Integration of microarray analysis into the clinical diagnosis of hematological malignancies: How much can we improve cytogenetic testing?

PurposeTo evaluate the clinical utility, diagnostic yield and rationale of integrating microarray analysis in the clinical diagnosis of hematological malignancies in comparison with classical chromosome karyotyping/fluorescence in situ hybridization (FISH).MethodsG-banded chromosome analysis, FISH and microarray studies using customized CGH and CGH+SNP designs were performed on 27 samples from patients with hematological malignancies. A comprehensive comparison of the results obtained by three methods was conducted to evaluate benefits and limitations of these techniques for clinical diagnosis.ResultsOverall, 89.7% of chromosomal abnormalities identified by karyotyping/FISH studies were also detectable by microarray. Among 183 acquired copy number alterations (CNAs) identified by microarray, 94 were additional findings revealed in 14 cases (52%), and at least 30% of CNAs were in genomic regions of diagnostic/prognostic significance. Approximately 30% of novel alterations detected by microarray were >20 Mb in size. Balanced abnormalities were not detected by microarray; however, of the 19 apparently "balanced" rearrangements, 55% (6/11) of recurrent and 13% (1/8) of non-recurrent translocations had alterations at the breakpoints discovered by microarray.ConclusionMicroarray technology enables accurate, cost-effective and time-efficient whole-genome analysis at a resolution significantly higher than that of conventional karyotyping and FISH. Array-CGH showed advantage in identification of cryptic imbalances and detection of clonal aberrations in population of non-dividing cancer cells and samples with poor chromosome morphology. The integration of microarray analysis into the cytogenetic diagnosis of hematologic malignancies has the potential to improve patient management by providing clinicians with additional disease specific and potentially clinically actionable genomic alterations

Are Ti44-Producing Supernovae Exceptional?

According to standard models supernovae produce radioactive $^{44}$Ti, which should be visible in gamma-rays following decay to $^{44}$Ca for a few centuries. $^{44}Ti production is believed to be the source of cosmic$^{44}$Ca, whose abundance is well established. Yet, gamma-ray telescopes have not seen the expected young remnants of core collapse events. The$^{44}$Ti mean life of$\tau \simeq$89 y and the Galactic supernova rate of$\simeq$3/100 y imply$\simeq$several detectable$^{44}Ti gamma-ray sources, but only one is clearly seen, the 340-year-old Cas A SNR. Furthermore, supernovae which produce much $^{44}Ti are expected to occur primarily in the inner part of the Galaxy, where young massive stars are most abundant. Because the Galaxy is transparent to gamma-rays, this should be the dominant location of expected gamma-ray sources. Yet the Cas A SNR as the only one source is located far from the inner Galaxy (at longitude 112 degree). We evaluate the surprising absence of detectable supernovae from the past three centuries. We discuss whether our understanding of SN explosions, their$^{44}Ti yields, their spatial distributions, and statistical arguments can be stretched so that this apparent disagreement may be accommodated within reasonable expectations, or if we have to revise some or all of the above aspects to bring expectations in agreement with the observations. We conclude that either core collapse supernovae have been improbably rare in the Galaxy during the past few centuries, or $^{44}Ti-producing supernovae are atypical supernovae. We also present a new argument based on$^{44}$Ca/$^{40}$Ca ratios in mainstream SiC stardust grains that may cast doubt on massive-He-cap Type I supernovae as the source of most galactic$^{44}$Ca.Comment: 23 pages, 14 figures, accepted for publication in Astronomy and Astrophysics 2006. Correcting the SN type of Tycho in Table B.1. and add its associated reference

Reddening law and interstellar dust properties along Magellanic sight-lines

This study establishes that SMC, LMC and Milky Way extinction curves obey the same extinction law which depends on the 2200A bump size and one parameter, and generalizes the Cardelli, Clayton and Mathis (1989) relationship. This suggests that extinction in all three galaxies is of the same nature. The role of linear reddening laws over all the visible/UV wavelength range, particularly important in the SMC but also present in the LMC and in the Milky Way, is also highlighted and discussed.Comment: accepted for publication in Astrophysics and Space Science. 16 pages, 12 figures. Some figures are colour plot

Linear/circular spectropolarimetry of diffuse interstellar bands

Context. The identification of the carriers of diffuse interstellar bands (DIBs) remains one of the long-standing mysteries in astronomy. The detection of a polarisation signal in a DIB profile can be used to distinguish between a dust or gas-phase carrier. The polarisation profile can give additional information on the grain or molecular properties of the absorber. In order to detect and measure the linear and circular polarisation of the DIBs we observed reddened lines of sight showing continuum polarisation. For this study we selected two stars HD 197770 and HD 194279. We used high-resolution (R~64.000) spectropolarimetry in the wavelength range from 3700 to 10480 Angstrom with the ESPaDOnS echelle spectrograph mounted at the CFHT. Results. High S/N and high resolution Stokes V (circular), Q and U (linear) spectra were obtained. We constrained upper limits by a factor of 10 for previously observed DIBs. Furthermore, we analysed ~30 additional DIBs for which no spectropolarimetry data has been obtained before. This included the 9577 A DIB and the 8621 A DIB. Conclusions. The lack of polarisation in 45 DIB profiles suggests that none of the absorption lines is induced by a grain-type carrier. The strict upper limits, less than ~0.01%, derived for the observed lines-of-sight imply that if DIBs are due to gas-phase molecules these carriers have polarisation efficiencies which are at least 6 times, and up to 300 times, smaller than those predicted for grain-related carriers.Comment: 6 pages + 13 pages online material, submitted to A&

Spitzer Space Telescope Infrared Imaging and Spectroscopy of the Crab Nebula

We present 3.6, 4.5, 5.8, 8.0, 24, and 70 micron images of the Crab Nebula obtained with the Spitzer Space Telescope IRAC and MIPS cameras, Low- and High-resolution Spitzer IRS spectra of selected positions within the nebula, and a near-infrared ground-based image made in the light of [Fe II]1.644 micron. The 8.0 micron image, made with a bandpass that includes [Ar II]7.0 micron, resembles the general morphology of visible H-alpha and near-IR [Fe II] line emission, while the 3.6 and 4.5 micron images are dominated by continuum synchrotron emission. The 24 micron and 70 micron images show enhanced emission that may be due to line emission or the presence of a small amount of warm dust in the nebula on the order of less than 1% of a solar mass. The ratio of the 3.6 and 4.5 micron images reveals a spatial variation in the synchrotron power law index ranging from approximately 0.3 to 0.8 across the nebula. Combining this information with optical and X-ray synchrotron images, we derive a broadband spectrum that reflects the superposition of the flatter spectrum jet and torus with the steeper diffuse nebula, and suggestions of the expected pileup of relativistic electrons just before the exponential cutoff in the X-ray. The pulsar, and the associated equatorial toroid and polar jet structures seen in Chandra and HST images (Hester et al. 2002) can be identified in all of the IRAC images. We present the IR photometry of the pulsar. The forbidden lines identified in the high resolution IR spectra are all double due to Doppler shifts from the front and back of the expanding nebula and give an expansion velocity of approximately 1264 km/s.Comment: 21 pages, 4 tables, 16 figure

The Role of Polycyclic Aromatic Hydrocarbons in Ultraviolet Extinction. I. Probing small molecular PAHs

We have obtained new STIS/HST spectra to search for structure in the ultraviolet interstellar extinction curve, with particular emphasis on a search for absorption features produced by polycyclic aromatic hydrocarbons (PAHs). The presence of these molecules in the interstellar medium has been postulated to explain the infrared emission features seen in the 3-13 $\mu$m spectra of numerous sources. UV spectra are uniquely capable of identifying specific PAH molecules. We obtained high S/N UV spectra of stars which are significantly more reddened than those observed in previous studies. These data put limits on the role of small (30-50 carbon atoms) PAHs in UV extinction and call for further observations to probe the role of larger PAHs. PAHs are of importance because of their ubiquity and high abundance inferred from the infrared data and also because they may link the molecular and dust phases of the interstellar medium. A presence or absence of ultraviolet absorption bands due to PAHs could be a definitive test of this hypothesis. We should be able to detect a 20 \AA wide feature down to a 3$\sigma$ limit of $\sim$0.02 A$_V$. No such absorption features are seen other than the well-known 2175 \AA bump.Comment: 16 pages, 3 figure, ApJ in pres

Repetitive elements in parasitic protozoa

A recent paper published in BMC Genomics suggests that retrotransposition may be active in the human gut parasite Entamoeba histolytica. This adds to our knowledge of the various types of repetitive elements in parasitic protists and the potential influence of such elements on pathogenicity

On metal-deficient barium stars and their link with yellow symbiotic stars

This paper addresses the question of why metal-deficient barium stars are not yellow symbiotic stars (YSyS). Samples of (suspected) metal-deficient barium (mdBa) stars and YSyS have been collected from the literature, and their properties reviewed. It appears in particular that the barium nature of the suspected mdBa stars needs to be ascertained by detailed abundance analyses. Abundances are therefore derived for two of them, HD 139409 and HD 148897, which reveal that HD 148897 should not be considered a barium star. HD 139409 is a mild barium star, with overabundances observed only for elements belonging to the first s-process peak (Y and Zr). The evidence for binarity among mdBa stars is then reviewed, using three different methods: (i) radial-velocity variations (from CORAVEL observations), (ii) Hipparcos astrometric data, and (iii) a method based on the comparison between the Hipparcos and Tycho-2 proper motions. A first-time orbit is obtained for HIP 55852, whereas evidence for the (so far unknown) binary nature of HIP 34795, HIP 76605, HIP 97874 and HIP 107478 is presented. Two stars with no evidence for binarity whatsoever (HIP 58596 and BD +3 2688) are candidates low-metallicity thermally-pulsing asymptotic giant branch stars, as inferred from their large luminosities. The reason why mdBa stars are not YSyS is suggested to lie in their different orbital period distributions: mdBa stars have on average longer orbital periods than YSyS, and hence their companion accretes matter at a lower rate, for a given mass loss rate of the giant star. The definite validation of this explanation should nevertheless await the determination of the orbital periods for the many mdBa stars still lacking periods, in order to make the comparison more significant.Comment: Astronomy & Astrophysics, in press; 16 pages, 14 figures; also available at http://www.astro.ulb.ac.be/Html/ps.html#PR

The Dust-to-Gas Ratio in the Small Magellanic Cloud Tail

The Tail region of the Small Magellanic Cloud (SMC) was imaged using the MIPS instrument on the Spitzer Space Telescope as part of the SAGE-SMC Spitzer Legacy. Diffuse infrared emission from dust was detected in all the MIPS bands. The Tail gas-to-dust ratio was measured to be 1200 +/- 350 using the MIPS observations combined with existing IRAS and HI observations. This gas-to-dust ratio is higher than the expected 500-800 from the known Tail metallicity indicating possible destruction of dust grains. Two cluster regions in the Tail were resolved into multiple sources in the MIPS observations and local gas-to-dust ratios were measured to be ~440 and ~250 suggests dust formation and/or significant amounts of ionized gas in these regions. These results support the interpretation that the SMC Tail is a tidal tail recently stripped from the SMC that includes gas, dust, and young stars.Comment: 6 pages, 3 figures, ApJ Letters, in press, (version with full resolution figures at http://www.stsci.edu/~kgordon/papers/PS_files/sage-smc_taildust_v1.62.pdf

Dust Emission Features in NGC 7023 between 0.35 and 2.5 micron: Extended Red Emission (0.7 micron) and Two New Emission Features (1.15 and 1.5 micron)

We present 0.35 to 2.5 micron spectra of the south and northwest filaments in the reflection nebula NGC 7023. These spectra were used to test the theory of Seahra & Duley that carbon nanoparticles are responsible for Extended Red Emission (ERE). Our spectra fail to show their predicted second emission band at 1.0 micron even though both filaments exhibit strong emission in the familiar 0.7 micron ERE band. The northwest filament spectrum does show one, and possibly two, new dust emission features in the near-infrared. We clearly detect a strong emission band at 1.5 micron which we tentatively attribute to beta-FeSi_2 grains. We tentatively detect a weaker emission band at 1.15 micron which coincides with the location expected for transitions from the conduction band to mid-gap defect states of silicon nanoparticles. This is added evidence that silicon nanoparticles are responsible for ERE as they already can explain the observed behavior of the main visible ERE band.Comment: 9 pages, color figures, accepted to the ApJ, color and b/w versions available at http://dirty.as.arizona.edu/~kgordon/papers/ere_1um.htm