Scalability of Hydrodynamic Simulations

Many hydrodynamic processes can be studied in a way that is scalable over a vastly relevant physical parameter space. We systematically examine this scalability, which has so far only briefly discussed in astrophysical literature. We show how the scalability is limited by various constraints imposed by physical processes and initial conditions. Using supernova remnants in different environments and evolutionary phases as application examples, we demonstrate the use of the scaling as a powerful tool to explore the interdependence among relevant parameters, based on a minimum set of simulations. In particular, we devise a scaling scheme that can be used to adaptively generate numerous seed remnants and plant them into 3D hydrodynamic simulations of the supernova-dominated interstellar medium.Comment: 12 pages, 1 figure, submitted to MNRAS; comments are welcom

The Nucleosynthetic Imprint of 15-40 Solar Mass Primordial Supernovae on Metal-Poor Stars

The inclusion of rotationally-induced mixing in stellar evolution can alter the structure and composition of presupernova stars. We survey the effects of progenitor rotation on nucleosynthetic yields in Population III and II supernovae using the new adaptive mesh refinement (AMR) code CASTRO. We examine spherical explosions in 15, 25 and 40 solar mass stars at Z = 0 and 10^-4 solar metallicity with three explosion energies and two rotation rates. Rotation in the Z = 0 models resulted in primary nitrogen production and a stronger hydrogen burning shell which led all models to die as red supergiants. On the other hand, the Z=10^-4 solar metallicity models that included rotation ended their lives as compact blue stars. Because of their extended structure, the hydrodynamics favors more mixing and less fallback in the metal free stars than the Z = 10^-4 models. As expected, higher energy explosions produce more enrichment and less fallback than do lower energy explosions, and less massive stars produce more enrichment and leave behind smaller remnants than do more massive stars. We compare our nucleosynthetic yields to the chemical abundances in the three most iron-poor stars yet found and reproduce the abundance pattern of one, HE 0557-4840, with a zero metallicity 15 solar mass, 2.4 x 10^51 erg supernova. A Salpeter IMF averaged integration of our yields for Z=0 models with explosion energies of 2.4x10^51 ergs or less is in good agreement with the abundances observed in larger samples of extremely metal-poor stars, provided 15 solar mass stars are included. Since the abundance patterns of extremely metal-poor stars likely arise from a representative sample of progenitors, our yields suggest that low-mass supernovae contributed the bulk of the metals to the early universe.Comment: 16 pages, 11 figures; submitted to Ap

Gender differences in virologic response after antiretroviral therapy in treatment-naïve HIV-infected individuals: Results from the 550 clinic HIV cohort study.

Background Controversy still exists regarding gender differences in virologic response between treatment-na•ve HIV-infected individuals. The objective of this study was to evaluate gender difference in virologic and immunologic response to antiretroviral therapy in treatment-na•ve HIV-infected individuals. Methods This was a retrospective, observational study of treatment-na•ve HIV-infected individuals managed at the 550 clinic who started antiretroviral therapy (ART) between January 1st, 2010 and December 31, 2015. Patients with available viral load and CD4 counts before and one year after initiating ART were included in this study. Virologic suppression was defined as \u3c 48 HIV-1 RNA copies/mL, and mmunologic recovery was defined as a CD4 count increase of at least 150 cells/mm3. Dichotomous variables were reported in number and percentages and analyzed using Chi-squared tests and Fisher’s exact (whichever was appropriate). Continuous variables were reported as median and interquartile range (IQR) and analyzed using Wilcox rank-sum tests. Multivariate analyses performed were logistic regressions with adjustment for other covariates. P value \u3c0.05 was considered statistically significant. R version 3.3.2 was used for the statistical analysis. Results A total of 70 women and 90 men were included in the study. Median age was 41 years (19) for women and 34 years (19) for men (P \u3c 0.001). Virologic suppression was documented in 76% of women and 64% of men (p 0.166). Immune recovery was documented in 60% of women and 68% of men (p 0.323). Multivariate analysis of virologic success is shown in Figure 1 and immunologic recovery is shown in Figure 2. Open in new tabDownload slide Open in new tabDownload slide Conclusion In our study, gender was not found to be associated with differences in response to ART. As expected, drug abuse continues to be an independent variable associated with lack of virologic suppression. If one of the goals of treatment is to achieve a rapid immunologic response, our study may indicate that regimens containing protease inhibitors should be the ones selected

Storm fronts over galaxy discs: Models of how waves generate extraplanar gas and its anomalous kinematics

The existence of partially ionized, diffuse gas and dust clouds at kiloparsec scale distances above the central planes of edge-on, galaxy discs was an unexpected discovery about 20 yrs ago. Subsequent observations showed that this EDIG (extended or extraplanar diffuse interstellar gas) has rotation velocities approximately 10-20% lower than those in the central plane, and have been hard to account for. Here we present results of hydrodynamic models, with radiative cooling and heating from star formation. We find that in models with star formation generated stochastically across the disc an extraplanar gas layer is generated as long as the star formation is sufficiently strong. However, this gas rotates at nearly the same speed as the mid-plane gas. We then studied a range of models with imposed spiral or bar waves in the disc. EDIG layers were also generated in these models, but primarily over the wave regions, not over the entire disc. Because of this partial coverage, the EDIG clouds move radially, as well as vertically, with the result that observed kinematic anomalies are reproduced. The implication is that the kinematic anomalies are the result of three-dimensional motions when the cylindrical symmetry of the disc is broken. Thus, the kinematic anomalies are the result of bars or strong waves, and more face-on galaxies with such waves should have an asymmetric EDIG component. The models also indicate that the EDIG can contain a significant fraction of cool gas, and that some star formation can be triggered at considerable heights above the disc midplane. We expect all of these effects to be more prominent in young, forming discs, to play a role in rapidly smoothing disc asymmetries, and in working to self-regulate disc structure.Comment: 30 pages, 9 figs., accepted for MNRAS with additional referee correction

Polymeric Nanoparticle PET/MR Imaging Allows Macrophage Detection in Atherosclerotic Plaques

Author Manuscript 2013 March 02.Rationale: Myeloid cell content in atherosclerotic plaques associates with rupture and thrombosis. Thus, imaging of lesional monocytes and macrophages could serve as a biomarker of disease progression and therapeutic intervention. Objective: To noninvasively assess plaque inflammation with dextran nanoparticle (DNP)-facilitated hybrid positron emission tomography/magnetic resonance imaging (PET/MRI). Methods and Results: Using clinically approved building blocks, we systematically developed 13-nm polymeric nanoparticles consisting of cross-linked short chain dextrans, which were modified with desferoxamine for zirconium-89 radiolabeling ([superscript 89]Zr-DNP) and a near-infrared fluorochrome (VT680) for microscopic and cellular validation. Flow cytometry of cells isolated from excised aortas showed DNP uptake predominantly in monocytes and macrophages (76.7%) and lower signal originating from other leukocytes, such as neutrophils and lymphocytes (11.8% and 0.7%, P<0.05 versus monocytes and macrophages). DNP colocalized with the myeloid cell marker CD11b on immunohistochemistry. PET/MRI revealed high uptake of [superscript 89]Zr-DNP in the aortic root of apolipoprotein E knock out (ApoE[superscript −/−]) mice (standard uptake value, ApoE[superscript −/−] mice versus wild-type controls, 1.9±0.28 versus 1.3±0.03; P<0.05), corroborated by ex vivo scintillation counting and autoradiography. Therapeutic silencing of the monocyte-recruiting receptor C-C chemokine receptor type 2 with short-interfering RNA decreased [superscript 89]Zr-DNP plaque signal (P<0.05) and inflammatory gene expression (P<0.05). Conclusions: Hybrid PET/MRI with a 13-nm DNP enables noninvasive assessment of inflammation in experimental atherosclerotic plaques and reports on therapeutic efficacy of anti-inflammatory therapy.National Heart, Lung, and Blood InstituteNational Institutes of Health (U.S.). Dept. of Health and Human Services (HHSN268201000044C)National Institutes of Health (U.S.). Dept. of Health and Human Services (R01-HL096576)National Institutes of Health (U.S.). Dept. of Health and Human Services (R01-HL095629)National Institutes of Health (U.S.). Dept. of Health and Human Services (T32-HL094301

Molecularly Self-Assembled Nucleic Acid Nanoparticles for Targeted In Vivo siRNA Delivery

Nanoparticles are employed for delivering therapeutics into cells1,2. However, size, shape, surface chemistry and the presentation of targeting ligands on the surface of nanoparticles can affect circulation half-life and biodistribution, cell specific internalization, excretion, toxicity, and efficacy3-7. A variety of materials have been explored for delivering small interfering RNAs (siRNAs) - a therapeutic agent that suppresses the expression of targeted genes8,9. However, conventional delivery nanoparticles such as liposomes and polymeric systems are heterogeneous in size, composition and surface chemistry, and this can lead to suboptimal performance, lack of tissue specificity and potential toxicity10-12. Here, we show that self-assembled DNA tetrahedral nanoparticles with a well-defined size can deliver siRNAs into cells and silence target genes in tumours. Monodisperse nanoparticles are prepared through the self-assembly of complementary DNA strands. Because the DNA strands are easily programmable, the size of the nanoparticles and the spatial orientation and density of cancer targeting ligands (such as peptides and folate) on the nanoparticle surface can be precisely controlled. We show that at least three folate molecules per nanoparticle is required for optimal delivery of the siRNAs into cells and, gene silencing occurs only when the ligands are in the appropriate spatial orientation. In vivo, these nanoparticles showed a longer blood circulation time (t1/2 ∼ 24.2 min) than the parent siRNA (t1/2 ∼ 6 min)

Monocyte-Directed RNAi Targeting CCR2 Improves Infarct Healing in Atherosclerosis-Prone Mice

Background—Exaggerated and prolonged inflammation after myocardial infarction (MI) accelerates left ventricular remodeling. Inflammatory pathways may present a therapeutic target to prevent post-MI heart failure. However, the appropriate magnitude and timing of interventions are largely unknown, in part because noninvasive monitoring tools are lacking. Here, we used nanoparticle-facilitated silencing of CCR2, the chemokine receptor that governs inflammatory Ly-6Chigh monocyte subset traffic, to reduce infarct inflammation in apolipoprotein E–deficient (apoE−/−) mice after MI. We used dual-target positron emission tomography/magnetic resonance imaging of transglutaminase factor XIII (FXIII) and myeloperoxidase (MPO) activity to monitor how monocyte subset–targeted RNAi altered infarct inflammation and healing. Methods and Results—Flow cytometry, gene expression analysis, and histology revealed reduced monocyte numbers and enhanced resolution of inflammation in infarcted hearts of apoE−/− mice that were treated with nanoparticle-encapsulated siRNA. To follow extracellular matrix cross-linking noninvasively, we developed a fluorine-18–labeled positron emission tomography agent (18F-FXIII). Recruitment of MPO-rich inflammatory leukocytes was imaged with a molecular magnetic resonance imaging sensor of MPO activity (MPO-Gd). Positron emission tomography/magnetic resonance imaging detected anti-inflammatory effects of intravenous nanoparticle-facilitated siRNA therapy (75% decrease of MPO-Gd signal; P<0.05), whereas 18F-FXIII positron emission tomography reflected unimpeded matrix cross-linking in the infarct. Silencing of CCR2 during the first week after MI improved ejection fraction on day 21 after MI from 29% to 35% (P<0.05). Conclusion—CCR2-targeted RNAi reduced recruitment of Ly-6Chigh monocytes, attenuated infarct inflammation, and curbed post-MI left ventricular remodeling.National Heart, Lung, and Blood InstituteUnited States. Dept. of Health and Human Services (contract No. HHSN268201000044C)National Institutes of Health (U.S.) (grant R01-HL096576)National Institutes of Health (U.S.) (grant R01-HL095629)National Institutes of Health (U.S.) (grant T32-HL094301)Deutsche Forschungsgemeinschaft (HE-6382/1-1

The role of stellar feedback in the formation of galaxies

We develop a new realistic prescription for modeling the stellar feedback, which minimizes any ad hoc assumptions about sub-grid physics. We start with developing high resolution models of the ISM and formulate the conditions required for its realistic functionality: formation of multi-phase medium with hot chimneys, super-bubbles, cold molecular phase, and very slow consumption of gas. Another important ingredient is the runaway stars. They greatly facilitate the feedback. Once these effects are implemented into cosmological simulations, we do not have the overcooling problem and the angular momentum problem (resulting in a too massive bulge) is also reduced substantially: the rotation curves are nearly flat. Just as it is often observed in QSO absorption lines, our models produce substantial outflows from forming and active galaxies. At high redshifts we routinely find gas with few hundred km/s and occasionally 1000-2000 km/s. The density profile of dark matter is still consistent with a cuspy profile. The simulations reproduce this picture only if the resolution is very high: better than 50 pc, which is much better than the typical resolution in previous cosmological simulations. Our simulations of galaxy formation reach the resolution of 35 pc. (Abridged)Comment: 24 pages, 16 figures, accepted for publication at ApJ. Full resolution version available at http://astronomy.nmsu.edu/dept/html/directory.grads.danielcv.shtm

Detectability of cold streams into high-redshift galaxies by absorption lines

Cold gas streaming along the dark-matter filaments of the cosmic web is predicted to be the major provider of resources for disc buildup, violent disk instability and star formation in massive galaxies in the early universe. We study to what extent these cold streams are traceable in the extended circum-galactic environment of galaxies via Ly alpha absorption and selected low ionisation metal absorption lines. We model the expected absorption signatures using high resolution zoom-in AMR cosmological simulations. In the postprocessing, we distinguish between self-shielded gas and unshielded gas. In the self-shielded gas, which is optically thick to Lyman continuum radiation, we assume pure collisional ionisation for species with an ionisation potential greater than 13.6 eV. In the optically thin, unshielded gas these species are also photoionised by the meta-galactic radiation. In addition to absorption of radiation from background quasars, we compute the absorption line profiles of radiation emitted by the galaxy at the centre of the same halo. We predict the strength of the absorption signal for individual galaxies without stacking. We find that the Ly alpha absorption profiles produced by the streams are consistent with observations of absorption and emission Ly alpha profiles in high redshift galaxies. Due to the low metallicities in the streams, and their low covering factors, the metal absorption features are weak and difficult to detect.Comment: 26 pages, 25 figures, 3 tables, final version accepted for publication in MNRA