Comparing Simulations of AGN Feedback

We perform adaptive mesh refinement (AMR) and smoothed particle hydrodynamics (SPH) cosmological zoom simulations of a region around a forming galaxy cluster, comparing the ability of the methods to handle successively more complex baryonic physics. In the simplest, non-radiative case, the two methods are in good agreement with each other, but the SPH simulations generate central cores with slightly lower entropies and virial shocks at slightly larger radii, consistent with what has been seen in previous studies. The inclusion of radiative cooling, star formation, and stellar feedback leads to much larger differences between the two methods. Most dramatically, at z=5, rapid cooling in the AMR case moves the accretion shock well within the virial radius, while this shock remains near the virial radius in the SPH case, due to excess heating, coupled with poorer capturing of the shock width. On the other hand, the addition of feedback from active galactic nuclei (AGN) to the simulations results in much better agreement between the methods. In this case both simulations display halo gas entropies of 100 keV cm^2, similar decrements in the star-formation rate, and a drop in the halo baryon content of roughly 30%. This is consistent with AGN growth being self-regulated, regardless of the numerical method. However, the simulations with AGN feedback continue to differ in aspects that are not self-regulated, such that in SPH a larger volume of gas is impacted by feedback, and the cluster still has a lower entropy central core.Comment: 22 pages, 20 figures, 3 tables, Accepted to ApJ, comments welcom

Performance engineering for microservices and serverless applications: the RADON approach

Microservices and serverless are becoming integral parts of mod-ern cloud-based applications. Tailored performance engineering isneeded for assuring that the applications meet their requirementsfor quality attributes such as timeliness, resource efficiency, andelasticity. A novel DevOps-based framework for developing mi-croservices and serverless applications is being developed in theRADON project. RADON contributes to performance engineeringby including novel approaches for modeling, deployment optimiza-tion, testing, and runtime management. This paper summarizes thecontents of our tutorial presented at the 11th ACM/SPEC Interna-tional Conference on Performance Engineering (ICPE)

Interleukin 21 Is a T Helper (Th) Cell 2 Cytokine that Specifically Inhibits the Differentiation of Naive Th Cells into Interferon γ–producing Th1 Cells

The cytokine potential of developing T helper (Th) cells is directly shaped both positively and negatively by the cytokines expressed by the effector Th cell subsets. Here we find that the recently identified cytokine, interleukin (IL)-21, is preferentially expressed by Th2 cells when compared with Th1 cells generated in vitro and in vivo. Exposure of naive Th precursors to IL-21 inhibits interferon (IFN)-γ production from developing Th1 cells. The repression of IFN-γ production is specific in that the expression of other Th1 and Th2 cytokines is unaffected. IL-21 decreases the IL-12 responsiveness of developing Th cells by specifically reducing both signal transducer and activator of transcription 4 protein and mRNA expression. These results suggest that Th2 cell-derived IL-21 regulates the development of IFN-γ–producing Th1 cells which could serve to amplify a Th2 response

RADON: Rational decomposition and orchestration for serverless computing

Emerging serverless computing technologies, such as function as a service (FaaS), enable developers to virtualize the internal logic of an application, simplifying the management of cloud-native services and allowing cost savings through billing and scaling at the level of individual functions. Serverless computing is therefore rapidly shifting the attention of software vendors to the challenge of developing cloud applications deployable on FaaS platforms. In this vision paper, we present the research agenda of the RADON project (http://radon-h2020.eu), which aims to develop a model-driven DevOps framework for creating and managing applications based on serverless computing. RADON applications will consist of fine-grained and independent microservices that can efficiently and optimally exploit FaaS and container technologies. Our methodology strives to tackle complexity in designing such applications, including the solution of optimal decomposition, the reuse of serverless functions as well as the abstraction and actuation of event processing chains, while avoiding cloud vendor lock-in through models

Invasive Mold Infections Following Hurricane Harvey-Houston, Texas

BACKGROUND: Characterizing invasive mold infection (IMI) epidemiology in the context of large flooding events is important for public health planning and clinical decision making. METHODS: We assessed IMI incidence (per 10 000 healthcare encounters) 1 year before and after Hurricane Harvey at 4 hospitals in Houston, Texas. Potential IMI cases were assigned as proven or probable cases using established definitions, and surveillance cases using a novel definition. We used rate ratios to describe IMI incidence and multivariable logistic regression to examine patient characteristics associated with IMI case status. RESULTS: IMI incidence was significantly higher posthurricane (3.69 cases) than prehurricane (2.50 cases) (rate ratio, 1.48 [95% confidence interval, 1.10-2.00]), largely driven by surveillance IMI cases. CONCLUSIONS: IMI incidence likely increased following Hurricane Harvey and outcomes for IMI patients were severe. Patient and clinician education on IMI prevention and identification is warranted, particularly as the frequency of extreme weather events increases due to climate change

Comparing simulations of AGN feedback

We perform adaptive mesh refinement (AMR) and smoothed particle hydrodynamics (SPH) cosmological zoom simulations of a region around a forming galaxy cluster, comparing the ability of the methods to handle successively more complex baryonic physics. In the simplest, non-radiative case, the two methods are in good agreement with each other, but the SPH simulations generate central cores with slightly lower entropies and virial shocks at slightly larger radii, consistent with what has been seen in previous studies. The inclusion of radiative cooling, star formation, and stellar feedback leads to much larger differences between the two methods. Most dramatically, at z=5, rapid cooling in the AMR case moves the accretion shock to well within the virial radius, while this shock remains near the virial radius in the SPH case, due to excess heating, coupled with poorer capturing of the shock width. On the other hand, the addition of feedback from active galactic nuclei (AGNs) to the simulations results in much better agreement between the methods. For our AGN model, both simulations display halo gas entropies of 100 keV cm2, similar decrements in the star formation rate, and a drop in the halo baryon content of roughly 30%. This is consistent with the AGN growth being self-regulated, regardless of the numerical method. However, the simulations with AGN feedback continue to differ in aspects that are not self-regulated, such that in SPH a larger volume of gas is impacted by feedback, and the cluster still has a lower entropy central core.Publisher PDFPeer reviewe

Spectroscopic Measurements in the Shock Relaxation Region of a Hypervelocity Mach Reflection

We examine the spatial temperature profile in the non-equilibrium relaxation region behind a stationary shock wave. The normal shock wave is established through a Mach reflection configuration from an opposing wedge arrangement for a hypervelocity air Mach 7.42 freestream. Schlieren images confirm that the shock configuration is steady and the location is repeatable. Emission spectroscopy is used to identify dissociated species and to obtain vibrational temperature measurements using the NO and OH A-X band sequences. Temperature measurements are presented at selected locations behind the normal shock. LIFBASE is used as the simulation spectrum software for OH temperature-fitting, however the need to access higher vibrational and rotational levels for NO leads to the use of an in-house developed algorithm. For NO, results demonstrate the contribution of higher vibrational and rotational levels to the spectra at the conditions of this study. Very good agreement is achieved between the experimentally measured NO vibrational temperatures and calculations performed using a state-resolved, one-dimensional forced harmonic oscillator thermochemical model

IL-10 transcription is negatively regulated by BAF180, a component of the SWI/SNF chromatin remodeling enzyme

<p>Abstract</p> <p>Background</p> <p>SWI/SNF chromatin remodeling enzymes play a critical role in the development of T helper lymphocytes, including Th2 cells, and directly program chromatin structure at Th2 cytokine genes. Different versions of SWI/SNF complexes, including BAF and PBAF, have been described based on unique subunit composition. However, the relative role of BAF and PBAF in Th cell function and cytokine expression has not been reported.</p> <p>Results</p> <p>Here we examine the role of the PBAF SWI/SNF complex in Th cell development and gene expression using mice deficient for a PBAF-specific component, BAF180. We find that T cell development in the thymus and lymphoid periphery is largely normal when the BAF180 gene is deleted late in thymic development. However, BAF180-deficient Th2 cells express high levels of the immunoregulatory cytokine IL-10. BAF180 binds directly to regulatory elements in the Il-10 locus but is replaced by BAF250 BAF complexes in the absence of BAF180, resulting in increased histone acetylation and CBP recruitment to the IL-10 locus.</p> <p>Conclusions</p> <p>These results demonstrate that BAF180 is a repressor of IL-10 transcription in Th2 cells and suggest that the differential recruitment of different SWI/SNF subtypes can have direct consequences on chromatin structure and gene transcription.</p

Interleukin-21 Is Required for the Development of Type 1 Diabetes in NOD Mice

OBJECTIVE: Interleukin (IL)-21 is a type 1 cytokine that has been implicated in the pathogenesis of type 1 diabetes via the unique biology of the nonobese diabetic (NOD) mouse strain. The aim of this study was to investigate a causal role for IL-21 in type 1 diabetes. RESEARCH DESIGN AND METHODS: We generated IL-21R–deficient NOD mice and C57Bl/6 mice expressing IL-21 in pancreatic β-cells, allowing the determination of the role of insufficient and excessive IL-21 signaling in type 1 diabetes. RESULTS: Deficiency in IL-21R expression renders NOD mice resistant to insulitis, production of insulin autoantibodies, and onset of type 1 diabetes. The lymphoid compartment in IL-21R−/− NOD is normal and does not contain an increased regulatory T-cell fraction or diminished effector cytokine responses. However, we observed a clear defect in autoreactive effector T-cells in IL-21R−/− NOD by transfer experiments. Conversely, overexpression of IL-21 in pancreatic β-cells induced inflammatory cytokine and chemokines, including IL-17A, IL17F, IFN-γ, monocyte chemoattractant protein (MCP)-1, MCP-2, and interferon-inducible protein-10 in the pancreas. The ensuing leukocytic infiltration in the islets resulted in destruction of β-cells and spontaneous type 1 diabetes in the normally diabetes-resistant C57Bl/6 and NOD × C57Bl/6 backgrounds. CONCLUSIONS: This work provides demonstration of the essential prodiabetogenic activities of IL-21 on diverse genetic backgrounds (NOD and C57BL/6) and indicates that IL-21 blockade could be a promising strategy for interventions in human type 1 diabetes

T follicular helper cells differentiate from Th2 cells in response to helminth antigens

The relationship of T follicular helper (TFH) cells to other T helper (Th) subsets is controversial. We find that after helminth infection, or immunization with helminth antigens, reactive lymphoid organs of 4get IL-4/GFP reporter mice contain populations of IL-4/GFP-expressing CD4+ T cells that display the TFH markers CXCR5, PD-1, and ICOS. These TFH cells express the canonical TFH markers BCL6 and IL-21, but also GATA3, the master regulator of Th2 cell differentiation. Consistent with a relationship between Th2 and TFH cells, IL-4 protein production, reported by expression of huCD2 in IL-4 dual reporter (4get/KN2) mice, was a robust marker of TFH cells in LNs responding to helminth antigens. Moreover, the majority of huCD2/IL-4–producing Th cells were found within B cell follicles, consistent with their definition as TFH cells. TFH cell development after immunization failed to occur in mice lacking B cells or CD154. The relationship of TFH cells to the Th2 lineage was confirmed when TFH cells were found to develop from CXCR5− PD-1− IL-4/GFP+ CD4+ T cells after their transfer into naive mice and antigen challenge in vivo