Sporadic hemangioblastomas are characterized by cryptic VHL inactivation

Hemangioblastomas consist of 10-20% neoplastic “stromal” cells within a vascular tumor cell mass of reactive pericytes, endothelium and lymphocytes. Familial cases of central nervous system hemangioblastoma uniformly result from mutations in the Von Hippel-Lindau (VHL) gene. In contrast, inactivation of VHL has been previously observed in only a minority of sporadic hemangioblastomas, suggesting an alternative genetic etiology. We performed deep-coverage DNA sequencing on 32 sporadic hemangioblastomas (whole exome discovery cohort n = 10, validation n = 22), followed by analysis of clonality, copy number alteration, and somatic mutation. We identified somatic mutation, loss of heterozygosity and/or deletion of VHL in 8 of 10 discovery cohort tumors. VHL inactivating events were ultimately detected in 78% (25/32) of cases. No other gene was significantly mutated. Overall, deep-coverage sequence analysis techniques uncovered VHL alterations within the neoplastic fraction of these tumors at higher frequencies than previously reported. Our findings support the central role of VHL inactivation in the molecular pathogenesis of both familial and sporadic hemangioblastomas

Rapid Intraoperative Molecular Characterization of Glioma

IMPORTANCE: Conclusive intraoperative pathologic confirmation of diffuse infiltrative glioma guides the decision to pursue definitive neurosurgical resection. Establishing the intraoperative diagnosis by histologic analysis can be difficult in low-cellularity infiltrative gliomas. Therefore, we developed a rapid and sensitive genotyping assay to detect somatic single-nucleotide variants in the telomerase reverse transcriptase (TERT) promoter and isocitrate dehydrogenase 1 (IDH1). OBSERVATIONS: This assay was applied to tissue samples from 190 patients with diffuse gliomas, including archived fixed and frozen specimens and tissue obtained intraoperatively. Results demonstrated 96% sensitivity (95% CI, 90%–99%) and 100% specificity (95% CI, 95%–100%) for World Health Organization grades II and III gliomas. In a series of live cases, glioma-defining mutations could be identified within 60 minutes, which could facilitate the diagnosis in an intraoperative timeframe. CONCLUSIONS AND RELEVANCE: The genotyping method described herein can establish the diagnosis of low-cellularity tumors like glioma and could be adapted to the point-of-care diagnosis of other lesions that are similarly defined by highly recurrent somatic mutations

Modulation of ZnO film thickness and formation of water-hyacinth nanostructure

The influence of precursor medium was investigated on the structural, morphological, optical and electrical properties of spray pyrolysis deposited nanostructured ZnO thin films. Three batches of ZnO thin films were deposited on glass substrates using three different solvents (water, water-ethanol [ratio of 1:1] and ethanol) based precursor solution of zinc nitrate hexahydrate. The substrate temperature was fixed at 523 K. The variation in film thickness from 150 to 875 nm was observed as the effect of changing solvent medium. X-ray diffraction (XRD) data confirmed the formation of polycrystalline ZnO thin films with hexagonal wurtzite crystallite structure and the estimated crystallite size was found to be ranging from 31 to 55 nm. Scanning electron micrographs revealed the formation of water-hyacinth shaped nanostructures when water-ethanol mixture was used as the solvent medium. Interestingly, UV-vis spectrophotometer revealed the formation of ZnO film with twin optical band gap of 3.15 eV and 3.56 eV when ethanol was used as the solvent medium. The modulation of film thickness and grain size by solvent medium has strongly influenced the electrical conductivity of ZnO thin films. The homogenous nano-spherical grains with uniform grain boundaries showed a good response towards 100 ppm of ammonia at room temperature

A closed-form analytical model for predicting 3D boundary layer displacement thickness for the validation of viscous flow solvers

A closed-form analytical model is developed for estimating the 3D boundary-layer-displacement thickness of an internal flow system at the Sanal flow choking condition for adiabatic flows obeying the physics of compressible viscous fluids. At this unique condition the boundary-layer blockage induced fluid-throat choking and the adiabatic wall-friction persuaded flow choking occur at a single sonic-fluid-throat location. The beauty and novelty of this model is that without missing the flow physics we could predict the exact boundary-layer blockage of both 2D and 3D cases at the sonic-fluid-throat from the known values of the inlet Mach number, the adiabatic index of the gas and the inlet port diameter of the internal flow system. We found that the 3D blockage factor is 47.33 % lower than the 2D blockage factor with air as the working fluid. We concluded that the exact prediction of the boundary-layer-displacement thickness at the sonic-fluid-throat provides a means to correctly pinpoint the causes of errors of the viscous flow solvers. The methodology presented herein with state-of-the-art will play pivotal roles in future physical and biological sciences for a credible verification, calibration and validation of various viscous flow solvers for high-fidelity 2D/3D numerical simulations of real-world flows. Furthermore, our closed-form analytical model will be useful for the solid and hybrid rocket designers for the grain-port-geometry optimization of new generation single-stage-to-orbit dual-thrust-motors with the highest promising propellant loading density within the given envelope without manifestation of the Sanal flow choking leading to possible shock waves causing catastrophic failures. (C) 2018 Author(s)

The theoretical prediction of the boundary-layer-blockage and external flow choking at moving aircraft in ground effects

The theoretical discoveries of the Sanal flow choking [V. R. Sanal Kumar et al., "Sanal flow choking: A paradigm shift in computational fluid dynamics code verification and diagnosing detonation and hemorrhage in real-world fluid-flow systems,"Global Challenges 4, 2000012 (2020)] and streamtube flow choking [V. R. Sanal Kumar et al., "Deflagration to detonation transition in chemical rockets with sudden expansion/divergence regions,"AIAA Paper No. 2020-3520, 2020] achieved significant contemplation in all branches of science and engineering for resolving various unanswered scientific questions brought onward from the beginning of this era [V. R. Sanal Kumar et al., "A closed-form analytical model for predicting 3D boundary layer displacement thickness for the validation of viscous flow solvers,"AIP Adv. 8, 025315 (2018)]. The applications of these flow choking phenomena are more significant in aerospace industries [V. R. Sanal Kumar et al., "Nanoscale flow choking and spaceflight effects on cardiovascular risk of astronauts - A new perspective,"AIAA Paper No. 2021-0357, 2021] and medical sciences [V. R. Sanal Kumar et al., "Lopsided blood-thinning drug increases the risk of internal flow choking leading to shock wave generation causing asymptomatic cardiovascular disease,"Global Challenges 2021, 2000076]. Herein, as an offshoot of the Sanal flow choking phenomena, the proof of the concept of boundary-layer-blockage (BLB) persuaded external-flow-choking (EFC) at aircraft-in-ground (AIG)-effect is presented. When the aircraft's ground clearance is relatively low, the evolving BLB factor from both planes (the bottom surface of the aircraft and the ground) creates a transient fluid-throat, leading to the Sanal flow choking and supersonic flow development in the duct flow region. In this physical situation, the pressure ratio (Ptotal/Pstatic) at the external flow choking region is exclusively a function of the specific heat ratio of the fluid. The EFC is more prone for the low wing aircraft flying in the near vicinity to the ground and/or sea with relatively high subsonic Mach number and low angle of attack. At this flying condition, the underside of the aircraft (fuselage and/or wing) and the ground creates the convergent-divergent duct flow effect leading to the EFC at the critical total-to-static pressure ratio. The accurate estimation of the BLB factor at the location of the EFC at AIG effect is presented in this manuscript as a universal yardstick for two-dimensional (2D) in silico simulation. For establishing the proof of the concept of external flow choking and supersonic flow development and shock wave generation, the 2D in silico results are presented for both stationary and moving airfoils in ground effect. In silico results show that the airfoil at stationary position exhibits relatively higher BLB factor and an immediate occurrence of the EFC than the same airfoil moving with the identical inflow Mach number and Reynolds number. We could establish herein that the moving vehicle simulation is inevitable for capturing actual flow physics and further precise examination of the BLB factor and the possibilities of the occurrence of the EFC for credible trajectory optimization of high-speed ground-effect vehicles. © 2021 Author(s).12 month embargo; published online: 11 March 2021This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]