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1.
Ultra-visokovakuumski sistem za naparevanje organskih polprevodnikov
Robert Hudej, Gvido Bratina, 2001, izvirni znanstveni članek

Opis: A new molecular-beam-epitaxy system for the growth of organic semiconductor layers was recently installed in the Laboratory for epitaxy and nanostructures of the Nova Gorica Polytechnic. The system is built around an ultra-high-vacuum chamber. The organic semiconductor material is evaporated from a low-temperature Knudsen cell. The system is equipped with a refraction high-energy electron-difraction system, a quadrupole mass spectrometer and a spectroscopic ellipsometer.
Najdeno v: ključnih besedah
Ključne besede: ultra-high vacuum, molecular-beam epitaxy, Knudsen cell, mass quadrupole spectrometer, spectroscopic ellipsometer, high-energy electrons
Objavljeno: 10.07.2015; Ogledov: 2679; Prenosov: 12
URL Polno besedilo (0,00 KB)

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Measurement of the muon content in air showers at the Pierre Auger Observatory
Marko Zavrtanik, Danilo Zavrtanik, Lili Yang, Serguei Vorobiov, Darko Veberič, Marta Trini, Samo Stanič, Ahmed Saleh, Gašper Kukec Mezek, Andrej Filipčič, Laura Collica, 2015, objavljeni znanstveni prispevek na konferenci

Opis: The muon content of extensive air showers is an observable sensitive to the primary composition and to the hadronic interaction properties. We present here different methods which allow us to estimate the muon number at the ground level and the muon production depth by exploiting the measurement of the longitudinal, lateral and temporal distribution of particles in air showers recorded at the Pierre Auger Observatory. The results, obtained at about 10[sup]19 eV (E[inf]CM ∼ 140 TeV center-of-mass energy for proton primaries), are compared to the predictions of LHC-tuned hadronic interaction models with different primary masses and suggest a deficit in the muon content at the ground predicted by simulations. The Pierre Auger Observatory uses water-Cherenkov detectors to measure particle densities at the ground and therefore has a good sensitivity to the muon content of air showers. Moreover, due to its hybrid design, the combination of muon measurements with other independent mass composition analyses such as Xmax provides additional constraints on hadronic interaction models.
Najdeno v: ključnih besedah
Ključne besede: Pierre Auger Observatory, ultra-high energy cosmic rays, muons, mass composition, hadronic interactions
Objavljeno: 03.03.2016; Ogledov: 1853; Prenosov: 139
.pdf Polno besedilo (298,46 KB)

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Azimuthal asymmetry in the risetime of the surface detector signals of the Pierre Auger Observatory
Marko Zavrtanik, Danilo Zavrtanik, Lili Yang, Serguei Vorobiov, Darko Veberič, Marta Trini, Samo Stanič, Ahmed Saleh, Gašper Kukec Mezek, Andrej Filipčič, A. Aab, 2016, izvirni znanstveni članek

Opis: The azimuthal asymmetry in the risetime of signals in Auger surface detector stations is a source of information on shower development. The azimuthal asymmetry is due to a combination of the longitudinal evolution of the shower and geometrical effects related to the angles of incidence of the particles into the detectors. The magnitude of the effect depends upon the zenith angle and state of development of the shower and thus provides a novel observable, (secθ)max, sensitive to the mass composition of cosmic rays above 3×1018  eV. By comparing measurements with predictions from shower simulations, we find for both of our adopted models of hadronic physics (QGSJETII-04 and EPOS-LHC) an indication that the mean cosmic-ray mass increases slowly with energy, as has been inferred from other studies. However, the mass estimates are dependent on the shower model and on the range of distance from the shower core selected. Thus the method has uncovered further deficiencies in our understanding of shower modeling that must be resolved before the mass composition can be inferred from (secθ)max.
Najdeno v: ključnih besedah
Ključne besede: ultra-high energy cosmic rays (UHECR), UHECR mass composition, Pierre Auger Observatory, extensive air showers, Auger Surface Detector signals risetime, azimuthal symmetry
Objavljeno: 15.04.2016; Ogledov: 2409; Prenosov: 0
.pdf Polno besedilo (698,19 KB)

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RAPID UPLC-ESI-MS/MS BASED ASSAY FOR DISCOVERY OF UDP-N-ACETYLMURAMOYL-L-ALANINE:D-GLUTAMATE (MurD) LIGASE INHIBITORS
Vjekoslava Car, 2016, magistrsko delo

Opis: A rapid, selective, robust and sensitive analytical assay method, operating in a short time frame with acceptable levels of precision, linear range and the accuracy necessary for successful Mur ligases inhibitors discovery, was developed. An LC-MS/MS analytical procedure was designed for the determination of a MurD ligase reaction product (UMAG). The special focus of this work was on UDP-N-acetylmuramyl-L-alanine:D-glutamate ligase (MurD) activity. The assay method is especially valuable as an orthogonal (secondary) assay for the primary high throughput fluorescent-based assay screening of potential Mur ligase inhibitors. The LC-MS/MS assay is fully compatible with the components from the primary fluorescent-based assay and enables the analysis of the same samples by both methodologies. The presented LC-MS/MS assay procedure is used for the evaluation of the false positive hits (molecules) from the primary, fluorescence based, high throughput screening assay experiments. This is important for the elimination of false positive hits from the prohibitively expensive and time-consuming investigation process. Method development describes the evaluation and optimization of the various stages of sample preparation, chromatographic separation, MS/MS determination and quantification. An enzyme reaction is performed in a 96-well plate. The quenched reaction mixture samples were spiked with an internal standard (phenacetin). The permeate was injected onto the U(H)PLC-MS/MS triple quadrupole system after sample ultrafiltration. Chromatographic separation was achieved on the ACQUITY UPLCTM HSS T3 column (100 x 2.1 mm i.d., 1.8 µm particle size) using an ammonium format buffer at pH 2.8 and acetonitrile as eluent. Elution initiated with an isocratic-hold for 1.1 min, followed by a two-step linear gradient of up to 3 min, giving a total run time of 5 min including equilibration. The flow rate was kept at a constant 0.4 mL/min. UMAG quantitative analysis was performed by positive electrospray ionization, followed by tandem mass spectrometry (ESI-MS/MS). The analytical assay quantifies UMAG in a linear range from 0.25 to 20 µM using 70 µL of samples. Validation results demonstrated that UMAG concentrations can be accurately and precisely determined in samples from the primary assay. Evaluation of inhibitory activities of compounds measured by both the fluorescence and the LC-MS/MS method demonstrated that the values were in a very good agreement. This analytical method can be used to screen a compound library at a defined concentration of each compound to obtain the percentage of inhibition, or with a series of compound concentrations to obtain inhibition potency of a compound (IC50). The selected Lek compounds no. 1 and 2 from the virtual screening campaign were presented, tested and further investigated due to the expression of significant MurD ligase inhibitory action acquired by primary high throughput tests. This assay has been developed for MurD, but during development, chromatographic and MS/MS conditions for UM and UMA were studied and defined as well. Therefore, this analytical assay method can easily be applied to other Mur ligases (i.e. MurC, MurE) enzyme activity monitoring in the process of bacteria cell wall peptidoglycan formation. This method enables the identification of many different Mur ligase inhibitors in a continued search for new Gram positive and Gram negative bacteria antibiotics.
Najdeno v: ključnih besedah
Ključne besede: Mur ligases, UDP-N-acetylmuramyl-L-alanine:D-glutamate (MurD) inhibitors, UNAM-Ala-Glu, LC-MS/MS, liquid chromatography, tandem mass spectrometry, antibiotics, drug discovery
Objavljeno: 23.09.2016; Ogledov: 3506; Prenosov: 188
.pdf Polno besedilo (2,62 MB)

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Development and Validation of a High- Performance Liquid Chromatography– Tandem Mass Spectrometry Method for the Simultaneous Determination of Irinotecan and Its Main Metabolites in Human Plasma and Its Application in a Clinical Pharmacokinetic Study
Giuseppe Toffoli, Elena Marangon, Elisa Mazzega, Bianca Posocco, 2015, izvirni znanstveni članek

Opis: 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.
Najdeno v: ključnih besedah
Ključne besede: Pharmacokinetic, pharmacodynamics, phase I clinical study, colorectal cancer, Mass spectrometry, pharmacogenetics
Objavljeno: 21.03.2017; Ogledov: 1776; Prenosov: 0
.pdf Polno besedilo (1018,06 KB)

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