Quantifying the limits of CAR T-cell delivery in mice and men

CAR (Chimeric Antigen Receptor) T cells have demonstrated clinical success for the treatment of multiple lymphomas and leukaemias, but not for various solid tumours, despite promising data from murine models. Lower effective CAR T-cell delivery rates to human solid tumours compared to haematological malignancies in humans and solid tumours in mice might partially explain these divergent outcomes. We used anatomical and physiological data for human and rodent circulatory systems to calculate the typical perfusion of healthy and tumour tissues, and estimated the upper limits of immune cell delivery rates across different organs, tumour types and species. Estimated maximum delivery rates were up to 10 000-fold greater in mice than humans yet reported CAR T-cell doses are typically only 10–100-fold lower in mice, suggesting that the effective delivery rates of CAR T cells into tumours in clinical trials are far lower than in corresponding mouse models. Estimated delivery rates were found to be consistent with published positron emission tomography data. Results suggest that higher effective human doses may be needed to drive efficacy comparable to mouse solid tumour models, and that lower doses should be tested in mice. We posit that quantitation of species and organ-specific delivery and homing of engineered T cells will be key to unlocking their potential for solid tumours.     

Effect of ZnO layer thickness upon optoelectrical properties of NiO/ ZnO heterojunction prepared at room temperature

In this work, p-NiO/n-ZnO heterostructures were successfully prepared at room temperature using RF sputtering technique. The influence of ZnO layer thickness on the performance of the heterojunction was investigated. The deposited ZnO layers have a hexagonal Wurtzite structure with preferable growth orientations along (002) and (103) for thinner films. Increasing the thickness results in more crystallographic orientation randomness. The current–voltage measurements of the realized heterojunctions showed a clear rectifying behavior. The measured ideality factor varies from 2.5 to 1.6 according to the thickness of ZnO layer. The series resistance of the device is enlarged with increasing ZnO thickness. The deduced parameters from the I–V characteristics suggest that 200 nm is the optimal thickness of the ZnO layer according to our experimental conditions. We attribute the relatively better performance of this thickness to achieving reasonable compensation between serial resistance and ideality factor. The best heterojunction was tested and successfully used as a UV detector.     

On Application of Carbon-Containing Electrode Materials in Technology of Electrospark Alloying: Part 1. Peculiarities of Coating Formation Using Electrospark Treatment of Titanium Alloy OT4-1

Electrospark treatment of OT4-1 titanium alloy was performed sequentially with a STIM-20N hard-alloy electrode (TiC–20% Ni) and carbon-containing material (graphite and carbon-based composite materials). Kinetics of the mass transfer of the hard-alloy electrode was studied. The cathode mass loss during the first minute of the treatment was established. The kinetics results were processed using the methods of mathematical statistics. The erosion resistance of the applied carbon-containing materials was determined. Phase composition and relief of the coatings formed were analyzed. It was found that the application of the carbon-containing material increases the content of refractory phases in the coatings. Increase in the time of the treatment using the carbon-containing materials decreases the roughness of the coatings.     

Medicine Meets Thermal Spray Technology: A Review of Patents

The patent literature concerning thermal spraying for biomedical applications is reviewed in this contribution. The patents were compiled from multiple databases search spanning the 2005-2018 period. For clarity and ease of reading, the results have been grouped into sections according to four individual material groups (apatites, titanium, oxide ceramics, other), with the secondary sorting criterion being related to the specific bioapplication areas (maxillofacial, orthopedic, methods). Lastly, the patents are grouped according to the selected thermal spray method within the individual subsections. In the paper, recent R&D trends in this field are further identified and briefly commented.     

Assessment of Dam Overtopping Reliability using SUFI Based Overtopping Threshold Curve

Estimation of earth-fill dam height and dimension of spillway are strongly depend on accurate evaluation of dam overtopping reliability. Ideally, whole random and effective variables on overtopping should be considered for dam overtopping reliability assessment. However, taking into account all affecting random variables as well as overtopping reliability assessment using algorithms such as Monte Carlo (MC) could be excessively time consuming and impossible in some cases. In this study, new approach has been introduced as conditional reliability method and it has been tried to reduce the simulations time significantly by using combination of rainfall threshold theory, SUFI (Sequential Uncertainty Fitting) and MC methods. According two defined indexes, the obtain results shown, the relative error of new approach in computation of Jamishan dam overtopping reliability is less than 0.23%. Also, time saving in new method against to regular MC method is more than 87%. So, the new introduced method has more efficiency with acceptable accuracy for assessment of dam overtopping reliability. In addition, among hydrological and hydraulic uncertainties, hydrological uncertainties have more effect on overtopping reliability.     

Liquid phase sintering and characterization of SiC ceramics

The present study focuses on the sintering of silicon carbide-based ceramics (SiC) by liquid phase sintering (LPS) followed by characterization of the produced ceramics. AlN/Re₂O₃ mixtures were used as additives in the LPS process. In the first step, the LPS-SiC materials were produced in a graphite resistance furnace in the form of discs at different temperatures. The conditions with the best results regarding real density and relative density were taken as reference for sintering in the form of prismatic bars. In the second step, these samples were evaluated regarding fracture toughness (K_IC), by the Single Edge V Notch Beam – SEVNB – method, and flexural strength. K_IC behavior was evaluated according to the depth and curvature radius of the notches. Reliable K_IC values were presented when the ceramic displayed a small curvature radius at the notch tip. When the radius was large, it did not maintain the square root singularity of the notch tip. Tests were carried out to determine K_IC values in atmospheric air and water. K_IC results were lower in water than air, with a decrease ranging between 2.56% and 11.26%. The observations indicated a direct grain size correlation between K_IC values and fracture strength of the SiC ceramics.