Adoptive Cell Therapy for Patients with Melanoma

Adoptive cell therapy can be an effective treatment for some patients with advanced cancer. This report summarizes clinical trial results from the Surgery Branch, NCI, investigating tumor infiltrating lymphocytes (TIL) and gene engineered peripheral blood T cells for the therapy of patients with melanoma and other solid tumors

Aircraft Emissions, Their Plume-Scale Effects, and the Spatio-Temporal Sensitivity of the Atmospheric Response:A Review

Non-CO2 aircraft emissions are responsible for the majority of aviation’s climate impact, however their precise effect is largely dependent on the environmental conditions of the ambient air in which they are released. Investigating the principal causes of this spatio-temporal sensitivity can bolster understanding of aviation-induced climate change, as well as offer potential mitigation solutions that can be implemented in the interim to low carbon flight regimes. This review paper covers the generation of emissions and their characteristic dispersion, air traffic distribution, local and global climate impact, and operational mitigation solutions, all aimed at improving scientific awareness of aviation’s non-CO2 climate impact

The Emissions of Water Vapour and NOx from Modelled Hydrogen-Fuelled Aircraft and the Impact of NOx Reduction on Climate Compared with Kerosene-Fuelled Aircraft

A kerosene fuelled aircraft was modelled within a performance tool and fuel burn and the emissions of nitrogen oxides (NOx) and water vapour at different stages of flight throughout the mission were estimated. Adaptions were made to engine and aircraft parameters within the performance tool to accommodate a liquid hydrogen fuel over the same given mission. Once an iterative design process had been completed to ensure the aircraft could perform the given mission, the performance tool was again used to calculate total fuel burn. Fuel burn results alongside predicted emission indices were used to estimate the emissions of NOx, water vapour from hydrogen-fuelled aircraft. The use of hydrogen fuel over kerosene fuel in the modelled aircraft resulted in the removal of carbon-based emission species alongside 86% reduction in NOx and 4.3 times increase in water vapour emission. The climate impact of this switch with the reduction in NOx emission was assessed by a 3D global atmospheric chemistry and transport model, STOCHEM-CRI, which found a significant reduction in the concentration of a potent greenhouse gas, ozone, and an oxidizing agent, OH, by up to 6% and 25%, respectively. The reduction of OH levels could induce a positive radiative forcing effect as the lifetime of another important greenhouse gas, methane, is increased. However, the magnitude of this increase is very small (~0.3%), thus the overall impact of the reduction in NOx emissions is likely to have a net negative radiative forcing effect, improving aviation’s impact on the environment. However, further work is warranted on effects of other emission species, specifically water vapour, particulate matter and unburned hydrogen

Abundance of NO3 derived organo-nitrates and their importance in the atmosphere

The chemistry of the nitrate radical and its contribution to organo-nitrate formation in the troposphere has been investigated using a mesoscale 3-D chemistry and transport model, WRF-Chem-CRI. The model-measurement comparisons of NO2, ozone and night-time N2O5 mixing ratios show good agreement supporting the model’s ability to represent nitrate (NO3) chemistry reasonably. Thirty-nine organo-nitrates in the model are formed exclusively either from the reaction of RO2 with NO or by the reaction of NO3 with alkenes. Temporal analysis highlighted a significant contribution of NO3-derived organo-nitrates, even during daylight hours. Night-time NO3-derived organo-nitrates were found to be 3-fold higher than that in the daytime. The reactivity of daytime NO3 could be more competitive than previously thought, with losses due to reaction with VOCs (and subsequent organo-nitrate formation) likely to be just as important as photolysis. This has highlighted the significance of NO3 in daytime organo-nitrate formation, with potential implications for air quality, climate and human health. Estimated atmospheric lifetimes of organo-nitrates showed that the organo-nitrates act as NOx reservoirs, with particularly short-lived species impacting on air quality as contributors to downwind ozone formation

Comparing plasma and faecal measures of steroid hormones in Adelie penguins Pygoscelis adeliae

Physiological measurements of both stress and sex hormones are often used to estimate the consequences of natural or human-induced change in ecological studies of various animals. Different methods of hormone measurement exist, potentially explaining variation in results across studies; methods should be cross-validated to ensure that they correlate. We directly compared faecal and plasma hormone measurements for the first time in a wild free-living species, the Adelie penguin (Pygoscelis adeliae). Blood and faecal samples were simultaneously collected from individual penguins for comparison and assayed for testosterone and corticosterone (or their metabolites). Sex differences and variability within each measure, and correlation of values across measures were compared. For both hormones, plasma samples showed greater variation than faecal samples. Males had higher mean corticosterone concentrations than females, but the difference was only statistically significant in faecal samples. Plasma testosterone, but not faecal testosterone, was significantly higher in males than females. Correlation between sample types was poor overall, and weaker in females than in males, perhaps because measures from plasma represent hormones that are both free and bound to globulins, whereas measures from faeces represent only the free portion. Faecal samples also represent a cumulative measure of hormones over time, as opposed to a plasma ‘snapshot’ concentration. Our data indicate that faecal sampling appears more suitable for assessing baseline hormone concentrations, whilst plasma sampling may best define immediate responses to environmental events. Consequently, future studies should ensure that they select the most appropriate matrix and method of hormone measurement to answer their research questions

New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer

A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL), are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs), chimeric antibody-T cell receptors (CARs) and cytokines. T cell subsets with more naïve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies

Investigations into the effectiveness of deuterium as a "protecting group" for C-H bonds in radical reactions involving hydrogen atom transfer.

addresses: School of Biosciences (originally Department of Chemistry), University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter, EX4 4QD, UK. [email protected]: Journal Article; Research Support, Non-U.S. Gov'tCopyright © 2008 Royal Society of ChemistryCompetition experiments have been carried out to determine the extent to which deuterium can be used as a protecting group for carbon-hydrogen bonds in radical-based intramolecular hydrogen atom transfer processes