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The risk of the use of toxic chemicals for unlawful acts has been a matter of concern for different governments and multilateral agencies. The Organisation for the Prohibition of Chemical Weapons (OPCW), which oversees the implementation of the Chemical Weapons Convention (CWC), considering recent events employing chemical warfare agents as means of assassination, has recently included in the CWC “Annex on Chemicals” some organophosphorus compounds that are regarded as acting in a similar fashion to the classical G- and V-series of nerve agents, inhibiting the pivotal enzyme acetylcholinesterase. Therefore, knowledge of the activity of the pyridinium oximes, the sole class of clinically available acetylcholinesterase reactivators to date, is plainly justified. In this paper, continuing our research efforts in medicinal chemistry on this class of toxic chemicals, we synthesized an A-230 nerve agent surrogate and applied a modified Ellman’s assay to evaluate its ability to inhibit our enzymatic model, acetylcholinesterase from Electrophorus eel, and if the clinically available antidotes are able to rescue the enzyme activity for the purpose of relating the findings to the previously disclosed in silico data for the authentic nerve agent and other studies with similar A-series surrogates. Our experimental data indicates that pralidoxime is the most efficient compound for reactivating acetylcholinesterase inhibited by A-230 surrogate, which is the opposite of the in silico data previously disclosed.

The misuse of novichok agents in assassination attempts has been reported in the international media since 2018. These relatively new class of neurotoxic agents is claimed to be more toxic than the agents of the G and V series and so far, there is no report yet in literature about potential antidotes against them. To shed some light into this issue, we report here the design and synthesis of NTMGMP, a surrogate of A-242 and also the first surrogate of a novichok agent useful for experimental evaluation of antidotes. Furthermore, the efficiency of the current commercial oximes to reactivate NTMGMP-inhibited acetylcholinesterase (AChE) was evaluated. The Ellman test was used to confirm the complete inhibition of AChE, and to compare the subsequent rates of reactivation in vitro as well as to evaluate aging. In parallel, molecular docking, molecular dynamics and MM-PBSA studies were performed on a computational model of the human AChE ( Hss AChE)/NTMGMP complex to assess the reactivation performances of the commercial oximes in silico. Experimental and theoretical studies matched the exact hierarchy of efficiency and pointed to trimedoxime as the most promising commercial oxime for reactivation of AChE inhibited by A-242.

Casualties caused by organophosphorus pesticides are a burden for health systems in developing and poor countries. Such compounds are potent acetylcholinesterase irreversible inhibitors, and share the toxic profile with nerve agents. Pyridinium oximes are the only clinically available antidotes against poisoning by these substances, but their poor penetration into the blood-brain barrier hampers the efficient enzyme reactivation at the central nervous system. In searching for structural factors that may be explored in future SAR studies, we evaluated neutral aryloximes as reactivators for paraoxon-inhibited Electrophorus eel acetylcholinesterase. Our findings may result into lead compounds, useful for development of more active compounds for emergencies and supportive care.

Understanding layer interplay is the key to utilizing layered heterostructures formed by the stacking of different two-dimensional materials for device applications. Boron nitride has been demonstrated to be an ideal substrate on which to build graphene devices with improved mobilities. Here we present studies on the morphology and optical response of annealed few-layer hexagonal boron nitride flakes deposited on a silicon substrate that reveal the formation of linear wrinkles along well-defined crystallographic directions. The wrinkles formed a network of primarily threefold and occasionally fourfold origami-type junctions throughout the sample, and all threefold junctions and wrinkles formed along the armchair crystallographic direction. Furthermore, molecular dynamics simulations yielded, through spontaneous symmetry breaking, wrinkle junction morphologies that are consistent with both the experimental results and the proposed origami-folding model. Our findings indicate that this morphology may be a general feature of several two-dimensional materials under proper stress-strain conditions, resulting in direct consequences in device strain engineering.

Extensive ecosystem restoration is increasingly seen as being central to conserving biodiversity 1 and stabilizing the climate of the Earth 2 . Although ambitious national and global targets have been set, global priority areas that account for spatial variation in benefits and costs have yet to be identified. Here we develop and apply a multicriteria optimization approach that identifies priority areas for restoration across all terrestrial biomes, and estimates their benefits and costs. We find that restoring 15% of converted lands in priority areas could avoid 60% of expected extinctions while sequestering 299 gigatonnes of CO 2 —30% of the total CO 2 increase in the atmosphere, or 14% of total emissions, since the Industrial Revolution. The inclusion of several biomes is key to achieving multiple benefits. Cost effectiveness can increase up to 13-fold when spatial allocation is optimized using our multicriteria approach, which highlights the importance of spatial planning. Our results confirm the vast potential contributions of restoration to addressing global challenges, while underscoring the necessity of pursuing these goals synergistically. Multicriteria optimization identifies global priority areas for ecosystem restoration and estimates their benefits for biodiversity and climate, providing cost–benefit analyses that highlight the importance of optimizing spatial planning and incorporating several biomes in restoration strategies.

Background: Dropout in higher education is a concern for students, families, educational institutions, and society. Tertiary education is an important mechanism for empowering people and STEM courses are vital to countries' development. Method: The study combined quantitative and qualitative data. Step 1 was an analysis of personal and contextual variables in a comprehensive examination of dropout in a sample of 1,016 engineering students. In step 2 a short interview by telephone were conducted with 82 students who dropped out, identifying their reasons and their academic/professional situation. In step 3 in-depth interviews were conducted with six students in order to understand the dynamic process of their decisions to leave. Results: The academic/professional situations of students who dropped out were quite varied, for example the same course or a different course at another institution, starting a job, not working or studying, or attending another level of professional training. There were three main reasons for dropping: vocational, learning process and achievement, and reconciling roles. Conclusions: Engineering student dropout is related to vocational and academic achievement. This should be considered in the implementation of programs to reduce the rate of dropout. Keywords: Higher education; engineering students; academic dropout; first-year students; academic trajectories. Abandono Universitario en Ingenieria: Motivos y Trayectorias de los Estudiantes. Antecedentes: la desercion en la educacion superior es una preocupacion para los estudiantes, las familias, las instituciones educativas y la sociedad. La educacion terciaria es un mecanismo importante para el empoderamiento de las personas, y los cursos STEM son vitales para el desarrollo de los paises. Metodo: estudio que combina datos cuantitativos y cualitativos. En el paso 1 analizamos variables personales y contextuales y la desercion de 1.016 estudiantes de ingenieria. En el paso 2 se realizd una breve entrevista telefonica a 82 estudiantes que desertaron, identificando sus motivos y situacion academica/profesional. En el paso 3 se realizaron entrevistas en profundidad a seis estudiantes para comprender el proceso dinamico de decision de abandonar. Resultados: la situacion academica/profesional de los estudiantes que desertaron es bastante diferente, por ejemplo cursar la misma o otra carrera en otra institucion, empezar trabajando, no trabajar ni estudiar y cursar otro nivel de formacion profesional. Los estudiantes informaron tres razones principales para la desercion: vocacional, proceso de aprendizaje y logro, y reconciliacion de roles. Conclusiones: la desercion de los estudiantes de ingenieria esta relacionada con el rendimiento academico y vocacional. Esto debe tenerse en cuenta en la implementacion de programas para reducir la desercion. Palabras clave: educacion superior; estudiantes de ingenieria; desercion academica; estudiantes de primer ano; trayectorias academicas.

University dropout is a phenomenon that is a concern in many countries all over the world. However, although there are studies in which the direct relationship of the personal and contextual variables is observed individually to predict dropout, there is little research to know whether any of these variables mediate each other in a more dynamic and complex model. Thus, the objective of this study was to analyze the extent to which the intention to drop out of university courses is predicted by (i) satisfaction and expectations with the course, (ii) engagement with the course, and (iii) by the use of Self-Regulated Learning (SRL) strategies. Eight hundred and seventy-seven students from two Spanish universities completed the CARE questionnaire. Path analyses were performed using Mplus 8.3. The data obtained indicate that the intention to drop out is directly and significantly explained by students´ engagement (in 17.8%) and indirectly explained by the use of SRL strategies through engagement. Changes in engagement and in the use of SRL strategies were seen to be associated with satisfaction. Finally, the effect of satisfaction and the use of SRL strategies explained a proportion of students’ engagement (53.6%). It is important for research or interventions focused on students’ intention to drop out to understand that there are multiple variables that both directly and indirectly influence those intentions.

International commitments for ecosystem restoration add up to one-quarter of the world’s arable land. Fulfilling them would ease global challenges such as climate change and biodiversity decline but could displace food production and impose financial costs on farmers. Here, we present a restoration prioritization approach capable of revealing these synergies and trade-offs, incorporating ecological and economic efficiencies of scale and modelling specific policy options. Using an actual large-scale restoration target of the Atlantic Forest hotspot, we show that our approach can deliver an eightfold increase in cost-effectiveness for biodiversity conservation compared with a baseline of non-systematic restoration. A compromise solution avoids 26% of the biome’s current extinction debt of 2,864 plant and animal species (an increase of 257% compared with the baseline). Moreover, this solution sequesters 1 billion tonnes of CO 2 -equivalent (a 105% increase) while reducing costs by US$28 billion (a 57% decrease). Seizing similar opportunities elsewhere would offer substantial contributions to some of the greatest challenges for humankind. A restoration prioritization approach applied to the Brazilian Atlantic Forest biodiversity hotspot considers 362 scenarios for synergies and trade-offs between ecological and economic costs, benefits and scales.

Brazil has a monitoring system to track annual forest conversion in the Amazon and most recently to monitor the Cerrado biome. However, there is still a gap of annual land use and land cover (LULC) information in all Brazilian biomes in the country. Existing countrywide efforts to map land use and land cover lack regularly updates and high spatial resolution time-series data to better understand historical land use and land cover dynamics, and the subsequent impacts in the country biomes. In this study, we described a novel approach and the results achieved by a multi-disciplinary network called MapBiomas to reconstruct annual land use and land cover information between 1985 and 2017 for Brazil, based on random forest applied to Landsat archive using Google Earth Engine. We mapped five major classes: forest, non-forest natural formation, farming, non-vegetated areas, and water. These classes were broken into two sub-classification levels leading to the most comprehensive and detailed mapping for the country at a 30 m pixel resolution. The average overall accuracy of the land use and land cover time-series, based on a stratified random sample of 75,000 pixel locations, was 89% ranging from 73 to 95% in the biomes. The 33 years of LULC change data series revealed that Brazil lost 71 Mha of natural vegetation, mostly to cattle ranching and agriculture activities. Pasture expanded by 46% from 1985 to 2017, and agriculture by 172%, mostly replacing old pasture fields. We also identified that 86 Mha of the converted native vegetation was undergoing some level of regrowth. Several applications of the MapBiomas dataset are underway, suggesting that reconstructing historical land use and land cover change maps is useful for advancing the science and to guide social, economic and environmental policy decision-making processes in Brazil.