1,667 research outputs found
Jurisprudence commentée - Les provisions pour arbitrage face à l’impécuniosité d’une partie
No full textJurisprudence commentée par Laurent POSOCCO, Maître de Conférence à L’Université Toulouse Capitole UT1
Cass. civ. 1re, 13 juill. 2016, FS-P+B, n° 15-19.38
Ten years of oxygen and hydrogen isotopic composition of daily precipitation at Concordia station, East Antarctica
No full textHere we present a 10year
(20082017)
record of the isotopic composition of precipitation at
Dome C. The winterover
personnel at Concordia Station have been continuously collecting
daily precipitation since 2008: this represents a unique record of the isotopic composition of
precipitation from the Antarctic Plateau. Snow is collected on a raised platform (height: 1 m) in
the clean area of the station and analyzed for d18O, dD and deuterium excess. A significant positive
correlation between d18O (dD) of precipitation and 2m
air temperature is observed at different
temporal scale; the lowest temperature and isotopic values are preferentially observed
during winters affected by a strongly positive Southern Annular Mode index [Stenni et al., 2016].
We have compared the isotopic data of Concordia samples with meteorological data from the
Dome C AWS of the Programma Nazionale di Ricerche in Antartide (PNRA), as well as with the
isotopeenabled
atmospheric general circulation models ECHAM5wiso
and ECHAM6wiso,
in
order to improve the understanding of the mechanisms governing the isotopic composition of
precipitation on the Antarctic plateau, which are yet to be fully understood, as well as the postdepositional
effects altering the pristine isotopic signal of precipitation. The comprehension of
these physical processes is fundamental for reconstructing past temperature variations using
the isotopic records from ice cores drilled in low accumulation areas of Antarctica [Casado et
al., 2018], e.g., the upcoming Beyond EPICA drilling at Little Dome C. Very few temporal relationships
between temperature and snow isotopic composition, mostly limited in time or sampling
frequency, have been calculated, while spatial relationships have been traditionally used
to reconstruct past temperature from ice core isotopic records [MassonDelmotte
et al., 2008]
“A new LC-MS/MS method for the simultaneous quantification of abemaciclib, its main active metabolites M2 and M20, and letrozole for therapeutic drug monitoring”
No full textAbemaciclib (ABEMA) is the last CDKi approved for the treatment of breast cancer. Adverse reactions to this drug are not experienced in the same manner by the entire patient population but in case of severe toxicity dose reductions and therapy discontinuation are required, suggesting that a TDM-guided treatment could be beneficial for these patients. ABEMA is extensively metabolized by the liver. The most abundant active metabolites are M2 and M20. This CDKi is administered together with anti-estrogen drugs, such as letrozole (LETRO). The aim of this work was to develop and validate a LC-MS/MS method for the simultaneous quantification of ABEMA, M2, M20, and LETRO. The chromatographic separation of the analytes was obtained using a SIL-20AC XR auto-sampler coupled to LC-20AD UFLC Prominence XR pumps (Shimadzu, Tokyo, Japan). The chromatographic column employed was an XTerra MS C18, (3,5 μm, 125 Å, 50x2.1 mm) coupled with a Security Guard Cartridge (MS C18, 125 Å, 3.9x5 mm) provided by Waters. Detection was performed by an API 4000 QTrap (SCIEX) mass spectrometer. The presented analytical method was fully validated according to EMA and FDA guidelines on bioanalytical method validation. Linearity was confirmed on 10 independent tests (R2 within 0.997–1.000) over the concentration ranges of 40–800 ng/mL for ABEMA, 10–200 ng/mL for M2 and M20, 20–400 ng/mL for LETRO. The method was applied to analyze plasma samples from patients enrolled in a clinical trial, collected at Cmin. Incurred sample reanalysis was performed on a set of 30 samples, confirming the reproducibility of the analytical method
A commitment to difference: An interview with Esther Newton
No full textEsther Newton (b. 1940) is an influential American anthropologist, whose pioneering work on drag queens and gay and lesbian communities has contributed to the emergence of gay and lesbian anthropology, and gradually also queer anthropology, as a recognized sub-field within socio-cultural anthropology. Newton undertook her graduate work at the University of Chicago under the tutelage of Professor David Schneider. Newton is currently Professor of Women’s Studies and American Culture, Department of Women’s Studies, University of Michigan. Her memoir, My Butch Career, is forthcoming from Duke University Press.
Newton was interviewed at the 113th American Anthropological Association Annual Meeting in Washington DC, on Friday 5 December 2014. Prior to the interview, co-editors Boyce, Engebretsen and Posocco along with Gonzalez-Polledo developed a list of themes and questions that guided the conversation that follows. We have aimed to maintain the sense of informal and jovial atmosphere that guided the interview, as it began over a lunch meal in the hotel lobby and continued afterwards in the quiet of Esther’s hotel room, with Elisabeth joining in on Skype from China, and Ellen Lewin – Esther’s room-mate and also notable feminist and queer anthropologist – entering the room and contributing to the latter part of the discussion.
The following conversation is between Esther Newton (EN) and Paul Boyce (PB), Elisabeth Engebretsen (EE), EJ Gonzalez-Polledo (EJG), Ellen Lewin (EL), Silvia Posocco (SP)
Polymer-Clay Nanocomposites: A Multiscale Molecular Modeling Approach
No full textA hierarchical procedure bridging the gap between atomistic and mesoscopic simulation for polymer-clay nanocomposite (PCN) design is presented. The dissipative particle dynamics (DPD) is adopted as the mesoscopic simulation technique, and the interaction parameters of the mesoscopic model are estimated by mapping the corresponding energy values obtained from atomistic molecular dynamics (MD) simulations. The predicted structure of the nylon 6 PCN system considered is in excellent agreement with previous experimental and atomistic simulation results
Modeling hierarchically structured nanoparticle/diblock copolymer systems
No full textDespite progress in theories and simulations, the structure prediction of self-assembled materials beyond simple model systems remains a grand challenge. In this work, we present a molecular modeling approach for predicting the nanostructure of hybrid systems based on AB diblock copolymers and nanoparticles decorated with A, B, or mixed A/B homopolymer ligands. Using mesoscopic simulations, we derived phase diagrams as a function of nanoparticle concentration and decoration
Creating a suprazyme: integrating a molecular enzyme mimic with a nanozyme for enhanced catalysis
No full textEnzyme mimics, due to their limited complexity, traditionally display low catalytic efficiency. Herein we present a strategy that enables the transformation of a slow-acting catalyst into a highly active one by creating a non-covalent suprastructure, termed “suprazyme”. We show that cucurbit[7]uril macrocycles, rudimentary molecular enzyme mimics, embedded within an anionic monolayer on the surface of gold nanoparticles, outperform individual cucurbit[7]urils as well as nanoparticles, which also exhibit catalytic enzyme-like activity and thus act as nanozymes, by over 50 times, showcasing a 1044-fold acceleration in a model oxime formation reaction. The superior performance of such a suprazyme is attributed to a synergistic interplay between the organic monolayer and macrocycles, which is accompanied by a decreased local polarity and pH that favors the acid-catalyzed condensation process. The proposed approach holds promise for developing diverse suprazymes, contingent upon achieving a complementary structure and mechanism of action between the molecular catalyst and nanoparticles.This research was funded by the National Science Centre of Poland (grant OPUS 18 no. 2019/35/B/ST4/01758). We acknowledge the CINECA award under the ISCRA initiative, for the availability of high-performance computing resources and support, along with the SISSA Computing Center (https://www.sissa.it)
Dried Blood Spot Technique Applied in Therapeutic Drug Monitoring of Anticancer Drugs: a Review on Conversion Methods to Correlate Plasma and Dried Blood Spot Concentrations
No full textBackground: Anticancer drugs are notoriously characterized by a low therapeutic index, the introduction of therapeutic drug monitoring (TDM) in oncologic clinical practice could therefore be fundamental to improve treatment efficacy. In this context, an attractive technique to overcome the conventional venous sampling limits and simplify TDM application is represented by dried blood spot (DBS). Despite the significant progress made in bioanalysis exploiting DBS, there is still the need to tackle some challenges that limit the application of this technology: one of the main issues is the comparison of drug concentrations obtained from DBS with those obtained from reference matrix (e.g., plasma). In fact, the use of DBS assays to estimate plasma concentrations is highly dependent on the chemical-physical characteristics of the measured analyte, in particular on how these properties determine the drug partition in whole blood. Methods: In the present review, we introduce a critical investigation of the DBS-to-plasma concentration conversion methods proposed in the last ten years and applied to quantitative bioanalysis of anticancer drugs in DBS matrix. To prove the concordance between DBS and plasma concentration, the results of statistical tests applied and the presence or absence of trends or biases were also considered
Field-assisted paper spray mass spectrometry for the quantitative evaluation of imatinib levels in plasma
No full textDrug levels in patients' bloodstreams vary among individuals and consequently therapeutic drug monitoring (TDM) is fundamental to controlling the effective therapeutic range. For TDM purposes, different analytical approaches have been used, mainly based on immunoassay, liquid chromatography-ultraviolet, liquid chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. More recently a matrix-assisted laser desorption/ionisation method has been proposed for the determination of irinotecan levels in the plasma of subjects under therapy and this method has been cross-validated by comparison with data achieved by LC-MS/MS. However, to reach an effective point-of-care monitoring of plasma drug concentrations, a TDM platform technology for fast, accurate, low-cost assays is required. In this frame, recently the use of paper spray mass spectrometry, which is becoming a popular and widely employed MS method, has been proposed. In this paper we report the results obtained by the development of a paper spray-based method for quantitative analysis in plasma samples of imatinib, a new generation of anticancer drug. Preliminary experiments showed that poor sensitivity, reproducibility and linear response were obtained by the "classical" paper spray set-up. In order to achieve better results, it was thought of interest to operate in presence of a higher and more homogeneous electrical field. For this aim, a stainless steel needle connected with the high voltage power supply was mounted below the paper triangle. Furthermore, in order to obtain valid quantitative data, we analysed the role of the different equilibria participating to the phenomena occurring in paper spray experiments, depending either on instrumental parameters or on the chemical nature of analyte and solvents. A calibration curve was obtained by spiking plasma samples containing different amounts of imatinib (1) with known amounts of deuterated imatinib (1d3) as internal standard, with molar ratios [1]/[1d3] in the range 0.00-2.00. A quite good linearity was obtained (R2 = 0.975) and some experiments performed on spiked plasma samples with known amounts of 1 confirmed the validity of this method
Mass spectrometry in the pharmacokinetic studies of anticancer natural products
No full textIn the history of medicine, nature has represented the main source of medical products. Indeed, the therapeutic use of plants certainly goes back to the Sumerian and Hippocrates and nowadays nature still represents the major source for new drugs discovery. Moreover, in the cancer treatment, drugs are either natural compounds or have been developed from naturally occurring parent compounds firstly isolated from plants and microbes from terrestrial and marine environment. A critical element of an anticancer drug is represented by its severe toxicities and, after administration, the drug concentrations have to remain in an appropriate range to be effective. Anyway, the drug dosage defined during the clinical studies could be inappropriate for an individual patient due to differences in drug absorption, metabolism and excretion. For this reason, personalized medicine, based on therapeutic drug monitoring (TDM), represents one of most important challenges in cancer therapy. Mass spectrometry sensitivity, specificity and fastness lead to elect this technique as the Golden Standard for pharmacokinetics and drug metabolism studies therefore for TDM. This review focuses on the mass spectrometry-based methods developed for pharmacokinetic quantification in human plasma of anticancer drugs derived from natural sources and already used in clinical practice. Particular emphasis was placed both on the pre-analytical and analytical steps, such as: sample preparation procedures, sample size required by the analysis and the limit of quantification of drugs and metabolites to give some insights on the clinical practice applicability. © 2015 Wiley Periodicals, Inc. Mass Spec Rev. 36:213–251, 2017
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