Bias correction and Bayesian analysis of aggregate counts in SAGE libraries

<p>Abstract</p> <p>Background</p> <p>Tag-based techniques, such as SAGE, are commonly used to sample the mRNA pool of an organism's transcriptome. Incomplete digestion during the tag formation process may allow for multiple tags to be generated from a given mRNA transcript. The probability of forming a tag varies with its relative location. As a result, the observed tag counts represent a biased sample of the actual transcript pool. In SAGE this bias can be avoided by ignoring all but the 3' most tag but will discard a large fraction of the observed data. Taking this bias into account should allow more of the available data to be used leading to increased statistical power.</p> <p>Results</p> <p>Three new hierarchical models, which directly embed a model for the variation in tag formation probability, are proposed and their associated Bayesian inference algorithms are developed. These models may be applied to libraries at both the tag and aggregate level. Simulation experiments and analysis of real data are used to contrast the accuracy of the various methods. The consequences of tag formation bias are discussed in the context of testing differential expression. A description is given as to how these algorithms can be applied in that context.</p> <p>Conclusions</p> <p>Several Bayesian inference algorithms that account for tag formation effects are compared with the DPB algorithm providing clear evidence of superior performance. The accuracy of inferences when using a particular non-informative prior is found to depend on the expression level of a given gene. The multivariate nature of the approach easily allows both univariate and joint tests of differential expression. Calculations demonstrate the potential for false positive and negative findings due to variation in tag formation probabilities across samples when testing for differential expression.</p

Stability of Spatial Optical Solitons

We present a brief overview of the basic concepts of the soliton stability theory and discuss some characteristic examples of the instability-induced soliton dynamics, in application to spatial optical solitons described by the NLS-type nonlinear models and their generalizations. In particular, we demonstrate that the soliton internal modes are responsible for the appearance of the soliton instability, and outline an analytical approach based on a multi-scale asymptotic technique that allows to analyze the soliton dynamics near the marginal stability point. We also discuss some results of the rigorous linear stability analysis of fundamental solitary waves and nonlinear impurity modes. Finally, we demonstrate that multi-hump vector solitary waves may become stable in some nonlinear models, and discuss the examples of stable (1+1)-dimensional composite solitons and (2+1)-dimensional dipole-mode solitons in a model of two incoherently interacting optical beams.Comment: 34 pages, 9 figures; to be published in: "Spatial Optical Solitons", Eds. W. Torruellas and S. Trillo (Springer, New York

Building professional discourse in emerging markets: Language, context and the challenge of sensemaking

Using ethnographic evidence from the former Soviet republics, this article examines a relatively new and mainly unobserved in the International Business (IB) literature phenomenon of communication disengagement that manifests itself in many emerging markets. We link it to the deficiencies of the local professional business discourse rooted in language limitations reflecting lack of experience with the market economy. This hampers cognitive coherence between foreign and local business entities, adding to the liability of foreignness as certain instances of professional experience fail to find adequate linguistic expression, and complicates cross-cultural adjustments causing multi-national companies (MNCs) financial losses. We contribute to the IB literature by examining cross-border semantic sensemaking through a retrospectively constructed observational study. We argue that a relative inadequacy of the national professional idiom is likely to remain a feature of business environment in post-communist economies for some time and therefore should be factored into business strategies of MNCs. Consequently, we recommend including discursive hazards in the risk evaluation of international projects

Differing Requirements for RAD51 and DMC1 in Meiotic Pairing of Centromeres and Chromosome Arms in Arabidopsis thaliana

During meiosis homologous chromosomes pair, recombine, and synapse, thus ensuring accurate chromosome segregation and the halving of ploidy necessary for gametogenesis. The processes permitting a chromosome to pair only with its homologue are not fully understood, but successful pairing of homologous chromosomes is tightly linked to recombination. In Arabidopsis thaliana, meiotic prophase of rad51, xrcc3, and rad51C mutants appears normal up to the zygotene/pachytene stage, after which the genome fragments, leading to sterility. To better understand the relationship between recombination and chromosome pairing, we have analysed meiotic chromosome pairing in these and in dmc1 mutant lines. Our data show a differing requirement for these proteins in pairing of centromeric regions and chromosome arms. No homologous pairing of mid-arm or distal regions was observed in rad51, xrcc3, and rad51C mutants. However, homologous centromeres do pair in these mutants and we show that this does depend upon recombination, principally on DMC1. This centromere pairing extends well beyond the heterochromatic centromere region and, surprisingly, does not require XRCC3 and RAD51C. In addition to clarifying and bringing the roles of centromeres in meiotic synapsis to the fore, this analysis thus separates the roles in meiotic synapsis of DMC1 and RAD51 and the meiotic RAD51 paralogs, XRCC3 and RAD51C, with respect to different chromosome domains

Representational Switching by Dynamical Reorganization of Attractor Structure in a Network Model of the Prefrontal Cortex

The prefrontal cortex (PFC) plays a crucial role in flexible cognitive behavior by representing task relevant information with its working memory. The working memory with sustained neural activity is described as a neural dynamical system composed of multiple attractors, each attractor of which corresponds to an active state of a cell assembly, representing a fragment of information. Recent studies have revealed that the PFC not only represents multiple sets of information but also switches multiple representations and transforms a set of information to another set depending on a given task context. This representational switching between different sets of information is possibly generated endogenously by flexible network dynamics but details of underlying mechanisms are unclear. Here we propose a dynamically reorganizable attractor network model based on certain internal changes in synaptic connectivity, or short-term plasticity. We construct a network model based on a spiking neuron model with dynamical synapses, which can qualitatively reproduce experimentally demonstrated representational switching in the PFC when a monkey was performing a goal-oriented action-planning task. The model holds multiple sets of information that are required for action planning before and after representational switching by reconfiguration of functional cell assemblies. Furthermore, we analyzed population dynamics of this model with a mean field model and show that the changes in cell assemblies' configuration correspond to those in attractor structure that can be viewed as a bifurcation process of the dynamical system. This dynamical reorganization of a neural network could be a key to uncovering the mechanism of flexible information processing in the PFC

Mitochondrial dysfunction and biogenesis: do ICU patients die from mitochondrial failure?

Mitochondrial functions include production of energy, activation of programmed cell death, and a number of cell specific tasks, e.g., cell signaling, control of Ca2+ metabolism, and synthesis of a number of important biomolecules. As proper mitochondrial function is critical for normal performance and survival of cells, mitochondrial dysfunction often leads to pathological conditions resulting in various human diseases. Recently mitochondrial dysfunction has been linked to multiple organ failure (MOF) often leading to the death of critical care patients. However, there are two main reasons why this insight did not generate an adequate resonance in clinical settings. First, most data regarding mitochondrial dysfunction in organs susceptible to failure in critical care diseases (liver, kidney, heart, lung, intestine, brain) were collected using animal models. Second, there is no clear therapeutic strategy how acquired mitochondrial dysfunction can be improved. Only the benefit of such therapies will confirm the critical role of mitochondrial dysfunction in clinical settings. Here we summarized data on mitochondrial dysfunction obtained in diverse experimental systems, which are related to conditions seen in intensive care unit (ICU) patients. Particular attention is given to mechanisms that cause cell death and organ dysfunction and to prospective therapeutic strategies, directed to recover mitochondrial function. Collectively the data discussed in this review suggest that appropriate diagnosis and specific treatment of mitochondrial dysfunction in ICU patients may significantly improve the clinical outcome

Gain through losses in nonlinear optics

Instabilities of uniform states are ubiquitous processes occurring in a variety of spatially extended nonlinear systems. These instabilities are at the heart of symmetry breaking, condensate dynamics, self-organization, pattern formation and noise amplification across diverse disciplines, including physics, chemistry, engineering and biology. In nonlinear optics, modulation instabilities are generally linked to the so-called parametric amplification process, which occurs when certain phase-matching or quasi-phase-matching conditions are satisfied. In the present review article, we summarize the principle results on modulation instabilities and parametric amplification in nonlinear optics, with special emphasis on optical fibres. We then review state-of-the-art research about a peculiar class of modulation instabilities and signal amplification processes induced by dissipation in nonlinear optical systems. Losses applied to certain parts of the spectrum counterintuitively lead to the exponential growth of the damped mode themselves, causing gain through losses. We discuss the concept of imaging of losses into gain, showing how to map a given spectral loss profile into a gain spectrum. We demonstrate with concrete examples that dissipation-induced modulation instability, apart from being of fundamental theoretical interest, may pave the way towards the design of a new class of tuneable fibre-based optical amplifiers, optical parametric oscillators, frequency comb sources and pulsed lasers

Moments of the Position of the Maximum for GUE Characteristic Polynomials and for Log-Correlated Gaussian Processes

We study three instances of log-correlated processes on the interval: the logarithm of the Gaussian unitary ensemble (GUE) characteristic polynomial, the Gaussian log-correlated potential in presence of edge charges, and the Fractional Brownian motion with Hurst index $H \to 0$ (fBM0). In previous collaborations we obtained the probability distribution function (PDF) of the value of the global minimum (equivalently maximum) for the first two processes, using the {\it freezing-duality conjecture} (FDC). Here we study the PDF of the position of the maximum $x_m$ through its moments. Using replica, this requires calculating moments of the density of eigenvalues in the $\beta$-Jacobi ensemble. Using Jack polynomials we obtain an exact and explicit expression for both positive and negative integer moments for arbitrary $\beta >0$ and positive integer $n$ in terms of sums over partitions. For positive moments, this expression agrees with a very recent independent derivation by Mezzadri and Reynolds. We check our results against a contour integral formula derived recently by Borodin and Gorin (presented in the Appendix A from these authors). The duality necessary for the FDC to work is proved, and on our expressions, found to correspond to exchange of partitions with their dual. Performing the limit $n \to 0$ and to negative Dyson index $\beta \to -2$, we obtain the moments of $x_m$ and give explicit expressions for the lowest ones. Numerical checks for the GUE polynomials, performed independently by N. Simm, indicate encouraging agreement. Some results are also obtained for moments in Laguerre, Hermite-Gaussian, as well as circular and related ensembles. The correlations of the position and the value of the field at the minimum are also analyzed.Comment: 64 page, 5 figures, with Appendix A written by Alexei Borodin and Vadim Gorin; The appendix H in the ArXiv version is absent in the published versio