Comet C/2012 S1 (ISON): Observations of the Dust Grains from SOFIA and of the Atomic Gas from NSO Dunn and McMath-Pierce Solar Telescopes (Invited)

Comet C/2012 S1 (ISON) is unique in that it is a dynamically new comet derived from the Oort cloud reservoir of comets with a sun-grazing orbit. Infrared (IR) and visible wavelength observing campaigns were planned on NASA's Stratospheric Observatory For Infrared Astronomy (SOFIA) and on National Solar Observatory Dunn (DST) and McMath-Pierce Solar Telescopes, respectively. We highlight our early results. SOFIA (+FORCAST [1]) mid- to far-IR images and spectroscopy (~5-35 μm) of the dust in the coma of ISON are to be obtained by the ISON-SOFIA Team during a flight window 2013 Oct 21-23 UT (r_h≈1.18 AU). Dust characteristics, identified through the 10 μm silicate emission feature and its strength [2], as well as spectral features from cometary crystalline silicates (Forsterite) at 11.05-11.2 μm, and near 16, 19, 23.5, 27.5, and 33 μm are compared with other Oort cloud comets that span the range of small and/or highly porous grains (e.g., C/1995 O1 (Hale-Bopp) [3,4,5] and C/2001 Q4 (NEAT) [6]) to large and/or compact grains (e.g., C/2007 N4 (Lulin) [7] and C/2006 P1 (McNaught) [8]). Measurement of the crystalline peaks in contrast to the broad 10 and 20 μm amorphous silicate features yields the cometary silicate crystalline mass fraction [9], which is a benchmark for radial transport in our protoplanetary disk [10]. The central wavelength positions, relative intensities, and feature asymmetries for the crystalline peaks may constrain the shapes of the crystals [11]. Only SOFIA can look for cometary organics in the 5-8 μm region. Spatially resolved measurements of atoms and simple molecules from when comet ISON is near the Sun (r_h<0.4 AU, near Nov-20--Dec-03 UT) were proposed for by the ISON-DST Team. Comet ISON is the first comet since comet Ikeya-Seki (1965f) [12,13] suitable for studying the alkalai metals Na and K and the atoms specifically attributed to dust grains including Mg, Si, Fe, as well as Ca. DST's Horizontal Grating Spectrometer (HGS) measures 4 settings: Na I, K, C2 to sample cometary organics (along with Mg I), and [O I] as a proxy for activity from water [14] (along with Si I and Fe I). State-of-the-art instruments that will also be employed include IBIS [15], which is a Fabry-Perot spectral imaging system that concurrently measures lines of Na, K, Ca II, or Fe, and ROSA (CSUN/QUB) [16], which is a rapid imager that simultaneously monitors Ca II or CN. From McMath-Pierce, the Solar-Stellar Spectrograph also will target ISON (320-900 nm, R~21,000, r_h

Large- and small-scale structure of the intermediate- and high-velocity clouds towards the LMC and SMC.

We employ Ca II K and Na I D interstellar absorption-line spectroscopy of early-type stars in the Large and Small Magellanic Clouds (LMC, SMC) to investigate the large- and small-scale structure in foreground intermediate- and high-velocity clouds (I/HVCs). Data include FLAMES-GIRAFFE Ca II K observations of 403 stars in four open clusters, plus FEROS or UVES spectra of 156 stars in the LMC and SMC. The FLAMES observations are amongst the most extensive probes to date of Ca II structures on ∼20 arcsec scales in Magellanic I/HVCs. From the FLAMES data within a 0 ∘.∘.∘.5 field of view, the Ca II K equivalent width in the I/HVC components towards three clusters varies by factors of ≥10. There are no detections of molecular gas in absorption at intermediate or high velocities, although molecular absorption is present at LMC and Galactic velocities towards some sightlines. The FEROS/UVES data show Ca II K I/HVC absorption in ∼60 per cent of sightlines. The range in the Ca II/Na I ratio in I/HVCs is from –0.45 to +1.5 dex, similar to previous measurements for I/HVCs. In 10 sightlines we find Ca II/O I ratios in I/HVC gas ranging from 0.2 to 1.5 dex below the solar value, indicating either dust or ionization effects. In nine sightlines I/HVC gas is detected in both H I and Ca II at similar velocities, implying that the two elements form part of the same structure.

The vascular targeting agent combretastatin-A4 and a novel cis-Restricted {beta}-Lactam Analogue, CA-432, induce apoptosis in human chronic myeloid leukemia cells and ex vivo patient samples including those displaying multidrug resistance

Combretastatin-A4 (CA-4) is a natural derivative of the African willow tree Combretum caffrum. CA-4 is one of the most potent antimitotic components of natural origin, but it is, however, intrinsically unstable. A novel series of CA-4 analogs incorporating a 3,4-diaryl-2-azetidinone (β-lactam) ring were designed and synthesized with the objective to prevent cis -trans isomerization and improve the intrinsic stability without altering the biological activity of CA-4. Evaluation of selected β-lactam CA-4 analogs demonstrated potent antitubulin, antiproliferative, and antimitotic effects in human leukemia cells. A lead β-lactam analog, CA-432, displayed comparable antiproliferative activities with CA-4. CA-432 induced rapid apoptosis in HL-60 acute myeloid leukemia cells, which was accompanied by depolymerization of the microtubular network, poly(ADP-ribose) polymerase cleavage, caspase-3 activation, and Bcl-2 cleavage. A prolonged G(2)M cell cycle arrest accompanied by a sustained phosphorylation of mitotic spindle checkpoint protein, BubR1, and the antiapoptotic proteins Bcl-2 and Bcl-x(L) preceded apoptotic events in K562 chronic myeloid leukemia (CML) cells. Molecular docking studies in conjunction with comprehensive cell line data rule out CA-4 and β-lactam derivatives as P-glycoprotein substrates. Furthermore, both CA-4 and CA-432 induced significantly more apoptosis compared with imatinib mesylate in ex vivo samples from patients with CML, including those positive for the T315I mutation displaying resistance to imatinib mesylate and dasatinib. In summary, synthetic intrinsically stable analogs of CA-4 that display significant clinical potential as antileukemic agents have been designed and synthesized.

Adaptor protein-2 sigma subunit mutations causing familial hypocalciuric hypercalcaemia type 3 (FHH3) demonstrate genotype-phenotype correlations, codon bias and dominant-negative effects

The adaptor protein-2 sigma subunit (AP2sigma;2) is pivotal for clathrin-mediated endocytosis of plasma membrane constituents such as the calcium-sensing receptor (CaSR). Mutations of the AP2sigma;2 Arg15 residue result in familial hypocalciuric hypercalcaemia type 3 (FHH3), a disorder of extracellular calcium (Ca&lt;inf>o</inf>²⁺) homeostasis. To elucidate the role of AP2sigma;2 in Ca&lt;inf>o</inf>²⁺ regulation, we investigated 65 FHH probands, without other FHH-associated mutations, for AP2sigma;2 mutations, characterized their functional consequences and investigated the genetic mechanisms leading to FHH3. AP2sigma;2 mutations were identified in 17 probands, comprising 5 Arg15Cys, 4 Arg15His and 8 Arg15Leu mutations. A genotype-phenotype correlation was observed with the Arg15Leu mutation leading to marked hypercalcaemia. FHH3 probands harboured additional phenotypes such as cognitive dysfunction. All three FHH3-causing AP2sigma;2 mutations impaired CaSR signal transduction in a dominant-negative manner. Mutational bias was observed at the AP2sigma;2 Arg15 residue as other predicted missense substitutions (Arg15Gly, Arg15Pro and Arg15Ser), which also caused CaSR loss-of-function, were not detected in FHH probands, and these mutations were found to reduce the numbers of CaSR-expressing cells. FHH3 probands had significantly greater serum calcium (sCa) and magnesium (sMg) concentrations with reduced urinary calcium to creatinine clearance ratios (CCCR) in comparison with FHH1 probands with CaSR mutations, and a calculated index of sCa × sMg/100 × CCCR, which was ≥ 5.0, had a diagnostic sensitivity and specificity of 83 and 86%, respectively, for FHH3. Thus, our studies demonstrate AP2sigma;2 mutations to result in a more severe FHH phenotype with genotype-phenotype correlations, and a dominant-negative mechanism of action with mutational bias at the Arg15 residue.

Expression of proteins associated with hypoxia and Wnt pathway activation is of prognostic significance in hepatocellular carcinoma

In the development and progression of hepatocellular carcinoma, tumor hypoxia plays an important role, as does activation of the Wnt pathway. The aim of this study was to characterize the expression and interrelationship between hypoxia and Wnt-pathway-associated proteins as prognostic factors for hepatocellular carcinoma. Expression of HIF-1α, CA-IX, E-cadherin, β-catenin, and Ki-67 was assessed by immunohistochemistry in 179 primary hepatocellular carcinoma cases. Univariate and multivariate analyses were performed to assess the relationship between the clinicopathological factors, protein expression, overall survival (OS), and recurrence-free survival (RFS). By univariate analysis, tumor stage, size, satellitosis, and vascular invasion were confirmed as prognostic factors for worse OS and RFS. High expression of HIF-1α, CA-IX, β-catenin, Ki-67, and E-cadherin was observed in 60, 15, 64, 8, and 64 % of tumors, respectively, and this was significantly associated with poor OS. CA-IX, HIF-1α, and E-cadherin were independent predictors of poor prognosis. We stratified 169 patients into four groups according to the expression level of hypoxia and Wnt pathway markers. The group with high expression of both hypoxia and Wnt-pathway-associated proteins showed worst OS. The poor survival of this group was also significant in patients with early stage disease and tumor size of less than 5 cm (p < 0.05). We identified a subgroup of hepatocellular carcinoma patients with high expression of both hypoxia and Wnt pathway proteins and found this predictive of poor survival. The therapeutic options for this group might need to be revisited.

CaII K interstellar observations towards early-type disc and halo stars

We present high-resolution (R = lambda/Deltalambda similar to 40 000) Ca II K interstellar observations (lambda(air) = 3933.66Angstrom) towards 88 mainly B-type stars, of which 74 are taken from the Edinburgh-Cape or Palomar-Green surveys, and 81 have > 25degrees. The majority of the data come from previously existing spectroscopy, although also included are 18 new observations of stars with echelle spectra taken with UVES on the Very Large Telescope UT2 (Kueyen). Some 49 of the sample stars have distance estimates above the Galactic plane (z) greater than or equal to 1 kpc, and are thus good probes of the halo interstellar medium. Of the 362 interstellar Ca K components that we detect, 75 (21 per cent) have absolute values of their LSR velocity values exceeding 40 km s(-1). In terms of the deviation velocity for the sightlines with distance estimates, 46/273 (17 per cent) of components have velocity values exceeding those predicted by standard Galactic rotation by more than 40 km s(-1). Combining this data set with previous observations, we find that the median value of the reduced equivalent width (REW) of stars with z greater than or equal to 1 kpc (EW x sin ) is similar to 115 mAngstrom (n = 80), similar to that observed in extragalactic sightlines by Bowen. Using data of all z distances, the REW at infinity is found to be similar to 130 mAngstrom, with the scaleheight (1) of the Ca II K column density distribution being;z 800 pc (n = 196) and reduced column density at infinity of log[N(Ca II K) cm(-2)] similar to 12.24. This implies that similar to30 per cent of Ca II K absorption occurs at distances exceeding similar to1 kpc. For nine sightlines, with distance exceeding 1 kpc and with a companion object within 5degrees, we find that all but two have values of Ca II reduced equivalent width the same to within similar to20 per cent, when the REW of the nearest object is extrapolated to the distance of the further of the pair, and assuming 1 = 800 pc. For 29 of our sightlines with z greater than or equal to 1 kpc and a H I detection from the Leiden-Dwingeloo survey (beamsize of 0.5degrees), we find log(N(Ca II K)IN(H I)) ranging from -7.4 to - 8.4. Values of the Ca II K abundance relative to neutral hydrogen (log[N(Ca II K) cm(-2)] - log[N(H I) cm(-2)]) are found to be more than similar to0.5 dex higher in stars with distances exceeding approximate to100 pc, when compared with the (log[N(Ca II K) cm(-2)] -log[N(H-tot) cm(-2)]) values found in nearby sightlines such as those in Wakker & Mathis (2000). Finally, stellar Ca II K equivalent widths of the sample are determined for 26 objects.

Early-type stars observed in the ESO UVES Paranal Observatory Project - I. Interstellar NaIUV, TiII and CaIIKobservations

We present an analysis of interstellar NaI (lambda(air) = 3302.37 and 3302.98 angstrom), TiII (lambda(air) = 3383.76 angstrom) and CaII K (lambda(air) = 3933.66 angstrom) absorption features for 74 sightlines towards O- and B-type stars in the Galactic disc. The data were obtained from the Ultraviolet and Visual Echelle Spectrograph Paranal Observatory Project, at a spectral resolution of 3.75 km s(-1) and with mean signal-to-noise ratios per pixel of 260, 300 and 430 for the NaI, TiII and CaII observations, respectively. Interstellar features were detected in all but one of the TiII sightlines and all of the CaII sightlines. The dependence of the column density of these three species with distance, height relative to the Galactic plane, HI column density, reddening and depletion relative to the solar abundance has been investigated. We also examine the accuracy of using the NaI column density as an indicator of that for HI. In general, we find similar strong correlations for both Ti and Ca, and weaker correlations for Na. Our results confirm the general belief that Ti and Ca occur in the same regions of the interstellar medium ( ISM) and also that the TiII/CaII ratio is constant over all parameters. We hence conclude that the absorption properties of Ti and Ca are essentially constant under the general ISM conditions of the Galactic disc.

Evidence for two endothelin Et(A) receptor subtypes in rabbit arteriolar smooth muscle.

1. Effects of endothelin-1 (Et-1) were studied on membrane currents in choroidal arteriolar smooth muscle by using perforated patch-clamp recordings. 2. Et-1 (10 nM) activated oscillatory Ca(2+)-activated Cl(-)-currents (I(Cl(Ca))) which could not be reversed by washing out. 3. Currents through L-type Ca(2+) channels were resolved in a divalent free medium (I(Ca(L)Na)). Et-1 reduced I(Ca(L)Na) by 75 +/- 7% within 30 s and this effect faded over 5 min, when the depression remained constant. On washing out Et-1, I(Ca(L)Na) almost completely recovered within 10 s. 4. BQ123 (1 microM), a peptide Et(A) receptor blocker, prevented the activation of I(Cl(Ca)), but failed to inhibit I(Cl(Ca)) transients once they had been initiated. In contrast, BQ123 not only prevented but also reversed the inhibition of I(Ca(L)Na) by Et-1. BQ788 (1 microM), an Et(B) receptor antagonist, did not prevent the activation of I(Cl(Ca)) or the inhibition of I(Ca(L)Na) by Et-1. 5. ABT-627 (10 nM), a non-peptide Et(A) receptor antagonist also blocked the activation of I(Cl(Ca)). However, on I(Ca(L)Na), ABT-627 (10 nM) mimicked the action of Et-1 an effect blocked by BQ123 suggesting that ABT-627 acted as an agonist. 6. The data are consistent with choroidal arteriolar smooth muscle cells having two types of Et(A) receptor, one where BQ123 is an antagonist and ABT-627 an agonist, where ligands dissociate freely and this receptor is coupled to inhibition of L-type Ca(2+) channels. In the other, BQ123 and ABT-627 are both antagonists and with Et-1 the receptor converts to a high affinity state producing the classical irreversible activation I(Cl(Ca)).

SN 2008S: an electron-capture SN from a super-AGB progenitor?

We present comprehensive photometric and spectroscopic observations of the faint transient SN 2008S discovered in the nearby galaxy NGC 6946. SN 2008S exhibited slow photometric evolution and almost no spectral variability during the first nine months, implying a long photon diffusion time and a high-density circumstellar medium. Its bolometric luminosity (similar or equal to 10(41) erg s(-1) at peak) is low with respect to most core-collapse supernovae but is comparable to the faintest Type II-P events. Our quasi-bolometric light curve extends to 300 d and shows a tail phase decay rate consistent with that of Co-56. We propose that this is evidence for an explosion and formation of Ni-56 (0.0014 +/- 0.0003 M-circle dot). Spectra of SN 2008S show intense emission lines of H alpha, [Ca II] doublet and Ca II near-infrared (NIR) triplet, all without obvious P-Cygni absorption troughs. The large mid-infrared (MIR) flux detected shortly after explosion can be explained by a light echo from pre-existing dust. The late NIR flux excess is plausibly due to a combination of warm newly formed ejecta dust together with shock-heated dust in the circumstellar environment. We reassess the progenitor object detected previously in Spitzer archive images, supplementing this discussion with a model of the MIR spectral energy distribution. This supports the idea of a dusty, optically thick shell around SN 2008S with an inner radius of nearly 90 AU and outer radius of 450 AU, and an inferred heating source of 3000 K. The luminosity of the central star is L similar or equal to 10(4.6) L-circle dot. All the nearby progenitor dust was likely evaporated in the explosion leaving only the much older dust lying further out in the circumstellar environment. The combination of our long-term multiwavelength monitoring data and the evidence from the progenitor analysis leads us to support the scenario of a weak electron-capture supernova explosion in a super-asymptotic giant branch progenitor star (of initial mass 6-8 M-circle dot) embedded within a thick circumstellar gaseous envelope. We suggest that all of main properties of the electron-capture SN phenomenon are observed in SN 2008S and future observations may allow a definitive answer.

Diabetes downregulates large-conductance Ca2+-activated potassium beta 1 channel subunit in retinal arteriolar smooth muscle

Retinal vasoconstriction and reduced retinal blood flow precede the onset of diabetic retinopathy. The pathophysiological mechanisms that underlie increased retinal arteriolar tone during diabetes remain unclear. Normally, local Ca(2+) release events (Ca(2+)-sparks), trigger the activation of large-conductance Ca(2+)-activated K(+)(BK)-channels which hyperpolarize and relax vascular smooth muscle cells, thereby causing vasodilatation. In the present study, we examined BK channel function in retinal vascular smooth muscle cells from streptozotocin-induced diabetic rats. The BK channel inhibitor, Penitrem A, constricted nondiabetic retinal arterioles (pressurized to 70mmHg) by 28%. The BK current evoked by caffeine was dramatically reduced in retinal arterioles from diabetic animals even though caffeine-evoked [Ca(2+)](i) release was unaffected. Spontaneous BK currents were smaller in diabetic cells, but the amplitude of Ca(2+)-sparks was larger. The amplitudes of BK currents elicited by depolarizing voltage steps were similar in control and diabetic arterioles and mRNA expression of the pore-forming BKalpha subunit was unchanged. The Ca(2+)-sensitivity of single BK channels from diabetic retinal vascular smooth muscle cells was markedly reduced. The BKbeta1 subunit confers Ca(2+)-sensitivity to BK channel complexes and both transcript and protein levels for BKbeta1 were appreciably lower in diabetic retinal arterioles. The mean open times and the sensitivity of BK channels to tamoxifen were decreased in diabetic cells, consistent with a downregulation of BKbeta1 subunits. The potency of blockade by Pen A was lower for BK channels from diabetic animals. Thus, changes in the molecular composition of BK channels could account for retinal hypoperfusion in early diabetes, an idea having wider implications for the pathogenesis of diabetic hypertension.

Optimization by quantum annealing: Lessons from simple cases

We investigate the basic behavior and performance of simulated quantum annealing (QA) in comparison with classical annealing (CA). Three simple one-dimensional case study systems are considered: namely, a parabolic well, a double well, and a curved washboard. The time-dependent Schrodinger evolution in either real or imaginary time describing QA is contrasted with the Fokker-Planck evolution of CA. The asymptotic decrease of excess energy with annealing time is studied in each case, and the reasons for differences are examined and discussed. The Huse-Fisher classical power law of double-well CA is replaced with a different power law in QA. The multiwell washboard problem studied in CA by Shinomoto and Kabashima and leading classically to a logarithmic annealing even in the absence of disorder turns to a power-law behavior when annealed with QA. The crucial role of disorder and localization is briefly discussed.

SN 2009ip at late times - an interacting transient at+2 years

We present photometric and spectroscopic observations of the interacting transient SN 2009ip taken during the 2013 and 2014 observing seasons. We characterize the photometric evolution as a steady and smooth decline in all bands, with a decline rate that is slower than expected for a solely Co-56-powered supernova at late phases. No further outbursts or eruptions were seen over a two year period from 2012 December until 2014 December. SN 2009ip remains brighter than its historic minimum from pre-discovery images. Spectroscopically, SN 2009ip continues to be dominated by strong, narrow (less than or similar to 2000 km s(-1)) emission lines of H, He, Ca, and Fe. While we make tenuous detections of [Fe II] lambda 7155 and [O I] lambda lambda 6300, 6364 lines at the end of 2013 June and the start of 2013 October, respectively, we see no strong broad nebular emission lines that could point to a core-collapse origin. In general, the lines appear relatively symmetric, with the exception of our final spectrum in 2014 May, when we observe the appearance of a redshifted shoulder of emission at +550 km s(-1). The lines are not blueshifted, and we see no significant near-or mid-infrared excess. From the spectroscopic and photometric evolution of SN 2009ip until 820 d after the start of the 2012a event, we still see no conclusive evidence for core-collapse, although whether any such signs could be masked by ongoing interaction is unclear.

Catchment and in-stream influences on metal concentration and ochre deposit density in upland streams, Northern Ireland

Metal concentrations from stream waters in two geological blocks in Northern Ireland were compared to determine the contributions of catchment characteristics and in-stream conditions. One block is composed of metamorphosed schist and unconsolidated glacial drift with peat or peaty podzol (mainly humic) soils, while the other block consists of tertiary basalt with brown earth and gley soils. Water samples were collected from 52 stream sites and analysed for Fe, Mn and Al as well as a range of other chemical determinands known to affect metal solubility. Densities of metal-rich ochre deposit were determined for stream bed stone samples. Higher conductivities and concentrations of bicarbonate, alkalinity, Ca and Mg occurred on basalt than on schist. Despite higher Fe and Mn oxide concentrations in basalt-derived non-humic soils, stream water concentrations were much lower and ochre deposit densities only one third of those on schist overlain by humic soils. Neither rock nor soil type predicted Al concentrations, but pH and dissolved oxygen did. Peat-generated acidity and the limited acid neutralising capacity of base-poor metamorphosed schist have resulted in elevated concentrations of metals and ochre deposit in surface waters.