The theological aspect of reformed judaism

by Max L. Margolis

Subcellular distribution of FTY720 and FTY720-phosphate in immune cells - another aspect of Fingolimod action relevant for therapeutic application

FTY720 (Fingolimod; Gilenya®) is an immune-modulatory prodrug which, after intracellular phosphorylation by sphingosine kinase 2 (SphK2) and export, mimics effects of the endogenous lipid mediator sphingosine-1-phosphate. Fingolimod has been introduced to treat relapsing-remitting multiple sclerosis. However, little has been published about the immune cell membrane penetration and subcellular distribution of FTY720 and FTY720-P. Thus, we applied a newly established LC-MS/MS method to analyze the subcellular distribution of FTY720 and FTY720-P in subcellular compartments of spleen cells of wild type, SphK1- and SphK2-deficient mice. These studies demonstrated that, when normalized to the original cell volume and calculated on molar basis, FTY720 and FTY720-P dramatically accumulated several hundredfold within immune cells reaching micromolar concentrations. The amount and distribution of FTY720 was differentially affected by SphK1- and SphK2-deficiency. On the background of recently described relevant intracellular FTY720 effects in the nanomolar range and the prolonged application in multiple sclerosis, this data showing a substantial intracellular accumulation of FTY720, has to be considered for benefit/risk ratio estimates.

Percutaneous embolization of arteriovenous malformations at the plantar aspect of the foot

Peripheral arteriovenous malformations (AVM) remain most challenging among various congenital vascular malformations to be treated. Here we present three illustrative patients with Yakes type IIIb and type IV AVM at the plantar aspect of the foot who were successfully treated by minimally invasive embolization. The value of the Yakes AVM classification system to guide the therapeutic decision making by directing specific therapeutic procedures to specific AVM types defined by their angioarchitecture is demonstrated. Direct percutaneous AVM puncture with coiling of aneurysmal outflow vein and subsequent ethanol embolization is shown. Finally, the report illustrates that several AVM types can coexist.

L'aspect linguistique des fusions-acquisitions d'entreprises

In the business world, mergers can also be seen as the joining of two or more "company-speaks". Contrasts between different "speaks" are brought out when the communities are together and this can be observed in the spoken and written language. This situation can be compared to that of languages in contact from the sociolinguistic and dialectological points of view. Terminology offers an adapted perspective on descriptive, historical and cultural levels.

L'aspect linguistique des fusions-acquisitions d'entreprises

In the business world, mergers can also be seen as the joining of two or more "company-speaks". Contrasts between different "speaks" are brought out when the communities are together and this can be observed in the spoken and written language. This situation can be compared to that of languages in contact from the sociolinguistic and dialectological points of view. Terminology offers an adapted perspective on descriptive, historical and cultural levels.

L'aspect linguistique des fusions-acquisitions d'entreprises

In the business world, mergers can also be seen as the joining of two or more "company-speaks". Contrasts between different "speaks" are brought out when the communities are together and this can be observed in the spoken and written language. This situation can be compared to that of languages in contact from the sociolinguistic and dialectological points of view. Terminology offers an adapted perspective on descriptive, historical and cultural levels.

An Aspect-Oriented Approach for Supporting Autonomic Reconfiguration of Software Architecture

The increasing complexity of current software systems is encouraging the development of self-managed software architectures, i.e. systems capable of reconfiguring their structure at runtime to fulfil a set of goals. Several approaches have covered different aspects of their development, but some issues remain open, such as the maintainability or the scalability of self-management subsystems. Centralized approaches, like self-adaptive architectures, offer good maintenance properties but do not scale well for large systems. On the contrary, decentralized approaches, like self-organising architectures, offer good scalability but are not maintainable: reconfiguration specifications are spread and often tangled with functional specifications. In order to address these issues, this paper presents an aspect-oriented autonomic reconfiguration approach where: (1) each subsystem is provided with self-management properties so it can evolve itself and the components that it is composed of; (2) self-management concerns are isolated and encapsulated into aspects, thus improving its reuse and maintenance. Povzetek: Predstavljen je pristop s samo-preoblikovanjem programske arhitekture.

Optimization of a label-free biosensor vertically characterized based on a periodic lattice of high aspect ratio SU-8 nano-pillars with a simplified 2D theoretical model

We have recently demonstrated a biosensor based on a lattice of SU8 pillars on a 1 μm SiO2/Si wafer by measuring vertically reflectivity as a function of wavelength. The biodetection has been proven with the combination of Bovine Serum Albumin (BSA) protein and its antibody (antiBSA). A BSA layer is attached to the pillars; the biorecognition of antiBSA involves a shift in the reflectivity curve, related with the concentration of antiBSA. A detection limit in the order of 2 ng/ml is achieved for a rhombic lattice of pillars with a lattice parameter (a) of 800 nm, a height (h) of 420 nm and a diameter(d) of 200 nm. These results correlate with calculations using 3D-finite difference time domain method. A 2D simplified model is proposed, consisting of a multilayer model where the pillars are turned into a 420 nm layer with an effective refractive index obtained by using Beam Propagation Method (BPM) algorithm. Results provided by this model are in good correlation with experimental data, reaching a reduction in time from one day to 15 minutes, giving a fast but accurate tool to optimize the design and maximizing sensitivity, and allows analyzing the influence of different variables (diameter, height and lattice parameter). Sensitivity is obtained for a variety of configurations, reaching a limit of detection under 1 ng/ml. Optimum design is not only chosen because of its sensitivity but also its feasibility, both from fabrication (limited by aspect ratio and proximity of the pillars) and fluidic point of view. (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)