628 research outputs found

    Ethics After New Materialism: A Modest Undertaking

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    Toroidal Variable-Line-Space Gratings: The Good, the Bad and The Ugly

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    Toroidal variable-line-space (VLS) gratings are an important factor in the design of an efficient VUV solar telescope that will measure the CIV (155nm) and MgII (280nm) emissions lines in the Sun's transition region. In 1983 Kita and Harada described spherical VLS gratings but the technology to commercially fabricate these devices is a recent development, especially for toroidal surfaces. This paper will describe why this technology is important in the development of the Solar Ultraviolet Magnetograph Investigation (SUMI) sounding rocket program (the good), the delays due to the conversion between the TVLS grating design and the optical fabrication (the bad), and finally the optical testing, alignment and tolerancing of the gratings (the ugly). The Solar Ultraviolet Magnetograph Investigation, SUMI, has been reported in several papers since this program began in 2000. The emphasis of this paper is to describe SUMI's Toroidal Variable-Line-Space (TVLS) gratings. These gratings help SUMI meet its scientific goals which require both high spectral resolution and high optical efficiency for magnetic field measurements in the vacuum ultraviolet wavelength band of the solar spectrum (the good). Unfortunately, the technology readiness level of these gratings has made their implementation difficult, especially for a sounding rocket payload (the bad). Therefore, this paper emphasizes the problems and solutions that were developed to use these gratings in SUMI (the ugly). Section 2 contains a short review of the scientific goals of SUMI and why this mission is important in the understanding of the 3D structure of the magnetic field on the Sun. The flight hardware that makes up the SUMI payload is described in Section 3 with emphasis on those components that affect the TVLS gratings. Section 4 emphasizes the alignment, testing and optical modeling that were developed to optimize the performance of these gratings

    Ethics After New Materialism: A Modest Undertaking

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    Performance of the FOS and GHRS Pt/(Cr)-Ne Hollow-cathode Lamps after their Return from Space and Comparison with Archival Data

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    The Space Telescope European Coordinating Facility (ST-ECF) and National Institute of Standards and Technology (NIST) are collaborating to study hollow cathode calibration lamps as used onboard the Hubble Space Telescope (HST). As part of the STIS Calibration Enhancement (STIS-CE) Project we are trying to improve our understanding of the performance of hollow cathode lamps and the physical processes involved in their long term operation. The original flight lamps from the Faint Object Spectrograph (FOS) and the Goddard High Resolution Spectrograph (GHRS) are the only lamps that have ever been returned to Earth after extended operation in space. We have taken spectra of all four lamps using NIST s 10.7-m normal-incidence spectrograph and Fourier transform spectrometer (FTS) optimized for use in the ultraviolet (UV). These spectra, together with spectra archived from six years of on-orbit operations and pre-launch spectra, provide a unique data set - covering a period of about 20 years - for studying aging effects in these lamps. Our findings represent important lessons for the choice and design of calibration sources and their operation in future UV and optical spectrographs in space

    Haemodynamics Regulate Fibronectin Assembly via PECAM

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    Fibronectin (FN) assembly and fibrillogenesis are critically important in both development and the adult organism, but their importance in vascular functions is not fully understood. Here we identify a novel pathway by which haemodynamic forces regulate FN assembly and fibrillogenesis during vascular remodelling. Induction of disturbed shear stress in vivo and in vitro resulted in complex FN fibril assembly that was dependent on the mechanosensor PECAM. Loss of PECAM also inhibited the cell-intrinsic ability to remodel FN. Gain- and loss-of-function experiments revealed that PECAM-dependent RhoA activation is required for FN assembly. Furthermore, PECAM−/− mice exhibited reduced levels of active β1 integrin that were responsible for reduced RhoA activation and downstream FN assembly. These data identify a new pathway by which endothelial mechanotransduction regulates FN assembly and flow-mediated vascular remodelling

    Proteostasis and resilience in the mechanically-stressed vascular endothelium

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    Endothelial homeostasis is a central feature of vascular health. The vascular endothelium is under constant mechanical stress resulting from blood flow and, therefore, requires a high degree of resilience to adapt to stresses and resist development of disease. In this review, we discuss the molecular mechanisms by which the endothelium maintains proteostasis in response to haemodynamic forces by regulating three key areas: protein synthesis, recycling and degradation

    The integrin αvβ6 drives pancreatic cancer through diverse mechanisms and represents an effective target for therapy

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    Pancreatic ductal adenocarcinoma (PDAC) has a five‐year survival rate of <4% and desperately needs novel effective therapeutics. Integrin αvβ6 has been linked with poor prognosis in cancer but its potential as a target in PDAC remains unclear. We report that transcriptional expression analysis revealed high levels of β6 mRNA correlated strongly with significantly poorer survival (n=491 cases, p= 3.17x10‐8). In two separate cohorts we showed that over 80% of PDAC expressed αvβ6 protein and that paired metastases retained αvβ6 expression. In vitro, integrin αvβ6 promoted PDAC cell growth, survival, migration and invasion. Treatment of both αvβ6‐positive human PDAC xenografts and transgenic mice bearing αvβ6‐positive PDAC with the αvβ6 blocking antibody 264RAD, combined with gemcitabine, significantly reduced tumour growth (p<0.0001) and increased survival (Log‐rank test, p<0.05). Antibody therapy was associated with suppression of both tumour cell activity (suppression of pErk growth signals, increased apoptosis seen as activated Caspase 3) and suppression of the pro‐tumourigenic microenvironment (suppression of TGFβ signalling, fewer αSMA‐positive myofibroblasts, decreased blood vessel density). These data show that αvβ6 promotes PDAC growth through both tumour cell and tumour microenvironment mechanisms and represents a valuable target for PDAC therapy
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