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Sample records for allele contrast model

  1. A limit to the divergent allele advantage model supported by variable pathogen recognition across HLA-DRB1 allele lineages.

    PubMed

    Lau, Q; Yasukochi, Y; Satta, Y

    2015-11-01

    Genetic diversity in human leukocyte antigen (HLA) molecules is thought to have arisen from the co-evolution between host and pathogen and maintained by balancing selection. Heterozygote advantage is a common proposed scenario for maintaining high levels of diversity in HLA genes, and extending from this, the divergent allele advantage (DAA) model suggests that individuals with more divergent HLA alleles bind and recognize a wider array of antigens. While the DAA model seems biologically suitable for driving HLA diversity, there is likely an upper threshold to the amount of sequence divergence. We used peptide-binding and pathogen-recognition capacity of DRB1 alleles as a model to further explore the DAA model; within the DRB1 locus, we examined binding predictions based on two distinct phylogenetic groups (denoted group A and B) previously identified based on non-peptide-binding region (PBR) nucleotide sequences. Predictions in this study support that group A allele and group B allele lineages have contrasting binding/recognition capacity, with only the latter supporting the DAA model. Furthermore, computer simulations revealed an inconsistency in the DAA model alone with observed extent of polymorphisms, supporting that the DAA model could only work effectively in combination with other mechanisms. Overall, we support that the mechanisms driving HLA diversity are non-exclusive. By investigating the relationships among HLA alleles, and pathogens recognized, we can provide further insights into the mechanisms on how humans have adapted to infectious diseases over time.

  2. Allele Frequencies at Microsatellite Loci: The Stepwise Mutation Model Revisited

    PubMed Central

    Valdes, A. M.; Slatkin, M.; Freimer, N. B.

    1993-01-01

    We summarize available data on the frequencies of alleles at microsatellite loci in human populations and compare observed distributions of allele frequencies to those generated by a simulation of the stepwise mutation model. We show that observed frequency distributions at 108 loci are consistent with the results of the model under the assumption that mutations cause an increase or decrease in repeat number by one and under the condition that the product Nu, where N is the effective population size and u is the mutation rate, is larger than one. We show that the variance of the distribution of allele sizes is a useful estimator of Nu and performs much better than previously suggested estimators for the stepwise mutation model. In the data, there is no correlation between the mean and variance in allele size at a locus or between the number of alleles and mean allele size, which suggests that the mutation rate at these loci is independent of allele size. PMID:8454213

  3. A genetic model of melanoma tumorigenesis based on allelic losses

    SciTech Connect

    Hayward, N.K.; Palmer, J.M.; Walters, M.K.

    1994-09-01

    Previous karyotypic studies have indicated a possible series of non-random chromosomal events involved in the progression of melanoma. We sought to define a model of melanocyte tumorigenesis by studying allelic deletions of polymorphic simple tandem repeat markers mapping to chromosome 1, 6q, 7, 9p, 10, 11, 17, and 21 in thirty matched pairs of melanoma and constitutional DNAs. The most frequent and earliest deletions were found on 9p (57%) and 10q (32%) and with the exception of one case, no sample has loss of markers on another chromosome without concomitant loss of markers on 9p and/or 10q. Losses on 6q were also a frequent (32%) event that sometimes occurred in primary melanomas, whereas losses of loci on distal 1p (26%) or 11q (26%) occurred only in metastic melanomas. A background rate (0-17%) of allele loss was seen on chromosomes 7, 17, and 21. Homozygous deletions in a panel of 31 melanoma cell lines were only detected for markers on 9p (4 cases). These data strongly support the previous model of melanoma tumorigenesis based primarily on karyotypic findings in melanocytic lesions. However, we have been able to further augment the model by delimiting the regions of loss on 10q to a region distal to D10S254, and on 1p, to between D1S243 and D1S160.

  4. Inverse modeling of human contrast response.

    PubMed

    Katkov, Mikhail; Tsodyks, Misha; Sagi, Dov

    2007-10-01

    Mathematical singularities found in the Signal Detection Theory (SDT) based analysis of the 2-Alternative-Forced-Choice (2AFC) method [Katkov, M., Tsodyks, M., & Sagi, D. (2006a). Analysis of two-alternative force-choice Signal Detection Theory model. Journal of Mathematical Psychology, 50, 411-420; Katkov, M., Tsodyks, M., & Sagi, D. (2006b). Singularities in the inverse modeling of 2AFC contrast discrimination data. Vision Research, 46, 256-266; Katkov, M., Tsodyks, M., & Sagi, D. (2007). Singularities explained: Response to Klein. Vision Research, doi:10.1016/j.visres.2006.10.030] imply that contrast discrimination data obtained with the 2AFC method cannot always be used to reliably estimate the parameters of the underlying model (internal response and noise functions) with a reasonable number of trials. Here we bypass this problem with the Identification Task (IT) where observers identify one of N contrasts. We have found that identification data varies significantly between experimental sessions. Stable estimates using individual session data showed Contrast Response Functions (CRF) with high gain in the low contrast regime and low gain in the high contrast regime. Noise Amplitudes (NA) followed a decreasing function of contrast at low contrast levels, and were practically constant above some contrast level. The transition between these two regimes corresponded approximately to the position of the dipper in the Threshold versus Contrast (TvC) curves that were computed using the estimated parameters and independently measured using 2AFC.

  5. Multiscale retinocortical model of contrast processing

    NASA Astrophysics Data System (ADS)

    Moorhead, Ian R.; Haig, Nigel D.

    1996-04-01

    Visual performance models have in the past, typically been empirical, relying on the user to supply numerical values such as target contrast and background luminance to describe the performance of the visual system, when undertaking a specified task. However, it is becoming increasingly easy to obtain computer images using for example digital cameras, scanners, imaging photometers and radiometers. We have therefore been examining the possibility of producing a quantitative model of human vision that is capable of directly processing images in order to provide predictions of performance. We are particularly interested in being able to process images of 'real' scenes. The model is inspired by human vision and the components have analogies with parts of the human visual system but their properties are governed primarily by existing psychophysical data. The first stage of the model generates a multiscale, difference of Gaussian (DoG) representation of the image (Burton, Haig and Moorhead), with a central foveal region of high resolution, and with a resolution that declines with eccentricity as the scale of the filter increases. Incorporated into this stage is a gain control process which ensures that the contrast sensitivity is consistent with the psychophysical data of van Nes and Bouman. The second stage incorporates a model of perceived contrast proposed by Cannon and Fullenkamp. Their model assumes the image is analyzed by oriented (Gabor) filters and produces a representation of the image in terms of perceived contrast.

  6. Fixation probability and the crossing time in the Wright-Fisher multiple alleles model

    NASA Astrophysics Data System (ADS)

    Gill, Wonpyong

    2009-08-01

    The fixation probability and crossing time in the Wright-Fisher multiple alleles model, which describes a finite haploid population, were calculated by switching on an asymmetric sharply-peaked landscape with a positive asymmetric parameter, r, such that the reversal allele of the optimal allele has higher fitness than the optimal allele. The fixation probability, which was evaluated as the ratio of the first arrival time at the reversal allele to the origination time, was double the selective advantage of the reversal allele compared with the optimal allele in the strong selection region, where the fitness parameter, k, is much larger than the critical fitness parameter, kc. The crossing time in a finite population for r>0 and kallele in the first generation should be greater than one individual in an asymmetric sharply-peaked landscape. It was also found that the crossing time in a finite population for r>0 and k≫kc scaled as a power law in the fitness parameter with a similar scaling exponent as the crossing time in an infinite population for r=0, and that the critical fitness parameter decreased with increasing sequence length with a fixed population size.

  7. Statistical Inference in the Wright-Fisher Model Using Allele Frequency Data.

    PubMed

    Tataru, Paula; Simonsen, Maria; Bataillon, Thomas; Hobolth, Asger

    2016-08-02

    The Wright-Fisher model provides an elegant mathematical framework for understanding allele frequency data. In particular, the model can be used to infer the demographic history of species and identify loci under selection. A crucial quantity for inference under the Wright-Fisher model is the distribution of allele frequencies (DAF). Despite the apparent simplicity of the model, the calculation of the DAF is challenging. We review and discuss strategies for approximating the DAF, and how these are used in methods that perform inference from allele frequency data. Various evolutionary forces can be incorporated in the Wright-Fisher model, and we consider these in turn. We begin our review with the basic bi-allelic Wright-Fisher model where random genetic drift is the only evolutionary force. We then consider mutation, migration, and selection. In particular, we compare diffusion-based and moment-based methods in terms of accuracy, computational efficiency, and analytical tractability. We conclude with a brief overview of the multi-allelic process with a general mutation model. [Allele frequency, diffusion, inference, moments, selection, Wright-Fisher.].

  8. On the maintenance of genetic variation: global analysis of Kimura's continuum-of-alleles model.

    PubMed

    Bürger, R

    1986-01-01

    Methods of functional analysis are applied to provide an exact mathematical analysis of Kimura's continuum-of-alleles model. By an approximate analysis, Kimura obtained the result that the equilibrium distribution of allelic effects determining a quantitative character is Gaussian if fitness decreases quadratically from the optimum and if production of new mutants follows a Gaussian density. Lande extended this model considerably and proposed that high levels of genetic variation can be maintained by mutation even when there is strong stabilizing selection. This hypothesis has been questioned recently by Turelli, who published analyses and computer simulations of some multiallele models, approximating the continuum-of-alleles model, and reviewed relevant data. He found that the Kimura and Lande predictions overestimate the amount of equilibrium variance considerably if selection is not extremely weak or mutation rate not extremely high. The present analysis provides the first proof that in Kimura's model an equilibrium in fact exists and, moreover, that it is globally stable. Finally, using methods from quantum mechanics, estimates of the exact equilibrium variance are derived which are in best accordance with Turelli's results. This shows that continuum-of-alleles models may be excellent approximations to multiallele models, if analysed appropriately.

  9. A hypomorphic allele of Tsc2 highlights the role of TSC1/TSC2 in signaling to AKT and models mild human TSC2 alleles.

    PubMed

    Pollizzi, Kristen; Malinowska-Kolodziej, Izabela; Doughty, Cheryl; Betz, Charles; Ma, Jian; Goto, June; Kwiatkowski, David J

    2009-07-01

    Tuberous sclerosis complex (TSC) is a tumor suppressor gene syndrome in which hamartomas develop in multiple organ systems. Knockout and conditional alleles of Tsc1 and Tsc2 have been previously reported. Here, we describe the generation of a novel hypomorphic allele of Tsc2 (del3), in which exon 3, encoding 37 amino acids near the N terminus of tuberin, is deleted. Embryos homozygous for the del3 allele survive until E13.5, 2 days longer than Tsc2 null embryos. Embryos die from underdevelopment of the liver, deficient hematopoiesis, aberrant vascular development and hemorrhage. Mice that are heterozygous for the del3 allele have a markedly reduced kidney tumor burden in comparison with conventional Tsc2(+/-) mice. Murine embryo fibroblast (MEF) cultures that are homozygous for the del3 allele express mutant tuberin at low levels, and show enhanced activation of mTORC1, similar to Tsc2 null MEFs. Furthermore, the mutant cells show prominent reduction in the activation of AKT. Similar findings were made in the analysis of homozygous del3 embryo lysates. Tsc2-del3 demonstrates GTPase activating protein activity comparable to that of wild-type Tsc2 in a functional assay. These findings indicate that the del3 allele is a hypomorphic allele of Tsc2 with partial function due to reduced expression, and highlight the consistency of AKT downregulation when Tsc1/Tsc2 function is reduced. Tsc2-del3 mice also serve as a model for hypomorphic TSC2 missense mutations reported in TSC patients.

  10. Efficient Simulation and Likelihood Methods for Non-Neutral Multi-Allele Models

    PubMed Central

    Joyce, Paul; Genz, Alan

    2012-01-01

    Abstract Throughout the 1980s, Simon Tavaré made numerous significant contributions to population genetics theory. As genetic data, in particular DNA sequence, became more readily available, a need to connect population-genetic models to data became the central issue. The seminal work of Griffiths and Tavaré (1994a, 1994b, 1994c) was among the first to develop a likelihood method to estimate the population-genetic parameters using full DNA sequences. Now, we are in the genomics era where methods need to scale-up to handle massive data sets, and Tavaré has led the way to new approaches. However, performing statistical inference under non-neutral models has proved elusive. In tribute to Simon Tavaré, we present an article in spirit of his work that provides a computationally tractable method for simulating and analyzing data under a class of non-neutral population-genetic models. Computational methods for approximating likelihood functions and generating samples under a class of allele-frequency based non-neutral parent-independent mutation models were proposed by Donnelly, Nordborg, and Joyce (DNJ) (Donnelly et al., 2001). DNJ (2001) simulated samples of allele frequencies from non-neutral models using neutral models as auxiliary distribution in a rejection algorithm. However, patterns of allele frequencies produced by neutral models are dissimilar to patterns of allele frequencies produced by non-neutral models, making the rejection method inefficient. For example, in some cases the methods in DNJ (2001) require 109 rejections before a sample from the non-neutral model is accepted. Our method simulates samples directly from the distribution of non-neutral models, making simulation methods a practical tool to study the behavior of the likelihood and to perform inference on the strength of selection. PMID:22697240

  11. Epidemiological and Evolutionary Outcomes in Gene-for-Gene and Matching Allele Models

    PubMed Central

    Thrall, Peter H.; Barrett, Luke G.; Dodds, Peter N.; Burdon, Jeremy J.

    2016-01-01

    Gene-for-gene (GFG) and matching-allele (MA) models are qualitatively different paradigms for describing the outcome of genetic interactions between hosts and pathogens. The GFG paradigm was largely built on the foundations of Flor’s early work on the flax–flax rust interaction and is based on the concept of genetic recognition leading to incompatible disease outcomes, typical of host immune recognition. In contrast, the MA model is based on the assumption that genetic recognition leads to compatible interactions, which can result when pathogens require specific host factors to cause infection. Results from classical MA and GFG models have led to important predictions regarding various coevolutionary phenomena, including the role of fitness costs associated with resistance and infectivity, the distribution of resistance genes in wild populations, patterns of local adaptation and the evolution and maintenance of sexual reproduction. Empirical evidence (which we review briefly here), particularly from recent molecular advances in understanding of the mechanisms that determine the outcome of host–pathogen encounters, suggests considerable variation in specific details of the functioning of interactions between hosts and pathogens, which may contain elements of both models. In this regard, GFG and MA scenarios likely represent endpoints of a continuum of potentially more complex interactions that occur in nature. Increasingly, this has been recognized in theoretical studies of coevolutionary processes in plant host–pathogen and animal host-parasite associations (e.g., departures from strict GFG/MA assumptions, diploid genetics, multi-step infection processes). However, few studies have explored how different genetic assumptions about host resistance and pathogen infectivity might impact on disease epidemiology or pathogen persistence within and among populations. Here, we use spatially explicit simulations of the basic MA and GFG scenarios to highlight

  12. A kinetic model-based algorithm to classify NGS short reads by their allele origin.

    PubMed

    Marinoni, Andrea; Rizzo, Ettore; Limongelli, Ivan; Gamba, Paolo; Bellazzi, Riccardo

    2015-02-01

    Genotyping Next Generation Sequencing (NGS) data of a diploid genome aims to assign the zygosity of identified variants through comparison with a reference genome. Current methods typically employ probabilistic models that rely on the pileup of bases at each locus and on a priori knowledge. We present a new algorithm, called Kimimila (KInetic Modeling based on InforMation theory to Infer Labels of Alleles), which is able to assign reads to alleles by using a distance geometry approach and to infer the variant genotypes accurately, without any kind of assumption. The performance of the model has been assessed on simulated and real data of the 1000 Genomes Project and the results have been compared with several commonly used genotyping methods, i.e., GATK, Samtools, VarScan, FreeBayes and Atlas2. Despite our algorithm does not make use of a priori knowledge, the percentage of correctly genotyped variants is comparable to these algorithms. Furthermore, our method allows the user to split the reads pool depending on the inferred allele origin.

  13. Characterization of behavioral and neuromuscular junction phenotypes in a novel allelic series of SMA mouse models.

    PubMed

    Osborne, Melissa; Gomez, Daniel; Feng, Zhihua; McEwen, Corissa; Beltran, Jose; Cirillo, Kim; El-Khodor, Bassem; Lin, Ming-Yi; Li, Yun; Knowlton, Wendy M; McKemy, David D; Bogdanik, Laurent; Butts-Dehm, Katherine; Martens, Kimberly; Davis, Crystal; Doty, Rosalinda; Wardwell, Keegan; Ghavami, Afshin; Kobayashi, Dione; Ko, Chien-Ping; Ramboz, Sylvie; Lutz, Cathleen

    2012-10-15

    A number of mouse models for spinal muscular atrophy (SMA) have been genetically engineered to recapitulate the severity of human SMA by using a targeted null mutation at the mouse Smn1 locus coupled with the transgenic addition of varying copy numbers of human SMN2 genes. Although this approach has been useful in modeling severe SMA and very mild SMA, a mouse model of the intermediate form of the disease would provide an additional research tool amenable for drug discovery. In addition, many of the previously engineered SMA strains are multi-allelic by design, containing a combination of transgenes and targeted mutations in the homozygous state, making further genetic manipulation difficult. A new genetic engineering approach was developed whereby variable numbers of SMN2 sequences were incorporated directly into the murine Smn1 locus. Using combinations of these alleles, we generated an allelic series of SMA mouse strains harboring no, one, two, three, four, five, six or eight copies of SMN2. We report here the characterization of SMA mutants in this series that displayed a range in disease severity from embryonic lethal to viable with mild neuromuscular deficits.

  14. Brightness contrast-contrast induction model predicts assimilation and inverted assimilation effects.

    PubMed

    Barkan, Yuval; Spitzer, Hedva; Einav, Shmuel

    2008-10-17

    In classical assimilation effects, intermediate luminance patches appear lighter when their immediate surround is comprised of white patches and appear darker when their immediate surround is comprised of dark patches. With patches either darker or lighter than both inducing patches, the direction of the brightness effect is reversed and termed as "inverted assimilation effect." Several explanations and models have been suggested, some are relevant to specific stimulus geometry, anchoring theory, and models that involve high level cortical processing (such as scission, etc.). None of these studies predicted the various types of assimilation effects and their inverted effects. We suggest here a compound brightness model, which is based on contrast-contrast induction (second-order adaptation mechanism). The suggested model predicts the various types of brightness assimilation effects and their inverted effects. The model is composed of three main stages: (1) composing post-retinal second-order opponent receptive fields, (2) calculations of local and remote contrast, and (3) adaptation of the second-order (contrast-contrast induction). We also utilize a variation of the Jacobi iteration process to enable elegant edge integration in order to evaluate the model is performance.

  15. Compare and Contrast Program Planning Models

    ERIC Educational Resources Information Center

    Baskas, Richard S.

    2011-01-01

    This paper will examine the differences and similarities between two program planning models, Tyler and Caffarella, to reveal their strengths and weaknesses. When adults are involved in training sessions, there are various program planning models that can be used, depending on the goal of the training session. Researchers developed these models…

  16. Addressing contrasting cognitive models in scientific collaboration

    NASA Astrophysics Data System (ADS)

    Diviacco, P.

    2012-04-01

    If the social aspects of scientific communities and their internal dynamics is starting to be recognized and acknowledged in the everyday lives of scientists, it is rather difficult for them to find tools that could support their activities consistently with this perspective. Issues span from gathering researchers to mutual awareness, from information sharing to building meaning, with the last one being particularly critical in research fields as the geo-sciences, that deal with the reconstruction of unique, often non-reproducible, and contingent processes. Reasoning here is, in fact, mainly abductive, allowing multiple and concurrent explanations for the same phenomenon to coexist. Scientists bias one hypothesis over another not only on strictly logical but also on sociological motivations. Following a vision, scientists tend to evolve and isolate themselves from other scientists creating communities characterized by different cognitive models, so that after some time these become incompatible and scientists stop understanding each other. We address these problems as a communication issue so that the classic distinction into three levels (syntactic, semantic and pragmatic) can be used. At the syntactic level, we highlight non-technical obstacles that condition interoperability and data availability and transparency. At the semantic level, possible incompatibilities of cognitive models are particularly evident, so that using ontologies, cross-domain reconciliation should be applied. This is a very difficult task to perform since the projection of knowledge by scientists, in the designated community, is political and thus can create a lot of tension. The strategy we propose to overcome these issues pertains to pragmatics, in the sense that it is intended to acknowledge the cultural and personal factors each partner brings into the collaboration and is based on the idea that meaning should remain a flexible and contingent representation of possibly divergent views

  17. Identification of genes escaping X inactivation by allelic expression analysis in a novel hybrid mouse model.

    PubMed

    Berletch, Joel B; Ma, Wenxiu; Yang, Fan; Shendure, Jay; Noble, William S; Disteche, Christine M; Deng, Xinxian

    2015-12-01

    X chromosome inactivation (XCI) is a female-specific mechanism that serves to balance gene dosage between the sexes whereby one X chromosome in females is inactivated during early development. Despite this silencing, a small portion of genes escape inactivation and remain expressed from the inactive X (Xi). Little is known about the distribution of escape from XCI in different tissues in vivo and about the mechanisms that control tissue-specific differences. Using a new binomial model in conjunction with a mouse model with identifiable alleles and skewed X inactivation we are able to survey genes that escape XCI in vivo. We show that escape from X inactivation can be a common feature of some genes, whereas others escape in a tissue specific manner. Furthermore, we characterize the chromatin environment of escape genes and show that expression from the Xi correlates with factors associated with open chromatin and that CTCF co-localizes with escape genes. Here, we provide a detailed description of the experimental design and data analysis pipeline we used to assay allele-specific expression and epigenetic characteristics of genes escaping X inactivation. The data is publicly available through the GEO database under ascension numbers GSM1014171, GSE44255, and GSE59779. Interpretation and discussion of these data are included in a previously published study (Berletch et al., 2015) [1].

  18. Risk prediction models for contrast induced nephropathy: systematic review

    PubMed Central

    Silver, Samuel A; Shah, Prakesh M; Chertow, Glenn M; Wald, Ron

    2015-01-01

    Objectives To look at the available literature on validated prediction models for contrast induced nephropathy and describe their characteristics. Design Systematic review. Data sources Medline, Embase, and CINAHL (cumulative index to nursing and allied health literature) databases. Review methods Databases searched from inception to 2015, and the retrieved reference lists hand searched. Dual reviews were conducted to identify studies published in the English language of prediction models tested with patients that included derivation and validation cohorts. Data were extracted on baseline patient characteristics, procedural characteristics, modelling methods, metrics of model performance, risk of bias, and clinical usefulness. Eligible studies evaluated characteristics of predictive models that identified patients at risk of contrast induced nephropathy among adults undergoing a diagnostic or interventional procedure using conventional radiocontrast media (media used for computed tomography or angiography, and not gadolinium based contrast). Results 16 studies were identified, describing 12 prediction models. Substantial interstudy heterogeneity was identified, as a result of different clinical settings, cointerventions, and the timing of creatinine measurement to define contrast induced nephropathy. Ten models were validated internally and six were validated externally. Discrimination varied in studies that were validated internally (C statistic 0.61-0.95) and externally (0.57-0.86). Only one study presented reclassification indices. The majority of higher performing models included measures of pre-existing chronic kidney disease, age, diabetes, heart failure or impaired ejection fraction, and hypotension or shock. No prediction model evaluated its effect on clinical decision making or patient outcomes. Conclusions Most predictive models for contrast induced nephropathy in clinical use have modest ability, and are only relevant to patients receiving contrast for

  19. The free energy method and the Wright-Fisher model with 2 alleles.

    PubMed

    Tran, Tat Dat; Hofrichter, Julian; Jost, Jürgen

    2015-12-01

    We systematically investigate the Wright-Fisher model of population genetics with the free energy functional formalism of statistical mechanics and in the light of recent mathematical work on the connection between Fokker-Planck equations and free energy functionals. In statistical physics, entropy increases, or equivalently, free energy decreases, and the asymptotic state is given by a Gibbs-type distribution. This also works for the Wright-Fisher model when rewritten in divergence to identify the correct free energy functional. We not only recover the known results about the stationary distribution, that is, the asymptotic equilibrium state of the model, in the presence of positive mutation rates and possibly also selection, but can also provide detailed formulae for the rate of convergence towards that stationary distribution. In the present paper, the method is illustrated for the simplest case only, that of two alleles.

  20. Simple model for spatial-frequency masking and contrast discrimination

    NASA Astrophysics Data System (ADS)

    Barten, Peter G. J.

    1995-04-01

    After some principal considerations about noise and the psychometric function,we present a model for the masking of a spatial frequency patten by nonwhite noise. From threshold elevation measurements by Stromeyer and Julesz, we derive a distribution function for the disturbing effect of one frequency on the detection of another frequency. We apply the resulting formulas on contrast sensitivity measurements with nonwhite noise by van Meeteren and Valeton. Next we use the same principles to derive a simple model for contrast discrimination. We consider the pedestal modulation as a nonwhite noise source of a single spatial frequency that hampers contrast detection. We show that contrast discrimination plots for different spatial frequencies will coincide if they are plotted in a normalized way. After a slight practical correction the model appears to be in very good agreement with measurements of various authors published in literature.

  1. Growth behavior of additional offspring with a beneficial reversal allele in the asymmetric sharply-peaked landscape in the coupled discrete-time mutation-selection model

    NASA Astrophysics Data System (ADS)

    Gill, Wonpyong

    2013-01-01

    The probability of additional offspring with a beneficial reversal allele for growing to a size NC for a range of population sizes N, sequence lengths L, selective advantages s, and measuring parameters C was calculated for a haploid, asexual population in the coupled discrete-time mutation-selection model in an asymmetric sharply-peaked landscape with a positive selective advantage of the reversal allele over the optimal allele. The growing probability in the stochastic region was inversely proportional to the measuring parameter when C < 1 /Ns, bent when C ≈ 1/ Ns and saturated when C > 1/ Ns. The crossing time and the time dependence of the increase in relative density of the reversal allele in the coupled discrete-time mutation-selection model was approximated using the Wright-Fisher two-allele model with the same selective advantage and corresponding effective mutation rate. The growth behavior of additional offspring with the reversal allele in the asymmetric sharply-peaked landscape in the coupled discrete-time mutation-selection model was controlled by the selective advantage of the reversal allele compared to the optimal allele and could be described by using the Wright-Fisher two-allele model, in spite of there being many other alleles with lower fitness, and in spite of there being two alleles, the optimal and reversal allele, separated by a low-fitness valley with a tunable depth and width.

  2. Modeling the bound conformation of Pemphigus Vulgaris-associated peptides to MHC Class II DR and DQ Alleles

    PubMed Central

    Tong, Joo Chuan; Bramson, Jeff; Kanduc, Darja; Chow, Selwyn; Sinha, Animesh A; Ranganathan, Shoba

    2006-01-01

    Background Pemphigus vulgaris (PV) is a severe autoimmune blistering disorder characterized by the presence of pathogenic autoantibodies directed against desmoglein-3 (Dsg3), involving specific DR4 and DR6 alleles in Caucasians and DQ5 allele in Asians. The development of sequence-based predictive algorithms to identify potential Dsg3 epitopes has encountered limited success due to the paucity of PV-associated allele-specific peptides as training data. Results In this work we constructed atomic models of ten PV associated, non-associated and protective alleles. Nine previously identified stimulatory Dsg3 peptides, Dsg3 96–112, Dsg3 191–205, Dsg3 206–220, Dsg3 252–266, Dsg3 342–356, Dsg3 380–394, Dsg3 763–777, Dsg3 810–824 and Dsg3 963–977, were docked into the binding groove of each model to analyze the structural aspects of allele-specific binding. Conclusion Our docking simulations are entirely consistent with functional data obtained from in vitro competitive binding assays and T cell proliferation studies in DR4 and DR6 PV patients. Our findings ascertain that DRB1*0402 plays a crucial role in the selection of specific self-peptides in DR4 PV. DRB1*0402 and DQB1*0503 do not necessarily share the same core residues, indicating that both alleles may have different binding specificities. In addition, our results lend credence to the hypothesis that the alleles DQB1*0201 and *0202 play a protective role by binding Dsg3 peptides with greater affinity than the susceptible alleles, allowing for efficient deletion of autoreactive T cells. PMID:16426456

  3. Contrasting allelic distribution of CO/Hd1 homologues in Miscanthus sinensis from the East Asian mainland and the Japanese archipelago

    DOE PAGES

    Nagano, Hironori; Clark, Lindsay V.; Zhao, Hua; ...

    2015-06-18

    The genus Miscanthus is a perennial C4 grass native to eastern Asia and is a promising candidate bioenergy crop for cool temperate areas. Flowering time is a crucial factor governing regional and seasonal adaptation; in addition, it is also a key target trait for extending the vegetative phase to improve biomass potential. Homologues of CONSTANS (CO)/Heading date 1(Hd1) were cloned from Miscanthus sinensis and named MsiHd1. Sequences of MsiHd1 homologues were compared among 24 wild M. sinensis accessions from Japan, 14 from China, and three from South Korea. Two to five MsiHd1 alleles in each accession were identified, suggesting thatmore » MsiHd1 consists of at least three loci in the Miscanthus genome. Verifying the open reading frame in MsiHd1, they were classified as putative functional alleles without mutations or non-functional alleles caused by indels. The Neighbor-Joining tree indicated that one of the multiple MsiHd1 loci is a pseudogene locus without any functional alleles. The pseudogene locus was named MsiHd1b, and the other loci were considered to be part of the MsiHd1a multi-locus family. Interestingly, in most Japanese accessions 50% or more of the MsiHd1a alleles were non-functional, whereas accessions from the East Asian mainland harboured only functional alleles. Five novel miniature inverted transposable elements (MITEs) (MsiMITE1-MsiMITE5) were observed in MsiHd1a/b. MsiMITE1, detected in exon 1 of MsiHd1a, was only observed in Japanese accessions and its revertant alleles derived from retransposition were predominantly in Chinese accessions. In conclusion, these differences in MsiHd1a show that the dependency on functional MsiHd1a alleles is different between accessions from the East Asian mainland and Japan.« less

  4. Optimization of Allelic Combinations Controlling Parameters of a Peach Quality Model

    PubMed Central

    Quilot-Turion, Bénédicte; Génard, Michel; Valsesia, Pierre; Memmah, Mohamed-Mahmoud

    2016-01-01

    Process-based models are effective tools to predict the phenotype of an individual in different growing conditions. Combined with a quantitative trait locus (QTL) mapping approach, it is then possible to predict the behavior of individuals with any combinations of alleles. However the number of simulations to explore the realm of possibilities may become infinite. Therefore, the use of an efficient optimization algorithm to intelligently explore the search space becomes imperative. The optimization algorithm has to solve a multi-objective problem, since the phenotypes of interest are usually a complex of traits, to identify the individuals with best tradeoffs between those traits. In this study we proposed to unroll such a combined approach in the case of peach fruit quality described through three targeted traits, using a process-based model with seven parameters controlled by QTL. We compared a current approach based on the optimization of the values of the parameters with a more evolved way to proceed which consists in the direct optimization of the alleles controlling the parameters. The optimization algorithm has been adapted to deal with both continuous and combinatorial problems. We compared the spaces of parameters obtained with different tactics and the phenotype of the individuals resulting from random simulations and optimization in these spaces. The use of a genetic model enabled the restriction of the dimension of the parameter space toward more feasible combinations of parameter values, reproducing relationships between parameters as observed in a real progeny. The results of this study demonstrated the potential of such an approach to refine the solutions toward more realistic ideotypes. Perspectives of improvement are discussed. PMID:28066450

  5. Optimization of Allelic Combinations Controlling Parameters of a Peach Quality Model.

    PubMed

    Quilot-Turion, Bénédicte; Génard, Michel; Valsesia, Pierre; Memmah, Mohamed-Mahmoud

    2016-01-01

    Process-based models are effective tools to predict the phenotype of an individual in different growing conditions. Combined with a quantitative trait locus (QTL) mapping approach, it is then possible to predict the behavior of individuals with any combinations of alleles. However the number of simulations to explore the realm of possibilities may become infinite. Therefore, the use of an efficient optimization algorithm to intelligently explore the search space becomes imperative. The optimization algorithm has to solve a multi-objective problem, since the phenotypes of interest are usually a complex of traits, to identify the individuals with best tradeoffs between those traits. In this study we proposed to unroll such a combined approach in the case of peach fruit quality described through three targeted traits, using a process-based model with seven parameters controlled by QTL. We compared a current approach based on the optimization of the values of the parameters with a more evolved way to proceed which consists in the direct optimization of the alleles controlling the parameters. The optimization algorithm has been adapted to deal with both continuous and combinatorial problems. We compared the spaces of parameters obtained with different tactics and the phenotype of the individuals resulting from random simulations and optimization in these spaces. The use of a genetic model enabled the restriction of the dimension of the parameter space toward more feasible combinations of parameter values, reproducing relationships between parameters as observed in a real progeny. The results of this study demonstrated the potential of such an approach to refine the solutions toward more realistic ideotypes. Perspectives of improvement are discussed.

  6. A Probabilistic Model of Phonological Relationships from Contrast to Allophony

    ERIC Educational Resources Information Center

    Hall, Kathleen Currie

    2009-01-01

    This dissertation proposes a model of phonological relationships, the Probabilistic Phonological Relationship Model (PPRM), that quantifies how predictably distributed two sounds in a relationship are. It builds on a core premise of traditional phonological analysis, that the ability to define phonological relationships such as contrast and…

  7. Coastal Digital Surface Model on Low Contrast Images

    NASA Astrophysics Data System (ADS)

    Rosu, A.-M.; Assenbaum, M.; De la Torre, Y.; Pierrot-Deseilligny, M.

    2015-08-01

    Coastal sandy environments are extremely dynamic and require regular monitoring that can easily be achieved by using an unmanned aerial system (UAS) including a drone and a photo camera. The acquired images have low contrast and homogeneous texture. Using these images and with very few, if any, ground control points (GCPs), it is difficult to obtain a digital surface model (DSM) by classical correlation and automatic interest points determination approach. A possible response to this problem is to work with enhanced, contrast filtered images. To achieve this, we use and tune the free open-source software MicMac.

  8. Saphenous Venous Ablation with Hot Contrast in a Canine Model

    SciTech Connect

    Prasad, Amit Qian Zhong; Kirsch, David; Eissa, Marna; Narra, Pavan; Lopera, Jorge; Espinoza, Carmen G.; Castaneda, Wifrido

    2008-01-15

    Purpose. To determine the feasibility, efficacy, and safety of thermal ablation of the saphenous vein with hot contrast medium. Methods. Twelve saphenous veins of 6 dogs were percutaneously ablated with hot contrast medium. In all animals, ablation was performed in the vein of one leg, followed by ablation in the contralateral side 1 month later. An occlusion balloon catheter was placed in the infragenicular segment of the saphenous vein via a jugular access to prevent unwanted thermal effects on the non-target segment of the saphenous vein. After inflation of the balloon, 10 ml of hot contrast medium was injected under fluoroscopic control through a sheath placed in the saphenous vein above the ankle. A second 10 ml injection of hot contrast medium was made after 5 min in each vessel. Venographic follow-up of the ablated veins was performed at 1 month (n = 12) and 2 months (n = 6). Results. Follow-up venograms showed that all ablated venous segments were occluded at 1 month. In 6 veins which were followed up to 2 months, 4 (66%) remained occluded, 1 (16%) was partially patent, and the remaining vein (16%) was completely patent. In these latter 2 cases, an inadequate amount of hot contrast was delivered to the lumen due to a closed balloon catheter downstream which did not allow contrast to displace blood within the vessel. Discussion. Hot contrast medium thermal ablation of the saphenous vein appears feasible, safe, and effective in the canine model, provided an adequate amount of embolization agent is used.

  9. Gene therapy by allele selection in a mouse model of beta-thalassemia.

    PubMed

    Eckardt, Sigrid; Leu, N Adrian; Yanchik, Ashley; Hatada, Seigo; Kyba, Michael; McLaughlin, K John

    2011-02-01

    To be of therapeutic use, autologous stem cells derived from patients with inherited genetic disorders require genetic modification via gene repair or insertion. Here, we present proof of principle that, for diseases associated with dominant alleles (gain-of-function or haploinsufficient loss-of-function), disease allele–free ES cells can be derived from afflicted individuals without genome manipulation. This approach capitalizes on the derivation of uniparental cells, such as parthenogenetic (PG) ES cell lines from disease allele–free gametes. Diploid mammalian uniparental embryos with only maternally (oocyte-) or paternally (sperm-)derived genomes fail early in development due to the nonequivalence of parental genomes caused by genomic imprinting. However, these uniparental embryos develop to the blastocyst stage, allowing the derivation of ES cell lines. Using a mouse model for dominant beta-thalassemia, we developed disease allele–free PG ES cell lines from the oocytes of affected animals. Phenotype correction was obtained in donor-genotype recipients after transplantation of in vitro hematopoietic ES cell derivatives. This genetic correction strategy without gene targeting is potentially applicable to any dominant disease. It could also be the sole approach for larger or more complex mutations that cannot be corrected by homologous recombination.

  10. Two-Dimensional Modeling Of Contrast-Enhanced Lithography

    NASA Astrophysics Data System (ADS)

    Griffing, B. F.; Lorensen, W. E.

    1984-05-01

    The aerial image produced by projection mask aligners can be readily visualized using high resolution computer graphics. This paper describes a computer model that calculates the aerial image using a mask pattern and the optical system characteristics as input. The program converts the digital result into a grey scale image. This image is an accu-rate representation of the image the photoresist actually "sees." The model is applied to contrast-enhanced lithography (CEL).1120 By combining the aerial image model with the known bleaching behavior of CEL materials it is possible to calculate the image intensity transmitted by the bleachable layer as a function of time. This result is presented in the form a computer-generated movie, which makes apparent the high contrast of the transmitted image. A second application of the aerial image model is to two-dimensional resist pattern modeling. Although not as sophisticated as SAMPLE4 this model is capable of modeling com-plete structures, such as a dynamic RAM cell. The output of the model is a three-dimensional surface which is displayed using a computer-generated, shaded surface. Linewidth variation with exposure is easily explored with this model. It is a best case model in that it assumes ideal optics and resist development conditions. Resist thickness is calculated using an experimentally determined thickness transfer function. These assumptions are necessary in order to minimize the time necessary for performing the calculations. The model calculates a pattern on a 512 X 512 point array from an image in 1-2 min. on a VAX-780. Since ideal conditions are assumed, the utility of the model is primarily in its ability to predict when a structure is beyond the limits of a given optical system. Applications of the model to CEL will be presented.

  11. Modeled and measured image-plane polychromatic speckle contrast

    NASA Astrophysics Data System (ADS)

    Van Zandt, Noah R.; McCrae, Jack E.; Fiorino, Steven T.

    2016-02-01

    The statistical properties of speckle relevant to short- to medium-range (tactical) active tracking involving polychromatic illumination are investigated. A numerical model is developed to allow rapid simulation of speckled images including the speckle contrast reduction effects of illuminator bandwidth, surface slope, and roughness, and the polarization properties of both the source and the reflection. Regarding surface slope (relative orientation of the surface normal and illumination/observation directions), Huntley's theory for speckle contrast, which employs geometrical approximations to decrease computation time, is modified to increase accuracy by incorporation of a geometrical correction factor and better treatment of roughness and polarization. The resulting model shows excellent agreement with more exact theory over a wide range. An experiment is conducted to validate both the numerical model developed here and existing theory. A diode laser source with coherence length of 259±7 μm is reflected off of a silver-coated diffuse surface. Speckle data are gathered for 16 surface slope angles corresponding to speckle contrast between about 0.55 and 1. Taking the measured data as truth, both equations show error mean and standard deviation of less than 3%. Thus, the theory is validated over the range of this experiment.

  12. Image contrast enhancement based on a local standard deviation model

    SciTech Connect

    Chang, Dah-Chung; Wu, Wen-Rong

    1996-12-31

    The adaptive contrast enhancement (ACE) algorithm is a widely used image enhancement method, which needs a contrast gain to adjust high frequency components of an image. In the literature, the gain is usually inversely proportional to the local standard deviation (LSD) or is a constant. But these cause two problems in practical applications, i.e., noise overenhancement and ringing artifact. In this paper a new gain is developed based on Hunt`s Gaussian image model to prevent the two defects. The new gain is a nonlinear function of LSD and has the desired characteristic emphasizing the LSD regions in which details are concentrated. We have applied the new ACE algorithm to chest x-ray images and the simulations show the effectiveness of the proposed algorithm.

  13. Modeling Pollinator Community Response to Contrasting Bioenergy Scenarios

    PubMed Central

    Bennett, Ashley B.; Meehan, Timothy D.; Gratton, Claudio; Isaacs, Rufus

    2014-01-01

    In the United States, policy initiatives aimed at increasing sources of renewable energy are advancing bioenergy production, especially in the Midwest region, where agricultural landscapes dominate. While policy directives are focused on renewable fuel production, biodiversity and ecosystem services will be impacted by the land-use changes required to meet production targets. Using data from field observations, we developed empirical models for predicting abundance, diversity, and community composition of flower-visiting bees based on land cover. We used these models to explore how bees might respond under two contrasting bioenergy scenarios: annual bioenergy crop production and perennial grassland bioenergy production. In the two scenarios, 600,000 ha of marginal annual crop land or marginal grassland were converted to perennial grassland or annual row crop bioenergy production, respectively. Model projections indicate that expansion of annual bioenergy crop production at this scale will reduce bee abundance by 0 to 71%, and bee diversity by 0 to 28%, depending on location. In contrast, converting annual crops on marginal soil to perennial grasslands could increase bee abundance from 0 to 600% and increase bee diversity between 0 and 53%. Our analysis of bee community composition suggested a similar pattern, with bee communities becoming less diverse under annual bioenergy crop production, whereas bee composition transitioned towards a more diverse community dominated by wild bees under perennial bioenergy crop production. Models, like those employed here, suggest that bioenergy policies have important consequences for pollinator conservation. PMID:25365559

  14. Modeling pollinator community response to contrasting bioenergy scenarios.

    PubMed

    Bennett, Ashley B; Meehan, Timothy D; Gratton, Claudio; Isaacs, Rufus

    2014-01-01

    In the United States, policy initiatives aimed at increasing sources of renewable energy are advancing bioenergy production, especially in the Midwest region, where agricultural landscapes dominate. While policy directives are focused on renewable fuel production, biodiversity and ecosystem services will be impacted by the land-use changes required to meet production targets. Using data from field observations, we developed empirical models for predicting abundance, diversity, and community composition of flower-visiting bees based on land cover. We used these models to explore how bees might respond under two contrasting bioenergy scenarios: annual bioenergy crop production and perennial grassland bioenergy production. In the two scenarios, 600,000 ha of marginal annual crop land or marginal grassland were converted to perennial grassland or annual row crop bioenergy production, respectively. Model projections indicate that expansion of annual bioenergy crop production at this scale will reduce bee abundance by 0 to 71%, and bee diversity by 0 to 28%, depending on location. In contrast, converting annual crops on marginal soil to perennial grasslands could increase bee abundance from 0 to 600% and increase bee diversity between 0 and 53%. Our analysis of bee community composition suggested a similar pattern, with bee communities becoming less diverse under annual bioenergy crop production, whereas bee composition transitioned towards a more diverse community dominated by wild bees under perennial bioenergy crop production. Models, like those employed here, suggest that bioenergy policies have important consequences for pollinator conservation.

  15. Stochastic Loss of Silencing of the Imprinted Ndn/NDN Allele, in a Mouse Model and Humans with Prader-Willi Syndrome, Has Functional Consequences

    PubMed Central

    Unmehopa, Unga; Matarazzo, Valery; Watrin, Françoise; Linke, Matthias; Georges, Beatrice; Bischof, Jocelyn; Dijkstra, Femke; Bloemsma, Monique; Corby, Severine; Michel, François J.; Wevrick, Rachel; Zechner, Ulrich; Swaab, Dick; Dudley, Keith; Bezin, Laurent; Muscatelli, Françoise

    2013-01-01

    Genomic imprinting is a process that causes genes to be expressed from one allele only according to parental origin, the other allele being silent. Diseases can arise when the normally active alleles are not expressed. In this context, low level of expression of the normally silent alleles has been considered as genetic noise although such expression has never been further studied. Prader-Willi Syndrome (PWS) is a neurodevelopmental disease involving imprinted genes, including NDN, which are only expressed from the paternally inherited allele, with the maternally inherited allele silent. We present the first in-depth study of the low expression of a normally silent imprinted allele, in pathological context. Using a variety of qualitative and quantitative approaches and comparing wild-type, heterozygous and homozygous mice deleted for Ndn, we show that, in absence of the paternal Ndn allele, the maternal Ndn allele is expressed at an extremely low level with a high degree of non-genetic heterogeneity. The level of this expression is sex-dependent and shows transgenerational epigenetic inheritance. In about 50% of mutant mice, this expression reduces birth lethality and severity of the breathing deficiency, correlated with a reduction in the loss of serotonergic neurons. In wild-type brains, the maternal Ndn allele is never expressed. However, using several mouse models, we reveal a competition between non-imprinted Ndn promoters which results in monoallelic (paternal or maternal) Ndn expression, suggesting that Ndn allelic exclusion occurs in the absence of imprinting regulation. Importantly, specific expression of the maternal NDN allele is also detected in post-mortem brain samples of PWS individuals. Our data reveal an unexpected epigenetic flexibility of PWS imprinted genes that could be exploited to reactivate the functional but dormant maternal alleles in PWS. Overall our results reveal high non-genetic heterogeneity between genetically identical individuals

  16. Contrast and lustre: A model that accounts for eleven different forms of contrast discrimination in binocular vision.

    PubMed

    Georgeson, Mark A; Wallis, Stuart A; Meese, Tim S; Baker, Daniel H

    2016-12-01

    Our goal here is a more complete understanding of how information about luminance contrast is encoded and used by the binocular visual system. In two-interval forced-choice experiments we assessed observers' ability to discriminate changes in contrast that could be an increase or decrease of contrast in one or both eyes, or an increase in one eye coupled with a decrease in the other (termed IncDec). The base or pedestal contrasts were either in-phase or out-of-phase in the two eyes. The opposed changes in the IncDec condition did not cancel each other out, implying that along with binocular summation, information is also available from mechanisms that do not sum the two eyes' inputs. These might be monocular mechanisms. With a binocular pedestal, monocular increments of contrast were much easier to see than monocular decrements. These findings suggest that there are separate binocular (B) and monocular (L,R) channels, but only the largest of the three responses, max(L,B,R), is available to perception and decision. Results from contrast discrimination and contrast matching tasks were described very accurately by this model. Stimuli, data, and model responses can all be visualized in a common binocular contrast space, allowing a more direct comparison between models and data. Some results with out-of-phase pedestals were not accounted for by the max model of contrast coding, but were well explained by an extended model in which gratings of opposite polarity create the sensation of lustre. Observers can discriminate changes in lustre alongside changes in contrast.

  17. The utility of ancient human DNA for improving allele age estimates, with implications for demographic models and tests of natural selection

    PubMed Central

    Sams, Aaron J.; Hawks, John; Keinan, Alon

    2015-01-01

    The age of polymorphic alleles in humans is often estimated from population genetic patterns in extant human populations, such as allele frequencies, linkage disequilibrium, and rate of mutations. Ancient DNA can improve the accuracy of such estimates, as well as facilitate testing the validity of demographic models underlying many population genetic methods. Specifically, the presence of an allele in a genome derived from an ancient sample testifies that the allele is at least as old as that sample. In this study, we consider a common method for estimating allele age based on allele frequency as applied to variants from the US National Institutes of Health (NIH) Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project. We view these estimates in the context of the presence or absence of each allele in the genomes of the 5300 year old Tyrolean Iceman, Ötzi, and of the 50,000 year old Altai Neandertal. Our results illuminate the accuracy of these estimates and their sensitivity to demographic events that were not included in the model underlying age estimation. Specifically, allele presence in the Iceman genome provides a good fit of allele age estimates to the expectation based on the age of that specimen. The equivalent based on the Neandertal genome leads to a poorer fit. This is likely due in part to the older age of the Neandertal and the older time of the split between modern humans and Neandertals, but also due to gene flow from Neandertals to modern humans not being considered in the underlying demographic model. Thus, the incorporation of ancient DNA can improve allele age estimation, demographic modeling, and tests of natural selection. Our results also point to the importance of considering a more diverse set of ancient samples for understanding the geographic and temporal range of individual alleles. PMID:25467111

  18. Population Bottlenecks and Nonequilibrium Models in Population Genetics. II. Number of Alleles in a Small Population That Was Formed by a Recent Bottleneck

    PubMed Central

    Maruyama, Takeo; Fuerst, Paul A.

    1985-01-01

    A model is presented in which a large population in mutation/drift equilibrium undergoes a severe restriction in size and subsequently remains at the small size. The rate of loss of genetic variability has been studied. Allelic loss occurs more rapidly than loss of genic heterozygosity. Rare alleles are lost especially rapidly. The result is a transient deficiency in the total number of alleles observed in samples taken from the reduced population when compared with the number expected in a sample from a steady-state population having the same observed heterozygosity. Alternatively, the population can be considered to posses excess gene diversity if the number of alleles is used as the statistical estimator of mutation rate. The deficit in allele number arises principally from a lack of those alleles that are expected to appear only once or twice in the sample. The magnitude of the allelic deficiency is less, however, than the excess that an earlier study predicted to follow a rapid population expansion. This suggests that populations that have undergone a single bottleneck event, followed by rapid population growth, should have an apparent excess number of alleles, given the observed level of genic heterozygosity and provided that the bottleneck has not occurred very recently. Conversely, such populations will be deficient for observed heterozygosity if allele number is used as the sufficient statistic for the estimation of 4Nev . Populations that have undergone very recent restrictions in size should show the opposite tendencies. PMID:4054612

  19. How attention and contrast gain control interact to regulate lightness contrast and assimilation: a computational neural model.

    PubMed

    Rudd, Michael E

    2010-12-31

    Recent theories of lightness perception assume that lightness (perceived reflectance) is computed by a process that contrasts the target's luminance with that of one or more regions in its spatial surround. A challenge for any such theory is the phenomenon of lightness assimilation, which occurs when increasing the luminance of a surround region increases the target lightness: the opposite of contrast. Here contrast and assimilation are studied quantitatively in lightness matching experiments utilizing concentric disk-and-ring displays. Whether contrast or assimilation is seen depends on a number of factors including: the luminance relations of the target, surround, and background; surround size; and matching instructions. When assimilation occurs, it is always part of a larger pattern in which assimilation and contrast both occur over different ranges of surround luminance. These findings are quantitatively modeled by a theory that assumes lightness is computed from a weighted sum of responses of edge detector neurons in visual cortex. The magnitude of the neural response to an edge is regulated by a combination of contrast gain control acting between neighboring edge detectors and a top-down attentional gain control that selectively weights the response to stimulus edges according to their task relevance.

  20. Uncovering Contrast Categories in Categorization with a Probabilistic Threshold Model

    ERIC Educational Resources Information Center

    Verheyen, Steven; De Deyne, Simon; Dry, Matthew J.; Storms, Gert

    2011-01-01

    A contrast category effect on categorization occurs when the decision to apply a category term to an entity not only involves a comparison between the entity and the target category but is also influenced by a comparison of the entity with 1 or more alternative categories from the same domain as the target. Establishing a contrast category effect…

  1. The Cascadia Subduction Zone: two contrasting models of lithospheric structure

    USGS Publications Warehouse

    Romanyuk, T.V.; Blakely, R.; Mooney, W.D.

    1998-01-01

    The Pacific margin of North America is one of the most complicated regions in the world in terms of its structure and present day geodynamic regime. The aim of this work is to develop a better understanding of lithospheric structure of the Pacific Northwest, in particular the Cascadia subduction zone of Southwest Canada and Northwest USA. The goal is to compare and contrast the lithospheric density structure along two profiles across the subduction zone and to interpet the differences in terms of active processes. The subduction of the Juan de Fuca plate beneath North America changes markedly along the length of the subduction zone, notably in the angle of subduction, distribution of earthquakes and volcanism, goelogic and seismic structure of the upper plate, and regional horizontal stress. To investigate these characteristics, we conducted detailed density modeling of the crust and mantle along two transects across the Cascadia subduction zone. One crosses Vancouver Island and the Canadian margin, the other crosses the margin of central Oregon.

  2. Homology modelling of frequent HLA class-II alleles: A perspective to improve prediction of HLA binding peptide and understand the HLA associated disease susceptibility.

    PubMed

    Kashyap, Manju; Farooq, Umar; Jaiswal, Varun

    2016-10-01

    Human leukocyte antigen (HLA) plays significant role via the regulation of immune system and contribute in the progression and protection of many diseases. HLA molecules bind and present peptides to T- cell receptors which generate the immune response. HLA peptide interaction and molecular function of HLA molecule is the key to predict peptide binding and understanding its role in different diseases. The availability of accurate three dimensional (3D) structures is the initial step towards this direction. In the present work, homology modelling of important and frequent HLA-DRB1 alleles (07:01, 11:01 and 09:01) was done and acceptable models were generated. These modelled alleles were further refined and cross validated by using several methods including Ramachandran plot, Z-score, ERRAT analysis and root mean square deviation (RMSD) calculations. It is known that numbers of allelic variants are related to the susceptibility or protection of various infectious diseases. Difference in amino acid sequences and structures of alleles were also studied to understand the association of HLA with disease susceptibility and protection. Susceptible alleles showed more amino acid variations than protective alleles in three selected diseases caused by different pathogens. Amino acid variations at binding site were found to be more than other part of alleles. RMSD values were also higher at variable positions within binding site. Higher RMSD values indicate that mutations occurring at peptide binding site alter protein structure more than rest of the protein. Hence, these findings and modelled structures can be used to design HLA-DRB1 binding peptides to overcome low prediction accuracy of HLA class II binding peptides. Furthermore, it may help to understand the allele specific molecular mechanisms involved in susceptibility/resistance against pathogenic diseases.

  3. Unraveling multiple MHC gene associations with systemic lupus erythematosus: model choice indicates a role for HLA alleles and non-HLA genes in Europeans.

    PubMed

    Morris, David L; Taylor, Kimberly E; Fernando, Michelle M A; Nititham, Joanne; Alarcón-Riquelme, Marta E; Barcellos, Lisa F; Behrens, Timothy W; Cotsapas, Chris; Gaffney, Patrick M; Graham, Robert R; Pons-Estel, Bernardo A; Gregersen, Peter K; Harley, John B; Hauser, Stephen L; Hom, Geoffrey; Langefeld, Carl D; Noble, Janelle A; Rioux, John D; Seldin, Michael F; Criswell, Lindsey A; Vyse, Timothy J

    2012-11-02

    We have performed a meta-analysis of the major-histocompatibility-complex (MHC) region in systemic lupus erythematosus (SLE) to determine the association with both SNPs and classical human-leukocyte-antigen (HLA) alleles. More specifically, we combined results from six studies and well-known out-of-study control data sets, providing us with 3,701 independent SLE cases and 12,110 independent controls of European ancestry. This study used genotypes for 7,199 SNPs within the MHC region and for classical HLA alleles (typed and imputed). Our results from conditional analysis and model choice with the use of the Bayesian information criterion show that the best model for SLE association includes both classical loci (HLA-DRB1(∗)03:01, HLA-DRB1(∗)08:01, and HLA-DQA1(∗)01:02) and two SNPs, rs8192591 (in class III and upstream of NOTCH4) and rs2246618 (MICB in class I). Our approach was to perform a stepwise search from multiple baseline models deduced from a priori evidence on HLA-DRB1 lupus-associated alleles, a stepwise regression on SNPs alone, and a stepwise regression on HLA alleles. With this approach, we were able to identify a model that was an overwhelmingly better fit to the data than one identified by simple stepwise regression either on SNPs alone (Bayes factor [BF] > 50) or on classical HLA alleles alone (BF > 1,000).

  4. The embedded feature model for the interpretation of chromospheric contrast profiles

    NASA Technical Reports Server (NTRS)

    Steinitz, R.; Gebbie, K. B.; Bar, V.

    1977-01-01

    Contrast profiles obtained from chromospheric filtergrams and spectra of bright and dark mottles have to date been interpreted almost exclusively in terms of Becker's cloud model. Here we demonstrate the failure of this model to account in a physically consistent way for the observed contrasts. As an alternative, we introduce an embedded-feature model, restricting our discussion in this paper to stationary features. Our model is then characterized by three independent parameters: the density of absorbing atoms, the geometrical depth, and the profile of the absorption coefficient. An analytic approximation to the contrast resulting from such a model reproduces well the observed behavior of all types of contrast profiles.

  5. Matching allele dynamics and coevolution in a minimal predator prey replicator model

    NASA Astrophysics Data System (ADS)

    Sardanyés, Josep; Solé, Ricard V.

    2008-01-01

    A minimal Lotka Volterra type predator prey model describing coevolutionary traits among entities with a strength of interaction influenced by a pair of haploid diallelic loci is studied with a deterministic time continuous model. We show a Hopf bifurcation governing the transition from evolutionary stasis to periodic Red Queen dynamics. If predator genotypes differ in their predation efficiency the more efficient genotype asymptotically achieves lower stationary concentrations.

  6. Words as alleles: connecting language evolution with Bayesian learners to models of genetic drift.

    PubMed

    Reali, Florencia; Griffiths, Thomas L

    2010-02-07

    Scientists studying how languages change over time often make an analogy between biological and cultural evolution, with words or grammars behaving like traits subject to natural selection. Recent work has exploited this analogy by using models of biological evolution to explain the properties of languages and other cultural artefacts. However, the mechanisms of biological and cultural evolution are very different: biological traits are passed between generations by genes, while languages and concepts are transmitted through learning. Here we show that these different mechanisms can have the same results, demonstrating that the transmission of frequency distributions over variants of linguistic forms by Bayesian learners is equivalent to the Wright-Fisher model of genetic drift. This simple learning mechanism thus provides a justification for the use of models of genetic drift in studying language evolution. In addition to providing an explicit connection between biological and cultural evolution, this allows us to define a 'neutral' model that indicates how languages can change in the absence of selection at the level of linguistic variants. We demonstrate that this neutral model can account for three phenomena: the s-shaped curve of language change, the distribution of word frequencies, and the relationship between word frequencies and extinction rates.

  7. Numerical and Qualitative Contrasts of Two Statistical Models ...

    EPA Pesticide Factsheets

    Two statistical approaches, weighted regression on time, discharge, and season and generalized additive models, have recently been used to evaluate water quality trends in estuaries. Both models have been used in similar contexts despite differences in statistical foundations and products. This study provided an empirical and qualitative comparison of both models using 29 years of data for two discrete time series of chlorophyll-a (chl-a) in the Patuxent River estuary. Empirical descriptions of each model were based on predictive performance against the observed data, ability to reproduce flow-normalized trends with simulated data, and comparisons of performance with validation datasets. Between-model differences were apparent but minor and both models had comparable abilities to remove flow effects from simulated time series. Both models similarly predicted observations for missing data with different characteristics. Trends from each model revealed distinct mainstem influences of the Chesapeake Bay with both models predicting a roughly 65% increase in chl-a over time in the lower estuary, whereas flow-normalized predictions for the upper estuary showed a more dynamic pattern, with a nearly 100% increase in chl-a in the last 10 years. Qualitative comparisons highlighted important differences in the statistical structure, available products, and characteristics of the data and desired analysis. This manuscript describes a quantitative comparison of two recently-

  8. An X-linked three allele model of hand preference and hand posture for writing.

    PubMed

    McKeever, Walter F

    2004-04-01

    This paper describes a genetic model of hand preferences for writing and for handwriting posture (HWP). The challenge of devising an X-linked model for these aspects of human handedness was posed by the results of a large family handedness study (McKeever, 2000) that showed evidence of such linkage. Because X-linkage for handedness has been widely regarded as untenable, the prospects for developing such a model were not initially encouraging, but ultimately a viable model did suggest itself. Family studies of handedness and leading theories of handedness are briefly described, as is some of the research on HWP motivated by the theory of Levy and Nagylaki (1972). It is argued that there is evidence that HWP reflects a biological dictate and not just individual "choices" or "adaptations" to writing in a left-to-right direction with the left hand. The model proposes that inverted handwriting posture is not necessarily highly related to speech and language lateralities of sinistrals, but that it reveals an interhemispheric mediation of writing. It is hypothesised that it reflects a specialisation of the left angular gyrus (with some possible extension into the supramarginal gyrus) for the storage of movement and timing sequences of cursive writing, and right hemisphere motor programming of the motor output of writing. It is also argued that no family handedness study conducted to date is adequate for testing the predictions of extant handedness theories, and the often wide variations between the results of family handedness studies are noted. It is suggested that fMRI studies could definitively test the HWP hypotheses of the model and that the hypothesis of X-linkage could be tested definitively should studies of the human genome identify a gene for handedness.

  9. A rat EEG model for evaluating contrast media neurotoxicity.

    PubMed

    Adams, M D; Hopkins, R M; Ferrendelli, J A

    1988-09-01

    The electroencephalographic (EEG) effects of intracisternally administered x-ray contrast media were evaluated in rats as a means of assessing neurotoxicity. Rats were ventilated with a mixture of nitrous oxide and oxygen (70/30) sufficient to maintain light anesthesia/analgesia and neuromuscular blockade was induced to prevent movement artifacts. A femoral artery was catheterized for monitoring arterial blood pressure (BP), heart rate, blood gases, and pH. Four 22-gauge stainless steel needle electrodes were inserted underneath the scalp for recording EEG. Approximately 1 hour after the start of EEG recording, test agents were injected via the cisterna magna and rats were placed in a 20 degrees head-down position. EEG and BP were monitored continuously for up to 160 minutes postinjection. Blood gases and pH were monitored periodically. The effects of meglumine iothalamate (IOT), metrizamide (MET), iogulamide (IOG), and ioversol (IOV) were compared at dose levels from 30 to 240 mgI/kg. Normal saline was injected as a control substance and caused no changes in EEG, blood gases, pH, and BP for up to 160 minutes postinjection. IOT (30 mg I/kg) produced profound EEG effects consistent with epileptogenic activity, followed by slowing and subsequent death in 3 of 4 animals. Metrizamide had minimal EEG effects at 30 mg I/kg but at 60 mg I/kg, and 120 mg I/kg produced moderate to severe EEG changes including epileptiform patterns and death in 33% of animals. IOV caused mild EEG abnormalities in 4 of 12 animals at 120 mg I/kg, mild EEG abnormalities in 6 of 11 animals, and moderate EEG abnormalities in 1 of 11 animals at 240 mg I/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Chromatic induction and contrast masking: similar models, different goals?

    NASA Astrophysics Data System (ADS)

    Jiménez, Sandra; Otazu, Xavier; Laparra, Valero; Malo, Jesús

    2013-03-01

    Normalization of signals coming from linear sensors is an ubiquitous mechanism of neural adaptation.1 Local interaction between sensors tuned to a particular feature at certain spatial position and neighbor sensors explains a wide range of psychophysical facts including (1) masking of spatial patterns, (2) non-linearities of motion sensors, (3) adaptation of color perception, (4) brightness and chromatic induction, and (5) image quality assessment. Although the above models have formal and qualitative similarities, it does not necessarily mean that the mechanisms involved are pursuing the same statistical goal. For instance, in the case of chromatic mechanisms (disregarding spatial information), different parameters in the normalization give rise to optimal discrimination or adaptation, and different non-linearities may give rise to error minimization or component independence. In the case of spatial sensors (disregarding color information), a number of studies have pointed out the benefits of masking in statistical independence terms. However, such statistical analysis has not been performed for spatio-chromatic induction models where chromatic perception depends on spatial configuration. In this work we investigate whether successful spatio-chromatic induction models,6 increase component independence similarly as previously reported for masking models. Mutual information analysis suggests that seeking an efficient chromatic representation may explain the prevalence of induction effects in spatially simple images.

  11. Visual detection of spatial contrast patterns: evaluation of five simple models

    NASA Technical Reports Server (NTRS)

    Watson, A. B.

    2000-01-01

    The ModelFest Phase One dataset is a collection of luminance contrast thresholds for 43 two-dimensional monochromatic spatial patterns confined to an area of approximately two by two degrees. These data were collected by a collaboration among twelve laboratories, and were designed to provide a common database for calibration and testing of spatial vision models. Here I report fits of the ModelFest data with five models: Peak Contrast, Contrast Energy, Generalized Energy, a Gabor Channels model, and a Discrete Cosine Transform model. The Gabor Channels model provides the best fit, though the other, simpler models, with the exception of Peak Contrast, provide remarkably good fits as well. Though there are clear individual differences, regularities in the data suggest the possibility of constructing a standard observer for spatial vision. c2000 Optical Society of America.

  12. Analysis of Pneumocystis jirovecii DHPS alleles implicated in sulfamethoxazole resistance using an Escherichia coli model system.

    PubMed

    Iliades, Peter; Meshnick, Steven R; Macreadie, Ian G

    2005-01-01

    Pneumocystis jirovecii is a major opportunistic pathogen that causes Pneumocystis pneumonia (PCP). Drug treatment failure has been associated epidemiologically with point mutations in the gene for dihydropteroate synthase which is part of a gene that encodes three covalently linked enzymes involved in folic acid synthesis (FAS). The evaluation of whether mutations found in P. jirovecii FAS lead to sulfa drug resistance is hampered by the lack of a culture system for P. jirovecii as well as the failure of P. jirovecii FAS to complement in a heterologous system. Therefore, we chose to model the P. jirovecii mutations in the Saccharomyces cerevisiae FAS protein (encoded by FOL1) via its expression in Escherichia coli. An optimized drug diffusion assay was used to evaluate the FAS mutants against 15 sulfa drugs. It was established that the single amino acid substitution, P599S, in the (DHPS) domain of FAS led to sulfa drug resistance, whereas the T597A substitution led to increased sensitivity. The presence of both mutations (T597A and P599S) was cooperative and led to increased sulfa drug resistance. Analysis of a novel double mutant, (T597V P599S) was found to have significantly higher sulfa drug resistance than the T597A P599S mutant. These data suggest that further amino acid substitutions may lead to the evolution of higher sulfa drug resistance. Two sulfa drugs (sulfachloropyridazine and sulfathiazole) were identified that had higher inhibitory potential than sulfamethoxazole, which is currently the preferred treatment for PCP.

  13. Response-Time Approach to Contrasting Models of Perceptual Classification

    DTIC Science & Technology

    2013-02-01

    For example, in Experiment 1 of Nosofsky et al. (2011), the stimuli were a set of 27 Munsell colors varying along dimensions of hue , saturation, and...develop and test models that explain the time course of classification and recognition decision making. The first specific goal involved the...Several empirical studies demonstrated successful applications of the new theory in this domain. The second goal involved the development and testing

  14. Modeling Graphene Contrast on Copper Surfaces Using Optical Microscopy

    DTIC Science & Technology

    2014-10-01

    requirement for transfer. Atomic force microscopy was used to determine copper oxide thickness, and a Matlab model based on Fresnel theory was used to...consuming process involving specialized techniques such as atomic force microscopy (AFM), scanning electron microscopy (SEM), transmission electron...laser was used as the excitation source. A Cypher SPM in noncontact mode was used for topography and phase imaging characterization. 2.4 Broadband

  15. MtDNA meta-analysis reveals both phenotype specificity and allele heterogeneity: a model for differential association

    PubMed Central

    Marom, Shani; Friger, Michael; Mishmar, Dan

    2017-01-01

    Human mtDNA genetic variants have traditionally been considered markers for ancient population migrations. However, during the past three decades, these variants have been associated with altered susceptibility to various phenotypes, thus supporting their importance for human health. Nevertheless, mtDNA disease association has frequently been supported only in certain populations, due either to population stratification or differential epistatic compensations among populations. To partially overcome these obstacles, we performed meta-analysis of the multiple mtDNA association studies conducted until 2016, encompassing 53,975 patients and 63,323 controls. Our findings support the association of mtDNA haplogroups and recurrent variants with specific phenotypes such as Parkinson’s disease, type 2 diabetes, longevity, and breast cancer. Strikingly, our assessment of mtDNA variants’ involvement with multiple phenotypes revealed significant impact for Caucasian haplogroups H, J, and K. Therefore, ancient mtDNA variants could be divided into those that affect specific phenotypes, versus others with a general impact on phenotype combinations. We suggest that the mtDNA could serve as a model for phenotype specificity versus allele heterogeneity. PMID:28230165

  16. The Rg1 allele as a valuable tool for genetic transformation of the tomato 'Micro-Tom' model system

    PubMed Central

    2010-01-01

    Background The cultivar Micro-Tom (MT) is regarded as a model system for tomato genetics due to its short life cycle and miniature size. However, efforts to improve tomato genetic transformation have led to protocols dependent on the costly hormone zeatin, combined with an excessive number of steps. Results Here we report the development of a MT near-isogenic genotype harboring the allele Rg1 (MT-Rg1), which greatly improves tomato in vitro regeneration. Regeneration was further improved in MT by including a two-day incubation of cotyledonary explants onto medium containing 0.4 μM 1-naphthaleneacetic acid (NAA) before cytokinin treatment. Both strategies allowed the use of 5 μM 6-benzylaminopurine (BAP), a cytokinin 100 times less expensive than zeatin. The use of MT-Rg1 and NAA pre-incubation, followed by BAP regeneration, resulted in high transformation frequencies (near 40%), in a shorter protocol with fewer steps, spanning approximately 40 days from Agrobacterium infection to transgenic plant acclimatization. Conclusions The genetic resource and the protocol presented here represent invaluable tools for routine gene expression manipulation and high throughput functional genomics by insertional mutagenesis in tomato. PMID:20929550

  17. Experimentally enhanced model-based deconvolution of propagation-based phase-contrast data

    NASA Astrophysics Data System (ADS)

    Pichotka, M.; Palma, K.; Hasn, S.; Jakubek, J.; Vavrik, D.

    2016-12-01

    In recent years phase-contrast has become a much investigated modality in radiographic imaging. The radiographic setups employed in phase-contrast imaging are typically rather costly and complex, e.g. high performance Talbot-Laue interferometers operated at synchrotron light sources. In-line phase-contrast imaging states the most pedestrian approach towards phase-contrast enhancement. Utilizing small angle deflection within the imaged sample and the entailed interference of the deflected and un-deflected beam during spatial propagation, in-line phase-contrast imaging only requires a well collimated X-ray source with a high contrast & high resolution detector. Employing high magnification the above conditions are intrinsically fulfilled in cone-beam micro-tomography. As opposed of 2D imaging, where contrast enhancement is generally considered beneficial, in tomographic modalities the in-line phase-contrast effect can be quite a nuisance since it renders the inverse problem posed by tomographic reconstruction inconsistent, thus causing reconstruction artifacts. We present an experimentally enhanced model-based approach to disentangle absorption and in-line phase-contrast. The approach employs comparison of transmission data to a system model computed iteratively on-line. By comparison of the forward model to absorption data acquired in continuous rotation strong local deviations of the data residual are successively identified as likely candidates for in-line phase-contrast. By inducing minimal vibrations (few mrad) to the sample around the peaks of such deviations the transmission signal can be decomposed into a constant absorptive fraction and an oscillating signal caused by phase-contrast which again allows to generate separate maps for absorption and phase-contrast. The contributions of phase-contrast and the corresponding artifacts are subsequently removed from the tomographic dataset. In principle, if a 3D handling of the sample is available, this method also

  18. Use of qualitative environmental and phenotypic variables in the context of allele distribution models: detecting signatures of selection in the genome of Lake Victoria cichlids.

    PubMed

    Joost, Stéphane; Kalbermatten, Michael; Bezault, Etienne; Seehausen, Ole

    2012-01-01

    When searching for loci possibly under selection in the genome, an alternative to population genetics theoretical models is to establish allele distribution models (ADM) for each locus to directly correlate allelic frequencies and environmental variables such as precipitation, temperature, or sun radiation. Such an approach implementing multiple logistic regression models in parallel was implemented within a computing program named MATSAM: . Recently, this application was improved in order to support qualitative environmental predictors as well as to permit the identification of associations between genomic variation and individual phenotypes, allowing the detection of loci involved in the genetic architecture of polymorphic characters. Here, we present the corresponding methodological developments and compare the results produced by software implementing population genetics theoretical models (DFDIST: and BAYESCAN: ) and ADM (MATSAM: ) in an empirical context to detect signatures of genomic divergence associated with speciation in Lake Victoria cichlid fishes.

  19. Choreography of Ig allelic exclusion.

    PubMed

    Cedar, Howard; Bergman, Yehudit

    2008-06-01

    Allelic exclusion guarantees that each B or T cell only produces a single antigen receptor, and in this way contributes to immune diversity. This process is actually initiated in the early embryo when the immune receptor loci become asynchronously replicating in a stochastic manner with one early and one late allele in each cell. This distinct differential replication timing feature then serves an instructive mark that directs a series of allele-specific epigenetic events in the immune system, including programmed histone modification, nuclear localization and DNA demethylation that ultimately bring about preferred rearrangement on a single allele, and this decision is temporally stabilized by feedback mechanisms that inhibit recombination on the second allele. In principle, these same molecular components are also used for controlling monoallelic expression at other genomic loci, such as those carrying interleukins and olfactory receptor genes that require the choice of one gene out of a large array. Thus, allelic exclusion appears to represent a general epigenetic phenomenon that is modeled on the same basis as X chromosome inactivation.

  20. Human Leukocyte Antigens-A, -B, -C, -DRB1 allele and haplotype frequencies in Americans originating from Southern Europe: Contrasting patterns of population differentiation between Italian and Spanish Americans

    PubMed Central

    Mack, Steven J.; Tu, Bin; Yang, Ruyan; Masaberg, Carly; Ng, Jennifer; Hurley, Carolyn Katovich

    2010-01-01

    High resolution DNA sequencing was used to identify the HLA-A, -B, -C, and -DRB1 alleles found in 552 individuals from the United States indicating Southern European (Italian or Spanish) heritage. A total of 46 HLA-A, 80 HLA-B, 32 HLA-C, and 50 DRB1 alleles were identified. Frequent alleles included A*02:01:01G (allele frequency = 0.26 in Italian Americans; 0.22 in Spanish Americans); B*07:02:01G (Italian Americans allele frequency = 0.11); B*44:03 (Spanish Americans allele frequency = 0.07); C*04:01:01G and C*07:01:01G (allele frequency = 0.13 and 0.16, respectively, in Italian Americans; 0.15 and 0.12, respectively, in Spanish Americans); and DRB1*07:01:01 (allele frequency = 0.12 in each population). The action of balancing selection was inferred at the HLA-B and -C loci in both populations. The A*01:01:01G-C*07:01:01G-B*08:01:01G-DRB1*03:01:01 haplotype was the most frequent A-C-B-DRB1 haplotype in Italian Americans (haplotype frequency = 0.049), and was the second most frequent haplotype in Spanish Americans (haplotype frequency = 0.021). A*29:02:01-C*16:01:01-B*44:03-DRB1*07:01:01 was the most frequent A-C-B-DRB1 haplotype in Spanish Americans (haplotype frequency = 0.023), and was observed at a frequency of 0.015 in Italian Americans. Pairwise F’st values measuring the degree of differentiation between these Southern European-American populations and European and European-American populations suggest that Spanish Americans constitute a distinct subset of the European-American population, most similar to Mexican Americans, whereas Italian Americans cannot be distinguished from the larger European-American population. PMID:20974205

  1. Contrasting allelic distribution of CO/Hd1 homologues in Miscanthus sinensis from the East Asian mainland and the Japanese archipelago

    SciTech Connect

    Nagano, Hironori; Clark, Lindsay V.; Zhao, Hua; Peng, Junhua; Yoo, Ji Hye; Heo, Kweon; Yu, Chang Yeon; Anzoua, Kossonou Guillaume; Matsuo, Tomoaki; Sacks, Erik J.; Yamada, Toshihiko

    2015-06-18

    The genus Miscanthus is a perennial C4 grass native to eastern Asia and is a promising candidate bioenergy crop for cool temperate areas. Flowering time is a crucial factor governing regional and seasonal adaptation; in addition, it is also a key target trait for extending the vegetative phase to improve biomass potential. Homologues of CONSTANS (CO)/Heading date 1(Hd1) were cloned from Miscanthus sinensis and named MsiHd1. Sequences of MsiHd1 homologues were compared among 24 wild M. sinensis accessions from Japan, 14 from China, and three from South Korea. Two to five MsiHd1 alleles in each accession were identified, suggesting that MsiHd1 consists of at least three loci in the Miscanthus genome. Verifying the open reading frame in MsiHd1, they were classified as putative functional alleles without mutations or non-functional alleles caused by indels. The Neighbor-Joining tree indicated that one of the multiple MsiHd1 loci is a pseudogene locus without any functional alleles. The pseudogene locus was named MsiHd1b, and the other loci were considered to be part of the MsiHd1a multi-locus family. Interestingly, in most Japanese accessions 50% or more of the MsiHd1a alleles were non-functional, whereas accessions from the East Asian mainland harboured only functional alleles. Five novel miniature inverted transposable elements (MITEs) (MsiMITE1-MsiMITE5) were observed in MsiHd1a/b. MsiMITE1, detected in exon 1 of MsiHd1a, was only observed in Japanese accessions and its revertant alleles derived from retransposition were predominantly in Chinese accessions. In conclusion, these differences in MsiHd1a show that the dependency on functional MsiHd1a alleles is different between accessions from the East Asian mainland and Japan.

  2. Transformation of QTL genotypic effects to allelic effects

    PubMed Central

    Nagamine, Yoshitaka

    2005-01-01

    The genotypic and allelic effect models are equivalent in terms of QTL detection in a simple additive model, but the QTL allelic model has the advantage of providing direct information for marker-assisted selection. However, the allelic matrix is four times as large as the genotypic IBD matrix, causing computational problems, especially in genome scans examining multiple positions. Transformation from genotypic to allelic effects, after estimating the genotypic effects with a smaller IBD matrix, can solve this problem. Although the validity of transformation from genotypic to allelic effects has been disputed, this work proves that transformation can successfully yield unique allelic effects when genotypic and allelic IBD matrixes exist. PMID:16093016

  3. Image Discrimination Predictions of a Single Channel Model with Contrast Gain Control

    NASA Technical Reports Server (NTRS)

    Ahumada, Albert J., Jr.; Null, Cynthia H.

    1995-01-01

    Image discrimination models predict the number of just-noticeable-differences between two images. We report the predictions of a single channel model with contrast masking for a range of standard discrimination experiments. Despite its computational simplicity, this model has performed as well as a multiple channel model in an object detection task.

  4. Computer simulation for the growing probability of additional offspring with an advantageous reversal allele in the decoupled continuous-time mutation-selection model

    NASA Astrophysics Data System (ADS)

    Gill, Wonpyong

    2016-01-01

    This study calculated the growing probability of additional offspring with the advantageous reversal allele in an asymmetric sharply-peaked landscape using the decoupled continuous-time mutation-selection model. The growing probability was calculated for various population sizes, N, sequence lengths, L, selective advantages, s, fitness parameters, k and measuring parameters, C. The saturated growing probability in the stochastic region was approximately the effective selective advantage, s*, when C≫1/Ns* and s*≪1. The present study suggests that the growing probability in the stochastic region in the decoupled continuous-time mutation-selection model can be described using the theoretical formula for the growing probability in the Moran two-allele model. The selective advantage ratio, which represents the ratio of the effective selective advantage to the selective advantage, does not depend on the population size, selective advantage, measuring parameter and fitness parameter; instead the selective advantage ratio decreases with the increasing sequence length.

  5. CRITIR: model-based reconstruction for x-ray phase contrast tomography (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Xiao, Xianghui; Mohan, Aditya; Bouman, Charles A.

    2016-10-01

    X-ray phase contrast imaging provides greater contrast compared to conventional absorption contrast imaging. It has higher sensitivity in discriminating mass density difference in a sample. Therefore phase contrast imaging has broad applications in dynamic tomography in which signal-to-noise ratio is usually traded off to the desired temporal resolution. Single-distance propagation phase contrast tomography is the most popular approach at many synchrotron facilities. The simple and flexible setup facilitates complicated in situ experiments. There are few phase retrieval algorithms available for phase-contrast image data processing. All the algorithms rely on certain models. In this talk we present a phase retrieval algorithm for phase-contrast tomography that is suitable for large propagation distance under phase-attenuation duality assumption. The validity of the algorithm is proved with both simulated and experimental data. The reconstruction results with the new algorithm show improved accuracy compared to other model based algorithms. The framework of this algorithm may be extended to the scenario in which phase-attenuation assumption is not satisfied, therefore a general model-free phase retrieval approach for single-distance phase contrast tomography.

  6. Particulate air pollutants, APOE alleles and their contributions to cognitive impairment in older women and to amyloidogenesis in experimental models

    PubMed Central

    Cacciottolo, M; Wang, X; Driscoll, I; Woodward, N; Saffari, A; Reyes, J; Serre, M L; Vizuete, W; Sioutas, C; Morgan, T E; Gatz, M; Chui, H C; Shumaker, S A; Resnick, S M; Espeland, M A; Finch, C E; Chen, J C

    2017-01-01

    Exposure to particulate matter (PM) in the ambient air and its interactions with APOE alleles may contribute to the acceleration of brain aging and the pathogenesis of Alzheimer's disease (AD). Neurodegenerative effects of particulate air pollutants were examined in a US-wide cohort of older women from the Women's Health Initiative Memory Study (WHIMS) and in experimental mouse models. Residing in places with fine PM exceeding EPA standards increased the risks for global cognitive decline and all-cause dementia respectively by 81 and 92%, with stronger adverse effects in APOE ɛ4/4 carriers. Female EFAD transgenic mice (5xFAD+/−/human APOE ɛ3 or ɛ4+/+) with 225 h exposure to urban nanosized PM (nPM) over 15 weeks showed increased cerebral β-amyloid by thioflavin S for fibrillary amyloid and by immunocytochemistry for Aβ deposits, both exacerbated by APOE ɛ4. Moreover, nPM exposure increased Aβ oligomers, caused selective atrophy of hippocampal CA1 neurites, and decreased the glutamate GluR1 subunit. Wildtype C57BL/6 female mice also showed nPM-induced CA1 atrophy and GluR1 decrease. In vitro nPM exposure of neuroblastoma cells (N2a-APP/swe) increased the pro-amyloidogenic processing of the amyloid precursor protein (APP). We suggest that airborne PM exposure promotes pathological brain aging in older women, with potentially a greater impact in ɛ4 carriers. The underlying mechanisms may involve increased cerebral Aβ production and selective changes in hippocampal CA1 neurons and glutamate receptor subunits. PMID:28140404

  7. THREE-DIMENSIONAL MODELING OF THE DYNAMICS OF THERAPEUTIC ULTRASOUND CONTRAST AGENTS

    PubMed Central

    Hsiao, Chao-Tsung; Lu, Xiaozhen; Chahine, Georges

    2010-01-01

    A 3-D thick-shell contrast agent dynamics model was developed by coupling a finite volume Navier-Stokes solver and a potential boundary element method flow solver to simulate the dynamics of thick-shelled contrast agents subjected to pressure waves. The 3-D model was validated using a spherical thick-shell model validated by experimental observations. We then used this model to study shell break-up during nonspherical deformations resulting from multiple contrast agent interaction or the presence of a nearby solid wall. Our simulations indicate that the thick viscous shell resists the contrast agent from forming a re-entrant jet, as normally observed for an air bubble oscillating near a solid wall. Instead, the shell thickness varies significantly from location to location during the dynamics, and this could lead to shell break-up caused by local shell thinning and stretching. PMID:20950929

  8. Long-term impacts of selective logging on two Amazonian tree species with contrasting ecological and reproductive characteristics: inferences from Eco-gene model simulations

    PubMed Central

    Vinson, C C; Kanashiro, M; Sebbenn, A M; Williams, T CR; Harris, S A; Boshier, D H

    2015-01-01

    The impact of logging and subsequent recovery after logging is predicted to vary depending on specific life history traits of the logged species. The Eco-gene simulation model was used to evaluate the long-term impacts of selective logging over 300 years on two contrasting Brazilian Amazon tree species, Dipteryx odorata and Jacaranda copaia. D. odorata (Leguminosae), a slow growing climax tree, occurs at very low densities, whereas J. copaia (Bignoniaceae) is a fast growing pioneer tree that occurs at high densities. Microsatellite multilocus genotypes of the pre-logging populations were used as data inputs for the Eco-gene model and post-logging genetic data was used to verify the output from the simulations. Overall, under current Brazilian forest management regulations, there were neither short nor long-term impacts on J. copaia. By contrast, D. odorata cannot be sustainably logged under current regulations, a sustainable scenario was achieved by increasing the minimum cutting diameter at breast height from 50 to 100 cm over 30-year logging cycles. Genetic parameters were only slightly affected by selective logging, with reductions in the numbers of alleles and single genotypes. In the short term, the loss of alleles seen in J. copaia simulations was the same as in real data, whereas fewer alleles were lost in D. odorata simulations than in the field. The different impacts and periods of recovery for each species support the idea that ecological and genetic information are essential at species, ecological guild or reproductive group levels to help derive sustainable management scenarios for tropical forests. PMID:24424164

  9. Long-term impacts of selective logging on two Amazonian tree species with contrasting ecological and reproductive characteristics: inferences from Eco-gene model simulations.

    PubMed

    Vinson, C C; Kanashiro, M; Sebbenn, A M; Williams, T C R; Harris, S A; Boshier, D H

    2015-08-01

    The impact of logging and subsequent recovery after logging is predicted to vary depending on specific life history traits of the logged species. The Eco-gene simulation model was used to evaluate the long-term impacts of selective logging over 300 years on two contrasting Brazilian Amazon tree species, Dipteryx odorata and Jacaranda copaia. D. odorata (Leguminosae), a slow growing climax tree, occurs at very low densities, whereas J. copaia (Bignoniaceae) is a fast growing pioneer tree that occurs at high densities. Microsatellite multilocus genotypes of the pre-logging populations were used as data inputs for the Eco-gene model and post-logging genetic data was used to verify the output from the simulations. Overall, under current Brazilian forest management regulations, there were neither short nor long-term impacts on J. copaia. By contrast, D. odorata cannot be sustainably logged under current regulations, a sustainable scenario was achieved by increasing the minimum cutting diameter at breast height from 50 to 100 cm over 30-year logging cycles. Genetic parameters were only slightly affected by selective logging, with reductions in the numbers of alleles and single genotypes. In the short term, the loss of alleles seen in J. copaia simulations was the same as in real data, whereas fewer alleles were lost in D. odorata simulations than in the field. The different impacts and periods of recovery for each species support the idea that ecological and genetic information are essential at species, ecological guild or reproductive group levels to help derive sustainable management scenarios for tropical forests.

  10. Singularities in the inverse modeling of 2AFC contrast discrimination data.

    PubMed

    Katkov, Mikhail; Tsodyks, Misha; Sagi, Dov

    2006-01-01

    Analytical calculations show that two-alternative force-choice data are not always suitable for specifying the parameters of the underlying discrimination model. Experimentally, we show here that in the case of contrast discrimination in humans, a variety of models spanning a large range of parameters can explain the data within an experimental error. Monte-Carlo simulations indicate that the number of trials in psychophysical experiments is not the limiting factor in estimating the parameters in contrast discrimination. These results can therefore explain the contradictory conclusions made by different groups about the relationship between the response to contrast and the noise amplitude.

  11. Achievement Motivation in High School: Contrasting Theoretical Models in the Classroom.

    ERIC Educational Resources Information Center

    Garcia-Celay, I. Montero; Tapia, J. Alonso

    1992-01-01

    Three models of achievement motivation in the classroom are contrasted. Results with 155 high school students suggest that the model of C. S. Dweck and E. S. Elliott offers a better explanation of the relationships among achievement motivation, attributions, emotional reactions, expectancies, and performance than do the other models. (SLD)

  12. Analytical model of the statistical properties of contrast of large-scale ionospheric inhomogeneities.

    NASA Astrophysics Data System (ADS)

    Vsekhsvyatskaya, I. S.; Evstratova, E. A.; Kalinin, Yu. K.; Romanchuk, A. A.

    1989-08-01

    A new analytical model is proposed for the distribution of variations of the relative electron-density contrast of large-scale ionospheric inhomogeneities. The model is characterized by other-than-zero skewness and kurtosis. It is shown that the model is applicable in the interval of horizontal dimensions of inhomogeneities from hundreds to thousands of kilometers.

  13. Modeling contrast agent flow in cerebral aneurysms: comparison of CFD with medical imaging

    NASA Astrophysics Data System (ADS)

    Rayz, Vitaliy; Vali, Alireza; Sigovan, Monica; Lawton, Michael; Saloner, David; Boussel, Loic

    2016-11-01

    PURPOSE: The flow in cerebral aneurysms is routinely assessed with X-ray angiography, an imaging technique based on a contrast agent injection. In addition to requiring a patient's catheterization and radiation exposure, the X-ray angiography may inaccurately estimate the flow residence time, as the injection alters the native blood flow patterns. Numerical modeling of the contrast transport based on MRI imaging, provides a non-invasive alternative for the flow diagnostics. METHODS: The flow in 3 cerebral aneurysms was measured in vivo with 4D PC-MRI, which provides time-resolved, 3D velocity field. The measured velocities were used to simulate a contrast agent transport by solving the advection-diffusion equation. In addition, the flow in the same patient-specific geometries was simulated with CFD and the velocities obtained from the Navier-Stokes solution were used to model the transport of a virtual contrast. RESULTS: Contrast filling and washout patterns obtained in simulations based on MRI-measured velocities were in agreement with those obtained using the Navier-Stokes solution. Some discrepancies were observed in comparison to the X-ray angiography data, as numerical modeling of the contrast transport is based on the native blood flow unaffected by the contrast injection. NIH HL115267.

  14. Sensitivity to gaze-contingent contrast increments in naturalistic movies: An exploratory report and model comparison

    PubMed Central

    Wallis, Thomas S. A.; Dorr, Michael; Bex, Peter J.

    2015-01-01

    Sensitivity to luminance contrast is a prerequisite for all but the simplest visual systems. To examine contrast increment detection performance in a way that approximates the natural environmental input of the human visual system, we presented contrast increments gaze-contingently within naturalistic video freely viewed by observers. A band-limited contrast increment was applied to a local region of the video relative to the observer's current gaze point, and the observer made a forced-choice response to the location of the target (≈25,000 trials across five observers). We present exploratory analyses showing that performance improved as a function of the magnitude of the increment and depended on the direction of eye movements relative to the target location, the timing of eye movements relative to target presentation, and the spatiotemporal image structure at the target location. Contrast discrimination performance can be modeled by assuming that the underlying contrast response is an accelerating nonlinearity (arising from a nonlinear transducer or gain control). We implemented one such model and examined the posterior over model parameters, estimated using Markov-chain Monte Carlo methods. The parameters were poorly constrained by our data; parameters constrained using strong priors taken from previous research showed poor cross-validated prediction performance. Atheoretical logistic regression models were better constrained and provided similar prediction performance to the nonlinear transducer model. Finally, we explored the properties of an extended logistic regression that incorporates both eye movement and image content features. Models of contrast transduction may be better constrained by incorporating data from both artificial and natural contrast perception settings. PMID:26057546

  15. Microsatellite Variation in Honey Bee (Apis Mellifera L.) Populations: Hierarchical Genetic Structure and Test of the Infinite Allele and Stepwise Mutation Models

    PubMed Central

    Estoup, A.; Garnery, L.; Solignac, M.; Cornuet, J. M.

    1995-01-01

    Samples from nine populations belonging to three African (intermissa, scutellata and capensis) and four European (mellifera, ligustica, carnica and cecropia) Apis mellifera subspecies were scored for seven microsatellite loci. A large amount of genetic variation (between seven and 30 alleles per locus) was detected. Average heterozygosity and average number of alleles were significantly higher in African than in European subspecies, in agreement with larger effective population sizes in Africa. Microsatellite analyses confirmed that A. mellifera evolved in three distinct and deeply differentiated lineages previously detected by morphological and mitochondrial DNA studies. Dendrogram analysis of workers from a given population indicated that super-sisters cluster together when using a sufficient number of microsatellite data whereas half-sisters do not. An index of classification was derived to summarize the clustering of different taxonomic levels in large phylogenetic trees based on individual genotypes. Finally, individual population X loci data were used to test the adequacy of the two alternative mutation models, the infinite allele model (IAM) and the stepwise mutation models. The better fit overall of the IAM probably results from the majority of the microsatellites used including repeats of two or three different length motifs (compound microsatellites). PMID:7498746

  16. Microsatellite variation in honey bee (Apis mellifera L.) populations: hierarchical genetic structure and test of the infinite allele and stepwise mutation models.

    PubMed

    Estoup, A; Garnery, L; Solignac, M; Cornuet, J M

    1995-06-01

    Samples from nine populations belonging to three African (intermissa, scutellata and capensis) and four European (mellifera, ligustica, carnica and cecropia) Apis mellifera subspecies were scored for seven microsatellite loci. A large amount of genetic variation (between seven and 30 alleles per locus) was detected. Average heterozygosity and average number of alleles were significantly higher in African than in European subspecies, in agreement with larger effective population sizes in Africa. Microsatellite analyses confirmed that A. mellifera evolved in three distinct and deeply differentiated lineages previously detected by morphological and mitochondrial DNA studies. Dendrogram analysis of workers from a given population indicated that super-sisters cluster together when using a sufficient number of microsatellite data whereas half-sisters do not. An index of classification was derived to summarize the clustering of different taxonomic levels in large phylogenetic trees based on individual genotypes. Finally, individual population x loci data were used to test the adequacy of the two alternative mutation models, the infinite allele model (IAM) and the stepwise mutation models. The better fit overall of the IAM probably results from the majority of the microsatellites used including repeats of two or three different length motifs (compound microsatellites).

  17. A Model of Compound Heterozygous, Loss-of-Function Alleles Is Broadly Consistent with Observations from Complex-Disease GWAS Datasets

    PubMed Central

    Sanjak, Jaleal S.; Long, Anthony D.; Thornton, Kevin R.

    2017-01-01

    The genetic component of complex disease risk in humans remains largely unexplained. A corollary is that the allelic spectrum of genetic variants contributing to complex disease risk is unknown. Theoretical models that relate population genetic processes to the maintenance of genetic variation for quantitative traits may suggest profitable avenues for future experimental design. Here we use forward simulation to model a genomic region evolving under a balance between recurrent deleterious mutation and Gaussian stabilizing selection. We consider multiple genetic and demographic models, and several different methods for identifying genomic regions harboring variants associated with complex disease risk. We demonstrate that the model of gene action, relating genotype to phenotype, has a qualitative effect on several relevant aspects of the population genetic architecture of a complex trait. In particular, the genetic model impacts genetic variance component partitioning across the allele frequency spectrum and the power of statistical tests. Models with partial recessivity closely match the minor allele frequency distribution of significant hits from empirical genome-wide association studies without requiring homozygous effect sizes to be small. We highlight a particular gene-based model of incomplete recessivity that is appealing from first principles. Under that model, deleterious mutations in a genomic region partially fail to complement one another. This model of gene-based recessivity predicts the empirically observed inconsistency between twin and SNP based estimated of dominance heritability. Furthermore, this model predicts considerable levels of unexplained variance associated with intralocus epistasis. Our results suggest a need for improved statistical tools for region based genetic association and heritability estimation. PMID:28103232

  18. Closing the contrast gap between testbed and model prediction with WFIRST-CGI shaped pupil coronagraph

    NASA Astrophysics Data System (ADS)

    Zhou, Hanying; Nemati, Bijan; Krist, John; Cady, Eric; Prada, Camilo M.; Kern, Brian; Poberezhskiy, Ilya

    2016-07-01

    JPL has recently passed an important milestone in its technology development for a proposed NASA WFIRST mission coronagraph: demonstration of better than 1x10-8 contrast over broad bandwidth (10%) on both shaped pupil coronagraph (SPC) and hybrid Lyot coronagraph (HLC) testbeds with the WFIRST obscuration pattern. Challenges remain, however, in the technology readiness for the proposed mission. One is the discrepancies between the achieved contrasts on the testbeds and their corresponding model predictions. A series of testbed diagnoses and modeling activities were planned and carried out on the SPC testbed in order to close the gap. A very useful tool we developed was a derived "measured" testbed wavefront control Jacobian matrix that could be compared with the model-predicted "control" version that was used to generate the high contrast dark hole region in the image plane. The difference between these two is an estimate of the error in the control Jacobian. When the control matrix, which includes both amplitude and phase, was modified to reproduce the error, the simulated performance closely matched the SPC testbed behavior in both contrast floor and contrast convergence speed. This is a step closer toward model validation for high contrast coronagraphs. Further Jacobian analysis and modeling provided clues to the possible sources for the mismatch: DM misregistration and testbed optical wavefront error (WFE) and the deformable mirror (DM) setting for correcting this WFE. These analyses suggested that a high contrast coronagraph has a tight tolerance in the accuracy of its control Jacobian. Modifications to both testbed control model as well as prediction model are being implemented, and future works are discussed.

  19. Improving the contrast of breast cancer masses in ultrasound using an autoregressive model based filter.

    PubMed

    von Lavante, Etienne; Noble, J Alison

    2007-01-01

    The assessment and diagnosis of breast cancer with ultrasound is a challenging problem due to the low contrast between cancer masses and benign tissue. Due to this low contrast it has proven to be difficult to achieve reliable segmentation results on breast cancer masses. An autoregressive model has been employed to filter out of the backscattered RF-signal from a tissue harmonic image which is not degraded by harmonic leakage. Measurements on the filtered image have shown a significant (up to 45%) increase in contrast between cancer masses and benign tissue.

  20. Computational Fluid Dynamics modeling of contrast transport in basilar aneurysms following flow-altering surgeries.

    PubMed

    Vali, Alireza; Abla, Adib A; Lawton, Michael T; Saloner, David; Rayz, Vitaliy L

    2017-01-04

    In vivo measurement of blood velocity fields and flow descriptors remains challenging due to image artifacts and limited resolution of current imaging methods; however, in vivo imaging data can be used to inform and validate patient-specific computational fluid dynamics (CFD) models. Image-based CFD can be particularly useful for planning surgical interventions in complicated cases such as fusiform aneurysms of the basilar artery, where it is crucial to alter pathological hemodynamics while preserving flow to the distal vasculature. In this study, patient-specific CFD modeling was conducted for two basilar aneurysm patients considered for surgical treatment. In addition to velocity fields, transport of contrast agent was simulated for the preoperative and postoperative conditions using two approaches. The transport of a virtual contrast passively following the flow streamlines was simulated to predict post-surgical flow regions prone to thrombus deposition. In addition, the transport of a mixture of blood with an iodine-based contrast agent was modeled to compare and verify the CFD results with X-ray angiograms. The CFD-predicted patterns of contrast flow were qualitatively compared to in vivo X-ray angiograms acquired before and after the intervention. The results suggest that the mixture modeling approach, accounting for the flow rates and properties of the contrast injection, is in better agreement with the X-ray angiography data. The virtual contrast modeling assessed the residence time based on flow patterns unaffected by the injection procedure, which makes the virtual contrast modeling approach better suited for prediction of thrombus deposition, which is not limited to the peri-procedural state.

  1. A model for oxygen-dependent backscattering spectroscopic contrast from single red blood cells (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Liu, Rongrong; Yi, Ji; Chen, Siyu; Zhang, Hao F.; Backman, Vadim

    2016-03-01

    The oxygen-dependent absorption of hemoglobin provides the fundamental contrast for all label-free techniques measuring blood oxygenation. When hemoglobin is packaged into red blood cells (RBCs), the structure of the cells creates light scattering which also depends on the absorption based on the Kramers-Kronig relationship. Thus a proper characterization of the optical behaviors of blood has been a key to any accurate measurement of blood oxygenation, particularly at the capillary level where RBCs are dispersed individually in contrast to a densely packed whole blood. Here we provided a theoretical model under Born Approximation to characterize the oxygen dependent backscattering spectroscopic contrast from single RBCs. Using this theoretical model, we conducted simulations on both oxygenated and deoxygenated single RBCs with different sizes for standard and possible deformed cell geometries in blood flow, all which suggested similar backscattering spectroscopic contrast and were confirmed by Mie Theory and experiments using visible Optical Coherence Tomography (visOCT). As long as the cell size satisfies Gaussian distribution with a coefficient variance (C.V.) large enough, there is clear absorption contrast between the backscattering spectra of oxygenated and deoxygenated single RBCs calculated by this model, so oxygen saturation can then be characterized. Thus, this theoretical model can be extended to extract absorption features of other scattering particles as long as they satisfy Born Approximation.

  2. The investigation of a relative contrast index model for fingerprint quantification.

    PubMed

    Vanderwee, Jana; Porter, Glenn; Renshaw, Adrian; Bell, Michael

    2011-01-30

    The quantification of fingerprint contrast is a relatively new concept in fingerprint enhancement research. It has emerged as a mode of fingerprint assessment to reduce the potential biased of visual qualitative assessment. Subjective qualitative methods that are currently reported in the literature include; side-by-side assessment, assigning a score to a treatment based on visible criteria and stating observed results without presenting supporting validation. These qualitative methods often do not state clearly the visual assessment parameters and produce a degree of ambiguity when defining the enhancement results. The relative contrast index model was constructed to empirically quantify the difference in contrast between fingerprint ridges and valleys, using measurements gained from a microspectrophotometer. This paper seeks to further investigate this recent research and test the model using three different microspectrophotometers. Data from these separate sources will determine whether the theoretical aspects of the model would pragmatically produce reliable and repeatable results across a range of microspectrophotometers found in forensic laboratories.

  3. Momentum transfer Monte Carlo model for the simulation of laser speckle contrast imaging (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Regan, Caitlin; Hayakawa, Carole K.; Choi, Bernard

    2016-03-01

    Laser speckle imaging (LSI) enables measurement of relative blood flow in microvasculature and perfusion in tissues. To determine the impact of tissue optical properties and perfusion dynamics on speckle contrast, we developed a computational simulation of laser speckle contrast imaging. We used a discrete absorption-weighted Monte Carlo simulation to model the transport of light in tissue. We simulated optical excitation of a uniform flat light source and tracked the momentum transfer of photons as they propagated through a simulated tissue geometry. With knowledge of the probability distribution of momentum transfer occurring in various layers of the tissue, we calculated the expected laser speckle contrast arising with coherent excitation using both reflectance and transmission geometries. We simulated light transport in a single homogeneous tissue while independently varying either absorption (.001-100mm^-1), reduced scattering (.1-10mm^-1), or anisotropy (0.05-0.99) over a range of values relevant to blood and commonly imaged tissues. We observed that contrast decreased by 49% with an increase in optical scattering, and observed a 130% increase with absorption (exposure time = 1ms). We also explored how speckle contrast was affected by the depth (0-1mm) and flow speed (0-10mm/s) of a dynamic vascular inclusion. This model of speckle contrast is important to increase our understanding of how parameters such as perfusion dynamics, vessel depth, and tissue optical properties affect laser speckle imaging.

  4. Transcriptomes and shRNA Suppressors in a TP53 Allele-specific Model of Early-onset Colon Cancer in African Americans

    PubMed Central

    Weige, Charles C.; Birtwistle, Marc R.; Mallick, Himel; Yi, Nengjun; Berrong, Zuzana; Cloessner, Emily; Duff, Keely; Tidwell, Josephine; Clendenning, Megan; Wilkerson, Brent; Farrell, Christopher; Bunz, Fred; Ji, Hao; Shtutman, Michael; Creek, Kim E.; Banister, Carolyn E.; Buckhaults, Phillip J.

    2014-01-01

    African Americans are disproportionately affected by early-onset, high-grade malignancies. A fraction of this cancer health disparity can be explained by genetic differences between individuals of African or European descent. Here the wild-type Pro/Pro genotype at the TP53Pro72Arg (P72R) polymorphism (SNP: rs1042522) is more frequent in African Americans with cancer than in African Americans without cancer (51% vs 37%), and is associated with a significant increase in the rates of cancer diagnosis in African Americans. To test the hypothesis that p53 allele-specific gene expression may contribute to African American cancer disparities, p53 hemizygous knockout variants were generated and characterized in the RKO colon carcinoma cell line, which is wild-type for p53 and heterozygous at the TP53Pro72Arg locus. Transcriptome profiling, using RNAseq, in response to the DNA-damaging agent etoposide revealed a large number of p53-regulated transcripts, but also a subset of transcripts that were TP53Pro72Arg allele specific. In addition, a shRNA-library suppressor screen for p53 allele-specific escape from p53-induced arrest was performed. Several novel RNAi suppressors of p53 were identified, one of which, PRDM1β (BLIMP-1), was confirmed to be an Arg-specific transcript. PRDM1β silences target genes by recruiting H3K9 trimethyl (H3K9me3) repressive chromatin marks, and is necessary for stem cell differentiation. These results reveal a novel model for African American cancer disparity, in which the TP53 codon 72 allele influences lifetime cancer risk by driving damaged cells to differentiation through an epigenetic mechanism involving gene silencing. Implications TP53 P72R polymorphism significantly contributes to increased African American cancer disparity. PMID:24743655

  5. Towards an Analytical Age-Dependent Model of Contrast Sensitivity Functions for an Ageing Society

    PubMed Central

    Joulan, Karine; Brémond, Roland

    2015-01-01

    The Contrast Sensitivity Function (CSF) describes how the visibility of a grating depends on the stimulus spatial frequency. Many published CSF data have demonstrated that contrast sensitivity declines with age. However, an age-dependent analytical model of the CSF is not available to date. In this paper, we propose such an analytical CSF model based on visual mechanisms, taking into account the age factor. To this end, we have extended an existing model from Barten (1999), taking into account the dependencies of this model's optical and physiological parameters on age. Age-dependent models of the cones and ganglion cells densities, the optical and neural MTF, and optical and neural noise are proposed, based on published data. The proposed age-dependent CSF is finally tested against available experimental data, with fair results. Such an age-dependent model may be beneficial when designing real-time age-dependent image coding and display applications. PMID:26078994

  6. Combined radio-colour contrast in the examination of ballistic head models.

    PubMed

    Schyma, C; Greschus, S; Urbach, H; Madea, B

    2012-07-01

    The conventional analysis of ballistic gelatine is performed by transillumination and scanning of 1-cm-thick slices. Previous research demonstrated the advantages of colour and radio contrast in gelatine for computed tomography (CT). The aim of this study was to determine whether this method could be applied to head models in order to facilitate their examination. Four head models of about 14 cm in diameter were prepared from two acryl hollow spheres and two polypropylene hollow spheres. Acryl paint was mixed with barium meal and sealed in a thin foil bag which was attached to the gelatine-filled sphere which was covered with about 3-mm-thick silicone. The head models were shot at using 9 mm × 19 expanding bullets from 4 m distance. The models were examined via multislice CT. The gelatine core was removed; the bullet track was photographed and cut into consecutive slices which were scanned optically. CT images were processed with Corel Photo-Paint. Optical and radiological images were analysed using the AxioVision software. The disruption of the gelatine within the head model was visualised by extensive distribution of paint up to the end of the finest cracks and fissures and along the whole bullet track. CT imaging with excellent radio contrast in the gelatine cracks caused by the temporary cavity allowed for multiplanar reconstruction. We conclude that the combination of colour contrast in gelatine with contrast material-enhanced CT facilitates accurate measurements in ballistic head models.

  7. Power laws for heavy-tailed distributions: modeling allele and haplotype diversity for the national marrow donor program.

    PubMed

    Slater, Noa; Louzoun, Yoram; Gragert, Loren; Maiers, Martin; Chatterjee, Ansu; Albrecht, Mark

    2015-04-01

    Measures of allele and haplotype diversity, which are fundamental properties in population genetics, often follow heavy tailed distributions. These measures are of particular interest in the field of hematopoietic stem cell transplant (HSCT). Donor/Recipient suitability for HSCT is determined by Human Leukocyte Antigen (HLA) similarity. Match predictions rely upon a precise description of HLA diversity, yet classical estimates are inaccurate given the heavy-tailed nature of the distribution. This directly affects HSCT matching and diversity measures in broader fields such as species richness. We, therefore, have developed a power-law based estimator to measure allele and haplotype diversity that accommodates heavy tails using the concepts of regular variation and occupancy distributions. Application of our estimator to 6.59 million donors in the Be The Match Registry revealed that haplotypes follow a heavy tail distribution across all ethnicities: for example, 44.65% of the European American haplotypes are represented by only 1 individual. Indeed, our discovery rate of all U.S. European American haplotypes is estimated at 23.45% based upon sampling 3.97% of the population, leaving a large number of unobserved haplotypes. Population coverage, however, is much higher at 99.4% given that 90% of European Americans carry one of the 4.5% most frequent haplotypes. Alleles were found to be less diverse suggesting the current registry represents most alleles in the population. Thus, for HSCT registries, haplotype discovery will remain high with continued recruitment to a very deep level of sampling, but population coverage will not. Finally, we compared the convergence of our power-law versus classical diversity estimators such as Capture recapture, Chao, ACE and Jackknife methods. When fit to the haplotype data, our estimator displayed favorable properties in terms of convergence (with respect to sampling depth) and accuracy (with respect to diversity estimates). This

  8. Inclusion of coherence in Monte Carlo models for simulation of x-ray phase contrast imaging.

    PubMed

    Cipiccia, Silvia; Vittoria, Fabio A; Weikum, Maria; Olivo, Alessandro; Jaroszynski, Dino A

    2014-09-22

    Interest in phase contrast imaging methods based on electromagnetic wave coherence has increased significantly recently, particularly at X-ray energies. This is giving rise to a demand for effective simulation methods. Coherent imaging approaches are usually based on wave optics, which require significant computational resources, particularly for producing 2D images. Monte Carlo (MC) methods, used to track individual particles/photons for particle physics, are not considered appropriate for describing coherence effects. Previous preliminary work has evaluated the possibility of incorporating coherence in Monte Carlo codes. However, in this paper, we present the implementation of refraction in a model that is based on time of flight calculations and the Huygens-Fresnel principle, which allow reproducing the formation of phase contrast images in partially and fully coherent experimental conditions. The model is implemented in the FLUKA Monte Carlo code and X-ray phase contrast imaging simulations are compared with experiments and wave optics calculations.

  9. Intravenous contrast media application using cone-beam computed tomography in a rabbit model

    PubMed Central

    Kim, Min-Sung; Kim, Bok-Yeol; Choi, Hwa-Young; Choi, Yoon-Joo; Oh, Song-Hee; Kang, Ju-Hee; Lee, Sae-Rom; Kang, Ju-Han; Kim, Gyu-Tae; Choi, Yong-Suk

    2015-01-01

    Purpose This study was performed to evaluate the feasibility of visualizing soft tissue lesions and vascular structures using contrast-enhanced cone-beam computed tomography (CE-CBCT) after the intravenous administration of a contrast medium in an animal model. Materials and Methods CBCT was performed on six rabbits after a contrast medium was administered using an injection dose of 2 mL/kg body weight and an injection rate of 1 mL/s via the ear vein or femoral vein under general anesthesia. Artificial soft tissue lesions were created through the transplantation of autologous fatty tissue into the salivary gland. Volume rendering reconstruction, maximum intensity projection, and multiplanar reconstruction images were reconstructed and evaluated in order to visualize soft tissue contrast and vascular structures. Results The contrast enhancement of soft tissue was possible using all contrast medium injection parameters. An adequate contrast medium injection parameter for facilitating effective CE-CBCT was a 5-mL injection before exposure combined with a continuous 5-mL injection during scanning. Artificial soft tissue lesions were successfully created in the animals. The CE-CBCT images demonstrated adequate opacification of the soft tissues and vascular structures. Conclusion Despite limited soft tissue resolution, the opacification of vascular structures was observed and artificial soft tissue lesions were visualized with sufficient contrast to the surrounding structures. The vascular structures and soft tissue lesions appeared well delineated in the CE-CBCT images, which was probably due to the superior spatial resolution of CE-CBCT compared to other techniques, such as multislice computed tomography. PMID:25793181

  10. Quantitative evaluation of mucosal vascular contrast in narrow band imaging using Monte Carlo modeling

    NASA Astrophysics Data System (ADS)

    Le, Du; Wang, Quanzeng; Ramella-Roman, Jessica; Pfefer, Joshua

    2012-06-01

    Narrow-band imaging (NBI) is a spectrally-selective reflectance imaging technique for enhanced visualization of superficial vasculature. Prior clinical studies have indicated NBI's potential for detection of vasculature abnormalities associated with gastrointestinal mucosal neoplasia. While the basic mechanisms behind the increased vessel contrast - hemoglobin absorption and tissue scattering - are known, a quantitative understanding of the effect of tissue and device parameters has not been achieved. In this investigation, we developed and implemented a numerical model of light propagation that simulates NBI reflectance distributions. This was accomplished by incorporating mucosal tissue layers and vessel-like structures in a voxel-based Monte Carlo algorithm. Epithelial and mucosal layers as well as blood vessels were defined using wavelength-specific optical properties. The model was implemented to calculate reflectance distributions and vessel contrast values as a function of vessel depth (0.05 to 0.50 mm) and diameter (0.01 to 0.10 mm). These relationships were determined for NBI wavelengths of 410 nm and 540 nm, as well as broadband illumination common to standard endoscopic imaging. The effects of illumination bandwidth on vessel contrast were also simulated. Our results provide a quantitative analysis of the effect of absorption and scattering on vessel contrast. Additional insights and potential approaches for improving NBI system contrast are discussed.

  11. TSCALE: A New Multidimensional Scaling Procedure Based on Tversky's Contrast Model.

    ERIC Educational Resources Information Center

    DeSarbo, Wayne S.; And Others

    1992-01-01

    TSCALE, a multidimensional scaling procedure based on the contrast model of A. Tversky for asymmetric three-way, two-mode proximity data, is presented. TSCALE conceptualizes a latent dimensional structure to describe the judgmental stimuli. A Monte Carlo analysis and two consumer psychology applications illustrate the procedure. (SLD)

  12. The Effectiveness of Ferritin as a Contrast Agent for Cell Tracking MRI in Mouse Cancer Models

    PubMed Central

    Lee, Chan Wha; Choi, Sun Il; Lee, Sang Jin; Oh, Young Taek; Park, Gunwoo; Park, Na Yeon; Yoon, Kyoung-Ah; Kim, Sunshin; Suh, Jin-Suck

    2017-01-01

    Purpose We aimed to investigate the effectiveness of ferritin as a contrast agent and a potential reporter gene for tracking tumor cells or macrophages in mouse cancer models. Materials and Methods Adenoviral human ferritin heavy chain (Ad-hFTH) was administrated to orthotopic glioma models and subcutaneous colon cancer mouse models using U87MG and HCT116 cells, respectively. Brain MR images were acquired before and daily for up to 6 days after the intracranial injection of Ad-hFTH. In the HCT116 tumor model, MR examinations were performed before and at 6, 24, and 48 h after intratumoral injection of Ad-hFTH, as well as before and every two days after intravenous injection of ferritin-labeled macrophages. The contrast effect of ferritin in vitro was measured by MR imaging of cell pellets. MRI examinations using a 7T MR scanner comprised a T1-weighted (T1w) spin-echo sequence, T2-weighted (T2w) relaxation enhancement sequence, and T2*-weighted (T2*w) fast low angle shot sequence. Results Cell pellet imaging of Ad-hFTH in vitro showed a strong negatively enhanced contrast in T2w and T2*w images, presenting with darker signal intensity in high concentrations of Fe. T2w images of glioma and subcutaneous HCT116 tumor models showed a dark signal intensity around or within the Ad-hFTH tumor, which was distinct with time and apparent in T2*w images. After injection of ferritin-labeled macrophages, negative contrast enhancement was identified within the tumor. Conclusion Ferritin could be a good candidate as an endogenous MR contrast agent and a potential reporter gene that is capable of maintaining cell labeling stability and cellular safety. PMID:27873495

  13. Idealized Land-sea Warming Contrast Experiments with Two Global Circulation Models: Preliminary results

    NASA Astrophysics Data System (ADS)

    Kim, J. E. E.; Lee, J. L.; Hong, S. Y.

    2014-12-01

    Simulations of warming climates with climate models have pointed out that land surface temperatures will increase more rapidly than sea surface temperature (SST), which is known as the "land-sea warming contrast". We investigate the response of a zonally symmetric atmosphere to robust land-sea surface warming contrast using two global circulation models (GCMs): Non-hydrostatic Icosahedral Model (NIM) and Global and Regional Integrated Model system (GRIMs). NIM is a Finite-volume icosahedral model developed as a next-generation operational model at National Oceanic and Atmospheric Administration Earth System Research Laboratory (NOAA ESRL). Full model physics were taken from Model for Prediction Across Scales (MPAS) physics suite. GRIMs is a spectral model which has been developed in Korea (Hong et al., 2013, APJAS). It has flexibility for selection of comparable physics options with NIM. Two sets of experiments are designed: one is the control experiment with zonally-symmetric distributions with maxima at the equator and varying off-equatorial temperature gradients on ocean and land. The other experiment will impose the land/sea warming ratio of 1.5. Since two models can be set up with identical physics parameterizations, general consensus on responses and model-dependent feedback can be suggested.

  14. Wavefront Amplitude Variation of TPF's High Contrast Imaging Testbed: Modeling and Experiment

    NASA Technical Reports Server (NTRS)

    Shi, Fang; Lowman, Andrew E.; Moody, Dwight C.; Niessner, Albert F.; Trauger, John T.

    2005-01-01

    Knowledge of wavefront amplitude is as important as the knowledge of phase for a coronagraphic high contrast imaging system. Efforts have been made to understand various contributions of the amplitude variation in Terrestrial Planet Finder's (TPF) High Contrast Imaging Testbed (HCIT). Modeling of HCIT with as-built mirror surfaces has shown an amplitude variation of 1.3% due to the phase-amplitude mixing for the testbed's front-end optics. Experimental measurements on the testbed have shown the amplitude variation is about 2.5% with the testbed's illumination pattern has a major contribution as the low order amplitude variation.

  15. Stochastic modelling of shifts in allele frequencies reveals a strongly polygynous mating system in the re-introduced Asiatic wild ass.

    PubMed

    Renan, Sharon; Greenbaum, Gili; Shahar, Naama; Templeton, Alan R; Bouskila, Amos; Bar-David, Shirli

    2015-04-01

    Small populations are prone to loss of genetic variation and hence to a reduction in their evolutionary potential. Therefore, studying the mating system of small populations and its potential effects on genetic drift and genetic diversity is of high importance for their viability assessments. The traditional method for studying genetic mating systems is paternity analysis. Yet, as small populations are often rare and elusive, the genetic data required for paternity analysis are frequently unavailable. The endangered Asiatic wild ass (Equus hemionus), like all equids, displays a behaviourally polygynous mating system; however, the level of polygyny has never been measured genetically in wild equids. Combining noninvasive genetic data with stochastic modelling of shifts in allele frequencies, we developed an alternative approach to paternity analysis for studying the genetic mating system of the re-introduced Asiatic wild ass in the Negev Desert, Israel. We compared the shifts in allele frequencies (as a measure of genetic drift) that have occurred in the wild ass population since re-introduction onset to simulated scenarios under different proportions of mating males. We revealed a strongly polygynous mating system in which less than 25% of all males participate in the mating process each generation. This strongly polygynous mating system and its potential effect on the re-introduced population's genetic diversity could have significant consequences for the long-term persistence of the population in the Negev. The stochastic modelling approach and the use of allele-frequency shifts can be further applied to systems that are affected by genetic drift and for which genetic data are limited.

  16. Maxwell rheological model for lipid-shelled ultrasound microbubble contrast agents.

    PubMed

    Doinikov, Alexander A; Dayton, Paul A

    2007-06-01

    The present paper proposes a model that describes the encapsulation of microbubble contrast agents by the linear Maxwell constitutive equation. The model also incorporates the translational motion of contrast agent microbubbles and takes into account radiation losses due to the compressibility of the surrounding liquid. To establish physical features of the proposed model, comparative analysis is performed between this model and two existing models, one of which treats the encapsulation as a viscoelastic solid following the Kelvin-Voigt constitutive equation and the other assumes that the encapsulating layer behaves as a viscous Newtonian fluid. Resonance frequencies, damping coefficients, and scattering cross sections for the three shell models are compared in the regime of linear oscillation. Translational displacements predicted by the three shell models are examined by numerically calculating the general, nonlinearized equations of motion for weakly nonlinear excitation. Analogous results for free bubbles are also presented as a basis to which calculations made for encapsulated bubbles can be related. It is shown that the Maxwell shell model possesses specific physical features that are unavailable in the two other models.

  17. Numerical Modeling of 3-D Dynamics of Ultrasound Contrast Agent Microbubbles Using the Boundary Integral Method

    NASA Astrophysics Data System (ADS)

    Calvisi, Michael; Manmi, Kawa; Wang, Qianxi

    2014-11-01

    Ultrasound contrast agents (UCAs) are microbubbles stabilized with a shell typically of lipid, polymer, or protein and are emerging as a unique tool for noninvasive therapies ranging from gene delivery to tumor ablation. The nonspherical dynamics of contrast agents are thought to play an important role in both diagnostic and therapeutic applications, for example, causing the emission of subharmonic frequency components and enhancing the uptake of therapeutic agents across cell membranes and tissue interfaces. A three-dimensional model for nonspherical contrast agent dynamics based on the boundary integral method is presented. The effects of the encapsulating shell are approximated by adapting Hoff's model for thin-shell, spherical contrast agents to the nonspherical case. A high-quality mesh of the bubble surface is maintained by implementing a hybrid approach of the Lagrangian method and elastic mesh technique. Numerical analyses for the dynamics of UCAs in an infinite liquid and near a rigid wall are performed in parameter regimes of clinical relevance. The results show that the presence of a coating significantly reduces the oscillation amplitude and period, increases the ultrasound pressure amplitude required to incite jetting, and reduces the jet width and velocity.

  18. Low contrast detectability performance of model observers based on CT phantom images: kVp influence.

    PubMed

    Hernandez-Giron, I; Calzado, A; Geleijns, J; Joemai, R M S; Veldkamp, W J H

    2015-11-01

    This paper studies low contrast detectability (LCD) performance of two model observers in CT phantom images acquired at different kVp levels and compares the results with humans in a 2-alternative forced choice experiment (2-AFC). Images of the Catphan phantom with objects of different contrasts (0.5 and 1%) and diameters (2-15 mm) were acquired in an Aquilion ONE 320-detector row CT (Toshiba Medical Systems, Tokyo, Japan), in two experiments, selecting (80-100-120-135 kV) with fixed mAs and varying the mAs to keep the dose constant, respectively. Four human observers evaluated the objects visibility obtaining a proportion correct (PC) for each case. LCD was also analyzed with two model observers (non-prewhitening matched filter with an eye filter, NPWE, and channelized Hotelling observer with Gabor channels, CHO). Object contrast was affected by kV, with differences up to 17% between the lowest and highest kV. Both models overestimated human performance and were corrected by efficiency and internal noise factors. The NPWE model reproduced better the human PC values trends showing Pearson's correlation coefficients ≥0.976 (0.954-0.987, 95% CI) for both experiments, whereas for CHO they were ≥0.706 (0.493-0.839). Bland-Altman plots showed better agreement between NPWE and humans being the average difference Δ and the range of the differences Δ±2σ (σ, standard deviation) of Δ=-0.3%, Δ±2σ = [-4.0%,4.5%]. For CHO, Δ=-1.2%, Δ± 2σ= [-10.7%,8.3%]. The NPWE model can be a useful tool to predict human performance in CT low contrast detection tasks in a standard phantom and be potentially used in protocol optimization based on kV selection.

  19. Modeling the effects of distortion, contrast, and signal-to-noise ratio on stereophotogrammetric range mapping

    NASA Astrophysics Data System (ADS)

    Sellar, R. Glenn; Deen, Robert G.; Huffman, William C.; Willson, Reginald G.

    2016-09-01

    Stereophotogrammetry typically employs a pair of cameras, or a single moving camera, to acquire pairs of images from different camera positions, in order to create a three dimensional `range map' of the area being observed. Applications of this technique for building three-dimensional shape models include aerial surveying, remote sensing, machine vision, and robotics. Factors that would be expected to affect the quality of the range maps include the projection function (distortion) of the lenses and the contrast (modulation) and signal-to-noise ratio (SNR) of the acquired image pairs. Basic models of the precision with which the range can be measured assume a pinhole-camera model of the geometry, i.e. that the lenses provide perspective projection with zero distortion. Very-wide-angle or `fisheye' lenses, however (for e.g. those used by robotic vehicles) typically exhibit projection functions that differ significantly from this assumption. To predict the stereophotogrammetric range precision for such applications, we extend the model to the case of an equidistant lens projection function suitable for a very-wide-angle lens. To predict the effects of contrast and SNR on range precision, we perform numerical simulations using stereo image pairs acquired by a stereo camera pair on NASA's Mars rover Curiosity. Contrast is degraded and noise is added to these data in a controlled fashion and the effects on the quality of the resulting range maps are assessed.

  20. Anthropomorphic model observer performance in three-dimensional detection task for low-contrast computed tomography.

    PubMed

    Ba, Alexandre; Eckstein, Miguel P; Racine, Damien; Ott, Julien G; Verdun, Francis; Kobbe-Schmidt, Sabine; Bochud, François O

    2016-01-01

    X-ray medical imaging is increasingly becoming three-dimensional (3-D). The dose to the population and its management are of special concern in computed tomography (CT). Task-based methods with model observers to assess the dose-image quality trade-off are promising tools, but they still need to be validated for real volumetric images. The purpose of the present work is to evaluate anthropomorphic model observers in 3-D detection tasks for low-contrast CT images. We scanned a low-contrast phantom containing four types of signals at three dose levels and used two reconstruction algorithms. We implemented a multislice model observer based on the channelized Hotelling observer (msCHO) with anthropomorphic channels and investigated different internal noise methods. We found a good correlation for all tested model observers. These results suggest that the msCHO can be used as a relevant task-based method to evaluate low-contrast detection for CT and optimize scan protocols to lower dose in an efficient way.

  1. Initial invasion of gametophytic self-incompatibility alleles in the absence of tight linkage between pollen and pistil S alleles.

    PubMed

    Sakai, Satoki; Wakoh, Haluka

    2014-08-01

    In homomorphic self-incompatibility (SI) systems of plants, the loci controlling the pollen and pistil types are tightly linked, and this prevents the generation of compatible combinations of alleles expressing pollen and pistil types, which would result in self-fertilization. We modeled the initial invasion of the first pollen and pistil alleles in gametophytic SI to determine whether these alleles can stably coexist in a population without tight linkage. We assume pollen and pistil loci each carry an incompatibility allele S and an allele without an incompatibility function N. We assume that pollen with an S allele are incompatible with pistils carrying S alleles, whereas other crosses are compatible. Ovules in pistils carrying an S allele suffer viability costs because recognition consumes resources. We found that the cost of carrying a pistil S allele allows pollen and pistil S alleles to coexist in a stable equilibrium if linkage is partial. This occurs because parents that carry pistil S alleles but are homozygous for pollen N alleles cannot avoid self-fertilization; however, they suffer viability costs. Hence, pollen N alleles are selected again. When pollen and pistil S alleles can coexist in a polymorphic equilibrium, selection will favor tighter linkage.

  2. Low-contrast photoresist development model for OPC application at 10nm node

    NASA Astrophysics Data System (ADS)

    Wu, Cheng-En; Wei, David; Zhang, Charlie; Song, Hua

    2015-03-01

    The Optical Proximity Correction (OPC) model, a key to process yield in the mask synthesis flow, is getting more and more complicated and challenging at advanced technology nodes (1X nm). To achieve accurate critical dimension (CD) prediction and model robustness on varied designed patterns, a rigorously tuned compact model (RTCM) [1] that takes the photoresist chemical effects into considerations is strongly desired. A lithography process consists of three main stages: Exposure, Post-Exposure Bake (PEB), and Photoresist Development. Each stage is characterized by its fundamental physics or chemistry that governs the process of illumination induced photo-acid generation, thermally activated chemical reaction-diffusion, and developer dependent photoresist dissolution, respectively. The final resist profile is determined by the process details of all these stages directly or indirectly. For an ideal resist that the development contrast approaches infinity, resist development is aptly represented by a threshold model applied to the PEB latent image (acid or inhibitor concentration). So the quality of OPC modeling is largely determined by the fidelity of PEB latent image [2,3]. However, for some types of resist and developer used in Negative Tone Development (NTD), the development contrast shows a long tail without a sharp transition. For such low-contrast resist, the developed resist profile is no longer described well by the equilevel surface of PEB latent image. Going beyond the threshold approximation, we start from the fundamental equations of resist development physics and analyze the time evolution of development front that determines the resist profile. In this paper, a new compact model is derived to catch the main physics in resist Development, which is also simple and computationally efficient to suit for OPC applications. Comparison with S-LITHO rigorous solutions and real-wafer experiments with 1D and 2D test patterns have showed that the new compact model

  3. Development and evaluation of a 3D model observer with nonlinear spatiotemporal contrast sensitivity

    NASA Astrophysics Data System (ADS)

    Avanaki, Ali R. N.; Espig, Kathryn S.; Maidment, Andrew D. A.; Marchessoux, Cedric; Bakic, Predrag R.; Kimpe, Tom R. L.

    2014-03-01

    We investigate improvements to our 3D model observer with the goal of better matching human observer performance as a function of viewing distance, effective contrast, maximum luminance, and browsing speed. Two nonlinear methods of applying the human contrast sensitivity function (CSF) to a 3D model observer are proposed, namely the Probability Map (PM) and Monte Carlo (MC) methods. In the PM method, the visibility probability for each frequency component of the image stack, p, is calculated taking into account Barten's spatiotemporal CSF, the component modulation, and the human psychometric function. The probability p is considered to be equal to the perceived amplitude of the frequency component and thus can be used by a traditional model observer (e.g., LG-msCHO) in the space-time domain. In the MC method, each component is randomly kept with probability p or discarded with 1-p. The amplitude of the retained components is normalized to unity. The methods were tested using DBT stacks of an anthropomorphic breast phantom processed in a comprehensive simulation pipeline. Our experiments indicate that both the PM and MC methods yield results that match human observer performance better than the linear filtering method as a function of viewing distance, effective contrast, maximum luminance, and browsing speed.

  4. New hypothesis elucidates self-incompatibility in the olive tree regarding S-alleles dominance relationships as in the sporophytic model.

    PubMed

    Breton, Catherine M; Bervillé, André

    2012-09-01

    Most olive varieties are not strictly self-incompatible, nevertheless, they request foreign pollen to enhance fruit yield, and consequently orchards should contain pollinisers to ensure fruit set of the main variety. The best way to choose pollinisers is to experiment numerous crosses in a diallel design. Here, the genetic mode of inheritance of SI in the olive is deciphered and it does not correspond to the GSI type, but to the SSI type. It leaves S-allele dominance relationship expression in the male (pollen and pollen tube), but not in the female (stigma and style). Thus, a pair-wise combination of varieties may be inter-compatible in one direction (male to female, or female to male) and inter-incompatible in the other direction. Dominance relationships also explain different levels of self-pollination observed in varieties. Little efficient pollinisers were found and predicted in varieties; nevertheless, some new efficient pair-wise allele combinations are predicted and could be created. This model enables one to forecast compatibility without waiting for several years of yield records and to choose pollinisers in silico.

  5. Allelic genealogies in sporophytic self-incompatibility systems in plants.

    PubMed Central

    Schierup, M H; Vekemans, X; Christiansen, F B

    1998-01-01

    Expectations for the time scale and structure of allelic genealogies in finite populations are formed under three models of sporophytic self-incompatibility. The models differ in the dominance interactions among the alleles that determine the self-incompatibility phenotype: In the SSIcod model, alleles act codominantly in both pollen and style, in the SSIdom model, alleles form a dominance hierarchy, and in SSIdomcod, alleles are codominant in the style and show a dominance hierarchy in the pollen. Coalescence times of alleles rarely differ more than threefold from those under gametophytic self-incompatibility, and transspecific polymorphism is therefore expected to be equally common. The previously reported directional turnover process of alleles in the SSIdomcod model results in coalescence times lower and substitution rates higher than those in the other models. The SSIdom model assumes strong asymmetries in allelic action, and the most recessive extant allele is likely to be the most recent common ancestor. Despite these asymmetries, the expected shape of the allele genealogies does not deviate markedly from the shape of a neutral gene genealogy. The application of the results to sequence surveys of alleles, including interspecific comparisons, is discussed. PMID:9799270

  6. A novel protective formulation of Palmitoylethanolamide in experimental model of contrast agent induced nephropathy.

    PubMed

    Cordaro, M; Impellizzeri, D; Bruschetta, G; Siracusa, R; Crupi, R; Di Paola, R; Esposito, E; Cuzzocrea, S

    2016-01-05

    Contrast-induced nephropathy (CIN) is a complication in patients after administration of iodinated contrast media. Several risk factors contribute to the development and progression of CIN, including hypertension, diabetes, and dyslipidemia. Animal models of CIN by surgical intervention to reproduce its clinical and pathology has been developed, and thus, therapeutic methods tested. Palmitoylethanolamide (PEA) is a member of the fatty acid ethanolamine family with analgesic and anti-inflammatory effects. In this study, we analyzed streptozotocin-induced diabetes model and in an another set of experiment a surgical remotion of the kidney with the aim of evaluating effect of ultramicronized Palmitoylethanolamide (PEA-um(®)) on contrast induced renal disfunction and glomerular morphology alteration. In a first step of our study, we demonstrated that PEA-um(®) significantly reduced CIN-mediated glomerular dysfunction, modulates Na(+) and K(+) levels in plasma and decreased urine and plasma NGAL levels and α-GST urine levels. Moreover, in a second set of experiment we investigated how PEA-um(®) reduced creatinine and BUN plasma levels after nephrectomy, ameliorate renal and medullary blood flow and re-established renal parenchymal after CIN induction as well as after nephrectomy. Take together our results demonstrated that PEA-um(®) are able to preventing CIN in diabetic rats and alteration of biochemical parameters after nephrectomy.

  7. Optically tunable nanoparticle contrast agents for early cancer detection: model-based analysis of gold nanoshells.

    PubMed

    Lin, Alex W H; Lewinski, Nastassja A; West, Jennifer L; Halas, Naomi J; Drezek, Rebekah A

    2005-01-01

    Many optical diagnostic approaches rely on changes in scattering and absorption properties to generate optical contrast between normal and diseased tissue. Recently, there has been increasing interest in using exogenous agents to enhance this intrinsic contrast with particular emphasis on the development for targeting specific molecular features of disease. Gold nanoshells are a class of core-shell nanoparticles with an extremely tunable peak optical resonance ranging from the near-UV to the mid-IR wavelengths. Using current chemistries, nanoshells of a wide variety of core and shell sizes can easily be fabricated to scatter and/or absorb light with optical cross sections often several times larger than the geometric cross section. Using gold nanoshells of different size and optical parameters, we employ Monte Carlo models to predict the effect of varying concentrations of nanoshells on tissue reflectance. The models demonstrate the importance of absorption from the nanoshells on remitted signals even when the optical extinction is dominated by scattering. Furthermore, because of the strong optical response of nanoshells, a considerable change in reflectance is observed with only a very small concentration of nanoshells. Characterizing the optical behavior of gold nanoshells in tissue will aid in developing nanoshells as contrast agents for optical diagnostics.

  8. Low contrast detectability in CT for human and model observers in multi-slice data sets

    NASA Astrophysics Data System (ADS)

    Ba, Alexandre; Racine, Damien; Ott, Julien G.; Verdun, Francis R.; Kobbe-Schmidt, Sabine; Eckstein, Miguel P.; Bochud, Francois O.

    2015-03-01

    Task-based medical image quality is often assessed by model observers for single slice images. The goal of the study was to determine if model observers can predict human detection performance of low contrast signals in CT for clinical multi-slice (ms) images. We collected 24 different data subsets from a low contrast phantom: 3 dose levels (40, 90, 150 mAs), 4 signals (6 and 8 mm diameter; 10 and 20 HU at 120kV) and 2 reconstruction algorithms (FBP and iterative (IR)). Images were assessed by human and model observers in 4-alternative forced choice (4AFC) experiments with ms data set in a signal-known-exactly (SKE) paradigm. Model observers with single (msCHOa) and multiple (msCHOb) templates were implemented in a train and test method analysis with Dense Difference of Gaussian (DDoG) and Gabor spatial channels. For human observers, we found that percent correct increased with the dose and was higher for iterative reconstructed images than FBP in all investigated conditions. All model observers implemented overestimated human performance in any condition except one case (6mm and 10HU) for msCHOa and msCHOb with Gabor channels. Internal noise could be implemented and a good agreement was found but necessitates independent fits according to the reconstruction method. Generally msCHOb shows higher detection performance than msCHOa with both types of channels. Gabor channels were less efficient than DDoG in this context. These results allow further developments in 3D analysis technique for low contrast CT.

  9. Assessment of wind power potential for two contrasting coastlines of South Africa using a numerical model

    SciTech Connect

    Diab, R.D.; Garstang, M.

    1984-12-01

    At two-dimensional numerical model is used to predict near surface wind velocities, and consequently wind power, for five distinct synoptic regines for contrasting east and west coasts of South Africa. The model results suggest that no one solution for optimizing a wid generatot location would safisfy both coastlines owing to their differing characteristics. On the east coast, the most favorable location is approximately 55 km inland on the high-lying terrain, whereas on the west coast the best location is generally about 10 km offshore. The application of the two-dimesional form of a primitive equation model in areas where the topography and the coastline are in accordance with model constraints is shown to provide a useful framework for measurements and analysis of the potential wind power of a such a region.

  10. Transferability of hydrological models and ensemble averaging methods between contrasting climatic periods

    NASA Astrophysics Data System (ADS)

    Broderick, Ciaran; Matthews, Tom; Wilby, Robert L.; Bastola, Satish; Murphy, Conor

    2016-10-01

    Understanding hydrological model predictive capabilities under contrasting climate conditions enables more robust decision making. Using Differential Split Sample Testing (DSST), we analyze the performance of six hydrological models for 37 Irish catchments under climate conditions unlike those used for model training. Additionally, we consider four ensemble averaging techniques when examining interperiod transferability. DSST is conducted using 2/3 year noncontinuous blocks of (i) the wettest/driest years on record based on precipitation totals and (ii) years with a more/less pronounced seasonal precipitation regime. Model transferability between contrasting regimes was found to vary depending on the testing scenario, catchment, and evaluation criteria considered. As expected, the ensemble average outperformed most individual ensemble members. However, averaging techniques differed considerably in the number of times they surpassed the best individual model member. Bayesian Model Averaging (BMA) and the Granger-Ramanathan Averaging (GRA) method were found to outperform the simple arithmetic mean (SAM) and Akaike Information Criteria Averaging (AICA). Here GRA performed better than the best individual model in 51%-86% of cases (according to the Nash-Sutcliffe criterion). When assessing model predictive skill under climate change conditions we recommend (i) setting up DSST to select the best available analogues of expected annual mean and seasonal climate conditions; (ii) applying multiple performance criteria; (iii) testing transferability using a diverse set of catchments; and (iv) using a multimodel ensemble in conjunction with an appropriate averaging technique. Given the computational efficiency and performance of GRA relative to BMA, the former is recommended as the preferred ensemble averaging technique for climate assessment.

  11. Kidney injury biomarkers in hypertensive, diabetic, and nephropathy rat models treated with contrast media.

    PubMed

    Rouse, Rodney L; Stewart, Sharron R; Thompson, Karol L; Zhang, Jun

    2013-01-01

    Contrast-induced nephropathy (CIN) refers to a decline in renal function following exposure to iodinated contrast media (CM). The present study was initiated to explore the role of known human risk factors (spontaneous hypertension, diabetes, protein-losing nephropathy) on CIN development in rodent models and to determine the effect of CM administration on kidney injury biomarkers in the face of preexisting kidney injury. Spontaneously hypertensive rats (hypertension), streptozotocin-treated Sprague Dawley rats (diabetes), and Dahl salt-sensitive rats (protein-losing nephropathy) were given single intravenous injections of the nonionic, low osmolar contrast medium, iohexol. Blood urea nitrogen (BUN), serum creatinine (sCr), and urinary biomarkers; albumin, lipocalin 2 (Lcn-2), osteopontin (Opn), kidney injury molecule 1 (Kim-1), renal papillary antigen 1 (Rpa-1), α-glutathione S-transferase (α-Gst), µ-glutathione S-transferase (µ-Gst), and beta-2 microglobulin (β2m) were measured in disease models and appropriate controls to determine the response of these biomarkers to CM administration. Each disease model produced elevated biomarkers of kidney injury without CM. Preexisting histopathology was exacerbated by CM but little or no significant increases in biomarkers were observed. When 1.5-fold or greater sCr increases from pre-CM were used to define true positives, receiver-operating characteristic curve analysis of biomarker performance showed sCr was the best predictor of CIN across disease models. β2m, Lcn-2, and BUN were the best predictors of histopathology defined kidney injury.

  12. Penetrance of craniofacial anomalies in mouse models of Smith-Magenis syndrome is modified by genomic sequence surrounding Rai1: not all null alleles are alike.

    PubMed

    Yan, Jiong; Bi, Weimin; Lupski, James R

    2007-03-01

    Craniofacial abnormality is one of the major clinical manifestations of Smith-Magenis syndrome (SMS). Previous analyses in a mixed genetic background of several SMS mouse models--including Df(11)17/+ and Df(11)17-1/+, which have 2-Mb and 590-kb deletions, respectively, and Rai1(-/+)--revealed that the penetrance of the craniofacial phenotype appears to be influenced by deletion size and genetic background. We generated an additional strain with a 1-Mb deletion intermediate in size between the two described above. Remarkably, the penetrance of its craniofacial anomalies in the mixed background was between those of Df(11)17 and Df(11)17-1. We further analyzed the deletion mutations and the Rai1(-/+) allele in a pure C57BL/6 background, to control for nonlinked modifier loci. The penetrance of the craniofacial anomalies was markedly increased for all the strains in comparison with the mixed background. Mice with Df(11)17 and Df(11)17-1 deletions had a similar penetrance, suggesting that penetrance may be less influenced by deletion size, whereas that of Rai1(-/+) mice was significantly lower than that of the deletion strains. We hypothesize that potential trans-regulatory sequence(s) or gene(s) that reside within the 590-kb genomic interval surrounding Rai1 are the major modifying genetic element(s) affecting the craniofacial penetrance. Moreover, we confirmed the influence of genetic background and different deletion sizes on the phenotype. The complicated control of the penetrance for one phenotype in SMS mouse models provides tools to elucidate molecular mechanisms for penetrance and clearly shows that a null allele caused by chromosomal deletion can have different phenotypic consequences than one caused by gene inactivation.

  13. Model-based pancreas segmentation in portal venous phase contrast-enhanced CT images.

    PubMed

    Hammon, Matthias; Cavallaro, Alexander; Erdt, Marius; Dankerl, Peter; Kirschner, Matthias; Drechsler, Klaus; Wesarg, Stefan; Uder, Michael; Janka, Rolf

    2013-12-01

    This study aims to automatically detect and segment the pancreas in portal venous phase contrast-enhanced computed tomography (CT) images. The institutional review board of the University of Erlangen-Nuremberg approved this study and waived the need for informed consent. Discriminative learning is used to build a pancreas tissue classifier incorporating spatial relationships between the pancreas and surrounding organs and vessels. Furthermore, discrete cosine and wavelet transforms are used to build texture features to describe local tissue appearance. Classification is used to guide a constrained statistical shape model to fit the data. The algorithm to detect and segment the pancreas was evaluated on 40 consecutive CT data that were acquired in the portal venous contrast agent phase. Manual segmentation of the pancreas was carried out by experienced radiologists and served as reference standard. Threefold cross validation was performed. The algorithm-based detection and segmentation yielded an average surface distance of 1.7 mm and an average overlap of 61.2 % compared with the reference standard. The overall runtime of the system was 20.4 min. The presented novel approach enables automatic pancreas segmentation in portal venous phase contrast-enhanced CT images which are included in almost every clinical routine abdominal CT examination. Reliable pancreatic segmentation is crucial for computer-aided detection systems and an organ-specific decision support.

  14. Carnitine Palmitoyltransferase 1B 531K Allele Carriers Sustain a Higher Respiratory Quotient after Aerobic Exercise, but β3-Adrenoceptor 64R Allele Does Not Affect Lipolysis: A Human Model

    PubMed Central

    Gómez-Gómez, Eduardo; Ríos-Martínez, Martín Efrén; Castro-Rodríguez, Elena Margarita; Del-Toro-Equíhua, Mario; Ramírez-Flores, Mario; Delgado-Enciso, Ivan; Pérez-Huitimea, Ana Lilia; Baltazar-Rodríguez, Luz Margarita; Velasco-Pineda, Gilberto; Muñiz-Murguía, Jesús

    2014-01-01

    Carnitine palmitoyltransferase IB (CPT1B) and adrenoceptor beta-3 (ADRB3) are critical regulators of fat metabolism. CPT1B transports free acyl groups into mitochondria for oxidation, and ADRB3 triggers lipolysis in adipocytes, and their respective polymorphisms E531K and W64R have been identified as indicators of obesity in population studies. It is therefore important to understand the effects of these mutations on ADRB3 and CPT1B function in adipose and skeletal muscle tissue, respectively. This study aimed to analyze the rate of lipolysis of plasma indicators (glycerol, free fatty acids, and beta hydroxybutyrate) and fat oxidation (through the non-protein respiratory quotient). These parameters were measured in 37 participants during 30 min of aerobic exercise at approximately 62% of maximal oxygen uptake, followed by 30 min of recovery. During recovery, mean respiratory quotient values were higher in K allele carriers than in non-carriers, indicating low post-exercise fatty acid oxidation rates. No significant differences in lipolysis or lipid oxidation were observed between R and W allele carriers of ADRB3 at any time during the aerobic load. The substitution of glutamic acid at position 531 by lysine in the CPT1B protein decreases the mitochondrial beta-oxidation pathway, which increases the non-protein respiratory quotient value during recovery from exercise. This may contribute to weight gain or reduced weight-loss following exercise. PMID:24905907

  15. Carnitine palmitoyltransferase 1B 531K allele carriers sustain a higher respiratory quotient after aerobic exercise, but β3-adrenoceptor 64R allele does not affect lipolysis: a human model.

    PubMed

    Gómez-Gómez, Eduardo; Ríos-Martínez, Martín Efrén; Castro-Rodríguez, Elena Margarita; Del-Toro-Equíhua, Mario; Ramírez-Flores, Mario; Delgado-Enciso, Ivan; Pérez-Huitimea, Ana Lilia; Baltazar-Rodríguez, Luz Margarita; Velasco-Pineda, Gilberto; Muñiz-Murguía, Jesús

    2014-01-01

    Carnitine palmitoyltransferase IB (CPT1B) and adrenoceptor beta-3 (ADRB3) are critical regulators of fat metabolism. CPT1B transports free acyl groups into mitochondria for oxidation, and ADRB3 triggers lipolysis in adipocytes, and their respective polymorphisms E531K and W64R have been identified as indicators of obesity in population studies. It is therefore important to understand the effects of these mutations on ADRB3 and CPT1B function in adipose and skeletal muscle tissue, respectively. This study aimed to analyze the rate of lipolysis of plasma indicators (glycerol, free fatty acids, and beta hydroxybutyrate) and fat oxidation (through the non-protein respiratory quotient). These parameters were measured in 37 participants during 30 min of aerobic exercise at approximately 62% of maximal oxygen uptake, followed by 30 min of recovery. During recovery, mean respiratory quotient values were higher in K allele carriers than in non-carriers, indicating low post-exercise fatty acid oxidation rates. No significant differences in lipolysis or lipid oxidation were observed between R and W allele carriers of ADRB3 at any time during the aerobic load. The substitution of glutamic acid at position 531 by lysine in the CPT1B protein decreases the mitochondrial beta-oxidation pathway, which increases the non-protein respiratory quotient value during recovery from exercise. This may contribute to weight gain or reduced weight-loss following exercise.

  16. Monte Carlo modeling of converging small-field contrast-enhanced radiotherapy of prostate.

    PubMed

    Garnica-Garza, H M

    2013-09-01

    Radiation therapy using a kilovoltage X-ray source to irradiate a target previously loaded with a radiological contrast agent, contrast-enhanced radiotherapy (CERT), has been shown both theoretically and in a preliminary experimental study to represent a potential alternative to high-energy treatments. It has also been shown, however, to produce an integral dose that can be up to twice that resulting from a conventional megavoltage treatment. In this work, using a realistic patient model and Monte Carlo simulation, a CERT prostate treatment plan is designed that makes use of a plurality of small circular beams aimed at the target in such a way as to minimize the radiological trajectory to the target volume. Gold nanoparticles are assumed to be the contrast agent. Two cases are examined, one with a concentration level in the target of 10 mg-Au per gram of tissue and the second with a concentration of 3 mg-Au per gram of tissue in the target. A background concentration of 1 mg of contrast agent per gram of tissue was assumed everywhere else in both cases. The Cimmino feasibility algorithm was then used to find each beam weight in order to obtain the prescribed target dose, set at 72 Gy to 100% of the tumor volume. It is shown that the approach using the small circular fields, a radiosurgery treatment, produces treatment plans with excellent absorbed dose distributions while at the same time it reduces by up to 60% the non-tumor integral dose imparted to the irradiated subject. A brief discussion on the technology necessary to clinically implement this treatment modality is also presented.

  17. Modeling of the dynamics of microbubble contrast agents in ultrasonic medicine: Survey

    NASA Astrophysics Data System (ADS)

    Doinikov, A. A.; Bouakaz, A.

    2013-11-01

    The survey is devoted to a new field of bubble dynamics that studies the behavior of ultrasound contrast agents. This name denotes man-made encapsulated microbubbles applied in diagnostic and therapeutic ultrasonic medicine to enhance the quality of ultrasonic images and to deliver drugs to target sites in the human body. The survey analyzes theoretical models that are currently applied for the description of the bubble shell, the interaction of bubbles with blood vessel walls, and the acoustical action of bubbles on the cell membrane.

  18. Correlation between human observer performance and model observer performance in differential phase contrast CT

    SciTech Connect

    Li, Ke; Garrett, John; Chen, Guang-Hong

    2013-11-15

    Purpose: With the recently expanding interest and developments in x-ray differential phase contrast CT (DPC-CT), the evaluation of its task-specific detection performance and comparison with the corresponding absorption CT under a given radiation dose constraint become increasingly important. Mathematical model observers are often used to quantify the performance of imaging systems, but their correlations with actual human observers need to be confirmed for each new imaging method. This work is an investigation of the effects of stochastic DPC-CT noise on the correlation of detection performance between model and human observers with signal-known-exactly (SKE) detection tasks.Methods: The detectabilities of different objects (five disks with different diameters and two breast lesion masses) embedded in an experimental DPC-CT noise background were assessed using both model and human observers. The detectability of the disk and lesion signals was then measured using five types of model observers including the prewhitening ideal observer, the nonprewhitening (NPW) observer, the nonprewhitening observer with eye filter and internal noise (NPWEi), the prewhitening observer with eye filter and internal noise (PWEi), and the channelized Hotelling observer (CHO). The same objects were also evaluated by four human observers using the two-alternative forced choice method. The results from the model observer experiment were quantitatively compared to the human observer results to assess the correlation between the two techniques.Results: The contrast-to-detail (CD) curve generated by the human observers for the disk-detection experiments shows that the required contrast to detect a disk is inversely proportional to the square root of the disk size. Based on the CD curves, the ideal and NPW observers tend to systematically overestimate the performance of the human observers. The NPWEi and PWEi observers did not predict human performance well either, as the slopes of their CD

  19. Broadband Performance of TPF's High-contrast Imaging Testbed: Modeling and Simulations

    NASA Technical Reports Server (NTRS)

    Sidick, Erkin; Kuhnert, Andreas C.; Trauger, John T.

    2006-01-01

    The broadband performance of the high-contrast imaging testbed (HCIT) at JPL is investigated through optical modeling and simulations. The analytical tool is an optical simulation algorithm developed by combining the HCIT's optical model with a speckle-nulling algorithm that operates directly on coronagraphic images, an algorithm identical to the one currently being used on the HCIT to actively suppress scattered light via a deformable mirror. It is capable of performing full three-dimensional end-to-end near-field diffraction analysis on the HCIT's optical system. By conducting speckle-nulling optimization, we clarify the HCIT's capability and limitations in terms of its broadband contrast performance under various realistic conditions. Considered cases include non-ideal occulting masks, such as a mask with optical density and wavelength dependent parasitic phase-delay errors (i.e., a not band-limited occulting mask) and the one with an optical-density profile corresponding to a measured, non-standard profile, as well as the independently measured phase errors of all optics. Most of the information gathered on the HCIT's optical components through measurement and characterization over the last several years at JPL has been used in this analysis to make the predictions as accurate as possible. The best contrast values predicted so far by our simulations obtainable on the HCIT illuminated with a broadband light having a bandwidth of 80nm and centered at 800nm wavelength are Cm=1.1x10-8 (mean) and C4=4.9x10-8 (at 4(lamda)/D), respectively. In this paper we report our preliminary findings about the broadband light performance of the HCIT.

  20. Optimized time-resolved imaging of contrast kinetics (TRICKS) in dynamic contrast-enhanced MRI after peptide receptor radionuclide therapy in small animal tumor models.

    PubMed

    Haeck, Joost; Bol, Karin; Bison, Sander; van Tiel, Sandra; Koelewijn, Stuart; de Jong, Marion; Veenland, Jifke; Bernsen, Monique

    2015-01-01

    Anti-tumor efficacy of targeted peptide-receptor radionuclide therapy (PRRT) relies on several factors, including functional tumor vasculature. Little is known about the effect of PRRT on tumor vasculature. With dynamic contrast-enhanced (DCE-) MRI, functional vasculature is imaged and quantified using contrast agents. In small animals DCE-MRI is a challenging application. We optimized a clinical sequence for fast hemodynamic acquisitions, time-resolved imaging of contrast kinetics (TRICKS), to obtain DCE-MRI images at both high spatial and high temporal resolution in mice and rats. Using TRICKS, functional vasculature was measured prior to PRRT and longitudinally to investigate the effect of treatment on tumor vascular characteristics. Nude mice bearing H69 tumor xenografts and rats bearing syngeneic CA20948 tumors were used to study perfusion following PRRT administration with (177) lutetium octreotate. Both semi-quantitative and quantitative parameters were calculated. Treatment efficacy was measured by tumor-size reduction. Optimized TRICKS enabled MRI at 0.032 mm(3) voxel size with a temporal resolution of less than 5 s and large volume coverage, a substantial improvement over routine pre-clinical DCE-MRI studies. Tumor response to therapy was reflected in changes in tumor perfusion/permeability parameters. The H69 tumor model showed pronounced changes in DCE-derived parameters following PRRT. The rat CA20948 tumor model showed more heterogeneity in both treatment outcome and perfusion parameters. TRICKS enabled the acquisition of DCE-MRI at both high temporal resolution (Tres ) and spatial resolutions relevant for small animal tumor models. With the high Tres enabled by TRICKS, accurate pharmacokinetic data modeling was feasible. DCE-MRI parameters revealed changes over time and showed a clear relationship between tumor size and Ktrans .

  1. Kinetic model optimization for characterizing tumour physiology by dynamic contrast-enhanced near-infrared spectroscopy.

    PubMed

    St Lawrence, K; Verdecchia, K; Elliott, J; Tichauer, K; Diop, M; Hoffman, L; Lee, T-Y

    2013-03-07

    Dynamic contrast-enhanced (DCE) methods are widely used with magnetic resonance imaging and computed tomography to assess the vascular characteristics of tumours since these properties can affect the response to radiotherapy and chemotherapy. In contrast, there have been far fewer studies using optical-based applications despite the advantages of low cost and safety. This study investigated an appropriate kinetic model for optical applications to characterize tumour haemodynamics (blood flow, F, blood volume, V(b), and vascular heterogeneity) and vascular leakage (permeability surface-area product, PS). DCE data were acquired with two dyes, indocyanine green (ICG) and 800 CW carboxylate (IRD(cbx)), from a human colon tumour xenograph model in rats. Due to the smaller molecular weight of IRD(cbx) (1166 Da) compared to albumin-bound ICG (67 kDa), PS of IRD(cbx) was significantly larger; however, no significant differences in F and V(b) were found between the dyes as expected. Error analysis demonstrated that all parameters could be estimated with an uncertainty less than 5% due to the high temporal resolution and signal-to-noise ratio of the optical measurements. The next step is to adapt this approach to optical imaging to generate haemodynamics and permeability maps, which should enhance the clinical interest in optics for treatment monitoring.

  2. Kinetic model optimization for characterizing tumour physiology by dynamic contrast-enhanced near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    St. Lawrence, K.; Verdecchia, K.; Elliott, J.; Tichauer, K.; Diop, M.; Hoffman, L.; Lee, T.-Y.

    2013-03-01

    Dynamic contrast-enhanced (DCE) methods are widely used with magnetic resonance imaging and computed tomography to assess the vascular characteristics of tumours since these properties can affect the response to radiotherapy and chemotherapy. In contrast, there have been far fewer studies using optical-based applications despite the advantages of low cost and safety. This study investigated an appropriate kinetic model for optical applications to characterize tumour haemodynamics (blood flow, F, blood volume, Vb, and vascular heterogeneity) and vascular leakage (permeability surface-area product, PS). DCE data were acquired with two dyes, indocyanine green (ICG) and 800 CW carboxylate (IRDcbx), from a human colon tumour xenograph model in rats. Due to the smaller molecular weight of IRDcbx (1166 Da) compared to albumin-bound ICG (67 kDa), PS of IRDcbx was significantly larger; however, no significant differences in F and Vb were found between the dyes as expected. Error analysis demonstrated that all parameters could be estimated with an uncertainty less than 5% due to the high temporal resolution and signal-to-noise ratio of the optical measurements. The next step is to adapt this approach to optical imaging to generate haemodynamics and permeability maps, which should enhance the clinical interest in optics for treatment monitoring.

  3. Modelled contrast in the response of the surface energy balance during heatwaves for forest and grassland

    NASA Astrophysics Data System (ADS)

    Stap, Lennert; van den Hurk, Bart; Neggers, Roel; van Heerwaarden, Chiel

    2013-04-01

    Observations have shown that differences in surface energy fluxes over grasslands and forests are amplified during heat waves. The role of land atmosphere feedbacks in this process in still uncertain. In this study, we use a single-column model (SCM) to investigate the difference between forest and grassland in their energy response to heat waves. Three simulations for the period 2005-2011 were carried out: a control run using vegetation characteristics for Cabauw (the Netherlands), a run where the vegetation is changed to 100% forest, and a run with 100% short grass as vegetation. A surface evaporation tendency equation is used to analyse the impact of the land atmosphere feedbacks on evapotranspiration and sensible heat release under normal summer and heatwave conditions with excessive shortwave radiation. Land atmosphere feedbacks modify the contrast in surface energy fluxes between forest and grass, particularly during heat wave conditions. The surface resistance feedback has the largest positive impact, while boundary layer feedbacks generally tend to reduce the contrast. This resulted in higher air temperatures, that tend to evaporate less. In offline land surface model simulations the difference between forest and grassland during heat waves cannot be diagnosed adequately owing to the absence of boundary layer feedbacks.

  4. Mathematical and computational modeling of a ferrofluid deformable mirror for high-contrast imaging

    NASA Astrophysics Data System (ADS)

    Lemmer, Aaron J.; Griffiths, Ian M.; Groff, Tyler D.; Rousing, Andreas W.; Kasdin, N. Jeremy

    2016-07-01

    Deformable mirrors (DMs) are an enabling and mission-critical technology in any coronagraphic instrument designed to directly image exoplanets. A new ferro fluid deformable mirror technology for high-contrast imaging is currently under development at Princeton, featuring a flexible optical surface manipulated by the local electromagnetic and global hydraulic actuation of a reservoir of ferro fluid. The ferro fluid DM is designed to prioritize high optical surface quality, high-precision/low-stroke actuation, and excellent low-spatial-frequency performance - capabilities that meet the unique demands of high-contrast coronagraphy in a space-based platform. To this end, the ferro-fluid medium continuously supports the DM face sheet, a configuration that eliminates actuator print-through (or, quilting) by decoupling the nominal surface figure from the geometry of the actuator array. The global pressure control allows independent focus actuation. In this paper we describe an analytical model for the quasi-static deformation response of the DM face sheet to both magnetic and pressure actuation. These modeling efforts serve to identify the key design parameters and quantify their contributions to the DM response, model the relationship between actuation commands and DM surface-profile response, and predict performance metrics such as achievable spatial resolution and stroke precision for specific actuator configurations. Our theoretical approach addresses the complexity of the boundary conditions associated with mechanical mounting of the face sheet, and makes use of asymptotic approximations by leveraging the three distinct length scales in the problem - namely, the low-stroke ( nm) actuation, face sheet thickness ( mm), and mirror diameter (cm). In addition to describing the theoretical treatment, we report the progress of computational multi physics simulations which will be useful in improving the model fidelity and in drawing conclusions to improve the design.

  5. Detection of nucleotide-specific CRISPR/Cas9 modified alleles using multiplex ligation detection

    PubMed Central

    KC, R.; Srivastava, A.; Wilkowski, J. M.; Richter, C. E.; Shavit, J. A.; Burke, D. T.; Bielas, S. L.

    2016-01-01

    CRISPR/Cas9 genome-editing has emerged as a powerful tool to create mutant alleles in model organisms. However, the precision with which these mutations are created has introduced a new set of complications for genotyping and colony management. Traditional gene-targeting approaches in many experimental organisms incorporated exogenous DNA and/or allele specific sequence that allow for genotyping strategies based on binary readout of PCR product amplification and size selection. In contrast, alleles created by non-homologous end-joining (NHEJ) repair of double-stranded DNA breaks generated by Cas9 are much less amenable to such strategies. Here we describe a novel genotyping strategy that is cost effective, sequence specific and allows for accurate and efficient multiplexing of small insertion-deletions and single-nucleotide variants characteristic of CRISPR/Cas9 edited alleles. We show that ligation detection reaction (LDR) can be used to generate products that are sequence specific and uniquely detected by product size and/or fluorescent tags. The method works independently of the model organism and will be useful for colony management as mutant alleles differing by a few nucleotides become more prevalent in experimental animal colonies. PMID:27557703

  6. Renormalized scattering series for frequency-domain waveform modelling of strong velocity contrasts

    NASA Astrophysics Data System (ADS)

    Jakobsen, M.; Wu, R. S.

    2016-08-01

    An improved description of scattering and inverse scattering processes in reflection seismology may be obtained on the basis of a scattering series solution to the Helmoltz equation, which allows one to separately model primary and multiple reflections. However, the popular scattering series of Born is of limited seismic modelling value, since it is only guaranteed to converge if the global contrast is relatively small. For frequency-domain waveform modelling of realistic contrasts, some kind of renormalization may be required. The concept of renormalization is normally associated with quantum field theory, where it is absolutely essential for the treatment of infinities in connection with observable quantities. However, the renormalization program is also highly relevant for classical systems, especially when there are interaction effects that act across different length scales. In the scattering series of De Wolf, a renormalization of the Green's functions is achieved by a split of the scattering potential operator into fore- and backscattering parts; which leads to an effective reorganization and partially re-summation of the different terms in the Born series, so that their order better reflects the physics of reflection seismology. It has been demonstrated that the leading (single return) term in the De Wolf series (DWS) gives much more accurate results than the corresponding Born approximation, especially for models with high contrasts that lead to a large accumulation of phase changes in the forward direction. However, the higher order terms in the DWS that are associated with internal multiples have not been studied numerically before. In this paper, we report from a systematic numerical investigation of the convergence properties of the DWS which is based on two new operator representations of the DWS. The first operator representation is relatively similar to the original scattering potential formulation, but more global and explicit in nature. The second

  7. Establishment of the intracranial hemodynamic model based on contrast medium and clinical applications

    PubMed Central

    Cheng, Yaoer; He, Wen

    2016-01-01

    Abstract Ischemic cerebrovascular diseases are one of the most common vascular diseases in aged people and CT perfusion (CTP) is a very popular tool to detect the ischemic changes in brain vascular. The present study aims to establish a novel intracranial hemodynamic model to simulate anterior cerebral artery blood flow, and compare the actual and simulated hemodynamic parameters of healthy people and patients with carotid stenosis or occlusion. A mathematical model of the intracranial hemodynamic was generated using MATLAB software, and data from patients with or without infarct disease (57 and 44 cases, respectively) were retrospectively collected to test the new model. The actual time-density curve (TDC) of anterior cerebral artery was obtained from the original intracranial CTP data, and simulated TDC was calculated from our intracranial hemodynamic model. All model parameters were adjusted according to patients’ sex, height, and weight. Time to peak enhancement (TTP), maximum enhancement (ME), and mean transit time (MTT) were selected to evaluate the status of hemodynamics. In healthy people, there were no significant differences of TTP and ME between actual and simulated curves. For patients with infarct symptoms, ME was significantly decreased in actual data compared with simulated curve, while there was no obvious difference of TTP between actual and simulated data. Moreover, MTT was delayed in infarct patients compared with healthy people. Our group generated a computer-based, physiologic model to simulate intracranial hemodynamics. The model successfully simulated anterior cerebral artery hemodynamics in normal healthy people and showed noncompliant ME and MTT in infarct patients, reflecting their abnormal cerebral hemodynamic status. The digital model is reliable and may help optimize the protocol of contrast medium enhancement in intracranial CT, and provide a solid tool to study intracranial hemodynamics. PMID:27930555

  8. A genetic investigation of various growth models to describe growth of lambs of two contrasting breeds.

    PubMed

    Lambe, N R; Navajas, E A; Simm, G; Bünger, L

    2006-10-01

    This study compared the use of various models to describe growth in lambs of 2 contrasting breeds from birth to slaughter. Live BW records (n = 7559) from 240 Texel and 231 Scottish Blackface (SBF) lambs weighed at 2-wk intervals were modeled. Biologically relevant variables were estimated for each lamb from modified versions of the logistic, Gompertz, Richards, and exponential models, and from linear regression. In both breeds, all nonlinear models fitted the data well, with an average coefficient of determination (R2) of > 0.98. The linear model had a lower average R2 than any of the nonlinear models (< 0.94). The variables used to describe the best 3 models (logistic, Gompertz, and Richards) included estimated final BW (A); maximum ADG (B); age at maximum ADG (C); position of point of inflection in relation to A (D, for Richards only). The Richards and Gompertz models provided the best fit (average R2 = 0.986 to 0.989) in both breeds. Richards estimated an extra variable, allowing increased flexibility in describing individual growth patterns, but the Akaike's information criteria value (which weighs log-likelihood by number of parameters estimated) was similar to that of the Gompertz model. Variables A, B, C, and D were moderately to highly heritable in Texel lambs (h2 = 0.33 to 0.87), and genetic correlations between variables within-model ranged from -0.80 to 0.89, suggesting some flexibility to change the shape of the growth curve when selecting for different variables. In SBF lambs, only variables from the logistic and Gompertz models had moderate heritabilities (0.17 to 0.56), but with high genetic correlations between variables within each model (< -0.88 or > 0.92). Selection on growth variables seems promising (in Texel more than SBF), but high genetic correlations between variables may restrict the possibilities to change the growth curve shape. A random regression model was also fitted to the data to allow predictions of growth rates at relevant time

  9. X-ray Scatter Imaging of Hepatocellular Carcinoma in a Mouse Model Using Nanoparticle Contrast Agents.

    PubMed

    Rand, Danielle; Derdak, Zoltan; Carlson, Rolf; Wands, Jack R; Rose-Petruck, Christoph

    2015-10-29

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and is almost uniformly fatal. Current methods of detection include ultrasound examination and imaging by CT scan or MRI; however, these techniques are problematic in terms of sensitivity and specificity, and the detection of early tumors (<1 cm diameter) has proven elusive. Better, more specific, and more sensitive detection methods are therefore urgently needed. Here we discuss the application of a newly developed x-ray imaging technique called Spatial Frequency Heterodyne Imaging (SFHI) for the early detection of HCC. SFHI uses x-rays scattered by an object to form an image and is more sensitive than conventional absorption-based x-radiography. We show that tissues labeled in vivo with gold nanoparticle contrast agents can be detected using SFHI. We also demonstrate that directed targeting and SFHI of HCC tumors in a mouse model is possible through the use of HCC-specific antibodies. The enhanced sensitivity of SFHI relative to currently available techniques enables the x-ray imaging of tumors that are just a few millimeters in diameter and substantially reduces the amount of nanoparticle contrast agent required for intravenous injection relative to absorption-based x-ray imaging.

  10. X-ray scatter imaging of hepatocellular carcinoma in a mouse model using nanoparticle contrast agents

    DOE PAGES

    Rand, Danielle; Derdak, Zoltan; Carlson, Rolf; ...

    2015-10-29

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and is almost uniformly fatal. Current methods of detection include ultrasound examination and imaging by CT scan or MRI; however, these techniques are problematic in terms of sensitivity and specificity, and the detection of early tumors (<1 cm diameter) has proven elusive. Better, more specific, and more sensitive detection methods are therefore urgently needed. Here we discuss the application of a newly developed x-ray imaging technique called Spatial Frequency Heterodyne Imaging (SFHI) for the early detection of HCC. SFHI uses x-rays scattered by an object to form anmore » image and is more sensitive than conventional absorption-based x-radiography. We show that tissues labeled in vivo with gold nanoparticle contrast agents can be detected using SFHI. We also demonstrate that directed targeting and SFHI of HCC tumors in a mouse model is possible through the use of HCC-specific antibodies. As a result, the enhanced sensitivity of SFHI relative to currently available techniques enables the x-ray imaging of tumors that are just a few millimeters in diameter and substantially reduces the amount of nanoparticle contrast agent required for intravenous injection relative to absorption-based x-ray imaging.« less

  11. X-ray scatter imaging of hepatocellular carcinoma in a mouse model using nanoparticle contrast agents

    SciTech Connect

    Rand, Danielle; Derdak, Zoltan; Carlson, Rolf; Wands, Jack R.; Rose-Petruck, Christoph

    2015-10-29

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and is almost uniformly fatal. Current methods of detection include ultrasound examination and imaging by CT scan or MRI; however, these techniques are problematic in terms of sensitivity and specificity, and the detection of early tumors (<1 cm diameter) has proven elusive. Better, more specific, and more sensitive detection methods are therefore urgently needed. Here we discuss the application of a newly developed x-ray imaging technique called Spatial Frequency Heterodyne Imaging (SFHI) for the early detection of HCC. SFHI uses x-rays scattered by an object to form an image and is more sensitive than conventional absorption-based x-radiography. We show that tissues labeled in vivo with gold nanoparticle contrast agents can be detected using SFHI. We also demonstrate that directed targeting and SFHI of HCC tumors in a mouse model is possible through the use of HCC-specific antibodies. As a result, the enhanced sensitivity of SFHI relative to currently available techniques enables the x-ray imaging of tumors that are just a few millimeters in diameter and substantially reduces the amount of nanoparticle contrast agent required for intravenous injection relative to absorption-based x-ray imaging.

  12. In vivo modeling of beta-glucan degradation in contrasting barley (Hordeum vulgare L.) genotypes.

    PubMed

    Gianinetti, Alberto; Ferrari, Barbara; Frigeri, Paolo; Stanca, Antonio Michele

    2007-04-18

    An important determinative of malt quality is the malt beta-glucan content, which in turn depends on the initial barley beta-glucan content as well as the beta-glucan depolymerization by beta-glucanase (EC 3.2.1.73) during malting. Another enzyme, named beta-glucan solubilase, has been suggested to act prior to beta-glucanase; its existence, however, has not been unequivocally proven. We monitored changes in beta-glucan levels and in the development of beta-glucan-degrading enzymes during malting of five lots of contrasting barley genotypes. Two models of in vivo kinetics for beta-glucan degradation were then compared as follows: (i) a biphasic model based on the sequential action of beta-glucan solubilase and beta-glucanase and (ii) a monophasic model assuming that all beta-glucans are depolymerized by beta-glucanase without the previous intervention of another enzyme. Confirmatory regression analysis was used to test the fit of the models to the observed data. Our results show that beta-glucan degradation is mostly monophasic, although some enzyme other than beta-glucanase seems to be required for the early solubilization of a small fraction of insoluble beta-glucans (on average, 7% of total beta-glucans). Furthermore, the genotype-dependent kinetic rate constant (indicating beta-glucan degradability), in addition to beta-glucanase activity, is suggested to play a major role in malting quality.

  13. Comparison of deep percolation rates below contrasting land covers with a joint canopy and soil model

    NASA Astrophysics Data System (ADS)

    Domínguez, C. G.; Pryet, A.; García Vera, M.; Gonzalez, A.; Chaumont, C.; Tournebize, J.; Villacis, M.; d'Ozouville, N.; Violette, S.

    2016-01-01

    A Rutter-type canopy interception model is combined with a 1-D physically-based soil water flow model to compare deep percolation rates below distinct land covers. The joint model allows the quantification of both evaporation and transpiration rates as well as deep percolation from vegetation and soil characteristics. Experimental observations are required to constitute the input and calibration datasets. An appropriate monitoring design is described which consists in meteorological monitoring together with throughfall and soil water tension measurements. The methodology is illustrated in Santa Cruz Island in the Galapagos Archipelago, which has been affected by significant land use changes. Two adjacent study plots are investigated: a secondary forest and a pasture. The results of the model reveal that evaporation of canopy interception is higher in the pasture due to the bigger canopy storage capacity, which promotes evaporation against canopy drainage. This is however compensated by higher transpiration in the secondary forest, due to the smaller surface resistance. As a consequence, total evapotranspiration is similar for the two plots and no marked difference in deep percolation can be observed. In both cases, deep percolation reaches ca. 2 m/year which corresponds to 80% of the incoming rainfall. This methodology not only allows the quantification of deep percolation, but can also be used to identify the controlling factors of deep percolation under contrasting land covers.

  14. Intraoperative laser speckle contrast imaging improves the stability of rodent middle cerebral artery occlusion model

    NASA Astrophysics Data System (ADS)

    Yuan, Lu; Li, Yao; Li, Hangdao; Lu, Hongyang; Tong, Shanbao

    2015-09-01

    Rodent middle cerebral artery occlusion (MCAO) model is commonly used in stroke research. Creating a stable infarct volume has always been challenging for technicians due to the variances of animal anatomy and surgical operations. The depth of filament suture advancement strongly influences the infarct volume as well. We investigated the cerebral blood flow (CBF) changes in the affected cortex using laser speckle contrast imaging when advancing suture during MCAO surgery. The relative CBF drop area (CBF50, i.e., the percentage area with CBF less than 50% of the baseline) showed an increase from 20.9% to 69.1% when the insertion depth increased from 1.6 to 1.8 cm. Using the real-time CBF50 marker to guide suture insertion during the surgery, our animal experiments showed that intraoperative CBF-guided surgery could significantly improve the stability of MCAO with a more consistent infarct volume and less mortality.

  15. Modeling of nonlinear viscous stress in encapsulating shells of lipid-coated contrast agent microbubbles

    PubMed Central

    Doinikov, Alexander A.; Haac, Jillian F.; Dayton, Paul A.

    2009-01-01

    A general theoretical approach to the development of zero-thickness encapsulation models for contrast microbubbles is proposed. The approach describes a procedure that allows one to recast available rheological laws from the bulk form to a surface form which is used in a modified Rayleigh-Plesset equation governing the radial dynamics of a contrast microbubble. By the use of the proposed procedure, the testing of different rheological laws for encapsulation can be carried out. Challenges of existing shell models for lipid-encapsulated microbubbles, such as the dependence of shell parameters on the initial bubble radius and the “compression-only” behavior, are discussed. Analysis of the rheological behavior of lipid encapsulation is made by using experimental radius-time curves for lipid-coated microbubbles with radii in the range 1.2 – 2.5 μm. The curves were acquired for a research phospholipid-coated contrast agent insonified with a 20-cycle, 3.0 MHz, 100 kPa acoustic pulse. The fitting of the experimental data by a model which treats the shell as a viscoelastic solid gives the values of the shell surface viscosity increasing from 0.30×10-8 kg/s to 2.63×10-8 kg/s for the range of bubble radii indicated above. The shell surface elastic modulus increases from 0.054 N/m to 0.37 N/m. It is proposed that this increase may be a result of the lipid coating possessing the properties of both a shear-thinning and a strain-softening material. We hypothesize that these complicated rheological properties do not allow the existing shell models to satisfactorily describe the dynamics of lipid encapsulation. In the existing shell models, the viscous and the elastic shell terms have the linear form which assumes that the viscous and the elastic stresses acting inside the lipid shell are proportional to the shell shear rate and the shell strain, respectively, with constant coefficients of proportionality. The analysis performed in the present paper suggests that a more

  16. Modeling of nonlinear viscous stress in encapsulating shells of lipid-coated contrast agent microbubbles.

    PubMed

    Doinikov, Alexander A; Haac, Jillian F; Dayton, Paul A

    2009-02-01

    A general theoretical approach to the development of zero-thickness encapsulation models for contrast microbubbles is proposed. The approach describes a procedure that allows one to recast available rheological laws from the bulk form to a surface form which is used in a modified Rayleigh-Plesset equation governing the radial dynamics of a contrast microbubble. By the use of the proposed procedure, the testing of different rheological laws for encapsulation can be carried out. Challenges of existing shell models for lipid-encapsulated microbubbles, such as the dependence of shell parameters on the initial bubble radius and the "compression-only" behavior, are discussed. Analysis of the rheological behavior of lipid encapsulation is made by using experimental radius-time curves for lipid-coated microbubbles with radii in the range 1.2-2.5 microm. The curves were acquired for a research phospholipid-coated contrast agent insonified with a 20 cycle, 3.0 MHz, 100 kPa acoustic pulse. The fitting of the experimental data by a model which treats the shell as a viscoelastic solid gives the values of the shell surface viscosity increasing from 0.30 x 10(-8) kg/s to 2.63 x 10(-8) kg/s for the range of bubble radii, indicated above. The shell surface elastic modulus increases from 0.054 N/m to 0.37 N/m. It is proposed that this increase may be a result of the lipid coating possessing the properties of both a shear-thinning and a strain-softening material. We hypothesize that these complicated rheological properties do not allow the existing shell models to satisfactorily describe the dynamics of lipid encapsulation. In the existing shell models, the viscous and the elastic shell terms have the linear form which assumes that the viscous and the elastic stresses acting inside the lipid shell are proportional to the shell shear rate and the shell strain, respectively, with constant coefficients of proportionality. The analysis performed in the present paper suggests that a more

  17. Effect of microgravity on visual contrast threshold during STS Shuttle missions: Visual Function Tester-Model 2 (VFT-2)

    NASA Technical Reports Server (NTRS)

    Oneal, Melvin R.; Task, H. Lee; Genco, Louis V.

    1992-01-01

    Viewgraphs on effect of microgravity on visual contrast threshold during STS shuttle missions are presented. The purpose, methods, and results are discussed. The visual function tester model 2 is used.

  18. Estimating the probability of allelic drop-out of STR alleles in forensic genetics.

    PubMed

    Tvedebrink, Torben; Eriksen, Poul Svante; Mogensen, Helle Smidt; Morling, Niels

    2009-09-01

    In crime cases with available DNA evidence, the amount of DNA is often sparse due to the setting of the crime. In such cases, allelic drop-out of one or more true alleles in STR typing is possible. We present a statistical model for estimating the per locus and overall probability of allelic drop-out using the results of all STR loci in the case sample as reference. The methodology of logistic regression is appropriate for this analysis, and we demonstrate how to incorporate this in a forensic genetic framework.

  19. A152T tau allele causes neurodegeneration that can be ameliorated in a zebrafish model by autophagy induction

    PubMed Central

    Lopez, Ana; Lee, Suzee E.; Wojta, Kevin; Ramos, Eliana Marisa; Klein, Eric; Chen, Jason; Boxer, Adam L.; Gorno-Tempini, Maria Luisa; Geschwind, Daniel H.; Schlotawa, Lars; Ogryzko, Nikolay V.; Bigio, Eileen H.; Rogalski, Emily; Weintraub, Sandra; Mesulam, Marsel M.; Coppola, Giovanni; Miller, Bruce L.; Rubinsztein, David C.

    2017-01-01

    Abstract Mutations in the gene encoding tau (MAPT) cause frontotemporal dementia spectrum disorders. A rare tau variant p.A152T was reported as a risk factor for frontotemporal dementia spectrum and Alzheimer’s disease in an initial case-control study. Such findings need replication in an independent cohort. We analysed an independent multinational cohort comprising 3100 patients with neurodegenerative disease and 4351 healthy control subjects and found p.A152T associated with significantly higher risk for clinically defined frontotemporal dementia and progressive supranuclear palsy syndrome. To assess the functional and biochemical consequences of this variant, we generated transgenic zebrafish models expressing wild-type or A152T-tau, where A152T caused neurodegeneration and proteasome compromise. Impaired proteasome activity may also enhance accumulation of other proteins associated with this variant. We increased A152T clearance kinetics by both pharmacological and genetic upregulation of autophagy and ameliorated the disease pathology observed in A152T-tau fish. Thus, autophagy-upregulating therapies may be a strategy for the treatment for tauopathies. PMID:28334843

  20. A General Framework for Modeling Sub- and Ultraharmonics of Ultrasound Contrast Agent Signals with MISO Volterra Series

    PubMed Central

    Charara, Jamal; Girault, Jean-Marc

    2013-01-01

    Sub- and ultraharmonics generation by ultrasound contrast agents makes possible sub- and ultraharmonics imaging to enhance the contrast of ultrasound images and overcome the limitations of harmonic imaging. In order to separate different frequency components of ultrasound contrast agents signals, nonlinear models like single-input single-output (SISO) Volterra model are used. One important limitation of this model is its incapacity to model sub- and ultraharmonic components. Many attempts are made to model sub- and ultraharmonics using Volterra model. It led to the design of mutiple-input singe-output (MISO) Volterra model instead of SISO Volterra model. The key idea of MISO modeling was to decompose the input signal of the nonlinear system into periodic subsignals at the subharmonic frequency. In this paper, sub- and ultraharmonics modeling with MISO Volterra model is presented in a general framework that details and explains the required conditions to optimally model sub- and ultraharmonics. A new decomposition of the input signal in periodic orthogonal basis functions is presented. Results of application of different MISO Volterra methods to model simulated ultrasound contrast agents signals show its efficiency in sub- and ultraharmonics imaging. PMID:23554840

  1. Quantification of tumor perfusion using dynamic contrast-enhanced ultrasound: impact of mathematical modeling

    NASA Astrophysics Data System (ADS)

    Doury, Maxime; Dizeux, Alexandre; de Cesare, Alain; Lucidarme, Olivier; Pellot-Barakat, Claire; Bridal, S. Lori; Frouin, Frédérique

    2017-02-01

    Dynamic contrast-enhanced ultrasound has been proposed to monitor tumor therapy, as a complement to volume measurements. To assess the variability of perfusion parameters in ideal conditions, four consecutive test-retest studies were acquired in a mouse tumor model, using controlled injections. The impact of mathematical modeling on parameter variability was then investigated. Coefficients of variation (CV) of tissue blood volume (BV) and tissue blood flow (BF) based-parameters were estimated inside 32 sub-regions of the tumors, comparing the log-normal (LN) model with a one-compartment model fed by an arterial input function (AIF) and improved by the introduction of a time delay parameter. Relative perfusion parameters were also estimated by normalization of the LN parameters and normalization of the one-compartment parameters estimated with the AIF, using a reference tissue (RT) region. A direct estimation (rRTd) of relative parameters, based on the one-compartment model without using the AIF, was also obtained by using the kinetics inside the RT region. Results of test-retest studies show that absolute regional parameters have high CV, whatever the approach, with median values of about 30% for BV, and 40% for BF. The positive impact of normalization was established, showing a coherent estimation of relative parameters, with reduced CV (about 20% for BV and 30% for BF using the rRTd approach). These values were significantly lower (p  <  0.05) than the CV of absolute parameters. The rRTd approach provided the smallest CV and should be preferred for estimating relative perfusion parameters.

  2. Analytical modeling of the statistical properties of the contrast of large-scale irregularities of the ionosphere

    NASA Astrophysics Data System (ADS)

    Vsekhsviatskaia, I. S.; Evstratova, E. A.; Kalinin, Iu. K.; Romanchuk, A. A.

    1989-08-01

    An analytical model is proposed for the distribution of variations of the relative contrast of the electron density of large-scale ionospheric irregularities. The model is characterized by nonzero asymmetry and excess. It is shown that the model can be applied to horizontal irregularity scales from hundreds to thousands of kilometers.

  3. Spatially Explicit Modeling Reveals Cephalopod Distributions Match Contrasting Trophic Pathways in the Western Mediterranean Sea

    PubMed Central

    Puerta, Patricia; Hunsicker, Mary E.; Quetglas, Antoni; Álvarez-Berastegui, Diego; Esteban, Antonio; González, María; Hidalgo, Manuel

    2015-01-01

    Populations of the same species can experience different responses to the environment throughout their distributional range as a result of spatial and temporal heterogeneity in habitat conditions. This highlights the importance of understanding the processes governing species distribution at local scales. However, research on species distribution often averages environmental covariates across large geographic areas, missing variability in population-environment interactions within geographically distinct regions. We used spatially explicit models to identify interactions between species and environmental, including chlorophyll a (Chla) and sea surface temperature (SST), and trophic (prey density) conditions, along with processes governing the distribution of two cephalopods with contrasting life-histories (octopus and squid) across the western Mediterranean Sea. This approach is relevant for cephalopods, since their population dynamics are especially sensitive to variations in habitat conditions and rarely stable in abundance and location. The regional distributions of the two cephalopod species matched two different trophic pathways present in the western Mediterranean Sea, associated with the Gulf of Lion upwelling and the Ebro river discharges respectively. The effects of the studied environmental and trophic conditions were spatially variant in both species, with usually stronger effects along their distributional boundaries. We identify areas where prey availability limited the abundance of cephalopod populations as well as contrasting effects of temperature in the warmest regions. Despite distributional patterns matching productive areas, a general negative effect of Chla on cephalopod densities suggests that competition pressure is common in the study area. Additionally, results highlight the importance of trophic interactions, beyond other common environmental factors, in shaping the distribution of cephalopod populations. Our study presents a valuable

  4. Spatially Explicit Modeling Reveals Cephalopod Distributions Match Contrasting Trophic Pathways in the Western Mediterranean Sea.

    PubMed

    Puerta, Patricia; Hunsicker, Mary E; Quetglas, Antoni; Álvarez-Berastegui, Diego; Esteban, Antonio; González, María; Hidalgo, Manuel

    2015-01-01

    Populations of the same species can experience different responses to the environment throughout their distributional range as a result of spatial and temporal heterogeneity in habitat conditions. This highlights the importance of understanding the processes governing species distribution at local scales. However, research on species distribution often averages environmental covariates across large geographic areas, missing variability in population-environment interactions within geographically distinct regions. We used spatially explicit models to identify interactions between species and environmental, including chlorophyll a (Chla) and sea surface temperature (SST), and trophic (prey density) conditions, along with processes governing the distribution of two cephalopods with contrasting life-histories (octopus and squid) across the western Mediterranean Sea. This approach is relevant for cephalopods, since their population dynamics are especially sensitive to variations in habitat conditions and rarely stable in abundance and location. The regional distributions of the two cephalopod species matched two different trophic pathways present in the western Mediterranean Sea, associated with the Gulf of Lion upwelling and the Ebro river discharges respectively. The effects of the studied environmental and trophic conditions were spatially variant in both species, with usually stronger effects along their distributional boundaries. We identify areas where prey availability limited the abundance of cephalopod populations as well as contrasting effects of temperature in the warmest regions. Despite distributional patterns matching productive areas, a general negative effect of Chla on cephalopod densities suggests that competition pressure is common in the study area. Additionally, results highlight the importance of trophic interactions, beyond other common environmental factors, in shaping the distribution of cephalopod populations. Our study presents a valuable

  5. Seasonal contrast in aerosol abundance over northern south Asia using a chemical transport model

    NASA Astrophysics Data System (ADS)

    Venkataraman, C.; Sadavarte, P.; Madhavan, B. L.; Kulkarni, S.; Carmichael, G. R.; Adhikary, B.; D'Allura, A.; Cherian, R.; Das, S.; Gupta, T.; Streets, D. G.; Wei, C.; Zhang, Q.

    2012-12-01

    Northern South-Asia, home to about half a billion people, experiences large aerosol abundances almost all year around. There are gaps in our understanding of seasonal variations in regional aerosol emissions, abundance and radiative effects. The present study uses chemical transport model simulations (at ~ 60km resolution), with regionally estimated emissions, to investigate the contrast in aerosol surface and columnar abundance during pre-monsoon transition, monsoon and inter-monsoon transition periods over than Gangetic plain (GP) and Tibetan plateau. The interplay between aerosol emissions and atmospheric transport is examined to explain the variability. Model predictions were evaluated with available in-situ measurements and AOD from AERONET and MODIS level-2 retrievals (at 10 km resolution) processed with quality weighting to the model resolution. During April, AOD was dominated by dust at most sites across the GP and Tibet. However, AOD from organic carbon (emitted from agricultural residue burning) is also significant at several sites (Pantnagar, Godavari, Kolkata, Dhaka, and at high altitude Pyramid and Lhasa sites), consistent with recently reported MISR climatology in this region. In contrast, during July and September, AOD was dominated by sulfate at all sites. In April, aerosols over the GP could be attributed to emissions from large industrial sources (thermal power plant, cement industries, iron & steel and other industries) and agricultural residue burning transported from the northwest, along with forest burning emissions transported from the east. Large fluxes of open burning emissions in the east GP, along with prevailing easterly wind flow into the GP led to an east-west gradient in anthropogenic aerosols. During July, there was little open burning, so aerosol concentrations were largely from industrial emissions transported out through the north. In the Tibet region, dust was predominant during both April and July. During September

  6. Specific contrast ultrasound using sterically stabilized microbubbles for early diagnosis of thromboembolic disease in a rabbit model.

    PubMed

    Vlašín, Michal; Lukáč, Robert; Kauerová, Zuzana; Kohout, Pavel; Mašek, Josef; Bartheldyová, Eliška; Koudelka, Štěpán; Korvasová, Zina; Plocková, Jana; Hronová, Nikola; Turánek, Jaroslav

    2014-04-01

    Specific contrast ultrasound is widely applied in diagnostic procedures on humans but remains underused in veterinary medicine. The objective of this study was to evaluate the use of microbubble-based contrast for rapid ultrasonographic diagnosis of thrombosis in small animals, using male New Zealand white rabbits (average weight about 3.5 kg) as a model. It was hypothesized that the use of microbubble-based contrast agents will result in a faster and more precise diagnosis in our model of thrombosis. A pro-coagulant environment had been previously established by combining endothelial denudation and external vessel wall damage. Visualization of thrombi was achieved by application of contrast microbubbles [sterically stabilized, phospholipid-based microbubbles filled with sulfur hexafluoride (SF₆) gas] and ultrasonography. As a result, rapid and clear diagnosis of thrombi in aorta abdominalis was achieved within 10 to 30 s (mean: 17.3 s) by applying microbubbles as an ultrasound contrast medium. In the control group, diagnosis was not possible or took 90 to 180 s. Therefore, sterically stabilized microbubbles were found to be a suitable contrast agent for the rapid diagnosis of thrombi in an experimental model in rabbits. This contrast agent could be of practical importance in small animal practice for rapid diagnosis of thrombosis.

  7. Colombia and Cuba, contrasting models in Latin America's health sector reform.

    PubMed

    De Vos, Pol; De Ceukelaire, Wim; Van der Stuyft, Patrick

    2006-10-01

    Latin American national health systems were drastically overhauled by the health sector reforms the 1990s. Governments were urged by donors and by the international financial institutions to make major institutional changes, including the separation of purchaser and provider functions and privatization. This article first analyses a striking paradox of the far-reaching reform measures: contrary to what is imposed on public health services, after privatization purchaser and provider functions are reunited. Then we compare two contrasting examples: Colombia, which is internationally promoted as a successful--and radical--example of 'market-oriented' health care reform, and Cuba, which followed a highly 'conservative' path to adapt its public system to the new conditions since the 1990s, going against the model of the international institutions. The Colombian reform has not been able to materialize its promises of universality, improved equity, efficiency and better quality, while Cuban health care remains free, accessible for everybody and of good quality. Finally, we argue that the basic premises of the ongoing health sector reforms in Latin America are not based on the people's needs, but are strongly influenced by the needs of foreign--especially North American--corporations. However, an alternative model of health sector reform, such as the Cuban one, can probably not be pursued without fundamental changes in the economic and political foundations of Latin American societies.

  8. Comparing Fourier optics and contrast transfer function modeling of image formation in low energy electron microscopy.

    PubMed

    Yu, K M; Locatelli, A; Altman, M S

    2017-03-24

    A theoretical understanding of image formation in cathode lens microscopy can facilitate image interpretation. We compare Fourier Optics (FO) and Contrast Transfer Function (CTF) approaches that were recently adapted from other realms of microscopy to model image formation in low energy electron microscopy (LEEM). Although these two approaches incorporate imaging errors from several sources similarly, they differ in the way that the image intensity is calculated. The simplification that is used in the CTF calculation advantageously leads to its computational efficiency. However, we find that lens aberrations, and spatial and temporal coherence may affect the validity of the CTF approach to model LEEM image formation under certain conditions. In particular, these effects depend strongly on the nature of the object being imaged and also become more pronounced with increasing defocus. While the use of the CTF approach appears to be justified for objects that are routinely imaged with LEEM, comparison of theory to experimental observations of a focal image series for rippled, suspended graphene reveals one example where FO works, but CTF does not. This work alerts us to potential pitfalls and guides the effective use of FO and CTF approaches. It also lays the foundation for quantitative image evaluation using these methods.

  9. A model for the dynamics of ultrasound contrast agents in vivo

    PubMed Central

    Qin, Shengping; Ferrara, Katherine W.

    2010-01-01

    The Rayleigh-Plesset (RP) equation for a clean gas bubble in an incompressible and infinite liquid has previously been applied to approximately simulate the behavior of ultrasound contrast agents (UCA) in vivo, and extended RP equations have been proposed to account for the effects of the UCA shell or surrounding soft tissue. These models produce results that are consistent with experimental measurements for low acoustic pressure scenarios. For applications of UCAs in therapeutic medicine, the transmitted acoustic pulse can have a peak negative pressure (PNP) up to a few megapascals, resulting in discrepancies between measurements and predictions using these extended RP equations. Here, a model was developed to describe the dynamics of UCAs in vivo while taking account of the effects of liquid compressibility, the shell and the surrounding tissue. Liquid compressibility is approximated to first order and the shell is treated either as a Voigt viscoelastic solid or a Newtonian viscous liquid. Finite deformation of the shell and tissue is derived. Dynamics of UCAs with a shell of lipid, polymer, albumin and liquid are investigated for typical therapeutic ultrasound pulses. The effects of liquid compressibility and shell and tissue parameters are analyzed. PMID:20815486

  10. Ex vivo micro-CT imaging of murine brain models using non-ionic iodinated contrast

    NASA Astrophysics Data System (ADS)

    Salas Bautista, N.; Martínez-Dávalos, A.; Rodríguez-Villafuerte, M.; Murrieta-Rodríguez, T.; Manjarrez-Marmolejo, J.; Franco-Pérez, J.; Calvillo-Velasco, M. E.

    2014-11-01

    Preclinical investigation of brain tumors is frequently carried out by means of intracranial implantation of brain tumor xenografts or allografts, with subsequent analysis of tumor growth using conventional histopathology. However, very little has been reported on the use contrast-enhanced techniques in micro-CT imaging for the study of malignant brain tumors in small animal models. The aim of this study has been to test a protocol for ex vivo imaging of murine brain models of glioblastoma multiforme (GBM) after treatment with non-ionic iodinated solution, using an in-house developed laboratory micro-CT. We have found that the best compromise between acquisition time and image quality is obtained using a 50 kVp, 0.5 mAs, 1° angular step on a 360 degree orbit acquisition protocol, with 70 μm reconstructed voxel size using the Feldkamp algorithm. With this parameters up to 4 murine brains can be scanned in tandem in less than 15 minutes. Image segmentation and analysis of three sample brains allowed identifying tumor volumes as small as 0.4 mm3.

  11. Evaluation of renal function with contrast MRI: mathematical modeling and error analysis

    NASA Astrophysics Data System (ADS)

    Rusinek, Roza

    1999-05-01

    Dynamic MR imaging with contrast media is increasingly used to provide a safe and noninvasive assessment of renal function. Following intravenous injection of a paramagnetic tracer such as Gd-DPTA, the time course of MR signal is measured in arterial blood and in the kidneys. We use mathematical modeling and Monte Carlo trials to evaluate errors in computed renal parameters such as mean transit time (sigma) m as a function of injected dose. The model assumes that tracer concentration in the renal compartments is the result of convolution of the arterial curve and unit response functions. Results indicate that (sigma) m is not a monotonic function of the dose: instead it reaches a minimum for 2.5 - 3.5 ml of 500 mmol/l solution of Gd-DPTA and it rapidly increases for doses lower than 1 ml. These results can help optimize MR protocol and establish the feasibility of MR measurements using reduced doses of Gd-DPTA.

  12. Disentangling the formation of contrasting tree-line physiognomies combining model selection and Bayesian parameterization for simulation models.

    PubMed

    Martínez, Isabel; Wiegand, Thorsten; Camarero, J Julio; Batllori, Enric; Gutiérrez, Emilia

    2011-05-01

    Alpine tree-line ecotones are characterized by marked changes at small spatial scales that may result in a variety of physiognomies. A set of alternative individual-based models was tested with data from four contrasting Pinus uncinata ecotones in the central Spanish Pyrenees to reveal the minimal subset of processes required for tree-line formation. A Bayesian approach combined with Markov chain Monte Carlo methods was employed to obtain the posterior distribution of model parameters, allowing the use of model selection procedures. The main features of real tree lines emerged only in models considering nonlinear responses in individual rates of growth or mortality with respect to the altitudinal gradient. Variation in tree-line physiognomy reflected mainly changes in the relative importance of these nonlinear responses, while other processes, such as dispersal limitation and facilitation, played a secondary role. Different nonlinear responses also determined the presence or absence of krummholz, in agreement with recent findings highlighting a different response of diffuse and abrupt or krummholz tree lines to climate change. The method presented here can be widely applied in individual-based simulation models and will turn model selection and evaluation in this type of models into a more transparent, effective, and efficient exercise.

  13. MHC genotyping of non-model organisms using next-generation sequencing: a new methodology to deal with artefacts and allelic dropout

    PubMed Central

    2013-01-01

    Background The Major Histocompatibility Complex (MHC) is the most important genetic marker to study patterns of adaptive genetic variation determining pathogen resistance and associated life history decisions. It is used in many different research fields ranging from human medical, molecular evolutionary to functional biodiversity studies. Correct assessment of the individual allelic diversity pattern and the underlying structural sequence variation is the basic requirement to address the functional importance of MHC variability. Next-generation sequencing (NGS) technologies are likely to replace traditional genotyping methods to a great extent in the near future but first empirical studies strongly indicate the need for a rigorous quality control pipeline. Strict approaches for data validation and allele calling to distinguish true alleles from artefacts are required. Results We developed the analytical methodology and validated a data processing procedure which can be applied to any organism. It allows the separation of true alleles from artefacts and the evaluation of genotyping reliability, which in addition to artefacts considers for the first time the possibility of allelic dropout due to unbalanced amplification efficiencies across alleles. Finally, we developed a method to assess the confidence level per genotype a-posteriori, which helps to decide which alleles and individuals should be included in any further downstream analyses. The latter method could also be used for optimizing experiment designs in the future. Conclusions Combining our workflow with the study of amplification efficiency offers the chance for researchers to evaluate enormous amounts of NGS-generated data in great detail, improving confidence over the downstream analyses and subsequent applications. PMID:23937623

  14. Intragenic allele pyramiding combines different specificities of wheat Pm3 resistance alleles.

    PubMed

    Brunner, Susanne; Hurni, Severine; Streckeisen, Philipp; Mayr, Gabriele; Albrecht, Mario; Yahiaoui, Nabila; Keller, Beat

    2010-11-01

    Some plant resistance genes occur as allelic series, with each member conferring specific resistance against a subset of pathogen races. In wheat, there are 17 alleles of the Pm3 gene. They encode nucleotide-binding (NB-ARC) and leucine-rich-repeat (LRR) domain proteins, which mediate resistance to distinct race spectra of powdery mildew. It is not known if specificities from different alleles can be combined to create resistance genes with broader specificity. Here, we used an approach based on avirulence analysis of pathogen populations to characterize the molecular basis of Pm3 recognition spectra. A large survey of mildew races for avirulence on the Pm3 alleles revealed that Pm3a has a resistance spectrum that completely contains that of Pm3f, but also extends towards additional races. The same is true for the Pm3b and Pm3c gene pair. The molecular analysis of these allelic pairs revealed a role of the NB-ARC protein domain in the efficiency of effector-dependent resistance. Analysis of the wild-type and chimeric Pm3 alleles identified single residues in the C-terminal LRR motifs as the main determinant of allele specificity. Variable residues of the N-terminal LRRs are necessary, but not sufficient, to confer resistance specificity. Based on these data, we constructed a chimeric Pm3 gene by intragenic allele pyramiding of Pm3d and Pm3e that showed the combined resistance specificity and, thus, a broader recognition spectrum compared with the parental alleles. Our findings support a model of stepwise evolution of Pm3 recognition specificities.

  15. Modelling of ‘sub-atomic’ contrast resulting from back-bonding on Si(111)-7×7

    PubMed Central

    Jarvis, Samuel P; Rashid, Mohammad A

    2016-01-01

    Summary It has recently been shown that ‘sub-atomic’ contrast can be observed during NC-AFM imaging of the Si(111)-7×7 substrate with a passivated tip, resulting in triangular shaped atoms [Sweetman et al. Nano Lett. 2014, 14, 2265]. The symmetry of the features, and the well-established nature of the dangling bond structure of the silicon adatom means that in this instance the contrast cannot arise from the orbital structure of the atoms, and it was suggested by simple symmetry arguments that the contrast could only arise from the backbonding symmetry of the surface adatoms. However, no modelling of the system has been performed in order to understand the precise origin of the contrast. In this paper we provide a detailed explanation for ‘sub-atomic’ contrast observed on Si(111)-7×7 using a simple model based on Lennard-Jones potentials, coupled with a flexible tip, as proposed by Hapala et al. [Phys. Rev. B 2014, 90, 085421] in the context of interpreting sub-molecular contrast. Our results show a striking similarity to experimental results, and demonstrate how ‘sub-atomic’ contrast can arise from a flexible tip exploring an asymmetric potential created due to the positioning of the surrounding surface atoms. PMID:27547610

  16. A novel allelic variant of the human TSG-6 gene encoding an amino acid difference in the CUB module. Chromosomal localization, frequency analysis, modeling, and expression.

    PubMed

    Nentwich, Hilke A; Mustafa, Zehra; Rugg, Marilyn S; Marsden, Brian D; Cordell, Martin R; Mahoney, David J; Jenkins, Suzanne C; Dowling, Barbara; Fries, Erik; Milner, Caroline M; Loughlin, John; Day, Anthony J

    2002-05-03

    Tumor necrosis factor-stimulated gene-6 (TSG-6) encodes a 35-kDa protein, which is comprised of contiguous Link and CUB modules. TSG-6 protein has been detected in the articular joints of osteoarthritis (OA) patients, with little or no constitutive expression in normal adult tissues. It interacts with components of cartilage matrix (e.g. hyaluronan and aggrecan) and thus may be involved in extracellular remodeling during joint disease. In addition, TSG-6 has been found to have anti-inflammatory properties in models of acute and chronic inflammation. Here we have mapped the human TSG-6 gene to 2q23.3, a region of chromosome 2 linked with OA. A single nucleotide polymorphism was identified that involves a non-synonymous G --> A transition at nucleotide 431 of the TSG-6 coding sequence, resulting in an Arg to Gln alteration in the CUB module (at residue 144 in the preprotein). Molecular modeling of the CUB domain indicated that this amino acid change might lead to functional differences. Typing of 400 OA cases and 400 controls revealed that the A(431) variant identified here is the major TSG-6 allele in Caucasians (with over 75% being A(431) homozygotes) but that this polymorphism is not a marker for OA susceptibility in the patients we have studied. Expression of the Arg(144) and Gln(144) allotypes in Drosophila Schneider 2 cells, and functional characterization, showed that there were no significant differences in the ability of these full-length proteins to bind hyaluronan or form a stable complex with inter-alpha-inhibitor.

  17. Allele-specific DNA methylation: beyond imprinting.

    PubMed

    Tycko, Benjamin

    2010-10-15

    Allele-specific DNA methylation (ASM) and allele-specific gene expression (ASE) have long been studied in genomic imprinting and X chromosome inactivation. But these types of allelic asymmetries, along with allele-specific transcription factor binding (ASTF), have turned out to be far more pervasive-affecting many non-imprinted autosomal genes in normal human tissues. ASM, ASE and ASTF have now been mapped genome-wide by microarray-based methods and NextGen sequencing. Multiple studies agree that all three types of allelic asymmetries, as well as the related phenomena of expression and methylation quantitative trait loci, are mostly accounted for by cis-acting regulatory polymorphisms. The precise mechanisms by which this occurs are not yet understood, but there are some testable hypotheses and already a few direct clues. Future challenges include achieving higher resolution maps to locate the epicenters of cis-regulated ASM, using this information to test mechanistic models, and applying genome-wide maps of ASE/ASM/ASTF to pinpoint functional regulatory polymorphisms influencing disease susceptibility.

  18. Using the magnetosome to model effective gene-based contrast for magnetic resonance imaging.

    PubMed

    Goldhawk, Donna E; Rohani, Roja; Sengupta, Anindita; Gelman, Neil; Prato, Frank S

    2012-01-01

    Formation of iron biominerals is a naturally occurring phenomenon, particularly among magnetotactic bacteria which produce magnetite (Fe(3) O(4) ) in a subcellular compartment termed the magnetosome. Under the control of numerous genes, the magnetosome serves as a model upon which to (1) develop gene-based contrast in mammalian cells and (2) provide a mechanism for reporter gene expression in magnetic resonance imaging (MRI). There are two main components to the magnetosome: the biomineral and the lipid bilayer that surrounds it. Both are essential for magnetotaxis in a variety of magnetotactic bacteria, but nonessential for cell survival. Through comparative genome analysis, a subset of genes characteristic of the magnetotactic phenotype has been found both within and outside a magnetosome genomic island. The functions of magnetosome-associated proteins reflect the complex nature of this intracellular structure and include vesicle formation, cytoskeletal attachment, iron transport, and crystallization. Examination of magnetosome genes and structure indicates a protein-directed and stepwise assembly of the magnetosome compartment. Attachment of magnetosomes along a cytoskeletal filament aligns the magnetic particles such that the cell may be propelled along an external magnetic field. Interest in this form of magnetotaxis has prompted research in several areas of medicine, including magnetotactic bacterial targeting of tumors, MR-guided movement of magnetosome-bearing cells through vessels and molecular imaging of mammalian cells using MRI, and its hybrid modalities. The potential adaptation of magnetosome genes for noninvasive medical imaging provides new opportunities for development of reporter gene expression for MRI.

  19. Streaming flow from ultrasound contrast agents by acoustic waves in a blood vessel model.

    PubMed

    Cho, Eunjin; Chung, Sang Kug; Rhee, Kyehan

    2015-09-01

    To elucidate the effects of streaming flow on ultrasound contrast agent (UCA)-assisted drug delivery, streaming velocity fields from sonicated UCA microbubbles were measured using particle image velocimetry (PIV) in a blood vessel model. At the beginning of ultrasound sonication, the UCA bubbles formed clusters and translated in the direction of the ultrasound field. Bubble cluster formation and translation were faster with 2.25MHz sonication, a frequency close to the resonance frequency of the UCA. Translation of bubble clusters induced streaming jet flow that impinged on the vessel wall, forming symmetric vortices. The maximum streaming velocity was about 60mm/s at 2.25MHz and decreased to 15mm/s at 1.0MHz for the same acoustic pressure amplitude. The effect of the ultrasound frequency on wall shear stress was more noticeable. Maximum wall shear stress decreased from 0.84 to 0.1Pa as the ultrasound frequency decreased from 2.25 to 1.0MHz. The maximum spatial gradient of the wall shear stress also decreased from 1.0 to 0.1Pa/mm. This study showed that streaming flow was induced by bubble cluster formation and translation and was stronger upon sonication by an acoustic wave with a frequency near the UCA resonance frequency. Therefore, the secondary radiant force, which is much stronger at the resonance frequency, should play an important role in UCA-assisted drug delivery.

  20. Above-threshold numerical modeling of high-index-contrast photonic-crystal quantum cascade lasers

    NASA Astrophysics Data System (ADS)

    Napartovich, A. P.; Elkin, N. N.; Vysotsky, D. V.; Kirch, J.; Sigler, C.; Botez, D.; Mawst, L. J.; Belyanin, A.

    2015-03-01

    Three-dimensional above-threshold analyses of high-index-contrast (HC) photonic-crystal (PC) quantum-cascade-laser arrays (QCLA) structures, for operation at watt-range CW powers in a single spatial mode, have been performed. Threeelement HC-PC structures are formed by alternating active- antiguided and passive-guided regions along with respective metal-electrode spatial profiling. The 3-D numerical code takes into account absorption and edge-radiation losses. Rigrod's approximation is used for the gain. The specific feature of QCLA is that only the transverse component of the magnetic field sees the gain. Results of above-threshold laser modeling in various approximate versions of laser-cavity description are compared with the results of linear, full-vectorial modeling by using the COMSOL package. Additionally, modal gains for several higher-order optical modes, on a `frozen gain background' produced by the fundamental-mode, are computed by the Arnoldi algorithm. The gain spatial-hole burning effect results in growth of the competing modes' gain with drive current. Approaching the lasing threshold for a competing higher-order mode sets a limit on the single-mode operation range. The modal structure and stability are studied over a wide range in the variation of the inter-element widths. Numerical analyses predict that the proper choice of construction parameters ensures stable single-mode operation at high drive levels above threshold. The output power from a single- mode operated QCLA at a wavelength of 4.7 μm is predicted to be available at multi-watt levels, although this power may be restricted by thermal effects.

  1. Quantitative ultrasound molecular imaging by modeling the binding kinetics of targeted contrast agent

    NASA Astrophysics Data System (ADS)

    Turco, Simona; Tardy, Isabelle; Frinking, Peter; Wijkstra, Hessel; Mischi, Massimo

    2017-03-01

    Ultrasound molecular imaging (USMI) is an emerging technique to monitor diseases at the molecular level by the use of novel targeted ultrasound contrast agents (tUCA). These consist of microbubbles functionalized with targeting ligands with high-affinity for molecular markers of specific disease processes, such as cancer-related angiogenesis. Among the molecular markers of angiogenesis, the vascular endothelial growth factor receptor 2 (VEGFR2) is recognized to play a major role. In response, the clinical-grade tUCA BR55 was recently developed, consisting of VEGFR2-targeting microbubbles which can flow through the entire circulation and accumulate where VEGFR2 is over-expressed, thus causing selective enhancement in areas of active angiogenesis. Discrimination between bound and free microbubbles is crucial to assess cancer angiogenesis. Currently, this is done non-quantitatively by looking at the late enhancement, about 10 min after injection, or by calculation of the differential targeted enhancement, requiring the application of a high-pressure ultrasound (US) burst to destroy all the microbubbles in the acoustic field and isolate the signal coming only from bound microbubbles. In this work, we propose a novel method based on mathematical modeling of the binding kinetics during the tUCA first pass, thus reducing the acquisition time and with no need for a destructive US burst. Fitting time-intensity curves measured with USMI by the proposed model enables the assessment of cancer angiogenesis at both the vascular and molecular levels. This is achieved by estimation of quantitative parameters related to the microvascular architecture and microbubble binding. The proposed method was tested in 11 prostate-tumor bearing rats by performing USMI after injection of BR55, and showed good agreement with current USMI methods. The novel information provided by the proposed method, possibly combined with the current non-quantitative methods, may bring deeper insight into

  2. Nicotinamide benefits both mothers and pups in two contrasting mouse models of preeclampsia

    PubMed Central

    Li, Feng; Fushima, Tomofumi; Oyanagi, Gen; Townley-Tilson, H. W. Davin; Sato, Emiko; Nakada, Hironobu; Oe, Yuji; Hagaman, John R.; Wilder, Jennifer; Li, Manyu; Sekimoto, Akiyo; Saigusa, Daisuke; Sato, Hiroshi; Ito, Sadayoshi; Jennette, J. Charles; Maeda, Nobuyo; Karumanchi, S. Ananth; Smithies, Oliver; Takahashi, Nobuyuki

    2016-01-01

    Preeclampsia (PE) complicates ∼5% of human pregnancies and is one of the leading causes of pregnancy-related maternal deaths. The only definitive treatment, induced delivery, invariably results in prematurity, and in severe early-onset cases may lead to fetal death. Many currently available antihypertensive drugs are teratogenic and therefore precluded from use. Nonteratogenic antihypertensives help control maternal blood pressure in PE, but results in preventing preterm delivery and correcting fetal growth restriction (FGR) that also occurs in PE have been disappointing. Here we show that dietary nicotinamide, a nonteratogenic amide of vitamin B3, improves the maternal condition, prolongs pregnancies, and prevents FGR in two contrasting mouse models of PE. The first is caused by endotheliosis due to excess levels in the mothers of a soluble form of the receptor for vascular endothelial growth factor (VEGF), which binds to and inactivates VEGF. The second is caused by genetic absence of Ankiryn-repeat-and-SOCS-box–containing-protein 4, a factor that contributes to the differentiation of trophoblast stem cells into the giant trophoblast cells necessary for embryo implantation in mice; its absence leads to impaired placental development. In both models, fetal production of ATP is impaired and FGR is observed. We show here that nicotinamide decreases blood pressure and endotheliosis in the mothers, probably by inhibiting ADP ribosyl cyclase (ADPRC), and prevents FGR, probably by normalizing fetal ATP synthesis via the nucleotide salvage pathway. Because nicotinamide benefits both dams and pups, it merits evaluation for preventing or treating PE in humans. PMID:27821757

  3. Explaining the suicide risk of sexual minority individuals by contrasting the minority stress model with suicide models.

    PubMed

    Plöderl, Martin; Sellmeier, Maximilian; Fartacek, Clemens; Pichler, Eva-Maria; Fartacek, Reinhold; Kralovec, Karl

    2014-11-01

    Many studies have found elevated levels of suicide ideation and attempts among sexual minority (homosexual and bisexual) individuals as compared to heterosexual individuals. The suicide risk difference has mainly been explained by minority stress models (MSTM), but the application of established suicidological models and testing their interrelations with the MSTM has been lacking so far. Therefore, we have contrasted two established models explaining suicide risk, the Interpersonal Psychological Theory (IPT) (Joiner, 2005) and the Clinical Model (CM) (Mann et al., 1999), with the MSTM (Meyer, 2003) in a Bavarian online-sample of 255 adult sexual minority participants and 183 heterosexual participants. The results suggested that the CM and the IPT model can well explain suicide ideation among sexual minorities according to the factors depression, hopelessness, perceived burdensomeness, and failed belongingness. The CM and the IPT were intertwined with the MSTM via internalized homophobia, social support, and early age of coming out. Early coming out was associated with an increased suicide attempt risk, perhaps through violent experiences that enhanced the capability for suicide; however, coming out likely changed to a protective factor for suicide ideation by enhanced social support and reduced internalized homophobia. These results give more insight into the development of suicide risk among sexual minority individuals and may be helpful to tailor minority-specific suicide prevention strategies.

  4. Monte Carlo modeling and optimization of contrast-enhanced radiotherapy of brain tumors

    NASA Astrophysics Data System (ADS)

    Pérez-López, C. E.; Garnica-Garza, H. M.

    2011-07-01

    Contrast-enhanced radiotherapy involves the use of a kilovoltage x-ray beam to impart a tumoricidal dose to a target into which a radiological contrast agent has previously been loaded in order to increase the x-ray absorption efficiency. In this treatment modality the selection of the proper x-ray spectrum is important since at the energy range of interest the penetration ability of the x-ray beam is limited. For the treatment of brain tumors, the situation is further complicated by the presence of the skull, which also absorbs kilovoltage x-ray in a very efficient manner. In this work, using Monte Carlo simulation, a realistic patient model and the Cimmino algorithm, several irradiation techniques and x-ray spectra are evaluated for two possible clinical scenarios with respect to the location of the target, these being a tumor located at the center of the head and at a position close to the surface of the head. It will be shown that x-ray spectra, such as those produced by a conventional x-ray generator, are capable of producing absorbed dose distributions with excellent uniformity in the target as well as dose differential of at least 20% of the prescribed tumor dose between this and the surrounding brain tissue, when the tumor is located at the center of the head. However, for tumors with a lateral displacement from the center and close to the skull, while the absorbed dose distribution in the target is also quite uniform and the dose to the surrounding brain tissue is within an acceptable range, hot spots in the skull arise which are above what is considered a safe limit. A comparison with previously reported results using mono-energetic x-ray beams such as those produced by a radiation synchrotron is also presented and it is shown that the absorbed dose distributions rendered by this type of beam are very similar to those obtained with a conventional x-ray beam.

  5. Rates of Change in Naturalistic Psychotherapy: Contrasting Dose-Effect and Good-Enough Level Models of Change

    ERIC Educational Resources Information Center

    Baldwin, Scott A.; Berkeljon, Arjan; Atkins, David C.; Olsen, Joseph A.; Nielsen, Stevan L.

    2009-01-01

    Most research on the dose-effect model of change has combined data across patients who vary in their total dose of treatment and has implicitly assumed that the rate of change during therapy is constant across doses. In contrast, the good-enough level model predicts that rate of change will be related to total dose of therapy. In this study, the…

  6. A yeast model reveals biochemical severity associated with each of three variant alleles of galactose-1P uridylyltransferase segregating in a single family.

    PubMed

    Chhay, J S; Openo, K K; Eaton, J S; Gentile, M; Fridovich-Keil, J L

    2008-02-01

    Classic galactosaemia is a potentially lethal inborn error of metabolism that results from profound impairment of galactose-1P uridylyltransferase (GALT). Like many autosomal recessive disorders, classic galactosaemia demonstrates marked allelic heterogeneity; many if not most patients are compound heterozygotes. Owing in part to the fact that most GALT mutations are never observed in patients in the homozygous state, in part to concerns of possible allelic interaction, and in part to the broad range of GALT activity levels associated with the affected, carrier, and control states, definition of the specific functional consequence of individual variant GALT alleles from studies of clinical samples alone can be a challenging task. To overcome this problem we previously developed and applied a null-background yeast system to enable functional analyses of human GALT alleles expressed individually or in defined pairs. We report here the application of this system to characterize three distinct variant alleles of GALT identified within a single family. Of these alleles, one carried a missense mutation (K285N) that has previously been reported and characterized, one carried a nonsense mutation (R204X) that has previously been reported but not characterized, and the third carried a missense substitution (T268N) that was novel. Our studies reported here reconfirm the profound nature of the K285N mutation, demonstrate that the R204X mutation severely compromises both expression and function of human GALT, and finally implicate T268N as one of a very small number of naturally occurring rare but neutral missense polymorphisms in human GALT.

  7. Material characterization of the encapsulation of an ultrasound contrast microbubble and its subharmonic response: Strain-softening interfacial elasticity model

    PubMed Central

    Paul, Shirshendu; Katiyar, Amit; Sarkar, Kausik; Chatterjee, Dhiman; Shi, William T.; Forsberg, Flemming

    2010-01-01

    Two nonlinear interfacial elasticity models—interfacial elasticity decreasing linearly and exponentially with area fraction—are developed for the encapsulation of contrast microbubbles. The strain softening (decreasing elasticity) results from the decreasing association between the constitutive molecules of the encapsulation. The models are used to find the characteristic properties (surface tension, interfacial elasticity, interfacial viscosity and nonlinear elasticity parameters) for a commercial contrast agent. Properties are found using the ultrasound attenuation measured through a suspension of contrast agent. Dynamics of the resulting models are simulated, compared with other existing models and discussed. Imposing non-negativity on the effective surface tension (the encapsulation experiences no net compressive stress) shows “compression-only” behavior. The exponential and the quadratic (linearly varying elasticity) models result in similar behaviors. The validity of the models is investigated by comparing their predictions of the scattered nonlinear response for the contrast agent at higher excitations against experimental measurement. All models predict well the scattered fundamental response. The nonlinear strain softening included in the proposed elastic models of the encapsulation improves their ability to predict subharmonic response. They predict the threshold excitation for the initiation of subharmonic response and its subsequent saturation. PMID:20550283

  8. Alleles versus mutations: Understanding the evolution of genetic architecture requires a molecular perspective on allelic origins.

    PubMed

    Remington, David L

    2015-12-01

    Perspectives on the role of large-effect quantitative trait loci (QTL) in the evolution of complex traits have shifted back and forth over the past few decades. Different sets of studies have produced contradictory insights on the evolution of genetic architecture. I argue that much of the confusion results from a failure to distinguish mutational and allelic effects, a limitation of using the Fisherian model of adaptive evolution as the lens through which the evolution of adaptive variation is examined. A molecular-based perspective reveals that allelic differences can involve the cumulative effects of many mutations plus intragenic recombination, a model that is supported by extensive empirical evidence. I discuss how different selection regimes could produce very different architectures of allelic effects under a molecular-based model, which may explain conflicting insights on genetic architecture from studies of variation within populations versus between divergently selected populations. I address shortcomings of genome-wide association study (GWAS) practices in light of more suitable models of allelic evolution, and suggest alternate GWAS strategies to generate more valid inferences about genetic architecture. Finally, I discuss how adopting more suitable models of allelic evolution could help redirect research on complex trait evolution toward addressing more meaningful questions in evolutionary biology.

  9. Whole tissue AC susceptibility after superparamagnetic iron oxide contrast agent administration in a rat model

    NASA Astrophysics Data System (ADS)

    Lázaro, Francisco José; Gutiérrez, Lucía; Rosa Abadía, Ana; Soledad Romero, María; López, Antonio; Jesús Muñoz, María

    2007-04-01

    A magnetic AC susceptibility characterisation of rat tissues after intravenous administration of superparamagnetic iron oxide (Endorem ®), at the same dose as established for Magnetic Resonance Imaging (MRI) contrast enhancement in humans, has been carried out. The measurements reveal the presence of the contrast agent as well as that of physiological ferritin in liver and spleen while no traces have been magnetically detected in heart and kidney. This preliminary work opens suggestive possibilities for future biodistribution studies of any type of magnetic carriers.

  10. Reverse-Contrast Imaging and Targeted Radiation Therapy of Advanced Pancreatic Cancer Models

    SciTech Connect

    Thorek, Daniel L.J.; Kramer, Robin M.; Chen, Qing; Jeong, Jeho; Lupu, Mihaela E.; Lee, Alycia M.; Moynahan, Mary E.; Lowery, Maeve; Ulmert, David; Zanzonico, Pat; Deasy, Joseph O.; Humm, John L.; Russell, James

    2015-10-01

    Purpose: To evaluate the feasibility of delivering experimental radiation therapy to tumors in the mouse pancreas. Imaging and treatment were performed using combined CT (computed tomography)/orthovoltage treatment with a rotating gantry. Methods and Materials: After intraperitoneal administration of radiopaque iodinated contrast, abdominal organ delineation was performed by x-ray CT. With this technique we delineated the pancreas and both orthotopic xenografts and genetically engineered disease. Computed tomographic imaging was validated by comparison with magnetic resonance imaging. Therapeutic radiation was delivered via a 1-cm diameter field. Selective x-ray radiation therapy of the noninvasively defined orthotopic mass was confirmed using γH2AX staining. Mice could tolerate a dose of 15 Gy when the field was centered on the pancreas tail, and treatment was delivered as a continuous 360° arc. This strategy was then used for radiation therapy planning for selective delivery of therapeutic x-ray radiation therapy to orthotopic tumors. Results: Tumor growth delay after 15 Gy was monitored, using CT and ultrasound to determine the tumor volume at various times after treatment. Our strategy enables the use of clinical radiation oncology approaches to treat experimental tumors in the pancreas of small animals for the first time. We demonstrate that delivery of 15 Gy from a rotating gantry minimizes background healthy tissue damage and significantly retards tumor growth. Conclusions: This advance permits evaluation of radiation planning and dosing parameters. Accurate noninvasive longitudinal imaging and monitoring of tumor progression and therapeutic response in preclinical models is now possible and can be expected to more effectively evaluate pancreatic cancer disease and therapeutic response.

  11. Histopathological Evaluation of Contrast-Induced Acute Kidney Injury Rodent Models

    PubMed Central

    2016-01-01

    Contrast-induced acute kidney injury (CI-AKI) can occur in 3–25% of patients receiving radiocontrast material (RCM) despite appropriate preventive measures. Often patients with an atherosclerotic vasculature have to receive large doses of RCM. Thus, animal studies to uncover the exact pathomechanism of CI-AKI are needed. Sensitive and specific histologic end-points are lacking; thus in the present review we summarize the histologic appearance of different rodent models of CI-AKI. Single injection of RCM causes overt renal damage only in rabbits. Rats and mice need an additional insult to the kidney to establish a clinically manifest CI-AKI. In this review we demonstrate that the concentrating ability of the kidney may be responsible for species differences in sensitivity to CI-AKI. The most commonly held theory about the pathomechanism of CI-AKI is tubular cell injury due to medullary hypoxia. Thus, the most common additional insult in rats and mice is some kind of ischemia. The histologic appearance is tubular epithelial cell (TEC) damage; however severe TEC damage is only seen if RCM is combined by additional ischemia. TEC vacuolization is the first sign of CI-AKI, as it is a consequence of RCM pinocytosis and lysosomal fusion; however it is not sensitive as it does not correlate with renal function and is not specific as other forms of TEC damage also cause vacuolization. In conclusion, histopathology alone is insufficient and functional parameters and molecular biomarkers are needed to closely monitor CI-AKI in rodent experiments. PMID:27975052

  12. Contrast of evolution models for agricultural contaminants in ground waters by means of fuzzy logic and data mining

    NASA Astrophysics Data System (ADS)

    Andujar, J. M.; Aroba, J.; de Torre, M. L. La; Grande, J. A.

    2006-01-01

    This work aims at contrasting, by means of a set of fuzzy logic- and data mining-based algorithms, the functioning model of a detritic aquifer undergoing overexploitation and nitrate excess input coming from strawberry and citrus intensive crops in its recharge zone. To provide researchers unskilled in data mining techniques with an easy and intuitive interpretation, the authors have developed a computer tool based on fuzzy logic that allows immediate qualitative analysis of the data contained in a data mass from the water chemical analyses, and serves as a contrast to functioning models previously proposed with classical statistics.

  13. Sequence analysis of the fragile X trinucleotide repeat: Correlations with stability and haplotype and implications for the origin of fragile X alleles

    SciTech Connect

    Snow, K.; Tester, D.J.; Kruckeberg, K.E.; Thibodeau, S.N.

    1994-09-01

    Fragile X (FX) syndrome is associated with amplification of a CGG trinucleotide repeat in the 5{prime} untranslated region of the gene FMR-1. To address mechanism of instability and concern related to overlap between sizes of normal stable alleles and FX unstable alleles, we have sequenced 165 alleles to analyze patterns of AGG interruptions within the CGG repeat, and have typed the (CA)n at DXS548 for 204 chromosomes. Overall, our data is consistent with the idea that the length of uninterrupted CGG repeats determines instability. For 17 stably transmitted alleles with total repeat lengths between 33 and 51, the longest stretch of uninterrupted CGGs was 41. In contrast, for 13 premutation alleles, the shortest stretch of uninterrupted CGGs was 48, suggesting a threshold for expansion between 41 and 48 pure CGGs. For expansion from a premutation to a full mutation, the threshold appears to be {ge}70 uninterrupted repeats. Interestingly, an AGG was detected in some carriers of a full mutation. Comparison of the number of {open_quote}shadow bands{close_quote} in PCR products from similar size alleles with different AGG interruption patterns supports replication slippage as a potential mechanism, i.e. replication slippage occurs more readily as the length of pure repeat increases. Alleles with high total repeat lengths but up to 3 AGGs may be relatively protected against expansion, whereas smaller alleles with pure CGG sequence could be at higher risk for instability. Comparison of sequence data and DXS548 (CA)n data revealed specific sequence trends for each of the DXS548 alleles, explaining the previously reported haplotype association with FX. Incorporating these observations into models for the origin of FX alleles, we consider replication slippage, unequal crossover within the CGG repeat region, recombination between FMR-1 and DXS548, and loss of AGGs by A to C transversion.

  14. Computational fluid dynamics modelling of perfusion measurements in dynamic contrast-enhanced computed tomography: development, validation and clinical applications

    NASA Astrophysics Data System (ADS)

    Peladeau-Pigeon, M.; Coolens, C.

    2013-09-01

    Dynamic contrast-enhanced computed tomography (DCE-CT) is an imaging tool that aids in evaluating functional characteristics of tissue at different stages of disease management: diagnostic, radiation treatment planning, treatment effectiveness, and monitoring. Clinical validation of DCE-derived perfusion parameters remains an outstanding problem to address prior to perfusion imaging becoming a widespread standard as a non-invasive quantitative measurement tool. One approach to this validation process has been the development of quality assurance phantoms in order to facilitate controlled perfusion ex vivo. However, most of these systems fail to establish and accurately replicate physiologically relevant capillary permeability and exchange performance. The current work presents the first step in the development of a prospective suite of physics-based perfusion simulations based on coupled fluid flow and particle transport phenomena with the goal of enhancing the understanding of clinical contrast agent kinetics. Existing knowledge about a controllable, two-compartmental fluid exchange phantom was used to validate the computational fluid dynamics (CFD) simulation model presented herein. The sensitivity of CFD-derived contrast uptake curves to contrast injection parameters, including injection duration and flow rate, were quantified and found to be within 10% accuracy. The CFD model was employed to evaluate two commonly used clinical kinetic algorithms used to derive perfusion parameters: Fick's principle and the modified Tofts model. Neither kinetic model was able to capture the true transport phenomena it aimed to represent but if the overall contrast concentration after injection remained identical, then successive DCE-CT evaluations could be compared and could indeed reflect differences in regional tissue flow. This study sets the groundwork for future explorations in phantom development and pharmaco-kinetic modelling, as well as the development of novel contrast

  15. Finite Element Modeling of the Magnetotelluric Phase Tensor Response to Evaluate Sensitivity to Lateral and Vertical Resistivity Contrasts

    NASA Astrophysics Data System (ADS)

    Hawkes, S.; McClain, J. S.

    2015-12-01

    Phase tensor analysis of magnetotelluric data is a relatively new technique introduced by Caldwell et. al. (2004) and requires substantial research efforts to evaluate the capabilities of the method. We have conducted finite element (FE) modeling using the AC/DC module of Comsol Multiphysics to determine the effect of resistivity structure on the phase tensor response. Measurements are made at eleven frequencies from 10-104 Hz at points on a 5x5 grid above various simple model geometries. Phase tensor plotting methods are adapted from Booker (2013) and involve displaying data graphically as stacks of colored ellipses. This allows for interpretation across the frequency spectrum vertically as well as laterally between stations. Two types of plot are presented for each model, a "ϕmin plot" where the ellipses are colored according to the minimum principle phase and a "delta plot" where the ellipses are colored according to the difference between the principle phases (ϕmax - ϕmin), which provides a quantification of the phase anisotropy. Results suggest that the principle phases ϕmin and ϕmax are sensitive to vertical resistivity contrasts but not lateral resistivity contrasts. Conversely, delta plots reveal sensitivity to lateral resistivity contrasts but not vertical resistivity contrasts. A clear distance relationship is observed with proximity to the boundary controlling the frequency range that senses a lateral resistivity contrast. Rotation of the phase tensor ellipses and increased skew values occur in the presence of resistivity contrasts that strike nonparallel to the source field, with the effect increasing towards lower frequencies. The total phase tensor response is confirmed to be sensitive to both vertical and lateral resistivity contrasts and can be used effectively to interpret subsurface resistivity structure.

  16. Assortative mating can impede or facilitate fixation of underdominant alleles.

    PubMed

    Newberry, Mitchell G; McCandlish, David M; Plotkin, Joshua B

    2016-12-01

    Underdominant mutations have fixed between divergent species, yet classical models suggest that rare underdominant alleles are purged quickly except in small or subdivided populations. We predict that underdominant alleles that also influence mate choice, such as those affecting coloration patterns visible to mates and predators alike, can fix more readily. We analyze a mechanistic model of positive assortative mating in which individuals have n chances to sample compatible mates. This one-parameter model naturally spans random mating (n=1) and complete assortment (n→∞), yet it produces sexual selection whose strength depends non-monotonically on n. This sexual selection interacts with viability selection to either inhibit or facilitate fixation. As mating opportunities increase, underdominant alleles fix as frequently as neutral mutations, even though sexual selection and underdominance independently each suppress rare alleles. This mechanism allows underdominant alleles to fix in large populations and illustrates how life history can affect evolutionary change.

  17. Frequency of FCGR3B Alleles in Thai Blood Donors

    PubMed Central

    Kaset, Chollanot; Leetrakool, Nipapan; Intharanut, Kamphon

    2013-01-01

    Background Human neutrophil antigens (HNAs) are involved in autoimmune and alloimmune neutropenia and transfusion-related acute lung injury. The HNA-1 system is important in immunogenetics, and allele frequencies have been described in different populations. This study investigated the frequency of FCGR3B alleles encoding HNA-1a, HNA-1b, and HNA-1c among Thai blood donors and compared these frequencies with those previously reported for other populations. Methods Eight hundred DNA samples obtained from unrelated healthy blood donors at the National Blood Centre, Thai Red Cross Society, Bangkok, and the Blood Bank, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand, were included. Samples were simultaneously typed for each FCGR3B allele using an in-house polymerase chain reaction with sequence-specific primer (PCR-SSP) technique. Results The frequencies of FCGR3B*1, FCGR3B*2, and FCGR3B*3 alleles in central Thai blood donors were 0.548, 0.452, and 0.004, respectively; only FCGR3B*1 and FCGR3B*2 alleles were found in northern Thai blood donors (0.68 and 0.32, respectively). Compared with other Asian populations, central Thais had higher frequencies of the FCGR3B*2 allele (P<0.001), while the frequencies of the FCGR3B*1 and FCGR3B*2 alleles in northern Thais were similar to those previously reported in Taiwanese and Japanese populations. In contrast, the frequencies of the FCGR3B*1 and FCGR3B*2 alleles in the northern Thai population were statistically different from those observed in central Thai, Korean, German, and Turkish populations. Conclusions FCGR3B allele frequencies were significantly different between central and northern Thai blood donors. Our in-house PCR-SSP method is a simple, cost-effective, and convenient method for FCGR3B allele detection. PMID:24205492

  18. Qualitative Contrast between Knowledge-Limited Mixed-State and Variable-Resources Models of Visual Change Detection

    ERIC Educational Resources Information Center

    Nosofsky, Robert M.; Donkin, Chris

    2016-01-01

    We report an experiment designed to provide a qualitative contrast between knowledge-limited versions of mixed-state and variable-resources (VR) models of visual change detection. The key data pattern is that observers often respond "same" on big-change trials, while simultaneously being able to discriminate between same and small-change…

  19. Contrast Materials

    MedlinePlus

    ... veins of the body, including vessels in the brain, neck, chest, abdomen, pelvis and legs soft tissues of the body, including the muscles, fat and skin brain breast Microbubble Contrast Materials Microbubble contrast materials are ...

  20. A Comparison of the AFGL Flash, Draper Dart and AWS Haze Models with the Rand Wetta Model for Calculating Atmospheric Contrast Reduction.

    DTIC Science & Technology

    1982-03-01

    AD-AI1S 425 AIR FORCE ENVIRON0ENTAL TECHNICAL APPLICATIONS CENTER--ETC F/G 4/2 A COMPARISON OF THE AFOL FLASH, DRAPER DART AND AWS HAZE MODELS--ETC(U...COMPARISON OF THE AFGL FLASH, DRAPER DART AND AWS HAZE MODELS WITH THE RAND WETTA MODEL FOR CALCULATING ATMOSPHERIC CONTRAST REDUCTION BY1 DR. PATRICK J...AFOL FLASH, DRAPER DART AND AWS HAE MODELS WITH THE RAND WETTA MODEL FOR CALCULATING ATMOIPlURIC CONTRAST REDUCTION, March 1982, is approved for public

  1. The genetic basis of resistance and matching-allele interactions of a host-parasite system: The Daphnia magna-Pasteuria ramosa model.

    PubMed

    Bento, Gilberto; Routtu, Jarkko; Fields, Peter D; Bourgeois, Yann; Du Pasquier, Louis; Ebert, Dieter

    2017-02-21

    Negative frequency-dependent selection (NFDS) is an evolutionary mechanism suggested to govern host-parasite coevolution and the maintenance of genetic diversity at host resistance loci, such as the vertebrate MHC and R-genes in plants. Matching-allele interactions of hosts and parasites that prevent the emergence of host and parasite genotypes that are universally resistant and infective are a genetic mechanism predicted to underpin NFDS. The underlying genetics of matching-allele interactions are unknown even in host-parasite systems with empirical support for coevolution by NFDS, as is the case for the planktonic crustacean Daphnia magna and the bacterial pathogen Pasteuria ramosa. We fine-map one locus associated with D. magna resistance to P. ramosa and genetically characterize two haplotypes of the Pasteuria resistance (PR-) locus using de novo genome and transcriptome sequencing. Sequence comparison of PR-locus haplotypes finds dramatic structural polymorphisms between PR-locus haplotypes including a large portion of each haplotype being composed of non-homologous sequences resulting in haplotypes differing in size by 66 kb. The high divergence of PR-locus haplotypes suggest a history of multiple, diverse and repeated instances of structural mutation events and restricted recombination. Annotation of the haplotypes reveals striking differences in gene content. In particular, a group of glycosyltransferase genes that is present in the susceptible but absent in the resistant haplotype. Moreover, in natural populations, we find that the PR-locus polymorphism is associated with variation in resistance to different P. ramosa genotypes, pointing to the PR-locus polymorphism as being responsible for the matching-allele interactions that have been previously described for this system. Our results conclusively identify a genetic basis for the matching-allele interaction observed in a coevolving host-parasite system and provide a first insight into its molecular basis.

  2. The genetic basis of resistance and matching-allele interactions of a host-parasite system: The Daphnia magna-Pasteuria ramosa model

    PubMed Central

    Fields, Peter D.; Bourgeois, Yann; Du Pasquier, Louis; Ebert, Dieter

    2017-01-01

    Negative frequency-dependent selection (NFDS) is an evolutionary mechanism suggested to govern host-parasite coevolution and the maintenance of genetic diversity at host resistance loci, such as the vertebrate MHC and R-genes in plants. Matching-allele interactions of hosts and parasites that prevent the emergence of host and parasite genotypes that are universally resistant and infective are a genetic mechanism predicted to underpin NFDS. The underlying genetics of matching-allele interactions are unknown even in host-parasite systems with empirical support for coevolution by NFDS, as is the case for the planktonic crustacean Daphnia magna and the bacterial pathogen Pasteuria ramosa. We fine-map one locus associated with D. magna resistance to P. ramosa and genetically characterize two haplotypes of the Pasteuria resistance (PR-) locus using de novo genome and transcriptome sequencing. Sequence comparison of PR-locus haplotypes finds dramatic structural polymorphisms between PR-locus haplotypes including a large portion of each haplotype being composed of non-homologous sequences resulting in haplotypes differing in size by 66 kb. The high divergence of PR-locus haplotypes suggest a history of multiple, diverse and repeated instances of structural mutation events and restricted recombination. Annotation of the haplotypes reveals striking differences in gene content. In particular, a group of glycosyltransferase genes that is present in the susceptible but absent in the resistant haplotype. Moreover, in natural populations, we find that the PR-locus polymorphism is associated with variation in resistance to different P. ramosa genotypes, pointing to the PR-locus polymorphism as being responsible for the matching-allele interactions that have been previously described for this system. Our results conclusively identify a genetic basis for the matching-allele interaction observed in a coevolving host-parasite system and provide a first insight into its molecular basis

  3. Unconscious and spontaneous and...complex: the three selves model of social comparison assimilation and contrast.

    PubMed

    Blanton, Hart; Stapel, Diederik A

    2008-06-01

    Several theoretical perspectives predict that social comparisons lead to simple, default-driven effects when triggered outside of conscious awareness. These theoretical perspectives differ, however, in the default effects they predict. Some theories argue for self-evaluative contrast, whereas others argue for self-evaluative assimilation. The current studies tested the prediction that the default effect would vary as a function of the social context and the type of self-concept activated. When attention was focused on the personal self, contrast effects emerged. When attention was focused on collective or possible selves, assimilation effects emerged. These findings suggest that a wide range of comparison effects can be triggered spontaneously and outside of conscious awareness. However, some results also show ways in which social comparison processes simplify when deliberate reflection is lacking.

  4. What Is a Recessive Allele?

    ERIC Educational Resources Information Center

    American Biology Teacher, 1991

    1991-01-01

    Presents four misconceptions students have concerning the concepts of recessive and dominant alleles. Discusses the spectrum of dominant-recessive relationships, different levels of analysis between phenotype and genotype, possible causes of dominance, and an example involving wrinkled peas. (MDH)

  5. Model selection in measures of vascular parameters using dynamic contrast-enhanced MRI: experimental and clinical applications.

    PubMed

    Ewing, James R; Bagher-Ebadian, Hassan

    2013-08-01

    A review of the selection of models in dynamic contrast-enhanced MRI (DCE-MRI) is conducted, with emphasis on the balance between the bias and variance required to produce stable and accurate estimates of vascular parameters. The vascular parameters considered as a first-order model are the forward volume transfer constant K(trans) , the plasma volume fraction vp and the interstitial volume fraction ve . To illustrate the critical issues in model selection, a data-driven selection of models in an animal model of cerebral glioma is followed. Systematic errors and extended models are considered. Studies with nested and non-nested pharmacokinetic models are reviewed; models considering water exchange are considered.

  6. FMT-PCCT: hybrid fluorescence molecular tomography-x-ray phase-contrast CT imaging of mouse models.

    PubMed

    Mohajerani, Pouyan; Hipp, Alexander; Willner, Marian; Marschner, Mathias; Trajkovic-Arsic, Marija; Ma, Xiaopeng; Burton, Neal C; Klemm, Uwe; Radrich, Karin; Ermolayev, Vladimir; Tzoumas, Stratis; Siveke, Jens T; Bech, Martin; Pfeiffer, Franz; Ntziachristos, Vasilis

    2014-07-01

    The implementation of hybrid fluorescence molecular tomography (FMT) and X-ray computed tomography (CT) has been shown to be a necessary development, not only for combining anatomical with functional and molecular contrast, but also for generating optical images of high accuracy. FMT affords highly sensitive 3-D imaging of fluorescence bio-distribution, but in stand-alone form it offers images of low resolution. It was shown that FMT accuracy significantly improves by considering anatomical priors from CT. Conversely, CT generally suffers from low soft tissue contrast. Therefore utilization of CT data as prior information in FMT inversion is challenging when different internal organs are not clearly differentiated. Instead, we combined herein FMT with emerging X-ray phase-contrast CT (PCCT). PCCT relies on phase shift differences in tissue to achieve soft tissue contrast superior to conventional CT. We demonstrate for the first time FMT-PCCT imaging of different animal models, where FMT and PCCT scans were performed in vivo and ex vivo, respectively. The results show that FMT-PCCT expands the potential of FMT in imaging lesions with otherwise low or no CT contrast, while retaining the cost benefits of CT and simplicity of hybrid device realizations. The results point to the most accurate FMT performance to date.

  7. Automatic segmentation of ground-glass opacity nodule on chest CT images by histogram modeling and local contrast

    NASA Astrophysics Data System (ADS)

    Jung, Julip; Hong, Helen; Goo, Jin Mo

    2012-03-01

    We propose an automatic segmentation of Ground Glass Opacity (GGO) nodules on chest CT images by histogram modeling and local contrast. First, optimal volume circumscribing a nodule is calculated by clicking inside of GGO nodule. To remove noises while preserving a nodule boundary, anisotropic diffusion filtering is applied to the optimal volume. Second, for deciding an appropriate threshold value of GGO nodule, histogram modeling is performed by Gaussian Mixture Modeling (GMM) with three components such as lung parenchyma, nodule, and chest wall or vessels. Third, the attached chest wall and vessels are separated from the GGO nodules by maximum curvature points linking and morphological erosion with adaptive circular mask. Fourth, initial boundary of GGO nodule is refined using local contrast information. Experimental results show that attached neighbor structures are well separated from GGO nodules while missed GGO region is refined. The proposed segmentation method can be used for measurement of the growth rate of nodule and the proportion of solid portion inside nodule.

  8. Contrast-Dependence of Surround Suppression in Macaque V1: Experimental Testing of a Recurrent Network Model

    PubMed Central

    Schwabe, Lars; Ichida, Jennifer M.; Shushruth, S.; Mangapathy, Pradeep; Angelucci, Alessandra

    2010-01-01

    Neuronal responses in primary visual cortex (V1) to optimally oriented high-contrast stimuli in the receptive field (RF) center are suppressed by stimuli in the RF surround, but can be facilitated when the RF center is stimulated at low contrast. The neural circuits and mechanisms for surround modulation are still unknown. We previously proposed that topdown feedback connections mediate suppression from the “far” surround, while “near” surround suppression is mediated primarily by horizontal connections. We implemented this idea in a recurrent network model of V1. A model assumption needed to account for the contrast-dependent sign of surround modulation is a response asymmetry between excitation and inhibition; accordingly, inhibition, but not excitation, is silent for weak visual inputs to the RF center, and surround stimulation can evoke facilitation. A prediction stemming from this same assumption is that surround suppression is weaker for low than for high contrast stimuli in the RF center. Previous studies are inconsistent with this prediction. Using single unit recordings in macaque V1, we confirm this model's prediction. Model simulations demonstrate that our results can be reconciled with those from previous studies. We also performed a systematic comparison of the experimentally-measured surround suppression strength with predictions of the model operated in different parameter regimes. We find that the original model, with strong horizontal and no feedback excitation of local inhibitory neurons, can only partially account quantitatively for the experimentally-measured suppression. Strong direct feedback excitation of V1 inhibitory neurons is necessary to account for the experimentally-measured surround suppression strength. PMID:20079853

  9. Delayed Contrast Enhancement Imaging of a Murine Model for Ischemia Reperfusion with Carbon Nanotube Micro-CT

    PubMed Central

    Burk, Laurel M.; Wang, Ko-Han; Wait, John Matthew; Kang, Eunice; Willis, Monte; Lu, Jianping; Zhou, Otto; Lee, Yueh Z.

    2015-01-01

    We aim to demonstrate the application of free-breathing prospectively gated carbon nanotube (CNT) micro-CT by evaluating a myocardial infarction model with a delayed contrast enhancement technique. Evaluation of murine cardiac models using micro-CT imaging has historically been limited by extreme imaging requirements. Newly-developed CNT-based x-ray sources offer precise temporal resolution, allowing elimination of physiological motion through prospective gating. Using free-breathing, cardiac-gated CNT micro-CT, a myocardial infarction model can be studied non-invasively and with high resolution. Myocardial infarction was induced in eight male C57BL/6 mice aged 8–12 weeks. The ischemia reperfusion model was achieved by surgically occluding the LAD artery for 30 minutes followed by 24 hours of reperfusion. Tail vein catheters were placed for contrast administration. Iohexol 300mgI/mL was administered followed by images obtained in diastole. Iodinated lipid blood pool contrast agent was then administered, followed with images at systole and diastole. Respiratory and cardiac signals were monitored externally and used to gate the scans of free-breathing subjects. Seven control animals were scanned using the same imaging protocol. After imaging, the heart was harvested, cut into 1mm slices and stained with TTC. Post-processing analysis was performed using ITK-Snap and MATLAB. All animals demonstrated obvious delayed contrast enhancement in the left ventricular wall following the Iohexol injection. The blood pool contrast agent revealed significant changes in cardiac function quantified by 3-D volume ejection fractions. All subjects demonstrated areas of myocardial infarct in the LAD distribution on both TTC staining and micro-CT imaging. The CNT micro-CT system aids straightforward, free-breathing, prospectively-gated 3-D murine cardiac imaging. Delayed contrast enhancement allows identification of infarcted myocardium after a myocardial ischemic event. We demonstrate

  10. Phase-contrast computed tomography for quantification of structural changes in lungs of asthma mouse models of different severity.

    PubMed

    Dullin, Christian; Larsson, Emanuel; Tromba, Giuliana; Markus, Andrea M; Alves, Frauke

    2015-07-01

    Lung imaging in mouse disease models is crucial for the assessment of the severity of airway disease but remains challenging due to the small size and the high porosity of the organ. Synchrotron inline free-propagation phase-contrast computed tomography (CT) with its intrinsic high soft-tissue contrast provides the necessary sensitivity and spatial resolution to analyse the mouse lung structure in great detail. Here, this technique has been applied in combination with single-distance phase retrieval to quantify alterations of the lung structure in experimental asthma mouse models of different severity. In order to mimic an in vivo situation as close as possible, the lungs were inflated with air at a constant physiological pressure. Entire mice were embedded in agarose gel and imaged using inline free-propagation phase-contrast CT at the SYRMEP beamline (Synchrotron Light Source, `Elettra', Trieste, Italy). The quantification of the obtained phase-contrast CT data sets revealed an increasing lung soft-tissue content in mice correlating with the degree of the severity of experimental allergic airways disease. In this way, it was possible to successfully discriminate between healthy controls and mice with either mild or severe allergic airway disease. It is believed that this approach may have the potential to evaluate the efficacy of novel therapeutic strategies that target airway remodelling processes in asthma.

  11. Phase-contrast computed tomography for quantification of structural changes in lungs of asthma mouse models of different severity

    PubMed Central

    Dullin, Christian; Larsson, Emanuel; Tromba, Giuliana; Markus, Andrea M.; Alves, Frauke

    2015-01-01

    Lung imaging in mouse disease models is crucial for the assessment of the severity of airway disease but remains challenging due to the small size and the high porosity of the organ. Synchrotron inline free-propagation phase-contrast computed tomography (CT) with its intrinsic high soft-tissue contrast provides the necessary sensitivity and spatial resolution to analyse the mouse lung structure in great detail. Here, this technique has been applied in combination with single-distance phase retrieval to quantify alterations of the lung structure in experimental asthma mouse models of different severity. In order to mimic an in vivo situation as close as possible, the lungs were inflated with air at a constant physiological pressure. Entire mice were embedded in agarose gel and imaged using inline free-propagation phase-contrast CT at the SYRMEP beamline (Synchrotron Light Source, ‘Elettra’, Trieste, Italy). The quantification of the obtained phase-contrast CT data sets revealed an increasing lung soft-tissue content in mice correlating with the degree of the severity of experimental allergic airways disease. In this way, it was possible to successfully discriminate between healthy controls and mice with either mild or severe allergic airway disease. It is believed that this approach may have the potential to evaluate the efficacy of novel therapeutic strategies that target airway remodelling processes in asthma. PMID:26134818

  12. A Novel Foam Contrast Agent Suitable for Fluoroscopic Interventional Procedure: Comparative Study of Physical Properties and Experimental Intervention in Animal Model.

    PubMed

    Hwang, Jin Ho; Park, Hong Suk; Seo, Soowon; Choo, In Wook; Do, Young Soo; Choo, Sung Wook; Shin, Sung Wook; Park, Kwang Bo; Cho, Sung Ki; Hyun, Dongho; Lim, Sooyoun

    2015-01-01

    In fluoroscopic contrast study for interventional procedure, liquid contrast agent may be diluted in body fluid, losing its contrast effect. We developed a novel contrast agent of "foam state" to maintain contrast effect for enough time and performed a comparative study of physical properties and its usefulness in experimental intervention in animal model. The mean size of microbubble of foam contrast was 13.8 ± 3.6 µm. The viscosity was 201.0 ± 0.624 cP (centipoise) and the specific gravity was 0.616. The foam decayed slowly and it had 97.5 minutes of half-life. In terms of the sustainability in a slow flow environment, foam contrast washed out much more slowly than a conventional contrast. In experimental colonic stent placement, foam contrast revealed significantly better results than conventional contrast in procedure time, total amount of contrast usage, and the number of injections (p < 0.05). Our foam contrast has high viscosity and low specific gravity and maintains foam state for a sufficient time. Foam contrast with these properties was useful in experimental intervention in animal model. We anticipate that foam contrast may be applied to various kinds of interventional procedures.

  13. Search for novel contrast materials in dual-energy x-ray breast imaging using theoretical modeling of contrast-to-noise ratio.

    PubMed

    Karunamuni, R; Maidment, A D A

    2014-08-07

    Contrast-enhanced (CE) dual-energy (DE) x-ray breast imaging uses a low- and high-energy x-ray spectral pair to eliminate soft-tissue signal variation and thereby increase the detectability of exogenous imaging agents. Currently, CEDE breast imaging is performed with iodinated contrast agents. These compounds are limited by several deficiencies, including rapid clearance and poor tumor targeting ability. The purpose of this work is to identify novel contrast materials whose contrast-to-noise ratio (CNR) is comparable or superior to that of iodine in the mammographic energy range. A monoenergetic DE subtraction framework was developed to calculate the DE signal intensity resulting from the logarithmic subtraction of the low- and high-energy signal intensities. A weighting factor is calculated to remove the dependence of the DE signal on the glandularity of the breast tissue. Using the DE signal intensity and weighting factor, the CNR for materials with atomic numbers (Z) ranging from 1 to 79 are computed for energy pairs between 10 and 50 keV. A group of materials with atomic numbers ranging from 42 to 63 were identified to exhibit the highest levels of CNR in the mammographic energy range. Several of these materials have been formulated as nanoparticles for various applications but none, apart from iodine, have been investigated as CEDE breast imaging agents. Within this group of materials, the necessary dose fraction to the LE image decreases as the atomic number increases. By reducing the dose to the LE image, the DE subtraction technique will not provide an anatomical image of sufficient quality to accompany the contrast information. Therefore, materials with Z from 42 to 52 provide nearly optimal values of CNR with energy pairs and dose fractions that provide good anatomical images. This work is intended to inspire further research into new materials for optimized CEDE breast functional imaging.

  14. Giant SCA8 alleles in nine children whose mother has two moderately large ones.

    PubMed

    Corral, Jordi; Genís, David; Banchs, Isabel; San Nicolás, Hector; Armstrong, Judith; Volpini, Víctor

    2005-04-01

    We report here a family in which each of nine children has inherited giant SCA8 CTG expansions from a homozygous mother who has two moderately large SCA8 CTG alleles. In contrast, three homozygous male individuals and a case of coexistence of two expansions of the FRDA gene and one of SCA8, all of them with moderately large alleles, have transmitted their respective SCA8 expanded alleles with minor changes, as usually occurs in heterozygous male transmissions.

  15. Numerical and Qualitative Contrasts of Two Statistical Models for Water Quality Change in Tidal Waters

    EPA Science Inventory

    Two statistical approaches, weighted regression on time, discharge, and season and generalized additive models, have recently been used to evaluate water quality trends in estuaries. Both models have been used in similar contexts despite differences in statistical foundations and...

  16. Impact of number of repeated scans on model observer performance for a low-contrast detection task in CT

    NASA Astrophysics Data System (ADS)

    Ma, Chi; Yu, Lifeng; Chen, Baiyu; Vrieze, Thomas; Favazza, Christopher; Leng, Shuai; McCollough, Cynthia

    2015-03-01

    In previous investigations on CT image quality, channelized Hotelling observer (CHO) models have been shown to well represent human observer performance in several phantom-based detection/discrimination tasks. In these studies, a large number of independent images was necessary to estimate the expectation images and covariance matrices for each test condition. The purpose of this study is to investigate how the number of repeated scans affects the precision and accuracy of the CHO's performance in a signal-known-exactly detection task. A phantom containing 21 low-contrast objects (3 contrast levels and 7 sizes) was scanned with a 128-slice CT scanner at three dose levels. For each dose level, 100 independent images were acquired for each test condition. All images were reconstructed using filtered-backprojection (FBP) and a commercial iterative reconstruction algorithm. For each combination of dose level and reconstruction method, the low-contrast detectability, quantified with the area under receiver operating characteristic curve (Az), was calculated using a previously validated CHO model. To determine the dependency of CHO performance on the number of repeated scans, the Az value was calculated for different number of channel filters, for each object size and contrast, and for different dose/reconstruction settings using all 100 repeated scans. The Az values were also calculated using randomly selected subsets of the scans (from 10 to 90 scans with an increment of 10 scans). Using the Az from the 100 scans as the reference, the accuracy of Az values calculated from a fewer number of scans was determined and the minimal number of scans was subsequently derived. For the studied signal-known-exactly detection task, results demonstrated that, the minimal number of scans depends on dose level, object size and contrast level, and channel filters.

  17. Rethinking the role of worry in generalized anxiety disorder: evidence supporting a model of emotional contrast avoidance.

    PubMed

    Llera, Sandra J; Newman, Michelle G

    2014-05-01

    The Contrast Avoidance model (Newman & Llera, 2011) proposes that individuals with generalized anxiety disorder (GAD) are hypersensitive to sharp upward shifts in negative emotion that typically accompany negative events, and use worry to maintain sustained intrapersonal negativity in an attempt to avoid these shifts. Although research shows that worry increases negative emotionality and mutes further emotional reactivity to a stressor when compared to the worry period (e.g., Llera & Newman, 2010), no study has tracked changes in negative emotionality from baseline to worry inductions followed by a range of emotional exposures. Further, no study has yet assessed participants' subjective appraisals of prior worry on helping to cope with such exposures. The present study tested the main tenets of the Contrast Avoidance model by randomly assigning participants with GAD (n=48) and nonanxious controls (n=47) to experience worry, relaxation, and neutral inductions prior to sequential exposure to fearful, sad, and humorous film clips. Both physiological (nonspecific skin conductance responses [NS-SCRs]) and self-reported emotional changes were observed. Results indicated that worry boosted negative emotionality from baseline, which was sustained across negative exposures, whereas low negative emotionality during relaxation and neutral inductions allowed for sharp increases in response to exposures. Furthermore, GAD participants found worry to be more helpful than other conditions in coping with exposures, whereas control participants reported the opposite pattern. Results provide preliminary support for the Contrast Avoidance model. This suggests that treatment should focus on underlying avoidance patterns before attempting to reduce worry behavior.

  18. Contrastive Lexicology.

    ERIC Educational Resources Information Center

    Hartmann, R. R. K.

    This paper deals with the relation between etymologically related words in different languages. A survey is made of seven stages in the development of contrastive lexicology. These are: prelinguistic word studies, semantics, lexicography, translation, foreign language learning, bilingualism, and finally contrastive analysis. Concerning contrastive…

  19. Contrastive Analysis.

    ERIC Educational Resources Information Center

    James, Carl

    Contrastive analysis is viewed as an interlinguistic, bidirectional phenomenon which is concerned with both the form and function of language. As such, contrastive analysis must view language psycholinguistically and sociolinguistically as a system to be both described and acquired. Due to the need for a psychological component in the analysis,…

  20. NPWE model observer as a validated alternative for contrast detail analysis of digital detectors in general radiography

    NASA Astrophysics Data System (ADS)

    Van Peteghem, N.; Bosmans, H.; Marshall, N. W.

    2016-11-01

    To propose and validate a non-prewhitening with eye filter (NPWE) model observer as an alternative means of quantifying and specifying imaging performance for general radiography detectors, in a comparative study with contrast detail analysis and detective quantum efficiency (DQE). Five different x-ray detectors were assessed, covering a range of detector technologies including powder computed radiography (CR), needle CR, and three indirect conversion flat panel digital radiography detectors (DR). For each detector, threshold contrast detail (c-d) detectability was measured using the Leeds TO20 test object. A tube voltage of 70 kV and 1 mm Cu added filtration was used and five target detector air kerma (DAK) levels were set, ranging from 0.625 µGy to 10 µGy. Three c-d images were acquired at the same DAK levels and these were scored by two observers. Presampling modulation transfer function (MTF) was measured using an edge method while contrast was measured with a 2 mm Al square of dimension 10  ×  10 mm. The normalized noise power spectrum (NNPS) was calculated at the target DAK values of the c-d images. The MTF, NNPS and contrast data were then used to calculate a detectability index (d‧) with the NPWE model and compared to the human observer c-d results. The standard quantitative means of evaluating detector performance i.e. DQE, was then calculated for each detector. A linear correlation was found between the logarithm of threshold contrast and the logarithm of d’ for all detectors, as DAK was increased. Furthermore, the absolute value of d‧ tracked threshold contrast between the five detectors, enabling the use of detectability to quantify image quality rather than the intrinsically subjective threshold contrast scored by human observers from c-d test object images. At 2.5 µGy target DAK, d’ followed the differences in DQE between the five detectors. The NPWE detectability index can be used an alternative parameter for the

  1. Modelling the buried human body environment in upland climes using three contrasting field sites.

    PubMed

    Wilson, Andrew S; Janaway, Robert C; Holland, Andrew D; Dodson, Hilary I; Baran, Eve; Pollard, A Mark; Tobin, Desmond J

    2007-06-14

    Despite an increasing literature on the decomposition of human remains, whether buried or exposed, it is important to recognise the role of specific microenvironments which can either trigger or delay the rate of decomposition. Recent casework in Northern England involving buried and partially buried human remains has demonstrated a need for a more detailed understanding of the effect of contrasting site conditions on cadaver decomposition and on the microenvironment created within the grave itself. Pigs (Sus scrofa) were used as body analogues in three inter-related taphonomy experiments to examine differential decomposition of buried human remains. They were buried at three contrasting field sites (pasture, moorland, and deciduous woodland) within a 15 km radius of the University of Bradford, West Yorkshire, UK. Changes to the buried body and the effect of these changes on hair and associated death-scene textile materials were monitored as was the microenvironment of the grave. At recovery, 6, 12 and 24 months post-burial, the extent of soft tissue decomposition was recorded and samples of fat and soil were collected for gas chromatography mass spectrometry (GCMS) analysis. The results of these studies demonstrated that (1) soil conditions at these three burial sites has a marked effect on the condition of the buried body but even within a single site variation can occur; (2) the process of soft tissue decomposition modifies the localised burial microenvironment in terms of microbiological load, pH, moisture and changes in redox status. These observations have widespread application for the investigation of clandestine burial and time since deposition, and in understanding changes within the burial microenvironment that may impact on biomaterials such as hair and other associated death scene materials.

  2. Buttonpusher or Partner? Two Contrasting Models of Film Production in a University Setting.

    ERIC Educational Resources Information Center

    Pfaff, Gunter

    There are two distinct models of film production. One model, characterized as assembly line production, is the most prevalent in commercial settings and in universities. The project is initiated through management and progresses in an ordered flow of assembly through the hands of the specialized film workers; power is from the top down. The…

  3. Crash testing hydrological models in contrasted climate conditions: An experiment on 216 Australian catchments

    NASA Astrophysics Data System (ADS)

    Coron, L.; AndréAssian, V.; Perrin, C.; Lerat, J.; Vaze, J.; Bourqui, M.; Hendrickx, F.

    2012-05-01

    This paper investigates the actual extrapolation capacity of three hydrological models in differing climate conditions. We propose a general testing framework, in which we perform series of split-sample tests, testing all possible combinations of calibration-validation periods using a 10 year sliding window. This methodology, which we have called the generalized split-sample test (GSST), provides insights into the model's transposability over time under various climatic conditions. The three conceptual rainfall-runoff models yielded similar results over a set of 216 catchments in southeast Australia. First, we assessed the model's efficiency in validation using a criterion combining the root-mean-square error and bias. A relation was found between this efficiency and the changes in mean rainfall (P) but not with changes in mean potential evapotranspiration (PE) or air temperature (T). Second, we focused on average runoff volumes and found that simulation biases are greatly affected by changes in P. Calibration over a wetter (drier) climate than the validation climate leads to an overestimation (underestimation) of the mean simulated runoff. We observed different magnitudes of these models deficiencies depending on the catchment considered. Results indicate that the transfer of model parameters in time may introduce a significant level of errors in simulations, meaning increased uncertainty in the various practical applications of these models (flow simulation, forecasting, design, reservoir management, climate change impact assessments, etc.). Testing model robustness with respect to this issue should help better quantify these uncertainties.

  4. DRD4 dopamine receptor allelic diversity in various primate species

    SciTech Connect

    Adamson, M.; Higley, D.; O`Brien, S.

    1994-09-01

    The DRD4 dopamine receptor is uniquely characterized by a 48 bp repeating segment within the coding region, located in exon III. Different DRD4 alleles are produced by the presence of additional 48 bp repeats, each of which adds 16 amino acids to the length of the 3rd intracytoplasmic loop of the receptor. The DRD4 receptor is therefore an intriguing candidate gene for behaviors which are influenced by dopamine function. In several human populations, DRD4 alleles with 2-8 and 10 repeats have previously been identified, and the 4 and 7 repeat alleles are the most abundant. We have determined DRD4 genotypes in the following nonhuman primate species: chimpanzee N=2, pygmy chimpanzee N=2, gorilla N=4, siamang N=2, Gelada baboon N=1, gibbon N=1, orangutan (Bornean and Sumatran) N=62, spider monkey N=4, owl monkey N=1, Colobus monkey N=1, Patas monkey N=1, ruffed lemur N=1, rhesus macaque N=8, and vervet monkey N=28. The degree of DRD4 polymorphism and which DRD4 alleles were present both showed considerable variation across primate species. In contrast to the human, rhesus macaque monkeys were monomorphic. The 4 and 7 repeat allels, highly abundant in the human, may not be present in certain other primates. For example, the four spider monkeys we studied showed the 7, 8 and 9 repeat length alleles and the only gibbon we analyzed was homozygous for the 9 repeat allele (thus far not observed in the human). Genotyping of other primate species and sequencing of the individual DRD4 repeat alleles in different species may help us determine the ancestral DRD4 repeat length and identify connections between DRD4 genotype and phenotype.

  5. [Contrastive analysis on soil alkalinization predicting models based on measured reflectance and TM image reflectance].

    PubMed

    Zhang, Fang; Xiong, Hei-Gang; Long, Tao; Lu, Wen-Juan

    2011-01-01

    Based on the monitored data of soil pH and measured Vis-NIR reflectance on spot in Qitai oasis alkalinized area in Xinjiang, as well as comparison of the relationship between measured reflectance and soil pH and the relationship between TM reflectance and soil pH, both of the reflectance multivariate linear regression models were built to evaluate soil alkalinization level, and the model accuracy of pH fitting was discussed with error inspection of post-sample. The results showed that there is a significant positive correlation between soil pH and reflectance. With pH rising the reflectance increased concurrently. So the alkalinization soil characterized by hardening had good spectral response characteristics. Both measured reflectance and TM image reflectance had good potential ability for change detection of the alkalinization soil. The pH predicting model of measured reflectance had higher accuracy and the major error was from different hardening state. If building model by TM reflectance directly, the accuracy of fitting was lower because of the vegetation information in image spectrum. With the vegetation factor removed with NDVI, the accuracy of TM predicting model was near the accuracy of measured reflectance predicting model, and both of the model levels were good.

  6. Adolescent mental health and academic functioning: empirical support for contrasting models of risk and vulnerability.

    PubMed

    Lucier-Greer, Mallory; O'Neal, Catherine W; Arnold, A Laura; Mancini, Jay A; Wickrama, Kandauda K A S

    2014-11-01

    Adolescents in military families contend with normative stressors that are universal and exist across social contexts (minority status, family disruptions, and social isolation) as well as stressors reflective of their military life context (e.g., parental deployment, school transitions, and living outside the United States). This study utilizes a social ecological perspective and a stress process lens to examine the relationship between multiple risk factors and relevant indicators of youth well-being, namely depressive symptoms and academic performance, as well as the mediating role of self-efficacy (N = 1,036). Three risk models were tested: an additive effects model (each risk factor uniquely influences outcomes), a full cumulative effects model (the collection of risk factors influences outcomes), a comparative model (a cumulative effects model exploring the differential effects of normative and military-related risks). This design allowed for the simultaneous examination of multiple risk factors and a comparison of alternative perspectives on measuring risk. Each model was predictive of depressive symptoms and academic performance through persistence; however, each model provides unique findings about the relationship between risk factors and youth outcomes. Discussion is provided pertinent to service providers and researchers on how risk is conceptualized and suggestions for identifying at-risk youth.

  7. Qualitative contrast between knowledge-limited mixed-state and variable-resources models of visual change detection.

    PubMed

    Nosofsky, Robert M; Donkin, Chris

    2016-10-01

    We report an experiment designed to provide a qualitative contrast between knowledge-limited versions of mixed-state and variable-resources (VR) models of visual change detection. The key data pattern is that observers often respond “same” on big-change trials, while simultaneously being able to discriminate between same and small-change trials. The mixed-state model provides a natural account of this data pattern: With some probability, the observer is in a zero-memory state and is forced to guess. Thus, even on big-change trials, there is a significant probability that the observer will respond “same.” On other trials, the observer retains memory for the probed study item, and these memory-based responses allow the observer to show above-chance discrimination between same and small-change trials. By contrast, we show that important versions of the VR models that we refer to as knowledge-limited models are stymied by this simple pattern of results. In agreement with Keshvari, van den Berg, and Ma (2012, 2013), alternative knowledge-rich VR models that employ ideal-observer decision rules provide a significant improvement over the knowledge-limited VR models; however, extant versions of the knowledge-rich VR models still fall short quantitatively compared to the descriptive mixed-state model. We discuss implications of the knowledge-rich assumptions that are posited in current versions of the VR models that have been used to fit change-detection data.

  8. Numerical modeling of the 3D dynamics of ultrasound contrast agent microbubbles using the boundary integral method

    NASA Astrophysics Data System (ADS)

    Wang, Qianxi; Manmi, Kawa; Calvisi, Michael L.

    2015-02-01

    Ultrasound contrast agents (UCAs) are microbubbles stabilized with a shell typically of lipid, polymer, or protein and are emerging as a unique tool for noninvasive therapies ranging from gene delivery to tumor ablation. While various models have been developed to describe the spherical oscillations of contrast agents, the treatment of nonspherical behavior has received less attention. However, the nonspherical dynamics of contrast agents are thought to play an important role in therapeutic applications, for example, enhancing the uptake of therapeutic agents across cell membranes and tissue interfaces, and causing tissue ablation. In this paper, a model for nonspherical contrast agent dynamics based on the boundary integral method is described. The effects of the encapsulating shell are approximated by adapting Hoff's model for thin-shell, spherical contrast agents. A high-quality mesh of the bubble surface is maintained by implementing a hybrid approach of the Lagrangian method and elastic mesh technique. The numerical model agrees well with a modified Rayleigh-Plesset equation for encapsulated spherical bubbles. Numerical analyses of the dynamics of UCAs in an infinite liquid and near a rigid wall are performed in parameter regimes of clinical relevance. The oscillation amplitude and period decrease significantly due to the coating. A bubble jet forms when the amplitude of ultrasound is sufficiently large, as occurs for bubbles without a coating; however, the threshold amplitude required to incite jetting increases due to the coating. When a UCA is near a rigid boundary subject to acoustic forcing, the jet is directed towards the wall if the acoustic wave propagates perpendicular to the boundary. When the acoustic wave propagates parallel to the rigid boundary, the jet direction has components both along the wave direction and towards the boundary that depend mainly on the dimensionless standoff distance of the bubble from the boundary. In all cases, the jet

  9. Assignment of SNP allelic configuration in polyploids using competitive allele-specific PCR: application to citrus triploid progeny

    PubMed Central

    Cuenca, José; Aleza, Pablo; Navarro, Luis; Ollitrault, Patrick

    2013-01-01

    Background Polyploidy is a major component of eukaryote evolution. Estimation of allele copy numbers for molecular markers has long been considered a challenge for polyploid species, while this process is essential for most genetic research. With the increasing availability and whole-genome coverage of single nucleotide polymorphism (SNP) markers, it is essential to implement a versatile SNP genotyping method to assign allelic configuration efficiently in polyploids. Scope This work evaluates the usefulness of the KASPar method, based on competitive allele-specific PCR, for the assignment of SNP allelic configuration. Citrus was chosen as a model because of its economic importance, the ongoing worldwide polyploidy manipulation projects for cultivar and rootstock breeding, and the increasing availability of SNP markers. Conclusions Fifteen SNP markers were successfully designed that produced clear allele signals that were in agreement with previous genotyping results at the diploid level. The analysis of DNA mixes between two haploid lines (Clementine and pummelo) at 13 different ratios revealed a very high correlation (average = 0·9796; s.d. = 0·0094) between the allele ratio and two parameters [θ angle = tan−1 (y/x) and y′ = y/(x + y)] derived from the two normalized allele signals (x and y) provided by KASPar. Separated cluster analysis and analysis of variance (ANOVA) from mixed DNA simulating triploid and tetraploid hybrids provided 99·71 % correct allelic configuration. Moreover, triploid populations arising from 2n gametes and interploid crosses were easily genotyped and provided useful genetic information. This work demonstrates that the KASPar SNP genotyping technique is an efficient way to assign heterozygous allelic configurations within polyploid populations. This method is accurate, simple and cost-effective. Moreover, it may be useful for quantitative studies, such as relative allele-specific expression analysis and bulk segregant analysis

  10. Assimilation of point SWE data into a distributed snow cover model comparing two contrasting methods

    NASA Astrophysics Data System (ADS)

    Magnusson, Jan; Gustafsson, David; Hüsler, Fabia; Jonas, Tobias

    2014-10-01

    In alpine and high-latitude regions, water resource decision making often requires large-scale estimates of snow amounts and melt rates. Such estimates are available through distributed snow models which in some situations can be improved by assimilation of remote sensing observations. However, in regions with frequent cloud cover, complex topography, or large snow amounts satellite observations may feature information of limited quality. In this study, we examine whether assimilation of snow water equivalent (SWE) data from ground observations can improve model simulations in a region largely lacking reliable remote sensing observations. We combine the model output with the point data using three-dimensional sequential data assimilation methods, the ensemble Kalman filter, and statistical interpolation. The filter performance was assessed by comparing the simulation results against observed SWE and snow-covered fraction. We find that a method which assimilates fluxes (snowfall and melt rates computed from SWE) showed higher model performance than a control simulation not utilizing the filter algorithms. However, an alternative approach for updating the model results using the SWE data directly did not show a significantly higher performance than the control simulation. The results show that three-dimensional data assimilation methods can be useful for transferring information from point snow observations to the distributed snow model.

  11. Modeling of the acoustic response from contrast agent microbubbles near a rigid wall

    PubMed Central

    Doinikov, Alexander A.; Zhao, Shukui; Dayton, Paul A.

    2009-01-01

    In ultrasonic targeted imaging, specially designed encapsulated microbubbles are used, which are capable of selectively adhering to the target site in the body. A challenging problem is to distinguish the echoes from such adherent agents from echoes produced by freely circulating agents. In the present paper, an equation of radial oscillation for an encapsulated bubble near a plane rigid wall is derived. The equation is then used to simulate the echo from a layer of contrast agents localized on a wall. The echo spectrum of adherent microbubbles is compared to that of free, randomly distributed microbubbles inside a vessel, in order to examine differences between the acoustic responses of free and adherent agents. It is shown that the fundamental spectral component of adherent bubbles is perceptibly stronger than that of free bubbles. This increase is accounted for by a more coherent summation of echoes from adherent agents and the acoustic interaction between the agents and the wall. For cases tested, the increase of the fundamental component caused by the above two effects is on the order of 8-9 dB. Bubble aggregates, which are observed experimentally to form near a wall due to secondary Bjerknes forces, increase the intensity of the fundamental component only if they are formed by bubbles whose radii are well below the resonant radius. If the formation of aggregates contributes to the growth of the fundamental component, the increase can exceed 17 dB. Statistical analysis for the comparison between adhering and free bubbles, performed over random space bubble distributions, gives p-values much smaller than 0.05. PMID:18789469

  12. Physical analog (centrifuge) model investigation of contrasting structural styles in the Salt Range and Potwar Plateau, northern Pakistan

    NASA Astrophysics Data System (ADS)

    Faisal, Shah; Dixon, John M.

    2015-08-01

    We use scaled physical analog (centrifuge) modeling to investigate along- and across-strike structural variations in the Salt Range and Potwar Plateau of the Himalayan foreland fold-thrust belt of Pakistan. The models, composed of interlayered plasticine and silicone putty laminae, comprise four mechanical units representing the Neoproterozoic Salt Range Formation (basal detachment), Cambrian-Eocene carapace sequence, and Rawalpindi and Siwalik Groups (Neogene molasse), on a rigid base representing the Indian craton. Pre-cut ramps simulate basement faults with various structural geometries. A pre-existing north-dipping basement normal fault under the model foreland induces a frontal ramp and a prominent fault-bend-fold culmination, simulating the Salt Range. The ramp localizes displacement on a frontal thrust that occurs out-of-sequence with respect to other foreland folds and thrusts. With a frontal basement fault terminating to the east against a right-stepping, east-dipping lateral ramp, deformation propagates further south in the east; strata to the east of the lateral ramp are telescoped in ENE-trending detachment folds, fault-propagation folds and pop-up structures above a thick basal detachment (Salt Range Formation), in contrast to translated but less-deformed strata with E-W-trending Salt-Range structures to the west. The models are consistent with Salt Range-Potwar Plateau structural style contrasts being due to basement fault geometry and variation in detachment thickness.

  13. Contrasting Models of Posttraumatic Stress Disorder: Reply to Monroe and Mineka (2008)

    ERIC Educational Resources Information Center

    Berntsen, Dorthe; Rubin, David C.; Bohni, Malene Klindt

    2008-01-01

    The authors address the 4 main points in S. M. Monroe and S. Mineka's comment. First, the authors show that the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; American Psychiatric Association, 2000) posttraumatic stress disorder (PTSD) diagnosis includes an etiology and that it is based on a theoretical model with a…

  14. Cavitation thresholds of contrast agents in an in vitro human clot model exposed to 120-kHz ultrasound

    PubMed Central

    Gruber, Matthew J.; Bader, Kenneth B.; Holland, Christy K.

    2014-01-01

    Ultrasound contrast agents (UCAs) can be employed to nucleate cavitation to achieve desired bioeffects, such as thrombolysis, in therapeutic ultrasound applications. Effective methods of enhancing thrombolysis with ultrasound have been examined at low frequencies (<1 MHz) and low amplitudes (<0.5 MPa). The objective of this study was to determine cavitation thresholds for two UCAs exposed to 120-kHz ultrasound. A commercial ultrasound contrast agent (Definity®) and echogenic liposomes were investigated to determine the acoustic pressure threshold for ultraharmonic (UH) and broadband (BB) generation using an in vitro flow model perfused with human plasma. Cavitation emissions were detected using two passive receivers over a narrow frequency bandwidth (540–900 kHz) and a broad frequency bandwidth (0.54–1.74 MHz). UH and BB cavitation thresholds occurred at the same acoustic pressure (0.3 ± 0.1 MPa, peak to peak) and were found to depend on the sensitivity of the cavitation detector but not on the nucleating contrast agent or ultrasound duty cycle. PMID:25234874

  15. Cavitation thresholds of contrast agents in an in vitro human clot model exposed to 120-kHz ultrasound.

    PubMed

    Gruber, Matthew J; Bader, Kenneth B; Holland, Christy K

    2014-02-01

    Ultrasound contrast agents (UCAs) can be employed to nucleate cavitation to achieve desired bioeffects, such as thrombolysis, in therapeutic ultrasound applications. Effective methods of enhancing thrombolysis with ultrasound have been examined at low frequencies (<1 MHz) and low amplitudes (<0.5 MPa). The objective of this study was to determine cavitation thresholds for two UCAs exposed to 120-kHz ultrasound. A commercial ultrasound contrast agent (Definity(®)) and echogenic liposomes were investigated to determine the acoustic pressure threshold for ultraharmonic (UH) and broadband (BB) generation using an in vitro flow model perfused with human plasma. Cavitation emissions were detected using two passive receivers over a narrow frequency bandwidth (540-900 kHz) and a broad frequency bandwidth (0.54-1.74 MHz). UH and BB cavitation thresholds occurred at the same acoustic pressure (0.3 ± 0.1 MPa, peak to peak) and were found to depend on the sensitivity of the cavitation detector but not on the nucleating contrast agent or ultrasound duty cycle.

  16. Diffraction modeling of finite subband EFC probing on dark hole contrast with WFIRST-CGI shaped pupil coronagraph

    NASA Astrophysics Data System (ADS)

    Zhou, Hanying; Krist, John; Nemati, Bijan

    2016-08-01

    Current coronagraph instrument design (CGI), as a part of a proposed NASA WFIRST (Wide-Field InfraRed Survey Telescope) mission, allocates two subband filters per full science band in order to contain system complexity and cost. We present our detailed investigation results on the adequacy of such limited number of finite subband filters in achieving full band dark hole contrast with shaped pupil coronagraph. The study is based on diffraction propagation modeling with realistic WFIRST optics, where each subband's complex field estimation is obtained, using Electric Field Conjugation (EFC) wavefront sensing / control algorithm, from pairwise pupil plane deformable mirror (DM) probing and image plane intensity averaging of the resulting fields of multiple (subband) wavelengths. Multiple subband choices and probing and control strategies are explored, including standard subband probing; mixed wavelength and/or weighted Jacobian matrix; subband probing with intensity subtraction; and extended subband probing with intensity subtraction. Overall, the investigation shows that the achievable contrast with limited number of finite subband EFC probing is about 2 2.5x worse than the designed post-EFC contrast for current SPC design. The result suggests that for future shaped pupil design, slightly larger over intended full bandwidth should be considered if it will be used with limited subbands for probing.

  17. Model-Assisted Estimation of the Genetic Variability in Physiological Parameters Related to Tomato Fruit Growth under Contrasted Water Conditions

    PubMed Central

    Constantinescu, Dario; Memmah, Mohamed-Mahmoud; Vercambre, Gilles; Génard, Michel; Baldazzi, Valentina; Causse, Mathilde; Albert, Elise; Brunel, Béatrice; Valsesia, Pierre; Bertin, Nadia

    2016-01-01

    Drought stress is a major abiotic stress threatening plant and crop productivity. In case of fleshy fruits, understanding mechanisms governing water and carbon accumulations and identifying genes, QTLs and phenotypes, that will enable trade-offs between fruit growth and quality under Water Deficit (WD) condition is a crucial challenge for breeders and growers. In the present work, 117 recombinant inbred lines of a population of Solanum lycopersicum were phenotyped under control and WD conditions. Plant water status, fruit growth and composition were measured and data were used to calibrate a process-based model describing water and carbon fluxes in a growing fruit as a function of plant and environment. Eight genotype-dependent model parameters were estimated using a multiobjective evolutionary algorithm in order to minimize the prediction errors of fruit dry and fresh mass throughout fruit development. WD increased the fruit dry matter content (up to 85%) and decreased its fresh weight (up to 60%), big fruit size genotypes being the most sensitive. The mean normalized root mean squared errors of the predictions ranged between 16–18% in the population. Variability in model genotypic parameters allowed us to explore diverse genetic strategies in response to WD. An interesting group of genotypes could be discriminated in which (i) the low loss of fresh mass under WD was associated with high active uptake of sugars and low value of the maximum cell wall extensibility, and (ii) the high dry matter content in control treatment (C) was associated with a slow decrease of mass flow. Using 501 SNP markers genotyped across the genome, a QTL analysis of model parameters allowed to detect three main QTLs related to xylem and phloem conductivities, on chromosomes 2, 4, and 8. The model was then applied to design ideotypes with high dry matter content in C condition and low fresh mass loss in WD condition. The ideotypes outperformed the RILs especially for large and medium

  18. A model for the time-order error in contrast discrimination.

    PubMed

    Alcala-Quintana, Rocı O; Garcı A-Perez, Miguel A

    2011-06-01

    Trials in a temporal two-interval forced-choice discrimination experiment consist of two sequential intervals presenting stimuli that differ from one another as to magnitude along some continuum. The observer must report in which interval the stimulus had a larger magnitude. The standard difference model from signal detection theory analyses poses that order of presentation should not affect the results of the comparison, something known as the balance condition (J.-C. Falmagne, 1985, in Elements of Psychophysical Theory). But empirical data prove otherwise and consistently reveal what Fechner (1860/1966, in Elements of Psychophysics) called time-order errors, whereby the magnitude of the stimulus presented in one of the intervals is systematically underestimated relative to the other. Here we discuss sensory factors (temporary desensitization) and procedural glitches (short interstimulus or intertrial intervals and response bias) that might explain the time-order error, and we derive a formal model indicating how these factors make observed performance vary with presentation order despite a single underlying mechanism. Experimental results are also presented illustrating the conventional failure of the balance condition and testing the hypothesis that time-order errors result from contamination by the factors included in the model.

  19. Development of a theoretical model describing sonoporation activity of cells exposed to ultrasound in the presence of contrast agents

    PubMed Central

    Forbes, Monica M.; O’Brien, William D.

    2012-01-01

    Sonoporation uses ultrasound, with the aid of ultrasound contrast agents (UCAs), to enhance cell permeabilization, thereby allowing delivery of therapeutic compounds noninvasively into specific target cells. The objective of this study was to determine if a computational model describing shear stress on a cell membrane due to microstreaming would successfully reflect sonoporation activity with respect to the peak rarefactional pressure. The theoretical models were compared to the sonoporation results from Chinese hamster ovary cells using Definity® at 0.9, 3.15, and 5.6 MHz and were found to accurately describe the maximum sonoporation activity, the pressure where a decrease in sonoporation activity occurs, and relative differences between maximum activity and the activity after that decrease. Therefore, the model supports the experimental findings that shear stress on cell membranes secondary to oscillating UCAs results in sonoporation. PMID:22501051

  20. Revision of the theory of tracer transport and the convolution model of dynamic contrast enhanced magnetic resonance imaging

    PubMed Central

    Bammer, Roland; Stollberger, Rudolf

    2012-01-01

    Counterexamples are used to motivate the revision of the established theory of tracer transport. Then dynamic contrast enhanced magnetic resonance imaging in particular is conceptualized in terms of a fully distributed convection–diffusion model from which a widely used convolution model is derived using, alternatively, compartmental discretizations or semigroup theory. On this basis, applications and limitations of the convolution model are identified. For instance, it is proved that perfusion and tissue exchange states cannot be identified on the basis of a single convolution equation alone. Yet under certain assumptions, particularly that flux is purely convective at the boundary of a tissue region, physiological parameters such as mean transit time, effective volume fraction, and volumetric flow rate per unit tissue volume can be deduced from the kernel. PMID:17429633

  1. Contrast Enhancement of MicroCT Scans to Aid 3D Modelling of Carbon Fibre Fabric Composites

    NASA Astrophysics Data System (ADS)

    Djukic, Luke P.; Pearce, Garth M.; Herszberg, Israel; Bannister, Michael K.; Mollenhauer, David H.

    2013-12-01

    This paper presents a methodology for volume capture and rendering of plain weave and multi-layer fabric meso-architectures within a consolidated, cured laminate. Micro X-ray Computed Tomography (MicroCT) is an excellent tool for the non-destructive visualisation of material microstructures however the contrast between tows and resin is poor for carbon fibre composites. Firstly, this paper demonstrates techniques to improve the contrast of the microCT images by introducing higher density materials such as gold, iodine and glass into the fabric. Two approaches were demonstrated to be effective for enhancing the differentiation between the tows in the reconstructed microCT visualisations. Secondly, a method of generating three-dimensional volume models of woven composites using microCT scan data is discussed. The process of generating a model is explained from initial manufacture with the aid of an example plain weave fabric. These methods are to be used in the finite element modelling of three-dimensional fabric preforms in future work.

  2. An approximate nonlinear model for time gain compensation of amplitude modulated images of ultrasound contrast agent perfusion.

    PubMed

    Mari, Jean; Hibbs, Kathryn; Stride, Eleanor; Eckersley, Robert; Tang, Meng

    2010-04-01

    Microbubble ultrasound contrast agents allow blood perfusion to be imaged at the cost of an increased attenuation that is not properly handled by existing time gain compensation methods. An automatic TGC has been developed that is able to account for different microbubble concentrations. The technique is an extension of a previously tested approach for modeling the nonlinear dependence of microbubble backscattering upon insonating pressure. The proposed method involves modeling in amplitude of the nonlinear attenuation for both forward and backward propagation, and the solution is achieved through an approximation set to overestimate the attenuation. The resulting equations are used to model and compensate amplitude modulation (AM) images; they are tested on radiofrequency data acquired using a clinical scanner from a gelatin tissue-mimicking phantom submerged in a contrast agent solution in the 0.08 MI to 0.51 MI range at 2 MHz. The nonlinear estimation equation presented here provides a significantly improved amplification profile compared with standard TGC algorithms, resulting in more accurate attenuation correction of the AM image.

  3. Identification of two novel human CD1E alleles.

    PubMed

    Mirones, I; Oteo, M; Parra-Cuadrado, J F; Martínez-Naves, E

    2000-08-01

    CD1 is a family of proteins structurally related to major histocompatibility complex (MHC) molecules and specialized in presenting lipids or glycolipids to T cells. In humans, there are five CD1 genes (CD1A to CD1E). It has been shown that, in contrast with classical MHC genes, CD1 loci display a very limited polymorphism. In the present work we describe two novel CD1E alleles found in two healthy Caucasian individuals. One allele differs from the wild-type by a point mutation resulting in a replacement of arginine at position 154 by a tryptophan. In the second allele we found a substitution of the leucine 184 by a proline.

  4. Dynamic contrast-enhanced x-ray CT measurement of cerebral blood volume in a rabbit tumor model

    NASA Astrophysics Data System (ADS)

    Cenic, Aleksa; Lee, Ting-Yim; Craen, Rosemary A.; Gelb, Adrian W.

    1998-07-01

    Cerebral blood volume (CBV) is a major determinant of intracranial pressure (ICP). Hyperventilation is commonly employed to reduce raised ICP (e.g. in brain tumour patients) presumably through its effect on CBV. With the advent of slip- ring CT scanners, dynamic contrast-enhanced imaging allows for the measurement of CBV with high spatial resolution. Using a two-compartment model to characterize the distribution of X- ray contrast agent in the brain, we have developed a non- equilibrium CT method to measure CBV in normal and pathological regions. We used our method to investigate the effect of hyperventilation on CBV during propofol anaesthesia in rabbits with implanted brain tumours. Eight New Zealand White rabbits with implanted VX2 carcinoma brain tumours were studied. For each rabbit, regional CBV measurements were initially made at normocapnia (PaCO2 40 mmHg) and then at hyperventilation (PaCO2 25 mmHg) during propofol anaesthesia. The head was positioned such that a coronal image through the brain incorporated a significant cross-section of the brain tumour as well as a radial artery in a forelimb. Images at the rate of 1 per second were acquired for 2 minutes as Omnipaque 300 (1.5 ml/kg rabbit weight) was injected via a peripheral vein. In these CT images, regions of interest in the brain tissue (e.g. tumour, contra-lateral normal, and peri-tumoural) and the radial artery were drawn. For each region, the mean CT number in pre-contrast images was subtracted from the mean CT number in post-contrast images to produce either the tissue contrast concentration curve, or the arterial contrast concentration curve. Using our non- equilibrium analysis method based on a two-compartment model, regional CBV values were determined from the measured contrast concentration curves. From our study, the mean CBV values [+/- SD] in the tumour, peri-tumoural, and contra-lateral normal regions during normocapnia were: 5.47 plus or minus 1.97, 3.28 plus or minus 1.01, and 1

  5. Modeling max-of-N fluence distribution using measured shot-to-shot beam contrast

    SciTech Connect

    Liao, Zhi M.; Huebel, John; Trenholme, John; Manes, Ken; Carr, C. Wren

    2011-07-10

    We have found the local temporal shot-to-shot variation of the NIF high-energy laser system to be relatively constant ({approx}3.4% to 4.2% of the mean fluence). We have developed a statistical model that predicts the maximum fluence distribution any particular location will be exposed to after N independent shots (the so-called max-of-N fluence distribution) using the measured shot-to-shot variance; this method allows for an estimate of maximum optics fluence exposure.

  6. Contrast lipocryolysis

    PubMed Central

    Pinto, Hernán; Melamed, Graciela

    2014-01-01

    Alternative crystal structures are possible for all lipids and each different crystal structure is called a polymorphic form. Inter-conversion between polymorphisms would imply the possibility of leaning crystal formation toward the most effective polymorphism for adipocyte destruction. Food industry has been tempering lipids for decades. Tempering technology applied to lipocryolysis gave birth to “contrast lipocryolysis”, which involves pre- and post-lipocryolysis fat layer heating as part of a specific tempering protocol. In this study, we evaluated the skinfold thickness of 10 subjects after a single contrast lipocryolysis session and witnessed important and fast reductions. PMID:25068088

  7. Correlated evolution of nucleotide substitution rates and allelic variation in Mhc-DRB lineages of primates

    PubMed Central

    Garamszegi, László Z; de Groot, Natasja G; Bontrop, Ronald E

    2009-01-01

    models that control for similarity between species, due to common descent, and focused on variations within a single lineage (DRB1*03), the positive relationship between different substitution rates and allelic polymorphisms was still robust. Finally, we found the same effects to emerge in the analyses that eliminated within-species variation in MHC traits by using strictly single population-level studies. However, in a set of contrasting analyses, in which we focused on the non-functional DRB6 locus, the correlation between substitution rates and allelic variation was not prevalent. Conclusion Our results indicate that positive selection for the generation of allelic polymorphism acting on the functional part of the protein has consequences for the nucleotide substitution rate along the whole exon 2 sequence of the Mhc-DRB gene. Additionally, we proved that an increased substitution rate can promote allelic variation within lineages. Consequently, the evolution of different characteristics of genetic polymorphism is not independent. PMID:19361342

  8. Contrasting Polymer Behavior Under Nanoconfinement using Thermomechanically Consistent Coarse-Grained Models

    NASA Astrophysics Data System (ADS)

    Keten, Sinan; Xia, Wenjie; Hsu, David

    2015-03-01

    We present a systematic, two-bead per monomer coarse graining strategy that simulates the thermomechanical behavior of polymers several hundred times faster than all-atom MD (Hsu et al. JCTC, 2014). The predictive capability of the technique is illustrated here for 5 different methacrylate monomers and polystyrene stereoisomers. The approach involves optimization of analytical bonded potentials from atomistic bonded distributions to emulate local structure, as validated by chain end-to-end length and the radius of gyration comparisons with experiments and random coil theory. Nonbonded Lennard-Jones potentials are tuned to reproduce the elastic modulus (E) and glass transition temperature (Tg) at a single thermodynamic state. Density-corrected parameters capture temperature-modulus dependence in the 150-600 K range. Flory-Fox constants of the CG models are commensurate with all atomistic and experimental results, even though all calibrations are done at a single molecular weight. Finally, we further demonstrate the predictive capabilities of the models by examining thin film nanoconfinement effects for different polymers, film thicknesses, interfacial energies, and molecular weights. Our technique, called thermomechanically consistent coarse graining (TCCG), is demonstrated, using polystyrene and poly(methylmethacrylate) as universal benchmarks, to be a robust and effective technique to understand the thermomechanical behavior of polymers thin films and nanocomposites.

  9. Scientific and Consumer Models of Recovery in Schizophrenia: Concordance, Contrasts, and Implications

    PubMed Central

    Bellack, Alan S.

    2006-01-01

    Schizophrenia has traditionally been viewed as a chronic condition with a very pessimistic outlook, but that assumption may not be valid. There has been a growing consumer movement among people with schizophrenia that has challenged both the traditional perspective on the course of illness and the associated assumptions about the possibility of people with the illness living a productive and satisfying life. This new conception of the illness is supported by long-term studies that suggest that as much as 50% of people with the illness have good outcomes. There has also been a change in political and public health perspectives of the illness, stimulated in part by the President's New Freedom Commission on Mental Health. The purpose of this article is to provide an overview of some key themes about the recovery concept, as applied to schizophrenia. The article will address 3 questions: (1) What is recovery? (2) Is recovery possible? and (3) What are the implications of a recovery model for a scientific approach to treatment (ie, the use of evidence-based practices)? Scientific and consumer models of recovery are described, and commonalities and differences are discussed. Priorities for future research are suggested. PMID:16461575

  10. Level of quality management in the Municipal Sports Services, contrast trough EFQM Excellence Model.

    PubMed

    Martínez-Moreno, Alfonso; Díaz Suárez, Arturo

    2016-01-01

    The quality management in the Municipal Sports Services is embedded in the servuction provided to the citizens, which are their internal customers who determine the quality improvement ensuring competitiveness with excellence criteria. The Model of the European Foundation for Quality Management enables the evaluation of organization progress towards achieving quality goals, from a structured, measurable and comparable methodology. The aim is to carry out a diagnosis of the level of implementation of quality in the Municipal Sports Services of the Region of Murcia, Spain. The sample of 287 workers of 30 sports services gets a high level of reliability at all scales, with a coefficient of variation of .985 (range .810-.943). The score in the criteria of Policy and Strategy, People Management, Alliances and Resources, Processes and People Results were significantly higher (p < .05) in the Municipalities with more than 25,000 inhabitants when compared with those less than 10,000 and with those from 10,000 to 25,000 inhabitants obtaining global ratings of 571 points, those less than 10,000, 590 points those from 10,000 to 25,000 and those higher than 25,000 reach 636, having a good level of quality in relation to the scale that determines the model.

  11. Modelling the Contrasting Viscoelastic Behaviours of Melt--Free and Melt--Bearing Olivine

    NASA Astrophysics Data System (ADS)

    Morris, S.; Jackson, I.

    2005-12-01

    Torsional oscillation experiments on polycrystalline olivine show that the viscoelastic behaviour is strongly affected by the presence of melt. For melt--free samples, the dissipation Q-1 per cycle decreases monotonically with increasing oscillation frequency ω, but melt--bearing samples exhibit a dissipation peak. To explain that difference, we analyse a simplified continuum model. In it, the sample occupies the gap -dmodel as a Voigt solid whose viscosity η' and shear modulus μ' represent respectively the viscous and elastic resistances to grain boundary sliding, the elastic resistance being caused by grain--boundary topography as discussed by Raj & Ashby ( Met. Trans., 2, 1113, 1971). Analysis of our model shows that the strain γ(t) measured at the boundaries y=± d is given in terms of the applied stress σ(t) by the differential equation 2M(d2γ/dt2 +2 dγ/dt)= d2σ/dt2 +{2(1+M) +HM} dσ/dt + 2HMσ, Equation (1) where time t and strain γ are respectively measured in units η' d/bμ' and σs/μ. The control parameters M and H are defined by M=μ/μ' >> and >> H= η' d/bη, so that H is the ratio of the sliding timescale η' d/μ b to the Maxwell timescale η/μ of the grain. The behaviour predicted by (1) proves to be identical to that of a Burgers solid. By solving (1) for periodic forcing, we find there are two cases: (a) if H<1/4, there is a dissipation peak for all values of M; (b) if H>1/4, there is a peak only if M> 2(4H-1)/(H+2). In case (a) the timescales are sufficiently separated that a peak always exists, but in case (b), the

  12. Two classes of deleterious recessive alleles in a natural population of zebrafish, Danio rerio.

    PubMed Central

    McCune, Amy R.; Houle, David; McMillan, Kyle; Annable, Rebecca; Kondrashov, Alexey S.

    2004-01-01

    Natural populations carry deleterious recessive alleles which cause inbreeding depression. We compared mortality and growth of inbred and outbred zebrafish, Danio rerio, between 6 and 48 days of age. Grandparents of the studied fish were caught in the wild. Inbred fish were generated by brother-sister mating. Mortality was 9% in outbred fish, and 42% in inbred fish, which implies at least 3.6 lethal equivalents of deleterious recessive alleles per zygote. There was no significant inbreeding depression in the growth, perhaps because the surviving inbred fish lived under less crowded conditions. In contrast to alleles that cause embryonic and early larval mortality in the same population, alleles responsible for late larval and early juvenile mortality did not result in any gross morphological abnormalities. Thus, deleterious recessive alleles that segregate in a wild zebrafish population belong to two sharply distinct classes: early-acting, morphologically overt, unconditional lethals; and later-acting, morphologically cryptic, and presumably milder alleles. PMID:15451692

  13. Robust identification of local adaptation from allele frequencies.

    PubMed

    Günther, Torsten; Coop, Graham

    2013-09-01

    Comparing allele frequencies among populations that differ in environment has long been a tool for detecting loci involved in local adaptation. However, such analyses are complicated by an imperfect knowledge of population allele frequencies and neutral correlations of allele frequencies among populations due to shared population history and gene flow. Here we develop a set of methods to robustly test for unusual allele frequency patterns and correlations between environmental variables and allele frequencies while accounting for these complications based on a Bayesian model previously implemented in the software Bayenv. Using this model, we calculate a set of "standardized allele frequencies" that allows investigators to apply tests of their choice to multiple populations while accounting for sampling and covariance due to population history. We illustrate this first by showing that these standardized frequencies can be used to detect nonparametric correlations with environmental variables; these correlations are also less prone to spurious results due to outlier populations. We then demonstrate how these standardized allele frequencies can be used to construct a test to detect SNPs that deviate strongly from neutral population structure. This test is conceptually related to FST and is shown to be more powerful, as we account for population history. We also extend the model to next-generation sequencing of population pools-a cost-efficient way to estimate population allele frequencies, but one that introduces an additional level of sampling noise. The utility of these methods is demonstrated in simulations and by reanalyzing human SNP data from the Human Genome Diversity Panel populations and pooled next-generation sequencing data from Atlantic herring. An implementation of our method is available from http://gcbias.org.

  14. The Tofts model in frequency domain: fast and robust determination of pharmacokinetic maps for dynamic contrast enhancement MRI

    NASA Astrophysics Data System (ADS)

    Vajuvalli, Nithin N.; Chikkemenahally, Dharmendra Kumar K.; Nayak, Krupa N.; Bhosale, Manoj G.; Geethanath, Sairam

    2016-12-01

    Dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) is a well-established method for non-invasive detection and therapeutic monitoring of pathologies through administration of intravenous contrast agent. Quantification of pharmacokinetic (PK) maps can be achieved through application of compartmental models relevant to the pathophysiology of the tissue under interrogation. The determination of PK parameters involves fitting of time-concentration data to these models. In this work, the Tofts model in frequency domain (TM-FD) is applied to a weakly vascularized tissue such as the breast. It is derived as a convolution-free model from the conventional Tofts model in the time domain (TM-TD). This reduces the dimensionality of the curve-fitting problem from two to one. The approaches of TM-FD and TM-TD were applied to two kinds of in silico phantoms and six in vivo breast DCE data sets with and without the addition of noise. The results showed that computational time taken to estimate PK maps using TM-FD was 16-25% less than with TM-TD. Normalized root mean square error (NRMSE) calculation and Pearson correlation analyses were performed to validate robustness and accuracy of the TM-FD and TM-TD approaches. These compared with ground truth values in the case of phantom studies for four different temporal resolutions. Results showed that NRMSE values for TM-FD were significantly lower than those of TM-TD as validated by a paired t-test along with reduced computational time. This approach therefore enables online evaluation of PK maps by radiologists in a clinical setting, aiding in the evaluation of 3D and/or increased coverage of the tissue of interest.

  15. Correction of hair shaft defects through allele-specific silencing of mutant Krt75

    PubMed Central

    Liu, Ying; Snedecor, Elizabeth R.; Zhang, Xu; Xu, Yan-Feng; Huang, Lan; Jones, Evan; Zhang, Lianfeng; Clark, Richard A.; Roop, Dennis R.; Qin, Chuan; Chen, Jiang

    2015-01-01

    Dominant mutations in keratin genes can cause a number of inheritable skin disorders characterized by intraepidermal blistering, epidermal hyperkeratosis, or abnormalities in skin appendages, such as nail plate dystrophy and structural defects in hair. Allele-specific silencing of mutant keratins through RNA interference is a promising therapeutic approach for suppressing the expression of mutant keratins and related phenotypes in the epidermis. However, its effectiveness on skin appendages remains to be confirmed in vivo. In this study, we developed allele specific siRNAs capable of selectively suppressing the expression of a mutant Krt75, which causes hair shaft structural defects characterized by the development of blebs along the hair shaft in mice. Hair regenerated from epidermal keratinocyte progenitor cells isolated from mutant Krt75 mouse models reproduced the blebbing phenotype when grafted in vivo. In contrast, mutant cells manipulated with a lentiviral vector expressing mutant Krt75-specific shRNA persistently suppressed this phenotype. The phenotypic correction was associated with significant reduction of mutant Krt75 mRNA in the skin grafts. Thus, data obtained from this study demonstrated the feasibility of utilizing RNA interference to achieve durable correction of hair structural phenotypes through allele-specific silencing of the mutant keratin genes. PMID:26763422

  16. Correction of Hair Shaft Defects through Allele-Specific Silencing of Mutant Krt75.

    PubMed

    Liu, Ying; Snedecor, Elizabeth R; Zhang, Xu; Xu, Yanfeng; Huang, Lan; Jones, Evan C; Zhang, Lianfeng; Clark, Richard A; Roop, Dennis R; Qin, Chuan; Chen, Jiang

    2016-01-01

    Dominant mutations in keratin genes can cause a number of inheritable skin disorders characterized by intraepidermal blistering, epidermal hyperkeratosis, or abnormalities in skin appendages, such as nail plate dystrophy and structural defects in hair. Allele-specific silencing of mutant keratins through RNA interference is a promising therapeutic approach for suppressing the expression of mutant keratins and related phenotypes in the epidermis. However, its effectiveness on skin appendages remains to be confirmed in vivo. In this study, we developed allele-specific small interfering RNAs capable of selectively suppressing the expression of a mutant Krt75, which causes hair shaft structural defects characterized by the development of blebs along the hair shaft in mice. Hair regenerated from epidermal keratinocyte progenitor cells isolated from mutant Krt75 mouse models reproduced the blebbing phenotype when grafted in vivo. In contrast, mutant cells manipulated with a lentiviral vector expressing mutant Krt75-specific short hairpin RNA (shRNA) persistently suppressed this phenotype. The phenotypic correction was associated with a significant reduction of mutant Krt75 mRNA in the skin grafts. Thus, data obtained from this study demonstrated the feasibility of utilizing RNA interference to achieve durable correction of hair structural phenotypes through allele-specific silencing of mutant keratin genes.

  17. Quantum dots as contrast agents for endoscopy: mathematical modeling and experimental validation of the optimal excitation wavelength

    NASA Astrophysics Data System (ADS)

    Roy, Mathieu; DaCosta, Ralph S.; Weersink, Robert; Netchev, George; Davidson, Sean R. H.; Chan, Warren; Wilson, Brian C.

    2007-02-01

    Our group is investigating the use of ZnS-capped CdSe quantum dot (QD) bioconjugates combined with fluorescence endoscopy for improved early cancer detection in the esophagus, colon and lung. A major challenge in using fluorescent contrast agents in vivo is to extract the relevant signal from the tissue autofluorescence (AF). Our studies are aimed at maximizing the QD signal to AF background ratio (SBR) to facilitate detection. This work quantitatively evaluates the effect of the excitation wavelength on the SBR, using both experimental measurements and mathematical modeling. Experimental SBR measurements were done by imaging QD solutions placed onto (surface) or embedded in (sub-surface) ex vivo murine tissue samples (brain, kidney, liver, lung), using a polymethylmethacrylate (PMMA) microchannel phantom. The results suggest that the maximum contrast is reached when the excitation wavelength is set at 400+/-20 μm for the surface configuration. For the sub-surface configuration, the optimal excitation wavelength varies with the tissue type and QD emission wavelengths. Our mathematical model, based on an approximation to the diffusion equation, successfully predicts the optimal excitation wavelength for the surface configuration, but needs further modifications to be accurate in the sub-surface configuration.

  18. Deuterium Labeling Strategies for Creating Contrast in Structure-Function Studies of Model Bacterial Outer Membranes Using Neutron Reflectometry.

    PubMed

    Le Brun, Anton P; Clifton, Luke A; Holt, Stephen A; Holden, Peter J; Lakey, Jeremy H

    2016-01-01

    Studying the outer membrane of Gram-negative bacteria is challenging due to the complex nature of its structure. Therefore, simplified models are required to undertake structure-function studies of processes that occur at the outer membrane/fluid interface. Model membranes can be created by immobilizing bilayers to solid supports such as gold or silicon surfaces, or as monolayers on a liquid support where the surface pressure and fluidity of the lipids can be controlled. Both model systems are amenable to having their structure probed by neutron reflectometry, a technique that provides a one-dimensional depth profile through a membrane detailing its thickness and composition. One of the strengths of neutron scattering is the ability to use contrast matching, allowing molecules containing hydrogen and those enriched with deuterium to be highlighted or matched out against the bulk isotopic composition of the solvent. Lipopolysaccharides, a major component of the outer membrane, can be isolated for incorporation into model membranes. Here, we describe the deuteration of lipopolysaccharides from rough strains of Escherichia coli for incorporation into model outer membranes, and how the use of deuterated materials enhances structural analysis of model membranes by neutron reflectometry.

  19. Comparing and contrasting size-based particle segregation models - Applying coarse-graining to perfectly bidisperse systems

    NASA Astrophysics Data System (ADS)

    Tunuguntla, Deepak R.; Weinhart, Thomas; Thornton, Anthony R.

    2016-10-01

    Over the last 12 years, numerous new theoretical continuum models have been formulated to predict particle segregation in the size-based bidisperse granular flows over inclined channels. Despite their presence, to our knowledge, no attempts have been made to compare and contrast the fundamental basis upon which these continuum models have been formulated. In this paper, firstly, we aim to illustrate the difference in these models including the incompatible nomenclature which impedes direct comparison. Secondly, we utilise (i) our robust and efficient in-house particle solver MercuryDPM, and (ii) our accurate micro-macro (discrete to continuum) mapping tool called coarse-graining, to compare several proposed models. Through our investigation involving size-bidisperse mixtures, we find that (i) the proposed total partial stress fraction expressions do not match the results obtained from our simulation, and (ii) the kinetic partial stress fraction dominates over the total partial stress fraction and the contact partial stress fraction. However, the proposed theoretical total stress fraction expressions do capture the kinetic partial stress fraction profile, obtained from simulations, very well, thus possibly highlighting the reason why mixture theory segregation models work for inclined channel flows. However, further investigation is required to strengthen the basis upon which the existing mixture theory segregation models are built upon.

  20. Negative BOLD response and serotonin concentration within rostral subgenual portion of the anterior cingulate cortex for long-allele carriers during perceptual processing of emotional tasks

    NASA Astrophysics Data System (ADS)

    Hadi, Shamil M.; Siadat, Mohamad R.; Babajani-Feremi, Abbas

    2012-03-01

    We investigated the effect of synaptic serotonin concentration on hemodynamic responses. The stimuli paradigm involved the presentation of fearful and threatening facial expressions to a set of 24 subjects who were either5HTTLPR long- or short-allele carriers (12 of each type in each group). The BOLD signals of the rACC from subjects of each group were averaged to increase the signal-to-noise ratio. We used a Bayesian approach to estimate the parameters of the underlying hemodynamic model. Our results, during this perceptual processing of emotional task, showed a negative BOLD signal in the rACC in the subjects with long-alleles. In contrast, the subjects with short-alleles showed positive BOLD signals in the rACC. These results suggest that high synaptic serotonin concentration in the rACC inhibits neuronal activity in a fashion similar to GABA, and a consequent negative BOLD signal ensues.

  1. Overdominant alleles in a population of variable size.

    PubMed Central

    Slatkin, M; Muirhead, C A

    1999-01-01

    An approximate method is developed to predict the number of strongly overdominant alleles in a population of which the size varies with time. The approximation relies on the strong-selection weak-mutation (SSWM) method introduced by J. H. Gillespie and leads to a Markov chain model that describes the number of common alleles in the population. The parameters of the transition matrix of the Markov chain depend in a simple way on the population size. For a population of constant size, the Markov chain leads to results that are nearly the same as those of N. Takahata. The Markov chain allows the prediction of the numbers of common alleles during and after a population bottleneck and the numbers of alleles surviving from before a bottleneck. This method is also adapted to modeling the case in which there are two classes of alleles, with one class causing a reduction in fitness relative to the other class. Very slight selection against one class can strongly affect the relative frequencies of the two classes and the relative ages of alleles in each class. PMID:10353917

  2. Local-scale models reveal ecological niche variability in amphibian and reptile communities from two contrasting biogeographic regions

    PubMed Central

    Santos, Xavier; Felicísimo, Ángel M.

    2016-01-01

    Ecological Niche Models (ENMs) are widely used to describe how environmental factors influence species distribution. Modelling at a local scale, compared to a large scale within a high environmental gradient, can improve our understanding of ecological species niches. The main goal of this study is to assess and compare the contribution of environmental variables to amphibian and reptile ENMs in two Spanish national parks located in contrasting biogeographic regions, i.e., the Mediterranean and the Atlantic area. The ENMs were built with maximum entropy modelling using 11 environmental variables in each territory. The contributions of these variables to the models were analysed and classified using various statistical procedures (Mann–Whitney U tests, Principal Components Analysis and General Linear Models). Distance to the hydrological network was consistently the most relevant variable for both parks and taxonomic classes. Topographic variables (i.e., slope and altitude) were the second most predictive variables, followed by climatic variables. Differences in variable contribution were observed between parks and taxonomic classes. Variables related to water availability had the larger contribution to the models in the Mediterranean park, while topography variables were decisive in the Atlantic park. Specific response curves to environmental variables were in accordance with the biogeographic affinity of species (Mediterranean and non-Mediterranean species) and taxonomy (amphibians and reptiles). Interestingly, these results were observed for species located in both parks, particularly those situated at their range limits. Our findings show that ecological niche models built at local scale reveal differences in habitat preferences within a wide environmental gradient. Therefore, modelling at local scales rather than assuming large-scale models could be preferable for the establishment of conservation strategies for herptile species in natural parks. PMID

  3. One-dimensional simulation of fire injection heights in contrasted meteorological scenarios with PRM and Meso-NH models

    NASA Astrophysics Data System (ADS)

    Strada, S.; Freitas, S. R.; Mari, C.; Longo, K. M.; Paugam, R.

    2013-02-01

    Wild-fires release huge amounts of aerosol and hazardous trace gases in the atmosphere. The residence time and the dispersion of fire pollutants in the atmosphere can range from hours to days and from local to continental scales. These various scenarios highly depend on the injection height of smoke plumes. The altitude at which fire products are injected in the atmosphere is controlled by fire characteristics and meteorological conditions. Injection height however is still poorly accounted in chemistry transport models for which fires are sub-grid scale processes which need to be parametrised. Only recently, physically-based approaches for estimating the fire injection heights have been developed which consider both the convective updrafts induced by the release of fire sensible heat and the impact of background meteorological environment on the fire convection dynamics. In this work, two different models are used to simulate fire injection heights in contrasted meteorological scenarios: a Mediterranean arson fire and two Amazonian deforestation fires. A Eddy-Diffusivity/Mass-Flux approach, formerly developed to reproduce convective boundary layer in the non-hydrostatic meteorological model Meso-NH, is compared to the 1-D Plume Rise Model. For both models, radiosonde data and re-analyses from the European Center for Medium-Range Weather Forecasts (ECMWF) have been used as initial conditions to explore the sensitivity of the models responses to different meteorological forcings. The two models predict injection heights for the Mediterranean fire between 1.7 and 3.3 km with the Meso-NH/EDMF model systematically higher than the 1-D PRM model. Both models show a limited sensitivity to the meteorological forcings with a 20-30% difference in the injection height between radiosondes and ECMWF data for this case. Injection heights calculated for the two Amazonian fires ranges from 5 to 6.5 km for the 1-D PRM model and from 2 to 4 km for the Meso-NH/EDMF model. The

  4. Ultrasound-Triggered Phase Transition Sensitive Magnetic Fluorescent Nanodroplets as a Multimodal Imaging Contrast Agent in Rat and Mouse Model

    PubMed Central

    Chen, Yunchao; Luo, Binhua; Liu, Xuhan; Liu, Wei; Xu, Haibo; Yang, Xiangliang

    2013-01-01

    Ultrasound-triggered phase transition sensitive nanodroplets with multimodal imaging functionality were prepared via premix Shirasu porous glass (SPG) membrane emulsification method. The nanodroplets with fluorescence dye DiR and SPIO nanoparticles (DiR-SPIO-NDs) had a polymer shell and a liquid perfluoropentane (PFP) core. The as-formed DiR-SPIO-NDs have a uniform size of 385±5.0 nm with PDI of 0.169±0.011. The TEM and microscopy imaging showed that the DiR-SPIO-NDs existed as core-shell spheres, and DiR and SPIO nanoparticles dispersed in the shell or core. The MTT and hemolysis studies demonstrated that the nanodroplets were biocompatible and safe. Moreover, the proposed nanodroplets exhibited significant ultrasound-triggered phase transition property under clinical diagnostic ultrasound irradiation due to the vaporization of PFP inside. Meanwhile, the high stability and R2 relaxivity of the DiR-SPIO-NDs suggested its applicability in MRI. The in vivo T2-weighted images of MRI and fluorescence images both showed that the image contrast in liver and spleen of rats and mice model were enhanced after the intravenous injection of DiR-SPIO-NDs. Furthermore, the ultrasound imaging (US) in mice tumor as well as MRI and fluorescence imaging in liver of rats and mice showed that the DiR-SPIO-NDs had long-lasting contrast ability in vivo. These in vitro and in vivo findings suggested that DiR-SPIO-NDs could potentially be a great MRI/US/fluorescence multimodal imaging contrast agent in the diagnosis of liver tissue diseases. PMID:24391983

  5. Multi-channel analysis of surface waves MASW of models with high shear-wave velocity contrast

    USGS Publications Warehouse

    Ivanov, J.; Miller, R.D.; Peterie, S.; Zeng, C.; Xia, J.; Schwenk, T.

    2011-01-01

    We use the multi-channel analysis of surface waves MASW method to analyze synthetic seismic data calculated using models with high shear-wave velocity Vs contrast. The MASW dispersion-curve images of the Rayleigh wave are obtained using various sets of source-offset and spread-size configurations from the synthetic seismic data and compared with the theoretically calculated fundamental- and higher-mode dispersion-curves. Such tests showed that most of the dispersion-curve images are dominated by higher-mode energy at the low frequencies, especially when analyzing data from long receiver offsets and thus significantly divert from numerically expected dispersion-curve trends, which can lead to significant Vs overestimation. Further analysis showed that using data with relatively short spread lengths and source offsets can image the desired fundamental-mode of the Rayleigh wave that matches the numerically expected dispersion-curve pattern. As a result, it was concluded that it might be possible to avoid higher-mode contamination at low frequencies at sites with high Vs contrast by appropriate selection of spread size and seismic source offset. ?? 2011 Society of Exploration Geophysicists.

  6. Basement depth estimation from gravity anomalies: two 2.5D approaches coupled with the exponential density contrast model

    NASA Astrophysics Data System (ADS)

    Chakravarthi, V.; Mallesh, K.; Ramamma, B.

    2017-03-01

    We develop two automatic techniques in the spatial domain using the exponential density contrast model (EDCM) to trace the bottom surface of a 2.5D sedimentary basin from the observed gravity anomalies. The interface between the sediments and basement is described with a finite strike polygonal source, whose depth ordinates become the unknown parameters to be estimated. The proposed automatic modeling technique makes use of the forward difference approximation and the inversion solves a system of normal equations using the ridge regression to estimate the unknown parameters. Furthermore, the proposed inversion technique simultaneously estimates the regional gravity background that is associated with the residual gravity anomaly. In either case, forward modeling is realized in the spatial domain through a method that combines both analytical and numerical approaches. The utility of each algorithm was successfully tested on a theoretically produced noisy residual gravity dataset. The validity of the inversion technique is also exemplified with the noisy gravity anomalies attributable to a synthetic structure in the presence of regional gravity background. We demonstrate that the magnitude of gravity anomaly is offset dependent and that it would influence the modeling result. Additionally, some applications with real gravity datasets from the Gediz and Büyük Menderes grabens in western Turkey using the derived EDCMs have produced geologically reasonable results which are in close agreement with those reported previously.

  7. The Value of the Model and Quantitative Parameters of Contrast-Enhanced Ultrasound in Judging the Severity of SHPT

    PubMed Central

    Liang, Xing-xin; Li, Fan; Gao, Feng; Liu, Yang; Qiao, Xiao-hui; Zhang, Zheng

    2016-01-01

    Using the model and quantitative parameters of contrast-enhanced ultrasound (CEUS) to assess the severity of secondary hyperparathyroidism (SHPT) was proposed. 42 SHPT patients who underwent CEUS examination were divided into three groups, light, moderate, and heavy as per parathyroid hormone (PTH). The process of CEUS was divided into two phases, wash-in phase and wash-out phase. The three groups were analyzed with their enhancing model in the two phases. The quantitative parameters of CEUS such as Arrival Time (AT), Time to Peak (TTP), Mean Transit Time (MTT), and Maximum Intensity (IMAX) were measured by time-intensity curve (TIC) and compared among the three groups. The enhancing model of light SHPT, moderate SHPT, and heavy SHPT showed statistical significance in wash-in phase and wash-out phase (P < 0.05). No difference was observed in AT and TTP among the three groups (P > 0.05) while MTT and IMAX showed statistical significance (P < 0.05). The CEUS of light SHPT was characterized by “slow-in, fast-out, and lower-enhancement” with short enhancement time; the CEUS of moderate SHPT was characterized by “fast-in, fast-out, and higher-enhancement” with slightly long enhancement time; the CEUS of heavy SHPT was characterized by “fast-in, slow-out, and higher-enhancement” with long enhancement time. Therefore, the model and quantitative parameters of CEUS can be benefit for the assessment of the severity of SHPT. PMID:28078296

  8. The use of error-category mapping in pharmacokinetic model analysis of dynamic contrast-enhanced MRI data.

    PubMed

    Gill, Andrew B; Anandappa, Gayathri; Patterson, Andrew J; Priest, Andrew N; Graves, Martin J; Janowitz, Tobias; Jodrell, Duncan I; Eisen, Tim; Lomas, David J

    2015-02-01

    This study introduces the use of 'error-category mapping' in the interpretation of pharmacokinetic (PK) model parameter results derived from dynamic contrast-enhanced (DCE-) MRI data. Eleven patients with metastatic renal cell carcinoma were enrolled in a multiparametric study of the treatment effects of bevacizumab. For the purposes of the present analysis, DCE-MRI data from two identical pre-treatment examinations were analysed by application of the extended Tofts model (eTM), using in turn a model arterial input function (AIF), an individually-measured AIF and a sample-average AIF. PK model parameter maps were calculated. Errors in the signal-to-gadolinium concentration ([Gd]) conversion process and the model-fitting process itself were assigned to category codes on a voxel-by-voxel basis, thereby forming a colour-coded 'error-category map' for each imaged slice. These maps were found to be repeatable between patient visits and showed that the eTM converged adequately in the majority of voxels in all the tumours studied. However, the maps also clearly indicated sub-regions of low Gd uptake and of non-convergence of the model in nearly all tumours. The non-physical condition ve ≥ 1 was the most frequently indicated error category and appeared sensitive to the form of AIF used. This simple method for visualisation of errors in DCE-MRI could be used as a routine quality-control technique and also has the potential to reveal otherwise hidden patterns of failure in PK model applications.

  9. Mutable R-Navajo Alleles of Cyclic Origin in Maize

    PubMed Central

    Brink, R. Alexander; Williams, Elizabeth

    1973-01-01

    The generation in cyclic fashion of 26 mutable R-Navajo (mRnj) alleles in maize involved transposition of a non-specific repressor of gene action, Modulator (Mp), first away from, and then back to, the R locus represented by the R-Navajo (Rnj) allele on chromosome 10. The mRnj alleles reconstituted in this way varied widely, and continuously, in mutability to Rnj—that is, in transposition of Mp away from the R locus, thus derepressing the Rnj gene. They were alike, or nearly so, however, in activating Ds chromosome breakage and in increasing the stability of variegated pericarp, another unstable compound allele comprising Mp conjoined with Prr on chromosomal 1. These latter two phenomena are based primarily on loci elsewhere in the genome. It is postulated that the 26 reconstituted mRnj alleles carry a common Mp which, however, is intercalated at a different site within each allele. Nucleotide sequence in the regions adjacent to Mp is assumed to determine the frequency with which a form of micro-nondisjunction occurs whereby Mp is released from a donor site. Transposition to a new site is interpreted in terms of a chromosome model that gives effect to nicking, or single strand breaks, occurring throughout the genome as a prerequisite to unwinding, strand separation, and replication, of the DNA double helix. PMID:17248592

  10. A High-Fidelity Solar System Model and High-Contrast Integral Field Spectrograph Prototype for Exoplanet Observations

    NASA Astrophysics Data System (ADS)

    Wilkins, A. N.; McElwain, M. W.; Roberge, A.; Nesvold, E.; Stark, C. C.; Kuchner, M. J.; Robinson, T.; Meadows, V. S.; Straughn, A. N.; Turnbull, M. C.; Gong, Q.; Woodgate, B.; Brandt, T.; Staplefelt, K.; Heap, S.; Hilton, G.

    2014-03-01

    As the possibility of discovering habitable, Earth-like planets around Sun-like stars improves, the need for both accurate model representations of such systems and advanced, dedicated high-contrast instrumentation in order to characterize and understand such systems becomes ever more pressing. We present a model and an instrument to address this need. The signals of habitability will be buried within spectral information like needles in haystacks, so we present a complete model of the Solar System we call "Hackstacks" that can be readily placed at various distances and inclinations to simulate an exoplanetary system with a known habitable planet. The Haystacks data product is a three-dimensional spectral cube. The spatial x-y plane spans 150 AU in both directions, centered on the Sun. The spectral zdimension is divided into four hundred slices ranging from 0.3 µm to 2.5 µm, evenly spaced in wavelength, yielding R ~ 200 in the V-band. In the model, we include the Solar System planets, inner (exo)zodiacal dust, outer Kuiper Belt dust, and extragalactic background, all sourced from a combination of observations and models. This makes the Haystacks model the most comprehensive, robust, and detailed model available for prediction of noise levels, confusion, and the ability to measure biomarkers in a directly observed system. The final data cubes are available for download by the public. Any user who accesses our NASA-hosted webpage simply inputs a desire wavelength range, a distance, and an inclination, and they are provided with the corresponding spectral cube. We demonstrate the power of such data cubes with several simulations of observations with various telescopes and instruments using the PROPER suite of algorithms, and present preliminary results on detectability and necessary instrument/telescope capabilities. In order to both detect and analyze an Earth-like planet in another system, we need an instrument dedicated to such a task, with high-contrast imaging

  11. The effect of landscape position and aspect on chemical weathering and soil formation: contrasting field and model results

    NASA Astrophysics Data System (ADS)

    Vanwalleghem, Tom; Román, Andrea; Giráldez, Juan

    2016-04-01

    Interest in modelling pedogenesis has increased greatly over the past few years, with the emergence of detailed pedon-scale models (e.g. Soilgen) on the one hand and landscape-scale models (e.g. marm3D, MILESD, LORICA) on the other. Pore water chemistry and chemical weathering is not (well) represented in the latter and needs to be improved in order to adequately model the evolution of soils and of the critical zone. The objective of this work is to analyse the spatial variability of chemical weathering and to develop a new soil landscape model that accounts for this. Here, we present field and model results from the Santa Clotilde Critical Zone Observatory, S Spain. A new model, MILESD2, was developed to integrate the effect of landscape evolution and soil formation. This model is based on a daily spatially-explicit soil water balance. Average soil water content, temperature and deep percolation fluxes are linked to weathering and soil formation processes. Model input (temperature and precipitation) for the last 25 000 years was generated on a daily time by combining palaeoclimate data and the WXGEN weather generator. The soil-landscape model was applied to a 48 km2 semi-natural catchment in Southern Spain, with soils developed on granite. Model-generated runoff was used for a first validation against discharge observations. Next, soil formation output was contrasted against experimental data from 10 soil profiles along two catenas. Field data showed an important variation in mobile regolith thickness, between 0,44 and 1,10m, and in chemical weathering along the catena. Southern slopes were characterized by shallower, stonier and carbon-poor soils, while soils on north-facing slopes were deeper, more fine-textured and had a higher carbon content. Chemical depletion fraction was found to vary between 0,41 and 0,72. The lowest overall weathering intensity was found on plateau positions. South facing slopes revealed slightly lower weathering compared to north facing

  12. Contrast cystography.

    PubMed

    Essman, Stephanie C

    2005-02-01

    Cystography is a radiographic study performed to aid in evaluation of the urinary bladder for extramural, mural, or intraluminal lesions. These lesions may primarily involve the urinary bladder or may be an extension of disease from adjacent organs. Cystography is easy to perform with relatively few complications. Different types of cystography (positive versus negative contrast) may be used depending on the type of information that the clinician hopes to obtain. Although a valuable technique, it is important to correlate the findings on cystography with other clinical information to arrive at the final diagnosis.

  13. Probabilistic graphical modeling of speckle statistics in laser speckle contrast imaging for noninvasive and label-free retinal angiography.

    PubMed

    Basak, Kausik; Dey, Goutam; Sheet, Debdoot; Mahadevappa, Manjunatha; Mandal, Mahitosh; Dutta, Pranab K

    2015-01-01

    This paper introduces a noninvasive and label-free approach for retinal angiography using Laser speckle contrast imaging (LSCI). Retinal vessel structure is segmented using a Hidden Markov Random Field (HMRF) based model. Prior to that, k-means clustering is used to obtain initial parameter set and labels for HMRF. Final parameter set for HMRF is estimated using expectation-maximization (EM) algorithm and final labeling is achieved using maximum aposteriori (MAP) algorithm. Clique energy for HMRF is computed from eigenvalue analysis of structure tensor for each pixel. This helps to get connectivity in the direction of strongest tangents in its neighborhood, facilitating the tracking of fine vessels in retinal vascular network. Quantitative evaluation shows an average vessel segmentation accuracy of 96.41% in normal condition with substantial improvement in tracking capability of fine vessels. Changes in blood flow can be tracked and observed at segmented output; particularly applicable for the study of different pathological conditions.

  14. Model for Electron-Beam-Induced Current Analysis of mc-Si Addressing Defect Contrast Behavior in Heavily Contaminated PV Material: Preprint

    SciTech Connect

    Guthrey, H.; Gorman, B.; Al-Jassim, M.

    2012-06-01

    Much work has been done to correlate electron-beam-induced current (EBIC) contrast behavior of extended defects with the character and degree of impurity decoration. However, existing models fail to account for recently observed contrast behavior of defects in heavily contaminated mc-Si PV cells. We have observed large increases in defect contrast with decreasing temperature for all electrically active defects, regardless of their initial contrast signatures at ambient temperature. This negates the usefulness of the existing models in identifying defect character and levels of impurity decoration based on the temperature dependence of the contrast behavior. By considering the interactions of transition metal impurities with the silicon lattice and extended defects, we attempt to provide an explanation for these observations. Our findings will enhance the ability of the PV community to understand and mitigate the effects of these types of defects as the adoption of increasingly lower purity feedstocks for mc-Si PV production continues.

  15. Dynamic contrast enhanced MRI parameters and tumor cellularity in a rat model of cerebral glioma at 7T

    NASA Astrophysics Data System (ADS)

    Aryal, Madhava Prasad

    This dissertation mainly focuses on establishing and evaluating a stable and reproducible procedure for assessing tumor microvasculature by measuring the tissue parameters: plasma volume (vp), forward transfer constant (Ktrans), interstitial volume (ve) and distribution volume (VD), utilizing T1-weighted dynamic contrast enhanced MRI (DCE-MRI) and examining their relationship with a histo measure, cell counting. In the first part of the work, two T1-weighted DCE-MRI studies at 24 hrs time interval, using a dual-echo gradient-echo pulse sequence, were performed in 18 athymic rats implanted with U251 cerebral glioma. Using the "standard," or "consensus" model, and a separate Logan graphical analysis, T1-weighted images before, during and after the injection of a gadolinium contrast agent were used to estimate the tissue parameters mentioned above. After MRI study rats were sacrificed, and sectioned brain tissues were stained with Hematoxylin and Eosin for cell counting. Measurements in a region where a model selection process demonstrates that it can be reliably shown that contrast agent leaks from the capillary into the interstitial space quickly enough, and a concentration sufficient to measure its back flux to the vasculature, especially for Ktrans and ve, showed a remarkable stability. The combined mean parameter values in this region were: vp = (0.79+/-0.36)%, Ktrans = (2.23+/-0.71) x10-2 min -1, ve = (6.99+/-2.14)%, and VD = (7.57+/-2.32)%. In the second part of this work, the Logan graphical approach, after establishing its stability in an untreated control group, was applied to investigate a cohort of animals in which a therapeutic dose of 20 Gy radiation had been administered. In this cohort, tissue normalization appeared to be the most effective at 8 h after irradiation; this implies that the 8 hrs post-treatment time might be an ideal combination time for optimized therapeutic outcome in combined modalities. The relationship between non-invasive DCE

  16. Accurate size comparison of short tandem repeat alleles amplified by PCR.

    PubMed

    Smith, R N

    1995-01-01

    A strategy is presented for classifying complex short tandem repeat (STR) alleles by size. Such alleles can differ in length by only 1 bp. The HUMACTBP2 locus was used as a model. Dye-labeled, PCR-amplified alleles were analyzed on an automated DNA sequencer with laser-induced fluorescence detection and fragment-sizing software. Between-gel allele sizes calculated against an in-lane allelic ladder or viral DNA size standard were too imprecise to distinguish a 1-bp difference. However, the size difference between a sample allele and its matching ladder allele provided a reliable criterion for size classification. The mean size difference +/- 3 SDs was 0.5 bp, and so an individual result within this interval signified a match. Statistically, 99.7% of the results should lie within +/- 3 SDs with virtually no chance of encountering the 9-SD difference from the mean necessary to misclassify an allele by 1 bp. The method was valid for sample alleles sized against the allelic ladder and for both sample and ladder alleles sized against the viral DNA standard. A correction for the effect of different dye labels on mobility was included in the calculations.

  17. A hypomorphic Artemis human disease allele causes aberrant chromosomal rearrangements and tumorigenesis

    PubMed Central

    Jacobs, Cheryl; Huang, Ying; Masud, Tehmina; Lu, William; Westfield, Gerwin; Giblin, William; Sekiguchi, JoAnn M.

    2011-01-01

    The Artemis gene encodes a DNA nuclease that plays important roles in non-homologous end-joining (NHEJ), a major double-strand break (DSB) repair pathway in mammalian cells. NHEJ factors repair general DSBs as well as programmed breaks generated during the lymphoid-specific DNA rearrangement, V(D)J recombination, which is required for lymphocyte development. Mutations that inactivate Artemis cause a human severe combined immunodeficiency syndrome associated with cellular radiosensitivity. In contrast, hypomorphic Artemis mutations result in combined immunodeficiency syndromes of varying severity, but, in addition, are hypothesized to predispose to lymphoid malignancy. To elucidate the distinct molecular defects caused by hypomorphic compared with inactivating Artemis mutations, we examined tumor predisposition in a mouse model harboring a targeted partial loss-of-function disease allele. We find that, in contrast to Artemis nullizygosity, the hypomorphic mutation leads to increased aberrant intra- and interchromosomal V(D)J joining events. We also observe that dysfunctional Artemis activity combined with p53 inactivation predominantly predisposes to thymic lymphomas harboring clonal translocations distinct from those observed in Artemis nullizygosity. Thus, the Artemis hypomorphic allele results in unique molecular defects, tumor spectrum and oncogenic chromosomal rearrangements. Our findings have significant implications for disease outcomes and treatment of patients with different Artemis mutations. PMID:21147755

  18. Assessing allelic dropout and genotype reliability using maximum likelihood.

    PubMed Central

    Miller, Craig R; Joyce, Paul; Waits, Lisette P

    2002-01-01

    A growing number of population genetic studies utilize nuclear DNA microsatellite data from museum specimens and noninvasive sources. Genotyping errors are elevated in these low quantity DNA sources, potentially compromising the power and accuracy of the data. The most conservative method for addressing this problem is effective, but requires extensive replication of individual genotypes. In search of a more efficient method, we developed a maximum-likelihood approach that minimizes errors by estimating genotype reliability and strategically directing replication at loci most likely to harbor errors. The model assumes that false and contaminant alleles can be removed from the dataset and that the allelic dropout rate is even across loci. Simulations demonstrate that the proposed method marks a vast improvement in efficiency while maintaining accuracy. When allelic dropout rates are low (0-30%), the reduction in the number of PCR replicates is typically 40-50%. The model is robust to moderate violations of the even dropout rate assumption. For datasets that contain false and contaminant alleles, a replication strategy is proposed. Our current model addresses only allelic dropout, the most prevalent source of genotyping error. However, the developed likelihood framework can incorporate additional error-generating processes as they become more clearly understood. PMID:11805071

  19. Phase-field-based lattice Boltzmann model for incompressible binary fluid systems with density and viscosity contrasts.

    PubMed

    Zu, Y Q; He, S

    2013-04-01

    A lattice Boltzmann model (LBM) is proposed based on the phase-field theory to simulate incompressible binary fluids with density and viscosity contrasts. Unlike many existing diffuse interface models which are limited to density matched binary fluids, the proposed model is capable of dealing with binary fluids with moderate density ratios. A new strategy for projecting the phase field to the viscosity field is proposed on the basis of the continuity of viscosity flux. The new LBM utilizes two lattice Boltzmann equations (LBEs): one for the interface tracking and the other for solving the hydrodynamic properties. The LBE for interface tracking can recover the Chan-Hilliard equation without any additional terms; while the LBE for hydrodynamic properties can recover the exact form of the divergence-free incompressible Navier-Stokes equations avoiding spurious interfacial forces. A series of 2D and 3D benchmark tests have been conducted for validation, which include a rigid-body rotation, stationary and moving droplets, a spinodal decomposition, a buoyancy-driven bubbly flow, a layered Poiseuille flow, and the Rayleigh-Taylor instability. It is shown that the proposed method can track the interface with high accuracy and stability and can significantly and systematically reduce the parasitic current across the interface. Comparisons with momentum-based models indicate that the newly proposed velocity-based model can better satisfy the incompressible condition in the flow fields, and eliminate or reduce the velocity fluctuations in the higher-pressure-gradient region and, therefore, achieve a better numerical stability. In addition, the test of a layered Poiseuille flow demonstrates that the proposed scheme for mixture viscosity performs significantly better than the traditional mixture viscosity methods.

  20. Comparing the performance of coupled soil-vegetation-atmosphere models at two contrasting field sites in South-West Germany

    NASA Astrophysics Data System (ADS)

    Gayler, S.; Wöhling, T.; Priesack, E.; Wizemann, H.-D.; Wulfmeyer, V.; Ingwersen, J.; Streck, T.

    2012-04-01

    The soil moisture, the energy balance at the land surface and the state of the lower atmosphere are closely linked by complex feedback processes. The vegetation acts as the interface between soil and atmosphere and plays an important role in this coupled system. Consequently, a consistent description of the fluxes of water, energy and carbon is a prerequisite for analyzing many problems in soil-, plant- and atmospheric research. To better understand the complex interplay of the involved processes, many numerical and physics-based soil-plant-atmosphere simulation models were developed during the last decades. As these models have been developed for different purposes, the degree of complexity in describing individual feedback processes can vary considerably. In models designed to predict soil moisture, for example, plants are often sufficiently represented by a simple sink term. If these models are calibrated, sometimes only one state variable and the corresponding calibration data type is used, e.g. soil water contents or pressure heads. In this case, vegetation properties and feedbacks between soil moisture, plant growth and stomatal conductivity are neglected to a large extent. Some crop models, in turn, pay little attention to modeling soil water transport. In a coupled soil-vegetation-atmosphere model, however, the interface between soil and atmosphere has to be consistent in all directions. As different data types such as soil moisture, leaf area development and evapotranspiration may contain contrasting information about the system under consideration, the fitting of such a model to a single data type may result in a poor agreement to another data type. The trade-off between the fittings to different data types can thereby be caused by structural inadequacies in the model or by errors in input and calibration data. In our study, we compare the Community Land Model CLM (version 3.5, offline mode) with different agricultural crop models to analyze the adequacy

  1. Evaluating dynamic contrast-enhanced and photoacoustic CT to assess intra-tumor heterogeneity in xenograft mouse models

    NASA Astrophysics Data System (ADS)

    Stantz, Keith M.; Liu, Bo; Cao, Minsong; Reinecke, Dan; Dzemidzic, Mario; Liang, Yun; Kruger, Robert

    2006-03-01

    Purpose: To evaluate photoacoustic CT spectroscopy (PCT-S) and dynamic contrast-enhanced CT (DCE-CT) ability to measure parameters - oxygen saturation and vascular physiology - associated with the intra-tumor oxygenation status. Material and Methods: Breast (VEGF165 enhance MCF-7) and ovarian (SKOV3x) cancer cells were implanted into the fat pads and flanks of immune deficient mice and allowed to grow to a diameter of 8-15 mm. CT was used to determine physiological parameters by acquiring a sequence of scans over a 10 minute period after an i.v. injection of a radio-opaque contrast agent (Isovue). These time-dependent contrast-enhanced curves were fit to a two-compartmental model determining tumor perfusion, fractional plasma volume, permeability-surface area produce, and fractional interstitial volume on a voxel-by-voxel basis. After which, the tumors were imaged using photoacoustic CT (Optosonics, Inc., Indianapolis, IN 46202). The near infrared spectra (700-910 nm) within the vasculature was fit to linear combination of measured oxy- and deoxy-hemoglobin blood samples to obtain oxygen saturation levels (SaO II). Results: The PCT-S scanner was first calibrated using different samples of oxygenated blood, from which a statistical error ranging from 2.5-6.5% was measured and a plot of the hemoglobin dissociation curve was consistent with empirical formula. In vivo determination of tumor vasculature SaO II levels were measurably tracked, and spatially correlated to the periphery of the tumor. Tumor depend variations in SaO II - 0.32 (ovarian) and 0.60 (breast) - and in vascular physiology - perfusion, 1.03 and 0.063 mL/min/mL, and fractional plasma volume, 0.20 and 0.07 - were observed. Conclusion: Combined, PCT-S and CED-CT has the potential to measure intra-tumor levels of tumor oxygen saturation and vascular physiology, key parameters associated with hypoxia.

  2. Uncertainty of streamwater solute fluxes in five contrasting headwater catchments including model uncertainty and natural variability (Invited)

    NASA Astrophysics Data System (ADS)

    Aulenbach, B. T.; Burns, D. A.; Shanley, J. B.; Yanai, R. D.; Bae, K.; Wild, A.; Yang, Y.; Dong, Y.

    2013-12-01

    There are many sources of uncertainty in estimates of streamwater solute flux. Flux is the product of discharge and concentration (summed over time), each of which has measurement uncertainty of its own. Discharge can be measured almost continuously, but concentrations are usually determined from discrete samples, which increases uncertainty dependent on sampling frequency and how concentrations are assigned for the periods between samples. Gaps between samples can be estimated by linear interpolation or by models that that use the relations between concentration and continuously measured or known variables such as discharge, season, temperature, and time. For this project, developed in cooperation with QUEST (Quantifying Uncertainty in Ecosystem Studies), we evaluated uncertainty for three flux estimation methods and three different sampling frequencies (monthly, weekly, and weekly plus event). The constituents investigated were dissolved NO3, Si, SO4, and dissolved organic carbon (DOC), solutes whose concentration dynamics exhibit strongly contrasting behavior. The evaluation was completed for a 10-year period at five small, forested watersheds in Georgia, New Hampshire, New York, Puerto Rico, and Vermont. Concentration regression models were developed for each solute at each of the three sampling frequencies for all five watersheds. Fluxes were then calculated using (1) a linear interpolation approach, (2) a regression-model method, and (3) the composite method - which combines the regression-model method for estimating concentrations and the linear interpolation method for correcting model residuals to the observed sample concentrations. We considered the best estimates of flux to be derived using the composite method at the highest sampling frequencies. We also evaluated the importance of sampling frequency and estimation method on flux estimate uncertainty; flux uncertainty was dependent on the variability characteristics of each solute and varied for

  3. Sildenafil citrate for prophylaxis of nephropathy in an animal model of contrast-induced acute kidney injury.

    PubMed

    Lauver, D Adam; Carey, E Grant; Bergin, Ingrid L; Lucchesi, Benedict R; Gurm, Hitinder S

    2014-01-01

    Contrast-induced acute kidney injury (CIAKI) is one of the commonest complications associated with contrast media (CM). Although the exact etiology of CIAKI remains unclear, one hypothesis involves vasoconstriction of afferent arterioles resulting in renal ischemia. Increased renal blood flow, therefore, might represent an attractive target for the treatment of CIAKI. In this study we evaluated the protective effects of the phosphodiesterase type 5 (PDE5) inhibitor, sildenafil citrate, in a rabbit model of CIAKI. New Zealand white rabbits were used due to their susceptibility to CIAKI. To evaluate the effects of sildenafil, the drug was administered before CM infusion and repeatedly throughout the remainder of the experiment (6 mg/kg, p.o.). Animals were sacrificed after 48 hours and kidneys were prepared for histological evaluation. Intravenous administration of CM produced marked kidney injury. Serum creatinine concentrations were elevated within two hours of the infusion and remained elevated for the duration of the experiment. Histological evaluation of the kidneys revealed significant tubular necrosis. The effects of the CM were dose dependent. Treatment with sildenafil was associated with lesser degree of histological injury, attenuation in markers of acute kidney injury (48 hour creatinine 1.54±0.21 versus 4.42±1.31 mg/dl, p<0.05) and reduction in electrolyte derangement (percent change in serum K+ at 48 hours 2.55±3.80% versus 15.53±4.47%, p<0.05; serum Na+ at 48 hours -0.14±0.26% versus -1.97±1.29%, p = 0.20). The results suggest a possible role for PDE5 inhibitors in the treatment of CIAKI and warrant further evaluation to determine the exact mechanism of protection.

  4. Testing the Efficacy of Contrast-Enhanced Ultrasound in Detecting Transplant Rejection Using a Murine Model of Heart Transplantation.

    PubMed

    Fischer, K; Ohori, S; Meral, F C; Uehara, M; Giannini, S; Ichimura, T; Smith, R N; Jolesz, F A; Guleria, I; Zhang, Y; White, P J; McDannold, N J; Hoffmeister, K; Givertz, M M; Abdi, R

    2016-12-23

    One of the key unmet needs to improve long-term outcomes of heart transplantation is to develop accurate, noninvasive, and practical diagnostic tools to detect transplant rejection. Early intragraft inflammation and endothelial cell injuries occur prior to advanced transplant rejection. We developed a novel diagnostic imaging platform to detect early declines in microvascular perfusion (MP) of cardiac transplants using contrast-enhanced ultrasonography (CEUS). The efficacy of CEUS in detecting transplant rejection was tested in a murine model of heart transplants, a standard preclinical model of solid organ transplant. As compared to the syngeneic groups, a progressive decline in MP was demonstrated in the allografts undergoing acute transplant rejection (40%, 64%, and 92% on days 4, 6, and 8 posttransplantation, respectively) and chronic rejection (33%, 33%, and 92% on days 5, 14, and 30 posttransplantation, respectively). Our perfusion studies showed restoration of MP following antirejection therapy, highlighting its potential to help monitor efficacy of antirejection therapy. Our data suggest that early endothelial cell injury and platelet aggregation contributed to the early MP decline observed in the allografts. High-resolution MP mapping may allow for noninvasive detection of heart transplant rejection. The data presented have the potential to help in the development of next-generation imaging approaches to diagnose transplant rejection.

  5. Automated segmentation of upper digestive tract from abdominal contrast-enhanced CT data using hierarchical statistical modeling of organ interrelations

    NASA Astrophysics Data System (ADS)

    Hirayama, S.; Otake, Y.; Okada, T.; Hori, M.; Tomiyama, N.; Sato, Y.

    2016-03-01

    We have been studying the automatic segmentation of multi-organ region from abdominal CT images. In previous work, we proposed an approach using a hierarchical statistical modeling using a relationship between organs. In this paper, we have proposed automatic segmentation of the upper digestive tract from abdominal contrast-enhanced CT using previously segmented multiple organs. We compared segmentation accuracy of the esophagus, stomach and duodenum between our proposed method using hierarchical statistical modeling and a conventional statistical atlas method. Additionally, preliminary experiment was performed which added the region representing gas to the candidate region at the segmentation step. The segmentation results were evaluated quantitatively by Dice coefficient, Jaccard index and the average symmetric surface distance of the segmented region and correct region data. Percentage of the average of Dice coefficient of esophagus, stomach and duodenum were 58.7, 68.3, and 38.6 with prediction-based method and 23.7, 51.1, and 24.4 with conventional atlas method.

  6. Characterization of Mhc-DRB allelic diversity in white-tailed deer (Odocoileus virginianus) provides insight into Mhc-DRB allelic evolution within Cervidae.

    PubMed

    Van Den Bussche, R A; Hoofer, S R; Lochmiller, R L

    1999-05-01

    Although white-tailed deer (Odocoileus virginianus) are one of North America's best studied mammals, no information is available concerning allelic diversity at any locus of the major histocompatibility complex in this taxon. Using the polymerase chain reaction, single-stranded conformation polymorphism analysis, and DNA sequencing techniques, 15 DRB exon 2 alleles were identified among 150 white-tailed deer from a single population in southeastern Oklahoma. These alleles represent a single locus and exhibit a high degree of nucleotide and amino acid polymorphism, with most amino acid variation occurring at positions forming the peptide binding sites. Furthermore, twenty-seven amino acid residues unique to white-tailed deer DRB alleles were detected, with 19 of these occurring at residues forming contact points of the peptide binding region. Significantly higher rates of nonsynonymous than synonymous substitutions were detected among these DRB alleles. In contrast to other studies of Artiodactyla DRB sequences, interallelic recombination does not appear to be playing a significant role in the generation of allelic diversity at this locus in white-tailed deer. To examine evolution of white-tailed deer (Odvi-DRB) alleles within Cervidae, we performed a phylogenetic analysis of all published red deer (Ceel-DRB), roe deer (Caca-DRB), and moose (Alal-DRB) DRB alleles. The phylogenetic tree clearly shows a trans-species persistence of DRB lineages among these taxa. Moreover, this phylogenetic tree provides insight into evolution of DRB allelic lineages within Cervidae and may aid in assignment of red deer DRB alleles to specific loci.

  7. Robust Data Driven Model Order Estimation for Independent Component Analysis of fMRI Data with Low Contrast to Noise

    PubMed Central

    Majeed, Waqas; Avison, Malcolm J.

    2014-01-01

    Independent component analysis (ICA) has been successfully utilized for analysis of functional MRI (fMRI) data for task related as well as resting state studies. Although it holds the promise of becoming an unbiased data-driven analysis technique, a few choices have to be made prior to performing ICA, selection of a method for determining the number of independent components (nIC) being one of them. Choice of nIC has been shown to influence the ICA maps, and various approaches (mostly relying on information theoretic criteria) have been proposed and implemented in commonly used ICA analysis packages, such as MELODIC and GIFT. However, there has been no consensus on the optimal method for nIC selection, and many studies utilize arbitrarily chosen values for nIC. Accurate and reliable determination of true nIC is especially important in the setting where the signals of interest contribute only a small fraction of the total variance, i.e. very low contrast-to-noise ratio (CNR), and/or very focal response. In this study, we evaluate the performance of different model order selection criteria and demonstrate that the model order selected based upon bootstrap stability of principal components yields more reliable and accurate estimates of model order. We then demonstrate the utility of this fully data-driven approach to detect weak and focal stimulus-driven responses in real data. Finally, we compare the performance of different multi-run ICA approaches using pseudo-real data. PMID:24788636

  8. SU-C-12A-03: The Impact of Contrast Medium On Radiation Dose in CT: A Systematic Evaluation Across 58 Patient Models

    SciTech Connect

    Sahbaee, P; Samei, E; Segars, W

    2014-06-01

    Purpose: To assess the effect of contrast medium on radiation dose as a function of time via Monte Carlo simulation from the liver CT scan across a library of 5D XCAT models Methods: A validated Monte Carlo simulation package (PENELOPE) was employed to model a CT system (LightSpeed 64 VCT, GE Healthcare). The radiation dose was estimated from a common abdomen CT examination. The dose estimation was performed on a library of adult extended cardiac-torso (5D XCAT) phantoms (35 male, 23 female, mean age 51.5 years, mean weight 80.2 kg). The 5D XCAT models were created based on patient-specific iodine concentration-time results from our computational contrast medium propagation model for different intravenous injection protocols. To enable a dynamic estimation of radiation dose, each organ in the model was assigned to its own time-concentration curve via the PENELOPE package, material.exe. Using the Monte Carlo, for each scan time point after the injection, 80 million photons were initiated and tracked through the phantoms. Finally, the dose to the liver was tallied from the deposited energy. Results: Monte Carlo simulation results of radiation dose delivered to the liver from the XCAT models indicated up to 30% increase in dose for different time after the administration of contrast medium. Conclusion: The contrast enhancement is employed in over 60% of imaging modalities, which not only remarkably affects the CT image quality, but also increases the radiation dose by as much as 70%. The postinjection multiple acquisition in several enhanced CT protocols, makes the radiation dose increment through the use of contrast medium, an inevitable factor in optimization of these protocols. The relationship between radiation dose and injected contrast medium as a function of time studied in this work allows optimization of contrast administration for vulnerable individuals.

  9. A Murine Niemann-Pick C1 I1061T Knock-In Model Recapitulates the Pathological Features of the Most Prevalent Human Disease Allele

    PubMed Central

    Praggastis, Maria; Tortelli, Brett; Zhang, Jessie; Fujiwara, Hideji; Sidhu, Rohini; Chacko, Anita; Chen, Zhouji; Chung, Chan; Lieberman, Andrew P.; Sikora, Jakub; Davidson, Cristin; Walkley, Steven U.; Pipalia, Nina H.; Maxfield, Frederick R.; Schaffer, Jean E.

    2015-01-01

    Niemann-Pick Type C1 (NPC1) disease is a rare neurovisceral, cholesterol–sphingolipid lysosomal storage disorder characterized by ataxia, motor impairment, progressive intellectual decline, and dementia. The most prevalent mutation, NPC1I1061T, encodes a misfolded protein with a reduced half-life caused by ER-associated degradation. Therapies directed at stabilization of the mutant NPC1 protein reduce cholesterol storage in fibroblasts but have not been tested in vivo because of lack of a suitable animal model. Whereas the prominent features of human NPC1 disease are replicated in the null Npc1−/− mouse, this model is not amenable to examining proteostatic therapies. The objective of the present study was to develop an NPC1 I1061T knock-in mouse in which to test proteostatic therapies. Compared with the Npc1−/− mouse, this Npc1tm(I1061T)Dso model displays a less severe, delayed form of NPC1 disease with respect to weight loss, decreased motor coordination, Purkinje cell death, lipid storage, and premature death. The murine NPC1I1061T protein has a reduced half-life in vivo, consistent with protein misfolding and rapid ER-associated degradation, and can be stabilized by histone deacetylase inhibition. This novel mouse model faithfully recapitulates human NPC1 disease and provides a powerful tool for preclinical evaluation of therapies targeting NPC1 protein variants with compromised stability. PMID:26019327

  10. Phase-Contrast MRI and CFD Modeling of Apparent 3He Gas Flow in Rat Pulmonary Airways

    SciTech Connect

    Minard, Kevin R.; Kuprat, Andrew P.; Kabilan, Senthil; Jacob, Rick E.; Einstein, Daniel R.; Carson, James P.; Corley, Richard A.

    2012-08-01

    Phase-contrast (PC) magnetic resonance imaging (MRI) with hyperpolarized 3He is potentially useful for developing and testing patient-specific models of pulmonary airflow. One challenge, however, is that PC-MRI provides apparent values of local 3He velocity that not only depend on actual airflow but also on gas diffusion. This not only blurs laminar flow patterns in narrow airways but also introduces anomalous airflow structure that reflects gas-wall interactions. Here, both effects are predicted in a live rat using computational fluid dynamics (CFD), and for the first time, simulated patterns of apparent 3He gas velocity are compared with in-vivo PC-MRI. Results show (1) that correlations (R2) between measured and simulated airflow patterns increase from 0.23 to 0.79 simply by accounting for apparent 3He transport, and that (2) remaining differences are mainly due to uncertain airway segmentation and partial volume effects stemming from relatively coarse MRI resolution. Higher-fidelity testing of pulmonary airflow predictions should therefore be possible with future imaging improvements.

  11. Evaluation of nonperfused myocardial ischemia with MRI and an intravascular USPIO contrast agent in an ex vivo pig model.

    PubMed

    Bjerner, T; Ericsson, A; Wikström, G; Johansson, L; Nilsson, S; Ahlström, H; Hemmingsson, A

    2000-12-01

    The ultrasmall superparamagnetic iron oxide (USPIO) preparation NC100150 Injection (Clariscan; Nycomed Imaging, Oslo, Norway) was tested for its ability to delineate nonperfused myocardium under steady-state conditions. An experimental animal model of focal myocardial ischemia induced by ligation of the distal part of the left anterior descending artery was used. The contrast agent was administered in four doses: 0, 4, 8, and 12 mg Fe/kg body weight. Magnetic resonance examination ex vivo, including T1-, T2-, and T2*-weighted sequences, was performed. Nonperfused myocardium was determined by fluorescein. The best delineation of nonperfused myocardium was found with a T1-weighted inversion recovery/turbo spin-echo sequence and doses of 4 and 8 mg Fe/kg body weight, where 95% of the volume was discernible at the dose of 4 mg Fe/kg body weight. The results suggest that steady-state imaging by T1-weighted sequence with the use of NC100150 Injection to delineate nonperfused myocardium is feasible. J. Magn. Reson. Imaging 2000;12:866-872.

  12. Evaluation and simplified measurement of infarct size by myocardial contrast echocardiography in a rat model of myocardial infarction.

    PubMed

    Chen, Xianghui; Cui, Kai; Xiu, Jiancheng; Lin, Huanbing; Lao, Yi; Zhou, Biying; Liang, Feixue; Zha, Daogang; Bin, Jianping; Liu, Yili

    2009-10-01

    To test the feasibility and accuracy of myocardial contrast echocardiography (MCE) for predicting infarct size (IS) in a rat model of myocardial infarction (MI) and to compare a simplified single plane-based measurement of IS with the conventional three plane-based approach. Fifty male SD rats underwent left anterior descending artery ligation and were evaluated by MCE 8 h post MI. IS was calculated by the single and three plane-based approaches, compared to that determined by triphenyltetrazolium chloride (TTC) staining method. Simplified single plane-based MCE approach and TTC method showed similar IS values (38.48 +/- 16.80% vs. 35.72 +/- 15.33%, P > 0.05) and presented a favorable positive correlation (r = 0.851, P < 0.001). IS values derived from simplified single plane-based approach was also highly significantly correlated with that by the conventional MCE method (r = 0.973, P < 0.001). Bland-Altman plots also displayed satisfactory agreement between them. MCE was validated as a novel technique to quantify infarct area in rats with MI. A single measurement at the mid-papillary muscle level may become a simple, efficient and reliable approach for in vivo IS assessment.

  13. A novel theory of experiential avoidance in generalized anxiety disorder: A review and synthesis of research supporting a contrast avoidance model of worry☆,☆☆

    PubMed Central

    Newman, Michelle G.; Llera, Sandra J.

    2011-01-01

    An important emphasis of the literature on generalized anxiety disorder (GAD) has been to achieve a greater understanding of the function of emotion (e.g., avoidance, dysregulation) in the etiology and maintenance of this disorder. The purpose of the following paper is to propose a new way of conceptualizing emotional sequelae in GAD by detailing the Contrast Avoidance Model of Worry. In presenting this model, we review theory and data that led to our current position, which is that individuals with GAD are more sensitive to feeling emotionally vulnerable to unexpected negative events, and that worry (the key pathological feature of GAD) is employed to prolong and maintain a negative emotional state thereby avoiding an unexpected negative emotional shift, or contrast experience. We also discuss implications for treatment given the presence of a new target for emotional exposure techniques. Finally, we establish the Contrast Avoidance Model within the framework of extant theories and models of pathogenic processes of GAD. PMID:21334285

  14. A novel theory of experiential avoidance in generalized anxiety disorder: a review and synthesis of research supporting a contrast avoidance model of worry.

    PubMed

    Newman, Michelle G; Llera, Sandra J

    2011-04-01

    An important emphasis of the literature on generalized anxiety disorder (GAD) has been to achieve a greater understanding of the function of emotion (e.g., avoidance, dysregulation) in the etiology and maintenance of this disorder. The purpose of the following paper is to propose a new way of conceptualizing emotional sequelae in GAD by detailing the Contrast Avoidance Model of Worry. In presenting this model, we review theory and data that led to our current position, which is that individuals with GAD are more sensitive to feeling emotionally vulnerable to unexpected negative events, and that worry (the key pathological feature of GAD) is employed to prolong and maintain a negative emotional state thereby avoiding an unexpected negative emotional shift, or contrast experience. We also discuss implications for treatment given the presence of a new target for emotional exposure techniques. Finally, we establish the Contrast Avoidance Model within the framework of extant theories and models of pathogenic processes of GAD.

  15. Effective marker alleles associated with type 2 resistance to Fusarium head blight infection in fields

    PubMed Central

    Li, Tao; Luo, Meng; Zhang, Dadong; Wu, Di; Li, Lei; Bai, Guihua

    2016-01-01

    Molecular markers associated with known quantitative trait loci (QTLs) for type 2 resistance to Fusarium head blight (FHB) in bi-parental mapping population usually have more than two alleles in breeding populations. Therefore, understanding the association of each allele with FHB response is particularly important to marker-assisted enhancement of FHB resistance. In this paper, we evaluated FHB severities of 192 wheat accessions including landraces and commercial varieties in three field growing seasons, and genotyped this panel with 364 genome-wide informative molecular markers. Among them, 11 markers showed reproducible marker-trait association (p < 0.05) in at least two experiments using a mixed model. More than two alleles were identified per significant marker locus. These alleles were classified into favorable, unfavorable and neutral alleles according to the normalized genotypic values. The distributions of effective alleles at these loci in each wheat accession were characterized. Mean FHB severities increased with decreased number of favorable alleles at the reproducible loci. Chinese wheat landraces and Japanese accessions have more favorable alleles at the majority of the reproducible marker loci. FHB resistance levels of varieties can be greatly improved by introduction of these favorable alleles and removal of unfavorable alleles simultaneously at these QTL-linked marker loci. PMID:27436944

  16. A Platform for Interrogating Cancer-Associated p53 Alleles

    PubMed Central

    D’Brot, Alejandro; Kurtz, Paula; Regan, Erin; Jakubowski, Brandon; Abrams, John M

    2016-01-01

    p53 is the most frequently mutated gene in human cancer. Compelling evidence argues that full transformation involves loss of growth suppression encoded by wild-type p53 together with poorly understood oncogenic activity encoded by missense mutations. Furthermore, distinguishing disease alleles from natural polymorphisms is an important clinical challenge. To interrogate the genetic activity of human p53 variants, we leveraged the Drosophila model as an in vivo platform. We engineered strains that replace the fly p53 gene with human alleles, producing a collection of stocks that are, in effect, ‘humanized’ for p53 variants. Like the fly counterpart, human p53 transcriptionally activated a biosensor and induced apoptosis after DNA damage. However, all humanized strains representing common alleles found in cancer patients failed to complement in these assays. Surprisingly, stimulus-dependent activation of hp53 occurred without stabilization, demonstrating that these two processes can be uncoupled. Like its fly counterpart, hp53 formed prominent nuclear foci in germline cells but cancer-associated p53 variants did not. Moreover, these same mutant alleles disrupted hp53 foci and inhibited biosensor activity, suggesting that these properties are functionally linked. Together these findings establish a functional platform for interrogating human p53 alleles and suggest that simple phenotypes could be used to stratify disease variants. PMID:26996664

  17. Dynamic imaging of cerebral blood flow in rat reperfused mini-stroke model using laser speckle temporal contrast analysis

    NASA Astrophysics Data System (ADS)

    Wang, Zhen; Luo, Weihua; Li, Pengcheng; Zeng, Shaoqun; Luo, Qingming

    2007-05-01

    Laser speckle temporal contrast analysis (LSTCA) was used to image the cerebral blood flow (CBF) of ischemic area in reperfused mini-stroke model in rats. Focal cortical ischemia in male Sprague-Dawley rats (n=20) was induced by deliberate ligation of multiple branches of the middle cerebral artery (MCA) together with a nylon ring and the dura. LSTCA was used to monitor the spatio-temporal characteristics of cerebral blood flow dynamics in the rat somatosensory cortex in the ischemic and reperfused stages. The infarction volume was measured by 2, 3, 5- triphenyltetrazolium chloride (TTC) staining 24 hours after reperfusion. The distribution of changes in cerebral blood flow which outlined by the laser speckle imaging represented the relative CBF gradient (21.98+/-1.96%, 67.2+/-1.67 %, 107.24+/-4.71 % of the baseline) from ischemic core, penumbra zone to normal tissue immediately after cortical ischemia, in which a central ischemic core had little or no perfusion surrounded by a penumbral region with reduced perfusion, in addition, we had shown the existence of a surrounding region of hyperemic tissue; Thereafter a postrecanalization hyperperfusion occurred in the same infarct core since 24 hours after reperfusion (242.62+/-18.52% of the baseline). Histology of the ischemic regions at 24 hours after reperfusion revealed small focal infarcts that were typically 3~4 mm in diameter, approximately equal to the nylon ring in size and position and essentially accordant with the spatial distribution of the ischemic cortex with below 30% residual CBF of the pre-ischemic baseline. It was demonstrated that this technique of LSTCA was easy to implement and availably used to image the spatial and temporal evolution of CBF changes with high resolution in rat reperfused mini-stroke model.

  18. A contrast between nocturnal flow regimes: Observations and modeling simulations of katabatic intrusions in the Laramie Valley

    NASA Astrophysics Data System (ADS)

    Juliano, Timothy W.

    Katabatic winds commonly occur in mountainous regions under statically stable conditions when a sufficient deficit exists in the net radiation budget. Observations of these stable boundary layer (SBL) downslope flows have extended back to the 1930s. Their interactions with other SBL processes, including cold air pools (CAPs) and mountain waves, are quite complex, however, and have only more recently been deeply investigated. The University of Wyoming (UW) wind tower (WT) and flux tower (WT), situated in the Laramie Valley, were utilized in examining a dataset spanning from 14 December 2011 to 12 September 2013. A set of criteria were developed to determine katabatic intrusion events, and establish a climatology of these events, at the WT. The 21-22 December 2012 nighttime period was then studied in detail using data from the aforementioned towers in addition to weather stations throughout the Laramie Valley and the Weather Research and Forecasting (WRF) model. Both observations and modeling results indicated a competition between two strongly contrasting flow regimes: synoptic and katabatic. The synoptic regime was characterized by strong, southwesterly winds, warm temperatures, and turbulent flow, while the katabatic regime featured weaker, southeasterly winds, cooler temperatures, and intermittently turbulent flow. Sonic and propeller anemometers on the WT elucidated the chaotic transition between the regimes. At the WT, it was found that between regimes the wind speed decreased by up to 60%, wind direction often shifted over 120°, and potential temperature usually decreased more than 2°C. The katabatic wind depth was postulated to be variable in time and space, with its head sloping towards the trailing CAP. Topographically generated mountain waves and local terrain forcing are suspected to play an integral role in the development and evolution of the katabatic wind in the Laramie Valley. Results from this research yield promising insight into the intricate

  19. MO-E-17A-02: Incorporation of Contrast Medium Dynamics in Anthropomorphic Phantoms: The Advent of 5D XCAT Models

    SciTech Connect

    Sahbaee, P; Samei, E; Segars, W

    2014-06-15

    Purpose: To develop a unique method to incorporate the dynamics of contrast-medium propagation into the anthropomorphic phantom, to generate a five-dimensional (5D) patient model for multimodality imaging studies. Methods: A compartmental model of blood circulation network within the body was embodied into an extended cardiac-torso (4D-XCAT) patient model. To do so, a computational physiologic model of the human cardiovascular system was developed which includes a series of compartments representing heart, vessels, and organs. Patient-specific cardiac output and blood volume were used as inputs influenced by the weight, height, age, and gender of the patient's model. For a given injection protocol and given XCAT model, the contrast-medium transmission within the body was described by a series of mass balance differential equations, the solutions to which provided the contrast enhancement-time curves for each organ; thereby defining the tissue materials including the contrastmedium within the XCAT model. A library of time-dependent organ materials was then defined. Each organ in each voxelized 4D-XCAT phantom was assigned to a corresponding time-varying material to create the 5D-XCAT phantom in which the fifth dimension is blood/contrast-medium within the temporal domain. Results: The model effectively predicts the time-varying concentration behavior of various contrast-medium administration in each organ for different patient models as function of patient size (weight/height) and different injection protocol factors (injection rate and pattern, iodine concentration or volume). The contrast enhanced XCAT patient models was developed based on the concentration of iodine as a function of time after injection. Conclusion: Majority of medical imaging systems take advantage of contrast-medium administration in terms of better image quality, the effect of which was ignored in previous optimization studies. The study enables a comprehensive optimization of contrast

  20. Concurrence of High Fat Diet and APOE Gene Induces Allele Specific Metabolic and Mental Stress Changes in a Mouse Model of Alzheimer’s Disease

    PubMed Central

    Segev, Yifat; Livne, Adva; Mints, Meshi; Rosenblum, Kobi

    2016-01-01

    Aging is the main risk factor for neurodegenerative diseases, including Alzheimer’s disease (AD). However, evidence indicates that the pathological process begins long before actual cognitive or pathological symptoms are apparent. The long asymptomatic phase and complex integration between genetic, environmental and metabolic factors make it one of the most challenging diseases to understand and cure. In the present study, we asked whether an environmental factor such as high-fat (HF) diet would synergize with a genetic factor to affect the metabolic and cognitive state in the Apolipoprotein E (ApoE4) mouse model of AD. Our data suggest that a HF diet induces diabetes mellitus (DM)-like metabolism in ApoE4 mice, as well as changes in β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) protein levels between the two ApoE strains. Furthermore, HF diet induces anxiety in this AD mouse model. Our results suggest that young ApoE4 carriers are prone to psychological stress and metabolic abnormalities related to AD, which can easily be triggered via HF nutrition. PMID:27656136

  1. Kinematic modeling and its implication in longitudinal chemotherapy study of tumor physiology: ovarian xenograft mouse model and contrast-enhanced dynamic CT (Honorable Mention Poster Award)

    NASA Astrophysics Data System (ADS)

    Stantz, Keith M.; Liang, Yun; Hutchins, Gary D.

    2004-04-01

    The purpose of this study is to demonstrate that dynamic CT provides the necessary sensitivity to quantify tumor physiology and differences in chemotherapeutic response. A compartmental mouse model utilizing measured contrast-enhanced dynamic CT scans is used to simulate systematic and statistical errors associated with tumor physiology: perfusion, permeability (PS), fractional plasma volume (fp), and fractional interstitial volume. The solute utilized is a small molecular weight radio-opaque contrast agent (isovue). For such an intravascular-interstitial medium, the kinematics simplifies to a two compartmental diffusive dominated set of coupled differential equations. Each combination of physiological parameters is repeatedly simulated fifteen times from which statistical errors calculated. The fractional change relative to the true value (systematic error) and standard deviation (statistical error) are plotted as a function of PS, fp, scanner temporal resolution and noise, and contrast media injection rates. By extrapolating from experimental data found in literature, a relative change in PS and fp of approximately 40% is required. Thus, the longitudinal response of two chemotherapeutic drugs under investigation - proteasome and IMPDH inhibitors - are hypothesized to induce different physiological responses. The first set of simulations varies PS from 0.05 to 0.40 mL/min/mL and fp from 0.01 to 0.07 mL/mL while holding all other physiological parameters constant. Errors in PS remain below 3% while statistical errors for fp increase significantly as the volume decreases toward 1-2%: errors remain less than 6% for fp>0.03 while increasing to above 15% for fp<0.02. The second set of simulations are performed quantifying the relationship between scanner temporal resolution and contrast media injection rate for various tumor permeabilities. For the majority of cases, the errors remain below 5%. As PS approaches perfusion, a total error less than 6% can be maintained

  2. ABNORMAL REGULATION OF MICROVASCULAR TONE IN A MURINE MODEL OF SICKLE CELL DISEASE ASSESSED BY CONTRAST ULTRASOUND

    PubMed Central

    Wu, Melinda D.; Belcik, J. Todd; Qi, Yue; Zhao, Yan; Benner, Cameron; Pei, Hong; Linden, Joel; Lindner, Jonathan R.

    2015-01-01

    Background Microvascular dysregulation, abnormal rheology, and vaso-occlusive events play a role in the pathophysiology of sickle cell disease (SCD). We hypothesized that abnormalities in skeletal muscle perfusion in a murine model of SCD could be parametrically assessed by quantitative contrast-enhanced ultrasound (CEU) perfusion imaging. Methods We studied a murine model of moderate SCD without anemia produced by homozygous β-globin deletion replaced by human βs-globin transgene (NY1DD−/−, n=18), heterozygous transgene replacement (NY1DD+/−, n=19), and C57Bl/6 control mice (n=14). Quantitative CEU of the proximal hindlimb skeletal muscle was performed at rest and during contractile exercise (2 Hz). Time-intensity data were analyzed to measure microvascular blood volume (MBV), microvascular blood transit rate (β), and microvascular blood flow (MBF). Erythrocyte deformability was measured by elongation at various rotational shears. Results At rest, muscle MBV was similar between strains whereas β was significantly (ANOVA p=0.0015) reduced to a similar degree in NY1DD−/− and NY1DD+/− compared to wild-type mice (0.24±0.10, 0.16±0.07, and 0.34±0.14 s−1, respectively), resulting in a reduction in MBF. During contractile exercise, there were no group-wise differences in β (1.43±0.67 s−1, 1.09±0.42 s−1, 1.36±0.49 s−1; for NY1DD−/−, NY1DD+/−, and wild-type, respectively), nor for MBF or MBV. Erythrocyte deformability at high shear stress (≥5 Pa) was mildly reduced in both transgenic groups, although it did not correlate with the blood flow or β. Conclusions CEU in skeletal muscle has revealed a lower microvascular blood transit rate in the NY1DD model of SCD and sickle trait but no alterations in MBV. The abnormality in microvascular blood transit rate is likely due to vasomotor dysfunction since it abrogated by contractile exercise and at rest is only weakly related to erythrocyte deformability. PMID:26123012

  3. Methylene blue microbubbles as a model dual-modality contrast agent for ultrasound and activatable photoacoustic imaging.

    PubMed

    Jeon, Mansik; Song, Wentao; Huynh, Elizabeth; Kim, Jungho; Kim, Jeesu; Helfield, Brandon L; Leung, Ben Y C; Goertz, David E; Zheng, Gang; Oh, Jungtaek; Lovell, Jonathan F; Kim, Chulhong

    2014-01-01

    Ultrasound and photoacoustic imaging are highly complementary modalities since both use ultrasonic detection for operation. Increasingly, photoacoustic and ultrasound have been integrated in terms of hardware instrumentation. To generate a broadly accessible dual-modality contrast agent, we generated microbubbles (a standard ultrasound contrast agent) in a solution of methylene blue (a standard photoacoustic dye). This MB2 solution was formed effectively and was optimized as a dual-modality contrast solution. As microbubble concentration increased (with methylene blue concentration constant), photoacoustic signal was attenuated in the MB2 solution. When methylene blue concentration increased (with microbubble concentration held constant), no ultrasonic interference was observed. Using an MB2 solution that strongly attenuated all photoacoustic signal, high powered ultrasound could be used to burst the microbubbles and dramatically enhance photoacoustic contrast (>800-fold increase), providing a new method for spatiotemporal control of photoacoustic signal generation.

  4. Methylene blue microbubbles as a model dual-modality contrast agent for ultrasound and activatable photoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Jeon, Mansik; Song, Wentao; Huynh, Elizabeth; Kim, Jungho; Kim, Jeesu; Helfield, Brandon L.; Leung, Ben Y. C.; Goertz, David E.; Zheng, Gang; Oh, Jungtaek; Lovell, Jonathan F.; Kim, Chulhong

    2014-01-01

    Ultrasound and photoacoustic imaging are highly complementary modalities since both use ultrasonic detection for operation. Increasingly, photoacoustic and ultrasound have been integrated in terms of hardware instrumentation. To generate a broadly accessible dual-modality contrast agent, we generated microbubbles (a standard ultrasound contrast agent) in a solution of methylene blue (a standard photoacoustic dye). This MB2 solution was formed effectively and was optimized as a dual-modality contrast solution. As microbubble concentration increased (with methylene blue concentration constant), photoacoustic signal was attenuated in the MB2 solution. When methylene blue concentration increased (with microbubble concentration held constant), no ultrasonic interference was observed. Using an MB2 solution that strongly attenuated all photoacoustic signal, high powered ultrasound could be used to burst the microbubbles and dramatically enhance photoacoustic contrast (>800-fold increase), providing a new method for spatiotemporal control of photoacoustic signal generation.

  5. A novel measurement of allele discrimination for assessment of allele-specific silencing by RNA interference.

    PubMed

    Takahashi, Masaki; Hohjoh, Hirohiko

    2014-11-01

    Allele-specific silencing by RNA interference (ASP-RNAi) is an atypical RNAi that is capable of discriminating target alleles from non-target alleles, and may be therapeutically useful for specific inhibition of disease-causing alleles without affecting their corresponding normal alleles. However, it is difficult to design and select small interfering RNA (siRNAs) that confer ASP-RNAi. A major problem is that there are few appropriate measures in determining optimal allele-specific siRNAs. Here we show two novel formulas for calculating a new measure of allele-discrimination, named "ASP-score". The formulas and ASP-score allow for an unbiased determination of optimal siRNAs, and may contribute to characterizing such allele-specific siRNAs.

  6. Multidetector computed tomography (MDCT) evaluation of myocardial viability: intraindividual comparison of monomeric vs. dimeric contrast media in a rabbit model.

    PubMed

    Mahnken, Andreas H; Jost, Gregor; Bruners, Philipp; Sieber, Martin; Seidensticker, Peter R; Günther, Rolf W; Pietsch, Hubertus

    2009-02-01

    To evaluate the influence of different types of iodinated contrast media on the assessment of myocardial viability, acute myocardial infarction (MI) was surgically induced in six rabbits. Over a period of 45 min, contrast-enhanced cardiac MDCT (64 x 0.6 mm, 80 kV, 680 mAs(eff.)) was repeatedly performed using a contrast medium dose of 600 mg iodine/kg body weight. Animals received randomized iopromide 300 and iodixanol 320, respectively. Attenuation values of healthy and infarcted myocardium were measured. The size of MI was computed and compared with nitroblue tetrazolium (NBT)-stained specimen. The highest attenuation differences between infarcted and healthy myocardium occurred during the arterial phase with 140.0+/-3.5 HU and 141.0+/-2.2 HU for iopromide and iodixanol, respectively. For iodixanol the highest attenuation difference on delayed contrast-enhanced images was achieved 3 min post injection (73.5 HU). A slightly higher attenuation difference was observed for iopromide 6 min after contrast medium injection (82.2 HU), although not statistically significant (p=0.6437). Mean infarct volume as measured by NBT staining was 33.5%+/-13.6%. There was an excellent agreement of infarct sizes among NBT-, iopromide- and iodixanol-enhanced MDCT with concordance-correlation coefficients ranging from rho(c)=0.9928-0.9982. Iopromide and iodixanol both allow a reliable assessment of MI with delayed contrast-enhanced MDCT.

  7. Low proarrhythmic potential of citalopram and escitalopram in contrast to haloperidol in an experimental whole-heart model.

    PubMed

    Frommeyer, Gerrit; Brücher, Benedict; von der Ahe, Henning; Kaese, Sven; Dechering, Dirk G; Kochhäuser, Simon; Bogossian, Harilaos; Milberg, Peter; Eckardt, Lars

    2016-10-05

    In several case reports proarrhythmic effects of citalopram and escitalopram have been reported. Systematic analyses on prorarrhythmic effects of these drugs are not yet available. The aim of the present study was to investigate if application of citalopram, escitalopram or haloperidol provokes polymorphic ventricular tachycardia in a sensitive model of proarrhythmia. In isolated rabbit hearts monophasic action potentials and ECG showed a significant QT-prolongation after application of citalopram (2µM: +47ms, 4µM: +56ms, P<0.05) accompanied by an increase of action potential duration (APD) but not dispersion of repolarization. Reduced potassium concentration in bradycardic AV-blocked hearts provoked early afterdepolarizations (EAD) in 2 of 12 hearts but no polymorphic ventricular tachycardia (pVT). Application of escitalopram also increased QT-interval (2µM: +3ms, 4µM: +30ms, P<0.05) and APD without effects on dispersion. 3 of 10 hearts showed EAD and pVT in 2 of 10 hearts (32 episodes). The results were compared to 12 rabbits treated with haloperidol which led to an increase in QT-interval (1µM:+62ms; 2µM:+96ms; P<0.01), APD and dispersion (1µM:+15ms, 2µM:+40ms; P<0.01) and induced EAD in all 12 and pVT in 10 of 12 hearts (152 episodes). Citalopram and escitalopram demonstrated a rather safe electrophysiologic profile despite significant QT prolongation. In contrast, haloperidol led to significant increase of dispersion of repolarization while this parameter remained stable under the influence of citalopram or escitalopram. These results imply that application of citalopram or escitalopram is not as proarrhythmic as some case reports might suggest while haloperidol is torsadogenic.

  8. Allelic Spectra of Risk SNPs Are Different for Environment/Lifestyle Dependent versus Independent Diseases.

    PubMed

    Gorlov, Ivan P; Gorlova, Olga Y; Amos, Christopher I

    2015-07-01

    Genome-wide association studies (GWAS) have generated sufficient data to assess the role of selection in shaping allelic diversity of disease-associated SNPs. Negative selection against disease risk variants is expected to reduce their frequencies making them overrepresented in the group of minor (<50%) alleles. Indeed, we found that the overall proportion of risk alleles was higher among alleles with frequency <50% (minor alleles) compared to that in the group of major alleles. We hypothesized that negative selection may have different effects on environment (or lifestyle)-dependent versus environment (or lifestyle)-independent diseases. We used an environment/lifestyle index (ELI) to assess influence of environmental/lifestyle factors on disease etiology. ELI was defined as the number of publications mentioning "environment" or "lifestyle" AND disease per 1,000 disease-mentioning publications. We found that the frequency distributions of the risk alleles for the diseases with strong environmental/lifestyle components follow the distribution expected under a selectively neutral model, while frequency distributions of the risk alleles for the diseases with weak environmental/lifestyle influences is shifted to the lower values indicating effects of negative selection. We hypothesized that previously selectively neutral variants become risk alleles when environment changes. The hypothesis of ancestrally neutral, currently disadvantageous risk-associated alleles predicts that the distribution of risk alleles for the environment/lifestyle dependent diseases will follow a neutral model since natural selection has not had enough time to influence allele frequencies. The results of our analysis suggest that prediction of SNP functionality based on the level of evolutionary conservation may not be useful for SNPs associated with environment/lifestyle dependent diseases.

  9. Allelic Spectra of Risk SNPs Are Different for Environment/Lifestyle Dependent versus Independent Diseases

    PubMed Central

    Amos, Christopher I.

    2015-01-01

    Genome-wide association studies (GWAS) have generated sufficient data to assess the role of selection in shaping allelic diversity of disease-associated SNPs. Negative selection against disease risk variants is expected to reduce their frequencies making them overrepresented in the group of minor (<50%) alleles. Indeed, we found that the overall proportion of risk alleles was higher among alleles with frequency <50% (minor alleles) compared to that in the group of major alleles. We hypothesized that negative selection may have different effects on environment (or lifestyle)-dependent versus environment (or lifestyle)-independent diseases. We used an environment/lifestyle index (ELI) to assess influence of environmental/lifestyle factors on disease etiology. ELI was defined as the number of publications mentioning “environment” or “lifestyle” AND disease per 1,000 disease-mentioning publications. We found that the frequency distributions of the risk alleles for the diseases with strong environmental/lifestyle components follow the distribution expected under a selectively neutral model, while frequency distributions of the risk alleles for the diseases with weak environmental/lifestyle influences is shifted to the lower values indicating effects of negative selection. We hypothesized that previously selectively neutral variants become risk alleles when environment changes. The hypothesis of ancestrally neutral, currently disadvantageous risk-associated alleles predicts that the distribution of risk alleles for the environment/lifestyle dependent diseases will follow a neutral model since natural selection has not had enough time to influence allele frequencies. The results of our analysis suggest that prediction of SNP functionality based on the level of evolutionary conservation may not be useful for SNPs associated with environment/lifestyle dependent diseases. PMID:26201053

  10. Quantitative Assessment of Inflammation in a Porcine Acute Terminal Ileitis Model: US with a Molecularly Targeted Contrast Agent

    PubMed Central

    Wang, Huaijun; Felt, Stephen A.; Machtaler, Steven; Guracar, Ismayil; Luong, Richard; Bettinger, Thierry; Tian, Lu; Lutz, Amelie M.

    2015-01-01

    Purpose To evaluate the feasibility and reproducibility of ultrasonography (US) performed with dual-selectin–targeted contrast agent microbubbles (MBs) for assessment of inflammation in a porcine acute terminal ileitis model, with histologic findings as a reference standard. Materials and Methods The study had institutional Animal Care and Use Committee approval. Acute terminal ileitis was established in 19 pigs; four pigs served as control pigs. The ileum was imaged with clinical-grade dual P- and E-selectin–targeted MBs (MBSelectin) at increasing doses (0.5, 1.0, 2.5, 5.0, 10, and 20 × 108 MB per kilogram of body weight) and with control nontargeted MBs (MBControl). For reproducibility testing, examinations were repeated twice after the MBSelectin and MBControl injections. After imaging, scanned ileal segments were analyzed ex vivo both for inflammation grade (by using hematoxylin-eosin staining) and for expression of selectins (by using quantitative immunofluorescence analysis). Statistical analysis was performed by using the t test, intraclass correlation coefficients (ICCs), and Spearman correlation analysis. Results Imaging signal increased linearly (P < .001) between a dose of 0.5 and a dose of 5.0 × 108 MB/kg and plateaued between a dose of 10 and a dose of 20 × 108 MB/kg. Imaging signals were reproducible (ICC = 0.70), and administration of MBSelectin in acute ileitis resulted in a significantly higher (P < .001) imaging signal compared with that in control ileum and MBControl. Ex vivo histologic grades of inflammation correlated well with in vivo US signal (ρ = 0.79), and expression levels of both P-selectin (37.4% ± 14.7 [standard deviation] of vessels positive; P < .001) and E-selectin (31.2% ± 25.7) in vessels in the bowel wall of segments with ileitis were higher than in control ileum (5.1% ± 3.7 for P-selectin and 4.8% ± 2.3 for E-selectin). Conclusion Quantitative measurements of inflammation obtained by using dual-selectin–targeted US

  11. A three dimensional model of an ultrasound contrast agent gas bubble and its mechanical effects on microvessels

    PubMed Central

    Hosseinkhah, N.; Hynynen, K.

    2012-01-01

    Ultrasound contrast agents inside a microvessel, when driven by ultrasound, oscillate and induce mechanical stresses on the vessel wall. These mechanical stresses can produce beneficial therapeutic effects but also induce vessel rupture if the stresses are too high. Therefore, it is important to use sufficiently low pressure amplitudes to avoid rupturing the vessels while still inducing the desired therapeutic effects. In this work, we developed a comprehensive three dimensional model of a confined microbubble inside a vessel while considering the bubble shell properties, blood viscosity, vessel wall curvature and the mechanical properties of the vessel wall. Two bubble models with the assumption of a spherical symmetric bubble and a simple asymmetrical bubble were simulated. This work was validated with previous experimental results and enabled us to evaluate the microbubbles’ behaviour and the resulting mechanical stresses induced on the vessel walls. In this study the fluid shear and circumferential stresses were evaluated as indicators of the mechanical stresses. The effects of acoustical parameters, vessel viscoelasticity and rigidity, vessel/bubble size and off-center bubbles on bubble behaviour and stresses on the vessel were investigated. The fluid shear and circumferential stresses acting on the vessel varied with time and location. As the frequency changed, the microbubble oscillated with the highest amplitude at its resonance frequency which was different from the resonance frequency of an unbound bubble. The bubble resonance frequency increased as the rigidity of a flexible vessel increased. The fluid shear and circumferential stresses peaked at frequencies above the bubble’s resonance frequency. The more rigid the vessels were, the more damped the bubble oscillations. The synergistic effect of acoustic frequency and vessel elasticity had also been investigated, since the circumferential stress showed either an increasing trend or a decreasing one

  12. Differential Expression of Chemokine and Matrix Re-Modelling Genes Is Associated with Contrasting Schistosome-Induced Hepatopathology in Murine Models

    PubMed Central

    Stenzel, Deborah J.; McManus, Donald P.; Ramm, Grant A.; Gobert, Geoffrey N.

    2011-01-01

    The pathological outcomes of schistosomiasis are largely dependent on the molecular and cellular mechanisms of the host immune response. In this study, we investigated the contribution of variations in host gene expression to the contrasting hepatic pathology observed between two inbred mouse strains following Schistosoma japonicum infection. Whole genome microarray analysis was employed in conjunction with histological and immunohistochemical analysis to define and compare the hepatic gene expression profiles and cellular composition associated with the hepatopathology observed in S. japonicum-infected BALB/c and CBA mice. We show that the transcriptional profiles differ significantly between the two mouse strains with high statistical confidence. We identified specific genes correlating with the more severe pathology associated with CBA mice, as well as genes which may confer the milder degree of pathology associated with BALB/c mice. In BALB/c mice, neutrophil genes exhibited striking increases in expression, which coincided with the significantly greater accumulation of neutrophils at granulomatous regions seen in histological sections of hepatic tissue. In contrast, up-regulated expression of the eosinophil chemokine CCL24 in CBA mice paralleled the cellular influx of eosinophils to the hepatic granulomas. Additionally, there was greater down-regulation of genes involved in metabolic processes in CBA mice, reflecting the more pronounced hepatic damage in these mice. Profibrotic genes showed similar levels of expression in both mouse strains, as did genes associated with Th1 and Th2 responses. However, imbalances in expression of matrix metalloproteinases (e.g. MMP12, MMP13) and tissue inhibitors of metalloproteinases (TIMP1) may contribute to the contrasting pathology observed in the two strains. Overall, these results provide a more complete picture of the molecular and cellular mechanisms which govern the pathological outcome of hepatic schistosomiasis. This

  13. Allelic selection of human IL-2 gene.

    PubMed

    Matesanz, F; Delgado, C; Fresno, M; Alcina, A

    2000-12-01

    The allelic expression of mouse IL-2 cannot be definitely extrapolated to what might happen in humans. Therefore, we investigated the regulation of allelic expression of the IL-2 gene in non-genetically manipulated human T lymphocytes by following natural allelic polymorphisms. We found a phenotypically silent punctual change in the human IL-2 at position 114 after the first nucleotide of the initiation codon, which represents a dimorphic polymorphism at the first exon of the IL-2 gene. This allowed the study by single-cell PCR of the regulation of the human IL-2 allelic expression in heterozygous CD4(+) T cells, which was found to be tightly controlled monoallelically. These findings may be used as a suitable marker for monitoring the IL-2 allelic contribution to effector activities and in immune responses against different infections or in pathological situations.

  14. Comparative analysis of Vening-Meinesz Moritz isostatic models using the constant and variable crust-mantle density contrast - a case study of Zealandia

    NASA Astrophysics Data System (ADS)

    Bagherbandi, Mohammad; Tenzer, Robert

    2013-04-01

    We compare three different numerical schemes of treating the Moho density contrast in gravimetric inverse problems for finding the Moho depths. The results are validated using the global crustal model CRUST2.0, which is determined based purely on seismic data. Firstly, the gravimetric recovery of the Moho depths is realized by solving Moritz's generalization of the Vening-Meinesz inverse problem of isostasy while the constant Moho density contrast is adopted. The Pratt-Hayford isostatic model is then facilitated to estimate the variable Moho density contrast. This variable Moho density contrast is subsequently used to determine the Moho depths. Finally, the combined least-squares approach is applied to estimate jointly the Moho depths and density contract based on a priori error model. The EGM2008 global gravity model and the DTM2006.0 global topographic/bathymetric model are used to generate the isostatic gravity anomalies. The comparison of numerical results reveals that the optimal isostatic inverse scheme should take into consideration both the variable depth and density of compensation. This is achieved by applying the combined least-squares approach for a simultaneous estimation of both Moho parameters. We demonstrate that the result obtained using this method has the best agreement with the CRUST2.0 Moho depths. The numerical experiments are conducted at the regional study area of New Zealand's continental shelf.

  15. Inter-allelic interactions play a major role in microsatellite evolution.

    PubMed

    Amos, William; Kosanović, Danica; Eriksson, Anders

    2015-11-07

    Microsatellite mutations identified in pedigrees confirm that most changes involve the gain or loss of single repeats. However, an unexpected pattern is revealed when the resulting data are plotted on standardized scales that range from the shortest to longest allele at a locus. Both mutation rate and mutation bias reveal a strong dependency on allele length relative to other alleles at the same locus. We show that models in which alleles mutate independently cannot explain these patterns. Instead, both mutation probability and direction appear to involve interactions between homologues in heterozygous individuals. Simple models in which the longer homologue in heterozygotes is more likely to mutate and/or biased towards contraction readily capture the observed trends. The exact model remains unclear in all its details but inter-allelic interactions are a vital component, implying a link between demographic history and the mode and tempo of microsatellite evolution.

  16. Inter-allelic interactions play a major role in microsatellite evolution

    PubMed Central

    Amos, William; Kosanović, Danica; Eriksson, Anders

    2015-01-01

    Microsatellite mutations identified in pedigrees confirm that most changes involve the gain or loss of single repeats. However, an unexpected pattern is revealed when the resulting data are plotted on standardized scales that range from the shortest to longest allele at a locus. Both mutation rate and mutation bias reveal a strong dependency on allele length relative to other alleles at the same locus. We show that models in which alleles mutate independently cannot explain these patterns. Instead, both mutation probability and direction appear to involve interactions between homologues in heterozygous individuals. Simple models in which the longer homologue in heterozygotes is more likely to mutate and/or biased towards contraction readily capture the observed trends. The exact model remains unclear in all its details but inter-allelic interactions are a vital component, implying a link between demographic history and the mode and tempo of microsatellite evolution. PMID:26511050

  17. Evaluation of Tumor Micro-Environment in an Animal Model using a Nanoparticle Contrast Agent in Computed Tomography Imaging

    PubMed Central

    Ghaghada, Ketan B.; Badea, Cristian T.; Karumbaiah, Lohitash; Fettig, Nicole; Bellamkonda, Ravi V.; Johnson, G A; Annapragada, Ananth

    2010-01-01

    RATIONALE AND OBJECTIVES Non-invasive longitudinal imaging of tumor vasculature could provide new insights into the development of solid tumors, facilitating efficient delivery of therapeutics. In this study, we report three-dimensional imaging and characterization of tumor vascular architecture using a nanoparticle contrast agent and high-resolution computed tomography (CT) imaging. MATERIALS AND METHODS Five Balb/c mice implanted with 4T1/Luc syngeneic breast tumors cells were used for the study. The nanoparticle contrast agent was systemically administered and longitudinal CT imaging was performed pre-contrast and at serial time-points post-contrast, for up to 7 days for studying the characteristics of tumor-associated blood vessels. Gene-expression of tumor angiogenic biomarkers was measured using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS Early-phase imaging demonstrated the presence of co-opted and newly developed tumor vessels. The co-opted vessels demonstrated wall-permeability and ‘leakiness’ characteristics evident by an increase in extra-vascular nanoparticle-based signal enhancement visible well beyond the margins of tumor. Diameters of tumor-associated vessels were larger than the contra-lateral normal vessels. Delayed-phase imaging also demonstrated significant accumulation of nanoparticle contrast agent both within and in areas surrounding the tumor. A heterogeneous pattern of signal enhancement was observed both within and among individual tumors. Gene-expression profiling demonstrated significant variability in several angiogenic biomarkers both within and among individual tumors. CONCLUSIONS The nanoparticle contrast agent and high-resolution CT imaging facilitated visualization of co-opted and newly developed tumors vessels as well as imaging of nanoparticle accumulation within tumors. The use of this agent could provide novel insights into tumor vascular biology and could have implications on the monitoring of tumor

  18. Combined off-resonance imaging and T2 relaxation in the rotating frame for positive contrast MR imaging of infection in a murine burn model

    PubMed Central

    Andronesi, Ovidiu C.; Mintzopoulos, Dionyssios; Righi, Valeria; Psychogios, Nikolaos; Kesarwani, Meenu; He, Jianxin; Yasuhara, Shingo; Dai, George; Rahme, Laurence G.; Tzika, Aria A.

    2010-01-01

    Purpose To develop novel magnetic resonance (MR) imaging methods to monitor accumulation of macrophages in inflammation and infection. Positive-contrast MR imaging provides an alternative to negative-contrast MRI, exploiting the chemical shift induced by ultra-small superparamagnetic iron-oxide (USPIO) nanoparticles to nearby water molecules. We introduce a novel combination of off-resonance (ORI) positive-contrast MRI and T2ρ relaxation in the rotating frame (ORI-T2ρ) for positive-contrast MR imaging of USPIO. Materials and Methods We tested ORI-T2ρ in phantoms and imaged in vivo the accumulation of USPIO-labeled macrophages at the infection site in a mouse model of burn trauma and infection with Pseudomonas aeruginosa (PA). PA infection is clinically important. The USPIO nanoparticles were injected directly in the animals in solution, and macrophage labeling occurred in vivo in the animal model. Results We observed a significant difference between ORI-T2ρ and ORI, which leads us to suggest that ORI-T2ρ is more sensitive in detecting USPIO signal. To this end, the ORI-T2ρ positive contrast method may prove to be of higher utility in future research. Conclusion Our results may have direct implications in the longitudinal monitoring of infection, and open perspectives for testing novel anti-infective compounds. PMID:21031524

  19. Seven novel HLA alleles reflect different mechanisms involved in the evolution of HLA diversity: description of the new alleles and review of the literature.

    PubMed

    Adamek, Martina; Klages, Cornelia; Bauer, Manuela; Kudlek, Evelina; Drechsler, Alina; Leuser, Birte; Scherer, Sabine; Opelz, Gerhard; Tran, Thuong Hien

    2015-01-01

    The human leukocyte antigen (HLA) loci are among the most polymorphic genes in the human genome. The diversity of these genes is thought to be generated by different mechanisms including point mutation, gene conversion and crossing-over. During routine HLA typing, we discovered seven novel HLA alleles which were probably generated by different evolutionary mechanisms. HLA-B*41:21, HLA-DQB1*02:10 and HLA-DQA1*01:12 likely emerged from the common alleles of their groups by point mutations, all of which caused non-synonymous amino acid substitutions. In contrast, a deletion of one nucleotide leading to a frame shift with subsequent generation of a stop codon is responsible for the appearance of a null allele, HLA-A*01:123N. Whereas HLA-B*35:231 and HLA-B*53:31 were probably products of intralocus gene conversion between HLA-B alleles, HLA-C*07:294 presumably evolved by interlocus gene conversion between an HLA-C and an HLA-B allele. Our analysis of these novel alleles illustrates the different mechanisms which may have contributed to the evolution of HLA polymorphism.

  20. Asynchronous Replication, Mono-Allelic Expression, and Long Range Cis-Effects of ASAR6

    PubMed Central

    Smith, Leslie; Montagna, Christina; Thayer, Mathew J.

    2013-01-01

    Mammalian chromosomes initiate DNA replication at multiple sites along their length during each S phase following a temporal replication program. The majority of genes on homologous chromosomes replicate synchronously. However, mono-allelically expressed genes such as imprinted genes, allelically excluded genes, and genes on female X chromosomes replicate asynchronously. We have identified a cis-acting locus on human chromosome 6 that controls this replication-timing program. This locus encodes a large intergenic non-coding RNA gene named Asynchronous replication and Autosomal RNA on chromosome 6, or ASAR6. Disruption of ASAR6 results in delayed replication, delayed mitotic chromosome condensation, and activation of the previously silent alleles of mono-allelic genes on chromosome 6. The ASAR6 gene resides within an ∼1.2 megabase domain of asynchronously replicating DNA that is coordinated with other random asynchronously replicating loci along chromosome 6. In contrast to other nearby mono-allelic genes, ASAR6 RNA is expressed from the later-replicating allele. ASAR6 RNA is synthesized by RNA Polymerase II, is not polyadenlyated, is restricted to the nucleus, and is subject to random mono-allelic expression. Disruption of ASAR6 leads to the formation of bridged chromosomes, micronuclei, and structural instability of chromosome 6. Finally, ectopic integration of cloned genomic DNA containing ASAR6 causes delayed replication of entire mouse chromosomes. PMID:23593023

  1. Characterization of the treefrog null allele, 1991

    SciTech Connect

    Guttman, S.I.

    1992-04-01

    Spring peeper (Hyla crucifer) tadpoles collected from the waste storage area during the Biological and Ecological Site Characterization of the Feed Materials Production Center (FEMP) in 1986 and 1987 appeared to be unique. A null (inactive) allele was found at the glucose phosphate isomerase enzyme locus in significant frequencies (approximately 20%) each year; this allele did not appear to occur in the offsite sample collected approximately 15km from the FEMP. Null alleles at this locus have not been reported in other amphibian populations; when they have been found in other organisms they have invariably been lethal in the homozygous condition.

  2. Characterization of the treefrog null allele

    SciTech Connect

    Guttman, S.I. . Dept. of Zoology)

    1990-12-01

    As part of the authors intensive year-long baseline ecological study, they characterized the degree of genetic polymorphism and heterozygosity in selected Feed Materials Production Center (FMPC) populations using electrophoretic techniques. These data are being used as an indicator of stress by comparing populations on and off the FMPC site. The current study was initiated to determine whether this GPI null allele is lethal, when homozygous, in spring peepers. Also, a sampling protocol was implemented to determine whether a linear effect occurs relative to the frequency of the null allele offsite and to determine the origination site of the null allele. 18 refs., 2 figs., 4 tabs.

  3. Efficient nonmeiotic allele introgression in livestock using custom endonucleases

    PubMed Central

    Tan, Wenfang; Carlson, Daniel F.; Lancto, Cheryl A.; Garbe, John R.; Webster, Dennis A.; Hackett, Perry B.; Fahrenkrug, Scott C.

    2013-01-01

    We have expanded the livestock gene editing toolbox to include transcription activator-like (TAL) effector nuclease (TALEN)- and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-stimulated homology-directed repair (HDR) using plasmid, rAAV, and oligonucleotide templates. Toward the genetic dehorning of dairy cattle, we introgressed a bovine POLLED allele into horned bull fibroblasts. Single nucleotide alterations or small indels were introduced into 14 additional genes in pig, goat, and cattle fibroblasts using TALEN mRNA and oligonucleotide transfection with efficiencies of 10–50% in populations. Several of the chosen edits mimic naturally occurring performance-enhancing or disease- resistance alleles, including alteration of single base pairs. Up to 70% of the fibroblast colonies propagated without selection harbored the intended edits, of which more than one-half were homozygous. Edited fibroblasts were used to generate pigs with knockout alleles in the DAZL and APC genes to model infertility and colon cancer. Our methods enable unprecedented meiosis-free intraspecific and interspecific introgression of select alleles in livestock for agricultural and biomedical applications. PMID:24014591

  4. Practical Dynamic Contrast Enhanced MRI in Small Animal Models of Cancer: Data Acquisition, Data Analysis, and Interpretation

    PubMed Central

    Barnes, Stephanie L.; Whisenant, Jennifer G.; Loveless, Mary E.; Yankeelov, Thomas E.

    2012-01-01

    Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) consists of the continuous acquisition of images before, during, and after the injection of a contrast agent. DCE-MRI allows for noninvasive evaluation of tumor parameters related to vascular perfusion and permeability and tissue volume fractions, and is frequently employed in both preclinical and clinical investigations. However, the experimental and analytical subtleties of the technique are not frequently discussed in the literature, nor are its relationships to other commonly used quantitative imaging techniques. This review aims to provide practical information on the development, implementation, and validation of a DCE-MRI study in the context of a preclinical study (though we do frequently refer to clinical studies that are related to these topics). PMID:23105959

  5. Nucleotide variation and identification of novel blast resistance alleles of Pib by allele mining strategy.

    PubMed

    Ramkumar, G; Madhav, M S; Devi, S J S Rama; Prasad, M S; Babu, V Ravindra

    2015-04-01

    Pib is one of significant rice blast resistant genes, which provides resistance to wide range of isolates of rice blast pathogen, Magnaporthe oryzae. Identification and isolation of novel and beneficial alleles help in crop enhancement. Allele mining is one of the best strategies for dissecting the allelic variations at candidate gene and identification of novel alleles. Hence, in the present study, Pib was analyzed by allele mining strategy, and coding and non-coding (upstream and intron) regions were examined to identify novel Pib alleles. Allelic sequences comparison revealed that nucleotide polymorphisms at coding regions affected the amino acid sequences, while the polymorphism at upstream (non-coding) region affected the motifs arrangements. Pib alleles from resistant landraces, Sercher and Krengosa showed better resistance than Pib donor variety, might be due to acquired mutations, especially at LRR region. The evolutionary distance, Ka/Ks and phylogenetic analyzes also supported these results. Transcription factor binding motif analysis revealed that Pib (Sr) had a unique motif (DPBFCOREDCDC3), while five different motifs differentiated the resistance and susceptible Pib alleles. As the Pib is an inducible gene, the identified differential motifs helps to understand the Pib expression mechanism. The identified novel Pib resistant alleles, which showed high resistance to the rice blast, can be used directly in blast resistance breeding program as alternative Pib resistant sources.

  6. Comparison of HLA allelic imputation programs.

    PubMed

    Karnes, Jason H; Shaffer, Christian M; Bastarache, Lisa; Gaudieri, Silvana; Glazer, Andrew M; Steiner, Heidi E; Mosley, Jonathan D; Mallal, Simon; Denny, Joshua C; Phillips, Elizabeth J; Roden, Dan M

    2017-01-01

    Imputation of human leukocyte antigen (HLA) alleles from SNP-level data is attractive due to importance of HLA alleles in human disease, widespread availability of genome-wide association study (GWAS) data, and expertise required for HLA sequencing. However, comprehensive evaluations of HLA imputations programs are limited. We compared HLA imputation results of HIBAG, SNP2HLA, and HLA*IMP:02 to sequenced HLA alleles in 3,265 samples from BioVU, a de-identified electronic health record database coupled to a DNA biorepository. We performed four-digit HLA sequencing for HLA-A, -B, -C, -DRB1, -DPB1, and -DQB1 using long-read 454 FLX sequencing. All samples were genotyped using both the Illumina HumanExome BeadChip platform and a GWAS platform. Call rates and concordance rates were compared by platform, frequency of allele, and race/ethnicity. Overall concordance rates were similar between programs in European Americans (EA) (0.975 [SNP2HLA]; 0.939 [HLA*IMP:02]; 0.976 [HIBAG]). SNP2HLA provided a significant advantage in terms of call rate and the number of alleles imputed. Concordance rates were lower overall for African Americans (AAs). These observations were consistent when accuracy was compared across HLA loci. All imputation programs performed similarly for low frequency HLA alleles. Higher concordance rates were observed when HLA alleles were imputed from GWAS platforms versus the HumanExome BeadChip, suggesting that high genomic coverage is preferred as input for HLA allelic imputation. These findings provide guidance on the best use of HLA imputation methods and elucidate their limitations.

  7. Comparison of HLA allelic imputation programs

    PubMed Central

    Shaffer, Christian M.; Bastarache, Lisa; Gaudieri, Silvana; Glazer, Andrew M.; Steiner, Heidi E.; Mosley, Jonathan D.; Mallal, Simon; Denny, Joshua C.; Phillips, Elizabeth J.; Roden, Dan M.

    2017-01-01

    Imputation of human leukocyte antigen (HLA) alleles from SNP-level data is attractive due to importance of HLA alleles in human disease, widespread availability of genome-wide association study (GWAS) data, and expertise required for HLA sequencing. However, comprehensive evaluations of HLA imputations programs are limited. We compared HLA imputation results of HIBAG, SNP2HLA, and HLA*IMP:02 to sequenced HLA alleles in 3,265 samples from BioVU, a de-identified electronic health record database coupled to a DNA biorepository. We performed four-digit HLA sequencing for HLA-A, -B, -C, -DRB1, -DPB1, and -DQB1 using long-read 454 FLX sequencing. All samples were genotyped using both the Illumina HumanExome BeadChip platform and a GWAS platform. Call rates and concordance rates were compared by platform, frequency of allele, and race/ethnicity. Overall concordance rates were similar between programs in European Americans (EA) (0.975 [SNP2HLA]; 0.939 [HLA*IMP:02]; 0.976 [HIBAG]). SNP2HLA provided a significant advantage in terms of call rate and the number of alleles imputed. Concordance rates were lower overall for African Americans (AAs). These observations were consistent when accuracy was compared across HLA loci. All imputation programs performed similarly for low frequency HLA alleles. Higher concordance rates were observed when HLA alleles were imputed from GWAS platforms versus the HumanExome BeadChip, suggesting that high genomic coverage is preferred as input for HLA allelic imputation. These findings provide guidance on the best use of HLA imputation methods and elucidate their limitations. PMID:28207879

  8. KIR2DL2/2DL3-E(35) alleles are functionally stronger than -Q(35) alleles.

    PubMed

    Bari, Rafijul; Thapa, Rajoo; Bao, Ju; Li, Ying; Zheng, Jie; Leung, Wing

    2016-03-31

    KIR2DL2 and KIR2DL3 segregate as alleles of a single locus in the centromeric motif of the killer cell immunoglobulin-like receptor (KIR) gene family. Although KIR2DL2/L3 polymorphism is known to be associated with many human diseases and is an important factor for donor selection in allogeneic hematopoietic stem cell transplantation, the molecular determinant of functional diversity among various alleles is unclear. In this study we found that KIR2DL2/L3 with glutamic acid at position 35 (E(35)) are functionally stronger than those with glutamine at the same position (Q(35)). Cytotoxicity assay showed that NK cells from HLA-C1 positive donors with KIR2DL2/L3-E(35) could kill more target cells lacking their ligands than NK cells with the weaker -Q(35) alleles, indicating better licensing of KIR2DL2/L3(+) NK cells with the stronger alleles. Molecular modeling analysis reveals that the glutamic acid, which is negatively charged, interacts with positively charged histidine located at position 55, thereby stabilizing KIR2DL2/L3 dimer and reducing entropy loss when KIR2DL2/3 binds to HLA-C ligand. The results of this study will be important for future studies of KIR2DL2/L3-associated diseases as well as for donor selection in allogeneic stem cell transplantation.

  9. KIR2DL2/2DL3-E35 alleles are functionally stronger than -Q35 alleles

    NASA Astrophysics Data System (ADS)

    Bari, Rafijul; Thapa, Rajoo; Bao, Ju; Li, Ying; Zheng, Jie; Leung, Wing

    2016-03-01

    KIR2DL2 and KIR2DL3 segregate as alleles of a single locus in the centromeric motif of the killer cell immunoglobulin-like receptor (KIR) gene family. Although KIR2DL2/L3 polymorphism is known to be associated with many human diseases and is an important factor for donor selection in allogeneic hematopoietic stem cell transplantation, the molecular determinant of functional diversity among various alleles is unclear. In this study we found that KIR2DL2/L3 with glutamic acid at position 35 (E35) are functionally stronger than those with glutamine at the same position (Q35). Cytotoxicity assay showed that NK cells from HLA-C1 positive donors with KIR2DL2/L3-E35 could kill more target cells lacking their ligands than NK cells with the weaker -Q35 alleles, indicating better licensing of KIR2DL2/L3+ NK cells with the stronger alleles. Molecular modeling analysis reveals that the glutamic acid, which is negatively charged, interacts with positively charged histidine located at position 55, thereby stabilizing KIR2DL2/L3 dimer and reducing entropy loss when KIR2DL2/3 binds to HLA-C ligand. The results of this study will be important for future studies of KIR2DL2/L3-associated diseases as well as for donor selection in allogeneic stem cell transplantation.

  10. Fast spatial ancestry via flexible allele frequency surfaces

    PubMed Central

    Rañola, John Michael; Novembre, John; Lange, Kenneth

    2014-01-01

    Motivation: Unique modeling and computational challenges arise in locating the geographic origin of individuals based on their genetic backgrounds. Single-nucleotide polymorphisms (SNPs) vary widely in informativeness, allele frequencies change non-linearly with geography and reliable localization requires evidence to be integrated across a multitude of SNPs. These problems become even more acute for individuals of mixed ancestry. It is hardly surprising that matching genetic models to computational constraints has limited the development of methods for estimating geographic origins. We attack these related problems by borrowing ideas from image processing and optimization theory. Our proposed model divides the region of interest into pixels and operates SNP by SNP. We estimate allele frequencies across the landscape by maximizing a product of binomial likelihoods penalized by nearest neighbor interactions. Penalization smooths allele frequency estimates and promotes estimation at pixels with no data. Maximization is accomplished by a minorize–maximize (MM) algorithm. Once allele frequency surfaces are available, one can apply Bayes’ rule to compute the posterior probability that each pixel is the pixel of origin of a given person. Placement of admixed individuals on the landscape is more complicated and requires estimation of the fractional contribution of each pixel to a person’s genome. This estimation problem also succumbs to a penalized MM algorithm. Results: We applied the model to the Population Reference Sample (POPRES) data. The model gives better localization for both unmixed and admixed individuals than existing methods despite using just a small fraction of the available SNPs. Computing times are comparable with the best competing software. Availability and implementation: Software will be freely available as the OriGen package in R. Contact: ranolaj@uw.edu or klange@ucla.edu Supplementary information: Supplementary data are available at

  11. Cytochrome P450 CYP2D6 genotypes: association with hair colour, Breslow thickness and melanocyte stimulating hormone receptor alleles in patients with malignant melanoma.

    PubMed

    Strange, R C; Ellison, T; Ichii-Jones, F; Bath, J; Hoban, P; Lear, J T; Smith, A G; Hutchinson, P E; Osborne, J; Bowers, B; Jones, P W; Fryer, A A

    1999-06-01

    We previously identified associations between polymorphism in the cytochrome P450 CYP2D6 gene and outcome in several cancers. We have now examined the hypothesis that homozygosity for the mutant alleles, CYP2D6*4 and CYP2D6*3, is associated with susceptibility and outcome in malignant melanoma. Outcome was assessed by Breslow thickness. We first confirmed previous reports that these mutant alleles are associated with increased susceptibility to malignant melanoma. For example, the frequency of homozygosity for CYP2D6*4 was significantly greater (P = 0.006, chi-squared 1 d.f. = 7.4, odds ratio 2.2, 95% confidence interval 1.2, 3.9) in cases (9.1%) than in control individuals (4.3%). The frequency of homozygosity for the mutant alleles was next examined in the malignant melanoma cases grouped on the basis of characteristics associated with malignant melanoma risk. Homozygosity was significantly more common (P = 0.038) in cases with red/blonde hair than in those with brown/black hair. We found no associations between the CYP2D6 genotype and sex, skin type or eye colour. The possible association of CYP2D6 with outcome was assessed by comparing genotype frequencies in patients with tumours of Breslow thickness < 1.5 mm with those whose tumours were > or = 1.5 mm. In patients with red/blonde, but not brown or black hair, homozygosity for CYP2D6*4 was significantly associated with thicker lesions in a multivariate model (P = 0.036). We further examined the association of CYP2D6*4 homozygosity with red/blonde hair by classifying patients on the basis of homo- or heterozygosity for wild-type or val92met, asp294his or asp84glu melanocyte stimulating hormone receptor (MC1R) alleles. None of the nine patients with brown/black hair with the asp294his allele were homozygotes for CYP2D6*4. By contrast, in the patients with red/blonde hair, three of five cases with asp294his were homozygotes for the mutant CYP2D6 allele. The difference in the frequency of CYP2D6*4 homozygotes in

  12. Allele Workbench: transcriptome pipeline and interactive graphics for allele-specific expression.

    PubMed

    Soderlund, Carol A; Nelson, William M; Goff, Stephen A

    2014-01-01

    Sequencing the transcriptome can answer various questions such as determining the transcripts expressed in a given species for a specific tissue or condition, evaluating differential expression, discovering variants, and evaluating allele-specific expression. Differential expression evaluates the expression differences between different strains, tissues, and conditions. Allele-specific expression evaluates expression differences between parental alleles. Both differential expression and allele-specific expression have been studied for heterosis (hybrid vigor), where the hybrid has improved performance over the parents for one or more traits. The Allele Workbench software was developed for a heterosis study that evaluated allele-specific expression for a mouse F1 hybrid using libraries from multiple tissues with biological replicates. This software has been made into a distributable package, which includes a pipeline, a Java interface to build the database, and a Java interface for query and display of the results. The required input is a reference genome, annotation file, and one or more RNA-Seq libraries with optional replicates. It evaluates allelic imbalance at the SNP and transcript level and flags transcripts with significant opposite directional allele-specific expression. The Java interface allows the user to view data from libraries, replicates, genes, transcripts, exons, and variants, including queries on allele imbalance for selected libraries. To determine the impact of allele-specific SNPs on protein folding, variants are annotated with their effect (e.g., missense), and the parental protein sequences may be exported for protein folding analysis. The Allele Workbench processing results in transcript files and read counts that can be used as input to the previously published Transcriptome Computational Workbench, which has a new algorithm for determining a trimmed set of gene ontology terms. The software with demo files is available from https://code.google.com/p/allele

  13. Ten novel HLA-DRB1 alleles and one novel DRB3 allele.

    PubMed

    Lazaro, A M; Steiner, N K; Moraes, M E; Moraes, J R; Ng, J; Hartzman, R J; Hurley, C K

    2005-10-01

    Ten novel HLA-DRB1 and one DRB3 alleles are described. Eight of the variants are single-nucleotide substitutions, four resulting in an amino acid change (DRB1*1145, *1148, *0828 and *1514) and four with silent substitutions (DRB1*040504, *130103, *160502 and DRB3*020204). Two alleles differ by two nucleotide changes altering one (DRB1*1447 and *1361) amino acid and one allele alters three nucleotides and two amino acids.

  14. Abnormal segregation of alleles in CEPH pedigree DNAs arising from allele loss in lymphoblastoid DNA

    SciTech Connect

    Royle, N.J.; Armour, J.A.L.; Crosier, M.; Jeffreys, A.J. )

    1993-01-01

    Somatic events that result in the reduction to hemior homozygosity at all loci affected by the event have been identified in lymphoblastoid DNA from mothers of two CEPH families. Using suitably informative probes, the allele deficiencies were detected by the abnormal transmission of alleles from grandparents to grandchildren, with the apparent absence of the alleles from the parent. Undetected somatic deficiencies in family DNAs could result in misscoring of recombination events and consequently introduce errors into linkage analysis. 15 refs., 2 figs.

  15. Synthesis and characterization of a porphyrazine–Gd(III) MRI contrast agent and in vivo imaging of a breast cancer xenograft model

    PubMed Central

    Trivedi, Evan R.; Ma, Zhidong; Waters, Emily A.; Macrenaris, Keith W.; Subramanian, Rohit; Barrettf, Anthony G. M.; Meade, Thomas J.; Hoffman, Brian M.

    2015-01-01

    Porphyrazines (Pz), or tetraazaporphyrins, are being studied for their potential use in detection and treatment of cancer. Here, an amphiphilic Cu–Pz–Gd(III) conjugate has been prepared via azide-alkyne Huisgen cycloaddition or ‘click’ chemistry between an azide functionalized Pz and alkyne functionalized DOTA–Gd(III) analog for use as an MRI contrast agent. This agent, Cu–Pz–Gd(III), is synthesized in good yield and exhibits solution-phase ionic relaxivity (r1 = 11.5 mm−1 s−1) that is approximately four times higher than that of a clinically used monomeric Gd (III) contrast agent, DOTA–Gd(III). Breast tumor cells (MDA-MB-231) associate with Cu–Pz–Gd(III) in vitro, where significant contrast enhancement (9.336 ± 0.335 contrast-to-noise ratio) is observed in phantom cell pellet MR images. This novel contrast agent was administered in vivo to an orthotopic breast tumor model in athymic nude mice and MR images were collected. The average T1 of tumor regions in mice treated with 50 mg kg−1 Cu–Pz–Gd (III) decreased relative to saline-treated controls. Furthermore, the decrease in T1 was persistent relative to mice treated with the monomeric Gd(III) contrast agent. An ex vivo biodistribution study confirmed that Cu–Pz–Gd(III) accumulates in the tumors and is rapidly cleared, primarily through the kidneys. Differential accumulation and T1 enhancement by Cu–Pz–Gd(III) in the tumor's core relative to the periphery offer preliminary evidence that this agent would find application in the imaging of necrotic tissue. PMID:24706615

  16. Ten Novel HLA-DRB1 Alleles and One Novel DRB3 Allele

    DTIC Science & Technology

    2006-05-31

    BRIEF COMMUNICATION Ten novel HLA-DRB1 alleles and one novel DRB3 allele A. M. Lazaro1, N. K. Steiner1, M. E. Moraes2, J. R. Moraes2, J. Ng1, R. J...accepted for publication 31 May 2005 doi: 10.1111/j.1399-0039.2005.00459.x Abstract Ten novel HLA-DRB1 and one DRB3 alleles are described. Eight of the...substitutions (DRB1*040504, *130103, *160502 and DRB3 *020204). Two alleles differ by two nucleotide changes altering one (DRB1*1447 and *1361) amino acid and

  17. Longitudinal multilevel models of the big-fish-little-pond effect on academic self-concept: counterbalancing contrast and reflected-glory effects in Hong Kong schools.

    PubMed

    Marsh, H W; Kong, C K; Hau, K T

    2000-02-01

    Longitudinal multilevel path models (7,997 students, 44 high schools, 4 years) evaluated effects of school-average achievement and perceived school status on academic self-concept in Hong Kong, which has a collectivist culture with a highly achievement-segregated high school system. Consistent with a priori predictions based on the big-fish-little-pond effect (BFLPE), higher school-average achievements led to lower academic self-concepts (contrast effect), whereas higher perceived school status had a counterbalancing positive effect on self-concept (reflected-glory, assimilation effect). The negative BFLPE is the net effect of counterbalancing influences, stronger negative contrast effects, and weaker positive assimilation effects so that controlling perceived school status led to purer--and even more negative--contrast effects. Attending a school where school-average achievement is high simultaneously resulted in a more demanding basis of comparison for one's own accomplishments (the stronger negative contrast effect) and a source of pride (the weaker positive assimilation effect).

  18. An automated serial Grinding, Imaging and Reconstruction Instrument (GIRI) for digital modeling of samples with weak density contrasts

    NASA Astrophysics Data System (ADS)

    Maloof, A. C.; Samuels, B.; Mehra, A.; Spatzier, A.

    2013-12-01

    We present the first results from the new Princeton University Grinder Lab dedicated to the digital reconstruction of hidden objects through serial grinding and imaging. The purpose of a destructive technique like serial grinding is to facilitate the discovery of embedded objects with weak density contrasts outside the sensitivity limits of X-ray CT-scanning devices (Feature segmentation and object reconstruction are based on color and textural contrasts in the stack of images rather than density). The device we have developed is a retrofit imaging station designed for a precision CNC surface. The instrument is capable of processing a sample 20x25x40 cm in size at 1 micron resolution in x, y and z axes. Directly coupled to the vertical axis of the grinder is an 80 megapixel medium format camera and specialty macro lens capable of imaging a 4x5 cm surface at 5 micron resolution in full 16 bit color. The system is automated such that after each surface grind, the sample is cleaned, travels to the opposite end of the bed from the grinder wheel, is photographed, and then moved back to the grinding position. This process establishes a comprehensive archive of the specimen that is used for digital reconstruction and quantitative analysis. For example, in one night, a 7 cm thick sample can be imaged completely at 20 micron horizontal and vertical resolution without human supervision. Some of the initial results we present here include new digital reconstructions of early animal fossils, 3D sedimentary bedforms, the size and shape distribution of chondrules in chondritic meteorites, and the porosity structure of carbonate cemented reservoir rocks.

  19. Magnetization transfer contrast imaging detects early white matter changes in the APP/PS1 amyloidosis mouse model.

    PubMed

    Praet, Jelle; Bigot, Christian; Orije, Jasmien; Naeyaert, Maarten; Shah, Disha; Mai, Zhenhua; Guns, Pieter-Jan; Van der Linden, Annemie; Verhoye, Marleen

    While no definitive cure for Alzheimer's disease exists yet, currently available treatments would benefit greatly from an earlier diagnosis. It has previously been shown that Magnetization transfer contrast (MTC) imaging is able to detect amyloid β plaques in old APP/PS1 mice. In the current study we investigated if MTC is also able to visualize early amyloid β (Aβ) induced pathological changes. In a cross-sectional study, a comparison was made between the MT ratio of wild type (WT) and APP/PS1 mice at 2, 4, 6, 8 and 24 months of age. We observed an increased MT-ratio in the cortex of 24 month old APP/PS1 mice as compared to WT mice. However, when comparing the MT-ratio of the cortex of WT mice with the MT-ratio of the APP/PS1 mice at 2, 4, 6 or 8 months of age, no significant changes could be observed. In contrast to the cortex, we consistently observed a decreased MT-ratio in the splenium of 4, 6 and 8 month old APP/PS1 mice as compared to age-matched WT mice. Lastly, the decreased MT-ratio in the splenium of APP/PS1 mice correlated to the Aβ plaque deposition, astrogliosis and microgliosis. This MT-ratio decrease did however not correlate to the myelin content. Combined, our results suggest that MTC is able to visualize early Aβ-induced changes in the splenium but not the cortex of APP/PS1 mice.

  20. A PP2C-1 Allele Underlying a Quantitative Trait Locus Enhances Soybean 100-Seed Weight.

    PubMed

    Lu, Xiang; Xiong, Qing; Cheng, Tong; Li, Qing-Tian; Liu, Xin-Lei; Bi, Ying-Dong; Li, Wei; Zhang, Wan-Ke; Ma, Biao; Lai, Yong-Cai; Du, Wei-Guang; Man, Wei-Qun; Chen, Shou-Yi; Zhang, Jin-Song

    2017-03-28

    Cultivated soybeans may lose some useful genetic locus during domestication. Introgression of genes from wild soybeans may broaden the genetic background and improve soybean agronomic traits. Here, through whole-genome sequencing of an RIL population derived from a cross between a wild soybean ZYD7 and a cultivated soybean HN44, and mapping of QTLs for seed weight, we discover that a phosphatase 2C-1 (PP2C-1) allele from wild soybean ZYD7 contributes to the increase of seed weight/size in transgenic plants. The PP2C-1 may achieve this function by enhancing cell size of integument and activating a subset of seed trait-related genes. The PP2C-1 was further found to associate with a transcription factor GmBZR1 and facilitate accumulation of dephosphorylated GmBZR1. In contrast, a PP2C-2 allele with variations of a few amino acids at N-terminus does not exhibit this function. Moreover, the GmBZR1 can promote seed weight/size in transgenic plants. Through analysis of cultivated soybean accessions, we find that 40% of the examined accessions do not have the PP2C-1 allele, suggesting that these accessions can be improved through introduction of the PP2C-1 allele. Our study identifies an elite allele PP2C-1, which can enhance seed weight/size. Manipulation of the allele by molecule-assisted breeding may increase production in soybean and other legumes/crops.

  1. AlleleSeq: analysis of allele-specific expression and binding in a network framework.

    PubMed

    Rozowsky, Joel; Abyzov, Alexej; Wang, Jing; Alves, Pedro; Raha, Debasish; Harmanci, Arif; Leng, Jing; Bjornson, Robert; Kong, Yong; Kitabayashi, Naoki; Bhardwaj, Nitin; Rubin, Mark; Snyder, Michael; Gerstein, Mark

    2011-08-02

    To study allele-specific expression (ASE) and binding (ASB), that is, differences between the maternally and paternally derived alleles, we have developed a computational pipeline (AlleleSeq). Our pipeline initially constructs a diploid personal genome sequence (and corresponding personalized gene annotation) using genomic sequence variants (SNPs, indels, and structural variants), and then identifies allele-specific events with significant differences in the number of mapped reads between maternal and paternal alleles. There are many technical challenges in the construction and alignment of reads to a personal diploid genome sequence that we address, for example, bias of reads mapping to the reference allele. We have applied AlleleSeq to variation data for NA12878 from the 1000 Genomes Project as well as matched, deeply sequenced RNA-Seq and ChIP-Seq data sets generated for this purpose. In addition to observing fairly widespread allele-specific behavior within individual functional genomic data sets (including results consistent with X-chromosome inactivation), we can study the interaction between ASE and ASB. Furthermore, we investigate the coordination between ASE and ASB from multiple transcription factors events using a regulatory network framework. Correlation analyses and network motifs show mostly coordinated ASB and ASE.

  2. Mutant power: using mutant allele collections for yeast functional genomics.

    PubMed

    Norman, Kaitlyn L; Kumar, Anuj

    2016-03-01

    The budding yeast has long served as a model eukaryote for the functional genomic analysis of highly conserved signaling pathways, cellular processes and mechanisms underlying human disease. The collection of reagents available for genomics in yeast is extensive, encompassing a growing diversity of mutant collections beyond gene deletion sets in the standard wild-type S288C genetic background. We review here three main types of mutant allele collections: transposon mutagen collections, essential gene collections and overexpression libraries. Each collection provides unique and identifiable alleles that can be utilized in genome-wide, high-throughput studies. These genomic reagents are particularly informative in identifying synthetic phenotypes and functions associated with essential genes, including those modeled most effectively in complex genetic backgrounds. Several examples of genomic studies in filamentous/pseudohyphal backgrounds are provided here to illustrate this point. Additionally, the limitations of each approach are examined. Collectively, these mutant allele collections in Saccharomyces cerevisiae and the related pathogenic yeast Candida albicans promise insights toward an advanced understanding of eukaryotic molecular and cellular biology.

  3. Molecular Imaging of Vasa Vasorum Neovascularization via DEspR-targeted Contrast-enhanced Ultrasound Micro-imaging in Transgenic Atherosclerosis Rat Model

    PubMed Central

    Decano, Julius L.; Moran, Anne Marie; Ruiz-Opazo, Nelson; Herrera, Victoria L. M.

    2011-01-01

    Purpose Given that carotid vasa vasorum neovascularization is associated with increased risk for stroke and cardiac events, the present in vivo study was designed to investigate molecular imaging of carotid artery vasa vasorum neovascularization via target-specific contrast-enhanced ultrasound (CEU) micro-imaging. Procedures Molecular imaging was performed in male transgenic rats with carotid artery disease and non-transgenic controls using dual endothelin1/VEGFsp receptor (DEspR)-targeted microbubbles (MBD) and the Vevo770 micro-imaging system and CEU imaging software. Results DEspR-targeted CEU-positive imaging exhibited significantly higher contrast intensity signal (CIS)-levels and pre-/post-destruction CIS-differences in seven of 13 transgenic rats, in contrast to significantly lower CIS-levels and differences in control isotype-targeted microbubble (MBC)-CEU imaging (n =8) and in MBD CEU-imaging of five non-transgenic control rats (P<0.0001). Ex vivo immunofluorescence analysis demonstrated binding of MBD to DEspR-positive endothelial cells; and association of DEspR-targeted increased contrast intensity signals with DEspR expression in vasa vasorum neovessel and intimal lesions. In vitro analysis demonstrated dose-dependent binding of MBD to DEspR-positive human endothelial cells with increasing %cells bound and number of MBD per cell, in contrast to MBC or non-labeled microbubbles (P<0.0001). Conclusion In vivo DEspR-targeted molecular imaging detected increased DEspR-expression in carotid artery lesions and in expanded vasa vasorum neovessels in transgenic rats with carotid artery disease. Future studies are needed to determine predictive value for stroke or heart disease in this transgenic atherosclerosis rat model and translational applications. PMID:20972637

  4. Magnetization Transfer Imaging of Rat Brain under Non-steady-state Conditions. Contrast Prediction Using a Binary Spin-Bath Model and a Super-Lorentzian Lineshape

    NASA Astrophysics Data System (ADS)

    Quesson, Bruno; Thiaudière, Eric; Delalande, Christophe; Chateil, Jean-Francois; Moonen, Chrit T. W.; Canioni, Paul

    1998-02-01

    Magnetization transfer contrast imaging using turbo spin echo and continuous wave off-resonance irradiation was carried out on rat brainin vivoat 4.7 T. By systematically varying the off-resonance irradiation power and the offset-frequency, the signal intensities obtained under steady-state for both transverse and longitudinal magnetization were successfully analyzed with a simple binary spin-bath model taking into account a free water compartment and a pool of protons with restricted motions bearing a super-Lorentzian lineshape. Due to important RF power deposition, such experimental conditions are not practical for routine imaging on humans. An extension of the model was derived to describe the system for shorter off-resonance pulse duration, i.e., when the longitudinal magnetization of the free protons has not reached a steady-state. Data sets obtained for three regions of interest, namely thecorpus callosum,the basal ganglia, and the temporal lobe, were correctly interpreted for off-resonance pulse durations varying from 0.3 to 3 s. The parameter sets obtained from the calculations made it possible to predict the contrast between the different regions as a function of the pulse power, the offset frequency, and pulse duration. Such an approach could be extended to contrast prediction for human brain at 1.5 T.

  5. Forensic Loci Allele Database (FLAD): Automatically generated, permanent identifiers for sequenced forensic alleles.

    PubMed

    Van Neste, Christophe; Van Criekinge, Wim; Deforce, Dieter; Van Nieuwerburgh, Filip

    2016-01-01

    It is difficult to predict if and when massively parallel sequencing of forensic STR loci will replace capillary electrophoresis as the new standard technology in forensic genetics. The main benefits of sequencing are increased multiplexing scales and SNP detection. There is not yet a consensus on how sequenced profiles should be reported. We present the Forensic Loci Allele Database (FLAD) service, made freely available on http://forensic.ugent.be/FLAD/. It offers permanent identifiers for sequenced forensic alleles (STR or SNP) and their microvariants for use in forensic allele nomenclature. Analogous to Genbank, its aim is to provide permanent identifiers for forensically relevant allele sequences. Researchers that are developing forensic sequencing kits or are performing population studies, can register on http://forensic.ugent.be/FLAD/ and add loci and allele sequences with a short and simple application interface (API).

  6. Temperature dependence of evolutionary diversification: differences between two contrasting model taxa support the metabolic theory of ecology.

    PubMed

    Machac, A; Zrzavý, J; Smrckova, J; Storch, D

    2012-12-01

    Biodiversity patterns are largely determined by variation of diversification rates across clades and geographic regions. Although there are multiple reasons for this variation, it has been hypothesized that metabolic rate is the crucial driver of diversification of evolutionary lineages. According to the metabolic theory of ecology (MTE), metabolic rate - and consequently speciation - is driven mainly by body size and environmental temperature. As environmental temperature affects metabolic rate in ecto- and endotherms differently, its impact on diversification rate should also differ between the two types of organisms. Employing two independent approaches, we analysed correlates of speciation rates and, ultimately, net diversification rates for two contrasting taxa: plethodontid salamanders and carnivoran mammals. Whereas in the ectothermic plethodontids speciation rates positively correlated with environmental temperature, in the endothermic carnivorans a reverse, negative correlation was detected. These findings comply with predictions of the MTE and suggest that similar geographic patterns of biodiversity across taxa (e.g. ecto- and endotherms) might have been generated by different ecological and evolutionary processes.

  7. Multi-planar dynamic contrast-enhanced ultrasound assessment of blood flow in a rabbit model of testicular torsion.

    PubMed

    Paltiel, Harriet J; Estrada, Carlos R; Alomari, Ahmad I; Stamoulis, Catherine; Passerotti, Carlo C; Meral, F Can; Lee, Richard S; Clement, Gregory T

    2014-02-01

    To assess correlation between multi-planar, dynamic contrast-enhanced ultrasound (US) blood flow measurements and radiolabeled microsphere blood flow measurements, five groups of six rabbits underwent unilateral testicular torsion of 0°, 180°, 360°, 540° or 720°. Five US measurements per testis (three transverse/two longitudinal) were obtained pre-operatively and immediately and 4 and 8 h post-operatively using linear transducers (7-4 MHz/center frequency 4.5 MHz/10 rabbits; 9-3 MHz/center frequency 5.5 MHz/20 rabbits). Björck's linear least-squares method fit the rise phase of mean pixel intensity over a 7-s period for each time curve. Slope of fit and intervention/control US pixel intensity ratios were calculated. Means of transverse, longitudinal and combined transverse/longitudinal US ratios as a function of torsion degree were compared with radiolabeled microsphere ratios using Pearson's correlation coefficient, ρ. There was high correlation between the two sets of ratios (ρ ≥ 0.88, p ≤ 0.05), except for the transverse US ratio in the immediate post-operative period (ρ = 0.79, p = 0.11). These results hold promise for future clinical applications.

  8. Multiplanar Dynamic Contrast-enhanced US Assessment of Blood Flow in a Rabbit Model of Testicular Torsion

    PubMed Central

    Paltiel, Harriet J.; Estrada, Carlos R.; Alomari, Ahmad I.; Stamoulis, Catherine; Passerotti, Carlo C.; Meral, F. Can; Lee, Richard S.; Clement, Gregory T.

    2013-01-01

    To assess correlation between multiplanar, dynamic contrast-enhanced US blood flow measurements and radiolabeled microsphere blood flow measurements, five groups of 6 rabbits underwent unilateral testicular torsion of 0, 180, 360, 540, or 720 degrees. Five US measurements per testis (3 transverse/2 longitudinal) were obtained preoperatively, immediately postoperatively, at 4 and 8 hours using linear transducers (7–4-MHz/center frequency 4.5 MHz/10 rabbits; 9–3-MHz/center frequency 5.5 MHz/20 rabbits). Björck’s linear least squares method fit the rise phase of mean pixel intensity over a 7-second period for each time curve. Slope of fit and intervention/control US pixel intensity ratios were calculated. Means of transverse, longitudinal, and combined transverse/longitudinal US ratios as a function of torsion degree were compared to radiolabeled microsphere ratios using Pearson’s correlation coefficient, ρ. There was high correlation between the two sets of ratios (ρ ≥ 0.88, p≤ 0.05) except for the transverse US ratio in the immediate postoperative period (ρ = 0.79, p = 0.11). These results hold promise for future clinical applications. PMID:24188690

  9. Assessment of a model of forest dynamics under contrasting climate and disturbance regimes in the Pacific Northwest [FORCLIM

    USGS Publications Warehouse

    Busing, Richard T.; Solomon, Allen M.

    2005-01-01

    An individual-based model of forest dynamics (FORCLIM) was tested for its ability to simulate forest composition and structure in the Pacific Northwest region of North America. Simulation results across gradients of climate and disturbance were compared to forest survey data from several vegetation zones in western Oregon. Modelled patterns of tree species composition, total basal area and stand height across climate gradients matched those in the forest survey data. However, the density of small stems (<50 cm DBH) was underestimated by the model. Thus actual size-class structure and other density-based parameters of stand structure were not simulated with high accuracy. The addition of partial-stand disturbances at moderate frequencies (<0.01 yr-1) often improved agreement between simulated and actual results. Strengths and weaknesses of the FORCLIM model in simulating forest dynamics and structure in the Pacific Northwest are discussed.

  10. Dual-input two-compartment pharmacokinetic model of dynamic contrast-enhanced magnetic resonance imaging in hepatocellular carcinoma

    PubMed Central

    Yang, Jian-Feng; Zhao, Zhen-Hua; Zhang, Yu; Zhao, Li; Yang, Li-Ming; Zhang, Min-Ming; Wang, Bo-Yin; Wang, Ting; Lu, Bao-Chun

    2016-01-01

    AIM: To investigate the feasibility of a dual-input two-compartment tracer kinetic model for evaluating tumorous microvascular properties in advanced hepatocellular carcinoma (HCC). METHODS: From January 2014 to April 2015, we prospectively measured and analyzed pharmacokinetic parameters [transfer constant (Ktrans), plasma flow (Fp), permeability surface area product (PS), efflux rate constant (kep), extravascular extracellular space volume ratio (ve), blood plasma volume ratio (vp), and hepatic perfusion index (HPI)] using dual-input two-compartment tracer kinetic models [a dual-input extended Tofts model and a dual-input 2-compartment exchange model (2CXM)] in 28 consecutive HCC patients. A well-known consensus that HCC is a hypervascular tumor supplied by the hepatic artery and the portal vein was used as a reference standard. A paired Student’s t-test and a nonparametric paired Wilcoxon rank sum test were used to compare the equivalent pharmacokinetic parameters derived from the two models, and Pearson correlation analysis was also applied to observe the correlations among all equivalent parameters. The tumor size and pharmacokinetic parameters were tested by Pearson correlation analysis, while correlations among stage, tumor size and all pharmacokinetic parameters were assessed by Spearman correlation analysis. RESULTS: The Fp value was greater than the PS value (FP = 1.07 mL/mL per minute, PS = 0.19 mL/mL per minute) in the dual-input 2CXM; HPI was 0.66 and 0.63 in the dual-input extended Tofts model and the dual-input 2CXM, respectively. There were no significant differences in the kep, vp, or HPI between the dual-input extended Tofts model and the dual-input 2CXM (P = 0.524, 0.569, and 0.622, respectively). All equivalent pharmacokinetic parameters, except for ve, were correlated in the two dual-input two-compartment pharmacokinetic models; both Fp and PS in the dual-input 2CXM were correlated with Ktrans derived from the dual-input extended Tofts model

  11. Poor Transferability of Species Distribution Models for a Pelagic Predator, the Grey Petrel, Indicates Contrasting Habitat Preferences across Ocean Basins

    PubMed Central

    Torres, Leigh G.; Sutton, Philip J. H.; Thompson, David R.; Delord, Karine; Weimerskirch, Henri; Sagar, Paul M.; Sommer, Erica; Dilley, Ben J.; Ryan, Peter G.; Phillips, Richard A.

    2015-01-01

    Species distribution models (SDMs) are increasingly applied in conservation management to predict suitable habitat for poorly known populations. High predictive performance of SDMs is evident in validations performed within the model calibration area (interpolation), but few studies have assessed SDM transferability to novel areas (extrapolation), particularly across large spatial scales or pelagic ecosystems. We performed rigorous SDM validation tests on distribution data from three populations of a long-ranging marine predator, the grey petrel Procellaria cinerea, to assess model transferability across the Southern Hemisphere (25-65°S). Oceanographic data were combined with tracks of grey petrels from two remote sub-Antarctic islands (Antipodes and Kerguelen) using boosted regression trees to generate three SDMs: one for each island population, and a combined model. The predictive performance of these models was assessed using withheld tracking data from within the model calibration areas (interpolation), and from a third population, Marion Island (extrapolation). Predictive performance was assessed using k-fold cross validation and point biserial correlation. The two population-specific SDMs included the same predictor variables and suggested birds responded to the same broad-scale oceanographic influences. However, all model validation tests, including of the combined model, determined strong interpolation but weak extrapolation capabilities. These results indicate that habitat use reflects both its availability and bird preferences, such that the realized distribution patterns differ for each population. The spatial predictions by the three SDMs were compared with tracking data and fishing effort to demonstrate the conservation pitfalls of extrapolating SDMs outside calibration regions. This exercise revealed that SDM predictions would have led to an underestimate of overlap with fishing effort and potentially misinformed bycatch mitigation efforts. Although

  12. Association of the HLA-B*52 allele with non-progression to AIDS in Brazilian HIV-1-infected individuals.

    PubMed

    Teixeira, S L M; de Sá, N B R; Campos, D P; Coelho, A B; Guimarães, M L; Leite, T C N F; Veloso, V G; Morgado, M G

    2014-04-01

    Several human leukocyte antigen (HLA) class I alleles are associated with the susceptibility to human immunodeficiency virus-1 (HIV-1) infection and/or AIDS progression. Of these, the HLA-B alleles are considered the strongest genetic determinant of disease outcome. We evaluated the influence of the HLA-B alleles on AIDS progression among HIV-1-positive individuals from Rio de Janeiro, Brazil, who were categorized as rapid progressors (RPs), typical progressors (TPs) or long-term non-progressors (LTNPs). In this study, significant differences in HLA-B allele frequencies were observed among the three progression groups for the B*48, B*49 and B*52 alleles. After controlling for other factors associated with AIDS progression, the presence of the B*52 allele was shown to be a significant protective factor (hazard ratio (HR) 0.49 (95% confidence interval (CI) 0.27-0.90) P<0.03). Although no direct association was observed between the presence of the B*27 or B*57 allele and the LTNP profile compared with the TP or RP groups, the adjusted model confirmed that these alleles are protective factors against AIDS progression (HR 0.62 (95% CI 0.38-0.99) P<0.05), as previously described. These data corroborate the existence of significant differences in HLA-B allele frequencies among the distinct AIDS progression profiles and further elucidate the role of HLA alleles in the outcome of HIV infections in diverse populations.

  13. Dealing with allelic dropout when reporting the evidential value in DNA relatedness analysis.

    PubMed

    Buckleton, John; Triggs, Chris

    2006-07-13

    A method is suggested that allows the use of loci that have shown allelic dropout in kinship analysis as used for disaster victim identification (DVI) and missing person work (MP). This approach uses an extension of a previously published approach to modelling allelic dropout. This method may salvage some information in cases where allelic dropout is hindering DVI or MP work particularly in reconciliations involving a large number of bodies and pedigrees. It should not replace the pursuit of more complete DNA profiles by the normal rework process for such samples.

  14. Contrasting determinants for the introduction and establishment success of exotic birds in Taiwan using decision trees models

    PubMed Central

    Liang, Shih-Hsiung; Walther, Bruno Andreas

    2017-01-01

    Background Biological invasions have become a major threat to biodiversity, and identifying determinants underlying success at different stages of the invasion process is essential for both prevention management and testing ecological theories. To investigate variables associated with different stages of the invasion process in a local region such as Taiwan, potential problems using traditional parametric analyses include too many variables of different data types (nominal, ordinal, and interval) and a relatively small data set with too many missing values. Methods We therefore used five decision tree models instead and compared their performance. Our dataset contains 283 exotic bird species which were transported to Taiwan; of these 283 species, 95 species escaped to the field successfully (introduction success); of these 95 introduced species, 36 species reproduced in the field of Taiwan successfully (establishment success). For each species, we collected 22 variables associated with human selectivity and species traits which may determine success during the introduction stage and establishment stage. For each decision tree model, we performed three variable treatments: (I) including all 22 variables, (II) excluding nominal variables, and (III) excluding nominal variables and replacing ordinal values with binary ones. Five performance measures were used to compare models, namely, area under the receiver operating characteristic curve (AUROC), specificity, precision, recall, and accuracy. Results The gradient boosting models performed best overall among the five decision tree models for both introduction and establishment success and across variable treatments. The most important variables for predicting introduction success were the bird family, the number of invaded countries, and variables associated with environmental adaptation, whereas the most important variables for predicting establishment success were the number of invaded countries and variables

  15. Conditional Allele Mouse Planner (CAMP): software to facilitate the planning and design of breeding strategies involving mice with conditional alleles.

    PubMed

    Hoffert, Jason D; Pisitkun, Trairak; Miller, R Lance

    2012-06-01

    Transgenic and conditional knockout mouse models play an important role in biomedical research and their use has grown exponentially in the last 5-10 years. Generating conditional knockouts often requires breeding multiple alleles onto the background of a single mouse or group of mice. Breeding these mice depends on parental genotype, litter size, transmission frequency, and the number of breeding rounds. Therefore, a well planned breeding strategy is critical for keeping costs to a minimum. However, designing a viable breeding strategy can be challenging. With so many different variables this would be an ideal task for a computer program. To facilitate this process, we created a Java-based program called Conditional Allele Mouse Planner (CAMP). CAMP is designed to provide an estimate of the number of breeders, amount of time, and costs associated with generating mice of a particular genotype. We provide a description of CAMP, how to use it, and offer it freely as an application.

  16. Recent trends of high-latitude vegetation activity assessed and explained by contrasting modelling approaches with earth observation data

    NASA Astrophysics Data System (ADS)

    Forkel, M.; Carvalhais, N.; Reichstein, M.; Thonicke, K.

    2012-04-01

    Satellite observations of Normalized Difference Vegetation Index (NDVI) showed increasing trends in the arctic tundra and the boreal forests since the 1980s. This greening is related to an increase in photosynthetic activity and is driven by increasing temperatures and a prolongation of the growing season. However, NDVI experienced a decrease in large regions of the boreal forests since the mid-1990s. This browning is related to fire disturbances, temperature-induced summer drought and potentially to insect infestations and diseases. Terrestrial biosphere models (TBM) can be used to assess the impacts of these changes in vegetation productivity on the carbon and water cycles and on the climate system. In general, these models provide descriptions of ecosystem processes and states that are forced by and feedback to the climate system such as photosynthesis and transpiration, ecosystem respiration, soil carbon and water stocks and vegetation composition. The evaluation of TBMs against observations is a necessary step to assess their suitability to simulate such processes and dynamics. The increasing availability of long-term observations of vegetation activity enables us to evaluate the model ability to diagnose these vegetation greening and browning trends in arctic and boreal regions. The first aim of this study is to evaluate trends in vegetation activity in high-latitude regions as simulated by TBMs against observed trends in vegetation activity. The second aim is to identify potential drivers of these observed and simulated trends to evaluate the ability of models to reproduce the observed functional relations between climatic and environmental drivers and the vegetation trends. The trends in vegetation activity were estimated for a set of satellite-based remote sensing products: NDVI from AVHRR (Advanced Very High Resolution Radiometer) and MODIS (Moderate Resolution Imaging Spectrometer), as well as FAPAR observations (Fraction of Observed Photosynthetically

  17. Modelling changes in nitrogen cycling to sustain increases in forest productivity under elevated atmospheric CO2 and contrasting site conditions

    NASA Astrophysics Data System (ADS)

    Grant, R. F.

    2013-04-01

    If increases in net primary productivity (NPP) caused by rising concentrations of atmospheric CO2 (Ca) are to be sustained, key N processes such as soil mineralization, biological fixation, root uptake and plant translocation must be hastened. Simulating the response of these processes to elevated Ca is therefore vital for models used to project the effects of rising Ca on NPP. In this modelling study, hypotheses are proposed for changes in soil mineralization, biological fixation, root uptake and plant translocation with changes in Ca. Algorithms developed from these hypotheses were tested in the ecosystem model ecosys against changes in N and C cycling measured over several years under ambient vs. elevatedCa in Free Air CO2 Enrichment (FACE) experiments at the Duke Forest in North Carolina, the Oak Ridge National Laboratory forest in Tennessee, and the USDA research forest in Wisconsin, USA. Simulating more rapid soil N mineralization was found to be vital for modelling sustained increases in NPP measured under elevated vs. ambient Ca at all three FACE sites. This simulation was accomplished by priming decomposition of N-rich humus from increases in microbial biomass generated by increased litterfall modelled under elevated Ca. Simulating more rapid nonsymbiotic N2 fixation, root N uptake and plant N translocation under elevated Ca was found to make much smaller contributions to modelled increases in NPP, although such contributions might be greater over longer periods and under more N-limited conditions than those simulated here. Greater increases in NPP with Ca were also modelled with increased temperature and water stress, and with coniferous vs. deciduous plant functional types. These increases were also associated with changes in N cycling.

  18. A novel contrast-induced acute kidney injury model based on the 5/6-nephrectomy rat and nephrotoxicological evaluation of iohexol and iodixanol in vivo.

    PubMed

    Liu, Tong-qiang; Luo, Wei-li; Tan, Xiao; Fang, Yi; Chen, Jing; Zhang, Hui; Yu, Xiao-fang; Cai, Jie-ru; Ding, Xiao-qiang

    2014-01-01

    Contrast-induced acute kidney injury (CI-AKI) is a serious complication in patients after administration of iodinated contrast media. Proper animal models of CI-AKI can help understand the mechanisms involved and prevent the disorder. We used the 5/6-nephrectomized (NE) rat to develop a CI-AKI model and to evaluate differences in the toxic effects on the kidney between iohexol and iodixanol. We found that six weeks after ablative surgery was the preferred time to induce CI-AKI. We compared multiple pretreatment plans and found that dehydration for 48 hours before iodixanol (320, 10 mL/kg) administration was optimal to induce CI-AKI in the 5/6 NE rats. Compared with iodixanol, iohexol induced a significantly greater reduction in renal function, severe renal tissue damage, intrarenal hypoxia, and apoptotic tubular cells. Iohexol and iodixanol resulted in similarly marked increases in levels of inflammation and oxidative stress. In summary, the 5/6 NE rat combined with dehydration for 48 hours is a useful pretreatment to establish a novel and reliable CI-AKI model. Iohexol induced more severe CI-AKI than iodixanol in this model.

  19. Ovine MHC class II DRB1 alleles associated with resistance or susceptibility to development of bovine leukemia virus-induced ovine lymphoma.

    PubMed

    Nagaoka, Y; Kabeya, H; Onuma, M; Kasai, N; Okada, K; Aida, Y

    1999-02-15

    For the further characterization of bovine leukemia virus (BLV)-induced leukemogenesis, we investigated the association between polymorphism of ovine leukocyte antigen (OLA)-DRB1 gene and tumor development after infection of sheep with BLV. We infected 28 sheep with BLV and cloned exon 2 of the OLA-DRB1 gene from asymptomatic animals and from animals with lymphoma Sequence analysis revealed that, among 12 healthy sheep without any evidence of tumor, ten (83.3%) carried DRB1 alleles encoding Arg-Lys (RK) at positions beta70/71 as compared with only 6 (37.5%) of the 16 sheep with lymphoma, which suggested that alleles encoding the RK motif might protect against development of tumors after infection by BLV. By contrast, alleles encoding Ser-Arg (SR) at positions beta70/71 were present at a significantly elevated frequency in sheep with lymphoma as compared with the healthy carriers, which indicated that OLA-DRB1 alleles encoding the SR motif might be positively related to susceptibility to tumor development. The two amino acids in these motifs line a pocket that accommodates the side chain of a bound peptide according to a model of the crystal structure of human leukocyte antigen (HLA)-DR1. To analyze immunoreactions of sheep with alleles that encoded RK or SR at beta70/71, we selected sheep with either the RK/SR genotypes or the SR/SR genotypes and immunized them with a mixture of multiple synthetic antigenic peptides that corresponded to T-helper, T-cytotoxic, and B-cell epitopes of the BLV envelope glycoprotein gp51. Two weeks after the last immunization, all of the sheep were challenged with BLV. Sheep with the RK/SR genotype produced neutralizing antibodies against BLV; they eliminated BLV completely within 28 weeks of the BLV challenge, and they gave strong lymphocyte-proliferative responses to the peptides used for immunization. Moreover, such animals did not develop lymphoma. By contrast, sheep with the SR/SR genotype continued to produce BLV throughout the

  20. Novel method for analysis of allele specific expression in triploid Oryzias latipes reveals consistent pattern of allele exclusion.

    PubMed

    Garcia, Tzintzuni I; Matos, Isa; Shen, Yingjia; Pabuwal, Vagmita; Coelho, Maria Manuela; Wakamatsu, Yuko; Schartl, Manfred; Walter, Ronald B

    2014-01-01

    Assessing allele-specific gene expression (ASE) on a large scale continues to be a technically challenging problem. Certain biological phenomena, such as X chromosome inactivation and parental imprinting, affect ASE most drastically by completely shutting down the expression of a whole set of alleles. Other more subtle effects on ASE are likely to be much more complex and dependent on the genetic environment and are perhaps more important to understand since they may be responsible for a significant amount of biological diversity. Tools to assess ASE in a diploid biological system are becoming more reliable. Non-diploid systems are, however, not uncommon. In humans full or partial polyploid states are regularly found in both healthy (meiotic cells, polynucleated cell types) and diseased tissues (trisomies, non-disjunction events, cancerous tissues). In this work we have studied ASE in the medaka fish model system. We have developed a method for determining ASE in polyploid organisms from RNAseq data and we have implemented this method in a software tool set. As a biological model system we have used nuclear transplantation to experimentally produce artificial triploid medaka composed of three different haplomes. We measured ASE in RNA isolated from the livers of two adult, triploid medaka fish that showed a high degree of similarity. The majority of genes examined (82%) shared expression more or less evenly among the three alleles in both triploids. The rest of the genes (18%) displayed a wide range of ASE levels. Interestingly the majority of genes (78%) displayed generally consistent ASE levels in both triploid individuals. A large contingent of these genes had the same allele entirely suppressed in both triploids. When viewed in a chromosomal context, it is revealed that these genes are from large sections of 4 chromosomes and may be indicative of some broad scale suppression of gene expression.

  1. Modeling the Evolution of the Atmospheric Boundary Layer Coupled to the Land Surface for Three Contrasting Nights in CASES-99.

    NASA Astrophysics Data System (ADS)

    Steeneveld, G. J.; van de Wiel, B. J. H.; Holtslag, A. A. M.

    2006-03-01

    The modeling and prediction of the stable boundary layer over land is a persistent, problematic feature in weather, climate, and air quality topics. Here, the performance of a state-of-the-art single-column boundary layer model is evaluated with observations from the 1999 Cooperative Atmosphere Surface Exchange Study (CASES-99) field experiment. Very high model resolution in the atmosphere and the soil is utilized to represent three different stable boundary layer archetypes, namely, a fully turbulent night, an intermittently turbulent night, and a radiative night with hardly any turbulence (all at clear skies). Each archetype represents a different class of atmospheric stability. In the current model, the atmosphere is fully coupled to a vegetation layer and the underlying soil. In addition, stability functions (local scaling) are utilized based on in situ observations.Overall it is found that the vertical structure, the surface fluxes (apart from the intermittent character) and the surface temperature in the stable boundary layer can be satisfactorily modeled for a broad stability range (at a local scale) with the current understanding of the physics of the stable boundary layer. This can also be achieved by the use of a rather detailed coupling between the atmosphere and the underlying soil and vegetation, together with high resolution in both the atmosphere and the soil. This is especially true for the very stable nights, when longwave radiative cooling is dominant. Both model outcome and observations show that in the latter case the soil heat flux is a dominant term of the surface energy budget.


  2. A "successful allele" at Campylobacter jejuni contingency locus Cj0170 regulates motility; "successful alleles" at locus Cj0045 are strongly associated with mouse colonization.

    PubMed

    Artymovich, Katherine; Kim, Joo-Sung; Linz, John E; Hall, David F; Kelley, Lauren E; Kalbach, Harrison L; Kathariou, Sophia; Gaymer, Jean; Paschke, Brenda

    2013-06-01

    Campylobacter jejuni is an important foodborne pathogen of humans and its primary reservoir is the gastrointestinal (GI) tract of chickens. Our previous studies demonstrated that phase variation to specific "successful alleles" at C. jejuni contingency loci Cj0045 (successful alleles carry 9G or 10G homopolymeric tracts) and Cj0170 (successful allele carries a 10G homopolymeric tract) in C. jejuni populations is strongly associated with colonization and enteritis in C57BL/6 IL-10 deficient mice. In the current study, we strengthened the association between locus Cj0170, Cj0045, and mouse colonization. We generated 8 independent strains derived from C. jejuni 11168 strain KanR4 that carried a Cj0170 gene disruption and these were all non motile. Two randomly chosen strains with the Cj0170 gene disruption (DM0170-2 and DM0170-6) were gavaged into mice. DM0170-2 and DM0170-6 failed to colonize mice while the control strain that carried a "successful"Cj0170 10G allele was motile and did colonize mice. In parallel studies, when we inoculated C. jejuni strain 33292 into mice, the "unsuccessful"Cj0045 11G allele experienced phase variation to "successful" 9G and 10G alleles in 2 independent experiments prior to d4 post inoculation in mice while the "successful" 9G allele in the control strain remained stable through d21 post inoculation or shifted to other successful alleles. These data confirm that locus Cj0170 regulates motility in C. jejuni strain KanR4 and is a virulence factor in the mouse model. The data also support a possible role of locus Cj0045 as a virulence factor in strain 33292 in infection of mice.

  3. Quantitative Myocardial Perfusion with Dynamic Contrast-Enhanced Imaging in MRI and CT: Theoretical Models and Current Implementation

    PubMed Central

    Handayani, A.; Dijkstra, H.; Prakken, N. H. J.; Slart, R. H. J. A.; Oudkerk, M.; Van Ooijen, P. M. A.; Vliegenthart, R.; Sijens, P. E.

    2016-01-01

    Technological advances in magnetic resonance imaging (MRI) and computed tomography (CT), including higher spatial and temporal resolution, have made the prospect of performing absolute myocardial perfusion quantification possible, previously only achievable with positron emission tomography (PET). This could facilitate integration of myocardial perfusion biomarkers into the current workup for coronary artery disease (CAD), as MRI and CT systems are more widely available than PET scanners. Cardiac PET scanning remains expensive and is restricted by the requirement of a nearby cyclotron. Clinical evidence is needed to demonstrate that MRI and CT have similar accuracy for myocardial perfusion quantification as PET. However, lack of standardization of acquisition protocols and tracer kinetic model selection complicates comparison between different studies and modalities. The aim of this overview is to provide insight into the different tracer kinetic models for quantitative myocardial perfusion analysis and to address typical implementation issues in MRI and CT. We compare different models based on their theoretical derivations and present the respective consequences for MRI and CT acquisition parameters, highlighting the interplay between tracer kinetic modeling and acquisition settings. PMID:27088083

  4. Speeded Classification in a Probabilistic Category Structure: Contrasting Exemplar-Retrieval, Decision-Boundary, and Prototype Models

    ERIC Educational Resources Information Center

    Nosofsky, Robert M.; Stanton, Roger D.

    2005-01-01

    Speeded perceptual classification experiments were conducted to distinguish among the predictions of exemplar-retrieval, decision-boundary, and prototype models. The key manipulation was that across conditions, individual stimuli received either probabilistic or deterministic category feedback. Regardless of the probabilistic feedback, however, an…

  5. Identification of Seasonal to Decadal Controls on Phenology by Contrasting and Integrating Models, Datasets and Detection Methods

    NASA Astrophysics Data System (ADS)

    Forkel, M.; Carvalhais, N.; Migliavacca, M.; Thonicke, K.; Schaphoff, S.; von Bloh, W.; Thurner, M.; Reichstein, M.

    2014-12-01

    Global land surface phenology regulates the climate system through the exchange of carbon, water and energy. Unfortunately, the climatic and ecosystem controls for seasonal, inter-annual and decadal dynamics of phenology are poorly understood. This lack of understanding is reflected in current dynamic global vegetation models that misrepresent vegetation phenology in comparison to satellite datasets of vegetation greenness. However, uncertainties on the spatial patterns and temporal dynamics of land surface phenology arise from the variety of datasets, and methods for time series smoothing and extraction of phenological events. Consequently, the application of dynamic global vegetation models to identify seasonal to decadal controls on phenology requires firstly model improvement, and secondly the consideration of uncertainties from datasets and detection methods. Here, we improved the LPJmL dynamic global vegetation model by implementing a new phenology scheme and by optimizing the model parameters against satellite datasets of vegetation greenness, albedo and gross primary production. We evaluated the phenology of LPJmL globally against three satellite datasets of FAPAR (fraction of absorbed photosynthetic active radiation) and by using ten methods for time series smoothing and phenology detection. Our results (1) demonstrate an improved performance of LPJmL with the new and optimized phenology model over the previous model version, and (2) show that the agreement between estimated start and end of season dates from LPJmL and the different satellite datasets is higher than the agreement between different datasets. Based on the improved LPJmL phenology, we quantify the effect of seasonal temperature, light and water controls and of processes as land use and land cover change, permafrost dynamics, fire disturbance and CO2 fertilization on the timing of start and end of the growing season. Our results demonstrate that water availability is an important seasonal

  6. Modelling changes in nitrogen cycling to sustain increases in forest productivity under elevated atmospheric CO2 and contrasting site conditions

    NASA Astrophysics Data System (ADS)

    Grant, R. F.

    2013-11-01

    If increases in net primary productivity (NPP) caused by rising concentrations of atmospheric CO2 (Ca) are to be sustained, key N processes such as soil mineralization, biological fixation, root uptake and nutrient conservation must also be increased. Simulating the response of these processes to elevated Ca is therefore vital for models used to project the effects of rising Ca on NPP. In this modelling study, hypotheses are proposed for changes in soil mineralization, biological fixation, root nutrient uptake and plant nutrient conservation with changes in Ca. Algorithms developed from these hypotheses were tested in the ecosystem model ecosys against changes in N and C cycling measured over several years under ambient vs. elevated Ca in Free Air CO2 Enrichment (FACE) experiments in the USA at the Duke Forest in North Carolina, the Oak Ridge National Laboratory forest in Tennessee, and the USDA research forest in Wisconsin. More rapid soil N mineralization was found to be vital for simulating sustained increases in NPP measured under elevated vs. ambient Ca at all three FACE sites. This simulation was accomplished by priming decomposition of N-rich humus from increases in microbial biomass generated by increased litterfall modelled under elevated Ca. Greater nonsymbiotic N2 fixation from increased litterfall, root N uptake from increased root growth, and plant N conservation from increased translocation under elevated Ca were found to make smaller contributions to simulated increases in NPP. However greater nutrient conservation enabled larger increases in NPP with Ca to be modelled with coniferous vs. deciduous plant functional types. The effects of these processes on productivity now need to be examined over longer periods under transient rises in Ca and a greater range of site conditions.

  7. In vitro stability analyses as a model for metabolism of ferromagnetic particles (Clariscan), a contrast agent for magnetic resonance imaging.

    PubMed

    Skotland, Tore; Sontum, Per Christian; Oulie, Inger

    2002-04-15

    Clariscan is a new contrast agent for magnetic resonance imaging. It is an aqueous suspension of ferromagnetic particles injected for blood pool and liver imaging. Previous experiments showed that particles made of 59Fe were taken up by the mononuclear phagocytic system and then solubilised. The present work aims at explaining a possible mechanism for the dissolution of these ferromagnetic particles in the body. The particles were diluted in 10-mM citrate or 10-mM acetate buffers at pH 4.5, 5.0 and 5.5 and incubated at 37 degrees C for up to 22 days, protected from light. The mixtures were analysed at different times during this incubation period using photon correlation spectroscopy, magnetic relaxation, visible spectroscopy and reactivity of the iron with the chelator, bathophenanthroline disulphonic acid. The data obtained with these techniques showed that the particles were almost completely solubilised within 4-7 days when incubated in 10 mM citrate, pH 4.5. Incubation in 10 mM citrate buffer, pH 5.0 revealed a slower solubilisation of the particles, as the changes observed after 72 h of incubation at pH 5.0 were 43-71% of the changes observed at pH 4.5. Incubation in 10 mM citrate, pH 5.5 revealed an even slower solubilisation of the particles, as the changes observed after 72 h of incubation at pH 5.5 were 12-34% of those observed at pH 4.5. Incubation of the particles in 10 mM acetate at pH 4.5, 5.0 and 5.5, as well as incubation of the particles in water pH adjusted to pH 5.1, resulted in only minor or no solubilisation of the particles. The results indicate that the low pH of endosomes and lysosomes, as well as endogenous iron-complexing substances, may be important for the solubilisation of these ferromagnetic particles following i.v. injection of Clariscan.

  8. Molecular characterization of the new defective P(brescia) alpha1-antitrypsin allele.

    PubMed

    Medicina, Daniela; Montani, Nadia; Fra, Anna M; Tiberio, Laura; Corda, Luciano; Miranda, Elena; Pezzini, Alessandro; Bonetti, Fausta; Ingrassia, Rosaria; Scabini, Roberta; Facchetti, Fabio; Schiaffonati, Luisa

    2009-08-01

    Alpha1-antitrypsin (alpha(1)AT) deficiency is a hereditary disorder associated with reduced alpha(1)AT serum level, predisposing adults to pulmonary emphysema. Among the known mutations of the alpha(1)AT gene (SERPINA1) causing alpha(1)AT deficiency, a few alleles, particularly the Z allele, may also predispose adults to liver disease. We have characterized a new defective alpha(1)AT allele (c.745G>C) coding for a mutant alpha(1)AT (Gly225Arg), named P(brescia). The P(brescia) alpha(1)AT allele was first identified in combination with the rare defective M(würzburg) allele in an 11-year-old boy showing significantly reduced serum alpha(1)AT level. Subsequently, the P(brescia) allele was found in the heterozygous state with the normal M or the defective Z allele in nine and three adults respectively. In cellular models of the disease, we show that the P(brescia) mutant is retained in the endoplasmic reticulum as ordered polymers and is secreted more slowly than the normal M alpha(1)AT. This behaviour recapitulates the abnormal cellular handling and fate of the Z alpha(1)AT and suggests that the mutation present in the P(brescia) alpha(1)AT causes a conformational change of the protein which, by favouring polymer formation, is etiologic to both severe alpha(1)AT deficiency in the plasma and toxic protein-overload in the liver.

  9. Quantifying the transcriptional output of single alleles in single living mammalian cells

    PubMed Central

    Yunger, Sharon; Rosenfeld, Liat; Garini, Yuval; Shav-Tal, Yaron

    2013-01-01

    Transcription kinetics of actively transcribing genes in vivo have generally been measured using tandem gene arrays. However, tandem arrays do not reflect the endogenous state of genome organization where genes appear as single alleles. We present here a robust technique for the quantification of mRNA synthesis from a single allele in real-time, in single living mammalian cells. The protocol describes how to generate cell clones harboring a tagged allele and how to detect in vivo transcription from this tagged allele at high spatial and temporal resolution throughout the cell cycle. Quantification of nascent mRNAs produced from the single tagged allele is performed using RNA fluorescence in situ hybridization (FISH) and live-cell imaging. Subsequent analyses and data modeling detailed in the protocol include measurements of: transcription rates of RNA polymerase II; determining the number of polymerases recruited to the tagged allele; and measuring the spacing between polymerases. Generating the cells containing the single tagged alleles should take up to a month; RNA FISH or live-cell imaging will require an additional week. PMID:23424748

  10. Contrast-enhanced, real-time volumetric ultrasound imaging of tissue perfusion: preliminary results in a rabbit model of testicular torsion

    NASA Astrophysics Data System (ADS)

    Paltiel, H. J.; Padua, H. M.; Gargollo, P. C.; Cannon, G. M., Jr.; Alomari, A. I.; Yu, R.; Clement, G. T.

    2011-04-01

    Contrast-enhanced ultrasound (US) imaging is potentially applicable to the clinical investigation of a wide variety of perfusion disorders. Quantitative analysis of perfusion is not widely performed, and is limited by the fact that data are acquired from a single tissue plane, a situation that is unlikely to accurately reflect global perfusion. Real-time perfusion information from a tissue volume in an experimental rabbit model of testicular torsion was obtained with a two-dimensional matrix phased array US transducer. Contrast-enhanced imaging was performed in 20 rabbits during intravenous infusion of the microbubble contrast agent Definity® before and after unilateral testicular torsion and contralateral orchiopexy. The degree of torsion was 0° in 4 (sham surgery), 180° in 4, 360° in 4, 540° in 4, and 720° in 4. An automated technique was developed to analyze the time history of US image intensity in experimental and control testes. Comparison of mean US intensity rate of change and of ratios between mean US intensity rate of change in experimental and control testes demonstrated good correlation with testicular perfusion and mean perfusion ratios obtained with radiolabeled microspheres, an accepted 'gold standard'. This method is of potential utility in the clinical evaluation of testicular and other organ perfusion.

  11. Contrast-enhanced, real-time volumetric ultrasound imaging of tissue perfusion: preliminary results in a rabbit model of testicular torsion.

    PubMed

    Paltiel, H J; Padua, H M; Gargollo, P C; Cannon, G M; Alomari, A I; Yu, R; Clement, G T

    2011-04-07

    Contrast-enhanced ultrasound (US) imaging is potentially applicable to the clinical investigation of a wide variety of perfusion disorders. Quantitative analysis of perfusion is not widely performed, and is limited by the fact that data are acquired from a single tissue plane, a situation that is unlikely to accurately reflect global perfusion. Real-time perfusion information from a tissue volume in an experimental rabbit model of testicular torsion was obtained with a two-dimensional matrix phased array US transducer. Contrast-enhanced imaging was performed in 20 rabbits during intravenous infusion of the microbubble contrast agent Definity® before and after unilateral testicular torsion and contralateral orchiopexy. The degree of torsion was 0° in 4 (sham surgery), 180° in 4, 360° in 4, 540° in 4, and 720° in 4. An automated technique was developed to analyze the time history of US image intensity in experimental and control testes. Comparison of mean US intensity rate of change and of ratios between mean US intensity rate of change in experimental and control testes demonstrated good correlation with testicular perfusion and mean perfusion ratios obtained with radiolabeled microspheres, an accepted 'gold standard'. This method is of potential utility in the clinical evaluation of testicular and other organ perfusion.

  12. CT Pulmonary Angiography at Reduced Radiation Exposure and Contrast Material Volume Using Iterative Model Reconstruction and iDose4 Technique in Comparison to FBP

    PubMed Central

    Laqmani, Azien; Kurfürst, Maximillian; Butscheidt, Sebastian; Sehner, Susanne; Schmidt-Holtz, Jakob; Behzadi, Cyrus; Nagel, Hans Dieter; Adam, Gerhard; Regier, Marc

    2016-01-01

    Purpose To assess image quality of CT pulmonary angiography (CTPA) at reduced radiation exposure (RD-CTPA) and contrast medium (CM) volume using two different iterative reconstruction (IR) algorithms (iDose4 and iterative model reconstruction (IMR)) in comparison to filtered back projection (FBP). Materials and Methods 52 patients (body weight < 100 kg, mean BMI: 23.9) with suspected pulmonary embolism (PE) underwent RD-CTPA (tube voltage: 80 kV; mean CTDIvol: 1.9 mGy) using 40 ml CM. Data were reconstructed using FBP and two different IR algorithms (iDose4 and IMR). Subjective and objective image quality and conspicuity of PE were assessed in central, segmental, and subsegmental arteries. Results Noise reduction of 55% was achieved with iDose4 and of 85% with IMR compared to FBP. Contrast-to-noise ratio significantly increased with iDose4 and IMR compared to FBP (p<0.05). Subjective image quality was rated significantly higher at IMR reconstructions in comparison to iDose4 and FBP. Conspicuity of central and segmental PE significantly improved with the use of IMR. In subsegmental arteries, iDose4 was superior to IMR. Conclusions CTPA at reduced radiation exposure and contrast medium volume is feasible with the use of IMR, which provides improved image quality and conspicuity of pulmonary embolism in central and segmental arteries. PMID:27611448

  13. Real-time tracking of dissociation of hyperpolarized 89Y-DTPA: a model for degradation of open-chain Gd3+ MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Ferguson, Sarah; Niedbalski, Peter; Parish, Christopher; Kiswandhi, Andhika; Kovacs, Zoltan; Lumata, Lloyd

    Gadolinium (Gd) complexes are widely used relaxation-based clinical contrast agents in magnetic resonance imaging (MRI). Gd-based MRI contrast agents with open-chain ligand such as Gd-DTPA, commercially known as magnevist, are less stable compared to Gd complexes with macrocyclic ligands such as GdDOTA (Dotarem). The dissociation of Gd-DPTA into Gd ion and DTPA ligand under certain biological conditions such as high zinc levels can potentially cause kidney damage. Since Gd is paramagnetic, direct NMR detection of the Gd-DTPA dissociation is quite challenging due to ultra-short relaxation times. In this work, we have investigated Y-DTPA as a model for Gd-DPTA dissociation under high zinc content solutions. Using dissolution dynamic nuclear polarization (DNP), the 89Y NMR signal is amplified by several thousand-fold. Due to the the relatively long T1 relaxation time of 89Y which translates to hyperpolarization lifetime of several minutes, the dissociation of Y-DTPA can be tracked in real-time by hyperpolarized 89Y NMR spectroscopy. Dissociation kinetic rates and implications on the degradation of open-chain Gd3+ MRI contrast agents will be discussed. This work was supported by the U.S. Department of Defense Award Number W81XWH-14-1-0048 and by the Robert A. Welch Foundation research Grant Number AT-1877.

  14. Modeling the Evolution of Riparian Woodlands Facing Climate Change in Three European Rivers with Contrasting Flow Regimes

    PubMed Central

    Rivaes, Rui P.; Rodríguez-González, Patricia M.; Ferreira, Maria Teresa; Pinheiro, António N.; Politti, Emilio; Egger, Gregory; García-Arias, Alicia; Francés, Felix

    2014-01-01

    Global circulation models forecasts indicate a future temperature and rainfall pattern modification worldwide. Such phenomena will become particularly evident in Europe where climate modifications could be more severe than the average change at the global level. As such, river flow regimes are expected to change, with resultant impacts on aquatic and riparian ecosystems. Riparian woodlands are among the most endangered ecosystems on earth and provide vital services to interconnected ecosystems and human societies. However, they have not been the object of many studies designed to spatially and temporally quantify how these ecosystems will react to climate change-induced flow regimes. Our goal was to assess the effects of climate-changed flow regimes on the existing riparian vegetation of three different European flow regimes. Cases studies were selected in the light of the most common watershed alimentation modes occurring across European regions, with the objective of appraising expected alterations in the riparian elements of fluvial systems due to climate change. Riparian vegetation modeling was performed using the CASiMiR-vegetation model, which bases its computation on the fluvial disturbance of the riparian patch mosaic. Modeling results show that riparian woodlands may undergo not only at least moderate changes for all flow regimes, but also some dramatic adjustments in specific areas of particular vegetation development stages. There are circumstances in which complete annihilation is feasible. Pluvial flow regimes, like the ones in southern European rivers, are those likely to experience more pronounced changes. Furthermore, regardless of the flow regime, younger and more water-dependent individuals are expected to be the most affected by climate change. PMID:25330151

  15. Modeling the evolution of riparian woodlands facing climate change in three European rivers with contrasting flow regimes.

    PubMed

    Rivaes, Rui P; Rodríguez-González, Patricia M; Ferreira, Maria Teresa; Pinheiro, António N; Politti, Emilio; Egger, Gregory; García-Arias, Alicia; Francés, Felix

    2014-01-01

    Global circulation models forecasts indicate a future temperature and rainfall pattern modification worldwide. Such phenomena will become particularly evident in Europe where climate modifications could be more severe than the average change at the global level. As such, river flow regimes are expected to change, with resultant impacts on aquatic and riparian ecosystems. Riparian woodlands are among the most endangered ecosystems on earth and provide vital services to interconnected ecosystems and human societies. However, they have not been the object of many studies designed to spatially and temporally quantify how these ecosystems will react to climate change-induced flow regimes. Our goal was to assess the effects of climate-changed flow regimes on the existing riparian vegetation of three different European flow regimes. Cases studies were selected in the light of the most common watershed alimentation modes occurring across European regions, with the objective of appraising expected alterations in the riparian elements of fluvial systems due to climate change. Riparian vegetation modeling was performed using the CASiMiR-vegetation model, which bases its computation on the fluvial disturbance of the riparian patch mosaic. Modeling results show that riparian woodlands may undergo not only at least moderate changes for all flow regimes, but also some dramatic adjustments in specific areas of particular vegetation development stages. There are circumstances in which complete annihilation is feasible. Pluvial flow regimes, like the ones in southern European rivers, are those likely to experience more pronounced changes. Furthermore, regardless of the flow regime, younger and more water-dependent individuals are expected to be the most affected by climate change.

  16. Sensitivity analysis and calibration of a soil carbon model (SoilGen2) in two contrasting loess forest soils

    NASA Astrophysics Data System (ADS)

    Yu, Y. Y.; Finke, P. A.; Wu, H. B.; Guo, Z. T.

    2013-01-01

    To accurately estimate past terrestrial carbon pools is the key to understanding the global carbon cycle and its relationship with the climate system. SoilGen2 is a useful tool to obtain aspects of soil properties (including carbon content) by simulating soil formation processes; thus it offers an opportunity for both past soil carbon pool reconstruction and future carbon pool prediction. In order to apply it to various environmental conditions, parameters related to carbon cycle process in SoilGen2 are calibrated based on six soil pedons from two typical loess deposition regions (Belgium and China). Sensitivity analysis using the Morris method shows that decomposition rate of humus (kHUM), fraction of incoming plant material as leaf litter (frecto) and decomposition rate of resistant plant material (kRPM) are the three most sensitive parameters that would cause the greatest uncertainty in simulated change of soil organic carbon in both regions. According to the principle of minimizing the difference between simulated and measured organic carbon by comparing quality indices, the suited values of kHUM, (frecto and kRPM in the model are deduced step by step and validated for independent soil pedons. The difference of calibrated parameters between Belgium and China may be attributed to their different vegetation types and climate conditions. This calibrated model allows more accurate simulation of carbon change in the whole pedon and has potential for future modeling of carbon cycle over long timescales.

  17. Sensitivity analysis and calibration of a soil carbon model (SoilGen2) in two contrasting loess forest soils

    NASA Astrophysics Data System (ADS)

    Yu, Y. Y.; Finke, P. A.; Wu, H. B.; Guo, Z. T.

    2012-07-01

    To accurately estimate past terrestrial carbon pools is the key to understand the global carbon cycle and its relationship with the climate system. SoilGen2 is a useful tool to obtain aspects of soil properties (including carbon content) by simulating soil formation processes; thus it offers an opportunity for past soil carbon pool reconstruction. In order to apply it to various environmental conditions, parameters related to carbon cycle process in SoilGen2 are calibrated based on 6 soil pedons from two typical loess deposition regions (Belgium and China). Sensitivity analysis using Morris' method shows that decomposition rate of humus (kHUM), fraction of incoming plant material as leaf litter (frecto) and decomposition rate of resistant plant material (kRPM) are 3 most sensitive parameters that would cause the greatest uncertainty in simulated change of soil organic carbon in both regions. According to the principle of minimizing the difference between simulated and measured organic carbon by comparing quality indices, the suited values of kHUM, frecto and kRPM in the model are deduced step by step. The difference of calibrated parameters between Belgium and China may be attributed to their different vegetation types and climate conditions. This calibrated model is improved for better simulation of carbon change in the whole pedon and has potential for future modeling of carbon cycle in paleosols.

  18. A multireader diagnostic performance study of low-contrast detectability on a third-generation dual-source CT scanner: filtered back projection versus advanced modeled iterative reconstruction

    NASA Astrophysics Data System (ADS)

    Solomon, Justin; Mileto, Achille; Ramirez-Giraldo, Juan Carlos; Samei, Ehsan

    2015-03-01

    The purpose of this work was to compare CT low-contrast detectability between two reconstruction algorithms, filtered back-projection (FBP) and advanced modeled iterative reconstruction (ADMIRE). A phantom was designed with a range of low-contrast circular inserts representing 5 contrast levels and 3 sizes. The phantom was imaged on a third-generation dual-source CT scanner (SOMATOM Definition Force, Siemens Healthcare) under various dose levels (0.74 - 5.8 mGy CTDIVol). Images were reconstructed using different settings of slice thickness (0.6 - 5 mm) and reconstruction algorithms (FBP and ADMIRE with strength of 3-5) and were assessed by eleven blinded and independent readers using a two alternative forced choice (2AFC) detection experiment. A second observer experiment was further performed in which observers scored the images based on the total number of visible object groups. Detection performance increased with increasing contrast, size, dose, with accuracy ranging from 50% (i.e., guessing) to 87% with an average inter-observer variability of ±7%. The use of ADMIRE-3 increased performance by 5.2% resulting in an estimated dose reduction potential of 56-60%. The results from the second experiment also showed increased number of visible object groups for increasing dose, slice thickness, and ADMIRE strength. The score difference between FBP and ADMIRE was 0.9, 1.3, and 2.1 for ADMIRE strengths of 3, 4, and 5, respectively, resulting in estimated dose reduction potentials between 4-80%. Overall, the data indicated potential to image at reduced doses while maintaining comparable image quality when using ADMIRE compared to FBP.

  19. A semi-Markov model for mitosis segmentation in time-lapse phase contrast microscopy image sequences of stem cell populations.

    PubMed

    Liu, An-An; Li, Kang; Kanade, Takeo

    2012-02-01

    We propose a semi-Markov model trained in a max-margin learning framework for mitosis event segmentation in large-scale time-lapse phase contrast microscopy image sequences of stem cell populations. Our method consists of three steps. First, we apply a constrained optimization based microscopy image segmentation method that exploits phase contrast optics to extract candidate subsequences in the input image sequence that contains mitosis events. Then, we apply a max-margin hidden conditional random field (MM-HCRF) classifier learned from human-annotated mitotic and nonmitotic sequences to classify each candidate subsequence as a mitosis or not. Finally, a max-margin semi-Markov model (MM-SMM) trained on manually-segmented mitotic sequences is utilized to reinforce the mitosis classification results, and to further segment each mitosis into four predefined temporal stages. The proposed method outperforms the event-detection CRF model recently reported by Huh as well as several other competing methods in very challenging image sequences of multipolar-shaped C3H10T1/2 mesenchymal stem cells. For mitosis detection, an overall precision of 95.8% and a recall of 88.1% were achieved. For mitosis segmentation, the mean and standard deviation for the localization errors of the start and end points of all mitosis stages were well below 1 and 2 frames, respectively. In particular, an overall temporal location error of 0.73 ± 1.29 frames was achieved for locating daughter cell birth events.

  20. Norm-Resolvent Convergence of One-Dimensional High-Contrast Periodic Problems to a Kronig-Penney Dipole-Type Model

    NASA Astrophysics Data System (ADS)

    Cherednichenko, Kirill D.; Kiselev, Alexander V.

    2017-01-01

    We prove operator-norm resolvent convergence estimates for one-dimensional periodic differential operators with rapidly oscillating coefficients in the non-uniformly elliptic high-contrast setting, which has been out of reach of the existing homogenisation techniques. Our asymptotic analysis is based on a special representation of the resolvent of the operator in terms of the M-matrix of an associated boundary triple ("Krein resolvent formula"). The resulting asymptotic behaviour is shown to be described, up to a unitary transformation, by a non-standard version of the Kronig-Penney model on R.

  1. Comparison between human and model observer performance in low-contrast detection tasks in CT images: application to images reconstructed with filtered back projection and iterative algorithms

    PubMed Central

    Calzado, A; Geleijns, J; Joemai, R M S; Veldkamp, W J H

    2014-01-01

    Objective: To compare low-contrast detectability (LCDet) performance between a model [non–pre-whitening matched filter with an eye filter (NPWE)] and human observers in CT images reconstructed with filtered back projection (FBP) and iterative [adaptive iterative dose reduction three-dimensional (AIDR 3D; Toshiba Medical Systems, Zoetermeer, Netherlands)] algorithms. Methods: Images of the Catphan® phantom (Phantom Laboratories, New York, NY) were acquired with Aquilion ONE™ 320-detector row CT (Toshiba Medical Systems, Tokyo, Japan) at five tube current levels (20–500 mA range) and reconstructed with FBP and AIDR 3D. Samples containing either low-contrast objects (diameters, 2–15 mm) or background were extracted and analysed by the NPWE model and four human observers in a two-alternative forced choice detection task study. Proportion correct (PC) values were obtained for each analysed object and used to compare human and model observer performances. An efficiency factor (η) was calculated to normalize NPWE to human results. Results: Human and NPWE model PC values (normalized by the efficiency, η = 0.44) were highly correlated for the whole dose range. The Pearson's product-moment correlation coefficients (95% confidence interval) between human and NPWE were 0.984 (0.972–0.991) for AIDR 3D and 0.984 (0.971–0.991) for FBP, respectively. Bland–Altman plots based on PC results showed excellent agreement between human and NPWE [mean absolute difference 0.5 ± 0.4%; range of differences (−4.7%, 5.6%)]. Conclusion: The NPWE model observer can predict human performance in LCDet tasks in phantom CT images reconstructed with FBP and AIDR 3D algorithms at different dose levels. Advances in knowledge: Quantitative assessment of LCDet in CT can accurately be performed using software based on a model observer. PMID:24837275

  2. Anisotropic contrast optical microscope.

    PubMed

    Peev, D; Hofmann, T; Kananizadeh, N; Beeram, S; Rodriguez, E; Wimer, S; Rodenhausen, K B; Herzinger, C M; Kasputis, T; Pfaunmiller, E; Nguyen, A; Korlacki, R; Pannier, A; Li, Y; Schubert, E; Hage, D; Schubert, M

    2016-11-01

    An optical microscope is described that reveals contrast in the Mueller matrix images of a thin, transparent, or semi-transparent specimen located within an anisotropic object plane (anisotropic filter). The specimen changes the anisotropy of the filter and thereby produces contrast within the Mueller matrix images. Here we use an anisotropic filter composed of a semi-transparent, nanostructured thin film with sub-wavelength thickness placed within the object plane. The sample is illuminated as in common optical microscopy but the light is modulated in its polarization using combinations of linear polarizers and phase plate (compensator) to control and analyze the state of polarization. Direct generalized ellipsometry data analysis approaches permit extraction of fundamental Mueller matrix object plane images dispensing with the need of Fourier expansion methods. Generalized ellipsometry model approaches are used for quantitative image analyses. These images are obtained from sets of multiple images obtained under various polarizer, analyzer, and compensator settings. Up to 16 independent Mueller matrix images can be obtained, while our current setup is limited to 11 images normalized by the unpolarized intensity. We demonstrate the anisotropic contrast optical microscope by measuring lithographically defined micro-patterned anisotropic filters, and we quantify the adsorption of an organic self-assembled monolayer film onto the anisotropic filter. Comparison with an isotropic glass slide demonstrates the image enhancement obtained by our method over microscopy without the use of an anisotropic filter. In our current instrument, we estimate the limit of detection for organic volumetric mass within the object plane of ≈49 fg within ≈7 × 7 μm(2) object surface area. Compared to a quartz crystal microbalance with dissipation instrumentation, where contemporary limits require a total load of ≈500 pg for detection, the instrumentation demonstrated here improves

  3. Anisotropic contrast optical microscope

    NASA Astrophysics Data System (ADS)

    Peev, D.; Hofmann, T.; Kananizadeh, N.; Beeram, S.; Rodriguez, E.; Wimer, S.; Rodenhausen, K. B.; Herzinger, C. M.; Kasputis, T.; Pfaunmiller, E.; Nguyen, A.; Korlacki, R.; Pannier, A.; Li, Y.; Schubert, E.; Hage, D.; Schubert, M.

    2016-11-01

    An optical microscope is described that reveals contrast in the Mueller matrix images of a thin, transparent, or semi-transparent specimen located within an anisotropic object plane (anisotropic filter). The specimen changes the anisotropy of the filter and thereby produces contrast within the Mueller matrix images. Here we use an anisotropic filter composed of a semi-transparent, nanostructured thin film with sub-wavelength thickness placed within the object plane. The sample is illuminated as in common optical microscopy but the light is modulated in its polarization using combinations of linear polarizers and phase plate (compensator) to control and analyze the state of polarization. Direct generalized ellipsometry data analysis approaches permit extraction of fundamental Mueller matrix object plane images dispensing with the need of Fourier expansion methods. Generalized ellipsometry model approaches are used for quantitative image analyses. These images are obtained from sets of multiple images obtained under various polarizer, analyzer, and compensator settings. Up to 16 independent Mueller matrix images can be obtained, while our current setup is limited to 11 images normalized by the unpolarized intensity. We demonstrate the anisotropic contrast optical microscope by measuring lithographically defined micro-patterned anisotropic filters, and we quantify the adsorption of an organic self-assembled monolayer film onto the anisotropic filter. Comparison with an isotropic glass slide demonstrates the image enhancement obtained by our method over microscopy without the use of an anisotropic filter. In our current instrument, we estimate the limit of detection for organic volumetric mass within the object plane of ≈49 fg within ≈7 × 7 μm2 object surface area. Compared to a quartz crystal microbalance with dissipation instrumentation, where contemporary limits require a total load of ≈500 pg for detection, the instrumentation demonstrated here improves

  4. The number of alleles at a microsatellite defines the allele frequency spectrum and facilitates fast accurate estimation of theta.

    PubMed

    Haasl, Ryan J; Payseur, Bret A

    2010-12-01

    Theoretical work focused on microsatellite variation has produced a number of important results, including the expected distribution of repeat sizes and the expected squared difference in repeat size between two randomly selected samples. However, closed-form expressions for the sampling distribution and frequency spectrum of microsatellite variation have not been identified. Here, we use coalescent simulations of the stepwise mutation model to develop gamma and exponential approximations of the microsatellite allele frequency spectrum, a distribution central to the description of microsatellite variation across the genome. For both approximations, the parameter of biological relevance is the number of alleles at a locus, which we express as a function of θ, the population-scaled mutation rate, based on simulated data. Discovered relationships between θ, the number of alleles, and the frequency spectrum support the development of three new estimators of microsatellite θ. The three estimators exhibit roughly similar mean squared errors (MSEs) and all are biased. However, across a broad range of sample sizes and θ values, the MSEs of these estimators are frequently lower than all other estimators tested. The new estimators are also reasonably robust to mutation that includes step sizes greater than one. Finally, our approximation to the microsatellite allele frequency spectrum provides a null distribution of microsatellite variation. In this context, a preliminary analysis of the effects of demographic change on the frequency spectrum is performed. We suggest that simulations of the microsatellite frequency spectrum under evolutionary scenarios of interest may guide investigators to the use of relevant and sometimes novel summary statistics.

  5. Vulnerable but aloof versus naughty and nice: contrasting the presentation of male and female nude models in Viva and Playboy.

    PubMed

    Beggan, James K; Vencill, Jennifer A; Garos, Sheila

    2014-01-01

    The current research examined contested meanings of nudity by comparing images of nude men and women that appeared in Viva, a 1970s women's magazine founded with the intention of foregrounding male nudity, to corresponding issues of Playboy. A major difference was obtained between male models and Playboy Playmates regarding direction of gaze and nudity. Although gaze aversion is often interpreted as a sign of submission and direct gaze is seen as a dominance cue, men in Viva displayed a high level of gaze aversion and women in Playboy often gazed directly at the camera, especially when their pubic area was exposed. Additional content analysis examined the personality characteristics attributed to male models in Viva and Playmates in Playboy in their biographical sketches. In Viva, men were presented as possessing "bad boy" traits that may have been intended to compensate for the loss of power associated with male nudity. Playmates could be viewed as being naughty (by virtue of posing nude) and nice in the characterization of their personalities.

  6. Feasibility of Single-Input Tracer Kinetic Modeling with Continuous-Time Formalism in Liver 4-Phase Dynamic Contrast-Enhanced CT.

    PubMed

    Lee, Sang Ho; Ryu, Yasuji; Hayano, Koichi; Yoshida, Hiroyuki

    2014-09-01

    The modeling of tracer kinetics with use of low-temporal-resolution data is of central importance for patient dose reduction in dynamic contrast-enhanced CT (DCE-CT) study. Tracer kinetic models of the liver vary according to the physiologic assumptions imposed on the model, and they can substantially differ in the ways how the input for blood supply and tissue compartments are modeled. In this study, single-input flow-limited (FL), Tofts-Kety (TK), extended TK (ETK), Hayton-Brady (HB), two compartment exchange (2CX), and adiabatic approximation to the tissue homogeneity (AATH) models were applied to the analysis of liver 4-phase DCE-CT data with fully continuous-time parameter formulation, including the bolus arrival time. The bolus arrival time for the 2CX and AATH models was described by modifying the vascular transport operator theory. Initial results indicate that single-input tracer kinetic modeling is feasible for distinguishing between hepatocellular carcinoma and normal liver parenchyma.

  7. A 3-D model for the Antarctic ice sheet: a sensitivity study on the glacial-interglacial contrast

    NASA Astrophysics Data System (ADS)

    Huybrechts, Philippe

    1990-12-01

    On the longer climatic time scales, changes in the elevation and extent of the Antarctic ice sheet have an important role in modulating global atmospheric and oceanographic processes, and contribute significantly to world-wide sea levels. In this paper, a 3-D time-dependent thermomechanical model for the entire ice sheet is presented, that is subsequently used to examine the effects of glacial-interglacial shifts in environmental boundary conditions on its geometry. The model takes into account a coupled ice shelf, grounding-line dynamics, basal sliding and isostatic bed adjustment and considers the fully coupled velocity and temperature fields. Ice flow is calculated on a fine mesh (40 km horizontal grid size and 10 layers in the vertical) for grounded and floating ice and a stress transition zone in between at the grounding line, where all stress components contribute in the effective stress in the flow law. There is free interaction between ice sheet and ice shelf, so that the entire geometry is internally generated. A simulation of the present ice sheet reveals that the model is able to yield realistic results. A series of sensitivity experiments are then performed, in which lower temperatures, reduced accumulation rates and lower global sea level stands are imposed, either singly or in combination. By comparing results of pairs of experiments, the effects of each of these environmental changes can be determined. In agreement with glacial-geological evidence, we found that the most pronounced changes show up in the West Antarctic ice sheet configuration. They appear to be essentially controlled by variations in eustatic sea level, whereas typical glacial-interglacial changes in temperature and ice deposition rates tend to balance one another. These findings support the hypothesis that the Antarctic ice sheet basically follows glacial episodes in the northern hemisphere by means of sea-level teleconnections. Grounding occurs more readily in the Weddell sea than

  8. High-Throughput Genotyping with TaqMan Allelic Discrimination and Allele-Specific Genotyping Assays.

    PubMed

    Heissl, Angelika; Arbeithuber, Barbara; Tiemann-Boege, Irene

    2017-01-01

    Real-time PCR-based genotyping methods, such as TaqMan allelic discrimination assays and allele-specific genotyping, are particularly useful when screening a handful of single nucleotide polymorphisms in hundreds of samples; either derived from different individuals, tissues, or pre-amplified DNA. Although real-time PCR-based methods such as TaqMan are well-established, alternative methods, like allele-specific genotyping, are powerful alternatives, especially for genotyping short tandem repeat (STR) length polymorphisms. Here, we describe all relevant aspects when developing an assay for a new SNP or STR using either TaqMan or allele-specific genotyping, respectively, such as primer and probe design, optimization of reaction conditions, the experimental procedure for typing hundreds of samples, and finally the data evaluation. Our goal is to provide a guideline for developing genotyping assays using these two approaches that render reliable and reproducible genotype calls involving minimal optimization.

  9. 21st century projections of ocean ecology and productivity across the CMIP5 models: contrasting the Southern Ocean and the Arctic

    NASA Astrophysics Data System (ADS)

    Marinov, I.; Cabre, A.; Leung, S.

    2014-12-01

    We use the newest generation of fully-coupled earth system models to study and contrast the response of Southern Ocean and Arctic phytoplankton productivity and biomass to 21st century climate change. The Arctic is warming at a rate much higher than the Southern high latitudes. Despite fundamental differences between the physical responses to climate in these regions, CMIP5 modes predict small increases in biological production both in the SO and the Arctic, partially compensating for the severe loss of primary production in the rest of the oceans. South of 40ºS, the CMIP5 models predict a complex, zonally-banded pattern of phytoplankton abundance and productivity changes driven by shifts in light and iron availability with future warming, in agreement with patterns and mechanisms emerging from a satellite trend analysis and other recent observational work. Increased SAM plays a major role in these projections, as increased Southern Ocean westerlies act both to increase mixing and phytoplankton light limitation in a band around 50S, and to modify iron supply to the surface in regions where phytoplankton are iron limited. By contrast, phytoplankton are light and nitrate co-limited in the strongly stratified Arctic ocean. Here we find that over 100 years, release of light limitation due to sea ice retreat is counter-balanced by an increase in nitrogen limitation due to increased stratification. While most models predict net increases in Arctic production by the end of the 21st century, the different strengths of nutrient-light co-limitation among models result in different magnitude changes in production across models. We assess the multi-model 100-year trend significance using a novel technique based on bootstrap combined with a weighting scheme based in similarity across models. We find that model uncertainty in ecological and biogeochemical parameters is higher than for the physical parameters. Additionally, the spread in model predictions is smaller than the

  10. HLA-B alleles of the Cayapa of Ecuador: new B39 and B15 alleles.

    PubMed

    Garber, T L; Butler, L M; Trachtenberg, E A; Erlich, H A; Rickards, O; De Stefano, G; Watkins, D I

    1995-01-01

    Recent data suggest that HLA-B locus alleles can evolve quickly in native South American populations. To investigate further this phenomenon of new HLA-B variants among Amerindians, we studied samples from another South American tribe, the Cayapa from Ecuador. We selected individuals for HLA-B molecular typing based upon their HLA class II typing results. Three new variants of HLA-B39 and one new variant of HLA-B15 were found in the Cayapa: HLA-B*3905, HLA-B*3906, HLA-B*3907, and HLA-B*1522. A total of thirteen new HLA-B alleles have now been found in the four South American tribes studied. Each of these four tribes studied, including the Cayapa, had novel alleles that were not found in any of the other tribes, suggesting that many of these new HLA-B alleles may have evolved since the Paleo-Indians originally populated South America. Each of these 13 new alleles contained predicted amino acid replacements that were located in the peptide binding site. These amino acid replacements may affect the sequence motif of the bound peptides, suggesting that these new alleles have been maintained by selection. New allelic variants have been found for all common HLA-B locus antigenic groups present in South American tribes with the exception of B48. In spite of its high frequency in South American tribes, no evidence for variants of B48 has been found in all the Amerindians studied, suggesting that B48 may have unique characteristics among the B locus alleles.

  11. Airborne ultraviolet imaging system for oil slick surveillance: oil-seawater contrast, imaging concept, signal-to-noise ratio, optical design, and optomechanical model.

    PubMed

    Shi, Zhenhua; Yu, Lei; Cao, Diansheng; Wu, Qingwen; Yu, Xiangyang; Lin, Guanyu

    2015-09-01

    The airborne ultraviolet imaging system, which assesses oil slick areas better than visible and infrared optical systems, was designed to monitor and track oil slicks in coastal regions. A model was built to achieve the upwelling radiance distribution of oil-covered sea and clean seawater, based on the radiance transfer software. With this model, the oil-seawater contrast, which affects the detection of oil-covered coastal areas, was obtained. The oil-seawater contrast, fundamental imaging concept, analog calculation of SNR, optical design, and optomechanical configuration of the airborne ultraviolet imaging system are illustrated in this paper. The study of an airborne ultraviolet imaging system with F-number 3.4 and a 40° field of view (FOV) in near ultraviolet channel (0.32-0.38 μm) was illustrated and better imaging quality was achieved. The ground sample distance (GSD) is from 0.35 to 0.7 m with flight height ranges from 0.5 to 1 km. Comparisons of detailed characteristics of the airborne ultraviolet imaging system with the corresponding characteristics of previous ultraviolet systems were tabulated, and these comparisons showed that this system can achieve a wide FOV and a relative high SNR. A virtual mechanical prototype and tolerances analysis are illustrated in this paper to verify the performance of fabrication and assembly of the ultraviolet system.

  12. Gold-nanorod contrast-enhanced photoacoustic micro-imaging of focused-ultrasound induced blood-brain-barrier opening in a rat model

    NASA Astrophysics Data System (ADS)

    Wang, Po-Hsun; Liu, Hao-Li; Hsu, Po-Hung; Lin, Chia-Yu; Chris Wang, Churng-Ren; Chen, Pin-Yuan; Wei, Kuo-Chen; Yen, Tzu-Chen; Li, Meng-Lin

    2012-06-01

    In this study, we develop a novel photoacoustic imaging technique based on gold nanorods (AuNRs) for quantitatively monitoring focused-ultrasound (FUS) induced blood-brain barrier (BBB) opening in a rat model in vivo. This study takes advantage of the strong near-infrared absorption (peak at ~800 nm) of AuNRs and the extravasation tendency from BBB opening foci due to their nano-scale size to passively label the BBB disruption area. Experimental results show that AuNR contrast-enhanced photoacoustic microscopy (PAM) successfully reveals the spatial distribution and temporal response of BBB disruption area in the rat brains. The quantitative measurement of contrast enhancement has potential to estimate the local concentration of AuNRs and even the dosage of therapeutic molecules when AuNRs are further used as nano-carrier for drug delivery or photothermal therapy. The photoacoustic results also provide complementary information to MRI, being helpful to discover more details about FUS induced BBB opening in small animal models.

  13. HLA-DQA1/B1 alleles as putative susceptibility markers in congenital toxoplasmosis

    PubMed Central

    Shimokawa, Paulo Tadashi; Targa, Lília Spaleta; Yamamoto, Lidia; Rodrigues, Jonatas Cristian; Kanunfre, Kelly Aparecida; Okay, Thelma Suely

    2016-01-01

    ABSTRACT Host and parasite genotypes are among the factors associated with congenital toxoplasmosis pathogenesis. As HLA class II molecules play a key role in the immune system regulation, the aim of this study was to investigate whether HLA-DQA1/B1 alleles are associated with susceptibility or protection to congenital toxoplasmosis. One hundred and twenty-two fetuses with and 103 without toxoplasmosis were studied. The two study groups were comparable according to a number of socio-demographic and genetic variables. HLA alleles were typed by PCR-SSP. In the HLA-DQA1 region, the allele frequencies showed that *01:03 and *03:02 alleles could confer susceptibility (OR= 3.06, p = 0.0002 and OR= 9.60, p= 0.0001, respectively) as they were more frequent among infected fetuses. Regarding the HLA-DQB1 region, the *05:04 allele could confer susceptibility (OR = 6.95, p < 0.0001). Of the 122 infected fetuses, 10 presented susceptibility haplotypes contrasting with only one in the non-infected group. This difference was not statistically significant after correction for multiple comparison (OR = 9.37, p=0.011). In the casuistic, there were two severely damaged fetuses with high parasite loads determined in amniotic fluid samples and HLA-DQA1 susceptibility alleles. In the present study, a discriminatory potential of HLA-DQA1/B1 alleles to identify susceptibility to congenital toxoplasmosis and the most severe cases has been shown. PMID:26856406

  14. Dynamic Contrast-Enhanced MRI in the Study of Brain Tumors. Comparison Between the Extended Tofts-Kety Model and a Phenomenological Universalities (PUN) Algorithm.

    PubMed

    Bergamino, Maurizio; Barletta, Laura; Castellan, Lucio; Mancardi, Gianluigi; Roccatagliata, Luca

    2015-12-01

    Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a well-established technique for studying blood-brain barrier (BBB) permeability that allows measurements to be made for a wide range of brain pathologies, including multiple sclerosis and brain tumors (BT). This latter application is particularly interesting, because high-grade gliomas are characterized by increased microvascular permeability and a loss of BBB function due to the structural abnormalities of the endothelial layer. In this study, we compared the extended Tofts-Kety (ETK) model and an extended derivate class from phenomenological universalities called EU1 in 30 adult patients with different BT grades. A total of 75 regions of interest were manually drawn on the MRI and subsequently analyzed using the ETK and EU1 algorithms. Significant linear correlations were found among the parameters obtained by these two algorithms. The means of R (2) obtained using ETK and EU1 models for high-grade tumors were 0.81 and 0.91, while those for low-grade tumors were 0.82 and 0.85, respectively; therefore, these two models are equivalent. In conclusion, we can confirm that the application of the EU1 model to the DCE-MRI experimental data might be a useful alternative to pharmacokinetic models in the study of BT, because the analytic results can be generated more quickly and easily than with the ETK model.

  15. Contrasting gene expression patterns induced by levodopa and pramipexole treatments in the rat model of Parkinson's disease.

    PubMed

    Taravini, Irene R; Larramendy, Celia; Gomez, Gimena; Saborido, Mariano D; Spaans, Floor; Fresno, Cristóbal; González, Germán A; Fernández, Elmer; Murer, Mario G; Gershanik, Oscar S

    2016-02-01

    Whether the treatment of Parkinson's disease has to be initiated with levodopa or a D2 agonist like pramipexole remains debatable. Levodopa is more potent against symptoms than D2 agonists, but D2 agonists are less prone to induce motor complications and may have neuroprotective effects. Although regulation of plastic changes in striatal circuits may be the key to their different therapeutic potential, the gene expression patterns induced by de novo treatments with levodopa or D2 agonists are currently unknown. By studying the whole striatal transcriptome in a rodent model of early stage Parkinson's disease, we have identified the gene expression patterns underlying therapeutically comparable chronic treatments with levodopa or pramipexole. Despite the overall relatively small size of mRNA expression changes at the level of individual transcripts, our data show a robust and complete segregation of the transcript expression patterns induced by both treatments. Moreover, transcripts related to oxidative metabolism and mitochondrial function were enriched in levodopa-treated compared to vehicle-treated and pramipexole-treated animals, whereas transcripts related to olfactory transduction pathways were enriched in both treatment groups compared to vehicle-treated animals. Thus, our data reveal the plasticity of genetic striatal networks possibly contributing to the therapeutic effects of the most common initial treatments for Parkinson's disease, suggesting a role for oxidative stress in the long term complications induced by levodopa and identifying previously overlooked signaling cascades as potentially new therapeutic targets.

  16. Binocular contrast discrimination needs monocular multiplicative noise

    PubMed Central

    Ding, Jian; Levi, Dennis M.

    2016-01-01

    The effects of signal and noise on contrast discrimination are difficult to separate because of a singularity in the signal-detection-theory model of two-alternative forced-choice contrast discrimination (Katkov, Tsodyks, & Sagi, 2006). In this article, we show that it is possible to eliminate the singularity by combining that model with a binocular combination model to fit monocular, dichoptic, and binocular contrast discrimination. We performed three experiments using identical stimuli to measure the perceived phase, perceived contrast, and contrast discrimination of a cyclopean sine wave. In the absence of a fixation point, we found a binocular advantage in contrast discrimination both at low contrasts (<4%), consistent with previous studies, and at high contrasts (≥34%), which has not been previously reported. However, control experiments showed no binocular advantage at high contrasts in the presence of a fixation point or for observers without accommodation. We evaluated two putative contrast-discrimination mechanisms: a nonlinear contrast transducer and multiplicative noise (MN). A binocular combination model (the DSKL model; Ding, Klein, & Levi, 2013b) was first fitted to both the perceived-phase and the perceived-contrast data sets, then combined with either the nonlinear contrast transducer or the MN mechanism to fit the contrast-discrimination data. We found that the best model combined the DSKL model with early MN. Model simulations showed that, after going through interocular suppression, the uncorrelated noise in the two eyes became anticorrelated, resulting in less binocular noise and therefore a binocular advantage in the discrimination task. Combining a nonlinear contrast transducer or MN with a binocular combination model (DSKL) provides a powerful method for evaluating the two putative contrast-discrimination mechanisms. PMID:26982370

  17. Binocular contrast discrimination needs monocular multiplicative noise.

    PubMed

    Ding, Jian; Levi, Dennis M

    2016-01-01

    The effects of signal and noise on contrast discrimination are difficult to separate because of a singularity in the signal-detection-theory model of two-alternative forced-choice contrast discrimination (Katkov, Tsodyks, & Sagi, 2006). In this article, we show that it is possible to eliminate the singularity by combining that model with a binocular combination model to fit monocular, dichoptic, and binocular contrast discrimination. We performed three experiments using identical stimuli to measure the perceived phase, perceived contrast, and contrast discrimination of a cyclopean sine wave. In the absence of a fixation point, we found a binocular advantage in contrast discrimination both at low contrasts (<4%), consistent with previous studies, and at high contrasts (≥34%), which has not been previously reported. However, control experiments showed no binocular advantage at high contrasts in the presence of a fixation point or for observers without accommodation. We evaluated two putative contrast-discrimination mechanisms: a nonlinear contrast transducer and multiplicative noise (MN). A binocular combination model (the DSKL model; Ding, Klein, & Levi, 2013b) was first fitted to both the perceived-phase and the perceived-contrast data sets, then combined with either the nonlinear contrast transducer or the MN mechanism to fit the contrast-discrimination data. We found that the best model combined the DSKL model with early MN. Model simulations showed that, after going through interocular suppression, the uncorrelated noise in the two eyes became anticorrelated, resulting in less binocular noise and therefore a binocular advantage in the discrimination task. Combining a nonlinear contrast transducer or MN with a binocular combination model (DSKL) provides a powerful method for evaluating the two putative contrast-discrimination mechanisms.

  18. Allele-Specific Interactions between CAST AWAY and NEVERSHED Control Abscission in Arabidopsis Flowers.

    PubMed

    Groner, William D; Christy, Megan E; Kreiner, Catherine M; Liljegren, Sarah J

    2016-01-01

    An advantage of analyzing abscission in genetically tractable model plants is the ability to make use of classic genetic tools such as suppression analysis. We have investigated the regulation of organ abscission by carrying out suppression analysis in Arabidopsis flowers. Plants carrying mutations in the NEVERSHED (NEV) gene, which encodes an ADP-ribosylation factor GTPase-activating protein, retain their outer floral organs after fertilization. Mutant alleles of CAST AWAY (CST), which encodes a receptor-like cytoplasmic kinase, were found to restore organ abscission in nev flowers in an allele-specific manner. To further explore the basis of the interactions between CST and NEV, we tested whether the site of a nev mutation is predictive of its ability to be suppressed. Our results suggest instead that the strength of a nev allele influences whether organ abscission can be rescued by a specific allele of CST.

  19. Spatial heterogeneity in the strength of selection against deleterious alleles and the mutation load

    PubMed Central

    Roze, D

    2012-01-01

    According to current estimates of genomic deleterious mutation rates (which are often of the order 0.1–1) the mutation load (defined as a reduction in the average fitness of a population due to the presence of deleterious alleles) may be important in many populations. In this paper, I use multilocus simulations to explore the effect of spatial heterogeneity in the strength of selection against deleterious alleles on the mutation load (for example, it has been suggested that stressful environments may increase the strength of selection). These simulations show contrasted results: in some situations, spatial heterogeneity may greatly reduce the mutation load, due to the fact that migrants coming from demes under stronger selection carry relatively few deleterious alleles, and benefit from a strong advantage within demes under weaker selection (where individuals carry many more deleterious alleles); in other situations, however, deleterious alleles accumulate within demes under stronger selection, due to migration pressure from demes under weaker selection, leading to fitness erosion within those demes. This second situation is more frequent when the productivity of the different demes is proportional to their mean fitness. The effect of spatial heterogeneity is greatly reduced, however, when the response to environmental differences is inconsistent across loci. PMID:22588129

  20. Allelic asymmetry of the Lethal hybrid rescue (Lhr) gene expression in the hybrid between Drosophila melanogaster and D. simulans: confirmation by using genetic variations of D. melanogaster.

    PubMed

    Shirata, Mika; Araye, Quenta; Maehara, Kazunori; Enya, Sora; Takano-Shimizu, Toshiyuki; Sawamura, Kyoichi

    2014-02-01

    In the cross between Drosophila melanogaster females and D. simulans males, hybrid males die at the late larval stage, and the sibling females also die at later stages at high temperatures. Removing the D. simulans allele of the Lethal hybrid rescue gene (Lhr (sim) ) improves the hybrid incompatibility phenotypes. However, the loss-of-function mutation of Lhr (sim) (Lhr (sim0) ) does not rescue the hybrid males in crosses with several D. melanogaster strains. We first describe the genetic factor possessed by the D. melanogaster strains. It has been suggested that removing the D. melanogaster allele of Lhr (Lhr (mel) ), that is Lhr (mel0) , does not have the hybrid male rescue effect, contrasting to Lhr (sim0) . Because the expression level of the Lhr gene is known to be Lhr (sim) > Lhr (mel) in the hybrid, Lhr (mel0) may not lead to enough of a reduction in total Lhr expression. Then, there is a possibility that the D. melanogaster factor changes the expression level to Lhr (sim) < Lhr (mel) . But in fact, the expression level was Lhr (sim) > Lhr (mel) in the hybrid irrespectively of the presence of the factor. At last, we showed that Lhr (mel0) slightly improves the viability of hybrid females, which was not realized previously. All of the present results are consistent with the allelic asymmetry model of the Lhr gene expression in the hybrid.

  1. Balancing Selection at a Frog Antimicrobial Peptide Locus: Fluctuating Immune Effector Alleles?

    PubMed Central

    Blouin, Michael S.

    2008-01-01

    Balancing selection is common on many defense genes, but it has rarely been reported for immune effector proteins such as antimicrobial peptides (AMPs). We describe genetic diversity at a brevinin-1 AMP locus in three species of leopard frogs (Rana pipiens, Rana blairi, and Rana palustris). Several highly divergent allelic lineages are segregating at this locus. That this unusual pattern results from balancing selection is demonstrated by multiple lines of evidence, including a ratio of nonsynonymous/synonymous polymorphism significantly higher than 1, the ZnS test, incongruence between the number of segregating sites and haplotype diversity, and significant Tajima's D values. Our data are more consistent with a model of fluctuating selection in which alleles change frequencies over time than with a model of stable balancing selection such as overdominance. Evidence for fluctuating selection includes skewed allele frequencies, low levels of synonymous variation, nonneutral values of Tajima's D within allelic lineages, an inverse relationship between the frequency of an allelic lineage and its degree of polymorphism, and divergent allele frequencies among populations. AMP loci could be important sites of adaptive genetic diversity, with consequences for host–pathogen coevolution and the ability of species to resist disease epidemics. PMID:18799711

  2. Do Heliconius butterfly species exchange mimicry alleles?

    PubMed Central

    Smith, Joel; Kronforst, Marcus R.

    2013-01-01

    Hybridization has the potential to transfer beneficial alleles across species boundaries, and there are a growing number of examples in which this has apparently occurred. Recent studies suggest that Heliconius butterflies have transferred wing pattern mimicry alleles between species via hybridization, but ancestral polymorphism could also produce a signature of shared ancestry around mimicry genes. To distinguish between these alternative hypotheses, we measured DNA sequence divergence around putatively introgressed mimicry loci and compared this with the rest of the genome. Our results reveal that putatively introgressed regions show strongly reduced sequence divergence between co-mimetic species, suggesting that their divergence times are younger than the rest of the genome. This is consistent with introgression and not ancestral variation. We further show that this signature of introgression occurs at sites throughout the genome, not just around mimicry genes. PMID:23864282

  3. Allelic melanism in American and British peppered moths.

    PubMed

    Grant, B S

    2004-01-01

    Parallel evolutionary changes in the incidence of melanism are well documented in widely geographically separated subspecies of the peppered moth (Biston betularia). The British melanic phenotype (f. carbonaria) and the American melanic phenotype (f. swettaria) are indistinguishable in appearance, and previous genetic analysis has established that both are inherited as autosomal dominants. This report demonstrates through hybridizations of the subspecies and Mendelian testcrosses of melanic progeny that carbonaria and swettaria are phenotypes produced by alleles (isoalleles) at a single locus. The possibility of close linkage at two loci remains, but the simpler one-locus model cannot be rejected in the absence of contrary evidence.

  4. Do Insect Populations Die at Constant Rates as They Become Older? Contrasting Demographic Failure Kinetics with Respect to Temperature According to the Weibull Model.

    PubMed

    Damos, Petros; Soulopoulou, Polyxeni

    2015-01-01

    Temperature implies contrasting biological causes of demographic aging in poikilotherms. In this work, we used the reliability theory to describe the consistency of mortality with age in moth populations and to show that differentiation in hazard rates is related to extrinsic environmental causes such as temperature. Moreover, experiments that manipulate extrinsic mortality were used to distinguish temperature-related death rates and the pertinence of the Weibull aging model. The Newton-Raphson optimization method was applied to calculate parameters for small samples of ages at death by estimating the maximum likelihoods surfaces using scored gradient vectors and the Hessian matrix. The study reveals for the first time that the Weibull function is able to describe contrasting biological causes of demographic aging for moth populations maintained at different temperature regimes. We demonstrate that at favourable conditions the insect death rate accelerates as age advances, in contrast to the extreme temperatures in which each individual drifts toward death in a linear fashion and has a constant chance of passing away. Moreover, slope of hazard rates shifts towards a constant initial rate which is a pattern demonstrated by systems which are not wearing out (e.g. non-aging) since the failure, or death, is a random event independent of time. This finding may appear surprising, because, traditionally, it was mostly thought as rule that in aging population force of mortality increases exponentially until all individuals have died. Moreover, in relation to other studies, we have not observed any typical decelerating aging patterns at late life (mortality leveling-off), but rather, accelerated hazard rates at optimum temperatures and a stabilized increase at the extremes.In most cases, the increase in aging-related mortality was simulated reasonably well according to the Weibull survivorship model that is applied. Moreover, semi log- probability hazard rate model

  5. Do Insect Populations Die at Constant Rates as They Become Older? Contrasting Demographic Failure Kinetics with Respect to Temperature According to the Weibull Model

    PubMed Central

    Damos, Petros; Soulopoulou, Polyxeni

    2015-01-01

    Temperature implies contrasting biological causes of demographic aging in poikilotherms. In this work, we used the reliability theory to describe the consistency of mortality with age in moth populations and to show that differentiation in hazard rates is related to extrinsic environmental causes such as temperature. Moreover, experiments that manipulate extrinsic mortality were used to distinguish temperature-related death rates and the pertinence of the Weibull aging model. The Newton-Raphson optimization method was applied to calculate parameters for small samples of ages at death by estimating the maximum likelihoods surfaces using scored gradient vectors and the Hessian matrix. The study reveals for the first time that the Weibull function is able to describe contrasting biological causes of demographic aging for moth populations maintained at different temperature regimes. We demonstrate that at favourable conditions the insect death rate accelerates as age advances, in contrast to the extreme temperatures in which each individual drifts toward death in a linear fashion and has a constant chance of passing away. Moreover, slope of hazard rates shifts towards a constant initial rate which is a pattern demonstrated by systems which are not wearing out (e.g. non-aging) since the failure, or death, is a random event independent of time. This finding may appear surprising, because, traditionally, it was mostly thought as rule that in aging population force of mortality increases exponentially until all individuals have died. Moreover, in relation to other studies, we have not observed any typical decelerating aging patterns at late life (mortality leveling-off), but rather, accelerated hazard rates at optimum temperatures and a stabilized increase at the extremes.In most cases, the increase in aging-related mortality was simulated reasonably well according to the Weibull survivorship model that is applied. Moreover, semi log- probability hazard rate model

  6. A theory of behavioral contrast.

    PubMed

    Killeen, Peter R

    2014-11-01

    The reinforcers that maintain target instrumental responses also reinforce other responses that compete with them for expression. This competition, and its imbalance at points of transition between different schedules of reinforcement, causes behavioral contrast. The imbalance is caused by differences in the rates at which different responses come under the control of component stimuli. A model for this theory of behavioral contrast is constructed by expanding the coupling coefficient of MPR (Killeen, 1994). The coupling coefficient gives the degree of association of a reinforcer with the target response (as opposed to other competing responses). Competing responses, often identified as interim or adjunctive or superstitious behavior, are intrinsic to reinforcement schedules, especially interval schedules. In addition to that base-rate of competition, additional competing responses may spill over from the prior component, causing initial contrast; and they may be modulated by conditioned reinforcement or punishment from stimuli associated with subsequent component change, causing terminal contrast. A formalization of these hypotheses employed (a) a hysteresis model of off-target responses giving rise to initial contrast, and (b) a competing traces model of the suppression or enhancement of ongoing competitive responses by signals of following-schedule transition. The theory was applied to transient contrast, the following schedule effect, and the component duration effect.

  7. Predictive model for contrast-enhanced ultrasound of the breast: Is it feasible in malignant risk assessment of breast imaging reporting and data system 4 lesions?

    PubMed Central

    Luo, Jun; Chen, Ji-Dong; Chen, Qing; Yue, Lin-Xian; Zhou, Guo; Lan, Cheng; Li, Yi; Wu, Chi-Hua; Lu, Jing-Qiao

    2016-01-01

    AIM: To build and evaluate predictive models for contrast-enhanced ultrasound (CEUS) of the breast to distinguish between benign and malignant lesions. METHODS: A total of 235 breast imaging reporting and data system (BI-RADS) 4 solid breast lesions were imaged via CEUS before core needle biopsy or surgical resection. CEUS results were analyzed on 10 enhancing patterns to evaluate diagnostic performance of three benign and three malignant CEUS models, with pathological results used as the gold standard. A logistic regression model was developed basing on the CEUS results, and then evaluated with receiver operating curve (ROC). RESULTS: Except in cases of enhanced homogeneity, the rest of the 9 enhancement appearances were statistically significant (P < 0.05). These 9 enhancement patterns were selected in the final step of the logistic regression analysis, with diagnostic sensitivity and specificity of 84.4% and 82.7%, respectively, and the area under the ROC curve of 0.911. Diagnostic sensitivity, specificity, and accuracy of the malignant vs benign CEUS models were 84.38%, 87.77%, 86.38% and 86.46%, 81.29% and 83.40%, respectively. CONCLUSION: The breast CEUS models can predict risk of malignant breast lesions more accurately, decrease false-positive biopsy, and provide accurate BI-RADS classification. PMID:27358688

  8. Allelic variation contributes to bacterial host specificity

    SciTech Connect

    Yue, Min; Han, Xiangan; Masi, Leon De; Zhu, Chunhong; Ma, Xun; Zhang, Junjie; Wu, Renwei; Schmieder, Robert; Kaushik, Radhey S.; Fraser, George P.; Zhao, Shaohua; McDermott, Patrick F.; Weill, François-Xavier; Mainil, Jacques G.; Arze, Cesar; Fricke, W. Florian; Edwards, Robert A.; Brisson, Dustin; Zhang, Nancy R.; Rankin, Shelley C.; Schifferli, Dieter M.

    2015-10-30

    Understanding the molecular parameters that regulate cross-species transmission and host adaptation of potential pathogens is crucial to control emerging infectious disease. Although microbial pathotype diversity is conventionally associated with gene gain or loss, the role of pathoadaptive nonsynonymous single-nucleotide polymorphisms (nsSNPs) has not been systematically evaluated. Here, our genome-wide analysis of core genes within Salmonella enterica serovar Typhimurium genomes reveals a high degree of allelic variation in surface-exposed molecules, including adhesins that promote host colonization. Subsequent multinomial logistic regression, MultiPhen and Random Forest analyses of known/suspected adhesins from 580 independent Typhimurium isolates identifies distinct host-specific nsSNP signatures. Moreover, population and functional analyses of host-associated nsSNPs for FimH, the type 1 fimbrial adhesin, highlights the role of key allelic residues in host-specific adherence in vitro. In conclusion, together, our data provide the first concrete evidence that functional differences between allelic variants of bacterial proteins likely contribute to pathoadaption to diverse hosts.

  9. Allelic variation contributes to bacterial host specificity

    DOE PAGES

    Yue, Min; Han, Xiangan; Masi, Leon De; ...

    2015-10-30

    Understanding the molecular parameters that regulate cross-species transmission and host adaptation of potential pathogens is crucial to control emerging infectious disease. Although microbial pathotype diversity is conventionally associated with gene gain or loss, the role of pathoadaptive nonsynonymous single-nucleotide polymorphisms (nsSNPs) has not been systematically evaluated. Here, our genome-wide analysis of core genes within Salmonella enterica serovar Typhimurium genomes reveals a high degree of allelic variation in surface-exposed molecules, including adhesins that promote host colonization. Subsequent multinomial logistic regression, MultiPhen and Random Forest analyses of known/suspected adhesins from 580 independent Typhimurium isolates identifies distinct host-specific nsSNP signatures. Moreover, population andmore » functional analyses of host-associated nsSNPs for FimH, the type 1 fimbrial adhesin, highlights the role of key allelic residues in host-specific adherence in vitro. In conclusion, together, our data provide the first concrete evidence that functional differences between allelic variants of bacterial proteins likely contribute to pathoadaption to diverse hosts.« less

  10. The Contrastive Analysis Hypothesis

    ERIC Educational Resources Information Center

    Wardhaugh, Ronald

    1970-01-01

    Discusses the strong contrastive analysis hypothesis, which claims predictive powers for contrastive analysis, and the weak hypothesis, which claims only that contrastive analysis can help account for observed difficulties in second language learning. The strong hypothesis is found untenable, and difficulties with the weak hypothesis are discussed…

  11. Increasing long term response by selecting for favorable minor alleles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long-term response of genomic selection can be improved by considering allele frequencies of selected markers or quantitative trait loci (QTLs). A previous formula to weight allele frequency of favorable minor alleles was tested, and 2 new formulas were developed. The previous formula used nonlinear...

  12. Mutant maize variety containing the glt1-1 allele

    DOEpatents

    Nelson, O.E.; Pan, D.

    1994-07-19

    A maize plant has in its genome a non-mutable form of a mutant allele designated vitX-8132. The allele is located at a locus designated as glt which conditions kernels having an altered starch characteristic. Maize plants including such a mutant allele produce a starch that does not increase in viscosity on cooling, after heating. 2 figs.

  13. Mutant maize variety containing the glt1-1 allele

    DOEpatents

    Nelson, Oliver E.; Pan, David

    1994-01-01

    A maize plant has in its genome a non-mutable form of a mutant allele designated vitX-8132. The allele is located at a locus designated as glt which conditions kernels having an altered starch characteristic. Maize plants including such a mutant allele produce a starch that does not increase in viscosity on cooling, after heating.

  14. PCR Strategies for Complete Allele Calling in Multigene Families Using High-Throughput Sequencing Approaches.

    PubMed

    Marmesat, Elena; Soriano, Laura; Mazzoni, Camila J; Sommer, Simone; Godoy, José A

    2016-01-01

    The characterization of multigene families with high copy number variation is often approached through PCR amplification with highly degenerate primers to account for all expected variants flanking the region of interest. Such an approach often introduces PCR biases that result in an unbalanced representation of targets in high-throughput sequencing libraries that eventually results in incomplete detection of the targeted alleles. Here we confirm this result and propose two different amplification strategies to alleviate this problem. The first strategy (called pooled-PCRs) targets different subsets of alleles in multiple independent PCRs using different moderately degenerate primer pairs, whereas the second approach (called pooled-primers) uses a custom-made pool of non-degenerate primers in a single PCR. We compare their performance to the common use of a single PCR with highly degenerate primers using the MHC class I of the Iberian lynx as a model. We found both novel approaches to work similarly well and better than the conventional approach. They significantly scored more alleles per individual (11.33 ± 1.38 and 11.72 ± 0.89 vs 7.94 ± 1.95), yielded more complete allelic profiles (96.28 ± 8.46 and 99.50 ± 2.12 vs 63.76 ± 15.43), and revealed more alleles at a population level (13 vs 12). Finally, we could link each allele's amplification efficiency with the primer-mismatches in its flanking sequences and show that ultra-deep coverage offered by high-throughput technologies does not fully compensate for such biases, especially as real alleles may reach lower coverage than artefacts. Adopting either of the proposed amplification methods provides the opportunity to attain more complete allelic profiles at lower coverages, improving confidence over the downstream analyses and subsequent applications.

  15. Semiparametric Allelic Tests for Mapping Multiple Phenotypes: Binomial Regression and Mahalanobis Distance.

    PubMed

    Majumdar, Arunabha; Witte, John S; Ghosh, Saurabh

    2015-12-01

    Binary phenotypes commonly arise due to multiple underlying quantitative precursors and genetic variants may impact multiple traits in a pleiotropic manner. Hence, simultaneously analyzing such correlated traits may be more powerful than analyzing individual traits. Various genotype-level methods, e.g., MultiPhen (O'Reilly et al. []), have been developed to identify genetic factors underlying a multivariate phenotype. For univariate phenotypes, the usefulness and applicability of allele-level tests have been investigated. The test of allele frequency difference among cases and controls is commonly used for mapping case-control association. However, allelic methods for multivariate association mapping have not been studied much. In this article, we explore two allelic tests of multivariate association: one using a Binomial regression model based on inverted regression of genotype on phenotype (Binomial regression-based Association of Multivariate Phenotypes [BAMP]), and the other employing the Mahalanobis distance between two sample means of the multivariate phenotype vector for two alleles at a single-nucleotide polymorphism (Distance-based Association of Multivariate Phenotypes [DAMP]). These methods can incorporate both discrete and continuous phenotypes. Some theoretical properties for BAMP are studied. Using simulations, the power of the methods for detecting multivariate association is compared with the genotype-level test MultiPhen's. The allelic tests yield marginally higher power than MultiPhen for multivariate phenotypes. For one/two binary traits under recessive mode of inheritance, allelic tests are found to be substantially more powerful. All three tests are applied to two different real data and the results offer some support for the simulation study. We propose a hybrid approach for testing multivariate association that implements MultiPhen when Hardy-Weinberg Equilibrium (HWE) is violated and BAMP otherwise, because the allelic approaches assume HWE.

  16. Microsatellite allele sizes: a simple test to assess their significance on genetic differentiation.

    PubMed Central

    Hardy, Olivier J; Charbonnel, Nathalie; Fréville, Hélène; Heuertz, Myriam

    2003-01-01

    The mutation process at microsatellite loci typically occurs at high rates and with stepwise changes in allele sizes, features that may introduce bias when using classical measures of population differentiation based on allele identity (e.g., F(ST), Nei's Ds genetic distance). Allele size-based measures of differentiation, assuming a stepwise mutation process [e.g., Slatkin's R(ST), Goldstein et al.'s (deltamu)(2)], may better reflect differentiation at microsatellite loci, but they suffer high sampling variance. The relative efficiency of allele size- vs. allele identity-based statistics depends on the relative contributions of mutations vs. drift to population differentiation. We present a simple test based on a randomization procedure of allele sizes to determine whether stepwise-like mutations contributed to genetic differentiation. This test can be applied to any microsatellite data set designed to assess population differentiation and can be interpreted as testing whether F(ST) = R(ST). Computer simulations show that the test efficiently identifies which of F(ST) or R(ST) estimates has the lowest mean square error. A significant test, implying that R(ST) performs better than F(ST), is obtained when the mutation rate, mu, for a stepwise mutation process is (a) >/= m in an island model (m being the migration rate among populations) or (b) >/= 1/t in the case of isolated populations (t being the number of generations since population divergence). The test also informs on the efficiency of other statistics used in phylogenetical reconstruction [e.g., Ds and (deltamu)(2)], a nonsignificant test meaning that allele identity-based statistics perform better than allele size-based ones. This test can also provide insights into the evolutionary history of populations, revealing, for example, phylogeographic patterns, as illustrated by applying it on three published data sets. PMID:12702690

  17. Selection of achromatic and non-neutral colors to fill lacunae in frescoes guided by a variational model of perceived contrast

    NASA Astrophysics Data System (ADS)

    Grementieri, Luca; Provenzi, Edoardo

    2017-02-01

    Many ancient paintings, in particular frescoes, have some parts ruined by time and events. Sometimes one or more non-negligible regions are completely lost, leaving a blank that is called by restaurateurs a `lacuna'. The general restoration philosophy adopted in these cases is to paint the interior part of the lacuna with an achromatic or non-neutral uniform color carefully selected in order to minimize its overall perception. In this paper, we present a computational model, based on a well-established variational theory of color perception, that may facilitate the job of a restaurateur by providing both achromatic and non-neutral colors which minimize the local contrast with the surrounding parts of the fresco.

  18. The Minor Allele of rs7574865 in the STAT4 Gene Is Associated with Increased mRNA and Protein Expression

    PubMed Central

    Lamana, Amalia; López-Santalla, Mercedes; Castillo-González, Raquel; Ortiz, Ana María; Martín, Javier; García-Vicuña, Rosario; González-Álvaro, Isidoro

    2015-01-01

    Objective The T allele of rs7574865 in STAT4 confers risk of developing autoimmune disorders. However, its functional significance remains unclear. Here we analyze how rs7574865 affects the transcription of STAT4 and its protein expression. Methods We studied 201 patients (80% female; median age, 54 years; median disease duration, 5.4 months) from PEARL study. Demographic, clinical, laboratory and therapeutic data were collected at each visit. IL-6 serum levels were measured by enzyme immune assay. The rs7574865 was genotyped using TaqMan probes. The expression levels of STAT4 mRNA were determined at 182 visits from 69 patients using quantitative real-time polymerase chain reaction. STAT4 protein was assessed by western blot in 62 samples from 34 patients. To determine the effect of different variables on the expression of STAT4 mRNA and protein, we performed multivariate longitudinal analyses using generalized linear models. Results After adjustment for age, disease activity and glucocorticoid dose as confounders, the presence of at least one copy of the T allele of rs7574865 was significantly associated with higher levels of STAT4 mRNA. Similarly, TT patients showed significantly higher levels of STAT4 protein than GG patients. IL-6 induced STAT4 and STAT5 phosphorylation in peripheral blood lymphocytes. Patients carrying at least one T allele of rs7574865 displayed lower levels of serum IL-6 compared to GG homozygous; by contrast the production of C-reactive protein was similar in both populations. Conclusion Our data suggest that the presence of the rs7574865 T allele enhances STAT4 mRNA transcription and protein expression. It may enhance the signaling of molecules depending on the STAT4 pathway. PMID:26569609

  19. Automated analysis of sequence polymorphism in STR alleles by PCR and direct electrospray ionization mass spectrometry.

    PubMed

    Planz, John V; Sannes-Lowery, Kristen A; Duncan, David D; Manalili, Sheri; Budowle, Bruce; Chakraborty, Ranajit; Hofstadler, Steven A; Hall, Thomas A

    2012-09-01

    Short tandem repeats (STRs) are the primary genetic markers used for the analysis of biological samples in forensic and human identity testing. The discrimination power of a combination of STRs is sufficient in many human identity testing comparisons unless the evidence is substantially compromised and/or there are insufficient relatives or a potential mutation may have arisen in kinship analyses. An automated STR assay system that is based on electrospray ionization mass spectrometry (ESI-MS) has been developed that can increase the discrimination power of some of the CODIS core STR loci and thus provide more information in typical and challenged samples and cases. Data from the ESI-MS STR system is fully backwards compatible with existing STR typing results generated by capillary electrophoresis. In contrast, however, the ESI-MS analytical system also reveals nucleotide polymorphisms residing within the STR alleles. The presence of these polymorphisms expands the number of alleles at a locus. Population studies were performed on the 13 core CODIS STR loci from African Americans, Caucasians and Hispanics capturing both the length of the allele, as well as nucleotide variations contained within repeat motifs or flanking regions. Such additional polymorphisms were identified in 11 of the 13 loci examined whereby several nominal length alleles were subdivided. A substantial increase in heterozygosity was observed, with close to or greater than 5% of samples analyzed being heterozygous with equal-length alleles in at least one of five of the core CODIS loci. This additional polymorphism increases discrimination power significantly, whereby the seven most polymorphic STR loci have a discrimination power equivalent to the 10 most discriminating of the CODIS core loci. An analysis of substructure among the three population groups revealed a higher θ than would be observed compared with using alleles designated by nominal length, i.e., repeats solely. Two loci, D3S1358

  20. Identification of the third/extra allele for forensic application in cases with TPOX tri-allelic pattern.

    PubMed

    Picanço, Juliane Bentes; Raimann, Paulo Eduardo; da Motta, Carlos Henrique Ares Silveira; Rodenbusch, Rodrigo; Gusmão, Leonor; Alho, Clarice Sampaio

    2015-05-01

    Genotyping of polymorphic short tandem repeats (STRs) loci is widely used in forensic DNA analysis. STR loci eventually present tri-allelic pattern as a genotyping irregularity and, in that situation, the doubt about the tri-allele locus frequency calculation can reduce the analysis strength. In the TPOX human STR locus, tri-allelic genotypes have been reported with a widely varied frequency among human populations. We investigate whether there is a single extra allele (the third allele) in the TPOX tri-allelic pattern, what it is, and where it is, aiming to understand its genomic anatomy and to propose the knowledge of this TPOX extra allele from genetic profile, thus preserving the two standard TPOX alleles in forensic analyses. We looked for TPOX tri-allelic subjects in 75,113 Brazilian families. Considering only the parental generation (mother+father) we had 150,226 unrelated subjects evaluated. From this total, we found 88 unrelated subjects with tri-allelic pattern in the TPOX locus (0.06%; 88/150,226). Seventy three of these 88 subjects (73/88; 83%) had the Clayton's original Type 2 tri-allelic pattern (three peaks of even intensity). The remaining 17% (15/88) show a new Type 2 derived category with heterozygote peak imbalance (one double dose peak plus one regular sized peak). In this paper we present detailed data from 66 trios (mother+father+child) with true biological relationships. In 39 of these families (39/66; 59%) the extra TPOX allele was transmitted either from the mother or from the father to the child. Evidences indicated the allele 10 as the extra TPOX allele, and it is on the X chromosome. The present data, which support the previous Lane hypothesis, improve the knowledge about tri-allelic pattern of TPOX CODIS' locus allowing the use of TPOX profile in forensic analyses even when with tri-allelic pattern. This evaluation is now available for different forensic applications.

  1. Contrasting strategic and Milan therapies.

    PubMed

    MacKinnon, L

    1983-12-01

    Three related models of therapy are often grouped together as the strategic therapies. These are brief therapy model associated with the Mental Research Institute, approaches developed by Jay Haley and Cloë Madanes, and the model developed by the Milan associates. Controversy exists, however, as to whether the Milan model should be included as a strategic therapy. It appears that the similarities among the three models can mask deeper differences, thus confounding the confusion. This paper contrast the models in their development, theory, and practice.

  2. Update on allele nomenclature for human cytochromes P450 and the Human Cytochrome P450 Allele (CYP-allele) Nomenclature Database.

    PubMed

    Sim, Sarah C; Ingelman-Sundberg, Magnus

    2013-01-01

    Interindividual variability in xenobiotic metabolism and drug response is extensive and genetic factors play an important role in this variation. A majority of clinically used drugs are substrates for the cytochrome P450 (CYP) enzyme system and interindividual variability in expression and function of these enzymes is a major factor for explaining individual susceptibility for adverse drug reactions and drug response. Because of the existence of many polymorphic CYP genes, for many of which the number of allelic variants is continually increasing, a universal and official nomenclature system is important. Since 1999, all functionally relevant polymorphic CYP alleles are named and published on the Human Cytochrome P450 Allele (CYP-allele) Nomenclature Web site (http://www.cypalleles.ki.se). Currently, the database covers nomenclature of more than 660 alleles in a total of 30 genes that includes 29 CYPs as well as the cytochrome P450 oxidoreductase (POR) gene. On the CYP-allele Web site, each gene has its own Webpage, which lists the alleles with their nucleotide changes, their functional consequences, and links to publications identifying or characterizing the alleles. CYP2D6, CYP2C9, CYP2C19, and CYP3A4 are the most important CYPs in terms of drug metabolism, which is also reflected in their corresponding highest number of Webpage hits at the CYP-allele Web site.The main advantage of the CYP-allele database is that it offers a rapid online publication of CYP-alleles and their effects and provides an overview of peer-reviewed data to the scientific community. Here, we provide an update of the CYP-allele database and the associated nomenclature.

  3. New modeling of reflection interference contrast microscopy including polarization and numerical aperture effects: application to nanometric distance measurements and object profile reconstruction.

    PubMed

    Theodoly, O; Huang, Z-H; Valignat, M-P

    2010-02-02

    We have developed a new and improved optical model of reflection interference contrast microscopy (RICM) to determine with a precision of a few nanometers the absolute thickness h of thin films on a flat surface in immersed conditions. The model takes into account multiple reflections between a planar surface and a multistratified object, finite aperture illumination (INA), and, for the first time, the polarization of light. RICM intensity I is typically oscillating with h. We introduce a new normalization procedure that uses the intensity extrema of the same oscillation order for both experimental and theoretical intensity values and permits us to avoid significant error in the absolute height determination, especially at high INA. We also show how the problem of solution degeneracy can be solved by taking pictures at two different INA values. The model is applied to filled polystyrene beads and giant unilamellar vesicles of radius 10-40 microm sitting on a glass substrate. The RICM profiles I(h) can be fitted for up to two to three oscillation orders, and extrema positions are correct for up to five to seven oscillation orders. The precision of the absolute distance and of the shape of objects near a substrate is about 5 nm in a range from 0 to 500 nm, even under large numerical aperture conditions. The method is especially valuable for dynamic RICM experiments and with living cells where large illumination apertures are required.

  4. Introgressive hybridization: brown bears as vectors for polar bear alleles.

    PubMed

    Hailer, Frank

    2015-03-01

    The dynamics and consequences of introgression can inform about numerous evolutionary processes. Biologists have therefore long been interested in hybridization. One challenge, however, lies in the identification of nonadmixed genotypes that can serve as a baseline for accurate quantification of admixture. In this issue of Molecular Ecology, Cahill et al. (2015) analyse a genomic data set of 28 polar bears, eight brown bears and one American black bear. Polar bear alleles are found to be introgressed into brown bears not only near a previously identified admixture zone on the Alaskan Admiralty, Baranof and Chichagof (ABC) Islands, but also far into the North American mainland. Elegantly contrasting admixture levels at autosomal and X chromosomal markers, Cahill and colleagues infer that male-biased dispersal has spread these introgressed alleles away from the Late Pleistocene contact zone. Compared to a previous study on the ABC Island population in which an Alaskan brown bear served as a putatively admixture-free reference, Cahill et al. (2015) utilize a newly sequenced Swedish brown bear as admixture baseline. This approach reveals that brown bears have been impacted by introgression from polar bears to a larger extent (up to 8.8% of their genome), than previously known, including the bear that had previously served as admixture baseline. No evidence for introgression of brown bear into polar bear is found, which the authors argue could be a consequence of selection. Besides adding new exciting pieces to the puzzle of polar/brown bear evolutionary history, the study by Cahill and colleagues highlights that wildlife genomics is moving from analysing single genomes towards a landscape genomics approach.

  5. Borrowed alleles and convergence in serpentine adaptation

    PubMed Central

    Arnold, Brian J.; Lahner, Brett; DaCosta, Jeffrey M.; Weisman, Caroline M.; Hollister, Jesse D.; Salt, David E.; Bomblies, Kirsten; Yant, Levi

    2016-01-01

    Serpentine barrens represent extreme hazards for plant colonists. These sites are characterized by high porosity leading to drought, lack of essential mineral nutrients, and phytotoxic levels of metals. Nevertheless, nature forged populations adapted to these challenges. Here, we use a population-based evolutionary genomic approach coupled with elemental profiling to assess how autotetraploid Arabidopsis arenosa adapted to a multichallenge serpentine habitat in the Austrian Alps. We first demonstrate that serpentine-adapted plants exhibit dramatically altered elemental accumulation levels in common conditions, and then resequence 24 autotetraploid individuals from three populations to perform a genome scan. We find evidence for highly localized selective sweeps that point to a polygenic, multitrait basis for serpentine adaptation. Comparing our results to a previous study of independent serpentine colonizations in the closely related diploid Arabidopsis lyrata in the United Kingdom and United States, we find the highest levels of differentiation in 11 of the same loci, providing candidate alleles for mediating convergent evolution. This overlap between independent colonizations in different species suggests that a limited number of evolutionary strategies are suited to overcome the multiple challenges of serpentine adaptation. Interestingly, we detect footprints of selection in A. arenosa in the context of substantial gene flow from nearby off-serpentine populations of A. arenosa, as well as from A. lyrata. In several cases, quantitative tests of introgression indicate that some alleles exhibiting strong selective sweep signatures appear to have been introgressed from A. lyrata. This finding suggests that migrant alleles may have facilitated adaptation of A. arenosa to this multihazard environment. PMID:27357660

  6. Biased gene conversion skews allele frequencies in human populations, increasing the disease burden of recessive alleles.

    PubMed

    Lachance, Joseph; Tishkoff, Sarah A

    2014-10-02

    Gene conversion results in the nonreciprocal transfer of genetic information between two recombining sequences, and there is evidence that this process is biased toward G and C alleles. However, the strength of GC-biased gene conversion (gBGC) in human populations and its effects on hereditary disease have yet to be assessed on a genomic scale. Using high-coverage whole-genome sequences of African hunter-gatherers, agricultural populations, and primate outgroups, we quantified the effects of GC-biased gene conversion on population genomic data sets. We find that genetic distances (FST and population branch statistics) are modified by gBGC. In addition, the site frequency spectrum is left-shifted when ancestral alleles are favored by gBGC and right-shifted when derived alleles are favored by gBGC. Allele frequency shifts due to gBGC mimic the effects of natural selection. As expected, these effects are strongest in high-recombination regions of the human genome. By comparing the relative rates of fixation of unbiased and biased sites, the strength of gene conversion was estimated to be on the order of Nb ≈ 0.05 to 0.09. We also find that derived alleles favored by gBGC are much more likely to be homozygous than derived alleles at unbiased SNPs (+42.2% to 62.8%). This results in a curse of the converted, whereby gBGC causes substantial increases in hereditary disease risks. Taken together, our findings reveal that GC-biased gene conversion has important population genetic and public health implications.

  7. Contrasting two models of academic self-efficacy--domain-specific versus cross-domain--in children receiving and not receiving special instruction in mathematics.

    PubMed

    Jungert, Tomas; Hesser, Hugo; Träff, Ulf

    2014-10-01

    In social cognitive theory, self-efficacy is domain-specific. An alternative model, the cross-domain influence model, would predict that self-efficacy beliefs in one domain might influence performance in other domains. Research has also found that children who receive special instruction are not good at estimating their performance. The aim was to test two models of how self-efficacy beliefs influence achievement, and to contrast children receiving special instruction in mathematics with normally-achieving children. The participants were 73 fifth-grade children who receive special instruction and 70 children who do not receive any special instruction. In year four and five, the children's skills in mathematics and reading were assessed by national curriculum tests, and in their fifth year, self-efficacy in mathematics and reading were measured. Structural equation modeling showed that in domains where children do not receive special instruction in mathematics, self-efficacy is a mediating variable between earlier and later achievement in the same domain. Achievement in mathematics was not mediated by self-efficacy in mathematics for children who receive special instruction. For normal achieving children, earlier achievement in the language domain had an influence on later self-efficacy in the mathematics domain, and self-efficacy beliefs in different domains were correlated. Self-efficacy is mostly domain specific, but may play a different role in academic performance depending on whether children receive special instruction. The results of the present study provided some support of the Cross-Domain Influence Model for normal achieving children.

  8. Enhanced low-template DNA analysis conditions and investigation of allele dropout patterns.

    PubMed

    Hedell, Ronny; Dufva, Charlotte; Ansell, Ricky; Mostad, Petter; Hedman, Johannes

    2015-01-01

    Forensic DNA analysis applying PCR enables profiling of minute biological samples. Enhanced analysis conditions can be applied to further push the limit of detection, coming with the risk of visualising artefacts and allele imbalances. We have evaluated the consecutive increase of PCR cycles from 30 to 35 to investigate the limitations of low-template (LT) DNA analysis, applying the short tandem repeat (STR) analysis kit PowerPlex ESX 16. Mock crime scene DNA extracts of four different quantities (from around 8-84 pg) were tested. All PCR products were analysed using 5, 10 and 20 capillary electrophoresis (CE) injection seconds. Bayesian models describing allele dropout patterns, allele peak heights and heterozygote balance were developed to assess the overall improvements in EPG quality with altered PCR/CE settings. The models were also used to evaluate the impact of amplicon length, STR marker and fluorescent label on the risk for allele dropout. The allele dropout probability decreased for each PCR cycle increment from 30 to 33 PCR cycles. Irrespective of DNA amount, the dropout probability was not affected by further increasing the number of PCR cycles. For the 42 and 84 pg samples, mainly complete DNA profiles were generated applying 32 PCR cycles. For the 8 and 17 pg samples, the allele dropouts decreased from 100% using 30 cycles to about 75% and 20%, respectively. The results for 33, 34 and 35 PCR cycles indicated that heterozygote balance and stutter ratio were mainly affected by DNA amount, and not directly by PCR cycle number and CE injection settings. We found 32 and 33 PCR cycles with 10 CE injection seconds to be optimal, as 34 and 35 PCR cycles did not improve allele detection and also included CE saturation problems. We find allele dropout probability differences between several STR markers. Markers labelled with the fluorescent dyes CXR-ET (red in electropherogram) and TMR-ET (shown as black) generally have higher dropout risks compared with those

  9. Allele-specific copy number profiling by next-generation DNA sequencing.

    PubMed

    Chen, Hao; Bell, John M; Zavala, Nicolas A; Ji, Hanlee P; Zhang, Nancy R

    2015-02-27

    The progression and clonal development of tumors often involve amplifications and deletions of genomic DNA. Estimation of allele-specific copy number, which quantifies the number of copies of each allele at each variant loci rather than the total number of chromosome copies, is an important step in the characterization of tumor genomes and the inference of their clonal history. We describe a new method, falcon, for finding somatic allele-specific copy number changes by next generation sequencing of tumors with matched normals. falcon is based on a change-point model on a bivariate mixed Binomial process, which explicitly models the copy numbers of the two chromosome haplotypes and corrects for local allele-specific coverage biases. By using the Binomial distribution rather than a normal approximation, falcon more effectively pools evidence from sites with low coverage. A modified Bayesian information criterion is used to guide model selection for determining the number of copy number events. Falcon is evaluated on in silico spike-in data and applied to the analysis of a pre-malignant colon tumor sample and late-stage colorectal adenocarcinoma from the same individual. The allele-specific copy number estimates obtained by falcon allows us to draw detailed conclusions regarding the clonal history of the individual's colon cancer.

  10. Kinetic analysis of superparamagnetic iron oxide nanoparticles in the liver of body-temperature-controlled mice using dynamic susceptibility contrast magnetic resonance imaging and an empirical mathematical model.

    PubMed

    Murase, Kenya; Assanai, Purapan; Takata, Hiroshige; Matsumoto, Nozomi; Saito, Shigeyoshi; Nishiura, Motoko

    2015-06-01

    The purpose of this study was to develop a method for analyzing the kinetic behavior of superparamagnetic iron oxide nanoparticles (SPIONs) in the murine liver under control of body temperature using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) and an empirical mathematical model (EMM). First, we investigated the influence of body temperature on the kinetic behavior of SPIONs in the liver by controlling body temperature using our temperature-control system. Second, we investigated the kinetic behavior of SPIONs in the liver when mice were injected with various doses of GdCl3, while keeping the body temperature at 36°C. Finally, we investigated it when mice were injected with various doses of zymosan, while keeping the body temperature at 36°C. We also investigated the effect of these substances on the number of Kupffer cells by immunohistochemical analysis using the specific surface antigen of Kupffer cells (CD68). To quantify the kinetic behavior of SPIONs in the liver, we calculated the upper limit of the relative enhancement (A), the rates of early contrast uptake (α) and washout or late contrast uptake (β), the parameter related to the slope of early uptake (q), the area under the curve (AUC), the maximum change of transverse relaxation rate (ΔR2) (ΔR2(max)), the time to ΔR2(max) (Tmax), and ΔR2 at the last time point (ΔR2(last)) from the time courses of ΔR2 using the EMM. The β and Tmax values significantly decreased and increased, respectively, with decreasing body temperature, suggesting that the phagocytic activity of Kupffer cells is significantly affected by body temperature. The AUC, ΔR2(max), and ΔR2(last) values decreased significantly with increasing dose of GdCl3, which was consistent with the change in the number of CD68-positive cells. They increased with increasing dose of zymosan, which was also consistent with the change in the number of CD68-positive cells. These results suggest that AUC, ΔR2(max), and ΔR2

  11. The Impact of Arterial Input Function Determination Variations on Prostate Dynamic Contrast-Enhanced Magnetic Resonance Imaging Pharmacokinetic Modeling: A Multicenter Data Analysis Challenge

    PubMed Central

    Huang, Wei; Chen, Yiyi; Fedorov, Andriy; Li, Xia; Jajamovich, Guido H.; Malyarenko, Dariya I.; Aryal, Madhava P.; LaViolette, Peter S.; Oborski, Matthew J.; O'Sullivan, Finbarr; Abramson, Richard G.; Jafari-Khouzani, Kourosh; Afzal, Aneela; Tudorica, Alina; Moloney, Brendan; Gupta, Sandeep N.; Besa, Cecilia; Kalpathy-Cramer, Jayashree; Mountz, James M.; Laymon, Charles M.; Muzi, Mark; Schmainda, Kathleen; Cao, Yue; Chenevert, Thomas L.; Taouli, Bachir; Yankeelov, Thomas E.; Fennessy, Fiona; Li, Xin

    2016-01-01

    Dynamic contrast-enhanced MRI (DCE-MRI) has been widely used in tumor detection and therapy response evaluation. Pharmacokinetic analysis of DCE-MRI time-course data allows estimation of quantitative imaging biomarkers such as Ktrans(rate constant for plasma/interstitium contrast reagent (CR) transfer) and ve (extravascular and extracellular volume fraction). However, the use of quantitative DCE-MRI in clinical prostate imaging islimited, with uncertainty in arterial input function (AIF, i.e., the time rate of change of the concentration of CR in the blood plasma) determination being one of the primary reasons. In this multicenter data analysis challenge to assess the effects of variations in AIF quantification on estimation of DCE-MRI parameters, prostate DCE-MRI data acquired at one center from 11 prostate cancer patients were shared among nine centers. Each center used its site-specific method to determine the individual AIF from each data set and submitted the results to the managing center. Along with a literature population averaged AIF, these AIFs and their reference-tissue-adjusted variants were used by the managing center to perform pharmacokinetic analysis of the DCE-MRI data sets using the Tofts model (TM). All other variables including tumor region of interest (ROI) definition and pre-contrast T1 were kept the same to evaluate parameter variations caused by AIF variations only. Considerable pharmacokinetic parameter variations were observed with the within-subject coefficient of variation (wCV) of Ktrans obtained with unadjusted AIFs as high as 0.74. AIF-caused variations were larger in Ktrans than ve and both were reduced when reference-tissue-adjusted AIFs were used. The parameter variations were largely systematic, resulting in nearly unchanged parametric map patterns. The CR intravasation rate constant, kep (= Ktrans/ve), was less sensitive to AIF variation than Ktrans (wCV for unadjusted AIFs: 0.45 for kep vs. 0.74 for Ktrans), suggesting that it

  12. Cyanine 5.5 Conjugated Nanobubbles as a Tumor Selective Contrast Agent for Dual Ultrasound-Fluorescence Imaging in a Mouse Model

    PubMed Central

    Li, Jing; Wei, Qiong; Yuchi, Ming; He, Xiaoling; Ding, Mingyue; Zhou, Qibing

    2013-01-01

    Nanobubbles and microbubbles are non-invasive ultrasound imaging contrast agents that may potentially enhance diagnosis of tumors. However, to date, both nanobubbles and microbubbles display poor in vivo tumor-selectivity over non-targeted organs such as liver. We report here cyanine 5.5 conjugated nanobubbles (cy5.5-nanobubbles) of a biocompatible chitosan–vitamin C lipid system as a dual ultrasound-fluorescence contrast agent that achieved tumor-selective imaging in a mouse tumor model. Cy5.5-nanobubble suspension contained single bubble spheres and clusters of bubble spheres with the size ranging between 400–800 nm. In the in vivo mouse study, enhancement of ultrasound signals at tumor site was found to persist over 2 h while tumor-selective fluorescence emission was persistently observed over 24 h with intravenous injection of cy5.5-nanobubbles. In vitro cell study indicated that cy5.5-flurescence dye was able to accumulate in cancer cells due to the unique conjugated nanobubble structure. Further in vivo fluorescence study suggested that cy5.5-nanobubbles were mainly located at tumor site and in the bladder of mice. Subsequent analysis confirmed that accumulation of high fluorescence was present at the intact subcutaneous tumor site and in isolated tumor tissue but not in liver tissue post intravenous injection of cy5.5-nanobubbles. All these results led to the conclusion that cy5.5-nanobubbles with unique crosslinked chitosan–vitamin C lipid system have achieved tumor-selective imaging in vivo. PMID:23637799

  13. Seasonal and interannual variations of carbon and oxygen isotopes of respired CO2 in a tallgrass prairie: Measurements and modeling results from 3 years with contrasting water availability

    NASA Astrophysics Data System (ADS)

    Lai, Chun-Ta; Riley, William; Owensby, Clenton; Ham, Jay; Schauer, Andrew; Ehleringer, James R.

    2006-04-01

    We made weekly measurements of carbon (δ13C) and oxygen (δ18O) isotopes of atmospheric CO2 in a C3/C4 tallgrass prairie during the growing season for 3 years with contrasting soil moisture conditions. Air samples above and within canopies were collected using 100-ml flasks at night to characterize isotopic composition of ecosystem respiration. We used a two-source mixing line (Keeling plot) approach to estimate isotope ratios of ecosystem respired CO2 for both carbon (δ13CR) and oxygen (δ18OR). Measured net ecosystem CO2 exchange (NEE) showed the largest net carbon uptake in 2004, followed by 2003 and 2002. This interannual difference in NEE strongly depends on the amount and distribution of precipitation received by this tallgrass prairie. Precipitation also affects the timing of the seasonal transition from C3 dominance in spring to C4 dominance in summer. Variations of δ13CR showed that C4 plants dominated ecosystem respiration in 2003 and 2004, except in early spring when C3 plants were more active. In contrast, contributions of C3 plants were relatively higher for an extended period in the summer of 2002, when a severe drought occurred. Typically, C3 forbs extract water and nutrients from soil layers below that of the C4 grasses and remain photosynthetically active in periods when C4 grasses have water stress that limits photosynthesis. Drought-reduced C4 grass photosynthesis was lower than temperature-limited C3 forb growth during this period. We used an integrated isotope land surface model (ISOLSM) to simulate (and compare to measurements) net CO2 fluxes, δ18O values of leaf and soil water, and δ18O values of aboveground and soil respiration. The Keeling plot analysis becomes less reliable for estimating δ18OR values when the surface soil is dry. We suspect this is due to low CO2 production in the soil when water is limiting, in which case the invasion (abiotic) effect is more significant. ISOLSM reasonably captured seasonal variations of measured

  14. Quantitative Assessment of Tumor Responses after Radiation Therapy in a DLD-1 Colon Cancer Mouse Model Using Serial Dynamic Contrast-Enhanced Magnetic Resonance Imaging

    PubMed Central

    Ahn, Sung Jun; Koom, Woong Sub; An, Chan Sik; Lim, Joon Seok; Lee, Seung-Koo; Suh, Jin-Suck

    2012-01-01

    Purpose The purpose of this study was to investigate the predictability of pretreatment values including Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) derived parameters (Ktrans, Kep and Ve), early changes in parameters (Ktrans, tumor volume), and heterogeneity (standard deviation of Ktrans) for radiation therapy responses via a human colorectal cancer xenograft model. Materials and Methods A human colorectal cancer xenograft model with DLD-1 cancer cells was produced in the right hind limbs of five mice. Tumors were irradiated with 3 fractions of 3 Gy each for 3 weeks. Baseline and follow up DCE-MRI were performed. Quantitative parameters (Ktrans, Kep and Ve) were calculated based on the Tofts model. Early changes in Ktrans, standard deviation (SD) of Ktrans, and tumor volume were also calculated. Tumor responses were evaluated based on histology. With a cut-off value of 0.4 for necrotic factor, a comparison between good and poor responses was conducted. Results The good response group (mice #1 and 2) exhibited higher pretreatment Ktrans than the poor response group (mice #3, 4, and 5). The good response group tended to show lower pretreatment Kep, higher pretreatment Ve, and larger baseline tumor volume than the poor response group. All the mice in the good response group demonstrated marked reductions in Ktrans and SD value after the first radiation. All tumors showed increased volume after the first radiation therapy. Conclusion The good response after radiation therapy group in the DLD-1 colon cancer xenograft nude mouse model exhibited a higher pretreatment Ktrans and showed an early reduction in Ktrans, demonstrating a more homogenous distribution. PMID:23074115

  15. Exquisite allele discrimination by toehold hairpin primers

    PubMed Central

    Byrom, Michelle; Bhadra, Sanchita; Jiang, Yu Sherry; Ellington, Andrew D.

    2014-01-01

    The ability to detect and monitor single nucleotide polymorphisms (SNPs) in biological samples is an enabling research and clinical tool. We have developed a surprising, inexpensive primer design method that provides exquisite discrimination between SNPs. The field of DNA computation is largely reliant on using so-called toeholds to initiate strand displacement reactions, leading to the execution of kinetically trapped circuits. We have now similarly found that the short toehold sequence to a target of interest can initiate both strand displacement within the hairpin and extension of the primer by a polymerase, both of which will further stabilize the primer:template complex. However, if the short toehold does not bind, neither of these events can readily occur and thus amplification should not occur. Toehold hairpin primers were used to detect drug resistance alleles in two genes, rpoB and katG, in the Mycobacterium tuberculosis genome, and ten alleles in the Escherichia coli genome. During real-time PCR, the primers discriminate between mismatched templates with Cq delays that are frequently so large that the presence or absence of mismatches is essentially a ‘yes/no’ answer. PMID:24990378

  16. Automatic segmentation of the liver using multi-planar anatomy and deformable surface model in abdominal contrast-enhanced CT images

    NASA Astrophysics Data System (ADS)

    Jang, Yujin; Hong, Helen; Chung, Jin Wook; Yoon, Young Ho

    2012-02-01

    We propose an effective technique for the extraction of liver boundary based on multi-planar anatomy and deformable surface model in abdominal contrast-enhanced CT images. Our method is composed of four main steps. First, for extracting an optimal volume circumscribing a liver, lower and side boundaries are defined by positional information of pelvis and rib. An upper boundary is defined by separating the lungs and heart from CT images. Second, for extracting an initial liver volume, optimal liver volume is smoothed by anisotropic diffusion filtering and is segmented using adaptively selected threshold value. Third, for removing neighbor organs from initial liver volume, morphological opening and connected component labeling are applied to multiple planes. Finally, for refining the liver boundaries, deformable surface model is applied to a posterior liver surface and missing left robe in previous step. Then, probability summation map is generated by calculating regional information of the segmented liver in coronal plane, which is used for restoring the inaccurate liver boundaries. Experimental results show that our segmentation method can accurately extract liver boundaries without leakage to neighbor organs in spite of various liver shape and ambiguous boundary.

  17. Deleterious alleles in the human genome are on average younger than neutral alleles of the same frequency.

    PubMed

    Kiezun, Adam; Pulit, Sara L; Francioli, Laurent C; van Dijk, Freerk; Swertz, Morris; Boomsma, Dorret I; van Duijn, Cornelia M; Slagboom, P Eline; van Ommen, G J B; Wijmenga, Cisca; de Bakker, Paul I W; Sunyaev, Shamil R

    2013-01-01

    Large-scale population sequencing studies provide a complete picture of human genetic variation within the studied populations. A key challenge is to identify, among the myriad alleles, those variants that have an effect on molecular function, phenotypes, and reproductive fitness. Most non-neutral variation consists of deleterious alleles segregating at low population frequency due to incessant mutation. To date, studies characterizing selection against deleterious alleles have been based on allele frequency (testing for a relative excess of rare alleles) or ratio of polymorphism to divergence (testing for a relative increase in the number of polymorphic alleles). Here, starting from Maruyama's theoretical prediction (Maruyama T (1974), Am J Hum Genet USA 6:669-673) that a (slightly) deleterious allele is, on average, younger than a neutral allele segregating at the same frequency, we devised an approach to characterize selection based on allelic age. Unlike existing methods, it compares sets of neutral and deleterious sequence variants at the same allele frequency. When applied to human sequence data from the Genome of the Netherlands Project, our approach distinguishes low-frequency coding non-synonymous variants from synonymous and non-coding variants at the same allele frequency and discriminates between sets of variants independently predicted to be benign or damaging for protein structure and function. The results confirm the abundance of slightly deleterious coding variation in humans.

  18. Microarrays for high-throughput genotyping of MICA alleles using allele-specific primer extension.

    PubMed

    Baek, I C; Jang, J-P; Choi, H-B; Choi, E-J; Ko, W-Y; Kim, T-G

    2013-10-01

    The role of major histocompatibility complex (MHC) class I chain-related gene A (MICA), a ligand of NKG2D, has been defined in human diseases by its allele associations with various autoimmune diseases, hematopoietic stem cell transplantation (HSCT) and cancer. This study describes a practical system to develop MICA genotyping by allele-specific primer extension (ASPE) on microarrays. From the results of 20 control primers, strict and reliable cut-off values of more than 30,000 mean fluorescence intensity (MFI) as positive and less than 3000 MFI as negative, were applied to select high-quality specific extension primers. Among 55 allele-specific primers, 44 primers could be initially selected as optimal primer. Through adjusting the length, six primers were improved. The other failed five primers were corrected by refractory modification. MICA genotypes by ASPE on microarrays showed the same results as those by nucleotide sequencing. On the basis of these results, ASPE on microarrays may provide high-throughput genotyping for MICA alleles for population studies, disease-gene associations and HSCT.

  19. Haplotypic Background of a Private Allele at High Frequency in the Americas

    PubMed Central

    Schroeder, Kari B.; Jakobsson, Mattias; Crawford, Michael H.; Schurr, Theodore G.; Boca, Simina M.; Conrad, Donald F.; Tito, Raul Y.; Osipova, Ludmilla P.; Tarskaia, Larissa A.; Zhadanov, Sergey I.; Wall, Jeffrey D.; Pritchard, Jonathan K.; Malhi, Ripan S.; Smith, David G.; Rosenberg, Noah A.

    2009-01-01

    Recently, the observation of a high-frequency private allele, the 9-repeat allele at microsatellite D9S1120, in all sampled Native American and Western Beringian populations has been interpreted as evidence that all modern Native Americans descend primarily from a single founding population. However, this inference assumed that all copies of the 9-repeat allele were identical by descent and that the geographic distribution of this allele had not been influenced by natural selection. To investigate whether these assumptions are satisfied, we genotyped 34 single nucleotide polymorphisms across ∼500 kilobases (kb) around D9S1120 in 21 Native American and Western Beringian populations and 54 other worldwide populations. All chromosomes with the 9-repeat allele share the same haplotypic background in the vicinity of D9S1120, suggesting that all sampled copies of the 9-repeat allele are identical by descent. Ninety-one percent of these chromosomes share the same 76.26 kb haplotype, which we call the “American Modal Haplotype” (AMH). Three observations lead us to conclude that the high frequency and widespread distribution of the 9-repeat allele are unlikely to be the result of positive selection: 1) aside from its association with the 9-repeat allele, the AMH does not have a high frequency in the Americas, 2) the AMH is not unusually long for its frequency compared with other haplotypes in the Americas, and 3) in Latin American mestizo populations, the proportion of Native American ancestry at D9S1120 is not unusual compared with that observed at other genomewide microsatellites. Using a new method for estimating the time to the most recent common ancestor (MRCA) of all sampled copies of an allele on the basis of an estimate of the length of the genealogy descended from the MRCA, we calculate the mean time to the MRCA of the 9-repeat allele to be between 7,325 and 39,900 years, depending on the demographic model used. The results support the hypothesis that all

  20. Ultrasound contrast agents

    PubMed Central

    Ignee, Andre; Atkinson, Nathan S. S.; Schuessler, Gudrun; Dietrich, Christoph F.

    2016-01-01

    Endoscopic ultrasound (EUS) plays an important role in imaging of the mediastinum and abdominal organs. Since the introduction of US contrast agents (UCA) for transabdominal US, attempts have been made to apply contrast-enhanced US techniques also to EUS. Since 2003, specific contrast-enhanced imaging was possible using EUS. Important studies have been published regarding contrast-enhanced EUS and the characterization of focal pancreatic lesions, lymph nodes, and subepithelial tumors. In this manuscript, we describe the relevant UCA, their application, and specific image acquisition as well as the principles of image tissue characterization using contrast-enhanced EUS. Safety issues, potential future developments, and EUS-specific issues are reviewed. PMID:27824024

  1. Extensive sharing of MHC class II alleles between rhesus and cynomolgus macaques.

    PubMed

    Doxiadis, Gaby G M; Rouweler, Annemiek J M; de Groot, Natasja G; Louwerse, Annet; Otting, Nel; Verschoor, Ernst J; Bontrop, Ronald E

    2006-05-01

    In contrast to rhesus monkeys, substantial knowledge on cynomolgus monkey major histocompatibility complex (MHC) class II haplotypes is lacking. Therefore, 17 animals, including one pedigreed family, were thoroughly characterized for polymorphic Mhc class II region genes as well as their mitochondrial DNA (mtDNA) sequences. Different cynomolgus macaque populations appear to exhibit unique mtDNA profiles reflecting their geographic origin. Within the present panel, 10 Mafa-DPB1, 14 Mafa-DQA1, 12 Mafa-DQB1, and 35 Mafa-DRB exon 2 sequences were identified. All of these alleles cluster into lineages that were previously described for rhesus macaques. Moreover, about half of the Mafa-DPB1, Mafa-DQA1, and Mafa-DQB1 alleles and one third of the Mafa-DRB exon 2 sequences are identical to rhesus macaque orthologues. Such a high level of Mhc class II allele sharing has not been reported for primate species. Pedigree analysis allowed the characterization of nine distinct Mafa class II haplotypes, and seven additional ones could be deduced. Two of these haplotypes harbor a duplication of the Mafa-DQB1 locus. Despite extensive allele sharing, rhesus and cynomolgus monkeys do not appear to possess identical Mhc class II haplotypes, thus illustrating that new haplotypes were generated after speciation by recombination-like processes.

  2. Phenotypic effects of an allele causing obligate parthenogenesis in a rotifer.

    PubMed

    Scheuerl, Thomas; Riss, Simone; Stelzer, Claus-Peter

    2011-01-01

    Transitions to obligate asexuality have been documented in almost all metazoan taxa, yet the conditions favoring such transitions remained largely unexplored. We address this problem in the rotifer Brachionus calyciflorus. In this species, a polymorphism at a single locus, op, can result in transitions to obligate parthenogenesis. Homozygotes for the op allele reproduce strictly by asexual reproduction, whereas heterozygous clones (+/op) and wild-type clones (+/+) are cyclical parthenogens that undergo sexual reproduction at high population densities. Here, we examine dosage effects of the op allele by analyzing various life-history characteristics and population traits in 10 clones for each of the 3 possible genotypes (op/op, +/op, and +/+). For most traits, we found that op/op clones differed significantly (P < 0.05) from the 2 cyclical parthenogenetic genotypes (+/+ and +/op). By contrast, the 2 cyclical parthenogenetic genotypes were almost indistinguishable, except that heterozygote individuals were slightly but significantly smaller in body size compared with wild-type individuals. Overall, this indicates that the op allele is selectively neutral in the heterozygous state. Thus, selective sweeps of this allele in natural populations would first require conditions favoring the generation of homozygotes. This may be given by inbreeding in very small populations or by double mutants in very large populations.

  3. Contrasting roles for CD4 vs. CD8 T-cells in a murine model of virally induced "T1 black hole" formation.

    PubMed

    Pirko, Istvan; Chen, Yi; Lohrey, Anne K; McDole, Jeremiah; Gamez, Jeffrey D; Allen, Kathleen S; Pavelko, Kevin D; Lindquist, Diana M; Dunn, R Scott; Macura, Slobodan I; Johnson, Aaron J

    2012-01-01

    MRI is sensitive to tissue pathology in multiple sclerosis (MS); however, most lesional MRI findings have limited correlation with disability. Chronic T1 hypointense lesions or "T1 black holes" (T1BH), observed in a subset of MS patients and thought to represent axonal damage, show moderate to strong correlation with disability. The pathogenesis of T1BH remains unclear. We previously reported the first and as of yet only model of T1BH formation in the Theiler's murine encephalitis virus induced model of acute CNS neuroinflammation induced injury, where CD8 T-cells are critical mediators of axonal damage and related T1BH formation. The purpose of this study was to further analyze the role of CD8 and CD4 T-cells through adoptive transfer experiments and to determine if the relevant CD8 T-cells are classic epitope specific lymphocytes or different subsets. C57BL/6 mice were used as donors and RAG-1 deficient mice as hosts in our adoptive transfer experiments. In vivo 3-dimensional MRI images were acquired using a 7 Tesla small animal MRI system. For image analysis, we used semi-automated methods in Analyze 9.1; transfer efficiency was monitored using FACS of brain infiltrating lymphocytes. Using a peptide depletion method, we demonstrated that the majority of CD8 T-cells are classic epitope specific cytotoxic cells. CD8 T-cell transfer successfully restored the immune system's capability to mediate T1BH formation in animals that lack adaptive immune system, whereas CD4 T-cell transfer results in an attenuated phenotype with significantly less T1BH formation. These findings demonstrate contrasting roles for these cell types, with additional evidence for a direct pathogenic role of CD8 T-cells in our model of T1 black hole formation.

  4. The APOE4 allele shows opposite sex bias in microbleeds and Alzheimer’s Disease of humans and mice

    PubMed Central

    Cacciottolo, Mafalda; Christensen, Amy; Moser, Alexandra; Liu, Jiahui; Pike, Christian J.; Sullivan, Patrick M.; Morgan, Todd E.; Dolzhenko, Egor; Charidimou, Andreas; Wahlund, Lars-Olaf; Wiberg, Maria Kristofferson; Shams, Sara; Chiang, Gloria Chia-Yi; Finch, Caleb E.

    2015-01-01

    The APOE4 allele confers greater risk of Alzheimer’s Disease (AD) for women than men, in conjunction with greater clinical deficits per unit of AD neuropathology (plaques, tangles). Cerebral microbleeds, which contribute to cognitive dysfunctions during AD, also show APOE4 excess, but sex-APOE allele interactions are not described. We report that elderly men diagnosed for mild cognitive impairment (MCI) and AD showed a higher risk of cerebral cortex microbleeds with APOE4 allele dose effect in two clinical cohorts (ADNI and KIDS). Sex-APOE interactions were further analyzed in EFAD mice carrying human APOE alleles and familial AD genes. At 7 months, E4FAD mice had cerebral cortex microbleeds with female excess, in contrast to humans. Cerebral amyloid angiopathy (CAA), plaques, and soluble Aβ also showed female excess. Both the cerebral microbleeds and CAA increased in proportion to individual Aβ load. In humans, the opposite sex bias of APOE4 allele for microbleeds vs the plaques and tangles is the first example of organ-specific, sex-linked APOE allele effects, and further shows AD as a uniquely human condition. PMID:26686669

  5. MspI allelic pattern of bovine growth hormone gene in Indian zebu cattle (Bos indicus) breeds.

    PubMed

    Sodhi, M; Mukesh, M; Prakash, B; Mishra, B P; Sobti, R C; Singh, Karn P; Singh, Satbir; Ahlawat, S P S

    2007-02-01

    The MspI allelic variation in intron III of the bovine growth hormone (bGH) gene was explored using PCR-RFLP in 750 animals belonging to 17 well-recognized breeds of Indian zebu cattle (Bos indicus) reared in different geographic locations of the country. Restriction digestion analysis of a 329-bp PCR fragment of the bGH intron III region with MspI restriction enzyme revealed two alleles (MspI- and MspI+) and two genotypes (-/- and +/-) across the 17 cattle breeds studied. The allelic frequency varied from 0.67 to 0.94 for MspI (-) and from 0.06 to 0.33 for MspI (+) across the 17 breeds, with a combined average frequency of 0.87 and 0.13, respectively. No animal with +/+ genotype was detected across the samples analyzed. The chi-square test showed that the difference in MspI allelic frequency was not significant (p > 0.05), regardless of the geographic origin, coat color, or utility of the cattle breed. The high MspI (-) allele frequencies obtained for Indian zebu cattle in this study are in sharp contrast to those reported for taurine breeds from northern Europe, Mediterranean countries, and America. Findings of this study further substantiate the hypothesis that the MspI (-) allele has an Indian origin.

  6. Use of allele scores as instrumental variables for Mendelian randomization

    PubMed Central

    Burgess, Stephen; Thompson, Simon G

    2013-01-01

    Background An allele score is a single variable summarizing multiple genetic variants associated with a risk factor. It is calculated as the total number of risk factor-increasing alleles for an individual (unweighted score), or the sum of weights for each allele corresponding to estimated genetic effect sizes (weighted score). An allele score can be used in a Mendelian randomization analysis to estimate the causal effect of the risk factor on an outcome. Methods Data were simulated to investigate the use of allele scores in Mendelian randomization where conventional instrumental variable techniques using multiple genetic variants demonstrate ‘weak instrument’ bias. The robustness of estimates using the allele score to misspecification (for example non-linearity, effect modification) and to violations of the instrumental variable assumptions was assessed. Results Causal estimates using a correctly specified allele score were unbiased with appropriate coverage levels. The estimates were generally robust to misspecification of the allele score, but not to instrumental variable violations, even if the majority of variants in the allele score were valid instruments. Using a weighted rather than an unweighted allele score increased power, but the increase was small when genetic variants had similar effect sizes. Naive use of the data under analysis to choose which variants to include in an allele score, or for deriving weights, resulted in substantial biases. Conclusions Allele scores enable valid causal estimates with large numbers of genetic variants. The stringency of criteria for genetic variants in Mendelian randomization should be maintained for all variants in an allele score. PMID:24062299

  7. Allele-specific disparity in breast cancer

    PubMed Central

    2011-01-01

    Background In a cancer cell the number of copies of a locus may vary due to amplification and deletion and these variations are denoted as copy number alterations (CNAs). We focus on the disparity of CNAs in tumour samples, which were compared to those in blood in order to identify the directional loss of heterozygosity. Methods We propose a numerical algorithm and apply it to data from the Illumina 109K-SNP array on 112 samples from breast cancer patients. B-allele frequency (BAF) and log R ratio (LRR) of Illumina were used to estimate Euclidian distances. For each locus, we compared genotypes in blood and tumour for subset of samples being heterozygous in blood. We identified loci showing preferential disparity from heterozygous toward either the A/B-allele homozygous (allelic disparity). The chi-squared and Cochran-Armitage trend tests were used to examine whether there is an association between high levels of disparity in single nucleotide polymorphisms (SNPs) and molecular, clinical and tumour-related parameters. To identify pathways and network functions over-represented within the resulting gene sets, we used Ingenuity Pathway Analysis (IPA). Results To identify loci with a high level of disparity, we selected SNPs 1) with a substantial degree of disparity and 2) with substantial frequency (at least 50% of the samples heterozygous for the respective locus). We report the overall difference in disparity in high-grade tumours compared to low-grade tumours (p-value < 0.001) and significant associations between disparity in multiple single loci and clinical parameters. The most significantly associated network functions within the genes represented in the loci of disparity were identified, including lipid metabolism, small-molecule biochemistry, and nervous system development and function. No evidence for over-representation of directional disparity in a list of stem cell genes was obtained, however genes appeared to be more often altered by deletion than by

  8. Attenuation of IL-7 receptor signaling is not required for allelic exclusion.

    PubMed

    Will, Wynette M; Aaker, Joshua D; Burchill, Matthew A; Harmon, Ian R; O'Neil, Jennifer J; Goetz, Christine A; Hippen, Keli L; Farrar, Michael A

    2006-03-15

    Allelic exclusion prevents pre-B cells from generating more than one functional H chain, thereby ensuring the formation of a unique pre-BCR. The signaling processes underlying allelic exclusion are not clearly understood. IL-7R-dependent signals have been clearly shown to regulate the accessibility of the Ig H chain locus. More recent work has suggested that pre-BCR-dependent attenuation of IL-7R signaling returns the H chain loci to an inaccessible state; this process has been proposed to underlie allelic exclusion. Importantly, this model predicts that preventing pre-BCR-dependent down-regulation of IL-7R signaling should interfere with allelic exclusion. To test this hypothesis, we made use of transgenic mice that express a constitutively active form of STAT5b (STAT5b-CA). STAT5b-CA expression restores V(D)J recombination in IL-7R(-/-) B cells, demonstrating that IL-7 regulates H chain locus accessibility and V(D)J recombination via STAT5 activation. To examine the effects of constitutively active STAT5b on allelic exclusion, we crossed STAT5b-CA mice (which express the IgM(b) allotype) to IgM(a) allotype congenic mice. We found no difference in the percentage of IgM(a)/IgM(b)-coexpressing B cells in STAT5b-CA vs littermate control mice; identical results were observed when crossing STAT5b-CA mice with hen egg lysozyme (HEL) H chain transgenic mice. The HEL transgene enforces allelic exclusion, preventing rearrangement of endogenous H chain genes; importantly, rearrangement of endogenous H chain genes was suppressed to a similar degree in STAT5b-CA vs HEL mice. Thus, attenuation of IL-7R/STAT5 signaling is not required for allelic exclusion.

  9. PCR Strategies for Complete Allele Calling in Multigene Families Using High-Throughput Sequencing Approaches

    PubMed Central

    Marmesat, Elena; Soriano, Laura; Mazzoni, Camila J.; Sommer, Simone

    2016-01-01

    The characterization of multigene families with high copy number variation is often approached through PCR amplification with highly degenerate primers to account for all expected variants flanking the region of interest. Such an approach often introduces PCR biases that result in an unbalanced representation of targets in high-throughput sequencing libraries that eventually results in incomplete detection of the targeted alleles. Here we confirm this result and propose two different amplification strategies to alleviate this problem. The first strategy (called pooled-PCRs) targets different subsets of alleles in multiple independent PCRs using different moderately degenerate primer pairs, whereas the second approach (called pooled-primers) uses a custom-made pool of non-degenerate primers in a single PCR. We compare their performance to the common use of a single PCR with highly degenerate primers using the MHC class I of the Iberian lynx as a model. We found both novel approaches to work similarly well and better than the conventional approach. They significantly scored more alleles per individual (11.33 ± 1.38 and 11.72 ± 0.89 vs 7.94 ± 1.95), yielded more complete allelic profiles (96.28 ± 8.46 and 99.50 ± 2.12 vs 63.76 ± 15.43), and revealed more alleles at a population level (13 vs 12). Finally, we could link each allele’s amplification efficiency with the primer-mismatches in its flanking sequences and show that ultra-deep coverage offered by high-throughput technologies does not fully compensate for such biases, especially as real alleles may reach lower coverage than artefacts. Adopting either of the proposed amplification methods provides the opportunity to attain more complete allelic profiles at lower coverages, improving confidence over the downstream analyses and subsequent applications. PMID:27294261

  10. Compressive Phase Contrast Tomography

    SciTech Connect

    Maia, Filipe; MacDowell, Alastair; Marchesini, Stefano; Padmore, Howard A.; Parkinson, Dula Y.; Pien, Jack; Schirotzek, Andre; Yang, Chao

    2010-09-01

    When x-rays penetrate soft matter, their phase changes more rapidly than their amplitude. Interference effects visible with high brightness sources creates higher contrast, edge enhanced images. When the object is piecewise smooth (made of big blocks of a few components), such higher contrast datasets have a sparse solution. We apply basis pursuit solvers to improve SNR, remove ring artifacts, reduce the number of views and radiation dose from phase contrast datasets collected at the Hard X-Ray Micro Tomography Beamline at the Advanced Light Source. We report a GPU code for the most computationally intensive task, the gridding and inverse gridding algorithm (non uniform sampled Fourier transform).

  11. (1) H-NMR relaxometric studies of interaction between apoptosis specific MRI paramagnetic contrast agents and micellar models of apoptotic cells.

    PubMed

    Van Koninckxloo, Aurore; Henoumont, Céline; Laurent, Sophie; Muller, Robert N; Vander Elst, Luce

    2016-07-01

    (1) H-NMR was previously used to analyze the interaction between peptides (E3 and R826) selected by phage display to target apoptotic cells and phospholipidic models of these cells. In order to avoid the use of apoptotic cells and to obtain a fast evaluation of the efficiency of the potential MRI contrast agents obtained by grafting these peptides and their scramble analogs on a paramagnetic gadolinium complex, their proton relaxometric behavior was investigated in the presence of micelles mimicking healthy and apoptotic cells. Their preferential interaction with 1,2-dipalmitoyl-sn-glycero-3-phospho-l-serine micelles mimicking apoptotic cells as compared with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine micelles modeling healthy cells was shown by nuclear magnetic relaxation dispersion profiles and the enhancement of the transverse proton relaxation rates at 60 MHz. The association constant values confirm the stronger interaction of the selected conjugated peptides (Ka Gd-PMN-E3(gadolinium 2,2',2'',2'''-[((4-carboxy)pyridine-2,6-diyl)bis(methylenenitrilo)]-tetrakis acetate) grafted with E3 peptide): 2.43 10(4)  m(-1) ; Ka Gd-DTPA-R826(gadolinium ((1-p-isothiocyanatobenzyl)-diethylenetriaminepentaacetate) grafted with R826 peptide): 2.91 10(4)  m(-1) ) as compared with their conjugated scrambles (Ka Gd-PMN-E3sc(gadolinium 2,2',2'',2'''-[((4-carboxy)pyridine-2,6-diyl)bis(methylenenitrilo)]-tetrakis acetate) grafted with E3 scramble peptide): 0.18 10(4)  m(-1) ; Ka Gd-DTPA-R826sc(gadolinium ((1-p-isothiocyanatobenzyl)-diethylenetriaminepentaacetate) grafted with R826 scramble peptide): 0.32 10(4)  m(-1) ) even if the conjugation of E3 and R826 seems to decrease their interaction. Copyright © 2015 John Wiley & Sons, Ltd.

  12. Differential X-ray phase contrast tomography of Alzheimer plaques in mouse models: perspectives for drug development and clinical imaging techniques

    NASA Astrophysics Data System (ADS)

    Pinzer, B. R.; Cacquevel, M.; Modregger, P.; Thuering, T.; Stampanoni, M.

    2013-05-01

    Alzheimer's disease (AD) is a looming threat on an ever-ageing population, with devastating effects on the human intellect. A particular characteristic lesion — the extracellular amyloid plaque — accumulates in the brain of AD patients during the course of the disease, and could therefore be used to monitor the progression of the disease, years before the first neurological symptoms appear. In addition, strategies for drug intervention in AD are often based on amyloid reduction, since amyloid plaques are hypothesized to be involved in a chain of reactions leading to the death of neurons. Developments in both fields would benefit from a microscopic technique that is capable of single plaque imaging, ideally in 3D. While such a non-destructive, single-plaque imaging technique does not yet exist for humans, it has been recently shown that synchrotron based differential X-ray phase contrast imaging can be used to visualize individual plaques at μm resolution in mouse models of AD ex-vivo. This method, which relies on a grating interferometer to measure refraction angles induced by fluctuations in the refractive index, yields a precise three-dimensional distribution of single plaques. These data could not only improve the understanding of the evolution of AD or the effectiveness of drugs, but could also help to improve reliable markers for current and future non-invasive clinical imaging techniques. In particular, validation of PET markers with small animal models could be rapidly carried out by co-registration of PET and DPC signals.

  13. Contrast Adaptation Implies Two Spatiotemporal Channels but Three Adapting Processes

    ERIC Educational Resources Information Center

    Langley, Keith; Bex, Peter J.

    2007-01-01

    The contrast gain control model of adaptation predicts that the effects of contrast adaptation correlate with contrast sensitivity. This article reports that the effects of high contrast spatiotemporal adaptors are maximum when adapting around 19 Hz, which is a factor of two or more greater than the peak in contrast sensitivity. To explain the…

  14. Identification of a novel HLA-A allele, A*3120.

    PubMed

    Chang, Y; Pascual, C J; Alonzo, P; Chamizo, A

    2009-03-01

    A novel human leukocyte antigen (HLA)-A allele, HLA-A*3120, was first identified in a National Marrow Donor Program (NMDP) donor. The A*3120 allele resulted from a single nucleotide substitution (T to G) at codon 92 of exon 3 of A*310102. The substitution caused an amino acid change (serine to alanine). This novel allele was also seen in two other unrelated NMDP donors.

  15. Alleles versus genotypes: Genetic interactions and the dynamics of selection in sexual populations

    NASA Astrophysics Data System (ADS)

    Neher, Richard

    2010-03-01

    Physical interactions between amino-acids are essential for protein structure and activity, while protein-protein interactions and regulatory interactions are central to cellular function. As a consequence of these interactions, the combined effect of two mutations can differ from the sum of the individual effects of the mutations. This phenomenon of genetic interaction is known as epistasis. However, the importance of epistasis and its effects on evolutionary dynamics are poorly understood, especially in sexual populations where recombination breaks up existing combinations of alleles to produce new ones. Here, we present a computational model of selection dynamics involving many epistatic loci in a recombining population. We demonstrate that a large number of polymorphic interacting loci can, despite frequent recombination, exhibit cooperative behavior that locks alleles into favorable genotypes leading to a population consisting of a set of competing clones. As the recombination rate exceeds a certain critical value this ``genotype selection'' phase disappears in an abrupt transition giving way to ``allele selection'' - the phase where different loci are only weakly correlated as expected in sexually reproducing populations. Clustering of interacting sets of genes on a chromosome leads to the emergence of an intermediate regime, where localized blocks of cooperating alleles lock into genetic modules. Large populations attain highest fitness at a recombination rate just below critical, suggesting that natural selection might tune recombination rates to balance the beneficial aspect of exploration of genotype space with the breaking up of synergistic allele combinations.

  16. HLA-DR alleles in amyloid beta-peptide autoimmunity: a highly immunogenic role for the DRB1*1501 allele.

    PubMed

    Zota, Victor; Nemirovsky, Anna; Baron, Rona; Fisher, Yair; Selkoe, Dennis J; Altmann, Daniel M; Weiner, Howard L; Monsonego, Alon

    2009-09-01

    Active amyloid beta-peptide (Abeta) immunization of patients with Alzheimer's disease (AD) caused meningoencephalitis in approximately 6% of immunized patients in a clinical trial. In addition, long-term studies of AD patients show varying degrees of Abeta Ab responses, which correlate with the extent of Abeta clearance from the brain. In this study, we examined the contribution of various HLA-DR alleles to these immune-response variations by assessing Abeta T cell reactivity, epitope specificity, and immunogenicity. Analysis of blood samples from 133 individuals disclosed that the abundant DR haplotypes DR15 (found in 36% of subjects), DR3 (in 18%), DR4 (12.5%), DR1 (11%), and DR13 (8%) were associated with Abeta-specific T cell responses elicited via distinct T cell epitopes within residues 15-42 of Abeta. Because the HLA-DRB1*1501 occurred most frequently, we examined the effect of Abeta challenge in humanized mice bearing this allele. The observed T cell response was remarkably strong, dominated by secretion of IFN-gamma and IL-17, and specific to the same T cell epitope as that observed in the HLA-DR15-bearing humans. Furthermore, following long-term therapeutic immunization of an AD mouse model bearing the DRB1*1501 allele, Abeta was effectively cleared from the brain parenchyma and brain microglial activation was reduced. The present study thus characterizes HLA-DR alleles directly associated with specific Abeta T cell epitopes and demonstrates the highly immunogenic properties of the abundant allele DRB1*1501 in a mouse model of AD. This new knowledge enables us to explore the basis for understanding the variations in naturally occurring Abeta-reactive T cells and Abeta immunogenicity among humans.

  17. Phase-contrast radiography.

    PubMed

    Gao, D; Pogany, A; Stevenson, A W; Wilkins, S W

    1998-01-01

    For the past 100 years, the paradigm for radiography has been premised on absorption as the sole means of contrast formation and on ray optics as the basis for image interpretation. A new conceptual approach to radiography has been developed that includes phase (ie, refractive) contrast and requires wave optics for proper treatment. This new approach greatly increases the amount of information that can be obtained with radiographic techniques and is particularly well suited to the imaging of soft tissue and of very small features in biologic samples. A key feature of the present technique o