Cyclebase.org—a comprehensive multi-organism online database of cell-cycle experiments

The past decade has seen the publication of a large number of cell-cycle microarray studies and many more are in the pipeline. However, data from these experiments are not easy to access, combine and evaluate. We have developed a centralized database with an easy-to-use interface, Cyclebase.org, for viewing and downloading these data. The user interface facilitates searches for genes of interest as well as downloads of genome-wide results. Individual genes are displayed with graphs of expression profiles throughout the cell cycle from all available experiments. These expression profiles are normalized to a common timescale to enable inspection of the combined experimental evidence. Furthermore, state-of-the-art computational analyses provide key information on both individual experiments and combined datasets such as whether or not a gene is periodically expressed and, if so, the time of peak expression. Cyclebase is available at http://www.cyclebase.org

Resonance-assisted tunneling in near-integrable systems

Dynamical tunneling between symmetry related invariant tori is studied in the near-integrable regime. Using the kicked Harper model as an illustration, we show that the exponential decay of the wave functions in the classically forbidden region is modified due to coupling processes that are mediated by classical resonances. This mechanism leads to a substantial deviation of the splitting between quasi-degenerate eigenvalues from the purely exponential decrease with 1 / hbar obtained for the integrable system. A simple semiclassical framework, which takes into account the effect of the resonance substructure on the KAM tori, allows to quantitatively reproduce the behavior of the eigenvalue splittings.Comment: 4 pages, 2 figures, gzipped tar file, to appear in Phys. Rev. Lett, text slightly condensed compared to first versio

Relating the thermodynamic arrow of time to the causal arrow

Consider a Hamiltonian system that consists of a slow subsystem S and a fast subsystem F. The autonomous dynamics of S is driven by an effective Hamiltonian, but its thermodynamics is unexpected. We show that a well-defined thermodynamic arrow of time (second law) emerges for S whenever there is a well-defined causal arrow from S to F and the back-action is negligible. This is because the back-action of F on S is described by a non-globally Hamiltonian Born-Oppenheimer term that violates the Liouville theorem, and makes the second law inapplicable to S. If S and F are mixing, under the causal arrow condition they are described by microcanonic distributions P(S) and P(S|F). Their structure supports a causal inference principle proposed recently in machine learning.Comment: 10 page

Analysis of dynamical corrections to baryon magnetic moments

We present and analyze QCD corrections to the baryon magnetic moments in terms of the one-, two-, and three-body operators which appear in the effective field theory developed in our recent papers. The main corrections are extended Thomas-type corrections associated with the confining interactions in the baryon. We investigate the contributions of low-lying angular excitations to the moments quantitatively and show that they are completely negligible. When the QCD corrections are combined with the non-quark model contributions of the meson loops, we obtain a model which describes the moments within a mean deviation of 0.04 $\mu_N$. The nontrivial interplay of the two types of corrections to the quark-model moments is analyzed in detail, and explains why the quark model is so successful. In the course of these calculations, we parametrize the general spin structure of the $j={1/2}^+$ baryon wave functions in a form which clearly displays the symmetry properties and the internal angular momentum content of the wave functions, and allows us to use spin-trace methods to calculate the many spin matrix elements which appear in the expressions for the moments. This representation may be useful elsewhere.Comment: 32 pages, 3 figures, submitted to Phys. Rev.

Algebraic approach in the study of time-dependent nonlinear integrable systems: Case of the singular oscillator

The classical and the quantal problem of a particle interacting in one-dimension with an external time-dependent quadratic potential and a constant inverse square potential is studied from the Lie-algebraic point of view. The integrability of this system is established by evaluating the exact invariant closely related to the Lewis and Riesenfeld invariant for the time-dependent harmonic oscillator. We study extensively the special and interesting case of a kicked quadratic potential from which we derive a new integrable, nonlinear, area preserving, two-dimensional map which may, for instance, be used in numerical algorithms that integrate the Calogero-Sutherland-Moser Hamiltonian. The dynamics, both classical and quantal, is studied via the time-evolution operator which we evaluate using a recent method of integrating the quantum Liouville-Bloch equations \cite{rau}. The results show the exact one-to-one correspondence between the classical and the quantal dynamics. Our analysis also sheds light on the connection between properties of the SU(1,1) algebra and that of simple dynamical systems.Comment: 17 pages, 4 figures, Accepted in PR

Time-Course Analysis of Cyanobacterium Transcriptome: Detecting Oscillatory Genes

The microarray technique allows the simultaneous measurements of the expression levels of thousands of mRNAs. By mining these data one can identify the dynamics of the gene expression time series. The detection of genes that are periodically expressed is an important step that allows us to study the regulatory mechanisms associated with the circadian cycle. The problem of finding periodicity in biological time series poses many challenges. Such challenge occurs due to the fact that the observed time series usually exhibit non-idealities, such as noise, short length, outliers and unevenly sampled time points. Consequently, the method for finding periodicity should preferably be robust against such anomalies in the data. In this paper, we propose a general and robust procedure for identifying genes with a periodic signature at a given significance level. This identification method is based on autoregressive models and the information theory. By using simulated data we show that the suggested method is capable of identifying rhythmic profiles even in the presence of noise and when the number of data points is small. By recourse of our analysis, we uncover the circadian rhythmic patterns underlying the gene expression profiles from Cyanobacterium Synechocystis

Principal-Oscillation-Pattern Analysis of Gene Expression

Principal-oscillation-pattern (POP) analysis is a multivariate and systematic technique for identifying the dynamic characteristics of a system from time-series data. In this study, we demonstrate the first application of POP analysis to genome-wide time-series gene-expression data. We use POP analysis to infer oscillation patterns in gene expression. Typically, a genomic system matrix cannot be directly estimated because the number of genes is usually much larger than the number of time points in a genomic study. Thus, we first identify the POPs of the eigen-genomic system that consists of the first few significant eigengenes obtained by singular value decomposition. By using the linear relationship between eigengenes and genes, we then infer the POPs of the genes. Both simulation data and real-world data are used in this study to demonstrate the applicability of POP analysis to genomic data. We show that POP analysis not only compares favorably with experiments and existing computational methods, but that it also provides complementary information relative to other approaches

Predicting Cell Cycle Regulated Genes by Causal Interactions

The fundamental difference between classic and modern biology is that technological innovations allow to generate high-throughput data to get insights into molecular interactions on a genomic scale. These high-throughput data can be used to infer gene networks, e.g., the transcriptional regulatory or signaling network, representing a blue print of the current dynamical state of the cellular system. However, gene networks do not provide direct answers to biological questions, instead, they need to be analyzed to reveal functional information of molecular working mechanisms. In this paper we propose a new approach to analyze the transcriptional regulatory network of yeast to predict cell cycle regulated genes. The novelty of our approach is that, in contrast to all other approaches aiming to predict cell cycle regulated genes, we do not use time series data but base our analysis on the prior information of causal interactions among genes. The major purpose of the present paper is to predict cell cycle regulated genes in S. cerevisiae. Our analysis is based on the transcriptional regulatory network, representing causal interactions between genes, and a list of known periodic genes. No further data are used. Our approach utilizes the causal membership of genes and the hierarchical organization of the transcriptional regulatory network leading to two groups of periodic genes with a well defined direction of information flow. We predict genes as periodic if they appear on unique shortest paths connecting two periodic genes from different hierarchy levels. Our results demonstrate that a classical problem as the prediction of cell cycle regulated genes can be seen in a new light if the concept of a causal membership of a gene is applied consequently. This also shows that there is a wealth of information buried in the transcriptional regulatory network whose unraveling may require more elaborate concepts than it might seem at first

The use of pure and impure placebo interventions in primary care - a qualitative approach

Background: Placebos play an important role in clinical trials and several surveys have shown that they are also common in daily practice. Previous research focused primarily on the frequency of placebo use in outpatient care. Our aim was to explore physicians' views on the use of placebos in daily practice, whereby distinction was made between pure placebos (substances with no pharmacological effect, e.g. sugar pills) and impure placebos (substances with pharmacological effect but not on the condition being treated, e.g. antibiotics in viral infections or vitamins). Methods: We performed semi-structured interviews with a sample of twelve primary care physicians (PCPs). The interview addressed individual definitions of a placebo, attitudes towards placebos and the participants' reasons for prescribing them. The interviews were transcribed and analysed using qualitative content analysis. Results: The definition of a placebo given by the majority of the PCPs in our study was one which actually only describes pure placebos. This definition, combined with the fact that most impure placebos were not regarded as placebos at all, means that most of the participating PCPs were not aware of the extent to which placebos are used in daily practice. The PCPs stated that they use placebos (both pure and impure) mainly in the case of non-severe diseases for which there was often no satisfactory somatic explanation. According to the PCPs, cases like this are often treated by complementary and alternative therapies and these, too, are associated with placebo effects. However, all PCPs felt that the ethical aspects of such treatment were unclear and they were unsure as to how to communicate the use of placebos to their patients. Most of them would appreciate ethical guidelines on how to deal with this issue. Conclusions: Many PCPs seem to be unaware that some of the drugs they prescribe are classified as impure placebos. Perceptions of effectiveness and doubts about the legal and ethical aspects of the use of placebos by PCPs may discourage their application. Dissemination of guidelines and consensus papers may be one approach, but it has to be acknowledged that the topic itself is in conflict with the PCPs' perception of themselves as professional and reliable physicians