Die DIN EN 13445 ist zur echten Alternative gereift

Das AD 2000-Regelwerk ist der dominierende Standard für den Druckbehälterbau in Deutschland. Die bereits in anderen europäischen Ländern verbreitete DIN EN 13445 findet kaum Berücksichtigung. Dies allerdings zu Unrecht, denn ein aktueller Vergleich, der im Rahmen einer Bachelorarbeit durchgeführte wurde, zeigt: Die EN 13445 ist zu einer echten Alternative gereift. Gerade das Hauptargument gegen eine Umstellung, die steigenden Kosten, ist längst überholt

OR-53: Plasma immunoreactive endothelin-1 levels in hypertensive rats and human subjects

Endothelin-1 (ET-1) is an endothelium-derived potent vasoconstrictor peptide of 21 amino acids. To establish reference values in different forms and models of hypertension and in human subjects an assay for plasma ET-1 was optimized. Immunoreactive (ir-) ET-1 is extracted by acetone from 1 ml plasma and subjected to a sensitive sandwich type enzyme linked immunosorbent assay. The detection limit for plasma ET-1 (3 SD above zero readings) is 0.05 fmol/ml. Mean recoveries of the 1, 2, 5, 10 fmol of ET-1 added to 1 ml plasma (n = 5, each) were 66, 75, 85 and 92 % respectively. The within-assay coefficients of variation were 12, 5, 3, 3 and 0.5 % for plasma ET-1 concentrations of 0.84, 1.5, 2.3, 5.2 and 9.9 fmol/ml respectively. Between-assay coefficients of variation for two human control plasmas containing 1.0 fmol/ml (n = 8) and 1.2 fmol/ml ET-1 (n = 7) were 8% and 10% respectively. Assay accuracy was demonstrated by the consistent recoveries of added ET-1 and by the linearity of ir-ET-1 concentrations measured in serially diluted plasma extracts (r = 0.99). No ir-ET-1 was detected when albumin buffer was extracted instead of plasma (buffer blank). Using this method, we found increased ir-ET-1 levels in plasma of three experimental rat models of hypertension. (i) Plasma ir-ET-1 concentrations were significantly higher in stroke-prone spontaneously hypertensive rats (SP-SHR) than in normotensive Wistar rats. (ii) DOCA-salt hypertensive rats exhibited 4 times higher ir-ET-1 levels than sham operated control rats. (iii) One kidney-one clip (1K-1C) hypertensive rats showed moderately increased ir-ET-1 levels compared to sham operated controls. In contrast, the ir-ET-1 levels in plasma of SHR were half that of normotensive Wistar rats. In two kidney-one clip (2K-1C) Goldblatt hypertensive rats, the plasma ir-ET-1 concentrations were not different from sham-operated control rats. The plasma ir-ET-1 concentrations of 37 healthy human subjects were 0.85 ± 0.26 fmol/ml (mean ± SD). We conclude that the present assay reliably measures plasma immunoreactive ET-1 levels in rats and in human subjects. Normal plasma ET-1 concentrations in humans and conscious rats are in the low picomolar rang

Mechanism of Islet Amyloid Polypeptide Fibrillation at Lipid Interfaces Studied by Infrared Reflection Absorption Spectroscopy

AbstractIslet amyloid polypeptide (IAPP) is a pancreatic hormone and one of a number of proteins that are involved in the formation of amyloid deposits in the islets of Langerhans of type II diabetes mellitus patients. Though IAPP-membrane interactions are known to play a major role in the fibrillation process, the mechanism and the peptide's conformational changes involved are still largely unknown. To obtain new insights into the conformational dynamics of IAPP upon its aggregation at membrane interfaces and to relate these structures to its fibril formation, we studied the association of IAPP at various interfaces including neutral as well as charged phospholipids using infrared reflection absorption spectroscopy. The results obtained reveal that the interaction of human IAPP with the lipid interface is driven by the N-terminal part of the peptide and is largely driven by electrostatic interactions, as the protein is able to associate strongly with negatively charged lipids only. A two-step process is observed upon peptide binding, involving a conformational transition from a largely α-helical to a β-sheet conformation, finally forming ordered fibrillar structures. As revealed by simulations of the infrared reflection absorption spectra and complementary atomic force microscopy studies, the fibrillar structures formed consist of parallel intermolecular β-sheets lying parallel to the lipid interface but still contain a significant number of turn structures. We may assume that these dynamical conformational changes observed for negatively charged lipid interfaces play an important role as the first steps of IAPP-induced membrane damage in type II diabetes

mVOC 2.0: a database of microbial volatiles

Metabolic capabilities of microorganisms include the production of secondary metabolites (e.g. antibiotics). The analysis of microbial volatile organic compounds (mVOCs) is an emerging research field with huge impact on medical, agricultural and biotechnical applied and basic science. The mVOC database (v1) has grown with microbiome research and integrated species information with data on emitted volatiles. Here, we present the mVOC 2.0 database with about 2000 compounds from almost 1000 species and new features to work with the database. The extended collection of compounds was augmented with data regarding mVOC-mediated effects on plants, fungi, bacteria and (in-)vertebrates. The mVOC database 2.0 now features a mass spectrum finder, which allows a quick mass spectrum comparison for compound identification and the generation of species-specific VOC signatures. Automatic updates, useful links and search for mVOC literature are also included. The mVOC database aggregates and refines available information regarding microbial volatiles, with the ultimate aim to provide a comprehensive and informative platform for scientists working in this research field. To address this need, we maintain a publicly available mVOC database at: http://bioinformatics.charite.de/mvoc

WITHDRAWN-a resource for withdrawn and discontinued drugs

Post-marketing drug withdrawals can be associated with various events, ranging from safety issues such as reported deaths or severe side-effects, to a multitude of non-safety problems including lack of efficacy, manufacturing, regulatory or business issues. During the last century, the majority of drugs voluntarily withdrawn from the market or prohibited by regulatory agencies was reported to be related to adverse drug reactions. Understanding the underlying mechanisms of toxicity is of utmost importance for current and future drug discovery. Here, we present WITHDRAWN, a resource for withdrawn and discontinued drugs publicly accessible at http://cheminfo.charite.de/withdrawn. Today, the database comprises 578 withdrawn or discontinued drugs, their structures, important physico-chemical properties, protein targets and relevant signaling pathways. A special focus of the database lies on the drugs withdrawn due to adverse reactions and toxic effects. For approximately one half of the drugs in the database, safety issues were identified as the main reason for withdrawal. Withdrawal reasons were extracted from the literature and manually classified into toxicity types representing adverse effects on different organs. A special feature of the database is the presence of multiple search options which will allow systematic analyses of withdrawn drugs and their mechanisms of toxicity

Super natural II -a database of natural products

Natural products play a significant role in drug discovery and development. Many topological pharmacophore patterns are common between natural products and commercial drugs. A better understanding of the specific physicochemical and structural features of natural products is important for corresponding drug development. Several encyclopedias of natural compounds have been composed, but the information remains scattered or not freely available. The first version of the Supernatural database containing ∼ 50,000 compounds was published in 2006 to face these challenges. Here we present a new, updated and expanded version of natural product database, Super Natural II (http://bioinformatics.charite.de/supernatural), comprising ∼ 326,000 molecules. It provides all corresponding 2D structures, the most important structural and physicochemical properties, the predicted toxicity class for ∼ 170,000 compounds and the vendor information for the vast majority of compounds. The new version allows a template-based search for similar compounds as well as a search for compound names, vendors, specific physical properties or any substructures. Super Natural II also provides information about the pathways associated with synthesis and degradation of the natural products, as well as their mechanism of action with respect to structurally similar drugs and their target proteins

UC-426 Cybersecurity Park

We are presenting two additional modules to the Cyber Security Park, a long-running game project that is part of the realities lab. Whack-a-Malware is an arcade game where the player has to whack various malware, each with unique effects that mimic real-world malware. This includes Adware, Spyware, Ransomware, Computer Worms, and Trojan Horses. The player is equipped with two hammers that instantly destroy malware. But it goes on a three-second cooldown every time they destroy something. The player can reduce the cooldown by destroying adware as they are the main cause of slowing down the computer. Digital Footprints Private Investigator is a complete rework of an existing module. The player will be tasked by their client to find the perpetrator who has been anonymously intimidating them online and in person. The Player will have to explore the city to find digital footprint clues that will provide alibis and evidence against the suspects in the case

Molecular basis for the sensitivity of TRP channels to polyunsaturated fatty acids

Transient receptor potential (TRP) channels represent a superfamily of unselective cation channels that are subdivided into seven subfamilies based on their sequence homology and differences in gating and functional properties. Little is known about the molecular mechanisms of TRP channel regulation, particularly of the "canonical" TRP (TRPC) subfamily and their activation by polyunsaturated fatty acids (PUFAs). Here, we analyzed the structure-function relationship of Drosophila fruit fly TRPC channels. The primary aim was to uncover the molecular basis of PUFA sensitivity of Drosophila TRP-like (TRPL) and TRPgamma channels. Amino acid (aa) sequence alignment of the three Drosophila TRPC channels revealed 50 aa residues highly conserved in PUFA-sensitive TRPL and TRPgamma channels but not in the PUFA-insensitive TRP channel. Substitution of respective aa in TRPL by corresponding aa of TRP identified 18 residues that are necessary for PUFA-mediated activation of TRPL. Most aa positions are located within a stretch comprising transmembrane domains S2-S4, whereas six aa positions have been assigned to the proximal cytosolic C-terminus. Interestingly, residues I465 and S471 are required for activation by 5,8,11,14-eicosatetraynoic acid (ETYA) but not 5,8,11-eicosatriynoic acid (ETI). As proof of concept, we generated a PUFA-sensitive TRP channel by exchanging the corresponding aa from TRPL to TRP. Our study demonstrates a specific aa pattern in the transmembrane domains S2-S4 and the proximal C-terminus essential for TRP channel activation by PUFAs