447 research outputs found
A (Co)algebraic Approach to Hennessy-Milner Theorems for Weakly Expressive Logics
No full textCoalgebraic modal logic, as in [9, 6], is a framework in which modal logics for specifying coalgebras can be developed parametric in the signature of the modal language and the coalgebra type functor T. Given a base logic (usually classical propositional logic), modalities are interpreted via so-called predicate liftings for the functor T. These are natural transformations that turn a predicate over the state space X into a predicate over TX. Given that T-coalgebras come with general notions of T-bisimilarity [11] and behavioral equivalence [7], coalgebraic modal logics are designed to respect those. In particular, if two states are behaviourally equivalent then they satisfy the same formulas. If the converse holds, then the logic is said to be expressive. and we have a generalisation of the classic Hennessy-Milner theorem [5] which states that over the class of image-fjnite Kripke models, two states are Kripke bisimilar if and only if they satisfy the same formulas in Hennessy-Milner logic
Additional_File_1___Cell_line_authentication – Supplemental material for Combined targeting EGFR and SRC as a potential novel therapeutic approach for the treatment of triple negative breast cancer
No full textSupplemental material, Additional_File_1___Cell_line_authentication for Combined targeting EGFR and SRC as a potential novel therapeutic approach for the treatment of triple negative breast cancer by Alexandra Canonici, Alacoque L. Browne, Mohamed F. K. Ibrahim, Kevin P. Fanning, Sandra Roche, Neil T. Conlon, Fiona O’Neill, Justine Meiller, Mattia Cremona, Clare Morgan, Bryan T. Hennessy, Alex J. Eustace, Flavio Solca, Norma O’Donovan and John Crown in Therapeutic Advances in Medical Oncology</p
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Characterization of a naturally occurring breast cancer subset enriched in EMT and stem cell characteristics
No full textHDAC4-regulated STAT1 activation mediates platinum resistance in ovarian cancer
No full textOvarian cancer frequently acquires resistance to platinum chemotherapy, representing a major challenge for improving patient survival. Recent work suggests that resistant clones exist within a larger drug-sensitive cell population prior to chemotherapy, implying that resistance is selected for rather than generated by treatment. We sought to compare clinically derived, intrapatient paired models of initial platinum response and subsequent resistant relapse to define molecular determinants of evolved resistance. Transcriptional analysis of a matched cell line series from three patients with high-grade serous ovarian cancer before and after development of clinical platinum resistance (PEO1/PEO4/PEO6, PEA1/PEA2, PEO14/PEO23) identified 91 up- and 126 downregulated genes common to acquired resistance. Significantly enhanced apoptotic response to platinum treatment in resistant cells was observed following knockdown of histone deacetylase (HDAC) 4, FOLR2, PIK3R1, or STAT1 (P <0.05). Interestingly, HDAC4 and STAT1 were found to physically interact. Acetyl-STAT1 was detected in platinum-sensitive cells but not in HDAC4 overexpressing platinum-resistant cells from the same patient. In resistant cells, STAT1 phosphorylation/nuclear translocation was seen following platinum exposure, whereas silencing of HDAC4 increased acetyl-STAT1 levels, prevented platinum-induced STAT1 activation, and restored cisplatin sensitivity. Conversely, matched sensitive cells were refractory to STAT1 phosphorylation on platinum treatment. Analysis of 16 paired tumor biopsies taken before and after development of clinical platinum resistance showed significantly increased HDAC4 expression in resistant tumors [n = 7 of 16 (44%); P = 0.04]. Therefore, clinical selection of HDAC4-overexpressing tumor cells upon exposure to chemotherapy promotes STAT1 deacetylation and cancer cell survival. Together, our findings identify HDAC4 as a novel, therapeutically tractable target to counter platinum resistance in ovarian cancer
Research methodology of grazing
No full textThroughout Europe, grass is the main feed for dairy cattle. This report presents the main results of the first meeting of the European Grassland Federation (EGF) Working Group Grazing in Kiel on 29 August 2010. The theme of the meeting was "Research methodology of grazing". There were three sessions: - setting the scene; - modelling of grazing; and - field measurements
Measurement of the ratio of prompt χ c to J / ψ production in pp collisions at √s = 7 TeV
No full textThe prompt production of charmonium χ c and J / ψ states is studied in proton-proton collisions at a centre-of-mass energy of √s = 7 TeV at the Large Hadron Collider. The χ c and J / ψ mesons are identified through their decays χ c → J / ψ γ and J / ψ → μ + μ - using 36 pb - 1 of data collected by the LHCb detector in 2010. The ratio of the prompt production cross-sections for χ c and J / ψ, σ (χ c → J / ψ γ) / σ (J / ψ), is determined as a function of the J / ψ transverse momentum in the range 2 < p T J / ψ < 15 GeV / c. The results are in excellent agreement with next-to-leading order non-relativistic expectations and show a significant discrepancy compared with the colour singlet model prediction at leading order, especially in the low p T J / ψ region
Obesity Correlation With Metastases Development and Response to First-Line Metastatic Chemotherapy in Breast Cancer
No full textStudy Objectives To compare breast cancer metastases between obese and nonobese women and to evaluate the effect of first-line metastatic chemotherapy in each group. Method A retrospective study was performed in an educational institute in Ireland. The study consisted of two parts: the first part was a comparative analysis of metastases development in obese (arm A) and nonobese patients (arm B). The second part was a comparison between both arms in relation to their response to first-line metastatic chemotherapy and their survival data. Results Between 2009 and 2014, we reviewed 118 patients with metastatic breast cancer. All the patients fulfilled our inclusion criteria. In all, 48% of patients were obese and 52% were nonobese. There were no statistically significant differences between the two groups. For arms A and B, the median interval between initial cancer diagnosis and distant metastases development (distant metastases-free survival) was 5.8 versus 7.6 years, respectively ( P value 0.04). Earlier visceral (liver and lung) metastases were observed in obese compared to nonobese women ( P values were 0.05 and 0.04, respectively). The most commonly used chemotherapy was weekly paclitaxel. Our treatments showed significantly better treatment response and better survival results in nonobese women than in obese ones, who were premenopausal with performance state 2, pathological grade 3, and four or more positive lymph nodes. Conclusion Obesity is linked with visceral metastases development, especially lung and liver metastases. Furthermore, first-line metastatic chemotherapy achieved better results in nonobese patients
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