Structural optimization and biological evaluation of 2-substituted 5-hydroxyindole-3-carboxylates as potent inhibitors of human 5-lipoxygenase.

Pharmacological suppression of leukotriene biosynthesis by inhibitors of 5-lipoxygenase (5-LO) is a strategy to intervene with inflammatory and allergic disorders. We recently presented 2-amino-5-hydroxy-1H-indoles as efficient 5-LO inhibitors in cell-based and cell-free assays. Structural optimization led to novel benzo[g]indole-3-carboxylates exemplified by ethyl 2-(3-chlorobenzyl)-5- hydroxy-1H-benzo[g]indole-3-carboxylate (compound 11a), which inhibits 5-LO activity in human neutrophils and recombinant human 5-LO with IC50 values of 0.23 and 0.086 μM, respectively. Notably, 11a efficiently blocks 5-LO product formation in human whole blood assays (IC50 = 0.83-1.6 μM) and significantly prevented leukotriene B4 production in pleural exudates of carrageenan-treated rats, associated with reduced severity of pleurisy. Together, on the basis of their high potency against 5-LO and the marked efficacy in biological systems, these novel and straightforward benzo[g]indole-3-carboxylates may have potential as anti-inflammatory therapeutics

Early transformation of the Chinese power sector to avoid additional coal lock-in

Emission reduction from the coal-dominated power sector is vital for achieving China's carbon mitigation targets. Although the coal expansion has been slowed down due to the cancellation of and delay in new construction, coal-based power was responsible for over one third of China's energy-related CO2 emissions by 2018. Moreover, with a technical lifetime of over 30 years, current investment in coal-based power could hinder CO2 mitigation until 2050. Therefore, it is important to examine whether the current coal-based power planning aligns with the long-term climate targets. This paper introduces China's Nationally Determined Contribution (NDC) goals and an ambitious carbon budget along with global pathways well-below 2 degrees that are divided into five integrated assessment models, which are two national and three global models. We compare the models' results with bottom-up data on current capacity additions and expansion plans to examine if the NDC targets are in line with 2-degree pathways. The key findings are: 1. NDC goals alone are unlikely to lead to significant reductions in coal-based power generation. On the contrary, more plants may be built before 2030; 2. this would require an average of 187–261 TWh of annual coal-based power capacity reduction between 2030 and 2050 to achieve a 2 °C compatible trajectory, which would lead to the stranding of large-scale coal-based power plants; 3. if the reduction in coal power can be brought forward to 2020, the average annual coal-based power reduction required would be 104–155 TWh from 2020 to 2050 and the emissions could peak earlier; 4. early regulations in coal-based power would require accelerated promotion of alternatives between 2020 and 2030, with nuclear, wind and solar power expected to be the most promising alternatives. By presenting the stranding risk and viability of alternatives, we suggest that both the government and enterprises should remain cautious about making new investment in coal-based power sector

Modeling of biomass smoke injection into the lower stratosphere by a large forest fire (Part I): reference simulation

Wildland fires in boreal regions have the potential to initiate deep convection, so-called pyro-convection, due to their release of sensible heat. Under favorable atmospheric conditions, large fires can result in pyro-convection that transports the emissions into the upper troposphere and the lower stratosphere. Here, we present three-dimensional model simulations of the injection of fire emissions into the lower stratosphere by pyro-convection. These model simulations are constrained and evaluated with observations obtained from the Chisholm fire in Alberta, Canada, in 2001. The active tracer high resolution atmospheric model (ATHAM) is initialized with observations obtained by radiosonde. Information on the fire forcing is obtained from ground-based observations of the mass and moisture of the burned fuel. Based on radar observations, the pyro-convection reached an altitude of about 13 km, well above the tropopause, which was located at about 11.2 km. The model simulation yields a similarly strong convection with an overshoot of the convection above the tropopause. The main outflow from the pyro-convection occurs at about 10.6 km, but a significant fraction (about 8%) of the emitted mass of the smoke aerosol is transported above the tropopause. In contrast to regular convection, the region with maximum updraft velocity in the pyro-convection is located close to the surface above the fire. This results in high updraft velocities >10 m s^−1 at cloud base. The temperature anomaly in the plume decreases rapidly with height from values above 50 K at the fire to about 5 K at about 3000 m above the fire. While the sensible heat released from the fire is responsible for the initiation of convection in the model, the release of latent heat from condensation and freezing dominates the overall energy budget. Emissions of water vapor from the fire do not significantly contribute to the energy budget of the convection

System integration of wind and solar power in Integrated Assessment Models: A cross-model evaluation of new approaches

Mitigation-Process Integrated Assessment Models (MP-IAMs) are used to analyze long-term transformation pathways of the energy system required to achieve stringent climate change mitigation targets. Due to their substantial temporal and spatial aggregation, IAMs cannot explicitly represent all detailed challenges of integrating the variable renewable energies (VRE) wind and solar in power systems, but rather rely on parameterized modeling approaches. In the ADVANCE project, six international modeling teams have developed new approaches to improve the representation of power sector dynamics and VRE integration in IAMs. In this study, we qualitatively and quantitatively evaluate the last years' modeling progress and study the impact of VRE integration modeling on VRE deployment in IAM scenarios. For a comprehensive and transparent qualitative evaluation, we first develop a framework of 18 features of power sector dynamics and VRE integration. We then apply this framework to the newly-developed modeling approaches to derive a detailed map of strengths and limitations of the different approaches. For the quantitative evaluation, we compare the IAMs to the detailed hourly-resolution power sector model REMIX. We find that the new modeling approaches manage to represent a large number of features of the power sector, and the numerical results are in reasonable agreement with those derived from the detailed power sector model. Updating the power sector representation and the cost and resources of wind and solar substantially increased wind and solar shares across models: Under a carbon price of 30$/tCO2 in 2020 (increasing by 5% per year), the model-average cost-minimizing VRE share over the period 2050–2100 is 62% of electricity generation, 24%-points higher than with the old model version

Assessment of wind and solar power in global low-carbon energy scenarios: An introduction

This preface introduces the special section on the assessment of wind and solar in global low-carbon energy scenarios. The special section documents the results of a coordinated research effort to improve the representation of variable renewable energies (VRE), including wind and solar power, in Integrated Assessment Models (IAM) and presents an overview of the results obtained in the underlying coordinated model inter-comparison exercise

Constant elasticity of substitution functions for energy modeling in general equilibrium integrated assessment models:a critical review and recommendations

Applying constant elasticity of substitution (CES) functions in general equilibrium integrated assessment models (GE-IAMs) for the substitution of technical factor inputs (e.g., replacing fossil fuels) fails to match historically observed patterns in energy transition dynamics. This method of substitution is also very sensitive to the structure of CES implementation (nesting) and parameter choice. The resulting methodology-related artifacts are (i) the extension of the status quo technology shares for future energy supply relying on fossil fuels with carbon capture, biomass, and nuclear; (ii) monotonically increasing marginal abatement costs of carbon; and (iii) substitution of energy with non-physical inputs (e.g., knowledge and capital) without conclusive evidence that this is possible to the extent modeled. We demonstrate these issues using simple examples and analyze how they are relevant in the case of four major CES-based GE-IAMs. To address this, we propose alternative formulations either by opting for carefully applied perfect substitution for alternative energy options or by introducing dynamically variable elasticity of substitution as a potential intermediate solution. Nevertheless, complementing the economic analysis with physical modeling accounting for storage and resource availability at a high resolution spatially and temporally would be preferable