BAYESIAN MODEL SEARCH AND MULTILEVEL INFERENCE FOR SNP ASSOCIATION STUDIES.

Technological advances in genotyping have given rise to hypothesis-based association studies of increasing scope. As a result, the scientific hypotheses addressed by these studies have become more complex and more difficult to address using existing analytic methodologies. Obstacles to analysis include inference in the face of multiple comparisons, complications arising from correlations among the SNPs (single nucleotide polymorphisms), choice of their genetic parametrization and missing data. In this paper we present an efficient Bayesian model search strategy that searches over the space of genetic markers and their genetic parametrization. The resulting method for Multilevel Inference of SNP Associations, MISA, allows computation of multilevel posterior probabilities and Bayes factors at the global, gene and SNP level, with the prior distribution on SNP inclusion in the model providing an intrinsic multiplicity correction. We use simulated data sets to characterize MISA's statistical power, and show that MISA has higher power to detect association than standard procedures. Using data from the North Carolina Ovarian Cancer Study (NCOCS), MISA identifies variants that were not identified by standard methods and have been externally "validated" in independent studies. We examine sensitivity of the NCOCS results to prior choice and method for imputing missing data. MISA is available in an R package on CRAN.

Nested dictionary learning for hierarchical organization of imagery and text

A tree-based dictionary learning model is developed for joint analysis of imagery and associated text. The dictionary learning may be applied directly to the imagery from patches, or to general feature vectors extracted from patches or superpixels (using any existing method for image feature extraction). Each image is associated with a path through the tree (from root to a leaf), and each of the multiple patches in a given image is associated with one node in that path. Nodes near the tree root are shared between multiple paths, representing image characteristics that are common among different types of images. Moving toward the leaves, nodes become specialized, representing details in image classes. If available, words (text) are also jointly modeled, with a path-dependent probability over words. The tree structure is inferred via a nested Dirichlet process, and a retrospective stick-breaking sampler is used to infer the tree depth and width.

Multilevel mesh partitioning for heterogeneous communication networks

Multilevel algorithms are a successful class of optimisation techniques which address the mesh partitioning problem for distributing unstructured meshes onto parallel computers. They usually combine a graph contraction algorithm together with a local optimisation method which refines the partition at each graph level. To date these algorithms have been used almost exclusively to minimise the cut edge weight in the graph with the aim of minimising the parallel communication overhead, but recently there has been a perceived need to take into account the communications network of the parallel machine. For example the increasing use of SMP clusters (systems of multiprocessor compute nodes with very fast intra-node communications but relatively slow inter-node networks) suggest the use of hierarchical network models. Indeed this requirement is exacerbated in the early experiments with meta-computers (multiple supercomputers combined together, in extreme cases over inter-continental networks). In this paper therefore, we modify a multilevel algorithm in order to minimise a cost function based on a model of the communications network. Several network models and variants of the algorithm are tested and we establish that it is possible to successfully guide the optimisation to reflect the chosen architecture.

Chapter 2: Predicting Newcomer Integration in Online Knowledge Communities by Automated Dialog Analysis

Nistor, N., Dascalu, M., Stavarache, L.L., Tarnai, C., & Trausan-Matu, S. (2015). Predicting Newcomer Integration in Online Knowledge Communities by Automated Dialog Analysis. In Y. Li, M. Chang, M. Kravcik, E. Popescu, R. Huang, Kinshuk & N.-S. Chen (Eds.), State-of-the-Art and Future Directions of Smart Learning (Vol. Lecture Notes in Educational Technology, pp. 13–17). Berlin, Germany: Springer-Verlag Singapur

Hierarchical random walks in trace fossils and the origin of optimal search behavior

Efficient searching is crucial for timely location of food and other resources. Recent studies show diverse living animals employ a theoretically optimal scale-free random search for sparse resources known as a Lévy walk, but little is known of the origins and evolution of foraging behaviour and the search strategies of extinct organisms. Here we show using simulations of self-avoiding trace fossil trails that randomly introduced strophotaxis (U-turns) – initiated by obstructions such as ¬¬¬self-trail avoidance or innate cueing – leads to random looping patterns with clustering across increasing scales that is consistent with the presence of Lévy walks. This predicts optimal Lévy searches can emerge from simple behaviours observed in fossil trails. We then analysed fossilized trails of benthic marine organisms using a novel path analysis technique and find the first evidence of Lévy-like search strategies in extinct animals. Our results show that simple search behaviours of extinct animals in heterogeneous environments give rise to hierarchically nested Brownian walk clusters that converge to optimal Lévy patterns. Primary productivity collapse and large-scale food scarcity characterising mass extinctions evident in the fossil record may have triggered adaptation of optimal Lévy-like searches. The findings suggest Lévy-like behaviour has been employed by foragers since at least the Eocene but may have a more ancient origin, which could explain recent widespread observations of such patterns among modern taxa.

Cost Estimation of Machined Parts within an Aerospace Supply Chain

A generic, hierarchical, and multifidelity unit cost of acquisition estimating methodology for outside production machined parts is presented. The originality of the work lies with the method’s inherent capability of being able to generate multilevel and multifidelity cost relations for large volumes of parts utilizing process, supply chain costing data, and varying degrees of part design definition information. Estimates can be generated throughout the life cycle of a part using different grades of the combined information available. Considering design development for a given part, additional design definition may be used as it becomes available within the developed method to improve the quality of the resulting estimate. Via a process of analogous classification, parts are classified into groups of increasing similarity using design-based descriptors. A parametric estimating method is then applied to each subgroup of the machined part commodity in the direction of improved classification and using which, a relationship which links design variables to manufacturing cycle time may be generated. A rate cost reflective of the supply chain is then applied to the cycle time estimate for a given part to arrive at an estimate of make cost which is then totalled with the material and treatments cost components respectively to give an overall estimate of unit acquisition cost. Both the rate charge applied and the treatments cost calculated for a given procured part is derived via the use of ratio analysis.

Higher incidence of childhood-onset type 1 diabetes mellitus in remote areas: a UK regional small-area analysis

Aims/hypothesis: We investigated the association between the incidence of type 1 diabetes mellitus and remoteness (a proxy measure for exposure to infections) using recently developed techniques for statistical analysis of small-area data.

Subjects, materials and methods: New cases in children aged 0 to 14 years in Northern Ireland were prospectively registered from 1989 to 2003. Ecological analysis was conducted using small geographical units (582 electoral wards) and area characteristics including remoteness, deprivation and child population density. Analysis was conducted using Poisson regression models and Bayesian
hierarchical models to allow for spatially correlated risks that were potentially caused by unmeasured explanatory variables.

Results: In Northern Ireland between 1989 and 2003, there were 1,433 new cases of type 1 diabetes, giving a directly standardised incidence rate of 24.7 per 100,000 personyears. Areas in the most remote fifth of all areas had a significantly (p=0.0006) higher incidence of type 1 diabetes mellitus (incidence rate ratio=1.27 [95% CI 1.07, 1.50]) than those in the most accessible fifth of all areas. There was also a higher incidence rate in areas that were less deprived (p<0.0001) and less densely populated (p=0.002). After adjustment for deprivation and additional adjustment for child population density the association between diabetes and remoteness remained significant (p=0.01 and p=0.03, respectively).

Conclusions/interpretation: In Northern Ireland, there is evidence that remote areas experience higher rates of type 1 diabetes mellitus. This could reflect a reduced or delayed exposure to infections, particularly early in life, in these areas.

Cultural policy models and cultural facilities models: from national to local models. Analysis of Barcelona’s case

The development of cultural policy analysis by social science has been produced a theorization about cultural policy models from sociology and political science. This analysis shows the influence of the national model of cultural policy on the forms of governance and management of cultural facilities. However, in this paper we will defend that currently the local model of cultural policy decisively influences the model of cultural institutions. This is explained by the growing importance of culture in local development strategies. In order to demonstrate this we will analyze the case of the Barcelona Model of local development and cultural policy, that is characterized for the level of local government leadership, multilevel governance, the use of culture in urban planning processes and a tendency to use public-private partnership in public management. This Model influences the genesis and development of the cultural facilities and it produces a singular and relatively successful model.

Impact of the intrinsic motivation on the academic performance through voluntary assignments: An empirical analysis

The students academic performance is a key aspect for all agents involved in a higher education quality program. However, there is no unanimity on how to measure it. Some professionals choose assessing only cognitive aspects while others lean towards assessing the acquisition of certain skills. The need to train increasingly adapted professionals in order to respond to the companies’ demands and being able to compete internationally in a global labour market requires a kind of training that goes beyond memorizing. Critical and logical thinking are amongst written language skills demanded in the field of Social Sciences. The objective of this study is to empirically demonstrate the impact of voluntary assignments on the academic performance of students. Our hypothesis is that students who complete high quality voluntary assignments are those more motivated and, therefore, those with higher grades. An experiment with students from the "Financial Accounting II" during the academic year of 2012/13 at the Business and Economics School of the UCM was carried out. A series of voluntary assessments involving the preparation of accounting essays were proposed in order to develop skills and competencies as a complement to the lessons included in the curriculum of the subject. At the end of the course, the carrying-out or not of the essay together with its critical, reflective quality and style, were compared. Our findings show a relationship between the voluntarily presented papers of quality and the final grade obtained throughout the course. These results show that the students intrinsic motivation is a key element in their academic performance. On the other hand, the teachers role focuses on being a motivating element through the learning process.

Hierarchical Video Summarization in Reference Subspace

In this paper, a hierarchical video structure summarization approach using Laplacian Eigenmap is proposed, where a small set of reference frames is selected from the video sequence to form a reference subspace to measure the dissimilarity between two arbitrary frames. In the proposed summarization scheme, the shot-level key frames are first detected from the continuity of inter-frame dissimilarity, and the sub-shot level and scene level representative frames are then summarized by using K-mean clustering. The experiment is carried on both test videos and movies, and the results show that in comparison with a similar approach using latent semantic analysis, the proposed approach using Laplacian Eigenmap can achieve a better recall rate in keyframe detection, and gives an efficient hierarchical summarization at sub shot, shot and scene levels subsequently.

Hierarchical coordination of periodic genes in the cell cycle of Saccharomyces cerevisiae

Background: Gene networks are a representation of molecular interactions among genes or products thereof and, hence, are forming causal networks. Despite intense studies during the last years most investigations focus so far on inferential methods to reconstruct gene networks from experimental data or on their structural properties, e.g., degree distributions. Their structural analysis to gain functional insights into organizational principles of, e.g., pathways remains so far under appreciated.

Exploratory analysis of spatiotemporal patterns of cellular automata by clustering compressibility

In this paper we study the classification of spatiotemporal pattern of one-dimensional cellular automata (CA) whereas the classification comprises CA rules including their initial conditions. We propose an exploratory analysis method based on the normalized compression distance (NCD) of spatiotemporal patterns which is used as dissimilarity measure for a hierarchical clustering. Our approach is different with respect to the following points. First, the classification of spatiotemporal pattern is comparative because the NCD evaluates explicitly the difference of compressibility among two objects, e.g., strings corresponding to spatiotemporal patterns. This is in contrast to all other measures applied so far in a similar context because they are essentially univariate. Second, Kolmogorov complexity, which underlies the NCD, was used in the classification of CA with respect to their spatiotemporal pattern. Third, our method is semiautomatic allowing us to investigate hundreds or thousands of CA rules or initial conditions simultaneously to gain insights into their organizational structure. Our numerical results are not only plausible confirming previous classification attempts but also shed light on the intricate influence of random initial conditions on the classification results.

Stratification and Monitoring of Juvenile Idiopathic Arthritis Patients by Synovial Proteome Analysis

Juvenile idiopathic arthritis (JIA) comprises a poorly understood group of chronic, childhood onset, autoimmune diseases with variable clinical outcomes. We investigated whether profiling of the synovial fluid (SF) proteome by a fluorescent dye based, two-dimensional gel (DIGE) approach could distinguish patients in whom inflammation extends to affect a large number of joints, early in the disease process. SF samples from 22 JIA patients were analyzed: 10 with oligoarticular arthritis, 5 extended oligoarticular and 7 polyarticular disease. SF samples were labeled with Cy dyes and separated by two-dimensional electrophoresis. Multivariate analyses were used to isolate a panel of proteins which distinguish patient subgroups. Proteins were identified using MALDI-TOF mass spectrometry with expression further verified by Western immunoblotting and immunohistochemistry. Hierarchical clustering based on the expression levels of a set of 40 proteins segregated the extended oligoarticular from the oligoarticular patients (p <0.05). Expression patterns of the isolated protein panel have also been observed over time, as disease spreads to multiple joints. The data indicates that synovial fluid proteome profiles could be used to stratify patients based on risk of disease extension. These protein profiles may also assist in monitoring therapeutic responses over time and help predict joint damage. © 2009 American Chemical Society.

WASP-22 b: A Transiting "Hot Jupiter" Planet in a Hierarchical Triple System

We report the discovery of a transiting planet orbiting the star TYC 6446-326-1. The star, WASP-22, is a moderately bright (V = 12.0) solar-type star (Teff = 6000 ± 100 K, [Fe/H] = -0.05 ± 0.08). The light curve of the star obtained with the WASP-South instrument shows periodic transit-like features with a depth of about 1% and a duration of 0.14 days. The presence of a transit-like feature in the light curve is confirmed using z-band photometry obtained with Faulkes Telescope South. High-resolution spectroscopy obtained with the CORALIE and HARPS spectrographs confirms the presence of a planetary mass companion with an orbital period of 3.533 days in a near-circular orbit. From a combined analysis of the spectroscopic and photometric data assuming that the star is a typical main-sequence star we estimate that the planet has a mass M p = 0.56 ± 0.02M Jup and a radius R p = 1.12 ± 0.04R Jup. In addition, there is a linear trend of 40 m s-1 yr-1 in the radial velocities measured over 16 months, from which we infer the presence of a third body with a long-period orbit in this system. The companion may be a low mass M-dwarf, a white dwarf, or a second planet.

Impact of Sample Heterogeneity on Methylation Analysis

The recent emergence of high-throughput arrays for methylation analysis has made the influence of tumor content on the interpretation of methylation levels increasingly pertinent. However, to what degree does tumor content have an influence, and what degree of tumor content makes a specimen acceptable for accurate analysis remains unclear. Taking a systematic approach, we analyzed 98 unselected formalin-fixed and paraffin-embedded gastric tumors and matched normal tissue samples using the Illumina GoldenGate methylation assay. Unsupervised hierarchical clustering showed 2 separate clusters with a significant difference in average tumor content levels. The probes identified to be significantly differentially methylated between the tumors and normals also differed according to the tumor content of the samples included, with the sensitivity of identifying the