The development of new renewable energy technologies is generally perceived as a critical factor in the fight against climate change. However, significant difficulties arise when estimating the ...future performance and costs of nascent technologies such as wave energy. Robust methods to estimate the commercial costs that emerging technologies may reach in the future are needed to inform decision-making. The aim of this paper is to increase the clarity, consistency, and utility of future cost estimates for emerging wave energy technologies. It proposes a novel three-step method: (1) using a combination of existing bottom-up and top-down approaches to derive the current cost breakdown; (2) assigning uncertainty ranges, depending on the estimation reliability then used, to derive the first-of-a-kind cost of the commercial technology; and (3) applying component-based learning rates to produce the LCOE of a mature technology using the upper bound from (2) to account for optimism bias. This novel method counters the human propensity toward over-optimism. Compared with state-of-the-art direct estimation approaches, it provides a tool that can be used to explore uncertainties and focus attention on the accuracy of cost estimates and potential learning from the early stage of technology development. Moreover, this approach delivers useful information to identify remaining technology challenges, concentrate innovation efforts, and collect evidence through testing activities.
Through an understanding of the conformational preferences of the polyketide natural product (-)-zampanolide, and the structural motifs that control these preferences, we developed a linear ...zampanolide analogue that exhibits potent cytotoxicity against cancer cell lines. This discovery provides a set of three structural handles for further structure-activity relationship (SAR) studies of this potent microtubule-stabilizing agent. Moreover, it provides additional evidence of the complex relationship between ligand preorganization, conformational flexibility, and biological potency. In contrast to medicinal chemistry dogma, these results demonstrate that increased overall conformational flexibility is not necessarily detrimental to protein binding affinity and biological activity.
We report a new strategy toward the synthesis of highly functionalized carbazoles via 2-(silyloxy)pentadienyl cation intermediates, which were generated upon ionization of vinyl-substituted ...α-hydroxy silyl enol ethers under Brønsted acid catalysis. These electrophilic species were found to readily undergo cascade reactions with substituted indoles to generate carbazole molecular scaffolds in good yields via a sequence of regioselective nucleophilic addition, followed by intramolecular dehydrative cyclization.
The purpose of this study was to evaluate the effect of sham surgery in a minimally invasive surgical model of permanent coronary artery occlusion used to generate myocardial infarction (MI) in mice. ...Adult male C57BL/6J mice (3-6 mo old) were divided into five groups: day (D) 0 (no surgical operation), D1 Sham, D1 MI, D7 Sham, and D7 MI. A refined MI surgery technique was used to approach the coronary artery without the ribs being cut. Both sham and MI mice had the left ventricle (LV) exposed through a small incision. To test the effects of surgery alone, the suture was passed around the coronary artery but not ligated. The MI mice were subjected to permanent coronary artery ligation. The mice were killed at D1 or D7 postsurgical procedure. Compared with D0 no surgery controls, the D1 and D7 sham groups exhibited no surgical mortality and similar necropsy and echocardiographic variables. Surgery alone did not induce an inflammatory cell response, as evidenced by the lack of leukocyte infiltration in the sham groups. Analysis of 165 inflammatory cytokines and extracellular matrix factors in sham revealed that a minor gene response was initiated but not translated to protein levels. Collagen deposition did not occur in the absence of MI. In contrast, the D1 and D7 MI groups showed the expected robust inflammatory and scar formation responses. When a minimally invasive procedure to generate MI in mice was used, the D0 (no surgical operation) control was an adequate replacement for the use of sham surgery groups.
The key market drivers for marine energy are to reduce carbon emissions, and improve the security and sustainability of supply. There are other technologies that also meet these requirements, and ...therefore the marine energy market is dependent on the technology being cost effective, and competitive. The potential UK wave and tidal stream energy market is assessed using ETI’s energy systems modelling environment (ESME) which uses a multi-vector approach including energy generation, demand, heat, transport, and infrastructure. This is used to identify scenarios where wave and tidal energy form part of the least-cost energy system for the UK by 2050, and will assess what Levelised Cost of Energy (LCOE) reductions are required to improve the commercialization rate. The results indicate that an installed capacity of 4.9 GW of wave and 2.5 GW of tidal stream could be deployed by 2050 if the LCOE is within 4.5 and 7 p/kWh for each respective technology. If there is a step reduction to the LCOE of wave energy, however, a similar capacity of 5 GW could be deployed by 2050 at a LCOE of 11 p/kWh.
An olefin‐assisted, palladium‐catalyzed oxidative alkynylation of enallenes for regio‐ and stereoselective synthesis of substituted trienynes has been developed. The reaction shows a broad substrate ...scope and good tolerance for various functional groups on the allene moiety, including carboxylic acid esters, free hydroxyls, imides, and alkyl groups. Also, a wide range of terminal alkynes with electron‐donating and electron‐withdrawing aryls, heteroaryls, alkyls, trimethylsilyl, and free hydroxyl groups are tolerated.
Highly selective palladium‐catalyzed oxidative alkynylation of enallenes has been developed, affording regio‐ and stereoselectively substituted trienynes. The reaction shows a broad substrate scope with good tolerance for various functional groups on the enallene and the terminal alkyne.
Understanding and supporting learning for different emerging low carbon energy supply technology fields is a key issue for policymakers, investors and researchers. A range of contrasting analytical ...approaches are available: energy system modelling using learning rates provides abstracted, quantitative and output oriented accounts, while innovation studies research offers contextualised, qualitative and process oriented accounts. Drawing on research literature and expert consultation on learning for several different emerging energy supply technologies, this paper introduces a ‘learning pathways’ matrix to help bridge between the rich contextualisation of innovation studies and the systematic comparability of learning rates. The learning pathways matrix characterises technology fields by their relative orientation to radical or incremental innovation, and to concentrated or distributed organisation. A number of archetypal learning pathways are outlined to help learning rates analyses draw on innovation studies research, so as to better acknowledge the different niche origins and learning dynamics of emerging energy supply technologies. Finally, a future research agenda is outlined, based on socio-technical learning scenarios for accelerated energy innovation.
An olefin-assisted, palladium-catalyzed oxidative alkynylation of enallenes for regio- and stereoselective synthesis of substituted trienynes has been developed. The reaction shows a broad substrate ...scope and good tolerance for various functional groups on the allene moiety, including carboxylic acid esters, free hydroxyls, imides, and alkyl groups. Also, a wide range of terminal alkynes with electron-donating and electron-withdrawing aryls, heteroaryls, alkyls, trimethylsilyl, and free hydroxyl groups are tolerated.
This report describes Brønsted acid catalyzed de novo synthesis of silyldienol ethers bearing tetrasubstituted double bonds via an intermediacy of 2-silyloxypentadienyl cations. The reactivity of ...these novel cationic intermediates could be modulated and harnessed toward direct nucleophilic additions regioselectively at the γ-position to produce highly functionalized silyldienol ethers with tunable control of the resulting double bond geometry.
Zampanolide and dactylolide are microtubule-stabilizing polyketides possessing potent cytotoxicity towards a variety of cancer cell lines. Using our understanding of the conformational preferences of ...the macrolide core in both natural products, we hypothesized that analogues lacking the C17-methyl group would maintain the necessary conformation for bioactivity while reducing the number of synthetic manipulations necessary for their synthesis. Analogues
3
,
4
and
5
were prepared
via
total synthesis, and their conformational preferences were determined through computational and high-field NMR studies. While no observable activities were present in dactylolide analogues
3
and
4
, zampanolide analogue
5
exhibited sub-micromolar cytotoxicity. Herein, we describe these efforts towards understanding the structure- and conformation-activity relationships of dactylolide and zampanolide.
Zampanolide and dactylolide are microtubule-stabilizing polyketides possessing potent cytotoxicity towards a variety of cancer cell lines.
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