On the existence of strongly normal ideals overP κ λ

For every uncountable regular cardinal and any cardinal,P denotes the set . Furthermore, < denotes=" the=" binary=" operation=" defined=">P byx<> iffxy¦x<>.By anideal over P we mean a proper, non-principal,-complete ideal overP extending the ideal dual to the filter generated by . For any idealI overP ,I ⁺ denotes the setP –I, andI ^* the filter dual toI.     

Crystal and molecular structure of delsoline

The crystal and molecular structure of the diterpenoid alkaloid delsoline (1) C₂₅H₄₁NO₇, M_r 467.61, has been determined by an X-ray analysis. The X-ray crystal structure which could not be solved earlier withMultan, has now been solved using the SIR 88 analysis program. The compound crystallizes in the space groupP2₁2₁2₁ with cell parameters:a=12.529(2),b=13.118(1),c=14.231(6)Å,V=2339(1)ų,Z=4,D _calc=1.33 g/cm^–3, (CuK)=1.54184 Å,(CuK )=7.4 cm^–1,R/R _w =0.068/0.040 for 2539 reflections. The A ring of delsoline exists in the boat conformation stabilized by an intramolecular N---H-O hydrogen bond. Ring D also is in a boat form. Unambiguous proton and carbon-13 nmr assignments have been made by a detailed analysis of the DEPT, COSY, NOESY, and HETCOR nmr spectra.     

High‐order implicit Runge–Kutta time integrators for fluid‐structure interactions

This paper presents an approach to develop high‐order, temporally accurate, finite element approximations of fluid‐structure interaction (FSI) problems. The proposed numerical method uses an implicit monolithic formulation in which the same implicit Runge–Kutta (IRK) temporal integrator is used for the incompressible flow, the structural equations undergoing large displacements, and the coupling terms at the fluid‐solid interface. In this context of stiff interaction problems, the fully implicit one‐step approach presented is an original alternative to traditional multistep or explicit one‐step finite element approaches. The numerical scheme takes advantage of an arbitrary Lagrangian–Eulerian formulation of the equations designed to satisfy the geometric conservation law and to guarantee that the high‐order temporal accuracy of the IRK time integrators observed on fixed meshes is preserved on arbitrary Lagrangian–Eulerian deforming meshes. A thorough review of the literature reveals that in most previous works, high‐order time accuracy (higher than second order) is seldom achieved for FSI problems. We present thorough time‐step refinement studies for a rigid oscillating‐airfoil on deforming meshes to confirm the time accuracy on the extracted aerodynamics reactions of IRK time integrators up to fifth order. Efficiency of the proposed approach is then tested on a stiff FSI problem of flow‐induced vibrations of a flexible strip. The time‐step refinement studies indicate the following: stability of the proposed approach is always observed even with large time step and spurious oscillations on the structure are avoided without added damping. While higher order IRK schemes require more memory than classical schemes (implicit Euler), they are faster for a given level of temporal accuracy in two dimensions. Copyright © 2015 John Wiley & Sons, Ltd.     

Cytotoxicity induced by engineered silver nanocrystallites is dependent on surface coatings and cell types

Due to their unique antimicrobial properties silver nanocrystallites have garnered substantial attention and are used extensively for biomedical applications as an additive to wound dressings, surgical instruments and bone substitute materials. They are also released into unintended locations such as the environment or biosphere. Therefore it is imperative to understand the potential interactions, fate and transport of nanoparticles with environmental biotic systems. Numerous factors including the composition, size, shape, surface charge, and capping molecule of nanoparticles are known to influence cell cytotoxicity. Our results demonstrate that the physical/chemical properties of the silver nanoparticles including surface charge, differential binding and aggregation potential, which are influenced by the surface coatings, are a major determining factor in eliciting cytotoxicity and in dictating potential cellular interactions. In the present investigation, silver nanocrystallites with nearly uniform size and shape distribution but with different surface coatings, imparting overall high negativity to high positivity, were synthesized. These nanoparticles included poly(diallyldimethylammonium) chloride-Ag, biogenic-Ag, colloidal-Ag (uncoated), and oleate-Ag with zeta potentials +45 ± 5, -12 ± 2, -42 ± 5, and -45 ± 5 mV, respectively; the particles were purified and thoroughly characterized so as to avoid false cytotoxicity interpretations. A systematic investigation on the cytotoxic effects, cellular response, and membrane damage caused by these four different silver nanoparticles was carried out using multiple toxicity measurements on mouse macrophage (RAW-264.7) and lung epithelial (C-10) cell lines. Our results clearly indicate that the cytotoxicity was dependent on various factors such as surface charge and coating materials used in the synthesis, particle aggregation, and the cell-type for the different silver nanoparticles that were investigated. Poly(diallyldimethylammonium)-coated Ag nanoparticles were found to be the most toxic, followed by biogenic-Ag and oleate-Ag nanoparticles, whereas uncoated or colloidal silver nanoparticles were found to be the least toxic to both macrophage and lung epithelial cells. Also, based on our cytotoxicity interpretations, lung epithelial cells were found to be more resistant to the silver nanoparticles than the macrophage cells, regardless of the surface coating.     

RNA-mediated sequestration of the RNA helicase eIF4A by Pateamine A inhibits translation initiation

Eukaryotic initiation factor 4A (eIF4A) is a member of the DEAD-box family of putative RNA helicases whose members are involved in many aspects of RNA metabolism. eIF4A is thought to facilitate binding of 43S preinitiation complexes to mRNAs by unwinding secondary structures present in the 5' untranslated region. Pateamine A, a small-molecule inhibitor of translation initiation, acts in an unusual manner by stimulating eIF4A activity. Herein, we report the elucidation of pateamine's mode of action. We demonstrate that Pateamine A is a chemical inducer of dimerization that forces an engagement between eIF4A and RNA and prevents eIF4A from participating in the ribosome-recruitment step of translation initiation.     

Unfolding the long-term pathophysiological processes following an acute inflammatory demyelinating lesion of multiple sclerosis

Background

Acute symptomatic inflammation is a main feature of multiple sclerosis but pathophysiological processes underlying total or partial recovery are poorly understood.

Objective

To characterize in vivo these processes at molecular, structural and functional levels using multimodal MR methods.

Methods

A neuroimaging 3-year follow-up (Weeks 0, 3, 11, 29, 59 and 169) was conducted on a 41-year-old woman presenting at baseline with a large acute demyelinating lesion of multiple sclerosis. Conventional magnetic resonance imaging (MRI), magnetization transfer imaging, diffusion-weighted imaging, functional MRI and magnetic resonance spectroscopy were conducted at 1.5 T.

Results

Patient presenting with subacute left hemiplegia recovered progressively (expended disability status scale 7 to 5.5). The MR exploration demonstrated structural functional and metabolic impairments at baseline. Despite restoration of the blood brain barrier integrity, high lactate levels persisted for several weeks concomitant with glial activation. Slow and progressive structural and metabolic restorations occurred from baseline to W169 (lesion volume −64%; apparent diffusion coefficient −14.7%, magnetization transfer ratio +14%, choline −51%, lipids −78%, N-acetylaspartate +77%) while functionality of the motor system recovered.

Conclusions

Multimodal MRI/MRS evidenced long-term dynamics recovery processes involving tissue repair, glial activation, recovery of neuronal function and functional systems. This may impact on customized rehabilitation strategies generally focused on the first months following the onset of symptoms.