Modeling Lac du Bonnet granite using a discrete element model

A discrete element method code developed by the authors is used to model Lac du Bonnet granite in triaxial compression. The paper first presents the features of the model and the algorithms used to identify the micro deformability and strength parameters. With these identification algorithms, the model was calibrated to match experimental triaxial test data on Lac du Bonnet granite. With the calibrated model, investigation on failure evolution was then performed. The monitored evolution of the number and type of contact failures (micro cracks) reveals that at micro level tensile failures occur first, followed by mobilization of residual friction. Three distinct stages of stress–strain curve can be well identified by the accumulated number of contact failures and the mode of contact failures.     

Phase change problems with free convection: fixed grid numerical simulation

A numerical and experimental study of unsteady natural convection during freezing of water is presented. The mathematical model for the numerical simulations is based on the enthalpy-porosity method in vorticity-velocity formulation, equations are discretised on a fixed grid by means of a finite volume technique. A fully implicit method has been adopted for the mass and momentum equations. Experiments are performed for water in a differentially heated cube surrounded by air. The experimental data for natural convection with freezing in the cavity are collected to create a reference for comparison with numerical results. The method of simultaneous measurement of the flow and temperature fields using liquid crystal tracers is used. It allows us to collect transient data on the interface position, and the temperature and velocity fields. In order to improve the capability of the numerical method to predict experimental results, a conjugate heat transfer problem was solved, with finite thickness and internal heat conductivity of the non-isothermal walls. These results have been compared with the simulations obtained for the idealised case of perfectly adiabatic side walls, and with our experimental findings. Results obtained for the improved numerical model shown a very good agreement with the experimental data only for pure convection and initial time of freezing process. As time passes the discrepancies between numerical predictions and the experiment became more significant, suggesting a necessity for further improvements of the physical model used for freezing water. Received: 30 April 1999 / Accepted: 17 June 1999     

Ovarian Cancer Cells in Ascites Form Aggregates That Display a Hybrid Epithelial-Mesenchymal Phenotype and Allows Survival and Proliferation of Metastasizing Cells

Peritoneal metastases are the leading cause of morbidity and mortality in ovarian cancer. Cancer cells float in peritoneal fluid, named ascites, together with a definitely higher number of non neo-neoplastic cells, as single cells or multicellular aggregates. The aim of this work is to uncover the features that make these aggregates the metastasizing units. Immunofluorescence revealed that aggregates are made almost exclusively of ovarian cancer cells expressing the specific nuclear PAX8 protein. The same cells expressed epithelial and mesenchymal markers, such as EPCAM and αSMA, respectively. Expression of fibronectin further supported a hybrid epithelia-mesenchymal phenotype, that is maintained when aggregates are cultivated and proliferate. Hematopoietic cells as well as macrophages are negligible in the aggregates, while abundant in the ascitic fluid confirming their prominent role in establishing an eco-system necessary for the survival of ovarian cancer cells. Using ovarian cancer cell lines, we show that cells forming 3D structures neo-expressed thoroughly fibronectin and αSMA. Functional assays showed that αSMA and fibronectin are necessary for the compaction and survival of 3D structures. Altogether these data show that metastasizing units display a hybrid phenotype that allows maintenance of the 3D structures and the plasticity necessary for implant and seeding into peritoneal lining.     

Synthesis and Biological Evaluation of Pyrazoline and Pyrrolidine-2,5-dione Hybrids as Potential Antitumor Agents

In search of novel and effective antitumor agents, pyrazoline-substituted pyrrolidine-2,5-dione hybrids were designed, synthesized and evaluated in silico, in vitro and in vivo for anticancer efficacy. All the compounds exhibited remarkable cytotoxic effects in MCF7 and HT29 cells. The excellent antiproliferative activity toward MCF7 (IC₅₀=0.78±0.01 μM), HT29 (IC₅₀=0.92±0.15 μM) and K562 (IC₅₀=47.25±1.24 μM) cell lines, prompted us to further investigate the antitumor effects of the best compound S2 (1-(2-(3-(4-fluorophenyl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-oxoethyl)pyrrolidine-2,5-dione). In cell-cycle analysis, S2 was found to disrupt the growth phases with increased cell population in G₁/G₀ phase and decreased cell population in G₂/M phase. The excellent in vitro effects were also supported by inhibition of anti-apoptotic protein Bcl-2. In vivo tumor regression studies of S2 in HT29 xenograft nude mice, exhibited equivalent and promising tumor regression with maximum TGI, 66 % (i. p. route) and 60 % (oral route) at 50 mg kg⁻¹ dose by both the routes, indicating oral bioavailability and antitumor efficacy. These findings advocate that hybridization of pyrazoline and pyrrolidine-2,5-dioes holds promise for the development of more potent and less toxic anticancer agents.     

Synthesis,SAR, and Biological Evaluation of α‐Sulfonylphosphonic Acids as Selective Matrix Metalloproteinase Inhibitors

Selective MMP inhibitors : Eleven α‐sulfonylphosphonates were synthesized and tested as MMP inhibitors. The IC₅₀ values for most of them are in the nanomolar range against MMP‐2, ‐8, ‐13, and ‐14, with an interesting selectivity profile versus MMP‐9.

     

Microsomal lipid peroxidation: Effect of vitamin E and its functional interaction with phospholipid hydroperoxide glutathione peroxidase

The role of vitamin E in the protection against iron dependent lipid peroxidation was studied in rat liver microsomes and Triton-dispersed microsomal lipid micelles. In these systems, an antioxidant effect of vitamin E at a physiological ratio to phospholipids could be observed only in the presence of phospholipid hydroperoxide glutathione peroxidase (PHGPX) and glutathione. The rationale of this cooperation is discussed on the basis of the hydroperoxyl radical scavenging capacity of vitamin E and the reduction of membrane hydroperoxides by PHGPX. The scavenging of lipid hydroperoxyl radicals by vitamin E, although inhibiting propagation of the peroxidative chain, produces lipid hydroperoxides from which ferrous iron generates alkoxyl radicals that react with vitamin E almost as fast as with fatty acids. Therefore, only if membrane hydroperoxides are continuously reduced by this specific peroxidase does the scavenging of hydroperoxyl radicals by vitamin E lead to an effective inhibition of lipid peroxidation.     

Perceived orientation of axis rotation in structure-from-motion.

Perceived orientation of axis of rotation and accuracy in discriminating fixed-axis from nonfixed-axis rotations were investigated for orthographic projections of three-dimensional rotating objects. The principal findings were (1) the slant of the axis of rotation was systematically misperceived; (2) in both two-view and multiview displays, the perceived slant of the axis of rotation was well-predicted by the ratio between the deformation (a property of the first-order optic flow) and the component parallel to the image plane of the global velocity vector; (3) if this ratio was kept constant in each frame transition of the stimulus sequence (or it was varied), then the stimuli tended to be judged as fixed-axis rotations (or as nonfixed-axis rotations), regardless of whether they simulated a fixed-axis rotation or not; and (4) the tilt of the axis of rotation was perceived in two-view displays with a very small error. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Radiation-Induced Synthesis of Fullerene-Silica Hybrid Nanomaterials

C₆₀ fullerene has been radiation grafted on bare and functionalized silica surface with mercaptopropyl moieties in toluene solution. The resulting fullerene-silica hybrid nanomaterials have been characterized by FT-IR and solid state ¹³C CP-MAS NMR spectroscopy and compared to the radiolysis products of C₆₀ in toluene. It has been found that fullerene is grafted on silica surface but, because the radiation grafting has been conducted in toluene, fullerene results arylated from radicals derived from toluene radiolysis. The fullerene-silica hybrid nanomaterials cannot be extracted by warm decalin, demonstrating that the fullerene cage is chemically bonded on the silica surface. The thermal behavior of fullerene-silica hybrid nanomaterials has been studied by thermogravimetric analysis (TGA) and differential thermal analysis (DTA) in air flow.     

Polymerization of bicyclic ethers

Summary Structure of copolymers obtained by ring opening cationic polymerization from 7-oxabicyclo[ 2.2.1] heptane and ethylene oxide has been recently reported. This study about the spin lattice relaxation times and Nuclear Overhauser enhancement factor in the carbon-13 NMR spectra was performed and the results interpreted in terms of different internal mobility of the units in the copolymer chain.Previous papers in this series are: G. CECCARELLI, F.ANDRUZZI, Makromol. Chem. 180, 1371(1979); F.ANDRUZZI, G.CECCARELLI, M.PACI Polymer 21, 1180(1980); and ref (M.PACI et al. 1981).     

Mixed micelles containing lipophilic gadolinium complexes as MRA contrast agents

Mixed micelles for MRA are multicomponent systems containing a phospholipid, a biocompatible non-ionic surfactant (e.g. Synporonic^(k) F-108) and a lipophilic gadolinium complex. A variety of lipophilic gadolinium complexes were designed taking into account features such as: (i) nature of ligand (cyclic versus acyclic); (ii) lipophilic moiety; (iii) global charge of the complex; and (iv) nature of bond connecting the complex to the lipophilic moiety. All the lipophilic gadolinium complexes after formulation as mixed micelles show high relaxivities in water and in blood (rat). Mixed micelles containing gadolinium complexes bearing only one aliphatic chain cannot be used as MRA contrast agents because they have a high haemolytic effect. Furthermore, in rats they are quickly eliminated from the blood stream. These drawbacks are completely circumvented using gadolinium complexes bearing two aliphatic chains. Mixed micelles containing such complexes show high relaxivities. no haemolytic effect and long blood permanence. This makes them promising candidates as MRA contrast agents. However, elimination, which occurs exclusively through the liver, is not complete, even after 7 days. Complexes containing labile (e.g. ester) bonds between the lipophilic moieties and the chelate subunit are eliminated through both the liver and the kidneys. However, elimination is stiil not complete after 7 days.