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Creativity is a complex, multi-faceted concept encompassing a variety of related aspects, abilities, properties and behaviours. If we wish to study creativity scientifically, then a tractable and well-articulated model of creativity is required. Such a model would be of great value to researchers investigating the nature of creativity and in particular, those concerned with the evaluation of creative practice. This paper describes a unique approach to developing a suitable model of how creative behaviour emerges that is based on the words people use to describe the concept. Using techniques from the field of statistical natural language processing, we identify a collection of fourteen key components of creativity through an analysis of a corpus of academic papers on the topic. Words are identified which appear significantly often in connection with discussions of the concept. Using a measure of lexical similarity to help cluster these words, a number of distinct themes emerge, which collectively contribute to a comprehensive and multi-perspective model of creativity. The components provide an ontology of creativity: a set of building blocks which can be used to model creative practice in a variety of domains. The components have been employed in two case studies to evaluate the creativity of computational systems and have proven useful in articulating achievements of this work and directions for further research. [ABSTRACT FROM AUTHOR]

Wang et al. proposed a method for obtaining elliptic curves with embedding degree 1 for securing critical infrastructures, and presented several elliptic curves generated by their method with torsion points of 160 bits and 189 bits orders. They also presented some experimental results and claimed that their implementation of an elliptic curve generated with their method is faster than an implementation for embedded devices presented by Bertoni et al. In this paper, we point out that the security and efficiency claims given by Wang et al. are flawed. Specifically, we show that it is possible to solve finite field discrete logarithm problems defined over their elliptic curves in practice. On the elliptic curves with torsion points of 160 bits orders generated by Wang et al., their instances of finite field discrete logarithm problems are solved in around 4 hours by using a standard desktop PC. On the torsion points of 189 bits orders, their instances are solved in around 10 days by using two standard desktop PCs. The hardness of the finite field discrete logarithm problems is one of the most important bases of security; therefore, their elliptic curves should not be used for cryptographic purposes. [ABSTRACT FROM AUTHOR]

Introduction: In this paper we perform a replication analysis of “Effect of a cash transfer programme for schooling on prevalence of HIV and herpes simplex type 2 in Malawi: a cluster randomised trial” by Sarah Baird and others published in “The Lancet” in 2012. The original study was a two-year cluster randomized intervention trial of never married girls aged 13–22 in Malawi. Enumeration areas were randomized to either an intervention involving cash transfer (conditional or unconditional of school enrollment) or control. The study included 1708 Malawian girls, who were enrolled at baseline and had biological testing for HIV and herpes simplex virus type 2 (HSV-2) at 18 months. The original findings showed that in the cohort of girls enrolled in school at baseline, the intervention had an effect on school enrollment, sexual outcomes, and HIV and HSV-2 prevalence. However, in the baseline school dropout cohort, the original study showed no intervention effect on HIV and HSV-2 prevalence. Methods: We performed a replication of the study to investigate the consistency and robustness of key results reported. A pre-specified replication plan was approved and published online. Cleaned data was obtained from the original authors. A pure replication was conducted by reading the methods section and reproducing the results and tables found in the original paper. Robustness of the results were examined with alternative analysis methods in a measurement and estimation analysis (MEA) approach. A theory of change analysis was performed testing a causal pathway, the effect of intervention on HIV awareness, and whether the intervention effect depended on the wealth of the individual. Results: The pure replication found that other than a few minor discrepancies, the original study was well replicated. However, the randomization and sampling weights could not be verified due to the lack of access to raw data and a detailed sample selection plan. Therefore, we are unable to determine how sampling influenced the results, which could be highly dependent on the sample. In MEA it was found that the intervention effect on HIV prevalence in the baseline schoolgirls cohort was somewhat sensitive to model choice, with a non-significant intervention effect for HIV depending on the statistical model used. The intervention effect on HSV-2 prevalence was more robust in terms of statistical significance, however, the odds ratios and confidence intervals differed from the original result by more than 10%. A theory of change analysis showed no effect of intervention on HIV awareness. In a causal pathway analysis, several variables were partial mediators, or potential mediators, indicating that the intervention could be working through its effect on school enrollment or selected sexual behaviors. Conclusions: The effect of intervention on HIV prevalence in the baseline schoolgirls was sensitive to the model choice; however, HSV-2 prevalence results were confirmed. We recommend that the results from the original published analysis indicating the impact of cash transfers on HIV prevalence be treated with caution. [ABSTRACT FROM AUTHOR]

This paper investigates a well-known complex combinatorial problem known as the vehicle routing problem with time windows (VRPTW). Unlike the standard vehicle routing problem, each customer in the VRPTW is served within a given time constraint. This paper solves the VRPTW using an improved artificial bee colony (IABC) algorithm. The performance of this algorithm is improved by a local optimization based on a crossover operation and a scanning strategy. Finally, the effectiveness of the IABC is evaluated on some well-known benchmarks. The results demonstrate the power of IABC algorithm in solving the VRPTW. [ABSTRACT FROM AUTHOR]

Classical null hypothesis significance tests are not appropriate in corpus linguistics, because the randomness assumption underlying these testing procedures is not fulfilled. Nevertheless, there are numerous scenarios where it would be beneficial to have some kind of test in order to judge the relevance of a result (e.g. a difference between two corpora) by answering the question whether the attribute of interest is pronounced enough to warrant the conclusion that it is substantial and not due to chance. In this paper, I outline such a test. [ABSTRACT FROM AUTHOR]

In this paper we investigate the changes in the functional connectivity intensity, and some related properties, in healthy people, across the life span and at resting state. For the explicit computation of the functional connectivity we exploit a recently proposed model, that bases not only on the correlations data provided by the acquisition equipment, but also on different parameters, such as the anatomical distances between nodes and their degrees. The leading purpose of the paper is to show that the proposed approach is able to recover the main aspects of resting state condition known from the available literature, as well as to suggest new insights, perspectives and speculations from a neurobiological point of view. Our study involves 133 subjects, both males and females of different ages, with no evidence of neurological diseases or systemic disorders. First, we show how the model applies to the sample, where the subjects are grouped into 28 different groups (14 of males and 14 of females), according to their age. This leads to the construction of two graphs (one for males and one for females), that can be realistically interpreted as representative of the neural network during the resting state. Second, following the idea that the brain network is better understood by focusing on specific nodes having a kind of centrality, we refine the two output graphs by introducing a new metric that favours the selection of nodes having higher degrees. As a third step, we extensively comment and discuss the obtained results. In particular, it is remarkable that, despite a great overlapping exists between the outcomes concerning males and females, some intriguing differences appear. This motivates a deeper local investigation, which represents the fourth part of the paper, carried out through a thorough statistical analysis. As a result, we are enabled to support that, for two special age groups, a few links contribute in differentiating the behaviour of males and females. In addition, we performed an average-based comparison between the proposed model and the traditional statistical correlation-based approach, then discussing and commenting the main outlined discrepancies. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) affects millions of people and is a major rising problem in health care worldwide. Recent research suggests that AD could have different subtypes, presenting differences in how the disease develops. Characterizing those subtypes could be key to deepen the understanding of this complex disease. In this paper, we used a multivariate, non-supervised clustering method over blood-based markers to find subgroups of patients defined by distinctive blood marker profiles. Our analysis on ADNI database identified 4 possible subgroups, each with a different blood profile. More importantly, we show that subgroups with different profiles have a different relationship between brain phenotypes detected in magnetic resonance imaging and disease condition. [ABSTRACT FROM AUTHOR]

Objectives: Professional sporting organisations invest considerable resources collecting and analysing data in order to better understand the factors that influence performance. Recent advances in non-invasive technologies, such as global positioning systems (GPS), mean that large volumes of data are now readily available to coaches and sport scientists. However analysing such data can be challenging, particularly when sample sizes are small and data sets contain multiple highly correlated variables, as is often the case in a sporting context. Multicollinearity in particular, if not treated appropriately, can be problematic and might lead to erroneous conclusions. In this paper we present a novel ‘leave one variable out’ (LOVO) partial least squares correlation analysis (PLSCA) methodology, designed to overcome the problem of multicollinearity, and show how this can be used to identify the training load (TL) variables that influence most ‘end fitness’ in young rugby league players. Methods: The accumulated TL of sixteen male professional youth rugby league players (17.7 ± 0.9 years) was quantified via GPS, a micro-electrical-mechanical-system (MEMS), and players’ session-rating-of-perceived-exertion (sRPE) over a 6-week pre-season training period. Immediately prior to and following this training period, participants undertook a 30–15 intermittent fitness test (30-15IFT), which was used to determine a players ‘starting fitness’ and ‘end fitness’. In total twelve TL variables were collected, and these along with ‘starting fitness’ as a covariate were regressed against ‘end fitness’. However, considerable multicollinearity in the data (VIF >1000 for nine variables) meant that the multiple linear regression (MLR) process was unstable and so we developed a novel LOVO PLSCA adaptation to quantify the relative importance of the predictor variables and thus minimise multicollinearity issues. As such, the LOVO PLSCA was used as a tool to inform and refine the MLR process. Results: The LOVO PLSCA identified the distance accumulated at very-high speed (>7 m·s-1) as being the most important TL variable to influence improvement in player fitness, with this variable causing the largest decrease in singular value inertia (5.93). When included in a refined linear regression model, this variable, along with ‘starting fitness’ as a covariate, explained 73% of the variance in v30-15IFT ‘end fitness’ (p<0.001) and eliminated completely any multicollinearity issues. Conclusions: The LOVO PLSCA technique appears to be a useful tool for evaluating the relative importance of predictor variables in data sets that exhibit considerable multicollinearity. When used as a filtering tool, LOVO PLSCA produced a MLR model that demonstrated a significant relationship between ‘end fitness’ and the predictor variable ‘accumulated distance at very-high speed’ when ‘starting fitness’ was included as a covariate. As such, LOVO PLSCA may be a useful tool for sport scientists and coaches seeking to analyse data sets obtained using GPS and MEMS technologies. [ABSTRACT FROM AUTHOR]

In this paper, a unique and more distinctive encryption algorithm is proposed. This is based on the complexity of highly nonlinear S box in Flesnelet domain. The nonlinear pattern is transformed further to enhance the confusion in the dummy data using Fresnelet technique. The security level of the encrypted image boosts using the algebra of Galois field in Fresnelet domain. At first level, the Fresnelet transform is used to propagate the given information with desired wavelength at specified distance. It decomposes given secret data into four complex subbands. These complex sub-bands are separated into two components of real subband data and imaginary subband data. At second level, the net subband data, produced at the first level, is deteriorated to non-linear diffused pattern using the unique S-box defined on the Galois field . In the diffusion process, the permuted image is substituted via dynamic algebraic S-box substitution. We prove through various analysis techniques that the proposed scheme enhances the cipher security level, extensively. [ABSTRACT FROM AUTHOR]

Managing the biodiversity extinction crisis requires wise decision-making processes able to account for the limited resources available. In most decision problems in conservation biology, several conflicting objectives have to be taken into account. Most methods used in conservation either provide suboptimal solutions or use strong assumptions about the decision-maker’s preferences. Our paper reviews some of the existing approaches to solve multi-objective decision problems and presents new multi-objective linear programming formulations of two multi-objective optimization problems in conservation, allowing the use of a reference point approach. Reference point approaches solve multi-objective optimization problems by interactively representing the preferences of the decision-maker with a point in the criteria (objectives) space, called the reference point. We modelled and solved the following two problems in conservation: a dynamic multi-species management problem under uncertainty and a spatial allocation resource management problem. Results show that the reference point method outperforms classic methods while illustrating the use of an interactive methodology for solving combinatorial problems with multiple objectives. The method is general and can be adapted to a wide range of ecological combinatorial problems. [ABSTRACT FROM AUTHOR]

The 3D orientation of clasts within a deposit are known to be informative on processes that formed that deposit. In archaeological sites, a portion of the clasts in the deposit are introduced by non-geological processes, and these are typically systematically recorded in archaeological excavations with total stations. By recording a second point on elongated clasts it is possible to quickly and precisely capture their orientation. The statistical and graphical techniques for analyzing these data are well published, and there is a growing set of actualistic and archaeological comparative data to help with the interpretation of the documented patterns. This paper advances this area of research in presenting methods to address some shortcomings in current methodologies. First, a method for calculating confidence intervals on orientation statistics is presented to help address the question of how many objects are needed to assess the formation of a deposit based on orientations. Second, a method for assessing the probability that two assemblages have different orientations is presented based on permutations testing. This method differs from existing ones in that it considers three-dimensional orientations rather than working separately with the two-dimensional bearing and plunge components. Third, a method is presented to examine spatial variability in orientations based on a moving windows approach. The raw data plus the R code to build this document and to implement these methods plus those already described by McPherron are included to help further their use in assessing archaeological site formation processes. [ABSTRACT FROM AUTHOR]

Background: DSC is used to determine thermally-induced conformational changes of biomolecules within a blood plasma sample. Recent research has indicated that DSC curves (or thermograms) may have different characteristics based on disease status and, thus, may be useful as a monitoring and diagnostic tool for some diseases. Since thermograms are curves measured over a range of temperature values, they are considered functional data. In this paper we apply functional data analysis techniques to analyze differential scanning calorimetry (DSC) data from individuals from the Lupus Family Registry and Repository (LFRR). The aim was to assess the effect of lupus disease status as well as additional covariates on the thermogram profiles, and use FD analysis methods to create models for classifying lupus vs. control patients on the basis of the thermogram curves. Methods: Thermograms were collected for 300 lupus patients and 300 controls without lupus who were matched with diseased individuals based on sex, race, and age. First, functional regression with a functional response (DSC) and categorical predictor (disease status) was used to determine how thermogram curve structure varied according to disease status and other covariates including sex, race, and year of birth. Next, functional logistic regression with disease status as the response and functional principal component analysis (FPCA) scores as the predictors was used to model the effect of thermogram structure on disease status prediction. The prediction accuracy for patients with Osteoarthritis and Rheumatoid Arthritis but without Lupus was also calculated to determine the ability of the classifier to differentiate between Lupus and other diseases. Data were divided 1000 times into separate 2/3 training and 1/3 test data for evaluation of predictions. Finally, derivatives of thermogram curves were included in the models to determine whether they aided in prediction of disease status. Results: Functional regression with thermogram as a functional response and disease status as predictor showed a clear separation in thermogram curve structure between cases and controls. The logistic regression model with FPCA scores as the predictors gave the most accurate results with a mean 79.22% correct classification rate with a mean sensitivity = 79.70%, and specificity = 81.48%. The model correctly classified OA and RA patients without Lupus as controls at a rate of 75.92% on average with a mean sensitivity = 79.70% and specificity = 77.6%. Regression models including FPCA scores for derivative curves did not perform as well, nor did regression models including covariates. Conclusion: Changes in thermograms observed in the disease state likely reflect covalent modifications of plasma proteins or changes in large protein-protein interacting networks resulting in the stabilization of plasma proteins towards thermal denaturation. By relating functional principal components from thermograms to disease status, our Functional Principal Component Analysis model provides results that are more easily interpretable compared to prior studies. Further, the model could also potentially be coupled with other biomarkers to improve diagnostic classification for lupus. [ABSTRACT FROM AUTHOR]

Code-based cryptography is one of few alternatives supposed to be secure in a post-quantum world. Meanwhile, identity-based identification and signature (IBI/IBS) schemes are two of the most fundamental cryptographic primitives, so several code-based IBI/IBS schemes have been proposed. However, with increasingly profound researches on coding theory, the security reduction and efficiency of such schemes have been invalidated and challenged. In this paper, we construct provably secure IBI/IBS schemes from code assumptions against impersonation under active and concurrent attacks through a provably secure code-based signature technique proposed by Preetha, Vasant and Rangan (PVR signature), and a security enhancement Or-proof technique. We also present the parallel-PVR technique to decrease parameter values while maintaining the standard security level. Compared to other code-based IBI/IBS schemes, our schemes achieve not only preferable public parameter size, private key size, communication cost and signature length due to better parameter choices, but also provably secure. [ABSTRACT FROM AUTHOR]

In a general (k, n) scalable secret image sharing (SSIS) scheme, the secret image is shared by n participants and any k or more than k participants have the ability to reconstruct it. The scalability means that the amount of information in the reconstructed image scales in proportion to the number of the participants. In most existing SSIS schemes, the size of each image shadow is relatively large and the dealer does not has a flexible control strategy to adjust it to meet the demand of differen applications. Besides, almost all existing SSIS schemes are not applicable under noise circumstances. To address these deficiencies, in this paper we present a novel SSIS scheme based on a brand-new technique, called compressed sensing, which has been widely used in many fields such as image processing, wireless communication and medical imaging. Our scheme has the property of flexibility, which means that the dealer can achieve a compromise between the size of each shadow and the quality of the reconstructed image. In addition, our scheme has many other advantages, including smooth scalability, noise-resilient capability, and high security. The experimental results and the comparison with similar works demonstrate the feasibility and superiority of our scheme. [ABSTRACT FROM AUTHOR]

In this paper we present a three-dimensional (3D) morphometrical assessment of human tibia sexual dimorphism based on whole bone digital representation. To detect shape–size and shape differences between sexes, we used geometric morphometric tools and colour-coded surface deviation maps. The surface-based methodology enabled analysis of sexually dimorphic features throughout the shaft and articular ends of the tibia. The overall study dataset consisted of 183 3D models of adult tibiae from three Czech population subsets, dating to the early medieval (9–10th century) (N = 65), early 20th century (N = 61) and 21st-century (N = 57). The time gap between the chronologically most distant and contemporary datasets was more than 1200 years. The results showed that, in all three datasets, sexual dimorphism was pronounced. There were some sex-dimorphic characteristics common to all three samples, such as tuberosity protrusion, anteriorly bowed shaft and relatively larger articular ends in males. Diachronic comparisons also revealed substantial shape variation related to the most dimorphic area. Male/female distinctions showed a consistent temporal trend regarding the location of dimorphic areas (shifting distally with time), while the maximal deviation between male and female digitized surfaces fluctuated and reached the lowest level in the 21st-century sample. Sex determination on a whole-surface basis yielded the lowest return of correct sex assignment in the 20th-century group, which represented the lowest socioeconomic status. The temporal variation could be attributed to changes in living conditions, the decreasing lower limb loading/labour division in the last 12 centuries having the greatest effect. Overall, the results showed that a surface-based approach is successful for analysing complex long bone geometry. [ABSTRACT FROM AUTHOR]

Data analysis and model-data comparisons in the environmental sciences require diagnostic measures that quantify time series dynamics and structure, and are robust to noise in observational data. This paper investigates the temporal dynamics of environmental time series using measures quantifying their information content and complexity. The measures are used to classify natural processes on one hand, and to compare models with observations on the other. The present analysis focuses on the global carbon cycle as an area of research in which model-data integration and comparisons are key to improving our understanding of natural phenomena. We investigate the dynamics of observed and simulated time series of Gross Primary Productivity (GPP), a key variable in terrestrial ecosystems that quantifies ecosystem carbon uptake. However, the dynamics, patterns and magnitudes of GPP time series, both observed and simulated, vary substantially on different temporal and spatial scales. We demonstrate here that information content and complexity, or Information Theory Quantifiers (ITQ) for short, serve as robust and efficient data-analytical and model benchmarking tools for evaluating the temporal structure and dynamical properties of simulated or observed time series at various spatial scales. At continental scale, we compare GPP time series simulated with two models and an observations-based product. This analysis reveals qualitative differences between model evaluation based on ITQ compared to traditional model performance metrics, indicating that good model performance in terms of absolute or relative error does not imply that the dynamics of the observations is captured well. Furthermore, we show, using an ensemble of site-scale measurements obtained from the FLUXNET archive in the Mediterranean, that model-data or model-model mismatches as indicated by ITQ can be attributed to and interpreted as differences in the temporal structure of the respective ecological time series. At global scale, our understanding of C fluxes relies on the use of consistently applied land models. Here, we use ITQ to evaluate model structure: The measures are largely insensitive to climatic scenarios, land use and atmospheric gas concentrations used to drive them, but clearly separate the structure of 13 different land models taken from the CMIP5 archive and an observations-based product. In conclusion, diagnostic measures of this kind provide data-analytical tools that distinguish different types of natural processes based solely on their dynamics, and are thus highly suitable for environmental science applications such as model structural diagnostics. [ABSTRACT FROM AUTHOR]

The joint analysis of multiple traits has recently become popular since it can increase statistical power to detect genetic variants and there is increasing evidence showing that pleiotropy is a widespread phenomenon in complex diseases. Currently, most of existing methods use all of the traits for testing the association between multiple traits and a single variant. However, those methods for association studies may lose power in the presence of a large number of noise traits. In this paper, we propose an “optimal” maximum heritability test (MHT-O) to test the association between multiple traits and a single variant. MHT-O includes a procedure of deleting traits that have weak or no association with the variant. Using extensive simulation studies, we compare the performance of MHT-O with MHT, Trait-based Association Test uses Extended Simes procedure (TATES), SUM_SCORE and MANOVA. Our results show that, in all of the simulation scenarios, MHT-O is either the most powerful test or comparable to the most powerful test among the five tests we compared. [ABSTRACT FROM AUTHOR]

Graphlets are small subgraphs, usually containing up to five vertices, that can be found in a larger graph. Identification of the graphlets that a vertex in an explored graph touches can provide useful information about the local structure of the graph around that vertex. Actually finding all graphlets in a large graph can be time-consuming, however. As the graphlets grow in size, more different graphlets emerge and the time needed to find each graphlet also scales up. If it is not needed to find each instance of each graphlet, but knowing the number of graphlets touching each node of the graph suffices, the problem is less hard. Previous research shows a way to simplify counting the graphlets: instead of looking for the graphlets needed, smaller graphlets are searched, as well as the number of common neighbors of vertices. Solving a system of equations then gives the number of times a vertex is part of each graphlet of the desired size. However, until now, equations only exist to count graphlets with 4 or 5 nodes. In this paper, two new techniques are presented. The first allows to generate the equations needed in an automatic way. This eliminates the tedious work needed to do so manually each time an extra node is added to the graphlets. The technique is independent on the number of nodes in the graphlets and can thus be used to count larger graphlets than previously possible. The second technique gives all graphlets a unique ordering which is easily extended to name graphlets of any size. Both techniques were used to generate equations to count graphlets with 4, 5 and 6 vertices, which extends all previous results. Code can be found at and . [ABSTRACT FROM AUTHOR]

This paper presents a high payload watermarking scheme for High Efficiency Video Coding (HEVC). HEVC is an emerging video compression standard that provides better compression performance as compared to its predecessor, i.e. H.264/AVC. Considering that HEVC may will be used in a variety of applications in the future, the proposed algorithm has a high potential of utilization in applications involving broadcast and hiding of metadata. The watermark is embedded into the Quantized Transform Coefficients (QTCs) during the encoding process. Later, during the decoding process, the embedded message can be detected and extracted completely. The experimental results show that the proposed algorithm does not significantly affect the video quality, nor does it escalate the bitrate. [ABSTRACT FROM AUTHOR]

The reconcilability of actions and beliefs in inter-country relationships, either in business or politics, is of vital importance as incorrect beliefs on foreigners’ behavior can have serious implications. We study a typical inter-country interaction by means of a controlled laboratory investment game experiment in Germany, Israel and Palestine involving 400 student participants in total. An investor has to take a risky decision in a foreign country that involves transferring money to an investee/allocator. We found a notable constellation of calibrated and un-calibrated beliefs. Within each country, transfer standards exist, which investees correctly anticipate within their country. However, across countries these standards differ. By attributing the standard of their own environment to the other countries investees are remarkably bad in predicting foreign investors’ behavior. The tendency to ignore this potential difference can be a source of misinterpreting motives in cross-country interaction. Foreigners might perceive behavior as unfavorable or favorable differentiation, even though—unknown to them—investors actually treat fellow-country people and foreigners alike. [ABSTRACT FROM AUTHOR]

Downscaled climate projections need to be linked to downscaled projections of population and economic growth to fully develop implications for land, natural resources, and ecosystems for future scenarios. We develop an empirical spatiotemporal approach for jointly projecting population and income at the county scale in the United States that is consistent with neoclassical economic growth theory and overlapping labor markets and that accounts for labor migration and spatial spillovers. Downscaled projections generated for the five Shared Socioeconomic Pathways used to support global scenario analysis generally show growth focused around relatively few centers especially in the southeast and western regions, with some areas in the Midwest and northeast experiencing population declines. Results are consistent with economic growth theory and with historical trends in population change and convergence of per capita personal income across US counties. [ABSTRACT FROM AUTHOR]

While prediction errors (PE) have been established to drive learning through adaptation of internal models, the role of model-compliant events in predictive processing is less clear. Checkpoints (CP) were recently introduced as points in time where expected sensory input resolved ambiguity regarding the validity of the internal model. Conceivably, these events serve as on-line reference points for model evaluation, particularly in uncertain contexts. Evidence from fMRI has shown functional similarities of CP and PE to be independent of event-related surprise, raising the important question of how these event classes relate to one another. Consequently, the aim of the present study was to characterise the functional relationship of checkpoints and prediction errors in a serial pattern detection task using electroencephalography (EEG). Specifically, we first hypothesised a joint P3b component of both event classes to index recourse to the internal model (compared to non-informative standards, STD). Second, we assumed the mismatch signal of PE to be reflected in an N400 component when compared to CP. Event-related findings supported these hypotheses. We suggest that while model adaptation is instigated by prediction errors, checkpoints are similarly used for model evaluation. Intriguingly, behavioural subgroup analyses showed that the exploitation of potentially informative reference points may depend on initial cue learning: Strict reliance on cue-based predictions may result in less attentive processing of these reference points, thus impeding upregulation of response gain that would prompt flexible model adaptation. Overall, present results highlight the role of checkpoints as model-compliant, informative reference points and stimulate important research questions about their processing as function of learning und uncertainty. [ABSTRACT FROM AUTHOR]

In this note we present a robust bootstrap test with good Type I error control for testing the general hypothesis H0: ρ = ρ0. In order to carry out this test we use what is termed a surrogate bootstrap distribution. The test was inspired by the studentized permutation for testing H0: ρ = 0, which was proven to be exact in certain scenarios and asymptotically correct overall. We show that the bootstrap based test is robust to a variety of distributional scenarios in terms of proper Type I error control. [ABSTRACT FROM AUTHOR]

Synchronized oscillatory gamma-band activity (30-100Hz) has been suggested to constitute a key mechanism to dynamically orchestrate sensory information integration across multiple spatio-temporal scales. We here tested whether interhemispheric functional connectivity and ensuing auditory perception can selectively be modulated by high-density transcranial alternating current stimulation (HD-tACS). For this purpose, we applied multi-site HD-tACS at 40Hz bilaterally with a phase lag of 180° and recorded a 64-channel EEG to study the oscillatory phase dynamics at the source-space level during a dichotic listening (DL) task in twenty-six healthy participants. In this study, we revealed an oscillatory phase signature at 40Hz which reflects different temporal profiles of the phase asymmetries during left and right ear percept. Here we report that 180°-tACS did not affect the right ear advantage during DL at group level. However, a follow-up analysis revealed that the intrinsic phase asymmetries during sham-tACS determined the directionality of the behavioral modulations: While a shift to left ear percept was associated with augmented interhemispheric asymmetry (closer to 180°), a shift to right ear processing was elicited in subjects with lower asymmetry (closer to 0°). Crucially, the modulation of the interhemispheric network dynamics depended on the deviation of the tACS-induced phase-lag from the intrinsic phase asymmetry. Our characterization of the oscillatory network trends is giving rise to the importance of phase-specific gamma-band coupling during ambiguous auditory perception, and emphasizes the necessity to address the inter-individual variability of phase asymmetries in future studies by tailored stimulation protocols. [ABSTRACT FROM AUTHOR]

We propose a set of family-based burden and kernel tests for censored traits (FamBAC and FamKAC). Here, censored traits refer to time-to-event outcomes, for instance, age-at-onset of a disease. To model censored traits in family-based designs, we used the frailty model, which incorporated not only fixed genetic effects of rare variants in a region of interest but also random polygenic effects shared within families. We first partitioned genotype scores of rare variants into orthogonal between- and within-family components, and then derived their corresponding efficient score statistics from the frailty model. Finally, FamBAC and FamKAC were constructed by aggregating the weighted efficient scores of the within-family components across rare variants and subjects. FamBAC collapsed rare variants within subject first to form a burden test that followed a chi-squared distribution; whereas FamKAC was a variant component test following a mixture of chi-squared distributions. For FamKAC, p-values can be computed by permutation tests or for computational efficiency by approximation methods. Through simulation studies, we showed that type I error was correctly controlled by FamBAC for various variant weighting schemes (0.0371 to 0.0527). However, FamKAC type I error rates based on approximation methods were deflated (max 0.0376) but improved by permutation tests. Our simulations also demonstrated that burden test FamBAC had higher power than kernel test FamKAC when high proportion (e.g. ≥ 80%) of causal variants had effects in the same direction. In contrast, when the effects of causal variants on the censored trait were in mixed directions, FamKAC outperformed FamBAC and had comparable or higher power than an existing method, RVFam. Our proposed framework has the flexibility to accommodate general nuclear families, and can be used to analyze sequence data for censored traits such as age-at-onset of a complex disease of interest. [ABSTRACT FROM AUTHOR]

We used an ensemble of statistical methods to build a model that predicts kidney transplant survival and identifies important predictive variables. The proposed model achieved better performance, measured by Harrell’s concordance index, than the Estimated Post Transplant Survival model used in the kidney allocation system in the U.S., and other models published recently in the literature. The model has a five-year concordance index of 0.724 (in comparison, the concordance index is 0.697 for the Estimated Post Transplant Survival model, the state of the art currently in use). It combines predictions from random survival forests with a Cox proportional hazards model. The rankings of importance for the model’s variables differ by transplant recipient age. Better survival predictions could eventually lead to more efficient allocation of kidneys and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Population stratification is a well-known confounding factor in both common and rare variant association analyses. Rare variants tend to be more geographically clustered than common variants, because of their more recent origin. However, it is not yet clear if population stratification at a very fine scale (neighboring administrative regions within a country) would lead to statistical bias in rare variant analyses. As the inclusion of convenience controls from external studies is indeed a common procedure, in order to increase the power to detect genetic associations, this problem is important. We studied through simulation the impact of a fine scale population structure on different rare variant association strategies, assessing type I error and power. We showed that principal component analysis (PCA) based methods of adjustment for population stratification adequately corrected type I error inflation at the largest geographical scales, but not at finest scales. We also showed in our simulations that adding controls obviously increased power, but at a considerably lower level when controls were drawn from another population. [ABSTRACT FROM AUTHOR]

Oscillations of the brain’s local field potential (LFP) may coordinate neural ensembles and brain networks. It has been difficult to causally test this model or to translate its implications into treatments, because there are few reliable ways to alter LFP oscillations. We developed a closed-loop analog circuit to enhance brain oscillations by feeding them back into cortex through phase-locked transcranial electrical stimulation. We tested the system in a rhesus macaque with chronically implanted electrode arrays, targeting 8–15 Hz (alpha) oscillations. Ten seconds of stimulation increased alpha oscillatory power for up to 1 second after stimulation offset. In contrast, open-loop stimulation decreased alpha power. There was no effect in the neighboring 15–30 Hz (beta) LFP rhythm or on a neighboring array that did not participate in closed-loop feedback. Analog closed-loop neurostimulation might thus be a useful strategy for altering brain oscillations, both for basic research and the treatment of neuro-psychiatric disease. [ABSTRACT FROM AUTHOR]

Accurate assessment of the association between continuous variables such as gene expression and survival is a critical aspect of precision medicine. In this report, we provide a review of some of the available survival analysis and validation tools by referencing published studies that have utilized these tools. We have identified pitfalls associated with the assumptions inherent in those applications that have the potential to impact scientific research through their potential bias. In order to overcome these pitfalls, we have developed a novel method that enables the logrank test method to handle continuous variables that comprehensively evaluates survival association with derived aggregate statistics. This is accomplished by exhaustively considering all the cutpoints across the full expression gradient. Direct side-by-side comparisons, global ROC analysis, and evaluation of the ability to capture relevant biological themes based on current understanding of RAS biology all demonstrated that the new method shows better consistency between multiple datasets of the same disease, better reproducibility and robustness, and better detection power to uncover biological relevance within the selected datasets over the available survival analysis methods on univariate gene expression and penalized linear model-based methods. [ABSTRACT FROM AUTHOR]

Interval mapping approaches have been playing significant role for quantitative trait locus (QTL) mapping to discover genetic architecture of diseases or traits with molecular markers. Composite interval mapping (CIM) is one of the superior approaches of the interval mapping for discovering both linked and unlinked putative QTL positions. However, estimators of this approach are not robust against phenotypic outliers. As a result, it fails to detect true QTL positions in presence of outliers. In this study, we investigated the performance of β-Composite Interval Mapping (BetaCIM) for detecting both linked and unlinked important QTLs positions from the robustness points of views. Performance of this approach depends on the value of tuning parameter β. It reduces to the classical CIM approach for β →0. We described and formulated the cross-validation procedure for selecting trait specific optimum value of β. It was observed that the optimum value of β depends on both amount of contaminated observations and their scatteredness. BetaCIM approach discover similar QTL positions as classical IM/CIM in absence of phenotypic outliers, but gives better results in presence of phenotypic outliers in terms of detecting true QTLs and effects estimation. We formulated the generalized forms of robust QTL analysis and developed an R-package named “BetaCIM” by implementing this robust approach. Left and right kidney weight data sets of mouse intercross population (129 S1/SvlmJ × A/J) were analyzed by using BetaCIM, CIM, and IM approaches. For right kidney weight (RKW) CIM and BetaCIM provided similar LOD score profile, and both approaches identified 3 QTL positions. IM approach also identified 3 QTL positions. For left kidney weight (LKW), there was evidence of one outlying observation; and in this case the BetaCIM approach identified 2 QTL positions. However, none of the QTLs were significant by CIM and IM approaches at 5% level of significance. Gene expression ontology (GEO) search showed that the candidate genes (Otof and A330033J07Rik) of the identified QTLs for LKW were expressed in kidney. Both simulation and real data analysis results showed that BetaCIM approach improves the performance over the existing methods in presence of phenotypic outliers. Otherwise, it keeps almost equal performance. [ABSTRACT FROM AUTHOR]

There is considerable interest in analyzing the complexity of electroencephalography (EEG) signals. However, some traditional complexity measure algorithms only quantify the complexities of signals, but cannot discriminate different signals very well. To analyze the complexity of epileptic EEG signals better, a new multiscale permutation Rényi entropy (MPEr) algorithm is proposed. In this algorithm, the coarse-grained procedure is introduced by using weighting-averaging method, and the weighted factors are determined by analyzing nonlinear signals. We apply the new algorithm to analyze epileptic EEG signals. The experimental results show that MPEr algorithm has good performance for discriminating different EEG signals. Compared with permutation Rényi entropy (PEr) and multiscale permutation entropy (MPE), MPEr distinguishes different EEG signals successfully. The proposed MPEr algorithm is effective and has good applications prospects in EEG signals analysis. [ABSTRACT FROM AUTHOR]

Team formation, which aims to form a team to complete a given task by covering its required skills, furnishes a natural way to help organizers complete projects effectively. In this work, we propose a new team hiring problem. Given a set of projects with required skills, and a pool of experts , each of which has his own skillset, compensation demand and participation constraint (i.e., the maximum number of projects the expert can participate in simultaneously), we seek to hire a team of participation-constrained experts to complete all the projects so that the overall compensation is minimized. We refer to this as the participation constrained team hire problem. To the best of our knowledge, this is the first work to investigate the problem. We also study a special case of the problem, where the number of projects is within the participation constraint of each expert and design an exact algorithm for it. Since participation constrained team hire problem is proven to be NP-hard, we design three novel efficient approximate algorithms as its solution, each of which focuses on a particular perspective of the problem. We perform extensive experimental studies, on both synthetic and real datasets, to evaluate the performance of our algorithms. Experimental results show that our exact algorithm far surpasses the brute-force solutions and works well in practice. Besides, the three algorithms behave differently when distinct facets of the problem are involved. [ABSTRACT FROM AUTHOR]

This article finds feasible solutions to the travelling salesman problem, obtaining the route with the shortest distance to visit n cities just once, returning to the starting city. The problem addressed is clustering the cities, then using the NEH heuristic, which provides an initial solution that is refined using a modification of the metaheuristic Multi-Restart Iterated Local Search MRSILS; finally, clusters are joined to end the route with the minimum distance to the travelling salesman problem. The contribution of this research is the use of the metaheuristic MRSILS, that in our knowledge had not been used to solve the travelling salesman problem using clusters. The main objective of this article is to demonstrate that the proposed algorithm is more efficient than Genetic Algorithms when clusters are used. To demonstrate the above, both algorithms are compared with some cases taken from the literature, also a comparison with the best-known results is done. In addition, statistical studies are made in the same conditions to demonstrate this fact. Our method obtains better results in all the 10 cases compared. [ABSTRACT FROM AUTHOR]

Identification of risk factors of treatment resistance may be useful to guide treatment selection, avoid inefficient trial-and-error, and improve major depressive disorder (MDD) care. We extended the work in predictive modeling of treatment resistant depression (TRD) via partition of the data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) cohort into a training and a testing dataset. We also included data from a small yet completely independent cohort RIS-INT-93 as an external test dataset. We used features from enrollment and level 1 treatment (up to week 2 response only) of STAR*D to explore the feature space comprehensively and applied machine learning methods to model TRD outcome at level 2. For TRD defined using QIDS-C16 remission criteria, multiple machine learning models were internally cross-validated in the STAR*D training dataset and externally validated in both the STAR*D testing dataset and RIS-INT-93 independent dataset with an area under the receiver operating characteristic curve (AUC) of 0.70–0.78 and 0.72–0.77, respectively. The upper bound for the AUC achievable with the full set of features could be as high as 0.78 in the STAR*D testing dataset. Model developed using top 30 features identified using feature selection technique (k-means clustering followed by χ2 test) achieved an AUC of 0.77 in the STAR*D testing dataset. In addition, the model developed using overlapping features between STAR*D and RIS-INT-93, achieved an AUC of > 0.70 in both the STAR*D testing and RIS-INT-93 datasets. Among all the features explored in STAR*D and RIS-INT-93 datasets, the most important feature was early or initial treatment response or symptom severity at week 2. These results indicate that prediction of TRD prior to undergoing a second round of antidepressant treatment could be feasible even in the absence of biomarker data. [ABSTRACT FROM AUTHOR]

We present a fast, robust and parsimonious approach to detecting signals in an ordered sequence of numbers. Our motivation is in seeking a suitable method to take a sequence of scores corresponding to properties of positions in virus genomes, and find outlying regions of low scores. Suitable statistical methods without using complex models or making many assumptions are surprisingly lacking. We resolve this by developing a method that detects regions of low score within sequences of real numbers. The method makes no assumptions a priori about the length of such a region; it gives the explicit location of the region and scores it statistically. It does not use detailed mechanistic models so the method is fast and will be useful in a wide range of applications. We present our approach in detail, and test it on simulated sequences. We show that it is robust to a wide range of signal morphologies, and that it is able to capture multiple signals in the same sequence. Finally we apply it to viral genomic data to identify regions of evolutionary conservation within influenza and rotavirus. [ABSTRACT FROM AUTHOR]

Several publications have reported structural changes in the brain of synesthetes compared to controls, either local differences or differences in connectivity. In the present study, we pursued this quest for structural brain differences that might support the subjective experience of synesthesia. In particular, for the first time in this field, we investigated brain folding in comparing 45 sulcal shapes in each hemisphere of control and grapheme-color synesthete populations. To overcome flaws relative to data interpretation based only on p-values, common in the synesthesia literature, we report confidence intervals of effect sizes. Moreover, our statistical maps are displayed without introducing the classical, but misleading, p-value level threshold. We adopt such a methodological procedure to facilitate appropriate data interpretation and promote the “New Statistics” approach. Based on structural or diffusion magnetic resonance imaging data, we did not find any strong cerebral anomaly, in sulci, tissue volume, tissue density or fiber organization that could support synesthetic color experience. Finally, by sharing our complete datasets, we strongly support the multi-center construction of a sufficient large dataset repository for detecting, if any, subtle brain differences that may help understanding how a subjective experience, such as synesthesia, is mentally constructed. [ABSTRACT FROM AUTHOR]

We propose a novel method to test the existence of community structure in undirected, real-valued, edge-weighted graphs. The method is based on the asymptotic behavior of extreme eigenvalues of a real symmetric edge-weight matrix. We provide a theoretical foundation for this method and report on its performance using synthetic and real data, suggesting that this new method outperforms other state-of-the-art methods. [ABSTRACT FROM AUTHOR]

Linguistic neutrosophic numbers (LNNs) can easily describe the incomplete and indeterminate information by the truth, indeterminacy, and falsity linguistic variables (LVs), and the Hamy mean (HM) operator is a good tool to deal with multiple attribute group decision making (MAGDM) problems because it can capture the interrelationship among the multi-input arguments. Motivated by these ideas, we develop linguistic neutrosophic HM (LNHM) operator and weighted linguistic neutrosophic HM (WLNHM) operator. Some desirable properties and special cases of two operators are discussed in detail. Furthermore, considering the situation in which the decision makers (DMs) can’t give the suitable weight of each attribute directly from various reasons, we propose the concept of entropy for linguistic neutrosophic set (LNS) to obtain the attribute weight vector objectively, and then the method for MAGDM problems with LNNs is proposed, and some examples are used to illustrate the effectiveness and superiority of the proposed method by comparing with the existing methods. [ABSTRACT FROM AUTHOR]

To explore the pathogenesis of Rhizoctonia solani and its phytotoxin phenylacetic acid (PAA) on maize leaves and sheaths, treated leaf and sheath tissues were analyzed and interpreted by ultra-performance liquid chromatography-mass spectrometry combined with chemometrics. The PAA treatment had similar effects to those of R. solani on maize leaves regarding the metabolism of traumatin, phytosphingosine, vitexin 2'' O-beta-D-glucoside, rutin and DIBOA-glucoside, which were up-regulated, while the synthesis of OPC-8:0 and 12-OPDA, precursors for the synthesis of jasmonic acid, a plant defense signaling molecule, was down-regulated under both treatments. However, there were also discrepancies in the influences exhibited by R. solani and PAA as the metabolic concentration of zeaxanthin diglucoside in the R. solani infected leaf group decreased. Conversely, in the PAA-treated leaf group, the synthesis of zeaxanthin diglucoside was enhanced. Moreover, although the synthesis of 12 metabolites were suppressed in both the R. solani- and PAA-treated leaf tissues, the inhibitory effect of R. solani was stronger than that of PAA. An increased expression of quercitrin and quercetin 3-O-glucoside was observed in maize sheaths treated by R. solani, while their concentrations were not changed significantly in the PAA-treated sheaths. Furthermore, a significant decrease in the concentration of L-Glutamate, which plays important roles in plant resistance to necrotrophic pathogens, only occurred in the R. solani-treated sheath tissues. The differentiated metabolite levels may be the partial reason of why maize sheaths were more susceptible to R. solani than leaves and may explain the underlying mechanisms of R. solani pathogenesis. [ABSTRACT FROM AUTHOR]

Disparities between perceived and actual physical abilities have been shown in older adults and may lead to balance loss or falls. However, it is unclear whether one’s misjudgment is an inherent trait and thus consistent across different tasks, and whether this misjudgment is age-related. We measured the degree of misjudgment in young and older adults on four different stepping tasks; stepping over a raised bar, crossing a declining cord by stepping over it at a self-selected height, crossing a virtual river by stepping over it at a self-selected width, and making a recovery step after release from an inclined position. Before comparison, we carefully checked the validity of the different tasks to determine the misjudgment. No substantial differences were found in the amplitude of the misjudgment between the age groups, and the degree of misjudgment did not transfer across different stepping tasks. However, since only one task (i.e., stepping over a raised bar) met our criteria for validly assessing one’s misjudgment, it remains unclear whether the degree of misjudgment is task-specific or an inherent trait. These findings stress the importance of testing the construct validity of the task, prior to the examination of the misjudgment of stepping ability. [ABSTRACT FROM AUTHOR]

Since anatomic MRI is presently not able to directly discern neuronal loss in Parkinson’s Disease (PD), studying the associated functional connectivity (FC) changes seems a promising approach toward developing non-invasive and non-radioactive neuroimaging markers for this disease. While several groups have reported such FC changes in PD, there are also significant discrepancies between studies. Investigating the reproducibility of PD-related FC changes on independent datasets is therefore of crucial importance. We acquired resting-state fMRI scans for 43 subjects (27 patients and 16 normal controls, with 2 replicate scans per subject) and compared the observed FC changes with those obtained in two independent datasets, one made available by the PPMI consortium (91 patients, 18 controls) and a second one by the group of Tao Wu (20 patients, 20 controls). Unfortunately, PD-related functional connectivity changes turned out to be non-reproducible across datasets. This could be due to disease heterogeneity, but also to technical differences. To distinguish between the two, we devised a method to directly check for disease heterogeneity using random splits of a single dataset. Since we still observe non-reproducibility in a large fraction of random splits of the same dataset, we conclude that functional heterogeneity may be a dominating factor behind the lack of reproducibility of FC alterations in different rs-fMRI studies of PD. While global PD-related functional connectivity changes were non-reproducible across datasets, we identified a few individual brain region pairs with marginally consistent FC changes across all three datasets. However, training classifiers on each one of the three datasets to discriminate PD scans from controls produced only low accuracies on the remaining two test datasets. Moreover, classifiers trained and tested on random splits of the same dataset (which are technically homogeneous) also had low test accuracies, directly substantiating disease heterogeneity. [ABSTRACT FROM AUTHOR]

We used eye-tracking to investigate if and when children show an incremental bias to assume that the first noun phrase in a sentence is the agent (first-NP-as-agent bias) while processing the meaning of English active and passive transitive sentences. We also investigated whether children can override this bias to successfully distinguish active from passive sentences, after processing the remainder of the sentence frame. For this second question we used eye-tracking (Study 1) and forced-choice pointing (Study 2). For both studies, we used a paradigm in which participants simultaneously saw two novel actions with reversed agent-patient relations while listening to active and passive sentences. We compared English-speaking 25-month-olds and 41-month-olds in between-subjects sentence structure conditions (Active Transitive Condition vs. Passive Condition). A permutation analysis found that both age groups showed a bias to incrementally map the first noun in a sentence onto an agent role. Regarding the second question, 25-month-olds showed some evidence of distinguishing the two structures in the eye-tracking study. However, the 25-month-olds did not distinguish active from passive sentences in the forced choice pointing task. In contrast, the 41-month-old children did reanalyse their initial first-NP-as-agent bias to the extent that they clearly distinguished between active and passive sentences both in the eye-tracking data and in the pointing task. The results are discussed in relation to the development of syntactic (re)parsing. [ABSTRACT FROM AUTHOR]

A new trend in medicine is the use of algorithms to analyze big datasets, e.g. using everything your phone measures about you for diagnostics or monitoring. However, these algorithms are commonly compared against weak baselines, which may contribute to excessive optimism. To assess how well an algorithm works, scientists typically ask how well its output correlates with medically assigned scores. Here we perform a meta-analysis to quantify how the literature evaluates their algorithms for monitoring mental wellbeing. We find that the bulk of the literature (∼77%) uses meaningless comparisons that ignore patient baseline state. For example, having an algorithm that uses phone data to diagnose mood disorders would be useful. However, it is possible to explain over 80% of the variance of some mood measures in the population by simply guessing that each patient has their own average mood—the patient-specific baseline. Thus, an algorithm that just predicts that our mood is like it usually is can explain the majority of variance, but is, obviously, entirely useless. Comparing to the wrong (population) baseline has a massive effect on the perceived quality of algorithms and produces baseless optimism in the field. To solve this problem we propose “user lift” that reduces these systematic errors in the evaluation of personalized medical monitoring. [ABSTRACT FROM AUTHOR]

Quantitative trait locus (QTL) analyses of intercross populations between widely used mouse inbred strains provide a powerful approach for uncovering genetic factors that influence susceptibility to atherosclerosis. Epistatic interactions are common in complex phenotypes and depend on genetic backgrounds. To dissect genetic architecture of atherosclerosis, we analyzed F2 progeny from a cross between apolipoprotein E-null mice on DBA/2J (DBA-apoE) and C57BL/6J (B6-apoE) genetic backgrounds and compared the results with those from two previous F2 crosses of apolipoprotein E-null mice on 129S6/SvEvTac (129-apoE) and DBA-apoE backgrounds, and B6-apoE and 129-apoE backgrounds. In these round-robin crosses, in which each parental strain was crossed with two others, large-effect QTLs are expected to be detectable at least in two crosses. On the other hand, observation of QTLs in one cross only may indicate epistasis and/or absence of statistical power. For atherosclerosis at the aortic arch, Aath4 on chromosome (Chr)2:66 cM follows the first pattern, with significant QTL peaks in (DBAx129)F2 and (B6xDBA)F2 mice but not in (B6x129)F2 mice. We conclude that genetic variants unique to DBA/2J at Aath4 confer susceptibility to atherosclerosis at the aortic arch. A similar pattern was observed for Aath5 on chr10:35 cM, verifying that the variants unique to DBA/2J at this locus protect against arch plaque development. However, multiple loci, including Aath1 (Chr1:49 cM), and Aath2 (Chr1:70 cM) follow the second type of pattern, showing significant peaks in only one of the three crosses (B6-apoE x 129-apoE). As for atherosclerosis at aortic root, the majority of QTLs, including Ath29 (Chr9:33 cM), Ath44 (Chr1:68 cM) and Ath45 (Chr2:83 cM), was also inconsistent, being significant in only one of the three crosses. Only the QTL on Chr7:37 cM was consistently suggestive in two of the three crosses. Thus QTL analysis of round-robin crosses revealed the genetic architecture of atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: We have analysed large data sets consisting of tens of thousands of time series from three Type B laser systems: a semiconductor laser in a photonic integrated chip, a semiconductor laser subject to optical feedback from a long free-space-external-cavity, and a solid-state laser subject to optical injection from a master laser. The lasers can deliver either constant, periodic, pulsed, or chaotic outputs when parameters such as the injection current and the level of external perturbation are varied. The systems represent examples of experimental nonlinear systems more generally and cover a broad range of complexity including systematically varying complexity in some regions. Methods: In this work we have introduced a new procedure for semi-automatically interrogating experimental laser system output power time series to calculate the correlation dimension (CD) using the commonly adopted Grassberger-Proccacia algorithm. The new CD procedure is called the ‘minimum gradient detection algorithm’. A value of minimum gradient is returned for all time series in a data set. In some cases this can be identified as a CD, with uncertainty. Findings: Applying the new ‘minimum gradient detection algorithm’ CD procedure, we obtained robust measurements of the correlation dimension for many of the time series measured from each laser system. By mapping the results across an extended parameter space for operation of each laser system, we were able to confidently identify regions of low CD (CD < 3) and assign these robust values for the correlation dimension. However, in all three laser systems, we were not able to measure the correlation dimension at all parts of the parameter space. Nevertheless, by mapping the staged progress of the algorithm, we were able to broadly classify the dynamical output of the lasers at all parts of their respective parameter spaces. For two of the laser systems this included displaying regions of high-complexity chaos and dynamic noise. These high-complexity regions are differentiated from regions where the time series are dominated by technical noise. This is the first time such differentiation has been achieved using a CD analysis approach. Conclusions: More can be known of the CD for a system when it is interrogated in a mapping context, than from calculations using isolated time series. This has been shown for three laser systems and the approach is expected to be useful in other areas of nonlinear science where large data sets are available and need to be semi-automatically analysed to provide real dimensional information about the complex dynamics. The CD/minimum gradient algorithm measure provides additional information that complements other measures of complexity and relative complexity, such as the permutation entropy; and conventional physical measurements. [ABSTRACT FROM AUTHOR]

Graphlets are small connected induced subgraphs of a larger graph G. Graphlets are now commonly used to quantify local and global topology of networks in the field. Methods exist to exhaustively enumerate all graphlets (and their orbits) in large networks as efficiently as possible using orbit counting equations. However, the number of graphlets in G is exponential in both the number of nodes and edges in G. Enumerating them all is already unacceptably expensive on existing large networks, and the problem will only get worse as networks continue to grow in size and density. Here we introduce an efficient method designed to aid statistical sampling of graphlets up to size k = 8 from a large network. We define graphettes as the generalization of graphlets allowing for disconnected graphlets. Given a particular (undirected) graphette g, we introduce the idea of the canonical graphette as a representative member of the isomorphism group Iso(g) of g. We compute the mapping , in the form of a lookup table, from all 2k ( k − 1)/2 undirected graphettes g of size k ≤ 8 to their canonical representatives , as well as the permutation that transforms g to . We also compute all automorphism orbits for each canonical graphette. Thus, given any k ≤ 8 nodes in a graph G, we can in constant time infer which graphette it is, as well as which orbit each of the k nodes belongs to. Sampling a large number N of such k-sets of nodes provides an approximation of both the distribution of graphlets and orbits across G, and the orbit degree vector at each node. [ABSTRACT FROM AUTHOR]

Co-expression networks have long been used as a tool for investigating the molecular circuitry governing biological systems. However, most algorithms for constructing co-expression networks were developed in the microarray era, before high-throughput sequencing—with its unique statistical properties—became the norm for expression measurement. Here we develop Bayesian Relevance Networks, an algorithm that uses Bayesian reasoning about expression levels to account for the differing levels of uncertainty in expression measurements between highly- and lowly-expressed entities, and between samples with different sequencing depths. It combines data from groups of samples (e.g., replicates) to estimate group expression levels and confidence ranges. It then computes uncertainty-moderated estimates of cross-group correlations between entities, and uses permutation testing to assess their statistical significance. Using large scale miRNA data from The Cancer Genome Atlas, we show that our Bayesian update of the classical Relevance Networks algorithm provides improved reproducibility in co-expression estimates and lower false discovery rates in the resulting co-expression networks. Software is available at . [ABSTRACT FROM AUTHOR]