The response rate to immune checkpoint inhibitor therapy for non-small-cell lung cancer (NSCLC) is just 20%. To improve this figure, several early phase clinical trials combining novel immunotherapeutics with immune checkpoint blockade have been initiated. Unfortunately, these trials have been designed without a strong foundational knowledge of the immune landscape present in NSCLC. Here, we use a flow cytometry panel capable of measuring 51 immune cell populations to comprehensively identify the immune cell composition and function in NSCLC. The results show that the immune cell composition is fundamentally different in lung adenocarcinoma as compared with lung squamous cell carcinoma, and that neutrophils are the most prevalent immune cell type. Using T-cell receptor-β sequencing and tumour reactivity assays, we predict that tumour reactive T cells are frequently present in NSCLC. These results should help to guide the design of clinical trials and the direction of future research in this area.
Stable isotopes in water have the potential to diagnose changes in the earth's hydrological budget in response to climate change and land use change. However, there have been few measurements in the vapour phase. Here, we present high-frequency measurements of oxygen isotopic compositions of water vapour (dv) and evapotranspiration (dET) above a soybean canopy using the tunable diode laser (TDL) technique for the entire 2006 growing season in Minnesota, USA. We observed a large variability in surface dv from the daily to the seasonal timescales, largely explained by Rayleigh processes, but also influenced by vertical atmospheric mixing, local evapotranspiration (ET) and dew formation. We used dET measurements to calculate the isotopic composition at the sites of evaporative enrichment in leaves (dL,e) and compared that with the commonly used steadystate prediction (dL,s).There was generally a good agreement averaged over the season, but larger differences on individual days. We also found that vertical variability in relative humidity and temperature associated with canopy structure must be addressed in canopy-scale leaf water models. Finally, we explored this data set for direct evidence of the Péclet effect.
[1] Biosphere-atmosphere exchange of water vapor isotopes plays an important role in the global atmospheric 18 O-CO 2 and 18 O-O 2 budgets. In this paper, we report the results of the first continuous measurements of isotope ratios of water vapor and the evapotranspiration flux in a temperate forest over one full growing season. We found that the 18 O/ 16 O isotopic signal of the whole-canopy transpiration (d T ) was not in steady state with respect to plant source water. The departure from steady state was greatest at night and on days of low transpiration rates. Relative humidity was an important driver on timescales shorter than a few hours; on the diurnal timescale, the nonsteady state behavior was driven by relative humidity and the covarying transpiration rate. On average, d T was lowest in midmorning and highest at midnight, with an average peak-to-peak variation on the order of 15% over the growing season. A diurnal variation of 60% or more was observed on some days. On the seasonal timescale, d T was tightly coupled with the precipitation isotope ratio in the early growing season and fluctuated around the isotope ratio of the stem water of overstory trees in the late growing season. The temporal shift suggests that the forest switched its water source from the shallow to the deep soil pool and that the overstory trees dominated the whole stand transpiration in the late growing season. Using isotopic partitioning, we estimated that the overstory trees contributed roughly 70% to the whole-stand transpiration water loss during the growing season.
Structures of the protein-chromophore complex and the apoprotein form of neocarzinostatin were determined at 1.8 angstrom resolution. Neocarzinostatin is composed of a labile chromophore with DNA-cleaving activity and a stabilizing protein. The chromophore displays marked nonlinearity of the triple bonds and is bound noncovalently in a pocket formed by the two protein domains. The chromophore pi-face interacts with the phenyl ring edges of Phe52 and Phe78. The amino sugar and carbonate groups of the chromophore are solvent exposed, whereas the epoxide, acetylene groups, and carbon C-12, the site of nucleophilic thiol addition during chromophore activation, are unexposed. The position of the amino group of the chromophore carbohydrate relative to C-12 supports the idea that the amino group plays a role in thiol activation.
We consider the family f a,b (x, y) = (y, (y + a)/(x + b)) of birational maps of the plane and the parameter values (a, b) for which f a,b gives an automorphism of a rational surface. In particular, we find values for which f a,b is an automorphism of positive entropy but no invariant curve. The Main Theorem: If f a,b is an automorphism with an invariant curve and positive entropy, then either (1) (a, b) is real, and the restriction of f to the real points has maximal entropy, or (2) f a,b has a rotation (Siegel) domain.
[1] The carbon and oxygen isotopes of CO 2 and the oxygen isotopes of H 2 O are powerful tracers for constraining the dynamics of carbon uptake and water flux on land. The role of land biota in the atmospheric budgets of these isotopes has been extensively explored through the lens of leaf-scale observations. At the ecosystem scale, kinetic fractionation is associated with molecular and turbulent diffusion. Intuitively, air turbulence, being nondiscriminative in diffusing materials, should act to erase the kinetic effect. Using the first canopy-scale isotopic flux measurements, we show just the opposite: that in the terrestrial environment, air turbulence enhances the effect, rather than suppressing it. The sensitivity of kinetic fractionation to turbulence is striking in situations where the canopy resistance is comparable to or lower than the aerodynamic resistance. Accounting for turbulent diffusion greatly improves land surface model predictions of the isoforcing of 18 O-CO 2 and transpiration enrichment of leaf water in 18 O-H 2 O in field conditions. Our results suggest that variations in surface roughness across the landscape can contribute to spatial variations in the composition of atmospheric 18 O-CO 2 and that temporal trends in wind circulation on land can play a role in the interannual variability of atmospheric 18 O-CO 2 . In comparison, air turbulence has a limited effect on the isoforcing of 13
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