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The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcinogenesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CARᴷᴼ-PXRᴷᴼ), double humanized CAR and PXR (CARʰ-PXRʰ), and wild-type C57BL/6 mice. Wild-type and CARʰ-PXRʰ mouse livers exhibited temporally and quantitatively similar transcriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were observed with peak expression occurring between 1 and 7 days PB exposure. All these transcriptional responses were absent in CARᴷᴼ-PXRᴷᴼ mouse livers and largely reversible in wild-type and CARʰ-PXRʰ mouse livers following 91 days of PB exposure and a subsequent 4-week recovery period. Furthermore, PB-mediated upregulation of the noncoding RNA Meg3, which has recently been associated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CARʰ-PXRʰ mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB.
As researchers continue to seek the expansion of the material base for additive manufacturing, there is a need to focus attention on the Ni–Cu group of alloys which conventionally has wide industrial applications. In this work, the G-NiCu30Nb casting alloy, a variant of the Monel family of alloys with Nb and high Si content is, for the first time, processed via the laser powder bed fusion process (LPBF). Being novel to the LPBF processes, optimum LPBF parameters were determined, and hardness and tensile tests were performed in as-built conditions and after heat treatment at 1000 °C. Microstructures of the as-cast and the as-built condition were compared. Highly dense samples (99.8% density) were achieved after varying hatch distance (80 µm and 140 µm) with scanning speed (550 mm/s–1500 mm/s). There was no significant difference in microhardness between varied hatch distance print sets. Microhardness of the as-built condition (247 HV0.2) exceeded the as-cast microhardness (179 HV0.2.). Tensile specimens built in vertical (V) and horizontal (H) orientations revealed degrees of anisotropy and were superior to conventionally reported figures. Post heat treatment increased ductility from 20% to 31% (V), as well as from 16% to 25% (H), while ultimate tensile strength (UTS) and yield strength (YS) were considerably reduced.
Der „Male Gaze“ bezeichnet das typische Erleben der Umwelt aus männlicher Perspektive und prägt in den sogenannten Mainstream-Medien die Gestaltung von Film, Fernsehen und Werbung. Dadurch werden von dargestellten Personen häufig die körperlichen Aspekte hervorgehoben. Im Gegensatz dazu gilt das weibliche Pendant, der „Female Gaze“, als besonders emotionsbetont. Weil Medien einen enormen Einfluss auf gesellschaftliches und individuelles Denken haben, stellt die Dominanz des „Male Gaze“ eine Unausgeglichenheit dar, die sich in verschiedenen Bereichen des gesellschaftlichen Lebens widerspiegelt. Deswegen möchte dieses Projekt die Medien um die weibliche Sichtweise erweitern und damit die dort transportierten Bilder diverser und ausgewogener machen. Die Fotografie fokussiert sich dabei auf die Gefühlswelt der Protagonistin, womit die Betrachter:Innen schrittweise in ihre Position hineinversetzt werden sollen. Mit Augen des Mitgefühls und eigenem Schönheitsbegriff lässt „Falling in love with the female gaze“ endlich auch die Frau zu Wort kommen.