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Cryo-ultrasonic testing utilizes polycrystalline ice coupling to enable the inspection of metallic components with complex shape. The relatively high velocity of compressional waves in ice (approximately 4000 m s−1) and its ability to support the propagation of shear waves, significantly strengthen the ultrasonic transmission through curved interfaces over conventional water coupling. This paper explores the possibility of further enhancing the ultrasonic properties of ice by dispersing solid particles in water before it is frozen. Complex physicochemical phenomena occur when aqueous dispersions freeze which can lead to a solid material with microstructural characteristics that may be unfavorable to the propagation of ultrasonic waves. Here, these effects are controlled to produce a composite material consisting of alumina nanoparticles in an ice matrix. The composite exhibits compressional and shear wave velocities of approximately 4800 m s−1 and 2700 m s−1 , respectively. Importantly, the mass density of the material is more than twice as large as the density of water. Finally, it is shown that a phenomenon similar to a glass transition occurs during freezing which results in low ultrasonic attenuation when the temperature approaches – 100 °C.more » « less
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A scalable approach for quantifying intact HIV-1 proviruses is critical for basic research and clinical trials directed at HIV-1 cure. The intact proviral DNA assay (IPDA) is a novel approach to characterizing the HIV-1 reservoir, focusing on the genetic integrity of individual proviruses independent of transcriptional status. It uses multiplex digital droplet PCR to distinguish and separately quantify intact proviruses, defined by a lack of overt fatal defects such as large deletions and APOBEC3G-mediated hypermutation, from the majority of proviruses that have such defects. This distinction is important because only intact proviruses cause viral rebound on ART interruption. To evaluate IPDA performance and provide benchmark data to support its implementation, we analyzed peripheral blood samples from 400 HIV-1 + adults on ART from several diverse cohorts, representing a robust sample of treated HIV-1 infection in the United States. We provide direct quantitative evidence that defective proviruses greatly outnumber intact proviruses (by >12.5 fold). However, intact proviruses are present at substantially higher frequencies (median, 54/10 6 CD4 + T cells) than proviruses detected by the quantitative viral outgrowth assay, which requires induction and in vitro growth (∼1/10 6 CD4 + T cells). IPDA amplicon signal issues resulting from sequence polymorphisms were observed in only 6.3% of individuals and were readily apparent and easily distinguished from low proviral frequency, an advantage of the IPDA over standard PCR assays which generate false-negative results in such situations. The large IPDA dataset provided here gives the clearest quantitative picture to date of HIV-1 proviral persistence on ART.more » « less
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