    Self-organized activation patterns in excitable media such as spiral waves and spatio-temporal chaos underlie dangerous cardiac arrhythmias. While the interaction of single spiral waves with different types of heterogeneity has been studied extensively, the effect of heterogeneity on fully developed spatio-temporal chaos remains poorly understood. We investigate how the complexity and stability properties of spatio-temporal chaos in the Bär-Eiswirth model of excitable media depend on the heterogeneity of the underlying medium. We employ different measures characterizing the chaoticity of the system and find that the spatial arrangement of multiple discrete lower excitability regions has a strong impact on the complexity of the dynamics. Varying the number, shape, and spatial arrangement of the heterogeneities, we observe strong emergent effects ranging from increases in chaoticity to the complete cessation of chaos, contrasting the expectation from the homogeneous behavior. The implications of our findings for the development and treatment of arrhythmias in the heterogeneous cardiac muscle are discussed.

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

    NASA Astrophysics Data System (ADS)

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

    2018-02-01

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

  3. Patterns and effects of GC3 heterogeneity and parsimony informative sites on the phylogenetic tree of genes.

    PubMed

    Ma, Shuai; Wu, Qi; Hu, Yibo; Wei, Fuwen

    2018-05-20

    The explosive growth in genomic data has provided novel insights into the conflicting signals hidden in phylogenetic trees. Although some studies have explored the effects of the GC content and parsimony informative sites (PIS) on the phylogenetic tree, the effect of the heterogeneity of the GC content at the first/second/third codon position on parsimony informative sites (GC1/2/3 PIS ) among different species and the effect of PIS on phylogenetic tree construction remain largely unexplored. Here, we used two different mammal genomic datasets to explore the patterns of GC1/2/3 PIS heterogeneity and the effect of PIS on the phylogenetic tree of genes: (i) all GC1/2/3 PIS have obvious heterogeneity between different mammals, and the levels of heterogeneity are GC3 PIS  > GC2 PIS  > GC1 PIS ; (ii) the number of PIS is positively correlated with the metrics of "good" gene tree topologies, and excluding the third codon position (C3) decreases the quality of gene trees by removing too many PIS. These results provide novel insights into the heterogeneity pattern of GC1/2/3 PIS in mammals and the relationship between GC3/PIS and gene trees. Additionally, it is necessary to carefully consider whether to exclude C3 to improve the quality of gene trees, especially in the super-tree method. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Heuristic Strategies for Persuader Selection in Contagions on Complex Networks.

    PubMed

    Wang, Peng; Zhang, Li-Jie; Xu, Xin-Jian; Xiao, Gaoxi

    2017-01-01

    Individual decision to accept a new idea or product is often driven by both self-adoption and others' persuasion, which has been simulated using a double threshold model [Huang et al., Scientific Reports 6, 23766 (2016)]. We extend the study to consider the case with limited persuasion. That is, a set of individuals is chosen from the population to be equipped with persuasion capabilities, who may succeed in persuading their friends to take the new entity when certain conditions are satisfied. Network node centrality is adopted to characterize each node's influence, based on which three heuristic strategies are applied to pick out persuaders. We compare these strategies for persuader selection on both homogeneous and heterogeneous networks. Two regimes of the underline networks are identified in which the system exhibits distinct behaviors: when networks are sufficiently sparse, selecting persuader nodes in descending order of node centrality achieves the best performance; when networks are sufficiently dense, however, selecting nodes with medium centralities to serve as the persuaders performs the best. Under respective optimal strategies for different types of networks, we further probe which centrality measure is most suitable for persuader selection. It turns out that for the first regime, degree centrality offers the best measure for picking out persuaders from homogeneous networks; while in heterogeneous networks, betweenness centrality takes its place. In the second regime, there is no significant difference caused by centrality measures in persuader selection for homogeneous network; while for heterogeneous networks, closeness centrality offers the best measure.

  5. Predation and landscape characteristics independently affect reef fish community organization.

    PubMed

    Stier, Adrian C; Hanson, Katharine M; Holbrook, Sally J; Schmitt, Russell J; Brooks, Andrew J

    2014-05-01

    Trophic island biogeography theory predicts that the effects of predators on prey diversity are context dependent in heterogeneous landscapes. Specifically, models predict that the positive effect of habitat area on prey diversity should decline in the presence of predators, and that predators should modify the partitioning of alpha and beta diversity across patchy landscapes. However, experimental tests of the predicted context dependency in top-down control remain limited. Using a factorial field experiment we quantify the effects of a focal predatory fish species (grouper) and habitat characteristics (patch size, fragmentation) on the partitioning of diversity and assembly of coral reef fish communities. We found independent effects of groupers and patch characteristics on prey communities. Groupers reduced prey abundance by 50% and gamma diversity by 45%, with a disproportionate removal of rare species relative to common species (64% and 36% reduction, respectively; an oddity effect). Further, there was a 77% reduction in beta diversity. Null model analysis demonstrated that groupers increased the importance of stochastic community assembly relative to patches without groupers. With regard to patch size, larger patches contained more fishes, but a doubling of patch size led to a modest (36%) increase in prey abundance. Patch size had no effect on prey diversity; however, fragmented patches had 50% higher species richness and modified species composition relative to unfragmented patches. Our findings suggest two different pathways (i.e., habitat or predator shifts) by which natural and/or anthropogenic processes can drive variation in fish biodiversity and community assembly.

  6. Avian Species and Functional Diversity in Agricultural Landscapes: Does Landscape Heterogeneity Matter?

    PubMed Central

    2017-01-01

    While the positive relationship between avian diversity and habitat heterogeneity is widely accepted, it is primarily based on observed species richness without accounting for imperfect detection. Other facets of diversity such as functional diversity are also rarely explored. We investigated the avian diversity-landscape heterogeneity relationship in agricultural landscapes by considering two aspects of diversity: taxonomic diversity (species richness) estimated from a multi-species dynamic occupancy model, and functional diversity (functional evenness [FEve] and divergence [FDiv]) based on traits of occurring species. We also assessed how agricultural lands enrolled in a conservation program managed on behalf of declining early successional bird species (hereafter CP38 fields, an agri-environment scheme) influenced avian diversity. We analyzed breeding bird data collected at CP38 fields in Mississippi, USA, during 2010–2012, and two principal components of environmental variables: a gradient of heterogeneity (Shannon’s landscape diversity index) and of the amount of CP38 fields (percent cover of CP38 fields; CP38). FEve did not show significant responses to environmental variables, whereas FDiv responded positively to heterogeneity and negatively to CP38. However, most FDiv values did not significantly differ from random expectations along an environmental gradient. When there was a significant difference, FDiv was lower than that expected. Unlike functional diversity, species richness showed a clear pattern. Species richness increased with increasing landscape heterogeneity but decreased with increasing amounts of CP38 fields. Only one species responded negatively to heterogeneity and positively to CP38. Our results suggest that the relationships between avian diversity and landscape heterogeneity may vary depending on the aspect of diversity considered: strong positive effects of heterogeneity on taxonomic diversity, but weakly positive or non-significant effects on functional diversity. Our results also indicate that effectiveness of CP38 in conserving avian diversity, particularly, taxonomic diversity, could be limited without the consideration of landscape heterogeneity. PMID:28125653

  7. Avian Species and Functional Diversity in Agricultural Landscapes: Does Landscape Heterogeneity Matter?

    PubMed

    Lee, Myung-Bok; Martin, James A

    2017-01-01

    While the positive relationship between avian diversity and habitat heterogeneity is widely accepted, it is primarily based on observed species richness without accounting for imperfect detection. Other facets of diversity such as functional diversity are also rarely explored. We investigated the avian diversity-landscape heterogeneity relationship in agricultural landscapes by considering two aspects of diversity: taxonomic diversity (species richness) estimated from a multi-species dynamic occupancy model, and functional diversity (functional evenness [FEve] and divergence [FDiv]) based on traits of occurring species. We also assessed how agricultural lands enrolled in a conservation program managed on behalf of declining early successional bird species (hereafter CP38 fields, an agri-environment scheme) influenced avian diversity. We analyzed breeding bird data collected at CP38 fields in Mississippi, USA, during 2010-2012, and two principal components of environmental variables: a gradient of heterogeneity (Shannon's landscape diversity index) and of the amount of CP38 fields (percent cover of CP38 fields; CP38). FEve did not show significant responses to environmental variables, whereas FDiv responded positively to heterogeneity and negatively to CP38. However, most FDiv values did not significantly differ from random expectations along an environmental gradient. When there was a significant difference, FDiv was lower than that expected. Unlike functional diversity, species richness showed a clear pattern. Species richness increased with increasing landscape heterogeneity but decreased with increasing amounts of CP38 fields. Only one species responded negatively to heterogeneity and positively to CP38. Our results suggest that the relationships between avian diversity and landscape heterogeneity may vary depending on the aspect of diversity considered: strong positive effects of heterogeneity on taxonomic diversity, but weakly positive or non-significant effects on functional diversity. Our results also indicate that effectiveness of CP38 in conserving avian diversity, particularly, taxonomic diversity, could be limited without the consideration of landscape heterogeneity.

  8. Double Your Major, Double Your Return?

    ERIC Educational Resources Information Center

    Del Rossi, Alison F.; Hersch, Joni

    2008-01-01

    We use the 2003 National Survey of College Graduates to provide the first estimates of the effect on earnings of having a double major. Overall, double majoring increases earnings by 2.3% relative to having a single major among college graduates without graduate degrees. Most of the gains from having a double major come from choosing fields across…

  9. Effectiveness of double fines as a speed control measure in safety corridors.

    DOT National Transportation Integrated Search

    2002-12-01

    The use of elevated traffic fines, and specifically doubling of applicable traffic fines under certain conditions, is widely used in Oregon as a speed control measure. Double fines have applied to safety corridors in Oregon since 1999. Double f...

  10. Treatment Effect Heterogeneity in a Science Professional Development Initiative: The Case for School Capacity

    ERIC Educational Resources Information Center

    Bruch, Sarah; Grigg, Jeffrey; Hanselman, Paul

    2010-01-01

    This study focuses on how the treatment effects of a teacher professional development initiative in science differed by school capacity. In other words, the authors are primarily concerned with treatment effect heterogeneity. As such, this paper complements ongoing evaluation of the average treatment effects of the initiative over time. The…

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

    PubMed Central

    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 workflow for analysis of heterogeneity in large scale biology projects. PMID:26476369

  12. Extended depth measurement for a Stokes sample imaging polarimeter

    NASA Astrophysics Data System (ADS)

    Dixon, Alexander W.; Taberner, Andrew J.; Nash, Martyn P.; Nielsen, Poul M. F.

    2018-02-01

    A non-destructive imaging technique is required for quantifying the anisotropic and heterogeneous structural arrangement of collagen in soft tissue membranes, such as bovine pericardium, which are used in the construction of bioprosthetic heart valves. Previously, our group developed a Stokes imaging polarimeter that measures the linear birefringence of samples in a transmission arrangement. With this device, linear retardance and optic axis orientation; can be estimated over a sample using simple vector algebra on Stokes vectors in the Poincaré sphere. However, this method is limited to a single path retardation of a half-wave, limiting the thickness of samples that can be imaged. The polarimeter has been extended to allow illumination of narrow bandwidth light of controllable wavelength through achromatic lenses and polarization optics. We can now take advantage of the wavelength dependence of relative retardation to remove ambiguities that arise when samples have a single path retardation of a half-wave to full-wave. This effectively doubles the imaging depth of this method. The method has been validated using films of cellulose of varied thickness, and applied to samples of bovine pericardium.

  13. Using confocal laser scanning microscopy to probe the milk fat globule membrane and associated proteins.

    PubMed

    Gallier, Sophie; Gragson, Derek; Jiménez-Flores, Rafael; Everett, David

    2010-04-14

    The bovine milk fat globule membrane (MFGM) is an important, biologically relevant membrane due to its functional and health properties. Its composition has been thoroughly studied, but its structure, especially the lateral organization of its components, still remains unclear. We have used confocal laser scanning microscopy (CLSM) to investigate the surface structure of the MFGM in globules with different degrees of processing using two types of fluorescently labeled phospholipid probes and a protein dye. Using this technique, we have observed heterogeneities in the distribution of MFGM lipids and proteins relating to the processing and size of the globules. The effect of pretreating the milk (centrifugation, pasteurization-homogenization and churning) was studied by double-staining the surface of the milk fat globules, followed by observation using CLSM, and by determining the phospholipid profile of raw milk, raw cream, processed milk and buttermilk powder. Our findings agree with other techniques by showing that the composition of the MFGM changes with processing through the loss of phospholipids and the adsorption of caseins and whey proteins onto the surface.

  14. Moral absolutism and the double-effect exception: reflections on Joseph Boyle's Who is entitled to double effect?

    PubMed

    Donagan, A

    1991-10-01

    Joseph Boyle raises important questions about the place of the double-effect exception in absolutist moral theories. His own absolutist theory (held by many, but not all, Catholic moralists), which derives from the principles that fundamental human goods may not be intentionally violated, cannot dispense with such exceptions, although he rightly rejects some widely held views about what they are. By contrast, Kantian absolutist theory, which derives from the principle that lawful freedom must not be violated, has a corollary--that it is a duty, where possible, to coerce those who try to violate lawful freedom--which makes superfluous many of the double-effect exceptions Boyle allows. Other implications of the two theories are contrasted. Inter alia, it is argued that, in Boyle's theory, that a violation of a fundamental human good can be viewed as a cost proportionate to a benefit obtained, cannot yield a double-effect exception to the prohibition of intentionally violating that good, because paying a cost cannot be unintentional.

  15. Effect of Heterogeneity on Decorrelation Mechanisms in Spiking Neural Networks: A Neuromorphic-Hardware Study

    NASA Astrophysics Data System (ADS)

    Pfeil, Thomas; Jordan, Jakob; Tetzlaff, Tom; Grübl, Andreas; Schemmel, Johannes; Diesmann, Markus; Meier, Karlheinz

    2016-04-01

    High-level brain function, such as memory, classification, or reasoning, can be realized by means of recurrent networks of simplified model neurons. Analog neuromorphic hardware constitutes a fast and energy-efficient substrate for the implementation of such neural computing architectures in technical applications and neuroscientific research. The functional performance of neural networks is often critically dependent on the level of correlations in the neural activity. In finite networks, correlations are typically inevitable due to shared presynaptic input. Recent theoretical studies have shown that inhibitory feedback, abundant in biological neural networks, can actively suppress these shared-input correlations and thereby enable neurons to fire nearly independently. For networks of spiking neurons, the decorrelating effect of inhibitory feedback has so far been explicitly demonstrated only for homogeneous networks of neurons with linear subthreshold dynamics. Theory, however, suggests that the effect is a general phenomenon, present in any system with sufficient inhibitory feedback, irrespective of the details of the network structure or the neuronal and synaptic properties. Here, we investigate the effect of network heterogeneity on correlations in sparse, random networks of inhibitory neurons with nonlinear, conductance-based synapses. Emulations of these networks on the analog neuromorphic-hardware system Spikey allow us to test the efficiency of decorrelation by inhibitory feedback in the presence of hardware-specific heterogeneities. The configurability of the hardware substrate enables us to modulate the extent of heterogeneity in a systematic manner. We selectively study the effects of shared input and recurrent connections on correlations in membrane potentials and spike trains. Our results confirm that shared-input correlations are actively suppressed by inhibitory feedback also in highly heterogeneous networks exhibiting broad, heavy-tailed firing-rate distributions. In line with former studies, cell heterogeneities reduce shared-input correlations. Overall, however, correlations in the recurrent system can increase with the level of heterogeneity as a consequence of diminished effective negative feedback.

  16. DRUG-NEM: Optimizing drug combinations using single-cell perturbation response to account for intratumoral heterogeneity

    PubMed Central

    Anchang, Benedict; Davis, Kara L.; Fienberg, Harris G.; Bendall, Sean C.; Karacosta, Loukia G.; Tibshirani, Robert; Nolan, Garry P.; Plevritis, Sylvia K.

    2018-01-01

    An individual malignant tumor is composed of a heterogeneous collection of single cells with distinct molecular and phenotypic features, a phenomenon termed intratumoral heterogeneity. Intratumoral heterogeneity poses challenges for cancer treatment, motivating the need for combination therapies. Single-cell technologies are now available to guide effective drug combinations by accounting for intratumoral heterogeneity through the analysis of the signaling perturbations of an individual tumor sample screened by a drug panel. In particular, Mass Cytometry Time-of-Flight (CyTOF) is a high-throughput single-cell technology that enables the simultaneous measurements of multiple (>40) intracellular and surface markers at the level of single cells for hundreds of thousands of cells in a sample. We developed a computational framework, entitled Drug Nested Effects Models (DRUG-NEM), to analyze CyTOF single-drug perturbation data for the purpose of individualizing drug combinations. DRUG-NEM optimizes drug combinations by choosing the minimum number of drugs that produce the maximal desired intracellular effects based on nested effects modeling. We demonstrate the performance of DRUG-NEM using single-cell drug perturbation data from tumor cell lines and primary leukemia samples. PMID:29654148

  17. Effects of Heterogeneous Diffuse Fibrosis on Arrhythmia Dynamics and Mechanism

    PubMed Central

    Kazbanov, Ivan V.; ten Tusscher, Kirsten H. W. J.; Panfilov, Alexander V.

    2016-01-01

    Myocardial fibrosis is an important risk factor for cardiac arrhythmias. Previous experimental and numerical studies have shown that the texture and spatial distribution of fibrosis may play an important role in arrhythmia onset. Here, we investigate how spatial heterogeneity of fibrosis affects arrhythmia onset using numerical methods. We generate various tissue textures that differ by the mean amount of fibrosis, the degree of heterogeneity and the characteristic size of heterogeneity. We study the onset of arrhythmias using a burst pacing protocol. We confirm that spatial heterogeneity of fibrosis increases the probability of arrhythmia induction. This effect is more pronounced with the increase of both the spatial size and the degree of heterogeneity. The induced arrhythmias have a regular structure with the period being mostly determined by the maximal local fibrosis level. We perform ablations of the induced fibrillatory patterns to classify their type. We show that in fibrotic tissue fibrillation is usually of the mother rotor type but becomes of the multiple wavelet type with increase in tissue size. Overall, we conclude that the most important factor determining the formation and dynamics of arrhythmia in heterogeneous fibrotic tissue is the value of maximal local fibrosis. PMID:26861111

  18. The effect of heterogeneous defectors on the evolution of public cooperation

    NASA Astrophysics Data System (ADS)

    Chen, Tong; Hu, Xuezhi; Wang, Yongjie; Wang, Le

    2018-06-01

    In recent years,more and more private capital join the construction of cultural facilities and the organization of cultural activities in China. Actually, the organization of cultural activities by crowd-funding mechanism is a kind of multi-player game. Not all players who donate different amount of money are real cooperators. In fact, some cunning defectors may donate a little money to avoid the gossip and punishment. This part of people are very tricky. They could be seen as heterogeneous defectors. The role of heterogeneous defectors is investigated in cooperative behaviors of complex social network. Numerical results show that heterogeneous defectors could be a buffer for maintaining the public pool when synergy factor is low in public goods game (PGG). It is relatively easy to be cooperators for heterogeneous defectors when synergy factor is high in PGG. To better improve cooperation, punishment towards heterogeneous defectors and complete defectors is introduced. We are glad to find that when the defectors' loss is equal to or larger than the altruistic cooperators' punishment cost, the mechanism could make great effect. In addition, the role of heterogeneous defectors depends on the relationship between the punishment cost and the defectors' loss.

  19. Effective chemotherapy of heterogeneous and drug-resistant early colon cancers by intermittent dose schedules: a computer simulation study.

    PubMed

    Axelrod, David E; Vedula, Sudeepti; Obaniyi, James

    2017-05-01

    The effectiveness of cancer chemotherapy is limited by intra-tumor heterogeneity, the emergence of spontaneous and induced drug-resistant mutant subclones, and the maximum dose to which normal tissues can be exposed without adverse side effects. The goal of this project was to determine if intermittent schedules of the maximum dose that allows colon crypt maintenance could overcome these limitations, specifically by eliminating mixtures of drug-resistant mutants from heterogeneous early colon adenomas while maintaining colon crypt function. A computer model of cell dynamics in human colon crypts was calibrated with measurements of human biopsy specimens. The model allowed simulation of continuous and intermittent dose schedules of a cytotoxic chemotherapeutic drug, as well as the drug's effect on the elimination of mutant cells and the maintenance of crypt function. Colon crypts can tolerate a tenfold greater intermittent dose than constant dose. This allows elimination of a mixture of relatively drug-sensitive and drug-resistant mutant subclones from heterogeneous colon crypts. Mutants can be eliminated whether they arise spontaneously or are induced by the cytotoxic drug. An intermittent dose, at the maximum that allows colon crypt maintenance, can be effective in eliminating a heterogeneous mixture of mutant subclones before they fill the crypt and form an adenoma.

  20. Functional Heterogeneity and Senior Management Team Effectiveness

    ERIC Educational Resources Information Center

    Benoliel, Pascale; Somech, Anit

    2016-01-01

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

  1. Reproductive consequences of farmland heterogeneity in little owls (Athene noctua).

    PubMed

    Michel, Vanja T; Naef-Daenzer, Beat; Keil, Herbert; Grüebler, Martin U

    2017-04-01

    The amount of high-quality habitat patches, their distribution, and the resource accessibility therein play a key role in regulating habitat effects on reproductive success. Heterogeneous habitats offer non-substitutable resources (e.g. nest sites and food) and substitutable resources (e.g. different types of food) in close proximity, thereby facilitating landscape complementation and supplementation. However, it remains poorly understood how spatial resource separation in homogeneous agricultural landscapes affects reproductive success. To fill this gap, we investigated the relationships between farmland heterogeneity and little owl (Athene noctua) reproductive success, including potential indirect effects of the heterogeneity-dependent home-range size on reproduction. Little owl home-ranges were related to field heterogeneity in summer and to structural heterogeneity in winter. Clutch size was correlated with the amount of food-rich habitat close to the nest irrespective of female home-range size, suggesting importance of landscape complementation. Nestling survival was positively correlated with male home-range size, suggesting importance of landscape supplementation. At the same time, fledgling condition was negatively correlated with male home-range size. We conclude that decreasing farmland heterogeneity constrains population productivity by two processes: increasing separation of food resources from nest or roost sites results in low landscape complementation, and reduction of alternative food resources limits landscape supplementation. Our results suggest that structural heterogeneity affects landscape complementation, whereas the heterogeneity and management of farmland fields affect landscape supplementation. Thus, to what extent a reduction of the heterogeneity within agricultural landscapes results in species-specific habitat degradation depends on the ecological processes (i.e. landscape complementation or supplementation) which are affected.

  2. 33 CFR Appendix G to Part 157 - Timetables for Application of Double Hull Requirements

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Double Hull Requirements G Appendix G to Part 157 Navigation and Navigable Waters COAST GUARD, DEPARTMENT... Application of Double Hull Requirements 1. Source. These timetables conform to 46 U.S.C. 3703a(c). 2... double hull or with a double containment system determined by the Coast Guard to be as effective as a...

  3. Histological changes of gastric mucosa after Helicobacter pylori eradication: a systematic review and meta-analysis.

    PubMed

    Kong, Yan-Jun; Yi, Hong-Gang; Dai, Jun-Cheng; Wei, Mu-Xin

    2014-05-21

    To systematically review pathological changes of gastric mucosa in gastric atrophy (GA) and intestinal metaplasia (IM) after Helicobacter pylori (H. pylori) eradication. A systematic search was made of PubMed, Web of Science, EMBASE, ClinicalTrials.gov, OVID and the Cochran Library databases for articles published before March 2013 pertaining to H. pylori and gastric premalignant lesions. Relevant outcomes from articles included in the meta-analysis were combined using Review Manager 5.2 software. A Begg's test was applied to test for publication bias using STATA 11 software. χ(2) and I(2) analyses were used to assess heterogeneity. Analysis of data with no heterogeneity (P > 0.1, I (2) < 25%) was carried out with a fixed effects model, otherwise the causes of heterogeneity were first analyzed and then a random effects model was applied. The results of the meta-analysis showed that the pooled weighted mean difference (WMD) with 95%CI was 0.23 (0.18-0.29) between eradication and non-eradication of H. pylori infection in antral IM with a significant overall effect (Z = 8.19; P <0.00001) and no significant heterogeneity (χ(2) = 27.54, I(2) = 16%). The pooled WMD with 95%CI was -0.01 (-0.04-0.02) for IM in the corpus with no overall effect (Z = 0.66) or heterogeneity (χ(2) = 14.87, I(2) =0%) (fixed effects model). In antral GA, the pooled WMD with 95% CI was 0.25 (0.15-0.35) with a significant overall effect (Z = 4.78; P < 0.00001) and significant heterogeneity (χ(2) = 86.12, I(2) = 71%; P < 0.00001). The pooled WMD with 95% CI for GA of the corpus was 0.14 (0.04-0.24) with a significant overall effect (Z = 2.67; P = 0.008) and significant heterogeneity (χ(2) = 44.79, I(2) = 62%; P = 0.0003) (random effects model). H. pylori eradication strongly correlates with improvement in IM in the antrum and GA in the corpus and antrum of the stomach.

  4. Effect of the surface heterogeneity of the stationary phase on the range of concentration for linear chromatography

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gritti, Fabrice; Guiochon, Georges A

    2005-02-01

    The range of sample sizes within which linear chromatographic behavior is achieved in a column depends on the surface heterogeneity of the RPLC adsorbents. Two widely different commercial adsorbents were tested, the end-capped XTerra-C{sub 18} and the non-end-capped Resolve-C{sub 18}. Adsorption isotherm data of caffeine were acquired by frontal analysis. These data were modeled and used to calculate the adsorption energy distribution (AED). This double analysis informs on the degree of surface heterogeneity. The best adsorption isotherm models are the bi-Langmuir and the tetra-Langmuir isotherms for XTerra and Resolve, respectively. Their respective AEDs are bimodal and quadrimodal distributions. This interpretationmore » of the results and the actual presence of a low density of high-energy adsorption sites on Resolve-C{sub 18} were validated by measuring the dependence of the peak retention times on the size of caffeine samples (20-{micro}L volume, concentrations 10, 1, 0.1, 1 x 10{sup -2}, 1 x 10{sup -3}, 1 x 10{sup -4}, and 1 x 10{sup -5} g/L). The experimental chromatograms agree closely with the band profiles calculated from the best isotherms. On Resolve-C{sub 18}, the retention time decreases by 40% when the sample concentration is increased from 1 x 10{sup -5} to 10 g/L. The decrease is only 10% for Xterra-C{sub 18} under the same conditions. The upper limit for linear behavior is 1 x 10{sup -4} g/L for the former adsorbent and 0.01 g/L for the latter. The presence of a few high-energy adsorption sites on Resolve-C{sub 18}, with an adsorption energy 20 kJ/mol larger than that of the low-energy sites while the same difference on Xterra is only 5 kJ/mol, explains this difference. The existence of adsorption sites with a very high energy for certain compounds affects the reproducibility of their retention times and a rapid loss of efficiency in a sample size range within which linear behavior is incorrectly anticipated.« less

  5. Losing Wallets, Retaining Trust? The Relationship Between Ethnic Heterogeneity and Trusting Coethnic and Non-coethnic Neighbours and Non-neighbours to Return a Lost Wallet.

    PubMed

    Tolsma, J; van der Meer, T W G

    2017-01-01

    The constrict claim that ethnic heterogeneity drives down social trust has been empirically tested across the globe. Meta-analyses suggest that neighbourhood ethnic heterogeneity generally undermines ties within the neighbourhood (such as trust in neighbours), but concurrently has an inconsistent or even positive effect on interethnic ties (such as outgroup trust). While the composition of the living environment thus often seems to matter, when and where remain unclear. We contribute to the literature by: (1) scrutinizing the extent to which ethnic heterogeneity drives down trust in coethnic neighbours, non-coethnic neighbours, unknown neighbours and unknown non-neighbours similarly; (2) comparing effects of heterogeneity aggregated to geographical areas that vary in scale and type of boundary; and (3) assessing whether the impact of heterogeneity of the local area depends on the wider geographic context. We test our hypotheses on the Religion in Dutch Society 2011-2012 dataset, supplemented with uniquely detailed GIS-data of Statistics Netherlands. Our dependent variables are four different so-called wallet-items, which we model through spatial and multilevel regression techniques. We demonstrate that both trust in non-coethnic and coethnic neighbours are lower in heterogeneous environments. Trust in people outside the neighbourhood is not affected by local heterogeneity. Measures of heterogeneity aggregated to relatively large scales, such as, administrative municipalities and egohoods with a 4000 m radius, demonstrate the strongest negative relationships with our trust indicators.

  6. CT Identification and Fractal Characterization of 3-D Propagation and Distribution of Hydrofracturing Cracks in Low-Permeability Heterogeneous Rocks

    NASA Astrophysics Data System (ADS)

    Liu, Peng; Ju, Yang; Gao, Feng; Ranjith, Pathegama G.; Zhang, Qianbing

    2018-03-01

    Understanding and characterization of the three-dimensional (3-D) propagation and distribution of hydrofracturing cracks in heterogeneous rock are key for enhancing the stimulation of low-permeability petroleum reservoirs. In this study, we investigated the propagation and distribution characteristics of hydrofracturing cracks, by conducting true triaxial hydrofracturing tests and computed tomography on artificial heterogeneous rock specimens. Silica sand, Portland cement, and aedelforsite were mixed to create artificial heterogeneous rock specimens using the data of mineral compositions, coarse gravel distribution, and mechanical properties that were measured from the natural heterogeneous glutenite cores. To probe the effects of material heterogeneity on hydrofracturing cracks, the artificial homogenous specimens were created using the identical matrix compositions of the heterogeneous rock specimens and then fractured for comparison. The effects of horizontal geostress ratio on the 3-D growth and distribution of cracks during hydrofracturing were examined. A fractal-based method was proposed to characterize the complexity of fractures and the efficiency of hydrofracturing stimulation of heterogeneous media. The material heterogeneity and horizontal geostress ratio were found to significantly influence the 3-D morphology, growth, and distribution of hydrofracturing cracks. A horizontal geostress ratio of 1.7 appears to be the upper limit for the occurrence of multiple cracks, and higher ratios cause a single crack perpendicular to the minimum horizontal geostress component. The fracturing efficiency is associated with not only the fractured volume but also the complexity of the crack network.

  7. The impact of heterogeneous response on coupled spreading dynamics in multiplex networks

    NASA Astrophysics Data System (ADS)

    Nie, Xiaoyu; Tang, Ming; Zou, Yong; Guan, Shuguang; Zhou, Jie

    2017-10-01

    Many recent studies have demonstrated that individual awareness of disease may significantly affect the spreading process of infectious disease. In the majority of these studies, the response of the awareness is generally treated homogeneously. Considering of diversity and heterogeneity in the human behavior which widely exist under different circumstances, in this paper we study heterogeneous response when people are aware of the prevalence of infectious diseases. Specifically, we consider that an individual with more neighbors may take more preventive measures as a reaction when he is aware of the disease. A suppression strength is introduced to describe such heterogeneity, and we find that a more evident heterogeneity may cause a more effective suppressing effect to the spreading of epidemics. A mean-field theory is developed to support the results which are verified on the multiplex networks with different interlayer degree correlation.

  8. The dosimetric effects of tissue heterogeneities in intensity-modulated radiation therapy (IMRT) of the head and neck

    NASA Astrophysics Data System (ADS)

    Al-Hallaq, H. A.; Reft, C. S.; Roeske, J. C.

    2006-03-01

    The dosimetric effects of bone and air heterogeneities in head and neck IMRT treatments were quantified. An anthropomorphic RANDO phantom was CT-scanned with 16 thermoluminescent dosimeter (TLD) chips placed in and around the target volume. A standard IMRT plan generated with CORVUS was used to irradiate the phantom five times. On average, measured dose was 5.1% higher than calculated dose. Measurements were higher by 7.1% near the heterogeneities and by 2.6% in tissue. The dose difference between measurement and calculation was outside the 95% measurement confidence interval for six TLDs. Using CORVUS' heterogeneity correction algorithm, the average difference between measured and calculated doses decreased by 1.8% near the heterogeneities and by 0.7% in tissue. Furthermore, dose differences lying outside the 95% confidence interval were eliminated for five of the six TLDs. TLD doses recalculated by Pinnacle3's convolution/superposition algorithm were consistently higher than CORVUS doses, a trend that matched our measured results. These results indicate that the dosimetric effects of air cavities are larger than those of bone heterogeneities, thereby leading to a higher delivered dose compared to CORVUS calculations. More sophisticated algorithms such as convolution/superposition or Monte Carlo should be used for accurate tailoring of IMRT dose in head and neck tumours.

  9. Nonlocal Poisson-Fermi double-layer models: Effects of nonuniform ion sizes on double-layer structure

    NASA Astrophysics Data System (ADS)

    Xie, Dexuan; Jiang, Yi

    2018-05-01

    This paper reports a nonuniform ionic size nonlocal Poisson-Fermi double-layer model (nuNPF) and a uniform ionic size nonlocal Poisson-Fermi double-layer model (uNPF) for an electrolyte mixture of multiple ionic species, variable voltages on electrodes, and variable induced charges on boundary segments. The finite element solvers of nuNPF and uNPF are developed and applied to typical double-layer tests defined on a rectangular box, a hollow sphere, and a hollow rectangle with a charged post. Numerical results show that nuNPF can significantly improve the quality of the ionic concentrations and electric fields generated from uNPF, implying that the effect of nonuniform ion sizes is a key consideration in modeling the double-layer structure.

  10. One size does not fit all: investigating doctors' stated preference heterogeneity for job incentives to inform policy in Thailand.

    PubMed

    Lagarde, Mylene; Pagaiya, Nonglak; Tangcharoensathian, Viroj; Blaauw, Duane

    2013-12-01

    This study investigates heterogeneity in Thai doctors' job preferences at the beginning of their career, with a view to inform the design of effective policies to retain them in rural areas. A discrete choice experiment was designed and administered to 198 young doctors. We analysed the data using several specifications of a random parameter model to account for various sources of preference heterogeneity. By modelling preference heterogeneity, we showed how sensitivity to different incentives varied in different sections of the population. In particular, doctors from rural backgrounds were more sensitive than others to a 45% salary increase and having a post near their home province, but they were less sensitive to a reduction in the number of on-call nights. On the basis of the model results, the effects of two types of interventions were simulated: introducing various incentives and modifying the population structure. The results of the simulations provide multiple elements for consideration for policy-makers interested in designing effective interventions. They also underline the interest of modelling preference heterogeneity carefully. Copyright © 2013 John Wiley & Sons, Ltd.

  11. Effect of homogenous-heterogeneous reactions on MHD Prandtl fluid flow over a stretching sheet

    NASA Astrophysics Data System (ADS)

    Khan, Imad; Malik, M. Y.; Hussain, Arif; Salahuddin, T.

    An analysis is performed to explore the effects of homogenous-heterogeneous reactions on two-dimensional flow of Prandtl fluid over a stretching sheet. In present analysis, we used the developed model of homogeneous-heterogeneous reactions in boundary layer flow. The mathematical configuration of presented flow phenomenon yields the nonlinear partial differential equations. Using scaling transformations, the governing partial differential equations (momentum equation and homogenous-heterogeneous reactions equations) are transformed into non-linear ordinary differential equations (ODE's). Then, resulting non-linear ODE's are solved by computational scheme known as shooting method. The quantitative and qualitative manners of concerned physical quantities (velocity, concentration and drag force coefficient) are examined under prescribed physical constrained through figures and tables. It is observed that velocity profile enhances verses fluid parameters α and β while Hartmann number reduced it. The homogeneous and heterogeneous reactions parameters have reverse effects on concentration profile. Concentration profile shows retarding behavior for large values of Schmidt number. Skin fraction coefficient enhances with increment in Hartmann number H and fluid parameter α .

  12. Optics of a Double Focussing Magnetic Sector by Fringe Effect; OPTIQUE D'UN SECTEUR MAGNETIQUE A DOUBLE FOCALISATION PAR EFFET DE FRANCES

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Krafft, J.

    1960-01-01

    A general study is made of the optical elements of a double-fccusing magnetic sector by the fringe effect, with a view to its application to the monochromation of the proton, deuteron, or triton beam of the 1.4 Mev accelerator. (auth)

  13. Molecular Structure of Humin and Melanoidin via Solid State NMR

    PubMed Central

    Herzfeld, Judith; Rand, Danielle; Matsuki, Yoh; Daviso, Eugenio; Mak-Jurkauskas, Melody; Mamajanov, Irena

    2011-01-01

    Sugar-derived humins and melanoidins figure significantly in food chemistry, agricultural chemistry, biochemistry and prebiotic chemistry. Despite wide interest and significant experimental attention, the amorphous and insoluble nature of the polymers has made them resistant to conventional structural characterization. Here we make use of solid-state NMR methods, including selective 13C substitution, 1H-dephasing, and double quantum filtration. The spectra, and their interpretation, are simplified by relying exclusively on hydronium for catalysis. The results for polymers derived from ribose, deoxyribose and fructose indicate diverse pathways to furans, suggest a simple route to pyrroles in the presence of amines, and reveal a heterogenous network-type polymer in which sugar molecules cross-link the heterocycles. PMID:21456563

  14. Neurocognitive effects of methylphenidate in adults with attention-deficit/hyperactivity disorder: A meta-analysis.

    PubMed

    Pievsky, Michelle A; McGrath, Robert E

    2018-05-08

    PIEVSKY, M. A., and R. E. McGrath. Neurocognitive effects of methylphenidate in adults with attention-deficit/hyperactivity disorder: A meta-analysis…NEUROSCI BIOBEHAV REV 81(1) XXX-XXX, 2017.- This meta-analysis summarized 21 double-blind randomized controlled trials with a mean study duration of 18 days comparing the neurocognitive functioning of adults with attention-deficit/hyperactivity disorder (ADHD) on methylphenidate vs placebo. Effect sizes were weighted using a random-effects model. Scores on neurocognitive measures and tests of driving ability were on average higher on methylphenidate than on placebo, g = 0.17, p < .01, 95% CI = [0.05, 0.28], with little heterogeneity, Q(20) = 15.05, p = .77, I 2  = 0. Performance on methylphenidate was significantly better than on placebo for the following domains: working memory (mean g = 0.13, 95% CI = [0.00, 0.26]), reaction time variability (0.16, [0.03, 0.28]), vigilance (0.22, [0.11, 0.33]), driving (0.22, [0.10, 0.34]), and response inhibition (0.23, [0.10, 0.36]). Quantitative and qualitative assessment revealed evidence of publication bias. Summarizing across studies, methylphenidate improved the performance of adults with ADHD on neurocognitive measures and tests of driving, suggesting that methylphenidate is an effective treatment for adults with ADHD and can improve processes related to attention and concentration. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Interventions for reducing fear of childbirth: A systematic review and meta-analysis of clinical trials.

    PubMed

    MoghaddamHosseini, Vahideh; Nazarzadeh, Milad; Jahanfar, Shayesteh

    2017-11-07

    Fear of childbirth is a problematic mental health issue during pregnancy. But, effective interventions to reduce this problem are not well understood. To examine effective interventions for reducing fear of childbirth. The Cochrane Central Register of Controlled Trials, PubMed, Embase and PsycINFO were searched since inception till September 2017 without any restriction. Randomised controlled trials and quasi-randomised controlled trials comparing interventions for treatment of fear of childbirth were included. The standardized mean differences were pooled using random and fixed effect models. The heterogeneity was determined using the Cochran's test and I 2 index and was further explored in meta-regression model and subgroup analyses. Ten studies inclusive of 3984 participants were included in the meta-analysis (2 quasi-randomized and 8 randomized clinical trials). Eight studies investigated education and two studies investigated hypnosis-based intervention. The pooled standardized mean differences of fear for the education intervention and hypnosis group in comparison with control group were -0.46 (95% CI -0.73 to -0.19) and -0.22 (95% CI -0.34 to -0.10), respectively. Both types of interventions were effective in reducing fear of childbirth; however our pooled results revealed that educational interventions may reduce fear with double the effect of hypnosis. Further large scale randomized clinical trials and individual patient data meta-analysis are warranted for assessing the association. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  16. Improved double-multiple streamtube model for the Darrieus-type vertical axis wind turbine

    NASA Astrophysics Data System (ADS)

    Berg, D. E.

    Double streamtube codes model the curved blade (Darrieus-type) vertical axis wind turbine (VAWT) as a double actuator fish arrangement (one half) and use conservation of momentum principles to determine the forces acting on the turbine blades and the turbine performance. Sandia National Laboratories developed a double multiple streamtube model for the VAWT which incorporates the effects of the incident wind boundary layer, nonuniform velocity between the upwind and downwind sections of the rotor, dynamic stall effects and local blade Reynolds number variations. The theory underlying this VAWT model is described, as well as the code capabilities. Code results are compared with experimental data from two VAWT's and with the results from another double multiple streamtube and a vortex filament code. The effects of neglecting dynamic stall and horizontal wind velocity distribution are also illustrated.

  17. Double uterus with obstructed hemivagina and ipsilateral renal agenesis: pelvic anatomic variants in 87 cases.

    PubMed

    Fedele, L; Motta, F; Frontino, G; Restelli, E; Bianchi, S

    2013-06-01

    What are the anatomic variants (and their frequencies) of double uterus, obstructed hemivagina and ipsilateral renal agenesis? Most cases examined (72.4%) were of the classic anatomic variant of the Herlyn-Werner-Wunderlich syndrome (with didelphys uterus, obstructed hemivagina and ipsilateral renal agenesis) but the 27.6% of cases are of a rare variant of the syndrome (with uterus septum or cervical agenesis), showing relevant clinical and surgical implications. The extreme variability of anatomic structures involved in this syndrome (both uterus, cervico-vaginal and renal anomalies) is well known, even if a complete and uniform analysis of all its heterogeneous presentations in a large series is lacking. This is a retrospective study with 87 patients referred to our third level referral center between 1981 and 2011. We analyzed the laparoscopic and chart records of 87 women, who referred to our institute with double uterus, unilateral cervico-vaginal obstruction and ipsilateral renal anomalies. Sixty-three of 87 patients had the more classic variant of didelphys uterus with obstructed hemivagina; 10/87 patients had septate bicollis uterus with obstructed hemivagina; 9/87 patients had bicornuate bicollis uterus with obstructed hemivagina; 4/87 patients had didelphys uterus with unilateral cervical atresia; 1/87 patients had bicornuate uterus with one septate cervix and unilateral obstructed hemivagina. This is a retrospective study with a long enrolling period (30 years). New insights in the anatomic variants of this rare syndrome with their relevant surgical implications.

  18. Determining the Influence of Heterogeneity in Graduate Institutions on University-Industry Collaboration Policy in Taiwan

    ERIC Educational Resources Information Center

    Weng, Hung-Jen; Chang, Dian-Fu

    2016-01-01

    In this study, we assumed that organizational heterogeneity is a key factor influencing the effects of university-industry cooperation policy in higher education institutes. Gender difference, faculty position, faculty member nationality, and diversity in academic expertise were considered as the indicators of heterogeneity. One-hundred graduate…

  19. Quantification of Spatial Heterogeneity in Old Growth Forst of Korean Pine

    Treesearch

    Wang Zhengquan; Wang Qingcheng; Zhang Yandong

    1997-01-01

    Spatial hetergeneity is a very important issue in studying functions and processes of ecological systems at various scales. Semivariogram analysis is an effective technique to summarize spatial data, and quantification of sptail heterogeneity. In this paper, we propose some principles to use semivariograms to characterize and compare spatial heterogeneity of...

  20. Criticality and Induction Time of Hot Spots in Detonating Heterogeneous Explosives

    NASA Astrophysics Data System (ADS)

    Hill, Larry

    2017-06-01

    Detonation reaction in physically heterogeneous explosives is-to an extent that depends on multiple material attributes-likewise heterogeneous. Like all heterogeneous reaction, detonation heterogeneous reaction begins at nucleation sites, which, in this case, comprise localized regions of higher-than-average temperature-so-called hot spots. Burning grows at, and then spreads from these nucleation sites, via reactive-thermal (R-T) waves, to consume the interstitial material. Not all hot spots are consequential, but only those that are 1) supercritical, and 2) sufficiently so as to form R-T waves before being consumed by those already emanating from neighboring sites. I explore aspects of these two effects by deriving simple formulae for hot spot criticality and the induction time of supercritical hot spots. These results serve to illustrate the non-intuitive, yet mathematically simplifying, effects of extreme dependence of reaction rate upon temperature. They can play a role in the development of better reactive burn models, for which we seek to homogenize the essentials of heterogeneous detonation reaction without introducing spurious complexity. Work supported by the US Dept. of Energy.

  1. Heterogeneous environments shape invader impacts: integrating environmental, structural and functional effects by isoscapes and remote sensing.

    PubMed

    Hellmann, Christine; Große-Stoltenberg, André; Thiele, Jan; Oldeland, Jens; Werner, Christiane

    2017-06-23

    Spatial heterogeneity of ecosystems crucially influences plant performance, while in return plant feedbacks on their environment may increase heterogeneous patterns. This is of particular relevance for exotic plant invaders that transform native ecosystems, yet, approaches integrating geospatial information of environmental heterogeneity and plant-plant interaction are lacking. Here, we combined remotely sensed information of site topography and vegetation cover with a functional tracer of the N cycle, δ 15 N. Based on the case study of the invasion of an N 2 -fixing acacia in a nutrient-poor dune ecosystem, we present the first model that can successfully predict (R 2  = 0.6) small-scale spatial variation of foliar δ 15 N in a non-fixing native species from observed geospatial data. Thereby, the generalized additive mixed model revealed modulating effects of heterogeneous environments on invader impacts. Hence, linking remote sensing techniques with tracers of biological processes will advance our understanding of the dynamics and functioning of spatially structured heterogeneous systems from small to large spatial scales.

  2. Accounting for heterogeneity in meta-analysis using a multiplicative model-an empirical study.

    PubMed

    Mawdsley, David; Higgins, Julian P T; Sutton, Alex J; Abrams, Keith R

    2017-03-01

    In meta-analysis, the random-effects model is often used to account for heterogeneity. The model assumes that heterogeneity has an additive effect on the variance of effect sizes. An alternative model, which assumes multiplicative heterogeneity, has been little used in the medical statistics community, but is widely used by particle physicists. In this paper, we compare the two models using a random sample of 448 meta-analyses drawn from the Cochrane Database of Systematic Reviews. In general, differences in goodness of fit are modest. The multiplicative model tends to give results that are closer to the null, with a narrower confidence interval. Both approaches make different assumptions about the outcome of the meta-analysis. In our opinion, the selection of the more appropriate model will often be guided by whether the multiplicative model's assumption of a single effect size is plausible. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Rethinking the Cultural Context of Schooling Decisions in Disadvantaged Neighborhoods: From Deviant Subculture to Cultural Heterogeneity

    PubMed Central

    Harding, David J.

    2012-01-01

    The literature on neighborhood effects on schooling theorizes that neighborhood cultural context is an important mechanism generating such effects. However, explanations that rely on subcultural theories, such as oppositional culture, have met with considerable criticism on empirical grounds, and no alternative account of the cultural context of disadvantaged neighborhoods has been developed in the education literature. This study develops a new account of the cultural context of schooling decisions in disadvantaged neighborhoods based on the concept of cultural heterogeneity, defined as the presence of a wide array of competing and conflicting cultural models. It applies this concept to neighborhood effects on college enrollment. Using survey data from the National Longitudinal Study of Adolescent Health, this study shows that disadvantaged neighborhoods exhibit greater heterogeneity in college goals and that adolescents in more heterogeneous neighborhoods are less likely to act in concert with the college goals that they articulate. PMID:22879683

  4. Interpreting Meta-Analyses of Genome-Wide Association Studies

    PubMed Central

    Han, Buhm; Eskin, Eleazar

    2012-01-01

    Meta-analysis is an increasingly popular tool for combining multiple genome-wide association studies in a single analysis to identify associations with small effect sizes. The effect sizes between studies in a meta-analysis may differ and these differences, or heterogeneity, can be caused by many factors. If heterogeneity is observed in the results of a meta-analysis, interpreting the cause of heterogeneity is important because the correct interpretation can lead to a better understanding of the disease and a more effective design of a replication study. However, interpreting heterogeneous results is difficult. The standard approach of examining the association p-values of the studies does not effectively predict if the effect exists in each study. In this paper, we propose a framework facilitating the interpretation of the results of a meta-analysis. Our framework is based on a new statistic representing the posterior probability that the effect exists in each study, which is estimated utilizing cross-study information. Simulations and application to the real data show that our framework can effectively segregate the studies predicted to have an effect, the studies predicted to not have an effect, and the ambiguous studies that are underpowered. In addition to helping interpretation, the new framework also allows us to develop a new association testing procedure taking into account the existence of effect. PMID:22396665

  5. Meta-analysis of cytomegalovirus seroprevalence in volunteer blood donors and healthy subjects in Iran from 1992 to 2013

    PubMed Central

    Shaiegan, Mojgan; Rasouli, Mahbobeh; Zadsar, Maryam; Zolfaghari, Sima

    2015-01-01

    Objective(s): Human cytomegalovirus (CMV), a double-strand DNA herpesvirus, can be transmitted via blood transfusion which is especially important for immunocompromised recipients and can cause a fatal infection. CMV seroprevalence in Iran was studied on blood donors, healthy subjects, and some patients. Highly variable rates were detected. The purpose of this study was to review CMV seroprevalence in blood donors and apparently healthy individuals, in Iran. Materials and Methods: One hundred and fifty-eight electronic and paper-based resources and databases including published articles in internal and external journals, seminars, dissertations, and theses available in the database and different websites were used to be systematically reviewed as a meta-analysis. Less related articles to the issue, papers of specific high risk population, and articles with not enough information, were excluded. Eventually 22 articles that satisfied our selection criteria were systematically reviewed and analyzed. To explore heterogeneity between studies the I square (I2) index was used. Data were analyzed using the statistical software package (STATA) 11. Results: The heterogeneity between selected studies was 97% with an I2 statistic. In this study a random effects model was used for meta-analysis. The prevalence of CMV IgG and CMV IgM antibodies in the country were estimated to be 92% (95% CI: 90-94) and 2.6% (95% CI: 1.7-3.6), respectively. Conclusion: Given high rate of CMV seropositivity in Iran, it seems that CMVAbs screening would not be a reasonable and affordable approach to prevent CMV infection via transfusion especially for immune compromised recipients, so alternative strategies should be considered. PMID:26351551

  6. Cellular Interrogation: Exploiting Cell-to-Cell Variability to Discriminate Regulatory Mechanisms in Oscillatory Signalling.

    PubMed

    Estrada, Javier; Andrew, Natalie; Gibson, Daniel; Chang, Frederick; Gnad, Florian; Gunawardena, Jeremy

    2016-07-01

    The molecular complexity within a cell may be seen as an evolutionary response to the external complexity of the cell's environment. This suggests that the external environment may be harnessed to interrogate the cell's internal molecular architecture. Cells, however, are not only nonlinear and non-stationary, but also exhibit heterogeneous responses within a clonal, isogenic population. In effect, each cell undertakes its own experiment. Here, we develop a method of cellular interrogation using programmable microfluidic devices which exploits the additional information present in cell-to-cell variation, without requiring model parameters to be fitted to data. We focussed on Ca2+ signalling in response to hormone stimulation, which exhibits oscillatory spiking in many cell types and chose eight models of Ca2+ signalling networks which exhibit similar behaviour in simulation. We developed a nonlinear frequency analysis for non-stationary responses, which could classify models into groups under parameter variation, but found that this question alone was unable to distinguish critical feedback loops. We further developed a nonlinear amplitude analysis and found that the combination of both questions ruled out six of the models as inconsistent with the experimentally-observed dynamics and heterogeneity. The two models that survived the double interrogation were mathematically different but schematically identical and yielded the same unexpected predictions that we confirmed experimentally. Further analysis showed that subtle mathematical details can markedly influence non-stationary responses under parameter variation, emphasising the difficulty of finding a "correct" model. By developing questions for the pathway being studied, and designing more versatile microfluidics, cellular interrogation holds promise as a systematic strategy that can complement direct intervention by genetics or pharmacology.

  7. Leading Causes of Death among Asian American Subgroups (2003-2011).

    PubMed

    Hastings, Katherine G; Jose, Powell O; Kapphahn, Kristopher I; Frank, Ariel T H; Goldstein, Benjamin A; Thompson, Caroline A; Eggleston, Karen; Cullen, Mark R; Palaniappan, Latha P

    2015-01-01

    Our current understanding of Asian American mortality patterns has been distorted by the historical aggregation of diverse Asian subgroups on death certificates, masking important differences in the leading causes of death across subgroups. In this analysis, we aim to fill an important knowledge gap in Asian American health by reporting leading causes of mortality by disaggregated Asian American subgroups. We examined national mortality records for the six largest Asian subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) and non-Hispanic Whites (NHWs) from 2003-2011, and ranked the leading causes of death. We calculated all-cause and cause-specific age-adjusted rates, temporal trends with annual percent changes, and rate ratios by race/ethnicity and sex. Rankings revealed that as an aggregated group, cancer was the leading cause of death for Asian Americans. When disaggregated, there was notable heterogeneity. Among women, cancer was the leading cause of death for every group except Asian Indians. In men, cancer was the leading cause of death among Chinese, Korean, and Vietnamese men, while heart disease was the leading cause of death among Asian Indians, Filipino and Japanese men. The proportion of death due to heart disease for Asian Indian males was nearly double that of cancer (31% vs. 18%). Temporal trends showed increased mortality of cancer and diabetes in Asian Indians and Vietnamese; increased stroke mortality in Asian Indians; increased suicide mortality in Koreans; and increased mortality from Alzheimer's disease for all racial/ethnic groups from 2003-2011. All-cause rate ratios revealed that overall mortality is lower in Asian Americans compared to NHWs. Our findings show heterogeneity in the leading causes of death among Asian American subgroups. Additional research should focus on culturally competent and cost-effective approaches to prevent and treat specific diseases among these growing diverse populations.

  8. JIM-13-0560 R1: Propensity scores for confounder adjustment when assessing the effects of medical interventions using non-experimental study designs

    PubMed Central

    Stürmer, Til; Wyss, Richard; Glynn, Robert J.; Brookhart, M. Alan

    2014-01-01

    Treatment effects, especially when comparing two or more therapeutic alternatives as in comparative effectiveness research, are likely to be heterogeneous across age, gender, co-morbidities, and co-medications. Propensity scores (PSs), an alternative to multivariable outcome models to control for measured confounding, have specific advantages in the presence of heterogeneous treatment effects. Implementing PSs using matching or weighting allows us to estimate different overall treatment effects in differently defined populations. Heterogeneous treatment effects can also be due to unmeasured confounding concentrated in those treated contrary to prediction. Sensitivity analyses based on PSs can help to assess such unmeasured confounding. PSs should be considered a primary or secondary analytic strategy in non-experimental medical research, including pharmacoepidemiology and non-experimental comparative effectiveness research. PMID:24520806

  9. Effects of the duration and inorganic nitrogen composition of a nutrient-rich patch on soil exploration by the roots of Lolium perenne in a heterogeneous environment.

    PubMed

    Nakamura, Ryoji; Kachi, N; Suzuki, J-I

    2010-05-01

    We investigated the growth of and soil exploration by Lolium perenne under a heterogeneous environment before its roots reached a nutrient-rich patch. Temporal changes in the distribution of inorganic nitrogen, i.e., NO(3)(-)-N and NH(4)(+)-N, in the heterogeneous environment during the experimental period were also examined. The results showed that roots randomly explored soil, irrespective of the patchy distribution of inorganic nitrogen and differences in the chemical composition of inorganic nitrogen distribution between heterogeneous and homogeneous environments. We have also elucidated the potential effects of patch duration and inorganic nitrogen distribution on soil exploration by roots and thus on plant growth.

  10. Facile Hydrothermal Preparation of ZNO/CO3O4 Heterogeneous Nanostructures and its Photovoltaic Effect

    NASA Astrophysics Data System (ADS)

    Wei, Fanan; Jiang, Minlin; Liu, Lianqing

    2015-07-01

    Photovoltaic technology offers great potential in the replacement of fossil fuel resources, but still suffers from high device fabrication cost. Herein, we attempted to provide a solution to these issues with heterogeneous nanostructures. Firstly, Zinc oxide (ZnO)/cobalt oxide (Co3O4) heterojunction nanowires are prepared through facile fabrication methods. By assembling Co(OH)2 nanoplates on ZnO nanowire arrays, the ZnO/Co3O4 heterogeneous nanostructures are uniformly synthesized on ITO coated glass and wafer. Current (I)-voltage (V) measurement through conductive atomic force microscope shows excellent photovoltaic effect. And, the heterojunction nanostructures shows unprecedented high open circuit voltage. Therefore, the potential application of the heterogeneous nanostructures in solar cells is demonstrated.

  11. An Effective Cache Algorithm for Heterogeneous Storage Systems

    PubMed Central

    Li, Yong; Feng, Dan

    2013-01-01

    Modern storage environment is commonly composed of heterogeneous storage devices. However, traditional cache algorithms exhibit performance degradation in heterogeneous storage systems because they were not designed to work with the diverse performance characteristics. In this paper, we present a new cache algorithm called HCM for heterogeneous storage systems. The HCM algorithm partitions the cache among the disks and adopts an effective scheme to balance the work across the disks. Furthermore, it applies benefit-cost analysis to choose the best allocation of cache block to improve the performance. Conducting simulations with a variety of traces and a wide range of cache size, our experiments show that HCM significantly outperforms the existing state-of-the-art storage-aware cache algorithms. PMID:24453890

  12. Theobromine for the treatment of persistent cough: a randomised, multicentre, double-blind, placebo-controlled clinical trial

    PubMed Central

    McGarvey, Lorcan; Pavord, Ian D.; Higgins, Bernard; Chung, Kian Fan; Birring, Surinder S.

    2017-01-01

    Background To investigate the effect of BC1036 on health-related quality of life (QOL) in subjects with persistent cough. The secondary objective was to investigate the effect of BC1036 on subjective cough severity. Methods This was a randomised, multicentre, double-blind, placebo-controlled, parallel-group study in 289 subjects with persistent cough. Subjects received BC1036 or placebo twice daily for 14 days. The primary endpoint comprised cough-related QOL assessed using the validated Leicester Cough Questionnaire (LCQ) at Day 14. Secondary endpoints comprised the LCQ scores at Day 7 and Day 28, cough severity VAS scores at each visit and pulmonary function tests. Results At baseline, mean total LCQ score in the BC1036 group was lower (i.e., worse QOL) than placebo (P<0.001), indicating significant between-group heterogeneity. Mean baseline-adjusted change in LCQ score at Day 14 was greater for BC1036 [mean (SD) 2.4±3.5] compared to placebo [mean (SD) score 2.2±3.0], but did not reach statistical significance (P=0.60). Mean cough severity VAS score decreased to a greater extent in the BC1036 group compared to placebo, but again the results were not statistically significant (−12.2±23.28 in BC1036 group and −11.0±21.34 in placebo group at Day 14, P=0.688). There was no significant change in pulmonary function measurements. The adverse event (AE) profile was similar in both groups. Conclusions This study showed that BC1036 was well tolerated and, although the primary endpoint did not achieve statistical significance, the magnitude of improvement was greater with BC1036 compared to placebo with respect to improving QOL and reducing cough severity. Clinical trial registration ClinicalTrials.gov: NCT01656668. PMID:28839984

  13. Magnetostructural coupling behavior at the ferromagnetic transition in double-perovskite S r2FeMo O6

    NASA Astrophysics Data System (ADS)

    Yang, Dexin; Harrison, Richard J.; Schiemer, Jason A.; Lampronti, Giulio I.; Liu, Xueyin; Zhang, Fenghua; Ding, Hao; Liu, Yan'gai; Carpenter, Michael A.

    2016-01-01

    The ordered double-perovskite S r2FeMo O6 (SFMO) possesses remarkable room-temperature low-field colossal magnetoresistivity and transport properties which are related, at least in part, to combined structural and magnetic instabilities that are responsible for a cubic-tetragonal phase transition near 420 K. A formal strain analysis combined with measurements of elastic properties from resonant ultrasound spectroscopy reveal a system with weak biquadratic coupling between two order parameters belonging to Γ4+ and m Γ4+ of parent space group F m 3 ¯m . The observed softening of the shear modulus by ˜50% is due to the classical effects of strain/order parameter coupling at an improper ferroelastic (Γ4+) transition which is second order in character, while the ferromagnetic order parameter (m Γ4+ ) couples only with volume strain. The influence of a third order parameter, for ordering of Fe and Mo on crystallographic B sites, is to change the strength of coupling between the Γ4+ order parameter and the tetragonal shear strain due to the influence of changes in local strain heterogeneity at a unit cell scale. High anelastic loss below the transition point reveals the presence of mobile ferroelastic twin walls which become pinned by oxygen vacancies in a temperature interval near 340 K. The twin walls must be both ferroelastic and ferromagnetic, but due to the weak coupling between the magnetic and structural order parameters it should be possible to pull them apart with a weak magnetic field. These insights into the role of strain coupling and relaxational effects in a system with only weak coupling between three order parameters allow rationalization and prediction of how static and dynamic properties of the material might be tuned in thin film form by choice of strain contrast with a substrate.

  14. A randomized, double-blind, placebo-controlled, multicenter study of a ginger extract in the management of chemotherapy-induced nausea and vomiting (CINV) in patients receiving high-dose cisplatin.

    PubMed

    Bossi, P; Cortinovis, D; Fatigoni, S; Cossu Rocca, M; Fabi, A; Seminara, P; Ripamonti, C; Alfieri, S; Granata, R; Bergamini, C; Agustoni, F; Bidoli, P; Nolè, F; Pessi, M A; Macchi, F; Michellini, L; Montanaro, F; Roila, F

    2017-10-01

    The activity of ginger in the management of chemotherapy-induced nausea and vomiting (CINV) has been suggested, but design inadequacies, heterogeneity of the population, small numbers and poor quality of tested products limit the possibility to offer generalizable results. We conducted a randomized, double-blind, placebo-controlled, multicenter study in patients planned to receive ≥2 chemotherapy cycles with high dose (>50 mg/m2) cisplatin. Patients received ginger 160 mg/day (with standardized dose of bioactive compounds) or placebo in addition to the standard antiemetic prophylaxis for CINV, starting from the day after cisplatin administration. CINV was assessed through daily visual-analogue scale and Functional Living Index Emesis questionnaires. The main objective was protection from delayed nausea; secondary end points included intercycle nausea and nausea anticipatory symptoms. In total, 121 patients received ginger and 123 placebo. Lung (49%) and head and neck cancer (HNC; 35%) were the most represented tumors. No differences were reported in terms of safety profile or compliance. The incidence of delayed, intercycle and anticipatory nausea did not differ between the two arms in the first cycle and second cycle. A benefit of ginger over placebo in Functional Living Index Emesis nausea score differences (day 6-day 1) was identified for females (P = 0.048) and HNC patients (P = 0.038). In patients treated with high-dose cisplatin, the daily addition of ginger, even if safe, did not result in a protective effect on CINV. The favorable effect observed on nausea in subgroups at particular risk of nausea (females; HNC) deserves specific investigation. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  15. The Effect of Variation in Permittivity of Different Tissues on Induced Electric Field in the Brain during Transcranial Magnetic Stimulation

    NASA Astrophysics Data System (ADS)

    Hadimani, Ravi; Porzig, Konstantin; Crowther, Lawrence; Brauer, Hartmut; Toepfer, Hannes; Jiles, David; Department of Electrical and Computer Engineering, Iowa State University Team; Department of Advanced Electromagnetics, Ilmenau University of Technology Team

    2013-03-01

    Estimation of electric field in the brain during Transcranial Magnetic Stimulation (TMS) requires knowledge of the electric property of brain tissue. Grey and white matters have unusually high relative permittivities of ~ 106 at low frequencies. However, relative permittivity of cerebrospinal fluid is ~ 102. With such a variation it is necessary to consider the effect of boundaries. A model consisting of 2 hemispheres was used in the model with the properties of one hemisphere kept constant at σ1 = 0.1Sm-1 and ɛr 1 = 10 while the properties of the second hemisphere were changed kept at σ2 = 0.1Sm-1 to 2Sm-1 and ɛr 2 = 102 to 105. A 70 mm diameter double coil was used as the source of the magnetic field. The amplitude of the current in the coil was 5488 A at a frequency of 2.9 kHz. The results show that the electric field, E induced during magnetic stimulation is independent of the relative permittivity, ɛr and varies with the conductivity. Thus the variation in E, calculated with homogeneous and heterogeneous head models was due to variation in conductivity of the tissues and not due to variation in permittivities.

  16. Transcranial Magnetic Stimulation to Address Mild Cognitive Impairment in the Elderly: A Randomized Controlled Study

    PubMed Central

    Drumond Marra, Hellen Livia; Myczkowski, Martin Luiz; Maia Memória, Cláudia; Arnaut, Débora; Leite Ribeiro, Philip; Sardinha Mansur, Carlos Gustavo; Lancelote Alberto, Rodrigo; Boura Bellini, Bianca; Alves Fernandes da Silva, Adriano; Ciampi de Andrade, Daniel; Teixeira, Manoel Jacobsen; Forlenza, Orestes Vicente; Marcolin, Marco Antonio

    2015-01-01

    Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique with potential to improve memory. Mild cognitive impairment (MCI), which still lacks a specific therapy, is a clinical syndrome associated with increased risk of dementia. This study aims to assess the effects of high-frequency repetitive TMS (HF rTMS) on everyday memory of the elderly with MCI. We conducted a double-blinded randomized sham-controlled trial using rTMS over the left dorsolateral prefrontal cortex (DLPFC). Thirty-four elderly outpatients meeting Petersen's MCI criteria were randomly assigned to receive 10 sessions of either active TMS or sham, 10 Hz rTMS at 110% of motor threshold, 2,000 pulses per session. Neuropsychological assessment at baseline, after the last session (10th) and at one-month follow-up, was applied. ANOVA on the primary efficacy measure, the Rivermead Behavioural Memory Test, revealed a significant group-by-time interaction (p = 0.05), favoring the active group. The improvement was kept after one month. Other neuropsychological tests were heterogeneous. rTMS at 10 Hz enhanced everyday memory in elderly with MCI after 10 sessions. These findings suggest that rTMS might be effective as a therapy for MCI and probably a tool to delay deterioration. PMID:26160997

  17. 4D in situ visualization of electrode morphology changes during accelerated degradation in fuel cells by X-ray computed tomography

    NASA Astrophysics Data System (ADS)

    White, Robin T.; Wu, Alex; Najm, Marina; Orfino, Francesco P.; Dutta, Monica; Kjeang, Erik

    2017-05-01

    A four-dimensional visualization approach, featuring three dimensions in space and one dimension in time, is proposed to study local electrode degradation effects during voltage cycling in fuel cells. Non-invasive in situ micro X-ray computed tomography (XCT) with a custom fuel cell fixture is utilized to track the same cathode catalyst layer domain throughout various degradation times from beginning-of-life (BOL) to end-of-life (EOL). With this unique approach, new information regarding damage features and trends are revealed, including crack propagation and catalyst layer thinning being quantified by means of image processing and analysis methods. Degradation heterogeneities as a result of local environmental variations under land and channel are also explored, with a higher structural degradation rate under channels being observed. Density and compositional changes resulting from carbon corrosion and catalyst layer collapse and thinning are observed by changes in relative X-ray attenuation from BOL to EOL, which also indicate possible vulnerable regions where crack initiation and propagation may occur. Electrochemical diagnostics and morphological features observed by micro-XCT are correlated by additionally collecting effective catalyst surface area, double layer capacitance, and polarization curves prior to imaging at various stages of degradation.

  18. Dynamic three-dimensional pore-scale imaging of reaction in a carbonate at reservoir conditions.

    PubMed

    Menke, Hannah P; Bijeljic, Branko; Andrew, Matthew G; Blunt, Martin J

    2015-04-07

    Quantifying CO2 transport and average effective reaction rates in the subsurface is essential to assess the risks associated with underground carbon capture and storage. We use X-ray microtomography to investigate dynamic pore structure evolution in situ at temperatures and pressures representative of underground reservoirs and aquifers. A 4 mm diameter Ketton carbonate core is injected with CO2-saturated brine at 50 °C and 10 MPa while tomographic images are taken at 15 min intervals with a 3.8 μm spatial resolution over a period of 2(1/2) h. An approximate doubling of porosity with only a 3.6% increase in surface area to volume ratio is measured from the images. Pore-scale direct simulation and network modeling on the images quantify an order of magnitude increase in permeability and an appreciable alteration of the velocity field. We study the uniform reaction regime, with dissolution throughout the core. However, at the pore scale, we see variations in the degree of dissolution with an overall reaction rate which is approximately 14 times lower than estimated from batch measurements. This work implies that in heterogeneous rocks, pore-scale transport of reactants limits dissolution and can reduce the average effective reaction rate by an order of magnitude.

  19. Moran-evolution of cooperation: From well-mixed to heterogeneous complex networks

    NASA Astrophysics Data System (ADS)

    Sarkar, Bijan

    2018-05-01

    Configurational arrangement of network architecture and interaction character of individuals are two most influential factors on the mechanisms underlying the evolutionary outcome of cooperation, which is explained by the well-established framework of evolutionary game theory. In the current study, not only qualitatively but also quantitatively, we measure Moran-evolution of cooperation to support an analytical agreement based on the consequences of the replicator equation in a finite population. The validity of the measurement has been double-checked in the well-mixed network by the Langevin stochastic differential equation and the Gillespie-algorithmic version of Moran-evolution, while in a structured network, the measurement of accuracy is verified by the standard numerical simulation. Considering the Birth-Death and Death-Birth updating rules through diffusion of individuals, the investigation is carried out in the wide range of game environments those relate to the various social dilemmas where we are able to draw a new rigorous mathematical track to tackle the heterogeneity of complex networks. The set of modified criteria reveals the exact fact about the emergence and maintenance of cooperation in the structured population. We find that in general, nature promotes the environment of coexistent traits.

  20. New Insights on Developmental Dyslexia Subtypes: Heterogeneity of Mixed Reading Profiles

    PubMed Central

    Zoubrinetzky, Rachel; Bielle, Frédérique; Valdois, Sylviane

    2014-01-01

    We examined whether classifications based on reading performance are relevant to identify cognitively homogeneous subgroups of dyslexic children. Each of the 71 dyslexic participants was selected to have a mixed reading profile, i.e. poor irregular word and pseudo-word reading performance (accuracy and speed). Despite their homogeneous reading profile, the participants were found to split into four distinct cognitive subgroups, characterized by a single phonological disorder, a single visual attention span disorder, a double deficit or none of these disorders. The two subgroups characterized by single and contrasted cognitive disorders were found to exhibit a very similar reading pattern but more contrasted spelling performance (quantitative analysis). A qualitative analysis of the error types produced in reading and spelling provided some cues about the participants' underlying cognitive deficit. The overall findings disqualify subtyping based on reading profiles as a classification method to identify cognitively homogeneous subgroups of dyslexic children. They rather show an opaque relationship between the cognitive underpinnings of developmental dyslexia and their behavioral manifestations in reading and spelling. Future neuroimaging and genetic studies should take this issue into account since synthesizing over cognitively heterogeneous children would entail potential pitfalls. PMID:24918441

  1. Membrane vesicles in sea water: heterogeneous DNA content and implications for viral abundance estimates

    PubMed Central

    Biller, Steven J; McDaniel, Lauren D; Breitbart, Mya; Rogers, Everett; Paul, John H; Chisholm, Sallie W

    2017-01-01

    Diverse microbes release membrane-bound extracellular vesicles from their outer surfaces into the surrounding environment. Vesicles are found in numerous habitats including the oceans, where they likely have a variety of functional roles in microbial ecosystems. Extracellular vesicles are known to contain a range of biomolecules including DNA, but the frequency with which DNA is packaged in vesicles is unknown. Here, we examine the quantity and distribution of DNA associated with vesicles released from five different bacteria. The average quantity of double-stranded DNA and size distribution of DNA fragments released within vesicles varies among different taxa. Although some vesicles contain sufficient DNA to be visible following staining with the SYBR fluorescent DNA dyes typically used to enumerate viruses, this represents only a small proportion (<0.01–1%) of vesicles. Thus DNA is packaged heterogeneously within vesicle populations, and it appears that vesicles are likely to be a minor component of SYBR-visible particles in natural sea water compared with viruses. Consistent with this hypothesis, chloroform treatment of coastal and offshore seawater samples reveals that vesicles increase epifluorescence-based particle (viral) counts by less than an order of magnitude and their impact is variable in space and time. PMID:27824343

  2. Electronic π-Delocalization Boosts Catalytic Water Oxidation by Cu(II) Molecular Catalysts Heterogenized on Graphene Sheets.

    PubMed

    Garrido-Barros, Pablo; Gimbert-Suriñach, Carolina; Moonshiram, Dooshaye; Picón, Antonio; Monge, Pere; Batista, Victor S; Llobet, Antoni

    2017-09-20

    A molecular water oxidation catalyst based on the copper complex of general formula [(L py )Cu II ] 2- , 2 2- , (L py is 4-pyrenyl-1,2-phenylenebis(oxamidate) ligand) has been rationally designed and prepared to support a more extended π-conjugation through its structure in contrast with its homologue, the [(L)Cu II ] 2- water oxidation catalyst, 1 2- (L is o-phenylenebis(oxamidate)). The catalytic performance of both catalysts has been comparatively studied in homogeneous phase and in heterogeneous phase by π-stacking anchorage to graphene-based electrodes. In the homogeneous system, the electronic perturbation provided by the pyrene functionality translates into a 150 mV lower overpotential for 2 2- with respect to 1 2- and an impressive increase in the k cat from 6 to 128 s -1 . Upon anchorage, π-stacking interactions with the graphene sheets provide further π-delocalization that improves the catalytic performance of both catalysts. In this sense, 2 2- turned out to be the most active catalyst due to the double influence of both the pyrene and the graphene, displaying an overpotential of 538 mV, a k cat of 540 s -1 and producing more than 5300 TONs.

  3. Heterogeneity of chromatoid bodies in adult pluripotent stem cells of planarian Dugesia japonica.

    PubMed

    Kashima, Makoto; Kumagai, Nobuyoshi; Agata, Kiyokazu; Shibata, Norito

    2016-02-01

    The robust regenerative ability of planarians is known to be dependent on adult pluripotent stem cells called neoblasts. One of the morphological features of neoblasts is cytoplasmic ribonucleoprotein granules (chromatoid bodies: CBs), which resemble germ granules present in germline cells in other animals. Previously, we showed by immuno-electron microscopic analysis that DjCBC-1, a planarian Me31B/Dhh1/DDX6 homologue, which is a component of ribonucleoprotein granules, was localized in CBs in the planarian Dugesia japonica. Also, recently it was reported using another planarian species that Y12 antibody recognizing symmetrical dimethylarginine (sDMA) specifically binds to CBs in which histone mRNA is co-localized. Here, we showed by double immunostaining and RNA interference (RNAi) that DjCBC-1-containing CBs and Y12-immunoreactive CBs are distinct structures, suggesting that CBs are composed of heterogeneous populations. We also found that the Y12-immunoreactive CBs specifically contained a cytoplasmic type of planarian PIWI protein (DjPiwiC). We revealed by RNAi experiments that Y12-immunoreactive CBs may have anti-transposable element activity involving the DjPiwiC protein in the neoblasts. © 2016 Japanese Society of Developmental Biologists.

  4. Piezo-phototronic effect enhanced UV photodetector based on CuI/ZnO double-shell grown on flexible copper microwire.

    PubMed

    Liu, Jingyu; Zhang, Yang; Liu, Caihong; Peng, Mingzeng; Yu, Aifang; Kou, Jinzong; Liu, Wei; Zhai, Junyi; Liu, Juan

    2016-12-01

    In this work, we present a facile, low-cost, and effective approach to fabricate the UV photodetector with a CuI/ZnO double-shell nanostructure which was grown on common copper microwire. The enhanced performances of Cu/CuI/ZnO core/double-shell microwire photodetector resulted from the formation of heterojunction. Benefiting from the piezo-phototronic effect, the presentation of piezocharges can lower the barrier height and facilitate the charge transport across heterojunction. The photosensing abilities of the Cu/CuI/ZnO core/double-shell microwire detector are investigated under different UV light densities and strain conditions. We demonstrate the I-V characteristic of the as-prepared core/double-shell device; it is quite sensitive to applied strain, which indicates that the piezo-phototronic effect plays an essential role in facilitating charge carrier transport across the CuI/ZnO heterojunction, then the performance of the device is further boosted under external strain.

  5. Ethnicity, obesity and the prevalence of impaired glucose tolerance and type 2 diabetes in PCOS: a systematic review and meta-regression.

    PubMed

    Kakoly, N S; Khomami, M B; Joham, A E; Cooray, S D; Misso, M L; Norman, R J; Harrison, C L; Ranasinha, S; Teede, H J; Moran, L J

    2018-03-26

    Our prior meta-analyses demonstrated an increased prevalence of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) with polycystic ovary syndrome (PCOS), but with substantial clinical heterogeneity. We aimed to update our previous review to quantify the prevalence of IGT and T2DM in PCOS with only quality studies (good and fair quality). We also aimed to examine the contribution of parameters including ethnicity, obesity and method of diagnosing T2DM in explaining the observed heterogeneity in IGT and T2DM prevalence in PCOS. We conducted a literature search (MEDLINE, CINAHL, EMBASE, clinical trial registries and hand-searching) up to June 2016 to identify studies reporting the prevalence of dysglycemia (IGT and T2DM) in women with and without PCOS. We included studies where women with PCOS (defined according to original National Institute of Health) were compared to women without PCOS for the end-points of the prevalence of IGT or T2DM. We excluded case reports, case series, editorials, and narrative reviews. Studies where PCOS was diagnosed by self-report, or where IGT or T2DM were measured by fasting glucose, only were excluded. We assessed the methodological quality of the included studies using a priori criteria based on the Newcastle-Ottawa Scaling (NOS) for non-randomized studies. Data are presented as odds ratio (OR) (95% CI) with random-effects meta-analysis by Mantel-Haenszel methods. We assessed the contribution of demographic and clinical factors to heterogeneity using subgroup and meta-regression analysis. We reviewed 4530 studies and included 40 eligible studies in the final analysis. On meta-analysis of quality studies, women with PCOS had an increased prevalence of IGT (OR = 3.26, 95% CI: 2.17-4.90) and T2DM (OR = 2.87, 95% CI: 1.44-5.72), which differed by ethnicity (for IGT, Asia: 5-fold, the Americas: 4-fold and Europe: 3-fold), was higher with obesity, and doubled among studies using self-report or administrative data for diagnosing diabetes. The ethnicity-related difference retained its significance for Asia and Europe in BMI-matched subgroups. Clear contributors to heterogeneity did not emerge in meta-regression. Our findings underscore the importance of PCOS as a cause of dysglycemia with a higher prevalence of IGT and T2DM. They support the relevance of ethnicity and obesity and emphasize the need for accurate diagnostic methods for diabetes. CRD42017056524.

  6. [Effectiveness of Vitex agnus-castus preparations].

    PubMed

    Gorkow, C; Wuttke, W; März, R W

    2002-01-01

    The prolactin-inhibiting effect of ACF-preparations, which is due to dopaminergic activities, has been shown in humans too and gives a pharmacological rationale for the clinical effects observed in the different indications (2, 11, 25, 26, 35, 41). Confirmation of efficacy in the treatment of mastalgia has been best endorsed by two recently published double-blind studies conducted according to the principles of GCP (14, 41). One double-blind study, several open and postmarketing surveillance studies have shown that the premenstrual syndrome, or individual symptoms, can be influenced positively (3, 6, 7, 9, 19, 21, 37). Design shortcomings in a second double-blind study should be eliminated in future studies in this indication to improve the body of evidence (18). Hither to there has been one controlled double-blind study of cycle disorders in the case of corpus luteum insufficiency with significant results and a number of non-controlled open studies (1, 4, 15, 16, 20, 24, 26, 27, 32, 35, 36). The high success rates in the open studies indicate therapeutic effects, and it should be possible to reproduce these results under double-blind conditions. The success rates on fertility disorders should be confirmed in controlled double-blind studies (10, 33, 34).

  7. Graphic report of the results from propensity score method analyses.

    PubMed

    Shrier, Ian; Pang, Menglan; Platt, Robert W

    2017-08-01

    To increase transparency in studies reporting propensity scores by using graphical methods that clearly illustrate (1) the number of participant exclusions that occur as a consequence of the analytic strategy and (2) whether treatment effects are constant or heterogeneous across propensity scores. We applied graphical methods to a real-world pharmacoepidemiologic study that evaluated the effect of initiating statin medication on the 1-year all-cause mortality post-myocardial infarction. We propose graphical methods to show the consequences of trimming and matching on the exclusion of participants from the analysis. We also propose the use of meta-analytical forest plots to show the magnitude of effect heterogeneity. A density plot with vertical lines demonstrated the proportion of subjects excluded because of trimming. A frequency plot with horizontal lines demonstrated the proportion of subjects excluded because of matching. An augmented forest plot illustrates the amount of effect heterogeneity present in the data. Our proposed techniques present additional and useful information that helps readers understand the sample that is analyzed with propensity score methods and whether effect heterogeneity is present. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Chromosome doubling method

    DOEpatents

    Kato, Akio

    2006-11-14

    The invention provides methods for chromosome doubling in plants. The technique overcomes the low yields of doubled progeny associated with the use of prior techniques for doubling chromosomes in plants such as grasses. The technique can be used in large scale applications and has been demonstrated to be highly effective in maize. Following treatment in accordance with the invention, plants remain amenable to self fertilization, thereby allowing the efficient isolation of doubled progeny plants.

  9. Nonidentifiability of population size from capture-recapture data with heterogeneous detection probabilities

    USGS Publications Warehouse

    Link, W.A.

    2003-01-01

    Heterogeneity in detection probabilities has long been recognized as problematic in mark-recapture studies, and numerous models developed to accommodate its effects. Individual heterogeneity is especially problematic, in that reasonable alternative models may predict essentially identical observations from populations of substantially different sizes. Thus even with very large samples, the analyst will not be able to distinguish among reasonable models of heterogeneity, even though these yield quite distinct inferences about population size. The problem is illustrated with models for closed and open populations.

  10. A kinetic model for heterogeneous condensation of vapor on an insoluble spherical particle.

    PubMed

    Luo, Xisheng; Fan, Yu; Qin, Fenghua; Gui, Huaqiao; Liu, Jianguo

    2014-01-14

    A kinetic model is developed to describe the heterogeneous condensation of vapor on an insoluble spherical particle. This new model considers two mechanisms of cluster growth: direct addition of water molecules from the vapor and surface diffusion of adsorbed water molecules on the particle. The effect of line tension is also included in the model. For the first time, the exact expression of evaporation coefficient is derived for heterogeneous condensation of vapor on an insoluble spherical particle by using the detailed balance. The obtained expression of evaporation coefficient is proved to be also correct in the homogeneous condensation and the heterogeneous condensation on a planar solid surface. The contributions of the two mechanisms to heterogeneous condensation including the effect of line tension are evaluated and analysed. It is found that the cluster growth via surface diffusion of adsorbed water molecules on the particle is more important than the direct addition from the vapor. As an example of our model applications, the growth rate of the cap shaped droplet on the insoluble spherical particle is derived. Our evaluation shows that the growth rate of droplet in heterogeneous condensation is larger than that in homogeneous condensation. These results indicate that an explicit kinetic model is benefit to the study of heterogeneous condensation on an insoluble spherical particle.

  11. A weighted U statistic for association analyses considering genetic heterogeneity.

    PubMed

    Wei, Changshuai; Elston, Robert C; Lu, Qing

    2016-07-20

    Converging evidence suggests that common complex diseases with the same or similar clinical manifestations could have different underlying genetic etiologies. While current research interests have shifted toward uncovering rare variants and structural variations predisposing to human diseases, the impact of heterogeneity in genetic studies of complex diseases has been largely overlooked. Most of the existing statistical methods assume the disease under investigation has a homogeneous genetic effect and could, therefore, have low power if the disease undergoes heterogeneous pathophysiological and etiological processes. In this paper, we propose a heterogeneity-weighted U (HWU) method for association analyses considering genetic heterogeneity. HWU can be applied to various types of phenotypes (e.g., binary and continuous) and is computationally efficient for high-dimensional genetic data. Through simulations, we showed the advantage of HWU when the underlying genetic etiology of a disease was heterogeneous, as well as the robustness of HWU against different model assumptions (e.g., phenotype distributions). Using HWU, we conducted a genome-wide analysis of nicotine dependence from the Study of Addiction: Genetics and Environments dataset. The genome-wide analysis of nearly one million genetic markers took 7h, identifying heterogeneous effects of two new genes (i.e., CYP3A5 and IKBKB) on nicotine dependence. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  12. Interval estimation of the overall treatment effect in a meta-analysis of a few small studies with zero events.

    PubMed

    Pateras, Konstantinos; Nikolakopoulos, Stavros; Mavridis, Dimitris; Roes, Kit C B

    2018-03-01

    When a meta-analysis consists of a few small trials that report zero events, accounting for heterogeneity in the (interval) estimation of the overall effect is challenging. Typically, we predefine meta-analytical methods to be employed. In practice, data poses restrictions that lead to deviations from the pre-planned analysis, such as the presence of zero events in at least one study arm. We aim to explore heterogeneity estimators behaviour in estimating the overall effect across different levels of sparsity of events. We performed a simulation study that consists of two evaluations. We considered an overall comparison of estimators unconditional on the number of observed zero cells and an additional one by conditioning on the number of observed zero cells. Estimators that performed modestly robust when (interval) estimating the overall treatment effect across a range of heterogeneity assumptions were the Sidik-Jonkman, Hartung-Makambi and improved Paul-Mandel. The relative performance of estimators did not materially differ between making a predefined or data-driven choice. Our investigations confirmed that heterogeneity in such settings cannot be estimated reliably. Estimators whose performance depends strongly on the presence of heterogeneity should be avoided. The choice of estimator does not need to depend on whether or not zero cells are observed.

  13. Parameter Heterogeneity In Breast Cancer Cost Regressions – Evidence From Five European Countries

    PubMed Central

    Banks, Helen; Campbell, Harry; Douglas, Anne; Fletcher, Eilidh; McCallum, Alison; Moger, Tron Anders; Peltola, Mikko; Sveréus, Sofia; Wild, Sarah; Williams, Linda J.; Forbes, John

    2015-01-01

    Abstract We investigate parameter heterogeneity in breast cancer 1‐year cumulative hospital costs across five European countries as part of the EuroHOPE project. The paper aims to explore whether conditional mean effects provide a suitable representation of the national variation in hospital costs. A cohort of patients with a primary diagnosis of invasive breast cancer (ICD‐9 codes 174 and ICD‐10 C50 codes) is derived using routinely collected individual breast cancer data from Finland, the metropolitan area of Turin (Italy), Norway, Scotland and Sweden. Conditional mean effects are estimated by ordinary least squares for each country, and quantile regressions are used to explore heterogeneity across the conditional quantile distribution. Point estimates based on conditional mean effects provide a good approximation of treatment response for some key demographic and diagnostic specific variables (e.g. age and ICD‐10 diagnosis) across the conditional quantile distribution. For many policy variables of interest, however, there is considerable evidence of parameter heterogeneity that is concealed if decisions are based solely on conditional mean results. The use of quantile regression methods reinforce the need to consider beyond an average effect given the greater recognition that breast cancer is a complex disease reflecting patient heterogeneity. © 2015 The Authors. Health Economics Published by John Wiley & Sons Ltd. PMID:26633866

  14. Accounting for Heterogeneity in Relative Treatment Effects for Use in Cost-Effectiveness Models and Value-of-Information Analyses

    PubMed Central

    Soares, Marta O.; Palmer, Stephen; Ades, Anthony E.; Harrison, David; Shankar-Hari, Manu; Rowan, Kathy M.

    2015-01-01

    Cost-effectiveness analysis (CEA) models are routinely used to inform health care policy. Key model inputs include relative effectiveness of competing treatments, typically informed by meta-analysis. Heterogeneity is ubiquitous in meta-analysis, and random effects models are usually used when there is variability in effects across studies. In the absence of observed treatment effect modifiers, various summaries from the random effects distribution (random effects mean, predictive distribution, random effects distribution, or study-specific estimate [shrunken or independent of other studies]) can be used depending on the relationship between the setting for the decision (population characteristics, treatment definitions, and other contextual factors) and the included studies. If covariates have been measured that could potentially explain the heterogeneity, then these can be included in a meta-regression model. We describe how covariates can be included in a network meta-analysis model and how the output from such an analysis can be used in a CEA model. We outline a model selection procedure to help choose between competing models and stress the importance of clinical input. We illustrate the approach with a health technology assessment of intravenous immunoglobulin for the management of adult patients with severe sepsis in an intensive care setting, which exemplifies how risk of bias information can be incorporated into CEA models. We show that the results of the CEA and value-of-information analyses are sensitive to the model and highlight the importance of sensitivity analyses when conducting CEA in the presence of heterogeneity. The methods presented extend naturally to heterogeneity in other model inputs, such as baseline risk. PMID:25712447

  15. Accounting for Heterogeneity in Relative Treatment Effects for Use in Cost-Effectiveness Models and Value-of-Information Analyses.

    PubMed

    Welton, Nicky J; Soares, Marta O; Palmer, Stephen; Ades, Anthony E; Harrison, David; Shankar-Hari, Manu; Rowan, Kathy M

    2015-07-01

    Cost-effectiveness analysis (CEA) models are routinely used to inform health care policy. Key model inputs include relative effectiveness of competing treatments, typically informed by meta-analysis. Heterogeneity is ubiquitous in meta-analysis, and random effects models are usually used when there is variability in effects across studies. In the absence of observed treatment effect modifiers, various summaries from the random effects distribution (random effects mean, predictive distribution, random effects distribution, or study-specific estimate [shrunken or independent of other studies]) can be used depending on the relationship between the setting for the decision (population characteristics, treatment definitions, and other contextual factors) and the included studies. If covariates have been measured that could potentially explain the heterogeneity, then these can be included in a meta-regression model. We describe how covariates can be included in a network meta-analysis model and how the output from such an analysis can be used in a CEA model. We outline a model selection procedure to help choose between competing models and stress the importance of clinical input. We illustrate the approach with a health technology assessment of intravenous immunoglobulin for the management of adult patients with severe sepsis in an intensive care setting, which exemplifies how risk of bias information can be incorporated into CEA models. We show that the results of the CEA and value-of-information analyses are sensitive to the model and highlight the importance of sensitivity analyses when conducting CEA in the presence of heterogeneity. The methods presented extend naturally to heterogeneity in other model inputs, such as baseline risk. © The Author(s) 2015.

  16. 56. PHOTOCOPY OF DRAWING AMMONIA LEACHING PLANT GENERAL, DOUBLE EFFECT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    56. PHOTOCOPY OF DRAWING AMMONIA LEACHING PLANT GENERAL, DOUBLE EFFECT EVAPORATOR UNIT - Kennecott Copper Corporation, On Copper River & Northwestern Railroad, Kennicott, Valdez-Cordova Census Area, AK

  17. 57. PHOTOCOPY OF DRAWING AMMONIA LEACHING PLANT GENERAL, DOUBLE EFFECT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    57. PHOTOCOPY OF DRAWING AMMONIA LEACHING PLANT GENERAL, DOUBLE EFFECT EVAPORATOR UNIT - Kennecott Copper Corporation, On Copper River & Northwestern Railroad, Kennicott, Valdez-Cordova Census Area, AK

  18. Heterogeneous Catalysis: On Bathroom Mirrors and Boiling Stones

    ERIC Educational Resources Information Center

    Philipse, Albert P.

    2011-01-01

    Though heterogeneous nucleation of liquid droplets on a smooth surface (such as a bathroom mirror) is a classical topic in nucleation theory, it is not well-known that this topic is actually a pedagogical example of heterogeneous catalysis: the one and only effect of the surface is to lower the activation Gibbs energy of droplet formation. In…

  19. Cardiac complications after stroke: protocol for a systematic review and meta-analysis.

    PubMed

    Kenmogne-Domning, Guidelle Héloïse; Kamtchum-Tatuene, Joseph; Noumegni, Steve Raoul; Fokoua-Dongmo, Christophe Maxime; Zafack, Joseline Guetsop; Noubiap, Jean Jacques

    2018-05-24

    Stroke is the second most common cause of death after ischaemic heart diseases and the third leading cause of disability worldwide. The contribution of cardiac complications to the mortality of patients with stroke is variable across studies, ranging from 12.5% to 22.7%. Many of these cardiac complications are preventable, and early recognition and adequate management guided by appropriate up-to-date knowledge of their relative incidence and fatality can help to improve patients' outcomes. This systematic review aims to summarise the available data on the burden of cardiac complications after stroke. This review will include all cross-sectional, case-control and cohort studies and clinical trials published between 1 January 1950 and 31 December 2017, involving adults and/or children, and reporting on the prevalence, the incidence and/or the mortality of cardiac complications after stroke. Two reviewers will independently screen titles and abstracts of records retrieved from PubMed, Excerpta Medica Database, ISI Web of Science and the Cumulative Index to Nursing and Allied Health Literature for eligibility, and then assess the risk of bias and quality of reporting to select the studies which will be included. All authors will contribute to the retrieval of full texts of eligible records and data extraction. Heterogeneity across studies will be evaluated by the χ 2 test on Cochran's Q statistic. Study-specific estimates of the prevalence, incidence and mortality of cardiac complications after stroke across studies will be pooled through random-effect or fixed-effect meta-analysis depending on the source of the heterogeneity, after stabilising the variance of individual studies using the Freeman-Tukey double arcsine transformation. Visual analysis of funnel plots and Egger's test will be done to detect small-study effect. This review and meta-analysis will be based on published data and will therefore not require a specific ethical clearance. The results will be published in peer-reviewed journals. CRD42018082551. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Therapeutic effects of Lactobacillus in treating irritable bowel syndrome: a meta-analysis.

    PubMed

    Tiequn, Bian; Guanqun, Chao; Shuo, Zhang

    2015-01-01

    As the lack of reliable treatment for irritable bowel syndrome (IBS) prompts interest in the development of new therapies, we aimed to systematically evaluate the effect of Lactobacillus in treating this disease. We searched MEDLIINE, PubMed, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials for the period from 1966 to August 2013 for double-blind, placebo-controlled trials investigating the efficacy of Lactobacillus treatment in the management of IBS. The studies were screened for inclusion based on randomization, controls and reported measurable outcomes. We used the Jadad score to assess the quality of the articles. The STATA 11.0 and Revman 5.0 software packages were used for the meta-analysis. The STATA 11.0 software program was also used to assess indicators of publication bias according to Begg's and Egger's tests. Six randomized, placebo-controlled clinical trials met the criteria and were included in the meta-analysis. The Jadad score of the articles was >3, and three articles were of high quality. We analyzed the heterogeneity of the studies and found no heterogeneity in the meta-analysis. In the forest plot, the diamond was on the right side of the vertical line and did not intersect with the line. The pooled relative risk for clinical improvement with Lactobacillus treatment was 7.69 (95% confidence interval: 2.33-25.43, p=0.0008). For adults, the pooled relative risk for clinical improvement with Lactobacillus treatment was 17.62 (95% confidence interval: 5.12-60.65, p<0.00001). For children, the pooled relative risk for clinical improvement with Lactobacillus treatment was 3.71 (95% confidence interval:1.05-13.11, p=0.04). Using the STATA 10.0 and Revman 5.0 software programs, we confirmed that Lactobacillus exhibited significant efficacy in treating IBS. Compared with the placebo, Lactobacillus treatment was found to be associated with a significantly higher rate of treatment responders in the overall population with IBS, without any side effects. As to limitations of the analysis, additional research is needed.

  1. Statin is a reasonable treatment option for patients with Polycystic Ovary Syndrome: a meta-analysis of randomized controlled trials.

    PubMed

    Gao, L; Zhao, F-L; Li, S-C

    2012-06-01

    To date no consensus has been reached on whether to administer statin to patients with Polycystic Ovary Syndrome (PCOS) routinely. Therefore, we conduct a meta-analysis to synthesize the literatures regarding therapeutic effects of statins on PCOS. A comprehensive literature search was performed using terms such as polycystic ovary syndrome, ovary polycystic disease, PCOS, hyperandrogaenemia; simvastatin, atorvastatin, lipidemic-modulating drugs, lipid lowering drugs, and testosterone; randomized controlled trials in the following bibliographic databases: Medline, Embase, Cochrane Controlled Trials Register. Identified reference lists were checked manually. In total, 4 RCTs were included. 3 of 4 studies were double-blinded while none reported whether of the data was analyzed using intention-to-treat analysis. Serum total testosterone and lipid profiles were included as investigation outcomes. Differences in reducing serum total testosterone were observed when comparing statin with placebo (Std MD= - 3.03, 95%CI - 5.85 ~ - 0.22, P=0.03) or statin + metformin with metformin (Std MD=- 1.07, 95%CI: - 2.06~ - 0.07, P=0.04). Heterogeneities were detected in both comparisons (I2=96% and 88% respectively). Meanwhile, statin was more effective than placebo in reducing LDL (WMD=- 0.87, 95%CI - 1.18~ - 0.55, P<0.0001), TC (WMD=- 1.23 95%CI - 1.35~ - 1.11, P<0.00001), TG (WMD= - 0.50, 95%CI - 0.73~ - 0.27, P<0.00001); and statin + metformin was more effective than metformin in lowering LDL (WMD= - 0.84, 95%CI: - 1.33 ~ - 0.354, P=0.0009), TC (WMD= - 1.28, 95%CI: - 1.47 ~ - 1.10, P<0.00001), and TG (WMD= - 0.27, 95%CI: - 0.36~ - 0.19, P<0.00001). Heterogeneities were detected during the meta-analysis. Statins can reduce the concentration of total testosterone, TC, TG and LDL. However, it cannot be concluded that statins have long-term benefit. A large-scale, randomized controlled study is needed to ascertain this uncertainty. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

  2. Heterogeneous continuous-time random walks

    NASA Astrophysics Data System (ADS)

    Grebenkov, Denis S.; Tupikina, Liubov

    2018-01-01

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

  3. Socio-economic and Climate Factors Associated with Dengue Fever Spatial Heterogeneity: A Worked Example in New Caledonia.

    PubMed

    Teurlai, Magali; Menkès, Christophe Eugène; Cavarero, Virgil; Degallier, Nicolas; Descloux, Elodie; Grangeon, Jean-Paul; Guillaumot, Laurent; Libourel, Thérèse; Lucio, Paulo Sergio; Mathieu-Daudé, Françoise; Mangeas, Morgan

    2015-12-01

    Understanding the factors underlying the spatio-temporal distribution of infectious diseases provides useful information regarding their prevention and control. Dengue fever spatio-temporal patterns result from complex interactions between the virus, the host, and the vector. These interactions can be influenced by environmental conditions. Our objectives were to analyse dengue fever spatial distribution over New Caledonia during epidemic years, to identify some of the main underlying factors, and to predict the spatial evolution of dengue fever under changing climatic conditions, at the 2100 horizon. We used principal component analysis and support vector machines to analyse and model the influence of climate and socio-economic variables on the mean spatial distribution of 24,272 dengue cases reported from 1995 to 2012 in thirty-three communes of New Caledonia. We then modelled and estimated the future evolution of dengue incidence rates using a regional downscaling of future climate projections. The spatial distribution of dengue fever cases is highly heterogeneous. The variables most associated with this observed heterogeneity are the mean temperature, the mean number of people per premise, and the mean percentage of unemployed people, a variable highly correlated with people's way of life. Rainfall does not seem to play an important role in the spatial distribution of dengue cases during epidemics. By the end of the 21st century, if temperature increases by approximately 3 °C, mean incidence rates during epidemics could double. In New Caledonia, a subtropical insular environment, both temperature and socio-economic conditions are influencing the spatial spread of dengue fever. Extension of this study to other countries worldwide should improve the knowledge about climate influence on dengue burden and about the complex interplay between different factors. This study presents a methodology that can be used as a step by step guide to model dengue spatial heterogeneity in other countries.

  4. Socio-economic and Climate Factors Associated with Dengue Fever Spatial Heterogeneity: A Worked Example in New Caledonia

    PubMed Central

    Teurlai, Magali; Menkès, Christophe Eugène; Cavarero, Virgil; Degallier, Nicolas; Descloux, Elodie; Grangeon, Jean-Paul; Guillaumot, Laurent; Libourel, Thérèse; Lucio, Paulo Sergio; Mathieu-Daudé, Françoise; Mangeas, Morgan

    2015-01-01

    Background/Objectives Understanding the factors underlying the spatio-temporal distribution of infectious diseases provides useful information regarding their prevention and control. Dengue fever spatio-temporal patterns result from complex interactions between the virus, the host, and the vector. These interactions can be influenced by environmental conditions. Our objectives were to analyse dengue fever spatial distribution over New Caledonia during epidemic years, to identify some of the main underlying factors, and to predict the spatial evolution of dengue fever under changing climatic conditions, at the 2100 horizon. Methods We used principal component analysis and support vector machines to analyse and model the influence of climate and socio-economic variables on the mean spatial distribution of 24,272 dengue cases reported from 1995 to 2012 in thirty-three communes of New Caledonia. We then modelled and estimated the future evolution of dengue incidence rates using a regional downscaling of future climate projections. Results The spatial distribution of dengue fever cases is highly heterogeneous. The variables most associated with this observed heterogeneity are the mean temperature, the mean number of people per premise, and the mean percentage of unemployed people, a variable highly correlated with people's way of life. Rainfall does not seem to play an important role in the spatial distribution of dengue cases during epidemics. By the end of the 21st century, if temperature increases by approximately 3°C, mean incidence rates during epidemics could double. Conclusion In New Caledonia, a subtropical insular environment, both temperature and socio-economic conditions are influencing the spatial spread of dengue fever. Extension of this study to other countries worldwide should improve the knowledge about climate influence on dengue burden and about the complex interplay between different factors. This study presents a methodology that can be used as a step by step guide to model dengue spatial heterogeneity in other countries. PMID:26624008

  5. Noninfectious complications in patients with pediatric-onset common variable immunodeficiency correlated with defects in somatic hypermutation but not in class-switch recombination.

    PubMed

    Almejún, María Belén; Campos, Bárbara Carolina; Patiño, Virginia; Galicchio, Miguel; Zelazko, Marta; Oleastro, Matías; Oppezzo, Pablo; Danielian, Silvia

    2017-03-01

    Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by impaired immunoglobulin production and usually presents with a normal quantity of peripheral B cells. Most attempts aiming to classify these patients have mainly been focused on T- or B-cell phenotypes and their ability to produce protective antibodies, but it is still a major challenge to find a suitable classification that includes the clinical and immunologic heterogeneity of these patients. In this study we evaluated the late stages of B-cell differentiation in a heterogeneous population of patients with pediatric-onset CVID to clinically correlate and assess their ability to perform somatic hypermutation (SHM), class-switch recombination (CSR), or both. We performed a previously reported assay, the restriction enzyme hotspot mutation assay (IgκREHMA), to evaluate in vivo SHM status. We amplified switch regions from genomic DNA to investigate the quality of the double-strand break repairs in the class-switch recombination process in vivo. We also tested the ability to generate immunoglobulin germline and circle transcripts and to upregulate the activation-induced cytidine deaminase gene through in vitro T-dependent and T-independent stimuli. Our results showed that patients could be classified into 2 groups according to their degree of SHM alteration. This stratification showed a significant association between patients of group A, severe alteration, and the presence of noninfectious complications. Additionally, 60% of patients presented with increased microhomology use at switched regions. In vitro activation revealed that patients with CVID behaved heterogeneously in terms of responsiveness to T-dependent stimuli. The correlation between noninfectious complications and SHM could be an important tool for physicians to further characterize patients with CVID. This categorization would help to improve elucidation of the complex mechanisms involved in B-cell differentiation pathways. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. Environmental heterogeneity, dispersal mode, and co-occurrence in stream macroinvertebrates

    PubMed Central

    Heino, Jani

    2013-01-01

    Both environmental heterogeneity and mode of dispersal may affect species co-occurrence in metacommunities. Aquatic invertebrates were sampled in 20–30 streams in each of three drainage basins, differing considerably in environmental heterogeneity. Each drainage basin was further divided into two equally sized sets of sites, again differing profoundly in environmental heterogeneity. Benthic invertebrate data were divided into three groups of taxa based on overland dispersal modes: passive dispersers with aquatic adults, passive dispersers with terrestrial winged adults, and active dispersers with terrestrial winged adults. The co-occurrence of taxa in each dispersal mode group, drainage basin, and heterogeneity site subset was measured using the C-score and its standardized effect size. The probability of finding high levels of species segregation tended to increase with environmental heterogeneity across the drainage basins. These patterns were, however, contingent on both dispersal mode and drainage basin. It thus appears that environmental heterogeneity and dispersal mode interact in affecting co-occurrence in metacommunities, with passive dispersers with aquatic adults showing random patterns irrespective of environmental heterogeneity, and active dispersers with terrestrial winged adults showing increasing segregation with increasing environmental heterogeneity. PMID:23467653

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

    NASA Astrophysics Data System (ADS)

    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.

  8. [An ADAA model and its analysis method for agronomic traits based on the double-cross mating design].

    PubMed

    Xu, Z C; Zhu, J

    2000-01-01

    According to the double-cross mating design and using principles of Cockerham's general genetic model, a genetic model with additive, dominance and epistatic effects (ADAA model) was proposed for the analysis of agronomic traits. Components of genetic effects were derived for different generations. Monte Carlo simulation was conducted for analyzing the ADAA model and its reduced AD model by using different generations. It was indicated that genetic variance components could be estimated without bias by MINQUE(1) method and genetic effects could be predicted effectively by AUP method; at least three generations (including parent, F1 of single cross and F1 of double-cross) were necessary for analyzing the ADAA model and only two generations (including parent and F1 of double-cross) were enough for the reduced AD model. When epistatic effects were taken into account, a new approach for predicting the heterosis of agronomic traits of double-crosses was given on the basis of unbiased prediction of genotypic merits of parents and their crosses. In addition, genotype x environment interaction effects and interaction heterosis due to G x E interaction were discussed briefly.

  9. Confronting the Paradox of Enrichment to the Metacommunity Perspective

    PubMed Central

    Hauzy, Céline; Nadin, Grégoire; Canard, Elsa; Gounand, Isabelle; Mouquet, Nicolas; Ebenman, Bo

    2013-01-01

    Resource enrichment can potentially destabilize predator-prey dynamics. This phenomenon historically referred as the "paradox of enrichment" has mostly been explored in spatially homogenous environments. However, many predator-prey communities exchange organisms within spatially heterogeneous networks called metacommunities. This heterogeneity can result from uneven distribution of resources among communities and thus can lead to the spreading of local enrichment within metacommunities. Here, we adapted the original Rosenzweig-MacArthur predator-prey model, built to study the paradox of enrichment, to investigate the effect of regional enrichment and of its spatial distribution on predator-prey dynamics in metacommunities. We found that the potential for destabilization was depending on the connectivity among communities and the spatial distribution of enrichment. In one hand, we found that at low dispersal regional enrichment led to the destabilization of predator-prey dynamics. This destabilizing effect was more pronounced when the enrichment was uneven among communities. In the other hand, we found that high dispersal could stabilize the predator-prey dynamics when the enrichment was spatially heterogeneous. Our results illustrate that the destabilizing effect of enrichment can be dampened when the spatial scale of resource enrichment is lower than that of organismss movements (heterogeneous enrichment). From a conservation perspective, our results illustrate that spatial heterogeneity could decrease the regional extinction risk of species involved in specialized trophic interactions. From the perspective of biological control, our results show that the heterogeneous distribution of pest resource could favor or dampen outbreaks of pests and of their natural enemies, depending on the spatial scale of heterogeneity. PMID:24358242

  10. Gene Expression and Pharmacodynamic Changes in 1,760 Systemic Lupus Erythematosus Patients From Two Phase III Trials of BAFF Blockade With Tabalumab.

    PubMed

    Hoffman, Robert W; Merrill, Joan T; Alarcón-Riquelme, Marta M E; Petri, Michelle; Dow, Ernst R; Nantz, Eric; Nisenbaum, Laura K; Schroeder, Krista M; Komocsar, Wendy J; Perumal, Narayanan B; Linnik, Matthew D; Airey, David C; Liu, Yushi; Rocha, Guilherme V; Higgs, Richard E

    2017-03-01

    To characterize baseline gene expression and pharmacodynamically induced changes in whole blood gene expression in 1,760 systemic lupus erythematosus (SLE) patients from 2 phase III, 52-week, randomized, placebo-controlled, double-blind studies in which patients were treated with the BAFF-blocking IgG4 monoclonal antibody tabalumab. Patient samples were obtained from SLE patients from the ILLUMINATE-1 and ILLUMINATE-2 studies, and control samples were obtained from healthy donors. Blood was collected in Tempus tubes at baseline, week 16, and week 52. RNA was analyzed using Affymetrix Human Transcriptome Array 2.0 and NanoString. At baseline, expression of the interferon (IFN) response gene was elevated in patients compared with controls, with 75% of patients being positive for this IFN response gene signature. There was, however, substantial heterogeneity of IFN response gene expression and complex relationships among gene networks. The IFN response gene signature was a predictor of time to disease flare, independent of anti-double-stranded DNA (anti-dsDNA) antibody and C3 and C4 levels, and overall disease activity. Pharmacodynamically induced changes in gene expression following tabalumab treatment were extensive, occurring predominantly in B cell-related and immunoglobulin genes, and were consistent with other pharmacodynamic changes including anti-dsDNA antibody, C3, and immunoglobulin levels. SLE patients demonstrated increased expression of an IFN response gene signature (75% of patients had an elevated IFN response gene signature) at baseline in ILLUMINATE-1 and ILLUMINATE-2. Substantial heterogeneity of gene expression was detected among individual patients and in gene networks. The IFN response gene signature was an independent risk factor for future disease flares. Pharmacodynamic changes in gene expression were consistent with the mechanism of BAFF blockade by tabalumab. © 2016, American College of Rheumatology.

  11. BI-31ANALYSIS AND QUANTIFICATION OF MULTIPLE ANTIGEN EXPRESSION IN GLIOBLASTOMA

    PubMed Central

    Weng, Lihong; Zhai, Yubo; D'Apuzzo, Massimo; Badie, Behnam; Forman, Stephen J.; Barish, Michael; Brown, Christine E.

    2014-01-01

    Glioblastoma (GBM), one of the most common and fatal types of brain tumor, is marked by significant antigenic heterogeneity. Identification and quantification of tumor related antigens in the context of GBM tissue is an essential step towards developing antigen- targeted therapies. Immunohistochemistry (IHC) on formalin-fixed paraffin embedded (FFPE) clinical specimens is a valuable technique for evaluating antigen expression in large study cohorts. To overcome the limitations of manual semi-quantitative scoring and subjectivity in the evaluation of IHC staining, we analyzed and quantified multiple antigens across entire tumor sections using Image Pro Premier v9.1 (DAB plug-in). For each slide, dense tumor regions (DTRs, tumor cells >60%), tumor infiltration regions (TIRs, tumor cells <50%) and pseudopalisading necrosis regions (PPNs) were defined from HE section by a neuropathologist. We quantified the expression of tumor-associated antigens IL13Rα2, HER2, EGFR and the proliferation marker Ki67 within these defined regions for 44 brain tumor samples (35 stage IV and 9 stage III). Our results demonstrate the heterogeneous expression patterns of IL13Rα2, HER2 and EGFR in GBMs. For example, in dense tumor regions 52%, 61% and 77% of samples showed IL13Rα2, HER2 or EGFR positivity, respectively. In correlation studies, 25% of samples were triple positive, 11% of samples showed double positivity for IL13Rα2 and HER2 or IL13Rα2 and EGFR, and 25% of samples were double positive of EGFR and HER2. Less than 7% of samples were negative for all three antigens. Interestingly, a higher percentage of samples showed triple positive expression in PPN regions (43%) versus the DTR (25%) and TIR (25%) regions. Also, Ki67 positivity was higher in PPN and DTR regions. In this study we developed methods for combining pathological annotations with DAB-capturing software, which allowed us to quantify protein expression in a more precise, consistent and efficient manner.

  12. Rank score and permutation testing alternatives for regression quantile estimates

    USGS Publications Warehouse

    Cade, B.S.; Richards, J.D.; Mielke, P.W.

    2006-01-01

    Performance of quantile rank score tests used for hypothesis testing and constructing confidence intervals for linear quantile regression estimates (0 ≤ τ ≤ 1) were evaluated by simulation for models with p = 2 and 6 predictors, moderate collinearity among predictors, homogeneous and hetero-geneous errors, small to moderate samples (n = 20–300), and central to upper quantiles (0.50–0.99). Test statistics evaluated were the conventional quantile rank score T statistic distributed as χ2 random variable with q degrees of freedom (where q parameters are constrained by H 0:) and an F statistic with its sampling distribution approximated by permutation. The permutation F-test maintained better Type I errors than the T-test for homogeneous error models with smaller n and more extreme quantiles τ. An F distributional approximation of the F statistic provided some improvements in Type I errors over the T-test for models with > 2 parameters, smaller n, and more extreme quantiles but not as much improvement as the permutation approximation. Both rank score tests required weighting to maintain correct Type I errors when heterogeneity under the alternative model increased to 5 standard deviations across the domain of X. A double permutation procedure was developed to provide valid Type I errors for the permutation F-test when null models were forced through the origin. Power was similar for conditions where both T- and F-tests maintained correct Type I errors but the F-test provided some power at smaller n and extreme quantiles when the T-test had no power because of excessively conservative Type I errors. When the double permutation scheme was required for the permutation F-test to maintain valid Type I errors, power was less than for the T-test with decreasing sample size and increasing quantiles. Confidence intervals on parameters and tolerance intervals for future predictions were constructed based on test inversion for an example application relating trout densities to stream channel width:depth.

  13. Examining the influence of heterogeneous porosity fields on conservative solute transport

    USGS Publications Warehouse

    Hu, B.X.; Meerschaert, M.M.; Barrash, W.; Hyndman, D.W.; He, C.; Li, X.; Guo, Laodong

    2009-01-01

    It is widely recognized that groundwater flow and solute transport in natural media are largely controlled by heterogeneities. In the last three decades, many studies have examined the effects of heterogeneous hydraulic conductivity fields on flow and transport processes, but there has been much less attention to the influence of heterogeneous porosity fields. In this study, we use porosity and particle size measurements from boreholes at the Boise Hydrogeophysical Research Site (BHRS) to evaluate the importance of characterizing the spatial structure of porosity and grain size data for solute transport modeling. Then we develop synthetic hydraulic conductivity fields based on relatively simple measurements of porosity from borehole logs and grain size distributions from core samples to examine and compare the characteristics of tracer transport through these fields with and without inclusion of porosity heterogeneity. In particular, we develop horizontal 2D realizations based on data from one of the less heterogeneous units at the BHRS to examine effects where spatial variations in hydraulic parameters are not large. The results indicate that the distributions of porosity and the derived hydraulic conductivity in the study unit resemble fractal normal and lognormal fields respectively. We numerically simulate solute transport in stochastic fields and find that spatial variations in porosity have significant effects on the spread of an injected tracer plume including a significant delay in simulated tracer concentration histories.

  14. Large-scale replication and heterogeneity in Parkinson disease genetic loci

    PubMed Central

    Ioannidis, John P.A.; Aasly, Jan O.; Annesi, Grazia; Brice, Alexis; Van Broeckhoven, Christine; Bertram, Lars; Bozi, Maria; Crosiers, David; Clarke, Carl; Facheris, Maurizio; Farrer, Matthew; Garraux, Gaetan; Gispert, Suzana; Auburger, Georg; Vilariño-Güell, Carles; Hadjigeorgiou, Georgios M.; Hicks, Andrew A.; Hattori, Nobutaka; Jeon, Beom; Lesage, Suzanne; Lill, Christina M.; Lin, Juei-Jueng; Lynch, Timothy; Lichtner, Peter; Lang, Anthony E.; Mok, Vincent; Jasinska-Myga, Barbara; Mellick, George D.; Morrison, Karen E.; Opala, Grzegorz; Pramstaller, Peter P.; Pichler, Irene; Park, Sung Sup; Quattrone, Aldo; Rogaeva, Ekaterina; Ross, Owen A.; Stefanis, Leonidas; Stockton, Joanne D.; Satake, Wataru; Silburn, Peter A.; Theuns, Jessie; Tan, Eng-King; Toda, Tatsushi; Tomiyama, Hiroyuki; Uitti, Ryan J.; Wirdefeldt, Karin; Wszolek, Zbigniew; Xiromerisiou, Georgia; Yueh, Kuo-Chu; Zhao, Yi; Gasser, Thomas; Maraganore, Demetrius; Krüger, Rejko

    2012-01-01

    Objective: Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown. Methods: Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry. Results: In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78–0.87 (LAMP3, BST1, and MAPT) and susceptibility per-allele odds ratios of 1.14–1.43 (STK39, GAK, SNCA, LRRK2, SYT11, and HIP1R). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes (I2 estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA, LRRK2, LAMP3, HIP1R, and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD. Conclusion: Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity. Neurology® 2012;79:659–667 PMID:22786590

  15. Assessment of the effect of three-dimensional mantle density heterogeneity on earth rotation in tidal frequencies.

    PubMed

    Liu, Lanbo; Chao, Benjamin F; Sun, Wenke; Kuang, Weijia

    2016-11-01

    In this paper we report the assessment of the effect of the three-dimensional (3D) density heterogeneity in the mantle on Earth Orientation Parameters (EOP) (i.e., the polar motion, or PM, and the length of day, or LOD) in the tidal frequencies. The 3D mantle density model is estimated based upon a global S-wave velocity tomography model (S16U6L8) and the mineralogical knowledge derived from laboratory experiment. The lateral density variation is referenced against the Preliminary Reference Earth Model (PREM). Using this approach the effects of the heterogeneous mantle density variation in all three tidal frequencies (zonal long periods, tesseral diurnal, and sectorial semidiurnal) are estimated in both PM and LOD. When compared with mass or density perturbations originated on the earth's surface such as the oceanic and barometric changes, the heterogeneous mantle only contributes less than 10% of the total variation in PM and LOD in tidal frequencies. Nevertheless, including the 3D variation of the density in the mantle into account explained a substantial portion of the discrepancy between the observed signals in PM and LOD extracted from the lump-sum values based on continuous space geodetic measurement campaigns (e.g., CONT94) and the computed contribution from ocean tides as predicted by tide models derived from satellite altimetry observations (e.g., TOPEX/Poseidon). In other word, the difference of the two, at all tidal frequencies (long-periods, diurnals, and semi-diurnals) contains contributions of the lateral density heterogeneity of the mantle. Study of the effect of mantle density heterogeneity effect on torque-free earth rotation may provide useful constraints to construct the Reference Earth Model (REM), which is the next major objective in global geophysics research beyond PREM.

  16. Large-scale replication and heterogeneity in Parkinson disease genetic loci.

    PubMed

    Sharma, Manu; Ioannidis, John P A; Aasly, Jan O; Annesi, Grazia; Brice, Alexis; Van Broeckhoven, Christine; Bertram, Lars; Bozi, Maria; Crosiers, David; Clarke, Carl; Facheris, Maurizio; Farrer, Matthew; Garraux, Gaetan; Gispert, Suzana; Auburger, Georg; Vilariño-Güell, Carles; Hadjigeorgiou, Georgios M; Hicks, Andrew A; Hattori, Nobutaka; Jeon, Beom; Lesage, Suzanne; Lill, Christina M; Lin, Juei-Jueng; Lynch, Timothy; Lichtner, Peter; Lang, Anthony E; Mok, Vincent; Jasinska-Myga, Barbara; Mellick, George D; Morrison, Karen E; Opala, Grzegorz; Pramstaller, Peter P; Pichler, Irene; Park, Sung Sup; Quattrone, Aldo; Rogaeva, Ekaterina; Ross, Owen A; Stefanis, Leonidas; Stockton, Joanne D; Satake, Wataru; Silburn, Peter A; Theuns, Jessie; Tan, Eng-King; Toda, Tatsushi; Tomiyama, Hiroyuki; Uitti, Ryan J; Wirdefeldt, Karin; Wszolek, Zbigniew; Xiromerisiou, Georgia; Yueh, Kuo-Chu; Zhao, Yi; Gasser, Thomas; Maraganore, Demetrius; Krüger, Rejko

    2012-08-14

    Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown. Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry. In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78-0.87 (LAMP3, BST1, and MAPT) and susceptibility per-allele odds ratios of 1.14-1.43 (STK39, GAK, SNCA, LRRK2, SYT11, and HIP1R). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes (I(2) estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA, LRRK2, LAMP3, HIP1R, and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD. Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity.

  17. [Application of Stata software to test heterogeneity in meta-analysis method].

    PubMed

    Wang, Dan; Mou, Zhen-yun; Zhai, Jun-xia; Zong, Hong-xia; Zhao, Xiao-dong

    2008-07-01

    To introduce the application of Stata software to heterogeneity test in meta-analysis. A data set was set up according to the example in the study, and the corresponding commands of the methods in Stata 9 software were applied to test the example. The methods used were Q-test and I2 statistic attached to the fixed effect model forest plot, H statistic and Galbraith plot. The existence of the heterogeneity among studies could be detected by Q-test and H statistic and the degree of the heterogeneity could be detected by I2 statistic. The outliers which were the sources of the heterogeneity could be spotted from the Galbraith plot. Heterogeneity test in meta-analysis can be completed by the four methods in Stata software simply and quickly. H and I2 statistics are more robust, and the outliers of the heterogeneity can be clearly seen in the Galbraith plot among the four methods.

  18. Group heterogeneity increases the risks of large group size: a longitudinal study of productivity in research groups.

    PubMed

    Cummings, Jonathon N; Kiesler, Sara; Bosagh Zadeh, Reza; Balakrishnan, Aruna D

    2013-06-01

    Heterogeneous groups are valuable, but differences among members can weaken group identification. Weak group identification may be especially problematic in larger groups, which, in contrast with smaller groups, require more attention to motivating members and coordinating their tasks. We hypothesized that as groups increase in size, productivity would decrease with greater heterogeneity. We studied the longitudinal productivity of 549 research groups varying in disciplinary heterogeneity, institutional heterogeneity, and size. We examined their publication and citation productivity before their projects started and 5 to 9 years later. Larger groups were more productive than smaller groups, but their marginal productivity declined as their heterogeneity increased, either because their members belonged to more disciplines or to more institutions. These results provide evidence that group heterogeneity moderates the effects of group size, and they suggest that desirable diversity in groups may be better leveraged in smaller, more cohesive units.

  19. Restoration of the fire-grazing interaction in Artemisia filifolia shrubland

    USGS Publications Warehouse

    Winter, S.L.; Fuhlendorf, S.D.; Goad, C.L.; Davis, C.A.; Hickman, K.R.; Leslie, David M.

    2012-01-01

    Patterns of landscape heterogeneity are crucial to the maintenance of biodiversity in shrublands and grasslands, yet management practices in these ecosystems typically seek to homogenize landscapes. Furthermore, there is limited understanding of how the interaction of ecological processes, such as fire and grazing, affects patterns of heterogeneity at different spatial scales. We conducted research in Artemisia filifolia (Asteraceae) shrublands located in the southern Great Plains of North America to determine the effect of restoring the fire-grazing interaction on vegetation structure. Data were collected for 3years in replicated pastures grazed by cattle Bos taurus where the fire-grazing interaction had been restored (fire and grazing=treatment pastures) and in pastures that were grazed but remained unburned (grazing only, no fire=control pastures). The effect of the fire-grazing interaction on heterogeneity (variance) of vegetation structure was assessed at scales from 12??5m 2 to 609ha. Most measurements of vegetation structure within treatment pastures differed from control pastures for 1-3years after being burned but were thereafter similar to the values found in unburned control pastures. Treatment pastures were characterized by a lower amount of total heterogeneity and a lower amount of heterogeneity through time. Heterogeneity of vegetation structure tended to decrease as the scale of measurement increased in both treatment and control pastures. There was deviation from this trend, however, in the treatment pastures that exhibited much higher heterogeneity at the patch scale (mean patch size=202ha) of measurement, the scale at which patch fires were conducted. Synthesis and applications.Vegetation structure in A. filifolia shrublands of our study was readily altered by the fire-grazing interaction but also demonstrated substantial resilience to these effects. The fire-grazing interaction also changed the total amount of heterogeneity characterizing this system, the scale at which heterogeneity in this system was expressed and the amount of heterogeneity expressed through time. Land managers seeking to impose a shifting mosaic of heterogeneity on this vegetation type can do so by restoring the fire-grazing interaction with potential conservation benefits similar to what has been achieved in other ecosystems where historic cycles of disturbance and rest have been restored. ?? 2011 The Authors. Journal of Applied Ecology ?? 2011 British Ecological Society.

  20. Triple-effect absorption refrigeration system with double-condenser coupling

    DOEpatents

    DeVault, R.C.; Biermann, W.J.

    1993-04-27

    A triple effect absorption refrigeration system is provided with a double-condenser coupling and a parallel or series circuit for feeding the refrigerant-containing absorbent solution through the high, medium, and low temperature generators utilized in the triple-effect system. The high temperature condenser receiving vaporous refrigerant from the high temperature generator is double coupled to both the medium temperature generator and the low temperature generator to enhance the internal recovery of heat within the system and thereby increase the thermal efficiency thereof.

  1. Triple-effect absorption refrigeration system with double-condenser coupling

    DOEpatents

    DeVault, Robert C.; Biermann, Wendell J.

    1993-01-01

    A triple effect absorption refrigeration system is provided with a double-condenser coupling and a parallel or series circuit for feeding the refrigerant-containing absorbent solution through the high, medium, and low temperature generators utilized in the triple-effect system. The high temperature condenser receiving vaporous refrigerant from the high temperature generator is double coupled to both the medium temperature generator and the low temperature generator to enhance the internal recovery of heat within the system and thereby increase the thermal efficiency thereof.

  2. Precision Tests of a Quantum Hall Effect Device DC Equivalent Circuit Using Double-Series and Triple-Series Connections

    PubMed Central

    Jeffery, A.; Elmquist, R. E.; Cage, M. E.

    1995-01-01

    Precision tests verify the dc equivalent circuit used by Ricketts and Kemeny to describe a quantum Hall effect device in terms of electrical circuit elements. The tests employ the use of cryogenic current comparators and the double-series and triple-series connection techniques of Delahaye. Verification of the dc equivalent circuit in double-series and triple-series connections is a necessary step in developing the ac quantum Hall effect as an intrinsic standard of resistance. PMID:29151768

  3. The effect of neonatal vitamin A supplementation on morbidity and mortality at 12 months: a randomized trial

    PubMed Central

    Smith, Emily R; Muhihi, Alfa; Mshamu, Salum; Sudfeld, Christopher R; Noor, Ramadhani Abdallah; Spiegelman, Donna; Shapiro, Roger L; Masanja, Honorati; Fawzi, Wafaie

    2016-01-01

    Abstract Background: Neonatal vitamin A supplementation (NVAS) is an intervention hypothesized to reduce infant morbidity and mortality. The objective of this study was to assess the efficacy of neonatal vitamin A supplementation in reducing infant morbidity and mortality and assess potential sources of heterogeneity of the effect of NVAS. Methods: We completed an individually randomized, double-blind, placebo-controlled trial in Tanzania. Infants were randomized within 3 days of birth to a single dose of vitamin A (50 000 IU) or placebo. We assessed infants at 1 and 3 days after supplementation, as well as 1, 3, 6 and 12 months after supplementation. We included all live births in the analysis and used relative risks (RR) and 95% confidence intervals (CI) to assess the risks of mortality and hospitalization by 12 months. We used general estimating equations to assess the incidence of morbidities during infancy. Results: A total of 31 999 infants were enrolled in the study between August 2010 and March 2013. At 12 months, vitamin A did not reduce all-cause infant mortality (RR 1.04; 95% CI 0.92-1.16), nor affect hospitalization (RR 1.09; 95% CI 0.97-1.22) or all-cause morbidity (RR 1.00; 95% CI 0.96-1.05). Postpartum maternal vitamin A supplementation modified the effect of neonatal vitamin A supplementation on mortality at 12 months (P-value, test for interaction = 0.04). Among infants born to women who received a mega-dose of vitamin A after delivery, NVAS appeared to increase the risk of death (RR 1.12; 95% CI 0.98-1.29), whereas the risk of death among infants born to women who did not receive a mega-dose was reduced (RR 0.86; 95% CI 0.70-1.06). We noted no modification of the effect of NVAS by infant gender, birthweight or maternal HIV status. Conclusion: NVAS did not affect the risk of death or incidence of common childhood morbidities. However, this study sheds light on potential sources of heterogeneity of the effect of neonatal vitamin A supplementation which should be further examined in a pooled analysis of all NVAS trials. PMID:27789674

  4. Layered double hydroxide catalyst for the conversion of crude vegetable oils to a sustainable biofuel

    NASA Astrophysics Data System (ADS)

    Mollaeian, Keyvan

    Over the last two decades, the U.S. has developed the production of biodiesel, a mixture of fatty acid methyl esters, using chiefly vegetable oils as feedstocks. However, there is much concern about the availability of high-quality vegetable oils for longterm biodiesel production. Problems have also risen due to the production of glycerol, an unwanted byproduct, as well as the need for process wash water. Therefore, this study was initiated to produce not only fatty acid methyl esters (FAMEs) but also fatty acid glycerol carbonates (FAGCs) by replacing methanol with dimethyl carbonate (DMC). The process would have no unnecessary byproducts and would be a simplified process compared to traditional biodiesel. In addition, this altering of the methylating agent could convert triglycerides, free fatty acids, and phospholipids to a sustainable biofuel. In this project, Mg-Al Layered Double Hydroxide (LDH) was optimized by calcination in different temperature varied from 250°C to 450°C. The gallery between layers was increased by intercalating sodium dodecylsulfate (SDS). During catalyst preparation, the pH was controlled ~10. In our experiment, triazabicyclodecene (TBD) was attached with trimethoxysilane (3GPS) as a coupling agent, and N-cetyl-N,N,N-trimethylammonium bromide (CTAB) was added to remove SDS from the catalyst. The catalyst was characterized by XRD, FTIR, and Raman spectroscopy. The effect of the heterogeneous catalyst on the conversion of canola oil, corn oil, and free fatty acids was investigated. To analyze the conversion of lipid oils to biofuel an in situ Raman spectroscopic method was developed. Catalyst synthesis methods and a proposed mechanism for converting triglycerides and free fatty acids to biofuel will be presented.

  5. Dosimetric feasibility of 4DCT-ventilation imaging guided proton therapy for locally advanced non-small-cell lung cancer.

    PubMed

    Huang, Qijie; Jabbour, Salma K; Xiao, Zhiyan; Yue, Ning; Wang, Xiao; Cao, Hongbin; Kuang, Yu; Zhang, Yin; Nie, Ke

    2018-04-25

    The principle aim of this study is to incorporate 4DCT ventilation imaging into functional treatment planning that preserves high-functioning lung with both double scattering and scanning beam techniques in proton therapy. Eight patients with locally advanced non-small-cell lung cancer were included in this study. Deformable image registration was performed for each patient on their planning 4DCTs and the resultant displacement vector field with Jacobian analysis was used to identify the high-, medium- and low-functional lung regions. Five plans were designed for each patient: a regular photon IMRT vs. anatomic proton plans without consideration of functional ventilation information using double scattering proton therapy (DSPT) and intensity modulated proton therapy (IMPT) vs. functional proton plans with avoidance of high-functional lung using both DSPT and IMPT. Dosimetric parameters were compared in terms of tumor coverage, plan heterogeneity, and avoidance of normal tissues. Our results showed that both DSPT and IMPT plans gave superior dose advantage to photon IMRTs in sparing low dose regions of the total lung in terms of V5 (volume receiving 5Gy). The functional DSPT only showed marginal benefit in sparing high-functioning lung in terms of V5 or V20 (volume receiving 20Gy) compared to anatomical plans. Yet, the functional planning in IMPT delivery, can further reduce the low dose in high-functioning lung without degrading the PTV dosimetric coverages, compared to anatomical proton planning. Although the doses to some critical organs might increase during functional planning, the necessary constraints were all met. Incorporating 4DCT ventilation imaging into functional proton therapy is feasible. The functional proton plans, in intensity modulated proton delivery, are effective to further preserve high-functioning lung regions without degrading the PTV coverage.

  6. Distinct CD4+CD8+ Double-Positive T Cells in the Blood and Liver of Patients during Chronic Hepatitis B and C

    PubMed Central

    Nascimbeni, Michelina; Pol, Stanislas; Saunier, Bertrand

    2011-01-01

    CD4+ and CD8+ T cells, the main effectors of adaptive cellular immune responses, differentiate from immature, non-functional CD4+CD8+ double-positive T (DPT) cells in the thymus. Increased proportions of circulating DPT lymphocytes have been observed during acute viral infections; in chronic viral diseases, the role and repartition of extra-thymic DPT cells remain largely uncharacterized. We performed a phenotypic analysis of DPT cells in blood and liver from patients chronically infected by hepatitis C (HCV) or B (HBV) viruses. The highest percentages of DPT cells, predominantly CD4highCD8low, were observed in patients infected by HCV, while HBV-infected patients mostly displayed CD4lowCD8high and CD4highCD8high DPT cells. All proportions of DPT cells were higher in liver than in blood with, for each subpopulation referred to above, a correlation between their frequencies in these two compartments. In HCV patients, intra-hepatic DPT cells displayed more heterogeneous activation, differentiation and memory phenotypes than in the blood; most of them expressed CD1a, a marker of T cell development in the thymus. Ex vivo, the inoculation of liver slices with HCV produced in cell culture was accompanied by a disappearance of CD8high cells, suggesting a direct effect of the virus on the phenotype of DPT cells in the liver. Our results suggest that, in half of the patients, chronic HCV infection promotes the production of DPT cells, perhaps by their re-induction in the thymus and selection in the liver. PMID:21647449

  7. A homozygous nonsense CEP250 mutation combined with a heterozygous nonsense C2orf71 mutation is associated with atypical Usher syndrome.

    PubMed

    Khateb, Samer; Zelinger, Lina; Mizrahi-Meissonnier, Liliana; Ayuso, Carmen; Koenekoop, Robert K; Laxer, Uri; Gross, Menachem; Banin, Eyal; Sharon, Dror

    2014-07-01

    Usher syndrome (USH) is a heterogeneous group of inherited retinitis pigmentosa (RP) and sensorineural hearing loss (SNHL) caused by mutations in at least 12 genes. Our aim is to identify additional USH-related genes. Clinical examination included visual acuity test, funduscopy and electroretinography. Genetic analysis included homozygosity mapping and whole exome sequencing (WES). A combination of homozygosity mapping and WES in a large consanguineous family of Iranian Jewish origin revealed nonsense mutations in two ciliary genes: c.3289C>T (p.Q1097*) in C2orf71 and c.3463C>T (p.R1155*) in centrosome-associated protein CEP250 (C-Nap1). The latter has not been associated with any inherited disease and the c.3463C>T mutation was absent in control chromosomes. Patients who were double homozygotes had SNHL accompanied by early-onset and severe RP, while patients who were homozygous for the CEP250 mutation and carried a single mutant C2orf71 allele had SNHL with mild retinal degeneration. No ciliary structural abnormalities in the respiratory system were evident by electron microscopy analysis. CEP250 expression analysis of the mutant allele revealed the generation of a truncated protein lacking the NEK2-phosphorylation region. A homozygous nonsense CEP250 mutation, in combination with a heterozygous C2orf71 nonsense mutation, causes an atypical form of USH, characterised by early-onset SNHL and a relatively mild RP. The severe retinal involvement in the double homozygotes indicates an additive effect caused by nonsense mutations in genes encoding ciliary proteins. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  8. Cross-diffusion-driven hydrodynamic instabilities in a double-layer system: General classification and nonlinear simulations

    NASA Astrophysics Data System (ADS)

    Budroni, M. A.

    2015-12-01

    Cross diffusion, whereby a flux of a given species entrains the diffusive transport of another species, can trigger buoyancy-driven hydrodynamic instabilities at the interface of initially stable stratifications. Starting from a simple three-component case, we introduce a theoretical framework to classify cross-diffusion-induced hydrodynamic phenomena in two-layer stratifications under the action of the gravitational field. A cross-diffusion-convection (CDC) model is derived by coupling the fickian diffusion formalism to Stokes equations. In order to isolate the effect of cross-diffusion in the convective destabilization of a double-layer system, we impose a starting concentration jump of one species in the bottom layer while the other one is homogeneously distributed over the spatial domain. This initial configuration avoids the concurrence of classic Rayleigh-Taylor or differential-diffusion convective instabilities, and it also allows us to activate selectively the cross-diffusion feedback by which the heterogeneously distributed species influences the diffusive transport of the other species. We identify two types of hydrodynamic modes [the negative cross-diffusion-driven convection (NCC) and the positive cross-diffusion-driven convection (PCC)], corresponding to the sign of this operational cross-diffusion term. By studying the space-time density profiles along the gravitational axis we obtain analytical conditions for the onset of convection in terms of two important parameters only: the operational cross-diffusivity and the buoyancy ratio, giving the relative contribution of the two species to the global density. The general classification of the NCC and PCC scenarios in such parameter space is supported by numerical simulations of the fully nonlinear CDC problem. The resulting convective patterns compare favorably with recent experimental results found in microemulsion systems.

  9. Macrophage Migration Inhibitory Factor and Stearoyl-CoA Desaturase 1: Potential Prognostic Markers for Soft Tissue Sarcomas Based on Bioinformatics Analyses

    PubMed Central

    Takahashi, Hiro; Nakayama, Robert; Hayashi, Shuhei; Nemoto, Takeshi; Murase, Yasuyuki; Nomura, Koji; Takahashi, Teruyoshi; Kubo, Kenji; Marui, Shigetaka; Yasuhara, Koji; Nakamura, Tetsuro; Sueo, Takuya; Takahashi, Anna; Tsutsumiuchi, Kaname; Ohta, Tsutomu; Kawai, Akira; Sugita, Shintaro; Yamamoto, Shinjiro; Kobayashi, Takeshi; Honda, Hiroyuki; Yoshida, Teruhiko; Hasegawa, Tadashi

    2013-01-01

    The diagnosis and treatment of soft tissue sarcomas (STSs) has been particularly difficult, because STSs are a group of highly heterogeneous tumors in terms of histopathology, histological grade, and primary site. Recent advances in genome technologies have provided an excellent opportunity to determine the complete biological characteristics of neoplastic tissues, resulting in improved diagnosis, treatment selection, and investigation of therapeutic targets. We had previously developed a novel bioinformatics method for marker gene selection and applied this method to gene expression data from STS patients. This previous analysis revealed that the extracted gene combination of macrophage migration inhibitory factor (MIF) and stearoyl-CoA desaturase 1 (SCD1) is an effective diagnostic marker to discriminate between subtypes of STSs with highly different outcomes. In the present study, we hypothesize that the combination of MIF and SCD1 is also a prognostic marker for the overall outcome of STSs. To prove this hypothesis, we first analyzed microarray data from 88 STS patients and their outcomes. Our results show that the survival rates for MIF- and SCD1-positive groups were lower than those for negative groups, and the p values of the log-rank test are 0.0146 and 0.00606, respectively. In addition, survival rates are more significantly different (p = 0.000116) between groups that are double-positive and double-negative for MIF and SCD1. Furthermore, in vitro cell growth inhibition experiments by MIF and SCD1 inhibitors support the hypothesis. These results suggest that the gene set is useful as a prognostic marker associated with tumor progression. PMID:24167613

  10. [Meta-analysis of diagnostic capability of frequency-doubling technology (FDT) for primary glaucoma].

    PubMed

    Liu, Ting; He, Xiang-ge

    2006-05-01

    To evaluate the overall diagnostic capabilities of frequency-doubling technology (FDT) in patients of primary glaucoma, with standard automated perimetry (SAP) and/or optic disc appearance as the gold standard. A comprehensive electric search in MEDLINE, EMBASE, Cochrane Library, BIOSIS, Previews, HMIC, IPA, OVID, CNKI, CBMdisc, VIP information, CMCC, CCPD, SSreader and 21dmedia and a manual search in related textbooks, journals, congress articles and their references were performed to identify relevant English and Chinese language articles. Criteria for adaptability were established according to validity criteria for diagnostic research published by the Cochrane Methods Group on Screening and Diagnostic Tests. Quality of the included articles was assessed and relevant materials were extracted for studying. Statistical analysis was performed with Meta Test version 0.6 software. Heterogeneity of the included articles was tested, which was used to select appropriate effect model to calculate pooled weighted sensitivity and specificity. Summary Receiver Operating Characteristic (SROC) curve was established and the area under the curve (AUC) was calculated. Finally, sensitivity analysis was performed. Fifteen English articles (21 studies) of 206 retrieved articles were included in the present study, with a total of 3172 patients. The reported sensitivity of FDT ranged from 0.51 to 1.00, and specificity from 0.58 to 1.00. The pooled weighted sensitivity and specificity for FDT with 95% confidence intervals (95% CI) after correction for standard error were 0.86 (0.80 - 0.90), 0.87 (0.81 - 0.91), respectively. The AUC of SROC was 93.01%. Sensitivity analysis demonstrated no disproportionate influences of individual study. The included articles are of good quality and FDT can be a highly efficient diagnostic test for primary glaucoma based on Meta-analysis. However, a high quality perspective study is still required for further analysis.

  11. Synchrotron Infrared Confocal Microspectroscopical Detection of Heterogeneity Within Chemically Modified Single Starch Granules

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wetzel, D.; Shi, Y; Reffner, J

    This reports the first detection of chemical heterogeneity in octenyl succinic anhydride modified single starch granules using a Fourier transform infrared (FT-IR) microspectroscopical technique that combines diffraction-limited infrared microspectroscopy with a step size that is less than the mask projected spot size focused on the plane of the sample. The high spatial resolution was achieved with the combination of the application of a synchrotron infrared source and the confocal image plane masking system of the double-pass single-mask Continuum{reg_sign} infrared microscope. Starch from grains such as corn and wheat exists in granules. The size of the granules depends on the plantmore » producing the starch. Granules used in this study typically had a median size of 15 {micro}m. In the production of modified starch, an acid anhydride typically is reacted with OH groups of the starch polymer. The resulting esterification adds the ester carbonyl (1723 cm{sup -1}) organic functional group to the polymer and the hydrocarbon chain of the ester contributes to the CH{sub 2} stretching vibration to enhance the intensity of the 2927 cm{sup -1} band. Detection of the relative modifying population on a single granule was accomplished by ratioing the baseline adjusted peak area of the carbonyl functional group to that of a carbohydrate band. By stepping a confocally defined infrared beam as small as 5 {micro}m x 5 {micro}m across a starch granule 1 {micro}m at a time in both the x and y directions, the heterogeneity is detected with the highest possible spatial resolution.« less

  12. Primary hyperoxaluria: genotype-phenotype correlation.

    PubMed

    Pirulli, Doroti; Marangella, Martino; Amoroso, Antonio

    2003-01-01

    Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder caused by a deficiency of alanine-glyoxylate aminotransferase (AGT), which is encoded by a single copy gene (AGXT). Molecular diagnosis was used in conjunction with clinical, biochemical and enzymological data to evaluate genotype-phenotype correlation. Patients can present a severe form of PH1, an adult form and a mild to moderate decrease in renal function. Biochemical diagnosis is made by plasma, urine and dialyzate oxalate and glycolate assays, and by liver AGT activity and pyridoxine responsitivity. Molecular genetic diagnosis can be made using different techniques, for example, the single strand conformation polymorphism technique (SSCP), followed by the sequencing of the 11 AGXT exons. The disease is clinically and genetically classified as highly heterogeneous. Mutant alleles can be recognised in 80- 90% of chromosomes, depending on the techniques used. Mutations in exons 1, 2, 4 and 10 are more frequent in Italian patients. Normalized AGT activity seems to be lower in the severe form than in the adult form. Double heterozygous patients present a lower age at disease onset and they were more frequent in the more severe than in mild severe disease. The 444T>C mutation was more frequent in the severe form, while the opposite was observed for 630G>A. 630G>A mutation homozygotes had a higher AGT residual activity. The presence of allelic heterogeneity of the AGXT could be responsible, to some extent, for the phenotypic heterogeneity in PH1. Homozygous genotypes were more frequent than expected and were associated with a less severe form of the disease.

  13. AGXT gene mutations and their influence on clinical heterogeneity of type 1 primary hyperoxaluria.

    PubMed

    Amoroso, A; Pirulli, D; Florian, F; Puzzer, D; Boniotto, M; Crovella, S; Zezlina, S; Spanò, A; Mazzola, G; Savoldi, S; Ferrettini, C; Berutti, S; Petrarulo, M; Marangella, M

    2001-10-01

    Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder that is caused by a deficiency of alanine: glyoxylate aminotransferase (AGT), which is encoded by a single copy gene (AGXT). Molecular diagnosis was used in conjunction with clinical, biochemical, and enzymological data to evaluate genotype-phenotype correlation. Twenty-three unrelated, Italian PH1 patients were studied, 20 of which were grouped according to severe form of PH1 (group A), adult form (group B), and mild to moderate decrease in renal function (group C). All 23 patients were analyzed by using the single-strand conformation polymorphism technique followed by the sequencing of the 11 AGXT exons. Relevant chemistries, including plasma, urine and dialyzate oxalate and glycolate assays, liver AGT activity, and pyridoxine responsiveness, were performed. Both mutant alleles were found in 21 out of 23 patients, and 13 different mutations were recognized in exons 1, 2, 4, and 10. Normalized AGT activity was lower in the severe form than in the adult form (P < 0.05). Double heterozygous patients presented a lower age at the onset of the disease (P = 0.025), and they were more frequent in group A (75%) than in the group B (14%; P = 0.0406). The T444C mutation was more frequent in the severe form (P < 0.05), and the opposite was observed for G630A (P < 0.05). G630A mutation homozygotes had a higher AGT residual activity (P = 0.00001). This study confirms the allelic heterogeneity of the AGXT, which could to some extent be responsible for the phenotypic heterogeneity in PH1.

  14. Likelihood-Based Random-Effect Meta-Analysis of Binary Events.

    PubMed

    Amatya, Anup; Bhaumik, Dulal K; Normand, Sharon-Lise; Greenhouse, Joel; Kaizar, Eloise; Neelon, Brian; Gibbons, Robert D

    2015-01-01

    Meta-analysis has been used extensively for evaluation of efficacy and safety of medical interventions. Its advantages and utilities are well known. However, recent studies have raised questions about the accuracy of the commonly used moment-based meta-analytic methods in general and for rare binary outcomes in particular. The issue is further complicated for studies with heterogeneous effect sizes. Likelihood-based mixed-effects modeling provides an alternative to moment-based methods such as inverse-variance weighted fixed- and random-effects estimators. In this article, we compare and contrast different mixed-effect modeling strategies in the context of meta-analysis. Their performance in estimation and testing of overall effect and heterogeneity are evaluated when combining results from studies with a binary outcome. Models that allow heterogeneity in both baseline rate and treatment effect across studies have low type I and type II error rates, and their estimates are the least biased among the models considered.

  15. Co-occurrence of m.1555A>G and m.11778G>A mitochondrial DNA mutations in two Indian families with strikingly different clinical penetrance of Leber hereditary optic neuropathy

    PubMed Central

    Khan, Nahid Akhtar; Govindaraj, Periyasamy; Jyothi, Vuskamalla; Meena, Angamuthu K

    2013-01-01

    Background Mitochondrial DNA (mtDNA) mutations are known to cause Leber hereditary optic neuropathy (LHON). However, the co-occurrence of double pathogenic mutations with different pathological significance in pedigrees is a rare event. Methods Detailed clinical investigation and complete mtDNA sequencing analysis was performed for two Indian families with LHON. The haplogroup was constructed based on evolutionarily important mtDNA variants. Results We observed the existence of double pathogenic mutations (m.11778G>A and m.1555A>G) in two Indian LHON families, who are from different haplogroup backgrounds (M5a and U2e1), with different clinical penetrance of the disease (visual impairment). The m.11778G>A mutation in the MT-ND4 gene is associated primarily with LHON; whereas, m.1555A>G in the 12S rRNA gene has been reported with aminoglycoside-induced non-syndromic hearing loss. Conclusions The absence of hearing abnormality and widely varying clinical expression of LHON suggest additional nuclear modifier genes, environmental factors, and population heterogeneity might play an important role in the expression of visual impairment in these families. PMID:23805034

  16. Detecting Compartmental non-Gaussian Diffusion with Symmetrized Double-PFG MRI

    PubMed Central

    Paulsen, Jeffrey L.; Özarslan, Evren; Komlosh, Michal E.; Basser, Peter J.; Song, Yi-Qiao

    2015-01-01

    Diffusion in tissue and porous media is known to be non-Gaussian and has been used for clinical indications of stroke and other tissue pathologies. However, when conventional NMR techniques are applied to biological tissues and other heterogeneous materials, the presence of multiple compartments (pores) with different Gaussian diffusivities will also contribute to the measurement of non-Gaussian behavior. Here we present Symmetrized Double PFG (sd-PFG), which can separate these two contributions to non-Gaussian signal decay as having distinct angular modulation frequencies. In contrast to prior angular d-PFG methods, sd-PFG can unambiguously extract kurtosis as an oscillation from samples with isotropic or uniformly oriented anisotropic pores, and can generally extract a combination of compartmental anisotropy and kurtosis. The method further fixes its sensitivity with respect to the time-dependence of the apparent diffusion coefficient. We experimentally demonstrate the measurement of the fourth moment (kurtosis) of diffusion and find it consistent with theoretical predictions. By enabling the unambiguous identification of contributions of compartmental kurtosis to the signal, sd-PFG has the potential to help identify the underlying micro-structural changes corresponding to current kurtosis based diagnostics and act as a novel source of contrast to better resolve tissue micro-structure. PMID:26434812

  17. Hollow Pd/MOF Nanosphere with Double Shells as Multifunctional Catalyst for Hydrogenation Reaction.

    PubMed

    Wan, Mingming; Zhang, Xinlu; Li, Meiyan; Chen, Bo; Yin, Jie; Jin, Haichao; Lin, Lin; Chen, Chao; Zhang, Ning

    2017-10-01

    A new type of hollow nanostructure featured double metal-organic frameworks shells with metal nanoparticles (MNPs) is designed and fabricated by the methods of ship in a bottle and bottle around the ship. The nanostructure material, hereinafter denoted as Void@HKUST-1/Pd@ZIF-8, is confirmed by the analyses of photograph, transmission electron microscopy, scanning electron microscopy, powder X-ray diffraction, inductively coupled plasma, and N 2 sorption. It possesses various multifunctionally structural characteristics such as hollow cavity which can improve mass transfer, the adjacent of the inner HKUST-1 shell to the void which enables the matrix of the shell to host and well disperse MNPs, and an outer ZIF-8 shell which acts as protective layer against the leaching of MNPs and a sieve to guarantee molecular-size selectivity. This makes the material eligible candidates for the heterogeneous catalyst. As a proof of concept, the liquid-phase hydrogenation of olefins with different molecular sizes as a model reaction is employed. It demonstrates the efficient catalytic activity and size-selectivity of Void@HKUST-1/Pd@ZIF-8. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Telomere-Internal Double-Strand Breaks Are Repaired by Homologous Recombination and PARP1/Lig3-Dependent End-Joining.

    PubMed

    Doksani, Ylli; de Lange, Titia

    2016-11-01

    Shelterin protects chromosome ends from the DNA damage response. Although the mechanism of telomere protection has been studied extensively, the fate of double-strand breaks (DSBs) inside telomeres is not known. Here, we report that telomere-internal FokI-induced DSBs activate ATM kinase-dependent signaling in S-phase but are well tolerated and repaired efficiently. Homologous recombination contributes to repair, leading to increased telomere length heterogeneity typical of the alternative lengthening of telomeres (ALT) pathway. Furthermore, cells accumulate extra chromosomal telomeric signals (ECTS), a second hallmark of ALT. Telomere-internal DSBs are also repaired by a PARP1- and Ligase3-dependent reaction, suggesting alternative non-homologous end-joining (alt-NHEJ), which relies on microhomology at DSBs. However, as resected telomere-internal DSBs have perfect homology, their PARP1/Lig3-dependent end-joining may be more akin to single strand break repair. We conclude that shelterin does not repress ATM kinase signaling or DSB repair at telomere-internal sites, thereby allowing DNA repair to maintain telomere integrity. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  19. Effects of spatial heterogeneity and material anisotropy on the fracture pattern and macroscopic effective toughness of Mancos Shale in Brazilian tests

    NASA Astrophysics Data System (ADS)

    Na, SeonHong; Sun, WaiChing; Ingraham, Mathew D.; Yoon, Hongkyu

    2017-08-01

    For assessing energy-related activities in the subsurface, it is important to investigate the impact of the spatial variability and anisotropy on the geomechanical behavior of shale. The Brazilian test, an indirect tensile-splitting method, is performed in this work, and the evolution of strain field is obtained using digital image correlation. Experimental results show the significant impact of local heterogeneity and lamination on the crack pattern characteristics. For numerical simulations, a phase field method is used to simulate the brittle fracture behavior under various Brazilian test conditions. In this study, shale is assumed to consist of two constituents including the stiff and soft layers to which the same toughness but different elastic moduli are assigned. Microstructural heterogeneity is simplified to represent mesoscale (e.g., millimeter scale) features such as layer orientation, thickness, volume fraction, and defects. The effect of these structural attributes on the onset, propagation, and coalescence of cracks is explored. The simulation results show that spatial heterogeneity and material anisotropy highly affect crack patterns and effective fracture toughness, and the elastic contrast of two constituents significantly alters the effective toughness. However, the complex crack patterns observed in the experiments cannot completely be accounted for by either an isotropic or transversely isotropic effective medium approach. This implies that cracks developed in the layered system may coalesce in complicated ways depending on the local heterogeneity, and the interaction mechanisms between the cracks using two-constituent systems may explain the wide range of effective toughness of shale reported in the literature.

  20. Effects of spatial heterogeneity and material anisotropy on the fracture pattern and macroscopic effective toughness of Mancos Shale in Brazilian tests

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Na, SeonHong; Sun, WaiChing; Ingraham, Mathew D.

    For assessing energy-related activities in the subsurface, it is important to investigate the impact of the spatial variability and anisotropy on the geomechanical behavior of shale. The Brazilian test, an indirect tensile-splitting method, is performed in this work, and the evolution of strain field is obtained using digital image correlation. Experimental results show the significant impact of local heterogeneity and lamination on the crack pattern characteristics. For numerical simulations, a phase field method is used to simulate the brittle fracture behavior under various Brazilian test conditions. In this study, shale is assumed to consist of two constituents including the stiffmore » and soft layers to which the same toughness but different elastic moduli are assigned. Microstructural heterogeneity is simplified to represent mesoscale (e.g., millimeter scale) features such as layer orientation, thickness, volume fraction, and defects. The effect of these structural attributes on the onset, propagation, and coalescence of cracks is explored. The simulation results show that spatial heterogeneity and material anisotropy highly affect crack patterns and effective fracture toughness, and the elastic contrast of two constituents significantly alters the effective toughness. However, the complex crack patterns observed in the experiments cannot completely be accounted for by either an isotropic or transversely isotropic effective medium approach. In conclusion, this implies that cracks developed in the layered system may coalesce in complicated ways depending on the local heterogeneity, and the interaction mechanisms between the cracks using two-constituent systems may explain the wide range of effective toughness of shale reported in the literature.« less

  1. Effects of spatial heterogeneity and material anisotropy on the fracture pattern and macroscopic effective toughness of Mancos Shale in Brazilian tests

    DOE PAGES

    Na, SeonHong; Sun, WaiChing; Ingraham, Mathew D.; ...

    2017-07-31

    For assessing energy-related activities in the subsurface, it is important to investigate the impact of the spatial variability and anisotropy on the geomechanical behavior of shale. The Brazilian test, an indirect tensile-splitting method, is performed in this work, and the evolution of strain field is obtained using digital image correlation. Experimental results show the significant impact of local heterogeneity and lamination on the crack pattern characteristics. For numerical simulations, a phase field method is used to simulate the brittle fracture behavior under various Brazilian test conditions. In this study, shale is assumed to consist of two constituents including the stiffmore » and soft layers to which the same toughness but different elastic moduli are assigned. Microstructural heterogeneity is simplified to represent mesoscale (e.g., millimeter scale) features such as layer orientation, thickness, volume fraction, and defects. The effect of these structural attributes on the onset, propagation, and coalescence of cracks is explored. The simulation results show that spatial heterogeneity and material anisotropy highly affect crack patterns and effective fracture toughness, and the elastic contrast of two constituents significantly alters the effective toughness. However, the complex crack patterns observed in the experiments cannot completely be accounted for by either an isotropic or transversely isotropic effective medium approach. In conclusion, this implies that cracks developed in the layered system may coalesce in complicated ways depending on the local heterogeneity, and the interaction mechanisms between the cracks using two-constituent systems may explain the wide range of effective toughness of shale reported in the literature.« less

  2. Toward heterogeneity in feedforward network with synaptic delays based on FitzHugh-Nagumo model

    NASA Astrophysics Data System (ADS)

    Qin, Ying-Mei; Men, Cong; Zhao, Jia; Han, Chun-Xiao; Che, Yan-Qiu

    2018-01-01

    We focus on the role of heterogeneity on the propagation of firing patterns in feedforward network (FFN). Effects of heterogeneities both in parameters of neuronal excitability and synaptic delays are investigated systematically. Neuronal heterogeneity is found to modulate firing rates and spiking regularity by changing the excitability of the network. Synaptic delays are strongly related with desynchronized and synchronized firing patterns of the FFN, which indicate that synaptic delays may play a significant role in bridging rate coding and temporal coding. Furthermore, quasi-coherence resonance (quasi-CR) phenomenon is observed in the parameter domain of connection probability and delay-heterogeneity. All these phenomena above enable a detailed characterization of neuronal heterogeneity in FFN, which may play an indispensable role in reproducing the important properties of in vivo experiments.

  3. Testing the influence of environmental heterogeneity on fish species richness in two biogeographic provinces.

    PubMed

    Massicotte, Philippe; Proulx, Raphaël; Cabana, Gilbert; Rodríguez, Marco A

    2015-01-01

    Environmental homogenization in coastal ecosystems impacted by human activities may be an important factor explaining the observed decline in fish species richness. We used fish community data (>200 species) from extensive surveys conducted in two biogeographic provinces (extent >1,000 km) in North America to quantify the relationship between fish species richness and local (grain <10 km(2)) environmental heterogeneity. Our analyses are based on samples collected at nearly 800 stations over a period of five years. We demonstrate that fish species richness in coastal ecosystems is associated locally with the spatial heterogeneity of environmental variables but not with their magnitude. The observed effect of heterogeneity on species richness was substantially greater than that generated by simulations from a random placement model of community assembly, indicating that the observed relationship is unlikely to arise from veil or sampling effects. Our results suggest that restoring or actively protecting areas of high habitat heterogeneity may be of great importance for slowing current trends of decreasing biodiversity in coastal ecosystems.

  4. Sediment heterogeneity and mobility in the morphodynamic modelling of gravel-bed braided rivers

    NASA Astrophysics Data System (ADS)

    Singh, Umesh; Crosato, Alessandra; Giri, Sanjay; Hicks, Murray

    2017-06-01

    The effects of sediment heterogeneity and sediment mobility on the morphology of braided rivers are still poorly studied, especially when the partial sediment mobility occurs. Nevertheless, increasing the bed sediment heterogeneity by coarse sediment supply is becoming a common practice in river restoration projects and habitat improvement all over the world. This research provides a step forward in the identification of the effects of sediment sorting on the evolution of sediment bars and braiding geometry of gravel-bed rivers. A two-dimensional morphodynamic model was used to simulate the long-term developments of a hypothetical braided system with discharge regime and morphodynamic parameters derived from the Waimakariri River, New Zealand. Several scenarios, differing in bed sediment heterogeneity and sediment mobility, were considered. The results agree with the tendencies already identified in linear analyses and experimental studies, showing that a larger sediment heterogeneity increases the braiding indes and reduces the bars length and height. The analyses allowed identifying the applicability limits of uniform sediment and variable discharge modelling approaches.

  5. A Novel Energy-Aware Distributed Clustering Algorithm for Heterogeneous Wireless Sensor Networks in the Mobile Environment

    PubMed Central

    Gao, Ying; Wkram, Chris Hadri; Duan, Jiajie; Chou, Jarong

    2015-01-01

    In order to prolong the network lifetime, energy-efficient protocols adapted to the features of wireless sensor networks should be used. This paper explores in depth the nature of heterogeneous wireless sensor networks, and finally proposes an algorithm to address the problem of finding an effective pathway for heterogeneous clustering energy. The proposed algorithm implements cluster head selection according to the degree of energy attenuation during the network’s running and the degree of candidate nodes’ effective coverage on the whole network, so as to obtain an even energy consumption over the whole network for the situation with high degree of coverage. Simulation results show that the proposed clustering protocol has better adaptability to heterogeneous environments than existing clustering algorithms in prolonging the network lifetime. PMID:26690440

  6. Lattice Boltzmann Simulation of Electroosmotic Micromixing by Heterogeneous Surface Charge

    NASA Astrophysics Data System (ADS)

    Tang, G. H.; Wang, F. F.; Tao, W. Q.

    Microelectroosmotic flow is usually restricted to low Reynolds number regime, and mixing in these microfluidic systems becomes problematic due to the negligible inertial effects. To gain an improved understanding of mixing enhancement in microchannels patterned with heterogeneous surface charge, the lattice Boltzmann method has been employed to obtain the electric potential distribution in the electrolyte, the flow field, and the species concentration distribution, respectively. The simulation results show that heterogeneous surfaces can significantly disturb the streamlines leading to apparently substantial improvements in mixing. However, the introduction of such a feature can reduce the mass flow rate in the channel. The reduction in flow rate effectively prolongs the available mixing time when the flow passes through the channel and the observed mixing enhancement by heterogeneous surfaces partly results from longer mixing time.

  7. Heterogeneity Coefficients for Mahalanobis' D as a Multivariate Effect Size.

    PubMed

    Del Giudice, Marco

    2017-01-01

    The Mahalanobis distance D is the multivariate generalization of Cohen's d and can be used as a standardized effect size for multivariate differences between groups. An important issue in the interpretation of D is heterogeneity, that is, the extent to which contributions to the overall effect size are concentrated in a small subset of variables rather than evenly distributed across the whole set. Here I present two heterogeneity coefficients for D based on the Gini coefficient, a well-known index of inequality among values of a distribution. I discuss the properties and limitations of the two coefficients and illustrate their use by reanalyzing some published findings from studies of gender differences.

  8. Impact of supersonic and subsonic aircraft on ozone: Including heterogeneous chemical reaction mechanisms

    NASA Technical Reports Server (NTRS)

    Kinnison, Douglas E.; Wuebbles, Donald J.

    1994-01-01

    Preliminary calculations suggest that heterogeneous reactions are important in calculating the impact on ozone from emissions of trace gases from aircraft fleets. In this study, three heterogeneous chemical processes that occur on background sulfuric acid aerosols are included and their effects on O3, NO(x), Cl(x), HCl, N2O5, ClONO2 are calculated.

  9. Mesoscale Computational Investigation of Shocked Heterogeneous Materials with Application to Large Impact Craters

    NASA Technical Reports Server (NTRS)

    Crawford, D. A.; Barnouin-Jha, O. S.; Cintala, M. J.

    2003-01-01

    The propagation of shock waves through target materials is strongly influenced by the presence of small-scale structure, fractures, physical and chemical heterogeneities. Pre-existing fractures often create craters that appear square in outline (e.g. Meteor Crater). Reverberations behind the shock from the presence of physical heterogeneity have been proposed as a mechanism for transient weakening of target materials. Pre-existing fractures can also affect melt generation. In this study, we are attempting to bridge the gap in numerical modeling between the micro-scale and the continuum, the so-called meso-scale. To accomplish this, we are developing a methodology to be used in the shock physics hydrocode (CTH) using Monte-Carlo-type methods to investigate the shock properties of heterogeneous materials. By comparing the results of numerical experiments at the micro-scale with experimental results and by using statistical techniques to evaluate the performance of simple constitutive models, we hope to embed the effect of physical heterogeneity into the field variables (pressure, stress, density, velocity) allowing us to directly imprint the effects of micro-scale heterogeneity at the continuum level without incurring high computational cost.

  10. Reporting heterogeneity in self-assessed health among elderly Europeans.

    PubMed

    Pfarr, Christian; Schmid, Andreas; Schneider, Udo

    2012-10-05

    Self-assessed health (SAH) is a frequently used measure of individuals' health status. It is also prone to reporting heterogeneity. To control for reporting heterogeneity objective measures of true health need to be included in an analysis. The topic becomes even more complex for cross-country comparisons, as many key variables tend to vary strongly across countries, influenced by cultural and institutional differences. This study aims at exploring the key drivers for reporting heterogeneity in SAH in an international context. To this end, country specific effects are accounted for and the objective health measure is concretized, distinguishing effects of mental and physical health conditions. We use panel data from the SHARE-project which provides a rich dataset on the elderly European population. To obtain distinct indicators for physical and mental health conditions two indices are constructed. Finally, to identify potential reporting heterogeneity in SAH a generalized ordered probit model is estimated. We find evidence that in addition to health behaviour, health care utilization, mental and physical health condition as well as country characteristics affect reporting behaviour. We conclude that observed and unobserved heterogeneity play an important role when analysing SAH and have to be taken into account.

  11. Neither fixed nor random: weighted least squares meta-analysis.

    PubMed

    Stanley, T D; Doucouliagos, Hristos

    2015-06-15

    This study challenges two core conventional meta-analysis methods: fixed effect and random effects. We show how and explain why an unrestricted weighted least squares estimator is superior to conventional random-effects meta-analysis when there is publication (or small-sample) bias and better than a fixed-effect weighted average if there is heterogeneity. Statistical theory and simulations of effect sizes, log odds ratios and regression coefficients demonstrate that this unrestricted weighted least squares estimator provides satisfactory estimates and confidence intervals that are comparable to random effects when there is no publication (or small-sample) bias and identical to fixed-effect meta-analysis when there is no heterogeneity. When there is publication selection bias, the unrestricted weighted least squares approach dominates random effects; when there is excess heterogeneity, it is clearly superior to fixed-effect meta-analysis. In practical applications, an unrestricted weighted least squares weighted average will often provide superior estimates to both conventional fixed and random effects. Copyright © 2015 John Wiley & Sons, Ltd.

  12. Trans-ethnic meta-regression of genome-wide association studies accounting for ancestry increases power for discovery and improves fine-mapping resolution

    PubMed Central

    Mägi, Reedik; Horikoshi, Momoko; Sofer, Tamar; Mahajan, Anubha; Kitajima, Hidetoshi; Franceschini, Nora; McCarthy, Mark I.; Morris, Andrew P.

    2017-01-01

    Abstract Trans-ethnic meta-analysis of genome-wide association studies (GWAS) across diverse populations can increase power to detect complex trait loci when the underlying causal variants are shared between ancestry groups. However, heterogeneity in allelic effects between GWAS at these loci can occur that is correlated with ancestry. Here, a novel approach is presented to detect SNP association and quantify the extent of heterogeneity in allelic effects that is correlated with ancestry. We employ trans-ethnic meta-regression to model allelic effects as a function of axes of genetic variation, derived from a matrix of mean pairwise allele frequency differences between GWAS, and implemented in the MR-MEGA software. Through detailed simulations, we demonstrate increased power to detect association for MR-MEGA over fixed- and random-effects meta-analysis across a range of scenarios of heterogeneity in allelic effects between ethnic groups. We also demonstrate improved fine-mapping resolution, in loci containing a single causal variant, compared to these meta-analysis approaches and PAINTOR, and equivalent performance to MANTRA at reduced computational cost. Application of MR-MEGA to trans-ethnic GWAS of kidney function in 71,461 individuals indicates stronger signals of association than fixed-effects meta-analysis when heterogeneity in allelic effects is correlated with ancestry. Application of MR-MEGA to fine-mapping four type 2 diabetes susceptibility loci in 22,086 cases and 42,539 controls highlights: (i) strong evidence for heterogeneity in allelic effects that is correlated with ancestry only at the index SNP for the association signal at the CDKAL1 locus; and (ii) 99% credible sets with six or fewer variants for five distinct association signals. PMID:28911207

  13. Transcriptome dynamics along axolotl regenerative development are consistent with an extensive reduction in gene expression heterogeneity in dedifferentiated cells

    PubMed Central

    2017-01-01

    Although in recent years the study of gene expression variation in the absence of genetic or environmental cues or gene expression heterogeneity has intensified considerably, many basic and applied biological fields still remain unaware of how useful the study of gene expression heterogeneity patterns might be for the characterization of biological systems and/or processes. Largely based on the modulator effect chromatin compaction has for gene expression heterogeneity and the extensive changes in chromatin compaction known to occur for specialized cells that are naturally or artificially induced to revert to less specialized states or dedifferentiate, I recently hypothesized that processes that concur with cell dedifferentiation would show an extensive reduction in gene expression heterogeneity. The confirmation of the existence of such trend could be of wide interest because of the biomedical and biotechnological relevance of cell dedifferentiation-based processes, i.e., regenerative development, cancer, human induced pluripotent stem cells, or plant somatic embryogenesis. Here, I report the first empirical evidence consistent with the existence of an extensive reduction in gene expression heterogeneity for processes that concur with cell dedifferentiation by analyzing transcriptome dynamics along forearm regenerative development in Ambystoma mexicanum or axolotl. Also, I briefly discuss on the utility of the study of gene expression heterogeneity dynamics might have for the characterization of cell dedifferentiation-based processes, and the engineering of tools that afforded better monitoring and modulating such processes. Finally, I reflect on how a transitional reduction in gene expression heterogeneity for dedifferentiated cells can promote a long-term increase in phenotypic heterogeneity following cell dedifferentiation with potential adverse effects for biomedical and biotechnological applications. PMID:29134148

  14. Heterogeneous chemistry: a mechanism missing in current models to explain secondary inorganic aerosol formation during the January 2013 haze episode in North China

    DOE PAGES

    Zheng, B.; Zhang, Q.; Zhang, Y.; ...

    2015-02-25

    Severe regional haze pollution events occurred in eastern and central China in January 2013, which had adverse effects on the environment and public health. Extremely high levels of particulate matter with aerodynamic diameter of 2.5 μm or less (PM 2.5) with dominant components of sulfate and nitrate are responsible for the haze pollution. Although heterogeneous chemistry is thought to play an important role in the production of sulfate and nitrate during haze episodes, few studies have comprehensively evaluated the effect of heterogeneous chemistry on haze formation in China by using the 3-D models due to of a lack of treatmentsmore » for heterogeneous reactions in most climate and chemical transport models. In this work, the WRF-CMAQ model with newly added heterogeneous reactions is applied to East Asia to evaluate the impacts of heterogeneous chemistry and the meteorological anomaly during January 2013 on regional haze formation. As the parameterization of heterogeneous reactions on different types of particles is not well established yet, we arbitrarily selected the uptake coefficients from reactions on dust particles and then conducted several sensitivity runs to find the value that can best match observations. The revised CMAQ with heterogeneous chemistry not only captures the magnitude and temporal variation of sulfate and nitrate, but also reproduces the enhancement of relative contribution of sulfate and nitrate to PM 2.5 mass from clean days to polluted haze days. Finally, these results indicate the significant role of heterogeneous chemistry in regional haze formation and improve the understanding of the haze formation mechanisms during the January 2013 episode.« less

  15. Expanding the Scope of Mindfulness-Based Cognitive Therapy: Evidence for Effectiveness in a Heterogeneous Psychiatric Sample

    ERIC Educational Resources Information Center

    Green, Sheryl M.; Bieling, Peter J.

    2012-01-01

    Mindfulness-based interventions (e.g., MBSR; Kabat-Zinn, 1990; MBCT; Segal, Williams, & Teasdale, 2002) have demonstrated effectiveness in a number of distinct clinical populations. However, few studies have evaluated MBCT within a heterogeneous group of psychiatric adult outpatients. This study examined whether a wider variety of patients…

  16. Heterogeneous Effects of Charter Schools: Unpacking Family Selection and Achievement Growth in Los Angeles

    ERIC Educational Resources Information Center

    Shin, Hyo Jeong; Fuller, Bruce; Dauter, Luke

    2017-01-01

    Disparate findings on whether students attending charter schools outperform peers in traditional public schools (TPS) may stem from mixing differing types of charters or inadequately accounting for pupil background. To gauge prior family selection and heterogeneous effects, we distinguish between conversion and start-up charter schools, along with…

  17. Allocating Sample Sizes to Reduce Budget for Fixed-Effect 2×2 Heterogeneous Analysis of Variance

    ERIC Educational Resources Information Center

    Luh, Wei-Ming; Guo, Jiin-Huarng

    2016-01-01

    This article discusses the sample size requirements for the interaction, row, and column effects, respectively, by forming a linear contrast for a 2×2 factorial design for fixed-effects heterogeneous analysis of variance. The proposed method uses the Welch t test and its corresponding degrees of freedom to calculate the final sample size in a…

  18. Adaptive Control of Synchronization in Delay-Coupled Heterogeneous Networks of FitzHugh-Nagumo Nodes

    NASA Astrophysics Data System (ADS)

    Plotnikov, S. A.; Lehnert, J.; Fradkov, A. L.; Schöll, E.

    We study synchronization in delay-coupled neural networks of heterogeneous nodes. It is well known that heterogeneities in the nodes hinder synchronization when becoming too large. We show that an adaptive tuning of the overall coupling strength can be used to counteract the effect of the heterogeneity. Our adaptive controller is demonstrated on ring networks of FitzHugh-Nagumo systems which are paradigmatic for excitable dynamics but can also — depending on the system parameters — exhibit self-sustained periodic firing. We show that the adaptively tuned time-delayed coupling enables synchronization even if parameter heterogeneities are so large that excitable nodes coexist with oscillatory ones.

  19. The Heterogeneity of the Cigarette Price Effect on Body Mass Index

    PubMed Central

    Courtemanche, Charles J.

    2012-01-01

    Previous studies estimate the average effect of cigarette price on body mass index (BMI), with recent research showing that their different methodologies all point to a negative effect after several years. This literature, however, ignores the possibility that the effect could vary throughout the BMI distribution or across socioeconomic and demographic groups due to differences in underlying obesity risks or preferences for health. We evaluate heterogeneity in the long-run impact of cigarette price on BMI by performing quantile regressions and stratifying the sample by race, education, age, and sex. Cigarette price has a highly heterogeneous negative effect that is more than three times as strong at high BMI levels – where weight loss is most beneficial for health – than at low levels. The effects are also strongest for blacks, college graduates, middle-aged adults, and women. We also assess the implications for disparities, conduct robustness checks, and evaluate potential mechanisms. PMID:22842751

  20. 78 FR 50335 - Double Hull Tanker Escorts on the Waters of Prince William Sound, Alaska

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-19

    ...-AB96 Double Hull Tanker Escorts on the Waters of Prince William Sound, Alaska AGENCY: Coast Guard, DHS... mandates two tug escorts for double hull tankers over 5,000 gross tons transporting oil in bulk in PWS. The... tug escort requirements apply to certain double hull tankers. DATES: This interim rule is effective...

  1. Influence of the charge double layer on solid oxide fuel cell stack behavior

    NASA Astrophysics Data System (ADS)

    Whiston, Michael M.; Bilec, Melissa M.; Schaefer, Laura A.

    2015-10-01

    While the charge double layer effect has traditionally been characterized as a millisecond phenomenon, longer timescales may be possible under certain operating conditions. This study simulates the dynamic response of a previously developed solid oxide fuel cell (SOFC) stack model that incorporates the charge double layer via an equivalent circuit. The model is simulated under step load changes. Baseline conditions are first defined, followed by consideration of minor and major deviations from the baseline case. This study also investigates the behavior of the SOFC stack with a relatively large double layer capacitance value, as well as operation of the SOFC stack under proportional-integral (PI) control. Results indicate that the presence of the charge double layer influences the SOFC stack's settling time significantly under the following conditions: (i) activation and concentration polarizations are significantly increased, or (ii) a large value of the double layer capacitance is assumed. Under normal (baseline) operation, on the other hand, the charge double layer effect diminishes within milliseconds, as expected. It seems reasonable, then, to neglect the charge double layer under normal operation. However, careful consideration should be given to potential variations in operation or material properties that may give rise to longer electrochemical settling times.

  2. Effect of Induced Charge Electroosmosis on the Dielectrophoretic Motion of Particles

    NASA Astrophysics Data System (ADS)

    Swaminathan, T.; Hu, Howard

    2006-11-01

    Most suspensions involve the formation of ionic double layers next to the surface of particles due to the induced-charge on the surface. These double layers affect the motion of the particle even under AC electric fields. They modify the net dipole moment of the particle and at the same time produce slip velocities on the surfaces of these particles. A method to numerically evaluate the effect of the double layer on the dielectrophoretic motion of particles has been previously developed to study these two effects. The technique involves a matched asymptotic expansion of the electric field near the particle surface, where the double layer is formed, and is written as a jump-boundary-condition for the electric potential when the thickness of the double layer is small compared to the size of the particle. The developed jump-boundary-condition is then used to calculate an effective zeta potential on the particle surface. Unlike classical electroosmosis, this zeta potential is no longer constant on every part of the surface and is dependent on the applied electric field. The effect of the induced-charge electroosmotic slip velocity on the dielectrophoretic motion of particles has been observed using this technique.

  3. Effects of the Heterogeneity in the Electron Beam Welded Joint on Mechanical Properties of Ti6Al4V Alloy

    NASA Astrophysics Data System (ADS)

    Liu, Jing; Gao, Xiao-Long; Zhang, Lin-Jie; Zhang, Jian-Xun

    2015-01-01

    The aim of this investigation was to evaluate the effect of microstructure heterogeneity on the tensile and low cycle fatigue properties of electron beam welded (EBW) Ti6Al4V sheets. To achieve this goal, the tensile and low cycle fatigue property in the EBW joints and base metal (BM) specimens is compared. During the tensile testing, digital image correlation technology was used to measure the plastic strain field evolution within the specimens. The experimental results showed that the tensile ductility and low cycle fatigue strength of EBW joints are lower than that of BM specimens, mainly because of the effect of microstructure heterogeneity of the welded joint. Moreover, the EBW joints exhibit the cyclic hardening behavior during low fatigue process, while BM specimens exhibit the cyclic softening behavior. Compared with the BM specimens with uniform microstructure, the heterogeneity of microstructure in the EBW joint is found to decrease the mechanical properties of welded joint.

  4. Environmental heterogeneity and biotic interactions mediate climate impacts on tropical forest regeneration.

    PubMed

    Uriarte, María; Muscarella, Robert; Zimmerman, Jess K

    2018-02-01

    Predicting the fate of tropical forests under a changing climate requires understanding species responses to climatic variability and extremes. Seedlings may be particularly vulnerable to climatic stress given low stored resources and undeveloped roots; they also portend the potential effects of climate change on future forest composition. Here we use data for ca. 50,000 tropical seedlings representing 25 woody species to assess (i) the effects of interannual variation in rainfall and solar radiation between 2007 and 2016 on seedling survival over 9 years in a subtropical forest; and (ii) how spatial heterogeneity in three environmental factors-soil moisture, understory light, and conspecific neighborhood density-modulate these responses. Community-wide seedling survival was not sensitive to interannual rainfall variability but interspecific variation in these responses was large, overwhelming the average community response. In contrast, community-wide responses to solar radiation were predominantly positive. Spatial heterogeneity in soil moisture and conspecific density were the predominant and most consistent drivers of seedling survival, with the majority of species exhibiting greater survival at low conspecific densities and positive or nonlinear responses to soil moisture. This environmental heterogeneity modulated impacts of rainfall and solar radiation. Negative conspecific effects were amplified during rainy years and at dry sites, whereas the positive effects of radiation on survival were more pronounced for seedlings existing at high understory light levels. These results demonstrate that environmental heterogeneity is not only the main driver of seedling survival in this forest but also plays a central role in buffering or exacerbating impacts of climate fluctuations on forest regeneration. Since seedlings represent a key bottleneck in the demographic cycle of trees, efforts to predict the long-term effects of a changing climate on tropical forests must take into account this environmental heterogeneity and how its effects on regeneration dynamics play out in long-term stand dynamics. © 2017 John Wiley & Sons Ltd.

  5. Association of vegetarian diet with inflammatory biomarkers: a systematic review and meta-analysis of observational studies.

    PubMed

    Haghighatdoost, Fahimeh; Bellissimo, Nick; Totosy de Zepetnek, Julia O; Rouhani, Mohammad Hossein

    2017-10-01

    Vegetarian diets contain various anti-inflammatory components. We aimed to investigate the effects of vegetarianism on inflammatory biomarkers when compared with omnivores. Systematic review and meta-analysis. Literature search was conducted in Science Direct, Proquest, MEDLINE and Google Scholar up to June 2016. Summary estimates and corresponding 95 % CI were derived via the DerSimonian and Laird method using random effects, subgroup analyses were run to find the source of heterogeneity and a fixed-effect model examined between-subgroup heterogeneity. Studies were included if they evaluated effects of any type of vegetarianism compared with omnivores on circulating levels of inflammatory biomarkers. No restriction was made in terms of language or the date of study publications. Eighteen articles were included. Pooled effect size showed no difference in high-sensitivity C-reactive protein (hs-CRP) levels in vegetarians v. omnivores (Hedges' g=-0·15; 95 % CI -0·35, 0·05), with high heterogeneity (I 2=75·6 %, P<0·01). A subgroup analysis by minimum duration of vegetarianism showed that a minimum duration of 2 years vegetarianism was associated with lower hs-CRP levels v. omnivores (Hedges' g=-0·29; 95 % CI -0·59, 0·01), with moderate heterogeneity (I 2=68·9 %, P<0·01). No significant effect was found in studies using a minimum duration of 6 months of vegetarianism, with low heterogeneity. Vegetarianism was associated with increased IL-6 concentrations (0·21 pg/ml; 95 % CI 0·18, 0·25), with no heterogeneity (I 2=0·0 %, P=0·60). The meta-analysis provides evidence that vegetarianism is associated with lower serum concentrations of hs-CRP when individuals follow a vegetarian diet for at least 2 years. Further research is necessary to draw appropriate conclusions regarding potential associations between vegetarianism and IL-6 levels. A vegetarian diet might be a useful approach to manage inflammaging in the long term.

  6. Double photoionization of atoms

    NASA Astrophysics Data System (ADS)

    Wiedenhoeft, Marco

    2003-10-01

    Double photoionization studies of atoms and molecules are new state-of-the-art studies providing a deeper knowledge of multi-electron excitations. This type of work advances the understanding of many-body problems. Double photoionization of atoms is of great interest to learn about electron-electron correlation and relaxation effects in atoms and molecules. In order to study double photoionization processes, a new electron-electron coincidence apparatus was built to carry out the measurements. I will present the apparatus I built as well as the results of the measurement of the triply-differential-cross-section (TDCS) for the predicted interference and Post-Collision-Interaction (PCI) effects in the Xenon N5O2,3 O2,3 Auger decay after 4d5/2 photoionization. Furthermore I present measurements for direct double photoionization of Helium at various photon energies.

  7. The scaling of oblique plasma double layers

    NASA Technical Reports Server (NTRS)

    Borovsky, J. E.

    1983-01-01

    Strong oblique plasma double layers are investigated using three methods, i.e., electrostatic particle-in-cell simulations, numerical solutions to the Poisson-Vlasov equations, and analytical approximations to the Poisson-Vlasov equations. The solutions to the Poisson-Vlasov equations and numerical simulations show that strong oblique double layers scale in terms of Debye lengths. For very large potential jumps, theory and numerical solutions indicate that all effects of the magnetic field vanish and the oblique double layers follow the same scaling relation as the field-aligned double layers.

  8. Thermal inertia and surface heterogeneity on Mars

    NASA Astrophysics Data System (ADS)

    Putzig, Nathaniel E.

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

  9. Scaling Effects of Cr(VI) Reduction Kinetics. The Role of Geochemical Heterogeneity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Li; Li, Li

    2015-10-22

    The natural subsurface is highly heterogeneous with minerals distributed in different spatial patterns. Fundamental understanding of how mineral spatial distribution patterns regulate sorption process is important for predicting the transport and fate of chemicals. Existing studies about the sorption was carried out in well-mixed batch reactors or uniformly packed columns, with few data available on the effects of spatial heterogeneities. As a result, there is a lack of data and understanding on how spatial heterogeneities control sorption processes. In this project, we aim to understand and develop modeling capabilities to predict the sorption of Cr(VI), an omnipresent contaminant in naturalmore » systems due to its natural occurrence and industrial utilization. We systematically examine the role of spatial patterns of illite, a common clay, in determining the extent of transport limitation and scaling effects associated with Cr(VI) sorption capacity and kinetics using column experiments and reactive transport modeling. Our results showed that the sorbed mass and rates can differ by an order of magnitude due to of the illite spatial heterogeneities and transport limitation. With constraints from data, we also developed the capabilities of modeling Cr(VI) in heterogeneous media. The developed model is then utilized to understand the general principles that govern the relationship between sorption and connectivity, a key measure of the spatial pattern characteristics. This correlation can be used to estimate Cr(VI) sorption characteristics in heterogeneous porous media. Insights gained here bridge gaps between laboratory and field application in hydrogeology and geochemical field, and advance predictive understanding of reactive transport processes in the natural heterogeneous subsurface. We believe that these findings will be of interest to a large number of environmental geochemists and engineers, hydrogeologists, and those interested in contaminant fate and transport, water quality and water composition, and natural attenuation processes in natural systems.« less

  10. [Effect of heterogenic irradiation on deviation from Bouguer-Lambert-Beer law in photometric measurements in ultraviolet, visible, and infrared spectra].

    PubMed

    Ovchinnikov, M M; Podgornyĭ, G N

    2004-03-01

    The passing and optic-density parameters registered by a photometric device were estimated, on the basis of a simple modeled system, with respect to the ratio between the absorption band width and the heterogeneous radiation degree. The impacts of heterogeneous radiation on the validity of the Bueguer'-Lambert's-Baire's law were elucidated.

  11. Increased cutaneous wound healing effect of biodegradable liposomes containing madecassoside: preparation optimization, in vitro dermal permeation, and in vivo bioevaluation.

    PubMed

    Li, Zehao; Liu, Meifeng; Wang, Huijuan; Du, Song

    2016-01-01

    Madecassoside (MA) is highly potent in treating skin disorders such as wounds and psoriasis. However, the topical wound healing effect of MA was hampered by its poor membrane permeability. In order to overcome this shortcoming, MA liposomes were designed and prepared by a double-emulsion method to enhance transdermal and wound healing effects. In this study, response surface methodology was adopted to yield the optimal preparation conditions of MA double-emulsion liposomes with average particle size of 151 nm and encapsulation efficiency of 70.14%. Moreover, MA double-emulsion liposomes demonstrated superior stability and homogeneous appearance in 5 months; their leakage rate was <12% even at 37°C and <5% at 4°C within 1 month. In vitro skin permeation, skin distribution, and burn wound healing of MA liposomal formulations were conducted for the first time to evaluate MA delivery efficiency and wound healing effect. The transdermal property and wound cure effect of MA double-emulsion liposomes were superior to those of MA film dispersion liposomes, and both the methods were endowed with an excellent performance by polyethylene glycol modification. In conclusion, double-emulsion liposome formulation was an applicable and promising pharmaceutical preparation for enhancing MA delivery toward wound healing effect and improving wound-healing progress.

  12. The effect of material heterogeneities in long term multiscale seismic cycle simulations

    NASA Astrophysics Data System (ADS)

    Kyriakopoulos, C.; Richards-Dinger, K. B.; Dieterich, J. H.

    2016-12-01

    A fundamental part of the simulation of the earthquake cycles in large-scale multicycle earthquake simulators is the pre-computation of elastostatic Greens functions collected into the stiffness matrix (K). The stiffness matrices are typically based on the elastostatic solutions of Okada (1992), Gimbutas et al. (2012), or similar. While these analytic solutions are computationally very fast, they are limited to modeling a homogeneous isotropic half-space. It is thus unknown how such simulations may be affected by material heterogeneity characterizing the earth medium. We are currently working on the estimation of the effects of heterogeneous material properties in the earthquake simulator RSQSim (Richards-Dinger and Dieterich, 2012). In order to do that we are calculating elastostatic solutions in a heterogeneous medium using the Finite Element (FE) method instead of any of the analytical solutions. The investigated region is a 400 x 400 km area centered on the Anza zone in southern California. The fault system geometry is based on that of the UCERF3 deformation models in the area of interest, which we then implement in a finite element mesh using Trelis 15. The heterogeneous elastic structure is based on available tomographic data (seismic wavespeeds and density) for the region (SCEC CVM and Allam et al., 2014). For computation of the Greens functions we are using the open source FE code Defmod (https://bitbucket.org/stali/defmod/wiki/Home) to calculate the elastostatic solutions due to unit slip on each patch. Earthquake slip on the fault plane is implemented through linear constraint equations (Ali et al., 2014, Kyriakopoulos et al., 2013, Aagard et al, 2015) and more specifically with the use of Lagrange multipliers adjunction. The elementary responses are collected into the "heterogeneous" stiffness matrix Khet and used in RSQSim instead of the ones generated with Okada. Finally, we compare the RSQSim results based on the "heterogeneous" Khet with results from Khom (stiffness matrix generated from the same mesh as Khet but using homogeneous material properties). The estimation of the effect of heterogeneous material properties in the seismic cycles simulated by RSQSim is a needed experiment that will allow us to evaluate the impact of heterogeneities in earthquake simulators.

  13. Seismoelectric effects due to mesoscopic heterogeneities

    NASA Astrophysics Data System (ADS)

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

    2013-05-01

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

  14. Association-heterogeneity mapping identifies an Asian-specific association of the GTF2I locus with rheumatoid arthritis

    PubMed Central

    Kim, Kwangwoo; Bang, So-Young; Ikari, Katsunori; Yoo, Dae Hyun; Cho, Soo-Kyung; Choi, Chan-Bum; Sung, Yoon-Kyoung; Kim, Tae-Hwan; Jun, Jae-Bum; Kang, Young Mo; Suh, Chang-Hee; Shim, Seung-Cheol; Lee, Shin-Seok; Lee, Jisoo; Chung, Won Tae; Kim, Seong-Kyu; Choe, Jung-Yoon; Momohara, Shigeki; Taniguchi, Atsuo; Yamanaka, Hisashi; Nath, Swapan K.; Lee, Hye-Soon; Bae, Sang-Cheol

    2016-01-01

    Considerable sharing of disease alleles among populations is well-characterized in autoimmune disorders (e.g., rheumatoid arthritis), but there are some exceptional loci showing heterogenic association among populations. Here we investigated genetic variants with distinct effects on the development of rheumatoid arthritis in Asian and European populations. Ancestry-related association heterogeneity was examined using Cochran’s homogeneity tests for the disease association data from large Asian (n = 14,465; 9,299 discovery subjects and 5,166 validation subjects; 4 collections) and European (n = 45,790; 11 collections) rheumatoid arthritis case-control cohorts with Immunochip and genome-wide SNP array data. We identified significant heterogeneity between the two ancestries for the common variants in the GTF2I locus (PHeterogeneity = 9.6 × 10−9 at rs73366469) and showed that this heterogeneity was due to an Asian-specific association effect (ORMeta = 1.37 and PMeta = 4.2 × 10−13 in Asians; ORMeta = 1.00 and PMeta = 1.00 in Europeans). Trans-ancestral comparison and bioinfomatics analysis revealed a plausibly causal or disease-variant-tagging SNP (rs117026326; in linkage disequilibrium with rs73366469), whose minor allele is common in Asians but rare in Europeans. In conclusion, we identified largest-ever effect on Asian rheumatoid arthritis across human non-HLA regions at GTF2I by heterogeneity mapping followed by replication studies, and pinpointed a possible causal variant. PMID:27272985

  15. Breeding site heterogeneity reduces variability in frog recruitment and population dynamics

    USGS Publications Warehouse

    McCaffery, Rebecca M.; Eby, Lisa A.; Maxell, Bryce A.; Corn, Paul Stephen

    2013-01-01

    Environmental stochasticity can have profound effects on the dynamics and viability of wild populations, and habitat heterogeneity provides one mechanism by which populations may be buffered against the negative effects of environmental fluctuations. Heterogeneity in breeding pond hydroperiod across the landscape may allow amphibian populations to persist despite variable interannual precipitation. We examined recruitment dynamics over 10 yr in a high-elevation Columbia spotted frog (Rana luteiventris) population that breeds in ponds with a variety of hydroperiods. We combined these data with matrix population models to quantify the consequences of heterogeneity in pond hydroperiod on net recruitment (i.e. number of metamorphs produced) and population growth rates. We compared our heterogeneous system to hypothetical homogeneous environments with only ephemeral ponds, only semi-permanent ponds, and only permanent ponds. We also examined the effects of breeding pond habitat loss on population growth rates. Most eggs were laid in permanent ponds each year, but survival to metamorphosis was highest in the semi-permanent ponds. Recruitment success varied by both year and pond type. Net recruitment and stochastic population growth rate were highest under a scenario with homogeneous semi-permanent ponds, but variability in recruitment was lowest in the scenario with the observed heterogeneity in hydroperiods. Loss of pond habitat decreased population growth rate, with greater decreases associated with loss of permanent and semi-permanent habitat. The presence of a diversity of pond hydroperiods on the landscape will influence population dynamics, including reducing variability in recruitment in an uncertain climatic future.

  16. Individual vision and peak distribution in collective actions

    NASA Astrophysics Data System (ADS)

    Lu, Peng

    2017-06-01

    People make decisions on whether they should participate as participants or not as free riders in collective actions with heterogeneous visions. Besides of the utility heterogeneity and cost heterogeneity, this work includes and investigates the effect of vision heterogeneity by constructing a decision model, i.e. the revised peak model of participants. In this model, potential participants make decisions under the joint influence of utility, cost, and vision heterogeneities. The outcomes of simulations indicate that vision heterogeneity reduces the values of peaks, and the relative variance of peaks is stable. Under normal distributions of vision heterogeneity and other factors, the peaks of participants are normally distributed as well. Therefore, it is necessary to predict distribution traits of peaks based on distribution traits of related factors such as vision heterogeneity and so on. We predict the distribution of peaks with parameters of both mean and standard deviation, which provides the confident intervals and robust predictions of peaks. Besides, we validate the peak model of via the Yuyuan Incident, a real case in China (2014), and the model works well in explaining the dynamics and predicting the peak of real case.

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

    PubMed

    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 the evolutionary dynamics, effectively guaranteeing eventual branching. Large mutations allow the second order disruptive selection to dominate the first order selection toward phenotypic heterogeneity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Sub-Grid Modeling of Electrokinetic Effects in Micro Flows

    NASA Technical Reports Server (NTRS)

    Chen, C. P.

    2005-01-01

    Advances in micro-fabrication processes have generated tremendous interests in miniaturizing chemical and biomedical analyses into integrated microsystems (Lab-on-Chip devices). To successfully design and operate the micro fluidics system, it is essential to understand the fundamental fluid flow phenomena when channel sizes are shrink to micron or even nano dimensions. One important phenomenon is the electro kinetic effect in micro/nano channels due to the existence of the electrical double layer (EDL) near a solid-liquid interface. Not only EDL is responsible for electro-osmosis pumping when an electric field parallel to the surface is imposed, EDL also causes extra flow resistance (the electro-viscous effect) and flow anomaly (such as early transition from laminar to turbulent flow) observed in pressure-driven microchannel flows. Modeling and simulation of electro-kinetic effects on micro flows poses significant numerical challenge due to the fact that the sizes of the double layer (10 nm up to microns) are very thin compared to channel width (can be up to 100 s of m). Since the typical thickness of the double layer is extremely small compared to the channel width, it would be computationally very costly to capture the velocity profile inside the double layer by placing sufficient number of grid cells in the layer to resolve the velocity changes, especially in complex, 3-d geometries. Existing approaches using "slip" wall velocity and augmented double layer are difficult to use when the flow geometry is complicated, e.g. flow in a T-junction, X-junction, etc. In order to overcome the difficulties arising from those two approaches, we have developed a sub-grid integration method to properly account for the physics of the double layer. The integration approach can be used on simple or complicated flow geometries. Resolution of the double layer is not needed in this approach, and the effects of the double layer can be accounted for at the same time. With this approach, the numeric grid size can be much larger than the thickness of double layer. Presented in this report are a description of the approach, methodology for implementation and several validation simulations for micro flows.

  19. Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source.

    PubMed

    Shi, Chengyu; Guo, Bingqi; Cheng, Chih-Yao; Eng, Tony; Papanikolaou, Nikos

    2010-09-21

    A low-energy electronic brachytherapy source (EBS), the model S700 Axxent x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V(100) reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as compared to 95.2% in water phantoms without RBE enhancement (planned BED). About 10% increase in the source output is required to raise BED PTV V(100) to 95%. As a conclusion, the composite effect of dose reduction in the target due to heterogeneities and RBE enhancement results in a net effect of 5.3% target BED coverage loss for electronic brachytherapy. Therefore, it is suggested that about 10% increase in the source output may be necessary to achieve sufficient target coverage higher than 95%.

  20. Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source

    NASA Astrophysics Data System (ADS)

    Shi, Chengyu; Guo, Bingqi; Cheng, Chih-Yao; Eng, Tony; Papanikolaou, Nikos

    2010-09-01

    A low-energy electronic brachytherapy source (EBS), the model S700 Axxent™ x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V100 reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as compared to 95.2% in water phantoms without RBE enhancement (planned BED). About 10% increase in the source output is required to raise BED PTV V100 to 95%. As a conclusion, the composite effect of dose reduction in the target due to heterogeneities and RBE enhancement results in a net effect of 5.3% target BED coverage loss for electronic brachytherapy. Therefore, it is suggested that about 10% increase in the source output may be necessary to achieve sufficient target coverage higher than 95%.

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