Optical Detection and Analysis of Pictor A's Jet

New images from the Hubble Space Telescope of the FRII radio galaxy Pictor A reveal a number of jet knot candidates which coincide with previously detected radio and x-ray knots. Previous observations in x-ray and radio bands show the entire jet to be 1.9' long, with interesting variability, but an optical component was previously unknown. The discovered optical component is faint, and knot candidates must be teased out from a bright host galaxy. Using three broadband filters, we extract knot fluxes and upper-bounds on the flux for multiple knot candidates at wavelengths of 1600nm, 814nm and 475nm. We find that the data suggest that localized particle re-accleration events followed by synchrotron emission could explain the observed knot candidates, but those electrons could not supply enough x-ray flux to match prior observations. Our data provide key evidence suggesting a second, higher energy electron population which was previously hypothesized, but could not be confirmed.Comment: B.Sc. Thesis, MIT; 78 pages, 20 figure

Enhanced Momentum Feedback from Clustered Supernovae

Young stars typically form in star clusters, so the supernovae (SNe) they produce are clustered in space and time. This clustering of SNe may alter the momentum per SN deposited in the interstellar medium (ISM) by affecting the local ISM density, which in turn affects the cooling rate. We study the effect of multiple SNe using idealized 1D hydrodynamic simulations which explore a large parameter space of the number of SNe, and the background gas density and metallicity. The results are provided as a table and an analytic fitting formula. We find that for clusters with up to ~100 SNe the asymptotic momentum scales super-linearly with the number of SNe, resulting in a momentum per SN that can be an order of magnitude larger than for a single SN, with a maximum efficiency for clusters with 10-100 SNe. We argue that additional physical processes not included in our simulations -- self-gravity, breakout from a galactic disk, and galactic shear -- can slightly reduce the momentum enhancement from clustering, but the average momentum per SN still remains a factor of 4 larger than the isolated SN value when averaged over a realistic cluster mass function for a star-forming galaxy. We conclude with a discussion of the possible role of mixing between hot and cold gas, induced by multi-dimensional instabilities or preexisting density variations, as a limiting factor in the buildup of momentum by clustered SNe, and suggest future numerical experiments to explore these effects.Comment: 19 pages, 26 figures, revised to reflect accepted version. Discussion regarding resolution effects has changed; additional analysis into galactic and gravitational effects has been adde

Progress toward a Soft X-ray Polarimeter

We are developing instrumentation for a telescope design capable of measuring linear X-ray polarization over a broad-band using conventional spectroscopic optics. Multilayer-coated mirrors are key to this approach, being used as Bragg reflectors at the Brewster angle. By laterally grading the multilayer mirrors and matching to the dispersion of a spectrometer, one may take advantage of high multilayer reflectivities and achieve modulation factors over 50% over the entire 0.2-0.8 keV band. We present progress on laboratory work to demonstrate the capabilities of an existing laterally graded multilayer coated mirror pair. We also present plans for a suborbital rocket experiment designed to detect a polarization level of 12-17% for an active galactic nucleus in the 0.1-1.0 keV band.Comment: 11 pages, 12 figures, to appear in the proceedings of the SPIE, volume 8861, on Optics for EUV, X-Ray, and Gamma-Ray Astronom

The momentum budget of clustered supernova feedback in a 3D, magnetised medium

While the evolution of superbubbles driven by clustered supernovae has been studied by numerous authors, the resulting radial momentum yield is uncertain by as much as an order of magnitude depending on the computational methods and assumed properties of the surrounding interstellar medium (ISM). In this work, we study the origin of these discrepancies, and seek to determine the correct momentum budget for a homogeneous ISM. We carry out 3D hydrodynamic (HD) and magnetohydrodynamic (MHD) simulations of clustered supernova explosions, using a Lagrangian method and checking for convergence with respect to resolution. We find that the terminal momentum of a shell driven by clustered supernovae is dictated primarily by the mixing rate across the contact discontinuity between the hot and cold phases, and that this energy mixing rate is dominated by numerical diffusion even at the highest resolution we can complete, 0.03 $M_\odot$. Magnetic fields also reduce the mixing rate, so that MHD simulations produce higher momentum yields than HD ones at equal resolution. As a result, we obtain only a lower limit on the momentum yield from clustered supernovae. Combining this with our previous 1D results, which provide an upper limit because they allow almost no mixing across the contact discontinuity, we conclude that the momentum yield per supernova from clustered supernovae in a homogeneous ISM is bounded between $2\times 10^5$ and $3\times 10^6$ $M_\odot$ km s$^{-1}$. A converged value for the simple homogeneous ISM remains elusive.Comment: 13 page, 11 figures, revised to reflect the published version. Added a deeper analysis estimating physical and numeric mixing rates (Section 4). Added addition simulations to the resolution stud

Frontotemporal Dementia Nonsense Mutation of Progranulin Rescued by Aminoglycosides

Frontotemporal dementia (FTD) is an early onset dementia and is characterized by progressive atrophy of the frontal and/or temporal lobes. FTD is highly heritable with mutations in progranulin accounting for 5-26% of cases in different populations. Progranulin is involved in endocytosis, secretion and lysosomal processes, but its function under physiological and pathological conditions remains to be defined. Many FTD-causing nonsense progranulin mutations contain a premature termination codon (PTC), thus progranulin haploinsufficiency has been proposed as a major disease mechanism. Currently, there is no effective FTD treatment or therapy. Aminoglycosides are a class of antibiotics that possess a less known function to induce eukaryotic ribosomal readthrough of PTCs to produce a full-length protein. The aminoglycoside-induced readthrough strategy has been utilized to treat multiple human diseases caused by PTCs. In this study, we tested the only clinically approved readthrough small molecule PTC124 and eleven aminoglycosides in a cell culture system on four PTCs responsible for FTD or a related neurodegenerative disease amyotrophic lateral sclerosis. We found that the aminoglycosides G418 and gentamicin B1 rescued the expression of the progranulin R493X mutation. G418 was more effective than gentamicin B1 (~50% rescue vs \u3c 10%), and the effect was dose and time-dependent. The proganulin readthrough protein displayed similar subcellular localization as the wild-type proganulin protein. These data provide an exciting proof-of-concept that aminoglycosides or other readthrough-promoting compounds are a therapeutic avenue for familial FTD caused by proganulin PTC mutations

Momentum injection by clustered supernovae: testing subgrid feedback prescriptions

Using a 1D Lagrangian code specifically designed to assess the impact of multiple, time-resolved supernovae (SNe) from a single-star cluster on the surrounding medium, we test three commonly used feedback recipes: delayed cooling (e.g. used in the GASOLINE-2 code), momentum-energy injection (a resolution-dependent transition between momentum-dominated feedback and energy-dominated feedback used, e.g. in the FIRE-2 code), and simultaneous energy injection (e.g. used in the EAGLE simulations). Our work provides an intermediary test for these recipes: we analyse a setting that is more complex than the simplified scenarios for which many were designed, but one more controlled than a full galactic simulation. In particular, we test how well these models reproduce the enhanced momentum efficiency seen for an 11 SN cluster simulated at high resolution (0.6 pc; a factor of 12 enhancement relative to the isolated SN case) when these subgrid recipes are implemented in low resolution (20 pc) runs. We find that: (1) the delayed cooling model performs well – resulting in 9 times the momentum efficiency of the fiducial isolated SN value – when SNe are clustered and 1051 erg are injected per SN, while clearly overpredicting the momentum efficiency in the single SN test case; (2) the momentum-energy model always achieves good results, with a factor of 5 boost in momentum efficiency; and (3) injecting the energy from all SNe simultaneously does little to prevent overcooling and greatly underproduces the momentum deposited by clustered SNe, resulting in a factor of 3 decrease in momentum efficiency on the average.We thank the anonymous reviewer for their useful comments and suggestions. This work was supported by the National Science Foundation (NSF) through grants AST-1405962 (ESG and MRK), AST-1229745 (PM) andDGE 1339067 (ESG), by the Australian Research Council through grant FT180100375 (MRK) and by National Aeronautics and Space Administration (NASA) through a contract to the WFIRST-EXPO Science Investigation Team (15-WFIRST15-0004), administered by the Goddard Space Flight Center (PM). This work made use of resources and services from the National Computational Infrastructure (NCI), which is supported by the Australian Government. MRK thanks the Simons Foundation, which contributed to this work through its support for the Simons Symposium ‘Galactic Superwinds: Beyond Phenomenology’

Enhanced momentum feedback from clustered supernovae

Young stars typically form in star clusters, so the supernovae (SNe) they produce are clustered in space and time. This clustering of SNe may alter the momentum per SN deposited in the interstellar medium (ISM) by affecting the local ISM density, which in turn affects the cooling rate. We study the effect of multiple SNe using idealized 1D hydrodynamic simulations which explore a large parameter space of the number of SNe, and the background gas density and metallicity. The results are provided as a table and an analytic fitting formula. We find that for clusters with up to ∼100 SNe, the asymptotic momentum scales superlinearly with the number of SNe, resulting in a momentum per SN which can be an order of magnitude larger than for a single SN, with a maximum efficiency for clusters with 10–100 SNe. We argue that additional physical processes not included in our simulations – self-gravity, breakout from a galactic disc, and galactic shear – can slightly reduce the momentum enhancement from clustering, but the average momentum per SN still remains a factor of 4 larger than the isolated SN value when averaged over a realistic cluster mass function for a star-forming galaxy. We conclude with a discussion of the possible role of mixing between hot and cold gas, induced by multidimensional instabilities or pre-existing density variations, as a limiting factor in the build-up of momentum by clustered SNe, and suggest future numerical experiments to explore these effects. Key words: hydrodynamics – ISM: bubbles – ISM: supernova remnants.This work was supported by the NSF through grants AST-1405962 (ESG, MRK, and AD), AST-1229745 (PM), and DGE 1339067 (ESG), by the Australian Research Council through grant ARC DP160100695 (MRK) and by NASA through grant NNX12AF87G (PM). AD’s work is also supported by the grants ISF 124/12, I-CORE Programme of the PBC/ISF 1829/12, and BSF 2014-273. MRK thanks the Simons Foundation, which contributed to this work through its support for the Simons Symposium ‘Galactic Superwinds: Beyond Phenomenology’. PM thanks the Prefecture of the Ile-de-France Re- ´ gion for the award of a Blaise Pascal International Research Chair, managed by the Fondation de l’Ecole Normale Superieure

Optical detection of the Pictor A jet and tidal tail : evidence against an IC/CMB jet

Date of Acceptance: 12/06/2015New images of the FR II radio galaxy Pictor A from the Hubble Space Telescope reveal a previously undiscovered tidal tail, as well as a number of jet knots coinciding with a known X-ray and radio jet. The tidal tail is approximately 5″ wide (3 kpc projected), starting 18″ (12 kpc) from the center of Pictor A, and extends more than 90″ (60 kpc). The knots are part of a jet observed to be about 4′ (160 kpc) long, extending to a bright hotspot. These images are the first optical detections of this jet, and by extracting knot flux densities through three filters, we set constraints on emission models. While the radio and optical flux densities are usually explained by synchrotron emission, there are several emission mechanisms that might be used to explain the X-ray flux densities. Our data rule out Doppler-boosted inverse Compton scattering as a source of the high-energy emission. Instead, we find that the observed emission can be well described by synchrotron emission from electrons with a low-energy index (p ∼ 2) that dominates the radio band, while a high-energy index (p ∼ 3) is needed for the X-ray band and the transition occurs in the optical/infrared band. This model is consistent with a continuous electron injection scenario.Peer reviewedFinal Accepted Versio

Whole-exome sequencing and clinical interpretation of FFPE tumor samples to guide precision cancer medicine

Translating whole exome sequencing (WES) for prospective clinical use may impact the care of cancer patients; however, multiple innovations are necessary for clinical implementation. These include: (1) rapid and robust WES from formalin-fixed paraffin embedded (FFPE) tumor tissue, (2) analytical output similar to data from frozen samples, and (3) clinical interpretation of WES data for prospective use. Here, we describe a prospective clinical WES platform for archival FFPE tumor samples. The platform employs computational methods for effective clinical analysis and interpretation of WES data. When applied retrospectively to 511 exomes, the interpretative framework revealed a “long tail” of somatic alterations in clinically important genes. Prospective application of this approach identified clinically relevant alterations in 15/16 patients. In one patient, previously undetected findings guided clinical trial enrollment leading to an objective clinical response. Overall, this methodology may inform the widespread implementation of precision cancer medicine