Charles Wesley and the Language of Evangelical Experience: The Poetical Hermeneutic Revisited

Charles Wesley is well remembered as the poet laureate of Methodism, whose rousing hymns continue to adorn Christian worship. This article suggests that he was also a significant theologian; a theologian of the experimental variety, who used religious experience as a means for translating theological doctrine into the realm of Christian life. Religious experience played an important role in Wesley\u27s poetical approach to the Bible, and allowed him to unite human hearts and minds in biblical affirmations. In this sense, Charles\u27s hymns were aptly described (by John Wesley) as practical divinity. A close examination of Charles Wesley\u27s vocabulary of religious experience (through words like feel, prove, to know, and taste ) indicates that his own creative synthesis of reason and experience produced a kind of practical divinity that still has potency for modern Christians. Based on this assessment it is concluded that Charles Wesley was a creative theologian, who blended evangelical theology with religious experience to form his own brand of religious empiricism. Formed in the language of religious praise, Charles\u27s hymns are first-order theology. They are not merely words said about God, they are in fact, words said (or sung) to God. As such, Charles Wesley’s hymns actually playa role in inducing the experiences they describe

A Hybrid Model of Mammalian Cell Cycle Regulation

The timing of DNA synthesis, mitosis and cell division is regulated by a complex network of biochemical reactions that control the activities of a family of cyclin-dependent kinases. The temporal dynamics of this reaction network is typically modeled by nonlinear differential equations describing the rates of the component reactions. This approach provides exquisite details about molecular regulatory processes but is hampered by the need to estimate realistic values for the many kinetic constants that determine the reaction rates. It is difficult to estimate these kinetic constants from available experimental data. To avoid this problem, modelers often resort to ‘qualitative’ modeling strategies, such as Boolean switching networks, but these models describe only the coarsest features of cell cycle regulation. In this paper we describe a hybrid approach that combines the best features of continuous differential equations and discrete Boolean networks. Cyclin abundances are tracked by piecewise linear differential equations for cyclin synthesis and degradation. Cyclin synthesis is regulated by transcription factors whose activities are represented by discrete variables (0 or 1) and likewise for the activities of the ubiquitin-ligating enzyme complexes that govern cyclin degradation. The discrete variables change according to a predetermined sequence, with the times between transitions determined in part by cyclin accumulation and degradation and as well by exponentially distributed random variables. The model is evaluated in terms of flow cytometry measurements of cyclin proteins in asynchronous populations of human cell lines. The few kinetic constants in the model are easily estimated from the experimental data. Using this hybrid approach, modelers can quickly create quantitatively accurate, computational models of protein regulatory networks in cells

Mathematical Analysis of Cytokine-Induced Differentiation of Granulocyte-Monocyte Progenitor Cells

Granulocyte-monocyte progenitor (GMP) cells play a vital role in the immune system by maturing into a variety of white blood cells, including neutrophils and macrophages, depending on exposure to cytokines such as various types of colony stimulating factors (CSF). Granulocyte-CSF (G-CSF) induces granulopoiesis and macrophage-CSF (M-CSF) induces monopoiesis, while granulocyte/macrophage-CSF (GM-CSF) favors monocytic and granulocytic differentiation at low and high concentrations, respectively. Although these differentiation pathways are well documented, the mechanisms behind the diverse behavioral responses of GMP cells to CSFs are not well understood. In this paper, we propose a mechanism of interacting CSF-receptors and transcription factors that control GMP differentiation, convert the mechanism into a set of differential equations, and explore the properties of this mathematical model using dynamical systems theory. Our model reproduces numerous experimental observations of GMP cell differentiation in response to varying dosages of G-CSF, M-CSF, and GM-CSF. In particular, we are able to reproduce the concentration-dependent behavior of GM-CSF induced differentiation, and propose a mechanism driving this behavior. In addition, we explore the differentiation of a fourth phenotype, monocytic myeloid-derived suppressor cells (M-MDSC), showing how they might fit into the classical pathways of GMP differentiation and how progenitor cells can be primed for M-MDSC differentiation. Finally, we use the model to make novel predictions that can be explored by future experimental studies

Tunable Pinning of Burst-Waves in Extended Systems with Discrete Sources

We study the dynamics of waves in a system of diffusively coupled discrete nonlinear sources. We show that the system exhibits burst waves which are periodic in a traveling-wave reference frame. We demonstrate that the burst waves are pinned if the diffusive coupling is below a critical value. When the coupling crosses the critical value the system undergoes a depinning instability via a saddle-node bifurcation, and the wave begins to move. We obtain the universal scaling for the mean wave velocity just above threshold.Comment: 4 pages, 5 figures, revte

MinION Analysis and Reference Consortium: Phase 1 data release and analysis

The advent of a miniaturized DNA sequencing device with a high-throughput contextual sequencing capability embodies the next generation of large scale sequencing tools. The MinION™ Access Programme (MAP) was initiated by Oxford Nanopore Technologies™ in April 2014, giving public access to their USB-attached miniature sequencing device. The MinION Analysis and Reference Consortium (MARC) was formed by a subset of MAP participants, with the aim of evaluating and providing standard protocols and reference data to the community. Envisaged as a multi-phased project, this study provides the global community with the Phase 1 data from MARC, where the reproducibility of the performance of the MinION was evaluated at multiple sites. Five laboratories on two continents generated data using a control strain of Escherichia coli K-12, preparing and sequencing samples according to a revised ONT protocol. Here, we provide the details of the protocol used, along with a preliminary analysis of the characteristics of typical runs including the consistency, rate, volume and quality of data produced. Further analysis of the Phase 1 data presented here, and additional experiments in Phase 2 of E. coli from MARC are already underway to identify ways to improve and enhance MinION performance