Generation of superparamagnetic liposomes revealed as highly efficient MRI contrast agents for in vivo imaging

Maghemite (gamma-Fe2O3) nanocrystals stable at neutral pH and in isotonic aqueous media were synthesized and encapsulated within large unilamellar vesicles of egg phosphatidylcholine (EPC) and distearoyl-SN-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (DSPE-PEG(2000), 5 mol %), formed by film hydration coupled with sequential extrusion. The nonentrapped particles were removed by flash gel exclusion chromatography. The magnetic-fluid-loaded liposomes (MFLs) were homogeneous in size (195 +/- 33 hydrodynamic diameters from quasi-elastic light scattering). Iron loading was varied from 35 up to 167 Fe(III)/lipid mol %. Physical and superparamagnetic characteristics of the iron oxide particles were preserved after liposome encapsulation as shown by cryogenic transmission electron microscopy and magnetization curve recording. In biological media, MFLs were highly stable and avoided ferrofluid flocculation while being nontoxic toward the J774 macrophage cell line. Moreover, steric stabilization ensured by PEG-surface-grafting significantly reduced liposome association with the macrophages. The ratios of the transversal (r2) and longitudinal (r1) magnetic resonance (MR) relaxivities of water protons in MFL dispersions (6 < r2/r1 < 18) ranked them among the best T2 contrast agents, the higher iron loading the better the T2 contrast enhancement. Magnetophoresis demonstrated the possible guidance of MFLs by applying a magnetic field gradient. Mouse MR imaging assessed MFLs efficiency as contrast agents in vivo: MR angiography performed 24 h after intravenous injection of the contrast agent provided the first direct evidence of the stealthiness of PEG-ylated magnetic-fluid-loaded liposomes.     

Preparation and characterization of oxorhenium(V) complexes with 2,2'-biimidazole: the strong affinity of coordinated biimidazole for chloride ions via N-H...Cl- hydrogen bonding

N,N'-Dimethylbiimidazole and bipyridine (N-N) react with ReOCl3(OPPh3)(Me2S) to give mer-ReOCl3(N-N) compounds. Nonmethylated biimidazole forms a trans-O,O [ReOCl2(OPPh3)(biimH2)]+ cation, which is tightly associated with the Cl- counterion via N-H...Cl- hydrogen bonding. Hydrolysis of ReOCl3(biimMe2) in wet acetone (5% water) leads to the linear oxo-bridged dinuclear species [(OReCl2(biimMe2)2(mu-O)] containing chelated biimMe2. Acetone solutions containing only 1% water yield the bent oxo-bridged dinuclear species [(OReCl2)2(mu-O)(mu-biimMe2)2], where each Re center retains the ReO2Cl2N2 coordination but the biimMe2 ligands are bridging. The linear oxo-bridged [(OReCl2(biimH2)2(mu-O)] complex obtained with nonmethylated biimidazole includes two Cl- ions held via N-H...Cl- hydrogen bonds, leading to a dianionic [(OReCl2(biimH2...Cl)2(mu-O)]2- unit in the crystals of the PPh4+ salt. The compounds are characterized by IR and NMR spectroscopies, and the structures of [ReOCl2(OPPh3)(biimH2)]Cl, [(OReCl2(biimH2)2(mu-O)](PPh4Cl)(2).2H2O, and [(OReCl2)2(mu-O)(mu-biimMe2)2].acetone are determined by X-ray diffraction.     

Total Synthesis of Cryptophycins and Their 16-(3-Phenylacryloyl) Derivatives

Cryptophycin A, a cyclic depsipeptide isolated from the blue-green alga (cyanobacterium) Nostocsp.GSV 224, has shown excellent activity against solid tumors implanted in mice. The benzylic epoxide, which was shown to be very important for biological activity, is also fairly unstable under both acidic and alkaline conditions. The high doses needed to observe in vivo activity might be a result of this instability. In order to solve this problem while preserving the electrophilic character of the benzylic position, enones 1 and 2 have been proposed as promising analogs of the natural product, and a convergent total synthesis of these compounds is described. In addition, the same strategy was used to prepare Cryptophycins A, B, C, and D.     

Piecewise convex formulations of binary and permutation problems

It is well known that the problem of maximization of any difference of convex functions can be turned into a convex maximization problem; here, the aim is a piecewise convex maximization problem instead. Although this may seem harder, sometimes the dimension may be reduced by 1, and the local search may be improved by using extreme points of the closure of the convex hull of better points. We show that it is always the case for both binary and permutation problems and give, as such instances, piecewise convex formulations for the maximum clique problem and the quadratic assignment problem.     

Piecewise Convex Maximization Problems: Piece Adding Technique

In this article, we provide a global search algorithm for maximizing a piecewise convex function F over a compact D. We propose to iteratively refine the function F at local solution y by a virtual cutting function p _y (⋅) and to solve max {min {F(x)−F(y),p _y (x)}∣x∈D} instead. We call this function either a patch, when it avoids returning back to the same local solutions, or a pseudo patch, when it possibly yields a better point. It is virtual in the sense that the role of cutting constraints is played by additional convex pieces in the objective function. We report some computational results, that represent an improvement on previous linearization based techniques.     

An adaptive remeshing strategy for viscoelastic fluid flow simulations

In the last few years, we have developed a fairly general adaptive finite element solution procedure which can be applied to a large variety of problems. In this paper, this strategy is briefly recalled and applied to the solution of two-dimensional viscoelastic fluid flow problems. A log-conformation formulation recently introduced by Fattal and Kupferman [R. Fattal, R. Kupferman, Time-dependent simulation of viscoelastic flows at high Weissenberg number using the log-conformation representation, J. Non-Newtonian Fluid Mech. 126 (2005) 23-37] was implemented in order to improve the convergence properties of the numerical scheme. We confirm some results obtained in Hulsen, Fattal and Kupferman [M. Hulsen, R. Fattal, R. Kupferman, Flow of viscoelastic fluids past a cylinder at high Weissenberg number: stabilized simulations using matrix logarithm, J. Non-Newtonian Fluid Mech. 127 (2005) 27-39] and in some instances, we show that mesh adaptation allows to almost automatically reproduce accurate results obtained on very fine structured meshes.     

How does γ-irradiation affect the properties of a microfiltration membrane constituted of two polymers with different radiolytic behavior?

The objective of this work is to present the behavior of a fluorinated microporous membrane composed of poly(vinylidene fluoride) (PVDF) mechanically reinforced by a polyamide-66 (PA-66) fabric under γ-irradiation with dose ranging between 0 and 100 kGy, in inert atmosphere and at room temperature. Particular attention was paid to the evolution of mechanical properties, the surface morphology and pores size distribution of this membrane, in order to study the filtration capacity and selectivity with increasing radiation dose. Moreover, the repartition of the generated radicals onto the two components of the membrane was achieved by electron spin resonance (ESR) spectroscopy. Two different regimes are observed depending on the dose range, and a correlation between the mechanical behavior of the membrane and the evolution of the concentration of the radicals in the PA fabric is observed. Globally, the porosity of the surface membrane does not vary whatever the dose may be, but the mechanical properties of the membrane as well as the permeability are strongly affected, even for low radiation dose such as 10 kGy. These results are related to chain scissions on the PA fabric, which occurred preferentially, compared to cross-linking, in the investigated dose range.