Identifying cancer subtypes in glioblastoma by combining genomic, transcriptomic and epigenomic data

We present a nonparametric Bayesian method for disease subtype discovery in multi-dimensional cancer data. Our method can simultaneously analyse a wide range of data types, allowing for both agreement and disagreement between their underlying clustering structure. It includes feature selection and infers the most likely number of disease subtypes, given the data. We apply the method to 277 glioblastoma samples from The Cancer Genome Atlas, for which there are gene expression, copy number variation, methylation and microRNA data. We identify 8 distinct consensus subtypes and study their prognostic value for death, new tumour events, progression and recurrence. The consensus subtypes are prognostic of tumour recurrence (log-rank p-value of $3.6 \times 10^{-4}$ after correction for multiple hypothesis tests). This is driven principally by the methylation data (log-rank p-value of $2.0 \times 10^{-3}$) but the effect is strengthened by the other 3 data types, demonstrating the value of integrating multiple data types. Of particular note is a subtype of 47 patients characterised by very low levels of methylation. This subtype has very low rates of tumour recurrence and no new events in 10 years of follow up. We also identify a small gene expression subtype of 6 patients that shows particularly poor survival outcomes. Additionally, we note a consensus subtype that showly a highly distinctive data signature and suggest that it is therefore a biologically distinct subtype of glioblastoma. The code is available from https://sites.google.com/site/multipledatafusion/

Phylogenetic relationships of the Chinese sisorid catfishes: a nuclear intron versus mitochondrial gene approach

Several recent molecular phylogenetic studies of the sisorid catfishes (Sisoridae) have challenged some aspects of their traditional taxonomy and cladistic hypotheses of their phylogeny. However, disagreement with respect to relationships within this family in these studies highlights the need for additional data and analyses. Here we subjected 15 taxa representing 12 sisorids genera to comprehensive phylogenetic analyses using the second intron of low-copy nuclear S7 ribosomal protein (rpS7) gene and the mitochondrial 16S rRNA gene segments both individually and in combination. The competing sisorid topologies were then tested by using the approximately unbiased (AU) test and the Shimodaira-Hasegawa (SH) test. Our results support previously suggested polyphyly of Pareuchiloglanis. The genus Pseudecheneis is likely to be nested in the glyptosternoids and Glaridoglanis might be basal to the tribe Glyptosternini. However, justified by AU and SH test, the sister-group relationship between Pseudecheneis and the monophyletic glyptosternoids cannot be rejected based on the second intron of rpS7 gene and combined data analyses. It follows that both gene segments are not suitable for resolving the phylogenetic relationships within the sisorid catfishes. Overall, the second intron of rpS7 gene yielded poor phylogenetic performance when compared to 16S rRNA gene, the evolutionary hypothesis of which virtually agreed with the combined data analyses tree. This phenomenon can be explained by the insufficient length and fast saturation of substitutions in the second intron of rpS7 gene, due to substitution patterns such as frequent indels (insertion/deletion events) of bases in the sequences during the evolution.

Phylogeny and biogeography of Chinese sisorid catfishes re-examined using mitochondrial cytochrome b and 16S rRNA gene sequences

The family Sisoridae is one of the largest and most diverse Asiatic catfish families, most species occurring in the water systems of the Qinhai-Tibetan Plateau and East Himalayas. To date published morphological and molecular phylogenetics hypotheses of sisorid catfishes are part congruent, and there are some areas of significant disagreement with respect to intergeneric relationships. We used mitochondrial cytochrome b and 16S rRNA gene sequences to clarify existing gaps in phylogenetics and to test conflicting vicariant and dispersal biogeographical hypotheses of Chinese sisorids using dispersal-vicariance analysis and weighted ancestral area analysis in combination with palaeogeographical data as well as molecular clock calibration. Our results suggest that: (1) Chinese sisorid catfishes form a monophyletic group with two distinct clades, one represented by (Gagata (Bagarius, Glyptothorax)) and the other by (glyptosternoids, Pseudecheneis); (2) the glyptosternoid is a monophyletic group and Glyptosternum, Glaridoglanis, and Exostoma are three basal species having a primitive position among it; (3) a hypothesis referring to Pseudecheneis as the sister group of the glyptosternoids, based on morphological evidence, is supported; (4) the genus Pareuchiloglanis, as presently defined, is not monophyletic; (5) congruent with previous hypotheses, the uplift of Qinghai-Tibetan Plateau played a primary role in the speciation and radiation of the Chinese sisorids; and (6) an evolutionary scenario combining aspects of both vicariance and dispersal theory is necessary to explain the distribution pattern of the glyptosternoids. In addition, using a cytochrome b substitution rate of 0.91% per million years and 0.23% for 16S rRNA, we tentatively date that the glyptosternoids most possibly originated in Oligocene-Miocene boundary (19-24Myr), and radiated from Miocene to Pleistocene, along with a center of origin in the Irrawaddy-Tsangpo drainages and several rapid speciation in a relatively short time. (c) 2005 Elsevier Inc. All rights reserved.

Effect of beta-irradiation on photoluminescence of MOCVD grown GaN

The effect of beta particles interaction on the optical properties of MOCVD grown GaN is reported. A significant change in luminescence properties of GaN is observed after exposing the material with 0.6 MeV beta particles with low dose of 10(12) cm(-2). The results obtained from photoluminescence measurements of irradiated GaN samples in low dose are found contradictory to those reported in literature for samples irradiated with heavy dose (> 10(15) cm(-2)) of electron. An increase in intensity of yellow luminescence has been observed with increasing dose of beta particles which is in disagreement to the already reported results in literature for heavily irradiated samples. A model has been proposed to sort out this inconsistency. The increase in YL intensity at low dose is attributed to the increase in concentration of VGaON complex whereas production of non-radiative VGaON clusters is assumed to justify the decrease in YL intensity at high dose.

A photonic crystal waveguide with silicon on insulator in the near-infrared band

A two-dimensional (2D) photonic crystal waveguide in the Gamma-K direction with triangular lattice on a silicon-on insulator (SOI) substrate in the near-infrared band is fabricated by the combination of electron beam lithography and inductively coupled plasma etching. Its transmission characteristics are analysed from the stimulated band diagram by the effective index and the 2D plane wave expansion (PWE) methods. In the experiment, the transmission band edge in a longer wavelength of the photonic crystal waveguide is about 1590 nm, which is in good qualitative agreement with the simulated value. However, there is a disagreement between the experimental and the simulated results when the wavelength ranges from 1607 to 1630 nm, which can be considered as due to the unpolarized source used in the transmission measurement.

Nonlinear Rashba model and spin relaxation in quantum wells

We find that the Rashba spin splitting is intrinsically a nonlinear function of the momentum, and the linear Rashba model may overestimate it significantly, especially in narrow-gap semiconductors. A nonlinear Rashba model is proposed, which is in good agreement with the numerical results from the eight-band k center dot p theory. Using this model, we find pronounced suppression of the D'yakonov-Perel' spin relaxation rate at large electron densities, and a nonmonotonic dependence of the resonance peak position of the electron spin lifetime on the electron density in [111]-oriented quantum wells, both in qualitative disagreement with the predictions of the linear Rashba model.

Cubic InGaN grown by MOCVD

We report on the growth of high-quality cubic phase InGaN on GaAs by MOCVD. The cubic InGaN layers are grown on cubic GaN buffer layers on GaAs (001) substrates. The surface morphology of the films are mirror-like. The cubic nature of the InGaN films is obtained by Xray diffraction (XRD) measurements. The InGaN layers show strong photoluminescence (PL) at room temperature. Neither emission peak from wurtzite GaN nor yellow luminescence is observed in our films. The highest In content as determined by XRD is about 17% with an PL emission wavelength of 450 nm. The FWHM of the cubic InGaN PL peak are 153 meV and 216 meV for 427 nm and 450 nm emissions, respectively. It is found that the In compositions determined from XRD are not in agreement with those estimated from PL measurements. The reasons for this disagreement are discussed.

Monte Carlo simulation of the grafting of maleic anhydride onto polypropylene at higher temperature

The graft of maleic anhydride (MAH) onto isotactic polypropylene (iPP) initiated by dicumyl peroxide (DCP) at 190 degreesC was studied by means of the Monte Carlo method. The ceiling temperature theory, i.e., no possibility for the homopolymerization of MA-H to occur at higher temperatures, was used in this study. The simulation results show that most MAH monomers were grafted onto the radical chain ends arising from beta scission at a lower MAH concentration, whereas the amount of MAH monomers attached to the tertiary carbons was much larger than that grafted onto the radical chain ends at a higher MAH concentration for various DCP concentrations. This conclusion gives a good interpretation for the disagreement on the grafting sites along a PP chain. Moreover, it was found that the grafting degree increased considerably up to a peak value; thereafter, it decreased continuously with increasing MA-H concentration. The peak shifted in the lower MAH concentration direction and became lower and lower with increasing DCP concentration. When the DCP concentration was below 0.1 wt %, the peak was hardly observed. Those results are in good agreement with the experiments.

What influences the timing of the introduction of solid food to infants?

The aim of the present study was to assess the factors which may influence the timing of the introduction of solid food to infants. The design was a prospective cohort study by interview and postal questionnaire. Primiparous women (n 541) aged between 16 and 40 years were approached in the Forth Park Maternity Hospital, Fife, Scotland. Of these, 526 women agreed to participate and seventy-eight were used as subjects in the pilot study. At 12 weeks we interviewed 338 women of the study sample. The postal questionnaire was returned by 286 of 448 volunteers. At 12 weeks 133 of 338 mothers said that they had introduced solids. Those that said that they had introduced solids early (<12 weeks) were compared with those who had introduced solids late (>12 weeks) by bivariate and multiple regression analysis. Psychosocial factors influencing the decision were measured with the main outcome measure being the time of introduction of solid food. The early introduction of solids was found to be associated with: the opinions of the infant's maternal grandmother; living in a deprived area; personal disagreement with the advice to wait until the baby was 4 months; lack of encouragement from friends to wait until the baby was 4 months; being in receipt of free samples of manufactured food. Answers to open-ended questions indicated that the early introduction appeared to be influenced by the mothers’ perceptions of the baby's needs. Some of the factors influencing a woman's decision to introduce solids are amenable to change, and these could be targeted in educational interventions.

Archipelag Senkaku. Źródło napięć na Morzu Wschodniochińskim

The article analyzes the question of Senkaku islands dispute between Japan, China and Taiwan. The aim of the text is to present how the dispute has affected Japan-China bilateral relations. At first, the paper focuses on characterization: the subject of dispute, claims of countries, its course and an international aspect. The second part considers: the incident in September 2010 and its consequences, the dispute effects and prosperities of its regulations. The relations between China and Japan are very complicated. The Senkaku Islands dispute and 2010 incident are presently one of the most important reasons for disagreement.

Comparison of deterministic, stochastic and fuzzy logic uncertainty modelling for capacity extension projects of DI/WFI pharmaceutical plant utilities with variable/dynamic demand

The last 30 years have seen Fuzzy Logic (FL) emerging as a method either complementing or challenging stochastic methods as the traditional method of modelling uncertainty. But the circumstances under which FL or stochastic methods should be used are shrouded in disagreement, because the areas of application of statistical and FL methods are overlapping with differences in opinion as to when which method should be used. Lacking are practically relevant case studies comparing these two methods. This work compares stochastic and FL methods for the assessment of spare capacity on the example of pharmaceutical high purity water (HPW) utility systems. The goal of this study was to find the most appropriate method modelling uncertainty in industrial scale HPW systems. The results provide evidence which suggests that stochastic methods are superior to the methods of FL in simulating uncertainty in chemical plant utilities including HPW systems in typical cases whereby extreme events, for example peaks in demand, or day-to-day variation rather than average values are of interest. The average production output or other statistical measures may, for instance, be of interest in the assessment of workshops. Furthermore the results indicate that the stochastic model should be used only if found necessary by a deterministic simulation. Consequently, this thesis concludes that either deterministic or stochastic methods should be used to simulate uncertainty in chemical plant utility systems and by extension some process system because extreme events or the modelling of day-to-day variation are important in capacity extension projects. Other reasons supporting the suggestion that stochastic HPW models are preferred to FL HPW models include: 1. The computer code for stochastic models is typically less complex than a FL models, thus reducing code maintenance and validation issues. 2. In many respects FL models are similar to deterministic models. Thus the need for a FL model over a deterministic model is questionable in the case of industrial scale HPW systems as presented here (as well as other similar systems) since the latter requires simpler models. 3. A FL model may be difficult to "sell" to an end-user as its results represent "approximate reasoning" a definition of which is, however, lacking. 4. Stochastic models may be applied with some relatively minor modifications on other systems, whereas FL models may not. For instance, the stochastic HPW system could be used to model municipal drinking water systems, whereas the FL HPW model should or could not be used on such systems. This is because the FL and stochastic model philosophies of a HPW system are fundamentally different. The stochastic model sees schedule and volume uncertainties as random phenomena described by statistical distributions based on either estimated or historical data. The FL model, on the other hand, simulates schedule uncertainties based on estimated operator behaviour e.g. tiredness of the operators and their working schedule. But in a municipal drinking water distribution system the notion of "operator" breaks down. 5. Stochastic methods can account for uncertainties that are difficult to model with FL. The FL HPW system model does not account for dispensed volume uncertainty, as there appears to be no reasonable method to account for it with FL whereas the stochastic model includes volume uncertainty.

Thomas Davis's education policies: theory and practice

This thesis explores the education policies of Thomas Davis. On the eve of the Great Famine Ireland was economically impoverished and politically dependent. The Irish people had a subservient mentality, were mainly uneducated and were unaware of their potential. He believed that education would develop a self-reliant, self-sufficient people; it would create a new generation of leaders and citizens necessary to transform Ireland into a prosperous, independent nation. This thesis explores his education philosophy which was political in orientation; he called for reform of university education so that it would educate leaders who were knowledgeable, patriotic and responsible. He formulated a curriculum which consisted of knowledge that would have direct use and application in public life; his curriculum included moral philosophy, oratory, philological studies and history. His contribution to the debate on the Queens Colleges bill, 1845, is explored including his public disagreement with Daniel O’Connell on the principle of multi-denominational education. This work also examines his policies on learning methodologies and teaching methods. It provides details of his thoughts on learning by experience, by observation, book learning and learning in the home. It focuses on the deficiencies evident in the system of teaching and learning that operated in Trinity College Dublin and it provides an analysis of his preferred method of instruction: Lyceum teaching. This thesis also explores his national curriculum in history and Irish culture which was designed to forge a sense of national identity, to win support for repeal and to develop the principle of nationality. He formulated a national curriculum to counteract the absence of national knowledge in the state schools, to provide the people with a positive self-image and ultimately to empower them to reclaim Ireland and to develop it. Davis knew the power of education and he used it as an instrument of political and social change.

Cross-cultural dimensions of meaning in the evaluation of events in world history? Perceptions of historical calamities and progress in cross-cultural data from 30 societies

The universality versus culture specificity of quantitative evaluations (negative-positive) of 40 events in world history was addressed using World History Survey data collected from 5,800 university students in 30 countries/societies. Multidimensional scaling using generalized procrustean analysis indicated poor fit of data from the 30 countries to an overall mean configuration, indicating lack of universal agreement as to the associational meaning of events in world history. Hierarchical cluster analysis identified one Western and two non-Western country clusters for which adequate multidimensional fit was obtained after item deletions. A two-dimensional solution for the three country clusters was identified, where the primary dimension was historical calamities versus progress and a weak second dimension was modernity versus resistance to modernity. Factor analysis further reduced the item inventory to identify a single concept with structural equivalence across cultures, Historical Calamities, which included man-made and natural, intentional and unintentional, predominantly violent but also nonviolent calamities. Less robust factors were tentatively named as Historical Progress and Historical Resistance to Oppression. Historical Calamities and Historical Progress were at the individual level both significant and independent predictors of willingness to fight for one’s country in a hierarchical linear model that also identified significant country-level variation in these relationships. Consensus around calamity but disagreement as to what constitutes historical progress is discussed in relation to the political culture of nations and lay perceptions of history as catastrophe.

Consistency of financial interest disclosures in the biomedical literature: the case of coronary stents.

BACKGROUND: Disclosure of authors' financial interests has been proposed as a strategy for protecting the integrity of the biomedical literature. We examined whether authors' financial interests were disclosed consistently in articles on coronary stents published in 2006. METHODOLOGY/PRINCIPAL FINDINGS: We searched PubMed for English-language articles published in 2006 that provided evidence or guidance regarding the use of coronary artery stents. We recorded article characteristics, including information about authors' financial disclosures. The main outcome measures were the prevalence, nature, and consistency of financial disclosures. There were 746 articles, 2985 authors, and 135 journals in the database. Eighty-three percent of the articles did not contain disclosure statements for any author (including declarations of no interests). Only 6% of authors had an article with a disclosure statement. In comparisons between articles by the same author, the types of disagreement were as follows: no disclosure statements vs declarations of no interests (64%); specific disclosures vs no disclosure statements (34%); and specific disclosures vs declarations of no interests (2%). Among the 75 authors who disclosed at least 1 relationship with an organization, there were 2 cases (3%) in which the organization was disclosed in every article the author wrote. CONCLUSIONS/SIGNIFICANCE: In the rare instances when financial interests were disclosed, they were not disclosed consistently, suggesting that there are problems with transparency in an area of the literature that has important implications for patient care. Our findings suggest that the inconsistencies we observed are due to both the policies of journals and the behavior of some authors.

What leads Indians to participate in clinical trials? A meta-analysis of qualitative studies.

BACKGROUND: With the globalization of clinical trials, large developing nations have substantially increased their participation in multi-site studies. This participation has raised ethical concerns, among them the fear that local customs, habits and culture are not respected while asking potential participants to take part in study. This knowledge gap is particularly noticeable among Indian subjects, since despite the large number of participants, little is known regarding what factors affect their willingness to participate in clinical trials. METHODS: We conducted a meta-analysis of all studies evaluating the factors and barriers, from the perspective of potential Indian participants, contributing to their participation in clinical trials. We searched both international as well as Indian-specific bibliographic databases, including Pubmed, Cochrane, Openjgate, MedInd, Scirus and Medknow, also performing hand searches and communicating with authors to obtain additional references. We enrolled studies dealing exclusively with the participation of Indians in clinical trials. Data extraction was conducted by three researchers, with disagreement being resolved by consensus. RESULTS: Six qualitative studies and one survey were found evaluating the main themes affecting the participation of Indian subjects. Themes included Personal health benefits, Altruism, Trust in physicians, Source of extra income, Detailed knowledge, Methods for motivating participants as factors favoring, while Mistrust on trial organizations, Concerns about efficacy and safety of trials, Psychological reasons, Trial burden, Loss of confidentiality, Dependency issues, Language as the barriers. CONCLUSION: We identified factors that facilitated and barriers that have negative implications on trial participation decisions in Indian subjects. Due consideration and weightage should be assigned to these factors while planning future trials in India.