Halo-Independent Direct Detection Analyses Without Mass Assumptions

Results from direct detection experiments are typically interpreted by employing an assumption about the dark matter velocity distribution, with results presented in the $m_\chi-\sigma_n$ plane. Recently methods which are independent of the DM halo velocity distribution have been developed which present results in the $v_{min}-\tilde{g}$ plane, but these in turn require an assumption on the dark matter mass. Here we present an extension of these halo-independent methods for dark matter direct detection which does not require a fiducial choice of the dark matter mass. With a change of variables from $v_{min}$ to nuclear recoil momentum ($p_R$), the full halo-independent content of an experimental result for any dark matter mass can be condensed into a single plot as a function of a new halo integral variable, which we call $\tilde{h}(p_R)$. The entire family of conventional halo-independent $\tilde{g}(v_{min})$ plots for all DM masses are directly found from the single $\tilde{h}(p_R)$ plot through a simple rescaling of axes. By considering results in $\tilde{h}(p_R)$ space, one can determine if two experiments are inconsistent for all masses and all physically possible halos, or for what range of dark matter masses the results are inconsistent for all halos, without the necessity of multiple $\tilde{g}(v_{min})$ plots for different DM masses. We conduct a sample analysis comparing the CDMS II Si events to the null results from LUX, XENON10, and SuperCDMS using our method and discuss how the mass-independent limits can be strengthened by imposing the physically reasonable requirement of a finite halo escape velocity.Comment: 23 pages, 8 figures. v2: footnote and references adde

Characterizing glucocorticoid receptor in metastatic castration resistant prostate cancer

The purpose of this paper is to characterize the glucocorticoid receptor (GR) signaling and relevance in the context of enzalutamide resistant prostate cancer cells. Enzalutamide is a drug that functions to dampen androgen receptor (AR) signaling, thus inhibiting cancer dependency on the receptor protein. Although the application of the drug reduces AR signaling in these cancer cells, an alternate pathway involving GR signaling may be upregulated as a compensatory bypass mechanism. Therefore, it possible that GR assumes the role of AR and facilitates tumor growth by promoting the expression of genes regulated by AR. To analyze how GR operates, we analyzed GR signaling in enzalutamide resistant metastatic prostate cancer cell lines. We assessed protein levels of AR and GR as well as mRNA expression of various AR targets. Our results illustrate the expected downregulation of AR and upregulation of GR in enzalutamide resistant cells. Furthermore, some canonical AR targets like prostate specific antigen (PSA), Prostate Specific Membrane Antigen (PSMA) and Prostatic Acid Phosphatase (PAP) were inhibited by a novel GR inhibitor. Thus, this GR inhibitor could be used in combination with enzalutamide and create a more potent AR signaling blockade. Prostate cancer is a very problematic disease in men and becomes especially challenging to treat during the metastatic stage as they are non-sensitive to anti-androgens. The significance of understanding how GR functions, as well as the potential benefit of blocking GR signaling, may provide insight into novel drugs and agents that could specifically target these pathways, control and mitigate cancer growth, and prolong the lives of patients

Where's the Doughnut? LBV bubbles and Aspherical Fast Winds

In this paper we address the issue of the origin of LBV bipolar bubbles. Previous studies have explained the shapes of LBV nebulae, such as $\eta$ Car, by invoking the interaction of an isotropic fast wind with a previously deposited, slow aspherical wind (a ``slow torus''). In this paper we focus on the opposite scenario where an aspherical fast wind expands into a previously deposited isotropic slow wind. Using high resolution hydrodynamic simulations, which include the effects of radiative cooling, we have completed a series of numerical experiments to test if and how aspherical fast winds effect wind blown bubble morphologies. Our experiments explore a variety of models for the latitudinal variations of fast wind flow parameters. The simulations demonstrate that aspherical fast winds can produce strongly bipolar outflows. In addition the properties of outflows recover some important aspects of LBV bubbles which the previous "slow torus" models can not.Comment: 23 pages, 6 figures, to appear the Astrophysical Journa

Reproducibility of serum IgE, Ara h2 skin prick testing and fraction of exhaled nitric oxide for predicting clinical peanut allergy in children

Background: Ara h2 sIgE serum levels improve the diagnostic accuracy for predicting peanut allergy, but the use of Ara h2 purified protein as a skin prick test (SPT), has not been substantially evaluated. The fraction of exhaled nitric oxide (FeNO) shows promise as a novel biomarker of peanut allergy. Reproducibility of these measures has not been determined. The aim was to assess the accuracy and reproducibility (over a time-period of at least 12 months) of SPT to Ara h2 in comparison with four predictors of clinical peanut allergy (Peanut SPT, Ara h2 specific Immunoglobulin E (sIgE), Peanut sIgE and FeNO). Methods: Twenty-seven children were recruited in a follow-up of a prospective cohort of fifty-six children at least 12 months after an open-labelled peanut food challenge. Their repeat assessment involved a questionnaire, SPT to peanut and Ara h2 purified protein, FeNO and sIgE to peanut and Ara h2 measurements. Results: Ara h2 SPT was no worse in accuracy when compared with peanut SPT, FeNO, Ara h2 sIgE and peanut sIgE (AUC 0.908 compared with 0.887, 0.889, 0.935 and 0.804 respectively) for predicting allergic reaction at previous food challenge. SPT for peanut and Ara h2 demonstrated limited reproducibility (ICC = 0.51 and 0.44); while FeNO demonstrated good reproducibility (ICC = 0.73) and sIgE for peanut and Ara h2 were highly reproducible (ICC = 0.81 and 0.85). Conclusions: In this population, Ara h2 SPT was no worse in accuracy when compared with current testing for the evaluation of clinical peanut allergy, but had—like peanut SPT—poor reproducibility. FeNO, peanut sIgE and Ara h2 sIgE were consistently reproducible despite an interval of at least 12 months between the repeated measurements

Very Late Thermal Pulses Influenced by Accretion in Planetary Nebulae

We consider the possibility that a mass of ~10^{-5}-10^{-3} Msun flows back from the dense shell of planetary nebulae and is accreted by the central star during the planetary nebula phase. This backflowing mass is expected to have a significant specific angular momentum even in (rare) spherical planetary nebulae, such that a transient accretion disk might be formed. This mass might influence the occurrence and properties of a very late thermal pulse (VLTP), and might even trigger it. For example, the rapidly rotating outer layer, and the disk if still exist, might lead to axisymmetrical mass ejection by the VLTP. Unstable burning of accreted hydrogen might result in a mild flash of the hydrogen shell, also accompanied by axisymmetrical ejection.Comment: Submitted to New Astronom

Hydrodynamical Models of Outflow Collimation in YSOs

We explore the physics of time-dependent hydrodynamic collimation of jets from Young Stellar Objects (YSOs). Using parameters appropriate to YSOs we have carried out high resolution hydrodynamic simulations modeling the interaction of a central wind with an environment characterized by a moderate opening angle toroidal density distribution. The results show that the the wind/environment interaction produces strongly collimated supersonic jets. The jet is composed of shocked wind gas. Using analytical models of wind blown bubble evolution we show that the scenario studied here should be applicable to YSOs and can, in principle, initiate collimation on the correct scales (R ~ 100 AU). The simulations reveal a number of time-dependent non-linear features not anticipated in previous analytical studies including: a prolate wind shock; a chimney of cold swept-up ambient material dragged into the bubble cavity; a plug of dense material between the jet and bow shocks. We find that the collimation of the jet occurs through both de Laval nozzles and focusing of the wind via the prolate wind shock. Using an analytical model for shock focusing we demonstrate that a prolate wind shock can, by itself, produce highly collimated supersonic jets.Comment: Accepted by ApJ, 31 pages with 12 figures (3 JPEG's) now included, using aasms.sty, Also available in postscript via a gzipped tar file at ftp://s1.msi.umn.edu/pub/afrank/SFIC1/SFIC.tar.g

Robotic-Assisted Percutaneous Coronary Intervention Through Transradial Approach: Experience in 4 Patients with Complex Lesions

Robotic-assisted percutaneous coronary intervention can reduce the exposure of interventional cardiologists to radiation and minimize the risk of occupational orthopedic injuries from wearing heavy protective aprons. The PRECISE (Percutaneous Robotically-Enhanced Coronary Intervention) study showed the efficacy and safety of robotic-assisted procedures for relatively low-risk lesions in single coronary arteries. Several reports have described robotic-assisted treatment of complex high-risk lesions, mostly through the transfemoral approach. We report 4 cases of patients in whom we used the transradial approach to treat complex lesions in the left anterior descending coronary artery with bifurcation balloon angioplasty reconstruction (2 cases), in the ostium of the first diagonal branch, and in the right coronary artery

MHD Stellar and Disk Winds: Application to Planetary Nebulae

MHD winds can emanate from both stars and surrounding accretion disks. It is of interest to know how much wind power is available and which (if either) of the two rotators dominates that power. We investigate this in the context of multi-polar planetary nebulae (PNe) and proto-planetary nebulae (PPNe), for which recent observations have revealed the need for a wind power source in excess of that available from radiation driving, and a possible need for magnetic shaping. We calculate the MHD wind power from a coupled disk and star, where the former results from binary disruption. The resulting wind powers depend only on the accretion rate and stellar properties. We find that if the stellar envelope were initially slowly rotating, the disk wind would dominate throughout the evolution. If the envelope of the star were rapidly rotating, the stellar wind could initially be of comparable power to the disk wind until the stellar wind carries away the star's angular momentum. Since an initially rapidly rotating star can have its spin and magnetic axes misaligned to the disk, multi-polar outflows can result from this disk wind system. For times greater than a spin-down time, the post-AGB stellar wind is slaved to the disk for both slow and rapid initial spin cases and the disk wind luminosity dominates. We find a reasonably large parameter space where a hybrid star+disk MHD driven wind is plausible and where both or either can account for PPNe and PNe powers. We also speculate on the morphologies which may emerge from the coupled system. The coupled winds might help explain the shapes of a number of remarkable multi-shell or multi-polar nebulae. Magnetic activity such as X-ray flares may be associated with the both central star and the disk and would be a valuable diagnostic for the dynamical role of MHD processes in PNe.Comment: ApJ accepted version, incorporating some important revisions. 25 Pages, LaTex, + 5 fig

High-throughput screen identifies non inflammatory small molecule inducers of trained immunity

Trained immunity is characterized by epigenetic and metabolic reprogramming in response to specific stimuli. This rewiring can result in increased cytokine and effector responses to pathogenic challenges, providing nonspecific protection against disease. It may also improve immune responses to established immunotherapeutics and vaccines. Despite its promise for next-generation therapeutic design, most current understanding and experimentation is conducted with complex and heterogeneous biologically derived molecules, such as β-glucan or the Bacillus Calmette-Guérin (BCG) vaccine. This limited collection of training compounds also limits the study of the genes most involved in training responses as each molecule has both training and nontraining effects. Small molecules with tunable pharmacokinetics and delivery modalities would both assist in the study of trained immunity and its future applications. To identify small molecule inducers of trained immunity, we screened a library of 2,000 drugs and drug-like compounds. Identification of well-defined compounds can improve our understanding of innate immune memory and broaden the scope of its clinical applications. We identified over two dozen small molecules in several chemical classes that induce a training phenotype in the absence of initial immune activation—a current limitation of reported inducers of training. A surprising result was the identification of glucocorticoids, traditionally considered immunosuppressive, providing an unprecedented link between glucocorticoids and trained innate immunity. We chose seven of these top candidates to characterize and establish training activity in vivo. In this work, we expand the number of compounds known to induce trained immunity, creating alternative avenues for studying and applying innate immune training