87 research outputs found
The XMM-Newton serendipitous survey. VII. The third XMM-Newton serendipitous source catalogue
Thanks to the large collecting area (3 x ~1500 cm at 1.5 keV) and wide
field of view (30' across in full field mode) of the X-ray cameras on board the
European Space Agency X-ray observatory XMM-Newton, each individual pointing
can result in the detection of hundreds of X-ray sources, most of which are
newly discovered. Recently, many improvements in the XMM-Newton data reduction
algorithms have been made. These include enhanced source characterisation and
reduced spurious source detections, refined astrometric precision, greater net
sensitivity and the extraction of spectra and time series for fainter sources,
with better signal-to-noise. Further, almost 50\% more observations are in the
public domain compared to 2XMMi-DR3, allowing the XMM-Newton Survey Science
Centre (XMM-SSC) to produce a much larger and better quality X-ray source
catalogue. The XMM-SSC has developed a pipeline to reduce the XMM-Newton data
automatically and using improved calibration a new catalogue version has been
produced from XMM-Newton data made public by 2013 Dec. 31 (13 years of data).
Manual screening ensures the highest data quality. This catalogue is known as
3XMM. In the latest release, 3XMM-DR5, there are 565962 X-ray detections
comprising 396910 unique X-ray sources. For the 133000 brightest sources,
spectra and lightcurves are provided. For all detections, the positions on the
sky, a measure of the quality of the detection, and an evaluation of the X-ray
variability is provided, along with the fluxes and count rates in 7 X-ray
energy bands, the total 0.2-12 keV band counts, and four hardness ratios. To
identify the detections, a cross correlation with 228 catalogues is also
provided for each X-ray detection. 3XMM-DR5 is the largest X-ray source
catalogue ever produced. Thanks to the large array of data products, it is an
excellent resource in which to find new and extreme objects.Comment: 23 pages, version accepted for publication in A&
The XMM-Newton serendipitous survey: VIII. the first XMM-Newton serendipitous source catalogue from overlapping observations
Context. XMM-Newton has observed the X-ray sky since early 2000. The XMM-Newton Survey Science Centre Consortium has published catalogues of X-ray and ultraviolet sources found serendipitously in the individual observations. This series is now augmented by a catalogue dedicated to X-ray sources detected in spatially overlapping XMM-Newton observations. Aims. The aim of this catalogue is to explore repeatedly observed sky regions. It thus makes use of the long(er) effective exposure time per sky area and offers the opportunity to investigate long-term flux variability directly through the source-detection process. Methods. A new standardised strategy for simultaneous source detection on multiple observations was introduced, including an adaptive-smoothing method to describe the image background. It was coded as a new task within the XMM-Newton Science Analysis System and used to compile a catalogue of sources from 434 stacks comprising 1789 overlapping XMM-Newton observations that entered the 3XMM-DR7 catalogue, have a low background and full-frame readout of all EPIC cameras. Results. The first stacked catalogue is called 3XMM-DR7s. It contains 71 951 unique sources with positions and parameters such as fluxes, hardness ratios, quality estimates, and information on inter-observation variability, directly derived from a simultaneous fit. Source parameters are calculated for the stack and for each contributing observation. About 15% of the sources are new with respect to 3XMM-DR7. Through stacked source detection, the parameters of repeatedly observed sources are determined with higher accuracy than in the individual observations. The method is more sensitive to faint sources and tends to produce fewer spurious detections. Conclusions. With this first stacked catalogue we demonstrate the feasibility and benefit of the approach. It supplements the large data base of XMM-Newton detections with additional, in particular faint, sources and adds variability information. In the future, the catalogue will be expanded to larger samples and continued within the series of serendipitous XMM-Newton source catalogues.FJC acknowledges financial support through grant AYA2015-64346-C2-1P (MINECO/FEDER) and MTC through grant ESP2016-76683-C3-1R (MINECO/FEDER
Removal of cell surface heparan sulfate increases TACE activity and cleavage of ErbB4 receptor
<p>Abstract</p> <p>Background</p> <p>Nuclear localization of proteolytically formed intracellular fragment of ErbB4 receptor tyrosine kinase has been shown to promote cell survival, and nuclear localization of ErbB4 receptor has been described in human breast cancer. Tumor necrosis factor alpha converting enzyme (TACE) initiates the proteolytic cascade leading to ErbB4 intracellular domain formation. Interactions between matrix metalloproteases and heparan sulfate have been described, but the effect of cell surface heparan sulfate on TACE activity has not been previously described.</p> <p>Results</p> <p>As indicated by immunodetection of increased ErbB4 intracellular domain formation and direct enzyme activity analysis, TACE activity was substantially amplified by enzymatic removal of cell surface heparan sulfate but not chondroitin sulfate.</p> <p>Conclusion</p> <p>In this communication, we suggest a novel role for cell surface heparan sulfate. Removal of cell surface heparan sulfate led to increased formation of ErbB4 intracellular domain. As ErbB4 intracellular domain has previously been shown to promote cell survival this finding may indicate a novel mechanism how HS degradation active in tumor tissue may favor cell survival.</p
High frequency of tumor cells with nuclear Egr-1 protein expression in human bladder cancer is associated with disease progression
<p>Abstract</p> <p>Background</p> <p>Egr-1 (early growth response-1 transcription factor) has been proposed to be involved in invasion and metastasis processes of human bladder cancer, but Egr-1 protein expression levels in human bladder cancer have not been investigated. In the present study we investigated the expression levels of Egr-1 protein in early stages of human bladder cancer and correlated it to later progression.</p> <p>Methods</p> <p>Expression of Egr-1 protein in human bladder cancer was examined by immunohistochemistry, on a tissue microarray constructed from tumors from 289 patients with non-muscle invasive urothelial bladder cancer.</p> <p>Results</p> <p>The frequency of tumor cells with nuclear Egr-1 immunolabelling correlated to bladder cancer stage, grade and to later progression to muscle-invasive bladder cancer (T2-4). Stage T1 tumors exhibited significantly higher frequencies of tumor cells with nuclear Egr-1 immunolabelling than Ta tumors (P = 0.001). Furthermore, Kaplan-Meier survival analysis showed that a high frequency of tumor cells with nuclear Egr-1 immunolabelling was significantly associated with a higher risk of progression to stage T2-4 (log-rank test, P = 0.035). Tumor cells with nuclear Egr-1 immunolabelling were found to localize at the tumor front in some of the tumor biopsies.</p> <p>Conclusion</p> <p>The results from this study support a potential involvement of Egr-1 in the progression from non-muscle invasive bladder cancers to muscle invasive bladder cancer.</p
The Evolution of Compact Binary Star Systems
We review the formation and evolution of compact binary stars consisting of
white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and
BHs are thought to be the primary astrophysical sources of gravitational waves
(GWs) within the frequency band of ground-based detectors, while compact
binaries of WDs are important sources of GWs at lower frequencies to be covered
by space interferometers (LISA). Major uncertainties in the current
understanding of properties of NSs and BHs most relevant to the GW studies are
discussed, including the treatment of the natal kicks which compact stellar
remnants acquire during the core collapse of massive stars and the common
envelope phase of binary evolution. We discuss the coalescence rates of binary
NSs and BHs and prospects for their detections, the formation and evolution of
binary WDs and their observational manifestations. Special attention is given
to AM CVn-stars -- compact binaries in which the Roche lobe is filled by
another WD or a low-mass partially degenerate helium-star, as these stars are
thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure
Expression and prognostic significance of THBS1, Cyr61 and CTGF in esophageal squamous cell carcinoma
<p>Abstract</p> <p>Background</p> <p>Thrombospondin1 (THBS1), cystene-rich protein 61 (Cyr61) and connective tissue growth factor (CTGF) are all involved in the transforming growth factor-beta (TGF-β) signal pathway, which plays an important role in the tumorigenesis. The purpose of this study is to explore the expression and prognostic significance of these proteins in esophageal squamous cell carcinoma (ESCC).</p> <p>Methods</p> <p>We used immunohistochemistry and western blotting to examine the expression status of THBS1, Cyr61 and CTGF in ESCC. Correlations of THBS1, Cyr61 and CTGF over-expressions with various clinicopathologic factors were also determined by using the Chi-square test or Fisher's exact probability test. Survival analysis was assessed by the Kaplan-Meier analysis and the log-rank test. Relative risk was evaluated by the multivariate Cox proportional hazards model.</p> <p>Results</p> <p>THBS1, Cyr61 and CTGF were all over-expressed in ESCC. THBS1 over-expression was significantly associated with TNM stage (<it>P </it>= 0.029) and regional lymph node involvement (<it>P </it>= 0.026). Kaplan-Meier survival analysis showed that over-expression of THBS1, Cyr61 or CTGF was related to poor survival of ESCC patients (<it>P </it>= 0.042, <it>P </it>= 0.020, <it>P </it>= 0.018, respectively). Multivariate Cox analysis demonstrated that Cyr61 and CTGF were independent factors in prognosis of ESCC.</p> <p>Conclusion</p> <p>Cyr61, CTGF and THBS1 were all over-expressed in ESCC and might be new molecular markers to predict the prognosis of ESCC patients.</p
Rare mutations predisposing to familial adenomatous polyposis in Greek FAP patients
BACKGROUND: Familial Adenomatous Polyposis (FAP) is caused by germline mutations in the APC (Adenomatous Polyposis Coli) gene. The vast majority of APC mutations are point mutations or small insertions / deletions which lead to truncated protein products. Splicing mutations or gross genomic rearrangements are less common inactivating events of the APC gene. METHODS: In the current study genomic DNA or RNA from ten unrelated FAP suspected patients was examined for germline mutations in the APC gene. Family history and phenotype were used in order to select the patients. Methods used for testing were dHPLC (denaturing High Performance Liquid Chromatography), sequencing, MLPA (Multiplex Ligation – dependent Probe Amplification), Karyotyping, FISH (Fluorescence In Situ Hybridization) and RT-PCR (Reverse Transcription – Polymerase Chain Reaction). RESULTS: A 250 Kbp deletion in the APC gene starting from intron 5 and extending beyond exon 15 was identified in one patient. A substitution of the +5 conserved nucleotide at the splice donor site of intron 9 in the APC gene was shown to produce frameshift and inefficient exon skipping in a second patient. Four frameshift mutations (1577insT, 1973delAG, 3180delAAAA, 3212delA) and a nonsense mutation (C1690T) were identified in the rest of the patients. CONCLUSION: Screening for APC mutations in FAP patients should include testing for splicing defects and gross genomic alterations
Pathobiological Implications of MUC16 Expression in Pancreatic Cancer
MUC16 (CA125) belongs to a family of high-molecular weight O-glycosylated proteins known as mucins. While MUC16 is well known as a biomarker in ovarian cancer, its expression pattern in pancreatic cancer (PC), the fourth leading cause of cancer related deaths in the United States, remains unknown. The aim of our study was to analyze the expression of MUC16 during the initiation, progression and metastasis of PC for possible implication in PC diagnosis, prognosis and therapy. In this study, a microarray containing tissues from healthy and PC patients was used to investigate the differential protein expression of MUC16 in PC. MUC16 mRNA levels were also measured by RT-PCR in the normal human pancreatic, pancreatitis, and PC tissues. To investigate its expression pattern during PC metastasis, tissue samples from the primary pancreatic tumor and metastases (from the same patient) in the lymph nodes, liver, lung and omentum from Stage IV PC patients were analyzed. To determine its association in the initiation of PC, tissues from PC patients containing pre-neoplastic lesions of varying grades were stained for MUC16. Finally, MUC16 expression was analyzed in 18 human PC cell lines. MUC16 is not expressed in the normal pancreatic ducts and is strongly upregulated in PC and detected in pancreatitis tissue. It is first detected in the high-grade pre-neoplastic lesions preceding invasive adenocarcinoma, suggesting that its upregulation is a late event during the initiation of this disease. MUC16 expression appears to be stronger in metastatic lesions when compared to the primary tumor, suggesting a role in PC metastasis. We have also identified PC cell lines that express MUC16, which can be used in future studies to elucidate its functional role in PC. Altogether, our results reveal that MUC16 expression is significantly increased in PC and could play a potential role in the progression of this disease
Growth of a human mammary tumor cell line is blocked by galangin, a naturally occurring bioflavonoid, and is accompanied by down-regulation of cyclins D3, E, and A
INTRODUCTION: This study was designed to determine if and how a non-toxic, naturally occurring bioflavonoid, galangin, affects proliferation of human mammary tumor cells. Our previous studies demonstrated that, in other cell types, galangin is a potent inhibitor of the aryl hydrocarbon receptor (AhR), an environmental carcinogen-responsive transcription factor implicated in mammary tumor initiation and growth control. Because some current breast cancer therapeutics are ineffective in estrogen receptor (ER) negative tumors and since the AhR may be involved in breast cancer proliferation, the effects of galangin on the proliferation of an ER(-), AhR(high )line, Hs578T, were studied. METHODS: AhR expression and function in the presence or absence of galangin, a second AhR inhibitor, α-naphthoflavone (α-NF), an AhR agonist, indole-3-carbinol, and a transfected AhR repressor-encoding plasmid (FhAhRR) were studied in Hs578T cells by western blotting for nuclear (for instance, constitutively activated) AhR and by transfection of an AhR-driven reporter construct, pGudLuc. The effects of these agents on cell proliferation were studied by (3)H-thymidine incorporation and by flow cytometry. The effects on cyclins implicated in mammary tumorigenesis were evaluated by western blotting. RESULTS: Hs578T cells were shown to express high levels of constitutively active AhR. Constitutive and environmental chemical-induced AhR activity was profoundly suppressed by galangin as was cell proliferation. However, the failure of α-NF or FhAhRR transfection to block proliferation indicated that galangin-mediated AhR inhibition was either insufficient or unrelated to its ability to significantly block cell proliferation at therapeutically relevant doses (IC(50 )= 11 μM). Galangin inhibited transition of cells from the G(0)/G(1 )to the S phases of cell growth, likely through the nearly total elimination of cyclin D3. Expression of cyclins A and E was also suppressed. CONCLUSION: Galangin is a strong inhibitor of Hs578T cell proliferation that likely mediates this effect through a relatively unique mechanism, suppression of cyclin D3, and not through the AhR. The results suggest that this non-toxic bioflavonoid may be useful as a chemotherapeutic, particularly in combination with agents that target other components of the tumor cell cycle and in situations where estrogen receptor-specific therapeutics are ineffective
Heparanase expression is a prognostic indicator for postoperative survival in pancreatic adenocarcinoma
Pancreatic ductal adenocarcinoma has a median survival of less than 6 months from diagnosis. This is due to the difficulty in early diagnosis, the aggressive biological behaviour of the tumour and a lack of effective therapies for advanced disease. Mammalian heparanase is a heparan-sulphate proteoglycan cleaving enzyme. It helps to degrade the extracellular matrix and basement membranes and is involved in angiogenesis. Degradation of extracellular matrix and basement membranes as well as angiogenesis are key conditions for tumour cell spreading. Therefore, we have analysed the expression of heparanase in human pancreatic cancer tissue and cell lines. Heparanase is expressed in cell lines derived from primary tumours as well as from metastatic sites. By immunohistochemical analysis, it is preferentially expressed at the invading edge of a tumour at both metastatic and primary tumour sites. There is a trend towards heparanase expression in metastasising tumours as compared to locally growing tumours. Postoperative survival correlates inversely with heparanase expression of the tumour reflected by a median survival of 34 and 17 month for heparanase negative and positive tumours, respectively. Our results suggest, that heparanase promotes cancer cell invasion in pancreatic carcinoma and could be used as a prognostic indicator for postoperative survival of patients
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