Astrophysical significance of the anisotropic kinetic alpha effect

The generation of large scale flows by the anisotropic kinetic alpha (AKA) effect is investigated in simulations with a suitable time-dependent space- and time-periodic anisotropic forcing lacking parity invariance. The forcing pattern moves relative to the fluid, which leads to a breaking of the Galilean invariance as required for the AKA effect to exist. The AKA effect is found to produce a clear large scale flow pattern when the Reynolds number, R, is small as only a few modes are excited in linear theory. In this case the non-vanishing components of the AKA tensor are dynamically independent of the Reynolds number. For larger values of R, many more modes are excited and the components of the AKA tensor are found to decrease rapidly with increasing value of R. However, once there is a magnetic field (imposed and of sufficient strength, or dynamo-generated and saturated) the field begins to suppress the AKA effect, regardless of the value of R. It is argued that the AKA effect is unlikely to be astrophysically significant unless the magnetic field is weak and R is small.Comment: 8 pages, 10 figures, submitted to A&

Simulations of core convection in rotating A-type stars: Differential rotation and overshooting

We present the results of 3--D simulations of core convection within A-type stars of 2 solar masses, at a range of rotation rates. We consider the inner 30% by radius of such stars, thereby encompassing the convective core and some of the surrounding radiative envelope. We utilize our anelastic spherical harmonic (ASH) code, which solves the compressible Navier-Stokes equations in the anelastic approximation, to examine highly nonlinear flows that can span multiple scale heights. The cores of these stars are found to rotate differentially, with central cylindrical regions of strikingly slow rotation achieved in our simulations of stars whose convective Rossby number (R_{oc}) is less than unity. Such differential rotation results from the redistribution of angular momentum by the nonlinear convection that strongly senses the overall rotation of the star. Penetrative convective motions extend into the overlying radiative zone, yielding a prolate shape (aligned with the rotation axis) to the central region in which nearly adiabatic stratification is achieved. This is further surrounded by a region of overshooting motions, the extent of which is greater at the equator than at the poles, yielding an overall spherical shape to the domain experiencing at least some convective mixing. We assess the overshooting achieved as the stability of the radiative exterior is varied, and the weak circulations that result in that exterior. The convective plumes serve to excite gravity waves in the radiative envelope, ranging from localized ripples of many scales to some remarkable global resonances.Comment: 48 pages, 16 figures, some color. Accepted to Astrophys. J. Color figures compressed with appreciable loss of quality; a PDF of the paper with better figures is available at http://lcd-www.colorado.edu/~brownim/core_convectsep24.pd

Turbulent Convection Under the Influence of Rotation: Sustaining a Strong Differential Rotation

The intense turbulence present in the solar convection zone is a major challenge to both theory and simulation as one tries to understand the origins of the striking differential rotation profile with radius and latitude that has been revealed by helioseismology. The differential rotation must be an essential element in the operation of the solar magnetic dynamo and its cycles of activity, yet there are many aspects of the interplay between convection, rotation and magnetic fields that are still unclear. We have here carried out a series of 3--D numerical simulations of turbulent convection within deep spherical shells using our anelastic spherical harmonic (ASH) code on massively parallel supercomputers. These studies of the global dynamics of the solar convection zone concentrate on how the differential rotation and meridional circulation are established. We have analyzed the transport of angular momentum in establishing such differential rotation, and clarified the roles played by Reynolds stresses and the meridional circulation in this process. We have found that the Reynolds stresses are crucial in transporting angular momentum toward the equator. The effects of baroclinicity (thermal wind) have been found to have a modest role in the resulting mean zonal flows. The simulations have produced differential rotation profiles within the bulk of the convection zone that make reasonable contact with ones inferred from helioseismic inversions, namely possessing a fast equator, an angular velocity difference of about 30% from equator to pole, and some constancy along radial lines at mid-latitudes.Comment: 25 pages, 14 very low resolution figures, shortened abstract, published by ApJ. High resolution/complete version can be found at http://lcd-www.colorado.edu/sabrun/index_cv.html then Scientific Publication

Accretion Disks and Dynamos: Toward a Unified Mean Field Theory

Conversion of gravitational energy into radiation in accretion discs and the origin of large scale magnetic fields in astrophysical rotators have often been distinct topics of research. In semi-analytic work on both problems it has been useful to presume large scale symmetries, necessarily resulting in mean field theories. MHD turbulence makes the underlying systems locally asymmetric and nonlinear. Synergy between theory and simulations should aim for the development of practical mean field models that capture essential physics and can be used for observational modeling. Mean field dynamo (MFD) theory and alpha-viscosity accretion theory exemplify such ongoing pursuits. 21st century MFD theory has more nonlinear predictive power compared to 20th century MFD theory, whereas accretion theory is still in a 20th century state. In fact, insights from MFD theory are applicable to accretion theory and the two are artificially separated pieces of what should be a single theory. I discuss pieces of progress that provide clues toward a unified theory. A key concept is that large scale magnetic fields can be sustained via local or global magnetic helicity fluxes or via relaxation of small scale magnetic fluctuations, without the kinetic helicity driver of 20th century textbooks. These concepts may help explain the formation of large scale fields that supply non-local angular momentum transport via coronae and jets in a unified theory of accretion and dynamos. In diagnosing the role of helicities and helicity fluxes in disk simulations, each disk hemisphere should be studied separately to avoid being misled by cancelation that occurs as a result of reflection asymmetry. The fraction of helical field energy in disks is expected to be small compared to the total field in each hemisphere as a result of shear, but can still be essential for large scale dynamo action.Comment: For the Proceedings of the Third International Conference and Advanced School "Turbulent Mixing and Beyond," TMB-2011 held on 21 - 28 August 2011 at the Abdus Salam International Centre for Theoretical Physics, Trieste, http://users.ictp.it/~tmb/index2011.html Italy, To Appear in Physica Scripta (corrected small items to match version in print

Physics of Solar Prominences: II - Magnetic Structure and Dynamics

Observations and models of solar prominences are reviewed. We focus on non-eruptive prominences, and describe recent progress in four areas of prominence research: (1) magnetic structure deduced from observations and models, (2) the dynamics of prominence plasmas (formation and flows), (3) Magneto-hydrodynamic (MHD) waves in prominences and (4) the formation and large-scale patterns of the filament channels in which prominences are located. Finally, several outstanding issues in prominence research are discussed, along with observations and models required to resolve them.Comment: 75 pages, 31 pictures, review pape

Immune Biomarkers in Metastatic Castration-resistant Prostate Cancer.

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease in which molecular stratification is needed to improve clinical outcomes. The identification of predictive biomarkers can have a major impact on the care of these patients, but the availability of metastatic tissue samples for research in this setting is limited. OBJECTIVE: To study the prevalence of immune biomarkers of potential clinical utility to immunotherapy in mCRPC and to determine their association with overall survival (OS). DESIGN, SETTING, AND PARTICIPANTS: From 100 patients, mCRPC biopsies were assayed by whole exome sequencing, targeted next-generation sequencing, RNA sequencing, tumor mutational burden, T-cell-inflamed gene expression profile (TcellinfGEP) score (Nanostring), and immunohistochemistry for programmed cell death 1 ligand 1 (PD-L1), ataxia-telangiectasia mutated (ATM), phosphatase and tensin homolog (PTEN), SRY homology box 2 (SOX2), and the presence of neuroendocrine features. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The phi coefficient determined correlations between biomarkers of interest. OS was assessed using Kaplan-Meier curves and adjusted hazard ratios (aHRs) from Cox regression. RESULTS AND LIMITATIONS: PD-L1 and SOX2 protein expression was detected by immunohistochemistry (combined positive score ≥1 and >5% cells, respectively) in 24 (33%) and 27 (27%) mCRPC biopsies, respectively; 23 (26%) mCRPC biopsies had high TcellinfGEP scores (>-0.318). PD-L1 protein expression and TcellinfGEP scores were positively correlated (phi 0.63 [0.45; 0.76]). PD-L1 protein expression (aHR: 1.90 [1.05; 3.45]), high TcellinfGEP score (aHR: 1.86 [1.04; 3.31]), and SOX2 expression (aHR: 2.09 [1.20; 3.64]) were associated with worse OS. CONCLUSIONS: PD-L1, TcellinfGEP score, and SOX2 are prognostic of outcome from the mCRPC setting. If validated, predictive biomarker studies incorporating survival endpoints need to take these findings into consideration. PATIENT SUMMARY: This study presents an analysis of immune biomarkers in biopsies from patients with metastatic prostate cancer. We describe tumor alterations that predict prognosis that can impact future studies

HER3 Is an Actionable Target in Advanced Prostate Cancer.

It has been recognized for decades that ERBB signaling is important in prostate cancer, but targeting ERBB receptors as a therapeutic strategy for prostate cancer has been ineffective clinically. However, we show here that membranous HER3 protein is commonly highly expressed in lethal prostate cancer, associating with reduced time to castration resistance (CR) and survival. Multiplex immunofluorescence indicated that the HER3 ligand NRG1 is detectable primarily in tumor-infiltrating myelomonocytic cells in human prostate cancer; this observation was confirmed using single-cell RNA sequencing of human prostate cancer biopsies and murine transgenic prostate cancer models. In castration-resistant prostate cancer (CRPC) patient-derived xenograft organoids with high HER3 expression as well as mouse prostate cancer organoids, recombinant NRG1 enhanced proliferation and survival. Supernatant from murine bone marrow-derived macrophages and myeloid-derived suppressor cells promoted murine prostate cancer organoid growth in vitro, which could be reversed by a neutralizing anti-NRG1 antibody and ERBB inhibition. Targeting HER3, especially with the HER3-directed antibody-drug conjugate U3-1402, exhibited antitumor activity against HER3-expressing prostate cancer. Overall, these data indicate that HER3 is commonly overexpressed in lethal prostate cancer and can be activated by NRG1 secreted by myelomonocytic cells in the tumor microenvironment, supporting HER3-targeted therapeutic strategies for treating HER3-expressing advanced CRPC. SIGNIFICANCE: HER3 is an actionable target in prostate cancer, especially with anti-HER3 immunoconjugates, and targeting HER3 warrants clinical evaluation in prospective trials