994 research outputs found

    Determination of the bending and buckling effect in the stress analysis of shell structures accessible from one side only

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    The present report describes a device for ascertaining the bending and buckling effect in stress measurements on shell structures accessible from one side only. Beginning with a discussion of the relationship between flexural strain and certain parameters, the respective errors of the test method for great or variable skin curvature within the test range are analyzed and illustrated by specimen example

    Cyclic pyrrole-imidazole polyamides targeted to the androgen response element

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    Hairpin pyrrole−imidazole (Py-Im) polyamides are a class of cell-permeable DNA-binding small molecules that can disrupt transcription factor−DNA binding and regulate endogenous gene expression. The covalent linkage of antiparallel Py-Im ring pairs with an γ-amino acid turn unit affords the classical hairpin Py-Im polyamide structure. Closing the hairpin with a second turn unit yields a cyclic polyamide, a lesser-studied architecture mainly attributable to synthetic inaccessibility. We have applied our methodology for solution-phase polyamide synthesis to cyclic polyamides with an improved high-yield cyclization step. Cyclic 8-ring Py-Im polyamides 1−3 target the DNA sequence 5′-WGWWCW-3′, which corresponds to the androgen response element (ARE) bound by the androgen receptor transcription factor to modulate gene expression. We find that cyclic Py-Im polyamides 1−3 bind DNA with exceptionally high affinities and regulate the expression of AR target genes in cell culture studies, from which we infer that the cycle is cell permeable

    Prior-predictive value from fast growth simulations

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    Building on a variant of the Jarzynski equation we propose a new method to numerically determine the prior-predictive value in a Bayesian inference problem. The method generalizes thermodynamic integration and is not hampered by equilibration problems. We demonstrate its operation by applying it to two simple examples and elucidate its performance. In the case of multi-modal posterior distributions the performance is superior to thermodynamic integration.Comment: 8 pages, 11 figure

    CPS Based Liquid Metal Divertor Target for EU-DEMO

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    AbstractPower exhaust is a key mission in the roadmap to the realization of a future fusion reactor. Among the different solutions, the use of liquid metals as plasma facing materials are of interest due to their potential increased lifetime. Several liquid metal limiters have been successfully tested in the Frascati Tokamak Upgrade over the last 10 years. Liquid materials such as lithium and tin have been investigated using capillary porous systems (CPSs), and their impact on plasma performance has been explored. From such experience, a liquid metal divertor (LMD) concept design, CPS-based, is here proposed. Tin has been preferred as plasma facing material. The proposed LMD would operate, in low evaporative regime, with matching heat exhausting capabilities to those of the baseline ITER-like divertor. Continuous refilling of the CPS is guaranteed with a reservoir at the back of the unit, where the metal is kept liquid through a gas heating circuit. The study has been carried out using ANSYS and the thermal results will be shown. All the design choices are compatible with the current materials and the constraints adopted for the DEMO W divertor. Using such configuration, thermal loads up to 20 MW/m2 are exhausted while keeping the surface temperature below 1250 °C. The design foresees values of pressure, temperature and flow rate of the water coolant in the same range expected for the W DEMO divertor, thus facilitating the integration of such solution in the current cassette design. Technological and practical aspects are addressed, i.e. tin corrosion and CPS wettability. Possible solutions to prevent tin corrosion, and its compatibility with structural materials, will be outlined

    Apolipoprotein E (APOE) genotype regulates body weight and fatty acid utilization—Studies in gene-targeted replacement mice

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    Scope Of the three human apolipoprotein E (APOE) alleles, the ε3 allele is most common, which may be a result of adaptive evolution. In this study, we investigated whether the APOE genotype affects body weight and energy metabolism through regulation of fatty acid utilization. Methods and results Targeted replacement mice expressing the human APOE3 were significantly heavier on low- and high-fat diets compared to APOE4 mice. Particularly on high-fat feeding, food intake and dietary energy yields as well as fat mass were increased in APOE3 mice. Fatty acid mobilization determined as activation of adipose tissue lipase and fasting plasma nonesterified fatty acid levels were significantly lower in APOE3 than APOE4 mice. APOE4 mice, in contrast, exhibited higher expression of proteins involved in fatty acid oxidation in skeletal muscle. Conclusion Our data suggest that APOE3 is associated with the potential to more efficiently harvest dietary energy and to deposit fat in adipose tissue, while APOE4 carriers tend to increase fatty acid mobilization and utilization as fuel substrates especially under high-fat intake. The different handling of dietary energy may have contributed to the evolution and worldwide distribution of the ε3 allele

    Single-cell analysis reveals individual spore responses to simulated space vacuum

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    Outer space is a challenging environment for all forms of life, and dormant spores of bacteria have been frequently used to study the survival of terrestrial life in a space journey. Previous work showed that outer space vacuum alone can kill bacterial spores. However, the responses and mechanisms of resistance of individual spores to space vacuum are unclear. Here, we examined spores’ molecular changes under simulated space vacuum (~10−5 Pa) using micro-Raman spectroscopy and found that this vacuum did not cause significant denaturation of spore protein. Then, live-cell microscopy was developed to investigate the temporal events during germination, outgrowth, and growth of individual Bacillus spores. The results showed that after exposure to simulated space vacuum for 10 days, viability of spores of two Bacillus species was reduced up to 35%, but all spores retained their large Ca2 +-dipicolinic acid depot. Some of the killed spores did not germinate, and the remaining germinated but did not proceed to vegetative growth. The vacuum treatment slowed spore germination, and changed average times of all major germination events. In addition, viable vacuum-treated spores exhibited much greater sensitivity than untreated spores to dry heat and hyperosmotic stress. Among spores’ resistance mechanisms to high vacuum, DNA-protective α/β−type small acid-soluble proteins, and non- homologous end joining and base excision repair of DNA played the most important roles, especially against multiple cycles of vacuum treatment. Overall, these results give new insight into individual spore’s responses to space vacuum and provide new techniques for microorganism analysis at the single-cell level
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