The diastereofacial selectivity of the addition of various 1-metalated 1-heptynes to substituted cyclopentanecarbaldehydes. – The use of 1-titanated 1-heptyne for the construction of the alkyl side chain of Prostaglandins

A highly diastereoselective addition of 1-heptyne to substituted cyclopentanecarbaldehydes is one of the indispensable prerequisites to the construction of the (S)-3-hydroxy-1(E)-octenyl side chain of prostaglandins by palladium(II)-catalyzed [3,3]-sigmatropic rearrangement of allylic acetates. It was found that 1-titanated 1-heptynes afford the Cram product at best with a diastereofacial selectivity of 92.5%. The corresponding lithium and magnesium compounds are less diastereoselective.     

Airway Delivery of Hydrogel-Encapsulated Niclosamide for the Treatment of Inflammatory Airway Disease

Repurposing of the anthelminthic drug niclosamide was proposed as an effective treatment for inflammatory airway diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease. Niclosamide may also be effective for the treatment of viral respiratory infections, such as SARS-CoV-2, respiratory syncytial virus, and influenza. While systemic application of niclosamide may lead to unwanted side effects, local administration via aerosol may circumvent these problems, particularly when the drug is encapsulated into small polyethylene glycol (PEG) hydrospheres. In the present study, we examined whether PEG-encapsulated niclosamide inhibits the production of mucus and affects the pro-inflammatory mediator CLCA1 in mouse airways in vivo, while effects on mucociliary clearance were assessed in excised mouse tracheas. The potential of encapsulated niclosamide to inhibit TMEM16A whole-cell Cl⁻ currents and intracellular Ca²⁺ signalling was assessed in airway epithelial cells in vitro. We achieved encapsulation of niclosamide in PEG-microspheres and PEG-nanospheres (Niclo-spheres). When applied to asthmatic mice via intratracheal instillation, Niclo-spheres strongly attenuated overproduction of mucus, inhibited secretion of the major proinflammatory mediator CLCA1, and improved mucociliary clearance in tracheas ex vivo. These effects were comparable for niclosamide encapsulated in PEG-nanospheres and PEG-microspheres. Niclo-spheres inhibited the Ca²⁺ activated Cl⁻ channel TMEM16A and attenuated mucus production in CFBE and Calu-3 human airway epithelial cells. Both inhibitory effects were explained by a pronounced inhibition of intracellular Ca²⁺ signals. The data indicate that poorly dissolvable compounds such as niclosamide can be encapsulated in PEG-microspheres/nanospheres and deposited locally on the airway epithelium as encapsulated drugs, which may be advantageous over systemic application.     

Sustainability of biofuels in Latin America: Risks and opportunities

Several Latin American countries are setting up biofuel programmes to establish alternative markets for agricultural commodities. This is mainly triggered by the current success of Brazilian bioethanol production for the domestic market and for export. Furthermore, the global biofuel market is expected to increase due to ambitious biofuel programmes in the EU and in the USA. Colombia, Venezuela, Costa Rica and Guatemala are focusing on bioethanol production from sugarcane whereas biofuel production in Argentina is based on soy biodiesel. Recent developments of the biofuel sector take place extremely rapid especially in Argentina, which became one of the five largest biodiesel producers in the world in 2008. Till date no specific biofuel sustainability certification systems have been implemented in Latin American, as well as on global level. This fact and the predominant use of food crops for biofuel production raise concerns about the sustainability of biofuel production related to environmental and social aspects. This paper provides an overview of the hotspots of conflicts in biofuel production in Latin America. It investigates presently available sustainability tools and initiatives to ensure sustainable biofuel production in Latin America. Finally, it provides an outlook on how to integrate sustainability in the Latin American biofuel sector.     

Progress in the Synthesis of Nanocrystalline BaTiO3 Powders for MLCC

Future improvements in the development of highly volume-efficient multilayer ceramic capacitors (MLCC) require manufacturing processes that allow for a reduced dielectric thickness well below 1 μm. Obviously, such thin dielectric layers can only be produced if nanosized dielectric powders are applied and deposited by techniques more advanced than tape casting and screen printing. These processes require high-purity, homogeneous, weakly agglomerated ultrafine powders. Over the past few years, significant progress has been made in the synthesis of nanocrystalline BaTiO₃-based powders for use in MLCC. The present review article aims to summarize the present state of the art with respect to some of the technically and industrially most relevant preparation routes, including methods based on solid-state reactions and, more importantly, solution-based approaches.     

21世纪城市设计和开放空间规划中的浪漫主义精神

人类文明发展史上每一次价值观的改变,都会引起新的城市设计和开放空间规划思想和手法的产生.1 8世纪浪漫主义思想的产生,是文化思想发展史上一次重要的转折,它对同时期的景观设计领域,也产生了重要的影响.以往的园林,代表的是内部实体与外在形式创造性的统一,而21世纪的景观设计语言,必须为人与人之间或人与自然之间的相互关系,提供现实主义层面的反映.浪漫主义,是对应于21世纪人类价值观的设计思想和手法的一个探索性回答.     

Extraction of heavy metals from soils using biodegradable chelating agents

Metal pollution of soils is widespread across the globe, and the clean up of these soils is a difficulttask. One possible remediation technique is ex-situ soil washing using chelating agents. Ethylenediaminetetraacetic acid (EDTA) is a very effective chelating agent for this purpose but has the disadvantage that it is quite persistent in the environment due to its low biodegradability. The aim of our work was to investigate the biodegradable chelating agents [S,S]-ethylenediaminedisuccinic acid (EDDS), iminodisuccinic acid (IDSA), methylglycine diacetic acid (MGDA), and nitrilotriacetic acid (NTA) as potential alternatives and compare them with EDTA for effectiveness. Kinetic experiments showed for all metals and soils that 24 h was the optimum extraction time. Longer times only gave minor additional benefits for heavy metal extraction but an unwanted increase in iron mobilization. For Cu at pH 7, the order of the extraction efficiency for equimolar ratios of chelating agent to metal was EDDS > NTA> IDSA > MGDA > EDTA and for Zn it was NTA > EDDS > EDTA >MGDA > IDSA. The comparatively low efficiency of EDTA resulted from competition between the heavy metals and co-extracted Ca. For Pb the order of extraction was EDTA > NTA >EDDS due to the much stronger complexation of Pb by EDTA compared to EDDS. At higher concentration of complexing agent, less difference between the agents was found and less pH dependence. There was an increase in heavy metal extraction with decreasing pH, but this was offset by an increase in Ca and Fe extraction. In sequential extractions EDDS extracted metals almost exclusively from the exchangeable, mobile, and Mn-oxide fractions. We conclude that the extraction with EDDS at pH 7 showed the best compromise between extraction efficiency for Cu, Zn, and Pb and loss of Ca and Fe from the soil.     

Dishwashing behaviour of European consumers with regard to the acceptance of long programme cycles

Since the introduction of the energy label for household dishwashers in the EU, manufacturers have been incentivised to reduce resource consumption and increase the energy efficiency of their appliances. Technological progress has led to very efficient programmes with cleaning cycles of 3 to 4 h or longer. The European Commission recently initiated a revision of the energy label and Ecodesign requirements, leading to their adjustment to the state of the art and to actual usage patterns. The University of Bonn was tasked with investigating dishwashing habits in Europe. An online survey was conducted in 11 countries of the EU with more than 5000 participants. The survey focused on the choice of programme, attitudes towards energy-saving programmes and practices and the willingness to apply them. It appears that consumers are willing to apply energy-saving practices and to use energy-saving programmes, but the acceptance of long cycles that take more than 2 h is low, which stands in contradiction to the fact that 19% of all dishwashing cycles are run in the Eco programme, which takes more than 2 h in most cases. The percentage of people who understand that long cycles can be energy-efficient is smaller than the percentage of those who do not believe this. The statements of the participants are contradictory regarding the importance of saving energy and of programme duration. The results of the survey point out the importance of better consumer education and better communication by manufacturers, consumer organisations and legislation.     

Patent families as macro level patent value indicators: applying weights to account for market differences

This paper introduces a methodology for the construction of a country level patent value indicator based on the family size of a country’s patent profile at the level of technology fields. Because individual family members target different markets and technologies have a different propensity to internationalization, family size has been shown to have a restricted power to assess the quality of patent profiles of countries. We address this gap by weighting the members of patent families filed at different patent offices before calculating the family size indicators, to account for the market potential in which the patents of these families were filed. We apply different weighting schemes and test which scheme is best able to explain the export performance of countries. In order to conduct our analyses, a panel dataset, consisting of annual data (1990–2002) on international trade from the UN-COMTRADE database and patent data from the “EPO Worldwide Patent Statistical Database” (PATSTAT), was compiled. Several bivariate analyses reveal that weighted and unweighted family counts are highly correlated, meaning that statistics based on absolute (weighted or unweighted) family counts are barely affected by the chosen weighting factor. This, however, is different when using the average family size, where weighting the family members by imports, as well as GDP, can be shown to have a robust positive effect to explaining export performance. The imports and the GDP weighted average family size are thus able to act as a consistent indicator of patent value at the country and technology field level.     

INDUCTIVE LEARNING FOR PARAMETER OPTIMIZATION

Optimization of simulation model output is one of the most important tasks in a simulation study of a complex system. Efficacy of an optimization approach is expressed in the accuracy of locating a global extremum, as well as in the number of investigated search points. The approach Machine Learning Optimization (ML-Opt), presented in this article, explores functional dependencies between search points in order to reduce the number of evaluations. Functional relations between search points are determined by an inductive learning algorithm, which generates a classifier used as a control structure in the optimization process. The classifier approximates the structure of the unknown goal function given by a simulation model and affects the generation of new search points. A discussion of a numerical example concludes the paper.