1,122 research outputs found

    Probe-specific mixed-model approach to detect copy number differences using multiplex ligation-dependent probe amplification (MLPA)

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    Background: MLPA method is a potentially useful semi-quantitative method to detect copy number alterations in targeted regions. In this paper, we propose a method for the normalization procedure based on a non-linear mixed-model, as well as a new approach for determining the statistical significance of altered probes based on linear mixed-model. This method establishes a threshold by using different tolerance intervals that accommodates the specific random error variability observed in each test sample. Results: Through simulation studies we have shown that our proposed method outperforms two existing methods that are based on simple threshold rules or iterative regression. We have illustrated the method using a controlled MLPA assay in which targeted regions are variable in copy number in individuals suffering from different disorders such as Prader-Willi, DiGeorge or Autism showing the best performace. Conclusion: Using the proposed mixed-model, we are able to determine thresholds to decide whether a region is altered. These threholds are specific for each individual, incorporating experimental variability, resulting in improved sensitivity and specificity as the examples with real data have revealed

    Global periodicity conditions for maps and recurrences via Normal Forms

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    We face the problem of characterizing the periodic cases in parametric families of (real or complex) rational diffeomorphisms having a fixed point. Our approach relies on the Normal Form Theory, to obtain necessary conditions for the existence of a formal linearization of the map, and on the introduction of a suitable rational parametrization of the parameters of the family. Using these tools we can find a finite set of values p for which the map can be p-periodic, reducing the problem of finding the parameters for which the periodic cases appear to simple computations. We apply our results to several two and three dimensional classes of polynomial or rational maps. In particular we find the global periodic cases for several Lyness type recurrences.Comment: 25 page

    A logical study of local and global graded similarities

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    In this work we study the relationship between global and local similarities in the graded framework of fuzzy class theory (FCT), in which there already exists a graded notion of similarity. In FCT we can express the fact that a fuzzy relation is reflexive, symmetric, or transitive up to a certain degree, and similarity is defined as a first-order sentence, which is the fusion of three sentences corresponding to the graded notions of reflexivity, symmetry, and transitivity. This allows us to speak in a natural way of the degree of similarity of a relation. We consider global similarities defined from local similarities using t-norms as aggregation operators, and we obtain some results in the framework of FCT that, adequately interpreted, allow us to say that when we take a t-norm as an aggregation operator, the properties of reflexivity, symmetry, and transitivity of fuzzy binary relations are inherited from the local to the global level, and that the global similarity is a congruence if some of the local similarities are congruence

    Obstructive Sleep Apnoea Syndrome, Endothelial Function and Markers of Endothelialization. Changes after CPAP

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    STUDY OBJECTIVES: This study tries to assess the endothelial function in vivo using flow-mediated dilatation (FMD) and several biomarkers of endothelium formation/restoration and damage in patients with obstructive sleep apnoea (OSA) syndrome at baseline and after three months with CPAP therapy. DESIGN: Observational study, before and after CPAP therapy. SETTING AND PATIENTS: We studied 30 patients with apnoea/hypopnoea index (AHI) >15/h that were compared with themselves after three months of CPAP therapy. FMD was assessed non-invasively in vivo using the Laser-Doppler flowmetry. Circulating cell-free DNA (cf-DNA) and microparticles (MPs) were measured as markers of endothelial damage and the vascular endothelial growth factor (VEGF) was determined as a marker of endothelial restoration process. MEASUREMENTS AND RESULTS: After three month with CPAP, FMD significantly increased (1072.26 ± 483.21 vs. 1604.38 ± 915.69 PU, p< 0.005) cf-DNA and MPs significantly decreased (187.93 ± 115.81 vs. 121.28 ± 78.98 pg/ml, p<0.01, and 69.60 ± 62.60 vs. 39.82 ± 22.14 U/μL, p<0.05, respectively) and VEGF levels increased (585.02 ± 246.06 vs. 641.11 ± 212.69 pg/ml, p<0.05). These changes were higher in patients with more severe disease. There was a relationship between markers of damage (r = -0.53, p<0.005) but not between markers of damage and restoration, thus suggesting that both types of markers should be measured together. CONCLUSIONS: CPAP therapy improves FMD. This improvement may be related to an increase of endothelial restoration process and a decrease of endothelial damage

    Multiple-membership multiple-classification models for social network and group dependences

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    The social network literature on network dependences has largely ignored other sources of dependence, such as the school that a student attends, or the area in which an individual lives. The multilevel modelling literature on school and area dependences has, in turn, largely ignored social networks. To bridge this divide, a multiple-membership multiple-classification modelling approach for jointly investigating social network and group dependences is presented. This allows social network and group dependences on individual responses to be investigated and compared. The approach is used to analyse a subsample of the Adolescent Health Study data set from the USA, where the response variable of interest is individual level educational attainment, and the three individual level covariates are sex, ethnic group and age. Individual, network, school and area dependences are accounted for in the analysis. The network dependences can be accounted for by including the network as a classification in the model, using various network configurations, such as ego-nets and cliques. The results suggest that ignoring the network affects the estimates of variation for the classifications that are included in the random part of the model (school, area and individual), as well as having some influence on the point estimates and standard errors of the estimates of regression coefficients for covariates in the fixed part of the model. From a substantive perspective, this approach provides a flexible and practical way of investigating variation in an individual level response due to social network dependences, and estimating the share of variation of an individual response for network, school and area classifications

    Some properties of the k-dimensional Lyness' map

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    This paper is devoted to study some properties of the k-dimensional Lyness' map. Our main result presentes a rational vector field that gives a Lie symmetry for F. This vector field is used, for k less or equal to 5 to give information about the nature of the invariant sets under F. When k is odd, we also present a new (as far as we know) first integral for F^2 which allows to deduce in a very simple way several properties of the dynamical system generated by F. In particular for this case we prove that, except on a given codimension one algebraic set, none of the positive initial conditions can be a periodic point of odd period.Comment: 22 pages; 3 figure

    The Social Climbing Game

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    The structure of a society depends, to some extent, on the incentives of the individuals they are composed of. We study a stylized model of this interplay, that suggests that the more individuals aim at climbing the social hierarchy, the more society's hierarchy gets strong. Such a dependence is sharp, in the sense that a persistent hierarchical order emerges abruptly when the preference for social status gets larger than a threshold. This phase transition has its origin in the fact that the presence of a well defined hierarchy allows agents to climb it, thus reinforcing it, whereas in a "disordered" society it is harder for agents to find out whom they should connect to in order to become more central. Interestingly, a social order emerges when agents strive harder to climb society and it results in a state of reduced social mobility, as a consequence of ergodicity breaking, where climbing is more difficult.Comment: 14 pages, 9 figure

    High-fidelity transmission of entanglement over a high-loss freespace channel

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    Quantum entanglement enables tasks not possible in classical physics. Many quantum communication protocols require the distribution of entangled states between distant parties. Here we experimentally demonstrate the successful transmission of an entangled photon pair over a 144 km free-space link. The received entangled states have excellent, noise-limited fidelity, even though they are exposed to extreme attenuation dominated by turbulent atmospheric effects. The total channel loss of 64 dB corresponds to the estimated attenuation regime for a two-photon satellite quantum communication scenario. We confirm that the received two-photon states are still highly entangled by violating the CHSH inequality by more than 5 standard deviations. From a fundamental point of view, our results show that the photons are virtually not subject to decoherence during their 0.5 ms long flight through air, which is encouraging for future world-wide quantum communication scenarios.Comment: 5 pages, 3 figures, replaced paper with published version, added journal referenc
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