Genetic aberrations of c-myc and CCND1 in the development of invasive bladder cancer

Detrusor muscle invasive transitional cell carcinoma is associated with poor prognosis and is responsible for the majority of bladder cancer related deaths. Amplifications of c-myc and CCND1 are associated with detrusor-muscle-invasive transitional cell carcinoma, however, their precise role in driving disease progression is unclear. Fluorescence in situ hybridisation on archival tissue from 16 patients with primary diagnosis of ⩾pT2 transitional cell carcinoma and 15 cases with primary pTa/pT1 disease subsequently progressing to detrusor-muscle-invasion was performed, in the latter group both pre and post muscle invasive events were studied. No patients presenting with ⩾pT2 had amplification of c-myc, two out of 16 (12.5%) had CCND1 amplification. Of patients who developed ⩾pT2, two out of 15 (13.3%) had amplification of c-myc, both in ⩾pT2, five out of 15 (33.3%) had CCND1 amplification, two in pTa/pT1 tumours, three in ⩾pT2 transitional cell carcinomas. In total, two out of 31 (6.5%) of patients' ⩾pT2 TCCs were amplified for c-myc and six out of 31 (19%) were amplified for CCND1. Eighty-seven per cent (40 out of 46) of tumours were polysomic for chromosome 8 and 80% (37 out of 46) were polysomic for chromosome 11 and this reflected the high copy numbers of c-myc and CCND1 observed. In almost all cases an increase in c-myc/CCND1 copy number occurred prior to invasion and persisted in advanced disease. Amplification of CCND1 or alterations in c-myc/CCND1 early in bladder cancer may have clinical relevance in promoting and predicting progression to detrusor-muscle-invasive transitional cell carcinoma

PSRs J0248+6021 and J2240+5832: Young Pulsars in the Northern Galactic Plane. Discovery, Timing, and Gamma-ray observations

Pulsars PSR J0248+6021 (rotation period P=217 ms and spin-down power Edot = 2.13E35 erg/s) and PSR J2240+5832 (P=140 ms, Edot = 2.12E35 erg/s) were discovered in 1997 with the Nancay radio telescope during a northern Galactic plane survey, using the Navy-Berkeley Pulsar Processor (NBPP) filter bank. GeV gamma-ray pulsations from both were discovered using the Fermi Large Area Telescope. Twelve years of radio and polarization data allow detailed investigations. The two pulsars resemble each other both in radio and in gamma-ray data. Both are rare in having a single gamma-ray pulse offset far from the radio peak. The high dispersion measure for PSR J0248+6021 (DM = 370 pc cm^-3) is most likely due to its being within the dense, giant HII region W5 in the Perseus arm at a distance of 2 kpc, not beyond the edge of the Galaxy as obtained from models of average electron distributions. Its high transverse velocity and the low magnetic field along the line-of-sight favor this small distance. Neither gamma-ray, X-ray, nor optical data yield evidence for a pulsar wind nebula surrounding PSR J0248+6021. The gamma-ray luminosity for PSR J0248+6021 is L_ gamma = (1.4 \pm 0.3)\times 10^34 erg/s. For PSR J2240+5832, we find either L_gamma = (7.9 \pm 5.2) \times 10^34 erg/s if the pulsar is in the Outer arm, or L_gamma = (2.2 \pm 1.7) \times 10^34 erg/s for the Perseus arm. These luminosities are consistent with an L_gamma ~ sqrt(Edot) rule. Comparison of the gamma-ray pulse profiles with model predictions, including the constraints obtained from radio polarization data, favor emission in the far magnetosphere. These two pulsars differ mainly in their inclination angles and acceleration gap widths, which in turn explains the observed differences in the gamma-ray peak widths.Comment: 13 pages, Accepted to Astronomy & Astrophysic

HER2/neu overexpression in the development of muscle-invasive transitional cell carcinoma of the bladder

The mortality from transitional cell carcinoma (TCC) of the urinary bladder increases significantly with the progression of superficial or locally invasive disease (pTa/pT1) to detrusor muscle-invasive disease (pT2+). The most common prognostic markers in clinical use are tumour stage and grade, which are subject to considerable intra- and interobserver variation. Polysomy 17 and HER2/neu gene amplification and protein overexpression have been associated with more advanced disease. Standardised techniques of fluorescence in situ hybridisation and immunohistochemistry, which are currently applied to other cancers with a view to offering anti-HER2/neu therapies, were applied to tumour pairs comprising pre- and postinvasive disease from 25 patients undergoing treatment for bladder cancer. In the preinvasive tumours, increased HER2/neu copy number was observed in 76% of cases and increased chromosome 17 copy number in 88% of cases, and in the postinvasive group these values were 92 and 96%, respectively (not significantly different P=0.09 and 0.07, respectively). HER2 gene amplification rates were 8% in both groups. Protein overexpression rates were 76 and 52%, respectively, in the pre- and postinvasive groups (P=0.06). These results suggest that HER2/neu abnormalities occur prior to and persist with the onset of muscle-invasive disease. Gene amplification is uncommon and other molecular mechanisms must account for the high rates of protein overexpression. Anti-HER2/neu therapy might be of use in the treatment of TCC

A Sleep to Remember: The Effects of Sleep on Memory.

For centuries, the functions of sleep have been researched. Multiple theories have been developed, but even now, scientists are unable to produce a conclusive explanation as to why we sleep. It is evident that sleep is vital, as even in animals, it has been argued that sleep deprivation leads to serious consequences. More recently, research has suggested that sleep plays a role in memory consolidation. This review aims to bring together the evidence concerning the link between sleep and different memory sub-classifications (episodic memory, semantic memory, procedural memory and conditioning) and its potential clinical application will be discussed

Pulsed Gamma Rays from the Original Millisecond and Black Widow Pulsars: a case for Caustic Radio Emission?

We report the detection of pulsed gamma-ray emission from the fast millisecond pulsars (MSPs) B1937+21 (also known as J1939+2134) and B1957+20 (J1959+2048) using 18 months of survey data recorded by the \emph{Fermi} Large Area Telescope (LAT) and timing solutions based on radio observations conducted at the Westerbork and Nan\c{c}ay radio telescopes. In addition, we analyzed archival \emph{RXTE} and \emph{XMM-Newton} X-ray data for the two MSPs, confirming the X-ray emission properties of PSR B1937+21 and finding evidence ($\sim 4\sigma$) for pulsed emission from PSR B1957+20 for the first time. In both cases the gamma-ray emission profile is characterized by two peaks separated by half a rotation and are in close alignment with components observed in radio and X-rays. These two pulsars join PSRs J0034-0534 and J2214+3000 to form an emerging class of gamma-ray MSPs with phase-aligned peaks in different energy bands. The modeling of the radio and gamma-ray emission profiles suggests co-located emission regions in the outer magnetosphere.Comment: Accepted for publication in the Astrophysical Journa

Fermi LAT observations of the Geminga pulsar

We report on the \textit{Fermi}-LAT observations of the Geminga pulsar, the second brightest non-variable GeV source in the $\gamma$-ray sky and the first example of a radio-quiet $\gamma$-ray pulsar. The observations cover one year, from the launch of the $Fermi$ satellite through 2009 June 15. A data sample of over 60,000 photons enabled us to build a timing solution based solely on $\gamma$ rays. Timing analysis shows two prominent peaks, separated by $\Delta \phi$ = 0.497 $\pm$ 0.004 in phase, which narrow with increasing energy. Pulsed $\gamma$ rays are observed beyond 18 GeV, precluding emission below 2.7 stellar radii because of magnetic absorption. The phase-averaged spectrum was fitted with a power law with exponential cut-off of spectral index $\Gamma$ = (1.30 $\pm$ 0.01 $\pm$ 0.04), cut-off energy $E_{0}$ = (2.46 $\pm$ 0.04 $\pm$ 0.17) GeV and an integral photon flux above 0.1 GeV of (4.14 $\pm$ 0.02 $\pm$ 0.32) $\times$ 10$^{-6}$ cm$^{-2}$ s$^{-1}$. The first uncertainties are statistical and the second are systematic. The phase-resolved spectroscopy shows a clear evolution of the spectral parameters, with the spectral index reaching a minimum value just before the leading peak and the cut-off energy having maxima around the peaks. Phase-resolved spectroscopy reveals that pulsar emission is present at all rotational phases. The spectral shape, broad pulse profile, and maximum photon energy favor the outer magnetospheric emission scenarios.Comment: 32 pages, 12 figures, 3 tables. Accepted for publication in The Astrophysical Journal. Corresponding authors: Denis Dumora ([email protected]), Fabio Gargano ([email protected]), Massimiliano Razzano ([email protected]

PSR J1907+0602: A Radio-Faint Gamma-Ray Pulsar Powering a Bright TeV Pulsar Wind Nebula

We present multiwavelength studies of the 106.6 ms gamma-ray pulsar PSR J1907+06 near the TeV source MGRO J1908+06. Timing observations with Fermi result in a precise position determination for the pulsar of R.A. = 19h07m547(2), decl. = +06:02:16(2) placing the pulsar firmly within the TeV source extent, suggesting the TeV source is the pulsar wind nebula of PSR J1907+0602. Pulsed gamma-ray emission is clearly visible at energies from 100 MeV to above 10 GeV. The phase-averaged power-law index in the energy range E > 0.1 GeV is = 1.76 \pm 0.05 with an exponential cutoff energy E_{c} = 3.6 \pm 0.5 GeV. We present the energy-dependent gamma-ray pulsed light curve as well as limits on off-pulse emission associated with the TeV source. We also report the detection of very faint (flux density of ~3.4 microJy) radio pulsations with the Arecibo telescope at 1.5 GHz having a dispersion measure DM = 82.1 \pm 1.1 cm^{-3}pc. This indicates a distance of 3.2 \pm 0.6 kpc and a pseudo-luminosity of L_{1400} ~ 0.035 mJy kpc^2. A Chandra ACIS observation revealed an absorbed, possibly extended, compact <(4 arcsec) X-ray source with significant non-thermal emission at R.A. = 19h07m54.76, decl. = +06:02:14.6 with a flux of 2.3^{+0.6}_{-1.4} X 10^{-14} erg cm^{-2} s^{-1}. From archival ASCA observations, we place upper limits on any arcminute scale 2--10 keV X-ray emission of ~ 1 X 10^{-13} erg cm^{-2} s^{-1}. The implied distance to the pulsar is compatible with that of the supernova remnant G40.5-0.5, located on the far side of the TeV nebula from PSR J1907+0602, and the S74 molecular cloud on the nearer side which we discuss as potential birth sites

Fermi Large Area Telescope Observations of the Crab Pulsar and Nebula

We report on gamma-ray observations of the Crab Pulsar and Nebula using 8 months of survey data with the Fermi Large Area Telescope (LAT). The high quality light curve obtained using the ephemeris provided by the Nancay and Jodrell Bank radio telescopes shows two main peaks stable in phase with energy. The first gamma-ray peak leads the radio main pulse by (281 \pm 12 \pm 21) mus, giving new constraints on the production site of non-thermal emission in pulsar magnetospheres. The improved sensitivity and the unprecedented statistics afforded by the LAT enable precise measurement of the Crab Pulsar spectral parameters: cut-off energy at E_c = (5.8 \pm 0.5 \pm 1.2) GeV, spectral index of Gamma = (1.97 \pm 0.02 \pm 0.06) and integral photon flux above 100 MeV of (2.09 \pm 0.03 \pm 0.18) x 10^{-6} cm^{-2} s^{-1}. The first errors represent the statistical error on the fit parameters, while the second ones are the systematic uncertainties. Pulsed gamma-ray photons are observed up to ~ 20 GeV which precludes emission near the stellar surface, below altitudes of around 4 to 5 stellar radii in phase intervals encompassing the two main peaks. The spectrum of the nebula in the energy range 100 MeV - 300 GeV is well described by the sum of two power-laws of indices Gamma_{sync} = (3.99 \pm 0.12 \pm 0.08) and Gamma_{IC} = (1.64 \pm 0.05 \pm 0.07), corresponding to the falling edge of the synchrotron and the rising edge of the inverse Compton components, respectively. This latter, which links up naturally with the spectral data points of Cherenkov experiments, is well reproduced via inverse Compton scattering from standard Magnetohydrodynamics (MHD) nebula models, and does not require any additional radiation mechanism.Comment: 17 pages, 9 figures, Accepted for publications in Astrophysical Journa