Relative Stability of Network States in Boolean Network Models of Gene Regulation in Development

Progress in cell type reprogramming has revived the interest in Waddington's concept of the epigenetic landscape. Recently researchers developed the quasi-potential theory to represent the Waddington's landscape. The Quasi-potential U(x), derived from interactions in the gene regulatory network (GRN) of a cell, quantifies the relative stability of network states, which determine the effort required for state transitions in a multi-stable dynamical system. However, quasi-potential landscapes, originally developed for continuous systems, are not suitable for discrete-valued networks which are important tools to study complex systems. In this paper, we provide a framework to quantify the landscape for discrete Boolean networks (BNs). We apply our framework to study pancreas cell differentiation where an ensemble of BN models is considered based on the structure of a minimal GRN for pancreas development. We impose biologically motivated structural constraints (corresponding to specific type of Boolean functions) and dynamical constraints (corresponding to stable attractor states) to limit the space of BN models for pancreas development. In addition, we enforce a novel functional constraint corresponding to the relative ordering of attractor states in BN models to restrict the space of BN models to the biological relevant class. We find that BNs with canalyzing/sign-compatible Boolean functions best capture the dynamics of pancreas cell differentiation. This framework can also determine the genes' influence on cell state transitions, and thus can facilitate the rational design of cell reprogramming protocols.Comment: 24 pages, 6 figures, 1 tabl

Two-transcript gene expression classifiers in the diagnosis and prognosis of human diseases.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Identification of molecular classifiers from genome-wide gene expression analysis is an important practice for the investigation of biological systems in the post-genomic era--and one with great potential for near-term clinical impact. The 'Top-Scoring Pair' (TSP) classification method identifies pairs of genes whose relative expression correlates strongly with phenotype. In this study, we sought to assess the effectiveness of the TSP approach in the identification of diagnostic classifiers for a number of human diseases including bacterial and viral infection, cardiomyopathy, diabetes, Crohn's disease, and transformed ulcerative colitis. We examined transcriptional profiles from both solid tissues and blood-borne leukocytes. RESULTS: The algorithm identified multiple predictive gene pairs for each phenotype, with cross-validation accuracy ranging from 70 to nearly 100 percent, and high sensitivity and specificity observed in most classification tasks. Performance compared favourably with that of pre-existing transcription-based classifiers, and in some cases was comparable to the accuracy of current clinical diagnostic procedures. Several diseases of solid tissues could be reliably diagnosed through classifiers based on the blood-borne leukocyte transcriptome. The TSP classifier thus represents a simple yet robust method to differentiate between diverse phenotypic states based on gene expression profiles. CONCLUSION: Two-transcript classifiers have the potential to reliably classify diverse human diseases, through analysis of both local diseased tissue and the immunological response assayed through blood-borne leukocytes. The experimental simplicity of this method results in measurements that can be easily translated to clinical practice

Explaining the rise of 'human rights' in analyses of Sino-African relations

Popular perceptions of China and its global role are often shaped by two words: 'made in'. Yet this vision of China that focuses primarily on Beijing as a coming economic superpower is relatively new, and it is not that long ago that two other words tended to dominate debates on and discourses of China: 'human rights'. To be sure, real interest in human rights in China was never the only issue in other states' relations with China, nor consistently pursued throughout the years (Nathan, 1994). Nor did human rights totally subsequently disappear from the political agenda.1 Nevertheless, the rhetorical importance of human rights - perhaps best epitomised by the narrow defeat of resolutions condemning Chinese policy in 1995 at the Human Rights Council in Geneva - stands in stark contrast to the relative silence thereafter as the bottom line of most states' relations with Beijing took on ever greater economic dimensions

Characterization of growth and metabolism of the haloalkaliphile Natronomonas pharaonis

Natronomonas pharaonis is an archaeon adapted to two extreme conditions: high salt concentration and alkaline pH. It has become one of the model organisms for the study of extremophilic life. Here, we present a genome-scale, manually curated metabolic reconstruction for the microorganism. The reconstruction itself represents a knowledge base of the haloalkaliphile's metabolism and, as such, would greatly assist further investigations on archaeal pathways. In addition, we experimentally determined several parameters relevant to growth, including a characterization of the biomass composition and a quantification of carbon and oxygen consumption. Using the metabolic reconstruction and the experimental data, we formulated a constraints-based model which we used to analyze the behavior of the archaeon when grown on a single carbon source. Results of the analysis include the finding that Natronomonas pharaonis, when grown aerobically on acetate, uses a carbon to oxygen consumption ratio that is theoretically near-optimal with respect to growth and energy production. This supports the hypothesis that, under simple conditions, the microorganism optimizes its metabolism with respect to the two objectives. We also found that the archaeon has a very low carbon efficiency of only about 35%. This inefficiency is probably due to a very low P/O ratio as well as to the other difficulties posed by its extreme environment

Towards a formalism for mapping the spacetimes of massive compact objects: Bumpy black holes and their orbits

Observations have established that extremely compact, massive objects are common in the universe. It is generally accepted that these objects are black holes. As observations improve, it becomes possible to test this hypothesis in ever greater detail. In particular, it is or will be possible to measure the properties of orbits deep in the strong field of a black hole candidate (using x-ray timing or with gravitational-waves) and to test whether they have the characteristics of black hole orbits in general relativity. Such measurements can be used to map the spacetime of a massive compact object, testing whether the object's multipoles satisfy the strict constraints of the black hole hypothesis. Such a test requires that we compare against objects with the ``wrong'' multipole structure. In this paper, we present tools for constructing bumpy black holes: objects that are almost black holes, but that have some multipoles with the wrong value. The spacetimes which we present are good deep into the strong field of the object -- we do not use a large r expansion, except to make contact with weak field intuition. Also, our spacetimes reduce to the black hole spacetimes of general relativity when the ``bumpiness'' is set to zero. We propose bumpy black holes as the foundation for a null experiment: if black hole candidates are the black holes of general relativity, their bumpiness should be zero. By comparing orbits in a bumpy spacetime with those of an astrophysical source, observations should be able to test this hypothesis, stringently testing whether they are the black holes of general relativity. (Abridged)Comment: 16 pages + 2 appendices + 3 figures. Submitted to PR

Critical Networks Exhibit Maximal Information Diversity in Structure-Dynamics Relationships

Network structure strongly constrains the range of dynamic behaviors available to a complex system. These system dynamics can be classified based on their response to perturbations over time into two distinct regimes, ordered or chaotic, separated by a critical phase transition. Numerous studies have shown that the most complex dynamics arise near the critical regime. Here we use an information theoretic approach to study structure-dynamics relationships within a unified framework and how that these relationships are most diverse in the critical regime

A Study of the Quasi-elastic (e,e'p) Reaction on 12^{12}C, 56^{56}Fe and 97^{97}Au

We report the results from a systematic study of the quasi-elastic (e,e'p) reaction on $^{12}$C, $^{56}$Fe and $^{197}$Au performed at Jefferson Lab. We have measured nuclear transparency and extracted spectral functions (corrected for radiation) over a Q$^2$ range of 0.64 - 3.25 (GeV/c)$^2$ for all three nuclei. In addition we have extracted separated longitudinal and transverse spectral functions at Q$^2$ of 0.64 and 1.8 (GeV/c)$^2$ for these three nuclei (except for $^{197}$Au at the higher Q$^2$). The spectral functions are compared to a number of theoretical calculations. The measured spectral functions differ in detail but not in overall shape from most of the theoretical models. In all three targets the measured spectral functions show considerable excess transverse strength at Q$^2$ = 0.64 (GeV/c)$^2$, which is much reduced at 1.8 (GeV/c)$^2$.Comment: For JLab E91013 Collaboration, 19 pages, 20 figures, 3 table

Identifying topological edge states in 2D optical lattices using light scattering

We recently proposed in a Letter [Physical Review Letters 108 255303] a novel scheme to detect topological edge states in an optical lattice, based on a generalization of Bragg spectroscopy. The scope of the present article is to provide a more detailed and pedagogical description of the system - the Hofstadter optical lattice - and probing method. We first show the existence of topological edge states, in an ultra-cold gas trapped in a 2D optical lattice and subjected to a synthetic magnetic field. The remarkable robustness of the edge states is verified for a variety of external confining potentials. Then, we describe a specific laser probe, made from two lasers in Laguerre-Gaussian modes, which captures unambiguous signatures of these edge states. In particular, the resulting Bragg spectra provide the dispersion relation of the edge states, establishing their chiral nature. In order to make the Bragg signal experimentally detectable, we introduce a "shelving method", which simultaneously transfers angular momentum and changes the internal atomic state. This scheme allows to directly visualize the selected edge states on a dark background, offering an instructive view on topological insulating phases, not accessible in solid-state experiments.Comment: 17 pages, 10 figures. Revised and extended version, to appear in EJP Special Topic for the special issue on "Novel Quantum Phases and Mesoscopic Physics in Quantum Gases". Extended version of arXiv:1203.124