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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. PMID:26392055

  2. Allele frequencies at microsatellite loci: The stepwise mutation model revisited

    SciTech Connect

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

    1993-03-01

    The authors 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. They 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. It is also shown 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. 39 refs., 6 figs., 4 tabs.

  3. A Computer Simulation Study of Vntr Population Genetics: Constrained Recombination Rules Out the Infinite Alleles Model

    PubMed Central

    Harding, R. M.; Boyce, A. J.; Martinson, J. J.; Flint, J.; Clegg, J. B.

    1993-01-01

    Extensive allelic diversity in variable numbers of tandem repeats (VNTRs) has been discovered in the human genome. For population genetic studies of VNTRs, such as forensic applications, it is important to know whether a neutral mutation-drift balance of VNTR polymorphism can be represented by the infinite alleles model. The assumption of the infinite alleles model that each new mutant is unique is very likely to be violated by unequal sister chromatid exchange (USCE), the primary process believed to generate VNTR mutants. We show that increasing both mutation rates and misalignment constraint for intrachromosomal recombination in a computer simulation model reduces simulated VNTR diversity below the expectations of the infinite alleles model. Maximal constraint, represented as slippage of single repeats, reduces simulated VNTR diversity to levels expected from the stepwise mutation model. Although misalignment rule is the more important variable, mutation rate also has an effect. At moderate rates of USCE, simulated VNTR diversity fluctuates around infinite alleles expectation. However, if rates of USCE are high, as for hypervariable VNTRs, simulated VNTR diversity is consistently lower than predicted by the infinite alleles model. This has been observed for many VNTRs and accounted for by technical problems in distinguishing alleles of neighboring size classes. We use sampling theory to confirm the intrinsically poor fit to the infinite alleles model of both simulated VNTR diversity and observed VNTR polymorphisms sampled from two Papua New Guinean populations. PMID:8293988

  4. MHC class II variation in a rare and ecological specialist mouse lemur reveals lower allelic richness and contrasting selection patterns compared to a generalist and widespread sympatric congener.

    PubMed

    Pechouskova, Eva; Dammhahn, Melanie; Brameier, Markus; Fichtel, Claudia; Kappeler, Peter M; Huchard, Elise

    2015-04-01

    The polymorphism of immunogenes of the major histocompatibility complex (MHC) is thought to influence the functional plasticity of immune responses and, consequently, the fitness of populations facing heterogeneous pathogenic pressures. Here, we evaluated MHC variation (allelic richness and divergence) and patterns of selection acting on the two highly polymorphic MHC class II loci (DRB and DQB) in the endangered primate Madame Berthe's mouse lemur (Microcebus berthae). Using 454 pyrosequencing, we examined MHC variation in a total of 100 individuals sampled over 9 years in Kirindy Forest, Western Madagascar, and compared our findings with data obtained previously for its sympatric congener, the grey mouse lemur (Microcebus murinus). These species exhibit a contrasting ecology and demography that were expected to affect MHC variation and molecular signatures of selection. We found a lower allelic richness concordant with its low population density, but a similar level of allelic divergence and signals of historical selection in the rare feeding specialist M. berthae compared to the widespread generalist M. murinus. These findings suggest that demographic factors may exert a stronger influence than pathogen-driven selection on current levels of allelic richness in M. berthae. Despite a high sequence similarity between the two congeners, contrasting selection patterns detected at DQB suggest its potential functional divergence. This study represents a first step toward unravelling factors influencing the adaptive divergence of MHC genes between closely related but ecologically differentiated sympatric lemurs and opens new questions regarding potential functional discrepancy that would explain contrasting selection patterns detected at DQB. PMID:25687337

  5. 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.

  6. PKD1 Mono-Allelic Knockout Is Sufficient to Trigger Renal Cystogenesis in a Mini-Pig Model

    PubMed Central

    He, Jin; Li, Qiuyan; Fang, Suyun; Guo, Ying; Liu, Tongxin; Ye, Jianhua; Yu, Zhengquan; Zhang, Ran; Zhao, Yaofeng; Hu, Xiaoxiang; Bai, Xueyuan; Chen, Xiangmei; Li, Ning

    2015-01-01

    PKD1 and PKD2 mutations could lead to autosomal dominant polycystic kidney disease (ADPKD), which afflicts millions of people worldwide. Due to the marked differences in the lifespan, size, anatomy, and physiology from humans, rodent ADPKD models cannot fully mimic the disease. To obtain a large animal model that recapitulates the disease, we constructed a mini-pig model by mono-allelic knockout (KO) of PKD1 using zinc finger nuclease. The mono-allelic KO pigs had lower PKD1 expression than their wild-type littermates at both the transcriptional and translational levels. After approximately six months, renal cysts appeared and grew progressively in the KO pigs. Histological analysis showed that renal cysts were scatteredly distributed in the mutant pig kidneys and were lined by either cuboidal or flattened epithelial cells. Contrast-enhanced computed tomography confirmed that all of the mutant pigs had renal and hepatic cysts, when they were 11-month-old. Immunohistochemical analysis revealed that most of the cysts were derived from the proximal tubules and collecting ducts. Therefore, the PKD1 mono-allelic knockout is sufficient to trigger renal cystogenesis, and this pig model may provide a platform for future study of renal cyst formation. PMID:25798056

  7. A revised Fisher model on analysis of quantitative trait loci with multiple alleles

    PubMed Central

    Wang, Tao

    2014-01-01

    Zeng et al. (2005) proposed a general two-allele (G2A) model to model bi-allelic quantitative trait loci (QTL). Comparing with the classical Fisher model, the G2A model can avoid using redundant parameters and be fitted directly using standard least square (LS) approach. In this study, we further extend the G2A model to general multi-allele (GMA) model. First, we propose a one-locus GMA model for phase known genotypes based on modeling the inheritance of paternal and maternal alleles. Next, we develop a one-locus GMA model for phase unknown genotypes by treating it as a special case of the phase known one-locus GMA model. Thirdly, we extend the one-locus GMA models to multiple loci. We discuss how the genetic variance components can be analyzed using these GMA models in equilibrium as well as disequilibrium populations. Finally, we apply the GMA model to a published experimental data set. PMID:25309580

  8. Functional isogenic modeling of BRCA1 alleles reveals distinct carrier phenotypes

    PubMed Central

    Cochran, Rory L.; Cidado, Justin; Kim, Minsoo; Zabransky, Daniel J.; Croessmann, Sarah; Chu, David; Wong, Hong Yuen; Beaver, Julia A.; Cravero, Karen; Erlanger, Bracha; Parsons, Heather; Heaphy, Christopher M.; Meeker, Alan K.; Lauring, Josh; Park, Ben Ho

    2015-01-01

    Clinical genetic testing of BRCA1 and BRCA2 is commonly performed to identify specific individuals at risk for breast and ovarian cancers who may benefit from prophylactic therapeutic interventions. Unfortunately, it is evident that deleterious BRCA1 alleles demonstrate variable penetrance and that many BRCA1 variants of unknown significance (VUS) exist. In order to further refine hereditary risks that may be associated with specific BRCA1 alleles, we performed gene targeting to establish an isogenic panel of immortalized human breast epithelial cells harboring eight clinically relevant BRCA1 alleles. Interestingly, BRCA1 mutations and VUS had distinct, quantifiable phenotypes relative to isogenic parental BRCA1 wild type cells and controls. Heterozygous cells with known deleterious BRCA1 mutations (185delAG, C61G and R71G) demonstrated consistent phenotypes in radiation sensitivity and genomic instability assays, but showed variability in other assays. Heterozygous BRCA1 VUS cells also demonstrated assay variability, with some VUS demonstrating phenotypes more consistent with deleterious alleles. Taken together, our data suggest that BRCA1 deleterious mutations and VUS can differ in their range of tested phenotypes, suggesting they might impart varying degrees of risk. These results demonstrate that functional isogenic modeling of BRCA1 alleles could aid in classifying BRCA1 mutations and VUS, and determining BRCA allele cancer risk. PMID:26246475

  9. Functional isogenic modeling of BRCA1 alleles reveals distinct carrier phenotypes.

    PubMed

    Cochran, Rory L; Cidado, Justin; Kim, Minsoo; Zabransky, Daniel J; Croessmann, Sarah; Chu, David; Wong, Hong Yuen; Beaver, Julia A; Cravero, Karen; Erlanger, Bracha; Parsons, Heather; Heaphy, Christopher M; Meeker, Alan K; Lauring, Josh; Park, Ben Ho

    2015-09-22

    Clinical genetic testing of BRCA1 and BRCA2 is commonly performed to identify specific individuals at risk for breast and ovarian cancers who may benefit from prophylactic therapeutic interventions. Unfortunately, it is evident that deleterious BRCA1 alleles demonstrate variable penetrance and that many BRCA1 variants of unknown significance (VUS) exist. In order to further refine hereditary risks that may be associated with specific BRCA1 alleles, we performed gene targeting to establish an isogenic panel of immortalized human breast epithelial cells harboring eight clinically relevant BRCA1 alleles. Interestingly, BRCA1 mutations and VUS had distinct, quantifiable phenotypes relative to isogenic parental BRCA1 wild type cells and controls. Heterozygous cells with known deleterious BRCA1 mutations (185delAG, C61G and R71G) demonstrated consistent phenotypes in radiation sensitivity and genomic instability assays, but showed variability in other assays. Heterozygous BRCA1 VUS cells also demonstrated assay variability, with some VUS demonstrating phenotypes more consistent with deleterious alleles. Taken together, our data suggest that BRCA1 deleterious mutations and VUS can differ in their range of tested phenotypes, suggesting they might impart varying degrees of risk. These results demonstrate that functional isogenic modeling of BRCA1 alleles could aid in classifying BRCA1 mutations and VUS, and determining BRCA allele cancer risk. PMID:26246475

  10. 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

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

    PubMed

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

    2015-01-01

    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 qualitative

  12. Contrasting effects of Deadend1 (Dnd1) gain and loss of function mutations on allelic inheritance, testicular cancer, and intestinal polyposis

    PubMed Central

    2013-01-01

    Background Certain mutations in the Deadend1 (Dnd1) gene are the most potent modifiers of testicular germ cell tumor (TGCT) susceptibility in mice and rats. In the 129 family of mice, the Dnd1Ter mutation significantly increases occurrence of TGCT-affected males. To test the hypothesis that he Dnd1Ter allele is a loss-of-function mutation; we characterized the consequences of a genetically-engineered loss-of-function mutation in mice, and compared these results with those for Dnd1Ter. Results We found that intercrossing Dnd1+/KO heterozygotes to generate a complete loss-of-function led to absence of Dnd1KO/KO homozygotes and significantly reduced numbers of Dnd1+/KO heterozygotes. Further crosses showed that Dnd1Ter partially rescues loss of Dnd1KO mice. We also found that loss of a single copy of Dnd1 in Dnd1KO/+ heterozygotes did not affect baseline occurrence of TGCT-affected males and that Dnd1Ter increased TGCT risk regardless whether the alternative allele was loss-of-function (Dnd1KO) or wild-type (Dnd1+). Finally, we found that the action of Dnd1Ter was not limited to testicular cancer, but also significantly increased polyp number and burden in the Apc+/Min model of intestinal polyposis. Conclusion These results show that Dnd1 is essential for normal allelic inheritance and that Dnd1Ter has a novel combination of functions that significantly increase risk for both testicular and intestinal cancer. PMID:23773267

  13. MHC allele frequency distributions under parasite-driven selection: A simulation model

    PubMed Central

    2010-01-01

    Background The extreme polymorphism that is observed in major histocompatibility complex (MHC) genes, which code for proteins involved in recognition of non-self oligopeptides, is thought to result from a pressure exerted by parasites because parasite antigens are more likely to be recognized by MHC heterozygotes (heterozygote advantage) and/or by rare MHC alleles (negative frequency-dependent selection). The Ewens-Watterson test (EW) is often used to detect selection acting on MHC genes over the recent history of a population. EW is based on the expectation that allele frequencies under balancing selection should be more even than under neutrality. We used computer simulations to investigate whether this expectation holds for selection exerted by parasites on host MHC genes under conditions of heterozygote advantage and negative frequency-dependent selection acting either simultaneously or separately. Results In agreement with simple models of symmetrical overdominance, we found that heterozygote advantage acting alone in populations does, indeed, result in more even allele frequency distributions than expected under neutrality, and this is easily detectable by EW. However, under negative frequency-dependent selection, or under the joint action of negative frequency-dependent selection and heterozygote advantage, distributions of allele frequencies were less predictable: the majority of distributions were indistinguishable from neutral expectations, while the remaining runs resulted in either more even or more skewed distributions than under neutrality. Conclusions Our results indicate that, as long as negative frequency-dependent selection is an important force maintaining MHC variation, the EW test has limited utility in detecting selection acting on these genes. PMID:20979635

  14. Microarray-based estimation of SNP allele-frequency in pooled DNA using the Langmuir kinetic model

    PubMed Central

    Yin, Bin-Cheng; Li, Honghua; Ye, Bang-Ce

    2008-01-01

    Background High throughput genotyping of single nucleotide polymorphisms (SNPs) for genome-wide association requires technologies for generating millions of genotypes with relative ease but also at a reasonable cost and with high accuracy. In this work, we have developed a theoretical approach to estimate allele frequency in pooled DNA samples, based on the physical principles of DNA immobilization and hybridization on solid surface using the Langmuir kinetic model and quantitative analysis of the allelic signals. Results This method can successfully distinguish allele frequencies differing by 0.01 in the actual pool of clinical samples, and detect alleles with a frequency as low as 2%. The accuracy of measuring known allele frequencies is very high, with the strength of correlation between measured and actual frequencies having an r2 = 0.9992. These results demonstrated that this method could allow the accurate estimation of absolute allele frequencies in pooled samples of DNA in a feasible and inexpensive way. Conclusion We conclude that this novel strategy for quantitative analysis of the ratio of SNP allelic sequences in DNA pools is an inexpensive and feasible alternative for detecting polymorphic differences in candidate gene association studies and genome-wide linkage disequilibrium scans. PMID:19087310

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

    PubMed Central

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

    2015-01-01

    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]. PMID:26693509

  16. Allele-specific RNAi Mitigates Phenotypic Progression in a Transgenic Model of Alzheimer's Disease

    PubMed Central

    Rodríguez-Lebrón, Edgardo; Gouvion, Cynthia M; Moore, Steven A; Davidson, Beverly L; Paulson, Henry L

    2009-01-01

    Despite recent advances suggesting new therapeutic targets, Alzheimer's disease (AD) remains incurable. Aberrant production and accumulation of the Aβ peptide resulting from altered processing of the amyloid precursor protein (APP) is central to the pathogenesis of disease, particularly in dominantly inherited forms of AD. Thus, modulating the production of APP is a potential route to effective AD therapy. Here, we describe the successful use of an allele-specific RNA interference (RNAi) approach targeting the Swedish variant of APP (APPsw) in a transgenic mouse model of AD. Using recombinant adeno-associated virus (rAAV), we delivered an anti-APPsw short-hairpin RNA (shRNA) to the hippocampus of AD transgenic mice (APP/PS1). In short- and long-term transduction experiments, reduced levels of APPsw transprotein were observed throughout targeted regions of the hippocampus while levels of wild-type murine APP remained unaltered. Moreover, intracellular production of transfer RNA (tRNA)-valine promoter–driven shRNAs did not lead to detectable neuronal toxicity. Finally, long-term bilateral hippocampal expression of anti-APPsw shRNA mitigated abnormal behaviors in this mouse model of AD. The difference in phenotype progression was associated with reduced levels of soluble Aβ but not with a reduced number of amyloid plaques. Our results support the development of allele-specific RNAi strategies to treat familial AD and other dominantly inherited neurodegenerative diseases. PMID:19532137

  17. 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. PMID:26589823

  18. 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.

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

    PubMed Central

    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

    2015-01-01

    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. These differences in MsiHd1a show that the dependency on functional MsiHd1a alleles is different between accessions from the East Asian mainland and Japan. PMID:26089536

  20. 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…

  1. DIVERSE MODELS FOR SOLVING CONTRASTING OUTFALL PROBLEMS

    EPA Science Inventory

    Mixing zone initial dilution and far-field models are useful for assuring that water quality criteria will be met when specific outfall discharge criteria are applied. Presented here is a selective review of mixing zone initial dilution models and relatively simple far-field tran...

  2. Modeling the effects of contrast enhancement on target acquisition performance

    NASA Astrophysics Data System (ADS)

    Du Bosq, Todd W.; Fanning, Jonathan D.

    2008-04-01

    Contrast enhancement and dynamic range compression are currently being used to improve the performance of infrared imagers by increasing the contrast between the target and the scene content, by better utilizing the available gray levels either globally or locally. This paper assesses the range-performance effects of various contrast enhancement algorithms for target identification with well contrasted vehicles. Human perception experiments were performed to determine field performance using contrast enhancement on the U.S. Army RDECOM CERDEC NVESD standard military eight target set using an un-cooled LWIR camera. The experiments compare the identification performance of observers viewing linearly scaled images and various contrast enhancement processed images. Contrast enhancement is modeled in the US Army thermal target acquisition model (NVThermIP) by changing the scene contrast temperature. The model predicts improved performance based on any improved target contrast, regardless of feature saturation or enhancement. To account for the equivalent blur associated with each contrast enhancement algorithm, an additional effective MTF was calculated and added to the model. The measured results are compared with the predicted performance based on the target task difficulty metric used in NVThermIP.

  3. 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

  4. Model of visual contrast gain control and pattern masking

    NASA Technical Reports Server (NTRS)

    Watson, A. B.; Solomon, J. A.

    1997-01-01

    We have implemented a model of contrast gain and control in human vision that incorporates a number of key features, including a contrast sensitivity function, multiple oriented bandpass channels, accelerating nonlinearities, and a devisive inhibitory gain control pool. The parameters of this model have been optimized through a fit to the recent data that describe masking of a Gabor function by cosine and Gabor masks [J. M. Foley, "Human luminance pattern mechanisms: masking experiments require a new model," J. Opt. Soc. Am. A 11, 1710 (1994)]. The model achieves a good fit to the data. We also demonstrate how the concept of recruitment may accommodate a variant of this model in which excitatory and inhibitory paths have a common accelerating nonlinearity, but which include multiple channels tuned to different levels of contrast.

  5. 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…

  6. Allele- and Tir-Independent Functions of Intimin in Diverse Animal Infection Models

    PubMed Central

    Mallick, Emily M.; Brady, Michael J.; Luperchio, Steven A.; Vanguri, Vijay K.; Magoun, Loranne; Liu, Hui; Sheppard, Barbara J.; Mukherjee, Jean; Donohue-Rolfe, Art; Tzipori, Saul; Leong, John M.; Schauer, David B.

    2012-01-01

    Upon binding to intestinal epithelial cells, enterohemorrhagic Escherichia coli (EHEC), enteropathogenic E. coli (EPEC), and Citrobacter rodentium trigger formation of actin pedestals beneath bound bacteria. Pedestal formation has been associated with enhanced colonization, and requires intimin, an adhesin that binds to the bacterial effector translocated intimin receptor (Tir), which is translocated to the host cell membrane and promotes bacterial adherence and pedestal formation. Intimin has been suggested to also promote cell adhesion by binding one or more host receptors, and allelic differences in intimin have been associated with differences in tissue and host specificity. We assessed the function of EHEC, EPEC, or C. rodentium intimin, or a set of intimin derivatives with varying Tir-binding abilities in animal models of infection. We found that EPEC and EHEC intimin were functionally indistinguishable during infection of gnotobiotic piglets by EHEC, and that EPEC, EHEC, and C. rodentium intimin were functionally indistinguishable during infection of C57BL/6 mice by C. rodentium. A derivative of EHEC intimin that bound Tir but did not promote robust pedestal formation on cultured cells was unable to promote C. rodentium colonization of conventional mice, indicating that the ability to trigger actin assembly, not simply to bind Tir, is required for intimin-mediated intestinal colonization. Interestingly, streptomycin pre-treatment of mice eliminated the requirement for Tir but not intimin during colonization, and intimin derivatives that were defective in Tir-binding still promoted colonization of these mice. These results indicate that EPEC, EHEC, and C. rodentium intimin are functionally interchangeable during infection of gnotobiotic piglets or conventional C57BL/6 mice, and that whereas the ability to trigger Tir-mediated pedestal formation is essential for colonization of conventional mice, intimin provides a Tir-independent activity during colonization

  7. Common alleles contribute to schizophrenia in CNV carriers

    PubMed Central

    Tansey, K E; Rees, E; Linden, D E; Ripke, S; Chambert, K D; Moran, J L; McCarroll, S A; Holmans, P; Kirov, G; Walters, J; Owen, M J; O'Donovan, M C

    2016-01-01

    The genetic architecture of schizophrenia is complex, involving risk alleles ranging from common alleles of weak effect to rare alleles of large effect, the best exemplar of the latter being large copy number variants (CNVs). It is currently unknown whether pathophysiology in those with defined rare mutations overlaps with that in other individuals with the disorder who do not share the same rare mutation. Under an extreme heterogeneity model, carriers of specific high-penetrance mutations form distinct subgroups. In contrast, under a polygenic threshold model, high-penetrance rare allele carriers possess many risk factors, of which the rare allele is the only one, albeit an important, factor. Under the latter model, cases with rare mutations can be expected to share some common risk alleles, and therefore pathophysiological mechanisms, with cases without the same mutation. Here we show that, compared with controls, individuals with schizophrenia who have known pathogenic CNVs carry an excess burden of common risk alleles (P=2.25 × 10−17) defined from a genome-wide association study largely based on individuals without known CNVs. Our finding is not consistent with an extreme heterogeneity model for CNV carriers, but does offer support for the polygenic threshold model of schizophrenia. That this is so provides support for the notion that studies aiming to model the effects of rare variation may uncover pathophysiological mechanisms of relevance to those with the disorder more widely. PMID:26390827

  8. Common alleles contribute to schizophrenia in CNV carriers.

    PubMed

    Tansey, K E; Rees, E; Linden, D E; Ripke, S; Chambert, K D; Moran, J L; McCarroll, S A; Holmans, P; Kirov, G; Walters, J; Owen, M J; O'Donovan, M C

    2016-08-01

    The genetic architecture of schizophrenia is complex, involving risk alleles ranging from common alleles of weak effect to rare alleles of large effect, the best exemplar of the latter being large copy number variants (CNVs). It is currently unknown whether pathophysiology in those with defined rare mutations overlaps with that in other individuals with the disorder who do not share the same rare mutation. Under an extreme heterogeneity model, carriers of specific high-penetrance mutations form distinct subgroups. In contrast, under a polygenic threshold model, high-penetrance rare allele carriers possess many risk factors, of which the rare allele is the only one, albeit an important, factor. Under the latter model, cases with rare mutations can be expected to share some common risk alleles, and therefore pathophysiological mechanisms, with cases without the same mutation. Here we show that, compared with controls, individuals with schizophrenia who have known pathogenic CNVs carry an excess burden of common risk alleles (P=2.25 × 10(-17)) defined from a genome-wide association study largely based on individuals without known CNVs. Our finding is not consistent with an extreme heterogeneity model for CNV carriers, but does offer support for the polygenic threshold model of schizophrenia. That this is so provides support for the notion that studies aiming to model the effects of rare variation may uncover pathophysiological mechanisms of relevance to those with the disorder more widely. PMID:26390827

  9. 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

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

    PubMed

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

    2015-02-01

    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

  11. 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.

  12. Comparing models of contrast gain using psychophysical experiments.

    PubMed

    DiMattina, Christopher

    2016-07-01

    In a wide variety of neural systems, neurons tuned to a primary dimension of interest often have responses that are modulated in a multiplicative manner by other features such as stimulus intensity or contrast. In this methodological study, we present a demonstration that it is possible to use psychophysical experiments to compare competing hypotheses of multiplicative gain modulation in a neural population, using the specific example of contrast gain modulation in orientation-tuned visual neurons. We demonstrate that fitting biologically interpretable models to psychophysical data yields physiologically accurate estimates of contrast tuning parameters and allows us to compare competing hypotheses of contrast tuning. We demonstrate a powerful methodology for comparing competing neural models using adaptively generated psychophysical stimuli and demonstrate that such stimuli can be highly effective for distinguishing qualitatively similar hypotheses. We relate our work to the growing body of literature that uses fits of neural models to behavioral data to gain insight into neural coding and suggest directions for future research. PMID:27380470

  13. 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.

  14. 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.

  15. 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.

  16. Sensitivity, noise and quantitative model of Laser Speckle Contrast Imaging

    NASA Astrophysics Data System (ADS)

    Yuan, Shuai

    In the dissertation, I present several studies on Laser Speckle Contrast Imaging (LSCI). The two major goals of those studies are: (1) to improve the signal-noise-ratio (SNR) of LSCI so it can be used to detect small blood flow change due to brain activities; (2) to find a reliable quantitative model so LSCI results can be compared among experiments and subjects and even with results from other blood flow monitoring techniques. We sought to improve SNR in the following ways: (1) We investigated the relationship between exposure time and the sensitivities of LSCI. We found that relative sensitivity reaches its maximum at an exposure time of around 5 ms. (2) We studied the relationship between laser speckle and camera aperture stop, which is actually the relationship between laser speckle and speckle/pixel size ratio. In general, speckle and pixel size should be approximately 1.5 - 2 to reach the maximum of detection factor beta as well as speckle contrast (SC) value and absolute sensitivity. This is also an important study for quantitative model development. (3) We worked on noise analysis and modeling. Noise affects both SNR and quantitative model. Usually random noise is more critical for SNR analysis. The main random noises in LSCI are statistical noise and physiological noise. Some physiological noises are caused by the small motions induced by heart beat or breathing. These are periodic and can be eliminated using methods discussed in this dissertation. Statistical noise is more fundamental and cannot be eliminated entirely. However it can be greatly reduced by increasing the effective pixel number N for speckle contrast processing. To develop the quantitative model, we did the following: (1) We considered more experimental factors in the quantitative model and removed several ideal case assumptions. In particular, in our model we considered the general detection factor beta, static scatterers and systematic noise. A simple calibration procedure is suggested

  17. 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

  18. 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. PMID:25365559

  19. Automatic image equalization and contrast enhancement using Gaussian mixture modeling.

    PubMed

    Celik, Turgay; Tjahjadi, Tardi

    2012-01-01

    In this paper, we propose an adaptive image equalization algorithm that automatically enhances the contrast in an input image. The algorithm uses the Gaussian mixture model to model the image gray-level distribution, and the intersection points of the Gaussian components in the model are used to partition the dynamic range of the image into input gray-level intervals. The contrast equalized image is generated by transforming the pixels' gray levels in each input interval to the appropriate output gray-level interval according to the dominant Gaussian component and the cumulative distribution function of the input interval. To take account of the hypothesis that homogeneous regions in the image represent homogeneous silences (or set of Gaussian components) in the image histogram, the Gaussian components with small variances are weighted with smaller values than the Gaussian components with larger variances, and the gray-level distribution is also used to weight the components in the mapping of the input interval to the output interval. Experimental results show that the proposed algorithm produces better or comparable enhanced images than several state-of-the-art algorithms. Unlike the other algorithms, the proposed algorithm is free of parameter setting for a given dynamic range of the enhanced image and can be applied to a wide range of image types. PMID:21775265

  20. Visual similarity measurement with the feature contrast model

    NASA Astrophysics Data System (ADS)

    Eidenberger, Horst; Breiteneder, Christian

    2003-01-01

    The focus of this paper is on similarity modeling. In the first part we revisit underlying concepts of similarity modeling and sketch the currently most used VIR similarity model (Linear Weighted Merging, LWM). Motivated by its drawbacks we introduce a new general similarity model called Logical Retrieval (LR) that offers more flexibility than LWM. In the second part we integrate the Feature Contrast Model (FCM) in this environment, developed by psychologists to explain human peculiarities in similarity perception. FCM is integrated as a general method for distance measurement. The results show that FCM performs (in the LR context) better than metric-based distance measurement. Euclidean distance is used for comparison because it is used in many VIR systems and is based on the questionable metric axioms. FCM minimizes the number of clusters in distance space. Therefore it is the ideal distance measure for LR. FCM allows a number of different parameterizations. The tests reveal that in average a symmetric, non-subtractive configuration that emphasizes common properties of visual objects performs best. Its major drawback in comparison to Euclidean distance is its worse performance (in terms of query execution time).

  1. Modeling and Analysis of Phase Contrast Imaging Measurements

    NASA Astrophysics Data System (ADS)

    Rost, J. C.; Porkolab, M.; Dorris, J. R.; Candy, J.; Burrell, K. H.

    2007-11-01

    The phase contrast imaging (PCI) diagnostic on DIII-D has been operated in several configurations over its lifetime. The beam path was changed in 2003 from tangential at the midplane LCFS to a path passing through the edge at an angle near 45 degrees and reaching typically r/a=0.8, and the maximum wavenumber has been increased from 7 to 30 cm-1. A synthetic diagnostic (SD) has been created to model all configurations of the PCI by post-processing the output of the GYRO gyrokinetic simulation. The SD includes line integration along the full path and models the detector to obtain the high- and low-k cutoffs. Modeling of a plasma discharge typical of DIII-D is used to interpret the PCI spectra S(k,f) in terms of turbulent ballooning modes and local S(kr,kθ,f). This allows us to identify parts of the PCI spectra with different plasma modes (ITG, TEM, ETG), separate effects of Doppler shift and intrinsic mode velocity in the measurement, and improve comparisons with other diagnostics. The SD will contribute to validation of the model through comparison between simulation and experiment.

  2. Maximum likelihood model based on minor allele frequencies and weighted Max-SAT formulation for haplotype assembly.

    PubMed

    Mousavi, Sayyed R; Khodadadi, Ilnaz; Falsafain, Hossein; Nadimi, Reza; Ghadiri, Nasser

    2014-06-01

    Human haplotypes include essential information about SNPs, which in turn provide valuable information for such studies as finding relationships between some diseases and their potential genetic causes, e.g., for Genome Wide Association Studies. Due to expensiveness of directly determining haplotypes and recent progress in high throughput sequencing, there has been an increasing motivation for haplotype assembly, which is the problem of finding a pair of haplotypes from a set of aligned fragments. Although the problem has been extensively studied and a number of algorithms have already been proposed for the problem, more accurate methods are still beneficial because of high importance of the haplotypes information. In this paper, first, we develop a probabilistic model, that incorporates the Minor Allele Frequency (MAF) of SNP sites, which is missed in the existing maximum likelihood models. Then, we show that the probabilistic model will reduce to the Minimum Error Correction (MEC) model when the information of MAF is omitted and some approximations are made. This result provides a novel theoretical support for the MEC, despite some criticisms against it in the recent literature. Next, under the same approximations, we simplify the model to an extension of the MEC in which the information of MAF is used. Finally, we extend the haplotype assembly algorithm HapSAT by developing a weighted Max-SAT formulation for the simplified model, which is evaluated empirically with positive results. PMID:24491253

  3. Invasive Allele Spread under Preemptive Competition

    NASA Astrophysics Data System (ADS)

    Yasi, J. A.; Korniss, G.; Caraco, T.

    We study a discrete spatial model for invasive allele spread in which two alleles compete preemptively, initially only the "residents" (weaker competitors) being present. We find that the spread of the advantageous mutation is well described by homogeneous nucleation; in particular, in large systems the time-dependent global density of the resident allele is well approximated by Avrami's law.

  4. 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…

  5. 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.

  6. Validation of SNP Allele Frequencies Determined by Pooled Next-Generation Sequencing in Natural Populations of a Non-Model Plant Species

    PubMed Central

    Rellstab, Christian; Zoller, Stefan; Tedder, Andrew; Gugerli, Felix; Fischer, Martin C.

    2013-01-01

    Sequencing of pooled samples (Pool-Seq) using next-generation sequencing technologies has become increasingly popular, because it represents a rapid and cost-effective method to determine allele frequencies for single nucleotide polymorphisms (SNPs) in population pools. Validation of allele frequencies determined by Pool-Seq has been attempted using an individual genotyping approach, but these studies tend to use samples from existing model organism databases or DNA stores, and do not validate a realistic setup for sampling natural populations. Here we used pyrosequencing to validate allele frequencies determined by Pool-Seq in three natural populations of Arabidopsis halleri (Brassicaceae). The allele frequency estimates of the pooled population samples (consisting of 20 individual plant DNA samples) were determined after mapping Illumina reads to (i) the publicly available, high-quality reference genome of a closely related species (Arabidopsis thaliana) and (ii) our own de novo draft genome assembly of A. halleri. We then pyrosequenced nine selected SNPs using the same individuals from each population, resulting in a total of 540 samples. Our results show a highly significant and accurate relationship between pooled and individually determined allele frequencies, irrespective of the reference genome used. Allele frequencies differed on average by less than 4%. There was no tendency that either the Pool-Seq or the individual-based approach resulted in higher or lower estimates of allele frequencies. Moreover, the rather high coverage in the mapping to the two reference genomes, ranging from 55 to 284x, had no significant effect on the accuracy of the Pool-Seq. A resampling analysis showed that only very low coverage values (below 10-20x) would substantially reduce the precision of the method. We therefore conclude that a pooled re-sequencing approach is well suited for analyses of genetic variation in natural populations. PMID:24244686

  7. 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.

  8. Population Bottlenecks and Nonequilibrium Models in Population Genetics. I. Allele Numbers When Populations Evolve from Zero Variability

    PubMed Central

    Maruyama, Takeo; Fuerst, Paul A.

    1984-01-01

    A simple numerical method was developed for the mean number and average age of alleles in a population that was initiated with no genetic variation following a sudden population expansion. The methods are used to examine the question of whether allele numbers are elevated compared with values seen in equilibrium populations having equivalent gene diversity. Excess allele numbers in expanding populations were found to be the rule. This was true whether the population began with zero variation or with low levels of variation in either of two initial distributions (initially an equilibrium allele frequency distribution or initially with loci occurring in only two classes of variation). Although the increase of alleles may persist for only a short time, when compared with the time which is required for approach to final equilibrium, the increase may be long when measured in absolute generation numbers. The pattern of increase in very rare alleles (those present only once in a sample) and the persistence of the original allele were also investigated. PMID:6500263

  9. Novel nano-sized MR contrast agent mediates strong tumor contrast enhancement in an oncogene-driven breast cancer model.

    PubMed

    Eriksson, Per-Olof; Aaltonen, Emil; Petoral, Rodrigo; Lauritzson, Petter; Miyazaki, Hideki; Pietras, Kristian; Månsson, Sven; Hansson, Lennart; Leander, Peter; Axelsson, Oskar

    2014-01-01

    The current study was carried out to test the potential of a new nanomaterial (Spago Pix) as a macromolecular magnetic MR contrast agent for tumor detection and to verify the presence of nanomaterial in tumor tissue. Spago Pix, synthesized by Spago Nanomedical AB, is a nanomaterial with a globular shape, an average hydrodynamic diameter of 5 nm, and a relaxivity (r1) of approximately 30 (mM Mn)-1 s-1 (60 MHz). The material consists of an organophosphosilane hydrogel with strongly chelated manganese (II) ions and a covalently attached PEG surface layer. In vivo MRI of the MMTV-PyMT breast cancer model was performed on a 3 T clinical scanner. Tissues were thereafter analyzed for manganese and silicon content using inductively coupled plasma-atomic emission spectroscopy (ICP-AES). The presence of nanomaterial in tumor and muscle tissue was assessed using an anti-PEG monoclonal antibody. MR imaging of tumor-bearing mice (n = 7) showed a contrast enhancement factor of 1.8 (tumor versus muscle) at 30 minutes post-administration. Contrast was retained and further increased 2-4 hours after administration. ICP-AES and immunohistochemistry confirmed selective accumulation of nanomaterial in tumor tissue. A blood pharmacokinetics analysis showed that the concentration of Spago Pix gradually decreased over the first hour, which was in good agreement with the time frame in which the accumulation in tumor occurred. In summary, we demonstrate that Spago Pix selectively enhances MR tumor contrast in a clinically relevant animal model. Based on the generally higher vascular leakiness in malignant compared to benign tissue lesions, Spago Pix has the potential to significantly improve cancer diagnosis and characterization by MRI. PMID:25296030

  10. 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.

  11. Comparison and contrast of genes and biological pathways responding to Marek’s disease virus infection using allele-specific expression and differential expression in broiler and layer chickens

    PubMed Central

    2013-01-01

    Background Marek’s disease (MD) is a commercially important neoplastic disease of chickens caused by the Marek’s disease virus (MDV), a naturally occurring oncogenic alphaherpesvirus. Enhancing MD genetic resistance is desirable to augment current vaccines and other MD control measures. High throughput sequencing was used to profile splenic transcriptomes from individual F1 progeny infected with MDV at 4 days of age from both outbred broilers (meat-type) and inbred layer (egg-type) chicken lines that differed in MD genetic resistance. The resulting information was used to identify SNPs, genes, and biological pathways exhibiting allele-specific expression (ASE) in response to MDV infection in each type of chicken. In addition, we compared and contrasted the results of pathway analyses (ASE and differential expression (DE)) between chicken types to help inform on the biological response to MDV infection. Results With 7 individuals per line and treatment group providing high power, we identified 6,132 single nucleotide polymorphisms (SNPs) in 4,768 genes and 4,528 SNPs in 3,718 genes in broilers and layers, respectively, that exhibited ASE in response to MDV infection. Furthermore, 548 and 434 genes in broilers and layers, respectively, were found to show DE following MDV infection. Comparing the datasets, only 72 SNPs and 850 genes for ASE and 20 genes for DE were common between the two bird types. Although the chicken types used in this study were genetically different, at the pathway level, both TLR receptor and JAK/STAT signaling pathways were enriched as well as exhibiting a high proportion of ASE genes, especially at the beginning of both above mentioned regulatory pathways. Conclusions RNA sequencing with adequate biological replicates is a powerful approach to identify high confidence SNPs, genes, and pathways that are associated with transcriptional response to MDV infection. In addition, the SNPs exhibiting ASE in response to MDV infection provide a

  12. Canopy resistance modelling for crops in contrasting water conditions

    NASA Astrophysics Data System (ADS)

    Rana, G.; Katerji, N.; Mastrorilli, M.

    Although canopy resistance to vapour water transport (r c) depends on climatic conditions and crop water status, standard constant daily values are usually used. Thus models using r c to predict evapotranspiration (ET) fail if applied to water stressed crops. On the other hand, in the scientific literature it is possible to find daily r c models dependent on soil moisture, but, in such cases, these need to be calibrated for each crop and site. Here a “climatic resistance” (r∗) is introduced as function of available energy, vapour pressure deficit and air temperature. Therefore a model of canopy resistance is presented on a hourly and daily time scale, where r c is expressed as function of r∗, aerodynamic resistance, r a, and predawn leaf water potential (PLWP), independently on the soil type. The model has been tested in Southern Italy on grass (reference crop), sorghum, sunflower and soybean and validated in France on soybean, without further calibration. The field crops were submitted to several water stress cycles: PLWP ranged between -0.1 and -1.2 MPa. The experiments showed that this model works well both under and without soil water constraints. On an hourly scale calculated ET in function of PLWP always presented a small underestimation (maximum 6% for soybean in Italy under senescence and water stress); on a daily scale these underestimations are reduced in general. The model test showed that it is independent of the site but depends only on the crop species. On a daily scale the model is presented also with available water (AW) as input, but in this case it needs local calibration. When AW is used as input the model showed an underestimation of 5% and 7% for sorghum and sunflower respectively.

  13. 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.

  14. 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

  15. Contrasting Models of the Healer's Role: South Texas Case Examples.

    ERIC Educational Resources Information Center

    Trotter, Robert T., II

    1982-01-01

    Two models of the healer's role are compared: physicians and Mexican American folk healers (curanderos). Effects of culture on the delivery of health care are manifested in the protection of patient modesty, locus of control over diagnosis and treatment, and the healer's role as a cultural interpreter of therapeutic regimens. (Author/NQA)

  16. 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. PMID:24424164

  17. 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

  18. Two nonlinear control schemes contrasted on a hydrodynamiclike model

    NASA Technical Reports Server (NTRS)

    Keefe, Laurence R.

    1993-01-01

    The principles of two flow control strategies, those of Huebler (Luescher and Huebler, 1989) and of Ott et al. (1990) are discussed, and the two schemes are compared for their ability to control shear flow, using fully developed and transitional solutions of the Ginzburg-Landau equation as models for such flows. It was found that the effectiveness of both methods in obtaining control of fully developed flows depended strongly on the 'distance' in state space between the uncontrolled flow and goal dynamics. There were conceptual difficulties in applying the Ott et al. method to transitional convectively unstable flows. On the other hand, the Huebler method worked well, within certain limitations, although at a large cost in energy terms.

  19. The contrast model method for the thermodynamical calculation of air-air wet heat exchanger

    NASA Astrophysics Data System (ADS)

    Yuan, Xiugan; Mei, Fang

    1989-02-01

    The 'contrast model' method thermodynamic calculation of air-air crossflow wet heat exchangers with initial air condensation is presented. Contrast-model equations are derived from the actual heat exchanger equations as well as imaginary ones; it is then possible to proceed to a proof that the enthalpy efficiency of the contrast model equations is similar to the temperature efficiency of the dry heat exchanger. Conditions are noted under which it becomes possible to unify thermodynamic calculations for wet and dry heat exchangers.

  20. 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.

  1. Power Laws for Heavy-Tailed Distributions: Modeling Allele and Haplotype Diversity for the National Marrow Donor Program

    PubMed Central

    Gragert, Loren; Maiers, Martin; Chatterjee, Ansu; Albrecht, Mark

    2015-01-01

    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

  2. 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

  3. X-Ray Phase-Contrast CT of a Pancreatic Ductal Adenocarcinoma Mouse Model

    PubMed Central

    Tapfer, Arne; Braren, Rickmer; Bech, Martin; Willner, Marian; Zanette, Irene; Weitkamp, Timm; Trajkovic-Arsic, Marija; Siveke, Jens T.; Settles, Marcus; Aichler, Michaela; Walch, Axel; Pfeiffer, Franz

    2013-01-01

    To explore the potential of grating-based x-ray phase-contrast computed tomography (CT) for preclinical research, a genetically engineered mouse model of pancreatic ductal adenocarcinoma (PDAC) was investigated. One ex-vivo mouse specimen was scanned with different grating-based phase-contrast CT imaging setups covering two different settings: i) high-resolution synchrotron radiation (SR) imaging and ii) dose-reduced imaging using either synchrotron radiation or a conventional x-ray tube source. These experimental settings were chosen to assess the potential of phase-contrast imaging for two different types of application: i) high-performance imaging for virtual microscopy applications and ii) biomedical imaging with increased soft-tissue contrast for in-vivo applications. For validation and as a reference, histological slicing and magnetic resonance imaging (MRI) were performed on the same mouse specimen. For each x-ray imaging setup, attenuation and phase-contrast images were compared visually with regard to contrast in general, and specifically concerning the recognizability of lesions and cancerous tissue. To quantitatively assess contrast, the contrast-to-noise ratios (CNR) of selected regions of interest (ROI) in the attenuation images and the phase images were analyzed and compared. It was found that both for virtual microscopy and for in-vivo applications, there is great potential for phase-contrast imaging: in the SR-based benchmarking data, fine details about tissue composition are accessible in the phase images and the visibility of solid tumor tissue under dose-reduced conditions is markedly superior in the phase images. The present study hence demonstrates improved diagnostic value with phase-contrast CT in a mouse model of a complex endogenous cancer, promoting the use and further development of grating-based phase-contrast CT for biomedical imaging applications. PMID:23536795

  4. 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

  5. Modeling of thickness dependent infrared radiance contrast of native and crude oil covered water surfaces.

    PubMed

    Shih, Wei-Chuan; Andrews, A Ballard

    2008-07-01

    We present a model for infrared radiance contrast of native and crude oil covered water surfaces. This model is based on the so called "direct" approach by treating individual volumetric elements as incoherent radiators. The total emitted radiation is calculated by the sum of individual contributions from the oil film and the underlying water, respectively. Therefore, different temperatures can be assigned to the oil film and water assuming quasi-static temperature distribution, enabling modeling of differential heating of the oil film during daytime. This model can be applied to remote sensing, particularly, to explain the historically observed thickness-dependent contrast in native and crude oil covered sea surfaces. PMID:18607467

  6. 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. PMID:25728575

  7. A normalized contrast-encoding model exhibits bright/dark asymmetries similar to early visual neurons.

    PubMed

    Cooper, Emily A

    2016-04-01

    Biological sensory systems share a number of organizing principles. One such principle is the formation of parallel streams. In the visual system, information about bright and dark features is largely conveyed via two separate streams: theONandOFFpathways. While brightness and darkness can be considered symmetric and opposite forms of visual contrast, the response properties of cells in theONandOFFpathways are decidedly asymmetric. Here, we ask whether a simple contrast-encoding model predicts asymmetries for brights and darks that are similar to the asymmetries found in theONandOFFpathways. Importantly, this model does not include any explicit differences in how the visual system represents brights and darks, but it does include a common normalization mechanism. The phenomena captured by the model include (1) nonlinear contrast response functions, (2) greater nonlinearities in the responses to darks, and (3) larger responses to dark contrasts. We report a direct, quantitative comparison between these model predictions and previously published electrophysiological measurements from the retina and thalamus (guinea pig and cat, respectively). This work suggests that the simple computation of visual contrast may account for a range of early visual processing nonlinearities. Assessing explicit models of sensory representations is essential for understanding which features of neuronal activity these models can and cannot predict, and for investigating how early computations may reverberate through the sensory pathways. PMID:27044852

  8. Computational Study of Computed Tomography Contrast Gradients in Models of Stenosed Coronary Arteries.

    PubMed

    Eslami, Parastou; Seo, Jung-Hee; Rahsepar, Amir Ali; George, Richard; Lardo, Albert C; Mittal, Rajat

    2015-09-01

    Recent computed tomography coronary angiography (CCTA) studies have noted higher transluminal contrast agent gradients in arteries with stenotic lesions, but the physical mechanism responsible for these gradients is not clear. We use computational fluid dynamics (CFD) modeling coupled with contrast agent dispersion to investigate the mechanism for these gradients. Simulations of blood flow and contrast agent dispersion in models of coronary artery are carried out for both steady and pulsatile flows, and axisymmetric stenoses of severities varying from 0% (unobstructed) to 80% are considered. Simulations show the presence of measurable gradients with magnitudes that increase monotonically with stenotic severity when other parameters are held fixed. The computational results enable us to examine and validate the hypothesis that transluminal contrast gradients (TCG) are generated due to the advection of the contrast bolus with time-varying contrast concentration that appears at the coronary ostium. Since the advection of the bolus is determined by the flow velocity in the artery, the magnitude of the gradient, therefore, encodes the coronary flow velocity. The correlation between the flow rate estimated from TCG and the actual flow rate in the computational model of a physiologically realistic coronary artery is 96% with a R2 value of 0.98. The mathematical formulae connecting TCG to flow velocity derived here represent a novel and potentially powerful approach for noninvasive estimation of coronary flow velocity from CT angiography. PMID:26102356

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. Retinal image contrast obtained by a model eye with combined correction of chromatic and spherical aberrations

    PubMed Central

    Ohnuma, Kazuhiko; Kayanuma, Hiroyuki; Lawu, Tjundewo; Negishi, Kazuno; Yamaguchi, Takefumi; Noda, Toru

    2011-01-01

    Correcting spherical and chromatic aberrations in vitro in human eyes provides substantial visual acuity and contrast sensitivity improvements. We found the same improvement in the retinal images using a model eye with/without correction of longitudinal chromatic aberrations (LCAs) and spherical aberrations (SAs). The model eye included an intraocular lens (IOL) and artificial cornea with human ocular LCAs and average human SAs. The optotypes were illuminated using a D65 light source, and the images were obtained using two-dimensional luminance colorimeter. The contrast improvement from the SA correction was higher than the LCA correction, indicating the benefit of an aspheric achromatic IOL. PMID:21698008

  14. A spatially-distributed computational model to quantify behaviour of contrast agents in MR perfusion imaging

    PubMed Central

    Cookson, A.N.; Lee, J.; Michler, C.; Chabiniok, R.; Hyde, E.; Nordsletten, D.; Smith, N.P.

    2014-01-01

    Contrast agent enhanced magnetic resonance (MR) perfusion imaging provides an early, non-invasive indication of defects in the coronary circulation. However, the large variation of contrast agent properties, physiological state and imaging protocols means that optimisation of image acquisition is difficult to achieve. This situation motivates the development of a computational framework that, in turn, enables the efficient mapping of this parameter space to provide valuable information for optimisation of perfusion imaging in the clinical context. For this purpose a single-compartment porous medium model of capillary blood flow is developed which is coupled with a scalar transport model, to characterise the behaviour of both blood-pool and freely-diffusive contrast agents characterised by their ability to diffuse through the capillary wall into the extra-cellular space. A parameter space study is performed on the nondimensionalised equations using a 2D model for both healthy and diseased myocardium, examining the sensitivity of system behaviour to Peclet number, Damköhler number (Da), diffusivity ratio and fluid porosity. Assuming a linear MR signal response model, sample concentration time series data are calculated, and the sensitivity of clinically-relevant properties of these signals to the model parameters is quantified. Both upslope and peak values display significant non-monotonic behaviour with regard to the Damköhler number, with these properties showing a high degree of sensitivity in the parameter range relevant to contrast agents currently in use. However, the results suggest that signal upslope is the more robust and discerning metric for perfusion quantification, in particular for correlating with perfusion defect size. Finally, the results were examined in the context of nonlinear signal response, flow quantification via Fermi deconvolution and perfusion reserve index, which demonstrated that there is no single best set of contrast agent parameters

  15. A discriminative-generative model for detecting intravenous contrast in CT images.

    PubMed

    Criminisi, Antonio; Juluru, Krishna; Pathak, Sayan

    2011-01-01

    This paper presents an algorithm for the automatic detection of intravenous contrast in CT scans. This is useful e.g. for quality control, given the unreliability of the existing DICOM contrast metadata. The algorithm is based on a hybrid discriminative-generative probabilistic model. A discriminative detector localizes enhancing regions of interest in the scan. Then a generative classifier optimally fuses evidence gathered from those regions into an efficient, probabilistic prediction. The main contribution is in the generative part. It assigns optimal weights to the detected organs based on their learned degree of enhancement under contrast material. The model is robust with respect to missing organs, patients geometry, pathology and settings. Validation is performed on a database of 400 highly variable patients CT scans. Results indicate detection accuracy greater than 91% at approximately 1 second per scan. PMID:22003683

  16. 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

  17. Investigation of lanthanide-based starch particles as a model system for liver contrast agents.

    PubMed

    Fossheim, S L; Kellar, K E; Mansson, S; Colet, J M; Rongved, P; Fahlvik, A K; Klaveness, J

    1999-02-01

    Gadolinium and dysprosium diethylenetriamine pentaacetic acid-labeled starch microparticles (Gd-DTPA-SP and Dy-DTPA-SP) were investigated as model liver contrast agents. The liver contrast efficacy of particles with low and high metal contents was compared in two imaging models: in vivo rat liver and ex vivo perfused rat liver. The biodistribution of intravenously injected particles was also assessed by ex vivo relaxometry and inductively coupled plasma atomic emission spectrophotometry of tissues. All particles reduced the liver signal intensity on T2-weighted spin-echo and gradient-recalled echo images as a result of susceptibility effects. Because of their higher magnetic susceptibility, the Dy-DTPA-SP were more effective negative contrast enhancers than the Gd-DTPA-SP. On T1-weighted spin-echo images, only the Gd-DTPA-SP with low metal content significantly increased the liver signal intensity. In addition, these low-loading Gd-DTPA-SP markedly reduced the blood T1. The two latter observations were not consistent with the anticipated blood circulation time of microparticles, but were a result of the lower stability of these particles in blood compared with Gd-DTPA-SP, which has a high metal content. Regardless of stability or imaging conditions, the paramagnetic starch particles investigated showed potential as negative liver contrast enhancers. However, the observed accumulation of particles in the lungs represented a biological limitation for their use as contrast agents. PMID:10077028

  18. Modelling Cue Interaction in the Perception of the Voiceless Fricative/Affricate Contrast.

    ERIC Educational Resources Information Center

    Faulkner, A.; And Others

    1995-01-01

    Reviews studies in which perceptual cue trading data have been compared with computational models and examines the perception of contrast between the voiceless fricative "s" and the voiceless affricate "ts." Nine subjects listened to a total of 6 tokens each of 193 stimuli and labeled each stimulus as containing either of the consonants "sh" or…

  19. 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.

  20. 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. PMID:24905907

  1. 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

  2. Modeling the subjective quality of highly contrasted videos displayed on LCD with local backlight dimming.

    PubMed

    Mantel, Claire; Bech, Søren; Korhonen, Jari; Forchhammer, Søren; Pedersen, Jesper Melgaard

    2015-02-01

    Local backlight dimming is a technology aiming at both saving energy and improving visual quality on television sets. As the rendition of the image is specified locally, the numerical signal corresponding to the displayed image needs to be computed through a model of the display. This simulated signal can then be used as input to objective quality metrics. The focus of this paper is on determining which characteristics of locally backlit displays influence quality assessment. A subjective experiment assessing the quality of highly contrasted videos displayed with various local backlight-dimming algorithms is set up. Subjective results are then compared with both objective measures and objective quality metrics using different display models. The first analysis indicates that the most significant objective features are temporal variations, power consumption (probably representing leakage), and a contrast measure. The second analysis shows that modeling of leakage is necessary for objective quality assessment of sequences displayed with local backlight dimming. PMID:25532206

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

    PubMed

    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

  4. 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

  5. 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.

  6. 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

  7. Extravasated Contrast Material in Penetrating Abdominopelvic Trauma: Dual-Contrast Dual-Energy CT for Improved Diagnosis—Preliminary Results in an Animal Model

    PubMed Central

    Mongan, John; Rathnayake, Samira; Fu, Yanjun; Gao, Dong-Wei

    2013-01-01

    Purpose: To compare the diagnostic performance of dual-energy (DE) computed tomography (CT) with two simultaneously administered contrast agents (hereafter, dual contrast) with that of conventional CT in the evaluation of the presence and source of extravasation in penetrating abdominopelvic trauma. Materials and Methods: Institutional animal care and use committee approval was obtained, and the study was performed in accordance with National Institutes of Health guidelines for the care and use of laboratory animals. Five rabbits with bowel trauma, vascular penetrating trauma, or both were imaged with simultaneous iodinated intravenous and bismuth subsalicylate enteric contrast material at DE CT. Four attending radiologists and six radiology residents without prior DE CT experience each evaluated 10 extraluminal collections to identify the vascular and/or enteric origin of extravasation and assess their level of diagnostic confidence, first with virtual monochromatic images simulating conventional CT and then with DE CT material decomposition attenuation maps. Results: Overall accuracy of identification of source of extravasation increased from 78% with conventional CT to 92% with DE CT (157 of 200 diagnoses vs 184 of 200 diagnoses, respectively; P < .001). Nine radiologists were more accurate with DE CT; one had no change. Mean confidence increased from 67% to 81% with DE CT (P < .001). Conclusion: In a rabbit abdominopelvic trauma model, dual-contrast DE CT significantly increased accuracy and confidence in the diagnosis of vascular versus enteric extravasated contrast material. © RSNA, 2013 PMID:23687174

  8. Improving image quality in poor visibility conditions using a physical model for contrast degradation.

    PubMed

    Oakley, J P; Satherley, B L

    1998-01-01

    In daylight viewing conditions, image contrast is often significantly degraded by atmospheric aerosols such as haze and fog. This paper introduces a method for reducing this degradation in situations in which the scene geometry is known. Contrast is lost because light is scattered toward the sensor by the aerosol particles and because the light reflected by the terrain is attenuated by the aerosol. This degradation is approximately characterized by a simple, physically based model with three parameters. The method involves two steps: first, an inverse problem is solved in order to recover the three model parameters; then, for each pixel, the relative contributions of scattered and reflected flux are estimated. The estimated scatter contribution is simply subtracted from the pixel value and the remainder is scaled to compensate for aerosol attenuation. This paper describes the image processing algorithm and presents an analysis of the signal-to-noise ratio (SNR) in the resulting enhanced image. This analysis shows that the SNR decreases exponentially with range. A temporal filter structure is proposed to solve this problem. Results are presented for two image sequences taken from an airborne camera in hazy conditions and one sequence in clear conditions. A satisfactory agreement between the model and the experimental data is shown for the haze conditions. A significant improvement in image quality is demonstrated when using the contrast enhancement algorithm in conjuction with a temporal filter. PMID:18267391

  9. 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.

  10. Monte Carlo model of a polychromatic laboratory based edge illumination x-ray phase contrast system.

    PubMed

    Millard, T P; Endrizzi, M; Diemoz, P C; Hagen, C K; Olivo, A

    2014-05-01

    A Monte Carlo model of a polychromatic laboratory based (coded aperture) edge illumination x-ray phase contrast imaging system has been developed and validated against experimental data. The ability for the simulation framework to be used to model two-dimensional images is also shown. The Monte Carlo model has been developed using the McXtrace engine and is polychromatic, i.e., results are obtained through the use of the full x-ray spectrum rather than an effective energy. This type of simulation can in future be used to model imaging of objects with complex geometry, for system prototyping, as well as providing a first step towards the development of a simulation for modelling dose delivery as a part of translating the imaging technique for use in clinical environments. PMID:24880377

  11. Automatic 3-D gravity modeling of sedimentary basins with density contrast varying parabolically with depth

    NASA Astrophysics Data System (ADS)

    Chakravarthi, V.; Sundararajan, N.

    2004-07-01

    A method to model 3-D sedimentary basins with density contrast varying with depth is presented along with a code GRAV3DMOD. The measured gravity fields, reduced to a horizontal plane, are assumed to be available at grid nodes of a rectangular/square mesh. Juxtaposed 3-D rectangular/square blocks with their geometrical epicenters on top coincide with grid nodes of a mesh to approximate a sedimentary basin. The algorithm based on Newton's forward difference formula automatically calculates the initial depth estimates of a sedimentary basin assuming that 2-D infinite horizontal slabs among which, the density contrast varies with depth could generate the measured gravity fields. Forward modeling is realized through an available code GR3DPRM, which computes the theoretical gravity field of a 3-D block. The lower boundary of a sedimentary basin is formulated by estimating the depth values of the 3-D blocks within predetermined limits. The algorithm is efficient in the sense that it automatically generates the grid files of the interpreted results that can be viewed in the form of respective contour maps. Measured gravity fields pertaining to the Chintalpudi sub-basin, India and the Los Angeles basin, California, USA in which the density contrast varies with depth are interpreted to show the applicability of the method.

  12. 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. PMID:16409100

  13. 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.

  14. Dynamic Contrast-Enhanced MRI Using a Macromolecular MR Contrast Agent (P792): Evaluation of Antivascular Drug Effect in a Rabbit VX2 Liver Tumor Model

    PubMed Central

    Park, Hee Sun; Lee, Jeong Min; Kim, Young Il; Woo, Sungmin; Yoon, Jung Hwan; Choi, Jin-Young; Choi, Byung Ihn

    2015-01-01

    Objective To evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using macromolecular contrast agent (P792) for assessment of vascular disrupting drug effect in rabbit VX2 liver tumor models. Materials and Methods This study was approved by our Institutional Animal Care and Use Committee. DCE-MRI was performed with 3-T scanner in 13 VX2 liver tumor-bearing rabbits, before, 4 hours after, and 24 hours after administration of vascular disrupting agent (VDA), using gadomelitol (P792, n = 7) or low molecular weight contrast agent (gadoterate meglumine [Gd-DOTA], n = 6). P792 was injected at a of dose 0.05 mmol/kg, while that of Gd-DOTA was 0.2 mmol/kg. DCE-MRI parameters including volume transfer coefficient (Ktrans) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) of tumors were compared between the 2 groups at each time point. DCE-MRI parameters were correlated with tumor histopathology. Reproducibility in measurement of DCE-MRI parameters and image quality of source MR were compared between groups. Results P792 group showed a more prominent decrease in Ktrans and iAUC at 4 hours and 24 hours, as compared to the Gd-DOTA group. Changes in DCE-MRI parameters showed a weak correlation with histologic parameters (necrotic fraction and microvessel density) in both groups. Reproducibility of DCE-MRI parameters and overall image quality was not significantly better in the P792 group, as compared to the Gd-DOTA group. Conclusion Dynamic contrast-enhanced magnetic resonance imaging using a macromolecular contrast agent shows changes of hepatic perfusion more clearly after administration of the VDA. Gadolinium was required at smaller doses than a low molecular contrast agent. PMID:26357497

  15. Comparison between PUN and Tofts models in the quantification of dynamic contrast-enhanced MR imaging

    NASA Astrophysics Data System (ADS)

    Mazzetti, S.; Gliozzi, A. S.; Bracco, C.; Russo, F.; Regge, D.; Stasi, M.

    2012-12-01

    Dynamic contrast-enhanced study in magnetic resonance imaging (DCE-MRI) is an important tool in oncology to visualize tissues vascularization and to define tumour aggressiveness on the basis of an altered perfusion and permeability. Pharmacokinetic models are generally used to extract hemodynamic parameters, providing a quantitative description of the contrast uptake and wash-out. Empirical functions can also be used to fit experimental data without the need of any assumption about tumour physiology, as in pharmacokinetic models, increasing their diagnostic utility, in particular when automatic diagnosis systems are implemented on the basis of an MRI multi-parametric approach. Phenomenological universalities (PUN) represent a novel tool for experimental research and offer a simple and systematic method to represent a set of data independent of the application field. DCE-MRI acquisitions can thus be advantageously evaluated by the extended PUN class, providing a convenient diagnostic tool to analyse functional studies, adding a new set of features for the classification of malignant and benign lesions in computer aided detection systems. In this work the Tofts pharmacokinetic model and the class EU1 generated by the PUN description were compared in the study of DCE-MRI of the prostate, evaluating complexity of model implementation, goodness of fitting results, classification performances and computational cost. The mean R2 obtained with the EU1 and Tofts model were equal to 0.96 and 0.90, respectively, and the classification performances achieved by the EU1 model and the Tofts implementation discriminated malignant from benign tissues with an area under the receiver operating characteristic curve equal to 0.92 and 0.91, respectively. Furthermore, the EU1 model has a simpler functional form which reduces implementation complexity and computational time, requiring 6 min to complete a patient elaboration process, instead of 8 min needed for the Tofts model analysis.

  16. Contrast/offset-invariant generic low-order MGRF models of uniform textures

    NASA Astrophysics Data System (ADS)

    Liu, Ni; Gimel'farb, Georgy; Delmas, Patrice; Chan, Yuk Hin

    2013-10-01

    Statistical properties of many textured objects on digital biomedical images are often nearly translation-invariant, except for sizeable spatially-variant perceptive (contrast and offset) deviations due to different imaging conditions and/or contrast agents. To make widely-used translation-invariant Markov-Gibbs random field (MGRF) models of uniform textures more suitable for biomedical objects, we introduce, in the context of semi-supervised texture recognition, a new class of generic low-order MGRFs. These models account for ordinal relations between signals, rather than signal magnitudes, and therefore are invariant also to arbitrary perceptive signal deviations. Since the numbers of the possible ordinal relations are considerably smaller, than of signal co-occurrences, our earlier fast framework for learning generic 2nd-order MGRFs with multiple translation-invariant pixel/voxel interactions is easily extended up to the 4th-or even higher-order ordinal models. To explore the class introduced, the learned generic 3rd-order ordinal and 2nd-order co-occurrence-based and ordinal MGRFs are experimentally compared on the popular OUTEX and Brodatz databases of realistic natural textures. The experiments have shown that the ordinal 3rd-order model not only has as good descriptive abilities as the conventional co-occurrence-based 2nd-order one, but also is both simpler and considerably more robust to the perceptive deviations.

  17. Generation and modelling of megavoltage photon beams for contrast-enhanced radiation therapy

    NASA Astrophysics Data System (ADS)

    Robar, J. L.

    2006-11-01

    Contrast-enhanced radiation therapy (CERT) is a treatment approach involving the irradiation of tumours containing high atomic number (Z) contrast media, using low-quality x-ray beams. This work describes the experimental generation of x-ray beams using a linear accelerator with low-Z target materials (beryllium and aluminium), in order to produce photon energy spectra appropriate for CERT. Measurements were made to compare the experimental beams to conventional linear accelerator photon beams in terms of per cent depth dose. Monte Carlo simulation was used to model the generation of each beam, and models were validated against experimental measurement. Validated models were used to demonstrate changes in photon spectra as well as to quantify the variation of tumour dose enhancement with iodinated contrast medium concentration in a simulated tumour volume. Finally, the ratio of the linear attenuation coefficient for iodinated contrast medium relative to water was determined experimentally as a function of iodine concentration. Beams created with low-Z targets show significant changes in energy spectra compared to conventional beams. For the 4 MeV/Be beam, for example, 33% of photons have energies below 60 keV. Measurements and calculation show that both the linear attenuation coefficient ratio and dose enhancement factor (DEF) increase most rapidly at concentrations below 46 mg I ml-1. There is a significant dependence of DEF on electron energy and a lesser dependence on target material. The 4 MeV/Be beam is the most promising in terms of magnitude of DEF—for example, DEF values of 1.16 and 1.29 are obtained for concentrations of 20 mg I ml-1 and 50 mg I ml-1, respectively. DEF will increase or decrease, respectively, for shallower or deeper tumours at a rate of approximately 1.1% cm-1. In summary, we show that significant dose enhancement is possible by altering the linear accelerator target and filtration, but the magnitude is highly dependent on contrast

  18. 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. PMID:23471751

  19. Biased Allelic Expression in Human Primary Fibroblast Single Cells

    PubMed Central

    Borel, Christelle; Ferreira, Pedro G.; Santoni, Federico; Delaneau, Olivier; Fort, Alexandre; Popadin, Konstantin Y.; Garieri, Marco; Falconnet, Emilie; Ribaux, Pascale; Guipponi, Michel; Padioleau, Ismael; Carninci, Piero; Dermitzakis, Emmanouil T.; Antonarakis, Stylianos E.

    2015-01-01

    The study of gene expression in mammalian single cells via genomic technologies now provides the possibility to investigate the patterns of allelic gene expression. We used single-cell RNA sequencing to detect the allele-specific mRNA level in 203 single human primary fibroblasts over 133,633 unique heterozygous single-nucleotide variants (hetSNVs). We observed that at the snapshot of analyses, each cell contained mostly transcripts from one allele from the majority of genes; indeed, 76.4% of the hetSNVs displayed stochastic monoallelic expression in single cells. Remarkably, adjacent hetSNVs exhibited a haplotype-consistent allelic ratio; in contrast, distant sites located in two different genes were independent of the haplotype structure. Moreover, the allele-specific expression in single cells correlated with the abundance of the cellular transcript. We observed that genes expressing both alleles in the majority of the single cells at a given time point were rare and enriched with highly expressed genes. The relative abundance of each allele in a cell was controlled by some regulatory mechanisms given that we observed related single-cell allelic profiles according to genes. Overall, these results have direct implications in cellular phenotypic variability. PMID:25557783

  20. 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

  1. 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.

  2. NAME modelling activities for the CAST-CONTRAST-ATTREX VSLS measurements

    NASA Astrophysics Data System (ADS)

    Filus, Michal; Harris, Neil; Pyle, John; Ashfold, Matt; Atlas, Eliott; Navarro, Maria; Meneguz, Elena; Manning, Alistair

    2015-04-01

    The Numerical Atmospheric dispersion Modeling Environment (NAME) model is used to assess the spatial and temporal variability of transport of very short-lived halogenated organic species (VSLS), in particular bromoform, dibromomethane and methyl iodide, within the West Pacific tropical region. The NAME modelling results are compared with airborne measurements of VSLS taken during NASA ATTREX, NCAR CONTRAST and NERC CAST campaigns in January-March, 2014. NAME model aims to link the aircraft measurements to examine the vertical distribution of VSLS in the West Pacific troposphere. The major focus will be on assessing vertical transport in deep convection which is one of the crucial factors in redistributing chemicals within the tropical troposphere. The work presented shows the analysis of NAME runs made from the ATTREX flights over the East Pacific in January-February, 2013 and the ATTREX and CONTRAST flight tracks over the West Pacific in January-March, 2014. Each ATTREX 2013 and 2014 flight track is divided into segments, from which particles are released and followed backward to identify the low-level sources of air. Particles (15,000 per single point along the flight track) are released from the flight altitudes tracks and followed 12-days backwards. Fractions of trajectories are calculated according to particles which crossed below 5 and 1 km (corresponding to low troposphere and oceanic boundary layer, respectively). Then, initial concentrations for VSLS are assigned to particles which originated from below 5/1 km and final concentrations at flight altitudes are determined. NAME modeled results are compared with ATTREX VSLS flight measurements. Interannual variability of atmospheric transport of VSLS in the Tropics is studied by performing mock ATTREX-flight NAME runs for years: 2005-2014, with emphasis put on strong ENSO phase years.

  3. 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 . PMID:25995102

  4. Longitudinal in vivo monitoring of rodent glioma models through thinned skull using laser speckle contrast imaging

    NASA Astrophysics Data System (ADS)

    Rege, Abhishek; Seifert, Alan C.; Schlattman, Dan; Ouyang, Yu; Li, Khan W.; Basaldella, Luca; Brem, Henry; Tyler, Betty M.; Thakor, Nitish V.

    2012-12-01

    Laser speckle contrast imaging (LSCI) is a contrast agent free imaging technique suited for longitudinal assessment of vascular remodeling that accompanies brain tumor growth. We report the use of LSCI to monitor vascular changes in a rodent glioma model. Ten rats are inoculated with 9L gliosarcoma cells, and the angiogenic response is monitored five times over two weeks through a thinned skull imaging window. We are able to visualize neovascularization and measure the number of vessels per unit area to assess quantitatively the microvessel density (MVD). Spatial spread of MVD reveals regions of high MVD that may correspond to tumor location. Whole-field average MVD values increase with time in the tumor group but are fairly stable in the control groups. Statistical analysis shows significant differences in MVD values between the tumor group and both saline-receiving and unperturbed control groups over the two-week period (p<0.05). In conclusion, LSCI is suitable for investigation of tumor angiogenesis in rodent models. In addition, the statistical difference (p<0.02) between MVD values of the tumor (24.40±1.41) and control groups (15.40±1.60) on the 14th day after inoculation suggests a potential use of LSCI in the clinic in distinguishing tumor environments from normal vasculature.

  5. Modelling contrasting responses of wetland productivity to changes in water table depth

    NASA Astrophysics Data System (ADS)

    Grant, R. F.; Desai, A. R.; Sulman, B. N.

    2012-05-01

    Responses of wetland productivity to changes in water table depth (WTD) are controlled by complex interactions among several soil and plant processes, and hence are site-specific rather than general in nature. Hydrological controls on wetland productivity were studied by representing these interactions in connected hummock and hollow sites in the ecosystem model ecosys, and by testing CO2 and energy fluxes from the model with those measured by eddy covariance (EC) during years with contrasting WTD in a shrub fen at Lost Creek, WI. Modelled interactions among coupled processes for O2 transfer, O2 uptake, C oxidation, N mineralization, N uptake and C fixation by diverse microbial, root, mycorrhizal and shoot populations enabled the model to simulate complex responses of CO2 exchange to changes in WTD that depended on the WTD at which change was occurring. At the site scale, greater WTD caused the model to simulate greater CO2 influxes and effluxes over hummocks vs. hollows, as has been found at field sites. At the landscape scale, greater WTD caused the model to simulate greater diurnal CO2 influxes and effluxes under cooler weather when water tables were shallow, but also smaller diurnal CO2 influxes and effluxes under warmer weather when water tables were deeper, as was also apparent in the EC flux measurements. At an annual time scale, these diurnal responses to WTD in the model caused lower net primary productivity (NPP) and heterotrophic respiration (Rh), but higher net ecosystem productivity (NEP = NPP - Rh), to be simulated in a cooler year with a shallower water table than in a warmer year with a deeper one. This difference in NEP was consistent with those estimated from gap-filled EC fluxes in years with different water tables at Lost Creek and at similar boreal fens elsewhere. In sensitivity test of the model, annual NEP declined with increasing WTD in a year with a shallow water table, but rose in a year with a deeper one. The model thus provided an

  6. Modelling contrasting responses of wetland productivity to changes in water table depth

    NASA Astrophysics Data System (ADS)

    Grant, R. F.; Desai, A. R.; Sulman, B. N.

    2012-11-01

    Responses of wetland productivity to changes in water table depth (WTD) are controlled by complex interactions among several soil and plant processes, and hence are site-specific rather than general in nature. Hydrological controls on wetland productivity were studied by representing these interactions in connected hummock and hollow sites in the ecosystem model ecosys, and by testing CO2 and energy fluxes from the model with those measured by eddy covariance (EC) during years with contrasting WTD in a shrub fen at Lost Creek, WI. Modelled interactions among coupled processes for O2 transfer, O2 uptake, C oxidation, N mineralization, N uptake and C fixation by diverse microbial, root and mycorrhizal populations enabled the model to simulate complex responses of CO2 exchange to changes in WTD that depended on the WTD at which change was occurring. At the site scale, greater WTD caused the model to simulate greater CO2 influxes and effluxes over hummocks vs. hollows, as has been found at field sites. At the landscape scale, greater WTD caused the model to simulate greater diurnal CO2 influxes and effluxes under cooler weather when water tables were shallow, but also smaller diurnal CO2 influxes and effluxes under warmer weather when water tables were deeper, as was also apparent in the EC flux measurements. At an annual time scale, these diurnal responses to WTD in the model caused lower net primary productivity (NPP) and heterotrophic respiration (Rh), but higher net ecosystem productivity (NEP = NPP - Rh), to be simulated in a cooler year with a shallower water table than in a warmer year with a deeper one. This difference in NEP was consistent with those estimated from gap-filled EC fluxes in years with different water tables at Lost Creek and at similar boreal fens elsewhere. In sensitivity tests of the model, annual NEP declined with increasing WTD in a year with a shallow water table, but rose in a year with a deeper one. The model thus provided an integrated

  7. Modelling Contrasting Responses of Wetland Productivity to Changes in Water Table Depth

    NASA Astrophysics Data System (ADS)

    Grant, R. F.; Desai, A. R.; Sulman, B. N.

    2012-12-01

    Responses of wetland productivity to changes in water table depth (WTD) are controlled by complex interactions among several soil and plant processes, and hence are site-specific rather than general in nature. Hydrological controls on wetland productivity were studied by representing these interactions in connected hummock and hollow sites in the ecosystem model ecosys, and by testing CO2 and energy fluxes from the model with those measured by eddy covariance (EC) during years with contrasting WTD in a shrub fen at Lost Creek, WI. Modelled interactions among coupled processes for O2 transfer, O2 uptake, C oxidation, N mineralization, N uptake and C fixation by diverse microbial, root and mycorrhizal populations enabled the model to simulate complex responses of CO2 exchange to changes in WTD that depended on the WTD at which change was occurring. At the site scale, greater WTD caused the model to simulate greater CO2 influxes and effluxes over hummocks vs. hollows, as has been found at field sites. At the landscape scale, greater WTD caused the model to simulate greater diurnal CO2 influxes and effluxes under cooler weather when water tables were shallow, but also smaller diurnal CO2 influxes and effluxes under warmer weather when water tables were deeper, as was also apparent in the EC flux measurements. At an annual time scale, these diurnal responses to WTD in the model caused lower net primary productivity (NPP) and heterotrophic respiration (Rh), but higher net ecosystem productivity (NEP = NPP - Rh), to be simulated in a cooler year with a shallower water table than in a warmer year with a deeper one. This difference in NEP was consistent with those estimated from gap-filled EC fluxes in years with different water tables at Lost Creek and at similar boreal fens elsewhere. In sensitivity test of the model, annual NEP declined with increasing WTD in a year with a shallow water table, but rose in a year with a deeper one. The model thus provided an integrated

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

    NASA Astrophysics Data System (ADS)

    Jakobsen, M.; Wu, R. S.

    2016-04-01

    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 garantied to converge if the global contrast is relatively small. For frequency domain waveform modelling of realistic contrasts, some kind of renormalization may be reguired. 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 acts across different length scales. In the scattering series of De Wolf, a renormalization of the Green functions is achieved by a split of the scattering potential operator into fore- and back-scattering 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

  9. 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

  10. Visualization of 3D geometric models of the breast created from contrast-enhanced MRI

    NASA Astrophysics Data System (ADS)

    Leader, J. Ken, III; Wang, Xiao Hui; Chang, Yuan-Hsiang; Chapman, Brian E.

    2002-05-01

    Contrast enhanced breast MRI is currently used as an adjuvant modality to x-ray mammography because of its ability to resolve ambiguities and determine the extent of malignancy. This study described techniques to create and visualize 3D geometric models of abnormal breast tissue. MRIs were performed on a General Electric 1.5 Tesla scanner using dual phased array breast coils. Image processing tasks included: 1) correction of image inhomogeneity caused by the coils, 2) segmentation of normal and abnormal tissue, and 3) modeling and visualization of the segmented tissue. The models were visualized using object-based surface rendering which revealed characteristics critical to differentiating benign from malignant tissue. Surface rendering illustrated the enhancement distribution and enhancement patterns. The modeling process condensed the multi-slice MRI data information and standardized its interpretation. Visualizing the 3D models should improve the radiologist's and/or surgeon's impression of the 3D shape, extent, and accessibility of the malignancy compared to viewing breast MRI data slice by slice.

  11. 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.

  12. Microsatellite allele frequencies in humans and chimpanzees, with implications for constraints on allele size.

    PubMed

    Garza, J C; Slatkin, M; Freimer, N B

    1995-07-01

    The distributions of allele sizes at eight simple-sequence repeat (SSR) or microsatellite loci in chimpanzees are found and compared with the distributions previously obtained from several human populations. At several loci, the differences in average allele size between chimpanzees and humans are sufficiently small that there might be a constraint on the evolution of average allele size. Furthermore, a model that allows for a bias in the mutation process shows that for some loci a weak bias can account for the observations. Several alleles at one of the loci (Mfd 59) were sequenced. Differences between alleles of different lengths were found to be more complex than previously assumed. An 8-base-pair deletion was present in the nonvariable region of the chimpanzee locus. This locus contains a previously unrecognized repeated region, which is imperfect in humans and perfect in chimpanzees. The apparently greater opportunity for mutation conferred by the two perfect repeat regions in chimpanzees is reflected in the higher variance in repeat number at Mfd 59 in chimpanzees than in humans. These data indicate that interspecific differences in allele length are not always attributable to simple changes in the number of repeats. PMID:7659015

  13. Characterization of Mechanical Properties of Tissue Scaffolds by Phase Contrast Imaging and Finite Element Modeling.

    PubMed

    Bawolin, Nahshon K; Dolovich, Allan T; Chen, Daniel X B; Zhang, Chris W J

    2015-08-01

    In tissue engineering, the cell and scaffold approach has shown promise as a treatment to regenerate diseased and/or damaged tissue. In this treatment, an artificial construct (scaffold) is seeded with cells, which organize and proliferate into new tissue. The scaffold itself biodegrades with time, leaving behind only newly formed tissue. The degradation qualities of the scaffold are critical during the treatment period, since the change in the mechanical properties of the scaffold with time can influence cell behavior. To observe in time the scaffold's mechanical properties, a straightforward method is to deform the scaffold and then characterize scaffold deflection accordingly. However, experimentally observing the scaffold deflection is challenging. This paper presents a novel study on characterization of mechanical properties of scaffolds by phase contrast imaging and finite element modeling, which specifically includes scaffold fabrication, scaffold imaging, image analysis, and finite elements (FEs) modeling of the scaffold mechanical properties. The innovation of the work rests on the use of in-line phase contrast X-ray imaging at 20 KeV to characterize tissue scaffold deformation caused by ultrasound radiation forces and the use of the Fourier transform to identify movement. Once deformation has been determined experimentally, it is then compared with the predictions given by the forward solution of a finite element model. A consideration of the number of separate loading conditions necessary to uniquely identify the material properties of transversely isotropic and fully orthotropic scaffolds is also presented, along with the use of an FE as a form of regularization. PMID:25902011

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

    DOE PAGESBeta

    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 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

  15. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26511147

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

    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.

  18. Fluorescent and scattering contrast agents in a mouse model of colorectal cancer

    NASA Astrophysics Data System (ADS)

    Winkler, Amy M.; Rice, Photini F. S.; Troutman, Timothy S.; Backer, Marina V.; Backer, Joseph M.; Drezek, Rebekah A.; Romanowski, Marek; Barton, Jennifer K.

    2008-02-01

    In previous work we have demonstrated the utility of laser-induced fluorescence (LIF) and optical coherence tomography (OCT) to identify adenoma in mouse models of colorectal cancer with high sensitivity and specificity. However, improved sensitivity to early disease, as well as the ability to distinguish confounders (e.g. fecal contamination, natural variations in mucosal thickness), is desired. In this study, we investigated the signal enhancement of fluorescent and scattering contrast agents in the colons of AOM-treated mice. The fluorescent tracer scVEGF/Cy, targeted to receptors for vascular endothelial growth factor, was visualized on a dual modality OCT/LIF endoscopic system with 1300-nm center wavelength OCT source and 635-nm LIF excitation. Scattering agents were tested with an 890-nm center wavelength endoscopic OCT system. Agents included nanoshells, 120-nm in diameter, and nanorods, 20-nm in diameter by 80-nm in length. Following imaging, colons were excised. Tissue treated with fluorophore was imaged on an epifluorescence microscope. Histological sections were obtained and stained with H&E and silver enhancer to verify disease and identify regions of gold uptake, respectively. Non-specific signal enhancement was observed with the scattering contrast agents. Specificity for adenoma was seen with the scVEGF/Cy dye.

  19. 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

  20. 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.

  1. 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.

  2. siRNA-mediated Allele-specific Silencing of a COL6A3 Mutation in a Cellular Model of Dominant Ullrich Muscular Dystrophy

    PubMed Central

    Bolduc, Véronique; Zou, Yaqun; Ko, Dayoung; Bönnemann, Carsten G

    2014-01-01

    Congenital muscular dystrophy type Ullrich (UCMD) is a severe disorder of early childhood onset for which currently there is no effective treatment. UCMD commonly is caused by dominant-negative mutations in the genes coding for collagen type VI, a major microfibrillar component of the extracellular matrix surrounding the muscle fibers. To explore RNA interference (RNAi) as a potential therapy for UCMD, we designed a series of small interfering RNA (siRNA) oligos that specifically target the most common mutations resulting in skipping of exon 16 in the COL6A3 gene and tested them in UCMD-derived dermal fibroblasts. Transcript analysis by semiquantitative and quantitative reverse transcriptase PCR showed that two of these siRNAs were the most allele-specific, i.e., they efficiently knocked down the expression from the mutant allele, without affecting the normal allele. In HEK293T cells, these siRNAs selectively suppressed protein expression from a reporter construct carrying the mutation, with no or minimal suppression of the wild-type (WT) construct, suggesting that collagen VI protein levels are as also reduced in an allele-specific manner. Furthermore, we found that treating UCMD fibroblasts with these siRNAs considerably improved the quantity and quality of the collagen VI matrix, as assessed by confocal microscopy. Our current study establishes RNAi as a promising molecular approach for treating dominant COL6-related dystrophies. PMID:24518369

  3. Regional differences of HFE (C282Y, H63D) allele frequencies in the Netherlands A model case illustrating the significance of genographics and prehistorical population migration.

    PubMed

    Cobbaert, C M; Delanghe, J; Boer, J M A; Feskens, E J M

    2012-01-01

    We investigated HFE C282Y and H63D allele frequencies in three Dutch towns in the Netherlands, as well as their association with cardiovascular disease (CVD) mortality. Study subjects were selected from participants of the Monitoring Project on Cardiovascular Disease Risk Factors in the Netherlands carried out in Amsterdam, Doetinchem and Maastricht among > 35000 subjects, 20-59 years of age. Mortality follow-up lasted 9 to 13 years. A random sample of the cohort (n = 1075) provided information on the total study population. The random sample and all CVD deaths (n = 301) were genotyped for the C282Y and H63D mutation. Adjusted hazard ratios (HR) for CVD mortality were calculated per genotype. C282Y allele frequencies differed significantly between the towns investigated (p = 0.017), whereas the allele frequencies of H63D were similar (p = 0.141) across towns. In Maastricht we found a C282Y allele frequency of 0.086 compared to 0.055 in Amsterdam and 0.054 in Doetinchem. C282Y and H63D heterozygosity did not predict fatal CVD in either men or women, whereas homozygosity for the H63D mutation increased fatal CVD in women (adjusted HR = 8.5; 95% CI = 2.3-31.1). The unexpected high C282Y allele frequency in Maastricht is in line with the recent evidence of a Celtic origin of citizens from the former southern Netherlands and with prehistorical population migrations revealed in the context of the international Genographic Project, a landmark study of prehistorical human migrations around the globe. We recommend that when designing national screening programmes and national registries for genetic disorders, potential regional prevalence differences should be taken into account. PMID:23340149

  4. Dose assessment in contrast enhanced digital mammography using simple phantoms simulating standard model breasts

    NASA Astrophysics Data System (ADS)

    Bouwman, R. W.; van Engen, R. E.; Young, K. C.; Veldkamp, W. J. H.; Dance, D. R.

    2015-01-01

    Slabs of polymethyl methacrylate (PMMA) or a combination of PMMA and polyethylene (PE) slabs are used to simulate standard model breasts for the evaluation of the average glandular dose (AGD) in digital mammography (DM) and digital breast tomosynthesis (DBT). These phantoms are optimized for the energy spectra used in DM and DBT, which normally have a lower average energy than used in contrast enhanced digital mammography (CEDM). In this study we have investigated whether these phantoms can be used for the evaluation of AGD with the high energy x-ray spectra used in CEDM. For this purpose the calculated values of the incident air kerma for dosimetry phantoms and standard model breasts were compared in a zero degree projection with the use of an anti scatter grid. It was found that the difference in incident air kerma compared to standard model breasts ranges between -10% to +4% for PMMA slabs and between 6% and 15% for PMMA-PE slabs. The estimated systematic error in the measured AGD for both sets of phantoms were considered to be sufficiently small for the evaluation of AGD in quality control procedures for CEDM. However, the systematic error can be substantial if AGD values from different phantoms are compared.

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

    PubMed Central

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

    2014-01-01

    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. PMID:24688175

  6. 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

  7. 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

  8. The role of lithological contrasts in the formation of sinkholes: a Distinct Element Method modelling perspective

    NASA Astrophysics Data System (ADS)

    Al-Halbouni, Djamil; Holohan, Eoghan P.; Dahm, Torsten

    2015-04-01

    Sinkhole formation is a geological phenomenon resulting from dissolution and subrosion of rocks or sediments at depth, where large secondary pore space and cavities may develop, and from the eventual subsidence of the overburden. Although sinkholes may develop slowly as a natural process, their formation is often intensified by human activities. For instance, sinkhole hazard has intensified at the Dead Sea shoreline in the Middle East since the beginning of the recession of the Dead Sea level. Another example concerns sinkhole formation induced by solution mining of salt rock in the Lorraine district, France. Signs of precursors to collapse sinkholes have sometimes been indicated by monitoring studies, but are not well understood in terms of quantitative models. Here we report on a general, simplified approach to simulating sinkhole formation by using 2D Distinct Element Method (PFC2D) models comprising elastically bonded particles. The presence of bonds leads to elastic rock deformation under loading conditions and bond breakage may result in spontaneous formation of faults and cracks. Using different rheological parameters like Young's modulus, density, cohesion and friction coefficients, this method is able to simulate realistic rock layering contrasts. The dissolution or subrosion process leading to the formation of underground cavities is simulated via simple incremental particle deletion, whereby an arbitrary dissolution rate can be determined. Model structures preceding a sinkhole collapse, as well as precursory changes in density or porosity, are explicitly simulated and may be linked to measured geophysical parameters such as microseismicity, seismic velocity and electric conductivity. As well as examining precursory phenomena, we study the effect of lithological contrasts on (1) the geometry of sinkholes (diameter to depth ratio) and (2) the onset of collapse. Beside the formulation of general relations, we compare our simulations to well documented case

  9. 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.

  10. 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. PMID:17002735

  11. 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. PMID:21508601

  12. 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)

  13. 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

  14. Modelling of 'sub-atomic' contrast resulting from back-bonding on Si(111)-7×7.

    PubMed

    Sweetman, Adam; Jarvis, Samuel P; Rashid, Mohammad A

    2016-01-01

    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

  15. Contrast studies.

    PubMed

    Anderson, Susan M

    2006-01-01

    Contrast media plays an important role in imaging soft tissues and organs. Though contrast imaging is considered safe, radiologic technologists can improve the safety of contrast examinations by reviewing institutional safety procedures, safe practices for different methods of contrast administration and possible complications. The need for efficient communication and attention to detail during contrast procedures is essential for patient safety. PMID:16998193

  16. Dyke Award. Evaluation of contrast-enhanced MR imaging in a brain-abscess model.

    PubMed

    Runge, V M; Clanton, J A; Price, A C; Herzer, W A; Allen, J H; Partain, C L; James, A E

    1985-01-01

    An alpha-streptococcus brain abscess was produced in five dogs and studied with magnetic resonance (MR) imaging (0.5 T) and computed tomography (CT). Non-contrast- and contrast-enhanced CT scans were obtained using gadolinium diethylenetriamine-pentaacetic acid (Gd DTPA) for MR imaging and meglumine iothalamate for CT scanning. Each animal was evaluated in the early and later cerebritis stages of abscess evolution. On MR, the area of cerebritis enhanced after administration of Gd DTPA in a manner similar to that observed with contrast-enhanced CT. However, contrast enhancement was greater on the MR examination. Early lesions in two animals were detected only with contrast-enhanced MR imaging. This experience suggests that intravenously administered agents such as Gd DTPA should increase the diagnostic potential of MR imaging in neurologic diseases, especially those altering the blood-brain barrier. PMID:3920873

  17. 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. PMID:26025507

  18. 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…

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

    PubMed

    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. PMID:21693793

  20. 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.

  1. A novel technique for modeling susceptibility-based contrast mechanisms for arbitrary microvascular geometries: the finite perturber method.

    PubMed

    Pathak, Arvind P; Ward, B Douglas; Schmainda, Kathleen M

    2008-04-15

    Recently, we demonstrated that vessel geometry is a significant determinant of susceptibility-induced contrast in MRI. This is especially relevant for susceptibility-contrast enhanced MRI of tumors with their characteristically abnormal vessel morphology. In order to better understand the biophysics of this contrast mechanism, it is of interest to model how various factors, including microvessel morphology contribute to the measured MR signal, and was the primary motivation for developing a novel computer modeling approach called the Finite Perturber Method (FPM). The FPM circumvents the limitations of traditional fixed-geometry approaches, and enables us to study susceptibility-induced contrast arising from arbitrary microvascular morphologies in 3D, such as those typically observed with brain tumor angiogenesis. Here we describe this new modeling methodology and some of its applications. The excellent agreement of the FPM with theory and the extant susceptibility modeling data, coupled with its computational efficiency demonstrates its potential to transform our understanding of the factors that engender susceptibility contrast in MRI. PMID:18308587

  2. Delimiting Allelic Imbalance of TYMS by Allele-Specific Analysis

    PubMed Central

    Balboa-Beltrán, Emilia; Cruz, Raquel; Carracedo, Angel; Barros, Francisco

    2015-01-01

    Abstract Allelic imbalance of thymidylate synthase (TYMS) is attributed to polymorphisms in the 5′- and 3′-untranslated region (UTR). These polymorphisms have been related to the risk of suffering different cancers, for example leukemia, breast or gastric cancer, and response to different drugs, among which are methotrexate glutamates, stavudine, and specifically 5-fluorouracil (5-FU), as TYMS is its direct target. A vast literature has been published in relation to 5-FU, even suggesting the sole use of these polymorphisms to effectively manage 5-FU dosage. Estimates of the extent to which these polymorphisms influence in TYMS expression have in the past been based on functional analysis by luciferase assays and quantification of TYMS mRNA, but both these studies, as the association studies with cancer risk or with toxicity or response to 5-FU, are very contradictory. Regarding functional assays, the artificial genetic environment created in luciferase assay and the problems derived from quantitative polymerase chain reactions (qPCRs), for example the use of a reference gene, may have distorted the results. To avoid these sources of interference, we have analyzed the allelic imbalance of TYMS by allelic-specific analysis in peripheral blood mononuclear cells (PBMCs) from patients. Allelic imbalance in PBMCs, taken from 40 patients with suspected myeloproliferative haematological diseases, was determined by fluorescent fragment analysis (for the 3′-UTR polymorphism), Sanger sequencing and allelic-specific qPCR in multiplex (for the 5′-UTR polymorphisms). For neither the 3′- nor the 5′-UTR polymorphisms did the observed allelic imbalance exceed 1.5 fold. None of the TYMS polymorphisms is statistically associated with allelic imbalance. The results acquired allow us to deny the previously established assertion of an influence of 2 to 4 fold of the rs45445694 and rs2853542 polymorphisms in the expression of TYMS and narrow its allelic imbalance to 1.5 fold

  3. Dynamic Contrast-Enhanced MR Microscopy: Functional Imaging in Preclinical Models of Cancer

    NASA Astrophysics Data System (ADS)

    Subashi, Ergys

    Dynamic contrast-enhanced (DCE) MRI has been widely used as a quantitative imaging method for monitoring tumor response to therapy. The pharmacokinetic parameters derived from this technique have been used in more than 100 phase I trials and investigator led studies. The simultaneous challenges of increasing the temporal and spatial resolution, in a setting where the signal from the much smaller voxel is weaker, have made this MR technique difficult to implement in small-animal imaging.Existing preclinical DCE-MRI protocols acquire a limited number of slices resulting in potentially lost information in the third dimension. Furthermore, drug efficacy studies measuring the effect of an anti-angiogenic treatment, often compare the derived biomarkers on manually selected tumor regions or over the entire volume. These measurements include domains where the interpretation of the biomarkers may be unclear (such as in necrotic areas). This dissertation describes and compares a family of four-dimensional (3D spatial + time), projection acquisition, keyhole-sampling strategies that support high spatial and temporal resolution. An interleaved 3D radial trajectory with a quasi-uniform distribution of points in k-space was used for sampling temporally resolved datasets. These volumes were reconstructed with three different k-space filters encompassing a range of possible keyhole strategies. The effect of k-space filtering on spatial and temporal resolution was studied in phantoms and in vivo. The statistical variation of the DCE-MRI measurement is analyzed by considering the fundamental sources of error in the MR signal intensity acquired with the spoiled gradient-echo (SPGR) pulse sequence. Finally, the technique was applied for measuring the extent of the opening of the blood-brain barrier in a mouse model of pediatric glioma and for identifying regions of therapeutic effect in a model of colorectal adenocarcinoma. It is shown that 4D radial keyhole imaging does not degrade

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. High-Contrast Near-Infrared Imaging and Modeling of Planets and Debris Disks

    NASA Astrophysics Data System (ADS)

    Rodigas, Timothy; Hinz, P.; Weinberger, A. J.; Close, L. M.; Debes, J. H.

    2014-01-01

    Planets are thought to form in circumstellar disks, leaving behind planetesimals that collide to produce dusty debris disks. Characterizing the architectures of planetary systems, along with the structures and compositions of debris disks, can therefore help answer questions about how planets form. In this talk, I will present the results of five papers concerning the properties of extrasolar planetary systems and their circumstellar environments. First I will discuss bias affecting radial velocity (RV) orbital eccentricity. For years astronomers have been puzzled about the large number of RV-detected planets that have eccentric orbits (e > 0.1). I will show that this problem can partially be explained by showing that two circular-orbit planets can masquerade as a single planet on an eccentric orbit. I use this finding to predict that planets with mildly eccentric orbits are the most likely to have massive companions on wide orbits, potentially detectable by future direct imaging observations. Next I will present recent high-contrast 2-4 μm imaging studies of the edge-on debris disks around HD 15115 and HD 32297. HD 15115’s color is found to be gray, implying large grains 1-10 μm in size reside in stable orbits in the disk. HD 32297’s disk color is red from 1-4 μm. Cometary material (carbon, silicates, and porous water ice) are a good match at 1-2 μm but not at L‧. Tholins, organic material that is found in outer solar system bodies, or small silicates can explain the disk’s red color but not the short wavelength data. I will then present my work on the dynamics of dust grains in the presence of massive planets. I will show that the width of a debris disk increases proportionally with the mass of its shepherding planet. I use this result to make predictions for the masses and orbits of putative planets in five well-known disks. Finally, I will present recent MagAO/Clio near-infrared imaging results on the debris disk around HR4796A spanning the 0.5-4 um

  10. Allelic disequilibrium and allele frequency distribution as a function of social and demographic history.

    PubMed Central

    Thompson, E A; Neel, J V

    1997-01-01

    Allelic disequilibrium between closely linked genes is a common observation in human populations and often gives rise to speculation concerning the role of selective forces. In a previous treatment, we have developed a population model of the expected distribution of rare variants (including private polymorphisms) in Amerindians and have argued that, because of the great expansion of Amerindian numbers with the advent of agriculture, most of these rare variants are of relatively recent origin. Many other populations have similar histories of striking recent expansions. In this treatment, we demonstrate that, in consequence of this fact, a high degree of linkage disequilibrium between two nonhomologous alleles <0.5 cM apart is the "normal" expectation, even in the absence of selection. This expectation is enhanced by the previous subdivision of human populations into relatively isolated tribes characterized by a high level of endogamy and inbreeding. We also demonstrate that the alleles associated with a recessive disease phenotype are expected to exist in a population in very variable frequencies: there is no need to postulate positive selection with respect to the more common disease-associated alleles for such entities as phenylketonuria or cystic fibrosis. PMID:8981963

  11. 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

  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. An evaluation of four parametric models of contrast enhancement for dynamic magnetic resonance imaging of the breast.

    PubMed

    Gal, Yaniv; Mehnert, Andrew; Bradley, Andrew; McMahon, Kerry; Crozier, Stuart

    2007-01-01

    This paper presents an empirical evaluation of the goodness-of-fit (GOF) of four parametric models of contrast enhancement for dynamic resonance imaging of the breast: the Tofts, Brix, and Hayton pharmacokinetic models, and a novel empiric model. The goodness-of-fit of each model was evaluated with respect to: (i) two model-fitting algorithms (Levenberg-Marquardt and Nelder-Mead) and two fitting tolerances; and (ii) temporal resolution. In the first case the GOF was measured using data from three dynamic contrast-enhanced (DCE) MRI data sets from routine clinical examinations: one case with benign enhancement, one with malignant enhancement, and one with normal findings. Results are presented for fits to both the whole breast volume and to a selected region of interest. In the second case the GOF was measured by first fitting the models to several temporally sub-sampled versions of a custom high temporal resolution data set (subset of the breast volume containing a malignant lesion), and then comparing the fitted results to the original full temporal resolution data. Our results demonstrate that under the various optimization conditions considered, in general, both the proposed empiric model and the Hayton model fit the data equally well and that both of these models fit the data better than the Tofts and Brix models. PMID:18001891

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

    PubMed Central

    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. PMID:26366422

  15. Delayed contrast enhancement imaging of a murine model for ischemia reperfusion with carbon nanotube micro-CT.

    PubMed

    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 300 mgI/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

  16. 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

  17. 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.

  18. 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. PMID:26763422

  19. 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

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

    NASA Astrophysics Data System (ADS)

    Karunamuni, R.; Maidment, A. D. A.

    2014-08-01

    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.

  1. 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.

  2. Physical modelling of a surface-wave survey over a laterally varying granular medium with property contrasts and velocity gradients

    NASA Astrophysics Data System (ADS)

    Bergamo, Paolo; Bodet, Ludovic; Socco, Laura Valentina; Mourgues, Régis; Tournat, Vincent

    2014-04-01

    Laboratory experiments using laser-based ultrasonic techniques can be used to simulate seismic surveys on highly controlled small-scale physical models of the subsurface. Most of the time, such models consist in assemblies of homogeneous and consolidated materials. To enable the physical modelling of unconsolidated, heterogeneous and porous media, the use of granular materials is suggested here. We describe a simple technique to build a two-layer physical model characterized by lateral variations, strong property contrasts and velocity gradients. We use this model to address the efficiency of an innovative surface-wave processing technique developed to retrieve 2-D structures from a limited number of receivers. A step by step inversion procedure of the extracted dispersion curves yields accurate results so that the 2-D structure of the physical model is satisfactorily reconstructed. The velocity gradients within each layer are accurately retrieved as well, confirming current theoretical and experimental studies regarding guided surface acoustic modes in unconsolidated granular media.

  3. Modelling and design of modified Wollaston prisms and the application in differential interference contrast microscopy

    NASA Astrophysics Data System (ADS)

    Zhang, Site; Zhong, Huiying; Wyrowski, Frank

    2016-03-01

    Wollaston prisms and the modified Wollaston prisms, which are interesting for various applications like optical metrology, topography of surfaces and biological imaging, has been theoretically studied and also been practically applied. The previous studies are mostly based on ray tracing analysis and, as a result, the information that can be obtained are somehow restricted. In this paper, we propose a geometric field tracing technique for the simulation of light propagation through Wollaston prisms. In geometric field tracing we seek for the solutions to Maxwell's equations under the geometrical optics approximation, so that all the properties of light as electromagnetic field are retained. Using the proposed simulation technique, we present the simulation of a differential interference contrast (DIC) microscopy, in which the modified Wollaston prism is used as the key component.

  4. Modeling and optimization of high index contrast gratings with aperiodic topologies

    NASA Astrophysics Data System (ADS)

    Maksimovic, Milan

    2013-05-01

    High-contrast gratings (HCG) are the ultra-thin elements set to operate in near-wavelength regime with the period of the grating smaller then wavelength and with the high-index grating fully surrounded by low-index material. We concentrate on topics scarcely explored in the literature such as the spectral response phenomenology of HCGs with the complex unit cells. We show that the spectral response is robust under the symmetric unit cell perturbations, while asymmetric unit cell perturbations may introduce completely new spectral response. Further, we show examples of highly fragmented spectra present in the case of HCGs with the aperiodic topology in the unit cell. Our results can serve as guidance for the design of the complex HCGs and help with the choice of the efficient initial grating topology prior to global optimization procedure.

  5. 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…

  6. 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.

  7. 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

  8. Modelling the dissipation kinetics of six commonly used pesticides in two contrasting soils of New Zealand.

    PubMed

    Sarmah, Ajit K; Close, Murray E

    2009-08-01

    We used three non-linear bi-phasic models, bi-exponential (BEXP), first-order double exponential decay (FODED), and first-order two-compartment (FOTC), to fit the measured degradation data for six commonly used pesticides (atrazine, terbuthylazine, bromacil, diazinon, hexazinone and procymidone) in two New Zealand soils. Corresponding DT(50) and DT(90) values for each compound were numerically obtained and compared against those estimated by simple first-order kinetic (SFOK) model. All 3 non-linear models gave good fit of the measured data under both soil depths and were well supported by the values obtained for the respective statistical indices (RMSE, CRM and r(2)). The FOTC model gave by far the best fit for most compounds, followed by the FODED and BEXP models. Overall, DT(50) values derived by non-linear models for the six compounds in soils from both sites were lower than the values obtained by the SFOK model. Differences in the SFOK and the three non-linear models derived DT(90)were, however, an order of magnitude higher for some compounds, while for others differences were very small. Although all three non-linear models described most data by giving excellent fits, in a few instances > 5-10% asymptotes hindered the estimation of DT(90) values. This work shows that when degradation deviates from first-order kinetic, application of non-linear decay models to describe the kinetics of degradation becomes important in order to derive the true end-points for pesticides in soil. PMID:20183056

  9. Contrast-enhanced sonothrombolysis in a porcine model of acute peripheral arterial thrombosis and prevention of anaphylactic shock.

    PubMed

    Nederhoed, Johanna H; Slikkerveer, Jeroen; Meyer, Klaas W; Wisselink, Willem; Musters, René J P; Yeung, Kak K

    2014-03-01

    Acute peripheral arterial thrombosis can be threatening to life and limb. Dissolution of the thrombus local catheter-directed intra-arterial infusion of fibrinolytic agents such as urokinase is the standard therapy for thrombosis; however, this method is time-intensive, and amputation of the affected limb is still needed in 10-30% of cases. Furthermore, thrombolytic therapy carries the risk of bleeding complications. The use of small gas-filled bubbles, or ultrasound contrast agents (UCAs), in combination with ultrasound has been investigated as an improved thrombolytic therapy in acute coronary and cerebral arterial thrombosis. The authors describe a porcine model of acute peripheral arterial occlusion to test contrast-enhanced sonothrombolysis approaches that combine ultrasound, UCAs and fibrinolytic agents and recommend a strategy for preventing severe allergic reactions to UCAs in the pigs. PMID:24552914

  10. A phase-contrast microscopy-based method for modeling the mechanical behavior of mesenchymal stem cells.

    PubMed

    Saeed, Mayssam; Sharabani-Yosef, Orna; Weihs, Daphne; Gefen, Amit

    2016-10-01

    We present three-dimensional (3D) finite element (FE) models of single, mesenchymal stem cells (MSCs), generated from images obtained by optical phase-contrast microscopy and used to quantify the structural responses of the studied cells to externally applied mechanical loads. Mechanical loading has been shown to affect cell morphology and structure, phenotype, motility and other biological functions. Cells experience mechanical loads naturally, yet under prolonged or sizable loading, damage and cell death may occur, which motivates research regarding the structural behavior of loaded cells. For example, near the weight-bearing boney prominences of the buttocks of immobile persons, tissues may become highly loaded, eventually leading to massive cell death that manifests as pressure ulcers. Cell-specific computational models have previously been developed by our group, allowing simulations of cell deformations under compressive or stretching loads. These models were obtained by reconstructing specific cell structures from series of 2D fluorescence, confocal image-slices, requiring cell-specific fluorescent-staining protocols and costly (confocal) microscopy equipment. Alternative modeling approaches represent cells simply as half-spheres or half-ellipsoids (i.e. idealized geometries), which neglects the curvature details of the cell surfaces associated with changes in concentrations of strains and stresses. Thus, we introduce here for the first time an optical image-based FE modeling, where loads are simulated on reconstructed 3D geometrical cell models from a single 2D, phase-contrast image. Our novel modeling method eliminates the need for confocal imaging and fluorescent staining preparations (both expensive), and makes cell-specific FE modeling affordable and accessible to the biomechanics community. We demonstrate the utility of this cost-effective modeling method by performing simulations of compression of MSCs embedded in a gel. PMID:26856632

  11. 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. PMID:25373055

  12. Modelling microbial exchanges between forms of soil nitrogen in contrasting ecosystems

    NASA Astrophysics Data System (ADS)

    Pansu, M.; Machado, D.; Bottner, P.; Sarmiento, L.

    2014-02-01

    Although nitrogen (N) is often combined with carbon (C) in organic molecules, C passes from the air to the soil through plant photosynthesis, whereas N passes from the soil to plants through a chain of microbial conversions. However, dynamic models do not fully consider the microorganisms at the centre of exchange processes between organic and mineral forms of N. This study monitored the transfer of 14C and 15N between plant materials, microorganisms, humified compartments, and inorganic forms in six very different ecosystems along an altitudinal transect. The microbial conversions of the 15N forms appear to be strongly linked to the previously modelled C cycle, and the same equations and parameters can be used to model both C and N cycles. The only difference is in the modelling of the flows between microbial and inorganic forms. The processes of mineralization and immobilization of N appear to be regulated by a two-way microbial exchange depending on the C : N ratios of microorganisms and available substrates. The MOMOS (Modelling of Organic Matter of Soils) model has already been validated for the C cycle and also appears to be valid for the prediction of microbial transformations of N forms. This study shows that the hypothesis of microbial homeostasis can give robust predictions at global scale. However, the microbial populations did not appear to always be independent of the external constraints. At some altitudes their C : N ratio could be better modelled as decreasing during incubation and increasing with increasing C storage in cold conditions. The ratio of potentially mineralizable-15N/inorganic-15N and the 15N stock in the plant debris and the microorganisms was modelled as increasing with altitude, whereas the 15N storage in stable humus was modelled as decreasing with altitude. This predicts that there is a risk that mineralization of organic reserves in cold areas may increase global warming.

  13. Identification of alleles of carotenoid pathway genes important for zeaxanthin accumulation in potato tubers

    PubMed Central

    Uitdewilligen, Jan G. A. M. L.; Kloosterman, Bjorn A.; Hutten, Ronald C. B.; Visser, Richard G. F.; van Eck, Herman J.

    2010-01-01

    We have investigated the genetics and molecular biology of orange flesh colour in potato (Solanum tuberosum L.). To this end the natural diversity in three genes of the carotenoid pathway was assessed by SNP analyses. Association analysis was performed between SNP haplotypes and flesh colour phenotypes in diploid and tetraploid potato genotypes. We observed that among eleven beta-carotene hydroxylase 2 (Chy2) alleles only one dominant allele has a major effect, changing white into yellow flesh colour. In contrast, none of the lycopene epsilon cyclase (Lcye) alleles seemed to have a large effect on flesh colour. Analysis of zeaxanthin epoxidase (Zep) alleles showed that all (diploid) genotypes with orange tuber flesh were homozygous for one specific Zep allele. This Zep allele showed a reduced level of expression. The complete genomic sequence of the recessive Zep allele, including the promoter, was determined, and compared with the sequence of other Zep alleles. The most striking difference was the presence of a non-LTR retrotransposon sequence in intron 1 of the recessive Zep allele, which was absent in all other Zep alleles investigated. We hypothesise that the presence of this large sequence in intron 1 caused the lower expression level, resulting in reduced Zep activity and accumulation of zeaxanthin. Only genotypes combining presence of the dominant Chy2 allele with homozygosity for the recessive Zep allele produced orange-fleshed tubers that accumulated large amounts of zeaxanthin. Electronic supplementary material The online version of this article (doi:10.1007/s11103-010-9647-y) contains supplementary material, which is available to authorized users. PMID:20490894

  14. A DOG filter model of the occurrence of Mach bands on spatial contrast discontinuities.

    PubMed

    Mazumdar, Debasis; Mitra, Soma; Ghosh, Kuntal; Bhaumik, Kamales

    2016-06-01

    The present work proposes a unified model to explain two previously reported properties of the Mach band illusion. The first is the frequently referenced fact that Mach bands are prominently visible at ramps, but practically vanish at intensity steps. The second property, less studied, on the other hand may also be related to the first. It concerns the fact that the width of the illusory Mach bands appears to be a function of the slope of the ramp itself. The model proposed here combines the difference of Gaussians (DOG) model of lateral inhibition in receptive fields with the models of feature detection, based on a holistic approach. The sharpness of discontinuity (SOD) concept for Mach band stimulus has been defined and is related to the slope of the ramp. It is suggested that calculation of SOD leads to an adaptive change in inhibitory surround, a notion that has the support of physiological experiments too. PMID:27016101

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

    PubMed Central

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

    2009-01-01

    We address the four main points in Monroe and Mineka (2008)’s Comment. First, we first show that the DSM PTSD diagnosis includes an etiology and that it is based on a theoretical model with a distinguished history in psychology and psychiatry. Two tenets of this theoretical model are that voluntary (strategic) recollections of the trauma are fragmented and incomplete while involuntary (spontaneous) recollections are vivid and persistent and yield privileged access to traumatic material. Second, we describe differences between our model and other cognitive models of PTSD. We argue that these other models share the same two tenets as the diagnosis and we show that these two tenets are largely unsupported by empirical evidence. Third, we counter arguments about the strength of the evidence favoring the mnemonic model, and fourth, we show that concerns about the causal role of memory in PTSD are based on views of causality that are generally inappropriate for the explanation of PTSD in the social and biological sciences. PMID:20808720

  16. 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.

  17. Contrast Materials

    MedlinePlus

    ... or other reactions to contrast materials are rare, radiology departments are well-equipped to deal with them. ... is given. However, both the American College of Radiology (ACR) and the European Society of Urogenital Radiology ...

  18. Contrasting effects of Na+, K+-ATPase activation on seizure activity in acute versus chronic models.

    PubMed

    Funck, V R; Ribeiro, L R; Pereira, L M; de Oliveira, C V; Grigoletto, J; Della-Pace, I D; Fighera, M R; Royes, L F F; Furian, A F; Larrick, J W; Oliveira, M S

    2015-07-01

    Epilepsy is a life-shortening brain disorder affecting approximately 1% of the worldwide population. Most epilepsy patients are refractory to currently available antiepileptic drugs (AEDs). Knowledge about the mechanisms underlying seizure activity and probing for new AEDs is fundamental to the discovery of new therapeutic strategies. Brain Na(+), K(+)-ATPase activity contributes to the maintenance of the electrochemical gradients underlying neuronal resting and action potentials as well as the uptake and release of neurotransmitters. Accordingly, a decrease of Na(+), K(+)-ATPase increases neuronal excitability and may predispose to appearing of seizure activity. In the present study, we tested the hypothesis that activation of Na(+), K(+)-ATPase activity with a specific antibody (DRRSAb) raised against a regulatory site in the α subunit would decrease seizure susceptibility. We found that incubation of hippocampal homogenates with DRRSAb (1 μM) increased total and α1 Na(+), K(+)-ATPase activities. A higher concentration (3 μM) increased total, α1 and α2/α3 Na(+), K(+)-ATPase activities. Intrahippocampal injection of DRRSAb decreased the susceptibility of post status epilepticus animals to pentylenetetrazol (PTZ)-induced myoclonic seizures. In contrast, administration of DRRSAb into the hippocampus of naïve animals facilitated the appearance of PTZ-induced seizures. Quantitative analysis of hippocampal electroencephalography (EEG) recordings revealed that DRRSAb increased the percentage of total power contributed by the delta frequency band (0-3 Hz) to a large irregular amplitude pattern of hippocampal EEG. On the other hand, we found no DRRSAb-induced changes regarding the theta functional state. Further studies are necessary to define the potential of Na(+), K(+)-ATPase activation as a new therapeutic approach for seizure disorders. PMID:25907445

  19. Shale Gas Petrophysical Models: an evaluation of contrasting approaches and assumptions

    NASA Astrophysics Data System (ADS)

    Inwood, Jennifer; Lovell, Mike; Davies, Sarah; Fishwick, Stewart; Taylor, Kevin

    2015-04-01

    Shale gas refers to fine-grained formations, or mudstones, where organic matter has matured sufficiently to produce predominantly gas, but that gas has not migrated any significant distance and hence the source rock is effectively the reservoir. Due to the success of shale gas extraction in the USA, many European countries are assessing their potential resources. A key uncertainty in evaluating the resource is the estimation of gas in place and most models are based on North American plays. However, it would seem that no single model to date can confidently predict the gas in place for a 'new' shale formation. Shale gas is frequently characterized by two distinct gas components: free gas is able to move and occupies the pores, while adsorbed gas is fixed onto organic surfaces and held in place by pressure. There are a number of different published methodologies that attempt to take account for this complicated distribution of gas within the rock ranging from models where the importance of the adsorbed gas is assumed to be negligible to those where all gas is assumed to exist within the organic pores and none within the mineral pore spaces. Models that assume both components are important and occupy adjacent volumes need to consider how to separate out the two to avoid double counting. Due to the heterogeneity of mudstones the most appropriate model may vary downhole as well as across adjacent wells. In this pilot study we consider the underlying assumptions and categorize models dependent on the deterministic or probabilistic approach used. We use an initial dataset from North America to test and compare a number of different approaches before expanding the analysis to further formations that span a range of geological and petrophysical characteristics. We then review and evaluate the models, identifying key variables and, where possible, determining their importance through sensitivity analysis. This work aims to establish guidelines for selecting the most

  20. 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

  1. Simulating canopy transpiration and photosynthesis of corn plants under contrasting water regimes using a coupled model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A process-based corn simulation model (MaizeSim) was coupled with a two-dimensional soil simulator (2DSOIL) to simulate the transpiration and photosynthesis of corn under drought stress. To simulate stomatal reaction to drought stress, two stomatal controlling algorithms (control by hydraulic signal...

  2. 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…

  3. Quantitative analysis of contrast-enhanced ultrasonography in acute radiation-induced liver injury: An animal model

    PubMed Central

    FENG, JUN; CHEN, SHU-BO; WU, SHU-JUN; SUN, PING; XIN, TIAN-YOU; CHEN, YING-ZHEN

    2015-01-01

    The aim of the present study was to examine and assess contrast-enhanced ultrasound in the early diagnosis of acute radiation-induced liver injury in a rat model. Sixty female rats were used, with 50 rats being utilized to produce an animal model of liver injury with a single dose of stereotactic X-ray irradiation of 20 Gy. Ten rats from the injury group and 2 rats from the control group were randomly selected on days 3, 7, 14, 21 and 28, and examined by contrast-enhanced ultrasound and histopathology of liver specimens. The rats were divided into four groups: the normal control group, mild, moderate, and severe radioactive liver injury groups based on the histopathological examination results. Hepatic artery arriving time (HAAT) and hepatic vein arriving time (HVAT) were recorded, and hepatic artery to vein transit time (HA-HVTT) was calculated. The time-intensity curve of liver parenchyma, the time to peak (TTP) and peak intensity (PI) were also obtained. Significant differences were observed between liver injury and control groups for PI and HA-HVTT (P<0.05). PI and HA-HVTT were shorter in the severe liver injury group compared to the mild and moderate liver injury groups (P<0.05). Compared to the control group, higher TTP was recorded in all the liver injury groups (P<0.05), and the highest TTP level was observed in the severe liver injury group compared to the mild or moderate group (P<0.05). However, no significant difference was observed between the mild and moderate groups for PI, HA-HVTT and TTP. In conclusion, the results showed that contrast-enhanced ultrasonography is useful for an earlier diagnosis in a rat model of acute radiation-induced liver injury. PMID:26640553

  4. 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

  5. Multi-model data fusion for river flow forecasting: an evaluation of six alternative methods based on two contrasting catchments

    NASA Astrophysics Data System (ADS)

    Abrahart, R. J.; See, L.

    This paper evaluates six published data fusion strategies for hydrological forecasting based on two contrasting catchments: the River Ouse and the Upper River Wye. The input level and discharge estimates for each river comprised a mixed set of single model forecasts. Data fusion was performed using: arithmetic-averaging, a probabilistic method in which the best model from the last time step is used to generate the current forecast, two different neural network operations and two different soft computing methodologies. The results from this investigation are compared and contrasted using statistical and graphical evaluation. Each location demonstrated several options and potential advantages for using data fusion tools to construct superior estimates of hydrological forecast. Fusion operations were better in overall terms in comparison to their individual modelling counterparts and two clear winners emerged. Indeed, the six different mechanisms on test revealed unequal aptitudes for fixing different categories of problematic catchment behaviour and, in such cases, the best method(s) were a good deal better than their closest rival(s). Neural network fusion of differenced data provided the best solution for a stable regime (with neural network fusion of original data being somewhat similar) — whereas a fuzzified probabilistic mechanism produced a superior output in a more volatile environment. The need for a data fusion research agenda within the hydrological sciences is discussed and some initial suggestions are presented.

  6. 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.

  7. 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

  8. Trend change detection in vegetation greenness time series: Contrasting methodologies, data sets and global vegetation models

    NASA Astrophysics Data System (ADS)

    Forkel, Matthias; Carvalhais, Nuno; Verbesselt, Jan; Mahecha, Miguel; Neigh, Christopher; Thonicke, Kirsten; Reichstein, Markus

    2014-05-01

    Newly developed satellite datasets and time series analysis methods allow the quantification of changes in vegetation greenness. However, the estimation of trends and trend changes depend often on the applied time series analysis method and the used satellite dataset. Thus, the environmental plausibility of the estimated trends and trend breakpoints is often questionable. We compared four trend and trend change detection methods to assess their performance. We applied the methods to NDVI and FAPAR time series from global satellite datasets and from global vegetation models. We generated surrogate time series with known trends and breakpoints and applied the methods to re-detect the known trends and trend changes. Our results demonstrate that the performance of methods decrease with increasing inter-annual variability of the time series. An overestimation of breakpoints in NDVI time series can result in wrong or even opposite trend estimates. Trend slope estimates based on annual aggregated time series or based on a seasonal-trend model show better performances than methods that remove the seasonal cycle of the time series. The application of the trend change detection methods to real time series allows assessing the multi-method ensemble of trend estimates. Nevertheless, the interpretation of the environmental plausibility of these trend estimates is challenging. For example, some methods suggest a weakening of greening trends in the Tundra after the early 2000s while other methods suggest an ongoing greening. Comparison with vegetation model simulations suggest that this weakening is not an artefact of the satellite dataset or of the applied trend change detection method but might be caused by real changes in environmental conditions. Our results demonstrate the need for a critical appraisal of trend change detection methods. All methods require a careful assessment of the environmental plausibility of detected trend changes in vegetation greenness time series.

  9. Two-Photon Excited Fluorescence Imaging of Endogenous Contrast in a Mouse Model of Ovarian Cancer

    PubMed Central

    Watson, Jennifer M.; Marion, Samuel L.; Rice, Photini F.; Utzinger, Urs; Brewer, Molly A.; Hoyer, Patricia B.; Barton, Jennifer K.

    2015-01-01

    Background and Objective Ovarian cancer has an extremely high mortality rate resulting from poor understanding of the disease. In order to aid understanding of disease etiology and progression, we identify the endogenous fluorophores present in a mouse model of ovarian cancer and describe changes in fluorophore abundance and distribution with age and disease. Study Design/Materials and Methods A mouse model of ovarian cancer was created by dosing with 4-vinylcyclohexene diepoxide, which induces follicular apoptosis (simulating menopause), and 7,12-dimethylbenz[a]anthracene, a known carcinogen. Imaging of ovarian tissue was completed ex vivo with a multiphoton microscope using excitation wavelength of 780 nm and emission collection from 405 to 505 nm. Two-photon excited fluorescence images and corresponding histologic sections with selective stains were used to identify endogenous fluorophores. Results The majority of collected fluorescence emission was attributed to NADH and lipofuscin, with additional contributions from collagen and elastin. Dim cellular fluorescence from NADH did not show observable changes with age. Changes in ovarian morphology with disease development frequently caused increased fluorescence contributions from collagen and adipose tissue-associated NADH. Lipofuscin fluorescence was much brighter than NADH fluorescence and increased as a function of both age and disease. Conclusions Our finding of NADH fluorescence patterns similar to that seen previously in human ovary, combined with the observation of lipofuscin accumulation with age and disease also seen in human organs, suggests that the findings from this model may be relevant to human ovarian disease. Increased lipofuscin fluorescence might be used as an indicator of disease in the ovary and this finding warrants further study. PMID:23362124

  10. 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.

  11. Contrasting features of urea cycle disorders in human patients and knockout mouse models.

    PubMed

    Deignan, Joshua L; Cederbaum, Stephen D; Grody, Wayne W

    2008-01-01

    The urea cycle exists for the removal of excess nitrogen from the body. Six separate enzymes comprise the urea cycle, and a deficiency in any one of them causes a urea cycle disorder (UCD) in humans. Arginase is the only urea cycle enzyme with an alternate isoform, though no known human disorder currently exists due to a deficiency in the second isoform. While all of the UCDs usually present with hyperammonemia in the first few days to months of life, most disorders are distinguished by a characteristic profile of plasma amino acid alterations that can be utilized for diagnosis. While enzyme assay is possible, an analysis of the underlying mutation is preferable for an accurate diagnosis. Mouse models for each of the urea cycle disorders exist (with the exception of NAGS deficiency), and for almost all of them, their clinical and biochemical phenotypes rather closely resemble the phenotypes seen in human patients. Consequently, all of the current mouse models are highly useful for future research into novel pharmacological and dietary treatments and gene therapy protocols for the management of urea cycle disorders. PMID:17933574

  12. 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

  13. 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

  14. 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

  15. Investigation of discrete imaging models and iterative image reconstruction in differential X-ray phase-contrast tomography

    PubMed Central

    Xu, Qiaofeng; Sidky, Emil Y.; Pan, Xiaochuan; Stampanoni, Marco; Modregger, Peter; Anastasio, Mark A.

    2012-01-01

    Differential X-ray phase-contrast tomography (DPCT) refers to a class of promising methods for reconstructing the X-ray refractive index distribution of materials that present weak X-ray absorption contrast. The tomographic projection data in DPCT, from which an estimate of the refractive index distribution is reconstructed, correspond to one-dimensional (1D) derivatives of the two-dimensional (2D) Radon transform of the refractive index distribution. There is an important need for the development of iterative image reconstruction methods for DPCT that can yield useful images from few-view projection data, thereby mitigating the long data-acquisition times and large radiation doses associated with use of analytic reconstruction methods. In this work, we analyze the numerical and statistical properties of two classes of discrete imaging models that form the basis for iterative image reconstruction in DPCT. We also investigate the use of one of the models with a modern image reconstruction algorithm for performing few-view image reconstruction of a tissue specimen. PMID:22565698

  16. Clarifying the Relationship between Average Excesses and Average Effects of Allele Substitutions.

    PubMed

    Alvarez-Castro, José M; Yang, Rong-Cai

    2012-01-01

    Fisher's concepts of average effects and average excesses are at the core of the quantitative genetics theory. Their meaning and relationship have regularly been discussed and clarified. Here we develop a generalized set of one locus two-allele orthogonal contrasts for average excesses and average effects, based on the concept of the effective gene content of alleles. Our developments help understand the average excesses of alleles for the biallelic case. We dissect how average excesses relate to the average effects and to the decomposition of the genetic variance. PMID:22509178

  17. 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. PMID:26791981

  18. Origins, distribution and expression of the Duarte-2 (D2) allele of galactose-1-phosphate uridylyltransferase

    PubMed Central

    Carney, Amanda E.; Sanders, Rebecca D.; Garza, Kerry R.; McGaha, Lee Anne; Bean, Lora J. H.; Coffee, Bradford W.; Thomas, James W.; Cutler, David J.; Kurtkaya, Natalie L.; Fridovich-Keil, Judith L.

    2009-01-01

    Duarte galactosemia is a mild to asymptomatic condition that results from partial impairment of galactose-1-phosphate uridylyltransferase (GALT). Patients with Duarte galactosemia demonstrate reduced GALT activity and carry one profoundly impaired GALT allele (G) along with a second, partially impaired GALT allele (Duarte-2, D2). Molecular studies reveal at least five sequence changes on D2 alleles: a p.N314D missense substitution, three intronic base changes and a 4 bp deletion in the 5′ proximal sequence. The four non-coding sequence changes are unique to D2. The p.N314D substitution, however, is not; it is found together with a silent polymorphism, p.L218(TTA), on functionally normal Duarte-1 alleles (D1, also called Los Angeles or LA alleles). The HapMap database reveals that p.N314D is a common human variant, and cross-species comparisons implicate D314 as the ancestral allele. The p.N314D substitution is also functionally neutral in mammalian cell and yeast expression studies. In contrast, the 4 bp 5′ deletion characteristic of D2 alleles appears to be functionally impaired in reporter gene transfection studies. Here we present allele-specific qRT–PCR evidence that D2 alleles express less mRNA in vivo than their wild-type counterparts; the difference is small but statistically significant. Furthermore, we characterize the prevalence of the 4 bp deletion in GG, NN and DG populations; the deletion appears exclusive to D2 alleles. Combined, these data strongly implicate the 4 bp 5′ deletion as a causal mutation in Duarte galactosemia and suggest that direct tests for this deletion, as proposed here, could enhance or supplant current tests, which define D2 alleles on the basis of the presence and absence of linked coding sequence polymorphisms. PMID:19224951

  19. Estimating allelic diversity generated by excision of different transposon types.

    PubMed

    Nordborg, M; Walbot, V

    1995-05-01

    Methods are presented for calculating the number and type of different DNA sequences generated by base excision and insertion events at a given site in a known DNA sequence. We calculate, for example, that excision of the Mu1 transposon from the bz1::Mu1 allele of maize should generate more than 500,000 unique alleles given the extent of base deletion (up to 34 bases removed) and base insertion (0-5 bases) observed thus far in sequenced excision alleles. Analysis of this universe of potential alleles can, for example, be used to predict the frequency of creation of stop codons or repair-generated duplications. In general, knowledge of the distribution of alleles can be used to evaluate models of both excision and repair by determining whether particular events occur more frequently than expected. Such quantitative analysis complements the qualitative description provided by the DNA sequence of individual events. Similar methods can be used to evaluate the outcome of other cases of DNA breakage and repair such as programmed V(D)J recombination in immunoglobin genes. PMID:24172918

  20. 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

  1. MR Molecular Imaging of Prostate Cancer with a Peptide Targeted Contrast Agent in a Mouse Orthotopic Prostate Cancer Model

    PubMed Central

    Tan, Mingqian; Burden-Gulley, Susan M.; Li, Wen; Wu, Xueming; Lindner, Daniel; Brady-Kalnay, Susann M.; Gulani, Vikas; Lu, Zheng-Rong

    2014-01-01

    Purpose To study the effectiveness of a peptide targeted nanoglobular Gd-DOTA complexes for MR molecular imaging of prostate cancer in a mouse orthotopic PC-3 prostate cancer model. Methods A CLT1 (CGLIIQKNEC) peptide targeted generation 2 nanoglobular Gd-DOTA monoamide conjugate [CLT1-G2-(Gd-DOTA)] was used for imaging fibrin-fibronectin complexes in prostate tumor using a non-specific peptide KAREC modified conjugate, KAREC-G2-(Gd-DOTA) as a control. Cy5 conjugates of CLT1 and KAREC were synthesized for binding studies. Orthotopic PC-3 prostate tumors were established in the prostate of athymic male nude mice. MRI study was performed on a Bruker 7T animal scanner. Results CLT1 peptide showed specific binding in the prostate tumor with no binding in normal tissues. The control peptide had little binding in both normal and tumor tissues. CLT1-G2-(Gd-DOTA) resulted in stronger contrast enhancement in the tumor tissue than the KAREC-G2-(Gd-DOTA). CLT1-G2-(Gd-DOTA) generated approximately 100% increase in contrast-to-noise ratio (CNR) in the tumor as compared to precontrast CNR at 1 minute post-injection, while the control agent KAREC-G2-(Gd-DOTA) only resulted in 8% CNR increase. Conclusion CLT1-G2-(Gd-DOTA) is a promising molecular MRI contrast agent for fibrin-fibronectin complexes in the tumor stroma. It has a potential for the diagnosis and assessing prognosis of malignant tumors with MRI. PMID:22139536

  2. 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

  3. 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.

  4. Contrast class cues and performance facilitation in a hypothesis-testing task: evidence for an iterative counterfactual model.

    PubMed

    Gale, Maggie; Ball, Linden J

    2012-04-01

    Hypothesis-testing performance on Wason's (Quarterly Journal of Experimental Psychology 12:129-140, 1960) 2-4-6 task is typically poor, with only around 20% of participants announcing the to-be-discovered "ascending numbers" rule on their first attempt. Enhanced solution rates can, however, readily be observed with dual-goal (DG) task variants requiring the discovery of two complementary rules, one labeled "DAX" (the standard "ascending numbers" rule) and the other labeled "MED" ("any other number triples"). Two DG experiments are reported in which we manipulated the usefulness of a presented MED exemplar, where usefulness denotes cues that can establish a helpful "contrast class" that can stand in opposition to the presented 2-4-6 DAX exemplar. The usefulness of MED exemplars had a striking facilitatory effect on DAX rule discovery, which supports the importance of contrast-class information in hypothesis testing. A third experiment ruled out the possibility that the useful MED triple seeded the correct rule from the outset and obviated any need for hypothesis testing. We propose that an extension of Oaksford and Chater's (European Journal of Cognitive Psychology 6:149-169, 1994) iterative counterfactual model can neatly capture the mechanisms by which DG facilitation arises. PMID:22069145

  5. 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

  6. Future changes in the African monsoon analysed with 8 CMIP5 models: contrasted rainfall dipole and delayed withdrawal

    NASA Astrophysics Data System (ADS)

    Monerie, P.

    2013-12-01

    Based on the approach of Fontaine et al. (2011) and Monerie et al. (2013) we study the African Monsoon (AM) future changes. We used 8 available CMIP5/AR5 AOGCMs from 8 different climate centres and the RCP4.5 emission scenario. Data are analysed with the 'one model one vote' concept and a multi-model approach. The results refer to the difference of a ';future horizon' (2031-2070) minus the ';present' period (1960-1999) and are discussed in terms of monsoon dynamics and climate change. CMIP5 AOGCMs produces a warmer world in the future, especially over land. The sea-band thermal gradient is enhanced and create therefore the basic energy conditions for a reinforced monsoon in the future. The future changes show a contrasted response with less (more) rainfall expected over the western (central-eastern) Sahel. The deficits are chiefly linked to subsidence anomalies in mid-troposphere preventing deep moist convection and precipitation due to modifications in the zonal circulation. The surplus are associated with a more intense monsoon circulation, an increasing of the mean moisture flux convergence over the continental Sahel favoured by the greater surface warming over the continent. An African Rainfall Pattern Index (ARPI), based on the standardized rainfall differences between these regions is defined for capturing the rainfall contrast over years 1900 to 2100. It has been compared to the thermal evolution on both the present and future periods. This allowed us to document the effect of the global warming on Sahelian rainfall patterns by extracting low-frequency signals (20-year-cut-off). The contrasted rainfall pattern change at Sahelian latitudes is therefore expected to occur more frequently in the future. These results are according to Fontaine et al. (2011) and Monerie et al. (2013) who shown through 12 CMIP3 models an increasing (decreasing) of rainfall amounts above the central part (western part) of the Sahel in a future period. In addition to these results we

  7. Shrimp predation on 0-group plaice: contrasts between field data and predictions of an individual-based model

    NASA Astrophysics Data System (ADS)

    Burrows, Michael T.; Gontarek, Steven J.; Nash, Richard D. M.; Gibson, Robin N.

    2001-06-01

    An individual-based model has been used to predict the effects of size-dependent predation by shrimp Crangon crangon on populations of newly settled 0-group plaice Pleuronectes platessa. The model predicted changes in population size and thus mortality rate of plaice during settlement and the following period until the plaice reached 30 mm in length and were invulnerable to further shrimp predation. Population parameters derived from seven years' catch data for 0-group plaice and shrimp from the west coast of Scotland were supplied to the model for direct comparison of predicted and observed mortality rates for each of the seven years. The contrast of predicted and observed mortality was used to test the hypothesis that predation by shrimp is a major factor regulating populations of juvenile plaice. There was no evidence for control of plaice populations by shrimp predation at the study site, since a negative relationship between plaice mortality and shrimp density was observed. Alternative explanations for the divergence of prediction and observations included (i) a general failure of the model to adequately describe predator and prey populations, (ii) limited effects of consumption of plaice by shrimp, and (iii) responses of both species to a third factor such as temperature producing an apparent association of survival and recruitment in the respective species.

  8. Hydrologic Model Development and Calibration: Contrasting a Single- and Multi-Objective Approach for Comparing Model Performance

    NASA Astrophysics Data System (ADS)

    Asadzadeh, M.; Maclean, A.; Tolson, B. A.; Burn, D. H.

    2009-05-01

    Hydrologic model calibration aims to find a set of parameters that adequately simulates observations of watershed behavior, such as streamflow, or a state variable, such as snow water equivalent (SWE). There are different metrics for evaluating calibration effectiveness that involve quantifying prediction errors, such as the Nash-Sutcliffe (NS) coefficient and bias evaluated for the entire calibration period, on a seasonal basis, for low flows, or for high flows. Many of these metrics are conflicting such that the set of parameters that maximizes the high flow NS differs from the set of parameters that maximizes the low flow NS. Conflicting objectives are very likely when different calibration objectives are based on different fluxes and/or state variables (e.g., NS based on streamflow versus SWE). One of the most popular ways to balance different metrics is to aggregate them based on their importance and find the set of parameters that optimizes a weighted sum of the efficiency metrics. Comparing alternative hydrologic models (e.g., assessing model improvement when a process or more detail is added to the model) based on the aggregated objective might be misleading since it represents one point on the tradeoff of desired error metrics. To derive a more comprehensive model comparison, we solved a bi-objective calibration problem to estimate the tradeoff between two error metrics for each model. Although this approach is computationally more expensive than the aggregation approach, it results in a better understanding of the effectiveness of selected models at each level of every error metric and therefore provides a better rationale for judging relative model quality. The two alternative models used in this study are two MESH hydrologic models (version 1.2) of the Wolf Creek Research basin that differ in their watershed spatial discretization (a single Grouped Response Unit, GRU, versus multiple GRUs). The MESH model, currently under development by Environment

  9. 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.

  10. 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

  11. 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. PMID:23679542

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

    NASA Astrophysics Data System (ADS)

    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.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. The allele frequency spectrum in genome-wide human variation data reveals signals of differential demographic history in three large world populations.

    PubMed Central

    Marth, Gabor T; Czabarka, Eva; Murvai, Janos; Sherry, Stephen T

    2004-01-01

    We have studied a genome-wide set of single-nucleotide polymorphism (SNP) allele frequency measures for African-American, East Asian, and European-American samples. For this analysis we derived a simple, closed mathematical formulation for the spectrum of expected allele frequencies when the sampled populations have experienced nonstationary demographic histories. The direct calculation generates the spectrum orders of magnitude faster than coalescent simulations do and allows us to generate spectra for a large number of alternative histories on a multidimensional parameter grid. Model-fitting experiments using this grid reveal significant population-specific differences among the demographic histories that best describe the observed allele frequency spectra. European and Asian spectra show a bottleneck-shaped history: a reduction of effective population size in the past followed by a recent phase of size recovery. In contrast, the African-American spectrum shows a history of moderate but uninterrupted population expansion. These differences are expected to have profound consequences for the design of medical association studies. The analytical methods developed for this study, i.e., a closed mathematical formulation for the allele frequency spectrum, correcting the ascertainment bias introduced by shallow SNP sampling, and dealing with variable sample sizes provide a general framework for the analysis of public variation data. PMID:15020430

  18. 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.

  19. 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.

  20. 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

  1. Generation of mice with a conditional Lbh null allele.

    PubMed

    Lindley, Linsey E; Briegel, Karoline J

    2013-07-01

    Limb bud and heart (LBH) is a developmentally expressed, tissue-specific transcription cofactor in vertebrates that acts in the WNT signaling pathway, a genetic program critical for embryogenesis and adult tissue homeostasis. Aberrant gain-of-function of LBH is implicated in both human congenital disease and cancer. The normal physiological function of LBH has remained elusive owing to a lack of genetic loss-of-function models. Here, we have generated mice with a conditional null allele of Lbh by flanking exon 2 with loxP sites (Lbh(flox)). Homozygous Lbh(flox) and Lbh(loxP) mice, in which the Neo cassette was removed through FLPe-mediated recombination, were viable and fertile, indicating that these conditional Lbh alleles are fully functional. Lbh(loxP) mice were then crossed with a Rosa26-Cre line, resulting in ubiquitous deletion of exon 2 and abolishment of LBH protein expression. Mice homozygous for the Lbh null allele (Lbh(Δ)(2)) displayed normal embryonic development and postnatal growth with morphologies indistinguishable from wild-type littermates. However, mammary gland development, which occurs primarily after birth, was perturbed. Thus, the conditional Lbh allele will be a valuable tool to uncover the currently unknown tissue-specific roles of LBH in postnatal development and disease. PMID:23495064

  2. Automated quantification of carotid artery stenosis on contrast-enhanced MRA data using a deformable vascular tube model.

    PubMed

    Suinesiaputra, Avan; de Koning, Patrick J H; Zudilova-Seinstra, Elena; Reiber, Johan H C; van der Geest, Rob J

    2012-08-01

    The purpose of this study was to develop and validate a method for automated segmentation of the carotid artery lumen from volumetric MR Angiographic (MRA) images using a deformable tubular 3D Non-Uniform Rational B-Splines (NURBS) model. A flexible 3D tubular NURBS model was designed to delineate the carotid arterial lumen. User interaction was allowed to guide the model by placement of forbidden areas. Contrast-enhanced MRA (CE-MRA) from 21 patients with carotid atherosclerotic disease were included in this study. The validation was performed against expert drawn contours on multi-planar reformatted image slices perpendicular to the artery. Excellent linear correlations were found on cross-sectional area measurement (r = 0.98, P < 0.05) and on luminal diameter (r = 0.98, P < 0.05). Strong match in terms of the Dice similarity indices were achieved: 0.95 ± 0.02 (common carotid artery), 0.90 ± 0.07 (internal carotid artery), 0.87 ± 0.07 (external carotid artery), 0.88 ± 0.09 (carotid bifurcation) and 0.75 ± 0.20 (stenosed segments). Slight overestimation of stenosis grading by the automated method was observed. The mean differences was 7.20% (SD = 21.00%) and 5.2% (SD = 21.96%) when validated against two observers. Reproducibility in stenosis grade calculation by the automated method was high; the mean difference between two repeated analyses was 1.9 ± 7.3%. In conclusion, the automated method shows high potential for clinical application in the analysis of CE-MRA of carotid arteries. PMID:22160666

  3. 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

  4. 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.

  5. Inferring Selection Intensity and Allele Age from Multilocus Haplotype Structure

    PubMed Central

    Chen, Hua; Slatkin, Montgomery

    2013-01-01

    It is a challenging task to infer selection intensity and allele age from population genetic data. Here we present a method that can efficiently estimate selection intensity and allele age from the multilocus haplotype structure in the vicinity of a segregating mutant under positive selection. We use a structured-coalescent approach to model the effect of directional selection on the gene genealogies of neutral markers linked to the selected mutant. The frequency trajectory of the selected allele follows the Wright-Fisher model. Given the position of the selected mutant, we propose a simplified multilocus haplotype model that can efficiently model the dynamics of the ancestral haplotypes under the joint influence of selection and recombination. This model approximates the ancestral genealogies of the sample, which reduces the number of states from an exponential function of the number of single-nucleotide polymorphism loci to a quadratic function. That allows parameter inference from data covering DNA regions as large as several hundred kilo-bases. Importance sampling algorithms are adopted to evaluate the probability of a sample by exploring the space of both allele frequency trajectories of the selected mutation and gene genealogies of the linked sites. We demonstrate by simulation that the method can accurately estimate selection intensity for moderate and strong positive selection. We apply the method to a data set of the G6PD gene in an African population and obtain an estimate of 0.0456 (95% confidence interval 0.0144−0.0769) for the selection intensity. The proposed method is novel in jointly modeling the multilocus haplotype pattern caused by recombination and mutation, allowing the analysis of haplotype data in recombining regions. Moreover, the method is applicable to data from populations under exponential growth and a variety of other demographic histories. PMID:23797107

  6. Pyrosequencing for Accurate Imprinted Allele Expression Analysis

    PubMed Central

    Yang, Bing; Damaschke, Nathan; Yao, Tianyu; McCormick, Johnathon; Wagner, Jennifer; Jarrard, David

    2016-01-01

    Genomic imprinting is an epigenetic mechanism that restricts gene expression to one inherited allele. Improper maintenance of imprinting has been implicated in a number of human diseases and developmental syndromes. Assays are needed that can quantify the contribution of each paternal allele to a gene expression profile. We have developed a rapid, sensitive quantitative assay for the measurement of individual allelic ratios termed Pyrosequencing for Imprinted Expression (PIE). Advantages of PIE over other approaches include shorter experimental time, decreased labor, avoiding the need for restriction endonuclease enzymes at polymorphic sites, and prevent heteroduplex formation which is problematic in quantitative PCR-based methods. We demonstrate the improved sensitivity of PIE including the ability to detect differences in allelic expression down to 1%. The assay is capable of measuring genomic heterozygosity as well as imprinting in a single run. PIE is applied to determine the status of Insulin-like Growth Factor-2 (IGF2) imprinting in human and mouse tissues. PMID:25581900

  7. The therapeutic effect of bevacizumab on plaque neovascularization in a rabbit model of atherosclerosis during contrast-enhanced ultrasonography

    PubMed Central

    Li, Yang; Zhu, Ying; Deng, Youbin; Liu, Yani; Mao, Yuhang; Wang, Junli; Sun, Jie

    2016-01-01

    The purpose of the study was to assess the therapeutic effect of the angiogenesis inhibitor bevacizumab on plaques of various stages in rabbit models using contrast-enhanced ultrasonography (CEUS). Abdominal aortic atherosclerosis was induced in 55 rabbits. Thirty-six randomly selected rabbits were divided into 2 groups according to the timing of the bevacizumab injection: an early-stage plaque group (Group ESP) and a later-stage plaque group (Group LSP). The remainder were considered the control group. Standard ultrasonography and CEUS imaging of the abdominal aorta were performed. The animals were euthanized after CEUS, and plaque specimens were harvested for histological staining of CD31. The control group exhibited a substantially higher enhanced intensity, a higher ratio of enhanced intensity in the plaque to that in the lumen, and an increased number of CD31-positive microvessels in the plaque sections than Groups ESP and LSP (P < 0.05 for all). A higher enhanced intensity (P = 0.044), a higher ratio of enhanced intensity in the plaque to that in the lumen (P = 0.023) and more CD31-positive microvessels in the plaque sections (P = 0.006) were found in Group LSP than in Group ESP. Bevacizumab demonstrated more advanced inhibition of neovascularization in early-stage plaques in rabbits. PMID:27452862

  8. 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.

  9. Phase-contrast MRI and CFD modeling of apparent ³He gas flow in rat pulmonary airways.

    PubMed

    Minard, Kevin R; Kuprat, Andrew P; Kabilan, Senthil; Jacob, Richard 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 (2) that 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. PMID:22771528

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

    PubMed Central

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

    2012-01-01

    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 2) that 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. PMID:22771528

  11. 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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27030405

  13. 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

  14. Contrasting non-local effects of shoreline stabilization methods in a model of large-scale coastline morphodynamics

    NASA Astrophysics Data System (ADS)

    Ells, K. D.; Murray, A.

    2011-12-01

    Advances in the understanding of the wave-angle dependence of large-scale sandy coastline evolution have allowed exploratory modeling investigations into the emergence of large-scale coastline features such as sandwaves, capes, and spits; the possible responses of these complex coastline shapes to changing wave climates; and the dynamic coupling of natural coastal processes with economic decisions for shoreline stabilization. Recent numerical-model experiments found that beach nourishment on a complex-shaped coastline can significantly alter rates of shoreline change on spatial scales commensurate with the alongshore distance of adjacent features (up to 100 km). While the effect of beach nourishment is to fix a given shoreline position while maintaining a saturated sediment flux locally, hard structured stabilization methods (e.g. seawalls, revetments, or groynes) tend to reduce local alongshore fluxes of sediment. In long-term numerical experiments (decades to centuries), the effects of local stabilization propagate both progressively alongshore and through a non-local mechanism (wave shadowing). Comparing these two fundamentally different methods of shoreline stabilization on various locations along a cuspate cape coastline, we find that both the local and regional responses to hard structures greatly contrast those of beach nourishment. Sustained nourishment near the tip of a cape tends to extend the cape both seaward and in the direction of alongshore flux, increasing the effect that wave shadowing would have otherwise had on distant shorelines, leading to a negative (landward) perturbation to an adjacent cape. A hard structure at the same location, however, completely fixes the cape's original location, decreasing the shadowing effect and resulting in a positive (seaward) perturbation to the downdrift cape. Recent extensions of this work examine how different stabilization methods affect long-term coastline morphodynamics on other coastline types, starting

  15. Schizotypy and leadership: a contrasting model for deficit symptoms, and a possible therapeutic role for sex hormones.

    PubMed

    Alias, A G

    2000-04-01

    Associational loosening, slow and faulty information processing, poor gating of irrelevant stimuli, poor ability to shift attention, poor working memory, passivity, ambivalence, anhedonia, and impaired motor coordination are cardinal features of schizophrenia but, unlike delusions and hallucinations, they are related more to negative/deficit symptoms. As summarized by Bass, numerous studies have correlated leadership with 'ambition, initiative and persistence' (opposite of passivity), 'speed and accuracy of thought', 'finality of decision,' or decisiveness (the opposite of ambivalence), 'mood control, optimism and sense of humor' (opposite of anhedonia), etc. Andreasen et al postulate that a disruption in the circuitry among nodes located in the prefrontal regions, the thalamic nuclei, and the cerebellum produces 'cognitive dysmetria', meaning difficulty in prioritizing, coordinating, and responding to information, and that it can account for the broad diversity of symptoms of schizophrenia. A relationship between cognitive processes and cerebellar and basal ganglia functions, and a role of neocerebellum in rapidly shifting attention, have been demonstrated. The cognitive styles, including a proficiency to quickly shift attention, of several famous leaders are used as examples of this contrasting model. Julius Caesar and Napoleon, for instance, could dictate to up to six secretaries simultaneously, using their exceptional working memories, and proficiency in quickly and effortlessly shifting attention while flawlessly gating irrelevant external and internal stimuli. It is suggested that specific brain imaging studies could illustrate this contrast. Gray et al noted positive correlations between 'dominance', an important leadership trait, and serum levels of dehydroepiandrosterone (DHEA) and testosterone (T), but not of more potent dihydrotestosterone (DHT), in over 1700 older men. Though not scientifically rigorous, the author noted positive correlations (P = 0

  16. 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

  17. 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

  18. 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

  19. Allele Workbench: Transcriptome Pipeline and Interactive Graphics for Allele-Specific Expression

    PubMed Central

    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

  20. 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

  1. 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

  2. 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

  3. Distribution of repeat unit differences between alleles at tandem repeat microsatellite loci

    SciTech Connect

    Jin, L. |; Zhong, Y.; Chakraborty, R.

    1994-09-01

    PCR-based assays of tandemly repeated microsatellite loci detect genetic variation from which alleles may be scored by their repeat unit lengths. Comparison of allele sizes from such data yields a probability distribution (P{sub k}) of repeat unit differences (k) between alleles segregating in a population. We show that this distribution (P{sub k}; k = 0, 1,2,...) provides insight regarding the mechanism of production of new alleles at such loci and the demographic history of populations, far better than that obtained from other summary measures (e.g., heterozygosity, number of alleles, and the range of allele sizes). The distributions of P{sub k} under multi-step stepwise models of mutation are analytically derived, which show that when a population is at equilibrium under the mutation-drift balance, the distribution of repeat unit differences between alleles is positively skewed with a mode larger than zero. However, when the heterozygosity at a locus is low (say, less than 40%), P{sub k} is a monotonically decreasing function of k. Applications of this theory to data on repeat unit sizes at over 1,240 microsatellite loci from the Caucasians, categorized by the average heterozygosity of loci, indicate that at most microsatellite loci new alleles are produced by stepwise mutations, and this is consistent with the replication slippage mechanism of mutations. The repeat size changes of mutants are probably within one or two units of alleles from which the mutants arise. Distributions of P{sub k} at microsatellite loci located within genes show evidence of allele size constraints. No significant evidence of recent expansion of population sizes in the Caucasians is detected by the distribution of P{sub k}.

  4. Accuracies and Contrasts of Models of the Diffusion-Weighted-Dependent Attenuation of the MRI Signal at Intermediate b-values

    PubMed Central

    Nicolas, Renaud; Sibon, Igor; Hiba, Bassem

    2015-01-01

    The diffusion-weighted-dependent attenuation of the MRI signal E(b) is extremely sensitive to microstructural features. The aim of this study was to determine which mathematical model of the E(b) signal most accurately describes it in the brain. The models compared were the monoexponential model, the stretched exponential model, the truncated cumulant expansion (TCE) model, the biexponential model, and the triexponential model. Acquisition was performed with nine b-values up to 2500 s/mm2 in 12 healthy volunteers. The goodness-of-fit was studied with F-tests and with the Akaike information criterion. Tissue contrasts were differentiated with a multiple comparison corrected nonparametric analysis of variance. F-test showed that the TCE model was better than the biexponential model in gray and white matter. Corrected Akaike information criterion showed that the TCE model has the best accuracy and produced the most reliable contrasts in white matter among all models studied. In conclusion, the TCE model was found to be the best model to infer the microstructural properties of brain tissue. PMID:26106263

  5. Sentinel Node Biopsy for the Head and Neck Using Contrast-Enhanced Ultrasonography Combined with Indocyanine Green Fluorescence in Animal Models: A Feasibility Study

    PubMed Central

    Sato, Dai; Ikeda, Tetsuya; Matsumoto, Yoshifumi; Moro, Yorihisa; Kimura, Toru; Hamanoue, Yasuhiro; Nakamura, Takehiro; Yamauchi, Koichi; Saito, Koichiro; Sugasawa, Masashi; Kohno, Naoyuki

    2015-01-01

    Background Sentinel node navigation surgery is gaining popularity in oral cancer. We assessed application of sentinel lymph node navigation surgery to pharyngeal and laryngeal cancers by evaluating the combination of contrast-enhanced ultrasonography and indocyanine green fluorescence in animal models. Methods This was a prospective, nonrandomized, experimental study in rabbit and swine animal models. A mixture of indocyanine green and Sonazoid was used as the tracer. The tracer mixture was injected into the tongue, larynx, or pharynx. The sentinel lymph nodes were identified transcutaneously by infra-red camera and contrast-enhanced ultrasonography. Detection time and extraction time of the sentinel lymph nodes were measured. The safety of the tracer mixture in terms of mucosal reaction was evaluated macroscopically and microscopically. Results Sentinel lymph nodes were detected transcutaneously by contrast-enhanced ultrasonography alone. The number of sentinel lymph nodes detected was one or two. Despite observation of contrast enhancement of Sonazoid for at least 90 minutes, the number of sentinel lymph nodes detected did not change. The average extraction time of sentinel lymph nodes was 4.8 minutes. Indocyanine green fluorescence offered visual information during lymph node biopsy. The safety of the tracer was confirmed by absence of laryngeal edema both macro and microscopically. Conclusions The combination method of indocyanine green fluorescence and contrast-enhanced ultrasonography for detecting sentinel lymph nodes during surgery for head and neck cancer seems promising, especially for pharyngeal and laryngeal cancer. Further clinical studies to confirm this are warranted. PMID:26161800

  6. Three allele combinations associated with Multiple Sclerosis

    PubMed Central

    Favorova, Olga O; Favorov, Alexander V; Boiko, Alexey N; Andreewski, Timofey V; Sudomoina, Marina A; Alekseenkov, Alexey D; Kulakova, Olga G; Gusev, Eugenyi I; Parmigiani, Giovanni; Ochs, Michael F

    2006-01-01

    Background Multiple sclerosis (MS) is an immune-mediated disease of polygenic etiology. Dissection of its genetic background is a complex problem, because of the combinatorial possibilities of gene-gene interactions. As genotyping methods improve throughput, approaches that can explore multigene interactions appropriately should lead to improved understanding of MS. Methods 286 unrelated patients with definite MS and 362 unrelated healthy controls of Russian descent were genotyped at polymorphic loci (including SNPs, repeat polymorphisms, and an insertion/deletion) of the DRB1, TNF, LT, TGFβ1, CCR5 and CTLA4 genes and TNFa and TNFb microsatellites. Each allele carriership in patients and controls was compared by Fisher's exact test, and disease-associated combinations of alleles in the data set were sought using a Bayesian Markov chain Monte Carlo-based method recently developed by our group. Results We identified two previously unknown MS-associated tri-allelic combinations: -509TGFβ1*C, DRB1*18(3), CTLA4*G and -238TNF*B1,-308TNF*A2, CTLA4*G, which perfectly separate MS cases from controls, at least in the present sample. The previously described DRB1*15(2) allele, the microsatellite TNFa9 allele and the biallelic combination CCR5Δ32, DRB1*04 were also reidentified as MS-associated. Conclusion These results represent an independent validation of MS association with DRB1*15(2) and TNFa9 in Russians and are the first to find the interplay of three loci in conferring susceptibility to MS. They demonstrate the efficacy of our approach for the identification of complex-disease-associated combinations of alleles. PMID:16872485

  7. Stable microsatellite length but frequent allele loss in SV40-immortalized Werner syndrome and control cell lines

    SciTech Connect

    Brokks-Wilson, A.R.; Monnat, R.J. Jr.

    1994-09-01

    We have determined the mitotic stability of microsatellite alleles and allele lengths in SV40-immortalized Werner syndrome (WS) and control cell lines. The impetus for this work was presence of a mutator phenotype in WS cells and cell lines and the association between a DNA mismatch repair deficit and microsatellite length instability in a heritable human tumor syndrome. Thus the identification of microsatellite length instability in WS cells might provide a clue to the primary biochemical defect in WS and a partial explanation for the mutator phenotype and the elevated cancer risk of WS patients. Five microsatellite loci (D2S123, D10S197, D10S141, D8S255, and D8S87) were PCR genotyped in 88 independent clones derived from four SV40-immortalized fibroblast cell lines (two WS lines: WV1 and PSV811; and two control lines: GM637 and GM639). Stable allele lengths were transmitted from cell line to clones in every case. WS cell line WV1 contained a preexisting faint third D2S123 allele which was transmitted with the other two D2S123 alleles to a majority of WV1 clones. In contrast, microsatellite allele loss was common: complete absence of one of two alleles was seen in 30% of control and in 3% of WS clones. Complete allele loss likely results from a clonal population being derived from a cell lacking a microsatellite allele. Altered relative band intensities in clones compared to parental lines were very common in both WS and control backgrounds (40% of all clones). This suggests that allele loss is common and continues upon post-cloning cell culture. These allele losses are likely to be a consequence of the genetic instability that accompanies SV40 immortalization. These results indicate that SV40-immortalized cell lines are genetically heterogeneous, and that the genotypes of individual clones may incompletely represent the genomes of the primary cells from which they were derived.

  8. 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. PMID:21870117

  9. Switching of a Mating-Type a Mutant Allele in Budding Yeast SACCHAROMYCES CEREVISIAE

    PubMed Central

    Klar, Amar J. S.; Fogel, Seymour; Radin, David N.

    1979-01-01

    Aimed at investigating the recovery of a specific mutant allele of the mating type locus (MAT) by switching a defective MAT allele, these experiments provide information bearing on several models proposed for MAT interconversion in bakers yeast, Saccharomyces cerevisiae. Hybrids between heterothallic (ho) cells carrying a mutant MATa allele, designated mata-2, and MATα ho strains show a high capacity for mating with MATa strains. The MATα/mata-2 diploids do not sporulate. However, zygotic clones obtained by mating MATα homothallic (HO) cells with mata-2 ho cells are unable to mate and can sporulate. Tetrad analysis of such clones revealed two diploid (MATα/MATa):two haploid segregants. Therefore, MAT switches occur in MATα/mata-2 HO/ho cells to produce MATα/MATa cells capable of sporulation. In heterothallic strains, the mata-2 allele can be switched to a functional MATα and subsequently to a functional MATa. Among 32 MATα to MATa switches tested, where the MATα was previously derived from the mata-2 mutant, only one mata-2 like isolate was observed. However, the recovered allele, unlike the parental allele, conplements the matα ste1–5 mutant, suggesting that these alleles are not identical and that the recovered allele presumably arose as a mutation of the MATα locus. No mata-2 was recovered by HO-mediated switching of MATα (previously obtained from mata-2 by HO) in 217 switches analyzed. We conclude that in homothallic and heterothallic strains, the mata-2 allele can be readily switched to a functional MATα and subsequently to a functional MATa locus. Overall, the results are in accord with the cassette model (Hicks, Strathern and Herskowitz 1977b) proposed to explain MAT interconversions. PMID:395020

  10. 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

  11. Allele-specific tumor spectrum in pten knockin mice.

    PubMed

    Wang, Hui; Karikomi, Matt; Naidu, Shan; Rajmohan, Ravi; Caserta, Enrico; Chen, Hui-Zi; Rawahneh, Maysoon; Moffitt, Julie; Stephens, Julie A; Fernandez, Soledad A; Weinstein, Michael; Wang, Danxin; Sadee, Wolfgang; La Perle, Krista; Stromberg, Paul; Rosol, Thomas J; Eng, Charis; Ostrowski, Michael C; Leone, Gustavo

    2010-03-16

    Germline mutations in the tumor suppressor gene PTEN (phosphatase and tensin homology deleted on chromosome 10) cause Cowden and Bannayan-Riley-Ruvalcaba (BRR) syndromes, two dominantly inherited disorders characterized by mental retardation, multiple hamartomas, and variable cancer risk. Here, we modeled three sentinel mutant alleles of PTEN identified in patients with Cowden syndrome and show that the nonsense Pten(4-5) and missense Pten(C124R) and Pten(G129E) alleles lacking lipid phosphatase activity cause similar developmental abnormalities but distinct tumor spectra with varying severity and age of onset. Allele-specific differences may be accounted for by loss of function for Pten(4-5), hypomorphic function for Pten(C124R), and gain of function for Pten(G129E). These data demonstrate that the variable tumor phenotypes observed in patients with Cowden and BRR syndromes can be attributed to specific mutations in PTEN that alter protein function through distinct mechanisms. PMID:20194734

  12. Tetrasomic Segregation for Multiple Alleles in Alfalfa

    PubMed Central

    Quiros, Carlos F.

    1982-01-01

    Evidence of tetrasomic inheritance in alfalfa, Medicago sativa L. and M. falcata L., for multiple codominant alleles at three isozymic loci is reported in this study. The locus Prx-1 governing anodal peroxidase and the loci Lap-1 and Lap-2 governing anodal leucine-aminopeptidase were studied by starch gel electrophoresis in seedling root tissue or seeds. The progenies from several di-, tri- or tetra-allelic plants belong to the species M. sativa and M. falcata and their hybrids were studied for the segregation of the three genes. In all cases, tetrasomic inheritance of chromosomal-type segregation was observed. In another progeny resulting from the crossing of two plants involving four different alleles at locus Lap-2, tetrasomic segregation with the possible occurrence of double reduction was observed. This study presents direct evidence of autotetraploidy and the existence of tetra-allelic loci in alfalfa. It also supports the concept that the species M. sativa and M. falcata are genetically close enough to be considered biotypes of a common species. PMID:17246077

  13. Quantitative evaluation of contrast-induced-nephropathy in vascular post-angiography patients: Feasibility study of a semi-empirical model.

    PubMed

    Pan, Lung Fa; Davaa, Otgonbaatar; Chen, Chien Yi; Pan, Lung Kwang

    2015-01-01

    In this study, the contrast-induced-nephropathy (CIN) of vascular patients who had undergone angiography was quantitatively evaluated using a semi-empirical model. The model compiled six essential serum readings and biological data from 70 patients in order to develop a 1st-order nonlinear equation with 16 defined terms. The expectation value of the model was used to predict the serum creatinine reading of patients that had been determined to be at high risk of CIN after contrast media (CM) administration. The other five variables included body surface area (BSA), administrated CM, serum creatinine level before CM administration, blood urea nitrogen (BUN), and systolic blood pressure level. A loss function was used to define the difference between the observed and predicted serum creatinine readings after CM administration. The dominant variables were proven to be systolic blood pressure, serum creatinine level before CM administration, and BSA. The cross interaction between the serum creatinine level before CM administration and systolic blood pressure was the decisive term of the model's performance, indicating that both should be specially considered in order to prevent CIN. The BSA, which was usually ignored by medical staff, was also proven to be a significant variable, whereas the BUN reading and amount of injected contrast media were negligible in the semi-empirical model. PMID:26406083

  14. HLA-DQA1/B1 alleles as putative susceptibility markers in congenital toxoplasmosis.

    PubMed

    Shimokawa, Paulo Tadashi; Targa, Lília Spaleta; Yamamoto, Lidia; Rodrigues, Jonatas Cristian; Kanunfre, Kelly Aparecida; Okay, Thelma Suely

    2016-05-18

    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

  15. Allelic associations of two polymorphic microsatellites in intron 40 of the human von Willebrand factor gene

    SciTech Connect

    Pena, S.D.J.; De Souza, K.T. ); De Andrade, M.; Chakraborty, R. )

    1994-01-18

    At intron 40 of the von Willebrand factor (vWF) gene, two GATA-repeat polymorphic sites exist that are physically separated by 212 bp. At the first site (vWF1 locus), seven segregating repeat alleles were observed in a Brazilian Caucasian population, and at the second (vWF2 locus) there were eight alleles, detected through PCR amplifications of this DNA region. Haplotype analysis of individuals revealed 36 different haplotypes in a sample of 338 chromosomes examined. Allele frequencies between generations and gender at each locus were not significantly different, and the genotype frequencies were consistent with their Hardy-Weinberg expectations. Linkage disequilibrium between loci is highly significant with positive allele size association; that is, large alleles at the loci tend to occur together, and so do the same alleles. Variability at each locus appeared to have arisen in a stepwise fashion, suggesting replication slippage as a possible mechanism of production of new alleles. However, the authors observed an increased number of haplotypes, in contrast with the predictions of a stepwise production of variation in the entire region, suggesting some form of cooperative changes between loci that could be due to either gene conversion, or a common control mechanism of production of new variation at these repeat polymorphism sites. The high degree of polymorphism (gene diversity values of 72% and 78% at vWF1 and vWF2, respectively, and of 93% at the haplotype level) makes these markers informative for paternity testing, genetic counseling, and individual-identification purposes.

  16. 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

  17. Restrictive flamenco alleles are maintained in Drosophila melanogaster population cages, despite the absence of their endogenous gypsy retroviral targets.

    PubMed

    Pélisson, Alain; Payen-Groschêne, Geneviève; Terzian, Christophe; Bucheton, Alain

    2007-02-01

    The flamenco (flam) locus, located at 20A1-3 in the centromeric heterochromatin of the Drosophila melanogaster X chromosome, is a major regulator of the gypsy/mdg4 endogenous retrovirus. In restrictive strains, functional flam alleles maintain gypsy proviruses in a repressed state. By contrast, in permissive strains, proviral amplification results from infection of the female germ line and subsequent insertions into the chromosomes of the progeny. A restrictive/permissive polymorphism prevails in natural and laboratory populations. This polymorphism was assumed to be maintained by the interplay of opposite selective forces; on one hand, the increase of genetic load caused by proviral insertions would favor restrictive flam alleles because they make flies resistant to these gypsy replicative transpositions and, on the other, a hypothetical resistance cost would select against such alleles in the absence of the retrovirus. However, the population cage data presented in this paper do not fit with this simple resistance cost hypothesis because restrictive alleles were not eliminated in the absence of functional gypsy proviruses; on the contrary, using 2 independent flam allelic pairs, the restrictive frequency rose to about 90% in every experimental population, whatever the pair of alleles and the allelic proportions in the initial inoculum. These data suggest that the flam polymorphism is maintained by some strong balancing selection, which would act either on flam itself, independently of the deleterious effect of gypsy, or on a hypothetical flanking gene, in linkage disequilibrium with flam. Alternatively, restrictive flam alleles might also be resistant to some other retroelements that would be still present in the cage populations, causing a positive selection for these alleles. Whatever selective forces that maintain high levels of restrictive alleles independently of gypsy, this unknown mechanism can set up an interesting kind of antiviral innate immunity, at

  18. Inference of Population Splits and Mixtures from Genome-Wide Allele Frequency Data

    PubMed Central

    Pickrell, Joseph K.; Pritchard, Jonathan K.

    2012-01-01

    Many aspects of the historical relationships between populations in a species are reflected in genetic data. Inferring these relationships from genetic data, however, remains a challenging task. In this paper, we present a statistical model for inferring the patterns of population splits and mixtures in multiple populations. In our model, the sampled populations in a species are related to their common ancestor through a graph of ancestral populations. Using genome-wide allele frequency data and a Gaussian approximation to genetic drift, we infer the structure of this graph. We applied this method to a set of 55 human populations and a set of 82 dog breeds and wild canids. In both species, we show that a simple bifurcating tree does not fully describe the data; in contrast, we infer many migration events. While some of the migration events that we find have been detected previously, many have not. For example, in the human data, we infer that Cambodians trace approximately 16% of their ancestry to a population ancestral to other extant East Asian populations. In the dog data, we infer that both the boxer and basenji trace a considerable fraction of their ancestry (9% and 25%, respectively) to wolves subsequent to domestication and that East Asian toy breeds (the Shih Tzu and the Pekingese) result from admixture between modern toy breeds and “ancient” Asian breeds. Software implementing the model described here, called TreeMix, is available at http://treemix.googlecode.com. PMID:23166502

  19. PoMo: An Allele Frequency-Based Approach for Species Tree Estimation

    PubMed Central

    De Maio, Nicola; Schrempf, Dominik; Kosiol, Carolin

    2015-01-01

    Incomplete lineage sorting can cause incongruencies of the overall species-level phylogenetic tree with the phylogenetic trees for individual genes or genomic segments. If these incongruencies are not accounted for, it is possible to incur several biases in species tree estimation. Here, we present a simple maximum likelihood approach that accounts for ancestral variation and incomplete lineage sorting. We use a POlymorphisms-aware phylogenetic MOdel (PoMo) that we have recently shown to efficiently estimate mutation rates and fixation biases from within and between-species variation data. We extend this model to perform efficient estimation of species trees. We test the performance of PoMo in several different scenarios of incomplete lineage sorting using simulations and compare it with existing methods both in accuracy and computational speed. In contrast to other approaches, our model does not use coalescent theory but is allele frequency based. We show that PoMo is well suited for genome-wide species tree estimation and that on such data it is more accurate than previous approaches. PMID:26209413

  20. Accounting for genotype uncertainty in the estimation of allele frequencies in autopolyploids.

    PubMed

    Blischak, Paul D; Kubatko, Laura S; Wolfe, Andrea D

    2016-05-01

    Despite the increasing opportunity to collect large-scale data sets for population genomic analyses, the use of high-throughput sequencing to study populations of polyploids has seen little application. This is due in large part to problems associated with determining allele copy number in the genotypes of polyploid individuals (allelic dosage uncertainty-ADU), which complicates the calculation of important quantities such as allele frequencies. Here, we describe a statistical model to estimate biallelic SNP frequencies in a population of autopolyploids using high-throughput sequencing data in the form of read counts. We bridge the gap from data collection (using restriction enzyme based techniques [e.g. GBS, RADseq]) to allele frequency estimation in a unified inferential framework using a hierarchical Bayesian model to sum over genotype uncertainty. Simulated data sets were generated under various conditions for tetraploid, hexaploid and octoploid populations to evaluate the model's performance and to help guide the collection of empirical data. We also provide an implementation of our model in the R package polyfreqs and demonstrate its use with two example analyses that investigate (i) levels of expected and observed heterozygosity and (ii) model adequacy. Our simulations show that the number of individuals sampled from a population has a greater impact on estimation error than sequencing coverage. The example analyses also show that our model and software can be used to make inferences beyond the estimation of allele frequencies for autopolyploids by providing assessments of model adequacy and estimates of heterozygosity. PMID:26607217

  1. HLA-B alleles of the Cayapa of Ecuador: New B39 and B15 alleles

    SciTech Connect

    Garber, T.L.; Butler, L.M.; Watkins, D.I.

    1995-05-01

    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. 70 refs., 2 figs., 2 tabs.

  2. Perceived contrast in complex images

    PubMed Central

    Haun, Andrew M.; Peli, Eli

    2013-01-01

    To understand how different spatial frequencies contribute to the overall perceived contrast of complex, broadband photographic images, we adapted the classification image paradigm. Using natural images as stimuli, we randomly varied relative contrast amplitude at different spatial frequencies and had human subjects determine which images had higher contrast. Then, we determined how the random variations corresponded with the human judgments. We found that the overall contrast of an image is disproportionately determined by how much contrast is between 1 and 6 c/°, around the peak of the contrast sensitivity function (CSF). We then employed the basic components of contrast psychophysics modeling to show that the CSF alone is not enough to account for our results and that an increase in gain control strength toward low spatial frequencies is necessary. One important consequence of this is that contrast constancy, the apparent independence of suprathreshold perceived contrast and spatial frequency, will not hold during viewing of natural images. We also found that images with darker low-luminance regions tended to be judged as having higher overall contrast, which we interpret as the consequence of darker local backgrounds resulting in higher band-limited contrast response in the visual system. PMID:24190908

  3. Variation in lipoprotein(a) concentration associated with different apolipoprotein(a) alleles.

    PubMed Central

    Perombelon, Y F; Soutar, A K; Knight, B L

    1994-01-01

    Plasma lipoprotein(a) (Lp(a)) concentrations vary considerably between individuals. To examine the variation for products of the same and different apolipoprotein(a) (apo(a)) alleles, conditions were established whereby phenotyping immunoblots could be used to estimate the concentration of Lp(a) associated with the constituent apo(a) isoforms. In these studies 28 distinct isoforms were identified, each differing by a single kringle IV unit. Tracking the isoforms through 10 families showed that there could be up to 200-fold difference in the Lp(a) concentration associated with the same-sized isoform produced from different alleles. In contrast there was typically < 2.5-fold variation in the Lp(a) concentration associated with the same allele. However, there were four occasions where the concentration associated with a particular allele was reduced below the typical range from one generation to the next. A nonlinear, inverse trend with isoform size was apparently superimposed upon the other factors that determine Lp(a) concentration. Inheritance of familial hypercholesterolemia or familial-defective apoB100 had little consistent effect upon Lp(a) concentration. In both the families and in other unrelated individuals the distribution of isoforms and their associated concentrations provided evidence for the presence of at least two and possibly more subpopulations of apo(a) alleles with different sizes and expression. Images PMID:8163653

  4. Feasibility Study of Myocardial Perfusion and Oxygenation by Non-Contrast MRI: Comparison with PET Study in a Canine Model

    PubMed Central

    McCommis, Kyle S.; Zhang, Haosen; Herrero, Pilar; Gropler, Robert J.; Zheng, Jie

    2008-01-01

    The purpose of this study was to examine the feasibility of quantifying myocardial blood flow (MBF) and rate of myocardial oxygen consumption (MVO2) during pharmacologically induced stress without using a contrast agent. The former was measured by the arterial spin labeling (ASL) method and the later was obtained by measuring the oxygen extraction fraction (OEF) with the magnetic resonance imaging (MRI) blood oxygenation level-dependent (BOLD) effect and Fick's law. The MRI results were compared with the established positron emission tomography (PET) methods. Six mongrel dogs with induced acute moderate left coronary artery stenosis were scanned using a clinical PET and a 1.5T MRI system, in the same day. Regional MBF, myocardial OEF, and MVO2 were measured with both imaging modalities. Correlation coefficients (R2) of the three myocardial indexes (MBF, OEF, and MVO2) between MRI and PET methods ranged from 0.70 to 0.93. Bland-Altman statistics demonstrated that the estimated precision of the limits of agreement between MRI and PET measurements varied from 18% (OEF), to 37% (MBF), and 45% (MVO2). The detected changes in these indexes, at rest and during dobutamine stress, were similar between two image modalities. The proposed non-contrast MRI technique is a promising method to quantitatively assess myocardial perfusion and oxygenation. PMID:17566684

  5. A Two-Criterion Model for Microvascular Bio-Effects Induced In Vivo by Contrast Microbubbles Exposed to Medical Ultrasound.

    PubMed

    Church, Charles C; Miller, Douglas L

    2016-06-01

    The mechanical index (MI) is a theoretical exposure parameter for cavitational bio-effects of diagnostic ultrasound. The theory for the MI assumed that bubbles of all relevant sizes exist in tissue, a condition that is approximated for tissues that include a microbubble contrast agent. Therefore, the MI should allow science-based safety guidance for contrast-enhanced diagnostic ultrasound. However, theoretical predictions of bio-effects thresholds based on the MI typically do not concur with the frequency dependence of experimentally measured thresholds for bio-effects. For example, experimental thresholds for glomerular capillary hemorrhage in rats infused with contrast microbubbles increased approximately linearly with frequency, whereas the MI predicted a square root dependence. Here, cavitation thresholds were computed for linear versions of the acoustic pulses used in that study assuming bubbles containing either air, C3F8, or a 1:1 mixture of the two and surrounded by either blood or kidney tissue. Although no single threshold criterion was successful, combining results for one criterion that maximized circumferential stress in the capillary wall with another that ensured an inertial collapse produced thresholds that were consistent with experimental data. This suggests that a contrast-specific safety metric may be achieved following validation of this two-criterion model. PMID:27033330

  6. 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

  7. Allele-specific expression assays using Solexa

    PubMed Central

    Main, Bradley J; Bickel, Ryan D; McIntyre, Lauren M; Graze, Rita M; Calabrese, Peter P; Nuzhdin, Sergey V

    2009-01-01

    Background Allele-specific expression (ASE) assays can be used to identify cis, trans, and cis-by-trans regulatory variation. Understanding the source of expression variation has important implications for disease susceptibility, phenotypic diversity, and adaptation. While ASE is commonly measured via relative fluorescence at a SNP, next generation sequencing provides an opportunity to measure ASE in an accurate and high-throughput manner using read counts. Results We introduce a Solexa-based method to perform large numbers of ASE assays using only a single lane of a Solexa flowcell. In brief, transcripts of interest, which contain a known SNP, are PCR enriched and barcoded to enable multiplexing. Then high-throughput sequencing is used to estimate allele-specific expression using sequencing counts. To validate this method, we measured the allelic bias in a dilution series and found high correlations between measured and expected values (r>0.9, p < 0.001). We applied this method to a set of 5 genes in a Drosophila simulans parental mix, F1 and introgression and found that for these genes the majority of expression divergence can be explained by cis-regulatory variation. Conclusion We present a new method with the capacity to measure ASE for large numbers of assays using as little as one lane of a Solexa flowcell. This will be a valuable technique for molecular and population genetic studies, as well as for verification of genome-wide data sets. PMID:19740431

  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 PAGESBeta

    Yue, Min; Han, Xiangan; Masi, Leon De; Zhu, Chunhong; Ma, Xun; Zhang, Junjie; Wu, Renwei; Schmieder, Robert; Kaushik, Radhey S.; Fraser, George P.; et al

    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. Allelic variation contributes to bacterial host specificity

    PubMed Central

    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.

    2015-01-01

    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. Together, our data provide the first concrete evidence that functional differences between allelic variants of bacterial proteins likely contribute to pathoadaption to diverse hosts. PMID:26515720

  11. Reconstructing the prior probabilities of allelic phylogenies.

    PubMed Central

    Golding, G Brian

    2002-01-01

    In general when a phylogeny is reconstructed from DNA or protein sequence data, it makes use only of the probabilities of obtaining some phylogeny given a collection of data. It is also possible to determine the prior probabilities of different phylogenies. This information can be of use in analyzing the biological causes for the observed divergence of sampled taxa. Unusually "rare" topologies for a given data set may be indicative of different biological forces acting. A recursive algorithm is presented that calculates the prior probabilities of a phylogeny for different allelic samples and for different phylogenies. This method is a straightforward extension of Ewens' sample distribution. The probability of obtaining each possible sample according to Ewens' distribution is further subdivided into each of the possible phylogenetic topologies. These probabilities depend not only on the identity of the alleles and on 4N(mu) (four times the effective population size times the neutral mutation rate) but also on the phylogenetic relationships among the alleles. Illustrations of the algorithm are given to demonstrate how different phylogenies are favored under different conditions. PMID:12072482

  12. Allelic variation contributes to bacterial host specificity.

    PubMed

    Yue, Min; Han, Xiangan; De Masi, Leon; 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

    2015-01-01

    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. Together, our data provide the first concrete evidence that functional differences between allelic variants of bacterial proteins likely contribute to pathoadaption to diverse hosts. PMID:26515720

  13. 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.

  14. 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

  15. 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. PMID:27294261

  16. Semi-parametric Allelic Tests For Mapping Multiple Phenotypes: Binomial Regression And Mahalanobis Distance

    PubMed Central

    Majumdar, Arunabha; Witte, John S.; Ghosh, Saurabh

    2016-01-01

    Binary phenotypes commonly arise due to multiple underlying quantitative precursors. 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., 2012], 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. We explore two allelic tests of multivariate association: one using a Binomial regression model based on inverted regression of genotype on phenotype (BAMP), and the other employing the Mahalanobis distance between two sample means of the multivariate phenotype vector for two alleles at a SNP (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 are compared with the genotype-level test MultiPhen. 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 substantially more powerful. All three tests are applied to two real data and the results offer some support for the simulation study. Since the allelic approaches assume Hardy-Weinberg Equilibrium (HWE), we propose a hybrid approach for testing multivariate association that implements MultiPhen when HWE is violated and BAMP otherwise. PMID:26493781

  17. 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...

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. Upgrade of the DIII-D Phase Contrast Imaging Diagnostic and Modeling of High-k Measurements

    NASA Astrophysics Data System (ADS)

    Dorris, J. R.; Rost, J. C.; Porkolab, M.; Ernst, D. R.; Burrell, K. H.

    2004-11-01

    Phase Contrast Imaging (PCI) has been used in the past to diagnose plasma fluctuations in several devices, generally focusing on wavelengths in the cm range, typical of ITG modes, TEM modes, and ICRF waves. However, the PCI technique is capable of measuring modes in the ETG range, and an upgrade to the DIII-D PCI system is underway which will allow access to these short-wavelength modes. Currently being installed are fast digitizers that will allow sampling up to 40 MHz, and new imaging optics that will extend the wave-number sensitivity up to 30/cm. A rotating mask system will take advantage of the vertical variation of radial magnetic field to make localized measurements along the PCI viewing chord. This mask system is currently undergoing design review; fabrication, testing, and installation will occur in the near term. Turbulence simulations are being conducted for comparison with the expected short wavelength PCI data. Results from initial GS2 simulations and hardware upgrade details will be presented.

  3. 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. PMID:24188690

  4. 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.

  5. 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

  6. Differential effects of the APOE e4 allele on different domains of cognitive ability across the life-course.

    PubMed

    Marioni, Riccardo E; Campbell, Archie; Scotland, Generation; Hayward, Caroline; Porteous, David J; Deary, Ian J

    2016-06-01

    The association between APOE genotype and cognitive function suggests a positive role for the e2 allele and a negative role for the e4 allele. Both alleles have relatively low frequencies in the general population; hence, meta-analyses have been based on many small, heterogeneous studies. Here, we report the APOE-cognition associations in the largest single analysis to date. APOE status and cognitive ability were measured in 18 337 participants from the Generation Scotland study between 2006 and 2011. The age range was 18-94 years with a mean of 47 (SD 15). Four cognitive domains were assessed: verbal declarative memory (paragraph recall), processing speed (digit symbol substitution), verbal fluency (phonemic verbal fluency), and vocabulary (Mill Hill synonyms). Linear regression was used to assess the associations between APOE genetic status and cognition. Possession of the e4 allele was associated with lower scores on the measures of memory and processing speed in subjects aged >60. Across all age ranges, the e4 allele was linked to better verbal fluency scores. In younger subjects (≤60 years) the e4 allele was linked to higher vocabulary scores. There were no associations between the e2 allele and cognitive ability. As seen in previous meta-analyses, the APOE e4 allele is linked to poorer cognitive performance in the domains of memory and processing speed. By contrast, positive associations were seen between the e4 allele and measures of verbal fluency and vocabulary. All associations were relatively small and, in many cases, nominally significant despite the very large sample size. PMID:26395552

  7. Poor transferability of species distribution models for a pelagic predator, the grey petrel, indicates contrasting habitat preferences across ocean basins.

    PubMed

    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

  8. 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

  9. Effective contrast of colored stimuli in the mesopic range: a metric for perceived contrast based on achromatic luminance contrast.

    PubMed

    Walkey, Helen C; Barbur, John L; Harlow, J Alister; Hurden, Antony; Moorhead, Ian R; Taylor, Julie A F

    2005-01-01

    Little is known about how color signals and cone- and rod-based luminance signals contribute to perceived contrast in the mesopic range. In this study the perceived contrast of colored, mesopic stimuli was matched with that of spatially equivalent achromatic stimuli. The objective was to develop a metric for perceived contrast in the mesopic range in terms of an equivalent achromatic luminance contrast, referred to here as effective contrast. Stimulus photopic luminance contrast, scotopic luminance contrast, and chromatic difference from the background all contributed to effective contrast over the mid-mesopic range, but their contributions were not independent and varied markedly with background luminance. Surprisingly, color made a significant contribution to effective contrast from 10 to approximately 0.003 cd m(-2). A model describing this relationship is introduced (R2 = 0.89) and compared with predictions of mesopic luminance contrast obtained from a number of models proposed as systems of mesopic photometry. PMID:15669611

  10. Effective contrast of colored stimuli in the mesopic range: a metric for perceived contrast based on achromatic luminance contrast

    NASA Astrophysics Data System (ADS)

    Walkey, Helen C.; Barbur, John L.; Harlow, J. Alister; Hurden, Antony; Moorhead, Ian R.; Taylor, Julie A. F.

    2005-01-01

    Little is known about how color signals and cone- and rod-based luminance signals contribute to perceived contrast in the mesopic range. In this study the perceived contrast of colored, mesopic stimuli was matched with that of spatially equivalent achromatic stimuli. The objective was to develop a metric for perceived contrast in the mesopic range in terms of an equivalent achromatic luminance contrast, referred to here as effective contrast. Stimulus photopic luminance contrast, scotopic luminance contrast, and chromatic difference from the background all contributed to effective contrast over the mid-mesopic range, but their contributions were not independent and varied markedly with background luminance. Surprisingly, color made a significant contribution to effective contrast from 10 to approximately 0.003 cd m-2. A model describing this relationship is introduced (R2=0.89) and compared with predictions of mesopic luminance contrast obtained from a number of models proposed as systems of mesopic photometry.

  11. Chromosome 5 allele loss in human colorectal carcinomas.

    PubMed

    Solomon, E; Voss, R; Hall, V; Bodmer, W F; Jass, J R; Jeffreys, A J; Lucibello, F C; Patel, I; Rider, S H

    That the sporadic and inherited forms of a particular cancer could both result from mutations in the same gene was first proposed by Knudson. He further proposed that these mutations act recessively at the cellular level, and that both copies of the gene must be lost for the cancer to develop. In sporadic cases both events occur somatically whereas in dominant familial cases susceptibility is inherited through a germline mutation and the cancer develops after a somatic change in the homologous allele. This model has since been substantiated in the case of retinoblastoma, Wilms tumour, acoustic neuroma and several other tumours, in which loss of heterozygosity was shown in tumour material compared to normal tissue from the same patient. The dominantly inherited disorder, familial adenomatous polyposis (FAP, also called familial polyposis coli), which gives rise to multiple adenomatous polyps in the colon that have a relatively high probability of progressing to a malignant adenocarcinoma, provides a basis for studying recessive genes in the far more common colorectal carcinomas using this approach. Following a clue as to the location of the FAP gene given by a case report of an individual with an interstitial deletion of chromosome 5q, who had FAP and multiple developmental abnormalities, we have examined sporadic colorectal adenocarcinomas for loss of alleles on chromosome 5. Using a highly polymorphic 'minisatellite' probe which maps to chromosome 5q we have shown that at least 20% of this highly heterogeneous set of tumours lose one of the alleles present in matched normal tissue. This parallels the assignment of the FAP gene to chromosome 5 (see accompanying paper) and suggests that becoming recessive for this gene may be a critical step in the progression of a relatively high proportion of colorectal cancers. PMID:2886919

  12. 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. PMID:25775930

  13. Catalogue of alleles of gliadin-coding loci in durum wheat (Triticum durum Desf.).

    PubMed

    Melnikova, N V; Kudryavtseva, A V; Kudryavtsev, A M

    2012-02-01

    Gliadins are seed storage proteins which are characterized by high intervarietal polymorphism and can be used as genetic markers. As a result of our work, a considerably extended catalogue of allelic variants of gliadin component blocks was compiled for durum wheat; 74 allelic variants for four gliadin-coding loci were identified for the first time. The extended catalogue includes a total of 131 allelic variants: 16 for locus Gli-A1(d), 19 for locus Gli-B1(d), 41 for locus Gli-A2(d), and 55 for locus Gli-B2(d). The electrophoretic pattern of the standard cultivar and a diagram are provided for every block identified. The number of alleles per family is quite small for loci Gli-A1(d) and Gli-B1(d) of durum wheat, as contrasted to loci Gli-A2(d) and Gli-B2(d) that are characterized by large families including many alleles. The presence of large block families determines a higher diversity of durum wheat for loci Gli-A2(d) and Gli-B2(d) as compared to Gli-A1(d) and Gli-B1(d). The catalogue of allelic variants of gliadin component blocks can be used by seed farmers to identify durum wheat cultivars and evaluate their purity; by breeders, to obtain homogenous cultivars and control the initial stages of selection; by gene bank experts, to preserve native varieties and the original biotypic composition of cultivars. PMID:21946233

  14. Fixation probability with multiple alleles and projected average allelic effect on selection.

    PubMed

    Lessard, Sabin; Lahaie, Philippe

    2009-06-01

    The first-order effect of selection on the probability of fixation of an allele, with respect to an intensity of selection s>0 in a diploid population of fixed finite size N, undergoing discrete, non-overlapping generations, is shown to be given by the sum of the average effects of that allele on the coefficient of selection in the current generation and all future generations, given the population state in the current generation. This projected average allelic effect is a weighted sum of average allelic effects in allozygous and autozygous offspring in the initial generation, with weights given in terms of expected coalescence times, under neutrality, for the lineages of two or three gametes chosen at random in the same generation. This is shown in the framework of multiple alleles at one locus, with genotypic values determining either viability or fertility differences, and with either multinomial or exchangeable reproduction schemes. In the limit of weak selection in a large population such that Ns tends to zero, the initial average allelic effects in allozygous offspring and autozygous offspring have the same weight on the fixation probability only in the domain of application of the Kingman coalescent. With frequency-dependent selection in a linear-game-theoretic context with two phenotypes determined by additive gene action, the first-order effect on the fixation probability is a combination of two effects of frequency-independent selection, one in a haploid population, the other in a diploid population. In the domain of application of the Kingman coalescent as the population size goes to infinity and Ns to zero, the first effect is three times more important than the second effect. This explains the one-third law of evolutionary dynamics in this domain, and shows how this law can be extended beyond this domain. PMID:19249322

  15. Contrasting response to nutrient manipulation in Arctic mesocosms are reproduced by a minimum microbial food web model

    PubMed Central

    Larsen, Aud; Egge, Jorun K; Nejstgaard, Jens C; Di Capua, Iole; Thyrhaug, Runar; Bratbak, Gunnar; Thingstad, T Frede

    2015-01-01

    A minimum mathematical model of the marine pelagic microbial food web has previously shown to be able to reproduce central aspects of observed system response to different bottom-up manipulations in a mesocosm experiment Microbial Ecosystem Dynamics (MEDEA) in Danish waters. In this study, we apply this model to two mesocosm experiments (Polar Aquatic Microbial Ecology (PAME)-I and PAME-II) conducted at the Arctic location Kongsfjorden, Svalbard. The different responses of the microbial community to similar nutrient manipulation in the three mesocosm experiments may be described as diatom-dominated (MEDEA), bacteria-dominated (PAME-I), and flagellated-dominated (PAME-II). When allowing ciliates to be able to feed on small diatoms, the model describing the diatom-dominated MEDEA experiment give a bacteria-dominated response as observed in PAME I in which the diatom community comprised almost exclusively small-sized cells. Introducing a high initial mesozooplankton stock as observed in PAME-II, the model gives a flagellate-dominated response in accordance with the observed response also of this experiment. The ability of the model originally developed for temperate waters to reproduce population dynamics in a 10°C colder Arctic fjord, does not support the existence of important shifts in population balances over this temperature range. Rather, it suggests a quite resilient microbial food web when adapted to in situ temperature. The sensitivity of the model response to its mesozooplankton component suggests, however, that the seasonal vertical migration of Arctic copepods may be a strong forcing factor on Arctic microbial food webs. PMID:26074626

  16. Factors Influencing Ascertainment Bias of Microsatellite Allele Sizes: Impact on Estimates of Mutation Rates

    PubMed Central

    Li, Biao; Kimmel, Marek

    2013-01-01

    Microsatellite loci play an important role as markers for identification, disease gene mapping, and evolutionary studies. Mutation rate, which is of fundamental importance, can be obtained from interspecies comparisons, which, however, are subject to ascertainment bias. This bias arises, for example, when a locus is selected on the basis of its large allele size in one species (cognate species 1), in which it is first discovered. This bias is reflected in average allele length in any noncognate species 2 being smaller than that in species 1. This phenomenon was observed in various pairs of species, including comparisons of allele sizes in human and chimpanzee. Various mechanisms were proposed to explain observed differences in mean allele lengths between two species. Here, we examine the framework of a single-step asymmetric and unrestricted stepwise mutation model with genetic drift. Analysis is based on coalescent theory. Analytical results are confirmed by simulations using the simuPOP software. The mechanism of ascertainment bias in this model is a tighter correlation of allele sizes within a cognate species 1 than of allele sizes in two different species 1 and 2. We present computations of the expected average allele size difference, given the mutation rate, population sizes of species 1 and 2, time of separation of species 1 and 2, and the age of the allele. We show that when the past demographic histories of the cognate and noncognate taxa are different, the rate and directionality of mutations affect the allele sizes in the two taxa differently from the simple effect of ascertainment bias. This effect may exaggerate or reverse the effect of difference in mutation rates. We reanalyze literature data, which indicate that despite the bias, the microsatellite mutation rate estimate in the ancestral population is consistently greater than that in either human or chimpanzee and the mutation rate estimate in human exceeds or equals that in chimpanzee with the rate

  17. Borrowed alleles and convergence in serpentine adaptation.

    PubMed

    Arnold, Brian J; Lahner, Brett; DaCosta, Jeffrey M; Weisman, Caroline M; Hollister, Jesse D; Salt, David E; Bomblies, Kirsten; Yant, Levi

    2016-07-19

    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

  18. 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

  19. Analytical model for quantitative prediction of material contrasts in scattering-type near-field optical microscopy.

    PubMed

    Cvitkovic, A; Ocelic, N; Hillenbrand, R

    2007-07-01

    Nanometer-scale mapping of complex optical constants by scattering-type near-field microscopy has been suffering from quantitative discrepancies between the theory and experiments. To resolve this problem, a novel analytical model is presented here. The comparison with experimental data demonstrates that the model quantitatively reproduces approach curves on a Au surface and yields an unprecedented agreement with amplitude and phase spectra recorded on a phonon-polariton resonant SiC sample. The simple closed-form solution derived here should enable the determination of the local complex dielectric function on an unknown sample, thereby identifying its nanoscale chemical composition, crystal structure and conductivity. PMID:19547189

  20. 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.

  1. 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.

  2. 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. PMID:25477383

  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. Quantitative Myocardial Perfusion with Dynamic Contrast-Enhanced Imaging in MRI and CT: Theoretical Models and Current Implementation.

    PubMed

    Pelgrim, G J; 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

  5. 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.

  6. Allelic analysis of sheath blight resistance with association mapping in rice.

    PubMed

    Jia, Limeng; Yan, Wengui; Zhu, Chengsong; Agrama, Hesham A; Jackson, Aaron; Yeater, Kathleen; Li, Xiaobai; Huang, Bihu; Hu, Biaolin; McClung, Anna; Wu, Dianxing

    2012-01-01

    Sheath blight (ShB) caused by the soil-borne pathogen Rhizoctonia solani is one of the most devastating diseases in rice world-wide. Global attention has focused on examining individual mapping populations for quantitative trait loci (QTLs) for ShB resistance, but to date no study has taken advantage of association mapping to examine hundreds of lines for potentially novel QTLs. Our objective was to identify ShB QTLs via association mapping in rice using 217 sub-core entries from the USDA rice core collection, which were phenotyped with a micro-chamber screening method and genotyped with 155 genome-wide markers. Structure analysis divided the mapping panel into five groups, and model comparison revealed that PCA5 with genomic control was the best model for association mapping of ShB. Ten marker loci on seven chromosomes were significantly associated with response to the ShB pathogen. Among multiple alleles in each identified loci, the allele contributing the greatest effect to ShB resistance was named the putative resistant allele. Among 217 entries, entry GSOR 310389 contained the most putative resistant alleles, eight out of ten. The number of putative resistant alleles presented in an entry was highly and significantly correlated with the decrease of ShB rating (r = -0.535) or the increase of ShB resistance. Majority of the resistant entries that contained a large number of the putative resistant alleles belonged to indica, which is consistent with a general observation that most ShB resistant accessions are of indica origin. These findings demonstrate the potential to improve breeding efficiency by using marker-assisted selection to pyramid putative resistant alleles from various loci in a cultivar for enhanced ShB resistance in rice. PMID:22427867

  7. Allele-Specific Deletions in Mouse Tumors Identify Fbxw7 as Germline Modifier of Tumor Susceptibility

    PubMed Central

    Perez-Losada, Jesus; Wu, Di; DelRosario, Reyno; Balmain, Allan; Mao, Jian-Hua

    2012-01-01

    Genome-wide association studies (GWAS) have been successful in finding associations between specific genetic variants and cancer susceptibility in human populations. These studies have identified a range of highly statistically significant associations between single nucleotide polymorphisms (SNPs) and susceptibility to development of a range of human tumors. However, the effect of each SNP in isolation is very small, and all of the SNPs combined only account for a relatively minor proportion of the total genetic risk (5–10%). There is therefore a major requirement for alternative routes to the discovery of genetic risk factors for cancer. We have previously shown using mouse models that chromosomal regions harboring susceptibility genes identified by linkage analysis frequently exhibit allele-specific genetic alterations in tumors. We demonstrate here that the Fbxw7 gene, a commonly mutated gene in a wide range of mouse and human cancers, shows allele-specific deletions in mouse lymphomas and skin tumors. Lymphomas from three different F1 hybrids show 100% allele-specificity in the patterns of allelic loss. Parental alleles from 129/Sv or Spretus/Gla mice are lost in tumors from F1 hybrids with C57BL/6 animals, due to the presence of a specific non-synonymous coding sequence polymorphism at the N-terminal portion of the gene. A specific genetic test of association between this SNP and lymphoma susceptibility in interspecific backcross mice showed a significant linkage (p = 0.001), but only in animals with a functional p53 gene. These data therefore identify Fbxw7 as a p53-dependent tumor susceptibility gene. Increased p53-dependent tumor susceptibility and allele-specific losses were also seen in a mouse skin model of skin tumor development. We propose that analysis of preferential allelic imbalances in tumors may provide an efficient means of uncovering genetic variants that affect mouse and human tumor susceptibility. PMID:22348067

  8. 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.

    2016-07-01

    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.

  9. 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

  10. Three-dimensional elastic wave modeling using a CG-FFT approach to the solution of a contrast-source stress-velocity integral-equation formulation

    NASA Astrophysics Data System (ADS)

    Yang, J.; Abubakar, A.

    2012-12-01

    The ability to accurately and efficiently simulate elastic wave scattering processes is very important in geophysical prospecting applications. A recently proposed formulation of an integral equation for solving three-dimensional elastic wave scattering problems is numerically implemented. The approach is formulated in terms of the stress tensor and particle velocity vector, where the symmetric tensors of rank two are decomposed into their omnidirectional and deviatoric constituents. Subsequently, this integral equation is used to obtain a contrast-source type integral equation. For solving these integral equations we employ a Conjugate Gradient Fast Fourier Transform (CG-FFT) scheme, which is based on quadrature formulas that provide (second-order) accurate approximations while retaining the convolution nature of the relevant integrals that make them amenable to efficient evaluation via Fast Fourier Transforms. As linear solvers we employ the Conjugate Gradient for Normal Residual (CGNR) scheme, which is always monotonically convergent, but has a slow convergent rate, and the Bi-Conjugate Gradient Stabilized (BiCGSTAB) scheme, which is more efficient, but it is less stable. The convergence rates of iterative schemes are further improved through the use of a simple diagonal preconditioner. We show a number of numerical results that demonstrate the accuracy and efficiency of the implemented 3D elastic modeling approach. Numerical models include both simple synthetic models and classic seismic test models (such as the SEG/EAGE salt model and the Marmousi2 model). Excellent benchmark results against a Finite Difference Time Domain (FDTD) algorithm are also presented. These features suggest that the present numerical scheme may provide the basis for the so-called contrast-source inversion method.

  11. The Coalescent Process in Models with Selection

    PubMed Central

    Kaplan, N. L.; Darden, T.; Hudson, R. R.

    1988-01-01

    Statistical properties of the process describing the genealogical history of a random sample of genes are obtained for a class of population genetics models with selection. For models with selection, in contrast to models without selection, the distribution of this process, the coalescent process, depends on the distribution of the frequencies of alleles in the ancestral generations. If the ancestral frequency process can be approximated by a diffusion, then the mean and the variance of the number of segregating sites due to selectively neutral mutations in random samples can be numerically calculated. The calculations are greatly simplified if the frequencies of the alleles are tightly regulated. If the mutation rates between alleles maintained by balancing selection are low, then the number of selectively neutral segregating sites in a random sample of genes is expected to substantially exceed the number predicted under a neutral model. PMID:3066685

  12. 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

  13. 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

  14. Feasibility of Single-Input Tracer Kinetic Modeling with Continuous-Time Formalism in Liver 4-Phase Dynamic Contrast-Enhanced CT

    PubMed Central

    Lee, Sang Ho; Ryu, Yasuji; Hayano, Koichi; Yoshida, Hiroyuki

    2015-01-01

    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. PMID:26236779

  15. Inferring the age of a fixed beneficial allele.

    PubMed

    Ormond, Louise; Foll, Matthieu; Ewing, Gregory B; Pfeifer, Susanne P; Jensen, Jeffrey D

    2016-01-01

    Estimating the age and strength of beneficial alleles is central to understanding how adaptation proceeds in response to changing environmental conditions. Several haplotype-based estimators exist for inferring the age of segregating beneficial mutations. Here, we develop an approximate Bayesian-based approach that rather estimates these parameters for fixed beneficial mutations in single populations. We integrate a range of existing diversity, site frequency spectrum, haplotype- and linkage disequilibrium-based summary statistics. We show that for strong selective sweeps on de novo mutations the method can estimate allele age and selection strength even in nonequilibrium demographic scenarios. We extend our approach to models of selection on standing variation, and co-infer the frequency at which selection began to act upon the mutation. Finally, we apply our method to estimate the age and selection strength of a previously identified mutation underpinning cryptic colour adaptation in a wild deer mouse population, and compare our findings with previously published estimates as well as with geological data pertaining to the presumed shift in selective pressure. PMID:26576754

  16. 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. PMID:23829482

  17. Schizophrenia susceptibility alleles are enriched for alleles that affect gene expression in adult human brain

    PubMed Central

    Richards, Alexander L; Jones, Lesley; Moskvina, Valentina; Kirov, George; Gejman, Pablo V; Levinson, Douglas F; Sanders, Alan R; Purcell, Shaun; Visscher, Peter M; Craddock, Nick; Owen, Michael J; Holmans, Peter; O’Donovan, Michael C

    2016-01-01

    It is widely thought that alleles that influence susceptibility to common diseases, including schizophrenia, will frequently do so through effects on gene expression. Since only a small proportion of the genetic variance for schizophrenia has been attributed to specific loci, this remains an unproven hypothesis. The International Schizophrenia Consortium (ISC) recently reported a substantial polygenic contribution to that disorder, and that schizophrenia risk alleles are enriched among SNPs selected for marginal evidence for association (p<0.5) from genome wide association studies (GWAS). It follows that if schizophrenia susceptibility alleles are enriched for those that affect gene expression, those marginally associated SNPs which are also eQTLs should carry more true association signals compared with SNPs which are not. To test this, we identified marginally associated (p<0.5) SNPs from two of the largest available schizophrenia GWAS datasets. We assigned eQTL status to those SNPs based upon an eQTL dataset derived from adult human brain. Using the polygenic score method of analysis reported by the ISC, we observed and replicated the observation that higher probability cis-eQTLs predicted schizophrenia better than those with a lower probability for being a cis-eQTL. Our data support the hypothesis that alleles conferring risk of schizophrenia are enriched among those that affect gene expression. Moreover, our data show that notwithstanding the likely developmental origin of schizophrenia, studies of adult brain tissue can in principle allow relevant susceptibility eQTLs to be identified. PMID:21339752

  18. Allelic Interactions Heritably Alter the Activity of a Metastable Maize Pl Allele

    PubMed Central

    Hollick, J. B.; Patterson, G. I.; Coe-Jr., E. H.; Cone, K. C.; Chandler, V. L.

    1995-01-01

    The maize pl locus encodes a transcriptional activator of anthocyanin biosynthetic genes. The Pl-Rhoades (Pl-Rh) allele confers robust purple anthocyanin pigment in several tissues. Spontaneous derivatives of Pl-Rh, termed Pl'-mahogany (Pl'-mah), arise that confer reduced pigment and are meiotically heritable. These derivatives influence other Pl-Rh alleles such that only Pl'-mah alleles are transmitted from a Pl-Rh/Pl'-mah heterozygote. Genetic crosses establish that chromosomal segregation distortion does not explain this exclusive transmission and suggest that Pl-Rh invariably changes to Pl'-mah when exposed to Pl'-mah. Such behavior is a hallmark of paramutation. Cosegregation experiments demonstrate that this paramutagenic activity is genetically linked to the pl locus. By visually quantifying pl action through successive crosses, we find that phenotypic expression is inversely related to paramutagenic strength. In addition, the paramutagenic state is metastable; reversion to a nonparamutagenic Pl-Rh state can occur. The behavior of Pl-Rh is unique, yet it shares characteristics with paramutation at two other maize loci, b and r. Previous analysis of b and r paramutation revealed extensive differences and led to suggestions of distinct molecular mechanisms. Consideration of the common features of all three systems reinvigorates the interpretation that the mechanistic processes of these three allelic interactions are similar. PMID:8647404

  19. Dominance of Deleterious Alleles Controls the Response to a Population Bottleneck

    PubMed Central

    Balick, Daniel J.; Do, Ron; Cassa, Christopher A.; Reich, David; Sunyaev, Shamil R.

    2015-01-01

    Population bottlenecks followed by re-expansions have been common throughout history of many populations. The response of alleles under selection to such demographic perturbations has been a subject of great interest in population genetics. On the basis of theoretical analysis and computer simulations, we suggest that this response qualitatively depends on dominance. The number of dominant or additive deleterious alleles per haploid genome is expected to be slightly increased following the bottleneck and re-expansion. In contrast, the number of completely or partially recessive alleles should be sharply reduced. Changes of population size expose differences between recessive and additive selection, potentially providing insight into the prevalence of dominance in natural populations. Specifically, we use a simple statistic, BR≡∑xipop1/∑xjpop2, where x i represents the derived allele frequency, to compare the number of mutations in different populations, and detail its functional dependence on the strength of selection and the intensity of the population bottleneck. We also provide empirical evidence showing that gene sets associated with autosomal recessive disease in humans may have a B R indicative of recessive selection. Together, these theoretical predictions and empirical observations show that complex demographic history may facilitate rather than impede inference of parameters of natural selection. PMID:26317225

  20. Dominance of Deleterious Alleles Controls the Response to a Population Bottleneck.

    PubMed

    Balick, Daniel J; Do, Ron; Cassa, Christopher A; Reich, David; Sunyaev, Shamil R

    2015-08-01

    Population bottlenecks followed by re-expansions have been common throughout history of many populations. The response of alleles under selection to such demographic perturbations has been a subject of great interest in population genetics. On the basis of theoretical analysis and computer simulations, we suggest that this response qualitatively depends on dominance. The number of dominant or additive deleterious alleles per haploid genome is expected to be slightly increased following the bottleneck and re-expansion. In contrast, the number of completely or partially recessive alleles should be sharply reduced. Changes of population size expose differences between recessive and additive selection, potentially providing insight into the prevalence of dominance in natural populations. Specifically, we use a simple statistic, [Formula: see text], where xi represents the derived allele frequency, to compare the number of mutations in different populations, and detail its functional dependence on the strength of selection and the intensity of the population bottleneck. We also provide empirical evidence showing that gene sets associated with autosomal recessive disease in humans may have a BR indicative of recessive selection. Together, these theoretical predictions and empirical observations show that complex demographic history may facilitate rather than impede inference of parameters of natural selection. PMID:26317225

  1. Allele Identification for Transcriptome-Based Population Genomics in the Invasive Plant Centaurea solstitialis

    PubMed Central

    Dlugosch, Katrina M.; Lai, Zhao; Bonin, Aurélie; Hierro, José; Rieseberg, Loren H.

    2013-01-01

    Transcriptome sequences are becoming more broadly available for multiple individuals of the same species, providing opportunities to derive population genomic information from these datasets. Using the 454 Life Science Genome Sequencer FLX and FLX-Titanium next-generation platforms, we generated 11−430 Mbp of sequence for normalized cDNA for 40 wild genotypes of the invasive plant Centaurea solstitialis, yellow starthistle, from across its worldwide distribution. We examined the impact of sequencing effort on transcriptome recovery and overlap among individuals. To do this, we developed two novel publicly available software pipelines: SnoWhite for read cleaning before assembly, and AllelePipe for clustering of loci and allele identification in assembled datasets with or without a reference genome. AllelePipe is designed specifically for cases in which read depth information is not appropriate or available to assist with disentangling closely related paralogs from allelic variation, as in transcriptome or previously assembled libraries. We find that modest applications of sequencing effort recover most of the novel sequences present in the transcriptome of this species, including single-copy loci and a representative distribution of functional groups. In contrast, the coverage of variable sites, observation of heterozygosity, and overlap among different libraries are all highly dependent on sequencing effort. Nevertheless, the information gained from overlapping regions was informative regarding coarse population structure and variation across our small number of population samples, providing the first genetic evidence in support of hypothesized invasion scenarios. PMID:23390612

  2. Extensive allele-specific translational regulation in hybrid mice

    PubMed Central

    Hou, Jingyi; Wang, Xi; McShane, Erik; Zauber, Henrik; Sun, Wei; Selbach, Matthias; Chen, Wei

    2015-01-01

    Translational regulation is mediated through the interaction between diffusible trans-factors and cis-elements residing within mRNA transcripts. In contrast to extensively studied transcriptional regulation, cis-regulation on translation remains underexplored. Using deep sequencing-based transcriptome and polysome profiling, we globally profiled allele-specific translational efficiency for the first time in an F1 hybrid mouse. Out of 7,156 genes with reliable quantification of both alleles, we found 1,008 (14.1%) exhibiting significant allelic divergence in translational efficiency. Systematic analysis of sequence features of the genes with biased allelic translation revealed that local RNA secondary structure surrounding the start codon and proximal out-of-frame upstream AUGs could affect translational efficiency. Finally, we observed that the cis-effect was quantitatively comparable between transcriptional and translational regulation. Such effects in the two regulatory processes were more frequently compensatory, suggesting that the regulation at the two levels could be coordinated in maintaining robustness of protein expression. PMID:26253569

  3. 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

  4. 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

  5. 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. PMID:26982370

  6. The APOE4 allele shows opposite sex bias in microbleeds and Alzheimer's disease of humans and mice.

    PubMed

    Cacciottolo, Mafalda; Christensen, Amy; Moser, Alexandra; Liu, Jiahui; Pike, Christian J; Smith, Conor; LaDu, Mary Jo; Sullivan, Patrick M; Morgan, Todd E; Dolzhenko, Egor; Charidimou, Andreas; Wahlund, Lars-Olof; Wiberg, Maria Kristofferson; Shams, Sara; Chiang, Gloria Chia-Yi; Finch, Caleb E

    2016-01-01

    The apolipoprotein 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 and AD showed a higher risk of cerebral cortex microbleeds with APOE4 allele dose effect in 2 clinical cohorts (ADNI and KIDS). Sex-APOE interactions were further analyzed in EFAD mice carrying human APOE alleles and familial AD genes (5XFAD (+/-) /human APOE(+/+)). At 7 months, E4FAD mice had cerebral cortex microbleeds with female excess, in contrast to humans. Cerebral amyloid angiopathy, plaques, and soluble Aβ also showed female excess. Both the cerebral microbleeds and cerebral amyloid angiopathy increased in proportion to individual Aβ load. In humans, the opposite sex bias of APOE4 allele for microbleeds versus 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

  7. 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. PMID:26368888

  8. 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

  9. Allele-Specific Quantitative PCR for Accurate, Rapid, and Cost-Effective Genotyping.

    PubMed

    Lee, Han B; Schwab, Tanya L; Koleilat, Alaa; Ata, Hirotaka; Daby, Camden L; Cervera, Roberto Lopez; McNulty, Melissa S; Bostwick, Hannah S; Clark, Karl J

    2016-06-01

    Customizable endonucleases such as transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) enable rapid generation of mutant strains at genomic loci of interest in animal models and cell lines. With the accelerated pace of generating mutant alleles, genotyping has become a rate-limiting step to understanding the effects of genetic perturbation. Unless mutated alleles result in distinct morphological phenotypes, mutant strains need to be genotyped using standard methods in molecular biology. Classic restriction fragment length polymorphism (RFLP) or sequencing is labor-intensive and expensive. Although simpler than RFLP, current versions of allele-specific PCR may still require post-polymerase chain reaction (PCR) handling such as sequencing, or they are more expensive if allele-specific fluorescent probes are used. Commercial genotyping solutions can take weeks from assay design to result, and are often more expensive than assembling reactions in-house. Key components of commercial assay systems are often proprietary, which limits further customization. Therefore, we developed a one-step open-source genotyping method based on quantitative PCR. The allele-specific qPCR (ASQ) does not require post-PCR processing and can genotype germline mutants through either threshold cycle (Ct) or end-point fluorescence reading. ASQ utilizes allele-specific primers, a locus-specific reverse primer, universal fluorescent probes and quenchers, and hot start DNA polymerase. Individual laboratories can further optimize this open-source system as we completely disclose the sequences, reagents, and thermal cycling protocol. We have tested the ASQ protocol to genotype alleles in five different genes. ASQ showed a 98-100% concordance in genotype scoring with RFLP or Sanger sequencing outcomes. ASQ is time-saving because a single qPCR without post-PCR handling suffices to score

  10. Allele-Specific Quantitative PCR for Accurate, Rapid, and Cost-Effective Genotyping

    PubMed Central

    Lee, Han B.; Schwab, Tanya L.; Koleilat, Alaa; Ata, Hirotaka; Daby, Camden L.; Cervera, Roberto Lopez; McNulty, Melissa S.; Bostwick, Hannah S.; Clark, Karl J.

    2016-01-01

    Customizable endonucleases such as transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) enable rapid generation of mutant strains at genomic loci of interest in animal models and cell lines. With the accelerated pace of generating mutant alleles, genotyping has become a rate-limiting step to understanding the effects of genetic perturbation. Unless mutated alleles result in distinct morphological phenotypes, mutant strains need to be genotyped using standard methods in molecular biology. Classic restriction fragment length polymorphism (RFLP) or sequencing is labor-intensive and expensive. Although simpler than RFLP, current versions of allele-specific PCR may still require post-polymerase chain reaction (PCR) handling such as sequencing, or they are more expensive if allele-specific fluorescent probes are used. Commercial genotyping solutions can take weeks from assay design to result, and are often more expensive than assembling reactions in-house. Key components of commercial assay systems are often proprietary, which limits further customization. Therefore, we developed a one-step open-source genotyping method based on quantitative PCR. The allele-specific qPCR (ASQ) does not require post-PCR processing and can genotype germline mutants through either threshold cycle (Ct) or end-point fluorescence reading. ASQ utilizes allele-specific primers, a locus-specific reverse primer, universal fluorescent probes and quenchers, and hot start DNA polymerase. Individual laboratories can further optimize this open-source system as we completely disclose the sequences, reagents, and thermal cycling protocol. We have tested the ASQ protocol to genotype alleles in five different genes. ASQ showed a 98–100% concordance in genotype scoring with RFLP or Sanger sequencing outcomes. ASQ is time-saving because a single qPCR without post-PCR handling suffices to score

  11. Allelic Variation of Cytochrome P450s Drives Resistance to Bednet Insecticides in a Major Malaria Vector.

    PubMed

    Ibrahim, Sulaiman S; Riveron, Jacob M; Bibby, Jaclyn; Irving, Helen; Yunta, Cristina; Paine, Mark J I; Wondji, Charles S

    2015-10-01

    Scale up of Long Lasting Insecticide Nets (LLINs) has massively contributed to reduce malaria mortality across Africa. However, resistance to pyrethroid insecticides in malaria vectors threatens its continued effectiveness. Deciphering the detailed molecular basis of such resistance and designing diagnostic tools is critical to implement suitable resistance management strategies. Here, we demonstrated that allelic variation in two cytochrome P450 genes is the most important driver of pyrethroid resistance in the major African malaria vector Anopheles funestus and detected key mutations controlling this resistance. An Africa-wide polymorphism analysis of the duplicated genes CYP6P9a and CYP6P9b revealed that both genes are directionally selected with alleles segregating according to resistance phenotypes. Modelling and docking simulations predicted that resistant alleles were better metabolizers of pyrethroids than susceptible alleles. Metabolism assays performed with recombinant enzymes of various alleles confirmed that alleles from resistant mosquitoes had significantly higher activities toward pyrethroids. Additionally, transgenic expression in Drosophila showed that flies expressing resistant alleles of both genes were significantly more resistant to pyrethroids compared with those expressing the susceptible alleles, indicating that allelic variation is the key resistance mechanism. Furthermore, site-directed mutagenesis and functional analyses demonstrated that three amino acid changes (Val109Ile, Asp335Glu and Asn384Ser) from the resistant allele of CYP6P9b were key pyrethroid resistance mutations inducing high metabolic efficiency. The detection of these first DNA markers of metabolic resistance to pyrethroids allows the design of DNA-based diagnostic tools to detect and track resistance associated with bednets scale up, which will improve the design of evidence-based resistance management strategies. PMID:26517127

  12. Allelic Variation of Cytochrome P450s Drives Resistance to Bednet Insecticides in a Major Malaria Vector

    PubMed Central

    Ibrahim, Sulaiman S.; Riveron, Jacob M.; Bibby, Jaclyn; Irving, Helen; Yunta, Cristina; Paine, Mark J. I.; Wondji, Charles S.

    2015-01-01

    Scale up of Long Lasting Insecticide Nets (LLINs) has massively contributed to reduce malaria mortality across Africa. However, resistance to pyrethroid insecticides in malaria vectors threatens its continued effectiveness. Deciphering the detailed molecular basis of such resistance and designing diagnostic tools is critical to implement suitable resistance management strategies. Here, we demonstrated that allelic variation in two cytochrome P450 genes is the most important driver of pyrethroid resistance in the major African malaria vector Anopheles funestus and detected key mutations controlling this resistance. An Africa-wide polymorphism analysis of the duplicated genes CYP6P9a and CYP6P9b revealed that both genes are directionally selected with alleles segregating according to resistance phenotypes. Modelling and docking simulations predicted that resistant alleles were better metabolizers of pyrethroids than susceptible alleles. Metabolism assays performed with recombinant enzymes of various alleles confirmed that alleles from resistant mosquitoes had significantly higher activities toward pyrethroids. Additionally, transgenic expression in Drosophila showed that flies expressing resistant alleles of both genes were significantly more resistant to pyrethroids compared with those expressing the susceptible alleles, indicating that allelic variation is the key resistance mechanism. Furthermore, site-directed mutagenesis and functional analyses demonstrated that three amino acid changes (Val109Ile, Asp335Glu and Asn384Ser) from the resistant allele of CYP6P9b were key pyrethroid resistance mutations inducing high metabolic efficiency. The detection of these first DNA markers of metabolic resistance to pyrethroids allows the design of DNA-based diagnostic tools to detect and track resistance associated with bednets scale up, which will improve the design of evidence-based resistance management strategies. PMID:26517127

  13. 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. PMID:25963416

  14. 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

  15. Tracking human migrations by the analysis of the distribution of HLA alleles, lineages and haplotypes in closed and open populations

    PubMed Central

    Vina, Marcelo A. Fernandez; Hollenbach, Jill A.; Lyke, Kirsten E.; Sztein, Marcelo B.; Maiers, Martin; Klitz, William; Cano, Pedro; Mack, Steven; Single, Richard; Brautbar, Chaim; Israel, Shosahna; Raimondi, Eduardo; Khoriaty, Evelyne; Inati, Adlette; Andreani, Marco; Testi, Manuela; Moraes, Maria Elisa; Thomson, Glenys; Stastny, Peter; Cao, Kai

    2012-01-01

    The human leucocyte antigen (HLA) system shows extensive variation in the number and function of loci and the number of alleles present at any one locus. Allele distribution has been analysed in many populations through the course of several decades, and the implementation of molecular typing has significantly increased the level of diversity revealing that many serotypes have multiple functional variants. While the degree of diversity in many populations is equivalent and may result from functional polymorphism(s) in peptide presentation, homogeneous and heterogeneous populations present contrasting numbers of alleles and lineages at the loci with high-density expression products. In spite of these differences, the homozygosity levels are comparable in almost all of them. The balanced distribution of HLA alleles is consistent with overdominant selection. The genetic distances between outbred populations correlate with their geographical locations; the formal genetic distance measurements are larger than expected between inbred populations in the same region. The latter present many unique alleles grouped in a few lineages consistent with limited founder polymorphism in which any novel allele may have been positively selected to enlarge the communal peptide-binding repertoire of a given population. On the other hand, it has been observed that some alleles are found in multiple populations with distinctive haplotypic associations suggesting that convergent evolution events may have taken place as well. It appears that the HLA system has been under strong selection, probably owing to its fundamental role in varying immune responses. Therefore, allelic diversity in HLA should be analysed in conjunction with other genetic markers to accurately track the migrations of modern humans. PMID:22312049

  16. 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

  17. 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

  18. 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. PMID:25244535

  19. Evaluating litter decomposition and soil organic matter dynamics in earth system models: contrasting analysis of long-term litter decomposition and steady-state soil carbon

    NASA Astrophysics Data System (ADS)

    Bonan, G. B.; Wieder, W. R.

    2012-12-01

    litterfall and model-derived climatic decomposition index. While comparison with the LIDET 10-year litterbag study reveals sharp contrasts between CLM4 and DAYCENT, simulations of steady-state soil carbon show less difference between models. Both CLM4 and DAYCENT significantly underestimate soil carbon. Sensitivity analyses highlight causes of the low soil carbon bias. The terrestrial biogeochemistry of earth system models must be critically tested with observations, and the consequences of particular model choices must be documented. Long-term litter decomposition experiments such as LIDET provide a real-world process-oriented benchmark to evaluate models and can critically inform model development. Analysis of steady-state soil carbon estimates reveal additional, but here different, inferences about model performance.

  20. 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

  1. Allele Specific p53 Mutant Reactivation

    PubMed Central

    Yu, Xin; Vazquez, Alexei; Levine, Arnold J.; Carpizo, Darren R.

    2012-01-01

    Summary Rescuing the function of mutant p53 protein is an attractive cancer therapeutic strategy. Using the NCI anticancer drug screen data, we identified two compounds from the thiosemicarbazone family that manifest increased growth inhibitory activity in mutant p53 cells, particularly for the p53R175 mutant. Mechanistic studies reveal that NSC319726 restores WT structure and function to the p53R175 mutant. This compound kills p53R172H knock-in mice with extensive apoptosis and inhibits xenograft tumor growth in a 175-allele specific mutant p53 dependent manner. This activity depends upon the zinc ion chelating properties of the compound as well as redox changes. These data identify NSC319726 as a p53R175 mutant reactivator and as a lead compound for p53 targeted drug development. PMID:22624712

  2. Dynamics of Neutral and Selected Alleles When the Offspring Distribution Is Skewed

    PubMed Central

    Der, Ricky; Epstein, Charles; Plotkin, Joshua B.

    2012-01-01

    We analyze the dynamics of two alternative alleles in a simple model of a population that allows for large family sizes in the distribution of offspring number. This population model was first introduced by Eldon and Wakeley, who described the backward-time genealogical relationships among sampled individuals, assuming neutrality. We study the corresponding forward-time dynamics of allele frequencies, with or without selection. We derive a continuum approximation, analogous to Kimura’s diffusion approximation, and we describe three distinct regimes of behavior that correspond to distinct regimes in the coalescent processes of Eldon and Wakeley. We demonstrate that the effect of selection is strongly amplified in the Eldon–Wakeley model, compared to the Wright–Fisher model with the same variance effective population size. Remarkably, an advantageous allele can even be guaranteed to fix in the Eldon–Wakeley model, despite the presence of genetic drift. We compute the selection coefficient required for such behavior in populations of Pacific oysters, based on estimates of their family sizes. Our analysis underscores that populations with the same effective population size may nevertheless experience radically different forms of genetic drift, depending on the reproductive mechanism, with significant consequences for the resulting allele dynamics. PMID:22661323

  3. 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.

  4. Allele, phenotype and disease data at Mouse Genome Informatics: improving access and analysis.

    PubMed

    Bello, Susan M; Smith, Cynthia L; Eppig, Janan T

    2015-08-01

    A core part of the Mouse Genome Informatics (MGI) resource is the collection of mouse mutations and the annotation phenotypes and diseases displayed by mice carrying these mutations. These data are integrated with the rest of data in MGI and exported to numerous other resources. The use of mouse phenotype data to drive translational research into human disease has expanded rapidly with the improvements in sequencing technology. MGI has implemented many improvements in allele and phenotype data annotation, search, and display to facilitate access to these data through multiple avenues. For example, the description of alleles has been modified to include more detailed categories of allele attributes. This allows improved discrimination between mutation types. Further, connections have been created between mutations involving multiple genes and each of the genes overlapping the mutation. This allows users to readily find all mutations affecting a gene and see all genes affected by a mutation. In a similar manner, the genes expressed by transgenic or knock-in alleles are now connected to these alleles. The advanced search forms and public reports have been updated to take advantage of these improvements. These search forms and reports are used by an expanding number of researchers to identify novel human disease genes and mouse models of human disease. PMID:26162703

  5. Frequency of alleles conferring resistance to the Bt toxins Cry1Ac and Cry2Ab in Australian populations of Helicoverpa armigera (Lepidoptera: Noctuidae).

    PubMed

    Mahon, R J; Olsen, K M; Downes, S; Addison, S

    2007-12-01

    Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) is an important lepidopteran pest of cotton (Gossypium spp.) in Australia and the Old World. From 2002, F2 screens were used to examine the frequency of resistance alleles in Australian populations of H. armigera to Bacillus thuringiensis (Bt) CrylAc and Cry2Ab, the two insecticidal proteins present in the transgenic cotton Bollgard II. At that time, Ingard (expressing Cry1Ac) cotton had been grown in Australia for seven seasons, and Bollgard II was about to be commercially released. The principal objective of our study was to determine whether sustained exposure caused an elevated frequency of alleles conferring resistance to Cry1Ac in a species with a track record of evolving resistance to conventional insecticides. No major alleles conferring resistance to Cry1Ac were found. The frequency of resistance alleles for Cry1Ac was <0.0003, with a 95% credibility interval between 0 and 0.0009. In contrast, alleles conferring resistance to Cry2Ab were found at a frequency of 0.0033 (0.0017, 0.0055). The first isolation of this allele was found before the widespread deployment of Bollgard II. For both toxins the experiment-wise detection probability was 94.4%. Our results suggest that alleles conferring resistance to Cry1Ac are rare and that a relatively high baseline frequency of alleles conferring resistance to Cry2Ab existed before the introduction of Bt cotton containing this toxin. PMID:18232402

  6. Characterization of bone perfusion by dynamic contrast-enhanced magnetic resonance imaging and positron emission tomography in the Dunkin-Hartley guinea pig model of advanced osteoarthritis.

    PubMed

    Dyke, Jonathan P; Synan, Michael; Ezell, Paula; Ballon, Douglas; Racine, Jennifer; Aaron, Roy K

    2015-03-01

    This study characterizes changes in subchondral bone circulation in OA and examines relationships to bone structure and cartilage degeneration in Dunkin-Hartley guinea pigs. We have used dynamic contrast-enhanced MRI (DCE-MRI) and PET, with pharmacokinetic modeling, to characterize subchondral bone perfusion. Assessments are made of perfusion kinetics and vascular permeability by MRI, and blood volume and flow, and radionuclide incorporation into bone, by PET. These parameters are compared to cartilage lesion severity and bone histomorphometry. Assessments of intraosseous thrombi are made morphologically. Prolonged signal enhancement during the clearance phase of MRI correlated with OA severity and suggested venous stasis. Vascular permeability was not increased indicating that transvascular migration of contrast agent was not responsible for signal enhancement. Intraosseous thrombi were not observed. Decreased perfusion associated with severe OA was confirmed by PET and was associated with reduced radionuclide incorporation and osteoporosis. MRI and PET can be used to characterize kinetic parameters of circulation in OA and correlate them with subchondral bone metabolism of interest to the pathophysiology of OA. The significance of these observations may lie in alterations induced in the expression of cytokines by OA osteoblasts that are related to bone remodeling and cartilage breakdown. PMID:25410523

  7. Characterization of Bone Perfusion by Dynamic Contrast-Enhanced Magnetic Resonance Imaging and Positron Emission Tomography in the Dunkin-Hartley Guinea Pig Model of Advanced Osteoarthritis

    PubMed Central

    Dyke, Jonathan P.; Synan, Michael; Ezell, Paula; Ballon, Douglas; Racine, Jennifer; Aaron, Roy K.

    2014-01-01

    Purpose This study characterizes changes in subchondral bone circulation in OA and examines relationships to bone structure and cartilage degeneration in Dunkin-Hartley guinea pigs. Methods We have used dynamic contrast-enhanced MRI (DCE-MRI) and PET, with pharmacokinetic modeling, to characterize subchondral bone perfusion. Assessments are made of perfusion kinetics and vascular permeability by MRI, and blood volume and flow, and radionuclide incorporation into bone, by PET. These parameters are compared to cartilage lesion severity and bone histomorphometry. Assessments of intraosseous thrombi are made morphologically. Results Prolonged signal enhancement during the clearance phase of MRI correlated with OA severity and suggested venous stasis. Vascular permeability was not increased indicating that transvascular migration of contrast agent was not responsible for signal enhancement. Intraosseous thrombi were not observed. Decreased perfusion associated with severe OA was confirmed by PET and was associated with reduced radionuclide incorporation and osteoporosis. Discussion MRI and PET can be used to characterize kinetic parameters of circulation in OA and correlate them with subchondral bone metabolism of interest to the pathophysiology of OA. The significance of these observations may lie in alterations induced in the expression of cytokines by OA osteoblasts that are related to bone remodeling and cartilage breakdown. PMID:25410523

  8. Dual-Energy Computed Tomography Imaging of Atherosclerotic Plaques in a Mouse Model Using a Liposomal-Iodine Nanoparticle Contrast Agent

    PubMed Central

    Bhavane, Rohan; Badea, Cristian; Ghaghada, Ketan B.; Clark, Darin; Vela, Deborah; Moturu, Anoosha; Annapragada, Akshaya; Johnson, G. Allan; Willerson, James T.; Annapragada, Ananth

    2013-01-01

    Background The accumulation of macrophages in inflamed atherosclerotic plaques has been long recognized. In an attempt to develop an imaging agent for detection of vulnerable plaques, we evaluated the feasibility of a liposomal-iodine nanoparticle contrast agent for computed tomography (CT) imaging of macrophage-rich atherosclerotic plaques in a mouse model. Methods and Results Liposomal-iodine formulations varying in particle size and polyethylene glycol coating were fabricated, and shown to stably encapsulate the iodine compound. In vitro uptake studies using optical and CT imaging in the RAW264.7 macrophage cell line identified the formulation that promoted maximal uptake. Dual-energy CT imaging using this formulation in Apolipoprotein E deficient (ApoE−/−) mice (n=8) and control C57BL/6 mice (n=6) followed by spectral decomposition of the dual-energy images enabled imaging of the liposomes localized in the plaque. Imaging cytometry confirmed the presence of liposomes in the plaque and their co-localization with a small fraction (~2%) of the macrophages in the plaque. Conclusions The results demonstrate the feasibility of imaging macrophage-rich atherosclerotic plaques using a liposomal-iodine nanoparticle contrast agent and dual-energy CT. PMID:23349231

  9. Tri-allelic pattern of short tandem repeats identifies the murderer among identical twins and suggests an embryonic mutational origin.

    PubMed

    Wang, Li-Feng; Yang, Ying; Zhang, Xiao-Nan; Quan, Xiao-Liang; Wu, Yuan-Ming

    2015-05-01

    Monozygotic twins can be co-identified by genotyping of short tandem repeats (STRs); however, for distinguishing them, STR genotyping is ineffective, especially in the case of murder. Here, a rarely occurring tri-allelic pattern in the vWA locus (16, 18, 19) was identified only in the DNA of one identical twin, which could help to exonerate the innocent twin in a murder charge. This mutation was defined as primary through genotyping of the family and could be detected in blood, buccal and semen samples from the individual; however, two alternative allele-balanced di-allelic patterns (16, 18 or 16, 19) were detected in hair root sheath cells. Such a kind of segregation indicates a one-step mutation occurs in cell mitosis, which is after embryonic zygote formation and during the early development of the individual after the division of the blastocyte. Sequencing revealed the insertion between the allele 18 and 19 is a repeat unit of TAGA/TCTA (plus/minus strand), which belongs to "AGAT/ATCT"-based core repeats identified from all tri-allelic pattern reports recorded in the STR base and a detailed model was proposed for STR repeat length variation caused by false priming during DNA synthesis. Our model illustrates the possible origination of allele-balanced and unbalanced tri-allelic pattern, clarifies that the genotypes of parent-child mismatches, aberrant di-allelic patterns, and type 1 or 2 tri-allelic patterns should be considered as independent, but interconnected forms of STR mutation. PMID:25732248

  10. RHCE variant allele: RHCE*ce254G,733G.

    PubMed

    Keller, Jessica A; Horn, Trina; Chiappa, Colleen; Melland, Camilla; Vietz, Christine; Castilho, Lilian; Keller, Margaret A

    2014-01-01

    A novel RHCE allele was identified in a 53-year-old African American female blood donor with an Rh phenotype of D+ CE-c+ e+ and a negative antibody screen. The donor's cells typed e+ with all antisera tested. By gel-based genotyping and Edna analysis, the two RHCE alleles in this donor were characterized.One allele was found to be the known allele RHCE*Ol.20.01(RHCE*ce733G) and the second was novel: RHCE*Ol.06.02(RHCE*ce254G,733G). PMID:25695437

  11. Nomenclature for human CYP2D6 alleles.

    PubMed

    Daly, A K; Brockmöller, J; Broly, F; Eichelbaum, M; Evans, W E; Gonzalez, F J; Huang, J D; Idle, J R; Ingelman-Sundberg, M; Ishizaki, T; Jacqz-Aigrain, E; Meyer, U A; Nebert, D W; Steen, V M; Wolf, C R; Zanger, U M

    1996-06-01

    To standardize CYP2D6 allele nomenclature, and to conform with international human gene nomenclature guidelines, an alternative to the current arbitrary system is described. Based on recommendations for human genome nomenclature, we propose that alleles be designated by CYP2D6 followed by an asterisk and a combination of roman letters and arabic numerals distinct for each allele with the number specifying the key mutation and, where appropriate, a letter specifying additional mutations. Criteria for classification as a separate allele and protein nomenclature are also presented. PMID:8807658

  12. The effect of deleterious alleles on adaptation in asexual populations.

    PubMed Central

    Johnson, Toby; Barton, Nick H

    2002-01-01

    We calculate the fixation probability of a beneficial allele that arises as the result of a unique mutation in an asexual population that is subject to recurrent deleterious mutation at rate U. Our analysis is an extension of previous works, which make a biologically restrictive assumption that selection against deleterious alleles is stronger than that on the beneficial allele of interest. We show that when selection against deleterious alleles is weak, beneficial alleles that confer a selective advantage that is small relative to U have greatly reduced probabilities of fixation. We discuss the consequences of this effect for the distribution of effects of alleles fixed during adaptation. We show that a selective sweep will increase the fixation probabilities of other beneficial mutations arising during some short interval afterward. We use the calculated fixation probabilities to estimate the expected rate of fitness improvement in an asexual population when beneficial alleles arise continually at some low rate proportional to U. We estimate the rate of mutation that is optimal in the sense that it maximizes this rate of fitness improvement. Again, this analysis relaxes the assumption made previously that selection against deleterious alleles is stronger than on beneficial alleles. PMID:12242249

  13. Mutated tumor alleles are expressed according to their DNA frequency

    PubMed Central

    Castle, John C.; Loewer, Martin; Boegel, Sebastian; Tadmor, Arbel D.; Boisguerin, Valesca; de Graaf, Jos; Paret, Claudia; Diken, Mustafa; Kreiter, Sebastian; Türeci, Özlem; Sahin, Ugur

    2014-01-01

    The transcription of tumor mutations from DNA into RNA has implications for biology, epigenetics and clinical practice. It is not clear if mutations are in general transcribed and, if so, at what proportion to the wild-type allele. Here, we examined the correlation between DNA mutation allele frequency and RNA mutation allele frequency. We sequenced the exome and transcriptome of tumor cell lines with large copy number variations, identified heterozygous single nucleotide mutations and absolute DNA copy number, and determined the corresponding DNA and RNA mutation allele fraction. We found that 99% of the DNA mutations in expressed genes are expressed as RNA. Moreover, we found a high correlation between the DNA and RNA mutation allele frequency. Exceptions are mutations that cause premature termination codons and therefore activate nonsense-mediated decay. Beyond this, we did not find evidence of any wide-scale mechanism, such as allele-specific epigenetic silencing, preferentially promoting mutated or wild-type alleles. In conclusion, our data strongly suggest that genes are equally transcribed from all alleles, mutated and wild-type, and thus transcribed in proportion to their DNA allele frequency. PMID:24752137

  14. Mutated tumor alleles are expressed according to their DNA frequency.

    PubMed

    Castle, John C; Loewer, Martin; Boegel, Sebastian; Tadmor, Arbel D; Boisguerin, Valesca; de Graaf, Jos; Paret, Claudia; Diken, Mustafa; Kreiter, Sebastian; Türeci, Özlem; Sahin, Ugur

    2014-01-01

    The transcription of tumor mutations from DNA into RNA has implications for biology, epigenetics and clinical practice. It is not clear if mutations are in general transcribed and, if so, at what proportion to the wild-type allele. Here, we examined the correlation between DNA mutation allele frequency and RNA mutation allele frequency. We sequenced the exome and transcriptome of tumor cell lines with large copy number variations, identified heterozygous single nucleotide mutations and absolute DNA copy number, and determined the corresponding DNA and RNA mutation allele fraction. We found that 99% of the DNA mutations in expressed genes are expressed as RNA. Moreover, we found a high correlation between the DNA and RNA mutation allele frequency. Exceptions are mutations that cause premature termination codons and therefore activate nonsense-mediated decay. Beyond this, we did not find evidence of any wide-scale mechanism, such as allele-specific epigenetic silencing, preferentially promoting mutated or wild-type alleles. In conclusion, our data strongly suggest that genes are equally transcribed from all alleles, mutated and wild-type, and thus transcribed in proportion to their DNA allele frequency. PMID:24752137

  15. Development and validation of a pre-percutaneous coronary intervention risk model of contrast-induced acute kidney injury with an integer scoring system.

    PubMed

    Inohara, Taku; Kohsaka, Shun; Abe, Takayuki; Miyata, Hiroaki; Numasawa, Yohei; Ueda, Ikuko; Nishi, Yutaro; Naito, Kotaro; Shibata, Masaru; Hayashida, Kentaro; Maekawa, Yuichiro; Kawamura, Akio; Sato, Yuji; Fukuda, Keiichi

    2015-06-15

    Previous models for contrast-induced acute kidney injury (CI-AKI) after percutaneous coronary intervention (PCI) include procedure-related variables in addition to pre-procedural variables. We sought to develop a risk model for CI-AKI based on pre-procedural variables and compare its predictability with a conventional risk model and also to develop an integer score system based on selected variables. A total of 5,936 consecutive PCIs registered in the Japanese Cardiovascular Database were analyzed (derivation cohort, n = 3,957; validation cohort, n = 1,979). CI-AKI was defined as an increase in serum creatinine of 50% or 0.3 mg/dl compared with baseline. From the derivation cohort, 2 different CI-AKI risk models were generated using logistic regression analyses: a pre-procedural model and a conventional model including both pre-procedural and procedure-related variables. The predictabilities of the models were compared by c-statistics. An integer score was assigned to each variable in proportion to each estimated regression coefficient for the final model. In our derivation cohort, the proportion of CI-AKI was 9.0% (n = 358). Predictors for CI-AKI included older age, heart failure, diabetes, previous PCI, hypertension, higher baseline creatinine level, and acute coronary syndrome. Presence of procedure-related complications and insertion of intra-aortic balloon pumping were included as procedure-related variables in the conventional model. Both the conventional model (c-statistics 0.789) and the pre-procedural model (c-statistics 0.799) demonstrated reasonable discrimination. The integer risk-scoring method demonstrated good agreement between the expected and observed risks of CI-AKI in the validation cohort. In conclusion, the pre-procedural risk model for CI-AKI had acceptable discrimination compared with the conventional model and may aid in risk stratification of CI-AKI before PCI. PMID:25891989

  16. Polarization contrast vision

    NASA Astrophysics Data System (ADS)

    Pugh, Edward N.

    1990-05-01

    An attempt is made to establish the possibility that the geometry of certain classes of vertebrate photoreceptors results in a birefringence that allows the animals to utilize the state of polarization of light striking their retinas as a meaningful stimulus parameter. Simulate the photoreceptors as dielectric waveguides using a simple physical model, and augment this theoretical work with empirical measurements of the light guiding properties of photoreceptors in isolated pieces of retina from a green sunfish (Lepomis cyanellus). With a classical conditioning paradigm, this fish's sensitivity to light is modulated by the orientation of the plane of polarization of linearly polarized light. This functional dependence was predicted by a hypothetical antagonistic mechanism between twin cones of two orientations in the animal's retinal mosaic. Further study is planned for the nature of the stimulus to which the fish is sensitive by creating a camera that will generate images based purely upon the contrast between orthogonal polarizations at each point in space.

  17. DNA-PKcs mutations in dogs and horses: allele frequency and association with neoplasia.

    PubMed

    Ding, Qi; Bramble, Lori; Yuzbasiyan-Gurkan, Vilma; Bell, Thomas; Meek, Katheryn

    2002-01-23

    Previously, spontaneous genetic immunodeficiencies in mice, Arabian foals, and recently in Jack Russell terriers have been ascribed to defects in DNA-PKcs (catalytic subunit of the DNA dependent protein kinase) expression. In severe combined immunodeficiency (SCID) foals, a 5 bp deletion at codon 9480 results in a frameshift and a 967 amino acid deletion from the C terminus (including the entire PI3 kinase domain) and an unstable mutant protein. In SCID mice, a single base pair mutation results in a premature stop codon and deletion of 83 amino acids; as in SCID foals, the mutant protein is unstable. Here, we define the mutation within the canine DNA-PKcs gene that results in SCID. In this case, a point mutation results in a stop codon at nucleotide 10,828 and premature termination at a position 517 amino acids before the normal C terminus resulting in a functionally null allele. Thus, this is the third documentation of a spontaneous germline mutation in the C terminus of DNA-PKcs. Emerging data implicate DNA repair factors as potential tumor suppressors. Here, we have ascertained the carrier frequency of the defective DNA-PKcs genes in Arabian horses and in Jack Russell terriers. Our data indicate (in good agreement with a previous report) that the carrier frequency of the equine SCID allele is approximately 8%; in contrast, the carrier frequency of the canine SCID allele is less than 1.1%. We also assessed the frequency of the equine SCID allele in a series of 295 tumors from Arabian horses. We find a statistically significant correlation between the development of a virally induced tumor (sarcoid) and heterozygosity for the equine SCID allele. These data provide further support for an emerging consensus: that DNA-PK may normally act as a tumor suppressor through its caretaker role in maintaining chromosomal stability. PMID:11867233

  18. A dosage-sensitive modifier of retrotransposon-induced alleles of the Drosophila white locus.

    PubMed Central

    Rabinow, L; Birchler, J A

    1989-01-01

    The apricot allele of the white locus results from the insertion of the retrotransposon copia. Mutations in a newly discovered locus, the Darkener-of-apricot (Doa), suppress wa and some of its revertants. Of 44 other white alleles tested, only wsp55 is affected by Doa, although, in contrast, it is enhanced by Doa mutations. The Doa locus modulates wa and wsp55 expression as a function of its own dosage. Mutations in Doa are dominant suppressors or enhancers and are recessive lethals. Rare Doa mutant homozygotes escaping lethality demonstrate extreme phenotypic suppression of wa and enhancement of wsp55. RNA from wa is substantially wild-type in structure in escapers, although reduced in quantity. Images PMID:2542025

  19. Allele-specific locus binding and genome editing by CRISPR at the p16INK4a locus

    PubMed Central

    Fujita, Toshitsugu; Yuno, Miyuki; Fujii, Hodaka

    2016-01-01

    The clustered regularly interspaced short palindromic repeats (CRISPR) system has been adopted for a wide range of biological applications including genome editing. In some cases, dissection of genome functions requires allele-specific genome editing, but the use of CRISPR for this purpose has not been studied in detail. In this study, using the p16INK4a gene in HCT116 as a model locus, we investigated whether chromatin states, such as CpG methylation, or a single-nucleotide gap form in a target site can be exploited for allele-specific locus binding and genome editing by CRISPR in vivo. First, we showed that allele-specific locus binding and genome editing could be achieved by targeting allele-specific CpG-methylated regions, which was successful for one, but not all guide RNAs. In this regard, molecular basis underlying the success remains elusive at this stage. Next, we demonstrated that an allele-specific single-nucleotide gap form could be employed for allele-specific locus binding and genome editing by CRISPR, although it was important to avoid CRISPR tolerance of a single nucleotide mismatch brought about by mismatched base skipping. Our results provide information that might be useful for applications of CRISPR in studies of allele-specific functions in the genomes. PMID:27465215

  20. The Regulation of White Locus Expression: A Dominant Mutant Allele at the White Locus of DROSOPHILA MELANOGASTER

    PubMed Central

    Bingham, Paul M.

    1980-01-01

    A new mutant allele (wDZL) at the white locus of Drosophila melanogaster is dominant to the wild-type allele, but apparently only when the two alleles are synapsed. When chromosomal rearrangements prevent somatic pairing between the two white alleles, wDZL is rendered recessive to wild type. This observation suggests that the dominance of wDZL is sensitive to a synapsis (transvection) effect. On the basis of this and other properties, it is proposed that wDZL causes the repression of transcription of a synapsed w+ allele, but not of a w+ allele elsewhere in the same nucleus. One model to account for this supposes that wDZL produces a repressor of white-locus transcription. This repressor is presumed to be so unstable that other white genes, removed from wDZL but in the same nucleus, are not detectably repressed. These properties may be simply understood if it is assumed that the repressor produced by the wDZL allele is an RNA molecule. PMID:17249039

  1. Combining measurements and modelling to quantify the contribution of atmospheric fallout, local industry and road traffic to PAH stocks in contrasting catchments.

    PubMed

    Gateuille, David; Evrard, Olivier; Lefevre, Irène; Moreau-Guigon, Elodie; Alliot, Fabrice; Chevreuil, Marc; Mouchel, Jean-Marie

    2014-06-01

    Various sources supply PAHs that accumulate in soils. The methodology we developed provided an evaluation of the contribution of local sources (road traffic, local industries) versus remote sources (long range atmospheric transport, fallout and gaseous exchanges) to PAH stocks in two contrasting subcatchments (46-614 km²) of the Seine River basin (France). Soil samples (n = 336) were analysed to investigate the spatial pattern of soil contamination across the catchments and an original combination with radionuclide measurements provided new insights into the evolution of the contamination with depth. Relationships between PAH concentrations and the distance to the potential sources were modelled. Despite both subcatchments are mainly rural, roadside areas appeared to concentrate 20% of the contamination inside the catchment while a local industry was found to be responsible for up to 30% of the stocks. Those results have important implications for understanding and controlling PAH contamination in rural areas of early-industrialized regions. PMID:24662001

  2. [Contrast sensitivity in glaucoma].

    PubMed

    Bartos, D

    1989-05-01

    Author reports on results of the contrast sensitivity examinations using the Cambridge low-contrast lattice test supplied by Clement Clarke International LTD, in patients with open-angle glaucoma and ocular hypertension. In glaucoma patients there was observed statistically significant decrease of the contrast sensitivity. In patients with ocular hypertension decrease of the contrast sensitivity was in patients affected by corresponding changes of the visual field and of the optical disc. The main advantages of the Cambridge low-contrast lattice test were simplicity, rapidity and precision of its performance. PMID:2743444

  3. Evolution of HLA class II molecules: Allelic and amino acid site variability across populations.

    PubMed Central

    Salamon, H; Klitz, W; Easteal, S; Gao, X; Erlich, H A; Fernandez-Viña, M; Trachtenberg, E A; McWeeney, S K; Nelson, M P; Thomson, G

    1999-01-01

    Analysis of the highly polymorphic beta1 domains of the HLA class II molecules encoded by the DRB1, DQB1, and DPB1 loci reveals contrasting levels of diversity at the allele and amino acid site levels. Statistics of allele frequency distributions, based on Watterson's homozygosity statistic F, reveal distinct evolutionary patterns for these loci in ethnically diverse samples (26 populations for DQB1 and DRB1 and 14 for DPB1). When examined over all populations, the DQB1 locus allelic variation exhibits striking balanced polymorphism (P < 10(-4)), DRB1 shows some evidence of balancing selection (P < 0.06), and while there is overall very little evidence for selection of DPB1 allele frequencies, there is a trend in the direction of balancing selection (P < 0.08). In contrast, at the amino acid level all three loci show strong evidence of balancing selection at some sites. Averaged over polymorphic amino acid sites, DQB1 and DPB1 show similar deviation from neutrality expectations, and both exhibit more balanced polymorphic amino acid sites than DRB1. Across ethnic groups, polymorphisms at many codons show evidence for balancing selection, yet data consistent with directional selection were observed at other codons. Both antigen-binding pocket- and non-pocket-forming amino acid sites show overall deviation from neutrality for all three loci. Only in the case of DRB1 was there a significant difference between pocket- and non-pocket-forming amino acid sites. Our findings indicate that balancing selection at the MHC occurs at the level of polymorphic amino acid residues, and that in many cases this selection is consistent across populations. PMID:10224269

  4. 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. PMID:25549886

  5. Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots.

    PubMed

    Baker, Christopher L; Petkova, Pavlina; Walker, Michael; Flachs, Petr; Mihola, Ondrej; Trachtulec, Zdenek; Petkov, Petko M; Paigen, Kenneth

    2015-09-01

    Genetic recombination during meiosis functions to increase genetic diversity, promotes elimination of deleterious alleles, and helps assure proper segregation of chromatids. Mammalian recombination events are concentrated at specialized sites, termed hotspots, whose locations are determined by PRDM9, a zinc finger DNA-binding histone methyltransferase. Prdm9 is highly polymorphic with most alleles activating their own set of hotspots. In populations exhibiting high frequencies of heterozygosity, questions remain about the influences different alleles have in heterozygous individuals where the two variant forms of PRDM9 typically do not activate equivalent populations of hotspots. We now find that, in addition to activating its own hotspots, the presence of one Prdm9 allele can modify the activity of hotspots activated by the other allele. PRDM9 function is also dosage sensitive; Prdm9+/- heterozygous null mice have reduced numbers and less active hotspots and increased numbers of aberrant germ cells. In mice carrying two Prdm9 alleles, there is allelic competition; the stronger Prdm9 allele can partially or entirely suppress chromatin modification and recombination at hotspots of the weaker allele. In cell cultures, PRDM9 protein variants form functional heteromeric complexes which can bind hotspots sequences. When a heteromeric complex binds at a hotspot of one PRDM9 variant, the other PRDM9 variant, which would otherwise not bind, can still methylate hotspot nucleosomes. We propose that in heterozygous individuals the underlying molecular mechanism of allelic suppression results from formation of PRDM9 heteromers, where the DNA binding activity of one protein variant dominantly directs recombination initiation towards its own hotspots, effectively titrating down recombination by the other protein variant. In natural populations with many heterozygous individuals, allelic competition will influence the recombination landscape. PMID:26368021

  6. 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. PMID:24952956

  7. Carbonated Eclogite Solidus Between 14 and 20 GPa: Results from the Model CMAS-CO2 System and Contrasting Solidus Behavior to Carbonated Peridotite

    NASA Astrophysics Data System (ADS)

    Keshav, S.; Gudfinnsson, G. H.

    2007-12-01

    , and magnesite. From average calculated melting reactions along these isobarically univariant curves, stishovite is produced upon melting at all pressures investigated. Significantly, cpx at 14 and 16 GPa and capv at 20 GPa are the dominant contributors toward melt production/composition, in contrast to lower pressures (3-8 GPa) where carbonate dominantly contributes toward melt generation/composition at the solidus. The solidus of model carbonated eclogite at 14, 16, and 20 GPa, lies at 1350, 1450, and 1600 degrees C, respectively, and is nearly linear in P-T space. Melts in equilibrium with all the crystalline phases are highly calcic (Ca no.-0.70), resembling calcio-carbonatites. When magnesite is exhausted from the crystalline assemblage, the melts become slightly less calcic (Ca no.-65). The model carbonated eclogite solidus is always lower than the model carbonated peridotite solidus in the same pressure range. The most remarkable feature of this work is the absence of a drop in the solidus of model carbonated eclogite between 14 and 16 GPa, a result that is in stark contrast to that observed for the model carbonated peridotite at identical pressures. Therefore, even though the solidus temperatures in both carbonated peridotite and eclogite are strongly influenced by the presence of crystalline carbonate, melt compositions and the shape of the solidus in the pressure range investigated seem to be dominantly controlled by the silicate component of the rock in question. Given these results, it is fair to say that a wide range of petrological and geochemical processes operate at these depths in the mantle, and that we have barely scratched the surface in our investigation.

  8. A gene feature enumeration approach for describing HLA allele polymorphism.

    PubMed

    Mack, Steven J

    2015-12-01

    HLA genotyping via next generation sequencing (NGS) poses challenges for the use of HLA allele names to analyze and discuss sequence polymorphism. NGS will identify many new synonymous and non-coding HLA sequence variants. Allele names identify the types of nucleotide polymorphism that define an allele (non-synonymous, synonymous and non-coding changes), but do not describe how polymorphism is distributed among the individual features (the flanking untranslated regions, exons and introns) of a gene. Further, HLA alleles cannot be named in the absence of antigen-recognition domain (ARD) encoding exons. Here, a system for describing HLA polymorphism in terms of HLA gene features (GFs) is proposed. This system enumerates the unique nucleotide sequences for each GF in an HLA gene, and records these in a GF enumeration notation that allows both more granular dissection of allele-level HLA polymorphism and the discussion and analysis of GFs in the absence of ARD-encoding exon sequences. PMID:26416087

  9. The frequency of HLA alleles in the Romanian population.

    PubMed

    Constantinescu, Ileana; Boșcaiu, Voicu; Cianga, Petru; Dinu, Andrei-Antoniu; Gai, Elena; Melinte, Mihaela; Moise, Ana

    2016-03-01

    Knowledge of human leukocyte antigen (HLA) allele frequencies is essential for bone marrow and kidney donor searches. The Romanian Caucasian population is heterogeneous and information on HLA polymorphism has not been well studied. We characterized the HLA genetic profile and allele frequencies of regional populations in Romania. HLA-A, B and DRB1 alleles were examined in 8252 individuals, belonging to the four main regions of Romania. The most common alleles found in the Romanian population are the following: HLA-A*01, A*02, A*03, A*11, A*24; HLA-B*18, B*35, B*44, B*51 and HLA-DRB1*01, DRB1*03, DRB1*07, DRB1*11, DRB1*13, DRB1*15, DRB1*16. More than half of the alleles are non-homogeneously spread in Romania. These results provide a starting point for future analyses of genetic heterogeneity in Romania. PMID:26711124

  10. 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

  11. Cyanine 5.5 conjugated nanobubbles as a tumor selective contrast agent for dual ultrasound-fluorescence imaging in a mouse model.

    PubMed

    Mai, Liyi; Yao, Anna; 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

  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. Measurement of glomerular filtration rate by dynamic contrast-enhanced magnetic resonance imaging using a subject-specific two-compartment model.

    PubMed

    Tipirneni-Sajja, Aaryani; Loeffler, Ralf B; Oesingmann, Niels; Bissler, John; Song, Ruitian; McCarville, Beth; Jones, Deborah P; Hudson, Melissa; Spunt, Sheri L; Hillenbrand, Claudia M

    2016-04-01

    Measuring glomerular filtration rate (GFR) by dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) as part of standard of care clinicalMRIexams (e.g., in pediatric solid tumor patients) has the potential to reduce diagnostic burden. However, enthusiasm for this relatively newGFRtest may be curbed by the limited amount of cross-calibration studies with referenceGFRtechniques and the vast variety ofMRtracer model algorithms causing confusion on the choice of model. To advanceMRI-basedGFRquantification via improvedGFRmodeling and comparison with associated(99m)Tc-DTPA-GFR, 29 long-term Wilms' tumor survivors (19.0-43.3 years, [median 32.0 ± 6.0 years]) treated with nephrectomy, nonnephrotoxic chemotherapy ± radiotherapy underwentMRIwith Gd-DTPAadministration and a(99m)Tc-DTPA GFRtest. ForDCE-MRI-basedGFRestimation, a subject-specific two-compartment (SS-2C) model was developed that uses individual hematocrit values, automatically defines subject-specific uptake intervals, and fits tracer-uptake curves by incorporating these measures. The association between reference(99m)Tc-DTPA GFRandMR-GFRs obtained bySS-2C, three published 2C uptake, and inflow-outflow models was investigated via linear regression analysis. Uptake intervals varied from 64 sec to 141 sec [96 sec ± 21 sec] and hematocrit values ranged from 30% to 49% [41% ± 4%]; these parameters can therefore not be assumed as constants in 2C modeling. OurMR-GFRestimates using theSS-2C model showed accordingly the highest correlation with(99m)Tc-DTPA-GFRs (R(2) = 0.76,P < 0.001) compared with other models (R(2)-range: 0.36-0.66). In conclusion,SS-2C modeling ofDCE-MRIdata improved the association betweenGFRobtained by(99m)Tc-DTPAand Gd-DTPA DCE-MRIto such a degree that this approach could turn into a viable, diagnosticGFRassay without radiation exposure to the patient. PMID:27081161

  14. Contrast Intravasation During Hysterosalpingography

    PubMed Central

    Bhoil, Rohit; Sood, Dinesh; Sharma, Tanupriya; Sood, Shilpa; Sharma, Jiten; Kumar, Nitesh; Ahluwalia, Ajay; Parekh, Dipen; Mistry, Kewal A.; Sood, Saurav

    2016-01-01

    Summary Hysterosalpingography is an imaging method to evaluate the endometrial and uterine morphology and fallopian tube patency. Contrast intravasation implies backflow of injected contrast into the adjoining vessels mostly the veins and may be related to factors altering endometrial vascularity and permeability. Radiologists and gynaecologists should be well acquainted with the technique of hysterosalpingography, its interpretation, and intravasation of contrast agents for safer procedure and to minimize the associated complications. PMID:27279925

  15. Characterizing noise structure in single-cell RNA-seq distinguishes genuine from technical stochastic allelic expression.

    PubMed

    Kim, Jong Kyoung; Kolodziejczyk, Aleksandra A; Ilicic, Tomislav; Illicic, Tomislav; Teichmann, Sarah A; Marioni, John C

    2015-01-01

    Single-cell RNA-sequencing (scRNA-seq) facilitates identification of new cell types and gene regulatory networks as well as dissection of the kinetics of gene expression and patterns of allele-specific expression. However, to facilitate such analyses, separating biological variability from the high level of technical noise that affects scRNA-seq protocols is vital. Here we describe and validate a generative statistical model that accurately quantifies technical noise with the help of external RNA spike-ins. Applying our approach to investigate stochastic allele-specific expression in individual cells, we demonstrate that a large fraction of stochastic allele-specific expression can be explained by technical noise, especially for lowly and moderately expressed genes: we predict that only 17.8% of stochastic allele-specific expression patterns are attributable to biological noise with the remainder due to technical noise. PMID:26489834

  16. Modeling the Importance of Baseflow and Sediment Supply on Armor Development: Contrasting Intermittent Dryland and Perennially-Flowing Gravel-Bedded Rivers

    NASA Astrophysics Data System (ADS)

    Goodwin, K.; Johnson, J. P.; Viparelli, E.

    2014-12-01

    Most gravel-bedded rivers with perennial base flow are often armored, defined as having a bed surface grain size distribution that is coarser than the subsurface. In contrast, ephemerally flowing rivers, which are commonly flash flood-dominated, are typically unarmored. Although both types of channels have high peak discharges during floods, a key difference between these hydrological settings is in flow intermittency and how much flow occurs during moderate and low flow periods. High sediment supply and elevated shear stresses during floods have been identified as processes that may reduce or prevent armor development, but the preferential transport of smaller grain sizes during lower flows may also strongly affect armor development. We use numerical modeling to explore the relative importance of these armor-related processes. Calculations are based on a previous model called the Spawning Gravel Refresher, which includes mixed grain size sediment transport, morphodynamic feedbacks with channel slope, variable discharge hydrographs, and interactions with the subsurface grain sizes as the bed surface aggrades and erodes. Model runs are calibrated to natural rivers with varying degrees of bed surface armoring and flood hydrograph shape. These natural rivers include: i) the Nahal Yatir, an ephemerally flowing unarmored river in the Negev Desert, Israel, and ii) Trinity River, California, a larger perennially flowing, armored mountain river with annual snowmelt floods. We present a thorough exploration of model parameters, including base flow duration and magnitude, flood hydrograph shape and sand supply, combined with data from natural rivers. This produces quantitative bounds on how armor development varies in a wide range of parameter spaces unobtainable in the field alone.

  17. 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.

  18. Population Dynamics of Sex-Determining Alleles in Honey Bees and Self-Incompatibility Alleles in Plants

    PubMed Central

    Yokoyama, Shozo; Nei, Masatoshi

    1979-01-01

    Mathematical theories of the population dynamics of sex-determining alleles in honey bees are developed. It is shown that in an infinitely large population the equilibrium frequency of a sex allele is 1/n, where n is the number of alleles in the population, and the asymptotic rate of approach to this equilibrium is 2/(3n) per generation. Formulae for the distribution of allele frequencies and the effective and actual numbers of alleles that can be maintained in a finite population are derived by taking into account the population size and mutation rate. It is shown that the allele frequencies in a finite population may deviate considerably from 1/n. Using these results, available data on the number of sex alleles in honey bee populations are discussed. It is also shown that the number of self-incompatibility alleles in plants can be studied in a much simpler way by the method used in this paper. A brief discussion about general overdominant selection is presented. PMID:17248901

  19. Dominance and parent-of-origin effects of coding and non-coding alleles at the acylCoA-diacylglycerol-acyltransferase (DGAT1) gene on milk production traits in German Holstein cows

    PubMed Central

    Kuehn, Christa; Edel, Christian; Weikard, Rosemarie; Thaller, Georg

    2007-01-01

    Background Substantial gene substitution effects on milk production traits have formerly been reported for alleles at the K232A and the promoter VNTR loci in the bovine acylCoA-diacylglycerol-acyltransferase 1 (DGAT1) gene by using data sets including sires with accumulated phenotypic observations of daughters (breeding values, daughter yield deviations). However, these data sets prevented analyses with respect to dominance or parent-of-origin effects, although an increasing number of reports in the literature outlined the relevance of non-additive gene effects on quantitative traits. Results Based on a data set comprising German Holstein cows with direct trait measurements, we first confirmed the previously reported association of DGAT1 promoter VNTR alleles with milk production traits. We detected a dominant mode of effects for the DGAT1 K232A and promoter VNTR alleles. Namely, the contrasts between the effects of heterozygous individuals at the DGAT1 loci differed significantly from the midpoint between the effects for the two homozygous genotypes for several milk production traits, thus indicating the presence of dominance. Furthermore, we identified differences in the magnitude of effects between paternally and maternally inherited DGAT1 promoter VNTR – K232A haplotypes indicating parent-of-origin effects on milk production traits. Conclusion Non-additive effects like those identified at the bovine DGAT1 locus have to be accounted for in more specific QTL detection models as well as in marker assisted selection schemes. The DGAT1 alleles in cattle will be a useful model for further investigations on the biological background of non-additive effects in mammals due to the magnitude and consistency of their effects on milk production traits. PMID:17892573

  20. Estimating copy numbers of alleles from population-scale high-throughput sequencing data

    PubMed Central

    2015-01-01

    Background With the recent development of microarray and high-throughput sequencing (HTS) technologies, a number of studies have revealed catalogs of copy number variants (CNVs) and their association with phenotypes and complex traits. In parallel, a number of approaches to predict CNV regions and genotypes are proposed for both microarray and HTS data. However, only a few approaches focus on haplotyping of CNV loci. Results We propose a novel approach to infer copy unit alleles and their numbers in each sample simultaneously from population-scale HTS data by variational Bayesian inference on a generative probabilistic model inspired by latent Dirichlet allocation, which is a well studied model for document classification problems. In simulation studies, we evaluated concordance between inferred and true copy unit alleles for lower-, middle-, and higher-copy number dataset, in which precision and recall were ≥ 0.9 for data with mean coverage ≥ 10× per copy unit. We also applied the approach to HTS data of 1123 samples at highly variable salivary amylase gene locus and a pseudogene locus, and confirmed consistency of the estimated alleles within samples belonging to a trio of CEPH/Utah pedigree 1463 with 11 offspring. Conclusions Our proposed approach enables detailed analysis of copy number variations, such as association study between copy unit alleles and phenotypes or biological features including human diseases. PMID:25707811

  1. Host mating system and the spread of a disease-resistant allele in a population

    USGS Publications Warehouse

    DeAngelis, D.L.; Koslow, Jennifer M.; Jiang, J.; Ruan, S.

    2008-01-01

    The model presented here modifies a susceptible-infected (SI) host-pathogen model to determine the influence of mating system on the outcome of a host-pathogen interaction. Both deterministic and stochastic (individual-based) versions of the model were used. This model considers the potential consequences of varying mating systems on the rate of spread of both the pathogen and resistance alleles within the population. We assumed that a single allele for disease resistance was sufficient to confer complete resistance in an individual, and that both homozygote and heterozygote resistant individuals had the same mean birth and death rates. When disease invaded a population with only an initial small fraction of resistant genes, inbreeding (selfing) tended to increase the probability that the disease would soon be eliminated from a small population rather than become endemic, while outcrossing greatly increased the probability that the population would become extinct due to the disease.

  2. Parallel Adaptation: One or Many Waves of Advance of an Advantageous Allele?

    PubMed Central

    Ralph, Peter; Coop, Graham

    2010-01-01

    Models for detecting the effect of adaptation on population genomic diversity are often predicated on a single newly arisen mutation sweeping rapidly to fixation. However, a population can also adapt to a new environment by multiple mutations of similar phenotypic effect that arise in parallel, at the same locus or different loci. These mutations can each quickly reach intermediate frequency, preventing any single one from rapidly sweeping to fixation globally, leading to a “soft” sweep in the population. Here we study various models of parallel mutation in a continuous, geographically spread population adapting to a global selection pressure. The slow geographic spread of a selected allele due to limited dispersal can allow other selected alleles to arise and start to spread elsewhere in the species range. When these different selected alleles meet, their spread can slow dramatically and so initially form a geographic patchwork, a random tessellation, which could be mistaken for a signal of local adaptation. This spatial tessellation will dissipate over time due to mixing by migration, leaving a set of partial sweeps within the global population. We show that the spatial tessellation initially formed by mutational types is closely connected to Poisson process models of crystallization, which we extend. We find that the probability of parallel mutation and the spatial scale on which parallel mutation occurs are captured by a single compound parameter, a characteristic length, which reflects the expected distance a spreading allele travels before it encounters a different spreading allele. This characteristic length depends on the mutation rate, the dispersal parameter, the effective local density of individuals, and to a much lesser extent the strength of selection. While our knowledge of these parameters is poor, we argue that even in widely dispersing species, such parallel geographic sweeps may be surprisingly common. Thus, we predict that as more data

  3. Relating Doses of Contrast Agent Administered to TIC and Semi-Quantitative Parameters on DCE-MRI: Based on a Murine Breast Tumor Model

    PubMed Central

    Zhang, Qi; Guo, Qi; Zhao, Feixiang; Li, Tongwei; Zhang, Xuening

    2016-01-01

    Objective To explore the changes in the time-signal intensity curve(TIC) type and semi-quantitative parameters of dynamic contrast-enhanced(DCE)imaging in relation to variations in the contrast agent(CA) dosage in the Walker 256 murine breast tumor model, and to determine the appropriate parameters for the evaluation ofneoadjuvantchemotherapy(NAC)response. Materials and Methods Walker 256 breast tumor models were established in 21 rats, which were randomly divided into three groups of7rats each. Routine scanning and DCE-magnetic resonance imaging (MRI) of the rats were performed using a 7T MR scanner. The three groups of rats were administered different dosages of the CA0.2mmol/kg, 0.3mmol/kg, and 0.5mmol/kg, respectively; and the corresponding TICs the semi-quantitative parameters were calculated and compared among the three groups. Results The TICs were not influenced by the CA dosage and presented a washout pattern in all of the tumors evaluated and weren’t influenced by the CA dose. The values of the initial enhancement percentage(Efirst), initial enhancement velocity(Vfirst), maximum signal(Smax), maximum enhancement percentage(Emax), washout percentage(Ewash), and signal enhancement ratio(SER) showed statistically significant differences among the three groups (F = 16.952, p = 0.001; F = 69.483, p<0.001; F = 54.838, p<0.001; F = 12.510, p = 0.003; F = 5.248, p = 0.031; F = 9.733, p = 0.006, respectively). However, the values of the time to peak(Tpeak), maximum enhancement velocity(Vmax), and washout velocity(Vwash)did not differ significantly among the three dosage groups (F = 0.065, p = 0.937; F = 1.505, p = 0.273; χ2 = 1.423, p = 0.319, respectively); the washout slope(Slopewash), too, was uninfluenced by the dosage(F = 1.654, p = 0.244). Conclusion The CA dosage didn’t affect the TIC type, Tpeak, Vmax, Vwash or Slopewash. These dose-independent parameters as well as the TIC type might be more useful for monitoring the NAC response because they allow

  4. Toward Critical Contrastive Rhetoric

    ERIC Educational Resources Information Center

    Kubota, Ryuko; Lehner, Al

    2004-01-01

    A traditional approach to contrastive rhetoric has emphasized cultural difference in rhetorical patterns among various languages. Despite its laudable pedagogical intentions to raise teachers' and students' cultural and rhetorical awareness in second language writing, traditional contrastive rhetoric has perpetuated static binaries between English…

  5. 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. PMID:22348089

  6. Contrast-Enhanced Nanofocus X-Ray Computed Tomography Allows Virtual Three-Dimensional Histopathology and Morphometric Analysis of Osteoarthritis in Small Animal Models

    PubMed Central

    Sainz, Julie; Maréchal, Marina; Wevers, Martine; Van de Putte, Tom; Geris, Liesbet; Schrooten, Jan

    2014-01-01

    Objective: One of the early hallmarks of osteoarthritis (OA) is a progressive degeneration of the articular cartilage. Early diagnosis of OA-associated cartilage alterations would be beneficial for disease prevention and control, and for the development of disease-modifying treatments. However, early diagnosis is still hampered by a lack of quantifiable readouts in preclinical models. Design: In this study, we have shown the potency of contrast-enhanced nanofocus x-ray computed tomography (CE-nanoCT) to be used for virtual 3-dimensional (3D) histopathology in established mouse models for OA, and we compared with standard histopathology. Results: We showed the equivalence of CE-nanoCT images to histopathology for the modified Mankin scoring of the cartilage structure and quality. Additionally, a limited set of 3D cartilage characteristics measured by CE-nanoCT image analysis in a user-independent and semiautomatic manner, that is, average and maximum of the noncalcified cartilage thickness distribution and loss in glycosaminoglycans, was shown to be predictive for the cartilage quality and structure as can be evaluated by histopathological scoring through the use of an empirical model. Conclusions: We have shown that CE-nanoCT is a tool that allows virtual histopathology and 3D morphological quantification of multitissue systems, such as the chondro-osseous junction. It provides faster and more quantitative data on cartilage structure and quality compared with standard histopathology while eliminating user bias. CE-nanoCT thus should allow capturing subtle differences in cartilage characteristics, carefully mapping OA progression and, ultimately, asses the beneficial changes when testing a candidate disease-modifying treatment. PMID:26069685

  7. Effects of antibiotic resistance alleles on bacterial evolutionary responses to viral parasites

    PubMed Central

    Hall, Alex R.

    2016-01-01

    Antibiotic resistance has wide-ranging effects on bacterial phenotypes and evolution. However, the influence of antibiotic resistance on bacterial responses to parasitic viruses remains unclear, despite the ubiquity of such viruses in nature and current interest in therapeutic applications. We experimentally investigated this by exposing various Escherichia coli genotypes, including eight antibiotic-resistant genotypes and a mutator, to different viruses (lytic bacteriophages). Across 960 populations, we measured changes in population density and sensitivity to viruses, and tested whether variation among bacterial genotypes was explained by their relative growth in the absence of parasites, or mutation rate towards phage resistance measured by fluctuation tests for each phage. We found that antibiotic resistance had relatively weak effects on adaptation to phages, although some antibiotic-resistance alleles impeded the evolution of resistance to phages via growth costs. By contrast, a mutator allele, often found in antibiotic-resistant lineages in pathogenic populations, had a relatively large positive effect on phage-resistance evolution and population density under parasitism. This suggests costs of antibiotic resistance may modify the outcome of phage therapy against pathogenic populations previously exposed to antibiotics, but the effects of any co-occurring mutator alleles are likely to be stronger. PMID:27194288

  8. Effects of antibiotic resistance alleles on bacterial evolutionary responses to viral parasites.

    PubMed

    Arias-Sánchez, Flor I; Hall, Alex R

    2016-05-01

    Antibiotic resistance has wide-ranging effects on bacterial phenotypes and evolution. However, the influence of antibiotic resistance on bacterial responses to parasitic viruses remains unclear, despite the ubiquity of such viruses in nature and current interest in therapeutic applications. We experimentally investigated this by exposing various Escherichia coli genotypes, including eight antibiotic-resistant genotypes and a mutator, to different viruses (lytic bacteriophages). Across 960 populations, we measured changes in population density and sensitivity to viruses, and tested whether variation among bacterial genotypes was explained by their relative growth in the absence of parasites, or mutation rate towards phage resistance measured by fluctuation tests for each phage. We found that antibiotic resistance had relatively weak effects on adaptation to phages, although some antibiotic-resistance alleles impeded the evolution of resistance to phages via growth costs. By contrast, a mutator allele, often found in antibiotic-resistant lineages in pathogenic populations, had a relatively large positive effect on phage-resistance evolution and population density under parasitism. This suggests costs of antibiotic resistance may modify the outcome of phage therapy against pathogenic populations previously exposed to antibiotics, but the effects of any co-occurring mutator alleles are likely to be stronger. PMID:27194288

  9. Natalizumab-related anaphylactoid reactions in MS patients are associated with HLA class II alleles

    PubMed Central

    de la Hera, Belén; Urcelay, Elena; Brassat, David; Chan, Andrew; Vidal-Jordana, Angela; Salmen, Anke; Villar, Luisa Maria; Álvarez-Cermeño, José Carlos; Izquierdo, Guillermo; Fernández, Oscar; Oliver, Begoña; Saiz, Albert; Ara, Jose Ramón; Vigo, Ana G.; Arroyo, Rafael; Meca, Virginia; Malhotra, Sunny; Fissolo, Nicolás; Horga, Alejandro; Montalban, Xavier

    2014-01-01

    Objectives: We aimed to investigate potential associations between human leukocyte antigen (HLA) class I and class II alleles and the development of anaphylactic/anaphylactoid reactions in patients with multiple sclerosis (MS) treated with natalizumab. Methods: HLA class I and II genotyping was performed in patients with MS who experienced anaphylactic/anaphylactoid reactions and in patients who did not develop infusion-related allergic reactions following natalizumab administration. Results: A total of 119 patients with MS from 3 different cohorts were included in the study: 54 with natalizumab-related anaphylactic/anaphylactoid reactions and 65 without allergic reactions. HLA-DRB1*13 and HLA-DRB1*14 alleles were significantly increased in patients who developed anaphylactic/anaphylactoid reactions (pM-H = 3 × 10−7; odds ratio [OR]M-H = 8.96, 95% confidence interval [CI] = 3.40–23.64), with a positive predictive value (PPV) of 82%. In contrast, the HLA-DRB1*15 allele was significantly more represented in patients who did not develop anaphylactic/anaphylactoid reactions to natalizumab (pM-H = 6 × 10−4; ORM-H = 0.2, 95% CI = 0.08–0.50), with a PPV of 81%. Conclusions: HLA-DRB1 genotyping before natalizumab treatment may help neurologists to identify patients with MS at risk for developing serious systemic hypersensitivity reactions associated with natalizumab administration. PMID:25520955

  10. Bayesian Inference of Natural Selection from Allele Frequency Time Series.

    PubMed

    Schraiber, Joshua G; Evans, Steven N; Slatkin, Montgomery

    2016-05-01

    The advent of accessible ancient DNA technology now allows the direct ascertainment of allele frequencies in ancestral populations, thereby enabling the use of allele frequency time series to detect and estimate natural selection. Such direct observations of allele frequency dynamics are expected to be more powerful than inferences made using patterns of linked neutral variation obtained from modern individuals. We developed a Bayesian method to make use of allele frequency time series data and infer the parameters of general diploid selection, along with allele age, in nonequilibrium populations. We introduce a novel path augmentation approach, in which we use Markov chain Monte Carlo to integrate over the space of allele frequency trajectories consistent with the observed data. Using simulations, we show that this approach has good power to estimate selection coefficients and allele age. Moreover, when applying our approach to data on horse coat color, we find that ignoring a relevant demographic history can significantly bias the results of inference. Our approach is made available in a C++ software package. PMID:27010022

  11. 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…

  12. Segment aberration effects on contrast.

    PubMed

    Crossfield, Ian J; Troy, Mitchell

    2007-07-20

    High-contrast imaging, particularly the direct detection of extrasolar planets, is a major science driver for the next generation of telescopes. This science requires the suppression of scattered starlight at extremely high levels and that telescopes be correctly designed today to meet these stringent requirements in the future. The challenge increases in systems with complicated aperture geometries such as obscured, segmented telescopes. Such systems can also require intensive modeling and simulation efforts in order to understand the trade-offs between different optical parameters. The feasibility and development of a contrast prediction tool for use in the design and systems engineering of these telescopes is described. The performance of a particular starlight suppression system on a large segmented telescope is described analytically. These analytical results and the results of a contrast predictor are then compared with the results of a full wave-optics simulation. PMID:17609697

  13. Identification of rare alleles and their carriers using compressed se(que)nsing

    PubMed Central

    Shental, Noam; Amir, Amnon; Zuk, Or

    2010-01-01

    Identification of rare variants by resequencing is important both for detecting novel variations and for screening individuals for known disease alleles. New technologies enable low-cost resequencing of target regions, although it is still prohibitive to test more than a few individuals. We propose a novel pooling design that enables the recovery of novel or known rare alleles and their carriers in groups of individuals. The method is based on a Compressed Sensing (CS) approach, which is general, simple and efficient. CS allows the use of generic algorithmic tools for simultaneous identification of multiple variants and their carriers. We model the experimental procedure and show via computer simulations that it enables the recovery of rare alleles and their carriers in larger groups than were possible before. Our approach can also be combined with barcoding techniques to provide a feasible solution based on current resequencing costs. For example, when targeting a small enough genomic region (∼100 bp) and using only ∼10 sequencing lanes and ∼10 distinct barcodes per lane, one recovers the identity of 4 rare allele carriers out of a population of over 4000 individuals. We demonstrate the performance of our approach over several publicly available experimental data sets. PMID:20699269

  14. Natural allelic variations of xenobiotic-metabolizing enzymes affect sexual dimorphism in Oryzias latipes

    PubMed Central

    Katsumura, Takafumi; Oda, Shoji; Nakagome, Shigeki; Hanihara, Tsunehiko; Kataoka, Hiroshi; Mitani, Hiroshi; Kawamura, Shoji; Oota, Hiroki

    2014-01-01

    Sexual dimorphisms, which are phenotypic differences between males and females, are driven by sexual selection. Interestingly, sexually selected traits show geographical variations within species despite strong directional selective pressures. This paradox has eluded many evolutionary biologists for some time, and several models have been proposed (e.g. ‘indicator model’ and ‘trade-off model’). However, disentangling which of these theories explains empirical patterns remains difficult, because genetic polymorphisms that cause variation in sexual differences are still unknown. In this study, we show that polymorphisms in cytochrome P450 (CYP) 1B1, which encodes a xenobiotic-metabolizing enzyme, are associated with geographical differences in sexual dimorphism in the anal fin morphology of medaka fish (Oryzias latipes). Biochemical assays and genetic cross experiments show that high- and low-activity CYP1B1 alleles enhanced and declined sex differences in anal fin shapes, respectively. Behavioural and phylogenetic analyses suggest maintenance of the high-activity allele by sexual selection, whereas the low-activity allele possibly has experienced positive selection due to by-product effects of CYP1B1 in inferred ancestral populations. The present data can elucidate evolutionary mechanisms behind genetic variations in sexual dimorphism and indicate trade-off interactions between two distinct mechanisms acting on the two alleles with pleiotropic effects of xenobiotic-metabolizing enzymes. PMID:25377463

  15. JAK2 Allele Burden in the Myeloproliferative Neoplasms: Effects on Phenotype, Prognosis and Change with Treatment

    PubMed Central

    Vannucchi, Alessandro M.; Pieri, Lisa; Guglielmelli, Paola

    2011-01-01

    The field of Philadelphia-chromosome-negative chronic myeloproliferative neoplasms (MPNs) has recently witnessed tremendous advances in the basic knowledge of disease pathophysiology that followed the identification of mutations in JAK2 and MPL. These discoveries led to a revision of the criteria employed for diagnosis by the World Health Organization. The prognostic role of the JAK2V617F mutation and of its allelic burden has been the objective of intensive research using a variety of cellular and animal models as well as in large series of patients. While a definitive position cannot yet been taken on all of the issues, there is a consensus that the presence of higher V617F allele burden, that is on the basis of a stronger activation of intracellular signalling pathways, is associated with the clinical phenotype of polycythemia vera and with defined haematological and clinical markers indicative of a more aggressive phenotype. On the other hand, a low allele burden in myelofibrosis is associated with reduced survival. Finally, a significant reduction of JAK2 V617F allele burden has been demonstrated in patients treated with interferon, while the effects of novel JAK1 and JAK2 inhibitors have not yet been fully ascertained. PMID:23556073

  16. Association between AgI-CA alleles and severity of autosomal recessive proximal spina lmuscular atrophy

    SciTech Connect

    DiDonato, C.J.; Carpten, J.D.; Fuerst, P.; Ingraham, S.E.; Mendell, J.R.; Burghes, A.H.M.; Morgan, K.; Prescott, G.; Simard, L.R.; McPherson, J.D.

    1994-12-01

    The gene for autosomal recessive proximal spinal muscular atrophy (SMA) has been mapped to an 850-kb interval on 5q11.2-q13.3, between the centromeric D5S823 and telomeric D5S557 markers. We report a new complex marker, Ag1-CA, that lies in this interval, whose primers produce one, two, or rarely three amplification-fragment-length variants (AFLVs) per allele. Class I chromosomes are those which amplify a single AFLV allele, and class II chromosomes are those which amplify an allele with two or three AFLVs. Ag1-CA shows highly significant allelic association with type I SMA in both the French Canadian (Hopital Sainte-Justine (HSJ)) and American (Ohio State University (OSU)) populations (P < .0001). Significant association between the Ag1-CA genotype and disease severity was also observed. Type I patients were predominantly homozygous for class I chromosomes (P = .0003 OSU; P = 0.0012 HSJ), whereas the majority of type II patients were heterozygous for class I and II chromosomes (P = .0014 OSU; P = .001 HSJ). There was no significant difference in Ag1-CA genotype frequencies between type III patients (P = .5 OSU; P = .25 HSJ) and the paired normal chromosomes from both carrier parents. Our results indicate that Ag1-CA is the most closely linked marker to SMA and defines the critical candidate-gene region. Finally, we have proposed a model that should be taken into consideration when screening candidates SMA genes.

  17. Modulation of penetrance by the wild-type allele in dominantly inherited erythropoietic protoporphyria and acute hepatic porphyrias.

    PubMed

    Gouya, Laurent; Puy, Hervé; Robreau, Anne-Marie; Lyoumi, Said; Lamoril, Jérome; Da Silva, Vasco; Grandchamp, Bernard; Deybach, Jean-Charles

    2004-02-01

    We have recently demonstrated that in an autosomal dominant porphyria, erythropoietic protoporphyria (EPP), the coinheritance of a ferrochelatase (FECH) gene defect and of a wild-type low-expressed FECH allele is generally involved in the clinical expression of EPP. This mechanism may provide a model for phenotype modulation by minor variations in the expression of the wild-type allele in the other three autosomal dominant porphyrias that exhibit incomplete penetrance: acute intermittent porphyria (AIP), variegata porphyria (VP) and hereditary coproporphyria (HC), which are caused by partial deficiencies of hydroxy-methyl bilane synthase (HMBS), protoporphyrinogen oxidase (PPOX) and coproporphyrinogen oxidase (CPO), respectively. Given the dominant mode of inheritance of EPP, VP, AIP and HC, we first confirmed that the 200 overtly porphyric subjects (55 EPP, 58 AIP, 56 VP; 31 HC) presented a single mutation restricted to one allele (20 novel mutations and 162 known mutations). We then analysed the available single-nucleotide polymorphisms (SNPs) present at high frequencies in the general population and spreading throughout the FECH, HMBS, PPOX and the CPO genes in four case-control association studies. Finally, we explored the functional consequences of polymorphisms on the abundance of wild-type RNA, and used relative allelic mRNA determinations to find out whether low-expressed HMBS, PPOX and the CPO alleles occur in the general population. We confirm that the wild-type low-expressed allele phenomenon is usually operative in the mechanism of variable penetrance in EPP, but conclude that this is not the case in AIP and VP. For HC, the CPO mRNA determinations strongly suggest that normal CPO alleles with low-expression are present, but whether this low-expression of the wild-type allele could modulate the penetrance of a CPO gene defect in HC families remains to be ascertained. PMID:14669009

  18. Efficient Hilbert transform-based alternative to Tofts physiological models for representing MRI dynamic contrast-enhanced images in computer-aided diagnosis of prostate cancer

    NASA Astrophysics Data System (ADS)

    Boehm, Kevin M.; Wang, Shijun; Burtt, Karen E.; Turkbey, Baris; Weisenthal, Samuel; Pinto, Peter; Choyke, Peter; Wood, Bradford J.; Petrick, Nicholas; Sahiner, Berkman; Summers, Ronald M.

    2015-03-01

    In computer-aided diagnosis (CAD) systems for prostate cancer, dynamic contrast enhanced (DCE) magnetic resonance imaging is useful for distinguishing cancerous and benign tissue. The Tofts physiological model is a commonly used representation of the DCE image data, but the parameters require extensive computation. Hence, we developed an alternative representation based on the Hilbert transform of the DCE images. The time maximum of the Hilbert transform, a binary metric of early enhancement, and a pre-DCE value was assigned to each voxel and appended to a standard feature set derived from T2-weighted images and apparent diffusion coefficient maps. A cohort of 40 patients was used for training the classifier, and 20 patients were used for testing. The AUC was calculated by pooling the voxel-wise prediction values and comparing with the ground truth. The resulting AUC of 0.92 (95% CI [0.87 0.97]) is not significantly different from an AUC calculated using Tofts physiological models of 0.92 (95% CI [0.87 0.97]), as validated by a Wilcoxon signed rank test on each patient's AUC (p = 0.19). The time required for calculation and feature extraction is 11.39 seconds (95% CI [10.95 11.82]) per patient using the Hilbert-based feature set, two orders of magnitude faster than the 1319 seconds (95% CI [1233 1404]) required for the Tofts parameter-based feature set (p<0.001). Hence, the features proposed herein appear useful for CAD systems integrated into clinical workflows where efficiency is important.

  19. Evaluation of Tumor-associated Stroma and Its Relationship with Tumor Hypoxia Using Dynamic Contrast-enhanced CT and (18)F Misonidazole PET in Murine Tumor Models.

    PubMed

    Koyasu, Sho; Tsuji, Yoshihisa; Harada, Hiroshi; Nakamoto, Yuji; Nobashi, Tomomi; Kimura, Hiroyuki; Sano, Kohei; Koizumi, Koji; Hamaji, Masatsugu; Togashi, Kaori

    2016-03-01

    Purpose To determine the relationship between the fractional interstitial volume (Fis), as calculated at dynamic contrast material-enhanced (DCE) computed tomography (CT), and tumor-associated stroma and to analyze its spatial relationship with tumor hypoxia in several xenograft tumor models. Materials and Methods All animal experiments were approved by the animal research committee. Mice with three different xenograft tumors (U251, CFPAC-1, and BxPC-3; n = 6, n = 8, and n = 6, respectively) underwent DCE CT then hypoxia imaging with fluorine 18 ((18)F) fluoromisonidazole (FMISO) positron emission tomography (PET) within 24 hours. Immunohistochemical analysis was performed in harvested tumors to detect hypoxia markers and to quantify microvascular and stromal density. Two DCE CT parameters (amount of interstitial space associated with the amount of stroma [Fis] and flow velocity [Fv]) were identified and quantitatively validated by using immunohistochemistry. FMISO uptake within the tumor was also assessed in relation to DCE CT parameters. Imaging and immunohistochemical parameters were assessed by using the Kruskal-Wallis test, Wilcoxon rank-sum test with Bonferroni correction, and Pearson correlation coefficient. Results Almost no α-smooth muscle actin-positive cells were found in the U251 xenograft, while abundant stroma was found in the entire BxPC-3 xenograft and in the periphery of the CFPAC-1 xenograft. Quantitative analysis showed a significant correlation (R = 0.83, P < .0001) between Fis and stromal density. FMISO uptake had a negative correlation with Fis (R = -0.58, P < .0001) and Fv (R = -0.53, P < .0001). Conclusion DCE CT can be used to quantify parameters associated with tumor-associated stroma. Tumor hypoxia was Complementarily localized in tumor-associated stroma in these models. (©) RSNA, 2015 Online supplemental material is available for this article. PMID:26393963

  20. (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. PMID:26647764

  1. 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.

  2. Comparison between subjects with long- and short-allele carriers in the BOLD signal within amygdala during emotional tasks

    NASA Astrophysics Data System (ADS)

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

    2012-03-01

    Emotional tasks may result in a strong blood oxygen level-dependent (BOLD) signal in the amygdala in 5- HTTLRP short-allele. Reduced anterior cingulate cortex (ACC)-amygdala connectivity in short-allele provides a potential mechanistic account for the observed increase in amygdala activity. In our study, fearful and threatening facial expressions were presented to two groups of 12 subjects with long- and short-allele carriers. The BOLD signals of the left amygdala of each group were averaged to increase the signal-to-noise ratio. A Bayesian approach was used to estimate the model parameters to elucidate the underlying hemodynamic mechanism. Our results showed a positive BOLD signal in the left amygdala for short-allele individuals, and a negative BOLD signal in the same region for long-allele individuals. This is due to the fact that short-allele is associated with lower availability of serotonin transporter (5-HTT) and this leads to an increase of serotonin (5-HT) concentration in the cACC-amygdala synapse.

  3. Genetic influences on bone density: Physiological correlates of vitamin D receptor gene alleles in premonopausal women

    SciTech Connect

    Howard, G.; Nguyen, T.; Morrison, N.

    1995-09-01

    Common vitamin D receptor (VDR) gene alleles have recently been shown to contribute to the genetic variability in bone mass and bone turnover; however, the physiological mechanisms involved are unknown. To examine this, the response to 7 days of 2 {mu}g oral 1,25-dihydroxyvitamin D[1,25-(OH){sub 2}D] (calcitrol) stimulation was assessed in 21 premenopausal women, homozygous for one or other of the common VDR alleles (bb, N = 11; BB, n = 10). Indices of bone turnover and calcium homeostasis were measured during 2 weeks. Baseline osteocalcin, 1,25-(OH){sub 2}D, type I collagen carboxyterminal telopeptide, and inorganic phosphate levels were significantly higher and spinal bone mineral density was significantly lower in the BB allelic group. After calcitrol administration, similar levels of 1,25-(OH){sub 2}D were attained throughout the study in both genotypic groups. The increase in serum osteocalcin levels in the BB group was significantly less than that in the bb group (11% vs. 32%, P = 0.01). The genotype-related baseline difference in osteocalcin levels was not apparent at the similar serum 1,25-(OH){sub 2}D levels. By contrast, the baseline differences in phosphate and type I collagen carboxyterminal telopeptide persisted throughout the study. Serum ionized calcium levels did not differ between genotypes, nor did it move out of normal range values. However, parathyroid hormone was less suppressed in the low bone density group (38% vs. 11%, P = 0.01). These data indicate that the VDR alleles are associated with differences in the vitamin D endocrine system and may have important implications in relation to the pathophysiology of osteoporosis. 35 refs., 2 figs., 1 tab.

  4. Allelic Specificity of Ube3a Expression in the Mouse Brain during Postnatal Development

    PubMed Central

    JUDSON, MATTHEW C.; SOSA-PAGAN, JASON O.; DEL CID, WILMER A.; HAN, JI EUN; PHILPOT, BENJAMIN D.

    2014-01-01

    Genetic alterations of the maternal UBE3A allele result in Angelman syndrome (AS), a neurodevelopmental disorder characterized by severe developmental delay, lack of speech, and difficulty with movement and balance. The combined effects of maternal UBE3A mutation and cell type-specific epigenetic silencing of paternal UBE3A are hypothesized to result in a complete loss of functional UBE3A protein in neurons. However, the allelic specificity of UBE3A expression in neurons and other cell types in the brain has yet to be characterized throughout development, including the early postnatal period when AS phenotypes emerge. Here we define maternal and paternal allele-specific Ube3a protein expression throughout postnatal brain development in the mouse, a species which exhibits orthologous epigenetic silencing of paternal Ube3a in neurons and AS-like behavioral phenotypes subsequent to maternal Ube3a deletion. We find that neurons downregulate paternal Ube3a protein expression as they mature and, with the exception of neurons born from postnatal stem cell niches, do not express detectable paternal Ube3a beyond the first postnatal week. By contrast, neurons express maternal Ube3a throughout postnatal development, during which time localization of the protein becomes increasingly nuclear. Unlike neurons, astrocytes and oligodendrotyes biallelically express Ube3a. Notably, mature oligodendrocytes emerge as the predominant Ube3a-expressing glial cell type in the cortex and white matter tracts during postnatal development. These findings demonstrate the spatiotemporal characteristics of allele-specific Ube3a expression in key brain cell types, thereby improving our understanding of the developmental parameters of paternal Ube3a silencing and the cellular basis of AS. PMID:24254964

  5. Compressive phase contrast tomography

    NASA Astrophysics Data System (ADS)

    Maia, F.; MacDowell, A.; Marchesini, S.; Padmore, H. A.; Parkinson, D. Y.; Pien, J.; Schirotzek, A.; Yang, C.

    2010-08-01

    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).

  6. 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).

  7. Characteristics and prevalence within serogroup O4 of a J96-like clonal group of uropathogenic Escherichia coli O4:H5 containing the class I and class III alleles of papG.

    PubMed Central

    Johnson, J R; Stapleton, A E; Russo, T A; Scheutz, F; Brown, J J; Maslow, J N

    1997-01-01

    The recent discovery of a geographically dispersed clonal group of Escherichia coli O4:H5 that includes prototypic uropathogenic strain J96 prompted us to determine the prevalence of J96-like strains within serogroup O4 and to further assess the characteristics of such strains. We used O:K:H;F serotyping, PCR-based genomic fingerprinting, pulsed-field gel electrophoresis (PFGE), multilocus enzyme electrophoresis (MLEE), and PCR detection of the three papG alleles and of the cytotoxic necrotizing factor 1 (cnf1) and aerobactin (aer) gene sequences to characterize the 15 O4 strains among 336 E. coli isolates from three clinical collections (187 from mixed-source bacteremia, 75 from urosepsis, and 74 from acute cystitis). J96-like strains constituted approximately half of the O4 strains, or 2% of the total population. In contrast to other O4 strains, the J96-like strains characteristically exhibited specific group III capsular antigens, the H5 flagellar and F13 fimbrial antigens, a distinctive PCR genomic fingerprint, the class III papG allele (plus, in 50% of strains, the enigmatic class I papG allele), and cnf1 but lacked aer. A subset of these strains was remarkably homogeneous with respect to all these characteristics and exhibited a distinctive PFGE fingerprint and MLEE pattern. These findings clarify the epidemiological relevance of J96 as a model extraintestinal pathogen, provide further evidence of the class I papG allele outside of strain J96, and offer insights into the evolution of E. coli serogroup O4. PMID:9169745

  8. Influence of contrast morphogenetic features of urban constructed soils on the functioning of Moscow green lawn urban ecosystems: analysis based on the field model experiment

    NASA Astrophysics Data System (ADS)

    Epikhina, Anna; Vizirskaya, Mariya; Mazirov, Ilya; Vasenev, Vyacheslav; Vasenev, Ivan; Valentini, Riccardo

    2014-05-01

    Green lawns are the key element of the urban environment. They occupy a considerable part of the city area and locate in different urban functional zones. Urban constructed soils under green lawns have a unique spatial variability in chemical and morphogenetic features. So far, there is lack of information on the influence of morphogenetic features of urban soils on the functioning of the green lawn ecosystems especially in Moscow - the biggest megalopolis in Europe. Urban lawns perform a number of principal functions including both aesthetic and environmental. The role of the green lawn ecosystems in global carbon cycle is one of their main environmental functions. It is traditionally assessed through carbon stocks and fluxes in the basic ecosystem components. So far, such a data for the urban lawn ecosystems of the Moscow megapolis is lacking. In addition to environmental functions, green lawns perform an important ornamental role, which is also a critical criterion of their optimal functioning. Considering the variability of driving factors, influencing green lawns in urban environment, we carry out the model experiment in order to analyze "pure" effect of soil morphogenetic features. The current study aimed to analyze the influence of contrast morphogenetic features of urban constructed soils on the environmental and aesthetic functions of lawn ecosystems in Moscow megapolis basing in the model experiment. We carry out the model experiment located at the experimental field of the Russian State Agrarian University. Special transparent containers developed for the experiment, provided an option to observe soil morphogenetic features dynamics, including the depth and material of the organic transformation. At the same soil body inside the containers was united with the outside environment through the system of holes in the bottom and walls. The set of urban constructed soils includ four contrast types of the top soil (turf (T), turf-sand (TSa), turf-soil (TSo) and

  9. A New Electrophoresis Technique to Seperate Microsatellite Alleles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Traditional agarose and polyacrylamide gel electrophoresis have been used commonly for microsatellite (simple sequence repeats, SSRs) analysis, but they are labor- intensive and not always able to provide accurate sizes for different alleles. Capillary sequencers provide automated analysis and accur...

  10. Differential and limited expression of mutant alleles in multiple myeloma

    PubMed Central

    Rashid, Naim U.; Sperling, Adam S.; Bolli, Niccolo; Wedge, David C.; Van Loo, Peter; Tai, Yu-Tzu; Shammas, Masood A.; Fulciniti, Mariateresa; Samur, Mehmet K.; Richardson, Paul G.; Magrangeas, Florence; Minvielle, Stephane; Futreal, P. Andrew; Anderson, Kenneth C.; Avet-Loiseau, Herve; Parmigiani, Giovanni

    2014-01-01

    Recent work has delineated mutational profiles in multiple myeloma and reported a median of 52 mutations per patient, as well as a set of commonly mutated genes across multiple patients. In this study, we have used deep sequencing of RNA from a subset of these patients to evaluate the proportion of expressed mutations. We find that the majority of previously identified mutations occur within genes with very low or no detectable expression. On average, 27% (range, 11% to 47%) of mutated alleles are found to be expressed, and among mutated genes that are expressed, there often is allele-specific expression where either the mutant or wild-type allele is suppressed. Even in the absence of an overall change in gene expression, the presence of differential allelic expression within malignant cells highlights the important contribution of RNA-sequencing in identifying clinically significant mutational changes relevant to our understanding of myeloma biology and also for therapeutic applications. PMID:25237203

  11. Differential and limited expression of mutant alleles in multiple myeloma.

    PubMed

    Rashid, Naim U; Sperling, Adam S; Bolli, Niccolo; Wedge, David C; Van Loo, Peter; Tai, Yu-Tzu; Shammas, Masood A; Fulciniti, Mariateresa; Samur, Mehmet K; Richardson, Paul G; Magrangeas, Florence; Minvielle, Stephane; Futreal, P Andrew; Anderson, Kenneth C; Avet-Loiseau, Herve; Campbell, Peter J; Parmigiani, Giovanni; Munshi, Nikhil C

    2014-11-13

    Recent work has delineated mutational profiles in multiple myeloma and reported a median of 52 mutations per patient, as well as a set of commonly mutated genes across multiple patients. In this study, we have used deep sequencing of RNA from a subset of these patients to evaluate the proportion of expressed mutations. We find that the majority of previously identified mutations occur within genes with very low or no detectable expression. On average, 27% (range, 11% to 47%) of mutated alleles are found to be expressed, and among mutated genes that are expressed, there often is allele-specific expression where either the mutant or wild-type allele is suppressed. Even in the absence of an overall change in gene expression, the presence of differential allelic expression within malignant cells highlights the important contribution of RNA-sequencing in identifying clinically significant mutational changes relevant to our understanding of myeloma biology and also for therapeutic applications. PMID:25237203

  12. Three-dimensional optoacoustic imaging as a new noninvasive technique to study long-term biodistribution of optical contrast agents in small animal models

    PubMed Central

    Ermilov, Sergey A.; Liopo, Anton V.; Oraevsky, Alexander A.

    2012-01-01

    Abstract. We used a 3-D optoacoustic (OA) tomography system to create maps of optical absorbance of mice tissues contrasted with gold nanorods (GNRs). Nude mice were scanned before and after injection of GNRs at time periods varying from 1 to 192 h. Synthesized GNRs were purified from hexadecyltrimethylammonium bromide and coated with polyethylene glycol (PEG) to obtain GNR-PEG complexes suitable for in vivo applications. Intravenous administration of purified GNR-PEG complexes resulted in enhanced OA contrast of internal organs and blood vessels compared to the same mouse before injection of the contrast agent. Maximum enhancement of the OA images was observed 24 to 48 h postinjection, followed by a slow clearance trend for the remaining part of the studied period (eight days). We demonstrate that OA imaging with two laser wavelengths can be used for noninvasive, long-term studies of biological distribution of contrast agents. PMID:23223982

  13. Allele-specific MMP-3 transcription under in vivo conditions

    SciTech Connect

    Zhu Chaoyong; Odeberg, Jacob; Hamsten, Anders; Eriksson, Per . E-mail: Per.Eriksson@ki.se

    2006-09-29

    A common matrix metalloproteinases-3 (MMP-3) -1612 5A/6A promoter polymorphism is associated with risk for cardiovascular disease, rheumatoid arthritis, and other diseases. Here we used the haplotype chromatin immunoprecipitation method to study allele-specific MMP-3 expression under in vivo conditions in heterozygous THP-1 cells. Pyrosequencing was used to analyse the ratio of 5A-allele to 6A-allele after chromatin immunoprecipitation using an antibody against phosphorylated active RNA polymerase II. There was no allele-specific difference in transcriptional activity during basal conditions, i.e., in unstimulated monocytic THP-1 cells. However, after stimulation of MMP-3 expression by monocyte differentiation or incubation with IL-1{beta}, the haplotype containing the 5A-allele was associated with higher transcriptional activity compared with the 6A-containing haplotype. Electromobility shift assay demonstrated increased binding of nuclear proteins to the 5A-allele after monocyte differentiation. In conclusion, the common MMP-3 5A/6A promoter polymorphism appears to be functional only during specific environmental conditions involving inflammation.

  14. The role of culture-gene coevolution in morality judgment: examining the interplay between tightness-looseness and allelic variation of the serotonin transporter gene.

    PubMed

    Mrazek, Alissa J; Chiao, Joan Y; Blizinsky, Katherine D; Lun, Janetta; Gelfand, Michele J

    2013-01-01

    This research provides novel insights into the evolutionary basis of cultural norm development and maintenance. We yield evidence for a unique culture-gene coevolutionary model between ecological threat, allelic frequency of the serotonin transporter polymorphism (5-HTTLPR), cultural tightness-looseness-the strength of norms and tolerance for deviance from norms-and moral justifiability. As hypothesized, the results across 21 nations show that: (a) propensity for ecological threat correlates with short (S) allele frequency in the 5-HTTLPR, (b) allelic frequency in the 5-HTTLPR and vulnerability to ecological threat both correlate with cultural tightness-looseness, (c) susceptibility to ecological threat predicts tightness-looseness via the mediation of S allele carriers, and (d) frequency of S allele carriers predicts justifiability of morally relevant behavior via tightness-looseness. This research highlights the importance of studying the interplay between environmental, genetic, and cultural factors underlying contemporary differences in social behavior and presents an empirical framework for future research. PMID:24404439

  15. Leukemia-associated NOTCH1 alleles are weak tumor initiators but accelerate K-ras–initiated leukemia

    PubMed Central

    Chiang, Mark Y.; Xu, Lanwei; Shestova, Olga; Histen, Gavin; L’Heureux, Sarah; Romany, Candice; Childs, M. Eden; Gimotty, Phyllis A.; Aster, Jon C.; Pear, Warren S.

    2008-01-01

    Gain-of-function NOTCH1 mutations are found in 50%–70% of human T cell acute lymphoblastic leukemia/lymphoma (T-ALL) cases. Gain-of-function NOTCH1 alleles that initiate strong downstream signals induce leukemia in mice, but it is unknown whether the gain-of-function NOTCH1 mutations most commonly found in individuals with T-ALL generate downstream signals of sufficient strength to induce leukemia. We addressed this question by expressing human gain-of-function NOTCH1 alleles of varying strength in mouse hematopoietic precursors. Uncommon gain-of-function NOTCH1 alleles that initiated strong downstream signals drove ectopic T cell development and induced leukemia efficiently. In contrast, although gain-of-function alleles that initiated only weak downstream signals also induced ectopic T cell development, these more common alleles failed to efficiently initiate leukemia development. However, weak gain-of-function NOTCH1 alleles accelerated the onset of leukemia initiated by constitutively active K-ras and gave rise to tumors that were sensitive to Notch signaling pathway inhibition. These data show that induction of leukemia requires doses of Notch1 greater than those needed for T cell development and that most NOTCH1 mutations found in T-ALL cells do not generate signals of sufficient strength to initiate leukemia development. Furthermore, low, nonleukemogenic levels of Notch1 can complement other leukemogenic events, such as activation of K-ras. Even when Notch1 participates secondarily, the resulting tumors show “addiction” to Notch, providing a further rationale for evaluating Notch signaling pathway inhibitors in leukemia. PMID:18677410

  16. Always Look on Both Sides: Phylogenetic Information Conveyed by Simple Sequence Repeat Allele Sequences

    PubMed Central

    Barthe, Stéphanie; Gugerli, Felix; Barkley, Noelle A.; Maggia, Laurent; Cardi, Céline; Scotti, Ivan

    2012-01-01

    Simple sequence repeat (SSR) markers are widely used tools for inferences about genetic diversity, phylogeography and spatial genetic structure. Their applications assume that variation among alleles is essentially caused by an expansion or contraction of the number of repeats and that, accessorily, mutations in the target sequences follow the stepwise mutation model (SMM). Generally speaking, PCR amplicon sizes are used as direct indicators of the number of SSR repeats composing an allele with the data analysis either ignoring the extent of allele size differences or assuming that there is a direct correlation between differences in amplicon size and evolutionary distance. However, without precisely knowing the kind and distribution of polymorphism within an allele (SSR and the associated flanking region (FR) sequences), it is hard to say what kind of evolutionary message is conveyed by such a synthetic descriptor of polymorphism as DNA amplicon size. In this study, we sequenced several SSR alleles in multiple populations of three divergent tree genera and disentangled the types of polymorphisms contained in each portion of the DNA amplicon containing an SSR. The patterns of diversity provided by amplicon size variation, SSR variation itself, insertions/deletions (indels), and single nucleotide polymorphisms (SNPs) observed in the FRs were compared. Amplicon size variation largely reflected SSR repeat number. The amount of variation was as large in FRs as in the SSR itself. The former contributed significantly to the phylogenetic information and sometimes was the main source of differentiation among individuals and populations contained by FR and SSR regions of SSR markers. The presence of mutations occurring at different rates within a marker’s sequence offers the opportunity to analyse evolutionary events occurring on various timescales, but at the same time calls for caution in the interpretation of SSR marker data when the distribution of within

  17. The regulatory element READ1 epistatically influences reading and language, with both deleterious and protective alleles

    PubMed Central

    Powers, Natalie R; Eicher, John D; Miller, Laura L; Kong, Yong; Smith, Shelley D; Pennington, Bruce F; Willcutt, Erik G; Olson, Richard K; Ring, Susan M; Gruen, Jeffrey R

    2016-01-01

    Background Reading disability (RD) and language impairment (LI) are heritable learning disabilities that obstruct acquisition and use of written and spoken language, respectively. We previously reported that two risk haplotypes, each in strong linkage disequilibrium (LD) with an allele of READ1, a polymorphic compound short tandem repeat within intron 2 of risk gene DCDC2, are associated with RD and LI. Additionally, we showed a non-additive genetic interaction between READ1 and KIAHap, a previously reported risk haplotype in risk gene KIAA0319, and that READ1 binds the transcriptional regulator ETV6. Objective To examine the hypothesis that READ1 is a transcriptional regulator of KIAA0319. Methods We characterised associations between READ1 alleles and RD and LI in a large European cohort, and also assessed interactions between READ1 and KIAHap and their effect on performance on measures of reading, language and IQ. We also used family-based data to characterise the genetic interaction, and chromatin conformation capture (3C) to investigate the possibility of a physical interaction between READ1 and KIAHap. Results and conclusions READ1 and KIAHap show interdependence—READ1 risk alleles synergise with KIAHap, whereas READ1 protective alleles act epistatically to negate the effects of KIAHap. The family data suggest that these variants interact in trans genetically, while the 3C results show that a region of DCDC2 containing READ1 interacts physically with the region upstream of KIAA0319. These data support a model in which READ1 regulates KIAA0319 expression through KIAHap and in which the additive effects of READ1 and KIAHap alleles are responsible for the trans genetic interaction. PMID:26660103

  18. Detection of ancestry informative HLA alleles confirms the admixed origins of Japanese population.

    PubMed

    Nakaoka, Hirofumi; Mitsunaga, Shigeki; Hosomichi, Kazuyoshi; Shyh-Yuh, Liou; Sawamoto, Taiji; Fujiwara, Tsutomu; Tsutsui, Naohisa; Suematsu, Koji; Shinagawa, Akira; Inoko, Hidetoshi; Inoue, Ituro

    2013-01-01

    The polymorphisms in the human leukocyte antigen (HLA) region are powerful tool for studying human evolutionary processes. We investigated genetic structure of Japanese by using five-locus HLA genotypes (HLA-A, -B, -C, -DRB1, and -DPB1) of 2,005 individuals from 10 regions of Japan. We found a significant level of population substructure in Japanese; particularly the differentiation between Okinawa Island and mainland Japanese. By using a plot of the principal component scores, we identified ancestry informative alleles associated with the underlying population substructure. We examined extent of linkage disequilibrium (LD) between pairs of HLA alleles on the haplotypes that were differentiated among regions. The LDs were strong and weak for pairs of HLA alleles characterized by low and high frequencies in Okinawa Island, respectively. The five-locus haplotypes whose alleles exhibit strong LD were unique to Japanese and South Korean, suggesting that these haplotypes had been recently derived from the Korean Peninsula. The alleles characterized by high frequency in Japanese compared to South Korean formed segmented three-locus haplotype that was commonly found in Aleuts, Eskimos, and North- and Meso-Americans but not observed in Korean and Chinese. The serologically equivalent haplotype was found in Orchid Island in Taiwan, Mongol, Siberia, and Arctic regions. It suggests that early Japanese who existed prior to the migration wave from the Korean Peninsula shared ancestry with northern Asian who moved to the New World via the Bering Strait land bridge. These results may support the admixture model for peopling of Japanese Archipelago. PMID:23577161

  19. Detection of Ancestry Informative HLA Alleles Confirms the Admixed Origins of Japanese Population

    PubMed Central

    Nakaoka, Hirofumi; Mitsunaga, Shigeki; Hosomichi, Kazuyoshi; Shyh-Yuh, Liou; Sawamoto, Taiji; Fujiwara, Tsutomu; Tsutsui, Naohisa; Suematsu, Koji; Shinagawa, Akira; Inoko, Hidetoshi; Inoue, Ituro

    2013-01-01

    The polymorphisms in the human leukocyte antigen (HLA) region are powerful tool for studying human evolutionary processes. We investigated genetic structure of Japanese by using five-locus HLA genotypes (HLA-A, -B, -C, -DRB1, and -DPB1) of 2,005 individuals from 10 regions of Japan. We found a significant level of population substructure in Japanese; particularly the differentiation between Okinawa Island and mainland Japanese. By using a plot of the principal component scores, we identified ancestry informative alleles associated with the underlying population substructure. We examined extent of linkage disequilibrium (LD) between pairs of HLA alleles on the haplotypes that were differentiated among regions. The LDs were strong and weak for pairs of HLA alleles characterized by low and high frequencies in Okinawa Island, respectively. The five-locus haplotypes whose alleles exhibit strong LD were unique to Japanese and South Korean, suggesting that these haplotypes had been recently derived from the Korean Peninsula. The alleles characterized by high frequency in Japanese compared to South Korean formed segmented three-locus haplotype that was commonly found in Aleuts, Eskimos, and North- and Meso-Americans but not observed in Korean and Chinese. The serologically equivalent haplotype was found in Orchid Island in Taiwan, Mongol, Siberia, and Arctic regions. It suggests that early Japanese who existed prior to the migration wave from the Korean Peninsula shared ancestry with northern Asian who moved to the New World via the Bering Strait land bridge. These results may support the admixture model for peopling of Japanese Archipelago. PMID:23577161

  20. Investigation of a Calcium-Responsive Contrast Agent in Cellular Model Systems: Feasibility for Use as a Smart Molecular Probe in Functional MRI

    PubMed Central

    2014-01-01

    Responsive or smart contrast agents (SCAs) represent a promising direction for development of novel functional MRI (fMRI) methods for the eventual noninvasive assessment of brain function. In particular, SCAs that respond to Ca2+ may allow tracking neuronal activity independent of brain vasculature, thus avoiding the characteristic limitations of current fMRI techniques. Here we report an in vitro proof-of-principle study with a Ca2+-sensitive, Gd3+-based SCA in an attempt to validate its potential use as a functional in vivo marker. First, we quantified its relaxometric response in a complex 3D cell culture model. Subsequently, we examined potential changes in the functionality of primary glial cells following administration of this SCA. Monitoring intracellular Ca2+ showed that, despite a reduction in the Ca2+ level, transport of Ca2+ through the plasma membrane remained unaffected, while stimulation with ATP induced Ca2+-transients suggested normal cellular signaling in the presence of low millimolar SCA concentrations. SCAs merely lowered the intracellular Ca2+ level. Finally, we estimated the longitudinal relaxation times (T1) for an idealized in vivo fMRI experiment with SCA, for extracellular Ca2+ concentration level changes expected during intense neuronal activity which takes place upon repetitive stimulation. The values we obtained indicate changes in T1 of around 1–6%, sufficient to be robustly detectable using modern MRI methods in high field scanners. Our results encourage further attempts to develop even more potent SCAs and appropriate fMRI protocols. This would result in novel methods that allow monitoring of essential physiological processes at the cellular and molecular level. PMID:24712900

  1. Perilesional Inflammation in Neurocysticercosis - Relationship Between Contrast-Enhanced Magnetic Resonance Imaging, Evans Blue Staining and Histopathology in the Pig Model

    PubMed Central

    Bustos, Javier A.; Calcina, Juan; Vargas-Calla, Ana; Suarez, Diego; Gonzalez, Armando E.; Chacaltana, Juan; Guerra-Giraldez, Cristina; Mahanty, Siddhartha; Nash, Theodore E.; García, Hector H.

    2016-01-01

    Background Disease manifestations in neurocysticercosis (NCC) are frequently due to inflammation of degenerating Taenia solium brain cysts. Exacerbated inflammation post anthelmintic treatment is associated with leakage of the blood brain barrier (BBB) using Evans blue (EB) staining. How well EB extravasation into the brain correlates with magnetic resonance imaging (MRI) using gadolinium (Gd) enhancement as a contrast agent and pericystic inflammation was analyzed in pigs harboring brain cysts of Taenia solium. Methodology/Principal Findings Three groups of 4 naturally infected pigs were assessed. The first and second groups were treated with both praziquantel plus albendazole and sacrificed two and five days post treatment, respectively. A third untreated group remained untreated. Pigs were injected with EB two hours prior to evaluation by Gd-enhanced T1-MRI, and euthanized. The EB staining for each cyst capsule was scored (EB grades were 0: 0%; 1: up to 50%; 2: over 50% but less than 100%; 3: 100%). Similarly, the Gd enhancement around each cyst was qualitatively and quantitatively scored from the MRI. The extent of pericystic inflammation on histology was scored in increasing severity as IS1, IS2, IS3 and IS4. Grade 3 EB staining and enhancement was only seen in treated capsules. Also, treated groups had higher Gd intensity than the untreated group. Grades of enhancement correlated significantly with Gd enhancement intensity. EB staining was correlated with Gd enhancement intensity and with IS4 in the treated groups. These correlations were stronger in internally located cysts compared to superficial cysts in treated groups. Significance EB staining and Gd enhancement strongly correlate. The intensity of enhancement determined by MRI is a good indication of the degree of inflammation. Similarly, EB staining highly correlates with the degree of inflammation and may be applied to study inflammation in the pig model of NCC. PMID:27459388

  2. Multiple Avirulence Loci and Allele-Specific Effector Recognition Control the Pm3 Race-Specific Resistance of Wheat to Powdery Mildew[OPEN

    PubMed Central

    Roffler, Stefan; Stirnweis, Daniel; Treier, Georges; Herren, Gerhard; Korol, Abraham B.; Wicker, Thomas

    2015-01-01

    In cereals, several mildew resistance genes occur as large allelic series; for example, in wheat (Triticum aestivum and Triticum turgidum), 17 functional Pm3 alleles confer agronomically important race-specific resistance to powdery mildew (Blumeria graminis). The molecular basis of race specificity has been characterized in wheat, but little is known about the corresponding avirulence genes in powdery mildew. Here, we dissected the genetics of avirulence for six Pm3 alleles and found that three major Avr loci affect avirulence, with a common locus_1 involved in all AvrPm3-Pm3 interactions. We cloned the effector gene AvrPm3a2/f2 from locus_2, which is recognized by the Pm3a and Pm3f alleles. Induction of a Pm3 allele-dependent hypersensitive response in transient assays in Nicotiana benthamiana and in wheat demonstrated specificity. Gene expression analysis of Bcg1 (encoded by locus_1) and AvrPm3 a2/f2 revealed significant differences between isolates, indicating that in addition to protein polymorphisms, expression levels play a role in avirulence. We propose a model for race specificity involving three components: an allele-specific avirulence effector, a resistance gene allele, and a pathogen-encoded suppressor of avirulence. Thus, whereas a genetically simple allelic series controls specificity in the plant host, recognition on the pathogen side is more complex, allowing flexible evolutionary responses and adaptation to resistance genes. PMID:26452600

  3. Psychophysical contrast calibration

    PubMed Central

    To, Long; Woods, Russell L; Goldstein, Robert B; Peli, Eli

    2013-01-01

    Electronic displays and computer systems offer numerous advantages for clinical vision testing. Laboratory and clinical measurements of various functions and in particular of (letter) contrast sensitivity require accurately calibrated display contrast. In the laboratory this is achieved using expensive light meters. We developed and evaluated a novel method that uses only psychophysical responses of a person with normal vision to calibrate the luminance contrast of displays for experimental and clinical applications. Our method combines psychophysical techniques (1) for detection (and thus elimination or reduction) of display saturating nonlinearities; (2) for luminance (gamma function) estimation and linearization without use of a photometer; and (3) to measure without a photometer the luminance ratios of the display’s three color channels that are used in a bit-stealing procedure to expand the luminance resolution of the display. Using a photometer we verified that the calibration achieved with this procedure is accurate for both LCD and CRT displays enabling testing of letter contrast sensitivity to 0.5%. Our visual calibration procedure enables clinical, internet and home implementation and calibration verification of electronic contrast testing. PMID:23643843

  4. Promising potential of new generation translocator protein tracers providing enhanced contrast of arthritis imaging by positron emission tomography in a rat model of arthritis

    PubMed Central

    2014-01-01

    Introduction Early diagnosis of and subsequent monitoring of therapy for rheumatoid arthritis (RA) could benefit from detection of (sub)clinical synovitis. Imaging of (sub)clinical arthritis by targeting the translocator protein (TSPO) on activated macrophages is feasible using (R)-[11C] PK11195-based positron emission tomography (PET), but clinical applications are limited by background uptake in peri-articular bone/bone marrow. The purpose of the present study was to evaluate two other TSPO ligands with potentially lower background uptake in neurological studies, [11C]DPA-713 and [18F]DPA-714, in a rat model of arthritis. Methods TSPO binding of DPA-713, DPA-714 and PK11195 were assessed by in vitro competition studies with [3H]DPA-713 using human macrophage THP-1 cells and CD14+ monocytes from healthy volunteers. In vivo studies were performed in rats with methylated bovine serum albumin-induced knee arthritis. Immunohistochemistry with anti-TSPO antibody was performed on paraffin-embedded sections. Rats were imaged with [11C]DPA-713 or [18F]DPA-714 PET, followed by ex vivo tissue distribution studies. Results were compared with those obtained with the tracer (R)-[11C]PK11195, the established ligand for TSPO. Results In THP-1 cells, relative TSPO binding of DPA-713 and DPA-714 were 7-fold and 25-fold higher, respectively, than in PK11195. Comparable results were observed in CD14+ monocytes from healthy volunteers. In the arthritis rat model, immunohistochemistry confirmed the presence of TSPO-positive inflammatory cells in the arthritic knee. PET images showed that uptake of [11C]DPA-713 and [18F]DPA-714 in arthritic knees was significantly increased compared with contralateral knees and knees of normal rats. Uptake in arthritic knees could be largely blocked by an excess of PK11195. [11C]DPA-713 and [18F]DPA-714 provided improved contrast compared with (R)-[11C]PK11195, as was shown by significantly higher arthritic knee-to-bone ratios of [11C]DPA-713 (1.60

  5. Assessment of Blood-Brain Barrier Permeability by Dynamic Contrast-Enhanced MRI in Transient Middle Cerebral Artery Occlusion Model after Localized Brain Cooling in Rats

    PubMed Central

    Kim, Eun Soo; Kwon, Mi Jung; Lee, Phil Hye; Ju, Young-Su; Yoon, Dae Young; Kim, Hye Jeong; Lee, Kwan Seop

    2016-01-01

    Objective The purpose of this study was to evaluate the effects of localized brain cooling on blood-brain barrier (BBB) permeability following transient middle cerebral artery occlusion (tMCAO) in rats, by using dynamic contrast-enhanced (DCE)-MRI. Materials and Methods Thirty rats were divided into 3 groups of 10 rats each: control group, localized cold-saline (20℃) infusion group, and localized warm-saline (37℃) infusion group. The left middle cerebral artery (MCA) was occluded for 1 hour in anesthetized rats, followed by 3 hours of reperfusion. In the localized saline infusion group, 6 mL of cold or warm saline was infused through the hollow filament for 10 minutes after MCA occlusion. DCE-MRI investigations were performed after 3 hours and 24 hours of reperfusion. Pharmacokinetic parameters of the extended Tofts-Kety model were calculated for each DCE-MRI. In addition, rotarod testing was performed before tMCAO, and on days 1-9 after tMCAO. Myeloperoxidase (MPO) immunohisto-chemistry was performed to identify infiltrating neutrophils associated with the inflammatory response in the rat brain. Results Permeability parameters showed no statistical significance between cold and warm saline infusion groups after 3-hour reperfusion 0.09 ± 0.01 min-1 vs. 0.07 ± 0.02 min-1, p = 0.661 for Ktrans; 0.30 ± 0.05 min-1 vs. 0.37 ± 0.11 min-1, p = 0.394 for kep, respectively. Behavioral testing revealed no significant difference among the three groups. However, the percentage of MPO-positive cells in the cold-saline group was significantly lower than those in the control and warm-saline groups (p < 0.05). Conclusion Localized brain cooling (20℃) does not confer a benefit to inhibit the increase in BBB permeability that follows transient cerebral ischemia and reperfusion in an animal model, as compared with localized warm-saline (37℃) infusion group. PMID:27587960

  6. Functional imaging of the angiogenic switch in a transgenic mouse model of human breast cancer by dynamic contrast enhanced magnetic resonance imaging.

    PubMed

    Consolino, Lorena; Longo, Dario Livio; Dastrù, Walter; Cutrin, Juan Carlos; Dettori, Daniela; Lanzardo, Stefania; Oliviero, Salvatore; Cavallo, Federica; Aime, Silvio

    2016-07-15

    Tumour progression depends on several sequential events that include the microenvironment remodelling processes and the switch to the angiogenic phenotype, leading to new blood vessels recruitment. Non-invasive imaging techniques allow the monitoring of functional alterations in tumour vascularity and cellularity. The aim of this work was to detect functional changes in vascularisation and cellularity through Dynamic Contrast Enhanced (DCE) and Diffusion Weighted (DW) Magnetic Resonance Imaging (MRI) modalities during breast cancer initiation and progression of a transgenic mouse model (BALB-neuT mice). Histological examination showed that BALB-neuT mammary glands undergo a slow neoplastic progression from simple hyperplasia to invasive carcinoma, still preserving normal parts of mammary glands. DCE-MRI results highlighted marked functional changes in terms of vessel permeability (K(trans) , volume transfer constant) and vascularisation (vp , vascular volume fraction) in BALB-neuT hyperplastic mammary glands if compared to BALB/c ones. When breast tissue progressed from simple to atypical hyperplasia, a strong increase in DCE-MRI biomarkers was observed in BALB-neuT in comparison to BALB/c mice (K(trans)  = 5.3 ± 0.7E-4 and 3.1 ± 0.5E-4; vp  = 7.4 ± 0.8E-2 and 4.7 ± 0.6E-2 for BALB-neuT and BALB/c, respectively) that remained constant during the successive steps of the neoplastic transformation. Consistent with DCE-MRI observations, microvessel counting revealed a significant increase in tumour vessels. Our study showed that DCE-MRI estimates can accurately detect the angiogenic switch at early step of breast cancer carcinogenesis. These results support the view that this imaging approach is an excellent tool to characterize microvasculature changes, despite only small portions of the mammary glands developed neoplastic lesions in a transgenic mouse model. PMID:26941084

  7. Impriniting of human H19: Allele-specific CpG methylation, loss of the active allele in Wilms tumor, and potential for somatic allele switching

    SciTech Connect

    Zhang, Y.; Shields, T.; Crenshaw, T.; Hao, Y.; Moulton, T.; Tycko, B. )

    1993-07-01

    Genomic imprinting and monoallelic gene expression appear to play a role in human genetic disease and tumorigenesis. The human H19 gene, at chromosome 11p15, has previously been shown to be monoallelically expressed. Since CpG methylation has been implicated in imprinting, the authors analyzed methylation of H19 DNA. In fetal and adult organs the transcriptionally silent H19 allele was extensively hypermethylated through the entire gene and its promoter, and, consistent with a functional role for DNA methylation, expression of an H19 promoter-reporter construct was inhibited by in vitro methylation. Gynogenetic ovarian teratomas were found to contain only hypomethylated H19 DNA, suggesting that the expressed H19 allele might be maternal. This was confirmed by analysis of 11p15 polymorphisms in a patient with Wilms tumor. The tumor had lost the maternal 11p15, and H19 expression in the normal kidney was exclusively from this allele. Imprinting of human H19 appears to be susceptible to tissue-specific modulation in somatic development; in one individual, cerebellar cells were found to express only the otherwise silent allele. Implications of these findings for the role of DNA methylation in imprinting and for H19 as a candidate imprinted tumor-suppressor gene are discussed. 57 refs., 7 figs.

  8. Trans-species polymorphism and allele-specific expression in the CBF gene family of wild tomatoes.

    PubMed

    Mboup, Mamadou; Fischer, Iris; Lainer, Hilde; Stephan, Wolfgang

    2012-12-01

    Abiotic stresses such as drought, extreme temperatures, and salinity have a strong impact on plant adaptation. They act as selective forces on plant physiology and morphology. These selective pressures leave characteristic footprints that can be detected at the DNA sequence level using population genetic tools. On the basis of a candidate gene approach, we investigated signatures of adaptation in two wild tomato species, Solanum peruvianum and S. chilense. These species are native to western South America and constitute a model system for studying adaptation, due to their ability to colonize diverse habitats and the available genetic resources. We have determined the selective forces acting on the C-repeat binding factor (CBF) gene family, which consists of three genes, and is known to be involved in tolerance to abiotic stresses, in particular in cold tolerance. We also analyzed the expression pattern of these genes after drought and cold stresses. We found that CBF3 evolves under very strong purifying selection, CBF2 is under balancing selection in some populations of both species (S. peruvianum/Quicacha and S. chilense/Nazca) maintaining a trans-species polymorphism, and CBF1 is a pseudogene. In contrast to previous studies of cultivated tomatoes showing that only CBF1 was cold induced, we found that all three CBF genes are cold induced in wild tomatoes. All three genes are also drought induced. CBF2 exhibits an allele-specific expression pattern associated with the trans-species polymorphism. PMID:22787283

  9. Aspiration of Barium Contrast

    PubMed Central

    Fuentes Santos, Cristina; Steen, Bárbara

    2014-01-01

    The aspiration of barium contrast is a rare complication that may occur during studies of the digestive tract. Barium is an inert material that can cause anywhere from an asymptomatic mechanical obstruction to serious symptoms of respiratory distress that can result in patient death. We present the case of a 79-year-old male patient in whom we observed the presence of contrast medium residue in the lung parenchyma as an incidental finding during hospitalization. When the patient's medical file was reviewed, images were found of a barium swallow study that the patient had undergone months earlier, and we were able to observe the exact moment of the aspiration of the contrast material. The patient had been asymptomatic since the test. PMID:25309769

  10. Confounded by sequencing depth in association studies of rare alleles.

    PubMed

    Garner, Chad

    2011-05-01

    Next-generation DNA sequencing technologies are facilitating large-scale association studies of rare genetic variants. The depth of the sequence read coverage is an important experimental variable in the next-generation technologies and it is a major determinant of the quality of genotype calls generated from sequence data. When case and control samples are sequenced separately or in different proportions across batches, they are unlikely to be matched on sequencing read depth and a differential misclassification of genotypes can result, causing confounding and an increased false-positive rate. Data from Pilot Study 3 of the 1000 Genomes project was used to demonstrate that a difference between the mean sequencing read depth of case and control samples can result in false-positive association for rare and uncommon variants, even when the mean coverage depth exceeds 30× in both groups. The degree of the confounding and inflation in the false-positive rate depended on the extent to which the mean depth was different in the case and control groups. A logistic regression model was used to test for association between case-control status and the cumulative number of alleles in a collapsed set of rare and uncommon variants. Including each individual's mean sequence read depth across the variant sites in the logistic regression model nearly eliminated the confounding effect and the inflated false-positive rate. Furthermore, accounting for the potential error by modeling the probability of the heterozygote genotype calls in the regression analysis had a relatively minor but beneficial effect on the statistical results. PMID:21328616

  11. Gadofullerene MRI contrast agents.

    PubMed

    Bolskar, Robert D

    2008-04-01

    A promising new class of MRI contrast-enhancing agents with high relaxivities is based on gadolinium-containing metallofullerenes, which are also termed gadofullerenes. Detailed study of the water-proton relaxivity properties and intermolecular nanoclustering behavior of gadofullerene derivatives has revealed valuable information about their relaxivity mechanisms and given a deeper understanding of this new class of paramagnetic contrast agent. Here, the latest findings on water-solubilized gadofullerene materials and how these findings relate to their future applications in MRI are reviewed and discussed. PMID:18373426

  12. How the Number of Alleles Influences Gene Expression

    NASA Astrophysics Data System (ADS)

    Hat, Beata; Paszek, Pawel; Kimmel, Marek; Piechor, Kazimierz; Lipniacki, Tomasz

    2007-07-01

    The higher organisms, eukaryotes, are diploid and most of their genes have two homological copies (alleles). However, the number of alleles in a cell is not constant. In the S phase of the cell cycle all the genome is duplicated and then in the G2 phase and mitosis, which together last for several hours, most of the genes have four copies instead of two. Cancer development is, in many cases, associated with a change in allele number. Several genetic diseases are caused by haploinsufficiency: Lack of one of the alleles or its improper functioning. In the paper we consider the stochastic expression of a gene having a variable number of copies. We applied our previously developed method in which the reaction channels are split into slow (connected with change of gene state) and fast (connected with mRNA/protein synthesis/decay), the later being approximated by deterministic reaction rate equations. As a result we represent gene expression as a piecewise deterministic time-continuous Markov process, which is further related with a system of partial differential hyperbolic equations for probability density functions (pdfs) of protein distribution. The stationary pdfs are calculated analytically for haploidal gene or numerically for diploidal and tetraploidal ones. We distinguished nine classes of simultaneous activation of haploid, diploid and tetraploid genes. This allows for analysis of potential consequences of gene duplication or allele loss. We show that when gene activity is autoregulated by a positive feedback, the change in number of gene alleles may have dramatic consequences for its regulation and may not be compensated by the change of efficiency of mRNA synthesis per allele.

  13. The Equilibrium Allele Frequency Distribution for a Population with Reproductive Skew

    PubMed Central

    Der, Ricky; Plotkin, Joshua B.

    2014-01-01

    We study the population genetics of two neutral alleles under reversible mutation in a model that features a skewed offspring distribution, called the Λ-Fleming–Viot process. We describe the shape of the equilibrium allele frequency distribution as a function of the model parameters. We show that the mutation rates can be uniquely identified from this equilibrium distribution, but the form of the offspring distribution cannot itself always be so identified. We introduce an estimator for the mutation rate that is consistent, independent of the form of reproductive skew. We also introduce a two-allele infinite-sites version of the Λ-Fleming–Viot process, and we use it to study how reproductive skew influences standing genetic diversity in a population. We derive asymptotic formulas for the expected number of segregating sites as a function of sample size and offspring distribution. We find that the Wright–Fisher model minimizes the equilibrium genetic diversity, for a given mutation rate and variance effective population size, compared to all other Λ-processes. PMID:24473932

  14. Association of HLA class II alleles with hepatitis C virus clearance and persistence in thalassemia patients from Iran.

    PubMed

    Samimi-Rad, Katayoun; Sadeghi, Farzin; Amirzargar, Aliakbar; Eshraghian, Mohamad Reza; Alavian, Seyed-Moayed; Rahimnia, Ramin

    2015-09-01

    There is no published data on association of HLA class II alleles with clearance or persistence after acute hepatitis C virus (HCV) infection in patients from Iran. HLA DRB1, DQA1, and DQB1 alleles were determined using polymerase chain reaction amplification with sequence specific primers (PCR-SSP) on a total of 117 thalassemia patients (63 with chronic infection, and 54 with viral clearance) and 120 healthy controls. HLA-DRB1*0301 and DQA1*0501 alleles were found significantly present in patients with HCV clearance compared to those with chronic infection (P = 0.03 and P = 0.0007, respectively). By contrast, DRB1*0701, DQA1*0201, and DQB1*0602 alleles occurred significantly in those with chronic infection compared to those with viral clearance (P = 0.004, P = 0.007, and P = 0.02, respectively). As compared to the controls, DRB1*0301, DRB1*11, DQA1*0501, and DQB1*0301 alleles showed a significant decrease in chronic patients (P = 0.002, P = 0.001, P = 0.0001, and P = 0.0004, respectively). Furthermore, the haplotype frequencies of DRB1*0301, DQA1*0501, DQB1*0201, and DRB1*1101, DQA1*0501, DQB1*0301 were found significantly higher (P = 0.004 and P = 0.04, respectively) in patients with HCV clearance than those with chronic infection. By contrast, the haplotype DRB1*0701, DQA1*0201, DQB1*0201 occurred more frequently (P = 0.02) in those with chronic infection compared with those with viral clearance. These findings suggest that particular HLA alleles and related haplotypes may have an influence on the outcome of HCV infection among the Iranian patients. Some of the HLA alleles found in the Iranian patients are different from those reported elsewhere, suggesting that the immunogenetic makeup for HCV clearance or persistence may vary based on the ethnicity. PMID:25970464

  15. Hadamard speckle contrast reduction

    NASA Astrophysics Data System (ADS)

    Trisnadi, Jahja I.

    2004-01-01

    The condition for a diffuser to produce the maximum speckle contrast reduction with the minimum number of distinct phase patterns is derived. A binary realization of this optimum diffuser is obtained by mapping the rows or columns of a Hadamard matrix to the phase patterns. The method is experimentally verified in the Grating Light Valve laser projection display.

  16. Phonation in Tonal Contrasts

    ERIC Educational Resources Information Center

    Kuang, Jianjing

    2013-01-01

    Phonation is used in many tonal languages, but how it should be incorporated into tonal systems is not well understood. The purpose of this dissertation thus is to examine the role of phonation in tonal contrasts, and to investigate how phonation and pitch interact in the tonal space. This dissertation presents close studies of tonal contrasts…

  17. Flashing anomalous color contrast.

    PubMed

    Pinna, Baingio; Spillmann, Lothar; Werner, John S

    2004-01-01

    A new visual phenomenon that we call flashing anomalous color contrast is described. This phenomenon arises from the interaction between a gray central disk and a chromatic annulus surrounded by black radial lines. In an array of such figures, the central gray disk no longer appears gray, but assumes a color complementary to that of the surrounding annulus. The induced color appears: (1) vivid and saturated; (2) self-luminous, not a surface property; (3) flashing with eye or stimulus movement; (4) floating out of its confines; and (5) stronger in extrafoveal than in foveal vision. The strength of the effect depends on the number, length, width, and luminance contrast of the radial lines. The results suggest that the chromatic ring bounding the inner tips of the black radial lines induces simultaneous color contrast, whereas the radial lines elicit, in conjunction with the gray disk and the ring, the flashing, vividness, and high saturation of the effect. The stimulus properties inducing the illusion suggest that flashing anomalous color contrast may be based on asynchronous interactions among multiple visual pathways. PMID:15518215

  18. Ecological interactions and the fitness effect of water-use efficiency: Competition and drought alter the impact of natural MPK12 alleles in Arabidopsis.

    PubMed

    Campitelli, Brandon E; Des Marais, David L; Juenger, Thomas E

    2016-04-01

    The presence of substantial genetic variation for water-use efficiency (WUE) suggests that natural selection plays a role in maintaining alleles that affect WUE. Soil water deficit can reduce plant survival, and is likely to impose selection to increase WUE, whereas competition for resources may select for decreased WUE to ensure water acquisition. We tested the fitness consequences of natural allelic variation in a single gene (MPK12) that influences WUE in Arabidopsis, using transgenic lines contrasting in MPK12 alleles, under four treatments; drought/competition, drought/no competition, well-watered/competition, well-watered/no competition. Results revealed an allele × environment interaction: Low WUE plants performed better in competition, resulting from increased resource consumption. Contrastingly, high WUE individuals performed better in no competition, irrespective of water availability, presumably from enhanced water conservation and nitrogen acquisition. Our findings suggest that selection can influence MPK12 evolution, and represents the first assessment of plant fitness resulting from natural allelic variation at a single locus affecting WUE. PMID:26868103

  19. Association between suicide attempt and a tri-allelic functional polymorphism in serotonin transporter gene promoter in Chinese patients with schizophrenia.

    PubMed

    Hung, Chi-Fa; Lung, For-Wey; Chen, Chien-Hsiun; O'Nions, Elizabeth; Hung, Tai-Hsin; Chong, Mian-Yoon; Wu, Ching-Kuan; Wen, Jung-Kwang; Lin, Pao-Yen

    2011-10-31

    Mounting evidence supports the association between a polymorphism in the serotonin transporter gene promoter region (5-HTTLPR) and suicidal behaviour. Recently, a novel variant of the 5-HTTLPR L allele was identified. The previously unknown L(G) allele produced similar levels of gene expression to the S allele and might have been misclassified as a "high-expression" allele in previous association studies. In this study, we aimed to compare the genotype distribution of the tri-allelic 5-HTTLPR polymorphism in 168 Chinese patients with schizophrenia, including 60 suicide attempters and 108 non-suicide attempters. In our analysis, which used the L(A) dominant model, it was found that the L(A) allele carriers were significantly more likely to have attempted suicide (p=0.035). Further analysis showed this association existed only in male patients (p=0.012). A similar association between the L(A) allele and violent suicide attempt was also found (p=0.028). In addition, logistic regression confirmed our findings that male L(A) allele carriers were at a higher risk of suicide, although the lack of a significant association in females may reflect insufficient power due to small sample size. However, no association was found when we examined the traditional bi-allelic 5-HTTLPR. These findings differ from those reported in Caucasian subjects, where no associations have been reported. Different genetic backgrounds may give rise to different allelic distribution, causing differential effects on the expression of endophenotypes of suicide behaviours. Although the potential influence of multiple comparisons might weaken our findings, our study provides preliminary evidence for a potentially gender-specific role of a "high-expression" 5-HTTLPR polymorphism in susceptibility to suicide in Chinese patients with schizophrenia. PMID:21964390

  20. Systematic Detection of Epistatic Interactions Based on Allele Pair Frequencies

    PubMed Central

    Ackermann, Marit; Beyer, Andreas

    2012-01-01

    Epistatic genetic interactions are key for understanding the genetic contribution to complex traits. Epistasis is always defined with respect to some trait such as growth rate or fitness. Whereas most existing epistasis screens explicitly test for a trait, it is also possible to implicitly test for fitness traits by searching for the over- or under-representation of allele pairs in a given population. Such analysis of imbalanced allele pair frequencies of distant loci has not been exploited yet on a genome-wide scale, mostly due to statistical difficulties such as the multiple testing problem. We propose a new approach called Imbalanced Allele Pair frequencies (ImAP) for inferring epistatic interactions that is exclusively based on DNA sequence information. Our approach is based on genome-wide SNP data sampled from a population with known family structure. We make use of genotype information of parent-child trios and inspect 3×3 contingency tables for detecting pairs of alleles from different genomic positions that are over- or under-represented in the population. We also developed a simulation setup which mimics the pedigree structure by simultaneously assuming independence of the markers. When applied to mouse SNP data, our method detected 168 imbalanced allele pairs, which is substantially more than in simulations assuming no interactions. We could validate a significant number of the interactions with external data, and we found that interacting loci are enriched for genes involved in developmental processes. PMID:22346757

  1. Rare allelic forms of PRDM9 associated with childhood leukemogenesis

    PubMed Central

    Hussin, Julie; Sinnett, Daniel; Casals, Ferran; Idaghdour, Youssef; Bruat, Vanessa; Saillour, Virginie; Healy, Jasmine; Grenier, Jean-Christophe; de Malliard, Thibault; Busche, Stephan; Spinella, Jean-François; Larivière, Mathieu; Gibson, Greg; Andersson, Anna; Holmfeldt, Linda; Ma, Jing; Wei, Lei; Zhang, Jinghui; Andelfinger, Gregor; Downing, James R.; Mullighan, Charles G.; Awadalla, Philip

    2013-01-01

    One of the most rapidly evolving genes in humans, PRDM9, is a key determinant of the distribution of meiotic recombination events. Mutations in this meiotic-specific gene have previously been associated with male infertility in humans and recent studies suggest that PRDM9 may be involved in pathological genomic rearrangements. In studying genomes from families with children affected by B-cell precursor acute lymphoblastic leukemia (B-ALL), we characterized meiotic recombination patterns within a family with two siblings having hyperdiploid childhood B-ALL and observed unusual localization of maternal recombination events. The mother of the family carries a rare PRDM9 allele, potentially explaining the unusual patterns found. From exomes sequenced in 44 additional parents of children affected with B-ALL, we discovered a substantial and significant excess of rare allelic forms of PRDM9. The rare PRDM9 alleles are transmitted to the affected children in half the cases; nonetheless there remains a significant excess of rare alleles among patients relative to controls. We successfully replicated this latter observation in an independent cohort of 50 children with B-ALL, where we found an excess of rare PRDM9 alleles in aneuploid and infant B-ALL patients. PRDM9 variability in humans is thought to influence genomic instability, and these data support a potential role for PRDM9 variation in risk of acquiring aneuploidies or genomic rearrangements associated with childhood leukemogenesis. PMID:23222848

  2. STR allele sequence variation: Current knowledge and future issues.

    PubMed

    Gettings, Katherine Butler; Aponte, Rachel A; Vallone, Peter M; Butler, John M

    2015-09-01

    This article reviews what is currently known about short tandem repeat (STR) allelic sequence variation in and around the twenty-four loci most commonly used throughout the world to perform forensic DNA investigations. These STR loci include D1S1656, TPOX, D2S441, D2S1338, D3S1358, FGA, CSF1PO, D5S818, SE33, D6S1043, D7S820, D8S1179, D10S1248, TH01, vWA, D12S391, D13S317, Penta E, D16S539, D18S51, D19S433, D21S11, Penta D, and D22S1045. All known reported variant alleles are compiled along with genomic information available from GenBank, dbSNP, and the 1000 Genomes Project. Supplementary files are included which provide annotated reference sequences for each STR locus, characterize genomic variation around the STR repeat region, and compare alleles present in currently available STR kit allelic ladders. Looking to the future, STR allele nomenclature options are discussed as they relate to next generation sequencing efforts underway. PMID:26197946

  3. Object-oriented Bayesian networks for paternity cases with allelic dependencies

    PubMed Central

    Hepler, Amanda B.; Weir, Bruce S.

    2008-01-01

    This study extends the current use of Bayesian networks by incorporating the effects of allelic dependencies in paternity calculations. The use of object-oriented networks greatly simplify the process of building and interpreting forensic identification models, allowing researchers to solve new, more complex problems. We explore two paternity examples: the most common scenario where DNA evidence is available from the alleged father, the mother and the child; a more complex casewhere DNA is not available from the alleged father, but is available from the alleged father’s brother. Object-oriented networks are built, using HUGIN, for each example which incorporate the effects of allelic dependence caused by evolutionary relatedness. PMID:19079769

  4. Statistics of Natural Populations. II. Estimating an Allele Probability in Families Descended from Cryptic Mothers

    PubMed Central

    Arnold, Jonathan; Morrison, Melvin L.

    1985-01-01

    In population studies, adults are frequently difficult or inconvenient to identify for genotype, but a family profile of genotypes can be obtained from an unidentified female crossed with a single unidentified male. The problem is to estimate an allele frequency in the cryptic parental gene pool from the observed family profiles. For example, a worker may wish to estimate inversion frequencies in Drosophila; inversion karyotypes are cryptic in adults but visible in salivary gland squashes from larvae. A simple mixture model, which assumes the Hardy-Weinberg law, Mendelian laws and a single randomly chosen mate per female, provides the vehicle for studying three competing estimators of an allele frequency. A simple, heuristically appealing estimator called the Dobzhansky estimator is compared with the maximum likelihood estimator and a close relative called the grouped profiles estimator. The Dobzhansky estimator is computationally simple, consistent and highly efficient and is recommended in practice over its competitors. PMID:17246258

  5. Recombinase-based conditional and reversible gene regulation via XTR alleles

    PubMed Central

    Robles-Oteiza, Camila; Taylor, Sarah; Yates, Travis; Cicchini, Michelle; Lauderback, Brian; Cashman, Christopher R.; Burds, Aurora A.; Winslow, Monte M.; Jacks, Tyler; Feldser, David M.

    2015-01-01

    Synthetic biological tools that enable precise regulation of gene function within in vivo systems have enormous potential to discern gene function in diverse physiological settings. Here we report the development and characterization of a synthetic gene switch that, when targeted in the mouse germline, enables conditional inactivation, reports gene expression and allows inducible restoration of the targeted gene. Gene inactivation and reporter expression is achieved through Cre-mediated stable inversion of an integrated gene-trap reporter, whereas inducible gene restoration is afforded by Flp-dependent deletion of the inverted gene trap. We validate our approach by targeting the p53 and Rb genes and establishing cell line and in vivo cancer model systems, to study the impact of p53 or Rb inactivation and restoration. We term this allele system XTR, to denote each of the allelic states and the associated expression patterns of the targeted gene: eXpressed (XTR), Trapped (TR) and Restored (R). PMID:26537451

  6. Recombinase-based conditional and reversible gene regulation via XTR alleles.

    PubMed

    Robles-Oteiza, Camila; Taylor, Sarah; Yates, Travis; Cicchini, Michelle; Lauderback, Brian; Cashman, Christopher R; Burds, Aurora A; Winslow, Monte M; Jacks, Tyler; Feldser, David M

    2015-01-01

    Synthetic biological tools that enable precise regulation of gene function within in vivo systems have enormous potential to discern gene function in diverse physiological settings. Here we report the development and characterization of a synthetic gene switch that, when targeted in the mouse germline, enables conditional inactivation, reports gene expression and allows inducible restoration of the targeted gene. Gene inactivation and reporter expression is achieved through Cre-mediated stable inversion of an integrated gene-trap reporter, whereas inducible gene restoration is afforded by Flp-dependent deletion of the inverted gene trap. We validate our approach by targeting the p53 and Rb genes and establishing cell line and in vivo cancer model systems, to study the impact of p53 or Rb inactivation and restoration. We term this allele system XTR, to denote each of the allelic states and the associated expression patterns of the targeted gene: eXpressed (XTR), Trapped (TR) and Restored (R). PMID:26537451

  7. Puroindoline allelic diversity in Indian wheat germplasm and identification of new allelic variants

    PubMed Central

    Kumar, Rohit; Arora, Shaweta; Singh, Kashmir; Garg, Monika

    2015-01-01

    Grain hardness is an important quality trait that influences product development in wheat. This trait is governed by variation in puroindoline proteins (PINA and PINB). Our study evaluated 551 Indian wheat germplasm lines for diversity in Pina and Pinb genes. Eighty-two lines were shortlisted for full length sequencing and grain hardness studies. Sequencing studies identified six unknown alleles: two for the Pina gene and four for the Pinb gene. Five of them were novel with non-synonymous changes in the corresponding amino acid sequences. Identified mutations in the deduced mature proteins and their pre- and pro-peptides influenced the hardness characteristics of the grain. We classified these 82 varieties into different hardness categories with reference to international and Indian systems of classification. The majority of Indian wheat varieties were categorized as hard. This study revealed that unexplored Indian wheat germplasm can be a good source of genetic variability for both Pina and Pinb genes, helping in marker-assisted breeding and in obtaining wheat with different textural properties. PMID:26366114

  8. Detection of Allelic Frequency Differences between the Sexes in Humans: A Signature of Sexually Antagonistic Selection.

    PubMed

    Lucotte, Elise A; Laurent, Romain; Heyer, Evelyne; Ségurel, Laure; Toupance, Bruno

    2016-01-01

    Sexually antagonistic (SA) selection, a form of selection that can occur when both sexes have different fitness optima for a trait, is a major force shaping the evolution of organisms. A seminal model developed by Rice (Rice WR. 1984. Sex chromosomes and the evolution of sexual dimorphism. Evolution 38:735-742.) predicts that the X chromosome should be a hotspot for the accumulation of loci under SA selection as compared with the autosomes. Here, we propose a methodological framework designed to detect a specific signature of SA selection on viability, differences in allelic frequencies between the sexes. Applying this method on genome-wide single nucleotide polymorphism (SNP) data in human populations where no sex-specific population stratification could be detected, we show that there are overall significantly more SNPs exhibiting differences in allelic frequencies between the sexes on the X chromosome as compared with autosomes, supporting the predictions of Rice's model. This pattern is consistent across populations and is robust to correction for potential biases such as differences in linkage disequilibrium, sample size, and genotyping errors between chromosomes. Although SA selection is not the only factor resulting in allelic frequency differences between the sexes, we further show that at least part of the identified X-linked loci is caused by such a sex-specific processes. PMID:27189992