A design of experiments concept for the minimization of nonspecific peptide adsorption in the mass spectrometric determination of substance P and related hemokinin‐1

Substance P and hemokinin‐1 were predominantly examined by immunoassays with their limitation to differentiate appropriately between both peptides. The use of liquid chromatography coupled with tandem mass spectrometry is a promising, highly selective alternative. Adsorption processes have been identified in preliminary experiments to play a crucial role in the loss of mass spectrometry intensity of both peptides. Therefore, a design of experiments concept was created to minimize nonspecific peptide adsorption. For this purpose, the most critical influencing parameters—(1) the composition of the injection solvent as well as (2) the most suitable container material—were systematically and concordantly investigated. The addition of modifiers, such as formic acid, dimethyl sulfoxide, and organic solvents, to the injection solvent led to a substantial gain of intensity of substance P and hemokinin‐1 compared to the start gradient as an injection solvent. Furthermore, the systematic investigation underlined the high impact of the container material, demonstrating polypropylene as the most favorable material. A conjoint injection solvent optimum was found to determine both peptides simultaneously by the conduction of a sweet‐spot analysis. The experimental design substantially reduced nonspecific peptide adsorption and enabled the simultaneous and selective determination of endogenous substance P and hemokinin‐1 plasma levels.     

Detection and identification of the designer benzodiazepine flubromazepam and preliminary data on its metabolism and pharmacokinetics

The appearance of pyrazolam in Internet shops selling ‘research chemicals’ in 2012 marked the beginning of designer benzodiazepines being sold as recreational drugs or ‘self medication’. With recent changes in national narcotics laws in many countries, where two uncontrolled benzodiazepines (phenazepam and etizolam), which were marketed by pharmaceutical companies in some countries, were scheduled, clandestine laboratories seem to turn to poorly characterized research drug candidates as legal substitutes. Following the appearance of pyrazolam, it comes with no surprise that recently, flubromazepam (7‐bromo‐5‐(2‐fluorophenyl)‐1,3‐dihydro‐2H‐1,4‐benzodiazepin‐2‐one), a second designer benzodiazepine, was offered on the market. In this article, this new compound was characterized using nuclear magnetic resonance, gas chromatography‐mass spectrometry (GC–MS), liquid chromatography–mass spectrometry (LC–MS/MS) and liquid chromatography quadrupole time‐of‐flight MS (LC–Q–ToF–MS). Additionally, a study was carried out, in which one of the authors consumed 4 mg of flubromazepam to gain preliminary data on the pharmacokinetic properties and the metabolism of this compound. For this purpose, serum as well as urine samples were collected for up to 31 days post‐ingestion and analyzed applying LC–MS/MS and LC–Q‐ToF‐MS techniques. On the basis of this study, flubromazepam appears to have an extremely long elimination half‐life of more than 100 h. One monohydroxylated compound and the debrominated compound could be identified as the predominant metabolites, the first allowing a detection of a consumption for up to 28 days post‐ingestion when analyzing urine samples in our case. Additionally, various immunochemical assays were evaluated, showing that the cross‐reactivity of the used assay seems not to be sufficient for safe detection of the applied dose in urine samples, bearing the risk that it could be misused in drug‐withdrawal settings or in other circumstances requiring regular drug testing. Furthermore, it may be used in drug‐facilitated crimes without being detected. Copyright © 2013 John Wiley & Sons, Ltd.     

Modeling,Simulation and Parameter Identification for Rate-Dependent Magnetoactive Polymer Response

A finite deformation framework for nonlinear magneto-viscoelasticity is introduced and applied to the constitutive and structural modeling of magnetoactive polymer (MAP) response. In this thermodynamically-consistent formulation the free energy function consists of purely elastic, purely magnetic and coupling contributions, where the rate-dependence is fully attributed to the non-magnetizable matrix material. The model consistently accounts for saturation in the magnetic as well as the magnetostrictive behavior. The identification of material parameters from experimental data is briefly described. Finally, a finite element model for the large strain magneto-mechanical problem is established and tested considering MAP behavior. (© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Photoinduced reconfiguration cycle in a molecular adsorbate layer studied by femtosecond inner-shell photoelectron spectroscopy

A time-resolved study of core-level chemical shifts in a monolayer of aromatic molecules reveals complex photoinduced reaction dynamics. The combination of electron spectroscopy for chemical analysis and ultrashort pulse excitation in the extreme ultraviolet allows performing time-correlated 4d-core-level spectroscopy of iodine atoms that probe the local chemical environment in the adsorbate molecule. The selectivity of the method unveils metastable molecular configurations that appear about 50 ps after the excitation and are efficiently quenched back to the ground state.     

Die Kerze

In this paper we discuss the physical chemistry of the candle light, which has shown to encompass thermodynamics, chemical kinetics, transport processes and quantum chemistry and physics. In a candle light all states of matter (solid, liquid, gas and plasma) are present. Solid wax is molten by the heat radiation of the flame and subsequently pumped through the wick by capillary forces to the interior of the flame, where the liquid wax is evaporated and ignited. Oxygen cannot penetrate deeply into the flame so that inside the flame reducing reaction conditions prevail. In the flame the wax molecules are pyrolized to small molecule fragments (including ions: plasma), which are the starting point for building up poly‐aromatic rings and finally soot particles. The almond‐shape of the candle light is the result of convection of the hot air around the flame. The candle light serves as a flow reactor with luminous effect where molecular oxygen from the atmosphere oxidized ultimately the wax molecules to CO₂ and water. Only a very small percentage (0.5 %) of the released heat in the combustion reaction is transformed into visible light, rendering the candle light an incredibly inefficient albeit romantic light source.     

Mechanism of disease in early osteoarthritis: application of modern MR imaging techniques — a technical report

The application of biomolecular magnetic resonance imaging becomes increasingly important in the context of early cartilage changes in degenerative and inflammatory joint disease before gross morphological changes become apparent. In this limited technical report, we investigate the correlation of MRI T1, T2 and T1ρ relaxation times with quantitative biochemical measurements of proteoglycan and collagen contents of cartilage in close synopsis with histologic morphology. A recently developed MRI sequence, T1ρ, was able to detect early intracartilaginous degeneration quantitatively and also qualitatively by color mapping demonstrating a higher sensitivity than standard T2-weighted sequences. The results correlated highly with reduced proteoglycan content and disrupted collagen architecture as measured by biochemistry and histology. The findings lend support to a clinical implementation that allows rapid visual capturing of pathology on a local, millimeter level. Further information about articular cartilage quality otherwise not detectable in vivo, via normal inspection, is needed for orthopedic treatment decisions in the present and future.     

Inequalities for the capacity of non-contractible annuli on cylinders of constant and variable negative curvature

We give elementary estimates for the capacity of non-contractible annuli on cylinders and provide examples, where these inequalities are sharp. Here the lower bound depends only on the area of the annulus. To obtain this result we use projection of gradients on curves to obtain a lower bound on the capacity, which we call directional capacity. In the case of constant curvature we then apply a symmetrization process that results in an annulus of minimal directional capacity. For this annulus the lower bound on the capacity is sharp. In the case of variable negative curvature we obtain the lower bound by constructing a comparison annulus with the same area but lower directional capacity on a cylinder of constant curvature. The methods developed here have been applied to estimate the energy of harmonic forms on Riemann surfaces in Muetzel (Math Zeitschrift, 2012, arXiv:1202.0782).     

Characterization and in vitro phase I microsomal metabolism of designer benzodiazepines — an update comprising adinazolam,cloniprazepam, fonazepam, 3‐hydroxyphenazepam,metizolam and nitrazolam

Designer benzodiazepines represent an emerging class of new psychoactive substances. While other classes of new psychoactive substances such as cannabinoid receptor agonists and designer stimulants are mainly consumed for hedonistic reasons, designer benzodiazepines may also be consumed as ‘self‐medication’ by persons suffering from anxiety or other psychiatric disorders or as stand‐by ‘antidote’ by users of stimulant and hallucinogenic drugs. In the present study, five benzodiazepines (adinazolam, cloniprazepam, fonazepam, 3‐hydroxyphenazepam and nitrazolam) and one thienodiazepine (metizolam) offered as ‘research chemicals’ on the Internet were characterized and their main in vitro phase I metabolites tentatively identified after incubation with pooled human liver microsomes. For all compounds, the structural formula declared by the vendor was confirmed by nuclear magnetic resonance spectroscopy, gas chromatography–mass spectrometry (MS), liquid chromatography MS/MS and liquid chromatography quadrupole time‐of‐flight MS analysis. The detected in vitro phase I metabolites of adinazolam were N‐desmethyladinazolam and N‐didesmethyladinazolam. Metizolam showed a similar metabolism to other thienodiazepines comprising monohydroxylations and dihydroxylation. Cloniprazepam was metabolized to numerous metabolites with the main metabolic steps being N‐dealkylation, hydroxylation and reduction of the nitro function. It has to be noted that clonazepam is a metabolite of cloniprazepam, which may lead to difficulties when interpreting analytical findings. Nitrazolam and fonazepam both underwent monohydroxylation and reduction of the nitro function. In the case of 3‐OH‐phenazepam, no in vitro phase I metabolites were detected. Formation of licensed benzodiazepines (clonazepam after uptake of cloniprazepam) and the sale of metabolites of prescribed benzodiazepines (fonazepam, identical to norflunitrazepam, and 3‐hydroxyphenazepam) present the risk of incorrect interpretation of analytical findings. Copyright © 2016 John Wiley & Sons, Ltd.     

Spectroelectrochemical cell for in situ studies of solid oxide fuel cells

Solid oxide fuel cells (SOFCs) are able to produce electricity and heat from hydrogen‐ or carbon‐containing fuels with high efficiencies and are considered important cornerstones for future sustainable energy systems. Performance, activation and degradation processes are crucial parameters to control before the technology can achieve breakthrough. They have been widely studied, predominately by electrochemical testing with subsequent micro‐structural analysis. In order to be able to develop better SOFCs, it is important to understand how the measured electrochemical performance depends on materials and structural properties, preferably at the atomic level. A characterization of these properties under operation is desired. As SOFCs operate at temperatures around 1073 K, this is a challenge. A spectroelectrochemical cell was designed that is able to study SOFCs at operating temperatures and in the presence of relevant gases. Simultaneous spectroscopic and electrochemical evaluation by using X‐ray absorption spectroscopy and electrochemical impedance spectroscopy is possible.