Online dosimetric evaluation of larynx SBRT: A pilot study to assess the necessity of adaptive replanning

PURPOSE: We have initiated a multi-institutional phase I trial of 5-fraction stereotactic body radiotherapy (SBRT) for Stage III-IVa laryngeal cancer. We conducted this pilot dosimetric study to confirm potential utility of online adaptive replanning to preserve treatment quality. METHODS: We evaluated ten cases: five patients enrolled onto the current trial and five patients enrolled onto a separate phase I SBRT trial for early-stage glottic larynx cancer. Baseline SBRT treatment plans were generated per protocol. Daily cone-beam CT (CBCT) or diagnostic CT images were acquired prior to each treatment fraction. Simulation CT images and target volumes were deformably registered to daily volumetric images, the original SBRT plan was copied to the deformed images and contours, delivered dose distributions were re-calculated on the deformed CT images. All of these were performed on a commercial treatment planning system. In-house software was developed to propagate the delivered dose distribution back to reference CT images using the deformation information exported from the treatment planning system. Dosimetric differences were evaluated via dose-volume histograms. RESULTS: We could evaluate dose within 10 minutes in all cases. Prescribed coverage to gross tumor volume (GTV) and clinical target volume (CTV) was uniformly preserved; however, intended prescription dose coverage of planning treatment volume (PTV) was lost in 53% of daily treatments (mean: 93.9%, range: 83.9-97.9%). Maximum bystander point dose limits to arytenoids, parotids, and spinal cord remained respected in all cases, although variances in carotid artery doses were observed in a minority of cases. CONCLUSIONS: Although GTV and CTV SBRT dose coverage is preserved with in-room three-dimensional image guidance, PTV coverage can vary significantly from intended plans and dose to critical structures may exceed tolerances. Online adaptive treatment re-planning is potentially necessary and clinically applicable to fully preserve treatment quality. Confirmatory trial accrual and analysis remains ongoing

Observation of superconductivity in the noncentrosymmetric nodal chain semimetal Ba5In4Bi5

The combination with superconductivity and topological nontrivial band structure provides a promising route towards novel quantum states such as topological superconductivity. Here, we report the first observation of superconductivity (4.1 K) in Ba5In4Bi5 single crystal, a noncentrosymmetric topological semimetal featuring nodal chain loops at the high-symmetry points R and X. The magnetization, resistivity, and specific heat capacity measurements reveal that Ba5In4Bi5 is a moderately coupled type-II Bardeen-Cooper-Schrieffer superconductor. Bulk superconductivity is suggested from the magnetic susceptibility and specific heat measurements. The results show that Ba5In4Bi5 provides a new platform for exploring the relationship of superconductivity and topological nontrivial band topology

Zinc oxide nanoparticle-coated films: fabrication, characterization, and antibacterial properties

In this article, novel antibacterial PVC-based films coated with ZnO nanoparticles (NPs) were fabricated, characterized, and studied for their antibacterial properties. It was shown that the ZnO NPs were coated on the surface of the PVC films uniformly and that the coating process did not affect the size and shape of the NPs on the surface of PVC films. Films coated with concentrations of either 0.2 or 0.075 g/L of ZnO NPs exhibited antibacterial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, but exhibited no antifungal activity against Aspergillus flavus and Penicillium citrinum. Smaller particles (100 nm) exhibited more potent antibacterial activity than larger particles (1000 nm). All ZnO-coated films maintained antibacterial activity after 30 days in water

Evaluation of a Novel Renewable Hepatic Cell Model for Prediction of Clinical CYP3A4 Induction Using a Correlation-Based Relative Induction Score Approach

ABSTRACT Metabolism enzyme induction-mediated drug-drug interactions need to be carefully characterized in vitro for drug candidates to predict in vivo safety risk and therapeutic efficiency. Currently, both the Food and Drug Administration and European Medicines Agency recommend using primary human hepatocytes as the gold standard in vitro test system for studying the induction potential of candidate drugs on cytochrome P450 (CYP), CYP3A4, CYP1A2, and CYP2B6. However, primary human hepatocytes are known to bear inherent limitations such as limited supply and large lot-to-lot variations, which result in an experimental burden to qualify new lots. To overcome these shortcomings, a renewable source of human hepatocytes (i.e., Corning HepatoCells) was developed from primary human hepatocytes and was evaluated for in vitro CYP3A4 induction using methods well established by the pharmaceutical industry. HepatoCells have shown mature hepatocyte-like morphology and demonstrated primary hepatocyte-like response to prototypical inducers of all three CYP enzymes with excellent consistency. Importantly, HepatoCells retain a phenobarbital-responsive nuclear translocation of human constitutive androstane receptor from the cytoplasm, characteristic to primary hepatocytes. To validate HepatoCells as a useful tool to predict potential clinical relevant CYP3A4 induction, we tested three different lots of HepatoCells with a group of clinical strong, moderate/weak CYP3A4 inducers, and noninducers. A relative induction score calibration curve-based approach was used for prediction. HepatoCells showed accurate prediction comparable to primary human hepatocytes. Together, these results demonstrate that Corning HepatoCells is a reliable in vitro model for drug-drug interaction studies during the early phase of drug testing

Climate Change Impacts on Residential and Commercial Loads in the Western U.S. Grid

This report presents a multi-disciplinary modeling approach to quickly quantify climate change impacts on energy consumption, peak load, and load composition of residential and commercial buildings. This research focuses on addressing the impact of temperature changes on the building cooling load in 10 major cities across the Western United States and Canada. Our results have shown that by the mid-century, building yearly energy consumption and peak load will increase in the Southwest. Moreover, the peak load months will spread out to not only the summer months but also spring and autumn months. The Pacific Northwest will experience more hot days in the summer months. The penetration of the air conditioning (a/c) system in this area is likely to increase significantly over the years. As a result, some locations in the Pacific Northwest may be shifted from winter peaking to summer peaking. Overall, the Western U.S. grid may see more simultaneous peaks across the North and South in summer months. Increased cooling load will result in a significant increase in the motor load, which consumes more reactive power and requires stronger voltage support from the grid. This study suggests an increasing need for the industry to implement new technology to increase the efficiency of temperature-sensitive loads and apply proper protection and control to prevent possible adverse impacts of a/c motor loads

Lattice Boltzmann simulation of alumina-water nanofluid in a square cavity

A lattice Boltzmann model is developed by coupling the density (D2Q9) and the temperature distribution functions with 9-speed to simulate the convection heat transfer utilizing Al2O3-water nanofluids in a square cavity. This model is validated by comparing numerical simulation and experimental results over a wide range of Rayleigh numbers. Numerical results show a satisfactory agreement between them. The effects of Rayleigh number and nanoparticle volume fraction on natural convection heat transfer of nanofluid are investigated in this study. Numerical results indicate that the flow and heat transfer characteristics of Al2O3-water nanofluid in the square cavity are more sensitive to viscosity than to thermal conductivity

Cancer-Associated Fibroblasts Induce a Collagen Cross-link Switch in Tumor Stroma

Intratumoral collagen cross-links heighten stromal stiffness and stimulate tumor cell invasion, but it is unclear how collagen cross-linking is regulated in epithelial tumors. To address this question, we used KrasLA1 mice, which develop lung adenocarcinomas from somatic activation of a KrasG12D allele. The lung tumors in KrasLA1 mice were highly fibrotic and contained cancer-associated fibroblasts (CAFs) that produced collagen and generated stiffness in collagen gels. In xenograft tumors generated by injection of wild-type mice with lung adenocarcinoma cells alone or in combination with CAFs, the total concentration of collagen cross-links was the same in tumors generated with or without CAFs, but co-injected tumors had higher hydroxylysine aldehyde-derived collagen cross-links (HLCCs) and lower lysine-aldehyde-derived collagen cross-links (LCCs). Therefore, we postulated that an LCC-to-HLCC switch induced by CAFs promotes the migratory and invasive properties of lung adenocarcinoma cells. To test this hypothesis, we created co-culture models in which CAFs are positioned interstitially or peripherally in tumor cell aggregates, mimicking distinct spatial orientations of CAFs in human lung cancer. In both contexts, CAFs enhanced the invasive properties of tumor cells in 3-dimensional (3D) collagen gels. Tumor cell aggregates that attached to CAF networks on a Matrigel surface dissociated and migrated on the networks. Lysyl hydroxylase 2 (PLOD2/LH2), which drives HLCC formation, was expressed in CAFs, and LH2 depletion abrogated the ability of CAFs to promote tumor cell invasion and migration

Submucosal Gland Myoepithelial Cells Are Reserve Stem Cells That Can Regenerate Mouse Tracheal Epithelium

The mouse trachea is thought to contain two distinct stem cell compartments that contribute to airway repair-basal cells in the surface airway epithelium (SAE) and an unknown submucosal gland (SMG) cell type. Whether a lineage relationship exists between these two stem cell compartments remains unclear. Using lineage tracing of glandular myoepithelial cells (MECs), we demonstrate that MECs can give rise to seven cell types of the SAE and SMGs following severe airway injury. MECs progressively adopted a basal cell phenotype on the SAE and established lasting progenitors capable of further regeneration following reinjury. MECs activate Wnt-regulated transcription factors (Lef-1/TCF7) following injury and Lef-1 induction in cultured MECs promoted transition to a basal cell phenotype. Surprisingly, dose-dependent MEC conditional activation of Lef-1 in vivo promoted self-limited airway regeneration in the absence of injury. Thus, modulating the Lef-1 transcriptional program in MEC-derived progenitors may have regenerative medicine applications for lung diseases