Long-Term Modeling of Wind Energy in the United States

An improved representation of wind energy has been developed for the ObjECTS MiniCAM integrated assessment modeling framework. The first version of this wind model was used for the CCTP scenarios, where wind accounts for between 9% and 17% of U.S. electricity generation by 2095. Climate forcing stabilization policies tend to increase projected deployment. Accelerated technological development in wind electric generation can both increase output and reduce the costs of wind energy. In all scenarios, wind generation is constrained by its costs relative to alternate electricity sources, particularly as less favorable wind farm sites are utilized. These first scenarios were based on exogenous resource estimates that do not allow evaluation of resource availability assumptions. A more detailed representation of wind energy is under development that uses spatially explicit resource information and explicit wind turbine technology characteristics

The Value of End-Use Energy Efficiency in Mitigation of U.S. Carbon Emissions

This report documents a scenario analysis exploring the value of advanced technologies in the U.S. buildings, industrial, and transportation sectors in stabilizing atmospheric greenhouse gas concentrations. The analysis was conducted by staff members of Pacific Northwest National Laboratory (PNNL), working at the Joint Global Change Research Institute (JGCRI) in support of the strategic planning process of the U.S. Department of Energy (U.S. DOE) Office of Energy Efficiency and Renewable Energy (EERE). The conceptual framework for the analysis is an integration of detailed buildings, industrial, and transportation modules into MiniCAM, a global integrated assessment model. The analysis is based on three technology scenarios, which differ in their assumed rates of deployment of new or presently available energy-saving technologies in the end-use sectors. These technology scenarios are explored with no carbon policy, and under two CO2 stabilization policies, in which an economic price on carbon is applied such that emissions follow prescribed trajectories leading to long-term stabilization of CO2 at roughly 450 and 550 parts per million by volume (ppmv). The costs of meeting the emissions targets prescribed by these policies are examined, and compared between technology scenarios. Relative to the reference technology scenario, advanced technologies in all three sectors reduce costs by 50% and 85% for the 450 and 550 ppmv policies, respectively. The 450 ppmv policy is more stringent and imposes higher costs than the 550 ppmv policy; as a result, the magnitude of the economic value of energy efficiency is four times greater for the 450 ppmv policy than the 550 ppmv policy. While they substantially reduce the costs of meeting emissions requirements, advanced end-use technologies do not lead to greenhouse gas stabilization without a carbon policy. This is due mostly to the effects of increasing service demands over time, the high consumption of fossil fuels in the electricity sector, and the use of unconventional feedstocks in the liquid fuel refining sector. Of the three end-use sectors, advanced transportation technologies have the greatest potential to reduce costs of meeting carbon policy requirements. Services in the buildings and industrial sectors can often be supplied by technologies that consume low-emissions fuels such as biomass or, in policy cases, electricity. Passenger transportation, in contrast, is especially unresponsive to climate policies, as the fuel costs are small compared to the time value of transportation and vehicle capital and operating costs. Delaying the transition from reference to advanced technologies by 15 years increases the costs of meeting 450 ppmv stabilization emissions requirements by 21%, but the costs are still 39% lower than the costs assuming reference technology. The report provides a detailed description of the end-use technology scenarios and provides a thorough analysis of the results. Assumptions are documented in the Appendix

Climate policy implications for agricultural water demand

Energy, water and land are scarce resources, critical to humans. Developments in each affect the availability and cost of the others, and consequently human prosperity. Measures to limit greenhouse gas concentrations will inevitably exact dramatic changes on energy and land systems and in turn alter the character, magnitude and geographic distribution of human claims on water resources. We employ the Global Change Assessment Model (GCAM), an integrated assessment model to explore the interactions of energy, land and water systems in the context of alternative policies to limit climate change to three alternative levels: 2.5 Wm-2 (445 ppm CO2-e), 3.5 Wm-2 (535 ppm CO2-e) and 4.5 Wm-2 (645 ppm CO2-e). We explore the effects of two alternative land-use emissions mitigation policy options—one which taxes terrestrial carbon emissions equally with fossil fuel and industrial emissions, and an alternative which only taxes fossil fuel and industrial emissions but places no penalty on land-use change emissions. We find that increasing populations and economic growth could be anticipated to almost triple demand for water for agricultural systems across the century even in the absence of climate policy. In general policies to mitigate climate change increase agricultural demands for water still further, though the largest changes occur in the second half of the century, under both policy regimes. The two policies examined profoundly affected both the sources and magnitudes of the increase in irrigation water demands. The largest increases in agricultural irrigation water demand occurred in scenarios where only fossil fuel emissions were priced (but not land-use change emission) and were primarily driven by rapid expansion in bioenergy production. In these scenarios water demands were large relative to present-day total available water, calling into question whether it would be physically possible to produce the associated biomass energy. We explored the potential of improved water delivery and irrigation system efficiencies. These could potentially reduce demands substantially. However, overall demands remained high under our fossil-fuel-only tax policy. In contrast, when all carbon was priced, increases in agricultural water demands were smaller than under the fossil-fuel-only policy and were driven primarily by increased demands for water by non-biomass crops such as rice. Finally we estimate the geospatial pattern of water demands and find that regions such as China, India and other countries in south and east Asia might be expected to experience greatest increases in water demands

Applying Small Molecule Signal Transducer and Activator of Transcription-3 (STAT3) Protein Inhibitors as Pancreatic Cancer Therapeutics

Constitutively activated STAT3 protein has been found to be a key regulator of pancreatic cancer and a target for molecular therapeutic intervention. In this study, PG-S3-001, a small molecule derived from the SH-4-54 class of STAT3 inhibitors, was found to inhibit patient-derived pancreatic cancer cell proliferation in vitro and in vivo in the low micromolar range. PG-S3-001 binds the STAT3 protein potently, Kd = 324 nmol/L by surface plasmon resonance, and showed no effect in a kinome screen (>100 cancer-relevant kinases). In vitro studies demonstrated potent cell killing as well as inhibition of STAT3 activation in pancreatic cancer cells. To better model the tumor and its microenvironment, we utilized three-dimensional (3D) cultures of patient-derived pancreatic cancer cells in the absence and presence of cancer-associated fibroblasts (CAF). In this coculture model, inhibition of tumor growth is maintained following STAT3 inhibition in the presence of CAFs. Confocal microscopy was used to verify tumor cell death following treatment of 3D cocultures with PG-S3-001. The 3D model was predictive of in vivo efficacy as significant tumor growth inhibition was observed upon administration of PG-S3-001. These studies showed that the inhibition of STAT3 was able to impact the survival of tumor cells in a relevant 3D model, as well as in a xenograft model using patient-derived cells

The Effects of Herbivory by a Mega- and Mesoherbivore on Tree Recruitment in Sand Forest, South Africa

Herbivory by megaherbivores on woody vegetation in general is well documented; however studies focusing on the individual browsing effects of both mega- and mesoherbivore species on recruitment are scarce. We determined these effects for elephant Loxodonta africana and nyala Tragelaphus angasii in the critically endangered Sand Forest, which is restricted to east southern Africa, and is conserved mainly in small reserves with high herbivore densities. Replicated experimental treatments (400 m2) in a single forest patch were used to exclude elephant, or both elephant and nyala. In each treatment, all woody individuals were identified to species and number of stems, diameter and height were recorded. Results of changes after two years are presented. Individual tree and stem densities had increased in absence of nyala and elephant. Seedling recruitment (based on height and diameter) was inhibited by nyala, and by elephant and nyala in combination, thereby preventing recruitment into the sapling stage. Neither nyala or elephant significantly reduced sapling densities. Excluding both elephant and nyala in combination enhanced recruitment of woody species, as seedling densities increased, indicating that forest regeneration is impacted by both mega- and mesoherbivores. The Sand Forest tree community approached an inverse J-shaped curve, with the highest abundance in the smaller size classes. However, the larger characteristic tree species in particular, such as Newtonia hildebrandtii, were missing cohorts in the middle size classes. When setting management goals to conserve habitats of key importance, conservation management plans need to consider the total herbivore assemblage present and the resulting browsing effects on vegetation. Especially in Africa, where the broadest suite of megaherbivores still persists, and which is currently dealing with the ‘elephant problem’, the individual effects of different herbivore species on recruitment and dynamics of forests and woodlands are important issues which need conclusive answers

Interobserver reliability of classification and characterization of proximal humeral fractures: a comparison of two and three-dimensional CT

Interobserver reliability for the classification of proximal humeral fractures is limited. The aim of this study was to test the null hypothesis that interobserver reliability of the AO classification of proximal humeral fractures, the preferred treatment, and fracture characteristics is the same for two-dimensional (2-D) and three-dimensional (3-D) computed tomography (CT). Members of the Science of Variation Group--fully trained practicing orthopaedic and trauma surgeons from around the world--were randomized to evaluate radiographs and either 2-D CT or 3-D CT images of fifteen proximal humeral fractures via a web-based survey and respond to the following four questions: (1) Is the greater tuberosity displaced? (2) Is the humeral head split? (3) Is the arterial supply compromised? (4) Is the glenohumeral joint dislocated? They also classified the fracture according to the AO system and indicated their preferred treatment of the fracture (operative or nonoperative). Agreement among observers was assessed with use of the multirater kappa (κ) measure. Interobserver reliability of the AO classification, fracture characteristics, and preferred treatment generally ranged from "slight" to "fair." A few small but statistically significant differences were found. Observers randomized to the 2-D CT group had slightly but significantly better agreement on displacement of the greater tuberosity (κ = 0.35 compared with 0.30, p < 0.001) and on the AO classification (κ = 0.18 compared with 0.17, p = 0.018). A subgroup analysis of the AO classification results revealed that shoulder and elbow surgeons, orthopaedic trauma surgeons, and surgeons in the United States had slightly greater reliability on 2-D CT, whereas surgeons in practice for ten years or less and surgeons from other subspecialties had slightly greater reliability on 3-D CT. Proximal humeral fracture classifications may be helpful conceptually, but they have poor interobserver reliability even when 3-D rather than 2-D CT is utilized. This may contribute to the similarly poor interobserver reliability that was observed for selection of the treatment for proximal humeral fractures. The lack of a reliable classification confounds efforts to compare the outcomes of treatment methods among different clinical trials and reports

'gcamdata': An R Package for Preparation, Synthesis, and Tracking of Input Data for the GCAM Integrated Human-Earth Systems Model

The increasing data requirements of complex models demand robust, reproducible, and transparent systems to track and prepare models’ inputs. Here we describe version 1.0 of the gcamdata R package that processes raw inputs to produce the hundreds of XML files needed by the GCAM integrated human-earth systems model. It features extensive functional and unit testing, data tracing and visualization, and enforces metadata, documentation, and flexibility in its component data-processing subunits. Although this package is specific to GCAM, many of its structural pieces and approaches should be broadly applicable to, and reusable by, other complex model/data systems aiming to improve transparency, reproducibility, and flexibility.   Funding statement: Primary support for this work was provided by the U.S. Department of Energy, Office of Science, as part of research in Multi-Sector Dynamics, Earth and Environmental System Modeling Program. Additional support was provided by the U.S. Department of Energy Offices of Fossil Energy, Nuclear Energy, and Energy Efficiency and Renewable Energy and the U.S. Environmental Protection Agency

Pathway-based predictive approaches for non-animal assessment of acute inhalation toxicity

New approaches are needed to assess the effects of inhaled substances on human health. These approaches will be based on mechanisms of toxicity, an understanding of dosimetry, and the use of in silico modeling and in vitro test methods. In order to accelerate wider implementation of such approaches, development of adverse outcome pathways (AOPs) can help identify and address gaps in our understanding of relevant parameters for model input and mechanisms, and optimize non-animal approaches that can be used to investigate key events of toxicity. This paper describes the AOPs and the toolbox of in vitro and in silico models that can be used to assess the key events leading to toxicity following inhalation exposure. Because the optimal testing strategy will vary depending on the substance of interest, here we present a decision tree approach to identify an appropriate non-animal integrated testing strategy that incorporates consideration of a substance's physicochemical properties, relevant mechanisms of toxicity, and available in silico models and in vitro test methods. This decision tree can facilitate standardization of the testing approaches. Case study examples are presented to provide a basis for proof-of-concept testing to illustrate the utility of non-animal approaches to inform hazard identification and risk assessment of humans exposed to inhaled substances

Asymmetric division coordinates collective cell migration in angiogenesis

The asymmetric division of stem or progenitor cells generates daughters with distinct fates and regulates cell diversity during tissue morphogenesis. However, roles for asymmetric division in other more dynamic morphogenetic processes, such as cell migration, have not previously been described. Here we combine zebrafish in vivo experimental and computational approaches to reveal that heterogeneity introduced by asymmetric division generates multicellular polarity that drives coordinated collective cell migration in angiogenesis. We find that asymmetric positioning of the mitotic spindle during endothelial tip cell division generates daughters of distinct size with discrete ‘tip’ or ‘stalk’ thresholds of pro-migratory Vegfr signalling. Consequently, post-mitotic Vegfr asymmetry drives Dll4/Notch-independent self-organization of daughters into leading tip or trailing stalk cells, and disruption of asymmetry randomizes daughter tip/stalk selection. Thus, asymmetric division seamlessly integrates cell proliferation with collective migration, and, as such, may facilitate growth of other collectively migrating tissues during development, regeneration and cancer invasion