139 research outputs found

    Sudbury project (University of Muenster-Ontario Geological Survey): Petrology, chemistry, and origin of breccia formations

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    Within the Sudbury Project of the University of Muenster and the Ontario Geological Survey special emphasis was put on the breccia formations exposed at the Sudbury structure (SS) because of their crucial role for the impact hypothesis. They were mapped and sampled in selected areas of the north, east, and south ranges of the SS. The relative stratigraphic positions of these units are summarized. Selected samples were analyzed by optical microscopy, SEM, microprobe, XRF and INAA, Rb-Sr and SM-Nd-isotope geochemistry, and carbon isotope analysis. The results of petrographic and chemical analysis for those stratigraphic units that were considered the main structural elements of a large impact basin are summarized

    Sudbury project (University of Muenster-Ontario Geological Survey): Field studies 1984-1989 - summary of results

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    In cooperation between the Ontario Geological Survey and the Institute of Geology and Institute of Planetology, geological, petrological, and geochemical studies were carried out on impact-related phenomena of the Sudbury structure during the last decade. The main results of the field studies are briefly reviewed. Footwall rocks, sublayer, and lower sections of the Sudbury Igneous Complex (SIC) were mainly mapped and sampled in the northern (Levack Township) and western (Trillabelle and Sultana Properties) parts of the north range. Within these mapping areas Sudbury Breccias (SB) and Footwall Breccias (FB) were studied; SB were also investigated along extended profiles beyond the north and south ranges up to 55 km from the SIC. The Onaping Formation (OF) and the upper section of the SIC were studied both in the north range (Morgan and Dowling Townships) and in the southern east range (Capreol and McLennan Townships)

    Sudbury project (University of Muenster-Ontario Geological Survey): Summary of results - an updated impact model

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    In 1984 the Ontario Geological Survey initiated a research project on the Sudbury structure (SS) in cooperation with the University of Muenster. The project included field mapping (1984-1989) and petrographic, chemical, and isotope analyses of the major stratigraphic units of the SS. Four diploma theses and four doctoral theses were performed during the project (1984-1992). Specific results of the various investigations are reported. Selected areas of the SS were mapped and sampled: Footwall rocks; Footwall breccia and parts of the sublayer and lower section of the Sudbury Igneous Complex (SIC); Onaping Formation and the upper section of the SIC; and Sudbury breccia and adjacent Footwall rocks along extended profiles up to 55 km from the SIC. All these stratigraphic units of the SS were studied in substantial detail by previous workers. The most important characteristic of the previous research is that it was based either on a volcanic model or on a mixed volcanic-impact model for the origin of the SS. The present project was clearly directed toward a test of the impact origin of the SS without invoking an endogenic component. In general, our results confirm the most widely accepted stratigraphic division of the SS. However, our interpretation of some of the major stratigraphic units is different from most views expressed. The stratigraphy of the SS and its new interpretation is given as a basis for discussion

    Physical fitness components associated with performance in a multiple-sprint test.

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    PURPOSE: The 5-m repeat-sprint test (5-m RST) measures resistance to fatigue after repeated bouts of short-duration, high-intensity activity. This study determined the components of fitness associated with performance in 5-m RSTs. METHODS: Speed (10-m and 40-m sprints), strength (bench press), agility, strength endurance (pull-ups and push-ups), and aerobic power (20-m shuttle-run test) were measured in male provincial- or national-level rugby (n = 110), hockey (n = 59), and soccer (n = 55) players. RESULTS: Subjects with either high (HI) or low (LO) resistance to fatigue in the 5-m RST differed in body mass (76.9 +/- 11.6 kg vs 102.1 +/- 18.9 kg, HI vs LO, respectively, P < .001), agility (14.55 +/- 0.41 seconds vs 15.56 +/- 0.30 seconds, P < .001), bench press (86 +/- 20 kg vs 114 +/- 33 kg, P = .03), pull-ups (13 +/- 4 vs 8 +/- 5, P = .02), push-ups (56 +/- 12 vs 39 +/- 13, P = .002), and 20-m shuttle-run test (20-m SRT; 133 +/- 11 vs 87 +/- 12 shuttles, P < .001). Body mass, strength, and aerobic power were the best predictors of 5-m RST performance: 5-m RST = -1.274(mass) + 0.756(1RM bench press) + 2.053(number of 20-m SRT shuttles) + 549.409 (R2 = .66). CONCLUSIONS: Performance in the 5-m RST is predicted best by a combination of factors including body mass, strength, and aerobic ability, rather than by any single component of fitness

    SIK2 inhibition enhances PARP inhibitor activity synergistically in ovarian and triple-negative breast cancers

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    Poly(ADP-ribose) polymerase inhibitors (PARP inhibitors) have had an increasing role in the treatment of ovarian and breast cancers. PARP inhibitors are selectively active in cells with homologous recombination DNA repair deficiency caused by mutations in BRCA1/2 and other DNA repair pathway genes. Cancers with homologous recombination DNA repair proficiency respond poorly to PARP inhibitors. Cancers that initially respond to PARP inhibitors eventually develop drug resistance. We have identified salt-inducible kinase 2 (SIK2) inhibitors, ARN3236 and ARN3261, which decreased DNA double-strand break (DSB) repair functions and produced synthetic lethality with multiple PARP inhibitors in both homologous recombination DNA repair deficiency and proficiency cancer cells. SIK2 is required for centrosome splitting and PI3K activation and regulates cancer cell proliferation, metastasis, and sensitivity to chemotherapy. Here, we showed that SIK2 inhibitors sensitized ovarian and triple-negative breast cancer (TNBC) cells and xenografts to PARP inhibitors. SIK2 inhibitors decreased PARP enzyme activity and phosphorylation of class-IIa histone deacetylases (HDAC4/5/7). Furthermore, SIK2 inhibitors abolished class-IIa HDAC4/5/7–associated transcriptional activity of myocyte enhancer factor-2D (MEF2D), decreasing MEF2D binding to regulatory regions with high chromatin accessibility in FANCD2, EXO1, and XRCC4 genes, resulting in repression of their functions in the DNA DSB repair pathway. The combination of PARP inhibitors and SIK2 inhibitors provides a therapeutic strategy to enhance PARP inhibitor sensitivity for ovarian cancer and TNBC

    Second surgery for progressive glioblastoma: a multi‐centre questionnaire and cohort‐based review of clinical decision‐making and patient outcomes in current practice

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    PURPOSE: Glioblastoma prognosis is poor. Treatment options are limited at progression. Surgery may benefit, but no quality guidelines exist to inform patient selection. We sought to describe variations in surgical management at progression, highlight where further evidence is needed, and build towards a consensus strategy. METHODS: Current practice in selection of patients with progressive GBM for second surgery was surveyed online amongst specialists in the UK and Europe. We complemented this with an assessment of practice in a retrospective cohort study from six United Kingdom neurosurgical units. We used descriptive statistics to analyse the data. RESULTS: 234 questionnaire responses were received. Maintaining or improving patient quality of life was key to decision making, with variation as to whether patient age, performance status or intended extent of resection was relevant. MGMT methylation status was not important. Half considered no minimum time after first surgery. 288 patients were reported in the cohort analysis. Median time to second surgery from first surgery 390 days. Median overall survival 815 days, with no association between time to second surgery and time to death (p = 0.874). CONCLUSIONS: This is the most wide-ranging examination of contemporaneous practice in management of GBM progression. Without evidence-based guidelines, the variation is unsurprising. We propose consensus guidelines for consideration, to reduce heterogeneity in decision making, support data collection and analysis of factors influencing outcomes, and to inform clinical trials to establish whether second surgery improves patient outcomes, or simply selects to patients already performing well

    Expression of miRNA-106b in conventional renal cell carcinoma is a potential marker for prediction of early metastasis after nephrectomy

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    <p>Abstract</p> <p>Background</p> <p>MicroRNAs are endogenously expressed regulatory noncoding RNAs. Previous studies have shown altered expression levels of several microRNAs in renal cell carcinoma.</p> <p>Methods</p> <p>We examined the expression levels of selected microRNAs in 38 samples of conventional renal cell carcinoma (RCC) and 10 samples of non-tumoral renal parenchyma using TaqMan real-time PCR method.</p> <p>Results</p> <p>The expression levels of miRNA-155 (p < 0.0001), miRNA-210 (p < 0.0001), miRNA-106a (p < 0.0001) and miRNA-106b (p < 0.0001) were significantly over-expressed in tumor tissue, whereas the expression of miRNA-141 (p < 0.0001) and miRNA-200c (p < 0.0001) were significantly decreased in RCC samples. There were no significant differences between expression levels of miRNA-182 and miRNA-200b in tumor samples and renal parenchyma. Our data suggest that expression levels of miRNA-106b are significantly lower in tumors of patients who developed metastasis (p = 0.030) and miR-106b is a potential predictive marker of early metastasis after nephrectomy in RCC patients (long-rank p = 0.032).</p> <p>Conclusions</p> <p>We have confirmed previous observations obtained by miRNA microarray analysis using standardized real-time PCR method. For the first time, we have identified a prognostic significance of miRNA-106b, which, after validation on a larger group of patients, maybe useful as a promising biomarker in patients with RCC.</p
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