Gene expression profiling in MDS and AML: potential and future avenues

Today, the classification systems for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) already incorporate cytogenetic and molecular genetic aberrations in an attempt to better reflect disease biology. However, in many MDS/AML patients no genetic aberrations have been identified yet, and even within some cytogenetically well-defined subclasses there is considerable clinical heterogeneity. Recent advances in genomics technologies such as gene expression profiling (GEP) provide powerful tools to further characterize myeloid malignancies at the molecular level, with the goal to refine the MDS/AML classification system, incorporating as yet unknown molecular genetic and epigenetic pathomechanisms, which are likely reflected by aberrant gene expression patterns. In this study, we provide a comprehensive review on how GEP has contributed to a refined molecular taxonomy of MDS and AML with regard to diagnosis, prediction of clinical outcome, discovery of novel subclasses and identification of novel therapeutic targets and novel drugs. As many challenges remain ahead, we discuss the pitfalls of this technology and its potential including future integrative studies with other genomics technologies, which will continue to improve our understanding of malignant transformation in myeloid malignancies and thereby contribute to individualized risk-adapted treatment strategies for MDS and AML patients. Leukemia (2011) 25, 909-920; doi:10.1038/leu.2011.48; published online 29 March 2011

Replication of EPHA1 and CD33 associations with late-onset Alzheimer’s disease: a multi-centre case-control study

A recently published genome-wide association study (GWAS) of late-onset Alzheimer's disease (LOAD) revealed genome-wide significant association of variants in or near MS4A4A, CD2AP, EPHA1 and CD33. Meta-analyses of this and a previously published GWAS revealed significant association at ABCA7 and MS4A, independent evidence for association of CD2AP, CD33 and EPHA1 and an opposing yet significant association of a variant near ARID5B. In this study, we genotyped five variants (in or near CD2AP, EPHA1, ARID5B, and CD33) in a large (2,634 LOAD, 4,201 controls), independent dataset comprising six case-control series from the USA and Europe. We performed meta-analyses of the association of these variants with LOAD and tested for association using logistic regression adjusted by age-at-diagnosis, gender, and APOE e4 dosage.

No Evidence that Extended Tracts of Homozygosity are Associated with Alzheimer’s Disease.

We sought to investigate the contribution of extended runs of homozygosity in a genome-wide association dataset of 1,955 Alzheimer's disease cases and 955 elderly screened controls genotyped for 529,205 autosomal single nucleotide polymorphisms. Tracts of homozygosity may mark regions inherited from a common ancestor and could reflect disease loci if observed more frequently in cases than controls. We found no excess of homozygous tracts in Alzheimer's disease cases compared to controls and no individual run of homozygosity showed association to Alzheimer's disease.

Correction for a possible reversible adsorption over an "inert" material

All TAP micro-reactor configurations contain inert particles which are used so that the catalyst zone can be maintained under isothermal conditions. Even on

SUPERNOVA 2009kf: AN ULTRAVIOLET BRIGHT TYPE IIP SUPERNOVA DISCOVERED WITH PAN-STARRS 1 AND GALEX

We present photometric and spectroscopic observations of a luminous Type IIP Supernova (SN) 2009kf discovered by the Pan-STARRS 1 (PS1) survey and also detected by the Galaxy Evolution Explorer. The SN shows a plateau in its optical and bolometric light curves, lasting approximately 70 days in the rest frame, with an absolute magnitude of M-V = - 18.4 mag. The P-Cygni profiles of hydrogen indicate expansion velocities of 9000 km s(-1) at 61 days after discovery which is extremely high for a Type IIP SN. SN 2009kf is also remarkably bright in the near-ultraviolet (NUV) and shows a slow evolution 10-20 days after optical discovery. The NUV and optical luminosity at these epochs can be modeled with a blackbody with a hot effective temperature (T similar to 16,000 K) and a large radius (R similar to 1 x 10(15) cm). The bright bolometric and NUV luminosity, the light curve peak and plateau duration, the high velocities, and temperatures suggest that 2009kf is a Type IIP SN powered by a larger than normal explosion energy. Recently discovered high-z SNe (0.7

SN 2009jf: a slow-evolving stripped-envelope core-collapse supernova

We present an extensive set of photometric and spectroscopic data for SN 2009jf, a nearby Type Ib supernova (SN), spanning from ˜20 d before B-band maximum to 1 yr after maximum. We show that SN 2009jf is a slowly evolving and energetic stripped-envelope SN and is likely from a massive progenitor (25-30 Msun). The large progenitor's mass allows us to explain the complete hydrogen plus helium stripping without invoking the presence of a binary companion. The SN occurred close to a young cluster, in a crowded environment with ongoing star formation. The spectroscopic similarity with the He-poor Type Ic SN 2007gr suggests a common progenitor for some SNe Ib and Ic. The nebular spectra of SN 2009jf are consistent with an asymmetric explosion, with an off-centre dense core. We also find evidence that He-rich Ib SNe have a rise time longer than other stripped-envelope SNe, however confirmation of this result and further observations are needed. This paper is based on observations with several telescopes, including NTT(184.D-1151), VLT-UT1(085.D-0750,386.D-0126), NOT, WHT, TNG, PROMPT, Ekar, Calar Alto and Liverpool Telescope.

The Yellow Supergiant Progenitor of the Type II Supernova 2011dh in M51

We present the detection of the putative progenitor of the Type IIb SN 2011dh in archival pre-explosion Hubble Space Telescope images. Using post-explosion Adaptive Optics imaging with Gemini NIRI+ALTAIR, the position of the supernova (SN) in the pre-explosion images was determined to within 23 mas. The progenitor candidate is consistent with an F8 supergiant star (logL/L sun = 4.92 ± 0.20 and T eff = 6000 ± 280 K). Through comparison with stellar evolution tracks, this corresponds to a single star at the end of core C-burning with an initial mass of M ZAMS = 13 ± 3 M sun. The possibility of the progenitor source being a cluster is rejected, on the basis of: (1) the source not being spatially extended, (2) the absence of excess Ha emission, and (3) the poor fit to synthetic cluster spectral energy distributions (SEDs). It is unclear if a binary companion is contributing to the observed SED, although given the excellent correspondence of the observed photometry to a single star SED we suggest that the companion does not contribute significantly. Early photometric and spectroscopic observations show fast evolution similar to the transitional Type IIb SN 2008ax and suggest that a large amount of the progenitor's hydrogen envelope was removed before explosion. Late-time observations will reveal if the yellow supergiant or the putative companion star were responsible for this SN explosion.

Abatement technologies for road surface run-off

Heavy metals, primarily zinc, copper, lead, and chromium, and Polycyclic Aromatic Hydrocarbons (PAHs) are the main hazardous constituents of road runoff. The main sources of these contaminants are vehicle emission, mostly through wear and leakage, although erosion of the road surface and de-icing salts are also recognised pollution sources. The bioavailability of these toxic compounds, and more importantly their potential biomagnification along food chains, could affect aquatic communities persistently exposed to road runoff. Several internationally approved abatement technologies are available for the management of road runoff on new motorway schemes. Recent studies conducted in Cork and Dublin, Ireland demonstrated the efficacy of infiltration trenches as abatement technologies in the removal of both heavy metals and PAHs prior to discharge; the technology was however inefficient in mitigating first flush events. Gully traps with sedimentation chambers, another technology investigated, demonstrated to have a substantially lower removal potential but appeared to be more effective in attenuating surges of contaminants attributed to first flush events. Consequently the employment of combined abatement techniques could efficiently minimise deviations from required effluent concentrations. The studies determined a relatively stationary accumulation of heavy metals and PAHs in sediments close to the point of discharge with a rapid decline in concentration in nearby downstream sediments (<50m). Further, Microtox® Solid Phase testing reported a negligible impact on assemblages exposed to contaminated sediments for all sites investigated. This paper describes pollutant loading from road runoff and mitigation measures from a freshwater deterioration in a water quality perspective. The results and analysis of field samples collected adjacent to a number of roads and motorways in Ireland is also presented. Finally sustainable drainage systems, abatement techniques and technologies available for onsite treatment of runoff are presented to improve and mitigate impacts of vehicular transport on the environment.

Comparison of the electron density measurements using Thomson scattering and emission spectroscopy for laser induced breakdown in one atmosphere of helium

Thomson scattering from laser-induced plasma in atmospheric helium was used to obtain temporally and spatially resolved electron temperature and density profiles. Electron density measurements at 5 s after breakdown are compared with those derived from the separation of the allowed and forbidden components of the 447.1 nm He I line. Plasma is created using 9 ns, 140 mJ pulses from Nd:YAG laser at 1064 nm. Electron densities of ~5 × 10 cm are in good agreement with Thomson scattering measurements, benchmarking this emission line as a useful diagnostic for high density plasmas. © 2011 American Institute of Physics.

Pan-STARRS1 DISCOVERY OF TWO ULTRALUMINOUS SUPERNOVAE AT(z) approximate to 0.9

We present the discovery of two ultraluminous supernovae (SNe) at z approximate to 0.9 with the Pan-STARRS1 Medium Deep Survey. These SNe, PS1-10ky and PS1-10awh, are among the most luminous SNe ever discovered, comparable to the unusual transients SN 2005ap and SCP 06F6. Like SN 2005ap and SCP 06F6, they show characteristic high luminosities (M-bol approximate to -22.5 mag), blue spectra with a few broad absorption lines, and no evidence for H or He. We have constructed a full multi-color light curve sensitive to the peak of the spectral energy distribution in the rest-frame ultraviolet, and we have obtained time series spectroscopy for these SNe. Given the similarities between the SNe, we combine their light curves to estimate a total radiated energy over the course of explosion of (0.9-1.4) x 10(51) erg. We find photospheric velocities of 12,000-19,000 km s(-1) with no evidence for deceleration measured across similar to 3 rest-frame weeks around light curve peak, consistent with the expansion of an optically thick massive shell of material. We show that, consistent with findings for other ultraluminous SNe in this class, radioactive decay is not sufficient to power PS1-10ky, and we discuss two plausible origins for these events: the initial spin-down of a newborn magnetar in a core-collapse SN, or SN shock breakout from the dense circumstellar wind surrounding a Wolf-Rayet star.

SN 2009md: another faint supernova from a low-mass progenitor

We present adaptive optics imaging of the core-collapse supernova (SN) 2009md, which we use together with archival Hubble Space Telescope data to identify a coincident progenitor candidate. We find the progenitor to have an absolute magnitude of V=-4.63+0.3-0.4 mag and a colour of V-I= 2.29+0.25-0.39 mag, corresponding to a progenitor luminosity of log L/L?similar to 4.54 +/- 0.19 dex. Using the stellar evolution code STARS, we find this to be consistent with a red supergiant progenitor with M= 8.5+6.5-1.5 M?. The photometric and spectroscopic evolution of SN 2009md is similar to that of the class of sub-luminous Type IIP SNe; in this paper we compare the evolution of SN 2009md primarily to that of the sub-luminous SN 2005cs. We estimate the mass of 56Ni ejected in the explosion to be (5.4 +/- 1.3) x 10-3 M? from the luminosity on the radioactive tail, which is in agreement with the low 56Ni masses estimated for other sub-luminous Type IIP SNe. From the light curve and spectra, we show the SN explosion had a lower energy and ejecta mass than the normal Type IIP SN 1999em. We discuss problems with stellar evolutionary models, and the discrepancy between low observed progenitor luminosities (log L/L?similar to 4.35 dex) and model luminosities after the second dredge-up for stars in this mass range, and consider an enhanced carbon burning rate as a possible solution. In conclusion, SN 2009md is a faint SN arising from the collapse of a progenitor close to the lower mass limit for core collapse. This is now the third discovery of a low-mass progenitor star producing a low-energy explosion and low 56Ni ejected mass, which indicates that such events arise from the lowest end of the mass range that produces a core-collapse SN (78 M?).

On the association of ULXs with young superclusters: M82 X-1 and a new candidate in NGC 7479

We investigate the spatial coincidence of ultraluminous X-ray sources (ULXs) with young massive stellar clusters. In particular, we perform astrometry on Chandra and Hubble Space Telescope (HST) data of two ULXs that are possibly associated with such clusters.

DISPLAYING THE HETEROGENEITY OF THE SN 2002cx-LIKE SUBCLASS OF TYPE Ia SUPERNOVAE WITH OBSERVATIONS OF THE Pan-STARRS-1 DISCOVERED SN 2009ku

SN 2009ku, discovered by Pan-STARRS-1, is a Type Ia supernova (SN Ia), and a member of the distinct SN 2002cx-like class of SNe Ia. Its light curves are similar to the prototypical SN 2002cx, but are slightly broader and have a later rise to maximum in g. SN 2009ku is brighter (similar to 0.6 mag) than other SN 2002cx-like objects, peaking at M-V = -18.4 mag, which is still significantly fainter than typical SNe Ia. SN 2009ku, which had an ejecta velocity of similar to 2000 km s(-1) at 18 days after maximum brightness, is spectroscopically most similar to SN 2008ha, which also had extremely low-velocity ejecta. However, SN 2008ha had an exceedingly low luminosity, peaking at M-V = -14.2 mag, similar to 4 mag fainter than SN 2009ku. The contrast of high luminosity and low ejecta velocity for SN 2009ku is contrary to an emerging trend seen for the SN 2002cx class. SN 2009ku is a counterexample of a previously held belief that the class was more homogeneous than typical SNe Ia, indicating that the class has a diverse progenitor population and/or complicated explosion physics. As the first example of a member of this class of objects from the new generation of transient surveys, SN 2009ku is an indication of the potential for these surveys to find rare and interesting objects.

THE VLT-FLAMES TARANTULA SURVEY: THE FASTEST ROTATING O-TYPE STAR AND SHORTEST PERIOD LMC PULSAR-REMNANTS OF A SUPERNOVA DISRUPTED BINARY?

We present a spectroscopic analysis of an extremely rapidly rotating late O-type star, VFTS102, observed during a spectroscopic survey of 30 Doradus. VFTS102 has a projected rotational velocity larger than 500 km s(-1) and probably as large as 600 km s-1; as such it would appear to be the most rapidly rotating massive star currently identified. Its radial velocity differs by 40 kms(-1) from the mean for 30 Doradus, suggesting that it is a runaway. VFTS102 lies 12 pc from the X-ray pulsar PSR J0537-6910 in the tail of its X-ray diffuse emission. We suggest that these objects originated from a binary system with the rotational and radial velocities of VFTS102 resulting from mass transfer from the progenitor of PSR J0537-691 and the supernova explosion, respectively.