Not the Simplest Christians: Vernacular Charming and The Limits of Orthodox Practice in Late Medieval England

The relationship between charmers and the keepers of religious orthodoxy has been over simplified in prior analysis. Both Keith Thomas and Eamon Duffy represent the Church’s message on religion and magic as relatively homogeneous. They find the impulse to employ charms as rooted in the parishioners’ faith in the ceremonies of the Church, part of either ‘the magic of the medieval church’ or as another element of the ‘multifaceted resonant symbolic house’ of medieval religion. Charms were an expression of the core mysteries of medieval religion. Even if they might technically be unorthodox, it could be excused as matter of religious ignorance. In this construction the individual collector and user of charms is treated as a passive receptor of ideas rather than an independent actor who engaged with the Church and its teachings, as well as the literature on magic, and made his own decisions. This thesis will employ charms and religious writings in the common place book of Robert Reynes to reconstruct the theological world of a medieval charmer. It will argue that charmers were not only more unorthodox than previously described, but also that they were active agents in the construction of their own religious experience as it pertained to protection, healing, and occasionally salvation

Overlapping Roles of CXCL13, Interleukin 7 Receptor α, and CCR7 Ligands in Lymph Node Development

Lymphoid tissue development is associated with local accumulation of CD4+ CD3− IL-7Rαhi hematopoietic cells that deliver lymphotoxin (LT)α1β2 signals to resident stromal cells. Previous studies have established an important role for CXCL13 (BLC) in the development of Peyer's patches (PP) and some peripheral lymph nodes (LNs), but the chemokine requirements for several LN types, including mesenteric LNs, remain undefined. Using CXCL13−/− mice that additionally carry the paucity of LN T cell mutation (plt/plt), we discovered that CCR7 ligands function in peripheral LN development. We also tested for a genetic interaction during LN development between CXCL13 and a cytokine receptor required in PP development, IL-7Rα. Mice deficient for both CXCL13 and IL-7Rα displayed a striking absence of LNs, including mesenteric LNs. These data extend the role of CXCL13 to the development of all LNs and establish a previously unappreciated role for IL-7Rα in this process. Both circulating and LN CD4+ CD3− IL-7Rαhi cells are shown to express LTα1β2 in an IL-7Rα–dependent manner. Furthermore, CXCL13 was found to be sufficient to mediate CD4+ CD3− IL-7Rαhi cell recruitment in vivo to an ectopic site. These findings indicate that CXCL13 and CCR7 ligands promote accumulation of CD4+ CD3− IL-7Rαhi cells, delivering IL-7Rα–dependent LTα1β2 signals critical for LN development

Autotuning Algorithmic Choice for Input Sensitivity

Empirical autotuning is increasingly being used in many domains to achieve optimized performance in a variety of different execution environments. A daunting challenge faced by such autotuners is input sensitivity, where the best autotuned configuration may vary with different input sets. In this paper, we propose a two level solution that: first, clusters to find input sets that are similar in input feature space; then, uses an evolutionary autotuner to build an optimized program for each of these clusters; and, finally, builds an adaptive overhead aware classifier which assigns each input to a specific input optimized program. Our approach addresses the complex trade-off between using expensive features, to accurately characterize an input, and cheaper features, which can be computed with less overhead. Experimental results show that by adapting to different inputs one can obtain up to a 3x speedup over using a single configuration for all inputs

Behavioural micro-dynamics of car ownership and travel in the Seattle metropolitan region from 1989 to 2002

In this paper data from 230 households observed in ten different occasions (waves) from 1989 to 2002 in the Puget Sound region are used to explore relationships among number of cars owned, number of trips driving alone, and number of trips sharing cars with household members. Using a mixture latent class Markov model we identify four distinct groups that are a High Mobility group with more cars and car trips, an Average Mobility group with lower car ownership and trips driving alone, a third group with relatively high car ownership but few car sharing trips, and a fourth group of Low Mobility characterized by the low car ownership and trips. Households change behaviour adapting to internal and external changes to their environment but they also anticipate changes and go through a "preparation" stage (e.g., adding another car in their fleet in expectation of adding another employed person). Land use plays a somewhat secondary role. The analysis also reveals three classes (hidden Markov chains) of households underlying behavioural dynamics with increases in the low car ownership categories (zero and one car per household), decreases in the high car ownership (three cars and four or more cars per household) and stable behaviour in the two cars per household group. Household membership in these classes is significantly influenced by householder ratings to parking availability, schedule flexibility, bus transfers, and day-to-day costs of driving. The findings here show attitudes and land use enhance understanding of longitudinal heterogeneity

Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs

Activation of naive CD8+ T cells with antigen induces their differentiation into effector cytolytic T lymphocytes (CTLs). CTLs lyse infected or aberrant target cells by exocytosis of lytic granules containing the pore-forming protein perforin and a family of proteases termed granzymes. We show that effector CTL differentiation occurs in two sequential phases in vitro, characterized by early induction of T-bet and late induction of Eomesodermin (Eomes), T-box transcription factors that regulate the early and late phases of interferon (IFN) γ expression, respectively. In addition, we demonstrate a critical role for the transcription factor Runx3 in CTL differentiation. Runx3 regulates Eomes expression as well as expression of three cardinal markers of the effector CTL program: IFN-γ, perforin, and granzyme B. Our data point to the existence of an elaborate transcriptional network in which Runx3 initially induces and then cooperates with T-box transcription factors to regulate gene transcription in differentiating CTLs

Predicting cell types and genetic variations contributing to disease by combining GWAS and epigenetic data

Genome-wide association studies (GWASs) identify single nucleotide polymorphisms (SNPs) that are enriched in individuals suffering from a given disease. Most disease-associated SNPs fall into non-coding regions, so that it is not straightforward to infer phenotype or function; moreover, many SNPs are in tight genetic linkage, so that a SNP identified as associated with a particular disease may not itself be causal, but rather signify the presence of a linked SNP that is functionally relevant to disease pathogenesis. Here, we present an analysis method that takes advantage of the recent rapid accumulation of epigenomics data to address these problems for some SNPs. Using asthma as a prototypic example; we show that non-coding disease-associated SNPs are enriched in genomic regions that function as regulators of transcription, such as enhancers and promoters. Identifying enhancers based on the presence of the histone modification marks such as H3K4me1 in different cell types, we show that the location of enhancers is highly cell-type specific. We use these findings to predict which SNPs are likely to be directly contributing to disease based on their presence in regulatory regions, and in which cell types their effect is expected to be detectable. Moreover, we can also predict which cell types contribute to a disease based on overlap of the disease-associated SNPs with the locations of enhancers present in a given cell type. Finally, we suggest that it will be possible to re-analyze GWAS studies with much higher power by limiting the SNPs considered to those in coding or regulatory regions of cell types relevant to a given disease

Visualizing B cell capture of cognate antigen from follicular dendritic cells

The prominent display of opsonized antigen by follicular dendritic cells (FDCs) has long favored the view that they serve as antigen-presenting cells for B cells. Surprisingly, however, although B cell capture of antigen from macrophages and dendritic cells has been visualized, acquisition from FDCs has not been directly observed. Using two-photon microscopy, we visualized B cell capture of cognate antigen from FDCs. B cell CXCR5 expression was required, and encounter with FDC-associated antigen could be detected for >1 wk after immunization. B cell–FDC contact times were often brief but occasionally persisted for >30 min, and B cells sometimes acquired antigen together with FDC surface proteins. These observations establish that FDCs can serve as sites of B cell antigen capture, with their prolonged display time ensuring that even rare B cells have the chance of antigen encounter, and they suggest possible information transfer from antigen-presenting cell to B cell