1H NMR determination of the self-association of an acridine homodimer and its complexation with ethidium bromide in aqueous solution

1H NMR spectroscopy (500MHz) has been used to investigate the self-association in aqueous buffered solution of a bis-intercalator, Acridine Homodimer (AcrH), and its hetero-association with the aromatic dye, Ethidium Bromide (EB). The equilibrium constants and thermodynamical parameters (enthalpy and entropy) of self-association have been determined from the observed concentration and temperature dependences of chemical shifts of AcrH protons and the results are consistent with a model consisting of at least four distinct forms of AcrH molecules in solution: unfolded (U), folded (F), a dimer formed from two folded molecules (F2) and a trimer formed from three folded molecules (F3). It has also been shown that Ethidium Bromide complexes strongly to the dimer form (F2) of the bis-acridine molecule, AcrH. Comparison of the calculated association parameters of AcrH with the previously studied Ethidium Homodimer (EBH) revealed a correlation between the effectiveness of complexation and the length of chain connecting the chromophores of a bis-intercalator

La construction en petit appareil modulaire des voûtes de caves à Bourges (Cher) entre le xiiie et le milieu du xvie siècle

L’étude récente des caves de l’hôtel Jacques Cœur de Bourges a mis en évidence la construction de voûtes en berceau construites en petit appareil numéroté selon des modules de hauteur d’assises (0 à VII et 0 barré), de 3,9 à 15,3 cm de haut. Ce type de construction a été retrouvé dans les caves de la ville dans des contextes très diversifiés allant de l’hôtel particulier à la petite unité d’habitation en pan de bois, entre le xiiie et le milieu du xvie siècle. L’étude macroscopique des pierres mises en œuvre et de celles citées par les archives, croisée avec les mesures d’appareil et les analyses de mortiers, autorisent à avancer certaines hypothèses sur les origines de cette technique. Foyer artistique de la création architecturale du second Moyen Âge jusqu’au début de la Renaissance, Bourges mit ainsi en place, en réponse à la nature de ses ressources lithiques, une économie de la pierre qui transparaît dans la permanence de ce savoir-faire

Analyse expérimentale et simulations numériques de l'interaction fluide-structure d'un hydofoil élastique en écoulements subcavitant et cavitant

Le développement de structures portantes flexibles dans le domaine naval, telles que les hélices ou les safrans, pose de nouveaux problèmes de dimensionnement. Cette thèse a pour but de développer une méthode de dimensionnement validée par des essais pour des structures portantes déformables soumises à des écoulements, éventuellement diphasiques de type cavitant. Les essais sont réalisés sur un hydrofoil de type NACA66-312(mod.), fabriqué en polyacetate, au sein du tunnel hydrodynamique de l'Institut de Recherche de l'Ecole Navale. Lors des essais, des mesures de déformations du profil portant ainsi que de niveaux vibratoires sont réalisées. Une méthode numérique couplant un code structure éléments finis (ANSYS Mechanical) avec un code fluide volumes finis (ANSYS CFX) par une méthode partitionnée, itérative, synchrone et séquentielle, laquelle est validée en terme de prédiction du déplacement et des contraintes pour des écoulements subcavitants dans un premier temps, puis pour des écoulements cavitants stables et instables.The design of flexible lifting bodies in the naval industry, such as propelleror rudders, create some new design problems. This thesis proposes a numerical method validated by experimental comparison for solving the case of lifting bodies loaded by flow with or whitout cavitation. The tests are carried out in the hydrodynamic tunnel of the French Naval Academy Research Institute, on a polyacetate flexible hydrofoil NACA66-312 (mod.). During tests, strains and vibrations are measured for comparisons with numerical results. The numerical method uses a sequential synchrone iterative partitionned coupling betweena structural finite-element code (ANSYS Mechanical) and a finite-volume code (ANSYS CFX). Good agreement between numerical and experimental results for displacements, and stresses of the structure is highlighted. For the cavitating flow, a good agreement for the cavitation dynamic is observed and the stresses are evaluated with satisfying accuracy.PARIS-Arts et Métiers (751132303) / SudocSudocFranceF

Fully automated screening of veterinary drugs in milk by turbulent flow chromatography and tandem mass spectrometry

There is an increasing interest in screening methods for quick and sensitive analysis of various classes of veterinary drugs with limited sample pre-treatment. Turbulent flow chromatography in combination with tandem mass spectrometry has been applied for the first time as an efficient screening method in routine analysis of milk samples. Eight veterinary drugs, belonging to seven different classes were selected for this study. After developing and optimising the method, parameters such as linearity, repeatability, matrix effects and carry-over were studied. The screening method was then tested in the routine analysis of 12 raw milk samples. Even without internal standards, the linearity of the method was found to be good in the concentration range of 50 to 500 µg/L. Regarding repeatability, RSDs below 12% were obtained for all analytes, with only a few exceptions. The limits of detection were between 0.1 and 5.2 µg/L, far below the maximum residue levels for milk set by the EU regulations. While matrix effects—ion suppression or enhancement—are obtained for all the analytes the method has proved to be useful for screening purposes because of its sensitivity, linearity and repeatability. Furthermore, when performing the routine analysis of the raw milk samples, no false positive or negative results were obtained

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Methoxy- and Acetoxy-8-oxoberbines-Synthesis, Antitumor-Activity, and Interaction with DNA

Most of the memoxy-8H-dibenzo[a,g]isoquinolin-8-ones 3a-h and their acetoxy derivatives 6a-e were synthesized by condensation of 1-oxo-1,2,3,4-tetrahydroisoquinolines 4a-c and homophthalic acid anhydrides 5a and b, ether cleavage and acetylation. These protoberberinones were tested for cytostatic activity in vitro using MDA-MB-231 mammary tumor cells and for interaction with native calf thymus DNA. Tetramethoxy-8-oxoberbine 3f shows an inhibition of cell proliferation of 87% at a concentration of 10-5 mole; its cytostatic effect does not depend on intercalation into DNA. Die meisten der Methoxy-8H-dibenzo[a,g]chinolizin-8-one 3a-h und ihre Acetoxyderjvate 6a-e wurden durch Kondensation der 1-Oxo-1,2,3,4-tetrahydroisochinoline 4a-c mit den Homophthalsäureanhydriden 5a und b, anschließende Etherspaltung und Acetylierung dargestellt. Die cytostatische Wirkung dieser Protoberberinone wurde an der MDA-MB-231-Zellinie, die DNA-Interaktion an nativer Kalbsthymus-DNA geprüft. Das Tetramethoxy- 8-oxoberbin 3f zeigt eine Hemmung der Zellproliferation von 87% bei einer Konzentration von 10-5 M, wobei die cytostatische Wirkung nicht auf eine Interkalation mit der DNA zurückzuführen ist

Utilization of mechanical power and associations with clinical outcomes in brain injured patients: a secondary analysis of the extubation strategies in neuro-intensive care unit patients and associations with outcome (ENIO) trial

Background: There is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes. Methods: In this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale ≤ 12 before intubation) who required mechanical ventilation (MV) ≥ 24 h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS). Results: We included 1217 patients (mean age 51.2 years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9 J/min [IQR 9.2-15.1], 13 J/min [IQR 10-17], and 14 J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9 J/min, aRR at 17 J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22). Conclusions: Exposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation

Utilization of mechanical power and associations with clinical outcomes in brain injured patients. a secondary analysis of the extubation strategies in neuro-intensive care unit patients and associations with outcome (ENIO) trial

BackgroundThere is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes.MethodsIn this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale <= 12 before intubation) who required mechanical ventilation (MV) >= 24 h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS).ResultsWe included 1217 patients (mean age 51.2 years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9 J/min [IQR 9.2-15.1], 13 J/min [IQR 10-17], and 14 J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9 J/min, aRR at 17 J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22).ConclusionsExposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation

Album lithograhique pour 1829

This is a digital photograph of an original print held by the Bibliothèque nationale de France. The original is a lithograph. Printed by Henry Gaugain. Published by Henry Gaugain