SAGA Vol. 82 / 2018-2019

https://digitalcommons.augustana.edu/saga/1004/thumbnail.jp

A Viennese in London: English Reception

In a culture conducive to refining his compositions, Haydn was able to find success through his patrons and musical techniques. London was the largest musical city at the time, where advertising played a key role in the attendance at concerts. Haydn attended performances there which educated him on London’s music. His patrons (such as violinist Johann Peter Salomon and author Charles Burney) were immensely helpful in his growing musical career in London. Haydn’s shift in compositional style accordingly reflected his stay in London. He combined the music he heard in the city with his own musical language to create his new style. Through studying London’s concert life and Haydn’s interaction with it, one can understand why Haydn’s style changed while within a new city

Between Two Worlds

“Original Sin”—evocative and powerful words, but what if they were applied to one of the world’s most popular fairy tales? This thesis explores Snow White in the context of the Seven Deadly Sins and the grand fall of Adam and Eve. The forbidden fruit manifests itself in different ways, pulling the prim and proper princess into places she never could have imagined. But what of the Wicked Queen, here known as Lilith? She too feels the bite of the world’s sick sense of humor, exacting revenge on those who have wronged her. Are these poems about them? Or are they about the author? Perhaps they are both: the innocent children learn quickly of life’s cruelty, handling it with equal parts grace and selfishness. Dive into the minds of Lilith and Snow White as they explore what it means to be themselves in a world that doesn’t care if they end up happy

The low redshift Lyman-α\alpha Forest as a constraint for models of AGN feedback

We study the low redshift Lyman-$\alpha$ Forest in the Illustris and IllustrisTNG (TNG) cosmological simulations to demonstrate their utility in constraining aspects of sub-grid models of feedback from active galactic nuclei (AGN). The two simulations share an identical Ultraviolet Background prescription and similar cosmological parameters, but TNG features an entirely reworked AGN feedback model. Therefore a comparison of these simulations is useful to assess the effects of an altered AGN sub-grid model on the low redshift Lyman-$\alpha$ Forest. We find significant differences in the IGM temperature-density relation between the two simulations due to changes in the gas heating rate due to AGN. We investigate Lyman-$\alpha$ Forest observables such as the column density distribution function, flux PDF, and Doppler width ($b$-parameter) distribution. Due to the AGN radio mode model, the original Illustris simulations have a factor of 2-3 fewer absorbers than TNG at column densities $N_{\rm HI}< 10^{15.5}$ cm$^{-2}$. We show that TNG is in much better agreement with the observed $z=0.1$ flux power spectrum than Illustris. The differences in the amplitude and shape of the flux PDF and power spectrum between Illustris and TNG cannot be attributed to simple changes in the photoheating rate. We also compare the simulated Forest statistics to UV data from the Cosmic Origins Spectrograph (COS) and find that neither simulation can reproduce the slope of the absorber distribution. Both Illustris and TNG also produce significantly smaller $b$-parameter distributions than observed in the COS data, possibly due to unresolved or missing sources of turbulence.Comment: Submitted to ApJL, comments welcom

An Exploration of AGN and Stellar Feedback Effects in the Intergalactic Medium via the Low Redshift Lyman-α\alpha Forest

We explore the role of galactic feedback on the low redshift Lyman-$\alpha$ (Ly$\alpha$)~forest ($z \lesssim 2$) statistics and its potential to alter the thermal state of the intergalactic medium. Using the Cosmology and Astrophysics with Machine Learning Simulations (CAMELS) suite, we explore variations of the AGN and stellar feedback models in the IllustrisTNG and Simba sub-grid models. We find that both AGN and stellar feedback in Simba play a role in setting the Ly$\alpha$ forest column density distribution function (CDD) and the Doppler width ($b$-value) distribution. The Simba AGN jet feedback mode is able to efficiently transport energy out to the diffuse IGM causing changes in the shape and normalization of the CDD and a broadening of the $b$-value distribution. We find that stellar feedback plays a prominent role in regulating supermassive black hole growth and feedback, highlighting the importance of constraining stellar and AGN feedback simultaneously. In IllustrisTNG, the AGN feedback variations explored in CAMELS do not affect the Ly$\alpha$ forest, but varying the stellar feedback model does produce subtle changes. Our results imply that the low-$z$ Ly$\alpha$ forest can be sensitive to changes in the ultraviolet background (UVB), stellar and black hole feedback, and that AGN jet feedback in particular can have a strong effect on the thermal state of the IGM.Comment: 26 pages, 11 figures, 2 tables, submitted to Ap

Acute vasoreactivity testing in pediatric idiopathic pulmonary arterial hypertension:an international survey on current practice

The aim of this study was to determine practice patterns and inter-institutional variability in how acute vasoreactivity testing (AVT) is performed and interpreted in pediatrics throughout the world. A survey was offered to physicians affiliated with the Pediatric & Congenital Heart Disease Taskforce of the Pulmonary Vascular Research Institute (PVRI), the Pediatric Pulmonary Hypertension Network (PPHNET), or the Spanish Registry for Pediatric Pulmonary Hypertension (REHIPED), from February to December 2016. The survey requested data about the site-specific protocol for AVT and subsequent management of pediatric patients with idiopathic pulmonary arterial hypertension (IPAH) or heritable PAH (HPAH). Twenty-eight centers from 13 countries answered the survey. AVT is performed in most centers using inhaled nitric oxide (iNO). Sitbon criteria was used in 39% of the centers, Barst criteria in 43%, and other criteria in 18%. First-line therapy for positive AVT responders in functional class (FC) I/II was calcium channel blocker (CCB) in 89%, but only in 68% as monotherapy. Most centers (71%) re-evaluated AVT-positive patients hemodynamics after 6-12 months; 29% of centers re-evaluated based only on clinical criteria. Most centers (64%) considered a good response as remaining in FC I or II, with near normalization of pulmonary arterial pressure and pulmonary vascular resistance, but a stable FC I/II alone was sufficient criteria in 25% of sites. Protocols and diagnostic criteria for AVT, and therapeutic approaches during follow-up, were highly variable across the world. Reported clinical practice is not fully congruent with current guidelines, suggesting the need for additional studies that better define the prognostic value of AVT for pediatric IPAH patients

Unjamming and cell shape in the asthmatic airway epithelium

From coffee beans flowing in a chute to cells remodelling in a living tissue, a wide variety of close-packed collective systems— both inert and living—have the potential to jam. The collective can sometimes flow like a fluid or jam and rigidify like a solid. The unjammed-to-jammed transition remains poorly understood, however, and structural properties characterizing these phases remain unknown. Using primary human bronchial epithelial cells, we show that the jamming transition in asthma is linked to cell shape, thus establishing in that system a structural criterion for cell jamming. Surprisingly, the collapse of critical scaling predicts a counter-intuitive relationship between jamming, cell shape and cell–cell adhesive stresses that is borne out by direct experimental observations. Cell shape thus provides a rigorous structural signature for classification and investigation of bronchial epithelial layer jamming in asthma, and potentially in any process in disease or development in which epithelial dynamics play a prominent role

A genome-wide survey of CD4+ lymphocyte regulatory genetic variants identifies novel asthma genes

Background: Genome-wide association studies have yet to identify the majority of genetic variants involved in asthma. We hypothesized that expression quantitative trait locus (eQTL) mapping can identify novel asthma genes by enabling prioritization of putative functional variants for association testing. Objective: We evaluated 6,706 cis-acting expression-associated variants (eSNP) identified through a genome-wide eQTL survey of CD4+ lymphocytes for association with asthma. Methods: eSNP were tested for association with asthma in 359 asthma cases and 846 controls from the Childhood Asthma Management Program, with verification using family-based testing. Significant associations were tested for replication in 579 parent-child trios with asthma from Costa Rica. Further functional validation was performed by Formaldehyde Assisted Isolation of Regulatory Elements (FAIRE)-qPCR and Chromatin-Immunoprecipitation (ChIP)-PCR in lung derived epithelial cell lines (Beas-2B and A549) and Jurkat cells, a leukemia cell line derived from T lymphocytes. Results: Cis-acting eSNP demonstrated associations with asthma in both cohorts. We confirmed the previously-reported association of ORMDL3/GSDMB variants with asthma (combined p=2.9 × 108). Reproducible associations were also observed for eSNP in three additional genes: FADS2 (p=0.002), NAGA (p=0.0002), and F13A1 (p=0.0001). We subsequently demonstrated that FADS2 mRNA is increased in CD4+ lymphocytes in asthmatics, and that the associated eSNPs reside within DNA segments with histone modifications that denote open chromatin status and confer enhancer activity. Conclusions: Our results demonstrate the utility of eQTL mapping in the identification of novel asthma genes, and provide evidence for the importance of FADS2, NAGA, and F13A1 in the pathogenesis of asthma

A meta-analysis of genome-wide association studies for serum total IgE in diverse study populations

Background: Immunoglobulin E (IgE) is both a marker and mediator of allergic inflammation. Despite reported differences in serum total IgE levels by race-ethnicity, African American and Latino individuals have not been well represented in genetic studies of total IgE. Objective: To identify the genetic predictors of serum total IgE levels. Methods: We used genome wide association (GWA) data from 4,292 individuals (2,469 African Americans, 1,564 European Americans, and 259 Latinos) in the EVE Asthma Genetics Consortium. Tests for association were performed within each cohort by race-ethnic group (i.e., African American, Latino, and European American) and asthma status. The resulting p-values were meta-analyzed accounting for sample size and direction of effect. Top single nucleotide polymorphism (SNP) associations from the meta-analysis were reassessed in six additional cohorts comprising 5,767 individuals. Results: We identified 10 unique regions where the combined association statistic was associated with total serum IgE levels (P-value <5.0×10−6) and the minor allele frequency was ≥5% in two or more population groups. Variant rs9469220, corresponding to HLA-DQB1, was the most significantly associated SNP with serum total IgE levels when assessed in both the replication cohorts and the discovery and replication sets combined (P-value = 0.007 and 2.45×10−7, respectively). In addition, findings from earlier GWA studies were also validated in the current meta-analysis. Conclusion: This meta-analysis independently identified a variant near HLA-DQB1 as a predictor of total serum IgE in multiple race-ethnic groups. This study also extends and confirms the findings of earlier GWA analyses in African American and Latino individuals

Further replication studies of the EVE Consortium meta-analysis identifies 2 asthma risk loci in European Americans

Background: Genome-wide association studies of asthma have implicated many genetic risk factors, with well-replicated associations at approximately 10 loci that account for only a small proportion of the genetic risk. Objectives—We aimed to identify additional asthma risk loci by performing an extensive replication study of the results from the EVE Consortium meta-analysis. Methods: We selected 3186 SNPs for replication based on the p-values from the EVE Consortium meta-analysis. These SNPs were genotyped in ethnically diverse replication samples from nine different studies, totaling to 7202 cases, 6426 controls, and 507 case-parent trios. Association analyses were conducted within each participating study and the resulting test statistics were combined in a meta-analysis. Results: Two novel associations were replicated in European Americans: rs1061477 in the KLK3 gene on chromosome 19 (combined OR = 1.18; 95% CI 1.10 – 1.25) and rs9570077 (combined OR =1.20 95% CI 1.12–1.29) on chromosome 13q21. We could not replicate any additional associations in the African American or Latino individuals. Conclusions: This extended replication study identified two additional asthma risk loci in populations of European descent. The absence of additional loci for African Americans and Latino individuals highlights the difficulty in replicating associations in admixed populations