B(OCH2CF3)3-mediated direct amidation of pharmaceutically relevant building blocks in cyclopentyl methyl ether

The use of B(OCH2CF3)3 for mediating direct amidation reactions of a wide range of pharmaceutically relevant carboxylic acids and amines is described, including numerous heterocycle-containing examples. An initial screen of solvents for the direct amidation reaction suggested that cyclopentyl methyl ether, a solvent with a very good safety profile suitable for use over a wide temperature range, was an excellent replacement for the previously used solvent acetonitrile. Under these conditions amides could be prepared from 18 of the 21 carboxylic acids and 18 of the 21 amines examined. Further optimisation of one of the low yielding amidation reactions (36% yield) via a design of experiments approach enabled an 84% yield of the amide to be obtained

The application of design of experiments (DoE) reaction optimisation and solvent selection in the development of new synthetic chemistry

This article outlines the benefits of using 'Design of Experiments' (DoE) optimisation during the development of new synthetic methodology. A particularly important factor in the development of new chemical reactions is the choice of solvent which can often drastically alter the efficiency and selectivity of a process. Whilst solvent optimisation is usually done in a non-systematic way based upon a chemist's intuition and previous laboratory experience, we illustrate how optimisation of the solvent for a reaction can be carried out by using a 'map of solvent space' in a DoE optimisation. A new solvent map has been developed specifically for optimisation of new chemical reactions using principle component analysis (PCA) incorporating 136 solvents with a wide range of properties. The new solvent map has been used to identify safer alternatives to toxic/hazardous solvents, and also in the optimisation of an SNAr reaction

Designing of space oriented body parts with the use of modern technologies

Proper selection of the gating system for investment pattern is a long and labor-intensive process that requires significant resources. The latest design technologies enable the calculation of the gating system and simulation of the casting process based on these calculations. Simulation and calculation of the gating system make it possible to determine defects which occur during the casting process at the design stage. The result of simulation is the distribution of flow and temperature velocity vectors. The process of cooling and crystallization is simulated, as well as a mold filling process. Analyzing these data and changing the characteristics of the gating system, it is possible to achieve the very high quality of castings

Phylogenetic Codivergence Supports Coevolution of Mimetic Heliconius Butterflies

The unpalatable and warning-patterned butterflies _Heliconius erato_ and _Heliconius melpomene_ provide the best studied example of mutualistic Müllerian mimicry, thought – but rarely demonstrated – to promote coevolution. Some of the strongest available evidence for coevolution comes from phylogenetic codivergence, the parallel divergence of ecologically associated lineages. Early evolutionary reconstructions suggested codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and this was initially hailed as the most striking known case of coevolution. However, subsequent molecular phylogenetic analyses found discrepancies in phylogenetic branching patterns and timing (topological and temporal incongruence) that argued against codivergence. We present the first explicit cophylogenetic test of codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and re-examine the timing of these radiations. We find statistically significant topological congruence between multilocus coalescent population phylogenies of _H. erato_ and _H. melpomene_, supporting repeated codivergence of mimetic populations. Divergence time estimates, based on a Bayesian coalescent model, suggest that the evolutionary radiations of _H. erato_ and _H. melpomene_ occurred over the same time period, and are compatible with a series of temporally congruent codivergence events. This evidence supports a history of reciprocal coevolution between Müllerian co-mimics characterised by phylogenetic codivergence and parallel phenotypic change

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Paving (through) Amazonia: Neoliberal Urbanism and the Reperipheralization of Roraima

This paper examines the neoliberal reshaping of infrastructure provision in Brazil's extreme north since the mid-1990s, when roadway investments resulted in unprecedented regional connectivity. The BR-174 upgrade, the era's most important project, marked a transition from resource-based developmentalism to free-market transnationalism. Primarily concerned with urban competitiveness, the federal government funded the trunk roadway's paving to facilitate manufacturing exports from Manaus. While an effort was made to minimize deforestation, planners sidelined development implications in adjacent Roraima. The state's urban system has thus experienced reperipheralization and intensified primacy. Market-led growth now compounds the inheritance of hierarchical centralism and ongoing governmental neglect. Our study shows a vast territory dependent on primate cities for basic goods and services. Travelling with Roraimans from bypassed towns, we detected long-distance passenger transportation and surface logistics with selective routes. Heterogeneous Roraiman (im)mobilities comprise middle-class tourism and heightened consumerism as well as informal mobility tactics and transnational circulations of precarious labor. The paper exhorts neoliberal urbanism research to look beyond both Euro America's metropoles and their Global South counterparts. Urbanization dynamics in Brazil's extreme north demonstrate that market-disciplined investments to globalize cities produce far-reaching spatial effects. These are felt even by functionally-articulated-yet-marginalized peripheries in ostensibly remote locations

Exploring subtle land use and land cover changes: a framework for future landscape studies

UMR AMAP, équipe 3International audienceLand cover and land use changes can have a wide variety of ecological effects, including significant impacts on soils and water quality. In rural areas, even subtle changes in farming practices can affect landscape features and functions, and consequently the environment. Fine-scale analyses have to be performed to better understand the land cover change processes. At the same time, models of land cover change have to be developed in order to anticipate where changes are more likely to occur next. Such predictive information is essential to propose and implement sustainable and efficient environmental policies. Future landscape studies can provide a framework to forecast how land use and land cover changes is likely to react differently to subtle changes. This paper proposes a four step framework to forecast landscape futures at fine scales by coupling scenarios and landscape modelling approaches. This methodology has been tested on two contrasting agricultural landscapes located in the United States and France, to identify possible landscape changes based on forecasting and backcasting agriculture intensification scenarios. Both examples demonstrate that relatively subtle land cover and land use changes can have a large impact on future landscapes. Results highlight how such subtle changes have to be considered in term of quantity, location, and frequency of land use and land cover to appropriately assess environmental impacts on water pollution (France) and soil erosion (US). The results highlight opportunities for improvements in landscape modelling

A meta-analysis and critical review of prospective memory in autism spectrum disorder

Prospective memory (PM) is the ability to remember to carry out a planned intention at an appropriate moment in the future. Research on PM in ASD has produced mixed results. We aimed to establish the extent to which two types of PM (event-based/time-based) are impaired in ASD. In part 1, a meta-analysis of all existing studies indicates a large impairment of time-based, but only a small impairment of event-based, PM in ASD. In Part 2, a critical review concludes that time-based PM appears diminished in ASD, in line with the meta-analysis, but that caution should be taken when interpreting event-based PM findings, given potential methodological limitations of several studies. Clinical implications and directions for future research are discussed

Guidelines for autopsy investigation of sudden cardiac death: 2017 update from the Association for European Cardiovascular Pathology.

Although sudden cardiac death (SCD) is one of the most important modes of death in Western countries, pathologists and public health physicians have not given this problem the attention it deserves. New methods of preventing potentially fatal arrhythmias have been developed and the accurate diagnosis of the causes of SCD is now of particular importance. Pathologists are responsible for determining the precise cause and mechanism of sudden death but there is still considerable variation in the way in which they approach this increasingly complex task. The Association for European Cardiovascular Pathology has developed these guidelines, which represent the minimum standard that is required in the routine autopsy practice for the adequate investigation of SCD. The present version is an update of our original article, published 10 years ago. This is necessary because of our increased understanding of the genetics of cardiovascular diseases, the availability of new diagnostic methods, and the experience we have gained from the routine use of the original guidelines. The updated guidelines include a detailed protocol for the examination of the heart and recommendations for the selection of histological blocks and appropriate material for toxicology, microbiology, biochemistry, and molecular investigation. Our recommendations apply to university medical centers, regionals hospitals, and all healthcare professionals practicing pathology and forensic medicine. We believe that their adoption throughout Europe will improve the standards of autopsy practice, allow meaningful comparisons between different communities and regions, and permit the identification of emerging patterns of diseases causing SCD. Finally, we recommend the development of regional multidisciplinary networks of cardiologists, geneticists, and pathologists. Their role will be to facilitate the identification of index cases with a genetic basis, to screen appropriate family members, and ensure that appropriate preventive strategies are implemented

Effects of episodic future thinking and self-projection on children’s prospective memory performance

The present study is the first to investigate the benefits of episodic future thinking (EFT) at encoding on prospective memory (PM) in preschool (age: M = 66.34 months, SD = 3.28)and primary school children (age: M = 88.36 months, SD = 3.12). A second aim was to examine if self-projection influences the possible effects of EFT instructions. PM was assessed using a standard PM paradigm in children with a picture-naming task as the ongoing activity in which the PM task was embedded. Further, two first- and two second-order ToM tasks were administered as indicator of children’s self-projection abilities. Forty-one preschoolers and 39 school-aged children were recruited. Half of the participants in each age group were instructed to use EFT as a strategy to encode the PM task, while the others received standard PM instructions. Results revealed a significant age effect, with school-aged children significantly outperforming preschoolers and a significant effect of encoding condition with overall better performance when receiving EFT instructions compared to the standard encoding condition. Even though the interaction between age group and encoding condition was not significant, planned comparisons revealed first evidence that compared to the younger age group, older children’s PM benefited more from EFT instructions during intention encoding. Moreover, results showed that although self-projection had a significant impact on PM performance, it did not influence the effects of EFT instructions. Overall, results indicate that children can use EFT encoding strategies to improve their PM performance once EFT abilities are sufficiently developed. Further, they provide first evidence that in addition to executive functions, which have already been shown to influence the development of PM across childhood, self-projection seems to be another key mechanism underlying this development