Iron-Dependent Gene Expression in Actinomyces Oris

Actinomyces oris is a Gram-positive bacterium that has been associated with healthy and diseased sites in the human oral cavity. Most pathogenic bacteria require iron to survive, and in order to acquire iron in the relatively iron-scarce oral cavity A. oris has been shown to produce iron-binding molecules known as siderophores. The genes encoding these siderophores and transporters are thought to be regulated by the amount of iron in the growth medium and by the metal-dependent repressor, AmdR, which we showed previously binds to the promoter of proposed iron-regulated genes

Synthesis of 3-D coronal-solar wind energetic particle acceleration modules

1. Introduction Acute space radiation hazards pose one of the most serious risks to future human and robotic exploration. Large solar energetic particle (SEP) events are dangerous to astronauts and equipment. The ability to predict when and where large SEPs will occur is necessary in order to mitigate their hazards. The Coronal-Solar Wind Energetic Particle Acceleration (C-SWEPA) modeling effort in the NASA/NSF Space Weather Modeling Collaborative [Schunk, 2014] combines two successful Living With a Star (LWS) (http://lws. gsfc.nasa.gov/) strategic capabilities: the Earth-Moon-Mars Radiation Environment Modules (EMMREM) [Schwadron et al., 2010] that describe energetic particles and their effects, with the Next Generation Model for the Corona and Solar Wind developed by the Predictive Science, Inc. (PSI) group. The goal of the C-SWEPA effort is to develop a coupled model that describes the conditions of the corona, solar wind, coronal mass ejections (CMEs) and associated shocks, particle acceleration, and propagation via physics-based modules. Assessing the threat of SEPs is a difficult problem. The largest SEPs typically arise in conjunction with X class flares and very fast (\u3e1000 km/s) CMEs. These events are usually associated with complex sunspot groups (also known as active regions) that harbor strong, stressed magnetic fields. Highly energetic protons generated in these events travel near the speed of light and can arrive at Earth minutes after the eruptive event. The generation of these particles is, in turn, believed to be primarily associated with the shock wave formed very low in the corona by the passage of the CME (injection of particles from the flare site may also play a role). Whether these particles actually reach Earth (or any other point) depends on their transport in the interplanetary magnetic field and their magnetic connection to the shock

Modeling Accelerated Pick-up Ion Distributions at an Interplanetary Shock

The acceleration of interstellar pick-up ions as well as solar wind species has been observed at a multitude of interplanetary (IP) shocks by different spacecraft. The efficiency of injection of the pick-up ion component differs from that of the solar wind, and is expected to be strongly enhanced at highly oblique and quasi-perpendicular shock events, in accord with inferences from {\it in situ} observations. This paper explores theoretical modeling of the phase space distributions of accelerated ions obtained by the Ulysses mission for the Day 292, 1991 shock associated with a corotating interaction region, encountered before Ulysses' fly-by of Jupiter. A Monte Carlo simulation is used to model the acceleration process, adapting a technique that has been successfully tested on earlier IP shocks possessing minimal pick-up ion presence. Phase space distributions from the simulation technique for various low mass ions are compared with SWICS and HI-SCALE data to deduce values of a ``turbulence parameter'' that controls the efficiency of injection, and the degree of cross-field diffusion. Acceptable fits are obtained for the $H^+$ and $He^+$ populations using standard prescriptions for the pick-up ion distribution; $He^{++}$ spectral data was only fit well for scenarios very close to the Bohm diffusion limit. It is also found that the simulation successfully accounts for the observation of energetic protons farther upstream of the forward shock than lower energy pick-up protons, using the same turbulence parameter that is required to achieve reasonable spectral fits.Comment: 15 pages, 2 embedded figures, Advances Space Research, in pres

On the Energy Dependence of Galactic Cosmic Ray Anisotropies in the Very Local Interstellar Medium

We report on the energy dependence of galactic cosmic rays (GCRs) in the very local interstellar medium (VLISM) as measured by the Low Energy Charged Particle (LECP) instrument on the Voyager 1 (V1) spacecraft. The LECP instrument includes a dual-ended solid state detector particle telescope mechanically scanning through 360 deg across eight equally-spaced angular sectors. As reported previously, LECP measurements showed a dramatic increase in GCR intensities for all sectors of the >=211 MeV count rate (CH31) at the V1 heliopause (HP) crossing in 2012, however, since then the count rate data have demonstrated systematic episodes of intensity decrease for particles around 90{\deg} pitch angle. To shed light on the energy dependence of these GCR anisotropies over a wide range of energies, we use V1 LECP count rate and pulse height analyzer (PHA) data from >=211 MeV channel together with lower energy LECP channels. Our analysis shows that while GCR anisotropies are present over a wide range of energies, there is a decreasing trend in the amplitude of second-order anisotropy with increasing energy during anisotropy episodes. A stronger pitch-angle scattering at the higher velocities is argued as a potential cause for this energy dependence. A possible cause for this velocity dependence arising from weak rigidity dependence of the scattering mean free path and resulting velocity-dominated scattering rate is discussed. This interpretation is consistent with a recently reported lack of corresponding GCR electron anisotropies

Imaging the initial condition of heavy-ion collisions and nuclear structure across the nuclide chart

A major goal of the hot QCD program, the extraction of the properties of the quark gluon plasma (QGP), is currently limited by our poor knowledge of the initial condition of the QGP, in particular how it is shaped from the colliding nuclei. To attack this limitation, we propose to exploit collisions of selected species to precisely assess how the initial condition changes under variations of the structure of the colliding ions. This knowledge, combined with event-by-event measures of particle correlations in the final state of heavy-ion collisions, will provide in turn a new way to probe the collective structure of nuclei, and to confront and exploit the predictions of state-of-the-art ab initio nuclear structure theories. The US nuclear community should capitalize on this interdisciplinary connection by pursuing collisions of well-motivated species at high-energy colliders.Comment: 23 pages, 6 figure

Acceleration of Solar Wind Ions by Nearby Interplanetary Shocks: Comparison of Monte Carlo Simulations with Ulysses Observations

The most stringent test of theoretical models of the first-order Fermi mechanism at collisionless astrophysical shocks is a comparison of the theoretical predictions with observational data on particle populations. Such comparisons have yielded good agreement between observations at the quasi-parallel portion of the Earth's bow shock and three theoretical approaches, including Monte Carlo kinetic simulations. This paper extends such model testing to the realm of oblique interplanetary shocks: here observations of proton and alpha particle distributions made by the SWICS ion mass spectrometer on Ulysses at nearby interplanetary shocks are compared with test particle Monte Carlo simulation predictions of accelerated populations. The plasma parameters used in the simulation are obtained from measurements of solar wind particles and the magnetic field upstream of individual shocks. Good agreement between downstream spectral measurements and the simulation predictions are obtained for two shocks by allowing the the ratio of the mean-free scattering length to the ionic gyroradius, to vary in an optimization of the fit to the data. Generally small values of this ratio are obtained, corresponding to the case of strong scattering. The acceleration process appears to be roughly independent of the mass or charge of the species.Comment: 26 pages, 6 figures, AASTeX format, to appear in the Astrophysical Journal, February 20, 199

Diffusive Acceleration of Particles at Oblique, Relativistic, Magnetohydrodynamic Shocks

Diffusive shock acceleration (DSA) at relativistic shocks is expected to be an important acceleration mechanism in a variety of astrophysical objects including extragalactic jets in active galactic nuclei and gamma ray bursts. These sources remain good candidate sites for the generation of ultra-high energy cosmic rays. In this paper, key predictions of DSA at relativistic shocks that are germane to production of relativistic electrons and ions are outlined. The technique employed to identify these characteristics is a Monte Carlo simulation of such diffusive acceleration in test-particle, relativistic, oblique, magnetohydrodynamic (MHD) shocks. Using a compact prescription for diffusion of charges in MHD turbulence, this approach generates particle angular and momentum distributions at any position upstream or downstream of the shock. Simulation output is presented for both small angle and large angle scattering scenarios, and a variety of shock obliquities including superluminal regimes when the de Hoffmann-Teller frame does not exist. The distribution function power-law indices compare favorably with results from other techniques. They are found to depend sensitively on the mean magnetic field orientation in the shock, and the nature of MHD turbulence that propagates along fields in shock environs. An interesting regime of flat spectrum generation is addressed; we provide evidence for it being due to shock drift acceleration, a phenomenon well-known in heliospheric shock studies. The impact of these theoretical results on blazar science is outlined. Specifically, Fermi-LAT gamma-ray observations of these relativistic jet sources are providing significant constraints on important environmental quantities for relativistic shocks, namely the field obliquity, the frequency of scattering and the level of field turbulence.Comment: 25 pages, 12 figures, accepted for publication in The Astrophysical Journa

Germline Genetic Variants and Pediatric Rhabdomyosarcoma Outcomes: A Report From the Children’s Oncology Group

BACKGROUND: Relative to other pediatric cancers, survival for rhabdomyosarcoma (RMS) has not improved in recent decades, suggesting the need to enhance risk stratification. Therefore, we conducted a genome-wide association study for event-free survival (EFS) and overall survival (OS) to identify genetic variants associated with outcomes in individuals with RMS. METHODS: The study included 920 individuals with newly diagnosed RMS who were enrolled in Children\u27s Oncology Group protocols. To assess the association of each single nucleotide polymorphism (SNP) with EFS and OS, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using multivariable Cox proportional hazards models, adjusted for clinical covariates. All statistical tests were two sided. We also performed stratified analyses by histological subtype (alveolar and embryonal RMS) and carried out sensitivity analyses of statistically significant SNPs by PAX3/7-FOXO1 fusion status and genetic ancestry group. RESULTS: We identified that rs17321084 was associated with worse EFS (HR = 2.01, 95% CI = 1.59 to 2.53, P = 5.39 × 10-9) and rs10094840 was associated with worse OS (HR = 1.84, 95% CI = 1.48 to 2.27, P = 2.13 × 10-8). Using publicly available data, we found that rs17321084 lies in a binding region for transcription factors GATA2 and GATA3, and rs10094840 is associated with SPAG1 and RNF19A expression. We also identified that CTNNA3 rs2135732 (HR = 3.75, 95% CI = 2.34 to 5.99, P = 3.54 × 10-8) and MED31 rs74504320 (HR = 3.21, 95% CI = 2.12 to 4.86, P = 3.60 × 10-8) were associated with worse OS among individuals with alveolar RMS. CONCLUSIONS: We demonstrated that common germline variants are associated with EFS and OS among individuals with RMS. Additional replication and investigation of these SNP effects may further support their consideration in risk stratification protocols

White paper on microbial anti-cancer therapy and prevention

In this White Paper, we discuss the current state of microbial cancer therapy. This paper resulted from a meeting (‘Microbial Based Cancer Therapy’) at the US National Cancer Institute in the summer of 2017. Here, we define ‘Microbial Therapy’ to include both oncolytic viral therapy and bacterial anticancer therapy. Both of these fields exploit tumor-specific infectious microbes to treat cancer, have similar mechanisms of action, and are facing similar challenges to commercialization. We designed this paper to nucleate this growing field of microbial therapeutics and increase interactions between researchers in it and related fields. The authors of this paper include many primary researchers in this field. In this paper, we discuss the potential, status and opportunities for microbial therapy as well as strategies attempted to date and important questions that need to be addressed. The main areas that we think will have the greatest impact are immune stimulation, control of efficacy, control of delivery, and safety. There is much excitement about the potential of this field to treat currently intractable cancer. Much of the potential exists because these therapies utilize unique mechanisms of action, difficult to achieve with other biological or small molecule drugs. By better understanding and controlling these mechanisms, we will create new therapies that will become integral components of cancer care

Giant Outer Transiting Exoplanet Mass (GOT 'EM) Survey. IV. Long-term Doppler Spectroscopy for 11 Stars Thought to Host Cool Giant Exoplanets

Discovering and characterizing exoplanets at the outer edge of the transit method's sensitivity has proven challenging owing to geometric biases and the practical difficulties associated with acquiring long observational baselines. Nonetheless, a sample of giant exoplanets on orbits longer than 100 days has been identified by transit hunting missions. We present long-term Doppler spectroscopy for 11 such systems with observation baselines spanning a few years to a decade. We model these radial velocity observations jointly with transit photometry to provide initial characterizations of these objects and the systems in which they exist. Specifically, we make new precise mass measurements for four long-period giant exoplanets (Kepler-111 c, Kepler-553 c, Kepler-849 b, and PH-2 b), we place new upper limits on mass for four others (Kepler-421 b, KOI-1431.01, Kepler-1513 b, and Kepler-952 b), and we show that several "confirmed" planets are in fact not planetary at all. We present these findings to complement similar efforts focused on closer-in short-period giant planets, and with the hope of inspiring future dedicated studies of cool giant exoplanets.Comment: 35 pages, 24 figures, 11 tables. Accepted for publication in ApJ Supplemen