Using Computer Programs In Higher Education - Good Practice In Mathematics

We report on our experience in teaching (applied) mathematics both for mathematicians and non-mathematicians using computer algebra systems and spreadsheet calculation programs. Advantages and disadvantages are discussed and some recommendations are given

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

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

The novel benzimidazole derivative BRP-7 inhibits leukotriene biosynthesis in vitro and in vivo by targeting 5-lipoxygenase-activating protein (FLAP).

BACKGROUND AND PURPOSE: Leukotrienes (LTs) are inflammatory mediators produced via the 5-lipoxygenase (5-LOX) pathway and are linked to diverse disorders, including asthma, allergic rhinitis and cardiovascular diseases. We recently identified the benzimidazole derivative BRP-7 as chemotype for anti-LT agents by virtual screening targeting 5-LOX-activating protein (FLAP). Here, we aimed to reveal the in vitro and in vivo pharmacology of BRP-7 as an inhibitor of LT biosynthesis. EXPERIMENTAL APPROACH: We analysed LT formation and performed mechanistic studies in human neutrophils and monocytes, in human whole blood (HWB) and in cell-free assays. The effectiveness of BRP-7 in vivo was evaluated in rat carrageenan-induced pleurisy and mouse zymosan-induced peritonitis. KEY RESULTS: BRP-7 potently suppressed LT formation in neutrophils and monocytes and this was accompanied by impaired 5-LOX co-localization with FLAP. Neither the cellular viability nor the activity of 5-LOX in cell-free assays was affected by BRP-7, indicating that a functional FLAP is needed for BRP-7 to inhibit LTs, and FLAP bound to BRP-7 linked to a solid matrix. Compared with the FLAP inhibitor MK-886, BRP-7 did not significantly inhibit COX-1 or microsomal prostaglandin E2 synthase-1, implying the selectivity of BRP-7 for FLAP. Finally, BRP-7 was effective in HWB and impaired inflammation in vivo, in rat pleurisy and mouse peritonitis, along with reducing LT levels. CONCLUSIONS AND IMPLICATIONS: BRP-7 potently suppresses LT biosynthesis by interacting with FLAP and exhibits anti-inflammatory effectiveness in vivo, with promising potential for further development

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

How much energy will buildings consume in 2100? A global perspective within a scenario framework

The demand for energy in buildings varies strongly across countries and climatic zones. These differences result from manifold factors, whose future evolution is uncertain. In order to assess buildings' energy demand across the 21st century, we develop an energy demand model—EDGE— and apply it in an analytical scenario framework—the shared socio-economic pathways (SSPs) — to take socio-economic uncertainty into consideration. EDGE projects energy demand for five energy services, four fuel categories, and eleven regions covering the world. The analysis shows that, without further climate policies, global final energy demand from buildings could increase from 116 EJ/yr in 2010 to a range of 120–378 EJ/yr in 2100. Our results show a paradigm shift in buildings' energy demand: appliances, lighting and space cooling dominate demand, while the weight of space heating and cooking declines. The importance of developing countries increases and electricity becomes the main energy carrier. Our results are of high relevance for climate mitigation studies as they create detailed baselines that define the mitigation challenge: the stress on the energy supply system stemming from buildings will grow, though mainly in the form of electricity for which a number of options to decrease GHG emissions exist

The CO2 reduction potential for the Europeanindustry via direct electrification of heat supply(power-to-heat)

The decarbonisation of industry is a bottleneck for the EU's 2050 target of climate neutrality. Replacing fossil fuels with low-carbon electricity is at the core of this challenge; however, the aggregate electrification potential and resulting system-wide CO2 reductions for diverse industrial processes are unknown. Here, we present the results from a comprehensive bottom-up analysis of the energy use in 11 industrial sectors (accounting for 92% of Europe's industry CO2 emissions), and estimate the technological potential for industry electrification in three stages. Seventy-eight per cent of the energy demand is electrifiable with technologies that are already established, while 99% electrification can be achieved with the addition of technologies currently under development. Such a deep electrification reduces CO2 emissions already based on the carbon intensity of today's electricity (∼300 gCO2 kWhel-1). With an increasing decarbonisation of the power sector IEA: 12 gCO2 kWhel-1 in 2050), electrification could cut CO2 emissions by 78%, and almost entirely abate the energy-related CO2 emissions, reducing the industry bottleneck to only residual process emissions. Despite its decarbonisation potential, the extent to which direct electrification will be deployed in industry remains uncertain and depends on the relative cost of electric technologies compared to other low-carbon options

Enhancing global climate policy ambition towards a 1.5 °C stabilization: a short-term multi-model assessment

The Paris Agreement is a milestone in international climate policy as it establishes a global mitigation framework towards 2030 and sets the ground for a potential 1.5 °C climate stabilization. To provide useful insights for the 2018 UNFCCC Talanoa facilitative dialogue, we use eight state-of-the-art climate-energy-economy models to assess the effectiveness of the Intended Nationally Determined Contributions (INDCs) in meeting high probability 1.5 and 2 °C stabilization goals. We estimate that the implementation of conditional INDCs in 2030 leaves an emissions gap from least cost 2 °C and 1.5 °C pathways for year 2030 equal to 15.6 (9.0–20.3) and 24.6 (18.5–29.0) GtCO2eq respectively. The immediate transition to a more efficient and low-carbon energy system is key to achieving the Paris goals. The decarbonization of the power supply sector delivers half of total CO2 emission reductions in all scenarios, primarily through high penetration of renewables and energy efficiency improvements. In combination with an increased electrification of final energy demand, low-carbon power supply is the main short-term abatement option. We find that the global macroeconomic cost of mitigation efforts does not reduce the 2020–2030 annual GDP growth rates in any model more than 0.1 percentage points in the INDC or 0.3 and 0.5 in the 2 °C and 1.5 °C scenarios respectively even without accounting for potential co-benefits and avoided climate damages. Accordingly, the median GDP reductions across all models in 2030 are 0.4%, 1.2% and 3.3% of reference GDP for each respective scenario. Costs go up with increasing mitigation efforts but a fragmented action, as implied by the INDCs, results in higher costs per unit of abated emissions. On a regional level, the cost distribution is different across scenarios while fossil fuel exporters see the highest GDP reductions in all INDC, 2 °C and 1.5 °C scenarios