QoS-Enabled B2B Integration

Business-To-Business Integration (B2Bi) is a key mechanism for enterprises to gain competitive advantage. However, developing B2Bi applications is far from trivial. Inter alia, agreement among integration partners about the business documents and the control flow of business document exchanges as well as applying suitable communication technologies for overcoming heterogeneous IT landscapes are major challenges. At the same time, choreography languages such as ebXML BPSS (ebBP), orchestration languages such as WS-BPEL and Web Services are promising to provide the foundations for seamless interactions among business partners. Automatically translating choreography agreements of integration partners into partner-specific orchestrations is an obvious idea for ensuring conformance of orchestration models to choreography models. Moreover, the application of such model-driven development methods facilitates productivity and cost-effectiveness whereas applying a service oriented architecture (SOA) based on WS-BPEL and Web Services leverages standardization and decoupling. By now, the realization of QoS attributes has not yet received the necessary attention that makes such approaches suitable for B2Bi. In this report, we describe a proof-of-concept implementation of the translation of ebBP choreographies into WS-BPEL orchestrations that respects B2Bi-relevant QoS attributes

Molecular Imaging of Cardiac Metabolism, Innervation, and Conduction

Cardiac diseases have complex molecular origins. However, current clinical diagnostic tools are often inadequate to uncover specific molecular components of cardiac pathologies. Thus, we are still lacking a detailed understanding of disease progression, and both patient diagnosis and treatment are often inaccurate. Molecular imaging could play a leading role in translating basic research to both preclinical and clinical cardiac research, ultimately improving our understanding and management of human disease. In this review, we highlight the diversity of current molecular imaging tools that have been used in clinical research or have reached the stage of clinical translation. Facilitated by the steadily increasing infrastructure of clinical positron emission tomography and positron emission tomography-magnetic resonance imaging cameras and advancing gating analysis, these tools allow the implementation of clinical cardiac molecular imaging trials to deepen our knowledge of human disease and improve patient care

Evans Blue is not a suitable inhibitor of the epithelial sodium channel delta-subunit

The Epithelial Sodium Channel (ENaC) is a heterotrimeric ion channel which can be either formed by assembly of its alpha-, beta- and gamma-subunits or, alternatively, its delta-, beta- and gamma-subunits. The physiological function of a alpha beta gamma-ENaC is well established, but the function of delta beta gamma-ENaC remains elusive. The azo-dye Evans Blue (EvB) has been routinely used to discriminate between the two channel isoforms by decreasing transmembrane currents and amiloride-sensitive current fractions of delta beta gamma-ENaC expressing Xenopus oocytes. Even though these results could be reproduced, it was found by precipitation experiments and spectroscopic methods that the cationic amiloride and the anionic EvB directly interact in solution, forming a strong complex. Thereby a large amount of pharmacologically available amiloride is removed from physiological buffer solutions and the effective amiloride concentration is reduced. This interaction did not occur in the presence of albumin. In microelectrode recordings, EvB was able to abrogate the block of delta beta gamma-ENaC by amiloride or its derivative benzamil. In sum, EvB reduces amiloride-sensitive ion current fractions in electrophysiological experiments. This is not a result of a specific inhibition of delta beta gamma-ENaC but rather represents a pharmacological artefact. EvB should therefore not be used as an inhibitor of delta-ENaC. (C) 2015 Elsevier Inc. All rights reserved

Development of a New Photochromic Ion Channel Blocker via Azologization of Fomocaine

Photochromic blockers of voltage gated ion channels are powerful tools for the control of neuronal systems with high spatial and temporal precision. We now introduce fotocaine, a new type of photochromic channel blocker based on the long-lasting anesthetic fomocaine. Fotocaine is readily taken up by neurons in brain slices and enables the optical control of action potential firing by switching between 350 and 450 nm light. It also provides an instructive example for “azologization”, that is, the systematic conversion of an established drug into a photoswitchable one

Imaging cardiac SCN5A using the novel F-18 radiotracer radiocaine

The key function of the heart, a well-orchestrated series of contractions, is controlled by cardiac action potentials. These action potentials are initiated and propagated by a single isoform of voltage gated sodium channels – SCN5A. However, linking changes in SCN5A expression levels to human disease in vivo has not yet been possible. Radiocaine, an F-18 radiotracer for positron emission tomography (PET), is the first SCN5A imaging agent in the heart. Explants from healthy and failing human hearts were compared using radiocaine autoradiography to determine that the failing heart has ~30% lower SCN5A levels - the first evidence of changes in SCN5A expression in humans as a function of disease. Paving the way for translational imaging, radiocaine proved to exhibit high in vivo specific binding to the myocardium of non-human primates. We envision that SCN5A measurements using PET imaging may serve as a novel diagnostic tool to stratify arrhythmia risk and assess for progression of heart failure in patients with a broad spectrum of cardiovascular diseases

Novel far-red fluorescent 1,4-dihydropyridines for L-type calcium channel imaging

Upregulation of L-type calcium channels (LTCCs) is implicated in a range of cardiovascular and neurological disorders. Therefore, the development of toolboxes that unlocks fast imaging protocols in live cells are coveted. Herein, we report a library of first-in-class novel far-red small-molecule-based fluorescent ligands (FluoDiPines), able to target LTCCs. All fluorescent ligands were evaluated in whole-cell patch-clamp and live-cell Ca2+ imaging whereby Fluodipine 6 was found the best candidate for live-cell fluorescence imaging. Low concentration of FluoDiPine 6 (50 nM) and a quick labelling protocol (5 min) are successfully applied to fixed- and live-cells to image LTCCs with good specificity

Interleukin-21 Receptor-Mediated Signals Control Autoreactive T Cell Infiltration in Pancreatic Islets

Tumorimmunolog