Within the scope of the characterization of a commercial pectate lyase (PAL) the pattern of substrate degradation by that enzyme was investigated with oligogalacturonic acids as well as pectins with various degrees of esterification as substrates. For this purpose an analytical size exclusion chromatographie method (HPSEC) was elaborated in order to evaluate the reaction products of the degraded substrates over the whole range of molecular weight with the main interest lying in the emerging oligogalacturonic acids. The degradation of polygalacturonic acid by PAL was additionally investigated by means of thin-layer chromatography (TLC) and viscosimetry. Furthermore spontaneous depolymerization and deesterification of the substrates occurring under the chosen conditions were examined. The PAL showed to be anendo-enzyme both by means of TLC and HPSEC. Polygalacturonic acid was broken down, mainly generating unsaturated tri- and digalacturonic acid; the corresponding monomer was not found. The mode of cleavage is discussed. 相似文献
When the microemulsion formulation of the critical dose drug cyclosporine A (CsA) (Sandimmun Optoral) was introduced in the mid-1990s, it became clear that this new formulation improves the oral bioavailability of CsA and has a positive influence on its pharmacokinetic variability. Previous studies with the original CsA formulation (Sandimmun) showed that the size of the emulsion droplets and concomitant food intake has an effect on the absorption of CsA from the small intestine when orally administered. It was suggested that these effects might have an influence on the drugs' pharmacokinetic parameters.In this study, we focused on the two above-mentioned aspects and compared the first and second generations of CsA products (Sandimmun, Sandimmun Optoral) to generic CsA formulations by analyzing the contents of cyclosporine A gel capsules with respect to their emulsion droplet and micelle sizes using photon correlation spectroscopy (PCS). We tried to discern any differences in droplet size between different generations of CsA formulations, primarily the second and third generation, through simple physical tests. Because a high fat content food may influence the absorption of CsA, we also determined the distribution of CsA between hydrophilic and lipophilic phases using high-performance liquid chromatography analysis.It became clear that when compared under simple physical conditions, established cyclosporine formulations and new generic products show significant differences in droplet size and distribution between an aqueous phase and a high fat content food. Whether these differences are of clinical relevance remains to be investigated. 相似文献
Direct stimulation of soluble guanylate cyclase (sGC) represents a promising therapeutic strategy for the treatment of a range of diseases, including the severely disabling pulmonary hypertension (PH). Optimization of the unfavorable DMPK profile of previous sGC stimulators provided riociguat, which is currently being investigated in phase III clinical trials for the oral treatment of PH.
n‐Si/CnH2n + 1/Hg junctions (n = 12, 14, 16 and 18) can be prepared with sufficient quality to assure that the transport characteristics are not anymore dominated by defects in the molecular monolayers. With such organic monolayers we can, using electron, UV and X‐ray irradiation, alter the charge transport through the molecular junctions on n‐ as well as on p‐type Si. Remarkably, the quality of the self‐assembled molecular monolayers following irradiation remains sufficiently high to provide the same very good protection of Si from oxidation in ambient atmosphere as provided by the pristine films. Combining spectroscopic (UV photoemission spectroscopy (UPS), X‐ray photoelectron spectroscopy (XPS), Auger, near edge‐X‐ray absorption fine structure (NEXAFS)) and electrical transport measurements, we show that irradiation induces defects in the alkyl films, most likely C?C bonds and C? C crosslinks, and that the density of defects can be controlled by irradiation dose. These altered intra‐ and intermolecular bonds introduce new electronic states in the highest occupied molecular orbital (HOMO)–lowest unoccupied molecular orbital (LUMO) gap of the alkyl chains and, in the process, dope the organic film. We demonstrate an enhancement of 1–2 orders of magnitude in current. This change is clearly distinguishable from the previous observed difference between transport through high quality and defective monolayers. A detailed analysis of the electrical transport at different temperatures shows that the dopants modify the transport mechanism from tunnelling to hopping. This study suggests a way to extend significantly the use of monolayers in molecular electronics. 相似文献
Current magnetic resonance imaging (MRI) technology allows the determination of patient-individual coronary tree structure, detection of infarctions, and assessment of myocardial perfusion. Joint inspection of these three aspects yields valuable information for therapy planning, e.g., through classification of myocardium into healthy tissue, regions showing a reversible hypoperfusion, and infarction with additional information on the corresponding supplying artery. Standard imaging protocols normally provide image data with different orientations, resolutions and coverages for each of the three aspects, which makes a direct comparison of analysis results difficult. The purpose of this work is to develop methods for the alignment and combined analysis of these images. The proposed approach is applied to 21 datasets of healthy and diseased patients from the clinical routine. The evaluation shows that, despite limitations due to typical MRI artifacts, combined inspection is feasible and can yield clinically useful information. 相似文献
Water shortage is often a challenge for industrial park developments. To ensure a more sustainable water supply, the Industrial Wastewater Management Concept with a focus on Reuse (IW2MC→R) provides a strategy to meet the challenges. Main requirements to achieve water reuse fit for purpose are optimized wastewater treatment, an optimized sewer and pipe system, and an innovative water quality monitoring concept. To evaluate water‐reuse concepts, a reuse factor is calculated, which relates to all wastewater inflows to the central wastewater treatment plant and all reuse‐water flows. 相似文献