Measurement of Helium Leakage Rates through Closures of Dangerous Goods Packagings for the Assessment of Potentially Explosive Mixtures in Freight Containers

The objective was to find out whether an explosive atmosphere can be created in a freight container by gaseous leakage flow of vapour‐air‐mixture through leaks in the closures of dangerous goods packagings filled with hazardous liquids. Because of high temperatures during intercontinental carriage, there is a gauge pressure in the free vapour phase inside the packagings which can cause a gaseous leakage flow. Two different methods were applied: Helium limit leakage rates for 23 quantitatively important hazardous liquids concerning their lower explosion limit (LEL) were calculated for a worst case transport scenario (Method 1). Helium leakage rates of five closure types of dangerous goods packagings with volumes of approximately 6 l were measured using the pressure technique by accumulation (Method 2). All types of closures of steel packagings were uncritical. The maximum measured leakage was 33% of the limit leakage rate. The leakage rates of screw closures of plastic jerricans can exceed the LEL if there are production‐related patterns such as non‐concentricity of the closures and flashes on the neck. Especially for plastic packagings it is important to minimize gaseous leakage flow, because an explosive atmosphere can also be reached by permeation of the individual filling substance or by a combination of both effects. For the assessment of potentially explosive mixtures in freight containers, both mass transfer mechanisms have to be taken into account. Copyright © 2015 John Wiley & Sons, Ltd.     

Feedback design in control reconfigurable systems

This paper is concerned with the design of reconfigurable control laws for fault-tolerant systems. From the control design point of view the issue of performance robustness during the system normal operation versus failure sensitivity at the time of a system component failure is addressed. To achieve a balanced design, a parametrized set of controllers satisfying a prescribed performance level is first constructed, and then the parameter is optimized under a detection criterion that sensitizes the measurements to some specific failures. An example involving aircraft surface impairment is given to explain the procedure for obtaining the optimized design.     

Der einfluß von faseroberflächen auf die matrixhärtung bei faserverbundwerkstoffen

The influence of extraction of reinforced fibres on surface properties and the curing reaction of epoxy resin matrix in composites were investigated. With increasing fibre surface polarity, as the result of the extraction, the resin wettability was improved and the reaction rate of curing of the epoxy resin matrix increased. The wettability and the reaction rate oppositely decreased with decreasing fibre surface polarity.     

Biological Implications of a Stroke Therapy Based in Neuroglobin Hyaluronate Nanoparticles. Neuroprotective Role and Molecular Bases

Exogenous neuroprotective protein neuroglobin (Ngb) cannot cross the blood–brain barrier. To overcome this difficulty, we synthesized hyaluronate nanoparticles (NPs), able to deliver Ngb into the brain in an animal model of stroke (MCAO). These NPs effectively reached neurons, and were microscopically identified after 24 h of reperfusion. Compared to MCAO non-treated animals, those treated with Ngb-NPs showed survival rates up to 50% higher, and better neurological scores. Tissue damage improved with the treatment, but no changes in the infarct volume or in the oxidative/nitrosative values were detected. A proteomics approach (p-value < 0.02; fold change = 0.05) in the infarcted areas showed a total of 219 proteins that significantly changed their expression after stroke and treatment with Ngb-NPs. Of special interest, are proteins such as FBXO7 and NTRK2, which were downexpressed in stroke, but overexpressed after treatment with Ngb-NPs; and ATX2L, which was overexpressed only under the effect of Ngb. Interestingly, the proteins affected by the treatment with Ngb were involved in mitochondrial function and cell death, endocytosis, protein metabolism, cytoskeletal remodeling, or synaptic function, and in regenerative processes, such as dendritogenesis, neuritogenesis, or sinaptogenesis. Consequently, our pharmaceutical preparation may open new therapeutic scopes for stroke and possibly for other neurodegenerative pathologies.     

Novel 1,3,5-Triazinyl Aminobenzenesulfonamides Incorporating Aminoalcohol,Aminochalcone and Aminostilbene Structural Motifs as Potent Anti-VRE Agents,and Carbonic Anhydrases I,II, VII,IX, and XII Inhibitors

A series of 1,3,5-triazinyl aminobenzenesulfonamides substituted by aminoalcohol, aminostilbene, and aminochalcone structural motifs was synthesized as potential human carbonic anhydrase (hCA) inhibitors. The compounds were evaluated on their inhibition of tumor-associated hCA IX and hCA XII, hCA VII isoenzyme present in the brain, and physiologically important hCA I and hCA II. While the test compounds had only a negligible effect on physiologically important isoenzymes, many of the studied compounds significantly affected the hCA IX isoenzyme. Several compounds showed activity against hCA XII; (E)-4-{2-[(4-[(2,3-dihydroxypropyl)amino]-6-[(4-styrylphenyl)amino]-1,3,5-triazin-2-yl)amino]ethyl}benzenesulfonamide (31) and (E)-4-{2-[(4-[(4-hydroxyphenyl)amino]-6-[(4-styrylphenyl)amino]-1,3,5-triazin-2-yl)amino]ethyl}benzenesulfonamide (32) were the most effective inhibitors with K_Is = 4.4 and 5.9 nM, respectively. In addition, the compounds were tested against vancomycin-resistant Enterococcus faecalis (VRE) isolates. (E)-4-[2-({4-[(4-cinnamoylphenyl)amino]-6-[(4-hydroxyphenyl)amino]-1,3,5-triazin-2-yl}amino)ethyl]benzenesulfonamide (21) (MIC = 26.33 µM) and derivative 32 (MIC range 13.80–55.20 µM) demonstrated the highest activity against all tested strains. The most active compounds were evaluated for their cytotoxicity against the Human Colorectal Tumor Cell Line (HCT116 p53 +/+). Only 4,4’-[(6-chloro-1,3,5-triazin-2,4-diyl)bis(iminomethylene)]dibenzenesulfonamide (7) and compound 32 demonstrated an IC₅₀ of ca. 6.5 μM; otherwise, the other selected derivatives did not show toxicity at concentrations up to 50 µM. The molecular modeling and docking of active compounds into various hCA isoenzymes, including bacterial carbonic anhydrase, specifically α-CA present in VRE, was performed to try to outline a possible mechanism of selective anti-VRE activity.     

Impact of Uremic Toxins on Endothelial Dysfunction in Chronic Kidney Disease: A Systematic Review

Patients with chronic kidney disease (CKD) are at a highly increased risk of cardiovascular complications, with increased vascular inflammation, accelerated atherogenesis and enhanced thrombotic risk. Considering the central role of the endothelium in protecting from atherogenesis and thrombosis, as well as its cardioprotective role in regulating vasorelaxation, this study aimed to systematically integrate literature on CKD-associated endothelial dysfunction, including the underlying molecular mechanisms, into a comprehensive overview. Therefore, we conducted a systematic review of literature describing uremic serum or uremic toxin-induced vascular dysfunction with a special focus on the endothelium. This revealed 39 studies analyzing the effects of uremic serum or the uremic toxins indoxyl sulfate, cyanate, modified LDL, the advanced glycation end products N-carboxymethyl-lysine and N-carboxyethyl-lysine, p-cresol and p-cresyl sulfate, phosphate, uric acid and asymmetric dimethylarginine. Most studies described an increase in inflammation, oxidative stress, leukocyte migration and adhesion, cell death and a thrombotic phenotype upon uremic conditions or uremic toxin treatment of endothelial cells. Cellular signaling pathways that were frequently activated included the ROS, MAPK/NF-κB, the Aryl-Hydrocarbon-Receptor and RAGE pathways. Overall, this review provides detailed insights into pathophysiological and molecular mechanisms underlying endothelial dysfunction in CKD. Targeting these pathways may provide new therapeutic strategies reducing increased the cardiovascular risk in CKD.     

Mitochondrial Processing Peptidases—Structure,Function and the Role in Human Diseases

Mitochondrial proteins are encoded by both nuclear and mitochondrial DNA. While some of the essential subunits of the oxidative phosphorylation (OXPHOS) complexes responsible for cellular ATP production are synthesized directly in the mitochondria, most mitochondrial proteins are first translated in the cytosol and then imported into the organelle using a sophisticated transport system. These proteins are directed mainly by targeting presequences at their N-termini. These presequences need to be cleaved to allow the proper folding and assembly of the pre-proteins into functional protein complexes. In the mitochondria, the presequences are removed by several processing peptidases, including the mitochondrial processing peptidase (MPP), the inner membrane processing peptidase (IMP), the inter-membrane processing peptidase (MIP), and the mitochondrial rhomboid protease (Pcp1/PARL). Their proper functioning is essential for mitochondrial homeostasis as the disruption of any of them is lethal in yeast and severely impacts the lifespan and survival in humans. In this review, we focus on characterizing the structure, function, and substrate specificities of mitochondrial processing peptidases, as well as the connection of their malfunctions to severe human diseases.     

Profiling of the Bacterial Microbiota along the Murine Alimentary Tract

Here, the spatial distribution of the bacterial flora along the murine alimentary tract was evaluated using high throughput sequencing in wild-type and Tff3-deficient (Tff3^KO) animals. Loss of Tff3 was linked to increased dextran sodium sulfate-induced colitis. This systematic study shows the results of 13 different regions from the esophagus to the rectum. The number of bacterial species (richness) increased from the esophagus to the rectum, from 50 to 200, respectively. Additionally, the bacterial community structure changed continuously; the highest changes were between the upper/middle and lower gastrointestinal compartments when comparing adjacent regions. Lactobacillus was the major colonizer in the upper/middle gastrointestinal tract, especially in the esophagus and stomach. From the caecum, a drastic diminution of Lactobacillus occurred, while members of Lachnospiraceae significantly increased. A significant change occurred in the bacterial community between the ascending and the transverse colon with Bacteroidetes being the major colonizers with relative constant abundance until the rectum. Interestingly, wild-type and Tff3^KO animals did not show significant differences in their bacterial communities, suggesting that Tff3 is not involved in alterations of intraluminal or adhesive microbiota but is obviously important for mucosal protection, e.g., of the sensitive stem cells in the colonic crypts probably by a mucus plume.     

Calcined Hydroxyapatite with Collagen I Foam Promotes Human MSC Osteogenic Differentiation

Collagen I-based foams were modified with calcined or noncalcined hydroxyapatite or calcium phosphates with various particle sizes and pores to monitor their effect on cell interactions. The resulting scaffolds thus differed in grain size, changing from nanoscale to microscopic, and possessed diverse morphological characteristics and resorbability. The materials’ biological action was shown on human bone marrow MSCs. Scaffold morphology was identified by SEM. Using viability test, qPCR, and immunohistochemical staining, we evaluated the biological activity of all of the materials. This study revealed that the most suitable scaffold composition for osteogenesis induction is collagen I foam with calcined hydroxyapatite with a pore size of 360 ± 130 µm and mean particle size of 0.130 µm. The expression of osteogenic markers RunX2 and ColI mRNA was promoted, and a strong synthesis of extracellular protein osteocalcin was observed. ColI/calcined HAP scaffold showed significant osteogenic potential, and can be easily manipulated and tailored to the defect size, which gives it great potential for bone tissue engineering applications.     

Electrostatic Adsorption of a Colloidal Sintering Agent on Silicon Nitride Particles

Pressureless sintering of silicon nitride requires addition of sintering agents. The main part of this study was done in order to homogenize the distribution of sintering agents, in this case Y₂O₃, in a silicon nitride matrix. Colloidal 10-nm Y₂O₃ Particles were electrostatically adsorbed on Si₃N₄ particle surfaces. The adsorption was studied by X-ray fluorescence analysis and electrophoretic measurements. Addition of Y₂O₃ sol to a Si₃N₄ suspension decreased the viscosity of the suspension. The slip casting properties of Si₃N₄ suspensions with added Y₂O₃ sol were examined, and the homogeneity of Y₂O₃ in the green compacts was compared with conventionally prepared samples. An improved microstructural homogeneity was obtained when Y₂O₃ sol particles were adsorbed on the Si₃N₄ particle surfaces.