Juxtaposition of Chemical and Mutation-Induced Developmental Defects in Zebrafish Reveal a Copper-Chelating Activity for Kalihinol F

SummaryA major hurdle in using complex systems for drug screening is the difficulty of defining the mechanistic targets of small molecules. The zebrafish provides an excellent model system for juxtaposing developmental phenotypes with mechanism discovery using organism genetics. We carried out a phenotype-based screen of uncharacterized small molecules in zebrafish that produced a variety of chemically induced phenotypes with potential genetic parallels. Specifically, kalihinol F caused an undulated notochord, defects in pigment formation, hematopoiesis, and neural development. These phenotypes were strikingly similar to the zebrafish mutant, calamity, an established model of copper deficiency. Further studies into the mechanism of action of kalihinol F revealed a copper-chelating activity. Our data support this mechanism of action for kalihinol F and the utility of zebrafish as an effective system for identifying therapeutic and target pathways

Exploring impulsive solar magnetic energy release and particle acceleration with focused hard X-ray imaging spectroscopy

How impulsive magnetic energy release leads to solar eruptions and how those eruptions are energized and evolve are vital unsolved problems in Heliophysics. The standard model for solar eruptions summarizes our current understanding of these events. Magnetic energy in the corona is released through drastic restructuring of the magnetic field via reconnection. Electrons and ions are then accelerated by poorly understood processes. Theories include contracting loops, merging magnetic islands, stochastic acceleration, and turbulence at shocks, among others. Although this basic model is well established, the fundamental physics is poorly understood. HXR observations using grazing-incidence focusing optics can now probe all of the key regions of the standard model. These include two above-the-looptop (ALT) sources which bookend the reconnection region and are likely the sites of particle acceleration and direct heating. The science achievable by a direct HXR imaging instrument can be summarized by the following science questions and objectives which are some of the most outstanding issues in solar physics (1) How are particles accelerated at the Sun? (1a) Where are electrons accelerated and on what time scales? (1b) What fraction of electrons is accelerated out of the ambient medium? (2) How does magnetic energy release on the Sun lead to flares and eruptions? A Focusing Optics X-ray Solar Imager (FOXSI) instrument, which can be built now using proven technology and at modest cost, would enable revolutionary advancements in our understanding of impulsive magnetic energy release and particle acceleration, a process which is known to occur at the Sun but also throughout the Universe

Q^2 Dependence of the S_{11}(1535) Photocoupling and Evidence for a P-wave resonance in eta electroproduction

New cross sections for the reaction $ep \to e'\eta p$ are reported for total center of mass energy $W$=1.5--2.3 GeV and invariant squared momentum transfer $Q^2$=0.13--3.3 GeV$^2$. This large kinematic range allows extraction of new information about response functions, photocouplings, and $\eta N$ coupling strengths of baryon resonances. A sharp structure is seen at $W\sim$ 1.7 GeV. The shape of the differential cross section is indicative of the presence of a $P$-wave resonance that persists to high $Q^2$. Improved values are derived for the photon coupling amplitude for the $S_{11}$(1535) resonance. The new data greatly expands the $Q^2$ range covered and an interpretation of all data with a consistent parameterization is provided.Comment: 31 pages, 9 figure

Measurement of the Polarized Structure Function σLT′\sigma_{LT^\prime} for p(e⃗,e′π+)np(\vec{e},e'\pi^+)n in the Δ(1232)\Delta(1232) Resonance Region

The polarized longitudinal-transverse structure function $\sigma_{LT^\prime}$ has been measured using the $p(\vec e,e'\pi^+)n$ reaction in the $\Delta(1232)$ resonance region at $Q^2=0.40$ and 0.65 GeV$^2$. No previous $\sigma_{LT^\prime}$ data exist for this reaction channel. The kinematically complete experiment was performed at Jefferson Lab with the CEBAF Large Acceptance Spectrometer (CLAS) using longitudinally polarized electrons at an energy of 1.515 GeV. A partial wave analysis of the data shows generally better agreement with recent phenomenological models of pion electroproduction compared to the previously measured $\pi^0 p$ channel. A fit to both $\pi^0 p$ and $\pi^+ n$ channels using a unitary isobar model suggests the unitarized Born terms provide a consistent description of the non-resonant background. The $t$-channel pion pole term is important in the $\pi^0 p$ channel through a rescattering correction, which could be model-dependent.Comment: 6 pages, LaTex, 5 eps figures: Submitted to PRC/Brief Reports v2: Updated referenc

Light Vector Mesons in the Nuclear Medium

The light vector mesons ($\rho$, $\omega$, and $\phi$) were produced in deuterium, carbon, titanium, and iron targets in a search for possible in-medium modifications to the properties of the $\rho$ meson at normal nuclear densities and zero temperature. The vector mesons were detected with the CEBAF Large Acceptance Spectrometer (CLAS) via their decays to $e^{+}e^{-}$. The rare leptonic decay was chosen to reduce final-state interactions. A combinatorial background was subtracted from the invariant mass spectra using a well-established event-mixing technique. The $\rho$ meson mass spectrum was extracted after the $\omega$ and $\phi$ signals were removed in a nearly model-independent way. Comparisons were made between the $\rho$ mass spectra from the heavy targets ($A > 2$) with the mass spectrum extracted from the deuterium target. With respect to the $\rho$-meson mass, we obtain a small shift compatible with zero. Also, we measure widths consistent with standard nuclear many-body effects such as collisional broadening and Fermi motion.Comment: 15 pages, 18 figures, 3 table

New Insights into White-Light Flare Emission from Radiative-Hydrodynamic Modeling of a Chromospheric Condensation

(abridged) The heating mechanism at high densities during M dwarf flares is poorly understood. Spectra of M dwarf flares in the optical and near-ultraviolet wavelength regimes have revealed three continuum components during the impulsive phase: 1) an energetically dominant blackbody component with a color temperature of T $\sim$ 10,000 K in the blue-optical, 2) a smaller amount of Balmer continuum emission in the near-ultraviolet at lambda $<$ 3646 Angstroms and 3) an apparent pseudo-continuum of blended high-order Balmer lines. These properties are not reproduced by models that employ a typical "solar-type" flare heating level in nonthermal electrons, and therefore our understanding of these spectra is limited to a phenomenological interpretation. We present a new 1D radiative-hydrodynamic model of an M dwarf flare from precipitating nonthermal electrons with a large energy flux of $10^{13}$ erg cm$^{-2}$ s$^{-1}$. The simulation produces bright continuum emission from a dense, hot chromospheric condensation. For the first time, the observed color temperature and Balmer jump ratio are produced self-consistently in a radiative-hydrodynamic flare model. We find that a T $\sim$ 10,000 K blackbody-like continuum component and a small Balmer jump ratio result from optically thick Balmer and Paschen recombination radiation, and thus the properties of the flux spectrum are caused by blue light escaping over a larger physical depth range compared to red and near-ultraviolet light. To model the near-ultraviolet pseudo-continuum previously attributed to overlapping Balmer lines, we include the extra Balmer continuum opacity from Landau-Zener transitions that result from merged, high order energy levels of hydrogen in a dense, partially ionized atmosphere. This reveals a new diagnostic of ambient charge density in the densest regions of the atmosphere that are heated during dMe and solar flares.Comment: 50 pages, 2 tables, 13 figures. Accepted for publication in the Solar Physics Topical Issue, "Solar and Stellar Flares". Version 2 (June 22, 2015): updated to include comments by Guest Editor. The final publication is available at Springer via http://dx.doi.org/10.1007/s11207-015-0708-

Search for medium modification of the ρ\rho meson

The photoproduction of vector mesons on various nuclei has been studied using the CEBAF Large Acceptance Spectrometer (CLAS) at Jefferson Laboratory. The vector mesons, $\rho$, $\omega$, and $\phi$, are observed via their decay to $e^+e^-$, in order to reduce the effects of final state interactions in the nucleus. Of particular interest are possible in-medium effects on the properties of the $\rho$ meson. The $\rho$ spectral function is extracted from the data on various nuclei, carbon, iron, and titanium, and compared to the spectrum from liquid deuterium, which is relatively free of nuclear effects. We observe no significant mass shift for the $\rho$ meson; however, there is some widening of the resonance in titanium and iron, which is consistent with expected collisional broadening.Comment: 8 pages, 4 figure

Measurement of Deeply Virtual Compton Scattering with a Polarized Proton Target

The longitudinal target-spin asymmetry A_UL for the exclusive electroproduction of high energy photons was measured for the first time in p(e,e'p\gamma). The data have been accumulated at Jefferson Lab with the CLAS spectrometer using 5.7 GeV electrons and a longitudinally polarized NH_3 target. A significant azimuthal angular dependence was observed, resulting from the interference of the Deeply Virtual Compton Scattering and Bethe-Heitler processes. The amplitude of the sin(phi) moment is 0.252 +/- 0.042(stat) +/- 0.020(sys). Theoretical calculations are in good agreement with the magnitude and the kinematic dependence of the target-spin asymmetry, which is sensitive to the generalized parton distributions H and H-tilde.Comment: Modified text slightly, added reference