Metabolism and growth inhibition of four retinoids in head and neck squamous normal and malignant cells

Isotretinoin (13- cis -retinoic acid, 13cRA) has proven to be active in chemoprevention of head and neck squamous cell carcinoma (HNSCC). Moreover, both all-trans-retinoic acid (ATRA) and 13cRA induce objective responses in oral premalignant lesions. After binding of retinoids to retinoic acid receptors (RARs and RXRs) dimers are formed that are able to regulate the expression of genes involved in growth and differentiation. We compared the metabolism and level of growth inhibition of 13cRA with that of ATRA, 9cRA and retinol in four HNSCC cell lines and normal oral keratinocyte cultures (OKC). These retinoid compounds are known to bind with different affinities to the retinoic acid receptors. We observed that all retinoids were similar with respect to their capacity to induce growth inhibition. One HNSCC line could be ranked as sensitive, one as moderately sensitive and the remaining two were totally insensitive; OKC were moderately sensitive. The rate at which the cells were able to catabolize the retinoid was similar for all compounds. Retinoid metabolism in HNSCC cells resulted in a profile of metabolites that was unique for each retinoid. These metabolic profiles were different in OKC. Our findings indicate that differences in retinoid receptor selectivity of these retinoids do not influence the level of growth inhibition and rate of metabolism. © 2001 Cancer Research Campaign http://www.bjcancer.co

In-situ spectroscopy of intrinsic Bi2Te3 topological insulator thin films and impact of extrinsic defects

Combined in-situ x-ray photoemission spectroscopy, scanning tunnelling spectroscopy and angle resolved photoemission spectroscopy of molecular beam epitaxy grown Bi2Te3 on lattice mismatched substrates reveal high quality stoichiometric thin films with topological surface states without a contribution from the bulk bands at the Fermi energy. The absence of bulk states at the Fermi energy is achieved without counter doping. We observe that the surface morphology and electronic band structure of Bi2Te3 are not affected by in-vacuo storage and exposure to oxygen, whereas major changes are observed when exposed to ambient conditions. These films help define a pathway towards intrinsic topological devices.Comment: 8 pages, 5 figure

The properties and polarization of the H2O and CH3OH maser environment of NGC7538-IRS1

NGC7538 is a complex massive star-forming region. The region is composed of several radio continuum sources, one of which is IRS1, a high-mass protostar, from which a 0.3 pc molecular bipolar outflow was detected. Several maser species have been detected around IRS1. The CH3OH masers have been suggested to trace a Keplerian-disk, while the H2O masers are almost aligned to the outflow. More recent results suggested that the region hosts a torus and potentially a disk, but with a different inclination than the Keplerian-disk that is supposed to be traced by the CH3OH masers. Tracing the magnetic field close to protostars is fundamental for determining the orientation of the disk/torus. Recent studies showed that during the protostellar phase of high-mass star formation the magnetic field is oriented along the outflows and around or on the surfaces of the disk/torus. The observations of polarized maser emissions at milliarcsecond resolution can make a crucial contribution to understanding the orientation of the magnetic field and, consequently, the orientation of the disk/torus in NGC7538-IRS1. The NRAO Very Long Baseline Array was used to measure the linear polarization and the Zeeman-splitting of the 22GHz H2O masers toward NGC7538-IRS1. The European VLBI Network and the MERLIN telescopes were used to measure the linear polarization and the Zeeman-splitting of the 6.7GHz CH3OH masers toward the same region. We detected 17 H2O masers and 49 CH3OH masers at high angular resolution. We detected linear polarization emission toward two H2O masers and toward twenty CH3OH masers. The CH3OH masers, most of which only show a core structure, seem to trace rotating and potentially infalling gas in the inner part of a torus. Significant Zeeman-splitting was measured in three CH3OH masers. [...] We also propose a new description of the structure of the NGC7538-IRS1 maser region.Comment: 13 pages, 9 figures, 4 Tables, accepted by Astronomy & Astrophysic

Vortex pinning by natural defects in thin films of YBa2Cu3O7−δ

Although vortex pinning in laser-ablated YBa2Cu3O7−δ films on (100) SrTiO3 is dominated by threading dislocations, many other natural pinning sites are present. To identify the contribution from twin planes, surface corrugations and point defects, we manipulate the relative densities of all defects by post-annealing films with various as-grown dislocation densities, ndisl. While a universal magnetic field B dependence of the transport current density js(B, T) is observed (independently of ndisl, temperature T and the annealing treatment), the defect structure changes considerably. Correlating the microstructure to js(B, T), it becomes clear that surface roughness, twins and point defects are not important at low magnetic fields compared to linear defect pinning. Transmission electron microscopy indicates that threading dislocations are not part of grain boundaries nor are they related to the twin domain structure. We conclude that js(B, T) is essentially determined by pinning along threading dislocations, naturally induced during the growth process. Even in high magnetic fields, where the vortex density outnumbers ndisl, it appears that linear defects stabilize the vortex lattice by means of the vortex–vortex interaction.

Strong Pinning in High Temperature Superconductors

Detailed measurements of the critical current density jc of YBa2Cu3O7 films grown by pulsed laser deposition reveal the increase of jc as function of the filmthickness. Both this thickness dependence and the field dependence of the critical current are consistently described using a generalization of the theory of strong pinning of Ovchinnikov and Ivlev [Phys. Rev. B 43, 8024 (1991)]. From the model, we deduce values of the defect density (10^21 m^-3) and the elementary pinning force, which are in good agreement with the generally accepted values for Y2O3-inclusions. In the absence of clear evidence that the critical current is determined by linear defects or modulations of the film thickness, our model provides an alternative explanation for the rather universal field dependence of the critical current density found in YBa2Cu3O7 films deposited by different methods.Comment: 11 pages; 8 Figures; Published Phys. Rev. B 66, 024523 (2002

Activation of Autophagy in a Rat Model of Retinal Ischemia following High Intraocular Pressure

Acute primary open angle glaucoma is an optic neuropathy characterized by the elevation of intraocular pressure, which causes retinal ischemia and neuronal death. Rat ischemia/reperfusion enhances endocytosis of both horseradish peroxidase (HRP) or fluorescent dextran into ganglion cell layer (GCL) neurons 24 h after the insult. We investigated the activation of autophagy in GCL-neurons following ischemia/reperfusion, using acid phosphatase (AP) histochemistry and immunofluorescence against LC3 and LAMP1. Retinal I/R lead to the appearance of AP-positive granules and LAMP1-positive vesicles 12 and 24 h after the insult, and LC3 labelling at 24 h, and induced a consistent retinal neuron death. At 48 h the retina was negative for autophagic markers. In addition, Western Blot analysis revealed an increase of LC3 levels after damage: the increase in the conjugated, LC3-II isoform is suggestive of autophagic activity. Inhibition of autophagy by 3-methyladenine partially prevented death of neurons and reduces apoptotic markers, 24 h post-lesion. The number of neurons in the GCL decreased significantly following I/R (I/R 12.21±1.13 vs controls 19.23±1.12 cells/500 µm); this decrease was partially prevented by 3-methyladenine (17.08±1.42 cells/500 µm), which potently inhibits maturation of autophagosomes. Treatment also prevented the increase in glial fibrillary acid protein immunoreactivity elicited by I/R. Therefore, targeting autophagy could represent a novel and promising treatment for glaucoma and retinal ischemia

Relating jet structure to photometric variability: the Herbig Ae star HD 163296

Herbig Ae/Be stars are intermediate-mass pre-main sequence stars surrounded by circumstellar dust disks. Some are observed to produce jets, whose appearance as a sequence of shock fronts (knots) suggests a past episodic outflow variability. This "jet fossil record" can be used to reconstruct the outflow history. We present the first optical to near-infrared (NIR) VLT/X-shooter spectra of the jet from the Herbig Ae star HD 163296. We determine physical conditions in the knots, as well as their kinematic "launch epochs". Knots are formed simultaneously on either side of the disk, with a regular interval of ~16 yr. The velocity dispersion versus jet velocity and the energy input are comparable in both lobes. However, the mass loss rate, velocity, and shock conditions are asymmetric. We find Mjet/Macc ~ 0.01-0.1, consistent with magneto-centrifugal jet launching models. No evidence for dust is found in the high-velocity jet, suggesting it is launched within the sublimation radius (<0.5 au). The jet inclination measured from proper motions and radial velocities confirms it is perpendicular to the disk. A tentative relation is found between the structure of the jet and the photometric variability of the source. Episodes of NIR brightening were previously detected and attributed to a dusty disk wind. We report for the first time significant optical fadings lasting from a few days up to a year, coinciding with the NIR brightenings. These are likely caused by dust lifted high above the disk plane; this supports the disk wind scenario. The disk wind is launched at a larger radius than the high-velocity atomic jet, although their outflow variability may have a common origin. No significant relation between outflow and accretion variability could be established. Our findings confirm that this source undergoes periodic ejection events, which may be coupled with dust ejections above the disk plane.Comment: 20 pages, 11 figures, accepted for publication in Astronomy & Astrophysic

Retinoid metabolism and all-trans retinoic acid-induced growth inhibition in head and neck squamous cell carcinoma cell lines.

Retinoids can reverse potentially premalignant lesions and prevent second primary tumours in patients with head and neck squamous cell carcinoma (HNSCC). Furthermore, it has been reported that acquired resistance to all-trans retinoic acid (RA) in leukaemia is associated with decreased plasma peak levels, probably the result of enhanced retinoid metabolism. The aim of this study was to investigate the metabolism of retinoids and relate this to growth inhibition in HNSCC. Three HNSCC cell lines were selected on the basis of a large variation in the all-trans RA-induced growth inhibition. Cells were exposed to 9.5 nM (radioactive) for 4 and 24 h, and to 1 and 10 microM (nonradioactive) all-trans RA for 4, 24, 48 and 72 h, and medium and cells were analysed for retinoid metabolites. At all concentrations studied, the amount of growth inhibition was proportional to the extent at which all-trans-, 13- and 9-cis RA disappeared from the medium as well as from the cells. This turnover process coincided with the formation of a group of as yet unidentified polar retinoid metabolites. The level of mRNA of cellular RA-binding protein II (CRABP-II), involved in retinoid homeostasis, was inversely proportional to growth inhibition. These findings indicate that for HNSCC retinoid metabolism may be associated with growth inhibition

On the Long Lasting “C‐Type” Structures in the Sodium Lidargram: The Lifetime of Kelvin‐Helmholtz Billows in the Mesosphere and Lower Thermosphere Region

In order to understand the characteristics of long‐lasting “C‐type” structure in the Sodium (Na) lidargram, six cases from different observational locations have been analyzed. The Na lidargram, collected from low‐, middle‐, and high‐latitude sites, show long lifetime of the C‐type structures which is believed to be the manifestation of Kelvin‐Helmholtz (KH) billows in the Mesosphere and Lower Thermosphere (MLT) region. In order to explore the characteristics of the long‐lasting C‐type structures, the altitude profile of square of Brunt‐Väisälä frequency in the MLT region has been derived using the temperature profile collected from the Na lidar instruments and the SABER instrument onboard TIMED satellite. It is found to be positive in the C‐type structure region for all the six cases which indicates that the regions are convectively stable. Simultaneous wind measurements, which allowed us to calculate the Richardson numbers and Reynolds numbers for three cases, suggest that the regions where the C‐type structure appeared were dynamically stable and nonturbulent. This paper brings out a hypothesis wherein the low temperature can increase the magnitude of the Prandtl number and convectively stable atmospheric region can cause the magnitude of Reynolds number to decrease. As a consequence, the remnant of previously generated KH billows in nearly “frozen‐in” condition can be advected through this conducive region to a different location by the background wind where they can sustain for a long time without much deformation. These long‐lived KH billows in the MLT region will eventually manifest the long‐lasting C‐type structures in the Na lidargram