134 research outputs found

    Interleukin 1 is a key driver of inflammatory bowel disease-demonstration in a murine IL-1Ra knockout model

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    Interleukin 1 (IL-1) is an important mediator of inflammation and tissue damage in inflammatory bowel disease (IBD). The balance between IL-1 and IL-1Ra as a natural inhibitor plays a vital role in a variety of diseases. Here, we investigated whether changes seen during IBD are induced spontaneously in mice lacking a functional IL-1rn gene. Histological staining was performed on the jejunum and ileum of BALB/c IL-1rn+/+ and IL-1rn-/- mice to characterize crypt-villus height, villus width, and number of goblet cells per villus. Pro-inflammatory cytokines, immune cell infiltration and matrix-degrading enzymes, together with the production of intestinal enzymes and the integrity of tight and adherent junction proteins were determined using immunohistochemistry. In the small intestine of BALB/c IL-1rn-/- mice the villus heights were significantly reduced; and in the ileum this was accompanied by a decrease in villi width. There was also an increase in goblet cell number and mucin production compared to wild-type mice. IL-1α and IL-1β immunopositivity were increased, whilst IL-1R1 expression was decreased in IL-1rn-/- mice. IL-15 and TNFα were also increased in older IL-1rn-/- mice. Increased polymorphonuclear and macrophage infiltration were seen in IL-1rn-/- mice, whilst expression of matrix-degrading enzymes and digestive enzymes were unchanged, except for dipeptidyl peptidase IV which was increased in younger IL-1rn-/- mice compared to wild type mice. The expression of tight and adhesion junctions were also dramatically decreased in IL-1rn-/- mice. In conclusion, IL-1rn-/- mice developed spontaneous abnormalities which displayed features associated with IBD, demonstrating a clear role for IL-1 in IBD

    The Red Sea under the Caliphal Dynasties, c. 639–1171

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    Students of world history will be familiar with the Red Sea as a strategic communications corridor linking the Mediterranean to the Indian Ocean. This paper examines the Red Sea region between the seventh and twelfth centuries, when it was ruled by a succession of Islamic caliphal dynasties, namely, the Umayyads, ʿAbbāsids, and Fāṭimids. It first sets out a sketch of the political history of the Red Sea and its constituent hinterland polities, including particularly Egypt, Sudan, al‐Ḥijāz, and Yemen, drawing attention to episodes and processes in which the Red Sea was significant. A section on Africa and Arabia explores the Red Sea as a zone of economic and social interaction; another section deals with the historic shift of Indian Ocean trade from the ʿAbbāsid Persian Gulf to the Fāṭimid Red Sea. Finally, the impact of the Red Sea on its constituent hinterland polities and the wider sweep of Islamic history is considered

    Analysis of the accuracy of actuation electronics in the laser interferometer space antenna pathfinder

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    The Laser Interferometer Space Antenna Pathfinder (LPF) main observable, labeled Δg, is the differential force per unit mass acting on the two test masses under free fall conditions after the contribution of all non-gravitational forces has been compensated. At low frequencies, the differential force is compensated by an applied electrostatic actuation force, which then must be subtracted from the measured acceleration to obtain Δg. Any inaccuracy in the actuation force contaminates the residual acceleration. This study investigates the accuracy of the electrostatic actuation system and its impact on the LPF main observable. It is shown that the inaccuracy is mainly caused by the rounding errors in the waveform processing and also by the random error caused by the analog to digital converter random noise in the control loop. Both errors are one order of magnitude smaller than the resolution of the commanded voltages. We developed a simulator based on the LPF design to compute the close-to-reality actuation voltages and, consequently, the resulting actuation forces. The simulator is applied during post-processing the LPF data

    Harmonization and standardization of nucleus pulposus cell extraction and culture methods

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    BACKGROUND: In vitro studies using nucleus pulposus (NP) cells are commonly used to investigate disc cell biology and pathogenesis, or to aid in the development of new therapies. However, lab-to-lab variability jeopardizes the much-needed progress in the field. Here, an international group of spine scientists collaborated to standardize extraction and expansion techniques for NP cells to reduce variability, improve comparability between labs and improve utilization of funding and resources. METHODS: The most commonly applied methods for NP cell extraction, expansion, and re-differentiation were identified using a questionnaire to research groups worldwide. NP cell extraction methods from rat, rabbit, pig, dog, cow, and human NP tissue were experimentally assessed. Expansion and re-differentiation media and techniques were also investigated. RESULTS: Recommended protocols are provided for extraction, expansion, and re-differentiation of NP cells from common species utilized for NP cell culture. CONCLUSIONS: This international, multilab and multispecies study identified cell extraction methods for greater cell yield and fewer gene expression changes by applying species-specific pronase usage, 60-100 U/ml collagenase for shorter durations. Recommendations for NP cell expansion, passage number, and many factors driving successful cell culture in different species are also addressed to support harmonization, rigor, and cross-lab comparisons on NP cells worldwide

    The Gravitational Universe

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    The last century has seen enormous progress in our understanding of the Universe. We know the life cycles of stars, the structure of galaxies, the remnants of the big bang, and have a general understanding of how the Universe evolved. We have come remarkably far using electromagnetic radiation as our tool for observing the Universe. However, gravity is the engine behind many of the processes in the Universe, and much of its action is dark. Opening a gravitational window on the Universe will let us go further than any alternative. Gravity has its own messenger: Gravitational waves, ripples in the fabric of spacetime. They travel essentially undisturbed and let us peer deep into the formation of the first seed black holes, exploring redshifts as large as z ~ 20, prior to the epoch of cosmic re-ionisation. Exquisite and unprecedented measurements of black hole masses and spins will make it possible to trace the history of black holes across all stages of galaxy evolution, and at the same time constrain any deviation from the Kerr metric of General Relativity. eLISA will be the first ever mission to study the entire Universe with gravitational waves. eLISA is an all-sky monitor and will offer a wide view of a dynamic cosmos using gravitational waves as new and unique messengers to unveil The Gravitational Universe. It provides the closest ever view of the early processes at TeV energies, has guaranteed sources in the form of verification binaries in the Milky Way, and can probe the entire Universe, from its smallest scales around singularities and black holes, all the way to cosmological dimensions

    Planck pre-launch status : The Planck mission

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