Magic as a Tool of Social Construction: Cultural and Gender Identity in Contemporary Fantasy

Contemporary fantasy is a genre that exists outside the boundaries of what consensus society constructs as socially normative. It re-appropriates and subverts facets of reality in order to place the reader in a position from which they can re-assess their own socially constructed identities, perspectives, and assumptions. Fantasy accomplishes this goal by expressing the familiar in a mode of hyper-exaggeration designed to highlight the ways in which the ideals and issues are constructed. In this way fantasy questions and critiques reality. This thesis examines how the contemporary fantasy genre uses magic as a tool to highlight the less visible social forces of reality such that the reader can gain insight into how and why social norms come to be established, as well as how they might be changed. It discusses the presentation of conflicting cultural and gender identities within fantasy worlds. Works by Brandon Sanderson, Robert Jordan, Jim Butcher, Peter V. Brett, and Patrick Rothfuss will be drawn on. By looking to the magic of the world as a focusing lens, these social conflicts and differences become clearer. The discussions undertaken in this thesis demonstrate an approach to contemporary fantasy literature that can be further utilised across a multitude of subgenres and social issues of contemporary reality

Tslp Production by Dendritic Cells Is Modulated by IL-1β and Components of the Endoplasmic Reticulum Stress Response

Thymic stromal lymphopoietin (TSLP) produced by epithelial cells acts on dendritic cells (DCs) to drive differentiation of TH2-cells, and is therefore important in allergic disease pathogenesis. However, DCs themselves make significant amounts of TSLP in response to microbial products, but little is known about the key downstream signals that induce and modulate this TSLP secretion from human DCs. We show that human monocyte derived DC (mDC) secretion of TSLP in response to Candida albicans and β-glucans requires dectin-1, Syk, NF-κB, and p38 MAPK signaling. In addition, TSLP production by mDCs is greatly enhanced by IL-1β, but not TNF-α, in contrast to epithelial cells. Furthermore, TSLP secretion is significantly increased by signals emanating from the endoplasmic reticulum (ER) stress response, specifically the unfolded protein response sensors, inositol-requiring transmembrane kinase/endonuclease 1 and protein kinase R-like ER kinase, which are activated by dectin-1 stimulation. Thus, TSLP production by mDCs requires the integration of signals from dectin-1, the IL-1 receptor, and ER stress signaling pathways. Autocrine TSLP production is likely to play a role in mDC-controlled immune responses at sites removed from epithelial cell production of the cytokine, such as lymphoid tissue

Dendritic Cell-Derived TSLP Negatively Regulates HIF-1α and IL-1β during Dectin-1 signaling

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Thymic stromal lymphopoietin (TSLP) is a functionally pleotropic cytokine important in immune regulation, and TSLP dysregulation is associated with numerous diseases. TSLP is produced by many cell types, but has predominantly been characterized as a secreted factor from epithelial cells which activates dendritic cells (DC) that subsequently prime T helper (TH) 2 immunity. However, DC themselves make significant amounts of TSLP in response to microbial products, but the functional role of DC-derived TSLP remains unclear. We show that TSLPR signaling negatively regulates IL-1β production during dectin-1 stimulation of human DC. This regulatory mechanism functions by dampening Syk phosphorylation and is mediated via NADPH oxidase-derived ROS, HIF-1α and pro-IL-1β expression. Considering the profound effect TSLPR signaling has on the metabolic status and the secretome of dectin-1 stimulated DC, these data suggest that autocrine TSLPR signaling could have a fundamental role in modulating immunological effector responses at sites removed from epithelial cell production of TSLP

Dendritic Cell-Derived TSLP Negatively Regulates HIF-1α and IL-1β During Dectin-1 Signaling

Thymic stromal lymphopoietin (TSLP) is a functionally pleotropic cytokine important in immune regulation, and TSLP dysregulation is associated with numerous diseases. TSLP is produced by many cell types, but has predominantly been characterized as a secreted factor from epithelial cells which activates dendritic cells (DC) that subsequently prime T helper (TH) 2 immunity. However, DC themselves make significant amounts of TSLP in response to microbial products, but the functional role of DC-derived TSLP remains unclear. We show that TSLPR signaling negatively regulates IL-1β production during dectin-1 stimulation of human DC. This regulatory mechanism functions by dampening Syk phosphorylation and is mediated via NADPH oxidase-derived ROS, HIF-1α and pro-IL-1β expression. Considering the profound effect TSLPR signaling has on the metabolic status and the secretome of dectin-1 stimulated DC, these data suggest that autocrine TSLPR signaling could have a fundamental role in modulating immunological effector responses at sites removed from epithelial cell production of TSLP

Crossover Scaling in Dendritic Evolution at Low Undercooling

We examine scaling in two-dimensional simulations of dendritic growth at low undercooling, as well as in three-dimensional pivalic acid dendrites grown on NASA's USMP-4 Isothermal Dendritic Growth Experiment. We report new results on self-similar evolution in both the experiments and simulations. We find that the time dependent scaling of our low undercooling simulations displays a cross-over scaling from a regime different than that characterizing Laplacian growth to steady-state growth

A cryogenic rotation stage with a large clear aperture for the half-wave plates in the Spider instrument

We describe the cryogenic half-wave plate rotation mechanisms built for and used in Spider, a polarization-sensitive balloon-borne telescope array that observed the Cosmic Microwave Background at 95 GHz and 150 GHz during a stratospheric balloon flight from Antarctica in January 2015. The mechanisms operate at liquid helium temperature in flight. A three-point contact design keeps the mechanical bearings relatively small but allows for a large (305 mm) diameter clear aperture. A worm gear driven by a cryogenic stepper motor allows for precise positioning and prevents undesired rotation when the motors are depowered. A custom-built optical encoder system monitors the bearing angle to an absolute accuracy of +/- 0.1 degrees. The system performed well in Spider during its successful 16 day flight.Comment: 11 pages, 7 figures, Published in Review of Scientific Instruments. v2 includes reviewer changes and longer literature revie

Analysis of long non-coding RNAs highlights tissue-specific expression patterns and epigenetic profiles in normal and psoriatic skin

Abstract Background Although analysis pipelines have been developed to use RNA-seq to identify long non-coding RNAs (lncRNAs), inference of their biological and pathological relevance remains a challenge. As a result, most transcriptome studies of autoimmune disease have only assessed protein-coding transcripts. Results We used RNA-seq data from 99 lesional psoriatic, 27 uninvolved psoriatic, and 90 normal skin biopsies, and applied computational approaches to identify and characterize expressed lncRNAs. We detect 2,942 previously annotated and 1,080 novel lncRNAs which are expected to be skin specific. Notably, over 40% of the novel lncRNAs are differentially expressed and the proportions of differentially expressed transcripts among protein-coding mRNAs and previously-annotated lncRNAs are lower in psoriasis lesions versus uninvolved or normal skin. We find that many lncRNAs, in particular those that are differentially expressed, are co-expressed with genes involved in immune related functions, and that novel lncRNAs are enriched for localization in the epidermal differentiation complex. We also identify distinct tissue-specific expression patterns and epigenetic profiles for novel lncRNAs, some of which are shown to be regulated by cytokine treatment in cultured human keratinocytes. Conclusions Together, our results implicate many lncRNAs in the immunopathogenesis of psoriasis, and our results provide a resource for lncRNA studies in other autoimmune diseases.http://deepblue.lib.umich.edu/bitstream/2027.42/110307/1/13059_2014_Article_570.pd

An Integrated Process for Co-Developing and Implementing Written and Computable Clinical Practice Guidelines

The goal of this article is to describe an integrated parallel process for the co-development of written and computable clinical practice guidelines (CPGs) to accelerate adoption and increase the impact of guideline recommendations in clinical practice. From February 2018 through December 2021, interdisciplinary work groups were formed after an initial Kaizen event and using expert consensus and available literature, produced a 12-phase integrated process (IP). The IP includes activities, resources, and iterative feedback loops for developing, implementing, disseminating, communicating, and evaluating CPGs. The IP incorporates guideline standards and informatics practices and clarifies how informaticians, implementers, health communicators, evaluators, and clinicians can help guideline developers throughout the development and implementation cycle to effectively co-develop written and computable guidelines. More efficient processes are essential to create actionable CPGs, disseminate and communicate recommendations to clinical end users, and evaluate CPG performance. Pilot testing is underway to determine how this IP expedites the implementation of CPGs into clinical practice and improves guideline uptake and health outcomes