Pavages additifs

The following article is one of introduction to additive frieze patterns, linking the subject to multiplicative frieze patterns. We also add two new theorems about additive frieze patterns (see theorem 2 and 5) and a conjecture about infinite multiplicative frieze patterns. (the parper is in french

Lysosomotropic cationic drugs induce cytostatic and cytotoxic effects : role of liposolubility and autophagic flux and antagonism by cholesterol ablation

Cation trapping in acidic cell compartments determines an antiproliferative effect that has a potential interest in oncology, as shown by clinical data and trials involving chloroquine and hydroxychloroquine. To further characterize the mechanism of this effect, we studied a series of 6 substituted triethylamine (s-Et3N) drugs that encompasses a wide range of liposolubility (amiodarone, quinacrine, chloroquine, hydroxychloroquine, lidocaine, and procainamide). Three tumor cell lines and primary human endothelial cells were exploited in proliferation assays (48 h, cell counts). Accumulation of the autophagic effector LC3 II and the apoptotic marker cleaved PARP1 (immunoblots), cytotoxicity, cell cycle analysis and endocytic function were further tested in the p53-null histiocytic lymphoma U937 line. A profound and desynchronized antiproliferative effect was observed in response to all s-Et3Ns with essentially no cell type specificity. Predictors of s-Et3N potency were liposolubility and the acute accumulation of the autophagic effector LC3 II (6 h-treatments). For each s-Et3N, there was an antiproliferative concentration range where cytotoxicity and apoptosis were not triggered in U937 cells (24–48 h-treatments). Quinacrine was the most potent cytostatic drug (1–5 μM). Co-treatment of cells with inhibitors of cholesterol, β-cyclodextrin or lovastatin, partially reversed the antiproliferative effect of each s-Et3N. The cytopathology induced by cationic drug accumulation includes a cytostatic effect. Its intensity is cell type- and p53-independent, but predicted by the inhibition of autophagic flux and by the liposolubility of individual drugs and alleviated by cholesterol ablation. The superiority of quinacrine, biomarker value of LC3 II and antagonism by a statin may be clinically relevant

An in vitro reconstitution system to address the mechanism of the vascular expression of the bradykinin B1 receptor in response to angiotensin converting enzyme inhibition

The expression of the bradykinin (BK) B1 receptor (B1R), lacking in normal vascular tissues, is induced following innate immune system activation and chronic blockade of angiotensin converting enzyme (ACE). To identify cytokine-dependent or -independent mechanisms for the latter phenomenon, the ACE inhibitor enalaprilat and several peptides potentiated in vivo by ACE blockade were applied either directly to human umbilical artery smooth muscle cells (hUA-SMCs) or to differentiated monoblastoid U937 cells to produce a conditioned medium (CM) that was later transferred to hUA-SMCs. A phagocyte stimulant, lipopolysaccharide, did not upregulate B1R, measured using [3H]Lys-des-Arg9-BK binding, or translocate NF-κB to the nuclei if applied directly to the hUA-SMCs. However, the CM of lipopolysaccharide-stimulated U937 cells was active in these respects (effects inhibited by etanercept and correlated to TNF-α presence in the CM). A peptidase-resistant B1R agonist had no significant direct or indirect acute effect (4 h) on B1R expression, but repeated hUA-SMC stimulations over 40 h were stimulatory in the absence of NF-κB activation. Other peptides regulated by ACE or enalaprilat did not directly or indirectly stimulate B1R expression. The reconstitution system supports the rapid cytokine-dependent vascular induction of B1Rs and a slow “autoregulatory” one potentially relevant for the ACE blockade effect

Orientational dynamics in supercooled glycerol computed from MD simulations: self and cross contributions

The orientational dynamics of supercooled glycerol using molecular dynamics simulations for temperatures ranging from 323 K to 253 K, is probed through correlation functions of first and second ranks of Legendre polynomials, pertaining respectively to dielectric spectroscopy (DS) and depolarized dynamic light scattering (DDLS). The self, cross, and total correlation functions are compared with relevant experimental data. The computations reveal the low sensitivity of DDLS to cross-correlations, in agreement with what is found in experimental work, and strengthen the idea of directly comparing DS and DDLS data to evaluate the effect of cross-correlations in polar liquids. The analysis of the net static cross-correlations and their spatial decomposition shows that, although cross-correlations extend over nanometric distances, their net magnitude originates, in the case of glycerol, from the first shell of neighbouring molecules. Accessing the angular dependence of the static correlation allows us to get a microscopic understanding of why the rank-1 correlation function is more sensitive to cross-correlation than its rank-2 counterpart.Comment: 9 pages, 6 figure

ACE ligands in endothelial cells

Angiotensin converting enzyme (ACE) is a drug target and an effective bradykinin (BK)-inactivating ectopeptidase. We exploited a recently described [3H]enalaprilat binding assay to quantify the full dynamic range of ACE expression in intact human umbilical vein endothelial cells (HUVECs) stimulated with known or novel modulators of ACE expression. Further, the affinities for ACE of a set of physiological substrates were determined using the same assay. BK has the highest affinity (Ki 525 nM) among known substrates to displace [3H]enalaprilat binding from ACE. Tumor necrosis factor (TNF)-α repressed the expression of ACE in HUVECs while phorbol 12-myristate 13-acetate (PMA) upregulated it in 24 h (∼12-fold dynamic range by [3H]enalaprilat binding, corroborated by ACE immunoblotting). Intermediate levels of ACE expression were seen in cells stimulated with both PMA and a cytokine. In contrast, high glucose, insulin or EGF failed to affect ACE expression. The effect of TNF-α was abated by etanercept, the IKK2 inhibitor TPCA-1, or a p38 inhibitor while that of PMA was reduced by inhibitors of PKC isoforms sensitive to phorbol esters and calcium. The short-term PKC- and MEK1-dependent increase of c-Fos expression was best correlated to PMA-induced ACE upregulation. The [3H]enalaprilat binding assay applied to HUVECs supports that ACE is a particularly active kininase and that endothelial ACE expression is dynamically and specifically regulated. This has potential importance in inflammatory diseases and diabetes

Du producteur à l'utilisateur: identification des trajectoires d'appropriation des données géographiques.

International audienceTo define, on a non technician face, the life cycle of geographic information, "from captor to decisions" we need, in a actor network theory perspective, to understand the process "from producer to user". In order to give an answer, we choose to study the spatial data appropriation process. This process opens the analysis of how data can be used by a group that has not produced the data itself, as well as in a multi-actor context. Distributed cognition theory offers a framework to understand data as a cognitive and collaborative artefact. Eight exploratory case studies help to identify typical appropriation trajectories, factors and socio-cognitive processes. This article offers a different vantage point on the spatial data sharing question and spatial data life cycle.Décliner sur un versant non technique le cycle de vie de l'information géographique " du capteur aux décisions " revient, du point de vue des jeux d'acteurs, à s'intéresser aux mécanismes qui influencent les étapes " du producteur à l'utilisateur ". Pour ce faire, nous avons choisi d'étudier les démarches d'appropriation des données géographiques. Elles nous permettent d'analyser comment, dans un contexte multi-acteurs, une donnée peut trouver une place et un usage au sein d'une organisation qui ne l'a pas produite. Le cadre unificateur qu'offre la cognition socialement distribuée permet, en particulier, de comprendre le rôle d'artefact cognitif et collaboratif que peut jouer la donnée. Huit études de cas exploratoires servent à identifier des trajectoires-types d'appropriation et les facteurs et processus socio-cognitifs qui y sont associés. Cet article offre, ainsi, un regard différent sur la problématique du partage et sur le cycle de vie des données géographiques généralement abordé d'un point de vue uniquement technique

Vasopeptidase-activated latent ligands of the histamine receptor-1

Whether peptidases present in vascular cells can activate prodrugs active on vascular cells has been tested with 2 potential latent ligands of the histamine H1 receptor (H1R). First, a peptide consisting of the antihistamine cetirizine (CTZ) condensed at the N-terminus of ε-aminocaproyl-bradykinin (εACA-BK) was evaluated for an antihistamine activity that could be revealed by degradation of the peptide part of the molecule. CTZ-εACA-BK had a submicromolar affinity for the BK B2 receptor (B2R; IC50 of 590 nM, [(3)H]BK binding competition), but a non-negligible affinity for the human H1 receptor (H1R; IC50 of 11 μM for [(3)H]pyrilamine binding). In the human isolated umbilical vein, a system where both endogenous B2R and H1R mediate strong contractions, CTZ-εACA-BK exerted mild antagonist effects on histamine-induced contraction that were not modified by omapatrilat or by a B2R antagonist that prevents endocytosis of the BK conjugate. Cells expressing recombinant ACE or B2R incubated with CTZ-εACA-BK did not release a competitor of [(3)H]pyrilamine binding to H1Rs. Thus, there is no evidence that CTZ-εACA-BK can release free cetirizine in biological environments. The second prodrug was a blocked agonist, L-alanyl-histamine, potentially activated by aminopeptidase N (APN). This compound did not compete for [(3)H]pyrilamine binding to H1Rs. The human umbilical vein contractility assay responded to L-alanyl-histamine (EC50 54.7 μM), but the APN inhibitor amastatin massively (17-fold) reduced its apparent potency. Amastatin did not influence the potency of histamine as a contractile agent. One of the 2 tested latent H1R ligands, L-alanyl-histamine, supported the feasibility of pro-drug activation by vascular ectopeptidase