Accelerating Bayesian hierarchical clustering of time series data with a randomised algorithm

We live in an era of abundant data. This has necessitated the development of new and innovative statistical algorithms to get the most from experimental data. For example, faster algorithms make practical the analysis of larger genomic data sets, allowing us to extend the utility of cutting-edge statistical methods. We present a randomised algorithm that accelerates the clustering of time series data using the Bayesian Hierarchical Clustering (BHC) statistical method. BHC is a general method for clustering any discretely sampled time series data. In this paper we focus on a particular application to microarray gene expression data. We define and analyse the randomised algorithm, before presenting results on both synthetic and real biological data sets. We show that the randomised algorithm leads to substantial gains in speed with minimal loss in clustering quality. The randomised time series BHC algorithm is available as part of the R package BHC, which is available for download from Bioconductor (version 2.10 and above) via http://bioconductor.org/packages/2.10/bioc/html/BHC.html. We have also made available a set of R scripts which can be used to reproduce the analyses carried out in this paper. These are available from the following URL. https://sites.google.com/site/randomisedbhc/

R/BHC: fast Bayesian hierarchical clustering for microarray data

BACKGROUND: Although the use of clustering methods has rapidly become one of the standard computational approaches in the literature of microarray gene expression data analysis, little attention has been paid to uncertainty in the results obtained. RESULTS: We present an R/Bioconductor port of a fast novel algorithm for Bayesian agglomerative hierarchical clustering and demonstrate its use in clustering gene expression microarray data. The method performs bottom-up hierarchical clustering, using a Dirichlet Process (infinite mixture) to model uncertainty in the data and Bayesian model selection to decide at each step which clusters to merge. CONCLUSION: Biologically plausible results are presented from a well studied data set: expression profiles of A. thaliana subjected to a variety of biotic and abiotic stresses. Our method avoids several limitations of traditional methods, for example how many clusters there should be and how to choose a principled distance metric

The pathogenesis of oral lichen planus

Both antigen-specific and non-specific mechanisms may be involved in the pathogenesis of oral lichen planus (OLP). Antigen-specific mechanisms in OLP include antigen presentation by basal keratinocytes and antigen-specific keratinocyte killing by CD8(+) cytotoxic T-cells. Non-specific mechanisms include mast cell degranulation and matrix metalloproteinase (MMP) activation in OLP lesions. These mechanisms may combine to cause T-cell accumulation in the superficial lamina propria, basement membrane disruption, intra-epithelial T-cell migration, and keratinocyte apoptosis in OLP. OLP chronicity may be due, in part, to deficient antigen-specific TGF-beta1-mediated immunosuppression. The normal oral mucosa may be an immune privileged site (similar to the eye, testis, and placenta), and breakdown of immune privilege could result in OLP and possibly other autoimmune oral mucosal diseases. Recent findings in mucocutaneous graft-versus-host disease, a clinical and histological correlate of lichen planus, suggest the involvement of TNF-alpha, CD40, Fas, MMPs, and mast cell degranulation in disease pathogenesis. Potential roles for oral Langerhans cells and the regional lymphatics in OLP lesion formation and chronicity are discussed. Carcinogenesis in OLP may be regulated by the integrated signal from various tumor inhibitors (TGF-beta1, TNF-alpha, IFN-gamma, IL-12) and promoters (MIF, MMP-9). We present our recent data implicating antigen-specific and non-specific mechanisms in the pathogenesis of OLP and propose a unifying hypothesis suggesting that both may be involved in lesion development. The initial event in OLP lesion formation and the factors that determine OLP susceptibility are unknown

Bimodal Coherence in Dense Self-Interacting Neutrino Gases

Analytical solutions are obtained to the nonlinear equations describing neutrino oscillations when explicit neutrino-antineutrino asymmetries are present. Such a system occurs in the early Universe if neutrinos have a non-zero chemical potential. Solutions to the equations lead to a new type of coherent behavior governed by two modes. These bimodal solutions provide new insights into dense neutrino gases and into neutrino oscillations in the early Universe, thereby allowing one to surmise the flavor behavior of neutrinos with a non-zero chemical potential.Comment: 21 pages in Latex, 11 figures packaged in one Postscript file. Figures also obtainable as 20 gif files at http://www.sci.ccny.cuny.edu/~ssamuel/bimodalfigs.html Revision on 4/19/96 was to pack the figures more sensibly. This paper is to appear in a May issue of Phys. Rev.

Two-Level Atom in an Optical Parametric Oscillator: Spectra of Transmitted and Fluorescent Fields in the Weak Driving Field Limit

We consider the interaction of a two-level atom inside an optical parametric oscillator. In the weak driving field limit, we essentially have an atom-cavity system driven by the occasional pair of correlated photons, or weakly squeezed light. We find that we may have holes, or dips, in the spectrum of the fluorescent and transmitted light. This occurs even in the strong-coupling limit when we find holes in the vacuum-Rabi doublet. Also, spectra with a sub-natural linewidth may occur. These effects disappear for larger driving fields, unlike the spectral narrowing obtained in resonance fluorescence in a squeezed vacuum; here it is important that the squeezing parameter $N$ tends to zero so that the system interacts with only one correlated pair of photons at a time. We show that a previous explanation for spectral narrowing and spectral holes for incoherent scattering is not applicable in the present case, and propose a new explanation. We attribute these anomalous effects to quantum interference in the two-photon scattering of the system.Comment: 10 pages, 17 figures, submitted to Phys Rev

Investment under ambiguity with the best and worst in mind

Recent literature on optimal investment has stressed the difference between the impact of risk and the impact of ambiguity - also called Knightian uncertainty - on investors' decisions. In this paper, we show that a decision maker's attitude towards ambiguity is similarly crucial for investment decisions. We capture the investor's individual ambiguity attitude by applying alpha-MEU preferences to a standard investment problem. We show that the presence of ambiguity often leads to an increase in the subjective project value, and entrepreneurs are more eager to invest. Thereby, our investment model helps to explain differences in investment behavior in situations which are objectively identical

Limits on Active-Sterile Neutrino Mixing and the Primordial Deuterium Abundance

Studies of limits on active-sterile neutrino mixing derived from big bang nucleosynthesis considerations are extended to consider the dependance of these constraints on the primordial deuterium abundance. This study is motivated by recent measurements of D/H in quasar absorption systems, which at present yield discordant results. Limits on active-sterile mixing are somewhat relaxed for high D/H. For low D/H ($\approx 2 \times 10^{-5}$), no active-sterile neutrino mixing is allowed by currently popular upper limits on the primordial $^4$He abundance $Y$. For such low primordial D/H values, the observational inference of active-sterile neutrino mixing by upcoming solar neutrino experiments would imply that $Y$ has been systematically underestimated, unless there is new physics not included in standard BBN.Comment: 10 pages + 2 figures, uses revtex macros, submitted to Phys. Rev. D. Corrected figure captions and an added referenc

Affleck-Dine dynamics and the dark sector of pangenesis

Pangenesis is the mechanism for jointly producing the visible and dark matter asymmetries via Affleck-Dine dynamics in a baryon-symmetric universe. The baryon-symmetric feature means that the dark asymmetry cancels the visible baryon asymmetry and thus enforces a tight relationship between the visible and dark matter number densities. The purpose of this paper is to analyse the general dynamics of this scenario in more detail and to construct specific models. After reviewing the simple symmetry structure that underpins all baryon-symmetric models, we turn to a detailed analysis of the required Affleck-Dine dynamics. Both gravity-mediated and gauge-mediated supersymmetry breaking are considered, with the messenger scale left arbitrary in the latter, and the viable regions of parameter space are determined. In the gauge-mediated case where gravitinos are light and stable, the regime where they constitute a small fraction of the dark matter density is identified. We discuss the formation of Q-balls, and delineate various regimes in the parameter space of the Affleck-Dine potential with respect to their stability or lifetime and their decay modes. We outline the regions in which Q-ball formation and decay is consistent with successful pangenesis. Examples of viable dark sectors are presented, and constraints are derived from big bang nucleosynthesis, large scale structure formation and the Bullet cluster. Collider signatures and implications for direct dark matter detection experiments are briefly discussed. The following would constitute evidence for pangenesis: supersymmetry, GeV-scale dark matter mass(es) and a Z' boson with a significant invisible width into the dark sector.Comment: 51 pages, 7 figures; v2: minor modifications, comments and references added; v3: minor changes, matches published versio

A sociologist teaches history: some epistemological and pedagogical reflections

This article discusses the concept of ‘historical sociology’ in relation to the teaching of a module on an undergraduate degree in Education Studies at a university in the United Kingdom. The module examines the history of education policy in England from 1870 until the present day. Drawing upon comparisons with Social Foundations of Education programs in the United States, I examine some key epistemological and pedagogical issues raised by the inter-disciplinary approach to teaching and learning followed within the module in which we combine historical and sociological perspectives as a means to understand the evolution of the English education system. In particular, using Bernstein’s concept of the pedagogic device as an analytical framework, I consider the epistemological congruence of sociology and history as the contributory disciplines of the undergraduate module. From a discussion of the concept of historical sociology, I conclude that although sociology and history are distinct subjects, they share a large amount of analytical ground which thus facilitates the inter-disciplinary approach pursued within the module. Following that, I examine some pedagogical issues that have arisen in my experience of teaching upon the module and I discuss how I have addressed these. I conclude the article by making comparisons to relevant examples from pedagogical practices in Social Foundations of Education programs in the United States