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Background: Acute mountain sickness (AMS) is the most common disease caused by hypobaric hypoxia (HH) in high-altitude (HA) associated with high mortality when progressing to high-altitude pulmonary edema (HAPE) and/or high-altitude cerebral edema (HACE). There is evidence for a role of pro- and anti-inflammatory cytokines in development of AMS, but biological pathways and molecular mechanisms underlying AMS remain elusive. We aimed to measure changes in blood cytokine levels and their possible association with the development of AMS.Method: 15 healthy mountaineers were included into this prospective clinical trial. All participants underwent baseline normoxic testing with venous EDTA blood sampling at the Bangor University in United Kingdom (69 m). The participants started from Beni at an altitude of 869 m and trekked same routes in four groups the Dhaulagiri circuit in the Nepali Himalaya. Trekking a 14-day route, the mountaineers reached the final HA of 5,050 m at the Hidden Valley Base Camp (HVBC). Venous EDTA blood sampling was performed after active ascent to HA the following morning after arrival at 5,050 m (HVBC). A panel of 21 cytokines, chemokines and growth factors were assessed using Luminex system (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-1ra, sIL-2Rα, IFN-γ, TNF-α, MCP-1, MIP-1α, MIP-1β, IP-10, G-CSF, GM-CSF, EGF, FGF-2, VEGF, and TGF-β1).Results: There was a significant main effect for the gradual ascent from sea-level (SL) to HA on nearly all cytokines. Serum levels for TNF-α, sIL-2Rα, G-CSF, VEGF, EGF, TGF-β1, IL-8, MCP-1, MIP-1β, and IP-10 were significantly increased at HA compared to SL, whereas levels for IFN-γ and MIP-1α were significantly decreased. Serum VEGF was higher in AMS susceptible versus AMS resistant subjects (p < 0.027, main effect of AMS) and increased after ascent to HA in both AMS groups (p < 0.011, main effect of HA). Serum VEGF increased more from SL values in the AMS susceptible group than in the AMS resistant group (p < 0.049, interaction effect).Conclusion: Cytokine concentrations are significantly altered in HA. Within short interval after ascent, cytokine concentrations in HH normalize to values at SL. VEGF is significantly increased in mountaineers suffering from AMS, indicating its potential role as a biomarker for AMS.

The first total synthesis of the actin‐stabilizing marine natural product geodiamolide H was achieved. Solid‐phase based peptide assembly paired with scalable stereoselective syntheses of polyketide building blocks and an optimized esterification set the stage for investigating the key ring‐closing metathesis. Geodiamolide H and synthetic analogues were characterized for their toxicity and for antiproliferative effects in cellulo, by characterising actin polymerization induction in vitro, and by docking on the F‐actin target and property computation in silico, for a better understanding of structure‐activity relationships (SAR). A non‐natural analogue of geodiamolide H was discovered to be most potent in the series, suggesting significant potential for tool compound design., The F‐actin stabilizing natural product geodiamolide H and its analogues were comprehensively investigated. The first total synthesis of geodiamolide H was enabled by optimized, scalable building block synthesis, improved couplings, and by a ring‐closing metathesis as a key step. Biological profiling of the synthesized library in cells, on target, and in silico uncovered potent and simplified non‐natural analogues. Additional structure‐activity relationship information was extracted for the whole class, useful for tool compound design.

Actin is essential for key processes in all eukaryotic cells. Cellpermeable optojasps provide spatiotemporal control of the actin cytoskeleton, confining toxicity and potentially rendering F‐actin druggable by photopharmacology. Here, we report cryo electron microscopy (cryo‐EM) structures of both isomeric states of one optojasp bound to actin filaments. The high‐resolution structures reveal for the first time the pronounced effects of photoswitching a functionalized azobenzene. By characterizing the optojasp binding site and identifying conformational changes within F‐actin that depend on the optojasp isomeric state, we refine determinants for the design of functional F‐actin photoswitches., Targeting actin requires spatiotemporal control of drug activity. Optojasps are photo‐switchable small molecules, providing direct optical spatiotemporal control of the actin cytoskeleton. We present high‐resolution cryo‐EM structures of both isomeric states of an optojasp bound to F‐actin and describe in detail the binding pocket and conformational changes associated with switching of the azobenzene.

The lattice Boltzmann method is a modern approach to simulate fluid flow. In its original formulation, it is restricted to regular grids, second-order discretizations, and a unity CFL number. This paper describes our new off-lattice Boltzmann solver NATriuM, an extensible and parallel C++ code to perform lattice Boltzmann simulations on irregular grids. NATriuM also allows high-order spatial discretizations and non-unity CFL numbers to be used. We demonstrate how these features can efficiently decrease the number of grid points required in a simulation and thus reduce the computational time, compared to the standard lattice Boltzmann method. We detail the implementation of a recently proposed semi-Lagrangian lattice Boltzmann method and prove its efficiency in comparisons to other state-of-the-art off-lattice Boltzmann schemes.

The pull-out resistance of fully threaded, self-tapping screws under axial loading has been investigated intensively in the past. Actual design models are based mainly on empirical data because the detailed interaction between the screw thread and the surrounding timber member remains unclear and might depend on the test set-up. An innovative screw sensor with 19 internal fibre Bragg gratings (FBGs) was developed to measure the forces along the screw axis. The screw diameter was 12 mm and the maximum embedding length was 360 mm. The FBG measurement screw was applied in pull-out tests under different support conditions. The results carried out show details of the axial forces along fully threaded screws depending on the magnitude of the screw axis to grain angle, the embedding length, the material and the support conditions. Load transfer between the screw and the surrounding timber was determined by means of the change of axial forces along the screw axis. A comparison of the experimental results with Volkersen’s theory points out the decisive dependency of the support conditions on the axial forces in fully threaded self-tapping screws. Additionally, the experimental test results show indications of shear and compressive stresses in the interface of the measurement screw.

The natural product jasplakinolide is a widely used tool compound to stabilize F-actin and influence actin dynamics. We have previously introduced photoswitchable jasplakinolides (optojasps) that are activated with violet light and deactivated with blue light. Based on insights from cryo-electron microscopy and structure-activity relationship (SAR) studies, we now developed a new generation of functionally superior optojasps that are better suited for biological investigations. These compounds are procured through chemical total synthesis and feature rationally designed red-shifted azobenzene photoswitches. Our new optojasps can be activated with longer wavelengths in the visible range (e.g. 440-477 nm) and rapidly return to their inactive state through thermal relaxation. This has enabled the reversible control of F-actin dynamics, as shown through live-cell imaging and cell migration, as well as cell proliferation assays. Brief sub-cellular activation with blue-green light resulted in highly localized F-actin clusters that gradually dissolved in the dark. Our light-responsive tools can be useful in diverse fields to study actin dynamics with outstanding spatiotemporal precision.Graphical Abstract

Chemical functionalization of molecular 2D materials toward the assembly of hierarchical functional nanostructures is of great importance for nanotechnology including areas like artificial photocatalytic systems, nanobiosensors, or ultrafiltration. To achieve the desired functionality of 2D materials, these need to be characterized down to the nanoscale. However, obtaining the respective chemical information is challenging and generally requires the application of complementary experimental techniques. Here, the synthesis and chemical characterization of hierarchically assembled molecular nanosheets based on ≈1 nm thin, molecular carbon nanomembrane (CNM) and covalently grafted, single‐molecule layer cobalt(III) catalysts for the light‐driven hydrogen evolution reaction (HER) is demonstrated. X‐ray photoelectron spectroscopy (XPS) and tip‐enhanced Raman spectroscopy (TERS) to access both the transversal and longitudinal chemical information of the synthesized nanosheets with nanometer resolution are employed. TERS and XPS data provide detailed information on the average and local surface distribution of the catalyst as well as mechanistic details of the grafting reaction. The proposed approach represents a general route toward a nanoscale structural analysis for a variety of molecular 2D materials—a rapidly growing materials class with broad prospects for fundamental science and applications., Hierarchically assembled nanosheets with ultimate molecular thickness, bearing functional cobalt(III) complexes are investigated by X‐ray photoelectron spectroscopy and tip‐enhanced Raman scattering. The combination of both techniques provides detailed insights into the structure of the formed 2D materials down to the nanoscale., publishedVersion

Cobaloximes are promising, earth-abundant catalysts for the light-driven hydrogen evolution reaction. Typically, these cobalt(III) complexes are prepared in situ or employed in their neutral form, e.g. [Co(dmgH 2 )(py)Cl], even though related complex salts have been reported previously and could in principle offer improved catalytic activity as well as more efficient immobilization on solid support. Here we report an interdisciplinary investigation into complex salts [Co(dmgH) 2 (py) 2 ] + [Co(dmgBPh 2 ) 2 Cl 2 ] - , TBA + [Co(dmgBPh 2 ) 2 Cl 2 ] - and [Co(dmgH) 2 (py) 2 ] + BArF - . We describe their strategic syntheses from commercially available complex [Co(dmgH) 2 (py)Cl] and demonstrate that these double and single complex salts are potent catalysts for the light-driven hydrogen evolution reaction. We also show that scanning electrochemical cell microscopy can be used to deposit arrays of catalysts [Co(dmgH) 2 (py) 2 ] + [Co(dmgBPh 2 ) 2 Cl 2 ] - and [Co(dmgH) 2 (py)Cl] on supported and free-standing amino-terminated ~ 1 nm thick carbon nanomembranes (CNMs). Photocatalytic H 2 evolution at such arrays was quantified with Pd microsensors using scanning electrochemical microscopy, thus providing a new approach for catalytic evaluation and opening up novel routes for the creation and analysis of “designer catalyst arrays”, nano-printed in a desired pattern on a solid support.

Cyclophellitols are potent inhibitors of exo- and endoglycosidases. Efficient synthetic methodologies are needed to fully capitalize on this intriguing class of mechanism-based enzyme deactivators. We report the synthesis of an orthogonally protected cyclitol from d-glucal (19% yield over 12 steps) and its use in the synthesis of α-(1,3)-linked di- and trisaccharide dextran mimetics. These new glycomimetics may find use as Dextranase inhibitors, and the developed chemistries in widening the palette of glycoprocessing enzyme-targeting glycomimetics.

Aromatic self-assembled monolayers (SAMs) can be cross-linked into molecular nanosheets  carbon nanomembranes (CNMs)  via low-energy electron irradiation. Due to their favorable mechanical stability and tunable functional properties, they possess a high potential for various applications including nanosensors, separation membrane for osmosis or energy conversion devices. Despite this potential, the mechanistic details of the electron irradiation induced cross-linking process still need to be understood in more detail. Here we studied the cross-linking of 4'-nitro-1,1 ́-biphenyl-4-thiol SAM on gold. The SAM samples were irradiated with different electron energies ranging from 2.5 to 100 eV in ultra-high vacuum and subsequently analysed by complementary techniques. We present results obtained via spectroscopy and microscopy characterization by high-resolution X-ray photoelectron spectroscopy (XPS), low-energy electron diffraction with micrometre sized electron beams (LEED) and low-energy electron microscopy (LEEM). To demostrate the formation of CNMs, the formed two-dimensional molecular materials were transferred onto grids and oxidized wafer and analyzed by optical, scanning electron (SEM) and atomic force microscopy (AFM). We found a strong energy dependence for the cross section for the cross-linking process, which rates decrease exponentially towards lower electron energies by about four orders of magnitude. We conduct a comparative analysis of the cross sections for the C-H bond scission via electron impact ionization and dissociative electron attachment and find out that these different ionization mechnisms are responsible for the variation of the cross-linking cross section with electron energy.

The spatiotemporally-controlled perturbation of cellular function using photopharmacology has facilitated the elucidation of biological networks and opens up new opportunities for precision medicine. Here, we introduce cell- permeable photoswitchable small molecules, termed optojasps, to optically control the dynamics of the actin cytoskeleton and cellular functions that depend on it. These light-dependent effectors were designed from the F-actin-stabilizing marine depsipeptide jasplakinolide by functionalizing them with azobenzene photoswitches. We demonstrate that optojasps can be employed to control cell viability, cell motility, and cytoskeletal signalling with the high spatial and temporal resolution that light affords. We expect that optojasps will find applications in diverse areas of cell biological research. They may also provide a template for the development of chemotherapeutics targeting the ubiquitous actin cytoskeleton with precision control in the μm range.

Plasmonic biosensing has emerged as the most sensitive label-free technique to detect various molecular species in solutions and has already proved crucial in drug discovery, food safety and studies of bio-reactions. This technique relies on surface plasmon resonances in ~50 nm metallic films and the possibility to functionalize the surface of the metal in order to achieve selectivity. At the same time, most metals corrode in bio-solutions, which reduces the quality factor and darkness of plasmonic resonances and thus the sensitivity. Furthermore, functionalization itself might have a detrimental effect on the quality of the surface, also reducing sensitivity. Here we demonstrate that the use of graphene and other layered materials for passivation and functionalization broadens the range of metals which can be used for plasmonic biosensing and increases the sensitivity by 3-4 orders of magnitude, as it guarantees stability of a metal in liquid and preserves the plasmonic resonances under biofunctionalization. We use this approach to detect low molecular weight HT-2 toxins (crucial for food safety), achieving phase sensitivity~0.5 fg/mL, three orders of magnitude higher than previously reported. This proves that layered materials provide a new platform for surface plasmon resonance biosensing, paving the way for compact biosensors for point of care testing.

The function of actin is coupled to the nucleotide bound to its active site. ATP hydrolysis is activated during polymerization; a delay between hydrolysis and inorganic phosphate (Pi) release results in a gradient of ATP, ADP–Pi and ADP along actin filaments (F-actin). Actin-binding proteins can recognize F-actin’s nucleotide state, using it as a local ‘age’ tag. The underlying mechanism is complex and poorly understood. Here we report six high-resolution cryo-EM structures of F-actin from rabbit skeletal muscle in different nucleotide states. The structures reveal that actin polymerization repositions the proposed catalytic base, His161, closer to the γ-phosphate. Nucleotide hydrolysis and Pi release modulate the conformational ensemble at the periphery of the filament, thus resulting in open and closed states, which can be sensed by coronin-1B. The drug-like toxin jasplakinolide locks F-actin in an open state. Our results demonstrate in detail how ATP hydrolysis links to F-actin’s conformational dynamics and protein interaction. Cryo-EM structures of F-actin captured in different nucleotide states, by using nucleotide analogs or small molecules, reveal different conformational states linked to ATP hydrolysis.

Pseudopotential (PP)-basierte Lattice-Boltzmann-Methoden werden zunehmend für die Simulation von Mehrphasenströmungen eingesetzt. Da sie auf einem phänomenologischen Ansatz basieren, ist ihr Einsatz mit einem hohen Modellierungsaufwand verbunden. Zudem entstehen an den Phasengrenzen sogenannte Scheingeschwindigkeiten, welche Genauigkeit und numerische Stabilität beeinträchtigen. Daher werden PP-Modelle in dieser Arbeit um drei neue Aspekte erweitert. Erstens wird gezeigt, dass bei der Modellierung unterschiedlicher Kontaktwinkel mit gängigen Methoden in Kombination mit verbesserten Kräfteschemata Scheintröpfchen entstehen. Diese werden durch einen neuartigen Ansatz eliminiert, der auf zusätzlichen Randbedingungen für alle Wechselwirkungskräfte basiert. Diese Technik verhindert nicht nur das Auftreten der Scheintröpfchen, sondern erhöht auch die Stabilität in wandgebundenen Strömungen. Zweitens wird ein neuartiges Verfahren zur Reduktion von Scheingeschwindigkeiten eingeführt. Dabei wird die Diskretisierung der Interaktionskräfte erweitert und die zusätzlichen, freien Koeffizienten in Simulationen statischer Tropfen numerisch optimiert. Die resultierende Diskretisierung wurde in Simulationen stationärer und dynamischer Testfälle validiert, wobei Scheingeschwindigkeiten deutlich reduziert werden konnten. Drittens und letztens wurden die Diffusionseigenschaften in Mehrstoffsystemen detailliert untersucht, wobei eine kritische Abhängigkeit zwischen den makroskopischen Diffusionskoeffizienten und dem Kräfteschema aufgezeigt wird. Diese Analyse bildet die Grundlage für den Vergleich und die zukünftige Entwicklung neuer Potentialfunktionen (für Mehrstoffsysteme) und reduziert den Modellierungsaufwand. Pseudopotential (PP)-based lattice Boltzmann methods are widely used to simulate multiphase flows. As they ground on a phenomenological approach, their usage involves a high modelling effort and, additionally, they suffer from so-called spurious velocities that compromise numerical stability and accuracy. Therefore, this work advances PP-models by three novel aspects. First, the PP-model is shown to develop spurious droplets when contact angles are modelled with common approaches in combination with enhanced forcing schemes. These droplets are eliminated by a novel approach that relies on additional boundary conditions for all interaction forces. This not only prevents the spurious droplets from emerging but also increases the stability in wallbound flows. Second, a novel procedure to reduce spurious velocities is introduced. Therefore, the discretization of the interaction forces is extended and the additional free coefficients are optimized numerically using static droplet simulations. The resulting scheme is shown to greatly reduce spurious velocities and is successfully validated in stationary and transient testcases. Third and final, the diffusion characteristics in multicomponent systems are investigated in detail, revealing a critical dependency between the macroscopic diffusion coefficients and the forcing scheme. This analysis forms the basis for the comparison and development of new potential functions (in multicomponent systems) and reduces the modeling effort.

Background: Although lichen planus (LP) is a common skin disorder, the prevalence of esophageal involvement (ELP) and its clinical manifestations are poorly defined. We aimed to establish diagnostic criteria and characterize disease outcomes of ELP. Methods: Clinical, endoscopic, histological, and immunofluorescence data from consecutive patients with known LP between 2013 and 2018 were analyzed. We established endoscopic (denudation and tearing of the mucosa, hyperkeratosis and trachealization) and histological criteria (mucosal detachment, T-lymphocytic infiltrate, intraepithelial apoptosis, dyskeratosis, and fibrinogen deposits along the basement membrane) to grade disease severity. Endoscopic findings were correlated with clinical symptoms. Response to medical therapy was monitored. Results: Fifty-two consecutive patients (median age 59.5 years) were analyzed. According to our grading system, 16 patients were considered as severe and 18 as mild ELP. Dysphagia was the only symptom which differentiated patients with severe (14/16) or mild ELP (8/18) from patients without ELP (1/18). Concomitant oral and genital involvement of LP was associated with the presence of ELP, while oral involvement alone was not. Follow-up of 14/16 patients with severe EPL for at least one year revealed that most of these patients responded to topical corticosteroids (budesonide: n = 9/10 or fluticasone n = 2/2). Three budesonide patients experienced a resolution of symptomatic esophageal stenosis. Conclusions: Esophageal involvement of LP is frequent, but may be asymptomatic. ELP can be diagnosed using the diagnostic criteria proposed here. Dysphagia and combined oral and genital manifestation are associated with ELP. Therapy with topical corticosteroids appears to be a prudent therapeutic approach for ELP.

In dem Vortrag wird gezeigt, wie die Wahl eines Forcing Schemas (bspw. von Shan & Doolen (1995) oder He & Doolen (1998)) über die Chapman-Enskog Entwicklung zu einem vom Forcing abhängigen Diffusionskoeffizienten für Mehrphasenströmungen führt. Der kritische Wert von G wird danach bestimmt und bekannte in der Literatur ad hoc verwendete Beziehungen abgeleitet (Huan et al. (2007)), sowie für tau=1 der bisher nicht erklärbare Shift um den Faktor 2 abgeleitet. Simulationen zeigen die exzellente Übereinstimmung des Diffusionskoeffizienten bspw. mit dem Fick’schen Gesetz für unterschiedliche Werte von G. The talk presents the influence of the choice of forcing schemes in pseudopotential-based LBM methods for multi-phase flows (e.g. Shan & Doolen (1995) or He & Doolen (1998)) on the diffusion coefficient, obtained via Chapman-Enskog analysis. The critical value of G is obtained und known relations used in the literature are subsequently derived based on this theory (e.g. Huan et al. (2007)). The often observed shift at tau=1 for the critical value of G can be directly derived. Simulation show excellent agreement between the diffusion coefficient and Fick’s law for various values of G.

Iatrogenic perforation of a hollow organ after diagnostic or therapeutic gastrointestinal endoscopic procedures is a rare but potentially life-threatening complication. The absolute incidence of iatrogenic perforation is assumed to increase worldwide (1, 2). The reason appears to be the more frequent use of colonoscopy screening and the more widespread use of interventional endoscopic techniques, such as endoscopic mucosal resection or endoscopic submucosal dissection. Both interventions are recommended in the guidelines to treat early neoplasia (3, 4). In Germany, approximately 4.4 million screening colonoscopies were performed between 2003 and 2012 (5). The incidence of iatrogenic perforation during solely diagnostic endoscopic procedures is low; for diagnostic colonoscopy/sigmoidoscopy, it is in the range of 0.03 to 0.8% (1, 6, 7). While iatrogenic perforation occurs in approximately 1 in 3000 solely diagnostic colonoscopies, the risk of perforation grows with increasing extent of the intervention (8). An almost linear relationship between polyp size in the colon and risk of perforation after endoscopic resection has been reported (9). The Munich Polypectomy Study found polypectomy-related perforations in altogether 1.1% of cases; for sessile lesions in the right colon, the incidence increased to 11.7% (9). In more recent studies, perforation rates for colorectal adenomas >20 mm, which were removed by means of endoscopic mucosal resection (EMR), were considerably lower (0.003% to 1.3%) (10, 11). Likewise, the risk of complications increases with the complexity of the intervention. With the introduction of the endoscopic submucosal dissection (ESD) technique from Japan, the endoscopic treatment of mucosal cancer

Für die Messung von Feldstärken im Frequenzbereich bis 30 MHz werden üblicherweise breitbandige geschirmte Magnetfeldantennen eingesetzt. Um die gewünschte Breitbandigkeit zu erreichen, werden die Antennen unterresonant betrieben und müssen somit elektrisch klein sein. Üblicherweise wird angenommen, dass die Antenne elektrisch klein ist, wenn ihr Umfang kleiner als ein Zehntel der Wellenläge bleibt, bei 30 MHz ist der maximale Antennenumfang also 1 m. Zum Schutz vor elektrischen Störfeldern ist die Leiterschleife mit einem leitfähigen Schirm umgeben. Um keine Kurzschlusswindung zu erzeugen, ist dieser ist mit einem Schlitz versehen, der mittig auf der senkrechten Symmetrieachse liegt. Im Fußpunkt der Antenne münden die beiden geschirmten, gleichlangen Antennenarme in ein Fußpunktnetzwerk (FPN), das die Verbindung zum Messempfänger mit üblicherweise koaxialem Anschluss herstellt. In Abbildung 1 ist der Aufbau einer solchen Antenne schematisch dargestellt. Verschiedene Untersuchungen [1,4] zu gängigen Kalibrierverfahren für Magnetfeldantennen haben gezeigt, dass die Antennenfaktoren auch vom jeweiligen verfahren abhängen. Zur Weiterentwicklung der Kalibrierverfahren ist ein genaues Verständnis der Funktionsweise geschirmter Magnetfeldantennen unumgänglich. Ein valides analytisches Modell ist dazu ein unentbehrliches Werkzeug und wird im Rahmen dieser Veröffentlichung vorgestellt.

Desorption electrospray ionization (DESI) mass spectrometry is an emerging technology for direct therapeutic drug monitoring in dried blood spots (DBS). Current DBS methods require manual application of small molecules as internal standards for absolute drug quantification. With industrial standardization in mind, we superseded the manual addition of standard and built a three-layer setup for robust quantification of salicylic acid directly from DBS. We combined a dioctyl sodium sulfosuccinate weave facilitating sample spreading with a cellulose layer for addition of isotope-labeled salicylic acid as internal standard and a filter paper for analysis of the standard-containing sample by DESI-MS. Using this setup, we developed a quantification method for salicylic acid from whole blood with a validated linear curve range from 10 to 2000 mg/L, a relative standard deviation (RSD%) ≤14%, and determination coefficients of 0.997. The limit of detection (LOD) was 8 mg/L and the lower limit of quantification (LLOQ) was 10 mg/L. Recovery rates in method verification by LC-MS/MS were 97 to 101% for blinded samples. Most importantly, a study in healthy volunteers after administration of a single dose of Aspirin provides evidence to suggest that the three-layer setup may enable individual pharmacokinetic and endpoint testing following blood collection by finger pricking by patients at home. Taken together, our data suggests that DBS-based quantification of drugs by DESI-MS on pre-manufactured three-layer cartridges may be a promising approach for future near-patient therapeutic drug monitoring.

Cannabinoids elicit hypotension mainly via activated CB(1) receptors and show complex cardiovascular actions. Effects on human heart muscle have not been studied yet. Isolated human atrial heart muscle preparations were stimulated by electrical field with 1 Hz to contract isometrically at optimal length and were challenged with the endogenous cannabinoid arachidonyl ethanolamide (anandamide), the metabolically stable analogue R-methanandamide, and the potent synthetic CB(1) receptor agonist HU-210. Anandamide dose-dependently decreased systolic force (82.2 +/- 4.8% and 60.8 +/- 6.8% of maximal systolic force for 0.1 and 1 microM, respectively, P < 0.05). The selective CB(1) receptor antagonist AM-251 (1 microM, P < 0.05), but not the CB(2) receptor antagonist, AM-630 (1 microM), the nitric oxide synthase inhibitor N omega-nitro-l-arginine methyl ester (l-NAME) (500 microM), or the cyclooxygenase inhibitor indomethacin (100 microM), prevented the effect. Contrary to indomethacin, l-NAME alone showed negative inotropic effects (72.1 +/- 3.54%, P < 0.001). The R-methanandamide (1 microM: 50.4 +/- 3.5%, P < 0.001) and HU-210 (1 microM: 60.1 +/- 3.8%, P < 0.001) had similar negative inotropic effects. The existence of CB(1) receptors on heart muscle was verified using Western blot analysis and immunofluorescence staining. The conclusion is that anandamide, R-methanandamide, and HU-210 decrease contractile performance in human atrial muscle via CB(1) receptors.

Aim: Self-monitoring of blood glucose (BG) by means of handheld BG systems is a cornerstone in diabetes therapy. The aim of this article is to describe a procedure with proven traceability for calibration and evaluation of BG systems to guarantee reliable BG measurements. Methods: Isotope dilution gas chromatography mass spectrometry (ID/GC/MS) is a method that fulfills all requirements to be used in a higher-order reference measurement procedure. However, this method is not applicable for routine measurements because of the time-consuming sample preparation. A hexokinase method with perchloric acid (PCA) sample pretreatment is used in a measurement procedure for such purposes. This method is directly linked to the ID/GC/MS method by calibration with a glucose solution that has an ID/GC/MS-determined target value. BG systems are calibrated with whole blood samples. The glucose levels in such samples are analyzed by this ID/GC/MS-linked hexokinase method to establish traceability to higher-order reference material. Results: For method comparison, the glucose concentrations in 577 whole blood samples were measured using the PCA-hexokinase method and the ID/GC/MS method; this resulted in a mean deviation of 0.1%. The mean deviation between BG levels measured in >500 valid whole blood samples with BG systems and the ID/GC/MS was 1.1%. Conclusions: BG systems allow a reliable glucose measurement if a true reference measurement procedure, with a noninterrupted traceability chain using ID/GC/MS linked hexokinase method for calibration of BG systems, is implemented. Systems should be calibrated by means of a traceable and defined measurement procedure to avoid bias.

In dieser Veröffentlichung werden Messungen der Dämpfung eines Flugzeughangars präsentiert, welcher für Flugzeuge vom Typ Airbus A320 geeignet ist. Beeinflussende Faktoren wie beispielsweise unterschiedliche Messpositionen, Polarisationen und geöffnete Türen werden gegenübergestellt. Schutzabstände um das Flugzeug sind eine mögliche Lösung um dieselbe Dämpfung wie in dem Hangar zu erreichen. Weiterhin zeigen zeitgleiche Messungen des Grundrauschens außerhalb und innerhalb des Hangas, dass eine Abwägung der erwähnten Vor- und Nachteile bei Störaussendungsmessungen erfolgen muss. Für das System des Radio Altimeters ist in [Rafael Rennó Nunes, Jens Schüür, Statistical Investigation of Electromagnetic Transfer Path in Research Aircraft, EMC Europe 2012, 17-11 September 2012 in Rom, Italien] gezeigt, dass der Hangar die Dämpfung zwischen Messantennen im Flugzeug und den Flugzeugantennen beeinflusst. Den realen Flugzeugbetrieb bildet eine Messung im Freien eher nach, als eine Messung innerhalb des Hangars - zumal innerhalb des Hangars die Störpegel insbesondere unterhalb von 1,2 GHz höher sind als außerhalb des Hangars. Die Beeinflussung der Messungen durch Resonanzen und Reflexionen im Hangar sollte vor der Messung bestimmt werden, da diese stark beispielsweise von der Flugzeugposition abhängen. Insbesondere bei Messung der Störaussendung kann sich dieser Einfluss auswirken. Aus Sicht der elektromagnetischen Verträglichkeit ist eine Messung außerhalb des Hangars zu bevorzugen, da Flugzeuge in dieser Umgebung betrieben werden.

Der in dieser Arbeit vorgestellte Messaufbau ist zur vergleichenden Messung der Störgrößenausbreitung und -emission in Höchstspannungssystemen geeignet. Aufgrund der Untersuchung von räumlich stark ausgedehnten und geometrisch teilweise sehr komplexen Systemen wird immer eine Mischung aus Nah- und Fernfeldern von den Antennen empfangen. Deshalb sollten analog zu dem in [IEEE Standard for Power Line Communication Equipment -- Electromagnetic Compatibility (EMC) Requirements --Testing and Measurement Methods, IEEE Std 1775-2010, pp. 1 - 66, Jan. 7, 2011, URL: http://ieeexplore.ieee.org/stamp/ stamp.jsp?tp=&arnumber=5682873&isnumber=5682872] beschriebenen Messaufbau immer drei zueinander orthogonale Antennenorientierungen pro Messpunkt durchgeführt und anschließend das geometrische Mittel der Orientierungen berechnet werden, um das einfallende Feld am Messort zu beschreiben. Ohne weitergehende Untersuchung auf dem Gebiet der Antennenkalibrierung kann bereits heute der Betriebszustand eines Leistungskonverters sowie der Einfluss eines Transformators auf das Spektrum messtechnisch erfasst werden. Ebenso wird eine gute Korrelation zwischen den theoretisch ermittelten Spektren und den Frequenzbereichen erhöhter Amplitude bei aktivem Wechselrichter nachgewiesen. Zusätzlich konnte eine mögliche Beeinflussung von sogenannten "Broadband Powerline Communication Devices" und Wechselrichtern durch das gemeinsam genutzte Frequenzband aufgezeigt werden. Damit der vorgestellte Messaufbau zu einer Absolutwertmessung genutzt werden kann, sind weitergehende Untersuchungen zur rückführbaren Bestimmung des Antennenfaktors von Magnetfeldantennen notwendig.