Ionization States and Plasma Structures of Mixed-morphology SNRs Observed with ASCA

We present the results of a systematic study using ASCA of the ionization state for six ``mixed-morphology'' supernova emnants (MMSNRs): IC 443, W49B, W28, W44, 3C391, and Kes 27. MMSNRs show centrally filled thermal X-ray emission, which contrasts to shell-like radio morphology, a set of haracteristics at odds with the standard model of SNR evolution (e.g., the Sedov model). We have therefore studied the evolution of the MMSNRs from the ionization conditions inferred from the X-ray spectra, independent of X-ray morphology. We find highly ionized plasmas approaching ionization equilibrium in all the mmsnrs. The degree of ionization is systematically higher than the plasma usually seen in shell-like SNRs. Radial temperature gradients are also observed in five remnants, with cooler plasma toward the limb. In IC 443 and W49B, we find a plasma structure consistent with shell-like SNRs, suggesting that at least some MMSNRs have experienced similar evolution to shell-like SNRs. In addition to the results above, we have discovered an ``overionized'' ionization state in W49B, in addition to that previously found in IC 443. Thermal conduction can cause the hot interior plasma to become overionized by reducing the temperature and density gradients, leading to an interior density increase and temperature decrease. Therefore, we suggest that the ``center-filled'' X-ray morphology develops as the result of thermal conduction, and should arise in all SNRs. This is consistent with the results that MMSNRs are near collisional ionization equilibrium since the conduction timescale is roughly similar to the ionization timescale. Hence, we conclude that MMSNRs are those that have evolved over$\sim10^4$ yr. We call this phase as the ``conduction phase.''Comment: 34 pages, 20 figures, 9 tables, accepted for publication in The Astrophysical Journa

Cold Dust in Kepler's Supernova Remnant

The timescales to replenish dust from the cool, dense winds of Asymptotic Giant Branch stars are believed to be greater than the timescales for dust destruction. In high redshift galaxies, this problem is further compounded as the stars take longer than the age of the Universe to evolve into the dust production stages. To explain these discrepancies, dust formation in supernovae (SNe) is required to be an important process but until very recently dust in supernova remnants has only been detected in very small quantities. We present the first submillimeter observations of cold dust in Kepler's supernova remnant (SNR) using SCUBA. A two component dust temperature model is required to fit the Spectral Energy Distribution (SED) with $T_{warm} \sim 102$K and $T_{cold} \sim 17$K. The total mass of dust implied for Kepler is $\sim 1M_{\odot}$ - 1000 times greater than previous estimates. Thus SNe, or their progenitors may be important dust formation sites.Comment: 12 pages, 2 figures, accepted to ApJL, corrected proof

A Giant Glitch in the Energetic 69 ms X-ray Pulsar AXS J161730-505505

We present new results on the recently discovered 69 ms X-ray pulsar AXS J161730-505505, the sixth youngest sample of all known pulsars. We have undertaken a comprehensive X-ray observing campaign of AXS J161730-505505 with the ASCA, SAX, and XTE observatories and follow its long term spin-down history between 1989 and 1999, using these, archival GINGA and ASCA data sets, and the radio ephemeris. The spin-down is not simply described by a linear function as originally thought, but instead we find evidence of a giant glitch (|Delta P/P| > 10E-6) between 1993 August and 1997 September, perhaps the largest yet observed from a young pulsar. The glitch is well described by steps in the period and its first derivative accompanied by a persistent second derivative similar to those in the Vela pulsar. The pulse profile of AXS J161730-505505 presents a single asymmetric peak which is maintained over all observation epochs. The energy spectrum is also steady over time, characterized by a highly absorbed power-law with a photon index 1.4 +/- 0.2, consistent with that found for other young rotation powered pulsars.Comment: 6 pages with 2 figures, LaTex, emulateapj.sty. To appear in the Astrophysical Journal Letter

Dense, Fe-rich Ejecta in Supernova Remnants DEM L238 and DEM L249: A New Class of Type Ia Supernova?

We present observations of two LMC supernova remnants (SNRs), DEM L238 and DEM L249, with the Chandra and XMM-Newton X-ray satellites. Bright central emission, surrounded by a faint shell, is present in both remnants. The central emission has an entirely thermal spectrum dominated by strong Fe L-shell lines, with the deduced Fe abundance in excess of solar and not consistent with the LMC abundance. This Fe overabundance leads to the conclusion that DEM L238 and DEM L249 are remnants of thermonuclear (Type Ia) explosions. The shell emission originates in gas swept up and heated by the blast wave. A standard Sedov analysis implies about 50 solar masses in both swept-up shells, SNR ages between 10,000 and 15,000 yr, low (< 0.05 cm^-3) preshock densities, and subluminous explosions with energies of 3x10^50 ergs. The central Fe-rich supernova ejecta are close to collisional ionization equilibrium. Their presence is unexpected, because standard Type Ia SNR models predict faint ejecta emission with short ionization ages. Both SNRs belong to a previously unrecognized class of Type Ia SNRs characterized by bright interior emission. Denser than expected ejecta and/or a dense circumstellar medium around the progenitors are required to explain the presence of Fe-rich ejecta in these SNRs. Substantial amounts of circumstellar gas are more likely to be present in explosions of more massive Type Ia progenitors. DEM L238, DEM L249, and similar SNRs could be remnants of ``prompt'' Type Ia explosions with young (~100 Myr old) progenitors.Comment: 24 pages, 8 figures, ApJ, in pres

The Earliest Optical Observations of GRB 030329

We present the earliest optical imaging observations of GRB 030329 related to SN 2003dh. The burst was detected by the HETE-2 satellite at 2003 March 29, 11:37:14.67 UT. Our wide-field monitoring started 97 minutes before the trigger and the burst position was continuously observed. We found no precursor or contemporaneous flare brighter than $V=5.1$ ($V=5.5$) in 32 s (64 s) timescale between 10:00 and 13:00 UT. Follow-up time series photometries started at 12:51:39 UT (75 s after position notice through the GCN) and continued for more than 5 hours. The afterglow was $Rc= 12.35\pm0.07$ at $t=74$ min after burst. Its fading between 1.2 and 6.3 hours is well characterized by a single power-law of the form $f{\rm(mJy)} = (1.99\pm0.02{\rm (statistic)}\pm0.14{\rm (systematic)}) \times (t/1 {\rm day})^{-0.890\pm 0.006 {\rm (statistic)}\pm 0.010 {\rm (systematic)}}$ in $Rc$-band. No significant flux variation was detected and upper limits are derived as $(\Delta f/f)_{\rm RMS} = 3-5$% in minutes to hours timescales and $(\Delta f/f)_{\rm RMS} = 35-5$% in seconds to minutes timescales. Such a featureless lightcurve is explained by the smooth distribution of circumburst medium. Another explanation is that the optical band was above the synchrotron cooling frequency where emergent flux is insensitive to the ambient density contrasts. Extrapolation of the afterglow lightcurve to the burst epoch excludes the presence of an additional flare component at $t<10$ minutes as seen in GRB 990123 and GRB 021211.Comment: ApJL, in pres

Berberine Overcomes Gemcitabine-Associated Chemoresistance through Regulation of Rap1/PI3K-Akt Signaling in Pancreatic Ductal Adenocarcinoma

Gemcitabine (Gem)-based chemotherapy is one of the first-line treatments for pancreatic ductal adenocarcinoma (PDAC). However, its clinical effect is limited due to development of chemoresistance. Various naturally occurring compounds, including Berberine (BBR), provide an anti-cancer efficacy with time-tested safety, individually and in combination with chemotherapeutic drugs. Accordingly, we hypothesized that BBR might enhance the chemosensitivity to Gem in PDAC. In this study, cell culture studies using MIA PaCa-2 and BxPC-3 cells, followed by analysis in patient-derived organoids were performed to evaluate the anti-cancer effects of BBR in PDAC. Considering that cancer is a significant manifestation of increased chronic inflammatory stress, systems biology approaches are prudent for the identification of molecular pathways and networks responsible for phytochemical-induced anti-cancer activity, we used these approaches for BBR-mediated chemosensitization to Gem. Firstly, Gem-resistant (Gem-R) PDAC cells were established, and the combination of BBR and Gem revealed superior anti-cancer efficacy in Gem-R cells. Furthermore, the combination treatment induced cell cycle arrest and apoptosis in Gem-R PDAC cells. Transcriptomic profiling investigated the Rap1 and PI3K-Akt signaling pathway as a key regulator of Gem-resistance and was a key mediator for BBR-mediated chemosensitization in PDAC cells. All cell culture-based findings were successfully validated in patient-derived organoids. In conclusion, we demonstrate that BBR-mediated reversal of chemoresistance to Gem manifests through Rap1/PI3K-Akt signaling in PDAC