665 research outputs found
Comparing computer-generated and pathologist-generated tumour segmentations for immunohistochemical scoring of breast tissue microarrays
BACKGROUND: Tissue microarrays (TMAs) have become a valuable resource for biomarker expression in translational research. Immunohistochemical (IHC) assessment of TMAs is the principal method for analysing large numbers of patient samples, but manual IHC assessment of TMAs remains a challenging and laborious task. With advances in image analysis, computer-generated analyses of TMAs have the potential to lessen the burden of expert pathologist review. METHODS: In current commercial software computerised oestrogen receptor (ER) scoring relies on tumour localisation in the form of hand-drawn annotations. In this study, tumour localisation for ER scoring was evaluated comparing computer-generated segmentation masks with those of two specialist breast pathologists. Automatically and manually obtained segmentation masks were used to obtain IHC scores for thirty-two ER-stained invasive breast cancer TMA samples using FDA-approved IHC scoring software. RESULTS: Although pixel-level comparisons showed lower agreement between automated and manual segmentation masks (κ=0.81) than between pathologists' masks (κ=0.91), this had little impact on computed IHC scores (Allred; [Image: see text]=0.91, Quickscore; [Image: see text]=0.92). CONCLUSIONS: The proposed automated system provides consistent measurements thus ensuring standardisation, and shows promise for increasing IHC analysis of nuclear staining in TMAs from large clinical trials
Renal insufficiency is an independent predictor of mortality after percutaneous coronary intervention: Current results from the NHLBI Dynamic Registry
The Mid-Infrared Instrument for the James Webb Space Telescope, III: MIRIM, The MIRI Imager
In this article, we describe the MIRI Imager module (MIRIM), which provides
broad-band imaging in the 5 - 27 microns wavelength range for the James Webb
Space Telescope. The imager has a 0"11 pixel scale and a total unobstructed
view of 74"x113". The remainder of its nominal 113"x113" field is occupied by
the coronagraphs and the low resolution spectrometer. We present the instrument
optical and mechanical design. We show that the test data, as measured during
the test campaigns undertaken at CEA-Saclay, at the Rutherford Appleton
Laboratory, and at the NASA Goddard Space Flight Center, indicate that the
instrument complies with its design requirements and goals. We also discuss the
operational requirements (multiple dithers and exposures) needed for optimal
scientific utilization of the MIRIM.Comment: 29 pages, 9 figure
Immunohistochemical Phenotype of Breast Cancer during 25-Year Follow-up of the Royal Marsden Tamoxifen Prevention Trial.
The randomized, double-blinded Royal Marsden Tamoxifen Breast Cancer Prevention Trial in healthy high-risk women started in 1986 and is still blinded. Eligible participants (n = 2,471) were randomly assigned to tamoxifen (20 mg/d) or placebo for 8 years. Analysis in 2006 showed a 30% risk reduction of estrogen receptor (ER)-positive invasive breast cancer mostly in the posttreatment period. Biomarker analysis in this population may identify any subgroup-specific preventive effects tamoxifen. After a median follow-up of 18.4 years, 242 patients had developed invasive cancer, 134 on placebo and 108 on tamoxifen. From these, 180 tissue blocks were available and ER, progesterone receptor (PgR), Ki67, HER2, and EGFR were immunohistochemically analyzed. A 32% reduction in ER+ and PgR+ invasive cancers resulted after 8 years of treatment. Quantitative levels of ER and PgR were lower in the tamoxifen-treated group, significantly so for ER (P = 0.001). These lower ER levels were restricted to the posttreatment period (P = 0.018). Among the ER+ group, there was a similar proportional decrease in PgR+ and PgR- tumors by tamoxifen. The median levels of Ki67 were similar in both arms. The numbers of HER2-positive and EGFR-positive cancers were higher in the tamoxifen arm but not significantly so. In conclusion, the preventive effects of tamoxifen result in reduced ER-positive but not ER-negative tumors and reduced ER expression in the ER-positive cases largely confined to the posttreatment period. Overall reductions in PgR expression are explained by lower frequency of ER-positive cases. Impact on Ki67, HER2, and EGFR was modest. Cancer Prev Res; 10(3); 171-6. ©2017 AACR
Characterizing Exoplanets in the Visible and Infrared: A Spectrometer Concept for the EChO Space Mission
Transit-spectroscopy of exoplanets is one of the key observational techniques
to characterize the extrasolar planet and its atmosphere. The observational
challenges of these measurements require dedicated instrumentation and only the
space environment allows an undisturbed access to earth-like atmospheric
features such as water or carbon-dioxide. Therefore, several exoplanet-specific
space missions are currently being studied. One of them is EChO, the Exoplanet
Characterization Observatory, which is part of ESA's Cosmic Vision 2015-2025
program, and which is one of four candidates for the M3 launch slot in 2024. In
this paper we present the results of our assessment study of the EChO
spectrometer, the only science instrument onboard this spacecraft. The
instrument is a multi-channel all-reflective dispersive spectrometer, covering
the wavelength range from 400 nm to 16 microns simultaneously with a moderately
low spectral resolution. We illustrate how the key technical challenge of the
EChO mission - the high photometric stability - influences the choice of
spectrometer concept and drives fundamentally the instrument design. First
performance evaluations underline the fitness of the elaborated design solution
for the needs of the EChO mission.Comment: 20 pages, 8 figures, accepted for publication in the Journal of
Astronomical Instrumentatio
Variable turbulent convection as the cause of the Blazhko effect - testing the Stothers model
The amplitude and phase modulation observed in a significant fraction of the
RR Lyrae variables - the Blazhko effect - represents a long-standing enigma in
stellar pulsation theory. No satisfactory explanation for the Blazhko effect
has been proposed so far. In this paper we focus on the Stothers (2006) idea,
in which modulation is caused by changes in the structure of the outer
convective zone, caused by a quasi-periodically changing magnetic field.
However, up to this date no quantitative estimates were made to investigate
whether such a mechanism can be operational and whether it is capable of
reproducing the light variation we observe in Blazhko variables. We address the
latter problem. We use a simplified model, in which the variation of turbulent
convection is introduced into the non-linear hydrodynamic models in an ad hoc
way, neglecting interaction with the magnetic field. We study the light curve
variation through the modulation cycle and properties of the resulting
frequency spectra. Our results are compared with Kepler observations of RR Lyr.
We find that reproducing the light curve variation, as is observed in RR Lyr,
requires a huge modulation of the mixing length, of the order of +/-50 per
cent, on a relatively short time-scale of less than 40 days. Even then, we are
not able to reproduce neither all the observed relations between modulation
components present in the frequency spectrum, nor the relations between Fourier
parameters describing the shape of the instantaneous light curves.Comment: 17 pages, 13 figures, accepted for publication in MNRAS; for
associated animation, see
http://homepage.univie.ac.at/radek.smolec/publications/KASC11a
MAGE-A cancer/testis antigens inhibit MDM2 ubiquitylation function and promote increased levels of MDM4
Melanoma antigen A (MAGE-A) proteins comprise a structurally and biochemically similar sub-family of Cancer/Testis antigens that are expressed in many cancer types and are thought to contribute actively to malignancy. MAGE-A proteins are established regulators of certain cancer-associated transcription factors, including p53, and are activators of several RING finger-dependent ubiquitin E3 ligases. Here, we show that MAGE-A2 associates with MDM2, a ubiquitin E3 ligase that mediates ubiquitylation of more than 20 substrates including mainly p53, MDM2 itself, and MDM4, a potent p53 inhibitor and MDM2 partner that is structurally related to MDM2. We find that MAGE-A2 interacts with MDM2 via the N-terminal p53-binding pocket and the RING finger domain of MDM2 that is required for homo/hetero-dimerization and for E2 ligase interaction. Consistent with these data, we show that MAGE-A2 is a potent inhibitor of the E3 ubiquitin ligase activity of MDM2, yet it does not have any significant effect on p53 turnover mediated by MDM2. Strikingly, however, increased MAGE-A2 expression leads to reduced ubiquitylation and increased levels of MDM4. Similarly, silencing of endogenous MAGE-A expression diminishes MDM4 levels in a manner that can be rescued by the proteasomal inhibitor, bortezomid, and permits increased MDM2/MDM4 association. These data suggest that MAGE-A proteins can: (i) uncouple the ubiquitin ligase and degradation functions of MDM2; (ii) act as potent inhibitors of E3 ligase function; and (iii) regulate the turnover of MDM4. We also find an association between the presence of MAGE-A and increased MDM4 levels in primary breast cancer, suggesting that MAGE-A-dependent control of MDM4 levels has relevance to cancer clinically
Original contribution Reduced susceptibility effects in perfusion fMRI with single-shot spin- echo EPI acquisitions at 1.5 Tesla
Abstract Arterial spin labeling (ASL) perfusion contrast is not based on susceptibility effects and can therefore be used to study brain function in regions of high static inhomogeneity. As a proof of concept, single-shot spin-echo echo-planar imaging (EPI) acquisition was carried out with a multislice continuous ASL (CASL) method at 1.5T. A bilateral finger tapping paradigm was used in the presence of an exogenously induced susceptibility artifact over left motor cortex. The spin-echo CASL technique was compared with a regular gradient-echo EPI sequence with the same slice thickness, as well as other imaging methods using thin slices and spin-echo acquisitions. The results demonstrate improved functional sensitivity and efficiency of the spin-echo CASL approach as compared with gradient-echo EPI techniques, and a trend of improved sensitivity as compared with spin-echo EPI approach in the brain regions affected by the susceptibility artifact. ASL images, either with or without subtraction of the control, provide a robust alternative to blood oxygenation level dependant (BOLD) methods for activation imaging in regions of high static field inhomogeneity
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