The National Aeronautics and Space Administration's Clouds and the Earth's Radiant Energy System (CERES) Project was designed to improve our understanding of the relationship between clouds and solar ...and longwave radiation. This is achieved using satellite broad-band instruments to map the top-of-atmosphere radiation fields with coincident data from satellite narrow-band imagers employed to retrieve the properties of clouds associated with those fields. This paper documents the CERES Edition-2 cloud property retrieval system used to analyze data from the Tropical Rainfall Measuring Mission Visible and Infrared Scanner and by the MODerate-resolution Imaging Spectrometer instruments on board the Terra and Aqua satellites covering the period 1998 through 2007. Two daytime retrieval methods are explained: the Visible Infrared Shortwave-infrared Split-window Technique for snow-free surfaces and the Shortwave-infrared Infrared Near-infrared Technique for snow or ice-covered surfaces. The Shortwave-infrared Infrared Split-window Technique is used for all surfaces at night. These methods, along with the ancillary data and empirical parameterizations of cloud thickness, are used to derive cloud boundaries, phase, optical depth, effective particle size, and condensed/frozen water path at both pixel and CERES footprint levels. Additional information is presented, detailing the potential effects of satellite calibration differences, highlighting methods to compensate for spectral differences and correct for atmospheric absorption and emissivity, and discussing known errors in the code. Because a consistent set of algorithms, auxiliary input, and calibrations across platforms are used, instrument and algorithm-induced changes in the data record are minimized. This facilitates the use of the CERES data products for studying climate-scale trends.
The Edition 2 (Ed2) cloud property retrieval algorithm system was upgraded and applied to the MODerate-resolution Imaging Spectroradiometer (MODIS) data for the Clouds and the Earth's Radiant Energy ...System (CERES) Edition 4 (Ed4) products. New calibrations for solar channels and the use of the 1.24-<inline-formula> <tex-math notation="LaTeX">\mu \text{m} </tex-math></inline-formula> channel for cloud optical depth (COD) over snow improve the daytime consistency between Terra and Aqua MODIS retrievals. Use of additional spectral channels and revised logic enhanced the cloud-top phase retrieval accuracy. A new ice crystal reflectance model and a CO 2 -channel algorithm retrieved higher ice clouds, while a new regional lapse rate technique produced more accurate water cloud heights than in Ed2. Ice cloud base heights are more accurate due to a new cloud thickness parameterization. Overall, CODs increased, especially over the polar (PO) regions. The mean particle sizes increased slightly for water clouds, but more so for ice clouds in the PO areas. New experimental parameters introduced in Ed4 are limited in utility, but will be revised for the next CERES edition. As part of the Ed4 retrieval evaluation, the average properties are compared with those from other algorithms and the differences between individual reference data and matched Ed4 retrievals are explored. Part II of this article provides a comprehensive, objective evaluation of selected parameters. More accurate interpretation of the CERES radiation measurements has resulted from the use of the Ed4 cloud properties.
Particulate respirators such as N95s are an essential component of personal protective equipment (PPE) for front-line workers. This study describes a rapid and effective UVC irradiation system that ...would facilitate the safe re-use of N95 respirators and provides supporting information for deploying UVC for decontamination of SARS-CoV-2 during the COVID-19 pandemic. To assess the inactivation potential of the proposed UVC germicidal device as a function of time by using 3 M 8211-N95 particulate respirators inoculated with SARS-CoV-2. A germicidal UVC device to deliver tailored UVC dose was developed and test coupons (2.5 cm
) of the 3 M-N95 respirator were inoculated with 10
plaque-forming units (PFU) of SARS-CoV-2 and were UV irradiated. Different exposure times were tested (0-164 s) by fixing the distance between the lamp and the test coupon to 15.2 cm while providing an exposure of at least 5.43 mWcm
. Primary measure of outcome was titration of infectious virus recovered from virus-inoculated respirator test coupons after UVC exposure. Other measures included the method validation of the irradiation protocol, using lentiviruses (biosafety level-2 agent) and establishment of the germicidal UVC exposure protocol. An average of 4.38 × 10
PFU ml
(SD 772.68) was recovered from untreated test coupons while 4.44 × 10
PFU ml
(SD 203.67), 4.00 × 10
PFU ml
(SD 115.47), 1.56 × 10
PFU ml
(SD 76.98) and 4.44 × 10
PFU ml
(SD 76.98) was recovered in exposures 2, 6, 18 and 54 s per side respectively. The germicidal device output and positioning was monitored and a minimum output of 5.43 mW cm
was maintained. Infectious SARS-CoV-2 was not detected by plaque assays (minimal level of detection is 67 PFU ml
) on N95 respirator test coupons when irradiated for 120 s per side or longer suggesting 3.5 log reduction in 240 s of irradiation, 1.3 J cm
. A scalable germicidal UVC device to deliver tailored UVC dose for rapid decontamination of SARS-CoV-2 was developed. UVC germicidal irradiation of N95 test coupons inoculated with SARS-CoV-2 for 120 s per side resulted in 3.5 log reduction of virus. These data support the reuse of N95 particle-filtrate apparatus upon irradiation with UVC and supports use of UVC-based decontamination of SARS-CoV-2 during the COVID-19 pandemic.
The interpretation of satellite-observed radiances to derive cloud optical depth and effective particle size requires radiative transfer calculations relating these parameters to the reflectance, ...transmittance, and emittance of the cloud.
Current satellite cloud retrievals are usually based on the assumption that all clouds consist of a homogenous single layer despite the frequent occurrence of cloud overlap. As such, cloud overlap ...will cause large errors in the retrievals of many cloud properties. To address this problem, a multilayered cloud retrieval system (MCRS) is developed by combining satellite visible and infrared radiances and surface microwave radiometer measurements. A two‐layer cloud model was used to simulate ice‐over‐water cloud radiative characteristics. The radiances emanating from the combined low cloud and surface are estimated using the microwave liquid water with an assumption of effective droplet size. These radiances replace the background radiances traditionally used in single‐layer cloud retrievals. The MCRS is applied to data from March through October 2000 over four Atmospheric Radiation Measurement (ARM) Southern Great Plains (SGP) sites. The results are compared to the available retrievals of ice water path (IWP) from radar data and show that the MCRS clearly produces a more accurate retrieval of ice‐over‐water cloud properties. MCRS yields values of IWP that are closest to those from the radar retrieval. For ice‐over‐water cloud systems, on average, the optical depth and IWP are reduced, from original overestimates, by approximately 30%. The March–October mean cloud effective temperatures from the MCRS are decreased by 10 ± 12 K, which translates to an average height difference of ∼1.4 km. These results indicate that ice‐cloud height derived from traditional single‐layer retrieval is underestimated, and the midlevel ice cloud coverage is over classified. Effective ice crystal particle sizes are increased by only a few percent with the new method. This new physically based technique should be robust and directly applicable when data are available simultaneously from a satellite imager and the appropriate satellite or surface microwave sensor.
A multilayered cloud retrieval system (MCRS) is updated and used to estimate ice water path in maritime ice‐over‐water clouds using Visible and Infrared Scanner (VIRS) and Tropical Rainfall Measuring ...Mission (TRMM) Microwave Imager (TMI) measurements acquired over the Tropics between January and August 1998. Lookup tables of top‐of‐atmosphere 0.65‐μm reflectance are developed for ice‐over‐water cloud systems using radiative transfer calculations for various combinations of ice‐over‐water cloud layers. The liquid and ice water paths, LWP and IWP, respectively, are determined with the MCRS using these lookup tables with a combination of microwave (MW), visible (VIS), and infrared (IR) data. LWP, determined directly from the TMI MW data, is used to define the lower‐level cloud properties to select the proper lookup table. The properties of the upper‐level ice clouds, such as optical depth and effective size, are then derived using the Visible–Infrared Solar‐infrared Split‐Window technique (VISST), which matches the VIRS IR, 3.9 μm, and VIS data to the multilayer cloud lookup table reflectances and a set of emittance parameterizations. Initial comparisons with surface‐based radar retrievals suggest that this enhanced MCRS can significantly improve the accuracy and decrease the IWP in overlapped clouds by 42 and 13% compared to using the single‐layer VISST and an earlier simplified MW–VIS–IR (MVI) differencing method, respectively, for ice‐over‐water cloud systems. The tropical distribution of ice‐over‐water clouds is the same as derived earlier from combined TMI and VIRS data, but the new values of IWP and optical depth are slightly larger than the older MVI values and exceed those of single‐layered clouds by 7 and 11%, respectively. The mean IWP from the MCRS is 8–14% greater than that retrieved from radar retrievals of overlapped clouds over two surface sites, and the standard deviations of the differences are similar to those for single‐layered clouds. Examples of a method for applying the MCRS over land without MW data yield similar differences with the surface retrievals. By combining the MCRS with other techniques that focus primarily on optically thin cirrus over low water clouds, it will be possible to more fully assess the IWP in all conditions over ocean except for precipitating systems.
This study develops and examines a multiangle, multisatellite method for determining effective cloud particle shapes from reflectances observed at visible wavelengths. The technique exploits the ...significant differences in the various cloud particle shape phase functions near the backscatter direction to infer particle shape from a combination of views from a near‐backscatter angle and a side scattering angle. Adding‐doubling calculations confirm that the optimal viewing combinations include one near‐backscatter angle and another between 60° and 150°. Sensitivity to shape increases with solar zenith angle. A total of 28 collocated, visible images from pairs of currently operating meteorological satellites with the desired viewing combinations were analyzed for particle shape. Matching reflectances from images with optimal viewing angles clearly separates water droplet from ice crystal clouds. Reflectance pairs from matched pixels containing ice crystals can be explained by the range of selected microphysical models. The most common retrieved shapes correspond to combinations of hexagonal compacts (aspect ratio of unity), hexagonal columns, and bullet rosettes. Although no single microphysical model can account for the observed variability, taken together, the models used for retrieving cloud particle size by the Clouds and the Earth's Radiant Energy System and the Moderate Resolution Imaging Spectroradiometer Projects can account for most of the reflectance variability observed in this limited data set. Additional studies are needed to assess the uncertainties in retrieved shapes due to temporal and spatial mismatches, anisotropic and bright background reflectances, and calibration errors and to validate the retrieved shapes. While applicable to a limited number of dual‐satellite viewing combinations for current research and operational meteorological satellites, this approach could be used most extensively to derive effective particle size, shape, and optical depth from a combination of an imaging satellite in an L1 orbit, like Triana, and any other lower Earth orbiting satellites.
Germinal‐center kinase‐like kinase (GLK, Map4k3), a GCK‐I family kinase, plays multiple roles in regulating apoptosis, amino acid sensing, and immune signaling. We describe here the crystal structure ...of an activation loop mutant of GLK kinase domain bound to an inhibitor. The structure reveals a weakly associated, activation‐loop swapped dimer with more than 20 amino acids of ordered density at the carboxy‐terminus. This C‐terminal PEST region binds intermolecularly to the hydrophobic groove of the N‐terminal domain of a neighboring molecule. Although the GLK activation loop mutant crystallized demonstrates reduced kinase activity, its structure demonstrates all the hallmarks of an “active” kinase, including the salt bridge between the C‐helix glutamate and the catalytic lysine. Our compound displacement data suggests that the effect of the Ser170Ala mutation in reducing kinase activity is likely due to its effect in reducing substrate peptide binding affinity rather than reducing ATP binding or ATP turnover. This report details the first structure of GLK; comparison of its activation loop sequence and P‐loop structure to that of Map4k4 suggests ideas for designing inhibitors that can distinguish between these family members to achieve selective pharmacological inhibitors.
Interactive Figure 3
PDB Code(s): 5J5T
Display omitted
For the past two decades, BTK a tyrosine kinase and member of the Tec family has been a drug target of significant interest due to its potential to selectively treat various B ...cell-mediated diseases such as CLL, MCL, RA, and MS. Owning to the challenges encountered in identifying drug candidates exhibiting the potency block B cell activation via BTK inhibition, the pharmaceutical industry has relied on the use of covalent/irreversible inhibitors to address this unmet medical need. Herein, we describe a medicinal chemistry campaign to identify structurally diverse reversible BTK inhibitors originating from HITS identified using a fragment base screen. The leads were optimized to improve the potency and in vivo ADME properties resulting in a structurally distinct chemical series used to develop and validate a novel in vivo CD69 and CD86 PD assay in rodents.
Severe combined immunodeficiency due to adenosine deaminase (ADA) deficiency (ADA-SCID) is a rare and life-threatening primary immunodeficiency.
We treated 50 patients with ADA-SCID (30 in the United ...States and 20 in the United Kingdom) with an investigational gene therapy composed of autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) transduced ex vivo with a self-inactivating lentiviral vector encoding human
. Data from the two U.S. studies (in which fresh and cryopreserved formulations were used) at 24 months of follow-up were analyzed alongside data from the U.K. study (in which a fresh formulation was used) at 36 months of follow-up.
Overall survival was 100% in all studies up to 24 and 36 months. Event-free survival (in the absence of reinitiation of enzyme-replacement therapy or rescue allogeneic hematopoietic stem-cell transplantation) was 97% (U.S. studies) and 100% (U.K. study) at 12 months; 97% and 95%, respectively, at 24 months; and 95% (U.K. study) at 36 months. Engraftment of genetically modified HSPCs persisted in 29 of 30 patients in the U.S. studies and in 19 of 20 patients in the U.K. study. Patients had sustained metabolic detoxification and normalization of ADA activity levels. Immune reconstitution was robust, with 90% of the patients in the U.S. studies and 100% of those in the U.K. study discontinuing immunoglobulin-replacement therapy by 24 months and 36 months, respectively. No evidence of monoclonal expansion, leukoproliferative complications, or emergence of replication-competent lentivirus was noted, and no events of autoimmunity or graft-versus-host disease occurred. Most adverse events were of low grade.
Treatment of ADA-SCID with ex vivo lentiviral HSPC gene therapy resulted in high overall and event-free survival with sustained
expression, metabolic correction, and functional immune reconstitution. (Funded by the National Institutes of Health and others; ClinicalTrials.gov numbers, NCT01852071, NCT02999984, and NCT01380990.).
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