WorldWideScience

Sample records for inferred functional association

  1. Posterior association networks and functional modules inferred from rich phenotypes of gene perturbations.

    Directory of Open Access Journals (Sweden)

    Xin Wang

    Full Text Available Combinatorial gene perturbations provide rich information for a systematic exploration of genetic interactions. Despite successful applications to bacteria and yeast, the scalability of this approach remains a major challenge for higher organisms such as humans. Here, we report a novel experimental and computational framework to efficiently address this challenge by limiting the 'search space' for important genetic interactions. We propose to integrate rich phenotypes of multiple single gene perturbations to robustly predict functional modules, which can subsequently be subjected to further experimental investigations such as combinatorial gene silencing. We present posterior association networks (PANs to predict functional interactions between genes estimated using a Bayesian mixture modelling approach. The major advantage of this approach over conventional hypothesis tests is that prior knowledge can be incorporated to enhance predictive power. We demonstrate in a simulation study and on biological data, that integrating complementary information greatly improves prediction accuracy. To search for significant modules, we perform hierarchical clustering with multiscale bootstrap resampling. We demonstrate the power of the proposed methodologies in applications to Ewing's sarcoma and human adult stem cells using publicly available and custom generated data, respectively. In the former application, we identify a gene module including many confirmed and highly promising therapeutic targets. Genes in the module are also significantly overrepresented in signalling pathways that are known to be critical for proliferation of Ewing's sarcoma cells. In the latter application, we predict a functional network of chromatin factors controlling epidermal stem cell fate. Further examinations using ChIP-seq, ChIP-qPCR and RT-qPCR reveal that the basis of their genetic interactions may arise from transcriptional cross regulation. A Bioconductor package

  2. Simple Math is Enough: Two Examples of Inferring Functional Associations from Genomic Data

    Science.gov (United States)

    Liang, Shoudan

    2003-01-01

    Non-random features in the genomic data are usually biologically meaningful. The key is to choose the feature well. Having a p-value based score prioritizes the findings. If two proteins share a unusually large number of common interaction partners, they tend to be involved in the same biological process. We used this finding to predict the functions of 81 un-annotated proteins in yeast.

  3. Functional associations between support use and forelimb shape in strepsirrhines and their relevance to inferring locomotor behavior in early primates.

    Science.gov (United States)

    Fabre, Anne-Claire; Marigó, Judit; Granatosky, Michael C; Schmitt, Daniel

    2017-07-01

    The evolution of primates is intimately linked to their initial invasion of an arboreal environment. However, moving and foraging in this milieu creates significant mechanical challenges related to the presence of substrates differing in their size and orientation. It is widely assumed that primates are behaviorally and anatomically adapted to movement on specific substrates, but few explicit tests of this relationship in an evolutionary context have been conducted. Without direct tests of form-function relationships in living primates it is impossible to reliably infer behavior in fossil taxa. In this study, we test a hypothesis of co-variation between forelimb morphology and the type of substrates used by strepsirrhines. If associations between anatomy and substrate use exist, these can then be applied to better understand limb anatomy of extinct primates. The co-variation between each forelimb long bone and the type of substrate used was studied in a phylogenetic context. Our results show that despite the presence of significant phylogenetic signal for each long bone of the forelimb, clear support use associations are present. A strong co-variation was found between the type of substrate used and the shape of the radius, with and without taking phylogeny into account, whereas co-variation was significant for the ulna only when taking phylogeny into account. Species that use a thin branch milieu show radii that are gracile and straight and have a distal articular shape that allows for a wide range of movements. In contrast, extant species that commonly use large supports show a relatively robust and curved radius with an increased surface area available for forearm and hand muscles in pronated posture. These results, especially for the radius, support the idea that strepsirrhine primates exhibit specific skeletal adaptations associated with the supports that they habitually move on. With these robust associations in hand it will be possible to explore the same

  4. Methodology for the inference of gene function from phenotype data.

    Science.gov (United States)

    Ascensao, Joao A; Dolan, Mary E; Hill, David P; Blake, Judith A

    2014-12-12

    Biomedical ontologies are increasingly instrumental in the advancement of biological research primarily through their use to efficiently consolidate large amounts of data into structured, accessible sets. However, ontology development and usage can be hampered by the segregation of knowledge by domain that occurs due to independent development and use of the ontologies. The ability to infer data associated with one ontology to data associated with another ontology would prove useful in expanding information content and scope. We here focus on relating two ontologies: the Gene Ontology (GO), which encodes canonical gene function, and the Mammalian Phenotype Ontology (MP), which describes non-canonical phenotypes, using statistical methods to suggest GO functional annotations from existing MP phenotype annotations. This work is in contrast to previous studies that have focused on inferring gene function from phenotype primarily through lexical or semantic similarity measures. We have designed and tested a set of algorithms that represents a novel methodology to define rules for predicting gene function by examining the emergent structure and relationships between the gene functions and phenotypes rather than inspecting the terms semantically. The algorithms inspect relationships among multiple phenotype terms to deduce if there are cases where they all arise from a single gene function. We apply this methodology to data about genes in the laboratory mouse that are formally represented in the Mouse Genome Informatics (MGI) resource. From the data, 7444 rule instances were generated from five generalized rules, resulting in 4818 unique GO functional predictions for 1796 genes. We show that our method is capable of inferring high-quality functional annotations from curated phenotype data. As well as creating inferred annotations, our method has the potential to allow for the elucidation of unforeseen, biologically significant associations between gene function and

  5. Functional networks inference from rule-based machine learning models.

    Science.gov (United States)

    Lazzarini, Nicola; Widera, Paweł; Williamson, Stuart; Heer, Rakesh; Krasnogor, Natalio; Bacardit, Jaume

    2016-01-01

    Functional networks play an important role in the analysis of biological processes and systems. The inference of these networks from high-throughput (-omics) data is an area of intense research. So far, the similarity-based inference paradigm (e.g. gene co-expression) has been the most popular approach. It assumes a functional relationship between genes which are expressed at similar levels across different samples. An alternative to this paradigm is the inference of relationships from the structure of machine learning models. These models are able to capture complex relationships between variables, that often are different/complementary to the similarity-based methods. We propose a protocol to infer functional networks from machine learning models, called FuNeL. It assumes, that genes used together within a rule-based machine learning model to classify the samples, might also be functionally related at a biological level. The protocol is first tested on synthetic datasets and then evaluated on a test suite of 8 real-world datasets related to human cancer. The networks inferred from the real-world data are compared against gene co-expression networks of equal size, generated with 3 different methods. The comparison is performed from two different points of view. We analyse the enriched biological terms in the set of network nodes and the relationships between known disease-associated genes in a context of the network topology. The comparison confirms both the biological relevance and the complementary character of the knowledge captured by the FuNeL networks in relation to similarity-based methods and demonstrates its potential to identify known disease associations as core elements of the network. Finally, using a prostate cancer dataset as a case study, we confirm that the biological knowledge captured by our method is relevant to the disease and consistent with the specialised literature and with an independent dataset not used in the inference process. The

  6. Inferring biological functions of guanylyl cyclases with computational methods

    KAUST Repository

    Alquraishi, May Majed; Meier, Stuart Kurt

    2013-01-01

    A number of studies have shown that functionally related genes are often co-expressed and that computational based co-expression analysis can be used to accurately identify functional relationships between genes and by inference, their encoded proteins. Here we describe how a computational based co-expression analysis can be used to link the function of a specific gene of interest to a defined cellular response. Using a worked example we demonstrate how this methodology is used to link the function of the Arabidopsis Wall-Associated Kinase-Like 10 gene, which encodes a functional guanylyl cyclase, to host responses to pathogens. © Springer Science+Business Media New York 2013.

  7. Inferring biological functions of guanylyl cyclases with computational methods

    KAUST Repository

    Alquraishi, May Majed

    2013-09-03

    A number of studies have shown that functionally related genes are often co-expressed and that computational based co-expression analysis can be used to accurately identify functional relationships between genes and by inference, their encoded proteins. Here we describe how a computational based co-expression analysis can be used to link the function of a specific gene of interest to a defined cellular response. Using a worked example we demonstrate how this methodology is used to link the function of the Arabidopsis Wall-Associated Kinase-Like 10 gene, which encodes a functional guanylyl cyclase, to host responses to pathogens. © Springer Science+Business Media New York 2013.

  8. Functional neuroanatomy of intuitive physical inference.

    Science.gov (United States)

    Fischer, Jason; Mikhael, John G; Tenenbaum, Joshua B; Kanwisher, Nancy

    2016-08-23

    To engage with the world-to understand the scene in front of us, plan actions, and predict what will happen next-we must have an intuitive grasp of the world's physical structure and dynamics. How do the objects in front of us rest on and support each other, how much force would be required to move them, and how will they behave when they fall, roll, or collide? Despite the centrality of physical inferences in daily life, little is known about the brain mechanisms recruited to interpret the physical structure of a scene and predict how physical events will unfold. Here, in a series of fMRI experiments, we identified a set of cortical regions that are selectively engaged when people watch and predict the unfolding of physical events-a "physics engine" in the brain. These brain regions are selective to physical inferences relative to nonphysical but otherwise highly similar scenes and tasks. However, these regions are not exclusively engaged in physical inferences per se or, indeed, even in scene understanding; they overlap with the domain-general "multiple demand" system, especially the parts of that system involved in action planning and tool use, pointing to a close relationship between the cognitive and neural mechanisms involved in parsing the physical content of a scene and preparing an appropriate action.

  9. Towards Bayesian Inference of the Fast-Ion Distribution Function

    DEFF Research Database (Denmark)

    Stagner, L.; Heidbrink, W.W.; Salewski, Mirko

    2012-01-01

    sensitivity of the measurements are incorporated into Bayesian likelihood probabilities, while prior probabilities enforce physical constraints. As an initial step, this poster uses Bayesian statistics to infer the DIII-D electron density profile from multiple diagnostic measurements. Likelihood functions....... However, when theory and experiment disagree (for one or more diagnostics), it is unclear how to proceed. Bayesian statistics provides a framework to infer the DF, quantify errors, and reconcile discrepant diagnostic measurements. Diagnostic errors and ``weight functions" that describe the phase space...

  10. Correlated measurement error hampers association network inference

    NARCIS (Netherlands)

    Kaduk, M.; Hoefsloot, H.C.J.; Vis, D.J.; Reijmers, T.; Greef, J. van der; Smilde, A.K.; Hendriks, M.M.W.B.

    2014-01-01

    Modern chromatography-based metabolomics measurements generate large amounts of data in the form of abundances of metabolites. An increasingly popular way of representing and analyzing such data is by means of association networks. Ideally, such a network can be interpreted in terms of the

  11. Inference

    DEFF Research Database (Denmark)

    Møller, Jesper

    2010-01-01

    Chapter 9: This contribution concerns statistical inference for parametric models used in stochastic geometry and based on quick and simple simulation free procedures as well as more comprehensive methods based on a maximum likelihood or Bayesian approach combined with markov chain Monte Carlo...... (MCMC) techniques. Due to space limitations the focus is on spatial point processes....

  12. Progress on Bayesian Inference of the Fast Ion Distribution Function

    DEFF Research Database (Denmark)

    Stagner, L.; Heidbrink, W.W,; Chen, X.

    2013-01-01

    . However, when theory and experiment disagree (for one or more diagnostics), it is unclear how to proceed. Bayesian statistics provides a framework to infer the DF, quantify errors, and reconcile discrepant diagnostic measurements. Diagnostic errors and weight functions that describe the phase space...... sensitivity of the measurements are incorporated into Bayesian likelihood probabilities. Prior probabilities describe physical constraints. This poster will show reconstructions of classically described, low-power, MHD-quiescent distribution functions from actual FIDA measurements. A description of the full...

  13. Inference

    DEFF Research Database (Denmark)

    Møller, Jesper

    (This text written by Jesper Møller, Aalborg University, is submitted for the collection ‘Stochastic Geometry: Highlights, Interactions and New Perspectives', edited by Wilfrid S. Kendall and Ilya Molchanov, to be published by ClarendonPress, Oxford, and planned to appear as Section 4.1 with the ......(This text written by Jesper Møller, Aalborg University, is submitted for the collection ‘Stochastic Geometry: Highlights, Interactions and New Perspectives', edited by Wilfrid S. Kendall and Ilya Molchanov, to be published by ClarendonPress, Oxford, and planned to appear as Section 4.......1 with the title ‘Inference'.) This contribution concerns statistical inference for parametric models used in stochastic geometry and based on quick and simple simulation free procedures as well as more comprehensive methods using Markov chain Monte Carlo (MCMC) simulations. Due to space limitations the focus...

  14. Classical methods for interpreting objective function minimization as intelligent inference

    Energy Technology Data Exchange (ETDEWEB)

    Golden, R.M. [Univ. of Texas, Dallas, TX (United States)

    1996-12-31

    Most recognition algorithms and neural networks can be formally viewed as seeking a minimum value of an appropriate objective function during either classification or learning phases. The goal of this paper is to argue that in order to show a recognition algorithm is making intelligent inferences, it is not sufficient to show that the recognition algorithm is computing (or trying to compute) the global minimum of some objective function. One must explicitly define a {open_quotes}relational system{close_quotes} for the recognition algorithm or neural network which identifies the: (i) sample space, (ii) the relevant sigmafield of events generated by the sample space, and (iii) the {open_quotes}relation{close_quotes} for that relational system. Only when such a {open_quotes}relational system{close_quotes} is properly defined, is it possible to formally establish the sense in which computing the global minimum of an objective function is an intelligent, inference.

  15. GWIS: Genome-Wide Inferred Statistics for Functions of Multiple Phenotypes

    NARCIS (Netherlands)

    Nieuwboer, H.A.; Pool, R.; Dolan, C.V.; Boomsma, D.I.; Nivard, M.G.

    2016-01-01

    Here we present a method of genome-wide inferred study (GWIS) that provides an approximation of genome-wide association study (GWAS) summary statistics for a variable that is a function of phenotypes for which GWAS summary statistics, phenotypic means, and covariances are available. A GWIS can be

  16. Information retrieval system with ability of analogical inference using semantic network and function of fuzzification

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, K; Iwai, S

    1982-01-01

    In information retrieval system, it is necessary to grasp user's subject of interest in order to present appropriate documents to the user. In this paper, the authors propose a model of human ability of analogical inference based on association between key words and, using it, construct an information retrieval system in which the computer with the ability learns its user's subject of interest through question-answering with the user. In this system, the association between key words is represented by a semantic network, and a function of fuzzification of input information is introduced in the semantic network to implement the ability of analogical inference based on the association. Finally, the effect of analogical inference on the learning efficiency of the system is investigated. 5 references.

  17. Systematic inference of functional phosphorylation events in yeast metabolism.

    Science.gov (United States)

    Chen, Yu; Wang, Yonghong; Nielsen, Jens

    2017-07-01

    Protein phosphorylation is a post-translational modification that affects proteins by changing their structure and conformation in a rapid and reversible way, and it is an important mechanism for metabolic regulation in cells. Phosphoproteomics enables high-throughput identification of phosphorylation events on metabolic enzymes, but identifying functional phosphorylation events still requires more detailed biochemical characterization. Therefore, development of computational methods for investigating unknown functions of a large number of phosphorylation events identified by phosphoproteomics has received increased attention. We developed a mathematical framework that describes the relationship between phosphorylation level of a metabolic enzyme and the corresponding flux through the enzyme. Using this framework, it is possible to quantitatively estimate contribution of phosphorylation events to flux changes. We showed that phosphorylation regulation analysis, combined with a systematic workflow and correlation analysis, can be used for inference of functional phosphorylation events in steady and dynamic conditions, respectively. Using this analysis, we assigned functionality to phosphorylation events of 17 metabolic enzymes in the yeast Saccharomyces cerevisiae , among which 10 are novel. Phosphorylation regulation analysis cannot only be extended for inference of other functional post-translational modifications but also be a promising scaffold for multi-omics data integration in systems biology. Matlab codes for flux balance analysis in this study are available in Supplementary material. yhwang@ecust.edu.cn or nielsenj@chalmers.se. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  18. Inference of gene-phenotype associations via protein-protein interaction and orthology.

    Directory of Open Access Journals (Sweden)

    Panwen Wang

    Full Text Available One of the fundamental goals of genetics is to understand gene functions and their associated phenotypes. To achieve this goal, in this study we developed a computational algorithm that uses orthology and protein-protein interaction information to infer gene-phenotype associations for multiple species. Furthermore, we developed a web server that provides genome-wide phenotype inference for six species: fly, human, mouse, worm, yeast, and zebrafish. We evaluated our inference method by comparing the inferred results with known gene-phenotype associations. The high Area Under the Curve values suggest a significant performance of our method. By applying our method to two human representative diseases, Type 2 Diabetes and Breast Cancer, we demonstrated that our method is able to identify related Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. The web server can be used to infer functions and putative phenotypes of a gene along with the candidate genes of a phenotype, and thus aids in disease candidate gene discovery. Our web server is available at http://jjwanglab.org/PhenoPPIOrth.

  19. Network inference from functional experimental data (Conference Presentation)

    Science.gov (United States)

    Desrosiers, Patrick; Labrecque, Simon; Tremblay, Maxime; Bélanger, Mathieu; De Dorlodot, Bertrand; Côté, Daniel C.

    2016-03-01

    Functional connectivity maps of neuronal networks are critical tools to understand how neurons form circuits, how information is encoded and processed by neurons, how memory is shaped, and how these basic processes are altered under pathological conditions. Current light microscopy allows to observe calcium or electrical activity of thousands of neurons simultaneously, yet assessing comprehensive connectivity maps directly from such data remains a non-trivial analytical task. There exist simple statistical methods, such as cross-correlation and Granger causality, but they only detect linear interactions between neurons. Other more involved inference methods inspired by information theory, such as mutual information and transfer entropy, identify more accurately connections between neurons but also require more computational resources. We carried out a comparative study of common connectivity inference methods. The relative accuracy and computational cost of each method was determined via simulated fluorescence traces generated with realistic computational models of interacting neurons in networks of different topologies (clustered or non-clustered) and sizes (10-1000 neurons). To bridge the computational and experimental works, we observed the intracellular calcium activity of live hippocampal neuronal cultures infected with the fluorescent calcium marker GCaMP6f. The spontaneous activity of the networks, consisting of 50-100 neurons per field of view, was recorded from 20 to 50 Hz on a microscope controlled by a homemade software. We implemented all connectivity inference methods in the software, which rapidly loads calcium fluorescence movies, segments the images, extracts the fluorescence traces, and assesses the functional connections (with strengths and directions) between each pair of neurons. We used this software to assess, in real time, the functional connectivity from real calcium imaging data in basal conditions, under plasticity protocols, and epileptic

  20. Nonparametric Bayesian inference for mean residual life functions in survival analysis.

    Science.gov (United States)

    Poynor, Valerie; Kottas, Athanasios

    2018-01-19

    Modeling and inference for survival analysis problems typically revolves around different functions related to the survival distribution. Here, we focus on the mean residual life (MRL) function, which provides the expected remaining lifetime given that a subject has survived (i.e. is event-free) up to a particular time. This function is of direct interest in reliability, medical, and actuarial fields. In addition to its practical interpretation, the MRL function characterizes the survival distribution. We develop general Bayesian nonparametric inference for MRL functions built from a Dirichlet process mixture model for the associated survival distribution. The resulting model for the MRL function admits a representation as a mixture of the kernel MRL functions with time-dependent mixture weights. This model structure allows for a wide range of shapes for the MRL function. Particular emphasis is placed on the selection of the mixture kernel, taken to be a gamma distribution, to obtain desirable properties for the MRL function arising from the mixture model. The inference method is illustrated with a data set of two experimental groups and a data set involving right censoring. The supplementary material available at Biostatistics online provides further results on empirical performance of the model, using simulated data examples. © The Author 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Explanation and inference: Mechanistic and functional explanations guide property generalization

    Directory of Open Access Journals (Sweden)

    Tania eLombrozo

    2014-09-01

    Full Text Available The ability to generalize from the known to the unknown is central to learning and inference. Two experiments explore the relationship between how a property is explained and how that property is generalized to novel species and artifacts. The experiments contrast the consequences of explaining a property mechanistically, by appeal to parts and processes, with the consequences of explaining the property functionally, by appeal to functions and goals. The findings suggest that properties that are explained functionally are more likely to be generalized on the basis of shared functions, with a weaker relationship between mechanistic explanations and generalization on the basis of shared parts and processes. The influence of explanation type on generalization holds even though all participants are provided with the same mechanistic and functional information, and whether an explanation type is freely generated (Experiment 1, experimentally provided (Experiment 2, or experimentally induced (Experiment 2. The experiments also demonstrate that explanations and generalizations of a particular type (mechanistic or functional can be experimentally induced by providing sample explanations of that type, with a comparable effect when the sample explanations come from the same domain or from a different domains. These results suggest that explanations serve as a guide to generalization, and contribute to a growing body of work supporting the value of distinguishing mechanistic and functional explanations.

  2. Explanation and inference: mechanistic and functional explanations guide property generalization.

    Science.gov (United States)

    Lombrozo, Tania; Gwynne, Nicholas Z

    2014-01-01

    The ability to generalize from the known to the unknown is central to learning and inference. Two experiments explore the relationship between how a property is explained and how that property is generalized to novel species and artifacts. The experiments contrast the consequences of explaining a property mechanistically, by appeal to parts and processes, with the consequences of explaining the property functionally, by appeal to functions and goals. The findings suggest that properties that are explained functionally are more likely to be generalized on the basis of shared functions, with a weaker relationship between mechanistic explanations and generalization on the basis of shared parts and processes. The influence of explanation type on generalization holds even though all participants are provided with the same mechanistic and functional information, and whether an explanation type is freely generated (Experiment 1), experimentally provided (Experiment 2), or experimentally induced (Experiment 2). The experiments also demonstrate that explanations and generalizations of a particular type (mechanistic or functional) can be experimentally induced by providing sample explanations of that type, with a comparable effect when the sample explanations come from the same domain or from a different domains. These results suggest that explanations serve as a guide to generalization, and contribute to a growing body of work supporting the value of distinguishing mechanistic and functional explanations.

  3. Inferring Parametric Energy Consumption Functions at Different Software Levels

    DEFF Research Database (Denmark)

    Liqat, Umer; Georgiou, Kyriakos; Kerrison, Steve

    2016-01-01

    The static estimation of the energy consumed by program executions is an important challenge, which has applications in program optimization and verification, and is instrumental in energy-aware software development. Our objective is to estimate such energy consumption in the form of functions...... on the input data sizes of programs. We have developed a tool for experimentation with static analysis which infers such energy functions at two levels, the instruction set architecture (ISA) and the intermediate code (LLVM IR) levels, and reflects it upwards to the higher source code level. This required...... the development of a translation from LLVM IR to an intermediate representation and its integration with existing components, a translation from ISA to the same representation, a resource analyzer, an ISA-level energy model, and a mapping from this model to LLVM IR. The approach has been applied to programs...

  4. Improved functional overview of protein complexes using inferred epistatic relationships

    LENUS (Irish Health Repository)

    Ryan, Colm

    2011-05-23

    Abstract Background Epistatic Miniarray Profiling(E-MAP) quantifies the net effect on growth rate of disrupting pairs of genes, often producing phenotypes that may be more (negative epistasis) or less (positive epistasis) severe than the phenotype predicted based on single gene disruptions. Epistatic interactions are important for understanding cell biology because they define relationships between individual genes, and between sets of genes involved in biochemical pathways and protein complexes. Each E-MAP screen quantifies the interactions between a logically selected subset of genes (e.g. genes whose products share a common function). Interactions that occur between genes involved in different cellular processes are not as frequently measured, yet these interactions are important for providing an overview of cellular organization. Results We introduce a method for combining overlapping E-MAP screens and inferring new interactions between them. We use this method to infer with high confidence 2,240 new strongly epistatic interactions and 34,469 weakly epistatic or neutral interactions. We show that accuracy of the predicted interactions approaches that of replicate experiments and that, like measured interactions, they are enriched for features such as shared biochemical pathways and knockout phenotypes. We constructed an expanded epistasis map for yeast cell protein complexes and show that our new interactions increase the evidence for previously proposed inter-complex connections, and predict many new links. We validated a number of these in the laboratory, including new interactions linking the SWR-C chromatin modifying complex and the nuclear transport apparatus. Conclusion Overall, our data support a modular model of yeast cell protein network organization and show how prediction methods can considerably extend the information that can be extracted from overlapping E-MAP screens.

  5. Self-Associations Influence Task-Performance through Bayesian Inference.

    Science.gov (United States)

    Bengtsson, Sara L; Penny, Will D

    2013-01-01

    The way we think about ourselves impacts greatly on our behavior. This paper describes a behavioral study and a computational model that shed new light on this important area. Participants were primed "clever" and "stupid" using a scrambled sentence task, and we measured the effect on response time and error-rate on a rule-association task. First, we observed a confirmation bias effect in that associations to being "stupid" led to a gradual decrease in performance, whereas associations to being "clever" did not. Second, we observed that the activated self-concepts selectively modified attention toward one's performance. There was an early to late double dissociation in RTs in that primed "clever" resulted in RT increase following error responses, whereas primed "stupid" resulted in RT increase following correct responses. We propose a computational model of subjects' behavior based on the logic of the experimental task that involves two processes; memory for rules and the integration of rules with subsequent visual cues. The model incorporates an adaptive decision threshold based on Bayes rule, whereby decision thresholds are increased if integration was inferred to be faulty. Fitting the computational model to experimental data confirmed our hypothesis that priming affects the memory process. This model explains both the confirmation bias and double dissociation effects and demonstrates that Bayesian inferential principles can be used to study the effect of self-concepts on behavior.

  6. Self-associations influence task-performance through Bayesian inference

    Directory of Open Access Journals (Sweden)

    Sara L Bengtsson

    2013-08-01

    Full Text Available The way we think about ourselves impacts greatly on our behaviour. This paper describes a behavioural study and a computational model that sheds new light on this important area. Participants were primed 'clever' and 'stupid' using a scrambled sentence task, and we measured the effect on response time and error-rate on a rule-association task. First, we observed a confirmation bias effect in that associations to being 'stupid' led to a gradual decrease in performance, whereas associations to being 'clever' did not. Second, we observed that the activated self-concepts selectively modified attention towards one's performance. There was an early to late double dissociation in RTs in that primed 'clever' resulted in RT increase following error responses, whereas primed 'stupid' resulted in RT increase following correct responses. We propose a computational model of subjects' behaviour based on the logic of the experimental task that involves two processes; memory for rules and the integration of rules with subsequent visual cues. The model also incorporates an adaptive decision threshold based on Bayes rule, whereby decision thresholds are increased if integration was inferred to be faulty. Fitting the computational model to experimental data confirmed our hypothesis that priming affects the memory process. This model explains both the confirmation bias and double dissociation effects and demonstrates that Bayesian inferential principles can be used to study the effect of self-concepts on behaviour.

  7. Pathogenomic inference of virulence-associated genes in Leptospira interrogans.

    Directory of Open Access Journals (Sweden)

    Jason S Lehmann

    Full Text Available Leptospirosis is a globally important, neglected zoonotic infection caused by spirochetes of the genus Leptospira. Since genetic transformation remains technically limited for pathogenic Leptospira, a systems biology pathogenomic approach was used to infer leptospiral virulence genes by whole genome comparison of culture-attenuated Leptospira interrogans serovar Lai with its virulent, isogenic parent. Among the 11 pathogen-specific protein-coding genes in which non-synonymous mutations were found, a putative soluble adenylate cyclase with host cell cAMP-elevating activity, and two members of a previously unstudied ∼15 member paralogous gene family of unknown function were identified. This gene family was also uniquely found in the alpha-proteobacteria Bartonella bacilliformis and Bartonella australis that are geographically restricted to the Andes and Australia, respectively. How the pathogenic Leptospira and these two Bartonella species came to share this expanded gene family remains an evolutionary mystery. In vivo expression analyses demonstrated up-regulation of 10/11 Leptospira genes identified in the attenuation screen, and profound in vivo, tissue-specific up-regulation by members of the paralogous gene family, suggesting a direct role in virulence and host-pathogen interactions. The pathogenomic experimental design here is generalizable as a functional systems biology approach to studying bacterial pathogenesis and virulence and should encourage similar experimental studies of other pathogens.

  8. Pathogenomic inference of virulence-associated genes in Leptospira interrogans.

    Science.gov (United States)

    Lehmann, Jason S; Fouts, Derrick E; Haft, Daniel H; Cannella, Anthony P; Ricaldi, Jessica N; Brinkac, Lauren; Harkins, Derek; Durkin, Scott; Sanka, Ravi; Sutton, Granger; Moreno, Angelo; Vinetz, Joseph M; Matthias, Michael A

    2013-01-01

    Leptospirosis is a globally important, neglected zoonotic infection caused by spirochetes of the genus Leptospira. Since genetic transformation remains technically limited for pathogenic Leptospira, a systems biology pathogenomic approach was used to infer leptospiral virulence genes by whole genome comparison of culture-attenuated Leptospira interrogans serovar Lai with its virulent, isogenic parent. Among the 11 pathogen-specific protein-coding genes in which non-synonymous mutations were found, a putative soluble adenylate cyclase with host cell cAMP-elevating activity, and two members of a previously unstudied ∼15 member paralogous gene family of unknown function were identified. This gene family was also uniquely found in the alpha-proteobacteria Bartonella bacilliformis and Bartonella australis that are geographically restricted to the Andes and Australia, respectively. How the pathogenic Leptospira and these two Bartonella species came to share this expanded gene family remains an evolutionary mystery. In vivo expression analyses demonstrated up-regulation of 10/11 Leptospira genes identified in the attenuation screen, and profound in vivo, tissue-specific up-regulation by members of the paralogous gene family, suggesting a direct role in virulence and host-pathogen interactions. The pathogenomic experimental design here is generalizable as a functional systems biology approach to studying bacterial pathogenesis and virulence and should encourage similar experimental studies of other pathogens.

  9. The Human Cochlear Mechanical Nonlinearity Inferred via Psychometric Functions

    Directory of Open Access Journals (Sweden)

    Nizami Lance

    2013-12-01

    Extension of the model of Schairer and colleagues results in credible cochlear nonlinearities in man, suggesting that forward-masking provides a non-invasive way to infer the human mechanical cochlear nonlinearity.

  10. Revised associative inference paradigm confirms relational memory impairment in schizophrenia.

    Science.gov (United States)

    Armstrong, Kristan; Williams, Lisa E; Heckers, Stephan

    2012-07-01

    Patients with schizophrenia have widespread cognitive impairments, with selective deficits in relational memory. We previously reported a differential relational memory deficit in schizophrenia using the Associative Inference Paradigm (AIP), a task suggested by the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative to examine relational memory. However, the AIP had limited feasibility for testing in schizophrenia because of high attrition of schizophrenia patients during training. Here we developed and tested a revised version of the AIP to improve feasibility. 30 healthy control and 37 schizophrenia subjects received 3 study-test sessions on 3 sets of paired associates: H-F1 (house paired with face), H-F2 (same house paired with new face), and F3-F4 (two novel faces). After training, subjects were tested on the trained, noninferential Face-Face pairs (F3-F4) and novel, inferential Face-Face pairs (F1-F2), constructed from the faces of the trained House-Face pairs. Schizophrenia patients were significantly more impaired on the inferential F1-F2 pairs than the noninferential F3-F4 pairs, providing evidence for a differential relational memory deficit. Only 8% of schizophrenia patients were excluded from testing because of poor training performance. The revised AIP confirmed the previous finding of a relational memory deficit in a larger and more representative sample of schizophrenia patients.

  11. CONSTRUCTING A FLEXIBLE LIKELIHOOD FUNCTION FOR SPECTROSCOPIC INFERENCE

    International Nuclear Information System (INIS)

    Czekala, Ian; Andrews, Sean M.; Mandel, Kaisey S.; Green, Gregory M.; Hogg, David W.

    2015-01-01

    We present a modular, extensible likelihood framework for spectroscopic inference based on synthetic model spectra. The subtraction of an imperfect model from a continuously sampled spectrum introduces covariance between adjacent datapoints (pixels) into the residual spectrum. For the high signal-to-noise data with large spectral range that is commonly employed in stellar astrophysics, that covariant structure can lead to dramatically underestimated parameter uncertainties (and, in some cases, biases). We construct a likelihood function that accounts for the structure of the covariance matrix, utilizing the machinery of Gaussian process kernels. This framework specifically addresses the common problem of mismatches in model spectral line strengths (with respect to data) due to intrinsic model imperfections (e.g., in the atomic/molecular databases or opacity prescriptions) by developing a novel local covariance kernel formalism that identifies and self-consistently downweights pathological spectral line “outliers.” By fitting many spectra in a hierarchical manner, these local kernels provide a mechanism to learn about and build data-driven corrections to synthetic spectral libraries. An open-source software implementation of this approach is available at http://iancze.github.io/Starfish, including a sophisticated probabilistic scheme for spectral interpolation when using model libraries that are sparsely sampled in the stellar parameters. We demonstrate some salient features of the framework by fitting the high-resolution V-band spectrum of WASP-14, an F5 dwarf with a transiting exoplanet, and the moderate-resolution K-band spectrum of Gliese 51, an M5 field dwarf

  12. FARNA: knowledgebase of inferred functions of non-coding RNA transcripts

    KAUST Repository

    Alam, Tanvir

    2016-10-12

    Non-coding RNA (ncRNA) genes play a major role in control of heterogeneous cellular behavior. Yet, their functions are largely uncharacterized. Current available databases lack in-depth information of ncRNA functions across spectrum of various cells/tissues. Here, we present FARNA, a knowledgebase of inferred functions of 10,289 human ncRNA transcripts (2,734 microRNA and 7,555 long ncRNA) in 119 tissues and 177 primary cells of human. Since transcription factors (TFs) and TF co-factors (TcoFs) are crucial components of regulatory machinery for activation of gene transcription, cellular processes and diseases in which TFs and TcoFs are involved suggest functions of the transcripts they regulate. In FARNA, functions of a transcript are inferred from TFs and TcoFs whose genes co-express with the transcript controlled by these TFs and TcoFs in a considered cell/tissue. Transcripts were annotated using statistically enriched GO terms, pathways and diseases across cells/tissues based on guilt-by-association principle. Expression profiles across cells/tissues based on Cap Analysis of Gene Expression (CAGE) are provided. FARNA, having the most comprehensive function annotation of considered ncRNAs across widest spectrum of human cells/tissues, has a potential to greatly contribute to our understanding of ncRNA roles and their regulatory mechanisms in human. FARNA can be accessed at: http://cbrc.kaust.edu.sa/farna

  13. FARNA: knowledgebase of inferred functions of non-coding RNA transcripts

    KAUST Repository

    Alam, Tanvir; Uludag, Mahmut; Essack, Magbubah; Salhi, Adil; Ashoor, Haitham; Hanks, John B.; Kapfer, Craig Eric; Mineta, Katsuhiko; Gojobori, Takashi; Bajic, Vladimir B.

    2016-01-01

    Non-coding RNA (ncRNA) genes play a major role in control of heterogeneous cellular behavior. Yet, their functions are largely uncharacterized. Current available databases lack in-depth information of ncRNA functions across spectrum of various cells/tissues. Here, we present FARNA, a knowledgebase of inferred functions of 10,289 human ncRNA transcripts (2,734 microRNA and 7,555 long ncRNA) in 119 tissues and 177 primary cells of human. Since transcription factors (TFs) and TF co-factors (TcoFs) are crucial components of regulatory machinery for activation of gene transcription, cellular processes and diseases in which TFs and TcoFs are involved suggest functions of the transcripts they regulate. In FARNA, functions of a transcript are inferred from TFs and TcoFs whose genes co-express with the transcript controlled by these TFs and TcoFs in a considered cell/tissue. Transcripts were annotated using statistically enriched GO terms, pathways and diseases across cells/tissues based on guilt-by-association principle. Expression profiles across cells/tissues based on Cap Analysis of Gene Expression (CAGE) are provided. FARNA, having the most comprehensive function annotation of considered ncRNAs across widest spectrum of human cells/tissues, has a potential to greatly contribute to our understanding of ncRNA roles and their regulatory mechanisms in human. FARNA can be accessed at: http://cbrc.kaust.edu.sa/farna

  14. Structure-based inference of molecular functions of proteins of unknown function from Berkeley Structural Genomics Center

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung-Hou; Shin, Dong Hae; Hou, Jingtong; Chandonia, John-Marc; Das, Debanu; Choi, In-Geol; Kim, Rosalind; Kim, Sung-Hou

    2007-09-02

    Advances in sequence genomics have resulted in an accumulation of a huge number of protein sequences derived from genome sequences. However, the functions of a large portion of them cannot be inferred based on the current methods of sequence homology detection to proteins of known functions. Three-dimensional structure can have an important impact in providing inference of molecular function (physical and chemical function) of a protein of unknown function. Structural genomics centers worldwide have been determining many 3-D structures of the proteins of unknown functions, and possible molecular functions of them have been inferred based on their structures. Combined with bioinformatics and enzymatic assay tools, the successful acceleration of the process of protein structure determination through high throughput pipelines enables the rapid functional annotation of a large fraction of hypothetical proteins. We present a brief summary of the process we used at the Berkeley Structural Genomics Center to infer molecular functions of proteins of unknown function.

  15. Inferring gene expression dynamics via functional regression analysis

    Directory of Open Access Journals (Sweden)

    Leng Xiaoyan

    2008-01-01

    Full Text Available Abstract Background Temporal gene expression profiles characterize the time-dynamics of expression of specific genes and are increasingly collected in current gene expression experiments. In the analysis of experiments where gene expression is obtained over the life cycle, it is of interest to relate temporal patterns of gene expression associated with different developmental stages to each other to study patterns of long-term developmental gene regulation. We use tools from functional data analysis to study dynamic changes by relating temporal gene expression profiles of different developmental stages to each other. Results We demonstrate that functional regression methodology can pinpoint relationships that exist between temporary gene expression profiles for different life cycle phases and incorporates dimension reduction as needed for these high-dimensional data. By applying these tools, gene expression profiles for pupa and adult phases are found to be strongly related to the profiles of the same genes obtained during the embryo phase. Moreover, one can distinguish between gene groups that exhibit relationships with positive and others with negative associations between later life and embryonal expression profiles. Specifically, we find a positive relationship in expression for muscle development related genes, and a negative relationship for strictly maternal genes for Drosophila, using temporal gene expression profiles. Conclusion Our findings point to specific reactivation patterns of gene expression during the Drosophila life cycle which differ in characteristic ways between various gene groups. Functional regression emerges as a useful tool for relating gene expression patterns from different developmental stages, and avoids the problems with large numbers of parameters and multiple testing that affect alternative approaches.

  16. Inferring the functional effect of gene expression changes in signaling pathways

    Science.gov (United States)

    Sebastián-León, Patricia; Carbonell, José; Salavert, Francisco; Sanchez, Rubén; Medina, Ignacio; Dopazo, Joaquín

    2013-01-01

    Signaling pathways constitute a valuable source of information that allows interpreting the way in which alterations in gene activities affect to particular cell functionalities. There are web tools available that allow viewing and editing pathways, as well as representing experimental data on them. However, few methods aimed to identify the signaling circuits, within a pathway, associated to the biological problem studied exist and none of them provide a convenient graphical web interface. We present PATHiWAYS, a web-based signaling pathway visualization system that infers changes in signaling that affect cell functionality from the measurements of gene expression values in typical expression microarray case–control experiments. A simple probabilistic model of the pathway is used to estimate the probabilities for signal transmission from any receptor to any final effector molecule (taking into account the pathway topology) using for this the individual probabilities of gene product presence/absence inferred from gene expression values. Significant changes in these probabilities allow linking different cell functionalities triggered by the pathway to the biological problem studied. PATHiWAYS is available at: http://pathiways.babelomics.org/. PMID:23748960

  17. ERC analysis: web-based inference of gene function via evolutionary rate covariation.

    Science.gov (United States)

    Wolfe, Nicholas W; Clark, Nathan L

    2015-12-01

    The recent explosion of comparative genomics data presents an unprecedented opportunity to construct gene networks via the evolutionary rate covariation (ERC) signature. ERC is used to identify genes that experienced similar evolutionary histories, and thereby draws functional associations between them. The ERC Analysis website allows researchers to exploit genome-wide datasets to infer novel genes in any biological function and to explore deep evolutionary connections between distinct pathways and complexes. The website provides five analytical methods, graphical output, statistical support and access to an increasing number of taxonomic groups. Analyses and data at http://csb.pitt.edu/erc_analysis/ nclark@pitt.edu. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Bayesian Inference for Functional Dynamics Exploring in fMRI Data

    Directory of Open Access Journals (Sweden)

    Xuan Guo

    2016-01-01

    Full Text Available This paper aims to review state-of-the-art Bayesian-inference-based methods applied to functional magnetic resonance imaging (fMRI data. Particularly, we focus on one specific long-standing challenge in the computational modeling of fMRI datasets: how to effectively explore typical functional interactions from fMRI time series and the corresponding boundaries of temporal segments. Bayesian inference is a method of statistical inference which has been shown to be a powerful tool to encode dependence relationships among the variables with uncertainty. Here we provide an introduction to a group of Bayesian-inference-based methods for fMRI data analysis, which were designed to detect magnitude or functional connectivity change points and to infer their functional interaction patterns based on corresponding temporal boundaries. We also provide a comparison of three popular Bayesian models, that is, Bayesian Magnitude Change Point Model (BMCPM, Bayesian Connectivity Change Point Model (BCCPM, and Dynamic Bayesian Variable Partition Model (DBVPM, and give a summary of their applications. We envision that more delicate Bayesian inference models will be emerging and play increasingly important roles in modeling brain functions in the years to come.

  19. Role of Utility and Inference in the Evolution of Functional Information

    Science.gov (United States)

    Sharov, Alexei A.

    2009-01-01

    Functional information means an encoded network of functions in living organisms from molecular signaling pathways to an organism’s behavior. It is represented by two components: code and an interpretation system, which together form a self-sustaining semantic closure. Semantic closure allows some freedom between components because small variations of the code are still interpretable. The interpretation system consists of inference rules that control the correspondence between the code and the function (phenotype) and determines the shape of the fitness landscape. The utility factor operates at multiple time scales: short-term selection drives evolution towards higher survival and reproduction rate within a given fitness landscape, and long-term selection favors those fitness landscapes that support adaptability and lead to evolutionary expansion of certain lineages. Inference rules make short-term selection possible by shaping the fitness landscape and defining possible directions of evolution, but they are under control of the long-term selection of lineages. Communication normally occurs within a set of agents with compatible interpretation systems, which I call communication system. Functional information cannot be directly transferred between communication systems with incompatible inference rules. Each biological species is a genetic communication system that carries unique functional information together with inference rules that determine evolutionary directions and constraints. This view of the relation between utility and inference can resolve the conflict between realism/positivism and pragmatism. Realism overemphasizes the role of inference in evolution of human knowledge because it assumes that logic is embedded in reality. Pragmatism substitutes usefulness for truth and therefore ignores the advantage of inference. The proposed concept of evolutionary pragmatism rejects the idea that logic is embedded in reality; instead, inference rules are

  20. Approximate inference for spatial functional data on massively parallel processors

    DEFF Research Database (Denmark)

    Raket, Lars Lau; Markussen, Bo

    2014-01-01

    With continually increasing data sizes, the relevance of the big n problem of classical likelihood approaches is greater than ever. The functional mixed-effects model is a well established class of models for analyzing functional data. Spatial functional data in a mixed-effects setting...... in linear time. An extremely efficient GPU implementation is presented, and the proposed methods are illustrated by conducting a classical statistical analysis of 2D chromatography data consisting of more than 140 million spatially correlated observation points....

  1. Generalised partition functions: inferences on phase space distributions

    Directory of Open Access Journals (Sweden)

    R. A. Treumann

    2016-06-01

    Full Text Available It is demonstrated that the statistical mechanical partition function can be used to construct various different forms of phase space distributions. This indicates that its structure is not restricted to the Gibbs–Boltzmann factor prescription which is based on counting statistics. With the widely used replacement of the Boltzmann factor by a generalised Lorentzian (also known as the q-deformed exponential function, where κ = 1∕|q − 1|, with κ, q ∈ R both the kappa-Bose and kappa-Fermi partition functions are obtained in quite a straightforward way, from which the conventional Bose and Fermi distributions follow for κ → ∞. For κ ≠ ∞ these are subject to the restrictions that they can be used only at temperatures far from zero. They thus, as shown earlier, have little value for quantum physics. This is reasonable, because physical κ systems imply strong correlations which are absent at zero temperature where apart from stochastics all dynamical interactions are frozen. In the classical large temperature limit one obtains physically reasonable κ distributions which depend on energy respectively momentum as well as on chemical potential. Looking for other functional dependencies, we examine Bessel functions whether they can be used for obtaining valid distributions. Again and for the same reason, no Fermi and Bose distributions exist in the low temperature limit. However, a classical Bessel–Boltzmann distribution can be constructed which is a Bessel-modified Lorentzian distribution. Whether it makes any physical sense remains an open question. This is not investigated here. The choice of Bessel functions is motivated solely by their convergence properties and not by reference to any physical demands. This result suggests that the Gibbs–Boltzmann partition function is fundamental not only to Gibbs–Boltzmann but also to a large class of generalised Lorentzian distributions as well as to the

  2. Atypical Learning in Autism Spectrum Disorders: A Functional Magnetic Resonance Imaging Study of Transitive Inference.

    Science.gov (United States)

    Solomon, Marjorie; Ragland, J Daniel; Niendam, Tara A; Lesh, Tyler A; Beck, Jonathan S; Matter, John C; Frank, Michael J; Carter, Cameron S

    2015-11-01

    To investigate the neural mechanisms underlying impairments in generalizing learning shown by adolescents with autism spectrum disorder (ASD). A total of 21 high-functioning individuals with ASD aged 12 to 18 years, and 23 gender-, IQ-, and age-matched adolescents with typical development (TYP), completed a transitive inference (TI) task implemented using rapid event-related functional magnetic resonance imaging (fMRI). Participants were trained on overlapping pairs in a stimulus hierarchy of colored ovals where A>B>C>D>E>F and then tested on generalizing this training to new stimulus pairings (AF, BD, BE) in a "Big Game." Whole-brain univariate, region of interest, and functional connectivity analyses were used. During training, the TYP group exhibited increased recruitment of the prefrontal cortex (PFC), whereas the group with ASD showed greater functional connectivity between the PFC and the anterior cingulate cortex (ACC). Both groups recruited the hippocampus and caudate comparably; however, functional connectivity between these regions was positively associated with TI performance for only the group with ASD. During the Big Game, the TYP group showed greater recruitment of the PFC, parietal cortex, and the ACC. Recruitment of these regions increased with age in the group with ASD. During TI, TYP individuals recruited cognitive control-related brain regions implicated in mature problem solving/reasoning including the PFC, parietal cortex, and ACC, whereas the group with ASD showed functional connectivity of the hippocampus and the caudate that was associated with task performance. Failure to reliably engage cognitive control-related brain regions may produce less integrated flexible learning in individuals with ASD unless they are provided with task support that, in essence, provides them with cognitive control; however, this pattern may normalize with age. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All

  3. Hippocampal Structure Predicts Statistical Learning and Associative Inference Abilities during Development.

    Science.gov (United States)

    Schlichting, Margaret L; Guarino, Katharine F; Schapiro, Anna C; Turk-Browne, Nicholas B; Preston, Alison R

    2017-01-01

    Despite the importance of learning and remembering across the lifespan, little is known about how the episodic memory system develops to support the extraction of associative structure from the environment. Here, we relate individual differences in volumes along the hippocampal long axis to performance on statistical learning and associative inference tasks-both of which require encoding associations that span multiple episodes-in a developmental sample ranging from ages 6 to 30 years. Relating age to volume, we found dissociable patterns across the hippocampal long axis, with opposite nonlinear volume changes in the head and body. These structural differences were paralleled by performance gains across the age range on both tasks, suggesting improvements in the cross-episode binding ability from childhood to adulthood. Controlling for age, we also found that smaller hippocampal heads were associated with superior behavioral performance on both tasks, consistent with this region's hypothesized role in forming generalized codes spanning events. Collectively, these results highlight the importance of examining hippocampal development as a function of position along the hippocampal axis and suggest that the hippocampal head is particularly important in encoding associative structure across development.

  4. Cultural effects on the association between election outcomes and face-based trait inferences.

    Directory of Open Access Journals (Sweden)

    Chujun Lin

    Full Text Available How competent a politician looks, as assessed in the laboratory, is correlated with whether the politician wins in real elections. This finding has led many to investigate whether the association between candidate appearances and election outcomes transcends cultures. However, these studies have largely focused on European countries and Caucasian candidates. To the best of our knowledge, there are only four cross-cultural studies that have directly investigated how face-based trait inferences correlate with election outcomes across Caucasian and Asian cultures. These prior studies have provided some initial evidence regarding cultural differences, but methodological problems and inconsistent findings have complicated our understanding of how culture mediates the effects of candidate appearances on election outcomes. Additionally, these four past studies have focused on positive traits, with a relative neglect of negative traits, resulting in an incomplete picture of how culture may impact a broader range of trait inferences. To study Caucasian-Asian cultural effects with a more balanced experimental design, and to explore a more complete profile of traits, here we compared how Caucasian and Korean participants' inferences of positive and negative traits correlated with U.S. and Korean election outcomes. Contrary to previous reports, we found that inferences of competence (made by participants from both cultures correlated with both U.S. and Korean election outcomes. Inferences of open-mindedness and threat, two traits neglected in previous cross-cultural studies, were correlated with Korean but not U.S. election outcomes. This differential effect was found in trait judgments made by both Caucasian and Korean participants. Interestingly, the faster the participants made face-based trait inferences, the more strongly those inferences were correlated with real election outcomes. These findings provide new insights into cultural effects and the

  5. Cultural effects on the association between election outcomes and face-based trait inferences.

    Science.gov (United States)

    Lin, Chujun; Adolphs, Ralph; Alvarez, R Michael

    2017-01-01

    How competent a politician looks, as assessed in the laboratory, is correlated with whether the politician wins in real elections. This finding has led many to investigate whether the association between candidate appearances and election outcomes transcends cultures. However, these studies have largely focused on European countries and Caucasian candidates. To the best of our knowledge, there are only four cross-cultural studies that have directly investigated how face-based trait inferences correlate with election outcomes across Caucasian and Asian cultures. These prior studies have provided some initial evidence regarding cultural differences, but methodological problems and inconsistent findings have complicated our understanding of how culture mediates the effects of candidate appearances on election outcomes. Additionally, these four past studies have focused on positive traits, with a relative neglect of negative traits, resulting in an incomplete picture of how culture may impact a broader range of trait inferences. To study Caucasian-Asian cultural effects with a more balanced experimental design, and to explore a more complete profile of traits, here we compared how Caucasian and Korean participants' inferences of positive and negative traits correlated with U.S. and Korean election outcomes. Contrary to previous reports, we found that inferences of competence (made by participants from both cultures) correlated with both U.S. and Korean election outcomes. Inferences of open-mindedness and threat, two traits neglected in previous cross-cultural studies, were correlated with Korean but not U.S. election outcomes. This differential effect was found in trait judgments made by both Caucasian and Korean participants. Interestingly, the faster the participants made face-based trait inferences, the more strongly those inferences were correlated with real election outcomes. These findings provide new insights into cultural effects and the difficult question of

  6. Cultural effects on the association between election outcomes and face-based trait inferences

    Science.gov (United States)

    Adolphs, Ralph; Alvarez, R. Michael

    2017-01-01

    How competent a politician looks, as assessed in the laboratory, is correlated with whether the politician wins in real elections. This finding has led many to investigate whether the association between candidate appearances and election outcomes transcends cultures. However, these studies have largely focused on European countries and Caucasian candidates. To the best of our knowledge, there are only four cross-cultural studies that have directly investigated how face-based trait inferences correlate with election outcomes across Caucasian and Asian cultures. These prior studies have provided some initial evidence regarding cultural differences, but methodological problems and inconsistent findings have complicated our understanding of how culture mediates the effects of candidate appearances on election outcomes. Additionally, these four past studies have focused on positive traits, with a relative neglect of negative traits, resulting in an incomplete picture of how culture may impact a broader range of trait inferences. To study Caucasian-Asian cultural effects with a more balanced experimental design, and to explore a more complete profile of traits, here we compared how Caucasian and Korean participants’ inferences of positive and negative traits correlated with U.S. and Korean election outcomes. Contrary to previous reports, we found that inferences of competence (made by participants from both cultures) correlated with both U.S. and Korean election outcomes. Inferences of open-mindedness and threat, two traits neglected in previous cross-cultural studies, were correlated with Korean but not U.S. election outcomes. This differential effect was found in trait judgments made by both Caucasian and Korean participants. Interestingly, the faster the participants made face-based trait inferences, the more strongly those inferences were correlated with real election outcomes. These findings provide new insights into cultural effects and the difficult question of

  7. Protein-driven inference of miRNA-disease associations

    DEFF Research Database (Denmark)

    Mørk, Søren; Pletscher-Frankild, Sune; Palleja, Albert

    2014-01-01

    MicroRNAs (miRNAs) are a highly abundant class of non-coding RNA genes involved in cellular regulation and thus also diseases. Despite miRNAs being important disease factors, miRNA-disease associations remain low in number and of variable reliability. Furthermore, existing databases and prediction...

  8. Inferring the Functions of Proteins from the Interrelationships between Functional Categories.

    Science.gov (United States)

    Taha, Kamal

    2018-01-01

    This study proposes a new method to determine the functions of an unannotated protein. The proteins and amino acid residues mentioned in biomedical texts associated with an unannotated protein can be considered as characteristics terms for , which are highly predictive of the potential functions of . Similarly, proteins and amino acid residues mentioned in biomedical texts associated with proteins annotated with a functional category can be considered as characteristics terms of . We introduce in this paper an information extraction system called IFP_IFC that predicts the functions of an unannotated protein by representing and each functional category by a vector of weights. Each weight reflects the degree of association between a characteristic term and (or a characteristic term and ). First, IFP_IFC constructs a network, whose nodes represent the different functional categories, and its edges the interrelationships between the nodes. Then, it determines the functions of by employing random walks with restarts on the mentioned network. The walker is the vector of . Finally, is assigned to the functional categories of the nodes in the network that are visited most by the walker. We evaluated the quality of IFP_IFC by comparing it experimentally with two other systems. Results showed marked improvement.

  9. An estimating function approach to inference for inhomogeneous Neyman-Scott processes

    DEFF Research Database (Denmark)

    Waagepetersen, Rasmus Plenge

    “This paper is concerned with inference for a certain class of inhomogeneous Neyman-Scott point processes depending on spatial covariates. Regression parameter estimates obtained from a simple estimating function are shown to be asymptotically normal when the “mother” intensity for the Neyman-Scott...

  10. An estimating function approach to inference for inhomogeneous Neyman-Scott processes

    DEFF Research Database (Denmark)

    Waagepetersen, Rasmus

    2007-01-01

    This article is concerned with inference for a certain class of inhomogeneous Neyman-Scott point processes depending on spatial covariates. Regression parameter estimates obtained from a simple estimating function are shown to be asymptotically normal when the "mother" intensity for the Neyman-Sc...

  11. Pragmatic Inference Abilities in Individuals with Asperger Syndrome or High-Functioning Autism. A Review

    Science.gov (United States)

    Loukusa, Soile; Moilanen, Irma

    2009-01-01

    This review summarizes studies involving pragmatic language comprehension and inference abilities in individuals with Asperger syndrome or high-functioning autism. Systematic searches of three electronic databases, selected journals, and reference lists identified 20 studies meeting the inclusion criteria. These studies were evaluated in terms of:…

  12. LEAP: biomarker inference through learning and evaluating association patterns.

    Science.gov (United States)

    Jiang, Xia; Neapolitan, Richard E

    2015-03-01

    Single nucleotide polymorphism (SNP) high-dimensional datasets are available from Genome Wide Association Studies (GWAS). Such data provide researchers opportunities to investigate the complex genetic basis of diseases. Much of genetic risk might be due to undiscovered epistatic interactions, which are interactions in which combination of several genes affect disease. Research aimed at discovering interacting SNPs from GWAS datasets proceeded in two directions. First, tools were developed to evaluate candidate interactions. Second, algorithms were developed to search over the space of candidate interactions. Another problem when learning interacting SNPs, which has not received much attention, is evaluating how likely it is that the learned SNPs are associated with the disease. A complete system should provide this information as well. We develop such a system. Our system, called LEAP, includes a new heuristic search algorithm for learning interacting SNPs, and a Bayesian network based algorithm for computing the probability of their association. We evaluated the performance of LEAP using 100 1,000-SNP simulated datasets, each of which contains 15 SNPs involved in interactions. When learning interacting SNPs from these datasets, LEAP outperformed seven others methods. Furthermore, only SNPs involved in interactions were found to be probable. We also used LEAP to analyze real Alzheimer's disease and breast cancer GWAS datasets. We obtained interesting and new results from the Alzheimer's dataset, but limited results from the breast cancer dataset. We conclude that our results support that LEAP is a useful tool for extracting candidate interacting SNPs from high-dimensional datasets and determining their probability. © 2015 The Authors. *Genetic Epidemiology published by Wiley Periodicals, Inc.

  13. Functional inference of complex anatomical tendinous networks at a macroscopic scale via sparse experimentation.

    Science.gov (United States)

    Saxena, Anupam; Lipson, Hod; Valero-Cuevas, Francisco J

    2012-01-01

    In systems and computational biology, much effort is devoted to functional identification of systems and networks at the molecular-or cellular scale. However, similarly important networks exist at anatomical scales such as the tendon network of human fingers: the complex array of collagen fibers that transmits and distributes muscle forces to finger joints. This network is critical to the versatility of the human hand, and its function has been debated since at least the 16(th) century. Here, we experimentally infer the structure (both topology and parameter values) of this network through sparse interrogation with force inputs. A population of models representing this structure co-evolves in simulation with a population of informative future force inputs via the predator-prey estimation-exploration algorithm. Model fitness depends on their ability to explain experimental data, while the fitness of future force inputs depends on causing maximal functional discrepancy among current models. We validate our approach by inferring two known synthetic Latex networks, and one anatomical tendon network harvested from a cadaver's middle finger. We find that functionally similar but structurally diverse models can exist within a narrow range of the training set and cross-validation errors. For the Latex networks, models with low training set error [functional structure of complex anatomical networks. This work expands current bioinformatics inference approaches by demonstrating that sparse, yet informative interrogation of biological specimens holds significant computational advantages in accurate and efficient inference over random testing, or assuming model topology and only inferring parameters values. These findings also hold clues to both our evolutionary history and the development of versatile machines.

  14. Examining Associations between Reading Motivation and Inference Generation beyond Reading Comprehension Skill

    Science.gov (United States)

    Clinton, Virginia

    2015-01-01

    The purpose of this study was to examine the associations between reading motivation and inference generation while reading. Undergraduate participants (N = 69) read two science articles while thinking aloud, completed a standardized reading comprehension assessment, and self reported their habitual reading motivation. Findings indicate that…

  15. Brain Activity Associated with Logical Inferences in Geometry: Focusing on Students with Different Levels of Ability

    Science.gov (United States)

    Waisman, Ilana; Leikin, Mark; Leikin, Roza

    2016-01-01

    Mathematical processing associated with solving short geometry problems requiring logical inference was examined among students who differ in their levels of general giftedness (G) and excellence in mathematics (EM) using ERP research methodology. Sixty-seven male adolescents formed four major research groups designed according to various…

  16. Ancestral sequence reconstruction in primate mitochondrial DNA: compositional bias and effect on functional inference.

    Science.gov (United States)

    Krishnan, Neeraja M; Seligmann, Hervé; Stewart, Caro-Beth; De Koning, A P Jason; Pollock, David D

    2004-10-01

    Reconstruction of ancestral DNA and amino acid sequences is an important means of inferring information about past evolutionary events. Such reconstructions suggest changes in molecular function and evolutionary processes over the course of evolution and are used to infer adaptation and convergence. Maximum likelihood (ML) is generally thought to provide relatively accurate reconstructed sequences compared to parsimony, but both methods lead to the inference of multiple directional changes in nucleotide frequencies in primate mitochondrial DNA (mtDNA). To better understand this surprising result, as well as to better understand how parsimony and ML differ, we constructed a series of computationally simple "conditional pathway" methods that differed in the number of substitutions allowed per site along each branch, and we also evaluated the entire Bayesian posterior frequency distribution of reconstructed ancestral states. We analyzed primate mitochondrial cytochrome b (Cyt-b) and cytochrome oxidase subunit I (COI) genes and found that ML reconstructs ancestral frequencies that are often more different from tip sequences than are parsimony reconstructions. In contrast, frequency reconstructions based on the posterior ensemble more closely resemble extant nucleotide frequencies. Simulations indicate that these differences in ancestral sequence inference are probably due to deterministic bias caused by high uncertainty in the optimization-based ancestral reconstruction methods (parsimony, ML, Bayesian maximum a posteriori). In contrast, ancestral nucleotide frequencies based on an average of the Bayesian set of credible ancestral sequences are much less biased. The methods involving simpler conditional pathway calculations have slightly reduced likelihood values compared to full likelihood calculations, but they can provide fairly unbiased nucleotide reconstructions and may be useful in more complex phylogenetic analyses than considered here due to their speed and

  17. Approximation Of Multi-Valued Inverse Functions Using Clustering And Sugeno Fuzzy Inference

    Science.gov (United States)

    Walden, Maria A.; Bikdash, Marwan; Homaifar, Abdollah

    1998-01-01

    Finding the inverse of a continuous function can be challenging and computationally expensive when the inverse function is multi-valued. Difficulties may be compounded when the function itself is difficult to evaluate. We show that we can use fuzzy-logic approximators such as Sugeno inference systems to compute the inverse on-line. To do so, a fuzzy clustering algorithm can be used in conjunction with a discriminating function to split the function data into branches for the different values of the forward function. These data sets are then fed into a recursive least-squares learning algorithm that finds the proper coefficients of the Sugeno approximators; each Sugeno approximator finds one value of the inverse function. Discussions about the accuracy of the approximation will be included.

  18. Evolutionary rates at codon sites may be used to align sequences and infer protein domain function

    Directory of Open Access Journals (Sweden)

    Hazelhurst Scott

    2010-03-01

    Full Text Available Abstract Background Sequence alignments form part of many investigations in molecular biology, including the determination of phylogenetic relationships, the prediction of protein structure and function, and the measurement of evolutionary rates. However, to obtain meaningful results, a significant degree of sequence similarity is required to ensure that the alignments are accurate and the inferences correct. Limitations arise when sequence similarity is low, which is particularly problematic when working with fast-evolving genes, evolutionary distant taxa, genomes with nucleotide biases, and cases of convergent evolution. Results A novel approach was conceptualized to address the "low sequence similarity" alignment problem. We developed an alignment algorithm termed FIRE (Functional Inference using the Rates of Evolution, which aligns sequences using the evolutionary rate at codon sites, as measured by the dN/dS ratio, rather than nucleotide or amino acid residues. FIRE was used to test the hypotheses that evolutionary rates can be used to align sequences and that the alignments may be used to infer protein domain function. Using a range of test data, we found that aligning domains based on evolutionary rates was possible even when sequence similarity was very low (for example, antibody variable regions. Furthermore, the alignment has the potential to infer protein domain function, indicating that domains with similar functions are subject to similar evolutionary constraints. These data suggest that an evolutionary rate-based approach to sequence analysis (particularly when combined with structural data may be used to study cases of convergent evolution or when sequences have very low similarity. However, when aligning homologous gene sets with sequence similarity, FIRE did not perform as well as the best traditional alignment algorithms indicating that the conventional approach of aligning residues as opposed to evolutionary rates remains the

  19. Implicit transitive inference and the human hippocampus: does intravenous midazolam function as a reversible hippocampal lesion?

    Directory of Open Access Journals (Sweden)

    Greene Anthony J

    2007-09-01

    Full Text Available Abstract Recent advances have led to an understanding that the hippocampus is involved more broadly than explicit or declarative memory alone. Tasks which involve the acquisition of complex associations involve the hippocampus whether the learning is explicit or implicit. One hippocampal-dependent implicit task is transitive inference (TI. Recently it was suggested that implicit transitive inference does not depend upon the hippocampus (Frank, M. J., O'Reilly, R. C., & Curran, T. 2006. When memory fails, intuition reigns: midazolam enhances implicit inference in humans. Psychological Science, 17, 700–707. The authors demonstrated that intravenous midazolam, which is thought to inactivate the hippocampus, may enhance TI performance. Three critical assumptions are required but not met: 1 that deactivations of other regions could not account for the effect 2 that intravenous midazolam does indeed deactivate the hippocampus and 3 that midazolam influences explicit but not implicit memory. Each of these assumptions is seriously flawed. Consequently, the suggestion that implicit TI does not depend upon the hippocampus is unfounded.

  20. Coordinate transformation and Polynomial Chaos for the Bayesian inference of a Gaussian process with parametrized prior covariance function

    KAUST Repository

    Sraj, Ihab

    2015-10-22

    This paper addresses model dimensionality reduction for Bayesian inference based on prior Gaussian fields with uncertainty in the covariance function hyper-parameters. The dimensionality reduction is traditionally achieved using the Karhunen-Loève expansion of a prior Gaussian process assuming covariance function with fixed hyper-parameters, despite the fact that these are uncertain in nature. The posterior distribution of the Karhunen-Loève coordinates is then inferred using available observations. The resulting inferred field is therefore dependent on the assumed hyper-parameters. Here, we seek to efficiently estimate both the field and covariance hyper-parameters using Bayesian inference. To this end, a generalized Karhunen-Loève expansion is derived using a coordinate transformation to account for the dependence with respect to the covariance hyper-parameters. Polynomial Chaos expansions are employed for the acceleration of the Bayesian inference using similar coordinate transformations, enabling us to avoid expanding explicitly the solution dependence on the uncertain hyper-parameters. We demonstrate the feasibility of the proposed method on a transient diffusion equation by inferring spatially-varying log-diffusivity fields from noisy data. The inferred profiles were found closer to the true profiles when including the hyper-parameters’ uncertainty in the inference formulation.

  1. Using Semantic Association to Extend and Infer Literature-Oriented Relativity Between Terms.

    Science.gov (United States)

    Cheng, Liang; Li, Jie; Hu, Yang; Jiang, Yue; Liu, Yongzhuang; Chu, Yanshuo; Wang, Zhenxing; Wang, Yadong

    2015-01-01

    Relative terms often appear together in the literature. Methods have been presented for weighting relativity of pairwise terms by their co-occurring literature and inferring new relationship. Terms in the literature are also in the directed acyclic graph of ontologies, such as Gene Ontology and Disease Ontology. Therefore, semantic association between terms may help for establishing relativities between terms in literature. However, current methods do not use these associations. In this paper, an adjusted R-scaled score (ARSS) based on information content (ARSSIC) method is introduced to infer new relationship between terms. First, set inclusion relationship between terms of ontology was exploited to extend relationships between these terms and literature. Next, the ARSS method was presented to measure relativity between terms across ontologies according to these extensional relationships. Then, the ARSSIC method using ratios of information shared of term's ancestors was designed to infer new relationship between terms across ontologies. The result of the experiment shows that ARSS identified more pairs of statistically significant terms based on corresponding gene sets than other methods. And the high average area under the receiver operating characteristic curve (0.9293) shows that ARSSIC achieved a high true positive rate and a low false positive rate. Data is available at http://mlg.hit.edu.cn/ARSSIC/.

  2. A new Bayesian Inference-based Phase Associator for Earthquake Early Warning

    Science.gov (United States)

    Meier, Men-Andrin; Heaton, Thomas; Clinton, John; Wiemer, Stefan

    2013-04-01

    State of the art network-based Earthquake Early Warning (EEW) systems can provide warnings for large magnitude 7+ earthquakes. Although regions in the direct vicinity of the epicenter will not receive warnings prior to damaging shaking, real-time event characterization is available before the destructive S-wave arrival across much of the strongly affected region. In contrast, in the case of the more frequent medium size events, such as the devastating 1994 Mw6.7 Northridge, California, earthquake, providing timely warning to the smaller damage zone is more difficult. For such events the "blind zone" of current systems (e.g. the CISN ShakeAlert system in California) is similar in size to the area over which severe damage occurs. We propose a faster and more robust Bayesian inference-based event associator, that in contrast to the current standard associators (e.g. Earthworm Binder), is tailored to EEW and exploits information other than only phase arrival times. In particular, the associator potentially allows for reliable automated event association with as little as two observations, which, compared to the ShakeAlert system, would speed up the real-time characterizations by about ten seconds and thus reduce the blind zone area by up to 80%. We compile an extensive data set of regional and teleseismic earthquake and noise waveforms spanning a wide range of earthquake magnitudes and tectonic regimes. We pass these waveforms through a causal real-time filterbank with passband filters between 0.1 and 50Hz, and, updating every second from the event detection, extract the maximum amplitudes in each frequency band. Using this dataset, we define distributions of amplitude maxima in each passband as a function of epicentral distance and magnitude. For the real-time data, we pass incoming broadband and strong motion waveforms through the same filterbank and extract an evolving set of maximum amplitudes in each passband. We use the maximum amplitude distributions to check

  3. Testing two mechanisms by which rational and irrational beliefs may affect the functionality of inferences.

    Science.gov (United States)

    Bond, F W; Dryden, W; Briscoe, R

    1999-12-01

    This article describes a role playing experiment that examined the sufficiency hypothesis of Rational Emotive Behaviour Therapy (REBT). This proposition states that it is sufficient for rational and irrational beliefs to refer to preferences and musts, respectively, if those beliefs are to affect the functionality of inferences (FI). Consistent with the REBT literature (e.g. Dryden, 1994; Dryden & Ellis, 1988; Palmer, Dryden, Ellis & Yapp, 1995) results from this experiment showed that rational and irrational beliefs, as defined by REBT, do affect FI. Specifically, results showed that people who hold a rational belief form inferences that are significantly more functional than those that are formed by people who hold an irrational belief. Contrary to REBT theory, the sufficiency hypothesis was not supported. Thus, results indicated that it is not sufficient for rational and irrational beliefs to refer to preferences and musts, respectively, if those beliefs are to affect the FI. It appears, then, that preferences and musts are not sufficient mechanisms by which rational and irrational beliefs, respectively, affect the FI. Psychotherapeutic implications of these findings are considered.

  4. Hierarchical Bayesian inference of the initial mass function in composite stellar populations

    Science.gov (United States)

    Dries, M.; Trager, S. C.; Koopmans, L. V. E.; Popping, G.; Somerville, R. S.

    2018-03-01

    The initial mass function (IMF) is a key ingredient in many studies of galaxy formation and evolution. Although the IMF is often assumed to be universal, there is continuing evidence that it is not universal. Spectroscopic studies that derive the IMF of the unresolved stellar populations of a galaxy often assume that this spectrum can be described by a single stellar population (SSP). To alleviate these limitations, in this paper we have developed a unique hierarchical Bayesian framework for modelling composite stellar populations (CSPs). Within this framework, we use a parametrized IMF prior to regulate a direct inference of the IMF. We use this new framework to determine the number of SSPs that is required to fit a set of realistic CSP mock spectra. The CSP mock spectra that we use are based on semi-analytic models and have an IMF that varies as a function of stellar velocity dispersion of the galaxy. Our results suggest that using a single SSP biases the determination of the IMF slope to a higher value than the true slope, although the trend with stellar velocity dispersion is overall recovered. If we include more SSPs in the fit, the Bayesian evidence increases significantly and the inferred IMF slopes of our mock spectra converge, within the errors, to their true values. Most of the bias is already removed by using two SSPs instead of one. We show that we can reconstruct the variable IMF of our mock spectra for signal-to-noise ratios exceeding ˜75.

  5. The impact of phenotypic and molecular data on the inference of Colletotrichum diversity associated with Musa.

    Science.gov (United States)

    Vieira, Willie A S; Lima, Waléria G; Nascimento, Eduardo S; Michereff, Sami J; Câmara, Marcos P S; Doyle, Vinson P

    2017-01-01

    Developing a comprehensive and reliable taxonomy for the Colletotrichum gloeosporioides species complex will require adopting data standards on the basis of an understanding of how methodological choices impact morphological evaluations and phylogenetic inference. We explored the impact of methodological choices in a morphological and molecular evaluation of Colletotrichum species associated with banana in Brazil. The choice of alignment filtering algorithm has a significant impact on topological inference and the retention of phylogenetically informative sites. Similarly, the choice of phylogenetic marker affects the delimitation of species boundaries, particularly if low phylogenetic signal is confounded with strong discordance, and inference of the species tree from multiple-gene trees. According to both phylogenetic informativeness profiling and Bayesian concordance analyses, the most informative loci are DNA lyase (APN2), intergenic spacer (IGS) between DNA lyase and the mating-type locus MAT1-2-1 (APN2/MAT-IGS), calmodulin (CAL), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), glutamine synthetase (GS), β-tubulin (TUB2), and a new marker, the intergenic spacer between GAPDH and an hypothetical protein (GAP2-IGS). Cornmeal agar minimizes the variance in conidial dimensions compared with potato dextrose agar and synthetic nutrient-poor agar, such that species are more readily distinguishable based on phenotypic differences. We apply these insights to investigate the diversity of Colletotrichum species associated with banana anthracnose in Brazil and report C. musae, C. tropicale, C. theobromicola, and C. siamense in association with banana anthracnose. One lineage did not cluster with any previously described species and is described here as C. chrysophilum.

  6. Eddington's demon: inferring galaxy mass functions and other distributions from uncertain data

    Science.gov (United States)

    Obreschkow, D.; Murray, S. G.; Robotham, A. S. G.; Westmeier, T.

    2018-03-01

    We present a general modified maximum likelihood (MML) method for inferring generative distribution functions from uncertain and biased data. The MML estimator is identical to, but easier and many orders of magnitude faster to compute than the solution of the exact Bayesian hierarchical modelling of all measurement errors. As a key application, this method can accurately recover the mass function (MF) of galaxies, while simultaneously dealing with observational uncertainties (Eddington bias), complex selection functions and unknown cosmic large-scale structure. The MML method is free of binning and natively accounts for small number statistics and non-detections. Its fast implementation in the R-package dftools is equally applicable to other objects, such as haloes, groups, and clusters, as well as observables other than mass. The formalism readily extends to multidimensional distribution functions, e.g. a Choloniewski function for the galaxy mass-angular momentum distribution, also handled by dftools. The code provides uncertainties and covariances for the fitted model parameters and approximate Bayesian evidences. We use numerous mock surveys to illustrate and test the MML method, as well as to emphasize the necessity of accounting for observational uncertainties in MFs of modern galaxy surveys.

  7. On the inference of function from structure using biomechanical modelling and simulation of extinct organisms

    Science.gov (United States)

    Hutchinson, John R.

    2012-01-01

    Biomechanical modelling and simulation techniques offer some hope for unravelling the complex inter-relationships of structure and function perhaps even for extinct organisms, but have their limitations owing to this complexity and the many unknown parameters for fossil taxa. Validation and sensitivity analysis are two indispensable approaches for quantifying the accuracy and reliability of such models or simulations. But there are other subtleties in biomechanical modelling that include investigator judgements about the level of simplicity versus complexity in model design or how uncertainty and subjectivity are dealt with. Furthermore, investigator attitudes toward models encompass a broad spectrum between extreme credulity and nihilism, influencing how modelling is conducted and perceived. Fundamentally, more data and more testing of methodology are required for the field to mature and build confidence in its inferences. PMID:21666064

  8. Pragmatic inferences in high-functioning adults with autism and Asperger syndrome.

    Science.gov (United States)

    Pijnacker, Judith; Hagoort, Peter; Buitelaar, Jan; Teunisse, Jan-Pieter; Geurts, Bart

    2009-04-01

    Although people with autism spectrum disorders (ASD) often have severe problems with pragmatic aspects of language, little is known about their pragmatic reasoning. We carried out a behavioral study on high-functioning adults with autistic disorder (n = 11) and Asperger syndrome (n = 17) and matched controls (n = 28) to investigate whether they are capable of deriving scalar implicatures, which are generally considered to be pragmatic inferences. Participants were presented with underinformative sentences like "Some sparrows are birds". This sentence is logically true, but pragmatically inappropriate if the scalar implicature "Not all sparrows are birds" is derived. The present findings indicate that the combined ASD group was just as likely as controls to derive scalar implicatures, yet there was a difference between participants with autistic disorder and Asperger syndrome, suggesting a potential differentiation between these disorders in pragmatic reasoning. Moreover, our results suggest that verbal intelligence is a constraint for task performance in autistic disorder but not in Asperger syndrome.

  9. Functional coupling networks inferred from prefrontal cortex activity show experience-related effective plasticity

    Directory of Open Access Journals (Sweden)

    Gaia Tavoni

    2017-10-01

    Full Text Available Functional coupling networks are widely used to characterize collective patterns of activity in neural populations. Here, we ask whether functional couplings reflect the subtle changes, such as in physiological interactions, believed to take place during learning. We infer functional network models reproducing the spiking activity of simultaneously recorded neurons in prefrontal cortex (PFC of rats, during the performance of a cross-modal rule shift task (task epoch, and during preceding and following sleep epochs. A large-scale study of the 96 recorded sessions allows us to detect, in about 20% of sessions, effective plasticity between the sleep epochs. These coupling modifications are correlated with the coupling values in the task epoch, and are supported by a small subset of the recorded neurons, which we identify by means of an automatized procedure. These potentiated groups increase their coativation frequency in the spiking data between the two sleep epochs, and, hence, participate to putative experience-related cell assemblies. Study of the reactivation dynamics of the potentiated groups suggests a possible connection with behavioral learning. Reactivation is largely driven by hippocampal ripple events when the rule is not yet learned, and may be much more autonomous, and presumably sustained by the potentiated PFC network, when learning is consolidated. Cell assemblies coding for memories are widely believed to emerge through synaptic modification resulting from learning, yet their identification from activity is very arduous. We propose a functional-connectivity-based approach to identify experience-related cell assemblies from multielectrode recordings in vivo, and apply it to the prefrontal cortex activity of rats recorded during a task epoch and the preceding and following sleep epochs. We infer functional couplings between the recorded cells in each epoch. Comparisons of the functional coupling networks across the epochs allow us

  10. Inference of Functionally-Relevant N-acetyltransferase Residues Based on Statistical Correlations.

    Science.gov (United States)

    Neuwald, Andrew F; Altschul, Stephen F

    2016-12-01

    Over evolutionary time, members of a superfamily of homologous proteins sharing a common structural core diverge into subgroups filling various functional niches. At the sequence level, such divergence appears as correlations that arise from residue patterns distinct to each subgroup. Such a superfamily may be viewed as a population of sequences corresponding to a complex, high-dimensional probability distribution. Here we model this distribution as hierarchical interrelated hidden Markov models (hiHMMs), which describe these sequence correlations implicitly. By characterizing such correlations one may hope to obtain information regarding functionally-relevant properties that have thus far evaded detection. To do so, we infer a hiHMM distribution from sequence data using Bayes' theorem and Markov chain Monte Carlo (MCMC) sampling, which is widely recognized as the most effective approach for characterizing a complex, high dimensional distribution. Other routines then map correlated residue patterns to available structures with a view to hypothesis generation. When applied to N-acetyltransferases, this reveals sequence and structural features indicative of functionally important, yet generally unknown biochemical properties. Even for sets of proteins for which nothing is known beyond unannotated sequences and structures, this can lead to helpful insights. We describe, for example, a putative coenzyme-A-induced-fit substrate binding mechanism mediated by arginine residue switching between salt bridge and π-π stacking interactions. A suite of programs implementing this approach is available (psed.igs.umaryland.edu).

  11. Inference of Functionally-Relevant N-acetyltransferase Residues Based on Statistical Correlations.

    Directory of Open Access Journals (Sweden)

    Andrew F Neuwald

    2016-12-01

    Full Text Available Over evolutionary time, members of a superfamily of homologous proteins sharing a common structural core diverge into subgroups filling various functional niches. At the sequence level, such divergence appears as correlations that arise from residue patterns distinct to each subgroup. Such a superfamily may be viewed as a population of sequences corresponding to a complex, high-dimensional probability distribution. Here we model this distribution as hierarchical interrelated hidden Markov models (hiHMMs, which describe these sequence correlations implicitly. By characterizing such correlations one may hope to obtain information regarding functionally-relevant properties that have thus far evaded detection. To do so, we infer a hiHMM distribution from sequence data using Bayes' theorem and Markov chain Monte Carlo (MCMC sampling, which is widely recognized as the most effective approach for characterizing a complex, high dimensional distribution. Other routines then map correlated residue patterns to available structures with a view to hypothesis generation. When applied to N-acetyltransferases, this reveals sequence and structural features indicative of functionally important, yet generally unknown biochemical properties. Even for sets of proteins for which nothing is known beyond unannotated sequences and structures, this can lead to helpful insights. We describe, for example, a putative coenzyme-A-induced-fit substrate binding mechanism mediated by arginine residue switching between salt bridge and π-π stacking interactions. A suite of programs implementing this approach is available (psed.igs.umaryland.edu.

  12. FPGA Acceleration of the phylogenetic likelihood function for Bayesian MCMC inference methods

    Directory of Open Access Journals (Sweden)

    Bakos Jason D

    2010-04-01

    Full Text Available Abstract Background Likelihood (ML-based phylogenetic inference has become a popular method for estimating the evolutionary relationships among species based on genomic sequence data. This method is used in applications such as RAxML, GARLI, MrBayes, PAML, and PAUP. The Phylogenetic Likelihood Function (PLF is an important kernel computation for this method. The PLF consists of a loop with no conditional behavior or dependencies between iterations. As such it contains a high potential for exploiting parallelism using micro-architectural techniques. In this paper, we describe a technique for mapping the PLF and supporting logic onto a Field Programmable Gate Array (FPGA-based co-processor. By leveraging the FPGA's on-chip DSP modules and the high-bandwidth local memory attached to the FPGA, the resultant co-processor can accelerate ML-based methods and outperform state-of-the-art multi-core processors. Results We use the MrBayes 3 tool as a framework for designing our co-processor. For large datasets, we estimate that our accelerated MrBayes, if run on a current-generation FPGA, achieves a 10× speedup relative to software running on a state-of-the-art server-class microprocessor. The FPGA-based implementation achieves its performance by deeply pipelining the likelihood computations, performing multiple floating-point operations in parallel, and through a natural log approximation that is chosen specifically to leverage a deeply pipelined custom architecture. Conclusions Heterogeneous computing, which combines general-purpose processors with special-purpose co-processors such as FPGAs and GPUs, is a promising approach for high-performance phylogeny inference as shown by the growing body of literature in this field. FPGAs in particular are well-suited for this task because of their low power consumption as compared to many-core processors and Graphics Processor Units (GPUs 1.

  13. Obesity as a risk factor for developing functional limitation among older adults: A conditional inference tree analysis

    Science.gov (United States)

    Objective: To examine the risk factors of developing functional decline and make probabilistic predictions by using a tree-based method that allows higher order polynomials and interactions of the risk factors. Methods: The conditional inference tree analysis, a data mining approach, was used to con...

  14. Integration of Multiple Genomic and Phenotype Data to Infer Novel miRNA-Disease Associations.

    Science.gov (United States)

    Shi, Hongbo; Zhang, Guangde; Zhou, Meng; Cheng, Liang; Yang, Haixiu; Wang, Jing; Sun, Jie; Wang, Zhenzhen

    2016-01-01

    MicroRNAs (miRNAs) play an important role in the development and progression of human diseases. The identification of disease-associated miRNAs will be helpful for understanding the molecular mechanisms of diseases at the post-transcriptional level. Based on different types of genomic data sources, computational methods for miRNA-disease association prediction have been proposed. However, individual source of genomic data tends to be incomplete and noisy; therefore, the integration of various types of genomic data for inferring reliable miRNA-disease associations is urgently needed. In this study, we present a computational framework, CHNmiRD, for identifying miRNA-disease associations by integrating multiple genomic and phenotype data, including protein-protein interaction data, gene ontology data, experimentally verified miRNA-target relationships, disease phenotype information and known miRNA-disease connections. The performance of CHNmiRD was evaluated by experimentally verified miRNA-disease associations, which achieved an area under the ROC curve (AUC) of 0.834 for 5-fold cross-validation. In particular, CHNmiRD displayed excellent performance for diseases without any known related miRNAs. The results of case studies for three human diseases (glioblastoma, myocardial infarction and type 1 diabetes) showed that all of the top 10 ranked miRNAs having no known associations with these three diseases in existing miRNA-disease databases were directly or indirectly confirmed by our latest literature mining. All these results demonstrated the reliability and efficiency of CHNmiRD, and it is anticipated that CHNmiRD will serve as a powerful bioinformatics method for mining novel disease-related miRNAs and providing a new perspective into molecular mechanisms underlying human diseases at the post-transcriptional level. CHNmiRD is freely available at http://www.bio-bigdata.com/CHNmiRD.

  15. Integration of Multiple Genomic and Phenotype Data to Infer Novel miRNA-Disease Associations.

    Directory of Open Access Journals (Sweden)

    Hongbo Shi

    Full Text Available MicroRNAs (miRNAs play an important role in the development and progression of human diseases. The identification of disease-associated miRNAs will be helpful for understanding the molecular mechanisms of diseases at the post-transcriptional level. Based on different types of genomic data sources, computational methods for miRNA-disease association prediction have been proposed. However, individual source of genomic data tends to be incomplete and noisy; therefore, the integration of various types of genomic data for inferring reliable miRNA-disease associations is urgently needed. In this study, we present a computational framework, CHNmiRD, for identifying miRNA-disease associations by integrating multiple genomic and phenotype data, including protein-protein interaction data, gene ontology data, experimentally verified miRNA-target relationships, disease phenotype information and known miRNA-disease connections. The performance of CHNmiRD was evaluated by experimentally verified miRNA-disease associations, which achieved an area under the ROC curve (AUC of 0.834 for 5-fold cross-validation. In particular, CHNmiRD displayed excellent performance for diseases without any known related miRNAs. The results of case studies for three human diseases (glioblastoma, myocardial infarction and type 1 diabetes showed that all of the top 10 ranked miRNAs having no known associations with these three diseases in existing miRNA-disease databases were directly or indirectly confirmed by our latest literature mining. All these results demonstrated the reliability and efficiency of CHNmiRD, and it is anticipated that CHNmiRD will serve as a powerful bioinformatics method for mining novel disease-related miRNAs and providing a new perspective into molecular mechanisms underlying human diseases at the post-transcriptional level. CHNmiRD is freely available at http://www.bio-bigdata.com/CHNmiRD.

  16. Extreme deconvolution: Inferring complete distribution functions from noisy, heterogeneous and incomplete observations

    Science.gov (United States)

    Bovy Jo; Hogg, David W.; Roweis, Sam T.

    2011-06-01

    We generalize the well-known mixtures of Gaussians approach to density estimation and the accompanying Expectation-Maximization technique for finding the maximum likelihood parameters of the mixture to the case where each data point carries an individual d-dimensional uncertainty covariance and has unique missing data properties. This algorithm reconstructs the error-deconvolved or "underlying" distribution function common to all samples, even when the individual data points are samples from different distributions, obtained by convolving the underlying distribution with the heteroskedastic uncertainty distribution of the data point and projecting out the missing data directions. We show how this basic algorithm can be extended with conjugate priors on all of the model parameters and a "split-and-"erge- procedure designed to avoid local maxima of the likelihood. We demonstrate the full method by applying it to the problem of inferring the three-dimensional veloc! ity distribution of stars near the Sun from noisy two-dimensional, transverse velocity measurements from the Hipparcos satellite.

  17. FuncPatch: a web server for the fast Bayesian inference of conserved functional patches in protein 3D structures.

    Science.gov (United States)

    Huang, Yi-Fei; Golding, G Brian

    2015-02-15

    A number of statistical phylogenetic methods have been developed to infer conserved functional sites or regions in proteins. Many methods, e.g. Rate4Site, apply the standard phylogenetic models to infer site-specific substitution rates and totally ignore the spatial correlation of substitution rates in protein tertiary structures, which may reduce their power to identify conserved functional patches in protein tertiary structures when the sequences used in the analysis are highly similar. The 3D sliding window method has been proposed to infer conserved functional patches in protein tertiary structures, but the window size, which reflects the strength of the spatial correlation, must be predefined and is not inferred from data. We recently developed GP4Rate to solve these problems under the Bayesian framework. Unfortunately, GP4Rate is computationally slow. Here, we present an intuitive web server, FuncPatch, to perform a fast approximate Bayesian inference of conserved functional patches in protein tertiary structures. Both simulations and four case studies based on empirical data suggest that FuncPatch is a good approximation to GP4Rate. However, FuncPatch is orders of magnitudes faster than GP4Rate. In addition, simulations suggest that FuncPatch is potentially a useful tool complementary to Rate4Site, but the 3D sliding window method is less powerful than FuncPatch and Rate4Site. The functional patches predicted by FuncPatch in the four case studies are supported by experimental evidence, which corroborates the usefulness of FuncPatch. The software FuncPatch is freely available at the web site, http://info.mcmaster.ca/yifei/FuncPatch golding@mcmaster.ca Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Perceptual inference.

    Science.gov (United States)

    Aggelopoulos, Nikolaos C

    2015-08-01

    Perceptual inference refers to the ability to infer sensory stimuli from predictions that result from internal neural representations built through prior experience. Methods of Bayesian statistical inference and decision theory model cognition adequately by using error sensing either in guiding action or in "generative" models that predict the sensory information. In this framework, perception can be seen as a process qualitatively distinct from sensation, a process of information evaluation using previously acquired and stored representations (memories) that is guided by sensory feedback. The stored representations can be utilised as internal models of sensory stimuli enabling long term associations, for example in operant conditioning. Evidence for perceptual inference is contributed by such phenomena as the cortical co-localisation of object perception with object memory, the response invariance in the responses of some neurons to variations in the stimulus, as well as from situations in which perception can be dissociated from sensation. In the context of perceptual inference, sensory areas of the cerebral cortex that have been facilitated by a priming signal may be regarded as comparators in a closed feedback loop, similar to the better known motor reflexes in the sensorimotor system. The adult cerebral cortex can be regarded as similar to a servomechanism, in using sensory feedback to correct internal models, producing predictions of the outside world on the basis of past experience. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. IntNetLncSim: an integrative network analysis method to infer human lncRNA functional similarity.

    Science.gov (United States)

    Cheng, Liang; Shi, Hongbo; Wang, Zhenzhen; Hu, Yang; Yang, Haixiu; Zhou, Chen; Sun, Jie; Zhou, Meng

    2016-07-26

    Increasing evidence indicated that long non-coding RNAs (lncRNAs) were involved in various biological processes and complex diseases by communicating with mRNAs/miRNAs each other. Exploiting interactions between lncRNAs and mRNA/miRNAs to lncRNA functional similarity (LFS) is an effective method to explore function of lncRNAs and predict novel lncRNA-disease associations. In this article, we proposed an integrative framework, IntNetLncSim, to infer LFS by modeling the information flow in an integrated network that comprises both lncRNA-related transcriptional and post-transcriptional information. The performance of IntNetLncSim was evaluated by investigating the relationship of LFS with the similarity of lncRNA-related mRNA sets (LmRSets) and miRNA sets (LmiRSets). As a result, LFS by IntNetLncSim was significant positively correlated with the LmRSet (Pearson correlation γ2=0.8424) and LmiRSet (Pearson correlation γ2=0.2601). Particularly, the performance of IntNetLncSim is superior to several previous methods. In the case of applying the LFS to identify novel lncRNA-disease relationships, we achieved an area under the ROC curve (0.7300) in experimentally verified lncRNA-disease associations based on leave-one-out cross-validation. Furthermore, highly-ranked lncRNA-disease associations confirmed by literature mining demonstrated the excellent performance of IntNetLncSim. Finally, a web-accessible system was provided for querying LFS and potential lncRNA-disease relationships: http://www.bio-bigdata.com/IntNetLncSim.

  20. Modulated modularity clustering as an exploratory tool for functional genomic inference.

    Directory of Open Access Journals (Sweden)

    Eric A Stone

    2009-05-01

    Full Text Available In recent years, the advent of high-throughput assays, coupled with their diminishing cost, has facilitated a systems approach to biology. As a consequence, massive amounts of data are currently being generated, requiring efficient methodology aimed at the reduction of scale. Whole-genome transcriptional profiling is a standard component of systems-level analyses, and to reduce scale and improve inference clustering genes is common. Since clustering is often the first step toward generating hypotheses, cluster quality is critical. Conversely, because the validation of cluster-driven hypotheses is indirect, it is critical that quality clusters not be obtained by subjective means. In this paper, we present a new objective-based clustering method and demonstrate that it yields high-quality results. Our method, modulated modularity clustering (MMC, seeks community structure in graphical data. MMC modulates the connection strengths of edges in a weighted graph to maximize an objective function (called modularity that quantifies community structure. The result of this maximization is a clustering through which tightly-connected groups of vertices emerge. Our application is to systems genetics, and we quantitatively compare MMC both to the hierarchical clustering method most commonly employed and to three popular spectral clustering approaches. We further validate MMC through analyses of human and Drosophila melanogaster expression data, demonstrating that the clusters we obtain are biologically meaningful. We show MMC to be effective and suitable to applications of large scale. In light of these features, we advocate MMC as a standard tool for exploration and hypothesis generation.

  1. Effects of Sample Size and Dimensionality on the Performance of Four Algorithms for Inference of Association Networks in Metabonomics

    NARCIS (Netherlands)

    Suarez Diez, M.; Saccenti, E.

    2015-01-01

    We investigated the effect of sample size and dimensionality on the performance of four algorithms (ARACNE, CLR, CORR, and PCLRC) when they are used for the inference of metabolite association networks. We report that as many as 100-400 samples may be necessary to obtain stable network estimations,

  2. An associative model of adaptive inference for learning word-referent mappings.

    Science.gov (United States)

    Kachergis, George; Yu, Chen; Shiffrin, Richard M

    2012-04-01

    People can learn word-referent pairs over a short series of individually ambiguous situations containing multiple words and referents (Yu & Smith, 2007, Cognition 106: 1558-1568). Cross-situational statistical learning relies on the repeated co-occurrence of words with their intended referents, but simple co-occurrence counts cannot explain the findings. Mutual exclusivity (ME: an assumption of one-to-one mappings) can reduce ambiguity by leveraging prior experience to restrict the number of word-referent pairings considered but can also block learning of non-one-to-one mappings. The present study first trained learners on one-to-one mappings with varying numbers of repetitions. In late training, a new set of word-referent pairs were introduced alongside pretrained pairs; each pretrained pair consistently appeared with a new pair. Results indicate that (1) learners quickly infer new pairs in late training on the basis of their knowledge of pretrained pairs, exhibiting ME; and (2) learners also adaptively relax the ME bias and learn two-to-two mappings involving both pretrained and new words and objects. We present an associative model that accounts for both results using competing familiarity and uncertainty biases.

  3. The Panchromatic Hubble Andromeda Treasury. IV. A Probabilistic Approach to Inferring the High-mass Stellar Initial Mass Function and Other Power-law Functions

    Science.gov (United States)

    Weisz, Daniel R.; Fouesneau, Morgan; Hogg, David W.; Rix, Hans-Walter; Dolphin, Andrew E.; Dalcanton, Julianne J.; Foreman-Mackey, Daniel T.; Lang, Dustin; Johnson, L. Clifton; Beerman, Lori C.; Bell, Eric F.; Gordon, Karl D.; Gouliermis, Dimitrios; Kalirai, Jason S.; Skillman, Evan D.; Williams, Benjamin F.

    2013-01-01

    We present a probabilistic approach for inferring the parameters of the present-day power-law stellar mass function (MF) of a resolved young star cluster. This technique (1) fully exploits the information content of a given data set; (2) can account for observational uncertainties in a straightforward way; (3) assigns meaningful uncertainties to the inferred parameters; (4) avoids the pitfalls associated with binning data; and (5) can be applied to virtually any resolved young cluster, laying the groundwork for a systematic study of the high-mass stellar MF (M >~ 1 M ⊙). Using simulated clusters and Markov Chain Monte Carlo sampling of the probability distribution functions, we show that estimates of the MF slope, α, are unbiased and that the uncertainty, Δα, depends primarily on the number of observed stars and on the range of stellar masses they span, assuming that the uncertainties on individual masses and the completeness are both well characterized. Using idealized mock data, we compute the theoretical precision, i.e., lower limits, on α, and provide an analytic approximation for Δα as a function of the observed number of stars and mass range. Comparison with literature studies shows that ~3/4 of quoted uncertainties are smaller than the theoretical lower limit. By correcting these uncertainties to the theoretical lower limits, we find that the literature studies yield langαrang = 2.46, with a 1σ dispersion of 0.35 dex. We verify that it is impossible for a power-law MF to obtain meaningful constraints on the upper mass limit of the initial mass function, beyond the lower bound of the most massive star actually observed. We show that avoiding substantial biases in the MF slope requires (1) including the MF as a prior when deriving individual stellar mass estimates, (2) modeling the uncertainties in the individual stellar masses, and (3) fully characterizing and then explicitly modeling the completeness for stars of a given mass. The precision on MF

  4. Structure, evolution and functional inference on the Mildew Locus O (MLO) gene family in three cultivated Cucurbitaceae spp.

    Science.gov (United States)

    Iovieno, Paolo; Andolfo, Giuseppe; Schiavulli, Adalgisa; Catalano, Domenico; Ricciardi, Luigi; Frusciante, Luigi; Ercolano, Maria Raffaella; Pavan, Stefano

    2015-12-29

    The powdery mildew disease affects thousands of plant species and arguably represents the major fungal threat for many Cucurbitaceae crops, including melon (Cucumis melo L.), watermelon (Citrullus lanatus L.) and zucchini (Cucurbita pepo L.). Several studies revealed that specific members of the Mildew Locus O (MLO) gene family act as powdery mildew susceptibility factors. Indeed, their inactivation, as the result of gene knock-out or knock-down, is associated with a peculiar form of resistance, referred to as mlo resistance. We exploited recently available genomic information to provide a comprehensive overview of the MLO gene family in Cucurbitaceae. We report the identification of 16 MLO homologs in C. melo, 14 in C. lanatus and 18 in C. pepo genomes. Bioinformatic treatment of data allowed phylogenetic inference and the prediction of several ortholog pairs and groups. Comparison with functionally characterized MLO genes and, in C. lanatus, gene expression analysis, resulted in the detection of candidate powdery mildew susceptibility factors. We identified a series of conserved amino acid residues and motifs that are likely to play a major role for the function of MLO proteins. Finally, we performed a codon-based evolutionary analysis indicating a general high level of purifying selection in the three Cucurbitaceae MLO gene families, and the occurrence of regions under diversifying selection in candidate susceptibility factors. Results of this study may help to address further biological questions concerning the evolution and function of MLO genes. Moreover, data reported here could be conveniently used by breeding research, aiming to select powdery mildew resistant cultivars in Cucurbitaceae.

  5. Vikodak--A Modular Framework for Inferring Functional Potential of Microbial Communities from 16S Metagenomic Datasets.

    Directory of Open Access Journals (Sweden)

    Sunil Nagpal

    Full Text Available The overall metabolic/functional potential of any given environmental niche is a function of the sum total of genes/proteins/enzymes that are encoded and expressed by various interacting microbes residing in that niche. Consequently, prior (collated information pertaining to genes, enzymes encoded by the resident microbes can aid in indirectly (reconstructing/ inferring the metabolic/ functional potential of a given microbial community (given its taxonomic abundance profile. In this study, we present Vikodak--a multi-modular package that is based on the above assumption and automates inferring and/ or comparing the functional characteristics of an environment using taxonomic abundance generated from one or more environmental sample datasets. With the underlying assumptions of co-metabolism and independent contributions of different microbes in a community, a concerted effort has been made to accommodate microbial co-existence patterns in various modules incorporated in Vikodak.Validation experiments on over 1400 metagenomic samples have confirmed the utility of Vikodak in (a deciphering enzyme abundance profiles of any KEGG metabolic pathway, (b functional resolution of distinct metagenomic environments, (c inferring patterns of functional interaction between resident microbes, and (d automating statistical comparison of functional features of studied microbiomes. Novel features incorporated in Vikodak also facilitate automatic removal of false positives and spurious functional predictions.With novel provisions for comprehensive functional analysis, inclusion of microbial co-existence pattern based algorithms, automated inter-environment comparisons; in-depth analysis of individual metabolic pathways and greater flexibilities at the user end, Vikodak is expected to be an important value addition to the family of existing tools for 16S based function prediction.A web implementation of Vikodak can be publicly accessed at: http

  6. THE PANCHROMATIC HUBBLE ANDROMEDA TREASURY. IV. A PROBABILISTIC APPROACH TO INFERRING THE HIGH-MASS STELLAR INITIAL MASS FUNCTION AND OTHER POWER-LAW FUNCTIONS

    Energy Technology Data Exchange (ETDEWEB)

    Weisz, Daniel R.; Fouesneau, Morgan; Dalcanton, Julianne J.; Clifton Johnson, L.; Beerman, Lori C.; Williams, Benjamin F. [Department of Astronomy, University of Washington, Box 351580, Seattle, WA 98195 (United States); Hogg, David W.; Foreman-Mackey, Daniel T. [Center for Cosmology and Particle Physics, New York University, 4 Washington Place, New York, NY 10003 (United States); Rix, Hans-Walter; Gouliermis, Dimitrios [Max Planck Institute for Astronomy, Koenigstuhl 17, D-69117 Heidelberg (Germany); Dolphin, Andrew E. [Raytheon Company, 1151 East Hermans Road, Tucson, AZ 85756 (United States); Lang, Dustin [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Bell, Eric F. [Department of Astronomy, University of Michigan, 500 Church Street, Ann Arbor, MI 48109 (United States); Gordon, Karl D.; Kalirai, Jason S. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Skillman, Evan D., E-mail: dweisz@astro.washington.edu [Minnesota Institute for Astrophysics, University of Minnesota, 116 Church Street SE, Minneapolis, MN 55455 (United States)

    2013-01-10

    We present a probabilistic approach for inferring the parameters of the present-day power-law stellar mass function (MF) of a resolved young star cluster. This technique (1) fully exploits the information content of a given data set; (2) can account for observational uncertainties in a straightforward way; (3) assigns meaningful uncertainties to the inferred parameters; (4) avoids the pitfalls associated with binning data; and (5) can be applied to virtually any resolved young cluster, laying the groundwork for a systematic study of the high-mass stellar MF (M {approx}> 1 M {sub Sun }). Using simulated clusters and Markov Chain Monte Carlo sampling of the probability distribution functions, we show that estimates of the MF slope, {alpha}, are unbiased and that the uncertainty, {Delta}{alpha}, depends primarily on the number of observed stars and on the range of stellar masses they span, assuming that the uncertainties on individual masses and the completeness are both well characterized. Using idealized mock data, we compute the theoretical precision, i.e., lower limits, on {alpha}, and provide an analytic approximation for {Delta}{alpha} as a function of the observed number of stars and mass range. Comparison with literature studies shows that {approx}3/4 of quoted uncertainties are smaller than the theoretical lower limit. By correcting these uncertainties to the theoretical lower limits, we find that the literature studies yield ({alpha}) = 2.46, with a 1{sigma} dispersion of 0.35 dex. We verify that it is impossible for a power-law MF to obtain meaningful constraints on the upper mass limit of the initial mass function, beyond the lower bound of the most massive star actually observed. We show that avoiding substantial biases in the MF slope requires (1) including the MF as a prior when deriving individual stellar mass estimates, (2) modeling the uncertainties in the individual stellar masses, and (3) fully characterizing and then explicitly modeling the

  7. THE PANCHROMATIC HUBBLE ANDROMEDA TREASURY. IV. A PROBABILISTIC APPROACH TO INFERRING THE HIGH-MASS STELLAR INITIAL MASS FUNCTION AND OTHER POWER-LAW FUNCTIONS

    International Nuclear Information System (INIS)

    Weisz, Daniel R.; Fouesneau, Morgan; Dalcanton, Julianne J.; Clifton Johnson, L.; Beerman, Lori C.; Williams, Benjamin F.; Hogg, David W.; Foreman-Mackey, Daniel T.; Rix, Hans-Walter; Gouliermis, Dimitrios; Dolphin, Andrew E.; Lang, Dustin; Bell, Eric F.; Gordon, Karl D.; Kalirai, Jason S.; Skillman, Evan D.

    2013-01-01

    We present a probabilistic approach for inferring the parameters of the present-day power-law stellar mass function (MF) of a resolved young star cluster. This technique (1) fully exploits the information content of a given data set; (2) can account for observational uncertainties in a straightforward way; (3) assigns meaningful uncertainties to the inferred parameters; (4) avoids the pitfalls associated with binning data; and (5) can be applied to virtually any resolved young cluster, laying the groundwork for a systematic study of the high-mass stellar MF (M ∼> 1 M ☉ ). Using simulated clusters and Markov Chain Monte Carlo sampling of the probability distribution functions, we show that estimates of the MF slope, α, are unbiased and that the uncertainty, Δα, depends primarily on the number of observed stars and on the range of stellar masses they span, assuming that the uncertainties on individual masses and the completeness are both well characterized. Using idealized mock data, we compute the theoretical precision, i.e., lower limits, on α, and provide an analytic approximation for Δα as a function of the observed number of stars and mass range. Comparison with literature studies shows that ∼3/4 of quoted uncertainties are smaller than the theoretical lower limit. By correcting these uncertainties to the theoretical lower limits, we find that the literature studies yield (α) = 2.46, with a 1σ dispersion of 0.35 dex. We verify that it is impossible for a power-law MF to obtain meaningful constraints on the upper mass limit of the initial mass function, beyond the lower bound of the most massive star actually observed. We show that avoiding substantial biases in the MF slope requires (1) including the MF as a prior when deriving individual stellar mass estimates, (2) modeling the uncertainties in the individual stellar masses, and (3) fully characterizing and then explicitly modeling the completeness for stars of a given mass. The precision on MF

  8. Obesity as a risk factor for developing functional limitation among older adults: A conditional inference tree analysis.

    Science.gov (United States)

    Cheng, Feon W; Gao, Xiang; Bao, Le; Mitchell, Diane C; Wood, Craig; Sliwinski, Martin J; Smiciklas-Wright, Helen; Still, Christopher D; Rolston, David D K; Jensen, Gordon L

    2017-07-01

    To examine the risk factors of developing functional decline and make probabilistic predictions by using a tree-based method that allows higher order polynomials and interactions of the risk factors. The conditional inference tree analysis, a data mining approach, was used to construct a risk stratification algorithm for developing functional limitation based on BMI and other potential risk factors for disability in 1,951 older adults without functional limitations at baseline (baseline age 73.1 ± 4.2 y). We also analyzed the data with multivariate stepwise logistic regression and compared the two approaches (e.g., cross-validation). Over a mean of 9.2 ± 1.7 years of follow-up, 221 individuals developed functional limitation. Higher BMI, age, and comorbidity were consistently identified as significant risk factors for functional decline using both methods. Based on these factors, individuals were stratified into four risk groups via the conditional inference tree analysis. Compared to the low-risk group, all other groups had a significantly higher risk of developing functional limitation. The odds ratio comparing two extreme categories was 9.09 (95% confidence interval: 4.68, 17.6). Higher BMI, age, and comorbid disease were consistently identified as significant risk factors for functional decline among older individuals across all approaches and analyses. © 2017 The Obesity Society.

  9. Designs and Methods for Association Studies and Population Size Inference in Statistical Genetics

    DEFF Research Database (Denmark)

    Waltoft, Berit Lindum

    method provides a simple goodness of t test by comparing the observed SFS with the expected SFS under a given model of population size changes. By the use of Monte Carlo estimation the expected time between coalescent events can be estimated and the expected SFS can thereby be evaluated. Using......). The OR is interpreted as the eect of an exposure on the probability of being diseased at the end of follow-up, while the interpretation of the IRR is the eect of an exposure on the probability of becoming diseased. Through a simulation study, the OR from a classical case-control study is shown to be an inconsistent...... the classical chi-square statistics we are able to infer single parameter models. Multiple parameter models, e.g. multiple epochs, are harder to identify. By introducing the inference of population size back in time as an inverse problem, the second procedure applies the theory of smoothing splines to infer...

  10. Prosecutor: parameter-free inference of gene function for prokaryotes using DNA microarray data, genomic context and multiple gene annotation sources

    Directory of Open Access Journals (Sweden)

    van Hijum Sacha AFT

    2008-10-01

    Full Text Available Abstract Background Despite a plethora of functional genomic efforts, the function of many genes in sequenced genomes remains unknown. The increasing amount of microarray data for many species allows employing the guilt-by-association principle to predict function on a large scale: genes exhibiting similar expression patterns are more likely to participate in shared biological processes. Results We developed Prosecutor, an application that enables researchers to rapidly infer gene function based on available gene expression data and functional annotations. Our parameter-free functional prediction method uses a sensitive algorithm to achieve a high association rate of linking genes with unknown function to annotated genes. Furthermore, Prosecutor utilizes additional biological information such as genomic context and known regulatory mechanisms that are specific for prokaryotes. We analyzed publicly available transcriptome data sets and used literature sources to validate putative functions suggested by Prosecutor. We supply the complete results of our analysis for 11 prokaryotic organisms on a dedicated website. Conclusion The Prosecutor software and supplementary datasets available at http://www.prosecutor.nl allow researchers working on any of the analyzed organisms to quickly identify the putative functions of their genes of interest. A de novo analysis allows new organisms to be studied.

  11. Inferring Social Functions Available in the Metro Station Area from Passengers’ Staying Activities in Smart Card Data

    Directory of Open Access Journals (Sweden)

    Yang Zhou

    2017-12-01

    Full Text Available The function of a metro station area is vital for city planners to consider when establishing a context-aware Transit-Oriented Development policy around the station area. However, the functions of metro station areas are hard to infer using the static land use distribution and other traditional survey datasets. In this paper, we propose a method to infer the functions occurring around the metro station catchment areas according to the patterns of staying activities derived from smart card data. We first define the staying activities by the spatial and temporal constraints of the two consecutive alighting and boarding records from the individual travel profile. Then we cluster and label the whole staying activities by considering the features of duration, frequency, and start time. By analyzing the percentage of different types of aggregated activities happening around each metro station, we cluster and explore the functions of the metro station area. Taking Wuhan as a case study, we analyze the results of Wuhan metro systems and discuss the similarities and differences between the functions and the land use distribution around the station area. The results show that although there exist some agreements, there is also a gap between the human activities and the land uses around the station area. These findings could give us deeper insight into how people act around the stations by metro systems, which will ultimately benefit the urban planning and policy development.

  12. Comparison of Generalized Estimating Equations and Quadratic Inference Functions in superior versus inferior Ahmed Glaucoma Valve implantation

    Directory of Open Access Journals (Sweden)

    Razieh Khajeh-Kazemi

    2011-01-01

    Full Text Available Background: The celebrated generalized estimating equations (GEE approach is often used in longitudinal data analysis While this method behaves robustly against misspecification of the working correlation structure, it has some limitations on efficacy of estimators, goodness-of-fit tests and model selection criteria The quadratic inference functions (QIF is a new statistical methodology that overcomes these limitations Methods : We administered the use of QIF and GEE in comparing the superior and inferior Ahmed glaucoma valve (AGV implantation, while our focus was on the efficiency of estimation and using model selection criteria, we compared the effect of implant location on intraocular pressure (IOP in refractory glaucoma patients We modeled the relationship between IOP and implant location, patient′s sex and age, best corrected visual acuity, history of cataract surgery, preoperative IOP and months after surgery with assuming unstructured working correlation Results : 63 eyes of 63 patients were included in this study, 28 eyes in inferior group and 35 eyes in superior group The GEE analysis revealed that preoperative IOP has a significant effect on IOP (p = 0 011 However, QIF showed that preoperative IOP, months after surgery and squared months are significantly associated with IOP after surgery (p < 0 05 Overall, estimates from QIF are more efficient than GEE (RE = 1 272 Conclusions : In the case of unstructured working correlation, the QIF is more efficient than GEE There were no considerable difference between these locations, our results confirmed previously published works which mentioned it is better that glaucoma patients undergo superior AGV implantation

  13. Rank of tensors of l-out-of-k functions: an application in probabilistic inference

    Czech Academy of Sciences Publication Activity Database

    Vomlel, Jiří

    2011-01-01

    Roč. 47, č. 3 (2011), s. 317-336 ISSN 0023-5954 R&D Projects: GA MŠk 1M0572; GA ČR GA201/09/1891; GA ČR GEICC/08/E010 Grant - others:GA MŠk(CZ) 2C06019 Institutional research plan: CEZ:AV0Z10750506 Keywords : Bayesian network * probabilistic inference * tensor rank Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 0.454, year: 2011 http://library.utia.cas.cz/separaty/2011/MTR/vomlel-0361630.pdf

  14. Gaussian likelihood inference on data from trans-Gaussian random fields with Matérn covariance function

    KAUST Repository

    Yan, Yuan

    2017-07-13

    Gaussian likelihood inference has been studied and used extensively in both statistical theory and applications due to its simplicity. However, in practice, the assumption of Gaussianity is rarely met in the analysis of spatial data. In this paper, we study the effect of non-Gaussianity on Gaussian likelihood inference for the parameters of the Matérn covariance model. By using Monte Carlo simulations, we generate spatial data from a Tukey g-and-h random field, a flexible trans-Gaussian random field, with the Matérn covariance function, where g controls skewness and h controls tail heaviness. We use maximum likelihood based on the multivariate Gaussian distribution to estimate the parameters of the Matérn covariance function. We illustrate the effects of non-Gaussianity of the data on the estimated covariance function by means of functional boxplots. Thanks to our tailored simulation design, a comparison of the maximum likelihood estimator under both the increasing and fixed domain asymptotics for spatial data is performed. We find that the maximum likelihood estimator based on Gaussian likelihood is overall satisfying and preferable than the non-distribution-based weighted least squares estimator for data from the Tukey g-and-h random field. We also present the result for Gaussian kriging based on Matérn covariance estimates with data from the Tukey g-and-h random field and observe an overall satisfactory performance.

  15. Gaussian likelihood inference on data from trans-Gaussian random fields with Matérn covariance function

    KAUST Repository

    Yan, Yuan; Genton, Marc G.

    2017-01-01

    Gaussian likelihood inference has been studied and used extensively in both statistical theory and applications due to its simplicity. However, in practice, the assumption of Gaussianity is rarely met in the analysis of spatial data. In this paper, we study the effect of non-Gaussianity on Gaussian likelihood inference for the parameters of the Matérn covariance model. By using Monte Carlo simulations, we generate spatial data from a Tukey g-and-h random field, a flexible trans-Gaussian random field, with the Matérn covariance function, where g controls skewness and h controls tail heaviness. We use maximum likelihood based on the multivariate Gaussian distribution to estimate the parameters of the Matérn covariance function. We illustrate the effects of non-Gaussianity of the data on the estimated covariance function by means of functional boxplots. Thanks to our tailored simulation design, a comparison of the maximum likelihood estimator under both the increasing and fixed domain asymptotics for spatial data is performed. We find that the maximum likelihood estimator based on Gaussian likelihood is overall satisfying and preferable than the non-distribution-based weighted least squares estimator for data from the Tukey g-and-h random field. We also present the result for Gaussian kriging based on Matérn covariance estimates with data from the Tukey g-and-h random field and observe an overall satisfactory performance.

  16. Hierarchy-associated semantic-rule inference framework for classifying indoor scenes

    Science.gov (United States)

    Yu, Dan; Liu, Peng; Ye, Zhipeng; Tang, Xianglong; Zhao, Wei

    2016-03-01

    Typically, the initial task of classifying indoor scenes is challenging, because the spatial layout and decoration of a scene can vary considerably. Recent efforts at classifying object relationships commonly depend on the results of scene annotation and predefined rules, making classification inflexible. Furthermore, annotation results are easily affected by external factors. Inspired by human cognition, a scene-classification framework was proposed using the empirically based annotation (EBA) and a match-over rule-based (MRB) inference system. The semantic hierarchy of images is exploited by EBA to construct rules empirically for MRB classification. The problem of scene classification is divided into low-level annotation and high-level inference from a macro perspective. Low-level annotation involves detecting the semantic hierarchy and annotating the scene with a deformable-parts model and a bag-of-visual-words model. In high-level inference, hierarchical rules are extracted to train the decision tree for classification. The categories of testing samples are generated from the parts to the whole. Compared with traditional classification strategies, the proposed semantic hierarchy and corresponding rules reduce the effect of a variable background and improve the classification performance. The proposed framework was evaluated on a popular indoor scene dataset, and the experimental results demonstrate its effectiveness.

  17. Functional morphology of the hallucal metatarsal with implications for inferring grasping ability in extinct primates.

    Science.gov (United States)

    Goodenberger, Katherine E; Boyer, Doug M; Orr, Caley M; Jacobs, Rachel L; Femiani, John C; Patel, Biren A

    2015-03-01

    Primate evolutionary morphologists have argued that selection for life in a fine branch niche resulted in grasping specializations that are reflected in the hallucal metatarsal (Mt1) morphology of extant "prosimians", while a transition to use of relatively larger, horizontal substrates explains the apparent loss of such characters in anthropoids. Accordingly, these morphological characters-Mt1 torsion, peroneal process length and thickness, and physiological abduction angle-have been used to reconstruct grasping ability and locomotor mode in the earliest fossil primates. Although these characters are prominently featured in debates on the origin and subsequent radiation of Primates, questions remain about their functional significance. This study examines the relationship between these morphological characters of the Mt1 and a novel metric of pedal grasping ability for a large number of extant taxa in a phylogenetic framework. Results indicate greater Mt1 torsion in taxa that engage in hallucal grasping and in those that utilize relatively small substrates more frequently. This study provides evidence that Carpolestes simpsoni has a torsion value more similar to grasping primates than to any scandentian. The results also show that taxa that habitually grasp vertical substrates are distinguished from other taxa in having relatively longer peroneal processes. Furthermore, a longer peroneal process is also correlated with calcaneal elongation, a metric previously found to reflect leaping proclivity. A more refined understanding of the functional associations between Mt1 morphology and behavior in extant primates enhances the potential for using these morphological characters to comprehend primate (locomotor) evolution. © 2014 Wiley Periodicals, Inc.

  18. Statistical inference

    CERN Document Server

    Rohatgi, Vijay K

    2003-01-01

    Unified treatment of probability and statistics examines and analyzes the relationship between the two fields, exploring inferential issues. Numerous problems, examples, and diagrams--some with solutions--plus clear-cut, highlighted summaries of results. Advanced undergraduate to graduate level. Contents: 1. Introduction. 2. Probability Model. 3. Probability Distributions. 4. Introduction to Statistical Inference. 5. More on Mathematical Expectation. 6. Some Discrete Models. 7. Some Continuous Models. 8. Functions of Random Variables and Random Vectors. 9. Large-Sample Theory. 10. General Meth

  19. Mobile sensing of point-source fugitive methane emissions using Bayesian inference: the determination of the likelihood function

    Science.gov (United States)

    Zhou, X.; Albertson, J. D.

    2016-12-01

    Natural gas is considered as a bridge fuel towards clean energy due to its potential lower greenhouse gas emission comparing with other fossil fuels. Despite numerous efforts, an efficient and cost-effective approach to monitor fugitive methane emissions along the natural gas production-supply chain has not been developed yet. Recently, mobile methane measurement has been introduced which applies a Bayesian approach to probabilistically infer methane emission rates and update estimates recursively when new measurements become available. However, the likelihood function, especially the error term which determines the shape of the estimate uncertainty, is not rigorously defined and evaluated with field data. To address this issue, we performed a series of near-source (using a specialized vehicle mounted with fast response methane analyzers and a GPS unit. Methane concentrations were measured at two different heights along mobile traversals downwind of the sources, and concurrent wind and temperature data are recorded by nearby 3-D sonic anemometers. With known methane release rates, the measurements were used to determine the functional form and the parameterization of the likelihood function in the Bayesian inference scheme under different meteorological conditions.

  20. Inferring Weighted Directed Association Networks from Multivariate Time Series with the Small-Shuffle Symbolic Transfer Entropy Spectrum Method

    Directory of Open Access Journals (Sweden)

    Yanzhu Hu

    2016-09-01

    Full Text Available Complex network methodology is very useful for complex system exploration. However, the relationships among variables in complex systems are usually not clear. Therefore, inferring association networks among variables from their observed data has been a popular research topic. We propose a method, named small-shuffle symbolic transfer entropy spectrum (SSSTES, for inferring association networks from multivariate time series. The method can solve four problems for inferring association networks, i.e., strong correlation identification, correlation quantification, direction identification and temporal relation identification. The method can be divided into four layers. The first layer is the so-called data layer. Data input and processing are the things to do in this layer. In the second layer, we symbolize the model data, original data and shuffled data, from the previous layer and calculate circularly transfer entropy with different time lags for each pair of time series variables. Thirdly, we compose transfer entropy spectrums for pairwise time series with the previous layer’s output, a list of transfer entropy matrix. We also identify the correlation level between variables in this layer. In the last layer, we build a weighted adjacency matrix, the value of each entry representing the correlation level between pairwise variables, and then get the weighted directed association network. Three sets of numerical simulated data from a linear system, a nonlinear system and a coupled Rossler system are used to show how the proposed approach works. Finally, we apply SSSTES to a real industrial system and get a better result than with two other methods.

  1. Inference of functional properties from large-scale analysis of enzyme superfamilies.

    Science.gov (United States)

    Brown, Shoshana D; Babbitt, Patricia C

    2012-01-02

    As increasingly large amounts of data from genome and other sequencing projects become available, new approaches are needed to determine the functions of the proteins these genes encode. We show how large-scale computational analysis can help to address this challenge by linking functional information to sequence and structural similarities using protein similarity networks. Network analyses using three functionally diverse enzyme superfamilies illustrate the use of these approaches for facile updating and comparison of available structures for a large superfamily, for creation of functional hypotheses for metagenomic sequences, and to summarize the limits of our functional knowledge about even well studied superfamilies.

  2. Inference of Functional Properties from Large-scale Analysis of Enzyme Superfamilies*

    Science.gov (United States)

    Brown, Shoshana D.; Babbitt, Patricia C.

    2012-01-01

    As increasingly large amounts of data from genome and other sequencing projects become available, new approaches are needed to determine the functions of the proteins these genes encode. We show how large-scale computational analysis can help to address this challenge by linking functional information to sequence and structural similarities using protein similarity networks. Network analyses using three functionally diverse enzyme superfamilies illustrate the use of these approaches for facile updating and comparison of available structures for a large superfamily, for creation of functional hypotheses for metagenomic sequences, and to summarize the limits of our functional knowledge about even well studied superfamilies. PMID:22069325

  3. A Genome-Scale Investigation of How Sequence, Function, and Tree-Based Gene Properties Influence Phylogenetic Inference.

    Science.gov (United States)

    Shen, Xing-Xing; Salichos, Leonidas; Rokas, Antonis

    2016-09-02

    Molecular phylogenetic inference is inherently dependent on choices in both methodology and data. Many insightful studies have shown how choices in methodology, such as the model of sequence evolution or optimality criterion used, can strongly influence inference. In contrast, much less is known about the impact of choices in the properties of the data, typically genes, on phylogenetic inference. We investigated the relationships between 52 gene properties (24 sequence-based, 19 function-based, and 9 tree-based) with each other and with three measures of phylogenetic signal in two assembled data sets of 2,832 yeast and 2,002 mammalian genes. We found that most gene properties, such as evolutionary rate (measured through the percent average of pairwise identity across taxa) and total tree length, were highly correlated with each other. Similarly, several gene properties, such as gene alignment length, Guanine-Cytosine content, and the proportion of tree distance on internal branches divided by relative composition variability (treeness/RCV), were strongly correlated with phylogenetic signal. Analysis of partial correlations between gene properties and phylogenetic signal in which gene evolutionary rate and alignment length were simultaneously controlled, showed similar patterns of correlations, albeit weaker in strength. Examination of the relative importance of each gene property on phylogenetic signal identified gene alignment length, alongside with number of parsimony-informative sites and variable sites, as the most important predictors. Interestingly, the subsets of gene properties that optimally predicted phylogenetic signal differed considerably across our three phylogenetic measures and two data sets; however, gene alignment length and RCV were consistently included as predictors of all three phylogenetic measures in both yeasts and mammals. These results suggest that a handful of sequence-based gene properties are reliable predictors of phylogenetic signal

  4. Functional equivalency inferred from "authoritative sources" in networks of homologous proteins.

    Science.gov (United States)

    Natarajan, Shreedhar; Jakobsson, Eric

    2009-06-12

    A one-on-one mapping of protein functionality across different species is a critical component of comparative analysis. This paper presents a heuristic algorithm for discovering the Most Likely Functional Counterparts (MoLFunCs) of a protein, based on simple concepts from network theory. A key feature of our algorithm is utilization of the user's knowledge to assign high confidence to selected functional identification. We show use of the algorithm to retrieve functional equivalents for 7 membrane proteins, from an exploration of almost 40 genomes form multiple online resources. We verify the functional equivalency of our dataset through a series of tests that include sequence, structure and function comparisons. Comparison is made to the OMA methodology, which also identifies one-on-one mapping between proteins from different species. Based on that comparison, we believe that incorporation of user's knowledge as a key aspect of the technique adds value to purely statistical formal methods.

  5. Inferring common cognitive mechanisms from brain blood-flow lateralisation data obtained with functional transcranial Doppler ultrasound.

    Directory of Open Access Journals (Sweden)

    Georg eMeyer

    2014-06-01

    Full Text Available Current neuroimaging techniques with high spatial resolution constrain participant motion so that many natural tasks cannot be carried out. The aim of this paper is to show how a time-locked correlation-analysis of cerebral blood flow velocity (CBFV lateralisation data, obtained with functional TransCranial Doppler (fTCD ultrasound, can be used to infer cerebral activation patterns across tasks. In a first experiment we demonstrate that the proposed analysis method results in data that are comparable with the standard Lateralisation Index (LI for within-task comparisons of CBFV patterns, recorded during cued word generation (CWG at two difficulty levels.In the main experiment we demonstrate that the proposed analysis method shows correlated blood-flow patterns for two different cognitive tasks that are known to draw on common brain areas, CWG and Music Synthesis. We show that CBFV patterns for Music and CWG are correlated only for participants with prior musical training.CBFV patterns for tasks that draw on distinct brain areas, the Tower of London and CWG, are not correlated.The proposed methodology extends conventional fTCD analysis by including temporal information in the analysis of cerebral blood-flow patterns to provide a robust, non-invasive method to infer whether common brain areas are used in different cognitive tasks. It complements conventional high resolution imaging techniques.

  6. LED Lighting System Reliability Modeling and Inference via Random Effects Gamma Process and Copula Function

    Directory of Open Access Journals (Sweden)

    Huibing Hao

    2015-01-01

    Full Text Available Light emitting diode (LED lamp has attracted increasing interest in the field of lighting systems due to its low energy and long lifetime. For different functions (i.e., illumination and color, it may have two or more performance characteristics. When the multiple performance characteristics are dependent, it creates a challenging problem to accurately analyze the system reliability. In this paper, we assume that the system has two performance characteristics, and each performance characteristic is governed by a random effects Gamma process where the random effects can capture the unit to unit differences. The dependency of performance characteristics is described by a Frank copula function. Via the copula function, the reliability assessment model is proposed. Considering the model is so complicated and analytically intractable, the Markov chain Monte Carlo (MCMC method is used to estimate the unknown parameters. A numerical example about actual LED lamps data is given to demonstrate the usefulness and validity of the proposed model and method.

  7. Pragmatic Inferences in High-Functioning Adults with Autism and Asperger Syndrome

    Science.gov (United States)

    Pijnacker, Judith; Hagoort, Peter; Buitelaar, Jan; Teunisse, Jan-Pieter; Geurts, Bart

    2009-01-01

    Although people with autism spectrum disorders (ASD) often have severe problems with pragmatic aspects of language, little is known about their pragmatic reasoning. We carried out a behavioral study on high-functioning adults with autistic disorder (n = 11) and Asperger syndrome (n = 17) and matched controls (n = 28) to investigate whether they…

  8. Pragmatic Inferences in High-Functioning Adults with Autism and Asperger Syndrome

    NARCIS (Netherlands)

    Pijnacker, J.; Hagoort, P.; Buitelaar, J.K.; Teunisse, J.P.W.M.; Geurts, L.B.W.

    2009-01-01

    Although people with autism spectrum disorders (ASD) often have severe problems with pragmatic aspects of language, little is known about their pragmatic reasoning. We carried out a behavioral study on high-functioning adults with autistic disorder (n = 11) and Asperger syndrome (n = 17) and matched

  9. Pragmatic inferences in high-functioning adults with autism and Asperger syndrome.

    NARCIS (Netherlands)

    Pijnacker, J.; Hagoort, P.; Buitelaar, J.K.; Teunisse, J.P.W.M.; Geurts, B.

    2009-01-01

    Although people with autism spectrum disorders (ASD) often have severe problems with pragmatic aspects of language, little is known about their pragmatic reasoning. We carried out a behavioral study on high-functioning adults with autistic disorder (n = 11) and Asperger syndrome (n = 17) and matched

  10. The cost of misremembering: Inferring the loss function in visual working memory.

    Science.gov (United States)

    Sims, Chris R

    2015-03-04

    Visual working memory (VWM) is a highly limited storage system. A basic consequence of this fact is that visual memories cannot perfectly encode or represent the veridical structure of the world. However, in natural tasks, some memory errors might be more costly than others. This raises the intriguing possibility that the nature of memory error reflects the costs of committing different kinds of errors. Many existing theories assume that visual memories are noise-corrupted versions of afferent perceptual signals. However, this additive noise assumption oversimplifies the problem. Implicit in the behavioral phenomena of visual working memory is the concept of a loss function: a mathematical entity that describes the relative cost to the organism of making different types of memory errors. An optimally efficient memory system is one that minimizes the expected loss according to a particular loss function, while subject to a constraint on memory capacity. This paper describes a novel theoretical framework for characterizing visual working memory in terms of its implicit loss function. Using inverse decision theory, the empirical loss function is estimated from the results of a standard delayed recall visual memory experiment. These results are compared to the predicted behavior of a visual working memory system that is optimally efficient for a previously identified natural task, gaze correction following saccadic error. Finally, the approach is compared to alternative models of visual working memory, and shown to offer a superior account of the empirical data across a range of experimental datasets. © 2015 ARVO.

  11. Inferring the physical connectivity of complex networks from their functional dynamics

    Directory of Open Access Journals (Sweden)

    Holm Liisa

    2010-05-01

    Full Text Available Abstract Background Biological networks, such as protein-protein interactions, metabolic, signalling, transcription-regulatory networks and neural synapses, are representations of large-scale dynamic systems. The relationship between the network structure and functions remains one of the central problems in current multidisciplinary research. Significant progress has been made toward understanding the implication of topological features for the network dynamics and functions, especially in biological networks. Given observations of a network system's behaviours or measurements of its functional dynamics, what can we conclude of the details of physical connectivity of the underlying structure? Results We modelled the network system by employing a scale-free network of coupled phase oscillators. Pairwise phase coherence (PPC was calculated for all the pairs of oscillators to present functional dynamics induced by the system. At the regime of global incoherence, we observed a Significant pairwise synchronization only between two nodes that are physically connected. Right after the onset of global synchronization, disconnected nodes begin to oscillate in a correlated fashion and the PPC of two nodes, either connected or disconnected, depends on their degrees. Based on the observation of PPCs, we built a weighted network of synchronization (WNS, an all-to-all functionally connected network where each link is weighted by the PPC of two oscillators at the ends of the link. In the regime of strong coupling, we observed a Significant similarity in the organization of WNSs induced by systems sharing the same substrate network but different configurations of initial phases and intrinsic frequencies of oscillators. We reconstruct physical network from the WNS by choosing the links whose weights are higher than a given threshold. We observed an optimal reconstruction just before the onset of global synchronization. Finally, we correlated the topology of the

  12. Characteristic function-based semiparametric inference for skew-symmetric models

    KAUST Repository

    Potgieter, Cornelis J.

    2012-12-26

    Skew-symmetric models offer a very flexible class of distributions for modelling data. These distributions can also be viewed as selection models for the symmetric component of the specified skew-symmetric distribution. The estimation of the location and scale parameters corresponding to the symmetric component is considered here, with the symmetric component known. Emphasis is placed on using the empirical characteristic function to estimate these parameters. This is made possible by an invariance property of the skew-symmetric family of distributions, namely that even transformations of random variables that are skew-symmetric have a distribution only depending on the symmetric density. A distance metric between the real components of the empirical and true characteristic functions is minimized to obtain the estimators. The method is semiparametric, in that the symmetric component is specified, but the skewing function is assumed unknown. Furthermore, the methodology is extended to hypothesis testing. Two tests for a hypothesis of specific parameter values are considered, as well as a test for the hypothesis that the symmetric component has a specific parametric form. A resampling algorithm is described for practical implementation of these tests. The outcomes of various numerical experiments are presented. © 2012 Board of the Foundation of the Scandinavian Journal of Statistics.

  13. Inferring Aggregated Functional Traits from Metagenomic Data Using Constrained Non-negative Matrix Factorization: Application to Fiber Degradation in the Human Gut Microbiota.

    Science.gov (United States)

    Raguideau, Sébastien; Plancade, Sandra; Pons, Nicolas; Leclerc, Marion; Laroche, Béatrice

    2016-12-01

    Whole Genome Shotgun (WGS) metagenomics is increasingly used to study the structure and functions of complex microbial ecosystems, both from the taxonomic and functional point of view. Gene inventories of otherwise uncultured microbial communities make the direct functional profiling of microbial communities possible. The concept of community aggregated trait has been adapted from environmental and plant functional ecology to the framework of microbial ecology. Community aggregated traits are quantified from WGS data by computing the abundance of relevant marker genes. They can be used to study key processes at the ecosystem level and correlate environmental factors and ecosystem functions. In this paper we propose a novel model based approach to infer combinations of aggregated traits characterizing specific ecosystemic metabolic processes. We formulate a model of these Combined Aggregated Functional Traits (CAFTs) accounting for a hierarchical structure of genes, which are associated on microbial genomes, further linked at the ecosystem level by complex co-occurrences or interactions. The model is completed with constraints specifically designed to exploit available genomic information, in order to favor biologically relevant CAFTs. The CAFTs structure, as well as their intensity in the ecosystem, is obtained by solving a constrained Non-negative Matrix Factorization (NMF) problem. We developed a multicriteria selection procedure for the number of CAFTs. We illustrated our method on the modelling of ecosystemic functional traits of fiber degradation by the human gut microbiota. We used 1408 samples of gene abundances from several high-throughput sequencing projects and found that four CAFTs only were needed to represent the fiber degradation potential. This data reduction highlighted biologically consistent functional patterns while providing a high quality preservation of the original data. Our method is generic and can be applied to other metabolic processes in

  14. Inferring Aggregated Functional Traits from Metagenomic Data Using Constrained Non-negative Matrix Factorization: Application to Fiber Degradation in the Human Gut Microbiota.

    Directory of Open Access Journals (Sweden)

    Sébastien Raguideau

    2016-12-01

    Full Text Available Whole Genome Shotgun (WGS metagenomics is increasingly used to study the structure and functions of complex microbial ecosystems, both from the taxonomic and functional point of view. Gene inventories of otherwise uncultured microbial communities make the direct functional profiling of microbial communities possible. The concept of community aggregated trait has been adapted from environmental and plant functional ecology to the framework of microbial ecology. Community aggregated traits are quantified from WGS data by computing the abundance of relevant marker genes. They can be used to study key processes at the ecosystem level and correlate environmental factors and ecosystem functions. In this paper we propose a novel model based approach to infer combinations of aggregated traits characterizing specific ecosystemic metabolic processes. We formulate a model of these Combined Aggregated Functional Traits (CAFTs accounting for a hierarchical structure of genes, which are associated on microbial genomes, further linked at the ecosystem level by complex co-occurrences or interactions. The model is completed with constraints specifically designed to exploit available genomic information, in order to favor biologically relevant CAFTs. The CAFTs structure, as well as their intensity in the ecosystem, is obtained by solving a constrained Non-negative Matrix Factorization (NMF problem. We developed a multicriteria selection procedure for the number of CAFTs. We illustrated our method on the modelling of ecosystemic functional traits of fiber degradation by the human gut microbiota. We used 1408 samples of gene abundances from several high-throughput sequencing projects and found that four CAFTs only were needed to represent the fiber degradation potential. This data reduction highlighted biologically consistent functional patterns while providing a high quality preservation of the original data. Our method is generic and can be applied to other

  15. The luminosity function at z ∼ 8 from 97 Y-band dropouts: Inferences about reionization

    International Nuclear Information System (INIS)

    Schmidt, Kasper B.; Treu, Tommaso; Kelly, Brandon C.; Trenti, Michele; Bradley, Larry D.; Stiavelli, Massimo; Oesch, Pascal A.; Holwerda, Benne W.; Shull, J. Michael

    2014-01-01

    We present the largest search to date for Y-band dropout galaxies (z ∼ 8 Lyman break galaxies, LBGs) based on 350 arcmin 2 of Hubble Space Telescope observations in the V, Y, J, and H bands from the Brightest of Reionizing Galaxies (BoRG) survey. In addition to previously published data, the BoRG13 data set presented here includes approximately 50 arcmin 2 of new data and deeper observations of two previous BoRG pointings, from which we present 9 new z ∼ 8 LBG candidates, bringing the total number of BoRG Y-band dropouts to 38 with 25.5 ≤ m J ≤ 27.6 (AB system). We introduce a new Bayesian formalism for estimating the galaxy luminosity function, which does not require binning (and thus smearing) of the data and includes a likelihood based on the formally correct binomial distribution as opposed to the often-used approximate Poisson distribution. We demonstrate the utility of the new method on a sample of 97 Y-band dropouts that combines the bright BoRG galaxies with the fainter sources published in Bouwens et al. from the Hubble Ultra Deep Field and Early Release Science programs. We show that the z ∼ 8 luminosity function is well described by a Schechter function over its full dynamic range with a characteristic magnitude M ⋆ =−20.15 −0.38 +0.29 , a faint-end slope of α=−1.87 −0.26 +0.26 , and a number density of log 10  ϕ ⋆ [Mpc −3 ]=−3.24 −0.24 +0.25 . Integrated down to M = –17.7, this luminosity function yields a luminosity density log 10  ϵ[erg s −1 Hz −1 Mpc −3 ]=25.52 −0.05 +0.05 . Our luminosity function analysis is consistent with previously published determinations within 1σ. The error analysis suggests that uncertainties on the faint-end slope are still too large to draw a firm conclusion about its evolution with redshift. We use our statistical framework to discuss the implication of our study for the physics of reionization. By assuming theoretically motivated priors on the clumping factor and the photon

  16. The luminosity function at z ∼ 8 from 97 Y-band dropouts: Inferences about reionization

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Kasper B.; Treu, Tommaso; Kelly, Brandon C. [Department of Physics, University of California, Santa Barbara, CA 93106-9530 (United States); Trenti, Michele [Kavli Institute for Cosmology and Institute of Astronomy, University of Cambridge, Madingley Road, Cambridge CB3 0HA (United Kingdom); Bradley, Larry D.; Stiavelli, Massimo [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Oesch, Pascal A. [UCO/Lick Observatory, University of California, Santa Cruz, CA 95064 (United States); Holwerda, Benne W. [Leiden Observatory, Leiden University, NL-2300 RA Leiden (Netherlands); Shull, J. Michael, E-mail: kschmidt@physics.ucsb.edu [CASA, Department of Astrophysical and Planetary Science, University of Colorado, Center for Astrophysics and Space Astronomy, 389-UCB, Boulder, CO 80309 (United States)

    2014-05-01

    We present the largest search to date for Y-band dropout galaxies (z ∼ 8 Lyman break galaxies, LBGs) based on 350 arcmin{sup 2} of Hubble Space Telescope observations in the V, Y, J, and H bands from the Brightest of Reionizing Galaxies (BoRG) survey. In addition to previously published data, the BoRG13 data set presented here includes approximately 50 arcmin{sup 2} of new data and deeper observations of two previous BoRG pointings, from which we present 9 new z ∼ 8 LBG candidates, bringing the total number of BoRG Y-band dropouts to 38 with 25.5 ≤ m{sub J} ≤ 27.6 (AB system). We introduce a new Bayesian formalism for estimating the galaxy luminosity function, which does not require binning (and thus smearing) of the data and includes a likelihood based on the formally correct binomial distribution as opposed to the often-used approximate Poisson distribution. We demonstrate the utility of the new method on a sample of 97 Y-band dropouts that combines the bright BoRG galaxies with the fainter sources published in Bouwens et al. from the Hubble Ultra Deep Field and Early Release Science programs. We show that the z ∼ 8 luminosity function is well described by a Schechter function over its full dynamic range with a characteristic magnitude M{sup ⋆}=−20.15{sub −0.38}{sup +0.29}, a faint-end slope of α=−1.87{sub −0.26}{sup +0.26}, and a number density of log{sub 10} ϕ{sup ⋆}[Mpc{sup −3}]=−3.24{sub −0.24}{sup +0.25}. Integrated down to M = –17.7, this luminosity function yields a luminosity density log{sub 10} ϵ[erg s{sup −1} Hz{sup −1} Mpc{sup −3}]=25.52{sub −0.05}{sup +0.05}. Our luminosity function analysis is consistent with previously published determinations within 1σ. The error analysis suggests that uncertainties on the faint-end slope are still too large to draw a firm conclusion about its evolution with redshift. We use our statistical framework to discuss the implication of our study for the physics of

  17. Function of pretribosphenic and tribosphenic mammalian molars inferred from 3D animation.

    Science.gov (United States)

    Schultz, Julia A; Martin, Thomas

    2014-10-01

    Appearance of the tribosphenic molar in the Late Jurassic (160 Ma) is a crucial innovation for food processing in mammalian evolution. This molar type is characterized by a protocone, a talonid basin and a two-phased chewing cycle, all of which are apomorphic. In this functional study on the teeth of Late Jurassic Dryolestes leiriensis and the living marsupial Monodelphis domestica, we demonstrate that pretribosphenic and tribosphenic molars show fundamental differences of food reduction strategies, representing a shift in dental function during the transition of tribosphenic mammals. By using the Occlusal Fingerprint Analyser (OFA), we simulated the chewing motions of the pretribosphenic Dryolestes that represents an evolutionary precursor condition to such tribosphenic mammals as Monodelphis. Animation of chewing path and detection of collisional contacts between virtual models of teeth suggests that Dryolestes differs from the classical two-phased chewing movement of tribosphenidans, due to the narrowing of the interdental space in cervical (crown-root transition) direction, the inclination angle of the hypoflexid groove, and the unicuspid talonid. The pretribosphenic chewing cycle is equivalent to phase I of the tribosphenic chewing cycle, but the former lacks phase II of the tribosphenic chewing. The new approach can analyze the chewing cycle of the jaw by using polygonal 3D models of tooth surfaces, in a way that is complementary to the electromyography and strain gauge studies of muscle function of living animals. The technique allows alignment and scaling of isolated fossil teeth and utilizes the wear facet orientation and striation of the teeth to reconstruct the chewing path of extinct mammals.

  18. Function of pretribosphenic and tribosphenic mammalian molars inferred from 3D animation

    Science.gov (United States)

    Schultz, Julia A.; Martin, Thomas

    2014-10-01

    Appearance of the tribosphenic molar in the Late Jurassic (160 Ma) is a crucial innovation for food processing in mammalian evolution. This molar type is characterized by a protocone, a talonid basin and a two-phased chewing cycle, all of which are apomorphic. In this functional study on the teeth of Late Jurassic Dryolestes leiriensis and the living marsupial Monodelphis domestica, we demonstrate that pretribosphenic and tribosphenic molars show fundamental differences of food reduction strategies, representing a shift in dental function during the transition of tribosphenic mammals. By using the Occlusal Fingerprint Analyser (OFA), we simulated the chewing motions of the pretribosphenic Dryolestes that represents an evolutionary precursor condition to such tribosphenic mammals as Monodelphis. Animation of chewing path and detection of collisional contacts between virtual models of teeth suggests that Dryolestes differs from the classical two-phased chewing movement of tribosphenidans, due to the narrowing of the interdental space in cervical (crown-root transition) direction, the inclination angle of the hypoflexid groove, and the unicuspid talonid. The pretribosphenic chewing cycle is equivalent to phase I of the tribosphenic chewing cycle, but the former lacks phase II of the tribosphenic chewing. The new approach can analyze the chewing cycle of the jaw by using polygonal 3D models of tooth surfaces, in a way that is complementary to the electromyography and strain gauge studies of muscle function of living animals. The technique allows alignment and scaling of isolated fossil teeth and utilizes the wear facet orientation and striation of the teeth to reconstruct the chewing path of extinct mammals.

  19. Potential and limitations of inferring ecosystem photosynthetic capacity from leaf functional traits

    Czech Academy of Sciences Publication Activity Database

    Musavi, T.; Migliavacca, M.; van de Weg, M. J.; Kattge, J.; Wohlfahrt, G.; van Bodegom, P. M.; Reichstein, M.; Bahn, M.; Carrara, A.; Domingues, T. F.; Gavazzi, M.; Gianelle, D.; Gimeno, C.; Granier, A.; Gruening, C.; Havránková, Kateřina; Herbst, M.; Hrynkiw, Ch.; Kalhori, A.; Kaminski, T.; Klumpp, K.; Kolari, P.; Longdoz, B.; Minerbi, S.; Montagnani, L.; Moors, E.; Oechel, W.; Reich, P. B.; Rohatyn, S.; Rossi, A.; Rotenberg, E.; Varlagin, A.; Wilkinson, M.; Wirth, C.; Mahecha, M. D.

    2016-01-01

    Roč. 6, č. 20 (2016), s. 7352-7366 ISSN 2045-7758 R&D Projects: GA MŠk(CZ) LO1415 Institutional support: RVO:67179843 Keywords : gross primary production * cross-biome analysis * relative growth-rate * plant traits * carbon-dioxide * forest productivity * wide-range * environmental variation * nutrient concentrations * terrestrial biosphere * ecosystem functional property * eddy covariance * fluxnet * interannual variability * photosynthetic capacity * plant traits * spatiotemporal variability * TRY database Subject RIV: EH - Ecology, Behaviour Impact factor: 2.440, year: 2016

  20. Bayesian nonparametric inference on quantile residual life function: Application to breast cancer data.

    Science.gov (United States)

    Park, Taeyoung; Jeong, Jong-Hyeon; Lee, Jae Won

    2012-08-15

    There is often an interest in estimating a residual life function as a summary measure of survival data. For ease in presentation of the potential therapeutic effect of a new drug, investigators may summarize survival data in terms of the remaining life years of patients. Under heavy right censoring, however, some reasonably high quantiles (e.g., median) of a residual lifetime distribution cannot be always estimated via a popular nonparametric approach on the basis of the Kaplan-Meier estimator. To overcome the difficulties in dealing with heavily censored survival data, this paper develops a Bayesian nonparametric approach that takes advantage of a fully model-based but highly flexible probabilistic framework. We use a Dirichlet process mixture of Weibull distributions to avoid strong parametric assumptions on the unknown failure time distribution, making it possible to estimate any quantile residual life function under heavy censoring. Posterior computation through Markov chain Monte Carlo is straightforward and efficient because of conjugacy properties and partial collapse. We illustrate the proposed methods by using both simulated data and heavily censored survival data from a recent breast cancer clinical trial conducted by the National Surgical Adjuvant Breast and Bowel Project. Copyright © 2012 John Wiley & Sons, Ltd.

  1. Simultaneous genome-wide inference of physical, genetic, regulatory, and functional pathway components.

    Directory of Open Access Journals (Sweden)

    Christopher Y Park

    2010-11-01

    Full Text Available Biomolecular pathways are built from diverse types of pairwise interactions, ranging from physical protein-protein interactions and modifications to indirect regulatory relationships. One goal of systems biology is to bridge three aspects of this complexity: the growing body of high-throughput data assaying these interactions; the specific interactions in which individual genes participate; and the genome-wide patterns of interactions in a system of interest. Here, we describe methodology for simultaneously predicting specific types of biomolecular interactions using high-throughput genomic data. This results in a comprehensive compendium of whole-genome networks for yeast, derived from ∼3,500 experimental conditions and describing 30 interaction types, which range from general (e.g. physical or regulatory to specific (e.g. phosphorylation or transcriptional regulation. We used these networks to investigate molecular pathways in carbon metabolism and cellular transport, proposing a novel connection between glycogen breakdown and glucose utilization supported by recent publications. Additionally, 14 specific predicted interactions in DNA topological change and protein biosynthesis were experimentally validated. We analyzed the systems-level network features within all interactomes, verifying the presence of small-world properties and enrichment for recurring network motifs. This compendium of physical, synthetic, regulatory, and functional interaction networks has been made publicly available through an interactive web interface for investigators to utilize in future research at http://function.princeton.edu/bioweaver/.

  2. Bayesian inference in an item response theory model with a generalized student t link function

    Science.gov (United States)

    Azevedo, Caio L. N.; Migon, Helio S.

    2012-10-01

    In this paper we introduce a new item response theory (IRT) model with a generalized Student t-link function with unknown degrees of freedom (df), named generalized t-link (GtL) IRT model. In this model we consider only the difficulty parameter in the item response function. GtL is an alternative to the two parameter logit and probit models, since the degrees of freedom (df) play a similar role to the discrimination parameter. However, the behavior of the curves of the GtL is different from those of the two parameter models and the usual Student t link, since in GtL the curve obtained from different df's can cross the probit curves in more than one latent trait level. The GtL model has similar proprieties to the generalized linear mixed models, such as the existence of sufficient statistics and easy parameter interpretation. Also, many techniques of parameter estimation, model fit assessment and residual analysis developed for that models can be used for the GtL model. We develop fully Bayesian estimation and model fit assessment tools through a Metropolis-Hastings step within Gibbs sampling algorithm. We consider a prior sensitivity choice concerning the degrees of freedom. The simulation study indicates that the algorithm recovers all parameters properly. In addition, some Bayesian model fit assessment tools are considered. Finally, a real data set is analyzed using our approach and other usual models. The results indicate that our model fits the data better than the two parameter models.

  3. Inference rule and problem solving

    Energy Technology Data Exchange (ETDEWEB)

    Goto, S

    1982-04-01

    Intelligent information processing signifies an opportunity of having man's intellectual activity executed on the computer, in which inference, in place of ordinary calculation, is used as the basic operational mechanism for such an information processing. Many inference rules are derived from syllogisms in formal logic. The problem of programming this inference function is referred to as a problem solving. Although logically inference and problem-solving are in close relation, the calculation ability of current computers is on a low level for inferring. For clarifying the relation between inference and computers, nonmonotonic logic has been considered. The paper deals with the above topics. 16 references.

  4. Why are dunkels sticky? Preschoolers infer functionality and intentional creation for artifact properties learned from generic language.

    Science.gov (United States)

    Cimpian, Andrei; Cadena, Cristina

    2010-10-01

    Artifacts pose a potential learning problem for children because the mapping between their features and their functions is often not transparent. In solving this problem, children are likely to rely on a number of information sources (e.g., others' actions, affordances). We argue that children's sensitivity to nuances in the language used to describe artifacts is an important, but so far unacknowledged, piece of this puzzle. Specifically, we hypothesize that children are sensitive to whether an unfamiliar artifact's features are highlighted using generic (e.g., "Dunkels are sticky") or non-generic (e.g., "This dunkel is sticky") language. Across two studies, older-but not younger-preschoolers who heard such features introduced via generic statements inferred that they are a functional part of the artifact's design more often than children who heard the same features introduced via non-generic statements. The ability to pick up on this linguistic cue may expand considerably the amount of conceptual information about artifacts that children derive from conversations with adults. Copyright 2010 Elsevier B.V. All rights reserved.

  5. Theta function identities associated with Ramanujan's modular ...

    Indian Academy of Sciences (India)

    In Chapter 20 of his second notebook [6], Ramanujan recorded several theta function identities associated with modular equations of composite degree 15. These identities have previously been proved by Berndt in [3]. But he proved most of these theta function identities using modular equations. These identities can also ...

  6. Seismic Discontinuities within the Crust and Mantle Beneath Indonesia as Inferred from P Receiver Functions

    Science.gov (United States)

    Woelbern, I.; Rumpker, G.

    2015-12-01

    Indonesia is situated at the southern margin of SE Asia, which comprises an assemblage of Gondwana-derived continental terranes, suture zones and volcanic arcs. The formation of SE Asia is believed to have started in Early Devonian. Its complex history involves the opening and closure of three distinct Tethys oceans, each accompanied by the rifting of continental fragments. We apply the receiver function technique to data of the temporary MERAMEX network operated in Central Java from May to October 2004 by the GeoForschungsZentrum Potsdam. The network consisted of 112 mobile stations with a spacing of about 10 km covering the full width of the island between the southern and northern coast lines. The tectonic history is reflected in a complex crustal structure of Central Java exhibiting strong topography of the Moho discontinuity related to different tectonic units. A discontinuity of negative impedance contrast is observed throughout the mid-crust interpreted as the top of a low-velocity layer which shows no depth correlation with the Moho interface. Converted phases generated at greater depth beneath Indonesia indicate the existence of multiple seismic discontinuities within the upper mantle and even below. The strongest signal originates from the base of the mantle transition zone, i.e. the 660 km discontinuity. The phase related to the 410 km discontinuity is less pronounced, but clearly identifiable as well. The derived thickness of the mantle-transition zone is in good agreement with the IASP91 velocity model. Additional phases are observed at roughly 33 s and 90 s relative to the P onset, corresponding to about 300 km and 920 km, respectively. A signal of reversed polarity indicates the top of a low velocity layer at about 370 km depth overlying the mantle transition zone.

  7. Lithospheric Structure of the Yamato Basin Inferred from Trans-dimensional Inversion of Receiver Functions

    Science.gov (United States)

    Akuhara, T.; Nakahigashi, K.; Shinohara, M.; Yamada, T.; Yamashita, Y.; Shiobara, H.; Mochizuki, K.

    2017-12-01

    The Yamato Basin, located at the southeast of the Japan Sea, has been formed by the back-arc opening of the Japan Sea. Wide-angle reflection surveys have revealed that the basin has anomalously thickened crust compared with a normal oceanic crust [e.g., Nakahigashi et al., 2013] while deeper lithospheric structure has not known so far. Revealing the lithospheric structure of the Yamato Basin will lead to better understanding of the formation process of the Japan Sea and thus the Japanese island. In this study, as a first step toward understanding the lithospheric structure, we aim to detect the lithosphere-asthenosphere boundary (LAB) using receiver functions (RFs). We use teleseismic P waveforms recorded by broad-band ocean-bottom seismometers (BBOBS) deployed at the Yamato Basin. We calculated radial-component RFs using the data with the removal of water reverberations from the vertical-component records [Akuhara et al., 2016]. The resultant RFs are more complicated than those calculated at an on-land station, most likely due to sediment-related reverberations. This complexity does not allow either direct detection of a Ps conversion from the LAB or forward modeling by a simple structure composed of a handful number of layers. To overcome this difficulty, we conducted trans-dimensional Markov Chain Monte Carlo inversion of RFs, where we do not need to assume the number of layers in advance [e.g., Bodin et al., 2012; Sambridge et al., 2014]. Our preliminary results show abrupt velocity reduction at 70 km depth, far greater depth than the expected LAB depth from the age of the lithosphere ( 20 Ma, although still debated). If this low-velocity jump truly reflects the LAB, the anomalously thickened lithosphere will provide a new constraint on the complex formation history of the Japan Sea. Further study, however, is required to deny the possibility that the obtained velocity jump is an artificial brought by the overfitting of noisy data.

  8. Genetic variants associated with lung function

    DEFF Research Database (Denmark)

    Thyagarajan, Bharat; Wojczynski, Mary; Minster, Ryan L

    2014-01-01

    with exceptional longevity have not been identified. METHOD: We conducted a genome wide association study (GWAS) to identify novel genetic variants associated with lung function in the Long Life Family Study (LLFS) (n = 3,899). Replication was performed using data from the CHARGE/SpiroMeta consortia...

  9. Probabilistic inductive inference: a survey

    OpenAIRE

    Ambainis, Andris

    2001-01-01

    Inductive inference is a recursion-theoretic theory of learning, first developed by E. M. Gold (1967). This paper surveys developments in probabilistic inductive inference. We mainly focus on finite inference of recursive functions, since this simple paradigm has produced the most interesting (and most complex) results.

  10. FGWAS: Functional genome wide association analysis.

    Science.gov (United States)

    Huang, Chao; Thompson, Paul; Wang, Yalin; Yu, Yang; Zhang, Jingwen; Kong, Dehan; Colen, Rivka R; Knickmeyer, Rebecca C; Zhu, Hongtu

    2017-10-01

    Functional phenotypes (e.g., subcortical surface representation), which commonly arise in imaging genetic studies, have been used to detect putative genes for complexly inherited neuropsychiatric and neurodegenerative disorders. However, existing statistical methods largely ignore the functional features (e.g., functional smoothness and correlation). The aim of this paper is to develop a functional genome-wide association analysis (FGWAS) framework to efficiently carry out whole-genome analyses of functional phenotypes. FGWAS consists of three components: a multivariate varying coefficient model, a global sure independence screening procedure, and a test procedure. Compared with the standard multivariate regression model, the multivariate varying coefficient model explicitly models the functional features of functional phenotypes through the integration of smooth coefficient functions and functional principal component analysis. Statistically, compared with existing methods for genome-wide association studies (GWAS), FGWAS can substantially boost the detection power for discovering important genetic variants influencing brain structure and function. Simulation studies show that FGWAS outperforms existing GWAS methods for searching sparse signals in an extremely large search space, while controlling for the family-wise error rate. We have successfully applied FGWAS to large-scale analysis of data from the Alzheimer's Disease Neuroimaging Initiative for 708 subjects, 30,000 vertices on the left and right hippocampal surfaces, and 501,584 SNPs. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Learning Convex Inference of Marginals

    OpenAIRE

    Domke, Justin

    2012-01-01

    Graphical models trained using maximum likelihood are a common tool for probabilistic inference of marginal distributions. However, this approach suffers difficulties when either the inference process or the model is approximate. In this paper, the inference process is first defined to be the minimization of a convex function, inspired by free energy approximations. Learning is then done directly in terms of the performance of the inference process at univariate marginal prediction. The main ...

  12. Inference comprehension in text reading: Performance of individuals with right- versus left-hemisphere lesions and the influence of cognitive functions.

    Directory of Open Access Journals (Sweden)

    Marcela Lima Silagi

    Full Text Available Right-hemisphere lesions (RHL may impair inference comprehension. However, comparative studies between left-hemisphere lesions (LHL and RHL are rare, especially regarding reading comprehension. Moreover, further knowledge of the influence of cognition on inferential processing in this task is needed.To compare the performance of patients with RHL and LHL on an inference reading comprehension task. We also aimed to analyze the effects of lesion site and to verify correlations between cognitive functions and performance on the task.Seventy-five subjects were equally divided into the groups RHL, LHL, and control group (CG. The Implicit Management Test was used to evaluate inference comprehension. In this test, subjects read short written passages and subsequently answer five types of questions (explicit, logical, distractor, pragmatic, and other, which require different types of inferential reasoning. The cognitive functional domains of attention, memory, executive functions, language, and visuospatial abilities were assessed using the Cognitive Linguistic Quick Test (CLQT.The LHL and RHL groups presented difficulties in inferential comprehension in comparison with the CG. However, the RHL group presented lower scores than the LHL group on logical, pragmatic and other questions. A covariance analysis did not show any effect of lesion site within the hemispheres. Overall, all cognitive domains were correlated with all the types of questions from the inference test (especially logical, pragmatic, and other. Attention and visuospatial abilities affected the scores of both the RHL and LHL groups, and only memory influenced the performance of the RHL group.Lesions in either hemisphere may cause difficulties in making inferences during reading. However, processing more complex inferences was more difficult for patients with RHL than for those with LHL, which suggests that the right hemisphere plays an important role in tasks with higher comprehension

  13. Inference comprehension in text reading: Performance of individuals with right- versus left-hemisphere lesions and the influence of cognitive functions.

    Science.gov (United States)

    Silagi, Marcela Lima; Radanovic, Marcia; Conforto, Adriana Bastos; Mendonça, Lucia Iracema Zanotto; Mansur, Leticia Lessa

    2018-01-01

    Right-hemisphere lesions (RHL) may impair inference comprehension. However, comparative studies between left-hemisphere lesions (LHL) and RHL are rare, especially regarding reading comprehension. Moreover, further knowledge of the influence of cognition on inferential processing in this task is needed. To compare the performance of patients with RHL and LHL on an inference reading comprehension task. We also aimed to analyze the effects of lesion site and to verify correlations between cognitive functions and performance on the task. Seventy-five subjects were equally divided into the groups RHL, LHL, and control group (CG). The Implicit Management Test was used to evaluate inference comprehension. In this test, subjects read short written passages and subsequently answer five types of questions (explicit, logical, distractor, pragmatic, and other), which require different types of inferential reasoning. The cognitive functional domains of attention, memory, executive functions, language, and visuospatial abilities were assessed using the Cognitive Linguistic Quick Test (CLQT). The LHL and RHL groups presented difficulties in inferential comprehension in comparison with the CG. However, the RHL group presented lower scores than the LHL group on logical, pragmatic and other questions. A covariance analysis did not show any effect of lesion site within the hemispheres. Overall, all cognitive domains were correlated with all the types of questions from the inference test (especially logical, pragmatic, and other). Attention and visuospatial abilities affected the scores of both the RHL and LHL groups, and only memory influenced the performance of the RHL group. Lesions in either hemisphere may cause difficulties in making inferences during reading. However, processing more complex inferences was more difficult for patients with RHL than for those with LHL, which suggests that the right hemisphere plays an important role in tasks with higher comprehension demands

  14. Entropic Inference

    Science.gov (United States)

    Caticha, Ariel

    2011-03-01

    In this tutorial we review the essential arguments behing entropic inference. We focus on the epistemological notion of information and its relation to the Bayesian beliefs of rational agents. The problem of updating from a prior to a posterior probability distribution is tackled through an eliminative induction process that singles out the logarithmic relative entropy as the unique tool for inference. The resulting method of Maximum relative Entropy (ME), includes as special cases both MaxEnt and Bayes' rule, and therefore unifies the two themes of these workshops—the Maximum Entropy and the Bayesian methods—into a single general inference scheme.

  15. Distributional Inference

    NARCIS (Netherlands)

    Kroese, A.H.; van der Meulen, E.A.; Poortema, Klaas; Schaafsma, W.

    1995-01-01

    The making of statistical inferences in distributional form is conceptionally complicated because the epistemic 'probabilities' assigned are mixtures of fact and fiction. In this respect they are essentially different from 'physical' or 'frequency-theoretic' probabilities. The distributional form is

  16. Characterization and functional inferences of a genome-wide DNA methylation profile in the loin ( muscle of swine

    Directory of Open Access Journals (Sweden)

    Woonsu Kim

    2018-01-01

    Full Text Available Objective DNA methylation plays a major role in regulating the expression of genes related to traits of economic interest (e.g., weight gain in livestock animals. This study characterized and investigated the functional inferences of genome-wide DNA methylome in the loin (longissimus dorsi muscle (LDM of swine. Methods A total of 8.99 Gb methylated DNA immunoprecipitation sequence data were obtained from LDM samples of eight Duroc pigs (four pairs of littermates. The reference pig genome was annotated with 78.5% of the raw reads. A total of 33,506 putative methylated regions (PMR were identified from methylated regions that overlapped at least two samples. Results Of these, only 3.1% were commonly observed in all eight samples. DNA methylation patterns between two littermates were as diverse as between unrelated individuals (p = 0.47, indicating that maternal genetic effects have little influence on the variation in DNA methylation of porcine LDM. The highest density of PMR was observed on chromosome 10. A major proportion (47.7% of PMR was present in the repeat regions, followed by introns (21.5%. The highest conservation of PMR was found in CpG islands (12.1%. These results show an important role for DNA methylation in species- and tissue-specific regulation of gene expression. PMR were also significantly related to muscular cell development, cell-cell communication, cellular integrity and transport, and nutrient metabolism. Conclusion This study indicated the biased distribution and functional role of DNA methylation in gene expression of porcine LDM. DNA methylation was related to cell development, cell-cell communication, cellular integrity and transport, and nutrient metabolism (e.g., insulin signaling pathways. Nutritional and environmental management may have a significant impact on the variation in DNA methylation of porcine LDM.

  17. Entropic Inference

    OpenAIRE

    Caticha, Ariel

    2010-01-01

    In this tutorial we review the essential arguments behing entropic inference. We focus on the epistemological notion of information and its relation to the Bayesian beliefs of rational agents. The problem of updating from a prior to a posterior probability distribution is tackled through an eliminative induction process that singles out the logarithmic relative entropy as the unique tool for inference. The resulting method of Maximum relative Entropy (ME), includes as special cases both MaxEn...

  18. Coordinate transformation and Polynomial Chaos for the Bayesian inference of a Gaussian process with parametrized prior covariance function

    KAUST Repository

    Sraj, Ihab; Le Maî tre, Olivier P.; Knio, Omar; Hoteit, Ibrahim

    2015-01-01

    using a coordinate transformation to account for the dependence with respect to the covariance hyper-parameters. Polynomial Chaos expansions are employed for the acceleration of the Bayesian inference using similar coordinate transformations, enabling us

  19. Introductory statistical inference

    CERN Document Server

    Mukhopadhyay, Nitis

    2014-01-01

    This gracefully organized text reveals the rigorous theory of probability and statistical inference in the style of a tutorial, using worked examples, exercises, figures, tables, and computer simulations to develop and illustrate concepts. Drills and boxed summaries emphasize and reinforce important ideas and special techniques.Beginning with a review of the basic concepts and methods in probability theory, moments, and moment generating functions, the author moves to more intricate topics. Introductory Statistical Inference studies multivariate random variables, exponential families of dist

  20. Comparison of Channel Catfish and Blue Catfish Gut Microbiota Assemblages Shows Minimal Effects of Host Genetics on Microbial Structure and Inferred Function

    Directory of Open Access Journals (Sweden)

    Jacob W. Bledsoe

    2018-05-01

    Full Text Available The microbiota of teleost fish has gained a great deal of research attention within the past decade, with experiments suggesting that both host-genetics and environment are strong ecological forces shaping the bacterial assemblages of fish microbiomes. Despite representing great commercial and scientific importance, the catfish within the family Ictaluridae, specifically the blue and channel catfish, have received very little research attention directed toward their gut-associated microbiota using 16S rRNA gene sequencing. Within this study we utilize multiple genetically distinct strains of blue and channel catfish, verified via microsatellite genotyping, to further quantify the role of host-genetics in shaping the bacterial communities in the fish gut, while maintaining environmental and husbandry parameters constant. Comparisons of the gut microbiota among the two catfish species showed no differences in bacterial species richness (observed and Chao1 or overall composition (weighted and unweighted UniFrac and UniFrac distances showed no correlation with host genetic distances (Rst according to Mantel tests. The microbiota of environmental samples (diet and water were found to be significantly more diverse than that of the catfish gut associated samples, suggesting that factors within the host were further regulating the bacterial communities, despite the lack of a clear connection between microbiota composition and host genotype. The catfish gut communities were dominated by the phyla Fusobacteria, Proteobacteria, and Firmicutes; however, differential abundance analysis between the two catfish species using analysis of composition of microbiomes detected two differential genera, Cetobacterium and Clostridium XI. The metagenomic pathway features inferred from our dataset suggests the catfish gut bacterial communities possess pathways beneficial to their host such as those involved in nutrient metabolism and antimicrobial biosynthesis, while

  1. Machine Learning-Assisted Network Inference Approach to Identify a New Class of Genes that Coordinate the Functionality of Cancer Networks.

    Science.gov (United States)

    Ghanat Bari, Mehrab; Ung, Choong Yong; Zhang, Cheng; Zhu, Shizhen; Li, Hu

    2017-08-01

    Emerging evidence indicates the existence of a new class of cancer genes that act as "signal linkers" coordinating oncogenic signals between mutated and differentially expressed genes. While frequently mutated oncogenes and differentially expressed genes, which we term Class I cancer genes, are readily detected by most analytical tools, the new class of cancer-related genes, i.e., Class II, escape detection because they are neither mutated nor differentially expressed. Given this hypothesis, we developed a Machine Learning-Assisted Network Inference (MALANI) algorithm, which assesses all genes regardless of expression or mutational status in the context of cancer etiology. We used 8807 expression arrays, corresponding to 9 cancer types, to build more than 2 × 10 8 Support Vector Machine (SVM) models for reconstructing a cancer network. We found that ~3% of ~19,000 not differentially expressed genes are Class II cancer gene candidates. Some Class II genes that we found, such as SLC19A1 and ATAD3B, have been recently reported to associate with cancer outcomes. To our knowledge, this is the first study that utilizes both machine learning and network biology approaches to uncover Class II cancer genes in coordinating functionality in cancer networks and will illuminate our understanding of how genes are modulated in a tissue-specific network contribute to tumorigenesis and therapy development.

  2. Association Between Brain Activation and Functional Connectivity.

    Science.gov (United States)

    Tomasi, Dardo; Volkow, Nora D

    2018-04-13

    The origin of the "resting-state" brain activity recorded with functional magnetic resonance imaging (fMRI) is still uncertain. Here we provide evidence for the neurovascular origins of the amplitude of the low-frequency fluctuations (ALFF) and the local functional connectivity density (lFCD) by comparing them with task-induced blood-oxygen level dependent (BOLD) responses, which are considered a proxy for neuronal activation. Using fMRI data for 2 different tasks (Relational and Social) collected by the Human Connectome Project in 426 healthy adults, we show that ALFF and lFCD have linear associations with the BOLD response. This association was significantly attenuated by a novel task signal regression (TSR) procedure, indicating that task performance enhances lFCD and ALFF in activated regions. We also show that lFCD predicts BOLD activation patterns, as was recently shown for other functional connectivity metrics, which corroborates that resting functional connectivity architecture impacts brain activation responses. Thus, our findings indicate a common source for BOLD responses, ALFF and lFCD, which is consistent with the neurovascular origin of local hemodynamic synchrony presumably reflecting coordinated fluctuations in neuronal activity. This study also supports the development of task-evoked functional connectivity density mapping.

  3. Probability biases as Bayesian inference

    Directory of Open Access Journals (Sweden)

    Andre; C. R. Martins

    2006-11-01

    Full Text Available In this article, I will show how several observed biases in human probabilistic reasoning can be partially explained as good heuristics for making inferences in an environment where probabilities have uncertainties associated to them. Previous results show that the weight functions and the observed violations of coalescing and stochastic dominance can be understood from a Bayesian point of view. We will review those results and see that Bayesian methods should also be used as part of the explanation behind other known biases. That means that, although the observed errors are still errors under the be understood as adaptations to the solution of real life problems. Heuristics that allow fast evaluations and mimic a Bayesian inference would be an evolutionary advantage, since they would give us an efficient way of making decisions. %XX In that sense, it should be no surprise that humans reason with % probability as it has been observed.

  4. Elliptic hypergeometric functions associated with root systems

    OpenAIRE

    Rosengren, Hjalmar; Warnaar, S. Ole

    2017-01-01

    We give a survey of elliptic hypergeometric functions associated with root systems, comprised of three main parts. The first two form in essence an annotated table of the main evaluation and transformation formulas for elliptic hypergeometric integeral and series on root systems. The third and final part gives an introduction to Rains' elliptic Macdonald-Koornwinder theory (in part also developed by Coskun and Gustafson).

  5. Association between thyroid function and gallstone disease

    Institute of Scientific and Technical Information of China (English)

    Henry V(o)lzke; Daniel M Robinson; Ulrich John

    2005-01-01

    AIM: To investigate those associations using data of the population-based Study of Health in Pomerania.METHODS: A study population of 3 749 residents aged 20-79 years without previously diagnosed thyroid disease was available for analyses. Serum TSH was used to assess thyroid function. Cholelithiasis was defined by either a prior history of cholecystectomy or the presence of gallstones on ultrasound. Logistic regression was performed to analyze independent associations between thyroid function and cholelithiasis.RESULTS: There were 385 persons (10.3%) with low (<0.3 mIU/L), 3 321 persons (88.6%) with normal and 43 persons (1.2%) with high serum TSH levels (>3 mIU/L).The proportion of cholelithiasis among males and females was 14.4% and 25.3%, respectively. Among males, there was an independent relation between high serum TSH and cholelithiasis (OR 3.77; 95%-CI 1.06-13.41; ,P<0.05). zAlso among males, there was a tendency towards an elevated risk of cholelithiasis in persons with low serum TSH (OR 1.40; 95%-CI 0.96-2.02; P = 0.07). In the female population, no such relation was identified.CONCLUSION: There is an association between thyroid and gallstone disease with a gender-specific relation between hypothyroidism and cholelithiasis.

  6. Is Sedentary Lifestyle Associated With Testicular Function?

    DEFF Research Database (Denmark)

    Priskorn, Lærke; Jensen, Tina Kold; Bang, Anne Kirstine

    2016-01-01

    Based on cross-sectional data on 1,210 healthy young Danish men, we investigated whether sedentary lifestyle was associated with testicular function (semen quality and reproductive hormones) independent of physical activity. The men were invited to participate in the study between 2008 and 2012......, when they attended a compulsory medical examination to determine their fitness for military service. Information on sedentary behavior (television watching and computer time) and physical activity was obtained by questionnaire. The men had a physical examination, delivered a semen sample, and had...... ratio were detected in men watching many hours of television. Self-rated physical fitness, but not time spent on physical activity, was positively associated with sperm counts....

  7. Large-scale inference of gene function through phylogenetic annotation of Gene Ontology terms: case study of the apoptosis and autophagy cellular processes.

    Science.gov (United States)

    Feuermann, Marc; Gaudet, Pascale; Mi, Huaiyu; Lewis, Suzanna E; Thomas, Paul D

    2016-01-01

    We previously reported a paradigm for large-scale phylogenomic analysis of gene families that takes advantage of the large corpus of experimentally supported Gene Ontology (GO) annotations. This 'GO Phylogenetic Annotation' approach integrates GO annotations from evolutionarily related genes across ∼100 different organisms in the context of a gene family tree, in which curators build an explicit model of the evolution of gene functions. GO Phylogenetic Annotation models the gain and loss of functions in a gene family tree, which is used to infer the functions of uncharacterized (or incompletely characterized) gene products, even for human proteins that are relatively well studied. Here, we report our results from applying this paradigm to two well-characterized cellular processes, apoptosis and autophagy. This revealed several important observations with respect to GO annotations and how they can be used for function inference. Notably, we applied only a small fraction of the experimentally supported GO annotations to infer function in other family members. The majority of other annotations describe indirect effects, phenotypes or results from high throughput experiments. In addition, we show here how feedback from phylogenetic annotation leads to significant improvements in the PANTHER trees, the GO annotations and GO itself. Thus GO phylogenetic annotation both increases the quantity and improves the accuracy of the GO annotations provided to the research community. We expect these phylogenetically based annotations to be of broad use in gene enrichment analysis as well as other applications of GO annotations.Database URL: http://amigo.geneontology.org/amigo. © The Author(s) 2016. Published by Oxford University Press.

  8. Inference as Prediction

    Science.gov (United States)

    Watson, Jane

    2007-01-01

    Inference, or decision making, is seen in curriculum documents as the final step in a statistical investigation. For a formal statistical enquiry this may be associated with sophisticated tests involving probability distributions. For young students without the mathematical background to perform such tests, it is still possible to draw informal…

  9. Biomaterial associated impairment of local neutrophil function.

    Science.gov (United States)

    Kaplan, S S; Basford, R E; Kormos, R L; Hardesty, R L; Simmons, R L; Mora, E M; Cardona, M; Griffith, B L

    1990-01-01

    The effect of biomaterials on neutrophil function was studied in vitro to determine if these materials activated neutrophils and to determine the subsequent response of these neutrophils to further stimulation. Two biomaterials--polyurethane, a commonly used substance, and Velcro pile (used in the Jarvik 7 heart)--were evaluated. Two control substances, polyethylene and serum-coated polystyrene, were used for comparison. Neutrophil superoxide release was measured following incubation with these materials for 10, 30, and 120 min in the absence of additional stimulation and after stimulation with formylmethionylleucylphenylalanine (fMLP) or phorbol myristate acetate (PMA). The authors observed that the incubation of neutrophils on both polyurethane and Velcro resulted in substantially increased superoxide release that was greater after the 10 min than after the 30 or 120 min association. These activated neutrophils exhibited a poor additional response to fMLP but responded well to PMA. The effect of implantation of the Novacor left ventricular assist device on peripheral blood neutrophil function was also evaluated. The peripheral blood neutrophils exhibited normal superoxide release and chemotaxis. These studies suggest that biomaterials may have a profound local effect on neutrophils, which may predispose the patient to periprosthetic infection, but that the reactivity of circulating neutrophils is unimpaired.

  10. Comparison of generalized estimating equations and quadratic inference functions using data from the National Longitudinal Survey of Children and Youth (NLSCY database

    Directory of Open Access Journals (Sweden)

    Browne Dillon

    2008-05-01

    Full Text Available Abstract Background The generalized estimating equations (GEE technique is often used in longitudinal data modeling, where investigators are interested in population-averaged effects of covariates on responses of interest. GEE involves specifying a model relating covariates to outcomes and a plausible correlation structure between responses at different time periods. While GEE parameter estimates are consistent irrespective of the true underlying correlation structure, the method has some limitations that include challenges with model selection due to lack of absolute goodness-of-fit tests to aid comparisons among several plausible models. The quadratic inference functions (QIF method extends the capabilities of GEE, while also addressing some GEE limitations. Methods We conducted a comparative study between GEE and QIF via an illustrative example, using data from the "National Longitudinal Survey of Children and Youth (NLSCY" database. The NLSCY dataset consists of long-term, population based survey data collected since 1994, and is designed to evaluate the determinants of developmental outcomes in Canadian children. We modeled the relationship between hyperactivity-inattention and gender, age, family functioning, maternal depression symptoms, household income adequacy, maternal immigration status and maternal educational level using GEE and QIF. Basis for comparison include: (1 ease of model selection; (2 sensitivity of results to different working correlation matrices; and (3 efficiency of parameter estimates. Results The sample included 795, 858 respondents (50.3% male; 12% immigrant; 6% from dysfunctional families. QIF analysis reveals that gender (male (odds ratio [OR] = 1.73; 95% confidence interval [CI] = 1.10 to 2.71, family dysfunctional (OR = 2.84, 95% CI of 1.58 to 5.11, and maternal depression (OR = 2.49, 95% CI of 1.60 to 2.60 are significantly associated with higher odds of hyperactivity-inattention. The results remained robust

  11. Estimating uncertainty of inference for validation

    Energy Technology Data Exchange (ETDEWEB)

    Booker, Jane M [Los Alamos National Laboratory; Langenbrunner, James R [Los Alamos National Laboratory; Hemez, Francois M [Los Alamos National Laboratory; Ross, Timothy J [UNM

    2010-09-30

    We present a validation process based upon the concept that validation is an inference-making activity. This has always been true, but the association has not been as important before as it is now. Previously, theory had been confirmed by more data, and predictions were possible based on data. The process today is to infer from theory to code and from code to prediction, making the role of prediction somewhat automatic, and a machine function. Validation is defined as determining the degree to which a model and code is an accurate representation of experimental test data. Imbedded in validation is the intention to use the computer code to predict. To predict is to accept the conclusion that an observable final state will manifest; therefore, prediction is an inference whose goodness relies on the validity of the code. Quantifying the uncertainty of a prediction amounts to quantifying the uncertainty of validation, and this involves the characterization of uncertainties inherent in theory/models/codes and the corresponding data. An introduction to inference making and its associated uncertainty is provided as a foundation for the validation problem. A mathematical construction for estimating the uncertainty in the validation inference is then presented, including a possibility distribution constructed to represent the inference uncertainty for validation under uncertainty. The estimation of inference uncertainty for validation is illustrated using data and calculations from Inertial Confinement Fusion (ICF). The ICF measurements of neutron yield and ion temperature were obtained for direct-drive inertial fusion capsules at the Omega laser facility. The glass capsules, containing the fusion gas, were systematically selected with the intent of establishing a reproducible baseline of high-yield 10{sup 13}-10{sup 14} neutron output. The deuterium-tritium ratio in these experiments was varied to study its influence upon yield. This paper on validation inference is the

  12. Utility and Limitations of Using Gene Expression Data to Identify Functional Associations.

    Directory of Open Access Journals (Sweden)

    Sahra Uygun

    2016-12-01

    Full Text Available Gene co-expression has been widely used to hypothesize gene function through guilt-by association. However, it is not clear to what degree co-expression is informative, whether it can be applied to genes involved in different biological processes, and how the type of dataset impacts inferences about gene functions. Here our goal is to assess the utility and limitations of using co-expression as a criterion to recover functional associations between genes. By determining the percentage of gene pairs in a metabolic pathway with significant expression correlation, we found that many genes in the same pathway do not have similar transcript profiles and the choice of dataset, annotation quality, gene function, expression similarity measure, and clustering approach significantly impacts the ability to recover functional associations between genes using Arabidopsis thaliana as an example. Some datasets are more informative in capturing coordinated expression profiles and larger data sets are not always better. In addition, to recover the maximum number of known pathways and identify candidate genes with similar functions, it is important to explore rather exhaustively multiple dataset combinations, similarity measures, clustering algorithms and parameters. Finally, we validated the biological relevance of co-expression cluster memberships with an independent phenomics dataset and found that genes that consistently cluster with leucine degradation genes tend to have similar leucine levels in mutants. This study provides a framework for obtaining gene functional associations by maximizing the information that can be obtained from gene expression datasets.

  13. Making Inferences: Comprehension of Physical Causality, Intentionality, and Emotions in Discourse by High-Functioning Older Children, Adolescents, and Adults with Autism

    Science.gov (United States)

    Bodner, Kimberly E.; Engelhardt, Christopher R.; Minshew, Nancy J.; Williams, Diane L.

    2015-01-01

    Studies investigating inferential reasoning in autism spectrum disorder (ASD) have focused on the ability to make socially-related inferences or inferences more generally. Important variables for intervention planning such as whether inferences depend on physical experiences or the nature of social information have received less consideration. A…

  14. Simultaneous inference of phenotype-associated genes and relevant tissues from GWAS data via Bayesian integration of multiple tissue-specific gene networks.

    Science.gov (United States)

    Wu, Mengmeng; Lin, Zhixiang; Ma, Shining; Chen, Ting; Jiang, Rui; Wong, Wing Hung

    2017-12-01

    Although genome-wide association studies (GWAS) have successfully identified thousands of genomic loci associated with hundreds of complex traits in the past decade, the debate about such problems as missing heritability and weak interpretability has been appealing for effective computational methods to facilitate the advanced analysis of the vast volume of existing and anticipated genetic data. Towards this goal, gene-level integrative GWAS analysis with the assumption that genes associated with a phenotype tend to be enriched in biological gene sets or gene networks has recently attracted much attention, due to such advantages as straightforward interpretation, less multiple testing burdens, and robustness across studies. However, existing methods in this category usually exploit non-tissue-specific gene networks and thus lack the ability to utilize informative tissue-specific characteristics. To overcome this limitation, we proposed a Bayesian approach called SIGNET (Simultaneously Inference of GeNEs and Tissues) to integrate GWAS data and multiple tissue-specific gene networks for the simultaneous inference of phenotype-associated genes and relevant tissues. Through extensive simulation studies, we showed the effectiveness of our method in finding both associated genes and relevant tissues for a phenotype. In applications to real GWAS data of 14 complex phenotypes, we demonstrated the power of our method in both deciphering genetic basis and discovering biological insights of a phenotype. With this understanding, we expect to see SIGNET as a valuable tool for integrative GWAS analysis, thereby boosting the prevention, diagnosis, and treatment of human inherited diseases and eventually facilitating precision medicine.

  15. Crustal structure of Tolfa domes complex (northern Latium - Italy) inferred from receiver functions analysis: an interplay between tectonics and magmatism

    Science.gov (United States)

    Buttinelli, M.; Bianchi, I.; Anselmi, M.; Chiarabba, C.; de Rita, D.; Quattrocchi, F.

    2010-12-01

    The Tolfa-Cerite volcanic district developed along the Tyrrhenian passive margin of central Italy, as part of magmatic processes started during the middle Pliocene. In this area the uncertainties on the deep crustal structures and the definition of the intrusive bodies geometry are focal issues that still need to be addressed. After the onset of the spreading of the Tyrrhenian sea during the Late Miocene, the emplacement of the intrusive bodies of the Tolfa complex (TDC), in a general back-arc geodynamical regime, generally occurred in a low stretching rate, in correspondence of the junctions between major lithospheric discontinuities. Normal faults, located at the edge of Mio-Pliocene basins, were used as preferential pathways for the rising of magmatic masses from the mantle to the surface. We used teleseismic recordings at the TOLF and MAON broad band station of the INGV seismic network (located between the Argentario promontory and Tolfa-Ceriti dome complexes -TDC-) to image the principal seismic velocity discontinuities by receiver function analysis (RF's). Together with RF’s velocity models of the area computed using the teleseismic events recorded by a temporary network of eight stations deployed around the TDC, we achieve a general crustal model of this area. The geometry of the seismic network has been defined to focus on the crustal structure beneath the TDC, trying to define the main velocity changes attributable to the intrusive bodies, the calcareous basal complex, the deep metamorphic basement, the lower crust and the Moho. The analysis of these data show the Moho at a depth of 23 km in the TDC area and 20 km in the Argentario area. Crustal models also show an unexpected velocity decrease between 12 and 18 km, consistent with a slight dropdown of the Vp/Vs ratio, imputable to a regional mid-crustal shear zone inherited from the previous alpine orogenesis, re-activated in extensional tectonic by the early opening phases of the Tyrrhenian sea. Above

  16. System-level insights into the cellular interactome of a non-model organism: inferring, modelling and analysing functional gene network of soybean (Glycine max.

    Directory of Open Access Journals (Sweden)

    Yungang Xu

    Full Text Available Cellular interactome, in which genes and/or their products interact on several levels, forming transcriptional regulatory-, protein interaction-, metabolic-, signal transduction networks, etc., has attracted decades of research focuses. However, such a specific type of network alone can hardly explain the various interactive activities among genes. These networks characterize different interaction relationships, implying their unique intrinsic properties and defects, and covering different slices of biological information. Functional gene network (FGN, a consolidated interaction network that models fuzzy and more generalized notion of gene-gene relations, have been proposed to combine heterogeneous networks with the goal of identifying functional modules supported by multiple interaction types. There are yet no successful precedents of FGNs on sparsely studied non-model organisms, such as soybean (Glycine max, due to the absence of sufficient heterogeneous interaction data. We present an alternative solution for inferring the FGNs of soybean (SoyFGNs, in a pioneering study on the soybean interactome, which is also applicable to other organisms. SoyFGNs exhibit the typical characteristics of biological networks: scale-free, small-world architecture and modularization. Verified by co-expression and KEGG pathways, SoyFGNs are more extensive and accurate than an orthology network derived from Arabidopsis. As a case study, network-guided disease-resistance gene discovery indicates that SoyFGNs can provide system-level studies on gene functions and interactions. This work suggests that inferring and modelling the interactome of a non-model plant are feasible. It will speed up the discovery and definition of the functions and interactions of other genes that control important functions, such as nitrogen fixation and protein or lipid synthesis. The efforts of the study are the basis of our further comprehensive studies on the soybean functional

  17. Structures of Xishan village landslide in Li County, Sichuan, China, inferred from high-frequency receiver functions of local earthquakes

    Science.gov (United States)

    Wei, Z.; Chu, R.

    2017-12-01

    Teleseismic receiver function methods are widely used to study the deep structural information beneath the seismic station. However, teleseismic waveforms are difficult to extract the high-frequency receiver function, which are insufficient to constrain the shallow structure because of the inelastic attenuation effect of the earth. In this study, using the local earthquake waveforms collected from 3 broadband stations deployed on the Xishan village landslide in Li County in Sichuan Province, we used the high-frequency receiver function method to study the shallow structure beneath the landslide. We developed the Vp-k (Vp/Vs) staking method of receiver functions, and combined with the H-k stacking and waveform inversion methods of receiver functions to invert the landslide's thickness, S-wave velocity and average Vp/Vs ratio beneath these stations, and compared the thickness with the borehole results. Our results show small-scale lateral variety of velocity structure, a 78-143m/s lower S-wave velocity in the bottom layer and 2.4-3.1 Vp/Vs ratio in the landslide. The observed high Vp/Vs ratio and low S-wave velocity in the bottom layer of the landslide are consistent with low electrical resistivity and water-rich in the bottom layer, suggesting a weak shear strength and potential danger zone in landslide h1. Our study suggest that the local earthquake receiver function can obtain the shallow velocity structural information and supply some seismic constrains for the landslide catastrophe mitigation.

  18. association between health status and visual functioning

    African Journals Online (AJOL)

    2014-01-31

    Jan 31, 2014 ... High blood pressure and abnormal body mass have been observed to correlate negatively with health status. Of interest in this study, is the impact such health status have on visual function indicated by near point of convergence. In this community based cross sectional study, 250 randomly selected ...

  19. Active inference and learning.

    Science.gov (United States)

    Friston, Karl; FitzGerald, Thomas; Rigoli, Francesco; Schwartenbeck, Philipp; O Doherty, John; Pezzulo, Giovanni

    2016-09-01

    This paper offers an active inference account of choice behaviour and learning. It focuses on the distinction between goal-directed and habitual behaviour and how they contextualise each other. We show that habits emerge naturally (and autodidactically) from sequential policy optimisation when agents are equipped with state-action policies. In active inference, behaviour has explorative (epistemic) and exploitative (pragmatic) aspects that are sensitive to ambiguity and risk respectively, where epistemic (ambiguity-resolving) behaviour enables pragmatic (reward-seeking) behaviour and the subsequent emergence of habits. Although goal-directed and habitual policies are usually associated with model-based and model-free schemes, we find the more important distinction is between belief-free and belief-based schemes. The underlying (variational) belief updating provides a comprehensive (if metaphorical) process theory for several phenomena, including the transfer of dopamine responses, reversal learning, habit formation and devaluation. Finally, we show that active inference reduces to a classical (Bellman) scheme, in the absence of ambiguity. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. The structure of tubulin-binding cofactor A from Leishmania major infers a mode of association during the early stages of microtubule assembly

    Energy Technology Data Exchange (ETDEWEB)

    Barrack, Keri L.; Fyfe, Paul K.; Hunter, William N., E-mail: w.n.hunter@dundee.ac.uk [University of Dundee, Dow Street, Dundee DD1 5EH, Scotland (United Kingdom)

    2015-04-21

    The structure of a tubulin-binding cofactor from L. major is reported and compared with yeast, plant and human orthologues. Tubulin-binding cofactor A (TBCA) participates in microtubule formation, a key process in eukaryotic biology to create the cytoskeleton. There is little information on how TBCA might interact with β-tubulin en route to microtubule biogenesis. To address this, the protozoan Leishmania major was targeted as a model system. The crystal structure of TBCA and comparisons with three orthologous proteins are presented. The presence of conserved features infers that electrostatic interactions that are likely to involve the C-terminal tail of β-tubulin are key to association. This study provides a reagent and template to support further work in this area.

  1. Relativistic invariance of dispersion-relations and their associated wave-operators and Green-functions

    International Nuclear Information System (INIS)

    Censor, Dan

    2010-01-01

    Identifying invariance properties helps in simplifying calculations and consolidating concepts. Presently the Special Relativistic invariance of dispersion relations and their associated scalar wave operators is investigated for general dispersive homogeneous linear media. Invariance properties of the four-dimensional Fourier-transform integrals is demonstrated, from which the invariance of the scalar Green-function is inferred. Dispersion relations and the associated group velocities feature in Hamiltonian ray tracing theory. The derivation of group velocities for moving media from the dispersion relation for these media at rest is discussed. It is verified that the group velocity concept satisfies the relativistic velocity-addition formula. In this respect it is considered to be 'real', i.e., substantial, physically measurable, and not merely a mathematical artifact. Conversely, if we assume the group velocity to be substantial, it follows that the dispersion relation must be a relativistic invariant. (orig.)

  2. Noise genetics: inferring protein function by correlating phenotype with protein levels and localization in individual human cells.

    Directory of Open Access Journals (Sweden)

    Shlomit Farkash-Amar

    2014-03-01

    Full Text Available To understand gene function, genetic analysis uses large perturbations such as gene deletion, knockdown or over-expression. Large perturbations have drawbacks: they move the cell far from its normal working point, and can thus be masked by off-target effects or compensation by other genes. Here, we offer a complementary approach, called noise genetics. We use natural cell-cell variations in protein level and localization, and correlate them to the natural variations of the phenotype of the same cells. Observing these variations is made possible by recent advances in dynamic proteomics that allow measuring proteins over time in individual living cells. Using motility of human cancer cells as a model system, and time-lapse microscopy on 566 fluorescently tagged proteins, we found 74 candidate motility genes whose level or localization strongly correlate with motility in individual cells. We recovered 30 known motility genes, and validated several novel ones by mild knockdown experiments. Noise genetics can complement standard genetics for a variety of phenotypes.

  3. The Association of Selected Conative Variables to Field-Dependence with Inferences for Reasoning Characteristics in Marketing Education.

    Science.gov (United States)

    Fritz, Robert L.

    A study examined the association between field-dependence and its related information processing characteristics, and educational cognitive style as a model of conative influence. Data were collected from 145 secondary marketing education students in nothern Georgia during spring 1991. Descriptive statistics, Pearson product moment correlations,…

  4. Identifying and exploiting trait-relevant tissues with multiple functional annotations in genome-wide association studies

    Science.gov (United States)

    Zhang, Shujun

    2018-01-01

    Genome-wide association studies (GWASs) have identified many disease associated loci, the majority of which have unknown biological functions. Understanding the mechanism underlying trait associations requires identifying trait-relevant tissues and investigating associations in a trait-specific fashion. Here, we extend the widely used linear mixed model to incorporate multiple SNP functional annotations from omics studies with GWAS summary statistics to facilitate the identification of trait-relevant tissues, with which to further construct powerful association tests. Specifically, we rely on a generalized estimating equation based algorithm for parameter inference, a mixture modeling framework for trait-tissue relevance classification, and a weighted sequence kernel association test constructed based on the identified trait-relevant tissues for powerful association analysis. We refer to our analytic procedure as the Scalable Multiple Annotation integration for trait-Relevant Tissue identification and usage (SMART). With extensive simulations, we show how our method can make use of multiple complementary annotations to improve the accuracy for identifying trait-relevant tissues. In addition, our procedure allows us to make use of the inferred trait-relevant tissues, for the first time, to construct more powerful SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28 GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and Roadmap. Our results reveal new trait-tissue relevance, pinpoint important annotations that are informative of trait-tissue relationship, and illustrate how we can use the inferred trait-relevant tissues to construct more powerful association tests in the Wellcome trust case control consortium study. PMID:29377896

  5. Identifying and exploiting trait-relevant tissues with multiple functional annotations in genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Xingjie Hao

    2018-01-01

    Full Text Available Genome-wide association studies (GWASs have identified many disease associated loci, the majority of which have unknown biological functions. Understanding the mechanism underlying trait associations requires identifying trait-relevant tissues and investigating associations in a trait-specific fashion. Here, we extend the widely used linear mixed model to incorporate multiple SNP functional annotations from omics studies with GWAS summary statistics to facilitate the identification of trait-relevant tissues, with which to further construct powerful association tests. Specifically, we rely on a generalized estimating equation based algorithm for parameter inference, a mixture modeling framework for trait-tissue relevance classification, and a weighted sequence kernel association test constructed based on the identified trait-relevant tissues for powerful association analysis. We refer to our analytic procedure as the Scalable Multiple Annotation integration for trait-Relevant Tissue identification and usage (SMART. With extensive simulations, we show how our method can make use of multiple complementary annotations to improve the accuracy for identifying trait-relevant tissues. In addition, our procedure allows us to make use of the inferred trait-relevant tissues, for the first time, to construct more powerful SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28 GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and Roadmap. Our results reveal new trait-tissue relevance, pinpoint important annotations that are informative of trait-tissue relationship, and illustrate how we can use the inferred trait-relevant tissues to construct more powerful association tests in the Wellcome trust case control consortium study.

  6. Chinese Herbs Containing Aristolochic Acid Associated with Renal Failure and Urothelial Carcinoma: A Review from Epidemiologic Observations to Causal Inference

    Directory of Open Access Journals (Sweden)

    Hsiao-Yu Yang

    2014-01-01

    Full Text Available Herbal remedies containing aristolochic acid (AA have been designated to be a strong carcinogen. This review summarizes major epidemiologic evidence to argue for the causal association between AA exposure and urothelial carcinoma as well as nephropathy. The exposure scenarios include the following: Belgian women taking slimming pills containing single material Guang Fang Ji, consumptions of mixtures of Chinese herbal products in the general population and patients with chronic renal failure in Taiwan, occupational exposure in Chinese herbalists, and food contamination in farming villages in valleys of the Danube River. Such an association is corroborated by detecting specific DNA adducts in the tumor tissue removed from affected patients. Preventive actions of banning such use and education to the healthcare professionals and public are necessary for the safety of herbal remedies.

  7. Chinese herbs containing aristolochic acid associated with renal failure and urothelial carcinoma: a review from epidemiologic observations to causal inference.

    Science.gov (United States)

    Yang, Hsiao-Yu; Chen, Pau-Chung; Wang, Jung-Der

    2014-01-01

    Herbal remedies containing aristolochic acid (AA) have been designated to be a strong carcinogen. This review summarizes major epidemiologic evidence to argue for the causal association between AA exposure and urothelial carcinoma as well as nephropathy. The exposure scenarios include the following: Belgian women taking slimming pills containing single material Guang Fang Ji, consumptions of mixtures of Chinese herbal products in the general population and patients with chronic renal failure in Taiwan, occupational exposure in Chinese herbalists, and food contamination in farming villages in valleys of the Danube River. Such an association is corroborated by detecting specific DNA adducts in the tumor tissue removed from affected patients. Preventive actions of banning such use and education to the healthcare professionals and public are necessary for the safety of herbal remedies.

  8. Chinese Herbs Containing Aristolochic Acid Associated with Renal Failure and Urothelial Carcinoma: A Review from Epidemiologic Observations to Causal Inference

    OpenAIRE

    Yang, Hsiao-Yu; Chen, Pau-Chung; Wang, Jung-Der

    2014-01-01

    Herbal remedies containing aristolochic acid (AA) have been designated to be a strong carcinogen. This review summarizes major epidemiologic evidence to argue for the causal association between AA exposure and urothelial carcinoma as well as nephropathy. The exposure scenarios include the following: Belgian women taking slimming pills containing single material Guang Fang Ji, consumptions of mixtures of Chinese herbal products in the general population and patients with chronic renal failure ...

  9. Obesity-associated biomarkers and executive function in children.

    Science.gov (United States)

    Miller, Alison L; Lee, Hannah J; Lumeng, Julie C

    2015-01-01

    There is a growing focus on links between obesity and cognitive decline in adulthood, including Alzheimer's disease. It is also increasingly recognized that obesity in youth is associated with poorer cognitive function, specifically executive functioning skills such as inhibitory control and working memory, which are critical for academic achievement. Emerging literature provides evidence for possible biological mechanisms driven by obesity; obesity-associated biomarkers such as adipokines, obesity-associated inflammatory cytokines, and obesity-associated gut hormones have been associated with learning, memory, and general cognitive function. To date, examination of obesity-associated biology with brain function has primarily occurred in animal models. The few studies examining such biologically mediated pathways in adult humans have corroborated the animal data, but this body of work has gone relatively unrecognized by the pediatric literature. Despite the fact that differences in these biomarkers have been found in association with obesity in children, the possibility that obesity-related biology could affect brain development in children has not been actively considered. We review obesity-associated biomarkers that have shown associations with neurocognitive skills, specifically executive functioning skills, which have far-reaching implications for child development. Understanding such gut-brain associations early in the lifespan may yield unique intervention implications.

  10. Development of diagnosis and maintenance support system for nuclear power plants with flexible inference function and knowledge base edition support function

    International Nuclear Information System (INIS)

    Fujii, Makoto; Seki, Eiji; Tai, Ichiro; Morioka, Toshihiko

    1988-01-01

    For the reliable and efficient diagnosis and inspection work of the nuclear power plant equipments, 'Diagnosis and Maintenance Support System' has been developed. This system has functions to assist operators or engineers to observe and evaluate equipment conditions based on the experts' knowledge. These functions are carried out through dialogue between the system and users. This system has two subsystems: diagnosis subsystem and knowledge base edition support subsystem. To achieve the functions of diagnosis subsystem, a new method of knowledge processing for equipment diagnosis is adopted. This method is based on the concept of 'Cause Generation and Checking'. Knowledge for diagnosis is represented with modularized production rules. And each rule module consists of four different type rules with hierarchical structure. With this approach, the system is equipped with sufficient performance not only in diagnosis function but also in flexible man-machine interface. Knowledge base edition support subsystem (Graphical Rule Editor) is provided for this system. This editor has functions to display and edit the contents of knowledge base with tree structures through the graphic display. With these functions, the efficiency of constructing expert system is highly improved. By applying this system to the maintenance support of neutron monitoring system, it is proved that this system has satisfactory performance as a diagnosis and maintenance support system. (author)

  11. Evidence for a Functional Hierarchy of Association Networks.

    Science.gov (United States)

    Choi, Eun Young; Drayna, Garrett K; Badre, David

    2018-05-01

    Patient lesion and neuroimaging studies have identified a rostral-to-caudal functional gradient in the lateral frontal cortex (LFC) corresponding to higher-order (complex or abstract) to lower-order (simple or concrete) cognitive control. At the same time, monkey anatomical and human functional connectivity studies show that frontal regions are reciprocally connected with parietal and temporal regions, forming parallel and distributed association networks. Here, we investigated the link between the functional gradient of LFC regions observed during control tasks and the parallel, distributed organization of association networks. Whole-brain fMRI task activity corresponding to four orders of hierarchical control [Badre, D., & D'Esposito, M. Functional magnetic resonance imaging evidence for a hierarchical organization of the prefrontal cortex. Journal of Cognitive Neuroscience, 19, 2082-2099, 2007] was compared with a resting-state functional connectivity MRI estimate of cortical networks [Yeo, B. T., Krienen, F. M., Sepulcre, J., Sabuncu, M. R., Lashkari, D., Hollinshead, M., et al. The organization of the human cerebral cortex estimated by intrinsic functional connectivity. Journal of Neurophysiology, 106, 1125-1165, 2011]. Critically, at each order of control, activity in the LFC and parietal cortex overlapped onto a common association network that differed between orders. These results are consistent with a functional organization based on separable association networks that are recruited during hierarchical control. Furthermore, corticostriatal functional connectivity MRI showed that, consistent with their participation in functional networks, rostral-to-caudal LFC and caudal-to-rostral parietal regions had similar, order-specific corticostriatal connectivity that agreed with a striatal gating model of hierarchical rule use. Our results indicate that hierarchical cognitive control is subserved by parallel and distributed association networks, together forming

  12. Emotion regulation strategies mediate the associations of positive and negative affect to upper extremity physical function.

    Science.gov (United States)

    Talaei-Khoei, Mojtaba; Nemati-Rezvani, Hora; Fischerauer, Stefan F; Ring, David; Chen, Neal; Vranceanu, Ana-Maria

    2017-05-01

    The Gross process model of emotion regulation holds that emotion-eliciting situations (e.g. musculoskeletal illness) can be strategically regulated to determine the final emotional and behavioral response. Also, there is some evidence that innate emotional traits may predispose an individual to a particular regulating coping style. We enrolled 107 patients with upper extremity musculoskeletal illness in this cross-sectional study. They completed self-report measures of positive and negative affect, emotion regulation strategies (cognitive reappraisal and expressive suppression), upper extremity physical function, pain intensity, and demographics. We used Preacher and Hayes' bootstrapping approach to process analysis to infer the direct effect of positive and negative affect on physical function as well as their indirect effects through activation of emotion regulation strategies. Negative affect was associated with decreased physical function. The association was partly mediated by expressive suppression (b (SE)=-.10 (.05), 95% BCa CI [-.21, -.02]). Positive affect was associated with increased physical function. Cognitive reappraisal partially mediated this association (b (SE)=.11 (.05), 95% BCa CI [.03, .24]). After controlling for pain intensity, the ratio of the mediated effect to total effect grew even larger in controlled model comparing to uncontrolled model (33% vs. 26% for expressive suppression and 32% vs. 30% for cognitive reappraisal). The relationships between affect, emotion regulation strategies and physical function appear to be more dependent on the emotional response to an orthopedic condition rather than the intensity of the nociceptive stimulation of the pain. Findings support integration of emotion regulation training in skill-based psychotherapy in this population to mitigate the effect of negative affect and enhance the influence of positive affect on physical function. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. The functional significance of the spinose keel structure of benthic foraminifera: inferences from Miliolina cristata Millett, 1898 (Miliolida) from northeast Romania

    Science.gov (United States)

    Dumitriţa Dumitriu, Simina; Dubicka, Zofia; Ionesi, Viorel

    2018-01-01

    The paper presents Miocene (lower Sarmatian) benthic foraminifera from the FH3P1 Rădăuţi Core section from the northwestern part of the Moldavian Platform, Romania. Based on foraminiferal assemblages we infer sediments were deposited in shallow-water, including marine-marginal environments, of varying salinities from brackish to normal marine with some short and rather small sea-level changes. Moreover, we describe for the first time in the Moldavian Platform a very rare species, Miliolina cristata Millett, which presents a characteristic spinose keel. Based on a detailed study of the test morphology and its variability, observed in picked material as well as in thin sections, we discuss some palaeoecological aspects of these foraminifera. M. cristata probably does not constitute a distinctive species, but it is more probable that some miliolid taxa developed such an exoskeletal feature in response to new environmental conditions, such as more turbulent water. Accordingly, our study would support the thesis that one of the functions of the benthic foraminiferal spines is to stabilize foraminiferal tests found in sandy substrates from high-energy environments.

  14. Intrapersonal and interpersonal functions of non suicidal self-injury: associations with emotional and social functioning.

    Science.gov (United States)

    Turner, Brianna J; Chapman, Alexander L; Layden, Brianne K

    2012-02-01

    Understanding the functions of nonsuicidal self-injury (NSSI) has important implications for the development and refinement of theoretical models and treatments of NSSI. Emotional and social vulnerabilities associated with five common functions of NSSI-emotion relief (ER), feeling generation (FG), self-punishment (SP), interpersonal influence (II), and interpersonal communication (IC)-were investigated to clarify why individuals use this behavior in the service of different purposes. Female participants (n = 162) with a history of NSSI completed online measures of self-injury, emotion regulation strategies and abilities, trait affectivity, social problem-solving styles, and interpersonal problems. ER functions were associated with more intense affectivity, expressive suppression, and limited access to emotion regulation strategies. FG functions were associated with a lack of emotional clarity. Similar to ER functions, SP functions were associated with greater affective intensity and expressive suppression. II functions were negatively associated with expressive suppression and positively associated with domineering/controlling and intrusive/needy interpersonal styles. IC functions were negatively associated with expressive suppression and positively associated with a vindictive or self-centered interpersonal style. These findings highlight the specific affective traits, emotional and social skill deficits, and interpersonal styles that may render a person more likely to engage in NSSI to achieve specific goals. © 2012 The American Association of Suicidology.

  15. Association between Cognitive Activity and Cognitive Function in Older Hispanics

    OpenAIRE

    Marquine, María J.; Segawa, Eisuke; Wilson, Robert S.; Bennett, David A.; Barnes, Lisa L.

    2012-01-01

    There is limited research on the association between participation in cognitively stimulating activity and cognitive function in older Hispanics. The main purpose of the present study was to explore whether frequency of cognitive activity and its association with cognitive function in Hispanics is comparable to that of non-Hispanics. In a multiethnic cohort of 1571 non-demented older adults, we assessed past and current cognitive activity, availability of cognitive resources in the home in ch...

  16. Obesity-Associated Biomarkers and Executive Function in Children

    OpenAIRE

    Miller, Alison L.; Jong, Hannah; Lumeng, Julie C.

    2014-01-01

    There is a growing focus on links between obesity and cognitive decline in adulthood, including Alzheimer’s disease. It is also increasingly recognized that obesity in youth is associated with poorer cognitive function, specifically executive functioning skills such as inhibitory control and working memory, which are critical for academic achievement. Emerging literature provides evidence for possible biological mechanisms driven by obesity; obesity-associated biomarkers such as adipokines, o...

  17. Longitudinal Associations Between Formal Volunteering and Cognitive Functioning.

    Science.gov (United States)

    Proulx, Christine M; Curl, Angela L; Ermer, Ashley E

    2018-03-02

    The present study examines the association between formal volunteering and cognitive functioning over time. We also examine the moderating roles of race, sex, education, and time. Using 11,100 participants aged 51 years and older and nine waves of data from the Health and Retirement Survey, we simultaneously modeled the longitudinal associations between engaging in formal volunteering and changes in cognitive functioning using multilevel models. Formal volunteering was associated with higher levels of cognitive functioning over time, especially with aspects of cognitive functioning related to working memory and processing. This association was stronger for women than it was for men, and for those with below average levels of education. The positive association between formal volunteering and cognitive functioning weakened over time when cognitive functioning was conceptualized as memory, but strengthened over time when conceptualized as working memory and processing. Volunteering is a productive activity that is beneficial not just to society, but to volunteers' levels of cognitive functioning in older age. For women and those with lower levels of education, formal volunteering appears particularly beneficial to working memory and processing. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. ON WEIGHTED GENERALIZED FUNCTIONS ASSOCIATED WITH QUADRATIC FORMS

    Directory of Open Access Journals (Sweden)

    E. L. Shishkina

    2016-12-01

    Full Text Available In this article we consider certain types of weighted generalized functions associated with nondegenerate quadratic forms. Such functions and their derivatives are used for constructing fundamental solutions of iterated ultra-hyperbolic equations with the Bessel operator and for constructing negative real powers of ultra-hyperbolic operators with the Bessel operator.

  19. Functional status and its associated factors in Nigerian adolescents ...

    African Journals Online (AJOL)

    Objective: This study assessed general functioning in Nigerian adolescents with bipolar disorder. It also determined the factors associated with functioning in these adolescents. Methods: Adolescents with bipolar disorder diagnosed over one year or more attending the outpatient unit of Federal Neuro-Psychiatric Hospital, ...

  20. Immune activation is associated with decreased thymic function in ...

    African Journals Online (AJOL)

    Background: Reduced thymic function causes poor immunological reconstitution in human immunodeficiency virus (HIV)-positive patients on combined antiretroviral therapy (cART). The association between immune activation and thymic function in asymptomatic HIVpositive treatment-naive individuals has thus far not been ...

  1. Extended likelihood inference in reliability

    International Nuclear Information System (INIS)

    Martz, H.F. Jr.; Beckman, R.J.; Waller, R.A.

    1978-10-01

    Extended likelihood methods of inference are developed in which subjective information in the form of a prior distribution is combined with sampling results by means of an extended likelihood function. The extended likelihood function is standardized for use in obtaining extended likelihood intervals. Extended likelihood intervals are derived for the mean of a normal distribution with known variance, the failure-rate of an exponential distribution, and the parameter of a binomial distribution. Extended second-order likelihood methods are developed and used to solve several prediction problems associated with the exponential and binomial distributions. In particular, such quantities as the next failure-time, the number of failures in a given time period, and the time required to observe a given number of failures are predicted for the exponential model with a gamma prior distribution on the failure-rate. In addition, six types of life testing experiments are considered. For the binomial model with a beta prior distribution on the probability of nonsurvival, methods are obtained for predicting the number of nonsurvivors in a given sample size and for predicting the required sample size for observing a specified number of nonsurvivors. Examples illustrate each of the methods developed. Finally, comparisons are made with Bayesian intervals in those cases where these are known to exist

  2. Depression in Schizophrenia: Associations With Cognition, Functional Capacity, Everyday Functioning, and Self-Assessment.

    Science.gov (United States)

    Harvey, Philip D; Twamley, Elizabeth W; Pinkham, Amy E; Depp, Colin A; Patterson, Thomas L

    2017-05-01

    Depressed mood has a complex relationship with self-evaluation of personal competence in multiple populations. The absence of depression may be associated with overestimation of abilities, while mild depression seems to lead to accurate self-assessment. Significant depression may lead to underestimation of functioning. In this study, we expand on our previous work by directly comparing the association between different levels of depression, everyday functioning, cognitive and functional capacity performance, and self-assessment of everyday functioning in a large (n = 406) sample of outpatients with schizophrenia. Participants with very low self-reported depression overestimated their everyday functioning compared with informant reports. Higher levels of depression were associated with more accurate self-assessment, but no subgroup of patients underestimated their functioning. Depressive symptom severity was associated with poorer informant-rated social functioning, but there were no differences in vocational functioning, everyday activities, cognitive performance, and functional capacity associated with the severity of self-reported depression. There was minimal evidence of impact of depression on most aspects of everyday functioning and objective test performance and a substantial relationship between depression and accuracy of self-assessment. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  3. Lower complexity bounds for lifted inference

    DEFF Research Database (Denmark)

    Jaeger, Manfred

    2015-01-01

    instances of the model. Numerous approaches for such “lifted inference” techniques have been proposed. While it has been demonstrated that these techniques will lead to significantly more efficient inference on some specific models, there are only very recent and still quite restricted results that show...... the feasibility of lifted inference on certain syntactically defined classes of models. Lower complexity bounds that imply some limitations for the feasibility of lifted inference on more expressive model classes were established earlier in Jaeger (2000; Jaeger, M. 2000. On the complexity of inference about...... that under the assumption that NETIME≠ETIME, there is no polynomial lifted inference algorithm for knowledge bases of weighted, quantifier-, and function-free formulas. Further strengthening earlier results, this is also shown to hold for approximate inference and for knowledge bases not containing...

  4. On Parameter Differentiation for Integral Representations of Associated Legendre Functions

    Directory of Open Access Journals (Sweden)

    Howard S. Cohl

    2011-05-01

    Full Text Available For integral representations of associated Legendre functions in terms of modified Bessel functions, we establish justification for differentiation under the integral sign with respect to parameters. With this justification, derivatives for associated Legendre functions of the first and second kind with respect to the degree are evaluated at odd-half-integer degrees, for general complex-orders, and derivatives with respect to the order are evaluated at integer-orders, for general complex-degrees. We also discuss the properties of the complex function f: C{−1,1}→C given by f(z=z/((z+1^{1/2}(z−1^{1/2}.

  5. Statistical learning and selective inference.

    Science.gov (United States)

    Taylor, Jonathan; Tibshirani, Robert J

    2015-06-23

    We describe the problem of "selective inference." This addresses the following challenge: Having mined a set of data to find potential associations, how do we properly assess the strength of these associations? The fact that we have "cherry-picked"--searched for the strongest associations--means that we must set a higher bar for declaring significant the associations that we see. This challenge becomes more important in the era of big data and complex statistical modeling. The cherry tree (dataset) can be very large and the tools for cherry picking (statistical learning methods) are now very sophisticated. We describe some recent new developments in selective inference and illustrate their use in forward stepwise regression, the lasso, and principal components analysis.

  6. Higher Genus Abelian Functions Associated with Cyclic Trigonal Curves

    Directory of Open Access Journals (Sweden)

    Matthew England

    2010-03-01

    Full Text Available We develop the theory of Abelian functions associated with cyclic trigonal curves by considering two new cases. We investigate curves of genus six and seven and consider whether it is the trigonal nature or the genus which dictates certain areas of the theory. We present solutions to the Jacobi inversion problem, sets of relations between the Abelian function, links to the Boussinesq equation and a new addition formula.

  7. Gauging Variational Inference

    Energy Technology Data Exchange (ETDEWEB)

    Chertkov, Michael [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Ahn, Sungsoo [Korea Advanced Inst. Science and Technology (KAIST), Daejeon (Korea, Republic of); Shin, Jinwoo [Korea Advanced Inst. Science and Technology (KAIST), Daejeon (Korea, Republic of)

    2017-05-25

    Computing partition function is the most important statistical inference task arising in applications of Graphical Models (GM). Since it is computationally intractable, approximate methods have been used to resolve the issue in practice, where meanfield (MF) and belief propagation (BP) are arguably the most popular and successful approaches of a variational type. In this paper, we propose two new variational schemes, coined Gauged-MF (G-MF) and Gauged-BP (G-BP), improving MF and BP, respectively. Both provide lower bounds for the partition function by utilizing the so-called gauge transformation which modifies factors of GM while keeping the partition function invariant. Moreover, we prove that both G-MF and G-BP are exact for GMs with a single loop of a special structure, even though the bare MF and BP perform badly in this case. Our extensive experiments, on complete GMs of relatively small size and on large GM (up-to 300 variables) confirm that the newly proposed algorithms outperform and generalize MF and BP.

  8. The anatomy of choice: active inference and agency

    Directory of Open Access Journals (Sweden)

    Karl eFriston

    2013-09-01

    Full Text Available This paper considers agency in the setting of embodied or active inference. In brief, we associate a sense of agency with prior beliefs about action and ask what sorts of beliefs underlie optimal behaviour. In particular, we consider prior beliefs that action minimises the Kullback-Leibler divergence between desired states and attainable states in the future. This allows one to formulate bounded rationality as approximate Bayesian inference that optimises a free energy bound on model evidence. We show that constructs like expected utility, exploration bonuses, softmax choice rules and optimism bias emerge as natural consequences of this formulation. Previous accounts of active inference have focused on predictive coding and Bayesian filtering schemes for minimising free energy. Here, we consider variational Bayes as an alternative scheme that provides formal constraints on the computational anatomy of inference and action – constraints that are remarkably consistent with neuroanatomy. Furthermore, this scheme contextualises optimal decision theory and economic (utilitarian formulations as pure inference problems. For example, expected utility theory emerges as a special case of free energy minimisation, where the sensitivity or inverse temperature (of softmax functions and quantal response equilibria has a unique and Bayes-optimal solution – that minimises free energy. This sensitivity corresponds to the precision of beliefs about behaviour, such that attainable goals are afforded a higher precision or confidence. In turn, this means that optimal behaviour entails a representation of confidence about outcomes that are under an agent's control.

  9. Reward inference by primate prefrontal and striatal neurons.

    Science.gov (United States)

    Pan, Xiaochuan; Fan, Hongwei; Sawa, Kosuke; Tsuda, Ichiro; Tsukada, Minoru; Sakagami, Masamichi

    2014-01-22

    The brain contains multiple yet distinct systems involved in reward prediction. To understand the nature of these processes, we recorded single-unit activity from the lateral prefrontal cortex (LPFC) and the striatum in monkeys performing a reward inference task using an asymmetric reward schedule. We found that neurons both in the LPFC and in the striatum predicted reward values for stimuli that had been previously well experienced with set reward quantities in the asymmetric reward task. Importantly, these LPFC neurons could predict the reward value of a stimulus using transitive inference even when the monkeys had not yet learned the stimulus-reward association directly; whereas these striatal neurons did not show such an ability. Nevertheless, because there were two set amounts of reward (large and small), the selected striatal neurons were able to exclusively infer the reward value (e.g., large) of one novel stimulus from a pair after directly experiencing the alternative stimulus with the other reward value (e.g., small). Our results suggest that although neurons that predict reward value for old stimuli in the LPFC could also do so for new stimuli via transitive inference, those in the striatum could only predict reward for new stimuli via exclusive inference. Moreover, the striatum showed more complex functions than was surmised previously for model-free learning.

  10. The anatomy of choice: active inference and agency.

    Science.gov (United States)

    Friston, Karl; Schwartenbeck, Philipp; Fitzgerald, Thomas; Moutoussis, Michael; Behrens, Timothy; Dolan, Raymond J

    2013-01-01

    This paper considers agency in the setting of embodied or active inference. In brief, we associate a sense of agency with prior beliefs about action and ask what sorts of beliefs underlie optimal behavior. In particular, we consider prior beliefs that action minimizes the Kullback-Leibler (KL) divergence between desired states and attainable states in the future. This allows one to formulate bounded rationality as approximate Bayesian inference that optimizes a free energy bound on model evidence. We show that constructs like expected utility, exploration bonuses, softmax choice rules and optimism bias emerge as natural consequences of this formulation. Previous accounts of active inference have focused on predictive coding and Bayesian filtering schemes for minimizing free energy. Here, we consider variational Bayes as an alternative scheme that provides formal constraints on the computational anatomy of inference and action-constraints that are remarkably consistent with neuroanatomy. Furthermore, this scheme contextualizes optimal decision theory and economic (utilitarian) formulations as pure inference problems. For example, expected utility theory emerges as a special case of free energy minimization, where the sensitivity or inverse temperature (of softmax functions and quantal response equilibria) has a unique and Bayes-optimal solution-that minimizes free energy. This sensitivity corresponds to the precision of beliefs about behavior, such that attainable goals are afforded a higher precision or confidence. In turn, this means that optimal behavior entails a representation of confidence about outcomes that are under an agent's control.

  11. SEMANTIC PATCH INFERENCE

    DEFF Research Database (Denmark)

    Andersen, Jesper

    2009-01-01

    Collateral evolution the problem of updating several library-using programs in response to API changes in the used library. In this dissertation we address the issue of understanding collateral evolutions by automatically inferring a high-level specification of the changes evident in a given set ...... specifications inferred by spdiff in Linux are shown. We find that the inferred specifications concisely capture the actual collateral evolution performed in the examples....

  12. A Network Inference Workflow Applied to Virulence-Related Processes in Salmonella typhimurium

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, Ronald C.; Singhal, Mudita; Weller, Jennifer B.; Khoshnevis, Saeed; Shi, Liang; McDermott, Jason E.

    2009-04-20

    Inference of the structure of mRNA transcriptional regulatory networks, protein regulatory or interaction networks, and protein activation/inactivation-based signal transduction networks are critical tasks in systems biology. In this article we discuss a workflow for the reconstruction of parts of the transcriptional regulatory network of the pathogenic bacterium Salmonella typhimurium based on the information contained in sets of microarray gene expression data now available for that organism, and describe our results obtained by following this workflow. The primary tool is one of the network inference algorithms deployed in the Software Environment for BIological Network Inference (SEBINI). Specifically, we selected the algorithm called Context Likelihood of Relatedness (CLR), which uses the mutual information contained in the gene expression data to infer regulatory connections. The associated analysis pipeline automatically stores the inferred edges from the CLR runs within SEBINI and, upon request, transfers the inferred edges into either Cytoscape or the plug-in Collective Analysis of Biological of Biological Interaction Networks (CABIN) tool for further post-analysis of the inferred regulatory edges. The following article presents the outcome of this workflow, as well as the protocols followed for microarray data collection, data cleansing, and network inference. Our analysis revealed several interesting interactions, functional groups, metabolic pathways, and regulons in S. typhimurium.

  13. Functional linear models for association analysis of quantitative traits.

    Science.gov (United States)

    Fan, Ruzong; Wang, Yifan; Mills, James L; Wilson, Alexander F; Bailey-Wilson, Joan E; Xiong, Momiao

    2013-11-01

    Functional linear models are developed in this paper for testing associations between quantitative traits and genetic variants, which can be rare variants or common variants or the combination of the two. By treating multiple genetic variants of an individual in a human population as a realization of a stochastic process, the genome of an individual in a chromosome region is a continuum of sequence data rather than discrete observations. The genome of an individual is viewed as a stochastic function that contains both linkage and linkage disequilibrium (LD) information of the genetic markers. By using techniques of functional data analysis, both fixed and mixed effect functional linear models are built to test the association between quantitative traits and genetic variants adjusting for covariates. After extensive simulation analysis, it is shown that the F-distributed tests of the proposed fixed effect functional linear models have higher power than that of sequence kernel association test (SKAT) and its optimal unified test (SKAT-O) for three scenarios in most cases: (1) the causal variants are all rare, (2) the causal variants are both rare and common, and (3) the causal variants are common. The superior performance of the fixed effect functional linear models is most likely due to its optimal utilization of both genetic linkage and LD information of multiple genetic variants in a genome and similarity among different individuals, while SKAT and SKAT-O only model the similarities and pairwise LD but do not model linkage and higher order LD information sufficiently. In addition, the proposed fixed effect models generate accurate type I error rates in simulation studies. We also show that the functional kernel score tests of the proposed mixed effect functional linear models are preferable in candidate gene analysis and small sample problems. The methods are applied to analyze three biochemical traits in data from the Trinity Students Study. © 2013 WILEY

  14. Functional networks in parallel with cortical development associate with executive functions in children.

    Science.gov (United States)

    Zhong, Jidan; Rifkin-Graboi, Anne; Ta, Anh Tuan; Yap, Kar Lai; Chuang, Kai-Hsiang; Meaney, Michael J; Qiu, Anqi

    2014-07-01

    Children begin performing similarly to adults on tasks requiring executive functions in late childhood, a transition that is probably due to neuroanatomical fine-tuning processes, including myelination and synaptic pruning. In parallel to such structural changes in neuroanatomical organization, development of functional organization may also be associated with cognitive behaviors in children. We examined 6- to 10-year-old children's cortical thickness, functional organization, and cognitive performance. We used structural magnetic resonance imaging (MRI) to identify areas with cortical thinning, resting-state fMRI to identify functional organization in parallel to cortical development, and working memory/response inhibition tasks to assess executive functioning. We found that neuroanatomical changes in the form of cortical thinning spread over bilateral frontal, parietal, and occipital regions. These regions were engaged in 3 functional networks: sensorimotor and auditory, executive control, and default mode network. Furthermore, we found that working memory and response inhibition only associated with regional functional connectivity, but not topological organization (i.e., local and global efficiency of information transfer) of these functional networks. Interestingly, functional connections associated with "bottom-up" as opposed to "top-down" processing were more clearly related to children's performance on working memory and response inhibition, implying an important role for brain systems involved in late childhood. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Review of Dermatology Associations and Their Functions on Internet

    Directory of Open Access Journals (Sweden)

    Sevda Gizlent

    2011-06-01

    Full Text Available Background and Design: Associations are the most important constituents of occupational organizations. The objective of this study was to determine dermatology associations and to investigate their structures and functions. Material and Method: Dermatology associations were reached through the internet via a search engine (www.google.com by entering the keywords “international, Asian, European, African, and the other nationalities and races” and “dermatology, cutaneous, skin, nail, hair, skin biology, cosmetic, laser, photobiology, dermoscopy, teledermatology, dermatoallergy, dermatoimmunology, sexually transmitted disease, dermatovenerology, dermatooncology, dermatosurgery, dermatologic imaging, dermatopathology, physchodermatology” and “foundation, association, society, organization”. The associations were classified into four groups according to the entities on the particular website and publication language. Associations were searched on the “International League of Dermatology Societies (ILDS” website in order to investigate membership status. Furthermore, we investigated history, aim, administrative structure, revenue sources, the number of members, membership requirements and benefits, training activities, periodicals, scientific working groups and social activities. Results: One hundred ninety-four associations worldwide have been determined. The countries with a significant number of associations were the United States of America - 22, Turkey - 14, Italy - 11 and England - 9. Fifty-three associations worldwide were international and 141 were national. The countries with a higher number of international associations were the United States of America - 12 and Germany - 5. There were 72 associations with an english website, 17 with a website in both english and local language, 53 with a website in only local language, 52 without a website. From Turkey, only one association had a website in english, but none of them were

  16. Associations among False Belief Understanding, Counterfactual Reasoning, and Executive Function

    Science.gov (United States)

    Guajardo, Nicole R.; Parker, Jessica; Turley-Ames, Kandi

    2009-01-01

    The primary purposes of the present study were to clarify previous work on the association between counterfactual thinking and false belief performance to determine (1) whether these two variables are related and (2) if so, whether executive function skills mediate the relationship. A total of 92 3-, 4-, and 5-year-olds completed false belief,…

  17. Nonlinear associations between plasma cholesterol levels and neuropsychological function.

    Science.gov (United States)

    Wendell, Carrington R; Zonderman, Alan B; Katzel, Leslie I; Rosenberger, William F; Plamadeala, Victoria V; Hosey, Megan M; Waldstein, Shari R

    2016-11-01

    Although both high and low levels of total and low-density lipoprotein (LDL) cholesterol have been associated with poor neuropsychological function, little research has examined nonlinear effects. We examined quadratic relations of cholesterol to performance on a comprehensive neuropsychological battery. Participants were 190 older adults (53% men, ages 54-83) free of major medical, neurologic, and psychiatric disease. Measures of fasting plasma total and high-density lipoprotein (HDL) cholesterol were assayed, and LDL cholesterol was calculated. Participants completed neuropsychological measures of attention, executive function, memory, visuospatial judgment, and manual speed and dexterity. Multiple regression analyses examined cholesterol levels as quadratic predictors of each measure of cognitive performance, with age (dichotomized as Reproduction II ( b = -.0020, p = .026) and log of the Trail Making Test, Part B (b = .0001, p = .044). Quadratic associations between HDL cholesterol and cognitive performance were nonsignificant. Results indicate differential associations between cholesterol and neuropsychological function across different ages and domains of function. High and low total and LDL cholesterol may confer both risk and benefit for suboptimal cognitive function at different ages. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  18. Diabetes Mellitus-Associated Functional Hypercortisolism Impairs Sexual Function in Male Late-Onset Hypogonadism.

    Science.gov (United States)

    Tirabassi, G; Corona, G; Lamonica, G R; Lenzi, A; Maggi, M; Balercia, G

    2016-01-01

    Functional hypercortisolism is generated by conditions able to chronically activate hypothalamic-pituitary-adrenal axis and has been proven to have a negative role in several complications. However, no study has evaluated the possible influence of diabetes mellitus-associated functional hypercortisolism on male hypogonadism and sexual function. We aimed to identify any association of hypothalamic-pituitary-adrenal axis dysregulation measures with testosterone and sexual function in men simultaneously affected by diabetes mellitus and late-onset hypogonadism. Fifteen diabetes mellitus and late-onset hypogonadism subjects suffering from functional hypercortisolism and fifteen diabetes mellitus and late-onset hypogonadism subjects who were free of functional hypercortisolism were retrospectively reviewed. Clinical, hormonal, and sexual parameters were considered. Hypercortisolemic subjects showed higher values of body mass index, waist, and glycated hemoglobin and lower ones of testosterone compared to normocortisolemic ones. All sexual parameters, except for orgasmic function, were significantly worse in hypercortisolemic than in normocortisolemic subjects. Hypercortisolemic patients showed higher values of cortisol after dexamethasone and urinary free cortisol as well as a lesser ACTH response after corticotropin releasing hormone test (ACTH area under curve) compared to normocortisolemic ones. No significant association was found at Poisson regression analysis between hormonal and sexual variables in normocortisolemic patients. In hypercortisolemic subjects, negative and significant associations of cortisol response after corticotropin releasing hormone (cortisol area under curve) with erectile function (β: -0.0008; p: 0.015) and total international index of erectile function score (β: -0.0006; p: 0.001) were evident. This study suggests for the first time the impairing influence of the dysregulated hypothalamic-pituitary-adrenal axis on sexual function in

  19. Genetic association between human chitinases and lung function in COPD.

    Science.gov (United States)

    Aminuddin, F; Akhabir, L; Stefanowicz, D; Paré, P D; Connett, J E; Anthonisen, N R; Fahy, J V; Seibold, M A; Burchard, E G; Eng, C; Gulsvik, A; Bakke, P; Cho, M H; Litonjua, A; Lomas, D A; Anderson, W H; Beaty, T H; Crapo, J D; Silverman, E K; Sandford, A J

    2012-07-01

    Two primary chitinases have been identified in humans--acid mammalian chitinase (AMCase) and chitotriosidase (CHIT1). Mammalian chitinases have been observed to affect the host's immune response. The aim of this study was to test for association between genetic variation in the chitinases and phenotypes related to chronic obstructive pulmonary disease (COPD). Polymorphisms in the chitinase genes were selected based on previous associations with respiratory diseases. Polymorphisms that were associated with lung function level or rate of decline in the Lung Health Study (LHS) cohort were analyzed for association with COPD affection status in four other COPD case-control populations. Chitinase activity and protein levels were also related to genotypes. In the caucasian LHS population, the baseline forced expiratory volume in one second (FEV(1)) was significantly different between the AA and GG genotypic groups of the AMCase rs3818822 polymorphism. Subjects with the GG genotype had higher AMCase protein and chitinase activity compared with AA homozygotes. For CHIT1 rs2494303, a significant association was observed between rate of decline in FEV(1) and the different genotypes. In the African American LHS population, CHIT1 rs2494303 and AMCase G339T genotypes were associated with rate of decline in FEV(1). Although a significant effect of chitinase gene alleles was found on lung function level and decline in the LHS, we were unable to replicate the associations with COPD affection status in the other COPD study groups.

  20. Characterizing genomic alterations in cancer by complementary functional associations.

    Science.gov (United States)

    Kim, Jong Wook; Botvinnik, Olga B; Abudayyeh, Omar; Birger, Chet; Rosenbluh, Joseph; Shrestha, Yashaswi; Abazeed, Mohamed E; Hammerman, Peter S; DiCara, Daniel; Konieczkowski, David J; Johannessen, Cory M; Liberzon, Arthur; Alizad-Rahvar, Amir Reza; Alexe, Gabriela; Aguirre, Andrew; Ghandi, Mahmoud; Greulich, Heidi; Vazquez, Francisca; Weir, Barbara A; Van Allen, Eliezer M; Tsherniak, Aviad; Shao, Diane D; Zack, Travis I; Noble, Michael; Getz, Gad; Beroukhim, Rameen; Garraway, Levi A; Ardakani, Masoud; Romualdi, Chiara; Sales, Gabriele; Barbie, David A; Boehm, Jesse S; Hahn, William C; Mesirov, Jill P; Tamayo, Pablo

    2016-05-01

    Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes.

  1. Resting Heart Rate Is Not Associated with Cognitive Function

    DEFF Research Database (Denmark)

    Wod, M; Jensen, M T; Galatius, S

    2018-01-01

    Aims: In order to examine the hypothesis that elevated resting heart rate (RHR) is associated with impaired cognitive score, we investigated the relationship between RHR and cognitive score in middle-aged, elderly and old Danish subjects from the general population. Methods: Composite cognitive s...... cognitive score (1,049 pairs of 2,049 pairs [51% (95% CI 49–53), p relation to cognitive function in the general population....... and hypertension, RHR was not associated with cognitive function. Furthermore, the intrapair analyses showed that RHR was not associated with cognitive score testing within twin pairs, as measured by the proportion of twin pairs in which the twin with higher RHR also was the twin with the lowest composite...

  2. Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function

    NARCIS (Netherlands)

    D.B. Hancock (Dana); M. Eijgelsheim (Mark); J.B. Wilk (Jemma); S.A. Gharib (Sina); L.R. Loehr (Laura); K. Marciante (Kristin); N. Franceschini (Nora); Y.M.T.A. van Durme; T.H. Chen; R.G. Barr (Graham); M.B. Schabath (Matthew); D.J. Couper (David); G.G. Brusselle (Guy); B.M. Psaty (Bruce); P. Tikka-Kleemola (Päivi); J.I. Rotter (Jerome); A.G. Uitterlinden (André); A. Hofman (Albert); N.M. Punjabi (Naresh); F. Rivadeneira Ramirez (Fernando); A.C. Morrison (Alanna); P.L. Enright (Paul); K.E. North (Kari); S.R. Heckbert (Susan); T. Lumley (Thomas); B.H.Ch. Stricker (Bruno); G.T. O'Connor (George); S.J. London (Stephanie)

    2010-01-01

    textabstractSpirometric measures of lung function are heritable traits that reflect respiratory health and predict morbidity and mortality. We meta-analyzed genome-wide association studies for two clinically important lung-function measures: forced expiratory volume in the first second (FEV1) and

  3. Inference in `poor` languages

    Energy Technology Data Exchange (ETDEWEB)

    Petrov, S.

    1996-10-01

    Languages with a solvable implication problem but without complete and consistent systems of inference rules (`poor` languages) are considered. The problem of existence of finite complete and consistent inference rule system for a ``poor`` language is stated independently of the language or rules syntax. Several properties of the problem arc proved. An application of results to the language of join dependencies is given.

  4. Bayesian statistical inference

    Directory of Open Access Journals (Sweden)

    Bruno De Finetti

    2017-04-01

    Full Text Available This work was translated into English and published in the volume: Bruno De Finetti, Induction and Probability, Biblioteca di Statistica, eds. P. Monari, D. Cocchi, Clueb, Bologna, 1993.Bayesian statistical Inference is one of the last fundamental philosophical papers in which we can find the essential De Finetti's approach to the statistical inference.

  5. Geometric statistical inference

    International Nuclear Information System (INIS)

    Periwal, Vipul

    1999-01-01

    A reparametrization-covariant formulation of the inverse problem of probability is explicitly solved for finite sample sizes. The inferred distribution is explicitly continuous for finite sample size. A geometric solution of the statistical inference problem in higher dimensions is outlined

  6. Practical Bayesian Inference

    Science.gov (United States)

    Bailer-Jones, Coryn A. L.

    2017-04-01

    Preface; 1. Probability basics; 2. Estimation and uncertainty; 3. Statistical models and inference; 4. Linear models, least squares, and maximum likelihood; 5. Parameter estimation: single parameter; 6. Parameter estimation: multiple parameters; 7. Approximating distributions; 8. Monte Carlo methods for inference; 9. Parameter estimation: Markov chain Monte Carlo; 10. Frequentist hypothesis testing; 11. Model comparison; 12. Dealing with more complicated problems; References; Index.

  7. Statistical inference an integrated approach

    CERN Document Server

    Migon, Helio S; Louzada, Francisco

    2014-01-01

    Introduction Information The concept of probability Assessing subjective probabilities An example Linear algebra and probability Notation Outline of the bookElements of Inference Common statistical modelsLikelihood-based functions Bayes theorem Exchangeability Sufficiency and exponential family Parameter elimination Prior Distribution Entirely subjective specification Specification through functional forms Conjugacy with the exponential family Non-informative priors Hierarchical priors Estimation Introduction to decision theoryBayesian point estimation Classical point estimation Empirical Bayes estimation Comparison of estimators Interval estimation Estimation in the Normal model Approximating Methods The general problem of inference Optimization techniquesAsymptotic theory Other analytical approximations Numerical integration methods Simulation methods Hypothesis Testing Introduction Classical hypothesis testingBayesian hypothesis testing Hypothesis testing and confidence intervalsAsymptotic tests Prediction...

  8. Nonparametric predictive inference in reliability

    International Nuclear Information System (INIS)

    Coolen, F.P.A.; Coolen-Schrijner, P.; Yan, K.J.

    2002-01-01

    We introduce a recently developed statistical approach, called nonparametric predictive inference (NPI), to reliability. Bounds for the survival function for a future observation are presented. We illustrate how NPI can deal with right-censored data, and discuss aspects of competing risks. We present possible applications of NPI for Bernoulli data, and we briefly outline applications of NPI for replacement decisions. The emphasis is on introduction and illustration of NPI in reliability contexts, detailed mathematical justifications are presented elsewhere

  9. Endothelial Function Is Associated with White Matter Microstructure and Executive Function in Older Adults

    Directory of Open Access Journals (Sweden)

    Nathan F. Johnson

    2017-08-01

    Full Text Available Age-related declines in endothelial function can lead to cognitive decline. However, little is known about the relationships between endothelial function and specific neurocognitive functions. This study explored the relationship between measures of endothelial function (reactive hyperemia index; RHI, white matter (WM health (fractional anisotropy, FA, and WM hyperintensity volume, WMH, and executive function (Trail Making Test (TMT; Trail B − Trail A. Participants were 36 older adults between the ages of 59 and 69 (mean age = 63.89 years, SD = 2.94. WMH volume showed no relationship with RHI or executive function. However, there was a positive relationship between RHI and FA in the genu and body of the corpus callosum. In addition, higher RHI and FA were each associated with better executive task performance. Tractography was used to localize the WM tracts associated with RHI to specific portions of cortex. Results indicated that the RHI-FA relationship observed in the corpus callosum primarily involved tracts interconnecting frontal regions, including the superior frontal gyrus (SFG and frontopolar cortex, linked with executive function. These findings suggest that superior endothelial function may help to attenuate age-related declines in WM microstructure in portions of the corpus callosum that interconnect prefrontal brain regions involved in executive function.

  10. Associative reinstatement memory measures hippocampal function in Parkinson's Disease.

    Science.gov (United States)

    Cohn, Melanie; Giannoylis, Irene; De Belder, Maya; Saint-Cyr, Jean A; McAndrews, Mary Pat

    2016-09-01

    In Parkinson's Disease (PD), hippocampal atrophy is associated with rapid cognitive decline. Hippocampal function is typically assessed using memory tests but current clinical tools (e.g., free recall) also rely on executive functions or use material that is not optimally engaging hippocampal memory networks. Because of the ubiquity of executive dysfunction in PD, our ability to detect true memory deficits is suboptimal. Our previous behavioural and neuroimaging work in other populations suggests that an experimental memory task - Associative Reinstatement Memory (ARM) - may prove useful in investigating hippocampal function in PD. In this study, we investigated whether ARM is compromised in PD and we assessed its convergent and divergent validity by comparing it to standardized measures of memory and of attention and executive functioning in PD, respectively. Using fMRI, we also investigated whether performance in PD relates to degree of hippocampal engagement. Fifteen participants with PD and 13 age-matched healthy controls completed neuropsychological testing as well as an ARM fMRI recognition paradigm in which they were instructed to identify word pairs comprised of two studied words (intact or rearranged pairs) and those containing at least one new word (new or half new pairs). ARM is measured by the differences in hit rates between intact and rearranged pairs. Behaviourally, ARM was poorer in PD relative to controls and was correlated with verbal memory measures, but not with attention or executive functioning in the PD group. Hippocampal activation associated with ARM was reduced in PD relative to controls and covaried with ARM scores in both groups. To conclude, ARM is a sensitive measure of hippocampal memory function that is unaffected by attention or executive dysfunction in PD. Our study highlights the benefit of integrating cognitive neuroscience frameworks and novel experimental tasks to improve the practice of clinical neuropsychology in PD

  11. Cesarean section and disease associated with immune function

    DEFF Research Database (Denmark)

    Kristensen, Kim; Henriksen, Lonny

    2016-01-01

    colitis and celiac disease, whereas children delivered by elective CS had an increased risk of lower respiratory tract infection and juvenile idiopathic arthritis. The effect of elective CS was higher than the effect of acute CS on the risk of asthma. CONCLUSION: Children delivered by CS are at increased......BACKGROUND: Earlier studies have shown that delivery by cesarean section (CS) is associated with an increased risk of disease associated with immune function in the offspring, but these studies have generally not discriminated between the effect of acute and elective CS. OBJECTIVE: We sought...... to further explore these associations using discrimination between the effects of acute versus elective CS. METHODS: We performed a population- and national register-based cohort study including all children born in Denmark from January 1997 through December 2012. Hazard ratios for diseases associated...

  12. Molecular and functional characterization of pigeon (Columba livia) tumor necrosis factor receptor-associated factor 3.

    Science.gov (United States)

    Zhou, Yingying; Kang, Xilong; Xiong, Dan; Zhu, Shanshan; Zheng, Huijuan; Xu, Ying; Guo, Yaxin; Pan, Zhiming; Jiao, Xinan

    2017-04-01

    Tumor necrosis factor receptor-associated factor 3 (TRAF3) plays a key antiviral role by promoting type I interferon production. We cloned the pigeon TRAF3 gene (PiTRAF3) according to its predicted mRNA sequence to investigate its function. The 1704-bp full-length open reading frame encodes a 567-amino acid protein. One Ring finger, two TRAF-type Zinc fingers, one Coiled coil, and one MATH domain were inferred. RT-PCR showed that PiTRAF3 was expressed in all tissues, with relatively weak expression in the heart and liver. In HEK293T cells, over-expression of wild-type, △Ring, △Zinc finger, and △Coiled coil PiTRAF3, but not a △MATH form, significantly increased IFN-β promoter activity. Zinc finger and Coiled coil domains were essential for NF-κB activation. In chicken HD11 cells, PiTRAF3 increased IFN-β promoter activity and four domains were all contributing. R848 stimulation of pigeon peripheral blood mononuclear cells and splenocytes significantly increased expression of PiTRAF3 and the inflammatory cytokine genes CCL5, IL-8, and IL-10. These data demonstrate TRAF3's innate immune function and improve understanding of its involvement in poultry antiviral defense. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. The Probabilistic Convolution Tree: Efficient Exact Bayesian Inference for Faster LC-MS/MS Protein Inference

    Science.gov (United States)

    Serang, Oliver

    2014-01-01

    Exact Bayesian inference can sometimes be performed efficiently for special cases where a function has commutative and associative symmetry of its inputs (called “causal independence”). For this reason, it is desirable to exploit such symmetry on big data sets. Here we present a method to exploit a general form of this symmetry on probabilistic adder nodes by transforming those probabilistic adder nodes into a probabilistic convolution tree with which dynamic programming computes exact probabilities. A substantial speedup is demonstrated using an illustration example that can arise when identifying splice forms with bottom-up mass spectrometry-based proteomics. On this example, even state-of-the-art exact inference algorithms require a runtime more than exponential in the number of splice forms considered. By using the probabilistic convolution tree, we reduce the runtime to and the space to where is the number of variables joined by an additive or cardinal operator. This approach, which can also be used with junction tree inference, is applicable to graphs with arbitrary dependency on counting variables or cardinalities and can be used on diverse problems and fields like forward error correcting codes, elemental decomposition, and spectral demixing. The approach also trivially generalizes to multiple dimensions. PMID:24626234

  14. Inferring relationships between clinical mastitis, productivity and fertility: a recursive model application including genetics, farm associated herd management, and cow-specific antibiotic treatments.

    Science.gov (United States)

    Rehbein, Pia; Brügemann, Kerstin; Yin, Tong; V Borstel, U König; Wu, Xiao-Lin; König, Sven

    2013-10-01

    A dataset of test-day records, fertility traits, and one health trait including 1275 Brown Swiss cows kept in 46 small-scale organic farms was used to infer relationships among these traits based on recursive Gaussian-threshold models. Test-day records included milk yield (MY), protein percentage (PROT-%), fat percentage (FAT-%), somatic cell score (SCS), the ratio of FAT-% to PROT-% (FPR), lactose percentage (LAC-%), and milk urea nitrogen (MUN). Female fertility traits were defined as the interval from calving to first insemination (CTFS) and success of a first insemination (SFI), and the health trait was clinical mastitis (CM). First, a tri-trait model was used which postulated the recursive effect of a test-day observation in the early period of lactation on liability to CM (LCM), and further the recursive effect of LCM on the following test-day observation. For CM and female fertility traits, a bi-trait recursive Gaussian-threshold model was employed to estimate the effects from CM to CTFS and from CM on SFI. The recursive effects from CTFS and SFI onto CM were not relevant, because CM was recorded prior to the measurements for CTFS and SFI. Results show that the posterior heritability for LCM was 0.05, and for all other traits, heritability estimates were in reasonable ranges, each with a small posterior SD. Lowest heritability estimates were obtained for female reproduction traits, i.e. h(2)=0.02 for SFI, and h(2)≈0 for CTFS. Posterior estimates of genetic correlations between LCM and production traits (MY and MUN), and between LCM and somatic cell score (SCS), were large and positive (0.56-0.68). Results confirm the genetic antagonism between MY and LCM, and the suitability of SCS as an indicator trait for CM. Structural equation coefficients describe the impact of one trait on a second trait on the phenotypic pathway. Higher values for FAT-% and FPR were associated with a higher LCM. The rate of change in FAT-% and in FPR in the ongoing lactation with

  15. Position of the American Dietetic Association: functional foods.

    Science.gov (United States)

    Hasler, Clare M; Brown, Amy C

    2009-04-01

    All foods are functional at some physiological level, but it is the position of the American Dietetic Association (ADA) that functional foods that include whole foods and fortified, enriched, or enhanced foods have a potentially beneficial effect on health when consumed as part of a varied diet on a regular basis, at effective levels. ADA supports research to further define the health benefits and risks of individual functional foods and their physiologically active components. Health claims on food products, including functional foods, should be based on the significant scientific agreement standard of evidence and ADA supports label claims based on such strong scientific substantiation. Food and nutrition professionals will continue to work with the food industry, allied health professionals, the government, the scientific community, and the media to ensure that the public has accurate information regarding functional foods and thus should continue to educate themselves on this emerging area of food and nutrition science. Knowledge of the role of physiologically active food components, from plant, animal, and microbial food sources, has changed the role of diet in health. Functional foods have evolved as food and nutrition science has advanced beyond the treatment of deficiency syndromes to reduction of disease risk and health promotion. This position paper reviews the definition of functional foods, their regulation, and the scientific evidence supporting this evolving area of food and nutrition. Foods can no longer be evaluated only in terms of macronutrient and micronutrient content alone. Analyzing the content of other physiologically active components and evaluating their role in health promotion will be necessary. The availability of health-promoting functional foods in the US diet has the potential to help ensure a healthier population. However, each functional food should be evaluated on the basis of scientific evidence to ensure appropriate integration

  16. Associations between executive functioning, coping, and psychosocial functioning after acquired brain injury.

    Science.gov (United States)

    Wolters Gregório, Gisela; Ponds, Rudolf W H M; Smeets, Sanne M J; Jonker, Frank; Pouwels, Climmy G J G; Verhey, Frans R; van Heugten, Caroline M

    2015-09-01

    To examine the relationships between executive functioning, coping, depressive symptoms, and quality of life in individuals with neuropsychiatric symptoms after acquired brain injury (ABI). Cross-sectional study. Individuals (n = 93) in the post-acute and chronic phase (>3 months) after ABI and their significant others (N = 58) were recruited from outpatient clinics of four mental health centres in the Netherlands. Outcome measures were the Trail Making Test, Stroop Colour Word Test, Frontal Systems Behavioural Scale, Utrecht Coping List, Patient Health Questionnaire, and Life Satisfaction Questionnaire. Data were analysed with multiple regression analyses. Self-reported executive dysfunction was associated with greater use of passive coping styles (β = .37, p executive functioning (β = -.94, p executive functioning tests were not associated with coping, depressive symptoms, or quality of life. For clinicians, these data indicate that individuals who report greater difficulties with executive functioning after ABI are inclined to use maladaptive passive coping styles, which should be targeted in treatment. In comparison, individuals who report greater difficulties with executive functioning should not be prompted to use problem-focused coping styles. These individuals may benefit from other coping styles, such as the use of seeking social support or acceptance of problems. Coping influences the association between executive functioning and quality of life. Individuals who report difficulties with executive functioning after ABI may be inclined to use passive coping styles, which are maladaptive. Problem-focused coping strategies may be more useful for individuals who have strong executive abilities. This study was a cross-sectional study; thus, a cause-and-effect relationship could not be established between executive functioning, coping, and psychosocial functioning. As this research was part of standard clinical care, non-traditional tests for executive

  17. Orofacial functions and oral health associated with Treacher Collins syndrome.

    Science.gov (United States)

    Asten, Pamela; Skogedal, Nina; Nordgarden, Hilde; Axelsson, Stefan; Akre, Harriet; Sjögreen, Lotta

    2013-01-01

    The aim of this study was to describe orofacial features and functions and oral health associated with Treacher Collins syndrome (TCS) in relation to the variable phenotypic expression of the condition. The Nordic Orofacial Test-Screening (NOT-S), MHC Questionnaire, MHC Observation chart and clinical examinations of nasal and pharyngeal conditions and chewing and swallowing function were used to assess 19 individuals aged 5-74 years (median 34 years). TCS severity scores were calculated by a clinical geneticist. Orofacial features characterizing the study group were altered profile, increased mandibular angle, narrow hypopharynx and facial asymmetry. Basic orofacial functions such as breathing, eating, facial expression and speech were affected in all subjects demonstrating orofacial dysfunction in at least two NOT-S domains (median NOT-S total score 4/12, range 2-7). Significant correlation was found between the TCS severity scores reflecting phenotypic expression and the NOT-S total scores reflecting orofacial function. Self-reported experience of dry oral mucosa was common. Overall, dental health was good with few carious lesions diagnosed, but considerable need for orthodontic treatment was documented. Altered orofacial features and functions in TCS are common and often persist into late adolescence and adulthood. The functional level was correlated with the phenotypic variability of the condition. The standard of oral health was satisfactory. The findings indicated that individuals with TCS are likely to require lifelong health services related to their oral condition.

  18. A functional data analysis approach for genetic association studies

    OpenAIRE

    Reimherr, Matthew; Nicolae, Dan

    2014-01-01

    We present a new method based on Functional Data Analysis (FDA) for detecting associations between one or more scalar covariates and a longitudinal response, while correcting for other variables. Our methods exploit the temporal structure of longitudinal data in ways that are otherwise difficult with a multivariate approach. Our procedure, from an FDA perspective, is a departure from more established methods in two key aspects. First, the raw longitudinal phenotypes are assembled into functio...

  19. The association between resting functional connectivity and dispositional optimism.

    Science.gov (United States)

    Ran, Qian; Yang, Junyi; Yang, Wenjing; Wei, Dongtao; Qiu, Jiang; Zhang, Dong

    2017-01-01

    Dispositional optimism is an individual characteristic that plays an important role in human experience. Optimists are people who tend to hold positive expectations for their future. Previous studies have focused on the neural basis of optimism, such as task response neural activity and brain structure volume. However, the functional connectivity between brain regions of the dispositional optimists are poorly understood. Previous study suggested that the ventromedial prefrontal cortex (vmPFC) are associated with individual differences in dispositional optimism, but it is unclear whether there are other brain regions that combine with the vmPFC to contribute to dispositional optimism. Thus, the present study used the resting-state functional connectivity (RSFC) approach and set the vmPFC as the seed region to examine if differences in functional brain connectivity between the vmPFC and other brain regions would be associated with individual differences in dispositional optimism. The results found that dispositional optimism was significantly positively correlated with the strength of the RSFC between vmPFC and middle temporal gyrus (mTG) and negativly correlated with RSFC between vmPFC and inferior frontal gyrus (IFG). These findings may be suggested that mTG and IFG which associated with emotion processes and emotion regulation also play an important role in the dispositional optimism.

  20. The association between resting functional connectivity and dispositional optimism.

    Directory of Open Access Journals (Sweden)

    Qian Ran

    Full Text Available Dispositional optimism is an individual characteristic that plays an important role in human experience. Optimists are people who tend to hold positive expectations for their future. Previous studies have focused on the neural basis of optimism, such as task response neural activity and brain structure volume. However, the functional connectivity between brain regions of the dispositional optimists are poorly understood. Previous study suggested that the ventromedial prefrontal cortex (vmPFC are associated with individual differences in dispositional optimism, but it is unclear whether there are other brain regions that combine with the vmPFC to contribute to dispositional optimism. Thus, the present study used the resting-state functional connectivity (RSFC approach and set the vmPFC as the seed region to examine if differences in functional brain connectivity between the vmPFC and other brain regions would be associated with individual differences in dispositional optimism. The results found that dispositional optimism was significantly positively correlated with the strength of the RSFC between vmPFC and middle temporal gyrus (mTG and negativly correlated with RSFC between vmPFC and inferior frontal gyrus (IFG. These findings may be suggested that mTG and IFG which associated with emotion processes and emotion regulation also play an important role in the dispositional optimism.

  1. Reasoning about Informal Statistical Inference: One Statistician's View

    Science.gov (United States)

    Rossman, Allan J.

    2008-01-01

    This paper identifies key concepts and issues associated with the reasoning of informal statistical inference. I focus on key ideas of inference that I think all students should learn, including at secondary level as well as tertiary. I argue that a fundamental component of inference is to go beyond the data at hand, and I propose that statistical…

  2. Brain Activity and Functional Connectivity Associated with Hypnosis.

    Science.gov (United States)

    Jiang, Heidi; White, Matthew P; Greicius, Michael D; Waelde, Lynn C; Spiegel, David

    2017-08-01

    Hypnosis has proven clinical utility, yet changes in brain activity underlying the hypnotic state have not yet been fully identified. Previous research suggests that hypnosis is associated with decreased default mode network (DMN) activity and that high hypnotizability is associated with greater functional connectivity between the executive control network (ECN) and the salience network (SN). We used functional magnetic resonance imaging to investigate activity and functional connectivity among these three networks in hypnosis. We selected 57 of 545 healthy subjects with very high or low hypnotizability using two hypnotizability scales. All subjects underwent four conditions in the scanner: rest, memory retrieval, and two different hypnosis experiences guided by standard pre-recorded instructions in counterbalanced order. Seeds for the ECN, SN, and DMN were left and right dorsolateral prefrontal cortex, dorsal anterior cingulate cortex (dACC), and posterior cingulate cortex (PCC), respectively. During hypnosis there was reduced activity in the dACC, increased functional connectivity between the dorsolateral prefrontal cortex (DLPFC;ECN) and the insula in the SN, and reduced connectivity between the ECN (DLPFC) and the DMN (PCC). These changes in neural activity underlie the focused attention, enhanced somatic and emotional control, and lack of self-consciousness that characterizes hypnosis. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Common Functional Gastroenterologic Disorders Associated With Abdominal Pain

    Science.gov (United States)

    Bharucha, Adil E.; Chakraborty, Subhankar; Sletten, Christopher D.

    2016-01-01

    Although abdominal pain is a symptom of several structural gastrointestinal disorders (eg, peptic ulcer disease), this comprehensive review will focus on the 4 most common nonstructural, or functional, disorders associated with abdominal pain: functional dyspepsia, constipation-predominant and diarrhea-predominant irritable bowel syndrome, and functional abdominal pain syndrome. Together, these conditions affect approximately 1 in 4 people in the United States. They are associated with comorbid conditions (eg, fibromyalgia, depression), impaired quality of life, and increased health care utilization. Symptoms are explained by disordered gastrointestinal motility and sensation, which are implicated in a variety of peripheral (eg, postinfectious inflammation, luminal irritants) and/or central (eg, stress and anxiety) factors. These disorders are defined and can generally be diagnosed by symptoms alone. Often prompted by alarm features, selected testing is useful to exclude structural disease. Identifying the specific diagnosis (eg, differentiating between functional abdominal pain and irritable bowel syndrome) and establishing an effective patient-physician relationship are the cornerstones of therapy. Many patients with mild symptoms can be effectively managed with limited tests, sensible dietary modifications, and over-the-counter medications tailored to symptoms. If these measures are not sufficient, pharmacotherapy should be considered for bowel symptoms (constipation or diarrhea) and/or abdominal pain; opioids should not be used. Behavioral and psychological approaches (eg, cognitive behavioral therapy) can be very helpful, particularly in patients with chronic abdominal pain who require a multidisciplinary pain management program without opioids. PMID:27492916

  4. Knowledge and inference

    CERN Document Server

    Nagao, Makoto

    1990-01-01

    Knowledge and Inference discusses an important problem for software systems: How do we treat knowledge and ideas on a computer and how do we use inference to solve problems on a computer? The book talks about the problems of knowledge and inference for the purpose of merging artificial intelligence and library science. The book begins by clarifying the concept of """"knowledge"""" from many points of view, followed by a chapter on the current state of library science and the place of artificial intelligence in library science. Subsequent chapters cover central topics in the artificial intellig

  5. Logical inference and evaluation

    International Nuclear Information System (INIS)

    Perey, F.G.

    1981-01-01

    Most methodologies of evaluation currently used are based upon the theory of statistical inference. It is generally perceived that this theory is not capable of dealing satisfactorily with what are called systematic errors. Theories of logical inference should be capable of treating all of the information available, including that not involving frequency data. A theory of logical inference is presented as an extension of deductive logic via the concept of plausibility and the application of group theory. Some conclusions, based upon the application of this theory to evaluation of data, are also given

  6. Synthesis and phase behavior of end-functionalized associating polymers

    Science.gov (United States)

    Wrue, Michelle H.

    chemical cleavage of the end-groups resulted in Tgs near those observed for polymer standards of comparable molecular weight. Aggregation of UPy end-groups in solution was observed using gel permeation chromatography. Aggregation was only observed for telechelic samples of low molecular weight, indicating that the aggregation of end-groups is dependent upon the concentration of the end-groups. The effect of UPy end-groups on blend miscibility was studied in solution using laser light scattering and in the melt state was using laser light scattering, optical microscopy and differential scanning calorimetry. The incorporation of associating groups onto one end of either blend component decreases miscibility relative to unfunctionalized parent blends. Lower miscibility was also observed for blends in which both components were mono-functionalized with associating end-groups. The largest decrease in miscibility was observed for blends containing telechelic UPy-functionalized polymers, which were immiscible across the entire composition range.

  7. Statistical inference on residual life

    CERN Document Server

    Jeong, Jong-Hyeon

    2014-01-01

    This is a monograph on the concept of residual life, which is an alternative summary measure of time-to-event data, or survival data. The mean residual life has been used for many years under the name of life expectancy, so it is a natural concept for summarizing survival or reliability data. It is also more interpretable than the popular hazard function, especially for communications between patients and physicians regarding the efficacy of a new drug in the medical field. This book reviews existing statistical methods to infer the residual life distribution. The review and comparison includes existing inference methods for mean and median, or quantile, residual life analysis through medical data examples. The concept of the residual life is also extended to competing risks analysis. The targeted audience includes biostatisticians, graduate students, and PhD (bio)statisticians. Knowledge in survival analysis at an introductory graduate level is advisable prior to reading this book.

  8. Nonparametric Bayesian inference in biostatistics

    CERN Document Server

    Müller, Peter

    2015-01-01

    As chapters in this book demonstrate, BNP has important uses in clinical sciences and inference for issues like unknown partitions in genomics. Nonparametric Bayesian approaches (BNP) play an ever expanding role in biostatistical inference from use in proteomics to clinical trials. Many research problems involve an abundance of data and require flexible and complex probability models beyond the traditional parametric approaches. As this book's expert contributors show, BNP approaches can be the answer. Survival Analysis, in particular survival regression, has traditionally used BNP, but BNP's potential is now very broad. This applies to important tasks like arrangement of patients into clinically meaningful subpopulations and segmenting the genome into functionally distinct regions. This book is designed to both review and introduce application areas for BNP. While existing books provide theoretical foundations, this book connects theory to practice through engaging examples and research questions. Chapters c...

  9. Probability and Statistical Inference

    OpenAIRE

    Prosper, Harrison B.

    2006-01-01

    These lectures introduce key concepts in probability and statistical inference at a level suitable for graduate students in particle physics. Our goal is to paint as vivid a picture as possible of the concepts covered.

  10. On quantum statistical inference

    NARCIS (Netherlands)

    Barndorff-Nielsen, O.E.; Gill, R.D.; Jupp, P.E.

    2003-01-01

    Interest in problems of statistical inference connected to measurements of quantum systems has recently increased substantially, in step with dramatic new developments in experimental techniques for studying small quantum systems. Furthermore, developments in the theory of quantum measurements have

  11. Causal learning and inference as a rational process: the new synthesis.

    Science.gov (United States)

    Holyoak, Keith J; Cheng, Patricia W

    2011-01-01

    Over the past decade, an active line of research within the field of human causal learning and inference has converged on a general representational framework: causal models integrated with bayesian probabilistic inference. We describe this new synthesis, which views causal learning and inference as a fundamentally rational process, and review a sample of the empirical findings that support the causal framework over associative alternatives. Causal events, like all events in the distal world as opposed to our proximal perceptual input, are inherently unobservable. A central assumption of the causal approach is that humans (and potentially nonhuman animals) have been designed in such a way as to infer the most invariant causal relations for achieving their goals based on observed events. In contrast, the associative approach assumes that learners only acquire associations among important observed events, omitting the representation of the distal relations. By incorporating bayesian inference over distributions of causal strength and causal structures, along with noisy-logical (i.e., causal) functions for integrating the influences of multiple causes on a single effect, human judgments about causal strength and structure can be predicted accurately for relatively simple causal structures. Dynamic models of learning based on the causal framework can explain patterns of acquisition observed with serial presentation of contingency data and are consistent with available neuroimaging data. The approach has been extended to a diverse range of inductive tasks, including category-based and analogical inferences.

  12. Covariance Association Test (CVAT) Identifies Genetic Markers Associated with Schizophrenia in Functionally Associated Biological Processes

    DEFF Research Database (Denmark)

    Rohde, Palle Duun; Demontis, Ditte; Castro Dias Cuyabano, Beatriz

    2016-01-01

    was among the top performers. When extending CVAT to utilize a mixture of SNP effects, we found an increase in power to detect the causal sets. Applying the methods to a Danish schizophrenia case–control data set, we found genomic evidence for association of schizophrenia with vitamin A metabolism......Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single-marker methods have limited...... genomic best linear unbiased prediction (GBLUP), the covariance association test (CVAT). We compared the performance of CVAT to other commonly used set tests. The comparison was conducted using a simulated study population having the same genetic parameters as for schizophrenia. We found that CVAT...

  13. INFERENCE BUILDING BLOCKS

    Science.gov (United States)

    2018-02-15

    expressed a variety of inference techniques on discrete and continuous distributions: exact inference, importance sampling, Metropolis-Hastings (MH...without redoing any math or rewriting any code. And although our main goal is composable reuse, our performance is also good because we can use...control paths. • The Hakaru language can express mixtures of discrete and continuous distributions, but the current disintegration transformation

  14. Functional Bowel Disorders Are Associated with a Central Immune Activation

    Directory of Open Access Journals (Sweden)

    Per G. Farup

    2017-01-01

    Full Text Available Background. Subjects with depression and unexplained neurological symptoms have a high prevalence of gastrointestinal comorbidity probably related to the brain-gut communication. This study explored associations between functional gastrointestinal disorders (FGID and inflammatory markers in subjects with these disorders. Methods. The FGID, including irritable bowel syndrome (IBS, were classified according to the Rome III criteria, and degree of symptoms was assessed with IBS symptom severity score (IBS-SSS. A range of interleukins (IL, chemokines and growth factors, tryptophan, and kynurenine were analysed in serum and the cerebrospinal fluid (CSF, and short-chain fatty acids (SCFA were analysed in the faeces. The results are reported as partial correlation (pc and p values. Results. Sixty-six subjects were included. IBS was associated with high levels of tryptophan (p=0.048 and kynurenine (p=0.019 and low level of IL-10 (p=0.047 in the CSF. IBS-SSS was associated with high tumor necrosis factor and low IL-10 in the CSF; pc=0.341 and p=0.009 and pc=−0.299 and p=0.023, respectively. Propionic minus butyric acid in faeces was negatively associated with IL-10 in the CSF (pc=−0.416, p=0.005. Conclusions. FGID were associated with a proinflammatory immune activation in the central nervous system and a disturbed tryptophan metabolism that could have been mediated by the faecal microbiota.

  15. Vitamin D status is associated with functional limitations and functional decline in older individuals.

    Science.gov (United States)

    Sohl, E; van Schoor, N M; de Jongh, R T; Visser, M; Deeg, D J H; Lips, P

    2013-09-01

    Vitamin D is known to influence muscle health. A reduction in muscle mass increases the risk of functional limitations among older individuals. The aim of this study was to examine the relationship between vitamin D status and functional limitations. Two independent cohorts of the Longitudinal Aging Study Amsterdam were used. Participants were aged 65 to 88 years (older cohort, n = 1237; baseline 1995) and 55 to 65 years (younger cohort, n = 725; baseline 2002). Questions on the ability and degree of difficulty to perform 6 functions of daily life were asked. Of the participants, 56% in the older cohort and 30% in the younger cohort had ≥1 limitation. Vitamin D deficiency (25-hydroxyvitamin D level of value in the reference group (>30 ng/mL) was related to the presence of functional limitations at baseline (odds ratio [OR] = 1.7; 95% confidence interval [CI], 1.2-2.5 and OR = 2.2; 95% CI 1.3-3.7 for the older and younger cohorts, respectively). In the older cohort, vitamin D deficiency was associated with an increase in limitations at 3 years (OR = 2.0; 95% CI, 1.1-3.5), whereas vitamin D deficiency in the younger cohort was associated with an increase in limitations at 6 years (OR = 3.3; 95% CI, 1.1-10.1). Analyses were adjusted for confounders. Vitamin D status is associated with functional limitations cross-sectionally and longitudinally in individuals aged 55 to 65 years and those 65 years and older. The possible association of vitamin D with functional limitations is present after a shorter follow-up time in the oldest age group compared with the younger age group.

  16. The functional importance of disease-associated mutation

    Directory of Open Access Journals (Sweden)

    Klein Teri E

    2002-09-01

    Full Text Available Abstract Background For many years, scientists believed that point mutations in genes are the genetic switches for somatic and inherited diseases such as cystic fibrosis, phenylketonuria and cancer. Some of these mutations likely alter a protein's function in a manner that is deleterious, and they should occur in functionally important regions of the protein products of genes. Here we show that disease-associated mutations occur in regions of genes that are conserved, and can identify likely disease-causing mutations. Results To show this, we have determined conservation patterns for 6185 non-synonymous and heritable disease-associated mutations in 231 genes. We define a parameter, the conservation ratio, as the ratio of average negative entropy of analyzable positions with reported mutations to that of every analyzable position in the gene sequence. We found that 84.0% of the 231 genes have conservation ratios less than one. 139 genes had eleven or more analyzable mutations and 88.0% of those had conservation ratios less than one. Conclusions These results indicate that phylogenetic information is a powerful tool for the study of disease-associated mutations. Our alignments and analysis has been made available as part of the database at http://cancer.stanford.edu/mut-paper/. Within this dataset, each position is annotated with the analysis, so the most likely disease-causing mutations can be identified.

  17. Factors associated with cognitive function in older adults in Mexico

    Directory of Open Access Journals (Sweden)

    Jenny Miu

    2016-03-01

    Full Text Available Background: As populations age, cognitive decline and dementia pose significant burdens for societies and health care systems, including low- and middle-income countries such as Mexico. Minor age-related declines in cognitive function appear to represent a stable but heterogeneous phase in the continuum between normal cognitive ageing and dementia. Loss of cognitive function has impacts at societal and individual levels and understanding the risk factors can help provide a framework for health policies and interventions to target at-risk groups. Design: A cohort of older Mexican adults (50+ from the World Health Organization's Study on global AGEing and adult health (WHO SAGE was used to examine cognitive function, including a total of 2315 respondents, with 325 respondents aged 80 years and older. Cognition was objectively evaluated using verbal recall, verbal fluency, forward digit span and backward digit span, with differences in an overall cognitive score assessed against sociodemographic variables, and associated factors using linear regression. Results: The most significant predictors of poorer cognitive function were found to be older age (β=−13.88, rural living (β=−2.25, low income (β=−8.28, self-reported severe or extreme memory difficulties (β=−6.62, and difficulty with two or more activities of daily living (β=−2.02. Conclusions: These findings can inform public health initiatives to address cognitive impairment in ageing populations in Mexico and other middle-income countries.

  18. HIV Infection Is Associated with Impaired Striatal Function during Inhibition with Normal Cortical Functioning on Functional MRI

    NARCIS (Netherlands)

    du Plessis, Stéfan; Vink, Matthijs; Joska, John A; Koutsilieri, Eleni; Bagadia, Asif; Stein, Dan J; Emsley, Robin

    2015-01-01

    The aim of the present study was to investigate the effect of HIV infection on cortical and subcortical regions of the frontal-striatal system involved in the inhibition of voluntary movement. Functional MRI (fMRI) studies suggest that human immunodeficiency virus (HIV) infection is associated with

  19. Covariance Association Test (CVAT) Identifies Genetic Markers Associated with Schizophrenia in Functionally Associated Biological Processes.

    Science.gov (United States)

    Rohde, Palle Duun; Demontis, Ditte; Cuyabano, Beatriz Castro Dias; Børglum, Anders D; Sørensen, Peter

    2016-08-01

    Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single-marker methods have limited power to detect genetic markers with small effects. Instead, aggregating genetic markers based on biological information might increase the power to identify sets of genetic markers of etiological significance. Several set test methods have been proposed: Here we propose a new set test derived from genomic best linear unbiased prediction (GBLUP), the covariance association test (CVAT). We compared the performance of CVAT to other commonly used set tests. The comparison was conducted using a simulated study population having the same genetic parameters as for schizophrenia. We found that CVAT was among the top performers. When extending CVAT to utilize a mixture of SNP effects, we found an increase in power to detect the causal sets. Applying the methods to a Danish schizophrenia case-control data set, we found genomic evidence for association of schizophrenia with vitamin A metabolism and immunological responses, which previously have been implicated with schizophrenia based on experimental and observational studies. Copyright © 2016 by the Genetics Society of America.

  20. Common Functional Gastroenterological Disorders Associated With Abdominal Pain.

    Science.gov (United States)

    Bharucha, Adil E; Chakraborty, Subhankar; Sletten, Christopher D

    2016-08-01

    Although abdominal pain is a symptom of several structural gastrointestinal disorders (eg, peptic ulcer disease), this comprehensive review will focus on the 4 most common nonstructural, or functional, disorders associated with abdominal pain: functional dyspepsia, constipation-predominant and diarrhea-predominant irritable bowel syndrome, and functional abdominal pain syndrome. Together, these conditions affect approximately 1 in 4 people in the United States. They are associated with comorbid conditions (eg, fibromyalgia and depression), impaired quality of life, and increased health care utilization. Symptoms are explained by disordered gastrointestinal motility and sensation, which are implicated in various peripheral (eg, postinfectious inflammation and luminal irritants) and/or central (eg, stress and anxiety) factors. These disorders are defined and can generally be diagnosed by symptoms alone. Often prompted by alarm features, selected testing is useful to exclude structural disease. Identifying the specific diagnosis (eg, differentiating between functional abdominal pain and irritable bowel syndrome) and establishing an effective patient-physician relationship are the cornerstones of therapy. Many patients with mild symptoms can be effectively managed with limited tests, sensible dietary modifications, and over-the-counter medications tailored to symptoms. If these measures are not sufficient, pharmacotherapy should be considered for bowel symptoms (constipation or diarrhea) and/or abdominal pain; opioids should not be used. Behavioral and psychological approaches (eg, cognitive behavioral therapy) can be helpful, particularly in patients with chronic abdominal pain who require a multidisciplinary pain management program without opioids. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  1. Associations between urinary diphenyl phosphate and thyroid function.

    Science.gov (United States)

    Preston, Emma V; McClean, Michael D; Claus Henn, Birgit; Stapleton, Heather M; Braverman, Lewis E; Pearce, Elizabeth N; Makey, Colleen M; Webster, Thomas F

    2017-04-01

    Triphenyl phosphate (TPHP) is a commonly used organophosphate flame retardant and plasticizer with widespread human exposure. Data on health effects of TPHP are limited. Recent toxicological studies suggest TPHP may alter thyroid function. We used repeated measures to assess the temporal variability in urinary concentrations of the TPHP metabolite, diphenyl phosphate (DPHP), and to examine relationships between DPHP concentrations and thyroid hormones. We sampled 51 adults at months 1, 6, and 12 from 2010 to 2011. Urine samples were analyzed for DPHP. Serum samples were analyzed for free and total thyroxine (fT 4 , TT 4 ), total triiodothyronine (TT 3 ), and thyroid stimulating hormone (TSH). We assessed variability in DPHP using intraclass correlation coefficients (ICCs) and kappa statistics. We used linear mixed-effects models to examine associations between DPHP and thyroid hormones. DPHP was detected in 95% of urine samples. Mean DPHP concentrations were 43% higher in women than men. DPHP showed high within-subject variability (ICC range, 0.13-0.39; kappa range, 0.16-0.39). High versus low (≥2.65 vs. <2.65ng/mL) DPHP in all participants was associated with a 0.43μg/dL (95% confidence interval: 0.15, 0.72) increase in mean TT 4 levels. In sex-stratified analyses, high versus low DPHP was associated with a 0.91μg/dL (95% CI: 0.47, 1.36) increase in mean TT 4 in women. The association was attenuated in men (βeta=0.19; 95% CI: -0.15, 0.52). We found no significant associations between DPHP and fT 4 , TT 3 , or TSH. We found evidence that TPHP exposure may be associated with increased TT 4 levels, especially in women. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Interest, Inferences, and Learning from Texts

    Science.gov (United States)

    Clinton, Virginia; van den Broek, Paul

    2012-01-01

    Topic interest and learning from texts have been found to be positively associated with each other. However, the reason for this positive association is not well understood. The purpose of this study is to examine a cognitive process, inference generation, that could explain the positive association between interest and learning from texts. In…

  3. Reveal genes functionally associated with ACADS by a network study.

    Science.gov (United States)

    Chen, Yulong; Su, Zhiguang

    2015-09-15

    Establishing a systematic network is aimed at finding essential human gene-gene/gene-disease pathway by means of network inter-connecting patterns and functional annotation analysis. In the present study, we have analyzed functional gene interactions of short-chain acyl-coenzyme A dehydrogenase gene (ACADS). ACADS plays a vital role in free fatty acid β-oxidation and regulates energy homeostasis. Modules of highly inter-connected genes in disease-specific ACADS network are derived by integrating gene function and protein interaction data. Among the 8 genes in ACADS web retrieved from both STRING and GeneMANIA, ACADS is effectively conjoined with 4 genes including HAHDA, HADHB, ECHS1 and ACAT1. The functional analysis is done via ontological briefing and candidate disease identification. We observed that the highly efficient-interlinked genes connected with ACADS are HAHDA, HADHB, ECHS1 and ACAT1. Interestingly, the ontological aspect of genes in the ACADS network reveals that ACADS, HAHDA and HADHB play equally vital roles in fatty acid metabolism. The gene ACAT1 together with ACADS indulges in ketone metabolism. Our computational gene web analysis also predicts potential candidate disease recognition, thus indicating the involvement of ACADS, HAHDA, HADHB, ECHS1 and ACAT1 not only with lipid metabolism but also with infant death syndrome, skeletal myopathy, acute hepatic encephalopathy, Reye-like syndrome, episodic ketosis, and metabolic acidosis. The current study presents a comprehensible layout of ACADS network, its functional strategies and candidate disease approach associated with ACADS network. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. The Association between Resting Functional Connectivity and Visual Creativity

    Science.gov (United States)

    Li, Wenfu; Yang, Junyi; Zhang, Qinglin; Li, Gongying; Qiu, Jiang

    2016-01-01

    Resting-state functional connectivity (RSFC), the temporal correlation of intrinsic activation between different brain regions, has become one of the most fascinating field in the functional imaging studies. To better understand the association between RSFC and individual creativity, we used RSFC and the figure Torrance Tests of Creative Thinking (TTCT-F) to investigate the relationship between creativity measured by TTCT and RSFC within two different brain networks, default mode network and the cognitive control network, in a large healthy sample (304). We took the medial prefrontal cortex (MPFC) and the bilateral dorsolateral prefrontal cortices (DLPFC) to be the seed regions and investigated the association across subjects between the score of TTCT-F and the strength of RSFC between these seed regions and other voxels in the whole brain. Results revealed that the strength of RSFC with the MPFC was significantly and negatively correlated with the score of TTCT-F in the precuneus. Meanwhile, we also found that the strength of RSFC with the left DLPFC was significantly and positively correlated with the score of TTCT-F in the right DLPFC. It suggests that the decreased RSFC within DMN and the increased RSFC within CCN presents a potential interaction mechanism between different region for higher creativity. PMID:27138732

  5. Genes2FANs: connecting genes through functional association networks

    Science.gov (United States)

    2012-01-01

    Background Protein-protein, cell signaling, metabolic, and transcriptional interaction networks are useful for identifying connections between lists of experimentally identified genes/proteins. However, besides physical or co-expression interactions there are many ways in which pairs of genes, or their protein products, can be associated. By systematically incorporating knowledge on shared properties of genes from diverse sources to build functional association networks (FANs), researchers may be able to identify additional functional interactions between groups of genes that are not readily apparent. Results Genes2FANs is a web based tool and a database that utilizes 14 carefully constructed FANs and a large-scale protein-protein interaction (PPI) network to build subnetworks that connect lists of human and mouse genes. The FANs are created from mammalian gene set libraries where mouse genes are converted to their human orthologs. The tool takes as input a list of human or mouse Entrez gene symbols to produce a subnetwork and a ranked list of intermediate genes that are used to connect the query input list. In addition, users can enter any PubMed search term and then the system automatically converts the returned results to gene lists using GeneRIF. This gene list is then used as input to generate a subnetwork from the user’s PubMed query. As a case study, we applied Genes2FANs to connect disease genes from 90 well-studied disorders. We find an inverse correlation between the counts of links connecting disease genes through PPI and links connecting diseases genes through FANs, separating diseases into two categories. Conclusions Genes2FANs is a useful tool for interpreting the relationships between gene/protein lists in the context of their various functions and networks. Combining functional association interactions with physical PPIs can be useful for revealing new biology and help form hypotheses for further experimentation. Our finding that disease genes in

  6. Renal function changes associated with aging and ionizing radiation

    International Nuclear Information System (INIS)

    Miller, C.W.; Norrdin, R.W.; Sawyer, S.S.; Nealeigh, R.C.

    1978-01-01

    Renal function testing of irradiated and unirradiated beagles at CRHL has been carried out for the past 7 years using a simultaneous estimation of sodium sulfanilate and sodium iodohippurate 131 I clearance. Evidence has been cited that the beagle kidney is markedly sensitive to whole-body ionizing radiation delivered in the perinatal period. The objectives of this continuing study are to determine the nature of the progression of chronic renal disease, its possible association to hypertension, the impact of unilateral nephrectomy upon an already compromised renal parenchyma, and the age-related changes in renal function. Thus far, data seem to indicate the following conclusions: sulfanilate clearance appears to be a sensitive indicator of impending renal failure, exhibiting earlier and more obvious indicators than BUN (blood urea nitrogen) levels; hypertension does not appear to be a factor in radiation-induced renal failure in the adult dogs studied here, since the average arterial blood pressure was as high in normal control dogs as in irradiated dogs suffering from renal failure; unilateral nephrectomy affected unirradiated dogs less than irradiated animals with mild renal insufficiency. The BUN levels returned to prenephrectomy levels in 8 weeks in the unirradiated group, but required up to 1 year in the dogs with renal insufficiency; and an age related decrease inrenal function was observed in a group of unirradiated dogs studied from 0 to 2 through 13 years of age

  7. Cardiac Autonomic Function Is Associated With the Coronary Microcirculatory Function in Patients With Type 2 Diabetes

    DEFF Research Database (Denmark)

    von Scholten, Bernt Johan; Hansen, Christian Stevns; Hasbak, Philip

    2016-01-01

    Cardiac autonomic dysfunction and cardiac microvascular dysfunction are diabetic complications associated with increased mortality, but the association between these has been difficult to assess. We applied new and sensitive methods to assess this in patients with type 2 diabetes mellitus (T2DM......). In a cross-sectional design, coronary flow reserve (CFR) assessed by cardiac (82)Rb-positron emission tomography/computed tomography, cardiac autonomic reflex tests, and heart rate variability indices were performed in 55 patients with T2DM, without cardiovascular disease, and in 28 control subjects. Cardiac....... A heart rate variability index, reflecting sympathetic and parasympathetic function (low-frequency power), and the late heart-to-mediastinum ratio, reflecting the function of adrenergic receptors and sympathetic activity, were positively correlated with CFR after adjustment for age and heart rate...

  8. Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function

    Science.gov (United States)

    Fuchsberger, Christian; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C.; O'Seaghdha, Conall M.; Glazer, Nicole; Isaacs, Aaron; Liu, Ching-Ti; Smith, Albert V.; O'Connell, Jeffrey R.; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Johnson, Andrew D.; Gierman, Hinco J.; Feitosa, Mary; Hwang, Shih-Jen; Atkinson, Elizabeth J.; Lohman, Kurt; Cornelis, Marilyn C.; Johansson, Åsa; Tönjes, Anke; Dehghan, Abbas; Chouraki, Vincent; Holliday, Elizabeth G.; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y.; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B.; Launer, Lenore J.; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D.; Boerwinkle, Eric; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; Hu, Frank B.; Demirkan, Ayse; Oostra, Ben A.; de Andrade, Mariza; Turner, Stephen T.; Ding, Jingzhong; Andrews, Jeanette S.; Freedman, Barry I.; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H.-Erich; Kolcic, Ivana; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E.; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H.; Wright, Alan F.; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Endlich, Karlhans; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K.; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; Aulchenko, Yurii S.; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Giulianini, Franco; Krämer, Bernhard K.; Portas, Laura; Ford, Ian; Buckley, Brendan M.; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Metzger, Marie; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K.; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J. Wouter; Probst-Hensch, Nicole M.; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Siscovick, David S.; van Duijn, Cornelia M.; Borecki, Ingrid; Kardia, Sharon L. R.; Liu, Yongmei; Curhan, Gary C.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Franke, Andre; Pramstaller, Peter P.; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline C. M.; Hayward, Caroline; Ridker, Paul; Parsa, Afshin; Bochud, Murielle; Heid, Iris M.; Goessling, Wolfram; Chasman, Daniel I.; Kao, W. H. Linda; Fox, Caroline S.

    2012-01-01

    Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD. PMID:22479191

  9. Genome-wide association and functional follow-up reveals new loci for kidney function.

    Science.gov (United States)

    Pattaro, Cristian; Köttgen, Anna; Teumer, Alexander; Garnaas, Maija; Böger, Carsten A; Fuchsberger, Christian; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; O'Seaghdha, Conall M; Glazer, Nicole; Isaacs, Aaron; Liu, Ching-Ti; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Johnson, Andrew D; Gierman, Hinco J; Feitosa, Mary; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Åsa; Tönjes, Anke; Dehghan, Abbas; Chouraki, Vincent; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; Hu, Frank B; Demirkan, Ayse; Oostra, Ben A; de Andrade, Mariza; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H-Erich; Kolcic, Ivana; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Endlich, Karlhans; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Giulianini, Franco; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Metzger, Marie; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Siscovick, David S; van Duijn, Cornelia M; Borecki, Ingrid; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline C M; Hayward, Caroline; Ridker, Paul; Parsa, Afshin; Bochud, Murielle; Heid, Iris M; Goessling, Wolfram; Chasman, Daniel I; Kao, W H Linda; Fox, Caroline S

    2012-01-01

    Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.

  10. Genome-wide association and functional follow-up reveals new loci for kidney function.

    Directory of Open Access Journals (Sweden)

    Cristian Pattaro

    Full Text Available Chronic kidney disease (CKD is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR, the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.

  11. REFLECTIVE FUNCTIONING AND PERSONALITY ORGANIZATION: ASSOCIATIONS WITH NEGATIVE MATERNAL BEHAVIORS.

    Science.gov (United States)

    Ensink, Karin; Rousseau, Marie-Eve; Biberdzic, Marko; Bégin, Michaël; Normandin, Lina

    2017-05-01

    The aim of this study was to examine whether mothers who manifest insensitive and disconnected behaviors in interaction with their infants differ in terms of maternal reflective functioning (RF), personality organization, and histories of abuse. A total of 86 mother-infant dyads, 28 of them with histories of abuse, participated in the study. RF was assessed with the Adult Attachment Interview (C. George, N. Kaplan, & M. Main, 1985), and personality organization was assessed with the self-report Inventory of Personality Organization (M.F. Lenzenweger, J.F. Clarkin, O.F. Kernberg, & P.A. Foelsh, 2001; L. Normandin et al., 2002), before the birth of the baby. Maternal behaviors were assessed using the Disconnected and Extremely Insensitive Parenting measure when the infants were 15 to 18 months old. The results of multivariate analyses of covariance indicate that both RF and personality organization were associated with disconnected and extremely insensitive maternal behaviors. Mothers classified as presenting intrusive/aggressive behaviors had significantly lower RF as well as significantly more difficulties in personality organization, including reality testing, identity, and defense mechanisms. Withdrawn and disconnected maternal behaviors were associated with the combination of difficulties in mentalization and personality organization rather than difficulties in one specific area. In sum, the study provides new evidence regarding the importance of a mentalizing stance about early attachment relationships for the modulation of maternal behaviors, especially intrusive/aggressive behaviors. © 2017 Michigan Association for Infant Mental Health.

  12. Inferring network structure from cascades

    Science.gov (United States)

    Ghonge, Sushrut; Vural, Dervis Can

    2017-07-01

    Many physical, biological, and social phenomena can be described by cascades taking place on a network. Often, the activity can be empirically observed, but not the underlying network of interactions. In this paper we offer three topological methods to infer the structure of any directed network given a set of cascade arrival times. Our formulas hold for a very general class of models where the activation probability of a node is a generic function of its degree and the number of its active neighbors. We report high success rates for synthetic and real networks, for several different cascade models.

  13. Bayesian inference for Hawkes processes

    DEFF Research Database (Denmark)

    Rasmussen, Jakob Gulddahl

    The Hawkes process is a practically and theoretically important class of point processes, but parameter-estimation for such a process can pose various problems. In this paper we explore and compare two approaches to Bayesian inference. The first approach is based on the so-called conditional...... intensity function, while the second approach is based on an underlying clustering and branching structure in the Hawkes process. For practical use, MCMC (Markov chain Monte Carlo) methods are employed. The two approaches are compared numerically using three examples of the Hawkes process....

  14. Bayesian inference for Hawkes processes

    DEFF Research Database (Denmark)

    Rasmussen, Jakob Gulddahl

    2013-01-01

    The Hawkes process is a practically and theoretically important class of point processes, but parameter-estimation for such a process can pose various problems. In this paper we explore and compare two approaches to Bayesian inference. The first approach is based on the so-called conditional...... intensity function, while the second approach is based on an underlying clustering and branching structure in the Hawkes process. For practical use, MCMC (Markov chain Monte Carlo) methods are employed. The two approaches are compared numerically using three examples of the Hawkes process....

  15. Type Inference with Inequalities

    DEFF Research Database (Denmark)

    Schwartzbach, Michael Ignatieff

    1991-01-01

    of (monotonic) inequalities on the types of variables and expressions. A general result about systems of inequalities over semilattices yields a solvable form. We distinguish between deciding typability (the existence of solutions) and type inference (the computation of a minimal solution). In our case, both......Type inference can be phrased as constraint-solving over types. We consider an implicitly typed language equipped with recursive types, multiple inheritance, 1st order parametric polymorphism, and assignments. Type correctness is expressed as satisfiability of a possibly infinite collection...

  16. Uncertainty in aiming movements and its association to hand function

    Directory of Open Access Journals (Sweden)

    Flávia Priscila de Paiva Silva

    2015-09-01

    Full Text Available AbstractThe purpose of this study was to analyze the influence of the uncertainty of target location on the planning and execution of aiming movements performed towards the ipsilateral and contralateral directions by the right and left upper limbs. In addition, the association between the performance of aiming movements and the performance of functional manual tasks was investigated. Two tasks were proposed: with prior knowledge of the movement direction (simple reaction time or not (choice reaction time. The grip strength and manual dexterity were measured. The choice option in response (i.e. uncertainty influenced planning of the aiming movements, but not its execution, while movements performed towards the contralateral direction were worse in execution as compared to the ipsilateral direction. Manual dexterity was significantly correlated with reaction times, while the performance during movement execution was significantly correlated with handgrip/pinch strength.

  17. Functional Associations by Response Overlap (FARO, a functional genomics approach matching gene expression phenotypes.

    Directory of Open Access Journals (Sweden)

    Henrik Bjørn Nielsen

    2007-08-01

    Full Text Available The systematic comparison of transcriptional responses of organisms is a powerful tool in functional genomics. For example, mutants may be characterized by comparing their transcript profiles to those obtained in other experiments querying the effects on gene expression of many experimental factors including treatments, mutations and pathogen infections. Similarly, drugs may be discovered by the relationship between the transcript profiles effectuated or impacted by a candidate drug and by the target disease. The integration of such data enables systems biology to predict the interplay between experimental factors affecting a biological system. Unfortunately, direct comparisons of gene expression profiles obtained in independent, publicly available microarray experiments are typically compromised by substantial, experiment-specific biases. Here we suggest a novel yet conceptually simple approach for deriving 'Functional Association(s by Response Overlap' (FARO between microarray gene expression studies. The transcriptional response is defined by the set of differentially expressed genes independent from the magnitude or direction of the change. This approach overcomes the limited comparability between studies that is typical for methods that rely on correlation in gene expression. We apply FARO to a compendium of 242 diverse Arabidopsis microarray experimental factors, including phyto-hormones, stresses and pathogens, growth conditions/stages, tissue types and mutants. We also use FARO to confirm and further delineate the functions of Arabidopsis MAP kinase 4 in disease and stress responses. Furthermore, we find that a large, well-defined set of genes responds in opposing directions to different stress conditions and predict the effects of different stress combinations. This demonstrates the usefulness of our approach for exploiting public microarray data to derive biologically meaningful associations between experimental factors. Finally, our

  18. Function of insulin in snail brain in associative learning.

    Science.gov (United States)

    Kojima, S; Sunada, H; Mita, K; Sakakibara, M; Lukowiak, K; Ito, E

    2015-10-01

    Insulin is well known as a hormone regulating glucose homeostasis across phyla. Although there are insulin-independent mechanisms for glucose uptake in the mammalian brain, which had contributed to a perception of the brain as an insulin-insensitive organ for decades, the finding of insulin and its receptors in the brain revolutionized the concept of insulin signaling in the brain. However, insulin's role in brain functions, such as cognition, attention, and memory, remains unknown. Studies using invertebrates with their open blood-vascular system have the promise of promoting a better understanding of the role played by insulin in mediating/modulating cognitive functions. In this review, the relationship between insulin and its impact on long-term memory (LTM) is discussed particularly in snails. The pond snail Lymnaea stagnalis has the ability to undergo conditioned taste aversion (CTA), that is, it associatively learns and forms LTM not to respond with a feeding response to a food that normally elicits a robust feeding response. We show that molluscan insulin-related peptides are up-regulated in snails exhibiting CTA-LTM and play a key role in the causal neural basis of CTA-LTM. We also survey the relevant literature of the roles played by insulin in learning and memory in other phyla.

  19. Hybrid Optical Inference Machines

    Science.gov (United States)

    1991-09-27

    with labels. Now, events. a set of facts cal be generated in the dyadic form "u, R 1,2" Eichmann and Caulfield (19] consider the same type of and can...these enceding-schemes. These architectures are-based pri- 19. G. Eichmann and H. J. Caulfield, "Optical Learning (Inference)marily on optical inner

  20. Association between aerobic fitness and cerebrovascular function with neurocognitive functions in healthy, young adults.

    Science.gov (United States)

    Hwang, Jungyun; Kim, Kiyoung; Brothers, R Matthew; Castelli, Darla M; Gonzalez-Lima, F

    2018-05-01

    Studies of the effects of physical activity on cognition suggest that aerobic fitness can improve cognitive abilities. However, the physiological mechanisms for the cognitive benefit of aerobic fitness are less well understood. We examined the association between aerobic fitness and cerebrovascular function with neurocognitive functions in healthy, young adults. Participants aged 18-29 years underwent measurements of cerebral vasomotor reactivity (CVMR) in response to rebreathing-induced hypercapnia, maximal oxygen uptake (VO 2 max) during cycle ergometry to voluntary exhaustion, and simple- and complex-neurocognitive assessments at rest. Ten subjects were identified as having low-aerobic fitness (LF aerobic fitness (HF > 80th fitness percentile). There were no LF versus HF group differences in cerebrovascular hemodynamics during the baseline condition. Changes in middle cerebral artery blood velocity and CVMR during hypercapnia were elevated more in the HF than the LF group. Compared to the LF, the HF performed better on a complex-cognitive task assessing fluid reasoning, but not on simple attentional abilities. Statistical modeling showed that measures of VO 2 max, CVMR, and fluid reasoning were positively inter-correlated. The relationship between VO 2 max and fluid reasoning, however, did not appear to be reliably mediated by CVMR. In conclusion, a high capacity for maximal oxygen uptake among healthy, young adults was associated with greater CVMR and better fluid reasoning, implying that high-aerobic fitness may promote cerebrovascular and cognitive functioning abilities.

  1. Multiple loci associated with renal function in African Americans.

    Directory of Open Access Journals (Sweden)

    Daniel Shriner

    Full Text Available The incidence of chronic kidney disease varies by ethnic group in the USA, with African Americans displaying a two-fold higher rate than European Americans. One of the two defining variables underlying staging of chronic kidney disease is the glomerular filtration rate. Meta-analysis in individuals of European ancestry has identified 23 genetic loci associated with the estimated glomerular filtration rate (eGFR. We conducted a follow-up study of these 23 genetic loci using a population-based sample of 1,018 unrelated admixed African Americans. We included in our follow-up study two variants in APOL1 associated with end-stage kidney disease discovered by admixture mapping in admixed African Americans. To address confounding due to admixture, we estimated local ancestry at each marker and global ancestry. We performed regression analysis stratified by local ancestry and combined the resulting regression estimates across ancestry strata using an inverse variance-weighted fixed effects model. We found that 11 of the 24 loci were significantly associated with eGFR in our sample. The effect size estimates were not significantly different between the subgroups of individuals with two copies of African ancestry vs. two copies of European ancestry for any of the 11 loci. In contrast, allele frequencies were significantly different at 10 of the 11 loci. Collectively, the 11 loci, including four secondary signals revealed by conditional analyses, explained 14.2% of the phenotypic variance in eGFR, in contrast to the 1.4% explained by the 24 loci in individuals of European ancestry. Our findings provide insight into the genetic basis of variation in renal function among admixed African Americans.

  2. Association Between Functional Dyspepsia And Severity Of Depression

    International Nuclear Information System (INIS)

    Jamil, O.; Sarwar, S.; Hussain, Z.; Fiaz, R. O.; Chaudary, R. D.

    2016-01-01

    Objective: To determine the association between functional dyspepsia and the severity of depression. Study Design: Cross-sectional study. Place and Duration of Study: Department of Medicine, King Edward Medical University/Mayo Hospital, Lahore, from September 2012 till January 2013. Methodology: After taking informed written consent, patients with symptoms of dyspepsia fulfilling the Rome III criteria were included in the study. All patients were evaluated for depression, using Hamilton depression rating scale (HDRS). Upper gastrointestinal endoscopy was done. Fischers' exact test and independent t-test were used for determining significance of association. Result: One hundred and one patients with mean age of 35.81 14.81) years and male to female ratio of 1.41:1 (54/47) were included. Predominant symptoms were early satiety (72.3 percentage), epigastric pain (65.3 percentage), bloating (49.5 percentage), postprandial fullness (40.6 percentage), and regurgitation (40.6 percentage). Alarm symptoms were positive in 44 (43.6 percentage) patients. Dyspepsia were classified as epigastric pain syndrome (EPS, 69.3 percentage), and postprandial distress syndrome (PDS, 30.7 percentage). Significantly more females had PDS (p=0.04), with positive endoscopic findings in EPS (p=0.03). Positive endoscopic findings noted were esophagitis in 21.8 percentage, and gastritis in 48.5 percentage patients. All patients except one had depression, mild in 22.8 percentage, moderate in 33.7 percentage, severe in 31.7 percentage, and very severe in 10.9 percentage patients. Severe depression was seen in 32 (45.7 percentage) patients with EPS and PDS; whereas very severe depression was in 11 (15.7 percentage) patients of EPS, while 11 (35.4 percentage) patients of PDS had severe depression but the difference was not significant. Conclusion: Functional dyspepsia is associated with depression, while positive endoscopic findings are more likely in patients with EPS. Very severe depression

  3. Bariatric surgery is associated with renal function improvement.

    Science.gov (United States)

    Holcomb, Carla N; Goss, Lauren E; Almehmi, Ammar; Grams, Jayleen M; Corey, Britney L

    2018-01-01

    Weight loss after bariatric surgery improves both blood pressure and glycemic control following surgery. The effect of bariatric surgery on renal function is not well characterized. In this study, we sought to quantify the change in renal function over time following surgery. We retrospectively reviewed all patients who underwent laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) between 2012 and 2014 at our institution. The glomerular filtration rate (GFR, mL/min) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Body mass index (BMI, kg/m 2 ) and percent weight loss (%WL) were calculated following the surgery. A total of 149 patients who underwent bariatric surgery were included in this study: LRYGB (n = 86 and LSG (n = 63). In LRYGB group, baseline BMI (kg/m 2 , ±SD) and GFR (mL/min, ±SD) were 48.5 ± 6.8 and 94.7 ± 23.8, respectively. In comparison, BMI and GFR were 49.1 ± 11.9 kg/m 2 and 93.1 ± 28.0 mL/min in the LSG group, respectively. Over the follow-up period (19.89 ± 10.93 months), the patients who underwent LRGYB lost a larger percentage of weight as compared to those in the LSG group (29.9 ± 11.7% vs 22.3 ± 10.7%; p = weight loss surgery (n = 62), 42% had improvement of their GFR to > 90 mL/min postoperatively (p weight loss percentage and GFR improvement (p = 0.8703). Bariatric surgery was associated with improvement in postoperative renal function at almost two years following surgery but was not different for LRYGB versus LSG. The gain in GFR was independent of percentage of weight lost suggesting an alternate mechanism in the improvement of renal function other than weight loss alone.

  4. Probabilistic Inference of Biological Networks via Data Integration

    Directory of Open Access Journals (Sweden)

    Mark F. Rogers

    2015-01-01

    Full Text Available There is significant interest in inferring the structure of subcellular networks of interaction. Here we consider supervised interactive network inference in which a reference set of known network links and nonlinks is used to train a classifier for predicting new links. Many types of data are relevant to inferring functional links between genes, motivating the use of data integration. We use pairwise kernels to predict novel links, along with multiple kernel learning to integrate distinct sources of data into a decision function. We evaluate various pairwise kernels to establish which are most informative and compare individual kernel accuracies with accuracies for weighted combinations. By associating a probability measure with classifier predictions, we enable cautious classification, which can increase accuracy by restricting predictions to high-confidence instances, and data cleaning that can mitigate the influence of mislabeled training instances. Although one pairwise kernel (the tensor product pairwise kernel appears to work best, different kernels may contribute complimentary information about interactions: experiments in S. cerevisiae (yeast reveal that a weighted combination of pairwise kernels applied to different types of data yields the highest predictive accuracy. Combined with cautious classification and data cleaning, we can achieve predictive accuracies of up to 99.6%.

  5. Polynomial Chaos Surrogates for Bayesian Inference

    KAUST Repository

    Le Maitre, Olivier

    2016-01-06

    The Bayesian inference is a popular probabilistic method to solve inverse problems, such as the identification of field parameter in a PDE model. The inference rely on the Bayes rule to update the prior density of the sought field, from observations, and derive its posterior distribution. In most cases the posterior distribution has no explicit form and has to be sampled, for instance using a Markov-Chain Monte Carlo method. In practice the prior field parameter is decomposed and truncated (e.g. by means of Karhunen- Lo´eve decomposition) to recast the inference problem into the inference of a finite number of coordinates. Although proved effective in many situations, the Bayesian inference as sketched above faces several difficulties requiring improvements. First, sampling the posterior can be a extremely costly task as it requires multiple resolutions of the PDE model for different values of the field parameter. Second, when the observations are not very much informative, the inferred parameter field can highly depends on its prior which can be somehow arbitrary. These issues have motivated the introduction of reduced modeling or surrogates for the (approximate) determination of the parametrized PDE solution and hyperparameters in the description of the prior field. Our contribution focuses on recent developments in these two directions: the acceleration of the posterior sampling by means of Polynomial Chaos expansions and the efficient treatment of parametrized covariance functions for the prior field. We also discuss the possibility of making such approach adaptive to further improve its efficiency.

  6. Funções psicofísicas para área percebida, inferida e relembrada: o efeito da idade Psychophysics functions for perceptive, inference, and memory area: the effect of age

    Directory of Open Access Journals (Sweden)

    Paula Mariza Zedu Alliprandini

    2000-01-01

    Full Text Available O objetivo deste trabalho foi verificar o efeito da idade no expoente da função-potência nas Condições experimentais Perceptiva, Memória e Inferência. Para cada Condição, as faixas etárias dos sujeitos variaram de 17 a 34 anos (I, 38 a 57 anos (II e 58 a 77 anos de idade (III. Os sujeitos estimaram áreas dos Estados do Brasil, utilizando o método psicofísico de estimação de magnitude. Os resultados obtidos pelas três Faixas etárias não diferiram para cada Condição experimental, com exceção da Condição Memória (24 horas. A análise entre as Condições experimentais e Faixas etárias evidenciou uma diferença da Condição Perceptiva em relação às demais, não havendo diferenças entre as Condições Memória e Inferência. Os dados apresentados sugerem que no processo de relembrar, não há perda da informação em função da idade.The purpose of the present work was to verify the effect of age on the exponent of power function in a Perceptive, Memory, and Inference experimental conditions. The age levels were: 17-34 years (I, 38-57 years (II and 58-77 years (III. The observers estimated areas of Brazilian States using the psychophysic method of magnitude estimates. No significant differences were obtained among age levels for each experimental condition, except in the 24 hours-memory condition. The analysis among experimental conditions and ages showed a significant difference of Perceptual Conditions in comparison with the others. No significant difference between the Inference and Memory Conditions was found. The results indicated no loss of information due to age.

  7. Inference of R 0 and Transmission Heterogeneity from the Size Distribution of Stuttering Chains

    Science.gov (United States)

    Blumberg, Seth; Lloyd-Smith, James O.

    2013-01-01

    For many infectious disease processes such as emerging zoonoses and vaccine-preventable diseases, and infections occur as self-limited stuttering transmission chains. A mechanistic understanding of transmission is essential for characterizing the risk of emerging diseases and monitoring spatio-temporal dynamics. Thus methods for inferring and the degree of heterogeneity in transmission from stuttering chain data have important applications in disease surveillance and management. Previous researchers have used chain size distributions to infer , but estimation of the degree of individual-level variation in infectiousness (as quantified by the dispersion parameter, ) has typically required contact tracing data. Utilizing branching process theory along with a negative binomial offspring distribution, we demonstrate how maximum likelihood estimation can be applied to chain size data to infer both and the dispersion parameter that characterizes heterogeneity. While the maximum likelihood value for is a simple function of the average chain size, the associated confidence intervals are dependent on the inferred degree of transmission heterogeneity. As demonstrated for monkeypox data from the Democratic Republic of Congo, this impacts when a statistically significant change in is detectable. In addition, by allowing for superspreading events, inference of shifts the threshold above which a transmission chain should be considered anomalously large for a given value of (thus reducing the probability of false alarms about pathogen adaptation). Our analysis of monkeypox also clarifies the various ways that imperfect observation can impact inference of transmission parameters, and highlights the need to quantitatively evaluate whether observation is likely to significantly bias results. PMID:23658504

  8. Leveraging Comparative Genomics to Identify and Functionally Characterize Genes Associated with Sperm Phenotypes in Python bivittatus (Burmese Python

    Directory of Open Access Journals (Sweden)

    Kristopher J. L. Irizarry

    2016-01-01

    Full Text Available Comparative genomics approaches provide a means of leveraging functional genomics information from a highly annotated model organism’s genome (such as the mouse genome in order to make physiological inferences about the role of genes and proteins in a less characterized organism’s genome (such as the Burmese python. We employed a comparative genomics approach to produce the functional annotation of Python bivittatus genes encoding proteins associated with sperm phenotypes. We identify 129 gene-phenotype relationships in the python which are implicated in 10 specific sperm phenotypes. Results obtained through our systematic analysis identified subsets of python genes exhibiting associations with gene ontology annotation terms. Functional annotation data was represented in a semantic scatter plot. Together, these newly annotated Python bivittatus genome resources provide a high resolution framework from which the biology relating to reptile spermatogenesis, fertility, and reproduction can be further investigated. Applications of our research include (1 production of genetic diagnostics for assessing fertility in domestic and wild reptiles; (2 enhanced assisted reproduction technology for endangered and captive reptiles; and (3 novel molecular targets for biotechnology-based approaches aimed at reducing fertility and reproduction of invasive reptiles. Additional enhancements to reptile genomic resources will further enhance their value.

  9. Moonlighting microtubule-associated proteins: regulatory functions by day and pathological functions at night.

    Science.gov (United States)

    Oláh, J; Tőkési, N; Lehotzky, A; Orosz, F; Ovádi, J

    2013-11-01

    The sensing, integrating, and coordinating features of the eukaryotic cells are achieved by the complex ultrastructural arrays and multifarious functions of the cytoskeletal network. Cytoskeleton comprises fibrous protein networks of microtubules, actin, and intermediate filaments. These filamentous polymer structures are highly dynamic and undergo constant and rapid reorganization during cellular processes. The microtubular system plays a crucial role in the brain, as it is involved in an enormous number of cellular events including cell differentiation and pathological inclusion formation. These multifarious functions of microtubules can be achieved by their decoration with proteins/enzymes that exert specific effects on the dynamics and organization of the cytoskeleton and mediate distinct functions due to their moonlighting features. This mini-review focuses on two aspects of the microtubule cytoskeleton. On the one hand, we describe the heteroassociation of tubulin/microtubules with metabolic enzymes, which in addition to their catalytic activities stabilize microtubule structures via their cross-linking functions. On the other hand, we focus on the recently identified moonlighting tubulin polymerization promoting protein, TPPP/p25. TPPP/p25 is a microtubule-associated protein and it displays distinct physiological or pathological (aberrant) functions; thus it is a prototype of Neomorphic Moonlighting Proteins. The expression of TPPP/p25 is finely controlled in the human brain; this protein is indispensable for the development of projections of oligodendrocytes that are responsible for the ensheathment of axons. The nonphysiological, higher or lower TPPP/p25 level leads to distinct CNS diseases. Mechanisms contributing to the control of microtubule stability and dynamics by metabolic enzymes and TPPP/p25 will be discussed. Copyright © 2013 Wiley Periodicals, Inc.

  10. Hypoandrogenism in association with diminished functional ovarian reserve.

    Science.gov (United States)

    Gleicher, Norbert; Kim, Ann; Weghofer, Andrea; Kushnir, Vitaly A; Shohat-Tal, Aya; Lazzaroni, Emanuela; Lee, Ho-Joon; Barad, David H

    2013-04-01

    Is diminished functional ovarian reserve (DFOR) associated with low androgen levels? Low androgen levels are associated with DFOR at all ages. Androgen supplementation via dehydroepiandrosterone (DHEA) has been reported to improve functional ovarian reserve (FOR); pregnancy rates in IVF cycles are associated with how well DHEA converts to testosterone (T); and androgen effects through the androgen receptor have been demonstrated in mice to beneficially affect early stages of follicle maturation. In a controlled cohort study we investigated consecutive women presenting to our center with two forms of DFOR, premature ovarian aging/occult primary ovarian insufficiency (POA/OPOI) and physiologic diminished ovarian reserve (DOR). As controls for POA/OPOI patients, infertile women with normal age-specific FOR were recruited. The study involved 140 women with POA/OPOI, defined as age women with DOR, defined as women age >40 years. Forty-nine control patients women early morning cortisol levels were also assessed. DHEAS marginally varied between the three groups (P = 0.04), with older women with DOR actually demonstrating higher levels than controls (P = 0.03). TT differed between the three groups more profoundly (P = 0.005), with women with POA/OPOI demonstrating significantly lower levels than controls (P = 0.009). Adjustment for body mass index, age and race in principle maintained observed differences in TT between groups, while adjustment for FMR1 (fragile X mental retardation 1) genotypes/sub-genotypes eliminated all differences. All three patient groups demonstrated low morning cortisol levels. While results support lower androgen levels in women with DOR, and even more so in women with POA/OPOI, presented data should be viewed as preliminary, considering the known variability of androgen levels and the small number of women in whom morning cortisol levels were available. Especially at young ages DFOR appears associated with significant hypoandrogenism (low T) in

  11. Skin-associated lymphoid tissues (SALT): origins and functions

    International Nuclear Information System (INIS)

    Streilein, J.W.

    1983-01-01

    The skin has an unusual set of immunologic requirements. It is confronted by a specialized set of pathogenic organisms and environmental chemicals that represent a distinctive spectrum of antigenic specificities. Skin is subjected to physicochemical stresses such as irradiation with ultraviolet light that alter dramatically its immunologic properties. It is proposed that nature has provided skin with a unique collection of lymphoid cells, reticular cells, and organized lymphoid organs to deal with these special demands. Evidence in favor of the existence of skin-associated lymphoid tissues (SALT) includes (1) the cutaneous microenvironment is capable on its own of accepting, processing, and presenting nominal antigen; (2) strategically located peripheral lymph nodes are able to accept immunogenic signals derived from skin; (3) subsets of T lymphocytes display differential affinity for skin and its associated peripheral nodes; and (4) acquisition of this affinity by T cells is determined at least in part by differentiation signals received in situ from resident cutaneous cells. Responsibility for the establishment and integration of SALT rests with keratinocytes, Langerhans cells, and immunocompetent lymphocytes, each of which contributes uniquely to the synthesis. Together they provide skin with immune surveillance that effectively prejudices against the development of cutaneous neoplasms and persistent infection with intracellular pathogens. In patients who have been under long-term immunosuppressive therapy, the large majority of nonlymphoid malignancies arise within the skin, rather than other types of tissues. These data suggest that immune surveillance, once thought to be an immune defense operative in all somatic tissues, is a specialized immune function dedicated to the skin and mediated by SALT

  12. Stochastic processes inference theory

    CERN Document Server

    Rao, Malempati M

    2014-01-01

    This is the revised and enlarged 2nd edition of the authors’ original text, which was intended to be a modest complement to Grenander's fundamental memoir on stochastic processes and related inference theory. The present volume gives a substantial account of regression analysis, both for stochastic processes and measures, and includes recent material on Ridge regression with some unexpected applications, for example in econometrics. The first three chapters can be used for a quarter or semester graduate course on inference on stochastic processes. The remaining chapters provide more advanced material on stochastic analysis suitable for graduate seminars and discussions, leading to dissertation or research work. In general, the book will be of interest to researchers in probability theory, mathematical statistics and electrical and information theory.

  13. Making Type Inference Practical

    DEFF Research Database (Denmark)

    Schwartzbach, Michael Ignatieff; Oxhøj, Nicholas; Palsberg, Jens

    1992-01-01

    We present the implementation of a type inference algorithm for untyped object-oriented programs with inheritance, assignments, and late binding. The algorithm significantly improves our previous one, presented at OOPSLA'91, since it can handle collection classes, such as List, in a useful way. Abo......, the complexity has been dramatically improved, from exponential time to low polynomial time. The implementation uses the techniques of incremental graph construction and constraint template instantiation to avoid representing intermediate results, doing superfluous work, and recomputing type information....... Experiments indicate that the implementation type checks as much as 100 lines pr. second. This results in a mature product, on which a number of tools can be based, for example a safety tool, an image compression tool, a code optimization tool, and an annotation tool. This may make type inference for object...

  14. Russell and Humean Inferences

    Directory of Open Access Journals (Sweden)

    João Paulo Monteiro

    2001-12-01

    Full Text Available Russell's The Problems of Philosophy tries to establish a new theory of induction, at the same time that Hume is there accused of an irrational/ scepticism about induction". But a careful analysis of the theory of knowledge explicitly acknowledged by Hume reveals that, contrary to the standard interpretation in the XXth century, possibly influenced by Russell, Hume deals exclusively with causal inference (which he never classifies as "causal induction", although now we are entitled to do so, never with inductive inference in general, mainly generalizations about sensible qualities of objects ( whether, e.g., "all crows are black" or not is not among Hume's concerns. Russell's theories are thus only false alternatives to Hume's, in (1912 or in his (1948.

  15. Causal inference in econometrics

    CERN Document Server

    Kreinovich, Vladik; Sriboonchitta, Songsak

    2016-01-01

    This book is devoted to the analysis of causal inference which is one of the most difficult tasks in data analysis: when two phenomena are observed to be related, it is often difficult to decide whether one of them causally influences the other one, or whether these two phenomena have a common cause. This analysis is the main focus of this volume. To get a good understanding of the causal inference, it is important to have models of economic phenomena which are as accurate as possible. Because of this need, this volume also contains papers that use non-traditional economic models, such as fuzzy models and models obtained by using neural networks and data mining techniques. It also contains papers that apply different econometric models to analyze real-life economic dependencies.

  16. Thick Filament Protein Network, Functions, and Disease Association.

    Science.gov (United States)

    Wang, Li; Geist, Janelle; Grogan, Alyssa; Hu, Li-Yen R; Kontrogianni-Konstantopoulos, Aikaterini

    2018-03-13

    Sarcomeres consist of highly ordered arrays of thick myosin and thin actin filaments along with accessory proteins. Thick filaments occupy the center of sarcomeres where they partially overlap with thin filaments. The sliding of thick filaments past thin filaments is a highly regulated process that occurs in an ATP-dependent manner driving muscle contraction. In addition to myosin that makes up the backbone of the thick filament, four other proteins which are intimately bound to the thick filament, myosin binding protein-C, titin, myomesin, and obscurin play important structural and regulatory roles. Consistent with this, mutations in the respective genes have been associated with idiopathic and congenital forms of skeletal and cardiac myopathies. In this review, we aim to summarize our current knowledge on the molecular structure, subcellular localization, interacting partners, function, modulation via posttranslational modifications, and disease involvement of these five major proteins that comprise the thick filament of striated muscle cells. © 2018 American Physiological Society. Compr Physiol 8:631-709, 2018. Copyright © 2018 American Physiological Society. All rights reserved.

  17. Is executive cognitive function associated with youth gambling?

    Science.gov (United States)

    Betancourt, Laura M; Brodsky, Nancy L; Brown, Caitlin A; McKenna, Kathleen A; Giannetta, Joan M; Yang, Wei; Romer, Daniel; Hurt, Hallam

    2012-06-01

    Our objectives for this report were to identify trajectories of youth gambling behavior, and to examine their relation to executive cognitive function (ECF) and associated problem behaviors. Philadelphia school children, enrolled at ages 10-12 years (n = 387; 49% male), completed three annual assessments of risk behaviors, ECF, impulsivity, problem behaviors and demographics. Across ages 10-15 years, using methods from Nagin et al., two groups were identified: Early Gamblers (n = 111) initiated early and continued in later assessments, and Later Gamblers (n = 276) initiated at later ages and gambled less. Betting money on cards and sports were the most frequently reported gambling behaviors. Using gambling group as outcome, final backward selection logistic regression model showed Early Gamblers are more likely male (P = 0.001), report more active coping (P = 0.042), impulsive behaviors (P ≤ 0.008), and have friends who gamble (P = 0.001). Groups were similar in ECF, parental monitoring, marital status, SES, and race. Early Gamblers had higher incidence of problem behaviors and drug use (all P ≤ 0.006). Two gambling groups were identified in early adolescence with Early Gamblers showing higher levels of impulsivity and comorbid problems but similar levels of ECF compared to Late Gamblers. As more gambling groups are identified through later adolescence, ECF may emerge as a relevant precursor of problem gambling at this later time.

  18. New Bessel-type function associated with SU(3) representation

    International Nuclear Information System (INIS)

    Tanimura, N.; Tanimura, O.

    1990-01-01

    A new set of functions that are given by the coefficients of the character expansion of the single-link action in the SU(3) lattice-gauge theory is studied. The function is specified by the indices λ and μ of the SU(3) representation of the Young tableau. From the Schwinger-Dyson variational method the recursion relations among the functions are derived. By combining the recursion relation and the relation of the differentiation, the linear differential equation of the sixth order for the function is derived. The properties of the function are discussed in detail in comparison with the functions in the SU(2) group

  19. Loss-of-Function FANCL Mutations Associate with Severe Fanconi Anemia Overlapping the VACTERL Association.

    Science.gov (United States)

    Vetro, Annalisa; Iascone, Maria; Limongelli, Ivan; Ameziane, Najim; Gana, Simone; Della Mina, Erika; Giussani, Ursula; Ciccone, Roberto; Forlino, Antonella; Pezzoli, Laura; Rooimans, Martin A; van Essen, Antoni J; Messa, Jole; Rizzuti, Tommaso; Bianchi, Paolo; Dorsman, Josephine; de Winter, Johan P; Lalatta, Faustina; Zuffardi, Orsetta

    2015-05-01

    The diagnosis of VACTERL syndrome can be elusive, especially in the prenatal life, due to the presence of malformations that overlap those present in other genetic conditions, including the Fanconi anemia (FA). We report on three VACTERL cases within two families, where the two who arrived to be born died shortly after birth due to severe organs' malformations. The suspicion of VACTERL association was based on prenatal ultrasound assessment and postnatal features. Subsequent chromosome breakage analysis suggested the diagnosis of FA. Finally, by next-generation sequencing based on the analysis of the exome in one family and of a panel of Fanconi genes in the second one, we identified novel FANCL truncating mutations in both families. We used ectopic expression of wild-type FANCL to functionally correct the cellular FA phenotype for both mutations. Our study emphasizes that the diagnosis of FA should be considered when VACTERL association is suspected. Furthermore, we show that loss-of-function mutations in FANCL result in a severe clinical phenotype characterized by early postnatal death. © 2015 WILEY PERIODICALS, INC.

  20. Causal inference in public health.

    Science.gov (United States)

    Glass, Thomas A; Goodman, Steven N; Hernán, Miguel A; Samet, Jonathan M

    2013-01-01

    Causal inference has a central role in public health; the determination that an association is causal indicates the possibility for intervention. We review and comment on the long-used guidelines for interpreting evidence as supporting a causal association and contrast them with the potential outcomes framework that encourages thinking in terms of causes that are interventions. We argue that in public health this framework is more suitable, providing an estimate of an action's consequences rather than the less precise notion of a risk factor's causal effect. A variety of modern statistical methods adopt this approach. When an intervention cannot be specified, causal relations can still exist, but how to intervene to change the outcome will be unclear. In application, the often-complex structure of causal processes needs to be acknowledged and appropriate data collected to study them. These newer approaches need to be brought to bear on the increasingly complex public health challenges of our globalized world.

  1. Association between preterm labour and pelvic floor muscle function.

    Science.gov (United States)

    Aran, Turhan; Pekgöz, Ipek; Bozkaya, Hasan; Osmanagaoglu, Mehmet A

    2018-03-23

    We hypothesised that the pressure on the cervix increases with advancing gestation and it may lead to a cervical shortening and cause preterm labour in women with weak pelvic floor muscles. The aim of this prospective study was to measure vaginal resting pressure and pelvic floor muscle strength in the first trimester of pregnancy and to investigate their effects on labour. A study was conducted on the pregnant women with a low risk for preterm birth. The pelvic floor muscle strength and vaginal resting pressure were assessed in 320 pregnant women at their first trimester with a vaginal pressure measurement device. Fifty-two pregnant women were hospitalised for tocolytic therapy because of spontaneous preterm labour. Thirty-two of them (10.2%) had a preterm delivery despite the tocolytic therapy. Both the vaginal resting pressure (p = .009, 95%CI: 0.8; 5.9) and the pelvic floor muscle strength (p = .01, 95%CI: 3.5; 13.1) were significantly lower in the women with a preterm labour. Impact statement What is already known on this subject? The pelvic floor muscles have an essential role in continence and provide support to the pelvic organs. They also have an impact on labour. The pelvic floor muscles should distend to allow the passage of the foetus during labour. The rotation and flexion of the foetal head is due to the pelvic floor resistance. The effect of a vaginal birth on the pelvic floor's function is readily understood. On the other hand, the effect of the pelvic floor muscle function on labour is still controversial. What do the results of this study add? This prospective study showed that there is a negative association between the pelvic floor muscle strength and preterm labour. This is the first clinical study indicating that weak pelvic floor muscles may cause a preterm labour. What are the implications of these findings for clinical practice and/or further research? Pelvic floor physical therapy may be an alternative preventive strategy to reduce

  2. Multimodel inference and adaptive management

    Science.gov (United States)

    Rehme, S.E.; Powell, L.A.; Allen, Craig R.

    2011-01-01

    Ecology is an inherently complex science coping with correlated variables, nonlinear interactions and multiple scales of pattern and process, making it difficult for experiments to result in clear, strong inference. Natural resource managers, policy makers, and stakeholders rely on science to provide timely and accurate management recommendations. However, the time necessary to untangle the complexities of interactions within ecosystems is often far greater than the time available to make management decisions. One method of coping with this problem is multimodel inference. Multimodel inference assesses uncertainty by calculating likelihoods among multiple competing hypotheses, but multimodel inference results are often equivocal. Despite this, there may be pressure for ecologists to provide management recommendations regardless of the strength of their study’s inference. We reviewed papers in the Journal of Wildlife Management (JWM) and the journal Conservation Biology (CB) to quantify the prevalence of multimodel inference approaches, the resulting inference (weak versus strong), and how authors dealt with the uncertainty. Thirty-eight percent and 14%, respectively, of articles in the JWM and CB used multimodel inference approaches. Strong inference was rarely observed, with only 7% of JWM and 20% of CB articles resulting in strong inference. We found the majority of weak inference papers in both journals (59%) gave specific management recommendations. Model selection uncertainty was ignored in most recommendations for management. We suggest that adaptive management is an ideal method to resolve uncertainty when research results in weak inference.

  3. No direct association among respiratory function, disease control and family functioning in a sample of Mexican children with intermittent asthma.

    Science.gov (United States)

    Rodriguez-Orozco, Alain Raimundo; Núñez-Tapia, Rosa María; Ramírez-Silva, Armando; Gómez-Alonso, Carlos

    2013-05-15

    Asthma has been linked to family disfunctioning and poor control of the disease.This study was conducted to analyze the interactions between the level of intermittent asthma control, family functioning and respiratory function and between quality of life of asthmatic patients and their caregivers.7 to 15 years old children with intermittent asthma were included. Asthma Control Test Questionnaire, Pediatric Asthma Quality of Life Questionnaire (PAQLQ) test, and flowmetry were applied to children and Pediatric Asthma Caregiver´s Quatily of Life Questionnaire (PAQCLQ) and the Family Functioning Perception Test (FF-SIL) were applied to their parents.The most affected areas of family functioning in dysfunctional families were adaptability and permeability. A medium to high strength of association was founded between the emotional function of parents and the emotional function of children, R2=0.552. The most remarkable associations were among parents' limitation of activities and parents' emotional function (r=0.837), parents' limitation of activities and child's emotional function (r=0.722), parents' emotional role and limitation of activities (r=0.837), parents' emotional role and emotional functioning of children with asthma (r=0.743) and the limitation of activities of children with asthma and the emotional function of children with asthma (r=0.870).No direct associations were founded among respiratory function, disease control and family functioning in Mexican children with intermittent asthma and emotional function of parents and children were associated in both groups.

  4. Cortical information flow during inferences of agency

    NARCIS (Netherlands)

    Dogge, Myrthel; Hofman, Dennis; Boersma, Maria; Dijkerman, H Chris; Aarts, Henk

    2014-01-01

    Building on the recent finding that agency experiences do not merely rely on sensorimotor information but also on cognitive cues, this exploratory study uses electroencephalographic recordings to examine functional connectivity during agency inference processing in a setting where action and outcome

  5. In search of functional association from time-series microarray data based on the change trend and level of gene expression

    Directory of Open Access Journals (Sweden)

    Zeng An-Ping

    2006-02-01

    interactions, including 443 known protein interactions and some known cell cycle related regulatory interactions. It should be emphasized that the overlapping of gene pairs detected by the three methods is normally not very high, indicating a necessity of combining the different methods in search of functional association of genes from time-series data. For a p-value threshold of 1E-5 the percentage of process-identity and function-similarity gene pairs among the shared part of the three methods reaches 60.2% and 55.6% respectively, building a good basis for further experimental and functional study. Furthermore, the combined use of methods is important to infer more complete regulatory circuits and network as exemplified in this study. Conclusion The TC method can significantly augment the current major methods to infer functional linkages and biological network and is well suitable for exploring temporal relationships of gene expression in time-series data.

  6. A formal model of interpersonal inference

    Directory of Open Access Journals (Sweden)

    Michael eMoutoussis

    2014-03-01

    Full Text Available Introduction: We propose that active Bayesian inference – a general framework for decision-making – can equally be applied to interpersonal exchanges. Social cognition, however, entails special challenges. We address these challenges through a novel formulation of a formal model and demonstrate its psychological significance. Method: We review relevant literature, especially with regards to interpersonal representations, formulate a mathematical model and present a simulation study. The model accommodates normative models from utility theory and places them within the broader setting of Bayesian inference. Crucially, we endow people's prior beliefs, into which utilities are absorbed, with preferences of self and others. The simulation illustrates the model's dynamics and furnishes elementary predictions of the theory. Results: 1. Because beliefs about self and others inform both the desirability and plausibility of outcomes, in this framework interpersonal representations become beliefs that have to be actively inferred. This inference, akin to 'mentalising' in the psychological literature, is based upon the outcomes of interpersonal exchanges. 2. We show how some well-known social-psychological phenomena (e.g. self-serving biases can be explained in terms of active interpersonal inference. 3. Mentalising naturally entails Bayesian updating of how people value social outcomes. Crucially this includes inference about one’s own qualities and preferences. Conclusion: We inaugurate a Bayes optimal framework for modelling intersubject variability in mentalising during interpersonal exchanges. Here, interpersonal representations are endowed with explicit functional and affective properties. We suggest the active inference framework lends itself to the study of psychiatric conditions where mentalising is distorted.

  7. Association between tobacco smoking and cognitive functioning in young adults

    DEFF Research Database (Denmark)

    Chamberlain, Samuel R; Odlaug, Brian Lawrence; Schreiber, Liana R N

    2012-01-01

    Tobacco smoking represents a considerable public health burden globally. Smoking in older adults is associated with cognitive impairment and more rapid age-associated cognitive decline, but there is a paucity of studies in younger people.......Tobacco smoking represents a considerable public health burden globally. Smoking in older adults is associated with cognitive impairment and more rapid age-associated cognitive decline, but there is a paucity of studies in younger people....

  8. Inference on carbon atom arrangement in the turbostatic graphene layers in Tikak coal (India) by X-ray pair distribution function analysis

    Energy Technology Data Exchange (ETDEWEB)

    Saikia, Binoy K. [Indian Oil Corporation Ltd., West Bengal (India)

    2010-07-01

    This paper communicates the distribution of carbon atoms in a single poly-cyclic aromatic (PCA) layer (graphene) in Tikak coal from Assam, India. The pair distribution function (PDF) analysis performed indicates no evidence of any graphite like structure in this coal. The aromatic fraction is observed to be 74%; with the aliphatic fraction correspondingly estimated to be 26% in this coal. The average carbon atom has 2.5 nearest carbon atom neighbours at an average bond distance of 1.50{angstrom}. The average stacking height of the parallel aromatic layers (Lc) and the average diameter of the aromatic layers (La) are estimated to be 9.86 {angstrom} and 4.80 {angstrom} respectively. For this coal, the average number of stacking layers and the average number of atoms per layer are estimated to be four and eight respectively. In addition, the gamma band is observed at a d-value of 4.34{angstrom}. The comparison of the atom-pair correlation function to simulated one-dimensional structure function calculated for a model compound benzene (C{sub 6}H{sub 6}) also indicates that C{sub 6} unit is the major components in this coal. The average carbon atom has at least one and one nearest aryl and alkyl C-C atom pairs separated by 1.39 and 1.54{angstrom} respectively.

  9. Nonparametric statistical inference

    CERN Document Server

    Gibbons, Jean Dickinson

    2010-01-01

    Overall, this remains a very fine book suitable for a graduate-level course in nonparametric statistics. I recommend it for all people interested in learning the basic ideas of nonparametric statistical inference.-Eugenia Stoimenova, Journal of Applied Statistics, June 2012… one of the best books available for a graduate (or advanced undergraduate) text for a theory course on nonparametric statistics. … a very well-written and organized book on nonparametric statistics, especially useful and recommended for teachers and graduate students.-Biometrics, 67, September 2011This excellently presente

  10. Emotional inferences by pragmatics

    OpenAIRE

    Iza-Miqueleiz, Mauricio

    2017-01-01

    It has for long been taken for granted that, along the course of reading a text, world knowledge is often required in order to establish coherent links between sentences (McKoon & Ratcliff 1992, Iza & Ezquerro 2000). The content grasped from a text turns out to be strongly dependent upon the reader’s additional knowledge that allows a coherent interpretation of the text as a whole. The world knowledge directing the inference may be of distinctive nature. Gygax et al. (2007) showed that m...

  11. Generic patch inference

    DEFF Research Database (Denmark)

    Andersen, Jesper; Lawall, Julia

    2010-01-01

    A key issue in maintaining Linux device drivers is the need to keep them up to date with respect to evolutions in Linux internal libraries. Currently, there is little tool support for performing and documenting such changes. In this paper we present a tool, spdiff, that identifies common changes...... developers can use it to extract an abstract representation of the set of changes that others have made. Our experiments on recent changes in Linux show that the inferred generic patches are more concise than the corresponding patches found in commits to the Linux source tree while being safe with respect...

  12. Statistical inference based on divergence measures

    CERN Document Server

    Pardo, Leandro

    2005-01-01

    The idea of using functionals of Information Theory, such as entropies or divergences, in statistical inference is not new. However, in spite of the fact that divergence statistics have become a very good alternative to the classical likelihood ratio test and the Pearson-type statistic in discrete models, many statisticians remain unaware of this powerful approach.Statistical Inference Based on Divergence Measures explores classical problems of statistical inference, such as estimation and hypothesis testing, on the basis of measures of entropy and divergence. The first two chapters form an overview, from a statistical perspective, of the most important measures of entropy and divergence and study their properties. The author then examines the statistical analysis of discrete multivariate data with emphasis is on problems in contingency tables and loglinear models using phi-divergence test statistics as well as minimum phi-divergence estimators. The final chapter looks at testing in general populations, prese...

  13. Deep Learning for Population Genetic Inference.

    Science.gov (United States)

    Sheehan, Sara; Song, Yun S

    2016-03-01

    Given genomic variation data from multiple individuals, computing the likelihood of complex population genetic models is often infeasible. To circumvent this problem, we introduce a novel likelihood-free inference framework by applying deep learning, a powerful modern technique in machine learning. Deep learning makes use of multilayer neural networks to learn a feature-based function from the input (e.g., hundreds of correlated summary statistics of data) to the output (e.g., population genetic parameters of interest). We demonstrate that deep learning can be effectively employed for population genetic inference and learning informative features of data. As a concrete application, we focus on the challenging problem of jointly inferring natural selection and demography (in the form of a population size change history). Our method is able to separate the global nature of demography from the local nature of selection, without sequential steps for these two factors. Studying demography and selection jointly is motivated by Drosophila, where pervasive selection confounds demographic analysis. We apply our method to 197 African Drosophila melanogaster genomes from Zambia to infer both their overall demography, and regions of their genome under selection. We find many regions of the genome that have experienced hard sweeps, and fewer under selection on standing variation (soft sweep) or balancing selection. Interestingly, we find that soft sweeps and balancing selection occur more frequently closer to the centromere of each chromosome. In addition, our demographic inference suggests that previously estimated bottlenecks for African Drosophila melanogaster are too extreme.

  14. Deep Learning for Population Genetic Inference.

    Directory of Open Access Journals (Sweden)

    Sara Sheehan

    2016-03-01

    Full Text Available Given genomic variation data from multiple individuals, computing the likelihood of complex population genetic models is often infeasible. To circumvent this problem, we introduce a novel likelihood-free inference framework by applying deep learning, a powerful modern technique in machine learning. Deep learning makes use of multilayer neural networks to learn a feature-based function from the input (e.g., hundreds of correlated summary statistics of data to the output (e.g., population genetic parameters of interest. We demonstrate that deep learning can be effectively employed for population genetic inference and learning informative features of data. As a concrete application, we focus on the challenging problem of jointly inferring natural selection and demography (in the form of a population size change history. Our method is able to separate the global nature of demography from the local nature of selection, without sequential steps for these two factors. Studying demography and selection jointly is motivated by Drosophila, where pervasive selection confounds demographic analysis. We apply our method to 197 African Drosophila melanogaster genomes from Zambia to infer both their overall demography, and regions of their genome under selection. We find many regions of the genome that have experienced hard sweeps, and fewer under selection on standing variation (soft sweep or balancing selection. Interestingly, we find that soft sweeps and balancing selection occur more frequently closer to the centromere of each chromosome. In addition, our demographic inference suggests that previously estimated bottlenecks for African Drosophila melanogaster are too extreme.

  15. Deep Learning for Population Genetic Inference

    Science.gov (United States)

    Sheehan, Sara; Song, Yun S.

    2016-01-01

    Given genomic variation data from multiple individuals, computing the likelihood of complex population genetic models is often infeasible. To circumvent this problem, we introduce a novel likelihood-free inference framework by applying deep learning, a powerful modern technique in machine learning. Deep learning makes use of multilayer neural networks to learn a feature-based function from the input (e.g., hundreds of correlated summary statistics of data) to the output (e.g., population genetic parameters of interest). We demonstrate that deep learning can be effectively employed for population genetic inference and learning informative features of data. As a concrete application, we focus on the challenging problem of jointly inferring natural selection and demography (in the form of a population size change history). Our method is able to separate the global nature of demography from the local nature of selection, without sequential steps for these two factors. Studying demography and selection jointly is motivated by Drosophila, where pervasive selection confounds demographic analysis. We apply our method to 197 African Drosophila melanogaster genomes from Zambia to infer both their overall demography, and regions of their genome under selection. We find many regions of the genome that have experienced hard sweeps, and fewer under selection on standing variation (soft sweep) or balancing selection. Interestingly, we find that soft sweeps and balancing selection occur more frequently closer to the centromere of each chromosome. In addition, our demographic inference suggests that previously estimated bottlenecks for African Drosophila melanogaster are too extreme. PMID:27018908

  16. Inferring Phylogenetic Networks Using PhyloNet.

    Science.gov (United States)

    Wen, Dingqiao; Yu, Yun; Zhu, Jiafan; Nakhleh, Luay

    2018-07-01

    PhyloNet was released in 2008 as a software package for representing and analyzing phylogenetic networks. At the time of its release, the main functionalities in PhyloNet consisted of measures for comparing network topologies and a single heuristic for reconciling gene trees with a species tree. Since then, PhyloNet has grown significantly. The software package now includes a wide array of methods for inferring phylogenetic networks from data sets of unlinked loci while accounting for both reticulation (e.g., hybridization) and incomplete lineage sorting. In particular, PhyloNet now allows for maximum parsimony, maximum likelihood, and Bayesian inference of phylogenetic networks from gene tree estimates. Furthermore, Bayesian inference directly from sequence data (sequence alignments or biallelic markers) is implemented. Maximum parsimony is based on an extension of the "minimizing deep coalescences" criterion to phylogenetic networks, whereas maximum likelihood and Bayesian inference are based on the multispecies network coalescent. All methods allow for multiple individuals per species. As computing the likelihood of a phylogenetic network is computationally hard, PhyloNet allows for evaluation and inference of networks using a pseudolikelihood measure. PhyloNet summarizes the results of the various analyzes and generates phylogenetic networks in the extended Newick format that is readily viewable by existing visualization software.

  17. Longitudinal Associations among Child Maltreatment, Social Functioning, and Cortisol Regulation

    Science.gov (United States)

    Alink, Lenneke R. A.; Cicchetti, Dante; Kim, Jungmeen; Rogosch, Fred A.

    2012-01-01

    Child maltreatment increases the risk for impaired social functioning and cortisol regulation. However, the longitudinal interplay among these factors is still unclear. This study aimed to shed light on the effect of maltreatment on social functioning and cortisol regulation over time. The sample consisted of 236 children (mean age 7.64 years, SD…

  18. Cognitive functioning and associated factors in older adults in South ...

    African Journals Online (AJOL)

    Mean variables in the sample were: 5.9 recalled words, a verbal fluency of 9.9 words in a specified category (animals), a forward and backward digit span of 5.2 and 3.2, respectively, and an overall mean cognition score of 48.5. Higher overall cognitive functioning (a combination of memory and executive functioning) was ...

  19. Likelihood inference for unions of interacting discs

    DEFF Research Database (Denmark)

    Møller, Jesper; Helisova, K.

    2010-01-01

    This is probably the first paper which discusses likelihood inference for a random set using a germ-grain model, where the individual grains are unobservable, edge effects occur and other complications appear. We consider the case where the grains form a disc process modelled by a marked point...... process, where the germs are the centres and the marks are the associated radii of the discs. We propose to use a recent parametric class of interacting disc process models, where the minimal sufficient statistic depends on various geometric properties of the random set, and the density is specified......-based maximum likelihood inference and the effect of specifying different reference Poisson models....

  20. Surname-inferred Andean ancestry is associated with child stature and limb lengths at high altitude in Peru, but not at sea level.

    Science.gov (United States)

    Pomeroy, Emma; Wells, Jonathan C K; Stanojevic, Sanja; Miranda, J Jaime; Moore, Lorna G; Cole, Tim J; Stock, Jay T

    2015-01-01

    Native Andean ancestry gives partial protection from reduced birthweight at high altitude in the Andes compared with European ancestry. Whether Andean ancestry is also associated with body proportions and greater postnatal body size at altitude is unknown. Therefore, we tested whether a greater proportion of Andean ancestry is associated with stature and body proportions among Peruvian children at high and low altitude. Height, head circumference, head-trunk height, upper and lower limb lengths, and tibia, ulna, hand and foot lengths, were measured in 133 highland and 169 lowland children aged 6 months to 8.5 years. For highland and lowland groups separately, age-sex-adjusted anthropometry z scores were regressed on the number of indigenous parental surnames as a proxy for Andean ancestry, adjusting for potential confounders (maternal age and education, parity, altitude [highlands only]). Among highland children, greater Andean ancestry was negatively associated with stature and tibia, ulna, and lower limb lengths, independent of negative associations with greater altitude for these measurements. Relationships were strongest for tibia length: each additional Andean surname or 1,000 m increase at altitude among highland children was associated with 0.18 and 0.65 z score decreases in tibia length, respectively. Anthropometry was not significantly associated with ancestry among lowland children. Greater Andean ancestry is associated with shorter stature and limb measurements at high but not low altitude. Gene-environment interactions between high altitude and Andean ancestry may exacerbate the trade-off between chest dimensions and stature that was proposed previously, though we could not test this directly. © 2015 Wiley Periodicals, Inc.

  1. Associations between physical performance and executive function in older adults with mild cognitive impairment: gait speed and the timed "up & go" test.

    Science.gov (United States)

    McGough, Ellen L; Kelly, Valerie E; Logsdon, Rebecca G; McCurry, Susan M; Cochrane, Barbara B; Engel, Joyce M; Teri, Linda

    2011-08-01

    Older adults with amnestic mild cognitive impairment (aMCI) are at higher risk for developing Alzheimer disease. Physical performance decline on gait and mobility tasks in conjunction with executive dysfunction has implications for accelerated functional decline, disability, and institutionalization in sedentary older adults with aMCI. The purpose of this study was to examine whether performance on 2 tests commonly used by physical therapists (usual gait speed and Timed "Up & Go" Test [TUG]) are associated with performance on 2 neuropsychological tests of executive function (Trail Making Test, part B [TMT-B], and Stroop-Interference, calculated from the Stroop Word Color Test) in sedentary older adults with aMCI. The study was a cross-sectional analysis of 201 sedentary older adults with memory impairment participating in a longitudinal intervention study of cognitive function, aging, exercise, and health promotion. Physical performance speed on gait and mobility tasks was measured via usual gait speed and the TUG (at fast pace). Executive function was measured with the TMT-B and Stroop-Interference measures. Applying multiple linear regression, usual gait speed was associated with executive function on both the TMT-B (β=-0.215, P=.003) and Stroop-Interference (β=-0.195, P=.01) measures, indicating that slower usual gait speed was associated with lower executive function performance. Timed "Up & Go" Test scores (in logarithmic transformation) also were associated with executive function on both the TMT-B (β=0.256, Pfunction performance. All associations remained statistically significant after adjusting for age, sex, depressive symptoms, medical comorbidity, and body mass index. The cross-sectional nature of this study does not allow for inferences of causation. Physical performance speed was associated with executive function after adjusting for age, sex, and age-related factors in sedentary older adults with aMCI. Further research is needed to determine

  2. Active Inference, homeostatic regulation and adaptive behavioural control.

    Science.gov (United States)

    Pezzulo, Giovanni; Rigoli, Francesco; Friston, Karl

    2015-11-01

    We review a theory of homeostatic regulation and adaptive behavioural control within the Active Inference framework. Our aim is to connect two research streams that are usually considered independently; namely, Active Inference and associative learning theories of animal behaviour. The former uses a probabilistic (Bayesian) formulation of perception and action, while the latter calls on multiple (Pavlovian, habitual, goal-directed) processes for homeostatic and behavioural control. We offer a synthesis these classical processes and cast them as successive hierarchical contextualisations of sensorimotor constructs, using the generative models that underpin Active Inference. This dissolves any apparent mechanistic distinction between the optimization processes that mediate classical control or learning. Furthermore, we generalize the scope of Active Inference by emphasizing interoceptive inference and homeostatic regulation. The ensuing homeostatic (or allostatic) perspective provides an intuitive explanation for how priors act as drives or goals to enslave action, and emphasises the embodied nature of inference. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. MAVL wastes containers functional demonstration and associated tests program

    International Nuclear Information System (INIS)

    Templier, J.C.

    2002-01-01

    In the framework of studies on the MAVL wastes, the CEA develops containers for middle time wastes storage. This program aims to realize a ''B wastes containers'' demonstrator. A demonstrator is a container, parts of a container or samples which must validate the tests. This document presents the state of the study in the following three chapters: functions description, base data and design choices; presentation of the functional demonstrators; demonstration tests description. (A.L.B.)

  4. Screening disrupted molecular functions and pathways associated with clear cell renal cell carcinoma using Gibbs sampling.

    Science.gov (United States)

    Nan, Ning; Chen, Qi; Wang, Yu; Zhai, Xu; Yang, Chuan-Ce; Cao, Bin; Chong, Tie

    2017-10-01

    To explore the disturbed molecular functions and pathways in clear cell renal cell carcinoma (ccRCC) using Gibbs sampling. Gene expression data of ccRCC samples and adjacent non-tumor renal tissues were recruited from public available database. Then, molecular functions of expression changed genes in ccRCC were classed to Gene Ontology (GO) project, and these molecular functions were converted into Markov chains. Markov chain Monte Carlo (MCMC) algorithm was implemented to perform posterior inference and identify probability distributions of molecular functions in Gibbs sampling. Differentially expressed molecular functions were selected under posterior value more than 0.95, and genes with the appeared times in differentially expressed molecular functions ≥5 were defined as pivotal genes. Functional analysis was employed to explore the pathways of pivotal genes and their strongly co-regulated genes. In this work, we obtained 396 molecular functions, and 13 of them were differentially expressed. Oxidoreductase activity showed the highest posterior value. Gene composition analysis identified 79 pivotal genes, and survival analysis indicated that these pivotal genes could be used as a strong independent predictor of poor prognosis in patients with ccRCC. Pathway analysis identified one pivotal pathway - oxidative phosphorylation. We identified the differentially expressed molecular functions and pivotal pathway in ccRCC using Gibbs sampling. The results could be considered as potential signatures for early detection and therapy of ccRCC. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Armored geckos: A histological investigation of osteoderm development in Tarentola (Phyllodactylidae) and Gekko (Gekkonidae) with comments on their regeneration and inferred function.

    Science.gov (United States)

    Vickaryous, M K; Meldrum, G; Russell, A P

    2015-11-01

    Osteoderms are bone-rich organs found in the dermis of many scleroglossan lizards sensu lato, but are only known for two genera of gekkotans (geckos): Tarentola and Gekko. Here, we investigate their sequence of appearance, mode of development, structural diversity and ability to regenerate following tail loss. Osteoderms were present in all species of Tarentola sampled (Tarentola annularis, T. mauritanica, T. americana, T. crombei, T. chazaliae) as well as Gekko gecko, but not G. smithii. Gekkotan osteoderms first appear within the integument dorsal to the frontal bone or within the supraocular scales. They then manifest as mineralized structures in other positions across the head. In Tarentola and G. gecko, discontinuous clusters subsequently form dorsal to the pelvis/base of the tail, and then dorsal to the pectoral apparatus. Gekkotan osteoderm formation begins once the dermis is fully formed. Early bone deposition appears to involve populations of fibroblast-like cells, which are gradually replaced by more rounded osteoblasts. In T. annularis and T. mauritanica, an additional skeletal tissue is deposited across the superficial surface of the osteoderm. This tissue is vitreous, avascular, cell-poor, lacks intrinsic collagen, and is herein identified as osteodermine. We also report that following tail loss, both T. annularis and T. mauritanica are capable of regenerating osteoderms, including osteodermine, in the regenerated part of the tail. We propose that osteoderms serve roles in defense against combative prey and intraspecific aggression, along with anti-predation functions. © 2015 Wiley Periodicals, Inc.

  6. Association between report of insomnia and daytime functioning.

    Science.gov (United States)

    Ustinov, Yuriy; Lichstein, Kenneth L; Wal, Gregory S Vander; Taylor, Daniel J; Riedel, Brant W; Bush, Andrew J

    2010-01-01

    The relationship between reports of insomnia and daytime functioning was investigated using hierarchical regression. The presence or absence of a report of insomnia was the predictor of primary interest. A number of covariates were included in the model: demographic variables, health variables, and quantitative sleep parameters. Data were collected from a community sample in the Memphis, Tennessee area. Data from 734 volunteers, ranging in age from 20 to 96years were analyzed. The sample included 235 individuals who reported having chronic insomnia and 499 individuals who reported no sleep problems. Participants completed a 2-week sleep diary, a battery of daytime functioning questionnaires, and a medical disorders checklist. Demographic information was also collected. The daytime functioning assessment included the Beck Depression Inventory, the State-Trait Anxiety Inventory, the Epworth Sleepiness Scale, the Insomnia Impact Scale, and the Fatigue Severity Scale. The hierarchical regression model included four sets. The first three sets consisted of 18 variables capturing demographic, health, and sleep diary parameters. The fourth set included a single dichotomous variable representing the presence or absence of a report of insomnia. Reports of insomnia were a significant predictor of all five daytime functioning measures, which is consistent with previous research. We also showed that reports of insomnia were able to uniquely explain a significant amount of variability in self-reported daytime functioning after controlling for demographics, health, and sleep diary variables. The pattern of individual variables that reached significance in the first three sets varied depending on which daytime functioning measure was predicted, however, age, the presence of pain, the presence of mental health problems, SOL, and WASO were the most commonly significant predictors of poor daytime functioning from these sets across measures. Individuals' perceptions of their sleep are

  7. An integrative approach to inferring biologically meaningful gene modules

    Directory of Open Access Journals (Sweden)

    Wang Kai

    2011-07-01

    Full Text Available Abstract Background The ability to construct biologically meaningful gene networks and modules is critical for contemporary systems biology. Though recent studies have demonstrated the power of using gene modules to shed light on the functioning of complex biological systems, most modules in these networks have shown little association with meaningful biological function. We have devised a method which directly incorporates gene ontology (GO annotation in construction of gene modules in order to gain better functional association. Results We have devised a method, Semantic Similarity-Integrated approach for Modularization (SSIM that integrates various gene-gene pairwise similarity values, including information obtained from gene expression, protein-protein interactions and GO annotations, in the construction of modules using affinity propagation clustering. We demonstrated the performance of the proposed method using data from two complex biological responses: 1. the osmotic shock response in Saccharomyces cerevisiae, and 2. the prion-induced pathogenic mouse model. In comparison with two previously reported algorithms, modules identified by SSIM showed significantly stronger association with biological functions. Conclusions The incorporation of semantic similarity based on GO annotation with gene expression and protein-protein interaction data can greatly enhance the functional relevance of inferred gene modules. In addition, the SSIM approach can also reveal the hierarchical structure of gene modules to gain a broader functional view of the biological system. Hence, the proposed method can facilitate comprehensive and in-depth analysis of high throughput experimental data at the gene network level.

  8. Functional status and its associated factors in Nigerian adolescents ...

    African Journals Online (AJOL)

    mortality among children and adolescents.1 Bipolar disorder course is known to be ... high prevalence and enormity of mood disorders among. Nigerian children ..... History of suicide attempts in pediatric bipolar disorder: factors associated ...

  9. A Functional Genomic Analysis of NF1-Associated Learning Disabilities

    National Research Council Canada - National Science Library

    Tang, Shao-Jun

    2008-01-01

    Learning disabilities severely deteriorate the life of many NF1 patients. However, the pathogenic process for NF1-associated learning disabilities has not been fully understood and an effective therapy is not available...

  10. A Functional Genomic Analysis of NF1-Associated Learning Disabilities

    National Research Council Canada - National Science Library

    Tang, Shao-Jun

    2007-01-01

    Learning disabilities severely deteriorate the life of many NF1 patients. However, the pathogenic process for NF1-associated learning disabilities has not been fully understood and an effective therapy is not available...

  11. A Functional Genomic Analysis of NF1-Associated Learning Disabilities

    National Research Council Canada - National Science Library

    Tang, Shao-Jun

    2006-01-01

    Learning disabilities severely deteriorate the life of many NFI patients. However, the pathogenic process for NFI-associated learning disabilities has not been fully understood and an effective therapy is not available...

  12. Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association?

    International Nuclear Information System (INIS)

    Erdas, Enrico; Mariotti, Stefano; Pomata, Mariano; Aste, Nicola; Pilloni, Luca; Nicolosi, Angelo; Licheri, Sergio; Cappai, Antonello; Mastinu, Marco; Cetani, Filomena; Pardi, Elena

    2012-01-01

    Diagnosis of multiple endocrine neoplasia type 1 (MEN1) is commonly based on clinical criteria, and confirmed by genetic testing. In patients without known MEN1-related germline mutations, the possibility of a casual association between two or more endocrine tumors cannot be excluded and subsequent management may be difficult to plan. We describe a very uncommon case of functioning glucagonoma associated with primary hyperparathyroidism (pHPT) in which genetic testing failed to detect germline mutations of MEN-1 and other known genes responsible for MEN1. The patient, a 65-year old woman, had been suffering for more than 1 year from weakness, progressive weight loss, angular cheilitis, glossitis and, more recently, skin rashes on the perineum, perioral skin and groin folds. After multidisciplinary investigations, functioning glucagonoma and asymptomatic pHPT were diagnosed and, since family history was negative, sporadic MEN1 was suspected. However, genetic testing revealed neither MEN-1 nor other gene mutations responsible for rarer cases of MEN1 (CDKN1B/p27 and other cyclin-dependent kinase inhibitor genes CDKN1A/p15, CDKN2C/p18, CDKN2B/p21). The patient underwent distal splenopancreatectomy and at the 4-month follow-up she showed complete remission of symptoms. Six months later, a thyroid nodule, suspected to be a malignant neoplasia, and two hyperfunctioning parathyroid glands were detected respectively by ultrasound with fine needle aspiration cytology and 99m Tc-sestamibi scan with SPECT acquisition. Total thyroidectomy was performed, whereas selective parathyroidectomy was preferred to a more extensive procedure because the diagnosis of MEN1 was not supported by genetic analysis and intraoperative intact parathyroid hormone had revealed “adenoma-like” kinetics after the second parathyroid resection. Thirty-nine and 25 months after respectively the first and the second operation, the patient is well and shows no signs or symptoms of recurrence. Despite

  13. Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association?

    Directory of Open Access Journals (Sweden)

    Erdas Enrico

    2012-12-01

    Full Text Available Abstract Background Diagnosis of multiple endocrine neoplasia type 1 (MEN1 is commonly based on clinical criteria, and confirmed by genetic testing. In patients without known MEN1-related germline mutations, the possibility of a casual association between two or more endocrine tumors cannot be excluded and subsequent management may be difficult to plan. We describe a very uncommon case of functioning glucagonoma associated with primary hyperparathyroidism (pHPT in which genetic testing failed to detect germline mutations of MEN-1 and other known genes responsible for MEN1. Case presentation The patient, a 65-year old woman, had been suffering for more than 1 year from weakness, progressive weight loss, angular cheilitis, glossitis and, more recently, skin rashes on the perineum, perioral skin and groin folds. After multidisciplinary investigations, functioning glucagonoma and asymptomatic pHPT were diagnosed and, since family history was negative, sporadic MEN1 was suspected. However, genetic testing revealed neither MEN-1 nor other gene mutations responsible for rarer cases of MEN1 (CDKN1B/p27 and other cyclin-dependent kinase inhibitor genes CDKN1A/p15, CDKN2C/p18, CDKN2B/p21. The patient underwent distal splenopancreatectomy and at the 4-month follow-up she showed complete remission of symptoms. Six months later, a thyroid nodule, suspected to be a malignant neoplasia, and two hyperfunctioning parathyroid glands were detected respectively by ultrasound with fine needle aspiration cytology and 99mTc-sestamibi scan with SPECT acquisition. Total thyroidectomy was performed, whereas selective parathyroidectomy was preferred to a more extensive procedure because the diagnosis of MEN1 was not supported by genetic analysis and intraoperative intact parathyroid hormone had revealed “adenoma-like” kinetics after the second parathyroid resection. Thirty-nine and 25 months after respectively the first and the second operation, the patient is well

  14. Some results associated with a generalized basic hypergeometric function

    Directory of Open Access Journals (Sweden)

    Rajeev K. Gupta

    2009-05-01

    Full Text Available In this paper, we define a q-extension of the new generalized hypergeometric function given by Saxena et al. in [13], and have investigated the properties of the above new function such as q-differentiation and q-integral representation. The results presented are of general character and the results given earlier by Saxena and Kalla in [14], Virchenko, Kalla and Al-Zamel in [15], Al-Musallam and Kalla in [2, 3], Kobayashi in [7, 8], Saxena et al. in [13], Kumbhat et al. in [11] follow as special cases.

  15. Functional and Structural Brain Changes Associated with Methamphetamine Abuse

    Directory of Open Access Journals (Sweden)

    Bruce R. Russell

    2012-10-01

    Full Text Available Methamphetamine (MA is a potent psychostimulant drug whose abuse has become a global epidemic in recent years. Firstly, this review article briefly discusses the epidemiology and clinical pharmacology of methamphetamine dependence. Secondly, the article reviews relevant animal literature modeling methamphetamine dependence and discusses possible mechanisms of methamphetamine-induced neurotoxicity. Thirdly, it provides a critical review of functional and structural neuroimaging studies in human MA abusers; including positron emission tomography (PET and functional and structural magnetic resonance imaging (MRI. The effect of abstinence from methamphetamine, both short- and long-term within the context of these studies is also reviewed.

  16. The Work Function Associated with Ultra-relativistic Electron ...

    Indian Academy of Sciences (India)

    The energy required to liberate an electron in the Fermi level is the work function and is ... potential difference will be developed across a thin gap, called the polar gap. This ... The emission of electrons from the polar region of neutron stars is.

  17. Environmental Exposure to Manganese in Air: Associations with Cognitive Functions

    Science.gov (United States)

    Manganese (Mn), an essential element, can be neurotoxic in high doses. This cross-sectional study explored the oognitive function of adults residing in two towns (Marietta and East Liverpool, Ohio, USA) identified as having high levels of environmental airborne Mn from indu...

  18. Associations between genetic risk, functional brain network organization and neuroticism

    NARCIS (Netherlands)

    Servaas, Michelle N.; Geerligs, Linda; Bastiaansen, Jojanneke A.; Renken, Remco J.; Marsman, Jan-Bernard C.; Nolte, Ilja M.; Ormel, Johan; Aleman, Andre; Riese, Harriette

    2017-01-01

    Neuroticism and genetic variation in the serotonin-transporter (SLC6A4) and catechol-O-methyltransferase (COMT) gene are risk factors for psychopathology. Alterations in the functional integration and segregation of neural circuits have recently been found in individuals scoring higher on

  19. Mediators of the association between depression and role functioning

    NARCIS (Netherlands)

    Buist-Bouwman, M. A.; Ormel, J.; de Graaf, R.; de Jonge, P.; van Sonderen, E.; Alonso, J.; Bruffaerts, R.; Vollebergh, W. A. M.

    2008-01-01

    While the adverse effect of Major Depressive Episode on role functioning is well established, the exact pathways remain unclear. Data from The European Study of the Epidemiology of Mental Disorders, a cross-sectional survey including 21 425 adults from six European countries, were used to assess

  20. Associations Between Quality of Life and Functioning in an Assertive Community Treatment Population.

    Science.gov (United States)

    Clausen, Hanne; Landheim, Anne; Odden, Sigrun; Heiervang, Kristin Sverdvik; Stuen, Hanne Kilen; Killaspy, Helen; Šaltytė Benth, Jurate; Ruud, Torleif

    2015-11-01

    Level of functioning is positively associated with subjective quality of life for people with severe mental illness, but a detailed relationship between functioning and satisfaction with various life domains is largely unknown, and this gap prompted this study. Demographic and clinical data were obtained from 149 patients engaged with 12 assertive community treatment teams in Norway. Multivariate regression analyses were used to explore associations between subjective quality of life and patient characteristics. Analyses confirmed positive associations between quality of life and age, functioning, and weekly contact with family and friends and a negative association with anxiety and depressive symptoms. Positive associations between several areas of practical and social functioning and satisfaction with related life domains also were found. Although a causal direction of the associations between functioning and life satisfaction has not been determined in this study, the positive findings might indicate that programs aiming to improve functioning could affect patients' quality of life.

  1. Relative telomere length is associated with a functional ...

    Indian Academy of Sciences (India)

    ated with several neuropsychiatric disorders, such as major depression ... with shorter telomeres in white blood cells of healthy indi- viduals (Starkweather et al. 2014). Recently, a systematic review identified a possible association between shorter TL and high levels of ... MAOA protein plays an important role in the regula-.

  2. Multiple functional self-association interfaces in plant TIR domains

    NARCIS (Netherlands)

    Zhang, Xiaoxiao; Bernoux, Maud; Bentham, Adam R; Newman, Toby E; Ve, Thomas; Casey, Lachlan W; Raaymakers, Tom M; Hu, Jian; Croll, Tristan I; Schreiber, Karl J; Staskawicz, Brian J; Anderson, Peter A; Sohn, Kee Hoon; Williams, Simon J; Dodds, Peter N; Kobe, Bostjan

    2017-01-01

    The self-association of Toll/interleukin-1 receptor/resistance protein (TIR) domains has been implicated in signaling in plant and animal immunity receptors. Structure-based studies identified different TIR-domain dimerization interfaces required for signaling of the plant nucleotide-binding

  3. BOLD signal and functional connectivity associated with loving kindness meditation

    Science.gov (United States)

    Garrison, Kathleen A; Scheinost, Dustin; Constable, R Todd; Brewer, Judson A

    2014-01-01

    Loving kindness is a form of meditation involving directed well-wishing, typically supported by the silent repetition of phrases such as “may all beings be happy,” to foster a feeling of selfless love. Here we used functional magnetic resonance imaging to assess the neural substrate of loving kindness meditation in experienced meditators and novices. We first assessed group differences in blood oxygen level-dependent (BOLD) signal during loving kindness meditation. We next used a relatively novel approach, the intrinsic connectivity distribution of functional connectivity, to identify regions that differ in intrinsic connectivity between groups, and then used a data-driven approach to seed-based connectivity analysis to identify which connections differ between groups. Our findings suggest group differences in brain regions involved in self-related processing and mind wandering, emotional processing, inner speech, and memory. Meditators showed overall reduced BOLD signal and intrinsic connectivity during loving kindness as compared to novices, more specifically in the posterior cingulate cortex/precuneus (PCC/PCu), a finding that is consistent with our prior work and other recent neuroimaging studies of meditation. Furthermore, meditators showed greater functional connectivity during loving kindness between the PCC/PCu and the left inferior frontal gyrus, whereas novices showed greater functional connectivity during loving kindness between the PCC/PCu and other cortical midline regions of the default mode network, the bilateral posterior insula lobe, and the bilateral parahippocampus/hippocampus. These novel findings suggest that loving kindness meditation involves a present-centered, selfless focus for meditators as compared to novices. PMID:24944863

  4. Cognitive impairment as measured by the THINC-integrated tool (THINC-it): Association with psychosocial function in major depressive disorder.

    Science.gov (United States)

    Cha, Danielle S; Carmona, Nicole E; Subramaniapillai, Mehala; Mansur, Rodrigo B; Lee, Yena; Hon Lee, Jae; Lee, JungGoo; Rosenblat, Joshua D; Shekotikhina, Margarita; Park, Caroline; Rong, Carola; Greer, Tracy L; Lam, Raymond; Baune, Bernhard T; Harrison, John; McIntyre, Roger S

    2017-11-01

    Psychosocial impairment represents an important treatment target in major depressive disorder (MDD). The majority of patients with MDD do not regain premorbid levels of psychosocial functioning despite the resolution of core depressive symptoms. This study aimed to investigate the respective effects of cognitive function and depression severity on impaired psychosocial function in MDD. Adults aged 18-65 with moderate-to-severe MDD (n = 100) and age-, sex-, and education-matched healthy controls participated in a cross-sectional study validating the THINC-integrated tool (THINC-it), a cognitive screening tool comprised of objective and subjective measures of cognitive function. Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale and psychosocial function was assessed using the Sheehan Disability Scale (SDS). Subjects with MDD reported greater impairment in psychosocial function than healthy controls, with significant differences in SDS total and domain scores (ps Depression severity was most strongly associated with SDS social life (RR = .08, p < .01) and economic days underproductive (RR = .07, p < .01). Objective cognitive function was not significantly associated with any SDS outcomes. The cross-sectional, observational study design limits temporal inferences. The self-report nature of measures included may have influenced associations observed. Potential medication effects are not noted. Cognitive deficits, as measured by the THINC-it, are associated with significant psychosocial impairment in MDD. These results provide empirical support for the assessment of both subjective and objective measures of cognition, as they are not associated with each other and have differential effects on functional trajectory. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Low cognitive ability in early adulthood is associated with reduced lung function in middle age

    DEFF Research Database (Denmark)

    Carroll, Douglas; Batty, G David; Mortensen, Laust Hvas

    2011-01-01

    Reduced lung function has been linked to poorer cognitive ability later in life. In the present study, the authors examined the converse: whether there was a prospective association between cognitive ability in early adulthood and lung function in middle age.......Reduced lung function has been linked to poorer cognitive ability later in life. In the present study, the authors examined the converse: whether there was a prospective association between cognitive ability in early adulthood and lung function in middle age....

  6. Priming in a free association task as a function of association directionality.

    Science.gov (United States)

    Zeelenberg, R; Shiffrin, R M; Raaijmakers, J G

    1999-11-01

    Two experiments investigated priming in free association, a conceptual implicit memory task. The stimuli consisted of bidirectionally associated word pairs (e.g., BEACH-SAND) and unidirectionally associated word pairs that have no association from the target response back to the stimulus cue (e.g., BONE-DOG). In the study phase, target words (e.g., SAND, DOG) were presented in an incidental learning task. In the test phase, participants generated an associate to the stimulus cues (e.g., BEACH, BONE). In both experiments, priming was obtained for targets (e.g., SAND) that had an association back to the cue, but not for targets (e.g., DOG) for which such a backward association was absent. These results are problematic for theoretical accounts that attribute priming in free association to the strengthening of target responses. It is argued that priming in free association depends on the strengthening of cue-target associations.

  7. Natural genetic variation in transcriptome reflects network structure inferred with major effect mutations: insulin/TOR and associated phenotypes in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Harshman Lawrence G

    2009-03-01

    Full Text Available Abstract Background A molecular process based genotype-to-phenotype map will ultimately enable us to predict how genetic variation among individuals results in phenotypic alterations. Building such a map is, however, far from straightforward. It requires understanding how molecular variation re-shapes developmental and metabolic networks, and how the functional state of these networks modifies phenotypes in genotype specific way. We focus on the latter problem by describing genetic variation in transcript levels of genes in the InR/TOR pathway among 72 Drosophila melanogaster genotypes. Results We observe tight co-variance in transcript levels of genes not known to influence each other through direct transcriptional control. We summarize transcriptome variation with factor analyses, and observe strong co-variance of gene expression within the dFOXO-branch and within the TOR-branch of the pathway. Finally, we investigate whether major axes of transcriptome variation shape phenotypes expected to be influenced through the InR/TOR pathway. We find limited evidence that transcript levels of individual upstream genes in the InR/TOR pathway predict fly phenotypes in expected ways. However, there is no evidence that these effects are mediated through the major axes of downstream transcriptome variation. Conclusion In summary, our results question the assertion of the 'sparse' nature of genetic networks, while validating and extending candidate gene approaches in the analyses of complex traits.

  8. Frequency distribution function of stellar flares in the Orion association

    International Nuclear Information System (INIS)

    Parsamian, E.S.

    1981-01-01

    The temporal distributions of flare stars in the Orion association and the numbers of stars with different flare frequencies are determined by means of Ambartsumian's (1978) method, which uses the chronology of discovery of 'first' flares and the chronology of confirmations, i.e., the temporal distributions of 'repeated' flares. It is shown that flare stars with high flare frequency (not greater than 1000 hours) in the Pleiades are basically stars of low luminosity with M(U) not less than 13m. Two independent methods of determining the number of flare stars in the aggregates confirm that there are about 1.5 times more flare stars in the Orion association than in the Pleiades

  9. Are a healthy diet and physical activity synergistically associated with cognitive functioning in older adults?

    NARCIS (Netherlands)

    Nijholt, W.; Jager-Wittenaar, H.; Visser, M.; Van der Schans, C. P.; Hobbelen, J. S. M.

    Previous research has demonstrated that being both physically active and adhering a healthy diet is associated with improved cognitive functioning; however, it remains unclear whether these factors act synergistically. We investigated the synergistic association of a healthy diet and being

  10. Are a Healthy Diet and Physical Activity Synergistically Associated with Cognitive Functioning in Older Adults?

    NARCIS (Netherlands)

    Nijholt, W; Jager-Wittenaar, H; Visser, M; van der Schans, C P; Hobbelen, J S M

    2016-01-01

    OBJECTIVES: Previous research has demonstrated that being both physically active and adhering a healthy diet is associated with improved cognitive functioning; however, it remains unclear whether these factors act synergistically. We investigated the synergistic association of a healthy diet and

  11. Are a healthy diet and physical activity synergistically associated with cognitive functioning in older adults?

    NARCIS (Netherlands)

    Nijholt, Willemke; Jager, Harriët; Visser, M.; van der Schans, Cees; Hobbelen, Hans

    2015-01-01

    Objectives: Previous research has demonstrated that being both physically active and adhering a healthy diet is associated with improved cognitive functioning; however, it remains unclear whether these factors act synergistically. We investigated the synergistic association of a healthy diet and

  12. Stress-associated or functional hypothalamic amenorrhea in the adolescent.

    Science.gov (United States)

    Liu, James H; Bill, Arthur H

    2008-01-01

    Stress-associated amenorrhea in the adolescent is likely similar to the disorder found in young reproductive-aged adults and is termed hypothalamic amenorrhea. The key defect is an abnormality in the secretion of gonadotropin-releasing hormone. This review examines the current studies that characterize the disorder and the plausible factor(s) that may account for the disturbances in gonadotropin-releasing hormone, and identifies directions for future research in this group of disorders.

  13. Dispersal of the Japanese pine sawyer, Monochamus alternatus (Coleoptera: Cerambycidae, in mainland China as inferred from molecular data and associations to indices of human activity.

    Directory of Open Access Journals (Sweden)

    Shao-ji Hu

    Full Text Available The Japanese pine sawyer, Monochamus alternatus Hope (Coleoptera: Cerambycidae, is an important forest pest as well as the principal vector of the pinewood nematode (PWN, Bursaphelenchus xylophilus (Steiner et Buhrer, in mainland China. Despite the economic importance of this insect-disease complex, only a few studies are available on the population genetic structure of M. alternatus and the relationship between its historic dispersal pattern and various human activities. The aim of the present study was to further explore aspects of human activity on the population genetic structure of M. alternatus in mainland China. The molecular data based on the combined mitochondrial cox1 and cox2 gene fragments from 140 individuals representing 14 Chinese populations yielded 54 haplotypes. Overall, a historical (natural expansion that originated from China's eastern coast to the western interior was revealed by the haplotype network, as well as several recent, long-distant population exchanges. Correlation analysis suggested that regional economic status and proximity to marine ports significantly influenced the population genetic structure of M. alternatus as indicated by both the ratio of shared haplotypes and the haplotype diversity, however, the PWN distribution in China was significantly correlated with only the ratio of shared haplotypes. Our results suggested that the modern logistical network (i.e., the transportation system in China is a key medium by which humans have brought about population exchange of M. alternatus in mainland China, likely through inadvertent movement of infested wood packaging material associated with trade, and that this genetic exchange was primarily from the economically well-developed east coast of China, westward, to the less-developed interior. In addition, this study demonstrated the existence of non-local M. alternatus in new PWN-infested localities in China, but not all sites with non-local M. alternatus were

  14. Feature Inference Learning and Eyetracking

    Science.gov (United States)

    Rehder, Bob; Colner, Robert M.; Hoffman, Aaron B.

    2009-01-01

    Besides traditional supervised classification learning, people can learn categories by inferring the missing features of category members. It has been proposed that feature inference learning promotes learning a category's internal structure (e.g., its typical features and interfeature correlations) whereas classification promotes the learning of…

  15. An Inference Language for Imaging

    DEFF Research Database (Denmark)

    Pedemonte, Stefano; Catana, Ciprian; Van Leemput, Koen

    2014-01-01

    We introduce iLang, a language and software framework for probabilistic inference. The iLang framework enables the definition of directed and undirected probabilistic graphical models and the automated synthesis of high performance inference algorithms for imaging applications. The iLang framewor...

  16. Association between functional performance and executive cognitive functions in an elderly population including patients with low ankle–brachial index

    Science.gov (United States)

    Ferreira, Naomi Vidal; Cunha, Paulo Jannuzzi; da Costa, Danielle Irigoyen; dos Santos, Fernando; Costa, Fernando Oliveira; Consolim-Colombo, Fernanda; Irigoyen, Maria Cláudia

    2015-01-01

    Introduction Peripheral arterial disease, as measured by the ankle–brachial index (ABI), is prevalent among the elderly, and is associated with functional performance, assessed by the 6-minute walk test (6MWT). Executive cognitive function (ECF) impairments are also prevalent in this population, but no existing study has investigated the association between ECF and functional performance in an elderly population including individuals with low ABI. Aim To investigate the association between functional performance, as measured by the 6MWT, and loss in ECF, in an elderly sample including individuals with low ABI. Method The ABI group was formed by 26 elderly individuals with low ABI (mean ABI: 0.63±0.19), and the control group was formed by 40 elderly individuals with normal ABI (mean ABI: 1.08±0.07). We analyzed functional performance using the 6MWT, global cognition using the Mini-Mental State Examination (MMSE), and ECF using the Digit Span for assessing attention span and working memory, the Stroop Color Word Test (SCWT) for assessing information processing speed and inhibitory control/impulsivity, and the Controlled Oral Word Association Test (COWAT) for assessing semantic verbal fluency and phonemic verbal fluency. We also used a factor analysis on all of the ECF tests (global ECF). Results Before adjustment, the ABI group performed worse on global cognition, attention span, working memory, inhibitory control/impulsivity, semantic verbal fluency, and phonemic verbal fluency. After adjustment, the ABI group performance remained worse for working memory and semantic verbal fluency. In a simple correlation analysis including all of the subjects, the 6MWT was associated with global cognition, attention span, working memory, information processing speed, inhibitory control/impulsivity, semantic verbal fluency, and global ECF. After adjustment, all the associations remained statistically significant. Conclusion This study found an independent association between

  17. Vitamin D status is associated with functional limitations and functional decline in older individuals.

    NARCIS (Netherlands)

    Sohl, E.; van Schoor, N.M.; de Jongh, R.T.; Visser, M.; Deeg, D.J.H.; Lips, P.

    2013-01-01

    Context: Vitamin D is known to influence muscle health. A reduction in muscle mass increases the risk of functional limitations among older individuals. Objective: The aim of this study was to examine the relationship between vitamin D status and functional limitations. Design, Setting, and

  18. Model averaging, optimal inference and habit formation

    Directory of Open Access Journals (Sweden)

    Thomas H B FitzGerald

    2014-06-01

    Full Text Available Postulating that the brain performs approximate Bayesian inference generates principled and empirically testable models of neuronal function – the subject of much current interest in neuroscience and related disciplines. Current formulations address inference and learning under some assumed and particular model. In reality, organisms are often faced with an additional challenge – that of determining which model or models of their environment are the best for guiding behaviour. Bayesian model averaging – which says that an agent should weight the predictions of different models according to their evidence – provides a principled way to solve this problem. Importantly, because model evidence is determined by both the accuracy and complexity of the model, optimal inference requires that these be traded off against one another. This means an agent’s behaviour should show an equivalent balance. We hypothesise that Bayesian model averaging plays an important role in cognition, given that it is both optimal and realisable within a plausible neuronal architecture. We outline model averaging and how it might be implemented, and then explore a number of implications for brain and behaviour. In particular, we propose that model averaging can explain a number of apparently suboptimal phenomena within the framework of approximate (bounded Bayesian inference, focussing particularly upon the relationship between goal-directed and habitual behaviour.

  19. HIERARCHICAL PROBABILISTIC INFERENCE OF COSMIC SHEAR

    International Nuclear Information System (INIS)

    Schneider, Michael D.; Dawson, William A.; Hogg, David W.; Marshall, Philip J.; Bard, Deborah J.; Meyers, Joshua; Lang, Dustin

    2015-01-01

    Point estimators for the shearing of galaxy images induced by gravitational lensing involve a complex inverse problem in the presence of noise, pixelization, and model uncertainties. We present a probabilistic forward modeling approach to gravitational lensing inference that has the potential to mitigate the biased inferences in most common point estimators and is practical for upcoming lensing surveys. The first part of our statistical framework requires specification of a likelihood function for the pixel data in an imaging survey given parameterized models for the galaxies in the images. We derive the lensing shear posterior by marginalizing over all intrinsic galaxy properties that contribute to the pixel data (i.e., not limited to galaxy ellipticities) and learn the distributions for the intrinsic galaxy properties via hierarchical inference with a suitably flexible conditional probabilitiy distribution specification. We use importance sampling to separate the modeling of small imaging areas from the global shear inference, thereby rendering our algorithm computationally tractable for large surveys. With simple numerical examples we demonstrate the improvements in accuracy from our importance sampling approach, as well as the significance of the conditional distribution specification for the intrinsic galaxy properties when the data are generated from an unknown number of distinct galaxy populations with different morphological characteristics

  20. Social Inference Through Technology

    Science.gov (United States)

    Oulasvirta, Antti

    Awareness cues are computer-mediated, real-time indicators of people’s undertakings, whereabouts, and intentions. Already in the mid-1970 s, UNIX users could use commands such as “finger” and “talk” to find out who was online and to chat. The small icons in instant messaging (IM) applications that indicate coconversants’ presence in the discussion space are the successors of “finger” output. Similar indicators can be found in online communities, media-sharing services, Internet relay chat (IRC), and location-based messaging applications. But presence and availability indicators are only the tip of the iceberg. Technological progress has enabled richer, more accurate, and more intimate indicators. For example, there are mobile services that allow friends to query and follow each other’s locations. Remote monitoring systems developed for health care allow relatives and doctors to assess the wellbeing of homebound patients (see, e.g., Tang and Venables 2000). But users also utilize cues that have not been deliberately designed for this purpose. For example, online gamers pay attention to other characters’ behavior to infer what the other players are like “in real life.” There is a common denominator underlying these examples: shared activities rely on the technology’s representation of the remote person. The other human being is not physically present but present only through a narrow technological channel.

  1. HFE gene: Structure, function, mutations, and associated iron abnormalities.

    Science.gov (United States)

    Barton, James C; Edwards, Corwin Q; Acton, Ronald T

    2015-12-15

    The hemochromatosis gene HFE was discovered in 1996, more than a century after clinical and pathologic manifestations of hemochromatosis were reported. Linked to the major histocompatibility complex (MHC) on chromosome 6p, HFE encodes the MHC class I-like protein HFE that binds beta-2 microglobulin. HFE influences iron absorption by modulating the expression of hepcidin, the main controller of iron metabolism. Common HFE mutations account for ~90% of hemochromatosis phenotypes in whites of western European descent. We review HFE mapping and cloning, structure, promoters and controllers, and coding region mutations, HFE protein structure, cell and tissue expression and function, mouse Hfe knockouts and knockins, and HFE mutations in other mammals with iron overload. We describe the pertinence of HFE and HFE to mechanisms of iron homeostasis, the origin and fixation of HFE polymorphisms in European and other populations, and the genetic and biochemical basis of HFE hemochromatosis and iron overload. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Functional brain activation associated with working memory training and transfer.

    Science.gov (United States)

    Clark, Cameron M; Lawlor-Savage, Linette; Goghari, Vina M

    2017-09-15

    While behavioural trials of working memory (WM) training have received much attention in recent years, a lesser explored parallel approach is functional neuroimaging. A small literature has suggested a complex time course for functional activation pattern changes following WM training (i.e. not simply increasing or decreasing due to training); however, no study to date has examined such neuroplastic effects in both the training task (dual n-back) and the fluid intelligence transfer task to which the training is purported to transfer (Raven's Matrices). This study investigated neural correlates of WM training in healthy young adults randomized to six weeks of WM training, or an active control condition (processing speed training) with a pre- and post-training fMRI design. Results indicated significant reductions in activation for the WM trained group in key WM-task related areas for trained WM tasks after training compared to the processing speed active control group. The same pattern of training related decreases in activation for the WM trained group was not observed for the transfer task, which is consistent with null results for all cognitive outcomes of the present trial. The observed pattern of results suggests that repetitive practice with a complex task does indeed lead to neuroplastic processes that very likely represent the reduced demand for attentional control while sub-components of the task become more routinized with practice. We suggest that future research investigate neural correlates of WM training in populations for which WM itself is impaired and/or behavioural trials of WM training have returned more promising results. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Functional imaging of implicit marijuana associations during performance on an Implicit Association Test (IAT)

    NARCIS (Netherlands)

    Ames, S.L.; Grenard, J.L.; Stacy, A.W.; Xiao, L.; He, Q.; Wong, S.W; Xue, G.; Wiers, R.W.; Bechara, A.

    2013-01-01

    This research evaluated the neural correlates of implicit associative memory processes (habit-based processes) through the imaging (fMRI) of a marijuana Implicit Association Test. Drug-related associative memory effects have been shown to consistently predict level of drug use. To observe

  4. Bayesian Inference for Linear Parabolic PDEs with Noisy Boundary Conditions

    KAUST Repository

    Ruggeri, Fabrizio; Sawlan, Zaid A; Scavino, Marco; Tempone, Raul

    2016-01-01

    In this work we develop a hierarchical Bayesian setting to infer unknown parameters in initial-boundary value problems (IBVPs) for one-dimensional linear parabolic partial differential equations. Noisy boundary data and known initial condition are assumed. We derive the likelihood function associated with the forward problem, given some measurements of the solution field subject to Gaussian noise. Such function is then analytically marginalized using the linearity of the equation. Gaussian priors have been assumed for the time-dependent Dirichlet boundary values. Our approach is applied to synthetic data for the one-dimensional heat equation model, where the thermal diffusivity is the unknown parameter. We show how to infer the thermal diffusivity parameter when its prior distribution is lognormal or modeled by means of a space-dependent stationary lognormal random field. We use the Laplace method to provide approximated Gaussian posterior distributions for the thermal diffusivity. Expected information gains and predictive posterior densities for observable quantities are numerically estimated for different experimental setups.

  5. Bayesian Inference for Linear Parabolic PDEs with Noisy Boundary Conditions

    KAUST Repository

    Ruggeri, Fabrizio

    2015-01-07

    In this work we develop a hierarchical Bayesian setting to infer unknown parameters in initial-boundary value problems (IBVPs) for one-dimensional linear parabolic partial differential equations. Noisy boundary data and known initial condition are assumed. We derive the likelihood function associated with the forward problem, given some measurements of the solution field subject to Gaussian noise. Such function is then analytically marginalized using the linearity of the equation. Gaussian priors have been assumed for the time-dependent Dirichlet boundary values. Our approach is applied to synthetic data for the one-dimensional heat equation model, where the thermal diffusivity is the unknown parameter. We show how to infer the thermal diffusivity parameter when its prior distribution is lognormal or modeled by means of a space-dependent stationary lognormal random field. We use the Laplace method to provide approximated Gaussian posterior distributions for the thermal diffusivity. Expected information gains and predictive posterior densities for observable quantities are numerically estimated for different experimental setups.

  6. Bayesian Inference for Linear Parabolic PDEs with Noisy Boundary Conditions

    KAUST Repository

    Ruggeri, Fabrizio

    2016-01-06

    In this work we develop a hierarchical Bayesian setting to infer unknown parameters in initial-boundary value problems (IBVPs) for one-dimensional linear parabolic partial differential equations. Noisy boundary data and known initial condition are assumed. We derive the likelihood function associated with the forward problem, given some measurements of the solution field subject to Gaussian noise. Such function is then analytically marginalized using the linearity of the equation. Gaussian priors have been assumed for the time-dependent Dirichlet boundary values. Our approach is applied to synthetic data for the one-dimensional heat equation model, where the thermal diffusivity is the unknown parameter. We show how to infer the thermal diffusivity parameter when its prior distribution is lognormal or modeled by means of a space-dependent stationary lognormal random field. We use the Laplace method to provide approximated Gaussian posterior distributions for the thermal diffusivity. Expected information gains and predictive posterior densities for observable quantities are numerically estimated for different experimental setups.

  7. Bayesian inference of chemical kinetic models from proposed reactions

    KAUST Repository

    Galagali, Nikhil; Marzouk, Youssef M.

    2015-01-01

    © 2014 Elsevier Ltd. Bayesian inference provides a natural framework for combining experimental data with prior knowledge to develop chemical kinetic models and quantify the associated uncertainties, not only in parameter values but also in model

  8. Human Inferences about Sequences: A Minimal Transition Probability Model.

    Directory of Open Access Journals (Sweden)

    Florent Meyniel

    2016-12-01

    Full Text Available The brain constantly infers the causes of the inputs it receives and uses these inferences to generate statistical expectations about future observations. Experimental evidence for these expectations and their violations include explicit reports, sequential effects on reaction times, and mismatch or surprise signals recorded in electrophysiology and functional MRI. Here, we explore the hypothesis that the brain acts as a near-optimal inference device that constantly attempts to infer the time-varying matrix of transition probabilities between the stimuli it receives, even when those stimuli are in fact fully unpredictable. This parsimonious Bayesian model, with a single free parameter, accounts for a broad range of findings on surprise signals, sequential effects and the perception of randomness. Notably, it explains the pervasive asymmetry between repetitions and alternations encountered in those studies. Our analysis suggests that a neural machinery for inferring transition probabilities lies at the core of human sequence knowledge.

  9. Value functions on simple algebras, and associated graded rings

    CERN Document Server

    Tignol, Jean-Pierre

    2015-01-01

    This monograph is the first book-length treatment of valuation theory on finite-dimensional division algebras, a subject of active and substantial research over the last forty years. Its development was spurred in the last decades of the twentieth century by important advances such as Amitsur's construction of noncrossed products and Platonov's solution of the Tannaka-Artin problem. This study is particularly timely because it approaches the subject from the perspective of associated graded structures. This new approach has been developed by the authors in the last few years and has significantly clarified the theory. Various constructions of division algebras are obtained as applications of the theory, such as noncrossed products and indecomposable algebras. In addition, the use of valuation theory in reduced Whitehead group calculations (after Hazrat and Wadsworth) and in essential dimension computations (after Baek and Merkurjev) is showcased. The intended audience consists of graduate students and researc...

  10. Association of Canine Osteosarcoma and Monocyte Phenotype and Chemotactic Function.

    Science.gov (United States)

    Tuohy, J L; Lascelles, B D X; Griffith, E H; Fogle, J E

    2016-07-01

    Monocytes/macrophages are likely key cells in immune modulation in dogs with osteosarcoma (OSA). Increased peripheral monocyte counts are negatively correlated with shorter disease-free intervals in dogs with OSA. Understanding the monocyte/macrophage's modulatory role in dogs with OSA can direct further studies in immunotherapy development for OSA. That OSA evades the immune response by down-regulating monocyte chemokine receptor expression and migratory function, and suppresses host immune responses. Eighteen dogs with OSA that have not received definitive treatment and 14 healthy age-matched controls Clinical study-expression of peripheral blood monocyte cell surface receptors, monocyte mRNA expression and cytokine secretion, monocyte chemotaxis, and survival were compared between clinical dogs with OSA and healthy control dogs. Cell surface expression of multiple chemokine receptors is significantly down-regulated in peripheral blood monocytes of dogs with OSA. The percentage expression of CCR2 (median 58%, range 2-94%) and CXCR2 expression (median 54%, range 2-92%) was higher in control dogs compared to dogs with OSA (CCR2 median 29%, range 3-45%, P = 0.0006; CXCR2 median 23%, range 0.2-52%, P = 0.0007). Prostaglandin E2 (PGE2 ) (OSA, median 347.36 pg/mL, range 103.4-1268.5; control, 136.23 pg/mL, range 69.93-542.6, P = .04) and tumor necrosis factor-alpha (TNF-α) (P = .02) levels are increased in OSA monocyte culture supernatants compared to controls. Peripheral blood monocytes of dogs with OSA exhibit decreased chemotactic function when compared to control dogs (OSA, median 1.2 directed to random migration, range 0.8-1.25; control, 1.6, range of 0.9-1.8, P = .018). Dogs with OSA have decreased monocyte chemokine receptor expression and monocyte chemotaxis, potential mechanisms by which OSA might evade the immune response. Reversal of monocyte dysfunction using immunotherapy could improve survival in dogs with OSA. Copyright © 2016 The Authors. Journal of

  11. 75 FR 70162 - Presumptive Service Connection for Diseases Associated With Persian Gulf War Service: Functional...

    Science.gov (United States)

    2010-11-17

    ... Diseases Associated With Persian Gulf War Service: Functional Gastrointestinal Disorders AGENCY: Department... theater of operations during the Persian Gulf War. DATES: Comments must be received by VA on or before... Service Connection for Diseases Associated With Persian Gulf War Service: Functional Gastrointestinal...

  12. CT-quantified emphysema distribution is associated with lung function decline

    NARCIS (Netherlands)

    Hoesein, F.A.A.M.; Rikxoort, E.M. van; Ginneken, B. van; de Jong, P. A.; Prokop, M.; Lammers, J.W.; Zanen, P.

    2012-01-01

    Emphysema distribution is associated with COPD. It is however unknown whether CT-quantified emphysema distribution (upper/lower lobe) is associated with lung function decline in heavy (former) smokers.587 male participants underwent lung CT-scanning and pulmonary function testing at baseline and

  13. Towards a sustainable healthy working life : associations between chronological age, functional age and work outcomes

    NARCIS (Netherlands)

    Koolhaas, Wendy; van der Klink, Jac J. L.; Groothoff, Johan W.; Brouwer, Sandra

    Background: The aims of this study were: (i) to determine the relation between chronological and functional age; (ii) to examine the association between chronological age and work outcomes; and (iii) to examine the association between functional age and work outcomes. An overview of the most

  14. Contingency inferences driven by base rates: Valid by sampling

    Directory of Open Access Journals (Sweden)

    Florian Kutzner

    2011-04-01

    Full Text Available Fiedler et al. (2009, reviewed evidence for the utilization of a contingency inference strategy termed pseudocontingencies (PCs. In PCs, the more frequent levels (and, by implication, the less frequent levels are assumed to be associated. PCs have been obtained using a wide range of task settings and dependent measures. Yet, the readiness with which decision makers rely on PCs is poorly understood. A computer simulation explored two potential sources of subjective validity of PCs. First, PCs are shown to perform above chance level when the task is to infer the sign of moderate to strong population contingencies from a sample of observations. Second, contingency inferences based on PCs and inferences based on cell frequencies are shown to partially agree across samples. Intriguingly, this criterion and convergent validity are by-products of random sampling error, highlighting the inductive nature of contingency inferences.

  15. The inference from a single case: moral versus scientific inferences in implementing new biotechnologies.

    Science.gov (United States)

    Hofmann, B

    2008-06-01

    Are there similarities between scientific and moral inference? This is the key question in this article. It takes as its point of departure an instance of one person's story in the media changing both Norwegian public opinion and a brand-new Norwegian law prohibiting the use of saviour siblings. The case appears to falsify existing norms and to establish new ones. The analysis of this case reveals similarities in the modes of inference in science and morals, inasmuch as (a) a single case functions as a counter-example to an existing rule; (b) there is a common presupposition of stability, similarity and order, which makes it possible to reason from a few cases to a general rule; and (c) this makes it possible to hold things together and retain order. In science, these modes of inference are referred to as falsification, induction and consistency. In morals, they have a variety of other names. Hence, even without abandoning the fact-value divide, there appear to be similarities between inference in science and inference in morals, which may encourage communication across the boundaries between "the two cultures" and which are relevant to medical humanities.

  16. Unique associations between young adult men's emotional functioning and their body dissatisfaction and disordered eating.

    Science.gov (United States)

    Griffiths, Scott; Angus, Douglas; Murray, Stuart B; Touyz, Stephen

    2014-03-01

    Research on emotional functioning, body dissatisfaction, and disordered eating in males is predominated by studies of negative affect and emotion regulation. Other aspects of emotional functioning, namely emotion recognition and attentional biases toward emotional stimuli, have received little empirical attention. The present study investigated the unique associations between different aspects of men's emotional functioning and their disordered eating attitudes, muscularity dissatisfaction, and body fat dissatisfaction. Results from 132 male undergraduates showed that muscularity dissatisfaction was uniquely associated with both emotion regulation difficulties and an attentional bias toward rejecting faces. Body fat dissatisfaction was not uniquely associated with any aspect of emotional functioning. Disordered eating was uniquely associated with emotion regulation difficulties. Collectively, the results indicate differences in the patterns of associations between men's emotional functioning and their body dissatisfaction and disordered eating. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Active inference, sensory attenuation and illusions.

    Science.gov (United States)

    Brown, Harriet; Adams, Rick A; Parees, Isabel; Edwards, Mark; Friston, Karl

    2013-11-01

    Active inference provides a simple and neurobiologically plausible account of how action and perception are coupled in producing (Bayes) optimal behaviour. This can be seen most easily as minimising prediction error: we can either change our predictions to explain sensory input through perception. Alternatively, we can actively change sensory input to fulfil our predictions. In active inference, this action is mediated by classical reflex arcs that minimise proprioceptive prediction error created by descending proprioceptive predictions. However, this creates a conflict between action and perception; in that, self-generated movements require predictions to override the sensory evidence that one is not actually moving. However, ignoring sensory evidence means that externally generated sensations will not be perceived. Conversely, attending to (proprioceptive and somatosensory) sensations enables the detection of externally generated events but precludes generation of actions. This conflict can be resolved by attenuating the precision of sensory evidence during movement or, equivalently, attending away from the consequences of self-made acts. We propose that this Bayes optimal withdrawal of precise sensory evidence during movement is the cause of psychophysical sensory attenuation. Furthermore, it explains the force-matching illusion and reproduces empirical results almost exactly. Finally, if attenuation is removed, the force-matching illusion disappears and false (delusional) inferences about agency emerge. This is important, given the negative correlation between sensory attenuation and delusional beliefs in normal subjects--and the reduction in the magnitude of the illusion in schizophrenia. Active inference therefore links the neuromodulatory optimisation of precision to sensory attenuation and illusory phenomena during the attribution of agency in normal subjects. It also provides a functional account of deficits in syndromes characterised by false inference

  18. Prospective associations between bilingualism and executive function in Latino children: sustained effects while controlling for biculturalism.

    Science.gov (United States)

    Riggs, Nathaniel R; Shin, Hee-Sung; Unger, Jennifer B; Spruijt-Metz, Donna; Pentz, Mary Ann

    2014-10-01

    The study purpose was to test 1-year prospective associations between English-Spanish bilingualism and executive function in 5th to 6th grade students while controlling for biculturalism. Participants included 182 US Latino students (50 % female). Self-report surveys assessed biculturalism, bilingualism, and executive function (i.e., working memory, organizational skills, inhibitory control, and emotional control, as well as a summary executive function score). General linear model regressions demonstrated that bilingualism significantly predicted the summary executive function score as well as working memory such that bilingual proficiency was positively related to executive function. Results are the first to demonstrate (a) prospective associations between bilingualism to executive function while controlling for the potential third variable of biculturalism, and (b) a principal role for working memory in this relationship. Since executive function is associated with a host of health outcomes, one implication of study findings is that bilingualism may have an indirect protective influence on youth development.

  19. Longitudinal associations between parental bonding, parenting stress, and executive functioning in toddlerhood

    OpenAIRE

    De Cock, E.S.A.; Henrichs, J.; Klimstra, T.A.; Maas, A.J.B.M.; Vreeswijk, C.M.J.M.; Meeus, W.H.J.; Van Bakel, H.J.A.

    2017-01-01

    Early executive functioning is an important predictor for future development of children’s cognitive skills and behavioral outcomes. Parenting behavior has proven to be a key environmental determinant of child executive functioning. However, the association of parental affect and cognitions directed to the child with child executive functioning has been understudied. Therefore, in the present study we examine the associations between parental bonding (i.e., the affective tie from parent to ch...

  20. Systemic Inflammation in Duchenne Muscular Dystrophy: Association with Muscle Function and Nutritional Status

    OpenAIRE

    Oriana del Rocío Cruz-Guzmán; Maricela Rodríguez-Cruz; Rosa Elena Escobar Cedillo

    2015-01-01

    Inflammation described in patients with Duchenne muscular dystrophy (DMD) may be related to loss of muscle function or to obesity. It is unknown if circulating proinflammatory cytokines (IL-6, IL-1, and TNF-α) levels are associated with muscle function. The purpose was to evaluate whether an association exists between systemic inflammation with muscle function and nutritional status in DMD patients. In 66 DMD patients without corticosteroid treatment, the following were evaluated in serum: cy...

  1. Functional Task Test: 1. Sensorimotor changes Associated with Postflight Alterations in Astronaut Functional Task Performance

    Science.gov (United States)

    Bloomberg, J. J.; Arzeno, N. H.; Buxton, R. E.; Feiveson, A. H.; Kofman, I. S.; Lee, S. M. C.; Miller, C. A.; Mulavara, A. P.; Platts, S. H.; Peters, B. T.; hide

    2011-01-01

    Space flight is known to cause alterations in multiple physiological systems including changes in sensorimotor, cardiovascular, and neuromuscular systems. These changes may affect a crewmember s ability to perform critical mission tasks immediately after landing on a planetary surface. The overall goal of this project is to determine the effects of space flight on functional tests that are representative of high priority exploration mission tasks and to identify the key underlying physiological factors that contribute to decrements in performance. This presentation will focus on the sensorimotor contributions to postflight functional performance.

  2. Optimization methods for logical inference

    CERN Document Server

    Chandru, Vijay

    2011-01-01

    Merging logic and mathematics in deductive inference-an innovative, cutting-edge approach. Optimization methods for logical inference? Absolutely, say Vijay Chandru and John Hooker, two major contributors to this rapidly expanding field. And even though ""solving logical inference problems with optimization methods may seem a bit like eating sauerkraut with chopsticks. . . it is the mathematical structure of a problem that determines whether an optimization model can help solve it, not the context in which the problem occurs."" Presenting powerful, proven optimization techniques for logic in

  3. Functional Associations by Response Overlap (FARO), a functional genomics approach matching gene expression phenotypes

    DEFF Research Database (Denmark)

    Nielsen, Henrik Bjørn; Mundy, J.; Willenbrock, Hanni

    2007-01-01

    The systematic comparison of transcriptional responses of organisms is a powerful tool in functional genomics. For example, mutants may be characterized by comparing their transcript profiles to those obtained in other experiments querying the effects on gene expression of many experimental facto...

  4. Inference of R(0 and transmission heterogeneity from the size distribution of stuttering chains.

    Directory of Open Access Journals (Sweden)

    Seth Blumberg

    Full Text Available For many infectious disease processes such as emerging zoonoses and vaccine-preventable diseases, [Formula: see text] and infections occur as self-limited stuttering transmission chains. A mechanistic understanding of transmission is essential for characterizing the risk of emerging diseases and monitoring spatio-temporal dynamics. Thus methods for inferring [Formula: see text] and the degree of heterogeneity in transmission from stuttering chain data have important applications in disease surveillance and management. Previous researchers have used chain size distributions to infer [Formula: see text], but estimation of the degree of individual-level variation in infectiousness (as quantified by the dispersion parameter, [Formula: see text] has typically required contact tracing data. Utilizing branching process theory along with a negative binomial offspring distribution, we demonstrate how maximum likelihood estimation can be applied to chain size data to infer both [Formula: see text] and the dispersion parameter that characterizes heterogeneity. While the maximum likelihood value for [Formula: see text] is a simple function of the average chain size, the associated confidence intervals are dependent on the inferred degree of transmission heterogeneity. As demonstrated for monkeypox data from the Democratic Republic of Congo, this impacts when a statistically significant change in [Formula: see text] is detectable. In addition, by allowing for superspreading events, inference of [Formula: see text] shifts the threshold above which a transmission chain should be considered anomalously large for a given value of [Formula: see text] (thus reducing the probability of false alarms about pathogen adaptation. Our analysis of monkeypox also clarifies the various ways that imperfect observation can impact inference of transmission parameters, and highlights the need to quantitatively evaluate whether observation is likely to significantly bias results.

  5. Inference of miRNA targets using evolutionary conservation and pathway analysis

    Directory of Open Access Journals (Sweden)

    van Nimwegen Erik

    2007-03-01

    Full Text Available Abstract Background MicroRNAs have emerged as important regulatory genes in a variety of cellular processes and, in recent years, hundreds of such genes have been discovered in animals. In contrast, functional annotations are available only for a very small fraction of these miRNAs, and even in these cases only partially. Results We developed a general Bayesian method for the inference of miRNA target sites, in which, for each miRNA, we explicitly model the evolution of orthologous target sites in a set of related species. Using this method we predict target sites for all known miRNAs in flies, worms, fish, and mammals. By comparing our predictions in fly with a reference set of experimentally tested miRNA-mRNA interactions we show that our general method performs at least as well as the most accurate methods available to date, including ones specifically tailored for target prediction in fly. An important novel feature of our model is that it explicitly infers the phylogenetic distribution of functional target sites, independently for each miRNA. This allows us to infer species-specific and clade-specific miRNA targeting. We also show that, in long human 3' UTRs, miRNA target sites occur preferentially near the start and near the end of the 3' UTR. To characterize miRNA function beyond the predicted lists of targets we further present a method to infer significant associations between the sets of targets predicted for individual miRNAs and specific biochemical pathways, in particular those of the KEGG pathway database. We show that this approach retrieves several known functional miRNA-mRNA associations, and predicts novel functions for known miRNAs in cell growth and in development. Conclusion We have presented a Bayesian target prediction algorithm without any tunable parameters, that can be applied to sequences from any clade of species. The algorithm automatically infers the phylogenetic distribution of functional sites for each miRNA, and

  6. On principles of inductive inference

    OpenAIRE

    Kostecki, Ryszard Paweł

    2011-01-01

    We propose an intersubjective epistemic approach to foundations of probability theory and statistical inference, based on relative entropy and category theory, and aimed to bypass the mathematical and conceptual problems of existing foundational approaches.

  7. Statistical inference via fiducial methods

    OpenAIRE

    Salomé, Diemer

    1998-01-01

    In this thesis the attention is restricted to inductive reasoning using a mathematical probability model. A statistical procedure prescribes, for every theoretically possible set of data, the inference about the unknown of interest. ... Zie: Summary

  8. Statistical inference for stochastic processes

    National Research Council Canada - National Science Library

    Basawa, Ishwar V; Prakasa Rao, B. L. S

    1980-01-01

    The aim of this monograph is to attempt to reduce the gap between theory and applications in the area of stochastic modelling, by directing the interest of future researchers to the inference aspects...

  9. Executive dysfunction is independently associated with reduced functional independence in heart failure.

    Science.gov (United States)

    Alosco, Michael L; Spitznagel, Mary Beth; Raz, Naftali; Cohen, Ronald; Sweet, Lawrence H; Colbert, Lisa H; Josephson, Richard; van Dulmen, Manfred; Hughes, Joel; Rosneck, Jim; Gunstad, John

    2014-03-01

    To examine the independent association between executive function with instrumental activities of daily living and health behaviours in older adults with heart failure. Executive function is an important contributor to functional independence as it consists of cognitive processes needed for decision-making, planning, organising and behavioural monitoring. Impairment in this domain is common in heart failure patients and associated with reduced performance of instrumental activities of daily living in many medical and neurological populations. However, the contribution of executive functions to functional independence and healthy lifestyle choices in heart failure patients has not been fully examined. Cross-sectional analyses. One hundred and seventy-five heart failure patients completed a neuropsychological battery and echocardiogram. Participants also completed the Lawton-Brody Instrumental Activities of Daily Living Scale and reported current cigarette use. Hierarchical regressions revealed that reduced executive function was independently associated with worse instrumental activity of daily living performance with a specific association for decreased ability to manage medications. Partial correlations showed that executive dysfunction was associated with current cigarette use. Our findings suggest that executive dysfunction is associated with poorer functional independence and contributes to unhealthy behaviours in heart failure. Future studies should examine whether heart failure patients benefit from formal organisation schema (i.e. pill organisers) to maintain independence. Screening of executive function in heart failure patients may provide key insight into their ability to perform daily tasks, including the management of treatment recommendations. © 2013 John Wiley & Sons Ltd.

  10. Lower lung function associates with cessation of menstruation: UK Biobank data.

    Science.gov (United States)

    Amaral, André F S; Strachan, David P; Gómez Real, Francisco; Burney, Peter G J; Jarvis, Deborah L

    2016-11-01

    Little is known about the effect of cessation of menstruation on lung function. The aims of the study were to examine the association of lung function with natural and surgical cessation of menstruation, and assess whether lower lung function is associated with earlier age at cessation of menstruation.The study was performed in 141 076 women from the UK Biobank, who had provided acceptable and reproducible spirometry measurements and information on menstrual status. The associations of lung function (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1 ), spirometric restriction (FVC menstruation and age at cessation of menstruation were assessed using regression analysis.Women who had natural cessation of menstruation showed a lower FVC (-42 mL; 95% CI -53- -30) and FEV 1 (-34 mL; 95% CI -43- -24) and higher risk of spirometric restriction (adjusted odds ratio 1.27; 95% CI 1.18-1.37) than women still menstruating. These associations were stronger in women who had had a hysterectomy and/or oophorectomy. The earlier the natural cessation of menstruation, the lower the lung function. There was no clear association of lung function with age at hysterectomy and/or oophorectomy. Airflow obstruction was not associated with cessation of menstruation.Lower lung function associates with cessation of menstruation, especially if it occurs early in life. Copyright ©ERS 2016.

  11. Physical Performance Is Associated with Executive Functioning in Older African American Women

    Directory of Open Access Journals (Sweden)

    Brooke C. Schneider

    2011-01-01

    Full Text Available An older adult's ability to perform physical tasks is predictive of disability onset and is associated with declines in cognition. Risk factors for physical performance declines among African Americans, a group with the highest rates of disability, remain understudied. This study sought to identify demographic, health, and cognitive factors associated with lower-extremity physical performance in a sample of 106 African American women ages 56 to 91. After controlling for global cognitive functioning (Mini Mental State Exam, physical performance was associated with executive functioning (Stroop Color/Word, but not visuospatial construction (WASI Block Design or processing speed (Trail Making Test, Part A. Executive functioning remained associated with physical performance after entry of demographic variables, exercise, depression, disease burden, and body mass index (BMI. Age, and BMI were also significant in this model. Executive functioning, age and BMI are associated with lower-extremity physical performance among older African American women.

  12. The association between cognitive function and white matter lesion location in older adults: a systematic review

    Directory of Open Access Journals (Sweden)

    Bolandzadeh Niousha

    2012-10-01

    Full Text Available Abstract Background Maintaining cognitive function is essential for healthy aging and to function autonomously within society. White matter lesions (WMLs are associated with reduced cognitive function in older adults. However, whether their anatomical location moderates these associations is not well-established. This review systematically evaluates peer-reviewed evidence on the role of anatomical location in the association between WMLs and cognitive function. Methods In accordance with the preferred reporting items for systematic reviews and meta-analysis (PRISMA statement, databases of EMBASE, PUBMED, MEDLINE, and CINAHL, and reference lists of selected papers were searched. We limited our search results to adults aged 60 years and older, and studies published in the English language from 2000 to 2011. Studies that investigated the association between cognitive function and WML location were included. Two independent reviewers extracted: 1 study characteristics including sample size, sample characteristic, and study design; 2 WML outcomes including WML location, WML quantification method (scoring or volume measurement, strength of the MRI magnet in Tesla, and MRI sequence used for WML detection; and 3 cognitive function outcomes including cognitive tests for two cognitive domains of memory and executive function/processing speed. Results Of the 14 studies included, seven compared the association of subcortical versus periventricular WMLs with cognitive function. Seven other studies investigated the association between WMLs in specific brain regions (e.g., frontal, parietal lobes and cognitive function. Overall, the results show that a greater number of studies have found an association between periventricular WMLs and executive function/processing speed, than subcortical WMLs. However, whether WMLs in different brain regions have a differential effect on cognitive function remains unclear. Conclusions Evidence suggests that periventricular

  13. Lack of association between a functional variant of the BRCA-1 related associated protein (BRAP) gene and ischemic stroke

    OpenAIRE

    Liao, Yi-Chu; Lin, Hsiu-Fen; Guo, Yuh-Cherng; Chen, Chung-Hung; Huang, Zhi-Zhang; Juo, Suh-Hang Hank; Lin, Ruey-Tay

    2013-01-01

    Abstract Background Atherosclerosis shares common pathogenic features with myocardial infarction (MI) and ischemic stroke. BRCA-1 associated protein (BRAP), a newly identified risk gene for MI, aggravates the inflammatory response in atherosclerosis. The aim of this study was to test the association between the BRAP gene and stroke in a Taiwanese population. Methods A total of 1,074 stroke patients and 1,936 controls were genotyped for the functional SNP rs11066001. In our previous studies, t...

  14. Active inference, communication and hermeneutics.

    Science.gov (United States)

    Friston, Karl J; Frith, Christopher D

    2015-07-01

    Hermeneutics refers to interpretation and translation of text (typically ancient scriptures) but also applies to verbal and non-verbal communication. In a psychological setting it nicely frames the problem of inferring the intended content of a communication. In this paper, we offer a solution to the problem of neural hermeneutics based upon active inference. In active inference, action fulfils predictions about how we will behave (e.g., predicting we will speak). Crucially, these predictions can be used to predict both self and others--during speaking and listening respectively. Active inference mandates the suppression of prediction errors by updating an internal model that generates predictions--both at fast timescales (through perceptual inference) and slower timescales (through perceptual learning). If two agents adopt the same model, then--in principle--they can predict each other and minimise their mutual prediction errors. Heuristically, this ensures they are singing from the same hymn sheet. This paper builds upon recent work on active inference and communication to illustrate perceptual learning using simulated birdsongs. Our focus here is the neural hermeneutics implicit in learning, where communication facilitates long-term changes in generative models that are trying to predict each other. In other words, communication induces perceptual learning and enables others to (literally) change our minds and vice versa. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Walking smoothness is associated with self-reported function after accounting for gait speed.

    Science.gov (United States)

    Lowry, Kristin A; Vanswearingen, Jessie M; Perera, Subashan; Studenski, Stephanie A; Brach, Jennifer S

    2013-10-01

    Gait speed has shown to be an indicator of functional status in older adults; however, there may be aspects of physical function not represented by speed but by the quality of movement. The purpose of this study was to determine the relations between walking smoothness, an indicator of the quality of movement based on trunk accelerations, and physical function. Thirty older adults (mean age, 77.7±5.1 years) participated. Usual gait speed was measured using an instrumented walkway. Walking smoothness was quantified by harmonic ratios derived from anteroposterior, vertical, and mediolateral trunk accelerations recorded during overground walking. Self-reported physical function was recorded using the function subscales of the Late-Life Function and Disability Instrument. Anteroposterior smoothness was positively associated with all function components of the Late-Life Function and Disability Instrument, whereas mediolateral smoothness exhibited negative associations. Adjusting for gait speed, anteroposterior smoothness remained associated with the overall and lower extremity function subscales, whereas mediolateral smoothness remained associated with only the advanced lower extremity subscale. These findings indicate that walking smoothness, particularly the smoothness of forward progression, represents aspects of the motor control of walking important for physical function not represented by gait speed alone.

  16. Inference of a Nonlinear Stochastic Model of the Cardiorespiratory Interaction

    Science.gov (United States)

    Smelyanskiy, V. N.; Luchinsky, D. G.; Stefanovska, A.; McClintock, P. V.

    2005-03-01

    We reconstruct a nonlinear stochastic model of the cardiorespiratory interaction in terms of a set of polynomial basis functions representing the nonlinear force governing system oscillations. The strength and direction of coupling and noise intensity are simultaneously inferred from a univariate blood pressure signal. Our new inference technique does not require extensive global optimization, and it is applicable to a wide range of complex dynamical systems subject to noise.

  17. Longstanding Hyperthyroidism Is Associated with Normal or Enhanced Intrinsic Cardiomyocyte Function despite Decline in Global Cardiac Function

    Science.gov (United States)

    Redetzke, Rebecca A.; Gerdes, A. Martin

    2012-01-01

    Thyroid hormones (THs) play a pivotal role in cardiac homeostasis. TH imbalances alter cardiac performance and ultimately cause cardiac dysfunction. Although short-term hyperthyroidism typically leads to heightened left ventricular (LV) contractility and improved hemodynamic parameters, chronic hyperthyroidism is associated with deleterious cardiac consequences including increased risk of arrhythmia, impaired cardiac reserve and exercise capacity, myocardial remodeling, and occasionally heart failure. To evaluate the long-term consequences of chronic hyperthyroidism on LV remodeling and function, we examined LV isolated myocyte function, chamber function, and whole tissue remodeling in a hamster model. Three-month-old F1b hamsters were randomized to control or 10 months TH treatment (0.1% grade I desiccated TH). LV chamber remodeling and function was assessed by echocardiography at 1, 2, 4, 6, 8, and 10 months of treatment. After 10 months, terminal cardiac function was assessed by echocardiography and LV hemodynamics. Hyperthyroid hamsters exhibited significant cardiac hypertrophy and deleterious cardiac remodeling characterized by myocyte lengthening, chamber dilatation, decreased relative wall thickness, increased wall stress, and increased LV interstitial fibrotic deposition. Importantly, hyperthyroid hamsters demonstrated significant LV systolic and diastolic dysfunction. Despite the aforementioned remodeling and global cardiac decline, individual isolated cardiac myocytes from chronically hyperthyroid hamsters had enhanced function when compared with myocytes from untreated age-matched controls. Thus, it appears that long-term hyperthyroidism may impair global LV function, at least in part by increasing interstitial ventricular fibrosis, in spite of normal or enhanced intrinsic cardiomyocyte function. PMID:23056390

  18. Longstanding hyperthyroidism is associated with normal or enhanced intrinsic cardiomyocyte function despite decline in global cardiac function.

    Directory of Open Access Journals (Sweden)

    Nathan Y Weltman

    Full Text Available Thyroid hormones (THs play a pivotal role in cardiac homeostasis. TH imbalances alter cardiac performance and ultimately cause cardiac dysfunction. Although short-term hyperthyroidism typically leads to heightened left ventricular (LV contractility and improved hemodynamic parameters, chronic hyperthyroidism is associated with deleterious cardiac consequences including increased risk of arrhythmia, impaired cardiac reserve and exercise capacity, myocardial remodeling, and occasionally heart failure. To evaluate the long-term consequences of chronic hyperthyroidism on LV remodeling and function, we examined LV isolated myocyte function, chamber function, and whole tissue remodeling in a hamster model. Three-month-old F1b hamsters were randomized to control or 10 months TH treatment (0.1% grade I desiccated TH. LV chamber remodeling and function was assessed by echocardiography at 1, 2, 4, 6, 8, and 10 months of treatment. After 10 months, terminal cardiac function was assessed by echocardiography and LV hemodynamics. Hyperthyroid hamsters exhibited significant cardiac hypertrophy and deleterious cardiac remodeling characterized by myocyte lengthening, chamber dilatation, decreased relative wall thickness, increased wall stress, and increased LV interstitial fibrotic deposition. Importantly, hyperthyroid hamsters demonstrated significant LV systolic and diastolic dysfunction. Despite the aforementioned remodeling and global cardiac decline, individual isolated cardiac myocytes from chronically hyperthyroid hamsters had enhanced function when compared with myocytes from untreated age-matched controls. Thus, it appears that long-term hyperthyroidism may impair global LV function, at least in part by increasing interstitial ventricular fibrosis, in spite of normal or enhanced intrinsic cardiomyocyte function.

  19. Inferring genetic interactions from comparative fitness data.

    Science.gov (United States)

    Crona, Kristina; Gavryushkin, Alex; Greene, Devin; Beerenwinkel, Niko

    2017-12-20

    Darwinian fitness is a central concept in evolutionary biology. In practice, however, it is hardly possible to measure fitness for all genotypes in a natural population. Here, we present quantitative tools to make inferences about epistatic gene interactions when the fitness landscape is only incompletely determined due to imprecise measurements or missing observations. We demonstrate that genetic interactions can often be inferred from fitness rank orders, where all genotypes are ordered according to fitness, and even from partial fitness orders. We provide a complete characterization of rank orders that imply higher order epistasis. Our theory applies to all common types of gene interactions and facilitates comprehensive investigations of diverse genetic interactions. We analyzed various genetic systems comprising HIV-1, the malaria-causing parasite Plasmodium vivax , the fungus Aspergillus niger , and the TEM-family of β-lactamase associated with antibiotic resistance. For all systems, our approach revealed higher order interactions among mutations.

  20. Parametric inference for biological sequence analysis.

    Science.gov (United States)

    Pachter, Lior; Sturmfels, Bernd

    2004-11-16

    One of the major successes in computational biology has been the unification, by using the graphical model formalism, of a multitude of algorithms for annotating and comparing biological sequences. Graphical models that have been applied to these problems include hidden Markov models for annotation, tree models for phylogenetics, and pair hidden Markov models for alignment. A single algorithm, the sum-product algorithm, solves many of the inference problems that are associated with different statistical models. This article introduces the polytope propagation algorithm for computing the Newton polytope of an observation from a graphical model. This algorithm is a geometric version of the sum-product algorithm and is used to analyze the parametric behavior of maximum a posteriori inference calculations for graphical models.

  1. Associations between soil bacterial community structure and nutrient cycling functions in long-term organic farm soils following cover crop and organic fertilizer amendment.

    Science.gov (United States)

    Fernandez, Adria L; Sheaffer, Craig C; Wyse, Donald L; Staley, Christopher; Gould, Trevor J; Sadowsky, Michael J

    2016-10-01

    Agricultural management practices can produce changes in soil microbial populations whose functions are crucial to crop production and may be detectable using high-throughput sequencing of bacterial 16S rRNA. To apply sequencing-derived bacterial community structure data to on-farm decision-making will require a better understanding of the complex associations between soil microbial community structure and soil function. Here 16S rRNA sequencing was used to profile soil bacterial communities following application of cover crops and organic fertilizer treatments in certified organic field cropping systems. Amendment treatments were hairy vetch (Vicia villosa), winter rye (Secale cereale), oilseed radish (Raphanus sativus), buckwheat (Fagopyrum esculentum), beef manure, pelleted poultry manure, Sustane(®) 8-2-4, and a no-amendment control. Enzyme activities, net N mineralization, soil respiration, and soil physicochemical properties including nutrient levels, organic matter (OM) and pH were measured. Relationships between these functional and physicochemical parameters and soil bacterial community structure were assessed using multivariate methods including redundancy analysis, discriminant analysis, and Bayesian inference. Several cover crops and fertilizers affected soil functions including N-acetyl-β-d-glucosaminidase and β-glucosidase activity. Effects, however, were not consistent across locations and sampling timepoints. Correlations were observed among functional parameters and relative abundances of individual bacterial families and phyla. Bayesian analysis inferred no directional relationships between functional activities, bacterial families, and physicochemical parameters. Soil functional profiles were more strongly predicted by location than by treatment, and differences were largely explained by soil physicochemical parameters. Composition of soil bacterial communities was predictive of soil functional profiles. Differences in soil function were

  2. Association Between Perceived Physical Activity and Cognitive Function in Older Adults.

    Science.gov (United States)

    Loprinzi, Paul D; Frith, Emily

    2018-01-01

    There is irrefutable evidence that regular participation in physical activity is favorably associated with numerous positive health outcomes, including cognitive function. Emerging work suggests that perceived physical activity, independent of actual physical activity behavior, is inversely associated with mortality risk. In this study, we evaluate whether perceived physical activity, independent of actual physical activity, is associated with cognitive function, a robust indicator of mortality risk. Data from the cross-sectional 1999-2002 National Health and Nutrition Examination Survey were employed ( N = 2352; 60+ years of age). Actual physical activity was assessed via a validated survey. Perceived physical activity was assessed using the following question: "Compared with others of the same age, would you say that you are: more active, less active, or about the same?" Cognitive function was assessed from the Digit Symbol Substitution Test. When examined in separate models, both actual and perceived physical activity were positively and statistically significantly associated with cognitive function. However, when considered in the same model, actual physical activity was no longer statistically significantly associated with cognitive function, but perceived physical activity was. Perceived physical activity, independent of actual physical activity, is independently associated with cognitive function. If these findings are replicated, future work should consider evaluating perceived physical activity when examining the effects of actual physical activity behavior on cognitive function.

  3. Fitness, but not physical activity, is related to functional integrity of brain networks associated with aging.

    Science.gov (United States)

    Voss, Michelle W; Weng, Timothy B; Burzynska, Agnieszka Z; Wong, Chelsea N; Cooke, Gillian E; Clark, Rachel; Fanning, Jason; Awick, Elizabeth; Gothe, Neha P; Olson, Erin A; McAuley, Edward; Kramer, Arthur F

    2016-05-01

    Greater physical activity and cardiorespiratory fitness are associated with reduced age-related cognitive decline and lower risk for dementia. However, significant gaps remain in the understanding of how physical activity and fitness protect the brain from adverse effects of brain aging. The primary goal of the current study was to empirically evaluate the independent relationships between physical activity and fitness with functional brain health among healthy older adults, as measured by the functional connectivity of cognitively and clinically relevant resting state networks. To build context for fitness and physical activity associations in older adults, we first demonstrate that young adults have greater within-network functional connectivity across a broad range of cortical association networks. Based on these results and previous research, we predicted that individual differences in fitness and physical activity would be most strongly associated with functional integrity of the networks most sensitive to aging. Consistent with this prediction, and extending on previous research, we showed that cardiorespiratory fitness has a positive relationship with functional connectivity of several cortical networks associated with age-related decline, and effects were strongest in the default mode network (DMN). Furthermore, our results suggest that the positive association of fitness with brain function can occur independent of habitual physical activity. Overall, our findings provide further support that cardiorespiratory fitness is an important factor in moderating the adverse effects of aging on cognitively and clinically relevant functional brain networks. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Fitness, but not physical activity, is related to functional integrity of brain networks associated with aging

    Science.gov (United States)

    Voss, Michelle W.; Weng, Timothy B.; Burzynska, Agnieszka Z.; Wong, Chelsea N.; Cooke, Gillian E.; Clark, Rachel; Fanning, Jason; Awick, Elizabeth; Gothe, Neha P.; Olson, Erin A.; McAuley, Edward; Kramer, Arthur F.

    2015-01-01

    Greater physical activity and cardiorespiratory fitness are associated with reduced age-related cognitive decline and lower risk for dementia. However, significant gaps remain in the understanding of how physical activity and fitness protect the brain from adverse effects of brain aging. The primary goal of the current study was to empirically evaluate the independent relationships between physical activity and fitness with functional brain health among healthy older adults, as measured by the functional connectivity of cognitively and clinically relevant resting state networks. To build context for fitness and physical activity associations in older adults, we first demonstrate that young adults have greater within-network functional connectivity across a broad range of cortical association networks. Based on these results and previous research, we predicted that individual differences in fitness and physical activity would be most strongly associated with functional integrity of the networks most sensitive to aging. Consistent with this prediction, and extending on previous research, we showed that cardiorespiratory fitness has a positive relationship with functional connectivity of several cortical networks associated with age-related decline, and effects were strongest in the Default Mode Network (DMN). Furthermore, our results suggest that the positive association of fitness with brain function can occur independent of habitual physical activity. Overall, our findings provide further support that cardiorespiratory fitness is an important factor in moderating the adverse effects of aging on cognitively and clinically relevant functional brain networks. PMID:26493108

  5. Optimal inference with suboptimal models: Addiction and active Bayesian inference

    Science.gov (United States)

    Schwartenbeck, Philipp; FitzGerald, Thomas H.B.; Mathys, Christoph; Dolan, Ray; Wurst, Friedrich; Kronbichler, Martin; Friston, Karl

    2015-01-01

    When casting behaviour as active (Bayesian) inference, optimal inference is defined with respect to an agent’s beliefs – based on its generative model of the world. This contrasts with normative accounts of choice behaviour, in which optimal actions are considered in relation to the true structure of the environment – as opposed to the agent’s beliefs about worldly states (or the task). This distinction shifts an understanding of suboptimal or pathological behaviour away from aberrant inference as such, to understanding the prior beliefs of a subject that cause them to behave less ‘optimally’ than our prior beliefs suggest they should behave. Put simply, suboptimal or pathological behaviour does not speak against understanding behaviour in terms of (Bayes optimal) inference, but rather calls for a more refined understanding of the subject’s generative model upon which their (optimal) Bayesian inference is based. Here, we discuss this fundamental distinction and its implications for understanding optimality, bounded rationality and pathological (choice) behaviour. We illustrate our argument using addictive choice behaviour in a recently described ‘limited offer’ task. Our simulations of pathological choices and addictive behaviour also generate some clear hypotheses, which we hope to pursue in ongoing empirical work. PMID:25561321

  6. ANGDelMut – a web-based tool for predicting and analyzing functional loss mechanisms of amyotrophic lateral sclerosis-associated angiogenin mutations [v2; ref status: indexed, http://f1000r.es/2mc

    Directory of Open Access Journals (Sweden)

    Aditya K Padhi

    2013-12-01

    Full Text Available ANGDelMut is a web-based tool for predicting the functional consequences of missense mutations in the angiogenin (ANG protein, which is associated with amyotrophic lateral sclerosis (ALS. Missense mutations in ANG result in loss of either ribonucleolytic activity or nuclear translocation activity or both of these functions, and in turn cause ALS. However, no web-based tools are available to predict whether a newly identified ANG mutation will possibly lead to ALS. More importantly, no web-implemented method is currently available to predict the mechanisms of loss-of-function(s of ANG mutants. In light of this observation, we developed the ANGDelMut web-based tool, which predicts whether an ANG mutation is deleterious or benign. The user selects certain attributes from the input panel, which serves as a query to infer whether a mutant will exhibit loss of ribonucleolytic activity or nuclear translocation activity or whether the overall stability will be affected. The output states whether the mutation is deleterious or benign, and if it is deleterious, gives the possible mechanism(s of loss-of-function. This web-based tool, freely available at http://bioschool.iitd.ernet.in/DelMut/, is the first of its kind to provide a platform for researchers and clinicians, to infer the functional consequences of ANG mutations and correlate their possible association with ALS ahead of experimental findings.

  7. ANGDelMut – a web-based tool for predicting and analyzing functional loss mechanisms of amyotrophic lateral sclerosis-associated angiogenin mutations [v3; ref status: indexed, http://f1000r.es/2yt

    Directory of Open Access Journals (Sweden)

    Aditya K Padhi

    2014-02-01

    Full Text Available ANGDelMut is a web-based tool for predicting the functional consequences of missense mutations in the angiogenin (ANG protein, which is associated with amyotrophic lateral sclerosis (ALS. Missense mutations in ANG result in loss of either ribonucleolytic activity or nuclear translocation activity or both of these functions, and in turn cause ALS. However, no web-based tools are available to predict whether a newly identified ANG mutation will possibly lead to ALS. More importantly, no web-implemented method is currently available to predict the mechanisms of loss-of-function(s of ANG mutants. In light of this observation, we developed the ANGDelMut web-based tool, which predicts whether an ANG mutation is deleterious or benign. The user selects certain attributes from the input panel, which serves as a query to infer whether a mutant will exhibit loss of ribonucleolytic activity or nuclear translocation activity or whether the overall stability will be affected. The output states whether the mutation is deleterious or benign, and if it is deleterious, gives the possible mechanism(s of loss-of-function. This web-based tool, freely available at http://bioschool.iitd.ernet.in/DelMut/, is the first of its kind to provide a platform for researchers and clinicians, to infer the functional consequences of ANG mutations and correlate their possible association with ALS ahead of experimental findings.

  8. Functional modifications associated with gastrointestinal tract organogenesis during metamorphosis in Atlantic halibut (Hippoglossus hippoglossus).

    Science.gov (United States)

    Gomes, Ana S; Kamisaka, Yuko; Harboe, Torstein; Power, Deborah M; Rønnestad, Ivar

    2014-02-19

    Flatfish metamorphosis is a hormone regulated post-embryonic developmental event that transforms a symmetric larva into an asymmetric juvenile. In altricial-gastric teleost fish, differentiation of the stomach takes place after the onset of first feeding, and during metamorphosis dramatic molecular and morphological modifications of the gastrointestinal (GI-) tract occur. Here we present the functional ontogeny of the developing GI-tract from an integrative perspective in the pleuronectiforme Atlantic halibut, and test the hypothesis that the multiple functions of the teleost stomach develop synchronously during metamorphosis. Onset of gastric function was determined with several approaches (anatomical, biochemical, molecular and in vivo observations). In vivo pH analysis in the GI-tract lumen combined with quantitative PCR (qPCR) of α and β subunits of the gastric proton pump (H+/K+-ATPase) and pepsinogen A2 indicated that gastric proteolytic capacity is established during the climax of metamorphosis. Transcript abundance of ghrelin, a putative orexigenic signalling molecule produced in the developing stomach, correlated (p metamorphosis, and was thus independent of this event. Mechanical breakdown of food and transportation of chyme through the GI-tract was observed in vivo and resulted from phasic and propagating contractions established well before metamorphosis. The number of contractions in the midgut decreased at metamorphic climax synchronously with establishment of the stomach's proteolytic capacity and its increased peristaltic activity. Putative osmoregulatory competence of the GI-tract, inferred by abundance of Na+/K+-ATPase α transcripts, was already established at the onset of exogenous feeding and was unmodified by metamorphosis. The functional specialization of the GI-tract was not exclusive to metamorphosis, and its osmoregulatory capacity and reservoir function were established before first feeding. Nonetheless, acid production and the

  9. Phylogenetic and functional diversity of the cultivable bacterial community associated with the paralytic shellfish poisoning dinoflagellate Gymnodinium catenatum.

    Science.gov (United States)

    Green, David H; Llewellyn, Lyndon E; Negri, Andrew P; Blackburn, Susan I; Bolch, Christopher J S

    2004-03-01

    Gymnodinium catenatum is one of several dinoflagellates that produce a suite of neurotoxins called the paralytic shellfish toxins (PST), responsible for outbreaks of paralytic shellfish poisoning in temperate and tropical waters. Previous research suggested that the bacteria associated with the surface of the sexual resting stages (cyst) were important to the production of PST by G. catenatum. This study sought to characterise the cultivable bacterial diversity of seven different strains of G. catenatum that produce both high and abnormally low amounts of PST, with the long-term aim of understanding the role the bacterial flora has in bloom development and toxicity of this alga. Sixty-one bacterial isolates were cultured and phylogenetically identified as belonging to the Proteobacteria (70%), Bacteroidetes (26%) or Actinobacteria (3%). The Alphaproteobacteria were the most numerous both in terms of the number of isolates cultured (49%) and were also the most abundant type of bacteria in each G. catenatum culture. Two phenotypic (functional) traits inferred from the phylogenetic data were shown to be a common feature of the bacteria present in each G. catenatum culture: firstly, Alphaproteobacteria capable of aerobic anoxygenic photosynthesis, and secondly, Gammaproteobacteria capable of hydrocarbon utilisation and oligotrophic growth. In relation to reports of autonomous production of PST by dinoflagellate-associated bacteria, PST production by bacterial isolates was investigated, but none were shown to produce any PST-like toxins. Overall, this study has identified a number of emergent trends in the bacterial community of G. catenatum which are mirrored in the bacterial flora of other dinoflagellates, and that are likely to be of especial relevance to the population dynamics of natural and harmful algal blooms.

  10. Association of demographic characteristics, symptomatology, retrospective and prospective memory, executive functioning and intelligence with social functioning in schizophrenia.

    Science.gov (United States)

    Xiang, Yu-Tao; Shum, David; Chiu, Helen F K; Tang, Wai-Kwong; Ungvari, Gabor S

    2010-12-01

    The objective of this study was to explore the influence of socio-demographic and clinical factors and neurocognitive variables (i.e. prospective and retrospective memory, executive functioning, and intelligence) on social functioning in Chinese schizophrenia patients. The study sample comprised 110 Chinese schizophrenia patients. Their clinical condition and social functioning were evaluated with the Brief Psychiatric Rating Scale (BPRS) and the Functional Needs Assessment (FNA), respectively. Three prospective memory (PM) tasks (time-, event-, and activity-based), three tests of executive functioning (the Design Fluency Test [DFT], Tower of London [TOL], and Wisconsin Card Sorting Test [WCST]), one test of intelligence (Raven's Progressive Matrices), and two retrospective memory (RM) tasks (the immediate and delayed recall conditions of the Logical Memory subtest of the Wechsler Memory Scales-Revised [WMS-R]) were administered to all patients. In correlation analyses higher education and better performance on the WCST (categories completed) and the Logical Memory subtests (delayed and immediate) of the WMS-R are significantly correlated with better social functioning, whereas a lower WCST score (perseverative errors) and more severe negative symptoms are associated with poorer social functioning. Multiple linear regression analysis revealed that higher education and a lower WCST score (perseverative errors) independently contribute to better social functioning. Unexpectedly, most socio-demographic and clinical factors do not seem to have a significant impact on social functioning of Chinese schizophrenia patients living in a Chinese society. Negative symptoms and certain cognitive deficits were the main predictors of social functioning and they should be the main targets for antipsychotic treatment and psychosocial interventions to improve social adjustment in Chinese schizophrenia patients.

  11. Is postural control associated with mental functioning in the persistent postconcussion syndrome?

    NARCIS (Netherlands)

    Geurts, A. C.; Knoop, J. A.; van Limbeek, J.

    1999-01-01

    Objective: To investigate whether balance is associated with mental functioning after mild traumatic brain injury (MTBI). Design: Experimental two-group design. Setting: Outpatient rehabilitation department. Patients and Other Participants: From a consecutive sample of referred MTBI patients, 15

  12. Association of pain intensity with quality of life and functional disability in university students with lumbago

    International Nuclear Information System (INIS)

    Fatima, A.; Tanveer, F.; Ahmed, A.; Gillani, S.A.

    2017-01-01

    To determine an association of pain intensity with quality of life and functional disability in university students with lumbago. Methodology: In this cross sectional study 213 students participated. Standard questionnaire Numeric pain rating scale, Utian quality of life scale Oswestry Low Back Pain Disability Questionnaire were used for the data collection. Results: Mean age of students was 21.0 +- 1.970 years (range 18-24). Out of 213 students, 143 had lower quality of life. There was an association between pain intensity and quality of life (p=0.006). Out of 213 students, 120 had minimal disability with lower quality of life. There was strong association (p=0.015) between quality of life and functional disability. Conclusion: There was a strong association between pain intensity and quality of life, pain intensity and functional disability, quality of life and functional disability in university students with low back ache. (author)

  13. Longitudinal Association Between Gross Motor Capacity and Neuromusculoskeletal Function in Children and Youth With Cerebral Palsy

    NARCIS (Netherlands)

    Vos, Rimke C.; Becher, Jules G.; Voorman, Jeanine M.; Gorter, Jan Willem; van Eck, Mirjam; van Meeteren, Jetty; Smits, Dirk Wouter; Twisk, Jos W.; Dallmeijer, Annet J.

    Objective: To examine associations over longitudinal measurements between neuromusculoskeletal function and gross motor capacity in children and youth with cerebral palsy (CP). Design: A prospective cohort study. Setting: Rehabilitation departments of university medical centers and rehabilitations

  14. Late-life depression symptom profiles are differentially associated with immunometabolic functioning

    NARCIS (Netherlands)

    Vogelzangs, N.; Comijs, H.C.; Voshaar, R.C.O.; Stek, M.L.; Penninx, B.W.J.H.

    2014-01-01

    Growing evidence suggests immune and metabolic dysregulation among depressed persons, possibly restricted to specific subgroups. This study explores the association between depressive disorders and characteristics with immunometabolic functioning among older persons. Data are from the baseline

  15. Working irregular shift patterns is associated with functional constipation among healthy trainee nurses

    Directory of Open Access Journals (Sweden)

    Ali Ebrahim

    2017-11-01

    Full Text Available The circadian system has a role in regulating gastrointestinal physiology. Perturbation of this system is associated with gastrointestinal tract dysfunction. Shiftwork and poor sleep quality are associated with functional gastrointestinal disorders among many professional groups. This study compared bowel habits between trainee nurses with regular and irregular patterns of shiftwork. Male and female nursing students, enrolled on the first year (regular shifts; n=49 and the fourth year (irregular shifts, n=48 of a nursing degree course were surveyed. Questionnaires were used to assess functional diarrhea and constipation over a three month period. The prevalence of functional constipation among regular shift workers was lower than that found among irregular shift workers; 31.3% and 61.2%, respectively. There was no difference between the two groups in relation to the prevalence of diarrhea. This suggests an association between shiftwork and functional constipation, but not with functional diarrhea.

  16. Urinary Leukotriene E4 Is Associated with Renal Function but Not with Endothelial Function in Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Arnar Rafnsson

    2013-01-01

    Full Text Available Leukotrienes are inflammatory and vasoactive mediators implicated in endothelium-dependent relaxations and atherosclerosis. Urinary leukotriene E4 (U-LTE4 is a validated disease marker of asthma and increases also in diabetes and acute coronary syndromes. The aim of the present study was to evaluate the association of U-LTE4 and CRP with endothelial function. Urine samples were obtained from 30 subjects (80% males; median age 65 with type 2 diabetes of at least two years duration and a median glomerular filtration rate (eGFR of 71 (14–129 mL/min. Reactive hyperemia index (RHI was used as a measure of microvascular endothelial function, whereas macrovascular endothelial function was determined be means of flow-mediated dilatation of the brachial artery (FMD. Decreased renal function was associated with lower concentrations of U-LTE4. In addition, U-LTE4 was correlated with serum creatinine (R=−0.572; P=0.001 and eGFR (R=0.517; P=0.0036. A stepwise multiple linear regression analysis identified eGFR as an independent predictor of U-LTE4 concentrations. In conclusion, the present results did not establish an association of U-LTE4 with endothelial dysfunction. However, eGFR was an independent predictor of U-LTE4, but not CRP, in this cohort, suggesting that GFR should be considered in biomarker studies of U-LTE4.

  17. Causal inference in biology networks with integrated belief propagation.

    Science.gov (United States)

    Chang, Rui; Karr, Jonathan R; Schadt, Eric E

    2015-01-01

    Inferring causal relationships among molecular and higher order phenotypes is a critical step in elucidating the complexity of living systems. Here we propose a novel method for inferring causality that is no longer constrained by the conditional dependency arguments that limit the ability of statistical causal inference methods to resolve causal relationships within sets of graphical models that are Markov equivalent. Our method utilizes Bayesian belief propagation to infer the responses of perturbation events on molecular traits given a hypothesized graph structure. A distance measure between the inferred response distribution and the observed data is defined to assess the 'fitness' of the hypothesized causal relationships. To test our algorithm, we infer causal relationships within equivalence classes of gene networks in which the form of the functional interactions that are possible are assumed to be nonlinear, given synthetic microarray and RNA sequencing data. We also apply our method to infer causality in real metabolic network with v-structure and feedback loop. We show that our method can recapitulate the causal structure and recover the feedback loop only from steady-state data which conventional method cannot.

  18. Association between insulin and executive functioning in alcohol dependence: a pilot study.

    Science.gov (United States)

    Han, Changwoo; Bae, Hwallip; Won, Sung-Doo; Lim, Jaeyoung; Kim, Dai-Jin

    2015-01-01

    Alcohol dependence is a disorder ascribable to multiple factors and leads to cognitive impairment. Given that insulin dysregulation can cause cognitive impairment, patients with alcohol dependence are likely to develop insulin dysregulation such as that in diabetes. The purposes of this study are to identify an association between cognitive functioning and insulin and to investigate insulin as the biomarker of cognitive functioning in alcohol-dependent patients. Serum insulin levels were measured and cognitive functions were assessed in 45 patients with chronic alcoholism. The Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K), a battery of cognitive function tests, was used to assess cognitive functioning. Serum insulin levels were not significantly correlated with most CERAD-K scores, but there was a significant negative correlation with scores on the Trail Making Test B, which is designed to measure executive functioning. Lower serum insulin levels were associated with slower executive functioning responses on the Trail Making Test B, suggesting that executive functioning may be in proportion to serum insulin levels. Thus, in patients with alcohol dependence, insulin level is associated with cognitive functioning. In addition, the present findings suggest that insulin level is a potential biomarker for determining cognitive functioning.

  19. Association between Global Assessment of Functioning scores and indicators of functioning, severity, and prognosis in first-time schizophrenia

    DEFF Research Database (Denmark)

    Köhler-Forsberg, Ole; Horsdal, Henriette Thisted; Baandrup, Lone

    2016-01-01

    are associated with other indicators of functioning, severity, and hospitalization. METHODS: A Danish population-based cohort study of adults (≥18 years) with a recorded GAF-F score at first-time schizophrenia diagnosis during 2004-2011 was performed. The internal validity of GAF-F was evaluated by assessing its...... of schizophrenia with a GAF-F score at first-time diagnosis (73.0% inpatients; 62.6% males). GAF-F was associated with several baseline measures of functioning and illness severity, such as female sex, being in work, and a longer baseline hospitalization. Lower GAF-F scores were associated with higher.......36-3.90), fitting a dose-response relationship (P=0.031). This association was not found in females. CONCLUSION: GAF-F at first-time schizophrenia diagnosis showed good internal validity against other measures of functionality in a Danish hospital setting. Severe impairment (as measured by the GAF-F score) at first...

  20. High-sensitive C-reactive protein is associated with reduced lung function in young adults

    DEFF Research Database (Denmark)

    Rasmussen, Finn; Mikkelsen, Dennis; Hancox, Robert

    2009-01-01

    levels of CRP at age 20 yrs were associated with a greater reduction in both FEV(1) and forced vital capacity between ages 20 and 29 yrs. The findings show that higher levels of C-reactive protein in young adults are associated with subsequent decline in lung function, suggesting that low-grade systemic...... inflammation in young adulthood may lead to impaired lung function independently of the effects of smoking, obesity, cardiorespiratory fitness, asthma and eosinophilic inflammation....

  1. A preliminary investigation of sleep quality in functional neurological disorders: Poor sleep appears common, and is associated with functional impairment.

    Science.gov (United States)

    Graham, Christopher D; Kyle, Simon D

    2017-07-15

    Functional neurological disorders (FND) are disabling conditions for which there are few empirically-supported treatments. Disturbed sleep appears to be part of the FND context; however, the clinical importance of sleep disturbance (extent, characteristics and impact) remains largely unknown. We described sleep quality in two samples, and investigated the relationship between sleep and FND-related functional impairment. We included a sample recruited online via patient charities (N=205) and a consecutive clinical sample (N=20). Participants completed validated measures of sleep quality and sleep characteristics (e.g. total sleep time, sleep efficiency), mood, and FND-related functional impairment. Poor sleep was common in both samples (89% in the clinical range), which was characterised by low sleep efficiency (M=65.40%) and low total sleep time (M=6.05h). In regression analysis, sleep quality was negatively associated with FND-related functional impairment, accounting for 16% of the variance and remaining significant after the introduction of mood variables. These preliminary analyses suggest that subjective sleep disturbance (low efficiency, short sleep) is common in FND. Sleep quality was negatively associated with the functional impairment attributed to FND, independent of depression. Therefore, sleep disturbance may be a clinically important feature of FND. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Cortical information flow during inferences of agency

    Directory of Open Access Journals (Sweden)

    Myrthel eDogge

    2014-08-01

    Full Text Available Building on the recent finding that agency experiences do not merely rely on sensorimotor information but also on cognitive cues, this exploratory study uses electroencephalographic recordings to examine functional connectivity during agency inference processing in a setting where action and outcome are independent. Participants completed a computerized task in which they pressed a button followed by one of two color words (red or blue and rated their experienced agency over producing the color. Before executing the action, a matching or mismatching color word was pre-activated by explicitly instructing participants to produce the color (goal condition or by briefly presenting the color word (prime condition. In both conditions, experienced agency was higher in matching versus mismatching trials. Furthermore, increased electroencephalography (EEG-based connectivity strength was observed between parietal and frontal nodes and within the (prefrontal cortex when color-outcomes matched with goals and participants reported high agency. This pattern of increased connectivity was not identified in trials where outcomes were pre-activated through primes. These results suggest that different connections are involved in the experience and in the loss of agency, as well as in inferences of agency resulting from different types of pre-activation. Moreover, the findings provide novel support for the involvement of a fronto-parietal network in agency inferences.

  3. Pain mediates the association between physical activity and the impact of fibromyalgia on daily function.

    Science.gov (United States)

    Umeda, Masataka; Corbin, Lisa W; Maluf, Katrina S

    2015-01-01

    This study quantified the association between recreational physical activity and daily function in women with fibromyalgia, and determined if this association is mediated by symptoms of pain, depression, or body mass. Twenty-three women diagnosed with fibromyalgia participated in an observational survey study. Recreational physical activity and the impact of fibromyalgia on daily function were assessed using the sport and leisure time physical activity subscales of the Baecke Physical Activity Questionnaire (BPAQ) and the Fibromyalgia Impact Questionnaire (FIQ), respectively. Potential mediators of the association between physical activity and daily function were assessed using the Visual Analogue Scale for pain intensity (VAS-Pain), the Beck Depression Inventory (BDI), and body mass index (BMI). BPAQ was inversely associated with FIQ (R (2) = 0.20) and VAS-Pain (R (2) = 0.39). VAS-Pain was positively associated with FIQ (R (2) = 0.23). The inverse association between BPAQ and FIQ was no longer significant after controlling for VAS-Pain. BDI was positively associated with FIQ (R (2) = 0.37), whereas BMI was not. BPAQ was not significantly associated with either BDI or BMI. These results indicate that the intensity of musculoskeletal pain, rather than depressive symptoms or body mass, mediates the association between physical activity and daily function among women with fibromyalgia.

  4. Implicit and Explicit Associations with Erotic Stimuli in Sexually Functional and Dysfunctional Men.

    Science.gov (United States)

    van Lankveld, Jacques; Odekerken, Ingrid; Kok-Verhoeven, Lydia; van Hooren, Susan; de Vries, Peter; van den Hout, Anja; Verboon, Peter

    2015-08-01

    Although conceptual models of sexual functioning have suggested a major role for implicit cognitive processing in sexual functioning, this has thus far, only been investigated in women. The aim of this study was to investigate the role of implicit cognition in sexual functioning in men. Men with (N = 29) and without sexual dysfunction (N = 31) were compared. Participants performed two single-target implicit association tests (ST-IAT), measuring the implicit association of visual erotic stimuli with attributes representing, respectively, valence ('liking') and motivation ('wanting'). Participants also rated the erotic pictures that were shown in the ST-IAT on the dimensions of valence, attractiveness, and sexual excitement to assess their explicit associations with these erotic stimuli. Participants completed the International Index of Erectile Functioning for a continuous measure of sexual functioning. Unexpectedly, compared with sexually functional men, sexually dysfunctional men were found to show stronger implicit associations of erotic stimuli with positive valence than with negative valence. Level of sexual functioning, however, was not predicted by explicit nor implicit associations. Level of sexual distress was predicted by explicit valence ratings, with positive ratings predicting higher levels of sexual distress. Men with and without sexual dysfunction differed significantly with regard to implicit liking. Research recommendations and implications are discussed. © 2015 International Society for Sexual Medicine.

  5. The Association Between Physical Activity and Cognitive Function With Considerations by Social Risk Status.

    Science.gov (United States)

    Frith, Emily; Loprinzi, Paul D

    2017-11-01

    We evaluated the association between physical activity and cognitive function among a national sample of the broader U.S. adult population, with consideration by social risk. Data from the 1999-2002 National Health and Nutrition Examination Survey (NHANES) were used to identify 2031 older adults, ages 60-85. Social risk was classified by measuring four NHANES variables, namely poverty level, education, minority status, and social living status, which were graded on a scale of 0-4, with higher scores corresponding with higher social risk. The Digit Symbol Substitution Test (DSST) was used to assess cognitive function. Physical activity was assessed via a validated self-report questionnaire. After adjustments, meeting physical activity guidelines (vs not) was associated with greater cognitive function (β = 3.0, 95% CI [1.5, 4.4], p cognitive function. Meeting physical activity guidelines (vs. not) was not associated with higher cognitive function among those with a social risk score of of 3 (β = -0.01; 95% CI [-6.3, 6.4], p = 0.99) or a social risk score of 4 (β = -6.8, 95% CI [-15.7, 2.0], p = 0.12). In this national sample of older adults, meeting physical activity guidelines, and degree of social risk were independently associated with cognitive function. However, physical activity was not associated with cognitive function among older adults with the highest degree of social risk.

  6. Longitudinal Associations Between Parental Bonding, Parenting Stress, and Executive Functioning in Toddlerhood

    NARCIS (Netherlands)

    de Cock, Evi S.A.; Henrichs, Jens; Klimstra, Theo A.; Janneke, A.; Vreeswijk, Charlotte M.J.M.; Meeus, Wim H.J.; van Bakel, Hedwig J.A.

    2017-01-01

    Early executive functioning is an important predictor for future development of children’s cognitive skills and behavioral outcomes. Parenting behavior has proven to be a key environmental determinant of child executive functioning. However, the association of parental affect and cognitions directed

  7. CT-quantified emphysema in male heavy smokers : association with lung function decline

    NARCIS (Netherlands)

    Mohamed Hoesein, Firdaus A A; de Hoop, Bartjan; Zanen, Pieter; Gietema, Hester; Kruitwagen, Cas L J J; van Ginneken, Bram; Isgum, Ivana; Mol, Christian; van Klaveren, Rob J; Dijkstra, Akkelies E; Groen, Hendricus; Boezen, Hendrika; Postma, Dirkje S; Prokop, Mathias; Lammers, Jan-Willem J

    BACKGROUND: Emphysema and small airway disease both contribute to chronic obstructive pulmonary disease (COPD), a disease characterised by accelerated decline in lung function. The association between the extent of emphysema in male current and former smokers and lung function decline was

  8. Developmental Trajectories of Acculturation in Hispanic Adolescents: Associations with Family Functioning and Adolescent Risk Behavior

    Science.gov (United States)

    Schwartz, Seth J.; Des Rosiers, Sabrina; Huang, Shi; Zamboanga, Byron L.; Unger, Jennifer B.; Knight, George P.; Pantin, Hilda; Szapocznik, Jose

    2013-01-01

    This study examined longitudinal acculturation patterns, and their associations with family functioning and adolescent risk behaviors, in Hispanic immigrant families. A sample of 266 Hispanic adolescents (M[subscript age] = 13.4) and their primary parents completed measures of acculturation, family functioning, and adolescent conduct problems,…

  9. Longitudinal associations between parental bonding, parenting stress, and executive functioning in toddlerhood

    NARCIS (Netherlands)

    De Cock, E.S.A.; Henrichs, J.; Klimstra, T.A.; Maas, A.J.B.M.; Vreeswijk, C.M.J.M.; Meeus, W.H.J.; Van Bakel, H.J.A.

    Early executive functioning is an important predictor for future development of children’s cognitive skills and behavioral outcomes. Parenting behavior has proven to be a key environmental determinant of child executive functioning. However, the association of parental affect and cognitions directed

  10. Associations between Parents' Marital Functioning, Maternal Parenting Quality, Maternal Emotion and Child Cortisol Levels

    Science.gov (United States)

    Pendry, Patricia; Adam, Emma K.

    2007-01-01

    Associations between family functioning and children's stress hormone levels are explored, by examining how aspects of the interparental relationship (parents' marital satisfaction and parent conflict styles), the mother-child relationship (maternal involvement and warmth) and maternal emotional functioning (depression, anxiety and self-esteem)…

  11. Family functioning in the context of parental bipolar disorder: associations with offspring age, sex, and psychopathology.

    Science.gov (United States)

    Freed, Rachel D; Tompson, Martha C; Wang, Christine H; Otto, Michael W; Hirshfeld-Becker, Dina R; Nierenberg, Andrew A; Henin, Aude

    2015-02-01

    Previous research has shown that families with a parent who has bipolar disorder (BD) may experience family functioning difficulties. However, the association between family functioning and psychopathology among offspring of parents with BD, and offspring characteristics that may moderate this association, remains poorly understood. This study examined the cross-sectional associations between family functioning (cohesion, expressiveness, and conflict) and psychopathology in 117 offspring (ages 5-18) of 75 parents with BD. We also examined whether age and sex differences moderated these associations. We measured offspring psychopathology by examining current dimensional symptoms and DSM-IV emotional and behavioral disorders. Correlational analyses indicated that higher family conflict and lower cohesion were associated with higher internalizing and externalizing symptoms in offspring. Lower family cohesion was also associated with current offspring mood disorders. Moderation analyses indicated, first, that the link between lower family cohesion and internalizing symptoms was stronger for younger offspring compared to older offspring. Second, higher family conflict and current mood disorder were associated in younger males but not in older males or in females. Results remained the same after controlling for parental anxiety or substance use disorder comorbidity. Our study highlights the importance of accounting for family functioning when working with offspring at risk for BD, while also recognizing that the connections between family functioning and offspring outcomes are complex and differ based on offspring sex and developmental stage. PsycINFO Database Record (c) 2015 APA, all rights reserved.

  12. Functional relevance for associations between genetic variants and systemic lupus erythematosus.

    Directory of Open Access Journals (Sweden)

    Fei-Yan Deng

    Full Text Available Systemic lupus erythematosus (SLE is a serious prototype autoimmune disease characterized by chronic inflammation, auto-antibody production and multi-organ damage. Recent association studies have identified a long list of loci that were associated with SLE with relatively high statistical power. However, most of them only established the statistical associations of genetic markers and SLE at the DNA level without supporting evidence of functional relevance. Here, using publically available datasets, we performed integrative analyses (gene relationship across implicated loci analysis, differential gene expression analysis and functional annotation clustering analysis and combined with expression quantitative trait loci (eQTLs results to dissect functional mechanisms underlying the associations for SLE. We found that 14 SNPs, which were significantly associated with SLE in previous studies, have cis-regulation effects on four eQTL genes (HLA-DQA1, HLA-DQB1, HLA-DQB2, and IRF5 that were also differentially expressed in SLE-related cell groups. The functional evidence, taken together, suggested the functional mechanisms underlying the associations of 14 SNPs and SLE. The study may serve as an example of mining publically available datasets and results in validation of significant disease-association results. Utilization of public data resources for integrative analyses may provide novel insights into the molecular genetic mechanisms underlying human diseases.

  13. Perceived social isolation is associated with altered functional connectivity in neural networks associated with tonic alertness and executive control.

    Science.gov (United States)

    Layden, Elliot A; Cacioppo, John T; Cacioppo, Stephanie; Cappa, Stefano F; Dodich, Alessandra; Falini, Andrea; Canessa, Nicola

    2017-01-15

    Perceived social isolation (PSI), colloquially known as loneliness, is associated with selectively altered attentional, cognitive, and affective processes in humans, but the neural mechanisms underlying these adjustments remain largely unexplored. Behavioral, eye tracking, and neuroimaging research has identified associations between PSI and implicit hypervigilance for social threats. Additionally, selective executive dysfunction has been evidenced by reduced prepotent response inhibition in social Stroop and dichotic listening tasks. Given that PSI is associated with pre-attentional processes, PSI may also be related to altered resting-state functional connectivity (FC) in the brain. Therefore, we conducted the first resting-state fMRI FC study of PSI in healthy young adults. Five-minute resting-state scans were obtained from 55 participants (31 females). Analyses revealed robust associations between PSI and increased brain-wide FC in areas encompassing the right central operculum and right supramarginal gyrus, and these associations were not explained by depressive symptomatology, objective isolation, or demographics. Further analyses revealed that PSI was associated with increased FC between several nodes of the cingulo-opercular network, a network known to underlie the maintenance of tonic alertness. These regions encompassed the bilateral insula/frontoparietal opercula and ACC/pre-SMA. In contrast, FC between the cingulo-opercular network and right middle/superior frontal gyrus was reduced, a finding associated with diminished executive function in prior literature. We suggest that, in PSI, increased within-network cingulo-opercular FC may be associated with hypervigilance to social threat, whereas reduced right middle/superior frontal gyrus FC to the cingulo-opercular network may be associated with diminished impulse control. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Inference of Transcription Regulatory Network in Low Phytic Acid Soybean Seeds

    Directory of Open Access Journals (Sweden)

    Neelam Redekar

    2017-11-01

    Full Text Available A dominant loss of function mutation in myo-inositol phosphate synthase (MIPS gene and recessive loss of function mutations in two multidrug resistant protein type-ABC transporter genes not only reduce the seed phytic acid levels in soybean, but also affect the pathways associated with seed development, ultimately resulting in low emergence. To understand the regulatory mechanisms and identify key genes that intervene in the seed development process in low phytic acid crops, we performed computational inference of gene regulatory networks in low and normal phytic acid soybeans using a time course transcriptomic data and multiple network inference algorithms. We identified a set of putative candidate transcription factors and their regulatory interactions with genes that have functions in myo-inositol biosynthesis, auxin-ABA signaling, and seed dormancy. We evaluated the performance of our unsupervised network inference method by comparing the predicted regulatory network with published regulatory interactions in Arabidopsis. Some contrasting regulatory interactions were observed in low phytic acid mutants compared to non-mutant lines. These findings provide important hypotheses on expression regulation of myo-inositol metabolism and phytohormone signaling in developing low phytic acid soybeans. The computational pipeline used for unsupervised network learning in this study is provided as open source software and is freely available at https://lilabatvt.github.io/LPANetwork/.

  15. Statistical theory and inference

    CERN Document Server

    Olive, David J

    2014-01-01

    This text is for  a one semester graduate course in statistical theory and covers minimal and complete sufficient statistics, maximum likelihood estimators, method of moments, bias and mean square error, uniform minimum variance estimators and the Cramer-Rao lower bound, an introduction to large sample theory, likelihood ratio tests and uniformly most powerful  tests and the Neyman Pearson Lemma. A major goal of this text is to make these topics much more accessible to students by using the theory of exponential families. Exponential families, indicator functions and the support of the distribution are used throughout the text to simplify the theory. More than 50 ``brand name" distributions are used to illustrate the theory with many examples of exponential families, maximum likelihood estimators and uniformly minimum variance unbiased estimators. There are many homework problems with over 30 pages of solutions.

  16. The Association of APOE Genotype with Cognitive Function in Persons Aged 35 Years or Older

    NARCIS (Netherlands)

    Izaks, Gerbrand J.; Gansevoort, Ron T.; van der Knaap, Aafke M.; Navis, Gerjan; Dullaart, Robin P. F.; Slaets, Joris P. J.

    2011-01-01

    APOE genotype is associated with the risk of Alzheimer's disease. In the present study, we investigated whether APOE genotype was associated with cognitive function in predominantly middle-aged persons. In a population-based cohort of 4,135 persons aged 35 to 82 years (mean age (SD), 55 (12) years),

  17. Gender-specific associations between physical functioning, bone quality and fracture risk in older people

    NARCIS (Netherlands)

    Furrer, R.; van Schoor, N.M.; de Haan, A.; Lips, P.; de Jongh, R.T.

    2014-01-01

    The aim of this study was to investigate which parameters of physical functioning are associated with bone quality and fracture risk and whether gender-specific differences exist within these associations. We studied 1,486 participants of the Longitudinal Aging Study Amsterdam. As measures of

  18. Mining for associations between text and brain activation in a functional neuroimaging database

    DEFF Research Database (Denmark)

    Nielsen, Finn Årup; Hansen, Lars Kai; Balslev, D.

    2004-01-01

    We describe a method for mining a neuroimaging database for associations between text and brain locations. The objective is to discover association rules between words indicative of cognitive function as described in abstracts of neuroscience papers and sets of reported stereotactic Talairach...

  19. Association between global functioning at first schizophrenia diagnosis and treatment resistance

    DEFF Research Database (Denmark)

    Horsdal, Henriette T; Wimberley, Theresa; Köhler-Forsberg, Ole

    2017-01-01

    individuals, severe functional impairment (GAF-F ≤ 30) was associated with TRS within 2 years after diagnosis (adjusted HR = 1.38 [95% confidence interval: 1.03-1.87). GAF-F had virtually no impact on the associations between investigated known risk factors and TRS. CONCLUSIONS: GAF-F was independently...

  20. Interactive Instruction in Bayesian Inference

    DEFF Research Database (Denmark)

    Khan, Azam; Breslav, Simon; Hornbæk, Kasper

    2018-01-01

    An instructional approach is presented to improve human performance in solving Bayesian inference problems. Starting from the original text of the classic Mammography Problem, the textual expression is modified and visualizations are added according to Mayer’s principles of instruction. These pri......An instructional approach is presented to improve human performance in solving Bayesian inference problems. Starting from the original text of the classic Mammography Problem, the textual expression is modified and visualizations are added according to Mayer’s principles of instruction....... These principles concern coherence, personalization, signaling, segmenting, multimedia, spatial contiguity, and pretraining. Principles of self-explanation and interactivity are also applied. Four experiments on the Mammography Problem showed that these principles help participants answer the questions...... that an instructional approach to improving human performance in Bayesian inference is a promising direction....

  1. On Maximum Entropy and Inference

    Directory of Open Access Journals (Sweden)

    Luigi Gresele

    2017-11-01

    Full Text Available Maximum entropy is a powerful concept that entails a sharp separation between relevant and irrelevant variables. It is typically invoked in inference, once an assumption is made on what the relevant variables are, in order to estimate a model from data, that affords predictions on all other (dependent variables. Conversely, maximum entropy can be invoked to retrieve the relevant variables (sufficient statistics directly from the data, once a model is identified by Bayesian model selection. We explore this approach in the case of spin models with interactions of arbitrary order, and we discuss how relevant interactions can be inferred. In this perspective, the dimensionality of the inference problem is not set by the number of parameters in the model, but by the frequency distribution of the data. We illustrate the method showing its ability to recover the correct model in a few prototype cases and discuss its application on a real dataset.

  2. Efficient Exact Inference With Loss Augmented Objective in Structured Learning.

    Science.gov (United States)

    Bauer, Alexander; Nakajima, Shinichi; Muller, Klaus-Robert

    2016-08-19

    Structural support vector machine (SVM) is an elegant approach for building complex and accurate models with structured outputs. However, its applicability relies on the availability of efficient inference algorithms--the state-of-the-art training algorithms repeatedly perform inference to compute a subgradient or to find the most violating configuration. In this paper, we propose an exact inference algorithm for maximizing nondecomposable objectives due to special type of a high-order potential having a decomposable internal structure. As an important application, our method covers the loss augmented inference, which enables the slack and margin scaling formulations of structural SVM with a variety of dissimilarity measures, e.g., Hamming loss, precision and recall, Fβ-loss, intersection over union, and many other functions that can be efficiently computed from the contingency table. We demonstrate the advantages of our approach in natural language parsing and sequence segmentation applications.

  3. A general Bayes weibull inference model for accelerated life testing

    International Nuclear Information System (INIS)

    Dorp, J. Rene van; Mazzuchi, Thomas A.

    2005-01-01

    This article presents the development of a general Bayes inference model for accelerated life testing. The failure times at a constant stress level are assumed to belong to a Weibull distribution, but the specification of strict adherence to a parametric time-transformation function is not required. Rather, prior information is used to indirectly define a multivariate prior distribution for the scale parameters at the various stress levels and the common shape parameter. Using the approach, Bayes point estimates as well as probability statements for use-stress (and accelerated) life parameters may be inferred from a host of testing scenarios. The inference procedure accommodates both the interval data sampling strategy and type I censored sampling strategy for the collection of ALT test data. The inference procedure uses the well-known MCMC (Markov Chain Monte Carlo) methods to derive posterior approximations. The approach is illustrated with an example

  4. The generalized Laguerre polynomials, the associated Bessel functions and application to propagation problems

    International Nuclear Information System (INIS)

    Dattoli, G.; Torre, A.; Mancho, A.M.

    2000-01-01

    The theory of generalized Bessel functions has found significant applications in the analysis of radiation phenomena, associated with charges moving in magnetic devices. In this paper we exploit the monomiality principle to discuss the theory of two-variable Laguerre polynomials and introduce the associated Laguerre-Bessel functions. We study their properties (addition and multiplication theorems, generating function, recurrence relations and so on) and discuss the link with the ordinary case. The usefulness of the obtained results to treat problems relevant to the paraxial propagation of electromagnetic waves is also discussed.

  5. Generalized coherent states related to the associated Bessel functions and Morse potential

    International Nuclear Information System (INIS)

    Mojaveri, B; Amiri Faseghandis, S

    2014-01-01

    Using the associated Bessel functions, a shape-invariant Lie algebra spanned by ladder operators plus the identity operator, is realized. The Hilbert space of the associated Bessel functions, representing the Lie algebra, are established and two kinds of generalized coherent states as an appropriate superposition of these functions are constructed. By implying appropriate similarity transformation on the constructed coherent states, the generalized coherent states for the Morse potential are obtained. By considering some statistical characteristics, it is revealed that the constructed coherent states indeed possess nonclassical features, such as squeezing and sub-Poissonian statistics. (paper)

  6. Human disease MiRNA inference by combining target information based on heterogeneous manifolds.

    Science.gov (United States)

    Ding, Pingjian; Luo, Jiawei; Liang, Cheng; Xiao, Qiu; Cao, Buwen

    2018-04-01

    The emergence of network medicine has provided great insight into the identification of disease-related molecules, which could help with the development of personalized medicine. However, the state-of-the-art methods could neither simultaneously consider target information and the known miRNA-disease associations nor effectively explore novel gene-disease associations as a by-product during the process of inferring disease-related miRNAs. Computational methods incorporating multiple sources of information offer more opportunities to infer disease-related molecules, including miRNAs and genes in heterogeneous networks at a system level. In this study, we developed a novel algorithm, named inference of Disease-related MiRNAs based on Heterogeneous Manifold (DMHM), to accurately and efficiently identify miRNA-disease associations by integrating multi-omics data. Graph-based regularization was utilized to obtain a smooth function on the data manifold, which constitutes the main principle of DMHM. The novelty of this framework lies in the relatedness between diseases and miRNAs, which are measured via heterogeneous manifolds on heterogeneous networks integrating target information. To demonstrate the effectiveness of DMHM, we conducted comprehensive experiments based on HMDD datasets and compared DMHM with six state-of-the-art methods. Experimental results indicated that DMHM significantly outperformed the other six methods under fivefold cross validation and de novo prediction tests. Case studies have further confirmed the practical usefulness of DMHM. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Association of nutritional status and functional capacity in gastrointestinal cancer patients.

    Science.gov (United States)

    Pérez-Cruz, Elizabeth; Camacho-Limas, Christian Patricio

    To determine the nutritional status and its association with functional capacity in patients with digestive tract cancer. We retrospectively studied all adult patients hospitalized who were diagnosed as having a cancer of the digestive tract. Nutritional status and functional capacity were assessed. Descriptive statistic and odds ratio were used to determine the association in SPSS 14.0. 57 patients were included, 96% had weight loss. Using subjective global assessment (SGA) as a method of screening, 82.5% of the patients were found malnutrition and by biochemical and immunological test 82% and 65% respectively. Functional capacity was assessed by Karnofsky index, finding that 75.5% of the patients have some activity limitation. Results show an association between malnutrition by SGA and limitation in functional capacity (c2 = 1.56; p = 0.212; OR: 2.46; 95% confidence interval [95% CI]: 0.581-10.465). In addition, we observe an association between the total lymphocyte count and limitation in functional capacity (χ2 = 6.94; p = 0.008; OR: 5.23; 95% CI: 1.441-19.025). Malnutrition in patients with digestive tract cancer was associated with limitation in functional capacity. Copyright: © 2017 SecretarÍa de Salud

  8. The longitudinal association between social functioning and theory of mind in first-episode psychosis.

    Science.gov (United States)

    Sullivan, Sarah; Lewis, Glyn; Mohr, Christine; Herzig, Daniela; Corcoran, Rhiannon; Drake, Richard; Evans, Jonathan

    2014-01-01

    There is some cross-sectional evidence that theory of mind ability is associated with social functioning in those with psychosis but the direction of this relationship is unknown. This study investigates the longitudinal association between both theory of mind and psychotic symptoms and social functioning outcome in first-episode psychosis. Fifty-four people with first-episode psychosis were followed up at 6 and 12 months. Random effects regression models were used to estimate the stability of theory of mind over time and the association between baseline theory of mind and psychotic symptoms and social functioning outcome. Neither baseline theory of mind ability (regression coefficients: Hinting test 1.07 95% CI -0.74, 2.88; Visual Cartoon test -2.91 95% CI -7.32, 1.51) nor baseline symptoms (regression coefficients: positive symptoms -0.04 95% CI -1.24, 1.16; selected negative symptoms -0.15 95% CI -2.63, 2.32) were associated with social functioning outcome. There was evidence that theory of mind ability was stable over time, (regression coefficients: Hinting test 5.92 95% CI -6.66, 8.92; Visual Cartoon test score 0.13 95% CI -0.17, 0.44). Neither baseline theory of mind ability nor psychotic symptoms are associated with social functioning outcome. Further longitudinal work is needed to understand the origin of social functioning deficits in psychosis.

  9. Functional polymorphisms in the P2X7 receptor gene are associated with osteoporosis

    DEFF Research Database (Denmark)

    Husted, L B; Harsløf, T; Stenkjær, L

    2013-01-01

    variant allele, which has been associated with increased receptor function in monocytes, was associated with increased total hip BMD in women. With the exception of His155Tyr for which we found conflicting results in men and women, our results are consistent with the phenotype of the knockout mouse......UNLABELLED: The P2X(7) receptor is an ATP-gated cation channel. We investigated the effect of both loss-of-function and gain-of-function polymorphisms in the P2X(7) receptor gene on BMD and risk of vertebral fractures and found that five polymorphisms and haplotypes containing three...... of these polymorphisms were associated with BMD and fracture risk. INTRODUCTION: The P2X(7) receptor is an ATP-gated cation channel. P2X(7) receptor knockout mice have reduced total bone mineral content, and because several functional polymorphisms have been identified in the human P2X(7) receptor gene, we wanted...

  10. Problem-Solving After Traumatic Brain Injury in Adolescence: Associations With Functional Outcomes.

    Science.gov (United States)

    Wade, Shari L; Cassedy, Amy E; Fulks, Lauren E; Taylor, H Gerry; Stancin, Terry; Kirkwood, Michael W; Yeates, Keith O; Kurowski, Brad G

    2017-08-01

    To examine the association of problem-solving with functioning in youth with traumatic brain injury (TBI). Cross-sectional evaluation of pretreatment data from a randomized controlled trial. Four children's hospitals and 1 general hospital, with level 1 trauma units. Youth, ages 11 to 18 years, who sustained moderate or severe TBI in the last 18 months (N=153). Problem-solving skills were assessed using the Social Problem-Solving Inventory (SPSI) and the Dodge Social Information Processing Short Stories. Everyday functioning was assessed based on a structured clinical interview using the Child and Adolescent Functional Assessment Scale (CAFAS) and via adolescent ratings on the Youth Self Report (YSR). Correlations and multiple regression analyses were used to examine associations among measures. The TBI group endorsed lower levels of maladaptive problem-solving (negative problem orientation, careless/impulsive responding, and avoidant style) and lower levels of rational problem-solving, resulting in higher total problem-solving scores for the TBI group compared with a normative sample (Pproblem-solving composites were associated with overall functioning on the CAFAS, only maladaptive problem-solving (PProblem-solving after TBI differs from normative samples and is associated with functional impairments. The relation of problem-solving deficits after TBI with global functioning merits further investigation, with consideration of the potential effects of problem-solving interventions on functional outcomes. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  11. Cranial computed tomography associated with development of functional dependence in a community-based elderly population

    International Nuclear Information System (INIS)

    Tsukishima, Eri; Shido, Koichi

    2002-01-01

    The purpose of this study was to investigate whether changes at computed tomography (CT) imaging in the ageing brain are associated with future risks for functional dependence. One hundred sixty residents aged 69 years and older at the cranial CT and were independently living in a rural community in Hokkaido, Japan. Cranial CT was performed between 1991 and 1993, graded for ventricular enlargement, sulcal enlargement, white matter change, and small infarction. Functional status was reassessed in 1998 in each participant. Multiple logistic regression analysis was performed to estimate the association of CT changes in the ageing brain with development of functional dependence over six years. Functional dependence was found in 19 residents at the second survey. After adjusting for age, sex, medical conditions, and cognitive functioning, small infarction and ventricular enlargement were significantly associated with development of functional dependence (adjusted odds ratio=9.27 and 4.62). After controlling for age, the age-related changes on cranial CT have significant association on development of functional dependence. (author)

  12. Physical activity and obesity mediate the association between childhood motor function and adolescents' academic achievement.

    Science.gov (United States)

    Kantomaa, Marko T; Stamatakis, Emmanuel; Kankaanpää, Anna; Kaakinen, Marika; Rodriguez, Alina; Taanila, Anja; Ahonen, Timo; Järvelin, Marjo-Riitta; Tammelin, Tuija

    2013-01-29

    The global epidemic of obesity and physical inactivity may have detrimental implications for young people's cognitive function and academic achievement. This prospective study investigated whether childhood motor function predicts later academic achievement via physical activity, fitness, and obesity. The study sample included 8,061 children from the Northern Finland Birth Cohort 1986, which contains data about parent-reported motor function at age 8 y and self-reported physical activity, predicted cardiorespiratory fitness (cycle ergometer test), obesity (body weight and height), and academic achievement (grades) at age 16 y. Structural equation models with unstandardized (B) and standardized (β) coefficients were used to test whether, and to what extent, physical activity, cardiorespiratory fitness, and obesity at age 16 mediated the association between childhood motor function and adolescents' academic achievement. Physical activity was associated with a higher grade-point average, and obesity was associated with a lower grade-point average in adolescence. Furthermore, compromised motor function in childhood had a negative indirect effect on adolescents' academic achievement via physical inactivity (B = -0.023, 95% confidence interval = -0.031, -0.015) and obesity (B = -0.025, 95% confidence interval = -0.039, -0.011), but not via cardiorespiratory fitness. These results suggest that physical activity and obesity may mediate the association between childhood motor function and adolescents' academic achievement. Compromised motor function in childhood may represent an important factor driving the effects of obesity and physical inactivity on academic underachievement.

  13. Physical activity and obesity mediate the association between childhood motor function and adolescents’ academic achievement

    Science.gov (United States)

    Kantomaa, Marko T.; Stamatakis, Emmanuel; Kankaanpää, Anna; Kaakinen, Marika; Rodriguez, Alina; Taanila, Anja; Ahonen, Timo; Järvelin, Marjo-Riitta; Tammelin, Tuija

    2013-01-01

    The global epidemic of obesity and physical inactivity may have detrimental implications for young people’s cognitive function and academic achievement. This prospective study investigated whether childhood motor function predicts later academic achievement via physical activity, fitness, and obesity. The study sample included 8,061 children from the Northern Finland Birth Cohort 1986, which contains data about parent-reported motor function at age 8 y and self-reported physical activity, predicted cardiorespiratory fitness (cycle ergometer test), obesity (body weight and height), and academic achievement (grades) at age 16 y. Structural equation models with unstandardized (B) and standardized (β) coefficients were used to test whether, and to what extent, physical activity, cardiorespiratory fitness, and obesity at age 16 mediated the association between childhood motor function and adolescents’ academic achievement. Physical activity was associated with a higher grade-point average, and obesity was associated with a lower grade-point average in adolescence. Furthermore, compromised motor function in childhood had a negative indirect effect on adolescents’ academic achievement via physical inactivity (B = –0.023, 95% confidence interval = –0.031, –0.015) and obesity (B = –0.025, 95% confidence interval = –0.039, –0.011), but not via cardiorespiratory fitness. These results suggest that physical activity and obesity may mediate the association between childhood motor function and adolescents’ academic achievement. Compromised motor function in childhood may represent an important factor driving the effects of obesity and physical inactivity on academic underachievement. PMID:23277558

  14. Inverse Ising Inference Using All the Data

    Science.gov (United States)

    Aurell, Erik; Ekeberg, Magnus

    2012-03-01

    We show that a method based on logistic regression, using all the data, solves the inverse Ising problem far better than mean-field calculations relying only on sample pairwise correlation functions, while still computationally feasible for hundreds of nodes. The largest improvement in reconstruction occurs for strong interactions. Using two examples, a diluted Sherrington-Kirkpatrick model and a two-dimensional lattice, we also show that interaction topologies can be recovered from few samples with good accuracy and that the use of l1 regularization is beneficial in this process, pushing inference abilities further into low-temperature regimes.

  15. Eight challenges in phylodynamic inference

    Directory of Open Access Journals (Sweden)

    Simon D.W. Frost

    2015-03-01

    Full Text Available The field of phylodynamics, which attempts to enhance our understanding of infectious disease dynamics using pathogen phylogenies, has made great strides in the past decade. Basic epidemiological and evolutionary models are now well characterized with inferential frameworks in place. However, significant challenges remain in extending phylodynamic inference to more complex systems. These challenges include accounting for evolutionary complexities such as changing mutation rates, selection, reassortment, and recombination, as well as epidemiological complexities such as stochastic population dynamics, host population structure, and different patterns at the within-host and between-host scales. An additional challenge exists in making efficient inferences from an ever increasing corpus of sequence data.

  16. Problem solving and inference mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Furukawa, K; Nakajima, R; Yonezawa, A; Goto, S; Aoyama, A

    1982-01-01

    The heart of the fifth generation computer will be powerful mechanisms for problem solving and inference. A deduction-oriented language is to be designed, which will form the core of the whole computing system. The language is based on predicate logic with the extended features of structuring facilities, meta structures and relational data base interfaces. Parallel computation mechanisms and specialized hardware architectures are being investigated to make possible efficient realization of the language features. The project includes research into an intelligent programming system, a knowledge representation language and system, and a meta inference system to be built on the core. 30 references.

  17. Financial literacy is associated with medial brain region functional connectivity in old age.

    Science.gov (United States)

    Han, S Duke; Boyle, Patricia A; Yu, Lei; Fleischman, Debra A; Arfanakis, Konstantinos; Leurgans, Sue; Bennett, David A

    2014-01-01

    Financial literacy refers to the ability to access and utilize financial information in ways that promote better outcomes. In old age, financial literacy has been associated with a wide range of positive characteristics; however, the neural correlates remain unclear. Recent work has suggested greater co-activity between anterior-posterior medial brain regions is associated with better brain functioning. We hypothesized financial literacy would be associated with this pattern. We assessed whole-brain functional connectivity to a posterior cingulate cortex (PCC) seed region of interest (ROI) in 138 participants of the Rush Memory and Aging Project. Results revealed financial literacy was associated with greater functional connectivity between the PCC and three regions: the right ventromedial prefrontal cortex (vmPFC), the left postcentral gyrus, and the right precuneus. Results also revealed financial literacy was associated negatively with functional connectivity between the PCC and left caudate. Post hoc analyses showed the PCC-vmPFC relationship accounted for the most variance in a regression model adjusted for all four significant functional connectivity relationships, demographic factors, and global cognition. These findings provide information on the neural mechanisms associated with financial literacy in old age. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Attentional avoidance of fearful facial expressions following early life stress is associated with impaired social functioning.

    Science.gov (United States)

    Humphreys, Kathryn L; Kircanski, Katharina; Colich, Natalie L; Gotlib, Ian H

    2016-10-01

    Early life stress is associated with poorer social functioning. Attentional biases in response to threat-related cues, linked to both early experience and psychopathology, may explain this association. To date, however, no study has examined attentional biases to fearful facial expressions as a function of early life stress or examined these biases as a potential mediator of the relation between early life stress and social problems. In a sample of 154 children (ages 9-13 years) we examined the associations among interpersonal early life stressors (i.e., birth through age 6 years), attentional biases to emotional facial expressions using a dot-probe task, and social functioning on the Child Behavior Checklist. High levels of early life stress were associated with both greater levels of social problems and an attentional bias away from fearful facial expressions, even after accounting for stressors occurring in later childhood. No biases were found for happy or sad facial expressions as a function of early life stress. Finally, attentional biases to fearful faces mediated the association between early life stress and social problems. Attentional avoidance of fearful facial expressions, evidenced by a bias away from these stimuli, may be a developmental response to early adversity and link the experience of early life stress to poorer social functioning. © 2016 Association for Child and Adolescent Mental Health.

  19. Serum chemerin levels are inversely associated with renal function in a general population

    DEFF Research Database (Denmark)

    Zylla, Stephanie; Rettig, Rainer; Völzke, Henry

    2018-01-01

    OBJECTIVE: Chemerin has been found to be highly expressed in the kidneys of rodents and has been suggested to affect metabolic syndrome (MetS)-related phenotypes which are in turn related to kidney damage. Only few clinical studies have addressed the relation between circulating chemerin and renal...... function in humans, and no population-based analyses have yet been performed. The potential influence of MetS-related phenotypes on the assumed association has been largely neglected. We aimed to investigate the association of serum chemerin with renal function in a general population with special regard......GFR and revealed that each increase in chemerin per 25 ng/mL was associated with an about threefold higher odds of chronic kidney disease [odds ratio 2.72 (95% confidence interval 2.26-3.29)]. CONCLUSIONS: Our results demonstrate a strong inverse association between serum chemerin levels and renal function...

  20. Associations between past bullying experiences and psychosocial and academic functioning among college students.

    Science.gov (United States)

    Holt, Melissa K; Greif Green, Jennifer; Reid, Gerald; DiMeo, Amanda; Espelage, Dorothy L; Felix, Erika D; Furlong, Michael J; Poteat, V Paul; Sharkey, Jill D

    2014-01-01

    This study examined whether childhood bullying victimization was associated with psychosocial and academic functioning at college. The sample consisted of 413 first-year students from a large northeastern university. Students completed an online survey in February 2012 that included items assessing past bullying involvement, current psychosocial and academic functioning, and victimization experiences since arriving at college. Regression analyses indicated that reports of past bullying and other peer victimization were associated with lower mental health functioning and perceptions of physical and mental health, but were not associated with perceptions of social life at college, overall college experience, or academic performance. Childhood bullying victimization is associated with poorer mental and physical health among first-year college students. Colleges should consider assessing histories of bullying victimization, along with other past victimization exposures, in their service provision to students.

  1. Associations of Adiposity and Aerobic Fitness with Executive Function and Math Performance in Danish Adolescents.

    Science.gov (United States)

    Huang, Tao; Tarp, Jakob; Domazet, Sidsel Louise; Thorsen, Anne Kær; Froberg, Karsten; Andersen, Lars Bo; Bugge, Anna

    2015-10-01

    To examine the associations of adiposity and aerobic fitness with executive function and math performance in Danish adolescents. Cross-sectional analyses were conducted with data on 525 adolescents attending sixth and seventh grades from 14 schools in the 5 main regions of Denmark. A modified Eriksen flanker task was used to assess inhibitory control, a key aspect of executive function. Academic performance was assessed by a customized math test. Aerobic fitness was assessed by an intermittent shuttle-run test (Andersen test). Body mass index (BMI) was negatively associated with accuracy on incongruent trials during the flanker task (P = .005). A higher BMI was associated with a larger accuracy interference score (P = .01). Similarly, waist circumference (WC) was negatively associated with accuracy on incongruent trials (P = .008). A higher WC was associated with a larger reaction time (RT) interference score (P = .02) and accuracy interference score (P = .009). Higher aerobic fitness was associated with a faster RT on congruent trials (P = .009) and incongruent trials (P = .003). Higher aerobic fitness was associated with a smaller RT interference score (P = .04). Aerobic fitness was positively associated with math score (P math score (P > .05). These results suggest that aerobic fitness is positively associated with both inhibitory control and math performance in adolescents. Adiposity is negatively associated with inhibitory control in adolescents. Adiposity is not associated with math performance. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Inferring Pre-shock Acoustic Field From Post-shock Pitot Pressure Measurement

    Science.gov (United States)

    Wang, Jian-Xun; Zhang, Chao; Duan, Lian; Xiao, Heng; Virginia Tech Team; Missouri Univ of Sci; Tech Team

    2017-11-01

    Linear interaction analysis (LIA) and iterative ensemble Kalman method are used to convert post-shock Pitot pressure fluctuations to static pressure fluctuations in front of the shock. The LIA is used as the forward model for the transfer function associated with a homogeneous field of acoustic waves passing through a nominally normal shock wave. The iterative ensemble Kalman method is then employed to infer the spectrum of upstream acoustic waves based on the post-shock Pitot pressure measured at a single point. Several test cases with synthetic and real measurement data are used to demonstrate the merits of the proposed inference scheme. The study provides the basis for measuring tunnel freestream noise with intrusive probes in noisy supersonic wind tunnels.

  3. Association between statin use and physical function among community-dwelling older Japanese adults.

    Science.gov (United States)

    Kawai, Hisashi; Ihara, Kazushige; Kera, Takeshi; Hirano, Hirohiko; Fujiwara, Yoshinori; Tanaka, Masashi; Kojima, Motonaga; Obuchi, Shuichi

    2018-04-01

    Statin-associated muscle symptoms (SAMS) are the muscle-related side-effects of statins, but the association between statin use and physical function among community-dwelling older adults is unclear. The objective of the present study was to examine the association between statin use and physical function among community-dwelling older Japanese adults by considering the risk factors of statin-associated muscle symptoms. The participants were 1022 community-dwelling older adults aged 65-88 years, who participated in comprehensive health checkups from 2013 to 2015. Statin use in the participants (381 men and 559 women) was verified by using data from their medicine notebooks. The differences between statin use (users and non-users) and physical functions (grip strength, knee extension torque, normal and maximum gait speed, Timed Up & Go test, one-legged stance, quadriceps muscle thickness and echo intensity) were analyzed using the t-test. Multiple regression analyses were also carried out to examine the association between statin use and physical function. A total of 93 men (24.4%) and 154 women (27.5%) were statin users. Grip strength, normal gait speed and one-legged stance declined significantly in statin users compared with the non-users. In multiple regression analysis while controlling for the risk factors of statin-associated muscle symptoms, including age, sex, body mass index and number of medicines, no independent association, between statin use and the reduction of physical functions, was observed. Statin use was not associated with the decline of physical function in community-dwelling older Japanese adults. Geriatr Gerontol Int 2018; 18: 623-630. © 2017 Japan Geriatrics Society.

  4. Assessment of network inference methods: how to cope with an underdetermined problem.

    Directory of Open Access Journals (Sweden)

    Caroline Siegenthaler

    Full Text Available The inference of biological networks is an active research area in the field of systems biology. The number of network inference algorithms has grown tremendously in the last decade, underlining the importance of a fair assessment and comparison among these methods. Current assessments of the performance of an inference method typically involve the application of the algorithm to benchmark datasets and the comparison of the network predictions against the gold standard or reference networks. While the network inference problem is often deemed underdetermined, implying that the inference problem does not have a (unique solution, the consequences of such an attribute have not been rigorously taken into consideration. Here, we propose a new procedure for assessing the performance of gene regulatory network (GRN inference methods. The procedure takes into account the underdetermined nature of the inference problem, in which gene regulatory interactions that are inferable or non-inferable are determined based on causal inference. The assessment relies on a new definition of the confusion matrix, which excludes errors associated with non-inferable gene regulations. For demonstration purposes, the proposed assessment procedure is applied to the DREAM 4 In Silico Network Challenge. The results show a marked change in the ranking of participating methods when taking network inferability into account.

  5. Association of lung function and chronic obstructive pulmonary disease with American Heart Association's Life's Simple 7 cardiovascular health metrics.

    Science.gov (United States)

    Fan, Wenjun; Lee, Hwa; Lee, Angela; Kieu, Chi; Wong, Nathan D

    2017-10-01

    Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the U.S. There is a strong association between COPD and cardiovascular (CV) disease; however, the relation between COPD and CV health factors is not well defined. We examined the relation between lung function and CV health factors defined by American Heart Association's (AHA) Life's Simple 7 (LS7). We studied 6352 adults aged ≥20 from the National Health and Nutrition Examination Survey (NHANES) 2009-2012. Analysis of variance was used to compare mean FEV1% of predicted across levels of each LS7 metric and population attributable risk was calculated based on COPD prevalence. We also conducted linear regression and logistic regression analyses to determine the association between lung function, COPD and LS7 score. Overall 19.9% of subjects were defined as having COPD. Subjects in the highest categories of the LS7 metrics had the highest mean values of FEV1% of predicted (p < 0.0001 except for total cholesterol). Current smoking and hypertension had a population attributed risk of 21.8% and 21.1% of COPD, respectively. Compared to subjects with 0 ideal health factors, the gender and ethnicity-adjusted odds (95% CI) for COPD were 0.45 (0.22-0.93), 0.22 (0.11-0.43) for those with 4 and 5-7 factors, but adjustment for age attenuated this relation. LS7 score is associated with lung function as well as the odds of COPD that is largely explained by age. Studies are needed to show if promotion of CV health will preserve healthy lung function. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Ensemble stacking mitigates biases in inference of synaptic connectivity

    Directory of Open Access Journals (Sweden)

    Brendan Chambers

    2018-03-01

    Full Text Available A promising alternative to directly measuring the anatomical connections in a neuronal population is inferring the connections from the activity. We employ simulated spiking neuronal networks to compare and contrast commonly used inference methods that identify likely excitatory synaptic connections using statistical regularities in spike timing. We find that simple adjustments to standard algorithms improve inference accuracy: A signing procedure improves the power of unsigned mutual-information-based approaches and a correction that accounts for differences in mean and variance of background timing relationships, such as those expected to be induced by heterogeneous firing rates, increases the sensitivity of frequency-based methods. We also find that different inference methods reveal distinct subsets of the synaptic network and each method exhibits different biases in the accurate detection of reciprocity and local clustering. To correct for errors and biases specific to single inference algorithms, we combine methods into an ensemble. Ensemble predictions, generated as a linear combination of multiple inference algorithms, are more sensitive than the best individual measures alone, and are more faithful to ground-truth statistics of connectivity, mitigating biases specific to single inference methods. These weightings generalize across simulated datasets, emphasizing the potential for the broad utility of ensemble-based approaches. Mapping the routing of spikes through local circuitry is crucial for understanding neocortical computation. Under appropriate experimental conditions, these maps can be used to infer likely patterns of synaptic recruitment, linking activity to underlying anatomical connections. Such inferences help to reveal the synaptic implementation of population dynamics and computation. We compare a number of standard functional measures to infer underlying connectivity. We find that regularization impacts measures

  7. Role of Educational Status in Explaining the Association between Body Mass Index and Cognitive Function.

    Science.gov (United States)

    Ho, Yi-Te; Kao, Tung-Wei; Peng, Tao-Chun; Liaw, Fang-Yih; Yang, Hui-Fang; Sun, Yu-Shan; Chang, Yaw-Wen; Chen, Wei-Liang

    2016-02-01

    Preserving physical and cognitive function becomes an important issue as people age. A growing number of studies have found that the correlation between body mass index (BMI) and cognitive function changes in different age groups. It is obvious that higher educational status is linked to higher cognitive function in terms of numerous risk factors that influence cognitive function. This study aimed to investigate the interplay between obesity and cognitive function categorized by different educational status.This study included 5021 participants aged 20 to 59 years who completed 3 neurocognitive function tests, including a simple reaction time test (SRTT), a symbol digit substitution test (SDST), and a serial digit learning test (SDLT) as reported in the National Health and Nutrition Examination Survey (NHANES) III database. The associations between neurocognitive function and BMI were analyzed using multivariate linear regression while controlling for confounders.After adjusting for pertinent covariates in mode 3, the β coefficients in the female participants with more than 12 years of education (interpreted as change of 3 neurocognitive function tests for each increment in BMI) comparing obesity groups to those with normal BMI were 16.2 (P education and female participants with fewer than 12 years of education demonstrated increased impairment as their BMI increased. However, this association was not significant after adjustments.Obese individuals had worse neurocognitive function than those of normal weight or overweight, especially in women with a high educational level.

  8. Abdominal pain localization is associated with non-diarrheic Rome III functional gastrointestinal disorders.

    Science.gov (United States)

    Bouchoucha, M; Fysekidis, M; Devroede, G; Raynaud, J-J; Bejou, B; Benamouzig, R

    2013-08-01

    Abdominal pain is common in patients with functional bowel disorders (FBDs). The aim of this study was to characterize the predominant sites of abdominal pain associated with FBD subtypes, as defined by the Rome III criteria. A total of 584 consecutive patients attending FBD consultations in a tertiary center participated in the study. Stool form, abdominal pain location (nine abdominal segments), and pain intensity (10-point Likert scale) during the previous week were recorded. Logistic regression analysis was used to characterize the association of abdominal pain sites with specific FBD subtypes. FBDs were associated with predominant pain sites. Irritable bowel syndrome (IBS) with constipation was associated with pain in the left flank and patients were less likely to report pain in the right hypochondrium. Patients with functional constipation reported pain in the right hypochondrium and were less likely to report pain in the left flank and left iliac site. IBS with alternating constipation and diarrhea was associated with pain in the right flank, and unsubtyped IBS with pain in the hypogastrium Patients with functional abdominal pain syndrome reported the lower right flank as predominant pain site. Patients with unspecified FBDs were least likely to report pain in the hypogastrium. Patients with functional diarrhea, IBS with diarrhea, or functional bloating did not report specific pain sites. The results from this study provide the basis for developing new criteria allowing for the identification of homogeneous groups of patients with non-diarrheic FBDs based on characteristic sites of pain. © 2013 John Wiley & Sons Ltd.

  9. Association of childhood trauma with cognitive function in healthy adults: a pilot study

    Directory of Open Access Journals (Sweden)

    Lin Jin-Mann S

    2010-07-01

    Full Text Available Abstract Background Animal and human studies suggest that stress experienced early in life has detrimental consequences on brain development, including brain regions involved in cognitive function. Cognitive changes are cardinal features of depression and posttraumatic stress disorder. Early-life trauma is a major risk factor for these disorders. Only few studies have measured the long-term consequences of childhood trauma on cognitive function in healthy adults. Methods In this pilot study, we investigated the relationship between childhood trauma exposure and cognitive function in 47 healthy adults, who were identified as part of a larger study from the general population in Wichita, KS. We used the Cambridge Neuropsychological Test Automated Battery (CANTAB and the Wide-Range-Achievement-Test (WRAT-3 to examine cognitive function and individual achievement. Type and severity of childhood trauma was assessed by the Childhood Trauma Questionnaire (CTQ. Data were analyzed using multiple linear regression on CANTAB measures with primary predictors (CTQ scales and potential confounders (age, sex, education, income. Results Specific CTQ scales were significantly associated with measures of cognitive function. Emotional abuse was associated with impaired spatial working memory performance. Physical neglect correlated with impaired spatial working memory and pattern recognition memory. Sexual abuse and physical neglect were negatively associated with WRAT-3 scores. However, the association did not reach the significance level of p Conclusions Our results suggest that physical neglect and emotional abuse might be associated with memory deficits in adulthood, which in turn might pose a risk factor for the development of psychopathology.

  10. The Association Between Physical Activity and Cognitive Function With Considerations by Social Risk Status

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    Emily Frith

    2017-11-01

    Full Text Available We evaluated the association between physical activity and cognitive function among a national sample of the broader U.S. adult population, with consideration by social risk. Data from the 1999-2002 National Health and Nutrition Examination Survey (NHANES were used to identify 2031 older adults, ages 60-85. Social risk was classified by measuring four NHANES variables, namely poverty level, education, minority status, and social living status, which were graded on a scale of 0-4, with higher scores corresponding with higher social risk. The Digit Symbol Substitution Test (DSST was used to assess cognitive function. Physical activity was assessed via a validated self-report questionnaire. After adjustments, meeting physical activity guidelines (vs not was associated with greater cognitive function (β = 3.0, 95% CI [1.5, 4.4], p < 0.001. In this same model, social risk status was also independently associated with cognitive function. Meeting physical activity guidelines (vs. not was not associated with higher cognitive function among those with a social risk score of of 3 (β = -0.01; 95% CI [-6.3, 6.4], p = 0.99 or a social risk score of 4 (β = -6.8, 95% CI [-15.7, 2.0], p = 0.12. In this national sample of older adults, meeting physical activity guidelines, and degree of social risk were independently associated with cognitive function. However, physical activity was not associated with cognitive function among older adults with the highest degree of social risk.

  11. Object-Oriented Type Inference

    DEFF Research Database (Denmark)

    Schwartzbach, Michael Ignatieff; Palsberg, Jens

    1991-01-01

    We present a new approach to inferring types in untyped object-oriented programs with inheritance, assignments, and late binding. It guarantees that all messages are understood, annotates the program with type information, allows polymorphic methods, and can be used as the basis of an op...

  12. Inference in hybrid Bayesian networks

    DEFF Research Database (Denmark)

    Lanseth, Helge; Nielsen, Thomas Dyhre; Rumí, Rafael

    2009-01-01

    Since the 1980s, Bayesian Networks (BNs) have become increasingly popular for building statistical models of complex systems. This is particularly true for boolean systems, where BNs often prove to be a more efficient modelling framework than traditional reliability-techniques (like fault trees...... decade's research on inference in hybrid Bayesian networks. The discussions are linked to an example model for estimating human reliability....

  13. Mixed normal inference on multicointegration

    NARCIS (Netherlands)

    Boswijk, H.P.

    2009-01-01

    Asymptotic likelihood analysis of cointegration in I(2) models, see Johansen (1997, 2006), Boswijk (2000) and Paruolo (2000), has shown that inference on most parameters is mixed normal, implying hypothesis test statistics with an asymptotic 2 null distribution. The asymptotic distribution of the

  14. Statistical inference and Aristotle's Rhetoric.

    Science.gov (United States)

    Macdonald, Ranald R

    2004-11-01

    Formal logic operates in a closed system where all the information relevant to any conclusion is present, whereas this is not the case when one reasons about events and states of the world. Pollard and Richardson drew attention to the fact that the reasoning behind statistical tests does not lead to logically justifiable conclusions. In this paper statistical inferences are defended not by logic but by the standards of everyday reasoning. Aristotle invented formal logic, but argued that people mostly get at the truth with the aid of enthymemes--incomplete syllogisms which include arguing from examples, analogies and signs. It is proposed that statistical tests work in the same way--in that they are based on examples, invoke the analogy of a model and use the size of the effect under test as a sign that the chance hypothesis is unlikely. Of existing theories of statistical inference only a weak version of Fisher's takes this into account. Aristotle anticipated Fisher by producing an argument of the form that there were too many cases in which an outcome went in a particular direction for that direction to be plausibly attributed to chance. We can therefore conclude that Aristotle would have approved of statistical inference and there is a good reason for calling this form of statistical inference classical.

  15. Association Between Chronic Conditions and Physical Function Among Veteran and Non-Veteran Women With Diabetes

    Science.gov (United States)

    Gray, Kristen E.; Katon, Jodie G.; Rillamas-Sun, Eileen; Bastian, Lori A.; Nelson, Karin M.; LaCroix, Andrea Z.; Reiber, Gayle E.

    2016-01-01

    Abstract Purpose of the Study: To compare the number of chronic conditions among a list of 12 and their association with physical function among postmenopausal non-Veteran and Veteran women with diabetes. Design and Methods: Among women with diabetes from the Women’s Health Initiative, we compared the average number of chronic conditions between non-Veterans and Veterans and the association between total number of chronic conditions on subsequent RAND-36 physical function. To examine associations between each condition and subsequent physical function, we compared women with diabetes plus one chronic condition to women with diabetes alone using linear regression in separate models for each condition and for non-Veterans and Veterans. Results: Both non-Veterans ( N = 23,542) and Veterans ( N = 618) with diabetes had a median of 3 chronic conditions. Decreases in physical function for each additional condition were larger among Veterans than non-Veterans (−6.3 vs. −4.1 points). Decreases in physical function among women with diabetes plus one chronic condition were greater than that reported for diabetes alone for all combinations and were more pronounced among Veterans (non-Veterans: −11.1 to −24.2, Veterans: −16.6 to −40.4 points). Hip fracture, peripheral artery disease, cerebrovascular disease, and coronary disease in combination with diabetes were associated with the greatest decreases in physical function. Implications: Chronic conditions were common among postmenopausal women with diabetes and were associated with large declines in physical function, particularly among Veterans. Interventions to prevent and reduce the impact of these conditions and facilitate coordination of care among women with diabetes may help them maintain physical function. PMID:26768385

  16. Phylodynamic Inference with Kernel ABC and Its Application to HIV Epidemiology.

    Science.gov (United States)

    Poon, Art F Y

    2015-09-01

    The shapes of phylogenetic trees relating virus populations are determined by the adaptation of viruses within each host, and by the transmission of viruses among hosts. Phylodynamic inference attempts to reverse this flow of information, estimating parameters of these processes from the shape of a virus phylogeny reconstructed from a sample of genetic sequences from the epidemic. A key challenge to phylodynamic inference is quantifying the similarity between two trees in an efficient and comprehensive way. In this study, I demonstrate that a new distance measure, based on a subset tree kernel function from computational linguistics, confers a significant improvement over previous measures of tree shape for classifying trees generated under different epidemiological scenarios. Next, I incorporate this kernel-based distance measure into an approximate Bayesian computation (ABC) framework for phylodynamic inference. ABC bypasses the need for an analytical solution of model likelihood, as it only requires the ability to simulate data from the model. I validate this "kernel-ABC" method for phylodynamic inference by estimating parameters from data simulated under a simple epidemiological model. Results indicate that kernel-ABC attained greater accuracy for parameters associated with virus transmission than leading software on the same data sets. Finally, I apply the kernel-ABC framework to study a recent outbreak of a recombinant HIV subtype in China. Kernel-ABC provides a versatile framework for phylodynamic inference because it can fit a broader range of models than methods that rely on the computation of exact likelihoods. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  17. The association between adult-type hypolactasia and symptoms of functional dyspepsia

    Directory of Open Access Journals (Sweden)

    André Castagna Wortmann

    2018-01-01

    Full Text Available Abstract Functional dyspepsia and lactose intolerance (adult-type hypolactasia, ATH are common conditions that may coexist or even be confounded. Their clinical presentation can be similar, however, lactose intolerance does not form part of the diagnostic investigation of functional dyspepsia. Studies on the association between functional dyspepsia and ATH are scarce. This study aimed to evaluate whether ATH is associated with symptoms of functional dyspepsia. Patients fulfilling the Rome III diagnostic criteria for functional dyspepsia underwent genetic testing for ATH. Dyspeptic symptoms were evaluated and scored according to a validated questionnaire. The diagnostic criteria for ATH was a CC genotype for the -13910C/T polymorphism, located upstream of the lactase gene. The mean scores for dyspeptic symptoms were compared between patients with ATH and those with lactase persistence. A total of 197 functional dyspeptic patients were included in the study. Mean age was 47.7 years and 82.7% patients were women. Eighty-eight patients (44.7% had a diagnosis of ATH. Abdominal bloating scores were higher in ATH patients compared to the lactase persistent patients (P=0.014. The remaining dyspeptic symptom scores were not significantly different between the two groups. The study results demonstrate an association between ATH and bloating in patients with functional dyspepsia.

  18. Family functioning is associated with depressive symptoms in caregivers of acute stroke survivors.

    Science.gov (United States)

    Epstein-Lubow, Gary P; Beevers, Christopher G; Bishop, Duane S; Miller, Ivan W

    2009-06-01

    To determine whether family functioning is uniquely associated with caregiver depressive symptoms in the immediate aftermath of stroke. Cross-sectional data from the baseline assessment of an intervention study for stroke survivors and their families. Neurology inpatient service of a large urban hospital. Stroke survivors (n=192), each with a primary caregiver. The mean age of stroke survivors was 66 years, and most, 57%, were men (n=110). The mean age of caregivers was 57 years, and 73% (n=140) of the caregivers were women. Eighty-five percent of caregivers were white. Not applicable. Measures were chosen to assess caregivers' depressive symptoms (Centers for Epidemiologic Studies Depression Scale), family functioning (Family Assessment Device), and additional factors such as health status (Medical Outcomes Study 36-Item Short-Form Health Survey) and stroke survivors' cognitive abilities (modified Mini-Mental State Examination) and functional impairments (FIM and Frenchay Activities Index). Depressive symptoms were mild to moderate in 14% and severe in 27% of caregivers. Family functioning was assessed as unhealthy in 34% of caregiver-patient dyads. In statistical regression models, caregiver depression was associated with patients' sex, caregivers' general health, and family functioning. Forty-one percent of caregivers experienced prominent depressive symptoms after their family member's stroke. Higher depression severity in caregivers was associated with caring for a man, and having worse health and poor family functioning. After stroke, the assessment of caregivers' health and family functioning may help determine which caregivers are most at risk for a depressive syndrome.

  19. Financial Exploitation Is Associated With Structural and Functional Brain Differences in Healthy Older Adults.

    Science.gov (United States)

    Spreng, R Nathan; Cassidy, Benjamin N; Darboh, Bri S; DuPre, Elizabeth; Lockrow, Amber W; Setton, Roni; Turner, Gary R

    2017-10-01

    Age-related brain changes leading to altered socioemotional functioning may increase vulnerability to financial exploitation. If confirmed, this would suggest a novel mechanism leading to heightened financial exploitation risk in older adults. Development of predictive neural markers could facilitate increased vigilance and prevention. In this preliminary study, we sought to identify structural and functional brain differences associated with financial exploitation in older adults. Financially exploited older adults (n = 13, 7 female) and a matched cohort of older adults who had been exposed to, but avoided, a potentially exploitative situation (n = 13, 7 female) were evaluated. Using magnetic resonance imaging, we examined cortical thickness and resting state functional connectivity. Behavioral data were collected using standardized cognitive assessments, self-report measures of mood and social functioning. The exploited group showed cortical thinning in anterior insula and posterior superior temporal cortices, regions associated with processing affective and social information, respectively. Functional connectivity encompassing these regions, within default and salience networks, was reduced, while between network connectivity was increased. Self-reported anger and hostility was higher for the exploited group. We observed financial exploitation associated with brain differences in regions involved in socioemotional functioning. These exploratory and preliminary findings suggest that alterations in brain regions implicated in socioemotional functioning may be a marker of financial exploitation risk. Large-scale, prospective studies are necessary to validate this neural mechanism, and develop predictive markers for use in clinical practice. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America.

  20. Sex on the brain! Associations between sexual activity and cognitive function in older age.

    Science.gov (United States)

    Wright, Hayley; Jenks, Rebecca A

    2016-03-01

    the relationship between cognition and sexual activity in healthy older adults is under-researched. A limited amount of research in this area has shown that sexual activity is associated with better cognition in older men. The current study explores the possible mediating factors in this association in men and women, and attempts to provide an explanation in terms of physiological influences on cognitive function. using newly available data from Wave 6 of the English Longitudinal Study of Ageing, the current study explored associations between sexual activity and cognition in adults aged 50-89 (n = 6,833). Two different tests of cognitive function were analysed: number sequencing, which broadly relates to executive function, and word recall, which broadly relates to memory. after adjusting for age, education, wealth, physical activity, depression, cohabiting, self-rated health, loneliness and quality of life, there were significant associations between sexual activity and number sequencing and recall in men. However, in women there was a significant association between sexual activity and recall, but not number sequencing. possible mediators of these associations (e.g. neurotransmitters) are discussed. The cross-sectional nature of the analysis is limiting, but provides a promising avenue for future explorations and longitudinal studies. The findings have implications for the promotion of sexual counselling in healthcare settings, where maintaining a healthy sex life in older age could be instrumental in improving cognitive function and well-being. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society.

  1. The association of mental health conditions with employment, interpersonal, and subjective functioning after intimate partner violence.

    Science.gov (United States)

    Beck, J Gayle; Clapp, Joshua D; Jacobs-Lentz, Jason; McNiff, Judiann; Avery, Megan; Olsen, Shira A

    2014-11-01

    This study explored the associations of posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), and depressive symptoms with employment, social support, and subjective functioning in 100 women who were seeking mental health assistance after intimate partner violence. Depressive disorders showed significant associations with low levels of social support, diminished self-esteem, reduced quality of life, and elevated negative social problem-solving orientation. PTSD severity was significantly associated with low self-esteem and elevated negative problem orientation, while severity of GAD was only associated with negative problem orientation. Results are discussed in light of current service models for women who have experienced intimate partner violence. © The Author(s) 2014.

  2. Bootstrapping phylogenies inferred from rearrangement data

    Directory of Open Access Journals (Sweden)

    Lin Yu

    2012-08-01

    Full Text Available Abstract Background Large-scale sequencing of genomes has enabled the inference of phylogenies based on the evolution of genomic architecture, under such events as rearrangements, duplications, and losses. Many evolutionary models and associated algorithms have been designed over the last few years and have found use in comparative genomics and phylogenetic inference. However, the assessment of phylogenies built from such data has not been properly addressed to date. The standard method used in sequence-based phylogenetic inference is the bootstrap, but it relies on a large number of homologous characters that can be resampled; yet in the case of rearrangements, the entire genome is a single character. Alternatives such as the jackknife suffer from the same problem, while likelihood tests cannot be applied in the absence of well established probabilistic models. Results We present a new approach to the assessment of distance-based phylogenetic inference from whole-genome data; our approach combines features of the jackknife and the bootstrap and remains nonparametric. For each feature of our method, we give an equivalent feature in the sequence-based framework; we also present the results of extensive experimental testing, in both sequence-based and genome-based frameworks. Through the feature-by-feature comparison and the experimental results, we show that our bootstrapping approach is on par with the classic phylogenetic bootstrap used in sequence-based reconstruction, and we establish the clear superiority of the classic bootstrap for sequence data and of our corresponding new approach for rearrangement data over proposed variants. Finally, we test our approach on a small dataset of mammalian genomes, verifying that the support values match current thinking about the respective branches. Conclusions Our method is the first to provide a standard of assessment to match that of the classic phylogenetic bootstrap for aligned sequences. Its

  3. Bootstrapping phylogenies inferred from rearrangement data.

    Science.gov (United States)

    Lin, Yu; Rajan, Vaibhav; Moret, Bernard Me

    2012-08-29

    Large-scale sequencing of genomes has enabled the inference of phylogenies based on the evolution of genomic architecture, under such events as rearrangements, duplications, and losses. Many evolutionary models and associated algorithms have been designed over the last few years and have found use in comparative genomics and phylogenetic inference. However, the assessment of phylogenies built from such data has not been properly addressed to date. The standard method used in sequence-based phylogenetic inference is the bootstrap, but it relies on a large number of homologous characters that can be resampled; yet in the case of rearrangements, the entire genome is a single character. Alternatives such as the jackknife suffer from the same problem, while likelihood tests cannot be applied in the absence of well established probabilistic models. We present a new approach to the assessment of distance-based phylogenetic inference from whole-genome data; our approach combines features of the jackknife and the bootstrap and remains nonparametric. For each feature of our method, we give an equivalent feature in the sequence-based framework; we also present the results of extensive experimental testing, in both sequence-based and genome-based frameworks. Through the feature-by-feature comparison and the experimental results, we show that our bootstrapping approach is on par with the classic phylogenetic bootstrap used in sequence-based reconstruction, and we establish the clear superiority of the classic bootstrap for sequence data and of our corresponding new approach for rearrangement data over proposed variants. Finally, we test our approach on a small dataset of mammalian genomes, verifying that the support values match current thinking about the respective branches. Our method is the first to provide a standard of assessment to match that of the classic phylogenetic bootstrap for aligned sequences. Its support values follow a similar scale and its receiver

  4. Association of functional MMP-2 gene variant with intracranial aneurysms: case-control genetic association study and meta-analysis.

    Science.gov (United States)

    Alg, Varinder S; Ke, Xiayi; Grieve, Joan; Bonner, Stephen; Walsh, Daniel C; Bulters, Diederik; Kitchen, Neil; Houlden, Henry; Werring, David J

    2018-01-15

    Abnormalities in Matrix Metalloproteinase (MMP) genes, which are important in extracellular matrix (ECM) maintenance and therefore arterial wall integrity are a plausible underlying mechanism of intracranial aneurysm (IA) formation, growth and subsequent rupture. We investigated whether the rs243865 C > T SNP (single nucleotide polymorphism) within the MMP-2 gene (which influences gene transcription) is associated with IA compared to matched controls. We conducted a case-control genetic association study, adjusted for known IA risk factors (smoking and hypertension), in a UK Caucasian population of 1409 patients with intracranial aneurysms (IA), and 1290 matched controls, to determine the association of the rs243865 C > T functional MMP-2 gene SNP with IA (overall, and classified as ruptured and unruptured). We also undertook a meta-analysis of two previous studies examining this SNP. The rs243865 T allele was associated with IA presence in univariate (OR 1.18 [95% CI 1.04-1.33], p = .01) and in multi-variable analyses adjusted for smoking and hypertension status (OR 1.16 [95% CI 1.01-1.35], p = .042). Subgroup analysis demonstrated an association of the rs243865 SNP with ruptured IA (OR 1.18 [95% CI 1.03-1.34] p = .017), but, not unruptured IA (OR 1.17 [95% CI 0.97-1.42], p = .11). Our study demonstrated an association between the functional MMP-2 rs243865 variant and IAs. Our findings suggest a genetic role for altered extracellular matrix integrity in the pathogenesis of IA development and rupture.

  5. The association between patient participation and functional gain following inpatient rehabilitation.

    Science.gov (United States)

    Morghen, Sara; Morandi, Alessandro; Guccione, Andrew A; Bozzini, Michela; Guerini, Fabio; Gatti, Roberto; Del Santo, Francesco; Gentile, Simona; Trabucchi, Marco; Bellelli, Giuseppe

    2017-08-01

    To evaluate patients' participation during physical therapy sessions as assessed with the Pittsburgh rehabilitation participation scale (PRPS) as a possible predictor of functional gain after rehabilitation training. All patients aged 65 years or older consecutively admitted to a Department of Rehabilitation and Aged Care (DRAC) were evaluated on admission regarding their health, nutritional, functional and cognitive status. Functional status was assessed with the functional independence measure (FIM) on admission and at discharge. Participation during rehabilitation sessions was measured with the PRPS. Functional gain was evaluated using the Montebello rehabilitation factor score (MRFS efficacy), and patients stratified in two groups according to their level of functional gain and their sociodemographic, clinical and functional characteristics were compared. Predictors of poor functional gain were evaluated using a multivariable logistic regression model adjusted for confounding factors. A total of 556 subjects were included in this study. Patients with poor functional gain at discharge demonstrated lower participation during physical therapy sessions were significantly older, more cognitively and functionally impaired on admission, more depressed, more comorbid, and more frequently admitted for cardiac disease or immobility syndrome than their counterparts. There was a significant linear association between PRPS scores and MRFS efficacy. In a multivariable logistic regression model, participation was independently associated with functional gain at discharge (odds ratio 1.51, 95 % confidence interval 1.19-1.91). This study showed that participation during physical therapy affects the extent of functional gain at discharge in a large population of older patients with multiple diseases receiving in-hospital rehabilitation.

  6. Are a Healthy Diet and Physical Activity Synergistically Associated with Cognitive Functioning in Older Adults?

    Science.gov (United States)

    Nijholt, W; Jager-Wittenaar, H; Visser, M; van der Schans, C P; Hobbelen, J S M

    2016-01-01

    Previous research has demonstrated that being both physically active and adhering a healthy diet is associated with improved cognitive functioning; however, it remains unclear whether these factors act synergistically. We investigated the synergistic association of a healthy diet and being physically active with cognitive functioning. Cross-sectional study. Data from the Longitudinal Aging Study Amsterdam (LASA) were used. We analyzed data from 2,165 community dwelling adults who were aged 55-85 years, 56% of whom were female. Cognitive functioning was assessed by the Mini-Mental State Examination (MMSE), an MMSE score of >26 indicates good cognitive functioning. Physical activity was assessed by the LASA Physical Activity Questionnaire and was considered sufficient if the person engaged in moderately intense physical activity ≥ 20 min/day. A healthy diet score was based on the intake of fruit, vegetables and fish. Each of the food groups was assigned a score that ranged from 1 (well below the Dutch guideline for a healthy diet) to 4 (well above the Dutch guideline for a healthy diet), and the scores were aggregated to determine a healthy diet (healthy ≥ 9 points). Multiple logistic and linear regression analyses were used to examine the (synergistic) association among physical activity, a healthy diet and cognitive functioning. All analyses were adjusted for potential chronic diseases and lifestyle confounders. Of all of the participants, 25% were diagnosed with a cognitive impairment (MMSE ≤26), 80% were physically active and 41% had a healthy diet. Sixty three percent of the participants both adhered to a healthy diet and were physically active. Sufficient daily physical activity (OR=2.545 phealthy diet (OR=1.766 p=.002) were associated with good cognitive functioning. After adjusting for confounding factors, sufficient physical activity was not significantly related to cognitive functioning (p=.163); however adherence to a healthy diet remained

  7. Functional substrate for memory function differences between patients with left and right mesial temporal lobe epilepsy associated with hippocampal sclerosis.

    Science.gov (United States)

    Jin, Seung-Hyun; Chung, Chun Kee

    2015-10-01

    Little is known about the functional substrate for memory function differences in patients with left or right mesial temporal lobe epilepsy (mTLE) associated with hippocampal sclerosis (HS) from an electrophysiological perspective. To characterize these differences, we hypothesized that hippocampal theta connectivity in the resting-state might be different between patients with left and right mTLE with HS and be correlated with memory performance. Resting-state hippocampal theta connectivity, identified via whole-brain magnetoencephalography, was evaluated. Connectivity and memory function in 41 patients with mTLE with HS (left mTLE=22; right mTLE=19) were compared with those in 46 age-matched healthy controls and 28 patients with focal cortical dysplasia (FCD) but without HS. Connectivity between the right hippocampus and the left middle frontal gyrus was significantly stronger in patients with right mTLE than in patients with left mTLE. Moreover, this connectivity was positively correlated with delayed verbal recall and recognition scores in patients with mTLE. Patients with left mTLE had greater delayed recall impairment than patients with right mTLE and FCD. Similarly, delayed recognition performance was worse in patients with left mTLE than in patients with right mTLE and FCD. No significant differences in memory function between patients with right mTLE and FCD were detected. Patients with right mTLE showed significantly stronger hippocampal theta connectivity between the right hippocampus and left middle frontal gyrus than patients with FCD and left mTLE. Our results suggest that right hippocampal-left middle frontal theta connectivity could be a functional substrate that can account for differences in memory function between patients with left and right mTLE. This functional substrate might be related to different compensatory mechanisms against the structural hippocampal lesions in left and right mTLE groups. Given the positive correlation between

  8. The association between depressive symptoms, cognitive function, and inflammation in major depression

    DEFF Research Database (Denmark)

    Krogh, Jesper; Benros, Michael E; Jørgensen, Martin Balslev

    2014-01-01

    The purpose of this study was to assess the association between IL-6 and CRP with depressive items and cognitive function. We included 112 outpatients with major depression from an exercise trial and 57 healthy controls. IL-6, high sensitive CRP (hsCRP), and cognitive function were assessed in all...... subjects. After baseline assessment, patients were randomised to either a 3months exercise intervention or an exercise control group. Post-intervention IL-6, hsCRP, depressive symptoms, and cognitive function were reassessed in the patient group. IL-6 and hsCRP were significantly increased in depressed...... patients compared to healthy controls (p=0.02 and 0.04). These differences were no longer significant after adjustment for lifestyle associated variables. We found no association between immune markers and specific depressive symptoms at baseline or as change over time. Regarding the cognitive tests, IL-6...

  9. Compensated reduction in Leydig cell function is associated with lower semen quality variables

    DEFF Research Database (Denmark)

    Jørgensen, N.; Joensen, U. N.; Toppari, J.

    2016-01-01

    STUDY QUESTION: Is the Leydig cell function of young European men associated with semen quality? SUMMARY ANSWER: Compensated reduction in Leydig cell function, defined as increased LH concentration combined with adequate testosterone production is associated with lower semen quality. WHAT...... IS ALREADY KNOWN: Semen quality of young European men shows a heterogeneous pattern. Many have sperm counts below and in the lower WHO reference where there nevertheless is a significant risk of subfecundity. Little is known about differences in Leydig cell function between men with semen quality below......, Lithuania, and Spain. The men originated from the general populations, all were young, almost all were unaware of their fecundity and each provided a semen and blood sample. Associations between semen parameters and serum levels of testosterone and luteinising hormone (LH), calculated free testosterone...

  10. Slimmer women's waist is associated with better erectile function in men independent of age.

    Science.gov (United States)

    Brody, Stuart; Weiss, Petr

    2013-10-01

    Previous research has indicated that men generally rate slimmer women as more sexually attractive, consistent with the increased morbidity risks associated with even mild abdominal adiposity. To assess the association of women's waist size with a more tangible measure of perceived sexual attractiveness (as well as reward value for both sexes), we examined the association of women's age and waist circumference with an index of men's erectile function (IIEF-5 scores), frequency of penile-vaginal intercourse (PVI), and sexual satisfaction in a representative sample of Czechs (699 men and 715 women) aged 35-65 years. Multivariate analyses indicated that better erectile function scores were independently associated with younger age of self and partner and women's slimmer waist. PVI frequency was independently associated with women's younger age and women's slimmer waist. Sexual satisfaction was independently associated with men's younger age and slimmer waist for both sexes. Better erectile function, greater PVI frequency, and greater sexual satisfaction were associated with women's slimmer waist, independently of both sexes' ages. Possible reasons for the waist effects were discussed, including women's abdominal body fat decreasing their own desire through neurohormonal mechanisms and decreasing their partner's desire through evolutionarily-related decreased sexual attractiveness.

  11. Automatic physical inference with information maximizing neural networks

    Science.gov (United States)

    Charnock, Tom; Lavaux, Guilhem; Wandelt, Benjamin D.

    2018-04-01

    Compressing large data sets to a manageable number of summaries that are informative about the underlying parameters vastly simplifies both frequentist and Bayesian inference. When only simulations are available, these summaries are typically chosen heuristically, so they may inadvertently miss important information. We introduce a simulation-based machine learning technique that trains artificial neural networks to find nonlinear functionals of data that maximize Fisher information: information maximizing neural networks (IMNNs). In test cases where the posterior can be derived exactly, likelihood-free inference based on automatically derived IMNN summaries produces nearly exact posteriors, showing that these summaries are good approximations to sufficient statistics. In a series of numerical examples of increasing complexity and astrophysical relevance we show that IMNNs are robustly capable of automatically finding optimal, nonlinear summaries of the data even in cases where linear compression fails: inferring the variance of Gaussian signal in the presence of noise, inferring cosmological parameters from mock simulations of the Lyman-α forest in quasar spectra, and inferring frequency-domain parameters from LISA-like detections of gravitational waveforms. In this final case, the IMNN summary outperforms linear data compression by avoiding the introduction of spurious likelihood maxima. We anticipate that the automatic physical inference method described in this paper will be essential to obtain both accurate and precise cosmological parameter estimates from complex and large astronomical data sets, including those from LSST and Euclid.

  12. Threat-related amygdala functional connectivity is associated with 5-HTTLPR genotype and neuroticism

    DEFF Research Database (Denmark)

    Madsen, Martin Korsbak; Mc Mahon, Brenda; Andersen, Sofie Bech

    2016-01-01

    between right amygdala and mPFC and visual cortex, and between both amygdalae and left lateral orbitofrontal (lOFC) and ventrolateral prefrontal cortex (vlPFC). Notably, 5-HTTLPR moderated the association between neuroticism and functional connectivity between both amygdalae and left l...... is not fully understood. Using functional magnetic resonance imaging, we evaluated independent and interactive effects of the 5-HTTLPR genotype and neuroticism on amygdala functional connectivity during an emotional faces paradigm in 76 healthy individuals. Functional connectivity between left amygdala......Communication between the amygdala and other brain regions critically regulates sensitivity to threat, which has been associated with risk for mood and affective disorders. The extent to which these neural pathways are genetically determined or correlate with risk-related personality measures...

  13. Genetic Variants in KLOTHO Associate With Cognitive Function in the Oldest Old Group

    DEFF Research Database (Denmark)

    Mengel-From, Jonas; Sørensen, Mette; Nygaard, Marianne

    2016-01-01

    , for example, growth factor signaling. In the present study, 19 tagging gene variants in KL were studied in relation to 2 measures of cognitive function, a 5-item cognitive composite score and the Mini Mental State Examination, in 1,480 Danes 92-100 years of age. We found that heterozygotes for the previously......Decline in cognitive abilities is a major concern in aging individuals. A potential important factor for functioning of the central nervous system in late-life stages is the KLOTHO (KL) gene. KL is expressed in various organs including the brain and is involved in multiple biological processes...... reported KL-VS had poorer cognitive function than noncarriers. Two other variants positioned in the 5' end of the gene, rs398655 and rs562020, were associated with better cognitive function independently of KL-VS, and the common haplotype AG was associated with poorer cognition, consistently across two...

  14. Impact of noise on molecular network inference.

    Directory of Open Access Journals (Sweden)

    Radhakrishnan Nagarajan

    Full Text Available Molecular entities work in concert as a system and mediate phenotypic outcomes and disease states. There has been recent interest in modelling the associations between molecular entities from their observed expression profiles as networks using a battery of algorithms. These networks have proven to be useful abstractions of the underlying pathways and signalling mechanisms. Noise is ubiquitous in molecular data and can have a pronounced effect on the inferred network. Noise can be an outcome of several factors including: inherent stochastic mechanisms at the molecular level, variation in the abundance of molecules, heterogeneity, sensitivity of the biological assay or measurement artefacts prevalent especially in high-throughput settings. The present study investigates the impact of discrepancies in noise variance on pair-wise dependencies, conditional dependencies and constraint-based Bayesian network structure learning algorithms that incorporate conditional independence tests as a part of the learning process. Popular network motifs and fundamental connections, namely: (a common-effect, (b three-chain, and (c coherent type-I feed-forward loop (FFL are investigated. The choice of these elementary networks can be attributed to their prevalence across more complex networks. Analytical expressions elucidating the impact of discrepancies in noise variance on pairwise dependencies and conditional dependencies for special cases of these motifs are presented. Subsequently, the impact of noise on two popular constraint-based Bayesian network structure learning algorithms such as Grow-Shrink (GS and Incremental Association Markov Blanket (IAMB that implicitly incorporate tests for conditional independence is investigated. Finally, the impact of noise on networks inferred from publicly available single cell molecular expression profiles is investigated. While discrepancies in noise variance are overlooked in routine molecular network inference, the

  15. Association between central obesity and executive function as assessed by stroop task performance: A functional near-infrared spectroscopy study

    Directory of Open Access Journals (Sweden)

    Zhangyan Deng

    2018-01-01

    Full Text Available Recent studies have suggested a link between executive function (EF and obesity. Studies often adopt body mass index (BMI, which reflects the distribution of subcutaneous fat, as the sole marker of obesity; however, BMI is inappropriate to distinguish central obesity, which indicates the centralized distribution of visceral fat. Visceral fat compared with subcutaneous fat represents greater relative lipid turnover and may increase the risk of cognitive decline in older adults. However, the relationship between EF and central obesity is largely unknown, particularly in young adults. Therefore, we used waist circumference (WC as a marker of central obesity and investigated different sensitivities between BMI and WC in the brain function. A total of 26 healthy young adults (aged 18–25 years; 42% female underwent functional near-infrared spectroscopy assessments. EF was assessed using the Stroop task, which is a classical measurement of EF. A significant Stroop effect was observed in the behavioral and hemodynamic data. In addition, we observed that behavioral interference on the Stroop task varied much more in subjects with higher BMI and WC than those subjects with lower. Elevated BMI and WC were associated with a decreased hemodynamic response during the Stroop task specifically in the prefrontal cortex (PFC. Compared to BMI, WC was more closely connected with inhibitory control and revealed right lateralized PFC activation. Our findings suggest that WC is a reliable indicator of brain function in young adults and propose a relationship between EF and central obesity.

  16. Inferring network topology from complex dynamics

    International Nuclear Information System (INIS)

    Shandilya, Srinivas Gorur; Timme, Marc

    2011-01-01

    Inferring the network topology from dynamical observations is a fundamental problem pervading research on complex systems. Here, we present a simple, direct method for inferring the structural connection topology of a network, given an observation of one collective dynamical trajectory. The general theoretical framework is applicable to arbitrary network dynamical systems described by ordinary differential equations. No interference (external driving) is required and the type of dynamics is hardly restricted in any way. In particular, the observed dynamics may be arbitrarily complex; stationary, invariant or transient; synchronous or asynchronous and chaotic or periodic. Presupposing a knowledge of the functional form of the dynamical units and of the coupling functions between them, we present an analytical solution to the inverse problem of finding the network topology from observing a time series of state variables only. Robust reconstruction is achieved in any sufficiently long generic observation of the system. We extend our method to simultaneously reconstructing both the entire network topology and all parameters appearing linear in the system's equations of motion. Reconstruction of network topology and system parameters is viable even in the presence of external noise that distorts the original dynamics substantially. The method provides a conceptually new step towards reconstructing a variety of real-world networks, including gene and protein interaction networks and neuronal circuits.

  17. Association of sarcopenia with depressive symptoms and functional status among ambulatory community-dwelling elderly.

    Science.gov (United States)

    Kilavuz, Asli; Meseri, Reci; Savas, Sumru; Simsek, Hatice; Sahin, Sevnaz; Bicakli, Derya Hopanci; Sarac, Fulden; Uyar, Mehmet; Akcicek, Fehmi

    Sarcopenia, functional disability, and depression are common problems in the elderly. Sarcopenia is associated with physical disability, functional impairment, depression, cardiometabolic diseases, and even mortality. This study aims to determine the association of sarcopenia with depression and functional status among ambulatory community-dwelling elderly aged 65 years and older. The sample of this cross-sectional study consisted of 28,323 people, aged 65 years and older, living in Bornova, Izmir. Multi-stage sample selection was performed to reach 1007 individuals. However, 966 elderly people could be reached, and 861 elderly people who can walk were included in the study. The data were collected by the interviewers at home through face-to-face interview. The mean age was 72.2 ± 5.8 (65-100) years. The prevalence of functional disability, depressive symptoms, and sarcopenia were 21.7%, 25.2%, and 4.6%, respectively. In multivariate analysis depression was associated with sarcopenia, being illiterate and divorced, perception of the economic situation as poor/moderate, increased number of chronic diseases, and having at least one physical disability. IADL associated functional disability with sarcopenia, being illiterate/literate and female, increased age and number of medications, and the BMI. Sarcopenia in ambulatory community-dwelling elderly is significantly associated with depressive symptoms and functional disability. Elderly people at high risk of sarcopenia should be screened for functional disability and depression. Appropriate interventions should also be implemented. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Study regarding the density evolution of messages and the characteristic functions associated of a LDPC code

    Science.gov (United States)

    Drăghici, S.; Proştean, O.; Răduca, E.; Haţiegan, C.; Hălălae, I.; Pădureanu, I.; Nedeloni, M.; (Barboni Haţiegan, L.

    2017-01-01

    In this paper a method with which a set of characteristic functions are associated to a LDPC code is shown and also functions that represent the evolution density of messages that go along the edges of a Tanner graph. Graphic representations of the density evolution are shown respectively the study and simulation of likelihood threshold that render asymptotic boundaries between which there are decodable codes were made using MathCad V14 software.

  19. Alterations of Brain Functional Architecture Associated with Psychopathic Traits in Male Adolescents with Conduct Disorder

    OpenAIRE

    Pu, Weidan; Luo, Qiang; Jiang, Yali; Gao, Yidian; Ming, Qingsen; Yao, Shuqiao

    2017-01-01

    Psychopathic traits of conduct disorder (CD) have a core callous-unemotional (CU) component and an impulsive-antisocial component. Previous task-driven fMRI studies have suggested that psychopathic traits are associated with dysfunction of several brain areas involved in different cognitive functions (e.g., empathy, reward, and response inhibition etc.), but the relationship between psychopathic traits and intrinsic brain functional architecture has not yet been explored in CD. Using a holist...

  20. Physical practice is associated with less functional disability in medical students with migraine

    OpenAIRE

    Domingues,Renan B.; Teixeira,Antônio Lúcio; Domingues,Simone A.

    2011-01-01

    The aim of this study was to investigate possible association between migraine and physical practice among 480 medical students who were submitted to a questionnaire about headaches and physical practices. Migraine diagnosis was assessed by ID-Migraine and functional disability was evaluated with MIDAS. The type (aerobic or strength training), the weekly frequency and the intensity of physical practice and body mass index (BMI) were assessed. There was a reduction in functional disability of ...

  1. Association of pulse wave velocity and pulse pressure with decline in kidney function.

    Science.gov (United States)

    Kim, Chang Seong; Kim, Ha Yeon; Kang, Yong Un; Choi, Joon Seok; Bae, Eun Hui; Ma, Seong Kwon; Kim, Soo Wan

    2014-05-01

    The association between arterial stiffness and decline in kidney function in patients with mild to moderate chronic kidney disease (CKD) is not well established. This study investigated whether pulse wave velocity (PWV) and pulse pressure (PP) are independently associated with glomerular filtration rate (GFR) and rapid decline in kidney function in early CKD. Carotid femoral PWV (cfPWV), brachial-ankle PWV (baPWV), and PP were measured in a cohort of 913 patients (mean age, 63±10 years; baseline estimated GFR, 84±18 mL/min/1.73 m(2) ). Estimated GFR was measured at baseline and at follow-up. The renal outcome examined was rapid decline in kidney function (estimated GFR loss, >3 mL/min/1.73 m(2) per year). The median follow-up duration was 3.2 years. Multivariable adjusted linear regression model indicated that arterial PWV (both cfPWV and baPWV) and PP increased as estimated GFR declined, but neither was associated with kidney function after adjustment for various covariates. Multivariable logistic regression analysis found that cfPWV and baPWV were not associated with rapid decline in kidney function (odds ratio [OR], 1.39, 95% confidence interval [CI], 0.41-4.65; OR, 2.51, 95% CI, 0.66-9.46, respectively), but PP was (OR, 1.22, 95% CI, 1.01-1.48; P=.045). Arterial stiffness assessed using cfPWV and baPWV was not correlated with lower estimated GFR and rapid decline in kidney function after adjustment for various confounders. Thus, PP is an independent risk factor for rapid decline in kidney function in populations with relatively preserved kidney function (estimated GFR ≥30 mL/min/1.73 m(2) ). ©2014 Wiley Periodicals, Inc.

  2. Associations and impact factors between living arrangements and functional disability among older Chinese adults.

    Directory of Open Access Journals (Sweden)

    Hui Wang

    Full Text Available OBJECTIVES: To examine the association of living arrangements with functional disability among older persons and explore the mediation of impact factors on the relationship. DESIGN: Cross-sectional analysis using data from Healthy Aging study in Zhejiang Province. PARTICIPANTS: Analyzed sample was drawn from a representative rural population of older persons in Wuyi County, Zhejiang Province, including 1542 participants aged 60 and over in the second wave of the study. MEASUREMENTS: Living arrangements, background, functional disability, self-rated health, number of diseases, along with contemporaneous circumstances including income, social support (physical assistance and emotional support. Instrument was Activities of Daily Living (ADL scale, including Basic Activities Daily Living (BADL and Instrumental Activities of Daily Living (IADL. RESULTS: Living arrangements were significantly associated with BADL, IADL and ADL disability. Married persons living with or without children were more advantaged on all three dimensions of functional disability. Unmarried older adults living with children only had the worst functional status, even after controlling for background, social support, income and health status variables (compared with the unmarried living alone, ß for BADL: -1.262, ß for IADL: -2.112, ß for ADL: -3.388; compared with the married living with children only, ß for BADL: -1.166, ß for IADL: -2.723, ß for ADL: -3.902. In addition, older adults without difficulty in receiving emotional support, in excellent health and with advanced age had significantly better BADL, IADL and ADL function. However, a statistically significant association between physical assistance and functional disability was not found. CONCLUSION: Functional disabilities vary by living arrangements with different patterns and other factors. Our results highlight the association of unmarried elders living with children only and functioning decline comparing with

  3. Moderate, Regular Alcohol Consumption is Associated with Higher Cognitive Function in Older Community-Dwelling Adults.

    Science.gov (United States)

    Reas, E T; Laughlin, G A; Kritz-Silverstein, D; Barrett-Connor, E; McEvoy, L K

    2016-09-01

    Evidence suggests that moderate alcohol consumption may protect against cognitive decline and dementia. However, uncertainty remains over the patterns of drinking that are most beneficial. To examine associations between amount and frequency of alcohol consumption with multiple domains of cognitive function in a well-characterized cohort of older community-dwelling adults in southern California. Observational, cross-sectional cohort study. A research visit between 1988-1992 in Rancho Bernardo, California. 1624 participants of the Rancho Bernardo Study (mean age ± SD = 73.2 ± 9.3 years). Measurements: Participants completed a neuropsychological test battery, self-administered questionnaires on alcohol consumption and lifestyle, and a clinical health evaluation. We classified participants according to average amount of alcohol intake into never, former, moderate, heavy and excessive drinkers, and according to frequency of alcohol intake, into non-drinkers, rare, infrequent, frequent and daily drinkers. We examined the association between alcohol intake and cognitive function, controlling for age, sex, education, exercise, smoking, waist-hip ratio, hypertension and self-assessed health. Amount and frequency of alcohol intake were significantly associated with cognitive function, even after controlling for potentially related health and lifestyle variables. Global and executive function showed positive linear associations with amount and frequency of alcohol intake, whereas visual memory showed an inverted U-shaped association with alcohol intake, with better performance for moderate and infrequent drinkers than for non-drinkers, excessive drinkers or daily drinkers. In several cognitive domains, moderate, regular alcohol intake was associated with better cognitive function relative to not drinking or drinking less frequently. This suggests that beneficial cognitive effects of alcohol intake may be achieved with low levels of drinking that are unlikely to be

  4. Association of sarcopenia with functional decline in community-dwelling elderly subjects in Japan.

    Science.gov (United States)

    Tanimoto, Yoshimi; Watanabe, Misuzu; Sun, Wei; Tanimoto, Keiji; Shishikura, Kanako; Sugiura, Yumiko; Kusabiraki, Toshiyuki; Kono, Koichi

    2013-10-01

    The present study aimed to determine the association of sarcopenia, defined by muscle mass, muscle strength and physical performance, with functional disability from a 2-year cohort study of community-dwelling elderly Japanese people. Participants were 743 community-dwelling elderly Japanese people aged 65 years or older. We used bioelectrical impedance analysis (BIA) to measure muscle mass, grip strength to measure muscle strength, and usual walking speed to measure physical performance in a baseline study. Functional disability was defined using an activities of daily living (ADL) scale and instrumental activities of daily living (IADL) scale at baseline and during follow-up examinations 2 years later. Logistic regression analysis, adjusted for age and body mass index, was used to examine the association between sarcopenia and the occurrence of functional disability. In the present study, 7.8% of men and 10.2% of women were classified as having sarcopenia. Among sarcopenia patients in the baseline study, 36.8% of men and 18.8% of women became dependent in ADL at 2-year follow up. From the logistic regression analysis adjusted by age and body mass index, sarcopenia was significantly associated with the occurrences of physical disability compared with normal subjects in both men and women. Sarcopenia, defined by muscle mass, muscle strength and physical performance, was associated with functional decline over a 2-year period in elderly Japanese. Interventions to prevent sarcopenia are very important to prevent functional decline among elderly individuals. © 2013 Japan Geriatrics Society.

  5. On computation and use of Fourier coefficients for associated Legendre functions

    Science.gov (United States)

    Gruber, Christian; Abrykosov, Oleh

    2016-06-01

    The computation of spherical harmonic series in very high resolution is known to be delicate in terms of performance and numerical stability. A major problem is to keep results inside a numerical range of the used data type during calculations as under-/overflow arises. Extended data types are currently not desirable since the arithmetic complexity will grow exponentially with higher resolution levels. If the associated Legendre functions are computed in the spectral domain, then regular grid transformations can be applied to be highly efficient and convenient for derived quantities as well. In this article, we compare three recursive computations of the associated Legendre functions as trigonometric series, thereby ensuring a defined numerical range for each constituent wave number, separately. The results to a high degree and order show the numerical strength of the proposed method. First, the evaluation of Fourier coefficients of the associated Legendre functions has been done with respect to the floating-point precision requirements. Secondly, the numerical accuracy in the cases of standard double and long double precision arithmetic is demonstrated. Following Bessel's inequality the obtained accuracy estimates of the Fourier coefficients are directly transferable to the associated Legendre functions