Leakage of Metallic Ball Seat Valves with Anisotropic Surfaces

Metallic ball seat valves are an essential component of many hydraulic systems. They are used for many different purposes such as pressure relief valves or check valves. Despite their universal usage, their sealing mechanism is not yet fully understood. In previous works, a successful method for the simulation of the fluid leakage of metallic ball seat valves has been developed and confirmed experimentally. The method is based on Persson's contact mechanics theory, which is based on surface roughness power spectrum C(q). This theory takes a wide range of roughness values at different length scales into account. The previous method has been restricted to isotropic surfaces, but most surfaces of practical interest are highly anisotropic. A method for the calculation of pressure flow factors using Persson's method is presented. Based on these, a model for the leakage calculation can be developed. The simulation results are validated using an experiment.     

Assessment of Bioactivity-Modulating Pseudo-Ring Formation in Psilocin and Related Tryptamines

Psilocybin ( 1 ) is the major alkaloid found in psychedelic mushrooms and acts as a prodrug to psilocin ( 2 , 4-hydroxy-N,N-dimethyltryptamine), a potent psychedelic that exerts remarkable alteration of human consciousness. In contrast, the positional isomer bufotenin ( 7 , 5-hydroxy-N,N-dimethyltryptamine) differs significantly in its reported pharmacology. A series of experiments was designed to explore chemical differences between 2 and 7 and specifically to test the hypothesis that the C-4 hydroxy group of 2 significantly influences the observed physical and chemical properties through pseudo-ring formation via an intramolecular hydrogen bond (IMHB). NMR spectroscopy, accompanied by quantum chemical calculations, was employed to compare hydrogen bond behavior in 4- and 5-hydroxylated tryptamines. The results provide evidence for a pseudo-ring in 2 and that sidechain/hydroxyl interactions in 4-hydroxytryptamines influence their oxidation kinetics. We conclude that the propensity to form IMHBs leads to a higher number of uncharged species that easily cross the blood-brain barrier, compared to 7 and other 5-hydroxytryptamines, which cannot form IMHBs. Our work helps understand a fundamental aspect of the pharmacology of 2 and should support efforts to introduce it (via the prodrug 1 ) as an urgently needed therapeutic against major depressive disorder.     

miR-16-5p Is a Stably-Expressed Housekeeping MicroRNA in Breast Cancer Tissues from Primary Tumors and from Metastatic Sites

For quantitative microRNA analyses in formalin-fixed paraffin-embedded (FFPE) tissue, expression levels have to be normalized to endogenous controls. To investigate the most stably-expressed microRNAs in breast cancer and its surrounding tissue, we used tumor samples from primary tumors and from metastatic sites. MiRNA profiling using TaqMan^® Array Human MicroRNA Cards, enabling quantification of 754 unique human miRNAs, was performed in FFPE specimens from 58 patients with metastatic breast cancer. Forty-two (72%) samples were collected from primary tumors and 16 (28%) from metastases. In a cross-platform analysis of a validation cohort of 32 FFPE samples from patients with early breast cancer genome-wide microRNA expression analysis using SurePrintG3 miRNA (8 × 60 K)^® microarrays from Agilent^® was performed. Eleven microRNAs could be detected in all samples analyzed. Based on NormFinder and geNorm stability values and the high correlation (rho ≥ 0.8) with the median of all measured microRNAs, miR-16-5p, miR-29a-3p, miR-126-3p, and miR-222-3p are suitable single gene housekeeper candidates. In the cross-platform validation, 29 human microRNAs were strongly expressed (mean log2-intensity > 10) and 21 of these microRNAs including miR-16-5p and miR-29a-3p were also stably expressed (CV < 5%). Thus, miR-16-5p and miR-29a-3p are both strong housekeeper candidates. Their Normfinder stability values calculated across the primary tumor and metastases subgroup indicate that miR-29a-3p can be considered as the strongest housekeeper in a cohort with mainly samples from primary tumors, whereas miR-16-5p might perform better in a metastatic sample enriched cohort.     

Doublecortin May Play a Role in Defining Chondrocyte Phenotype

Embryonic development of articular cartilage has not been well understood and the role of doublecortin (DCX) in determination of chondrocyte phenotype is unknown. Here, we use a DCX promoter-driven eGFP reporter mouse model to study the dynamic gene expression profiles in mouse embryonic handplates at E12.5 to E13.5 when the condensed mesenchymal cells differentiate into either endochondral chondrocytes or joint interzone cells. Illumina microarray analysis identified a variety of genes that were expressed differentially in the different regions of mouse handplate. The unique expression patterns of many genes were revealed. Cytl1 and 3110032G18RIK were highly expressed in the proximal region of E12.5 handplate and the carpal region of E13.5 handplate, whereas Olfr538, Kctd15, and Cited1 were highly expressed in the distal region of E12.5 and the metacarpal region of E13.5 handplates. There was an increasing gradient of Hrc expression in the proximal to distal direction in E13.5 handplate. Furthermore, when human DCX protein was expressed in human adipose stem cells, collagen II was decreased while aggrecan, matrilin 2, and GDF5 were increased during the 14-day pellet culture. These findings suggest that DCX may play a role in defining chondrocyte phenotype.     

Rapid Assessment of Frying Performance Using Small Size Samples of Oils/Fats

A rapid, effective test mimicking actual frying was developed to assess the frying performance of oils and fats using small size samples. To a small volume of the oil to be tested, a formulated food consisting of gelatinized potato starch, glucose and silica gel (4:1:1 w/w) were added and content heated at 185 ± 5 °C with mixing for 2 h. Thermo-oxidative degradation of the oil was assessed by the measurement of the total amount of polar components and their composition, including degradation of tocopherols. The developed fast test accurately mimics actual frying done using an institutional fryer as assessed by the accumulation and composition of total polar components and the amount of residual tocopherols. The validity of the test was assessed using the following oils: regular canola, high oleic– low linolenic canola, and high oleic sunflower. Comparison of data between the fast frying test and institutional frying revealed a lack of significant differences. The developed frying test provides reliable quantitative and qualitative data describing the performance of the frying oil/fat. The rapid frying procedure allows assessment of the frying performance of oils at the early stages of development where usually only small amounts of the sample are available and when a large number of samples have to be tested assessing effects of oil additives.     

Optimizing substrate surface and catalyst conditions for high yield chemical vapor deposition grown epitaxially aligned single-walled carbon nanotubes

Single-crystal stable-temperature (ST)-cut quartz substrates, which have a (0 1 1 1) crystallographic plane with their surface normal lying close to 38° from the y axis ([0 1 0]), were annealed in air prior to use as a support for aligned carbon nanotube growth by chemical vapor deposition. Very smooth substrate surfaces were obtained with annealing times in the vicinity of 15 h at a temperature of 750 °C. These smooth surfaces are ideal for the growth of horizontally aligned SWCNTs with high spatial density, while less dense SWCNTs were obtained with less smooth surfaces. Under optimized growth conditions, only SWCNT are observed and they can grow to lengths in excess of 100 μm. Our findings suggest structural defects interfere with the growth process. A binary Fe/Co catalyst was employed to grow the nanotubes. No obvious dependence on the Fe:Co ratio is observed.     

Regulation of polyisoprenylated methylated protein methyl esterase by polyunsaturated fatty acids and prostaglandins

Polyisoprenylation is a set of secondary modifications involving proteins whose aberrant activities are implicated in cancers and degenerative disorders. The last step of the pathway involves an ester‐forming polyisoprenylated protein methyl transferase‐ and hydrolytic polyisoprenylated methylated protein methyl esterase (PMPMEase)‐catalyzed reactions. Omega‐3 and omega‐6 PUFAs have been linked with antitumorigeneis and tumorigenesis, respectively. PUFAs are structurally similar to the polyisoprenyl groups and may interfere with polyisoprenylated protein metabolism. It was hypothesized that PUFAs may be more potent inhibitors of PMPMEase than their more polar oxidative metabolites, the prostaglandins. As such, the relative effects of PUFAs and prostaglandins on PMPMEase could explain the association between cyclooxygenase‐2 (COX‐2) expression in tumors, the chemopreventive effects of the non‐steroidal anti‐inflammatory (NSAIDs) COX‐2 inhibitors and PUFAs. PUFAs such as AA, EPA, and DHA inhibited PMPMEase activity with K_i values of 0.12–3.7 µM. The most potent prostaglandin was 63‐fold less potent than AA. The PUFAs were also more effective at inducing neuroblastoma cell death at physiologically equivalent concentrations. The lost PMPMEase activity in AA‐treated degenerating cells was restored by incubating the lysates with COX‐1 or COX‐2. PUFAs may thus be physiological regulators of cell growth and could owe these effects to PMPMEase inhibition. Practical applications: Some PUFAs have been widely reported to have anticancer benefits. However, the molecular mechanisms for these effects are not well understood. The findings in the current paper appear to suggest that inhibition of PMPMEase may underlie their effects. They also imply that the expression of COX‐2 in various tumors may serve to convert the PUFAs into significantly less inhibitory prostaglandins. From these findings, AA and the other PUFAs, rather than being substrates for the synthesis of tumorigenic agents may actually contribute in suppressing cell proliferation. This being congruent with the lower cancer risks associated with long term use of anti‐inflammatory agents, the practical implications will likely include the nutritional and/or therapeutic management of cancer with the goal of maintaining suitable levels of the fatty acids in tissues.