Connections between discontinuous Galerkin and nonconforming finite element methods for the Stokes equations

We study a discontinuous Galerkin finite element method (DGFEM) for the Stokes equations with a weak stabilization of the viscous term. We prove that, as the stabilization parameter γ tends to infinity, the solution converges at speed γ^?1 to the solution of some stable and well‐known nonconforming finite element methods (NCFEM) for the Stokes equations. In addition, we show that an a posteriori error estimator for the DGFEM‐solution based on the reconstruction of a locally conservative H(div, Ω)‐tensor tends at the same speed to a classical a posteriori error estimator for the NCFEM‐solution. These results can be used to affirm the robustness of the DGFEM‐method and also underline the close relationship between the two approaches. © 2011 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2011     

Functionalization of multi-walled carbon nanotubes with coumarin derivatives and their biological evaluation

We report the synthesis and the characterization of different multi-walled carbon nanotubes (MWCNTs) linked to natural molecules, 5,7-coumarins and/or oleic acid, obtained from purified pristine MWCNTs by a cascade of chemical functionalization. The activities of these modified MWCNTs were investigated in vitro on human umbilical vein endothelial cells (HUVECs) by evaluating their ability to influence cell viability and to induce cell apoptosis. Our data showed that pristine MWCNTs are markedly cytotoxic; conversely, the carboxylated carbon nanotubes, much more readily dispersed in aqueous solutions and CNT-Link, the key intermediate designed by us for the drug anchorage, are biocompatible at the tested concentrations (1 and 10 μg ml(-1)).     

Regiodivergent synthesis of trisubstituted furans through Tf(2)O-catalyzed Friedel-Crafts acylation: a tool for access to tetrahydrofuran lignan analogues

3- or 4-Aroylfurans have been prepared selectively and in high yields from a common precursor by simple tuning of reaction conditions in Friedel-Crafts acylation promoted by triflic anhydride. The formation of products can be explained on the basis of the ring-chain tautomerism occurring in compounds equipped with two neighbouring carboxylic functions. Since 4-aroylfuran derivatives show a typical lignan backbone, suitable hydrogenation conditions were found out to gain tetrahydrofuran lignans.     

Synthesis of polyester nanoparticles in miniemulsion obtained by radical ring-opening of BMDO and their potential as biodegradable drug carriers

5,6-Benzo-2-methylene-1,3-dioxepane (BMDO) is used to obtain degradable polymeric nanoparticles via a statistical free-radical copolymerization with MMA and styrene in direct miniemulsion. The nanoparticles are analyzed by means of IR, NMR, DLS, SEM, and TEM. They show excellent cellular uptake and drug delivery properties. The cellular uptake into HeLa cells of particles resulting from copolymerization of BMDO with styrene is drastically enhanced compared to pure polystyrene. As a model drug system, paclitaxel is incorporated in PBMDO particles and its release and the effect on HeLa cells is studied and compared to commercial drug formulations. It is found that a drug delivery system based on PBMDO shows an excellent pharmacological effect.     

Identification of the plant origin of the botanical biomarkers of Mediterranean type propolis

Propolis is a honeybee product which bees produce by collecting resins from various botanical sources. The chemical composition of propolis is directly dependant on the availability of resinous plant materials in different geographic regions. This study was undertaken to evaluate the resinous plant sources used by bees to produce Mediterranean type propolis. Although this propolis type has already been the subject of numerous studies, its major botanical source had not yet been identified. In this study, using GC-MS analysis, we identify the resin of the common cypress, Cupressus_sempervirens, as the major plant source of the characteristic diterpene fingerprint profile of Mediterranean propolis.     

Longitudinal brain imaging of five malignant glioma patients treated with bevacizumab using susceptibility-weighted magnetic resonance imaging at 7 T

Malignant glioma is a rare tumor type characterized by prominent vascular proliferation. Antiangiogenic therapy with the monoclonal antibody bevacizumab is considered as a promising therapeutic strategy, although the effect on tumor vascularization is unclear. High-field susceptibility-weighted imaging (SWI) visualizes the microvasculature and may contribute to the investigation of antiangiogenic therapy responses in gliomas. We prospectively studied five adult malignant glioma patients treated with bevacizumab-containing regimens. In each patient, we performed three 7-T SWI and T1-weighted imaging investigations (baseline and 2 and 4 weeks after the start of bevacizumab treatment). In addition, we imaged a postmortem brain of a patient with glioblastoma using 7-T SWI and performed detailed histopathological analysis. We observed almost total resolution of brain edema in three of five patients after initiation of bevacizumab therapy. In one case with rapid increase of the lesion size despite bevacizumab therapy, SWI showed progressive increase of irregular hypointense structures, most likely corresponding to increasing amounts of pathological microvasculature. In one case with progressive neurological decline, 7-T images showed multiple intratumoral microhemorrhages after the first bevacizumab application. Correlation of postmortem neuroimaging with histopathology confirmed that SWI-positive structures correspond to tumor vasculature. The experience from our case series indicates that longitudinal 7-T SWI seems to be an appropriate method for investigation of changes in brain tumor vascularization over time under antiangiogenic therapy.     

Towards a universal LC–MS screening procedure – can an LIT LC–MSn screening approach and reference library be used on a quadrupole‐LIT hybrid instrument?

In contrast to libraries with highly reproducible gas chromatography electron ionization mass spectra, current liquid chromatography (LC–MS) libraries are limited to specific instrument types. Therefore, the aim of the study was to prove whether a recently developed linear ion trap (LIT) LC–MSⁿ screening approach and reference library can be transferred to an LC–MS/MS system with a quadrupole‐LIT hybrid mass analyzer using SmileMS, a sophisticated search algorithm. The LIT reference library was built with MS² and MS³ wideband spectra recorded on a ThermoFisher LXQ LIT with electrospray ionization in positive mode and full‐scan data‐dependent acquisition (DDA). Collision parameter optimizations, including different scan types and energies, were performed on an Applied Biosystems QTRAP 4000 system using electrospray ionization in positive mode and full‐scan DDA. Modified library sets were generated to improve the detection of a compound by the used search algorithm. Additionally, 100 authentic human urine samples were screened by both systems for proof of applicability. In the applicability study, 533 compounds were detected by the LXQ and 477 by the QTRAP system using enhanced product ion scan and a modified database. The presented data showed that the LIT screening approach and reference library could be used successfully on a QTRAP instrument with some limitations. These should be overcome by further optimizations regarding DDA settings for better sensitivity and further library modifications to reduce spectra mismatches. Copyright © 2012 John Wiley & Sons, Ltd.     

A facile and ecofriendly functionalization of multiwalled carbon nanotubes by an old mesoionic compound

This work reports for the first time a straightforward solvent-free chemical procedure to gain access to Δ-1-pyrroline grafted onto multiwalled carbon nanotubes by the 1,3-dipolar cycloaddition of the mesoionic 4-methyl-2-phenyloxazol-5(4H)-one.     

Serendipitous fragment-based drug discovery: ketogenic diet metabolites and statins effectively inhibit several carbonic anhydrases

Acetoacetic acid and R-3-hydroxy-butyric acid (BHB) are "ketone bodies", metabolites produced during the ketogenic diet. We discovered that they inhibit in the submicromolar-micromolar range several carbonic anhydrase (CA, EC 4.2.1.1) isoforms involved in relevant physiologic processes such as lipogenesis and tumorigenesis. The BHB fragment is also present in the molecules of most statins, widely used drugs for inhibiting cholesterol biosynthesis through the 3-hydroxy-3-methyl-glutaryl-CoA reductase pathway. Three such statins, atorvastatin, fluvastatin and rosuvastatin, showed submicromolar-low nanomolar inhibition of the fifteen human isoforms hCA I-XIV. Our data point out that in addition to their cholesterol lowering properties, these drugs may exert a therapeutic effect by inhibiting lipogenesis through mitochondrial CA inhibition. The statins are also low nanomolar inhibitors of the tumor-associated isoforms CA IX and XII. Based on the BHB/statin scaffolds, antiepileptic, antiobesity and antitumor compounds with higher affinity for the various CA isoforms involved in epileptogenesis (CA VA, VB, VII), lipogenesis (CA III, CA VA, CA VB) and tumorigenesis (CA IX and CA XII) may be designed.