Dynamic changes during the treatment of pancreatic cancer

This manuscript follows a single patient with pancreatic adenocarcinoma for a five year period, detailing the clinical record, pathology, the dynamic evolution of molecular and cellular alterations as well as the responses to treatments with chemotherapies, targeted therapies and immunotherapies. DNA and RNA samples from biopsies and blood identified a dynamic set of changes in allelic imbalances and copy number variations in response to therapies. Organoid cultures established from biopsies over time were employed for extensive drug testing to determine if this approach was feasible for treatments. When an unusual drug response was detected, an extensive RNA sequencing analysis was employed to establish novel mechanisms of action of this drug. Organoid cell cultures were employed to identify possible antigens associated with the tumor and the patient\u27s T-cells were expanded against one of these antigens. Similar and identical T-cell receptor sequences were observed in the initial biopsy and the expanded T-cell population. Immunotherapy treatment failed to shrink the tumor, which had undergone an epithelial to mesenchymal transition prior to therapy. A warm autopsy of the metastatic lung tumor permitted an extensive analysis of tumor heterogeneity over five years of treatment and surgery. This detailed analysis of the clinical descriptions, imaging, pathology, molecular and cellular evolution of the tumors, treatments, and responses to chemotherapy, targeted therapies, and immunotherapies, as well as attempts at the development of personalized medical treatments for a single patient should provide a valuable guide to future directions in cancer treatment

Basalt-CO2-brine wettability at storage conditions in basaltic formations

© 2020 Elsevier Ltd CO2 geo-storage in basaltic formations has recently been demonstrated as a viable solution to rapidly sequester and mineralize CO2. In case CO2 is injected into such basalt reservoirs in supercritical form, a two-phase system (reservoir brine and supercritical CO2) is created, and it is of key importance to specify the associated CO2-basalt wettability so that fluid distributions and CO2 flow through the reservoir can be predicted. However, there is a serious lack of data for basalt CO2-wettability. We therefore measured water contact angles on basalt substrates in CO2 atmosphere. The results indicate that at shallow depth (below 500 m) basalt is strongly water-wet. With increasing depth the basalt becomes less hydrophilic, and turns intermediate-wet at a depth of 900 m. We conclude that basalt is more CO2-wet than chemically clean minerals (quartz, calcite), especially at depths below 900 m. However, the basalt had a CO2-wettability similar to some caprock samples and a gas-reservoir sandstone. The data presented in this paper will thus aid in the prediction and optimization of CO2 geo-storage in basalt formations

Radiative absorption enhancements by black carbon controlled by particle-to-particle heterogeneity in composition.

Black carbon (BC) absorbs solar radiation, leading to a strong but uncertain warming effect on climate. A key challenge in modeling and quantifying BC's radiative effect on climate is predicting enhancements in light absorption that result from internal mixing between BC and other aerosol components. Modeling and laboratory studies show that BC, when mixed with other aerosol components, absorbs more strongly than pure, uncoated BC; however, some ambient observations suggest more variable and weaker absorption enhancement. We show that the lower-than-expected enhancements in ambient measurements result from a combination of two factors. First, the often used spherical, concentric core-shell approximation generally overestimates the absorption by BC. Second, and more importantly, inadequate consideration of heterogeneity in particle-to-particle composition engenders substantial overestimation in absorption by the total particle population, with greater heterogeneity associated with larger model-measurement differences. We show that accounting for these two effects-variability in per-particle composition and deviations from the core-shell approximation-reconciles absorption enhancement predictions with laboratory and field observations and resolves the apparent discrepancy. Furthermore, our consistent model framework provides a path forward for improving predictions of BC's radiative effect on climate

Effect of thermodenuding on the structure of nascent flame soot aggregates

The optical properties (absorption and scattering) of soot particles depend on soot size and index of refraction, but also on the soot complex morphology and the internal mixing with materials that can condense on a freshly emitted (nascent) soot particle and coat it. This coating can affect the soot optical properties by refracting light, or by changing the soot aggregate structure. A common approach to studying the effect of coating on soot optical properties is to measure the absorption and scattering coefficients in ambient air, and then measure them again after removing the coating using a thermodenuder. In this approach, it is assumed that: (1) most of the coating material is removed; (2) charred organic coating does not add to the refractory carbon; (3) oxidation of soot is negligible; and, (4) the structure of the pre-existing soot core is left unaltered, despite the potential oxidation of the core at elevated temperatures. In this study, we investigated the validity of the last assumption, by studying the effect of thermodenuding on the morphology of nascent soot. To this end, we analyzed the morphological properties of laboratory generated nascent soot, before and after thermodenuding. Our investigation shows that there is only minor restructuring of nascent soot by thermodenuding

Measurement and modeling of the multiwavelength optical properties of uncoated flame-generated soot

Optical properties of flame-generated black carbon (BC) containing soot particles were quantified at multiple wavelengths for particles produced using two different flames: a methane diffusion flame and an ethylene premixed flame. Measurements were made for (i) nascent soot particles, (ii) thermally denuded nascent particles, and (iii) particles that were coated and then thermally denuded, leading to the collapse of the initially lacy, fractal-like morphology. The measured mass absorption coefficients (MACs) depended on soot maturity and generation but were similar between flames for similar conditions. For mature soot, here corresponding to particles with volume-equivalent diameters \u3e∼160 nm, the MAC and absorption Ångström exponent (AAE) values were independent of particle collapse while the single-scatter albedo increased. The MAC values for these larger particles were also size-independent. The mean MAC value at 532 nm for larger particles was 9.1±1.1 m2 g−1, about 17 % higher than that recommended by Bond and Bergstrom (2006), and the AAE was close to unity. Effective, theory-specific complex refractive index (RI) values are derived from the observations with two widely used methods: Lorenz–Mie theory and the Rayleigh–Debye–Gans (RDG) approximation. Mie theory systematically underpredicts the observed absorption cross sections at all wavelengths for larger particles (with x\u3e0.9) independent of the complex RI used, while RDG provides good agreement. (The dimensionless size parameter x=πdp/λ, where dp is particle diameter and λ is wavelength.) Importantly, this implies that the use of Mie theory within air quality and climate models, as is common, likely leads to underpredictions in the absorption by BC, with the extent of underprediction depending on the assumed BC size distribution and complex RI used. We suggest that it is more appropriate to assume a constant, size-independent (but wavelength-specific) MAC to represent absorption by uncoated BC particles within models

P2X receptors: epithelial ion channels and regulators of salt and water transport.

When the results from electrophysiological studies of renal epithelial cells are combined with data from in vivo tubule microperfusion experiments and immunohistochemical surveys of the nephron, the accumulated evidence suggests that ATP-gated ion channels, P2X receptors, play a specialized role in the regulation of ion and water movement across the renal tubule and are integral to electrolyte and fluid homeostasis. In this short review, we discuss the concept of P2X receptors as regulators of salt and water salvage pathways, as well as acknowledging their accepted role as ATP-gated ion channels

Isotopic signature in isolated south-western populations of European brown bear (Ursus arctos)

Stable isotope analysis of animal tissue samples is increasingly used to study the trophic ecology of target species. The isotopic signatures respond to the type of diet, but also to the environmental conditions of their habitat. In the case of omnivorous, seasonal or opportunistic feeding species, the interpretation of isotopic values is more complex, as it is largely determined by food selection, either due to individual choice or because of availability. We analysed C and N isotopes in brown bear (Ursus arctos) hair from four isolated populations of south-western Europe (Cantabrian, Pyrenees, Central Apennines and Alpine) accounting for the geographical and climatic differences among the four areas. We found inter-population differences in isotopic signatures that cannot be attributed to climatic differences alone, indicating that at least some bears from relatively higher altitude populations experiencing higher precipitation (Pyrenees) show a greater consumption of animal foods than those from lower altitudes (Cantabrian and Apennines). The quantification of isotopic niche space using Layman's metrics identified significant similarities between the Cantabrian and Central Apennine samples that markedly differ from the Pyrenean and Alpine. Our study provides a baseline to allow further comparisons in isotopic niche spaces in a broad ranged omnivorous mammal, whose European distribution requires further conservation attention especially for southern isolated populations

Diurnal and Seasonal Mapping of Martian Ices With EMIRS

Condensation and sublimation of ices at the surface of the planet is a key part of both the Martian H$_2$O and CO$_2$ cycles, either from a seasonal or diurnal aspect. While most of the ice is located within the polar caps, surface frost is known to be formed during nighttime down to equatorial latitudes. Here, we use data from the Emirates Mars Infrared Spectrometer (EMIRS) onboard the Emirates Mars Mission (EMM) to monitor the diurnal and seasonal evolution of the ices at the surface of Mars over almost one Martian year. The unique local time coverage provided by the instrument allows us to observe the apparition of equatorial CO$_2$ frost in the second half of the Martian night around the equinoxes, to its sublimation at sunrise