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A High-Throughput Functional Complementation Assay for Classification of BRCA1 Missense Variants
(2013)
Operational Modal Analysis (OMA) is a promising candidate for flutter testing and Structural Health Monitoring (SHM) of aircraft wings that are passively excited by wind loads. However, no studies have been published where OMA is tested in transonic flows, which is the dominant condition for large civil aircraft and is characterized by complex and unique aerodynamic phenomena. We use data from the HIRENASD large-scale wind tunnel experiment to automatically extract modal parameters from an ambiently excited wing operated in the transonic regime using two OMA methods: Stochastic Subspace Identification (SSI) and Frequency Domain Decomposition (FDD). The system response is evaluated based on accelerometer measurements. The excitation is investigated from surface pressure measurements. The forcing function is shown to be non-white, non-stationary and contaminated by narrow-banded transonic disturbances. All these properties violate fundamental OMA assumptions about the forcing function. Despite this, all physical modes in the investigated frequency range were successfully identified, and in addition transonic pressure waves were identified as physical modes as well. The SSI method showed superior identification capabilities for the investigated case. The investigation shows that complex transonic flows can interfere with OMA. This can make existing approaches for modal tracking unsuitable for their application to aircraft wings operated in the transonic flight regime. Approaches to separate the true physical modes from the transonic disturbances are discussed.
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.
Magnetic nanoparticles (MNPs) are used as therapeutic and diagnostic agents for local delivery of heat and image contrast enhancement in diseased tissue. Besides magnetization, the most important parameter that determines their performance for these applications is their magnetic relaxation, which can be affected when MNPs immobilize and agglomerate inside tissues. In this letter, we investigate different MNP agglomeration states for their magnetic relaxation properties under excitation in alternating fields and relate this to their heating efficiency and imaging properties. With focus on magnetic fluid hyperthermia, two different trends in MNP heating efficiency are measured: an increase by up to 23% for agglomerated MNP in suspension and a decrease by up to 28% for mixed states of agglomerated and immobilized MNP, which indicates that immobilization is the dominant effect. The same comparatively moderate effects are obtained for the signal amplitude in magnetic particle spectroscopy.