Discovery of SARxxxx92, a pan-PIM kinase inhibitor, efficacious in a KG1 tumor model
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In this work, the partially averaged Navier–Stokes (PANS) equations are used to predict the variable-density Rayleigh–Taylor (RT) flow at Atwood number 0.5 and maximum Reynolds number 500. This is a prototypical problem of material mixing, featuring laminar, transitional, and turbulent flow, instabilities and coherent structures, density fluctuations, and production of turbulence kinetic energy by both shear and buoyancy mechanisms. These features pose numerous challenges to modeling and simulation, making the RT flow ideal to develop the validation space of the recently proposed PANS Besnard–Harlow–Rauenzahn-linear eddy viscosity model closure. The numerical simulations are conducted at different levels of physical resolution and test three approaches to set the parameters $f_\phi$ defining the range of physically resolved scales. The computations demonstrate the efficiency (accuracy vs cost) of the PANS model predicting the spatiotemporal development of the RT flow. Results comparable to large-eddy simulations and direct numerical simulations are obtained at significantly lower physical resolution without the limitations of the Reynolds-averaged Navier–Stokes equations in these transitional flows. The data also illustrate the importance of appropriate selection of the physical resolution and the resolved fraction of each dependent quantity $\phi$ of the turbulent closure, $f_\phi$. These two aspects determine the ability of the model to resolve the flow phenomena not amenable to modeling by the closure and, as such, the computations’ fidelity.
Bemnifosbuvir (BEM) is a potent, pan-genotypic inhibitor targeting the hepatitis C virus (HCV) NS5B polymerase. Its antiviral activity was evaluated in an ascending dose phase I clinical trial involving 30 patients treated once a day for 7 days. After treatment initiation, plasma HCV RNA declined in a biphasic manner with a mean reduction of 2.3 log 10 IU/mL after 24 hours and 4.4 log10 IU/mL by day 7 for the highest dose. Alanine aminotransferase (ALT) also normalized in most patients. We employed a multiscale mathematical model fitted to the HCV RNA and ALT dynamics to quantify the antiviral activity and evaluate the modes of action of BEM. We found that models in which BEM only acted as a typical HCV RNA polymerase inhibitor and reduced the intracellular production of HCV RNA did not fit the data as well as models in which BEM had multiple modes of action, including suppressing viral assembly and secretion and enhancing intracellular HCV RNA degradation. BEM's effectiveness in inhibiting intracellular HCV RNA production increased with dose (150 mg/day: 88.2%, 300 mg/day: 98.8%, 600 mg/day: 99.5%), while inhibition of viral assembly and release was ~95% effective regardless of dose. We observed a dose-dependent enhancement in the degradation of intracellular HCV RNA, with degradation rates 1.5-fold higher in patients receiving 300 mg/day and 2.7-fold higher in those receiving 600 mg/day than in patients receiving 150 mg/day. No significant differences in antiviral activity were detected between HCV genotypes 1b and 3 or between patients with and without compensated cirrhosis.
This data product represents the integration of new code capability for arctic tundra hillslope hydrologic processes into the Energy Exascale Earth System Model (E3SM), through the E3SM Land Model (ELM) component. This code integration is the result of collaborative effort between the NGEE Arctic project and the E3SM project. The current ELM represents water movement primarily through vertical processes, such as precipitation, canopy interception, evaporation, infiltration, and soil water movement. Lateral water movement—such as surface runoff, subsurface flow, and river transport—plays a significant role in the hydrological cycle, especially in regions with varied topography. While E3SM includes a runoff routing component representing water transport in the river network, the lateral transport of water at the subgrid scale within the land model has previously not been taken into account. With the recent development of topographic units within the ELM subgrid data structure, there is an opportunity to simulate hillslope hydrologic connectivity by introducing water transport along topographic gradients. We expect that more realistic representation of hillslope hydrologic processes will lead to improved predictions of both soil water content and river network flows. Lateral transport of water at and near the surface is represented as a sub-grid process in this new code development. Water is tracked as it moves from higher to lower elevations within a gridcell. This capability uses the nested hierarchical sub-grid scheme within ELM to connect water fluxes from sub-grid elements with higher elevation to those with lower elevation. This data record consists of a single document (pdf format) that describes the theoretical basis for the hillslope hydrology processes added to ELM, and describes the modifications made to the ELM code. The Methods section of this metadata record includes a link to the public E3SM code repository where the exact code modifications as integrated in E3SM can be accessed. The Next-Generation Ecosystem Experiments: Arctic (NGEE Arctic), was a research effort to reduce uncertainty in Earth System Models by developing a predictive understanding of carbon-rich Arctic ecosystems and feedbacks to climate. NGEE Arctic was supported by the Department of Energy's Office of Biological and Environmental Research. The NGEE Arctic project had two field research sites: 1) located within the Arctic polygonal tundra coastal region on the Barrow Environmental Observatory (BEO) and the North Slope near Utqiagvik (Barrow), Alaska and 2) multiple areas on the discontinuous permafrost region of the Seward Peninsula north of Nome, Alaska. Through observations, experiments, and synthesis with existing datasets, NGEE Arctic provided an enhanced knowledge base for multi-scale modeling and contributed to improved process representation at global pan-Arctic scales within the Department of Energy's Earth system Model (the Energy Exascale Earth System Model, or E3SM), and specifically within the E3SM Land Model component (ELM).
This data product represents the integration of new code capability for arctic tundra snow-vegetation-terrain interactions into the Energy Exascale Earth System Model (E3SM), through the E3SM Land Model (ELM) component. This code integration is the result of collaborative effort between the NGEE Arctic project and the E3SM project. The NGEE Arctic project developed a total of six Integrated Modeling (IM) modules informed by observations and experiments. New ELM capability represented by this data product (IM3) falls into three categories: 1) Downscaling from gridcell to topographic unit level when working through the existing coupler bypass code. 2) Four new parameters (taper, stocking, bendresist, and vegshape) have been added to ELM to allow for flexible definition of snow-vegetation interactions. 3) Vegshape and bendresist parameters are used to calculate the fraction of leaf area and/or stem area buried by snow for a given snow depth. This data record consists of a single document (pdf format) that describes the theoretical basis for the snow-vegetation-terrain interactions added to ELM, and describes the modifications made to the ELM code. The Methods section of this metadata record includes a link to the public E3SM code repository where the exact code modifications as integrated in E3SM can be accessed. The Next-Generation Ecosystem Experiments: Arctic (NGEE Arctic), was a research effort to reduce uncertainty in Earth System Models by developing a predictive understanding of carbon-rich Arctic ecosystems and feedbacks to climate. NGEE Arctic was supported by the Department of Energy's Office of Biological and Environmental Research. The NGEE Arctic project had two field research sites: 1) located within the Arctic polygonal tundra coastal region on the Barrow Environmental Observatory (BEO) and the North Slope near Utqiagvik (Barrow), Alaska and 2) multiple areas on the discontinuous permafrost region of the Seward Peninsula north of Nome, Alaska. Through observations, experiments, and synthesis with existing datasets, NGEE Arctic provided an enhanced knowledge base for multi-scale modeling and contributed to improved process representation at global pan-Arctic scales within the Department of Energy's Earth system Model (the Energy Exascale Earth System Model, or E3SM), and specifically within the E3SM Land Model component (ELM).
Field soil respiration data collected in 2023 and 2024 from burned and unburned tussock tundra sites in the Kougarok Fire Complex, near Nome, on the Seward Peninsula of Alaska. Specifically, we measured soil properties and late-growing season CO2 fluxes in patches of unique plant functional types (forbs, shrubs, and graminoids) across two years in tundra recovering from repeated wildfires over the decade. The goal was to identify the main drivers of soil respiration in Arctic tundra underlain by discontinuous permafrost that is recovering from two recent, repeated wildfires that differed in fire age and number of times burned, thereby resulting in different levels of vegetation and subsurface property changes (i.e., successional trajectories). There are five files in *.csv format with one data file and four data description files including data, dictionary, methods, terminology, and file-level metadata. The Next-Generation Ecosystem Experiments: Arctic (NGEE Arctic), is a research effort to reduce uncertainty in Earth System Models by developing a predictive understanding of carbon-rich Arctic ecosystems and feedbacks to climate. NGEE Arctic was supported by the Department of Energy's Office of Biological and Environmental Research. The NGEE Arctic Phase 3 project had two field research sites: 1) located within the Arctic polygonal tundra coastal region on the Barrow Environmental Observatory (BEO) and the North Slope near Utqiagvik (Barrow), Alaska and 2) multiple areas on the discontinuous permafrost region of the Seward Peninsula north of Nome, Alaska. Through observations, experiments, and synthesis with existing datasets, NGEE Arctic provided an enhanced knowledge base for multi-scale modeling and contributed to improved process representation at global pan-Arctic scales within the Department of Energy's Earth system Model (the Energy Exascale Earth System Model, or E3SM), and specifically within the E3SM Land Model component (ELM).
The Arctic is warming twice as fast as the rest of the globe, resulting in dramatic loss of ice across the Arctic system. Models project 7% to 90% of permafrost could be lost by the end of the century. Permafrost thaw is driving landscape degradation and infrastructure disruption through thermokarst and thermal erosion. Previous pan-arctic modeling shows potential for significant subsidence (Lee et al. 2014). CLM4.5 pan-Arctic simulations from PCNMIP were used to calculate change in projected ALT from 2010-2030.
This article deals with the sizing of submodule capacitors for modular multilevel converters (MMCs) used for variable speed drives for medium voltage and high voltage electric machines. Variable speed drives are required to run over a wide frequency range from zero to a few hundred Hz or even over 1 kHz. Under low frequency operation (<30 Hz), a large current ripple flowing through the MMC submodule capacitors will cause significant capacitor voltage fluctuation. This article proposes an optimal submodule capacitor selection method based on the common-mode voltage injection. The proposed sizing model includes two functions: 1) accurately estimating the capacitor voltage ripple based on the drive system parameters; and 2) identifying the minimum capacitance of the submodule capacitors based on the allowed maximum capacitor voltage fluctuations. Simulation and experimental results show that the error between the actual and estimated values of the voltage fluctuation is within 3% using the proposed model.
This paper summarizes the technical activities of the IEEE Task Force on Solving Large Scale Optimization Problems in Electricity Market and Power System Applications. This Task Force was established by the IEEE Technology and Innovation Subcommittee to first review the state-of-the-art of the security-constrained unit commitment (SCUC) business model, its mathematical formulation, and solution techniques in solving electricity market clearing problems. The Task Force then investigated the emerging challenges of future market clearing problems and presented efforts in building benchmark mathematical and business models.
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As the third most important greenhouse gas (GHG) after carbon dioxide (CO 2 ) and methane (CH 4 ), tropospheric ozone (O 3 ) is also an air pollutant causing damage to human health and ecosystems. This study brings together recent research on observations and modeling of tropospheric O 3 in the Arctic, a rapidly warming and sensitive environment. At different locations in the Arctic, the observed surface O 3 seasonal cycles are quite different. Coastal Arctic locations, for example, have a minimum in the springtime due to O 3 depletion events resulting from surface bromine chemistry. In contrast, other Arctic locations have a maximum in the spring. The 12 state-of-the-art models used in this study lack the surface halogen chemistry needed to simulate coastal Arctic surface O 3 depletion in the springtime; however, the multi-model median (MMM) has accurate seasonal cycles at non-coastal Arctic locations. There is a large amount of variability among models, which has been previously reported, and we show that there continues to be no convergence among models or improved accuracy in simulating tropospheric O 3 and its precursor species. The MMM underestimates Arctic surface O 3 by 5% to 15% depending on the location. The vertical distribution of tropospheric O 3 is studied from recent ozonesonde measurements and the models. The models are highly variable, simulating free-tropospheric O 3 within a range of ±50% depending on the model and the altitude. The MMM performs best, within ±8% for most locations and seasons. However, nearly all models overestimate O 3 near the tropopause (~300 hPa or ~8 km), likely due to ongoing issues with underestimating the altitude of the tropopause and excessive downward transport of stratospheric O 3 at high latitudes. For example, the MMM is biased high by about 20% at Eureka. Observed and simulated O 3 precursors (CO, NO x , and reservoir PAN) are evaluated throughout the troposphere. Models underestimate wintertime CO everywhere, likely due to a combination of underestimating CO emissions and possibly overestimating OH. Throughout the vertical profile (compared to aircraft measurements), the MMM underestimates both CO and NO x but overestimates PAN. Perhaps as a result of competing deficiencies, the MMM O 3 matches the observed O 3 reasonably well. Our findings suggest that despite model updates over the last decade, model results are as highly variable as ever and have not increased in accuracy for representing Arctic tropospheric O 3 .
Temporally continuous snow depth estimates are vital for understanding changing snow patterns and impacts on permafrost in the Arctic. We train a random forest machine learning model to predict snow depth from variability in ground surface temperature. To our knowledge, this is the first time that small ground surface temperature sensors have been used to estimate snow depth. The model performs well at sites where the model was trained and at pan-arctic evaluation sites (RMSE <= 0.15 m). Small temperature sensors are cheap and easy-to-deploy, so this technique enables spatially distributed and temporally continuous snowpack monitoring to an extent previously infeasible. The model is flexible and can be applied to datasets retroactively to retrieve snow depth estimates at additional sites. This code package includes a *.joblib file of the trained random forest model and a *.ipynb file showing how to clean input data, train the random forest model, and apply the model.
Remote sensing data collected from Lawrence Berkeley National Laboratory’s (LBNL) unmanned aerial system (UAS) quadcopter platform – Inspire-1 – operated by the Ameriflux Management Project (ameriflux.lbl.gov) Technical Team. The Insprire-1 is a visible imagery UAS platform that simultaneously measures very high spatial resolution optical red/green/blue (RGB) at regular intervals along each flight path. This package includes data from four flight paths over the NGEE Arctic Council Road Site near mile marker 71 in the Seward Peninsula, Alaska in July 2017. Derived image products for each flight include ortho-mosaiced RGB, an RGB-based digital surface model (DSM) using the structure from motion (SfM) technique, and a digital terrain model (DTM). Ancillary aircraft data, flight mission parameters, and general flight conditions are also included. Unprocessed and processed data products are included in this package (processing levels 0-2). This metadata document contains flight campaign, instrument and file metadata, along with a description of data processing levels, data products and file naming scheme.The Next-Generation Ecosystem Experiments: Arctic (NGEE Arctic) was a research effort to reduce uncertainty in Earth System Models by developing a predictive understanding of carbon-rich Arctic ecosystems and feedbacks to climate. NGEE Arctic was supported by the Department of Energy’s Office of Biological and Environmental Research. The NGEE Arctic project had two field research sites: 1) located within the Arctic polygonal tundra coastal region on the Barrow Environmental Observatory (BEO) and the North Slope near Utqiagvik (Barrow), Alaska and 2) multiple areas on the discontinuous permafrost region of the Seward Peninsula north of Nome, Alaska. Through observations, experiments, and synthesis with existing datasets, NGEE Arctic provided an enhanced knowledge base for multi-scale modeling and contributed to improved process representation at global pan-Arctic scales within the Department of Energy’s Earth system Model (the Energy Exascale Earth System Model, or E3SM), and specifically within the E3SM Land Model component (ELM).
Remote sensing data collected from Lawrence Berkeley National Laboratory’s (LBNL) unmanned aerial system (UAS) quadcopter platform – Inspire-1 – operated by the Ameriflux Management Project (ameriflux.lbl.gov) Technical Team. The Insprire-1 is a visible imagery UAS platform that simultaneously measures very high spatial resolution optical red/green/blue (RGB) at regular intervals along the flight path. This package includes data from a flight path over the NGEE Arctic Teller Site, west of mile marker 27 Bob Blodgett Highway in the Seward Peninsula, Alaska in July 2017. Derived image products include ortho-mosaiced RGB, an RGB-based digital surface model (DSM) using the structure from motion (SfM) technique, and a digital terrain model (DTM). Ancillary aircraft data, flight mission parameters, and general flight conditions are also included. Unprocessed and processed data products are included in this package (processing levels 0-2). This metadata document contains flight campaign, instrument and file metadata, along with a description of data processing levels, data products and file naming scheme.The Next-Generation Ecosystem Experiments: Arctic (NGEE Arctic) was a research effort to reduce uncertainty in Earth System Models by developing a predictive understanding of carbon-rich Arctic ecosystems and feedbacks to climate. NGEE Arctic was supported by the Department of Energy’s Office of Biological and Environmental Research. The NGEE Arctic project had two field research sites: 1) located within the Arctic polygonal tundra coastal region on the Barrow Environmental Observatory (BEO) and the North Slope near Utqiagvik (Barrow), Alaska and 2) multiple areas on the discontinuous permafrost region of the Seward Peninsula north of Nome, Alaska. Through observations, experiments, and synthesis with existing datasets, NGEE Arctic provided an enhanced knowledge base for multi-scale modeling and contributed to improved process representation at global pan-Arctic scales within the Department of Energy’s Earth system Model (the Energy Exascale Earth System Model, or E3SM), and specifically within the E3SM Land Model component (ELM).
Remote sensing data collected from Lawrence Berkeley National Laboratory’s (LBNL) unmanned aerial system (UAS) quadcopter platform – Inspire-1 – operated by the Ameriflux Management Project (ameriflux.lbl.gov) Technical Team. The Insprire-1 is a visible imagery UAS platform that simultaneously measures very high spatial resolution optical red/green/blue (RGB) at regular intervals along each flight path. This package includes data from four flight paths over the NGEE Arctic Kougarok Site, west of mile marker 64 on Kuzitrin Road in the Seward Peninsula, Alaska in July 2017. Derived image products include ortho-mosaiced RGB, an RGB-based digital surface model (DSM) using the structure from motion (SfM) technique, and a digital terrain model (DTM). Ancillary aircraft data, flight mission parameters, and general flight conditions are also included. Unprocessed and processed data products are included in this package (processing levels 0-2). This metadata document contains flight campaign, instrument and file metadata, along with a description of data processing levels, data products and file naming scheme.The Next-Generation Ecosystem Experiments: Arctic (NGEE Arctic) was a research effort to reduce uncertainty in Earth System Models by developing a predictive understanding of carbon-rich Arctic ecosystems and feedbacks to climate. NGEE Arctic was supported by the Department of Energy’s Office of Biological and Environmental Research. The NGEE Arctic project had two field research sites: 1) located within the Arctic polygonal tundra coastal region on the Barrow Environmental Observatory (BEO) and the North Slope near Utqiagvik (Barrow), Alaska and 2) multiple areas on the discontinuous permafrost region of the Seward Peninsula north of Nome, Alaska. Through observations, experiments, and synthesis with existing datasets, NGEE Arctic provided an enhanced knowledge base for multi-scale modeling and contributed to improved process representation at global pan-Arctic scales within the Department of Energy’s Earth system Model (the Energy Exascale Earth System Model, or E3SM), and specifically within the E3SM Land Model component (ELM).
The dataset comprises Soil Temperature and Deformation monitoring data gathered from a watershed situated along the Nome-Teller road at Mile 47 in Alaska. Its primary objective is to enhance comprehension of deformation mechanisms in permafrost environments by using 51 probes designed following Wielandt et al. (2022). The dataset comprises a description of Probe_ID, Location, start time, end time and probe length in the "ProbesLocations_StartEndDates.csv" file, the 51 data files encapsulated within "Data_files.zip" and the computed deformation for 2023 and 2022 in "Deformation_T47.zip".Each file in Data_files.zip is named as followed "ProbeId_StartMonth_EndMonth.csv". Within each file, the initial column denotes the timestamp in UTC, followed by the sensor’s battery voltage and temperature and acceleration values (X, Y, Z) in subsequent columns. The data collection frequency is set at 30-minute intervals. Each file in Deformation_T47.zip is named as followed "ProbeId_Temp_def_year.csv". Within each file, the initial column denotes the timestamp in UTC, followed by the temperature at each sensor and cumulative deformation from last to first sensor in subsequent columns. The data collection is daily averaged.This dataset forms an integral component of the Next-Generation Ecosystem Experiments: Arctic (NGEE Arctic). The Next-Generation Ecosystem Experiments: Arctic (NGEE Arctic), was a research effort to reduce uncertainty in Earth System Models by developing a predictive understanding of carbon-rich Arctic ecosystems and feedbacks to climate. NGEE Arctic was supported by the Department of Energy's Office of Biological and Environmental Research.The NGEE Arctic project had two field research sites: 1) located within the Arctic polygonal tundra coastal region on the Barrow Environmental Observatory (BEO) and the North Slope near Utqiagvik (Barrow), Alaska and 2) multiple areas on the discontinuous permafrost region of the Seward Peninsula north of Nome, Alaska.Through observations, experiments, and synthesis with existing datasets, NGEE Arctic provided an enhanced knowledge base for multi-scale modeling and contributed to improved process representation at global pan-Arctic scales within the Department of Energy's Earth system Model (the Energy Exascale Earth System Model, or E3SM), and specifically within the E3SM Land Model component (ELM).
The dataset contains depth-resolved soil temperature measured at 45 discrete locations in a watershed located along the Nome-Teller road at Mile 27 in Seward Peninsula, Alaska. The dataset was generated to understand the local heterogeneity of soil thermal dynamics and their controls in a discontinuous permafrost region. At each location, temperatures were measured by a distributed temperature profiling probe designed based on Dafflon et al (2022). The dataset includes a description of the probe locations in the "Probe_locations.csv" file and the 45 data files (Soil_temperatures_*.csv). Metadata files include data descriptions (_dd.csv) for tabular data. All included files are listed and described in NGA513_flmd.csv.The Next-Generation Ecosystem Experiments: Arctic (NGEE Arctic), was a research effort to reduce uncertainty in Earth System Models by developing a predictive understanding of carbon-rich Arctic ecosystems and feedbacks to climate. NGEE Arctic was supported by the Department of Energy's Office of Biological and Environmental Research.The NGEE Arctic project had two field research sites: 1) located within the Arctic polygonal tundra coastal region on the Barrow Environmental Observatory (BEO) and the North Slope near Utqiagvik (Barrow), Alaska and 2) multiple areas on the discontinuous permafrost region of the Seward Peninsula north of Nome, Alaska.Through observations, experiments, and synthesis with existing datasets, NGEE Arctic provided an enhanced knowledge base for multi-scale modeling and contributed to improved process representation at global pan-Arctic scales within the Department of Energy's Earth system Model (the Energy Exascale Earth System Model, or E3SM), and specifically within the E3SM Land Model component (ELM).
Multiple photogrammetric surveys using an unoccupied aerial system (UAS) were performed across a watershed along Teller road on the Seward Peninsula (Alaska) to investigate terrain, vegetation and snowpack properties. This work was led by the environmental geophysics team from Lawrence Berkeley National Laboratory as part of the Next-Generation Ecosystem Experiments: Arctic (NGEE Arctic). The multiple photogrammetric surveys used mostly a DJI Matrice 210 UAS with a DJI X5S camera, Ground Control Points (GCPs) surveyed with a Real Time Kinematic (RTK)-GPS, and a structure from motion (SfM) technique for photogrammetric reconstruction. Digital Surface elevation Models (DSMs) were inferred at various times of year, including near peak in plant and leaf density (July 19 2017), close to peak in snow depth (April 1 2019 and April 11 2022), and at low plant and leaf density of tall after the first bare-ground date (June 9 2019). Snow and canopy height were obtained by subtracting DSMs from a Digital Terrain Model (DTM) proxy inferred from the June 9 2019 survey. The derived products include ortho-mosaiced RGB map, DSMs, a DTM proxy, snow depth (April 2019 and 2022) and canopy height (July 2017). Unprocessed and processed data products are included in this package (processing levels 0-2). Data and metadata are provided as text (*.csv), image (*.jpg), and GeoTiff (*.tif) formats. This metadata document contains a description of the survey and processing steps and the inferred products.The Next-Generation Ecosystem Experiments: Arctic (NGEE Arctic) was a 15-year research effort (2012-2027) to reduce uncertainty in Earth System Models by developing a predictive understanding of carbon-rich Arctic ecosystems and feedbacks to climate. NGEE Arctic was supported by the Department of Energy’s Office of Biological and Environmental Research. The NGEE Arctic project had two field research sites: 1) located within the Arctic polygonal tundra coastal region on the Barrow Environmental Observatory (BEO) and the North Slope near Utqiagvik (Barrow), Alaska and 2) multiple areas on the discontinuous permafrost region of the Seward Peninsula north of Nome, Alaska. Through observations, experiments, and synthesis with existing datasets, NGEE Arctic provided an enhanced knowledge base for multi-scale modeling and contributed to improved process representation at global pan-Arctic scales within the Department of Energy’s Earth system Model (the Energy Exascale Earth System Model, or E3SM), and specifically within the E3SM Land Model component (ELM).