ALBERT

Description: The Convective Precipitation Experiment (COPE) was a joint U.K.–U.S. field campaign held during the summer of 2013 in the southwest peninsula of England, designed to study convective clouds that produce heavy rain leading to flash floods. The clouds form along convergence lines that develop regularly as a result of the topography. Major flash floods have occurred in the past, most famously at Boscastle in 2004. It has been suggested that much of the rain was produced by warm rain processes, similar to some flash floods that have occurred in the United States. The overarching goal of COPE is to improve quantitative convective precipitation forecasting by understanding the interactions of the cloud microphysics and dynamics and thereby to improve numerical weather prediction (NWP) model skill for forecasts of flash floods. Two research aircraft, the University of Wyoming King Air and the U.K. BAe 146, obtained detailed in situ and remote sensing measurements in, around, and below storms on several days. A new fast-scanning X-band dual-polarization Doppler radar made 360° volume scans over 10 elevation angles approximately every 5 min and was augmented by two Met Office C-band radars and the Chilbolton S-band radar. Detailed aerosol measurements were made on the aircraft and on the ground. This paper i) provides an overview of the COPE field campaign and the resulting dataset, ii) presents examples of heavy convective rainfall in clouds containing ice and also in relatively shallow clouds through the warm rain process alone, and iii) explains how COPE data will be used to improve high-resolution NWP models for operational use.

Description: We present a range of airborne in situ observations of biomass burning carbonaceous aerosol over tropical South America, including a case study of a large tropical forest wildfire and a series of regional survey flights across the Brazilian Amazon and Cerrado. The study forms part of the South American Biomass Burning Analysis (SAMBBA) project, which was conducted during September and October 2012. We find limited evidence for net increases in aerosol mass through atmospheric ageing combined with substantial changes in the chemical properties of organic aerosol (OA). Oxidation of the OA increases significantly and rapidly on the scale of 2.5–3 h based on our case study analysis and is consistent with secondary organic aerosol production. The observations of limited net enhancement in OA coupled with such changes in chemical composition imply that evaporation of OA is also occurring to balance these changes. We observe significant coatings on black carbon particles at source, but with limited changes with ageing in both particle core size and coating thickness. We quantify variability in the ratio of OA to carbon monoxide across our study as a key parameter representing both initial fire conditions and an indicator of net aerosol production with atmospheric ageing. We observe ratios of 0.075–0.13 µgsm-3ppbv-1 in the west of our study region over the Amazon tropical forest in air masses less influenced by precipitation and a value of 0.095 µgsm-3ppbv-1 over the Cerrado environment in the east (where sm−3 refers to standard metre cubed). Such values are consistent with emission factors used by numerical models to represent biomass burning OA emissions. Black carbon particle core sizes typically range from mean mass diameters of 250 to 290 nm, while coating thicknesses range from 40 to 110 nm in air masses less influenced by precipitation. The primary driver of the variability we observe appears to be related to changes at the initial fire source. A key lesson from our study is that simply aggregating our observations as a function of atmospheric ageing would have been misleading due to the complex nature of the regional aerosol and its drivers, due to the many conflating and competing factors that are present. Our study explores and quantifies key uncertainties in the evolution of biomass burning aerosol at both near-field and regional scales. Our results suggest that the initial conditions of the fire are the primary driver of carbonaceous aerosol physical and chemical properties over tropical South America, aside from significant oxidation of OA during atmospheric ageing. Such findings imply that uncertainties in the magnitude of the aerosol burden and its impact on weather, climate, health and natural ecosystems most likely lie in quantifying emission sources, alongside atmospheric dispersion, transport and removal rather than chemical enhancements in mass.

Description: Over the Indian region, aerosol absorption is considered to have a potential impact on the regional climate, monsoon and hydrological cycle. Black carbon (BC) is the dominant absorbing aerosol, whose absorption potential is determined mainly by its microphysical properties, including its concentration, size and mixing state with other aerosol components. The Indo-Gangetic Plain (IGP) is one of the regional aerosol hot spots with diverse sources, both natural and anthropogenic, but still the information on the mixing state of the IGP aerosols, especially BC, is limited and a significant source of uncertainty in understanding their climatic implications. In this context, we present the results from intensive measurements of refractory BC (rBC) carried out over Bhubaneswar, an urban site in the eastern coast of India, which experiences contrasting air masses (the IGP outflow or coastal/marine air masses) in different seasons. This study helps to elucidate the microphysical characteristics of BC over this region and delineates the IGP outflow from the other air masses. The observations were carried out as part of South West Asian Aerosol Monsoon Interactions (SWAAMI) collaborative field experiment during July 2016–May 2017, using a single-particle soot photometer (SP2) that uses a laser-induced incandescence technique to measure the mass and mixing state of individual BC particles and an aerosol chemical speciation monitor (ACSM) to infer the possible coating material. Results highlighted the distinctiveness in aerosol microphysical properties in the IGP air masses. BC mass concentration was highest during winter (December–February) (∼1.94±1.58 µg m−3), when the prevailing air masses were mostly of IGP origin, followed by post-monsoon (October–November) (mean ∼1.34±1.40 µg m−3). The mass median diameter (MMD) of the BC mass size distributions was in the range 0.190–0.195 µm, suggesting mixed sources of BC, and, further, higher values (∼ 1.3–1.8) of bulk relative coating thickness (RCT) (ratio of optical and core diameters) were seen, indicating a significant fraction of highly coated BC aerosols in the IGP outflow. During the pre-monsoon (March–May), when marine/coastal air masses prevailed, BC mass concentration was lowest (∼0.82±0.84 µg m−3), and larger BC cores (MMD 〉 0.210 µm) were seen, suggesting distinct source processes, while RCT was ∼ 1.2–1.3, which may translate into higher extent of absolute coating on BC cores, which may have crucial regional climate implications. During the summer monsoon (July–September), BC size distributions were dominated by smaller cores (MMD ≤ 0.185 µm), with the lowest coating indicating fresher BC, likely from fossil fuel sources. A clear diurnal variation pattern of BC and RCT was noticed in all the seasons, and daytime peak in RCT suggested enhanced coating on BC due to the condensable coating material originating from photochemistry. Examination of submicrometre aerosol chemical composition highlighted that the IGP outflow was dominated by organics (47 %–49 %), and marine/coastal air masses contained higher amounts of sulfate (41 %–47 %), while ammonium and nitrate were seen in minor amounts, with significant concentrations only during the IGP air mass periods. The diurnal pattern of sulfate resembled that of the RCT of rBC particles, whereas organic mass showed a pattern similar to that of the rBC mass concentration. Seasonally, the coating on BC showed a negative association with the mass concentration of sulfate during the pre-monsoon season and with organics during the post-monsoon season. These are the first experimental data on the mixing state of BC from a long time series over the Indian region and include new information on black carbon in the IGP outflow region. These data help in improving the understanding of regional BC microphysical characteristics and their climate implications.

Description: The optical properties of black carbon (BC) are a major source of uncertainty in regional and global climate studies. In the past, detailed investigation of BC absorption has been hampered by systematic biases in the measurement instrumentation. We present airborne measurements of aerosol absorption and black carbon microphysical properties in highly aged biomass burning plumes measured 4–8 d from their source over the southeast Atlantic Ocean during CLARIFY-2017, using a suite of novel photoacoustic spectrometers to measure aerosol absorption at 405, 514, and 655 nm and a single-particle soot photometer to measure the BC mass concentration, size, and mixing state. These measurements are of sufficient quality and detail to provide constraint on optical schemes used in climate models for the first time in biomass burning plumes far from their source – an aerosol environment that is one of the most important climatically. The average absorption Ångström exponents (AAE) were 1.38 over the wavelength range from 405 to 514 nm and 0.88 over the range from 514 to 655 nm, suggesting that brown carbon (BrC) contributed to 11±2 % of absorption at 405 nm. The effective organic aerosol (OA) mass absorption coefficient (MAC) was 0.31±0.09 m2 g−1 at 405 nm. The BC particles were universally thickly coated, and almost no externally mixed BC particles were detected. The average MAC of BC was 20±4, 15±3, and 12±2 m2g−1 at wavelengths of 405, 514, and 655 nm respectively, with equivalent absorption enhancements of around 1.85±0.45 at all three wavelengths, suggesting that the thick coatings acted as a lens that enhanced light absorption by the BC. We compared the measured MAC and AAE values with those calculated using several optical models and absorption parameterisations that took the measured BC mass and mixing state as inputs. Homogeneous grey-sphere Mie models were only able to replicate MAC for some low (real and imaginary) values of the complex BC refractive index (mBC) at the shortest wavelength, but they would have to use unrealistically low values of mBC to accurately replicate the AAE. A core–shell Mie model was able to generate good agreement for MAC in the green–red end of the visible spectrum for most values of mBC. However, there are no possible values of mBC that produce MAC values that agree with our observations at all three wavelengths, due to a wavelength-dependent underestimation of the MAC of the underlying BC core. Four semiempirical parameterisations from the literature were also tested, linking the BC mixing state to either the MAC or absorption enhancement. Two of these schemes produced results that agreed within a few percent with the measured MAC at all three wavelengths, and the AAE agreed well when discounting the effects of BrC. Our results uniquely demonstrate the validity of absorption parameterisations, as well as the failings of Mie calculations, in this highly aged environment. We recommend that future work should conduct similar analyses in environments where BC has different properties; future studies should also investigate the impact of implementing these types of schemes within climate models as well as the impact of developing equivalent schemes for light scattering by soot particles at visible wavelengths.

Description: ADCT-301, currently in Phase I clinical trial, is an ADC composed of a recombinant human IgG1, HuMax®-TAC against human IL-2R-α (CD25) conjugated through a cleavable linker to a PBD dimer warhead with a drug-antibody ratio of 2.3. In vitro and ex vivo, ADCT-301 binds human CD25 with picomolar affinity. ADCT-301 has highly potent and targeted cytotoxicity against a panel of human lymphoma cell lines. On release, PBD dimers bind in the DNA minor groove and exert their cytotoxic action via the formation of DNA interstrand cross-links. In vivo, ADCT-301 demonstrates dose-dependent antitumor activity against subcutaneous and disseminated lymphoma models. For example, in the Karpas 299 xenograft model, 10/10 tumor-free survivors are observed following a single dose of 0.5 mg/kg, whereas Adcetris® gives only a modest delay in mean tumor growth at 0.5 mg/kg, despite this tumor expressing three-fold higher target antigen levels for this drug. The current study aimed to further define the mechanism of action of ADCT-301 and validate pharmacodynamic assays for clinical development. In Karpas 299 cells, evidence for internalization of ADCT-301 was shown by a reduction of CD25 molecules on the cell surface over the first three hours post-treatment followed by a return to pre-treatment levels by 16 hours. This is consistent with the documented rapid recycling of CD25 to the membrane after exposure to IL-2 (Hemar et al Journal of Cell Biology 1995). Furthermore, ADCT-301 on the cell surface declined by 〉70% over four hours. Following a two-hour exposure to ADCT-301, DNA interstrand cross-linking, measured using a modification of the single cell gel electrophoresis (comet) assay, reached a peak between 4 and 8 hours after which cross-links persisted up to 36 hours. In contrast, the peak of cross-link formation for an equimolar concentration of warhead was immediately following drug exposure and a non-targeted PBD-containing ADC did not produce crosslinks in these cells. A strong correlation (r = 0.97) between loss of viability and DNA cross-link formation provides support for this DNA damage being the critical initiating mechanism of cytotoxicity of ADCT-301. We have previously shown that PBD-induced DNA interstrand cross-links elicit a robust, but delayed γ-H2AX response (Wu et al Clinical Cancer Research 2013). In Karpas 299 cells phosphorylation of H2AX was observed 24 hours after a two-hour exposure to sub-GI50 concentrations of ADCT-301. In these cells continuous exposure to ADCT-301 resulted in a dose-dependent G2/M arrest, peaking at 48 hours, later than for the naked warhead. The peak of the early apoptosis marker annexin-V on the cell surface of Karpas 299 cells was observed between 60 and 72 hours and maximal loss of viability was at 96 hours. Significant bystander killing of CD25-negative human Burkitt's lymphoma-derived Ramos cells was demonstrated for ADCT-301 both by co-culture experiments with CD25-positive Karpas 299 cells, and by media transfer from Karpas 299 cells treated with ADCT-301. This is important as many lymphomas are heterogeneous in their CD25 expression profile (Strauchen et al American Journal of Pathology 1987). In SCID mice with Karpas 299 subcutaneous tumors a single dose of ADCT-301 was administered at 0.2 or 0.6 mg/kg. 24 hours after treatment, excised tumors showed a dose proportional increase in intensity of membrane and cytoplasmic staining by an anti-PBD payload antibody. Cross-linking was determined as 23% (0.2 mg/kg) vs 49% (0.6 mg/kg) (p ≤ 0.01) reduction in Tail Moment using the comet assay and dose-dependent γ-H2AX formation measured by immunohistochemistry was observed. No cross-linking was observed in matched lymphocyte samples. These data confirm the mechanism of cell killing of ADCT-301 and provide relevant pharmacodynamic assays for use in the clinical development of PBD-based ADCs. Disclosures Flynn: Spirogen/Medimmune: Employment. van Berkel:ADC Therapeutics: Employment, Equity Ownership, Patents & Royalties. Zammarchi:ADC Therapeutics: Employment. Tyrer:Spirogen/Medimmune: Employment. Williams:Spirogen/Medimmune: Employment. Howard:ADCT Spirogen/Medimmune: Employment, Equity Ownership, Patents & Royalties. Hartley:ADCT Spirogen/Medimmune: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees.