Power-Law Scaling in the Internal Variability of Cumulus Cloud Size Distributions due to Subsampling and Spatial Organization

In this study, the spatial structure of cumulus cloud populations is investigated using three-dimensional snapshots from large-domain LES experiments. The aim is to understand and quantify the internal variability in cloud size distributions due to subsampling effects and spatial organization. A set of idealized shallow cumulus cases is selected with varying degrees of spatial organization, including a slowly organizing marine precipitating case and five more quickly organizing diurnal cases over land. A subdomain analysis is applied, yielding cloud number distributions at sample sizes ranging from severely undersampled to nearly complete. A strong power-law scaling is found in the relation between cloud number variability and subdomain size, reflecting an inverse linear relation. Scaling subdomain size by cloud size yields a data collapse across time points and cases, highlighting the role played by cloud spacing in controlling the stochastic variability. Spatial organization acts on top of this baseline model by increasing the maximum cloud size and by enhancing the variability in the number of smallest clouds. This reflects that the smaller clouds start to live on top of larger-scale thermodynamic structures, such as cold pools, which favor or inhibit their formation. Compositing all continental cumulus cases suggests the existence of a prototype diurnal time dependence in the spatial organization. A simple stochastic expression for cloud number variability is proposed that is formulated in terms of two dimensionless groups, which allows objective estimation of the degree of spatial organization in simulated and observed cumulus cloud populations

Improving Breast Cancer Treatment Specificity Using Aptamers Obtained by 3D Cell-SELEX

Three-dimensional spheroids of non-malignant MCF10A and malignant SKBR3 breast cells were used for subsequent 3D Cell-SELEX to generate aptamers for specific binding and treatment of breast cancer cells. Using 3D Cell-SELEX combined with Next-Generation Sequencing and bioinformatics, ten abundant aptamer families with specific structures were identified that selectively bind to SKBR3, and not to MCF10A cells. Multivalent aptamer polymers were synthesized by co-polymerization and analyzed for binding performance as well as therapeutic efficacy. Binding performance was determined by confocal fluorescence imaging and revealed specific binding and efficient internalization of aptamer polymers into SKBR3 spheroids. For therapeutic purposes, DNA sequences that intercalate the cytotoxic drug doxorubicin were co-polymerized into the aptamer polymers. Viability tests show that the drug-loaded polymers are specific and effective in killing SKBR3 breast cancer cells. Thus, the 3D-selected aptamers enhanced the specificity of doxorubicin against malignant over non-malignant breast cells. The innovative modular DNA aptamer platform based on 3D Cell SELEX and polymer multivalency holds great promise for diagnostics and treatment of breast cancer

CGILS Phase 2 LES Intercomparison of Response of Subtropical Marine Low Cloud Regimes to CO2\u3c/sub\u3e Quadrupling and a CMIP3 Composite Forcing Change

© 2016. The Authors. Phase 1 of the CGILS large-eddy simulation (LES) intercomparison is extended to understand if subtropical marine boundary-layer clouds respond to idealized climate perturbations consistently in six LES models. Here the responses to quadrupled carbon dioxide (“fast adjustment”) and to a composite climate perturbation representative of CMIP3 multimodel mean 2×CO2 near-equilibrium conditions are analyzed. As in Phase 1, the LES is run to equilibrium using specified steady summertime forcings representative of three locations in the Northeast Pacific Ocean in shallow well-mixed stratocumulus, decoupled stratocumulus, and shallow cumulus cloud regimes. The results are generally consistent with a single-LES study of Bretherton et al. () on which this intercomparison was based. Both quadrupled CO2 and the composite climate perturbation result in less cloud and a shallower boundary layer for all models in well-mixed stratocumulus and for all but a single LES in decoupled stratocumulus and shallow cumulus, corroborating similar findings from global climate models (GCMs). For both perturbations, the amount of cloud reduction varies across the models, but there is less intermodel scatter than in GCMs. The cloud radiative effect changes are much larger in the stratocumulus-capped regimes than in the shallow cumulus regime, for which precipitation buffering may damp the cloud response. In the decoupled stratocumulus and cumulus regimes, both the CO2 increase and CMIP3 perturbations reduce boundary-layer decoupling, due to the shallowing of inversion height

Marine Low Cloud Sensitivity to An Idealized Climate Change: The CGILS LES Intercomparison

Subtropical marine low cloud sensitivity to an idealized climate change is compared in six large-eddy simulation (LES) models as part of CGILS. July cloud cover is simulated at three locations over the subtropical northeast Pacific Ocean, which are typified by cold sea surface temperatures (SSTs) under well-mixed stratocumulus, cool SSTs under decoupled stratocumulus, and shallow cumulus clouds overlying warmer SSTs. The idealized climate change includes a uniform 2 K SST increase with corresponding moist-adiabatic warming aloft and subsidence changes, but no change in free-tropospheric relative humidity, surface wind speed, or CO2. For each case, realistic advective forcings and boundary conditions are generated for the control and perturbed states which each LES runs for 10 days into a quasi-steady state. For the control climate, the LESs correctly produce the expected cloud type at all three locations. With the perturbed forcings, all models simulate boundary-layer deepening due to reduced subsidence in the warmer climate, with less deepening at the warm-SST location due to regulation by precipitation. The models do not show a consistent response of liquid water path and albedo in the perturbed climate, though the majority predict cloud thickening (negative cloud feedback) at the cold-SST location and slight cloud thinning (positive cloud feedback) at the cool-SST and warm-SST locations. In perturbed climate simulations at the cold-SST location without the subsidence decrease, cloud albedo consistently decreases across the models. Thus, boundary-layer cloud feedback on climate change involves compensating thermodynamic and dynamic effects of warming and may interact with patterns of subsidence change

Marine Low Cloud Sensitivity to An Idealized Climate Change: The CGILS LES Intercomparison

Subtropical marine low cloud sensitivity to an idealized climate change is compared in six large-eddy simulation (LES) models as part of CGILS. July cloud cover is simulated at three locations over the subtropical northeast Pacific Ocean, which are typified by cold sea surface temperatures (SSTs) under well-mixed stratocumulus, cool SSTs under decoupled stratocumulus, and shallow cumulus clouds overlying warmer SSTs. The idealized climate change includes a uniform 2 K SST increase with corresponding moist-adiabatic warming aloft and subsidence changes, but no change in free-tropospheric relative humidity, surface wind speed, or CO2. For each case, realistic advective forcings and boundary conditions are generated for the control and perturbed states which each LES runs for 10 days into a quasi-steady state. For the control climate, the LESs correctly produce the expected cloud type at all three locations. With the perturbed forcings, all models simulate boundary-layer deepening due to reduced subsidence in the warmer climate, with less deepening at the warm-SST location due to regulation by precipitation. The models do not show a consistent response of liquid water path and albedo in the perturbed climate, though the majority predict cloud thickening (negative cloud feedback) at the cold-SST location and slight cloud thinning (positive cloud feedback) at the cool-SST and warm-SST locations. In perturbed climate simulations at the cold-SST location without the subsidence decrease, cloud albedo consistently decreases across the models. Thus, boundary-layer cloud feedback on climate change involves compensating thermodynamic and dynamic effects of warming and may interact with patterns of subsidence change

The Second ARM Training and Science Application Event : Training the Next Generation of Atmospheric Scientists

Non peer reviewe

Phase I and pharmacokinetic study of DE-310 in patients with advanced solid tumors

PURPOSE: To assess the maximum-tolerated dose, toxicity, and pharmacokinetics of DE-310, a macromolecular prodrug of the topoisomerase I inhibitor exatecan (DX-8951f). in patients with advanced solid tumors. EXPERIMENTAL DESIGN: Patients received DE-310 as a 3-hour infusion once every 2 weeks (dose, 1.0-2.0 mg/m(2)) or once every 6 weeks (dose, 6.0-9.0 mg/m(2)). Because pharmacokinetics revealed a drug terminal half-life exceeding the 2 weeks administration interval, the protocol was amended to a 6-week interval between administrations also based on available information from a parallel trial using an every 4 weeks schedule. Conjugated DX-8951 (the carrier-linked molecule), and the metabolites DX-8951 and glycyl-DX-8951 were assayed in various matrices up to 35 days post first and second dose. RESULTS: Twenty-seven patients were enrolled into the study and received a total of 86 administrations. Neutropenia and grade 3 thrombocytopenia, and grade 3 hepatotoxicity with veno-occlusive disease, were dose-limiting toxicities. Other hematologic and nonhematologic toxicities were mild to moderate and reversible. The apparent half-life of conjugated DX-8951, glycyl-DX-8951, and DX-8951 was 13 days. The area under the curve ratio for conjugated DX-8951 to DX-8951 was 600. No drug concentration was detectable in erythrocytes, skin, and saliva, although low levels of glycyl-DX-8951 and DX-8951 were detectable in tumor biopsies. One patient with metastatic adenocarcinoma of unknown primary achieved a histologically proven complete remission. One confirmed partial remission was observed in a patient with metastatic pancreatic cancer and disease stabilization was noted in 14 additional patients. CONCLUSIONS: The recommended phase II dose of DE-310 is 7.5 mg/m(2) given once every 6 weeks. The active moiety DX-8951 is released slowly from DE-310 and over an extended period, achieving the desired prolonged exposure to this topoisomerase I inhibitor

1H and 13C resonance assignments of a guanine sensing riboswitch’s terminator hairpin

Here we report the nearly complete base assignments and partial sugar assignments of the 35-residue terminator hairpin of the Bacillus subtilisxpt-pbuX-mRNA guanine sensing riboswitch