The use of gamma-irradiation and ultraviolet-irradiation in the preparation of human melanoma cells for use in autologous whole-cell vaccines

<p>Abstract</p> <p>Background</p> <p>Human cancer vaccines incorporating autologous tumor cells carry a risk of implantation and subsequent metastasis of viable tumor cells into the patient who is being treated. Despite the fact that the melanoma cell preparations used in a recent vaccine trial (Mel37) were gamma-irradiated (200 Gy), approximately 25% of the preparations failed quality control release criteria which required that the irradiated cells incorporate ³H-thymidine at no more than 5% the level seen in the non-irradiated cells. We have, therefore, investigated ultraviolet (UV)-irradiation as a possible adjunct to, or replacement for gamma-irradiation.</p> <p>Methods</p> <p>Melanoma cells were gamma- and/or UV-irradiated. ³H-thymidine uptake was used to assess proliferation of the treated and untreated cells. Caspase-3 activity and DNA fragmentation were measured as indicators of apoptosis. Immunohistochemistry and Western blot analysis was used to assess antigen expression.</p> <p>Results</p> <p>UV-irradiation, either alone or in combination with gamma-irradiation, proved to be extremely effective in controlling the proliferation of melanoma cells. In contrast to gamma-irradiation, UV-irradiation was also capable of inducing significant levels of apoptosis. UV-irradiation, but not gamma-irradiation, was associated with the loss of tyrosinase expression. Neither form of radiation affected the expression of gp100, MART-1/MelanA, or S100.</p> <p>Conclusion</p> <p>These results indicate that UV-irradiation may increase the safety of autologous melanoma vaccines, although it may do so at the expense of altering the antigenic profile of the irradiated tumor cells.</p

Grand Challenges in global eye health: a global prioritisation process using Delphi method

Background We undertook a Grand Challenges in Global Eye Health prioritisation exercise to identify the key issues that must be addressed to improve eye health in the context of an ageing population, to eliminate persistent inequities in health-care access, and to mitigate widespread resource limitations. Methods Drawing on methods used in previous Grand Challenges studies, we used a multi-step recruitment strategy to assemble a diverse panel of individuals from a range of disciplines relevant to global eye health from all regions globally to participate in a three-round, online, Delphi-like, prioritisation process to nominate and rank challenges in global eye health. Through this process, we developed both global and regional priority lists. Findings Between Sept 1 and Dec 12, 2019, 470 individuals complete round 1 of the process, of whom 336 completed all three rounds (round 2 between Feb 26 and March 18, 2020, and round 3 between April 2 and April 25, 2020) 156 (46%) of 336 were women, 180 (54%) were men. The proportion of participants who worked in each region ranged from 104 (31%) in sub-Saharan Africa to 21 (6%) in central Europe, eastern Europe, and in central Asia. Of 85 unique challenges identified after round 1, 16 challenges were prioritised at the global level; six focused on detection and treatment of conditions (cataract, refractive error, glaucoma, diabetic retinopathy, services for children and screening for early detection), two focused on addressing shortages in human resource capacity, five on other health service and policy factors (including strengthening policies, integration, health information systems, and budget allocation), and three on improving access to care and promoting equity. Interpretation This list of Grand Challenges serves as a starting point for immediate action by funders to guide investment in research and innovation in eye health. It challenges researchers, clinicians, and policy makers to build collaborations to address specific challenge

Untersuchung zur Temperaturverteilung mittels CARS-Thermometrie in einer Modellstaubrennkammer beim Abbrand von Festbrennstoffplatten

Der Verbrennungsprozeß von Festbrennstoffen mit und ohne Borpartikel-Zusatz wurde in einer ebenen Stufenbrennkammer mit optischem Zugang mittels der Kohärenten anti-Stokes Raman Spektroskopie (CARS) untersucht. Die in der Rezirkulationszone hinter der Stufe und die in der brennstoffreichen Zone unmittelbar über der Festbrennstoffplatte ermittelten CARS-Spektren zeigen starke Interferenzen mit dem Swan-Bandensystem von C2-Radikalen. Die in der äußeren Zone der reagierenden Grenzschichtströmung ermittelten Temperaturhistogramme haben teilweise stark ausgeprägte bimodale Temperaturverteilungen. Dies zeigt den intensiven Vermischungsprozeß und das Eindringen kälterer Gase aus der äußeren Strömungsregion in die äußere Zone der reagierenden Grenzschichtströmung durch wirbelförmige Strukturen

Investigation of the Combustion Process of Boron Particle Containing Solid Fuel Slabs in a Rearward Facing Step Combustor

In order to get a better insight in solid fuel ramjet combustion processes the combustion behavior of solid fuel slabs with and without boron particle addition had been investigated in a planar step combustor under ramjet relevant conditions concerning the air inlet temperature. Various intrusive and non-intrusive diagnostic techniques had been used to analyze the highly turbulent multiphase combustion process. Large scale vortical structures can be seen in the outer zone above the diffusion flame in the developing boundary layer behind the recirculation zone with Colour Schlieren as well as with PIV. Distributions of the gas phase temperature, velocities of reacting particles as well as concentrations of stable reaction products have been determined and are presented here, too