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In this work, we compare large scale structure observables for stellar mass selected samples at $z=0$, as predicted by two galaxy models, the hydrodynamical simulation IllustrisTNG and the Santa-Cruz semi-analytic model (SC-SAM). Although both models have been independently calibrated to match observations, rather than each other, we find good agreement between the two models for two-point clustering and galaxy assembly bias signatures. The models also show a qualitatively similar response of occupancy and clustering to secondary halo paramaters other than mass, such as formation history and concentration, although with some quantitative differences. Thus, our results demonstrate that the galaxy-halo relationships in SC-SAM and TNG are quite similar to first order. However, we also find areas in which the models differ. For example, we note a strong correlation between halo gas content and environment in TNG, which is lacking in the SC-SAM, as well as differences in the occupancy predictions for low-mass haloes. Moreover, we show that higher-order statistics, such as cumulants of the density field, help to accurately describe the galaxy distribution and discriminate between models that show degenerate behavior for two-point statistics. Our results suggest that SAMs are a promising cost-effective and intuitive method for generating mock catalogues for next generation cosmological surveys., Comment: 20 pages, 12 plots, 2 appendices, submitted to MNRAS for review

Through a longitudinal ethnographic study of new recruits into an English police service we explain how different ‘identity work orientations’ (i.e. legitimacy, authenticity and competence seeking)...

Characterizing the mechanical behavior of living tissue presents an interesting challenge because the elasticity varies by eight orders of magnitude, from 50Pa to 5GPa. In the present work, a non-destructive optical fiber photoelastic polarimetry system is used to analyze the mechanical properties of resected samples from porcine liver, kidney, and pancreas. Using a quasi-linear viscoelastic fit, the elastic modulus values of the different organ systems are determined. They are in agreement with previous work. In addition, a histological assessment of compressed and uncompressed tissues confirms that the tissue is not damaged during testing.

Background Urinary tract infections (UTIs) are common in outpatient settings. Evidence-based recommendations suggest empiric treatment of healthy female patients presenting with two or more classic symptoms of UTIs, rather than urine testing. It is unknown how often urine testing is ordered in the community, and if there are opportunities to reduce the number of unnecessary urine tests. This study aims to describe urine testing practices for uncomplicated UTIs in outpatient settings. Methods Using the 2009–2013 Truven Health Analytics MarketScan database, we extracted outpatient claims data for premenopausal, nonpregnant women aged 18–44 years who met criteria for an uncomplicated UTI or cystitis with antibiotic prescribed ±5 days of diagnosis. Women with recent infections, hospitalizations, urologic abnormalities, diabetes, chronic kidney disease, immune compromise, or other complicating factors were excluded. Urine laboratory tests coded within ±5 days of index UTI were identified. To explore variation in urine testing practices, we compared frequencies of urine testing types according to patient age, region, provider type, testing location, residence in a metropolitan statistical area (MSA), and office visit using Chi-square tests. Results Of 669,892 eligible patients with an uncomplicated UTI, 584,863 (87%) received at least one urine test. Of the patients who received at least one test, 285,639 (49%) patients received both a urinalysis (UA) and culture, 247,740 (42%) received a UA only, and 51,484 (9%) received culture only. Significant variation in testing was observed by patient age, region, provider type, testing location, and office visit (Table 1). Patients in the Northeast and in urban locations more frequently received both a UA and culture. Patients who received both UA and culture were more likely to have been seen by an OB/GYN, whereas patients treated empirically without testing were more likely to have been seen by emergency physicians. Conclusion In contrast to evidence-based recommendations, the vast majority of patients with uncomplicated UTI received at least one urine test. We observed variation in urine testing practices, which suggests that diagnostic testing stewardship opportunities exist for outpatients with UTIs. Disclosures All authors: No reported disclosures.

Tissue stiffness has emerged as an important regulator in the maintenance of normal cellular processes. In general, solid tumors are known to be much stiffer than normal tissue, with increased extracellular matrix (ECM) density being indicative of a higher risk for many cancers, including those of the breast. Over the course of breast cancer progression, the ECM becomes increasingly stiffer, a phenomenon which is known to be a driver of malignancy. In a 3D culture system using self-assembling peptide (SAP) gels, we grew MCF10A acini under a dynamic range of stiffness environments (140-5800 Pa). Under normal breast tissue elasticity, mammary epithelial cells form rounded, polarized acini with cleared lumens. However, in tumor-like stiffnesses, the same cells form non-polarized, collapsed structures that invade into the gel. To investigate the specific genes and pathways affected by stiffness, we have conducted tandem mass spectrometry to identify protein expression changes in MCF10A cells grown on SAP gels of increasing stiffness. Interestingly, the resulting analysis showed that cells grown on higher stiffnesses exhibit greater variation in protein expression. These divergent force-regulated molecular pathways are involved in a variety of cellular functions, including cell adhesion and migration, metabolism, and the immune response, among others. This study underscores the significance of mechanical forces exerted by the ECM, and signifies the first large-scale proteomic screen carried out to analyze heterogeneous cellular responses to changing stiffness environments. Citation Format: Sonya Liu, Russell Bainer, Yoshihiro Yui, Colin Flinders, Parag Mallick, Valerie Weaver, Shannon Mumenthaler. Characterization of diverging molecular and phenotypic responses under changing extracellular matrix stiffness in MCF10A cells. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr A23.

Introduction: Metastasis is responsible for over 90% of cancer related mortality; however, somatic mutations unique to the metastatic phenotype have yet to be identified. This raises the possibility that the metastatic phenotype is the result of a transcriptional profile adopted by cells of the primary tumor enabling them to spread to distal regions of the body. The tumor microenvironment (TME) is capable of influencing gene expression and cellular behavior. Hypoxia is a component of the TME that arises due to improper vascular architecture, which leads to reduced oxygen delivery to tissues and correlates with poor survival outcome. Stabilization of the transcription factor HIF-1α during hypoxia induces the expression of genes involved in metastasis through direct activation or through the alteration of the epigenome. However, upon re-oxygenation, HIF-1α is degraded and can no longer induce expression of hypoxic responsive genes. During metastasis, cells that have adopted hypoxia induced metastatic behavior such as increased motility and invasiveness must transit through regions of normoxia on their way to metastatic colonization. Hypothesis: As hypoxic cells migrate away from regions of low oxygen toward oxygen rich environments (e.g. venous blood) genes induced by hypoxia would be expected to return to basal levels of expression. Those genes whose expression does not return to levels associated with normoxia, but instead remain elevated following re-oxygenation may be crucial for maintaining the hypoxia induced metastatic phenotype. Experimental Design: To study the stability of hypoxia induced gene expression alterations following re-oxygenation, colon cancer cell lines were grown under hypoxic conditions (1% O2) for up to 3 weeks and then transitioned back to normoxic conditions. Gene expression changes were assessed during hypoxia adaptation and for 3 additional weeks following re-oxygenation. Results: The continued expression of hypoxia induced genes following re-oxygenation varied greatly among those tested. Gene transcription associated with epithelial-to-mesenchymal transition (EMT) such as VIM and ZEB1 were induced by 3 weeks of hypoxic conditioning and remained elevated following their return to normoxic culturing conditions. However, in contrast, hypoxia induced genes involved in the Warburg effect such as PDK1 were induced during hypoxia, yet quickly returned to at or below basal levels following re-oxygenation. Conclusion: Continued expression of hypoxia induced genes following re-oxygenation varies from gene to gene and from pathway to pathway. There appears to be some consistency in expression of genes following re-oxygenation that are involved in migration and invasion such as ZEB1. These results suggest that certain pathways such as EMT may be vital for the maintenance of the hypoxia induced metastatic phenotype as these cells transit from regions of low oxygen to regions of higher or normal oxygen levels. Citation Format: Colin Flinders, Sonya Liu, Shannon Mumenthaler. Stability of hypoxia induced expression of colon cancer metastasis-associated genes. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr C08.

T1D is a tissue specific and T cell–mediated autoimmune disease characterized by the inflammation of pancreatic islets, namely insulitis, resulting in selective destruction of insulin-producing beta islet cells and development of overt diabetes (Atkinson & Leiter, 1999, Bach, 1994, Mathis et al., 2001, McDevitt, 2001, Nepom & Kwok, 1998, Quinn et al., 2001). The onset of T1D is preceded by at least two main inflammatory stages during insulitis development (Bach, 1994, Robles et al., 2003). In the first stage, termed peri-insulitis, a mixed population of leukocytes, including macrophages, dendritic cells, and T cells, migrate from draining lymph nodes to the peripheral space to the islets. In the second stage, the leukocytes further migrate and infiltrate into the islets, resulting in invasive insulitis. Overt T1D will develop when the majority of insulin-producing  cells in the islets are destroyed by the invading leukocytes and insufficient insulin is produced to control blood glucose levels in the body. Among leukocytes that infiltrate the islets, the autoantigenspecific diabetogenic T cells play a critical role in development of T1D. Recruitment or homing of these diabetogenic T cells into the islets is a critical component of insulitis leading to T1D. Thus inhibition of their homing to the islets would prevent the development of insulitis and T1D. Consequently, it is necessary to understand the homing or trafficking behavior of diabetogenic T cells during the formation of peri-insulitis and invasive insulitis. The knowledge gained from studies addressing those questions is imperative to the development of early diagnosis methods and immune modulatory approaches to treat T1D. Due to the low number and frequency of T cells specific for an autoantigenic peptide, it has been difficult to identify and trace autoantigen-specific T cells in animals. We have previously addressed this problem by generating novel MHC class II tetramers that can stain T cells specific for a self peptide recognized presented by the MHC class II molecules such as the I-Ag7 in NOD mice (Liu et al., 2000, Chen et al., 2003, You et al., 2003). Using this approach, we have been able to successfully identify and trace autoantigen-specific T cells, such as the CD4+ BDC2.5 (BDC) T cells. The tissue localization of various T cell populations at any given time point can be identified using techniques such as flow cytometry and immunofluorescence. However, these methods involve an invasive approach requiring tissue removal from animals, and therefore only provide terminal data. As such, these