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Abstract: The findings so far of the Pierre Auger Observatory and those of the Telescope Array define some requirements for a possible next generation global cosmic ray observatory: it needs to be considerably increased in size, it needs enhanced sensitivity to composition, and it has to cover the full sky. At the Pierre Auger Observatory, AugerNext aims to conduct some innovative initial research studies on a design of a sophisticated hybrid detector fulfilling these demands. Within a European supported ASPERA/APPEC (Astroparticle Physics European Consortium) project for the years 2011-2014, such R&D studies primarily focused on the following areas: i) consolidation of the detection of cosmic rays using MHz radio antennas; ii) proof- of-principle of cosmic ray microwave detection; iii) test of the large-scale application of new generation photo sensors; iv) generalization of data communication techniques; and v) development of new schemes for muon detection with surface arrays. The AugerNext Consortium consists of 14 principal investigators from 9 countries. This contribution summarizes some achievements of the R&D studies within the AugerNext project.
Found in: ključnih besedah
Keywords: ultra-high energy cosmic-ray experiments, Pierre Auger Observatory, Telescope Array, AugerNext research and development study
Published: 03.03.2016; Views: 3760; Downloads: 190
Fulltext (594,23 KB)

Abstract: Irinotecan is currently used in several cancer regimens mainly in colorectal cancer (CRC). This drug has a narrow therapeutic range and treatment can lead to side effects, mainly neutropenia and diarrhea, frequently requiring discontinuing or lowering the drug dose. A wide inter-individual variability in irinotecan pharmacokinetic parameters and pharmacodynamics has been reported and associated to patients’ genetic background. In particular, a polymorphism in the UGT1A1 gene (UGT1A1*28) has been linked to an impaired detoxification of SN-38 (irinotecan active metabolite) to SN-38 glucuronide (SN-38G) leading to increased toxicities. Therefore, therapeutic drug monitoring of irinotecan, SN-38 and SN-38G is recommended to personalize therapy. In order to quantify simultaneously irinotecan and its main metabolites in patients’ plasma, we developed and validated a new, sensitive and specific HPLC–MS/MS method applicable to all irinotecan dosages used in clinic. This method required a small plasma volume, addition of camptothecin as internal standard and simple protein precipitation. Chromatographic separation was done on a Gemini C18 column (3 μM, 100 mm x 2.0 mm) using 0.1% acetic acid/bidistilled water and 0.1% acetic acid/acetonitrile as mobile phases. The mass spectrometer worked with electrospray ionization in positive ion mode and selected reaction monitoring. The standard curves were linear (R20.9962) over the concentration ranges (10–10000 ng/mL for irinotecan, 1–500 ng/mL for SN-38 and SN-38G and 1–5000 ng/mL for APC) and had good back-calculated accuracy and precision. The intra- and inter-day precision and accuracy, determined on three quality control levels for all the analytes, were always <12.3% and between 89.4% and 113.0%, respectively. Moreover, we evaluated this bioanalytical method by re-analysis of incurred samples as an additional measure of assay reproducibility. This method wassuccessfully applied to a pharmacokinetic study in metastatic CRC patients enrolled in a genotype-guided phase Ib study of irinotecan administered in combination with 5-fluorouracil/ leucovorin and bevacizumab.
Found in: ključnih besedah
Keywords: Pharmacokinetic, pharmacodynamics, phase I clinical study, colorectal cancer, Mass spectrometry, pharmacogenetics
Published: 21.03.2017; Views: 3668; Downloads: 0
Fulltext (1018,06 KB)

Found in: ključnih besedah
Summary of found: ... study, research, employment prospects, university, higher education, quality...
Keywords: study, research, employment prospects, university, higher education, quality assurance
Published: 05.02.2018; Views: 2693; Downloads: 0
Fulltext (68,29 KB)

Found in: ključnih besedah
Summary of found: ...in the disruption and thus enable the study of quiescent SMBHs, which represent a large...
Keywords: The observing strategy with continuous scanning and large sky coverage of the upcoming ground-based Large Synoptic Survey Telescope (LSST) will make it a perfect tool in search of rare transients, such as Tidal Disruption Events (TDEs). Bright optical flares resulting from tidal disruption of stars by their host supermassive black hole (SMBH) can provide us with important information about the mass of the SMBH involved in the disruption and thus enable the study of quiescent SMBHs, which represent a large majority of SMBHs found in centres of galaxies. These types of transients are extremely rare, with only about few tens of candidates discovered so far. It is expected that the LSST will provide a large sample of new TDE light curves. Here we present simulations of TDE observations using an end-to-end LSST simulation framework. Based on the analysis of simulated light curves we estimate the number of TDEs with good quality light curves the LSST is expected to discover in 10 years of observations. In addition, we investigate whether TDEs observed by the LSST could be used to probe the SMBH mass distribution in the universe. The participation at this conference is supported by the Action CA16104 Gravitational waves, black holes and fundamental physics (GWverse), supported by COST (European Cooperation in Science and Technology).
Published: 04.01.2021; Views: 1720; Downloads: 0