Sustainability of water transfer projects: A systematic review.

Inter-basin water transfer projects (IBTs) have significantly increased in number in recent decades due to the unremitting need to solve the problem of global water imbalance. However, given the complex challenges inherent in implementing and maintaining IBTs, there is a need to characterize the multi-faceted aspects of sustainability (or unsustainability) that result from these megaprojects. Through a systematic review of the literature, we sought to identify and characterize the positive and negative impacts that most often influence the sustainability of IBTs, focusing on impacts within the environmental, social, and economic pillars of sustainability. Based on an eligibility criterion, the systematic review selected 68 documents out of an initial total of 1567 for information quality analysis and content evaluation. The qualitative coding of the documents allowed us to characterize the landscape of impacts that result from IBTs across the three pillars of sustainability. The study findings revealed that the most frequently coded positive impacts related to the environmental pillar of sustainability, while the most frequently coded negative impacts related to both social and environmental pillars. In addition, the most frequently coded positive impact overall related to the economic benefits generated by the IBTs. Through a critical analysis of the study findings, we provide an assessment of future IBTs with a focus on the UN sustainable development goals.

Oxygen use in Atacama large millimeter and submillimeter (ALMA) arrays in Chajnantor valley at 5050 m / Uso de oxígeno en Atacama large millimeter and submillimeter (ALMA) en el valle de Chajnantor a 5050 m

The Chilean workforce has over 200,000 people that are intermittently exposed to altitudes over 4000 m. In 2012, the Ministry of Health provided a technical guide for high altitude workers that included a series of actions to mitigate the effects of hypoxia. Previous studies have shown the positive effect of oxygen enrichment at high altitudes. The Atacama Large Millimeter / submillimeter Arrays (ALMA) radiotelescope operate at 5,050 m (Array Operation Site, AOS) and is the only place in the world where Pressure Swing Adsorption (PSA) and Liquid Oxygen technologies have been installed at a large scale. Here we discuss our experience using oxygen supplementation at ALMA, to prevent the malaise and/or risks associated with exposure at 5,050 m. Antenna operators experienced chronic intermittent hypobaric hypoxia (CIHH, shiftwork 8 days HA*6 days rest SL) over 4 years. Studies to define normal O2 saturation values were performed in OSF and AOS by continuous recording during the shift. The outcomes showed no differences between production procedures (PSA or Liquid oxygen) in regulating oxygen availability at AOS facilities. As a result, big-scale installations have difficulties reaching the appropriate oxygen concentration due to leaks in high mobility areas. In addition, the PSA plant requires adequation and maintenance to operate at a very high altitude.

La fuerza laboral chilena cuenta con más de 200.000 personas que están expuestas intermitentemente a altitudes superiores a los 4000 m. En 2012, el Ministerio de Salud entregó una guía técnica para trabajadores de altura que incluía una serie de acciones para mitigar los efectos de la hipoxia. Estudios anteriores han demostrado el efecto positivo del enriquecimiento de oxígeno en altitudes elevadas. El radiotelescopio Atacama Large Millimeter/submillimeter Arrays (ALMA) opera a 5.050 m (Array Operation Site, AOS) y es el único lugar en el mundo donde se han instalado tecnologías de adsorción por cambio de presión (PSA) y oxígeno líquido a gran escala. Aquí discutimos nuestra experiencia usando suplementos de oxígeno en ALMA, para prevenir el malestar y/o los riesgos asociados con la exposición a 5.050 m. Los operadores de antena experimentaron hipoxia hipobárica intermitente crónica (CIHH, trabajo por turnos 8 días HA*6 días descanso SL) durante 4 años. Se realizaron estudios para definir valores normales de saturación de O2 en OSF y AOS mediante registro continuo durante el turno. Los resultados no mostraron diferencias entre los procedimientos de producción (PSA u oxígeno líquido) en la regulación de la disponibilidad de oxígeno en las instalaciones de AOS. Como resultado, las instalaciones a gran escala tienen dificultades para alcanzar la concentración de oxígeno adecuada debido a fugas en áreas de alta movilidad. Además, la planta de PSA requiere de adecuación y mantenimiento para operar a gran altura.

Role of the Cys Loop and Transmembrane Domain in the Allosteric Modulation of α4ß2 Nicotinic Acetylcholine Receptors.

Allosteric modulators of pentameric ligand-gated ion channels are thought to act on elements of the pathways that couple agonist binding to channel gating. Using α4ß2 nicotinic acetylcholine receptors and the α4ß2-selective positive modulators 17ß-estradiol (ßEST) and desformylflustrabromine (dFBr), we have identified pathways that link the binding sites for these modulators to the Cys loop, a region that is critical for channel gating in all pentameric ligand-gated ion channels. Previous studies have shown that the binding site for potentiating ßEST is in the C-terminal (post-M4) region of the α4 subunit. Here, using homology modeling in combination with mutagenesis and electrophysiology, we identified the binding site for potentiating dFBr on the top half of a cavity between the third (M3) and fourth transmembrane (M4) α-helices of the α4 subunit. We found that the binding sites for ßEST and dFBr communicate with the Cys loop, through interactions between the last residue of post-M4 and Phe170 of the conserved FPF sequence of the Cys loop, and that these interactions affect potentiating efficacy. In addition, interactions between a residue in M3 (Tyr309) and Phe167, a residue adjacent to the Cys loop FPF motif, also affect dFBr potentiating efficacy. Thus, the Cys loop acts as a key control element in the allosteric transduction pathway for potentiating ßEST and dFBr. Overall, we propose that positive allosteric modulators that bind the M3-M4 cavity or post-M4 region increase the efficacy of channel gating through interactions with the Cys loop.

Non-equivalent ligand selectivity of agonist sites in (α4ß2)2α4 nicotinic acetylcholine receptors: a key determinant of agonist efficacy.

The α4ß2 nicotinic acetylcholine receptor (nAChR) is the most abundant nAChR type in the brain, and this receptor type exists in alternate (α4ß2)2α4 and (α4ß2)2ß2 forms, which are activated by agonists with strikingly differing efficacies. Recent breakthroughs have identified an additional operational agonist binding site in the (α4ß2)2α4 nAChR that is responsible for the signature sensitivity of this receptor to activation by agonists, yet the structural mechanisms determining agonist efficacy at this receptor type are not yet fully understood. In this study, we characterized the ligand selectivity of the individual agonist sites of the (α4ß2)2α4 nAChR to determine whether differences in agonist selectivity influence agonist efficacy. Applying the substituted cysteine accessibility method to individual agonist sites in concatenated (α4ß2)2α4 receptors, we determined the agonist selectivity of the agonist sites of the (α4ß2)2α4 receptor. We show that (a) accessibility of substituted cysteines to covalent modification by methanesulfonate reagent depends on the agonist site at which the modification occurs and (b) that agonists such as sazetidine-A and TC-2559 are excluded from the site at the α4/α4 interface. Given that additional binding to the agonist site in the α4/α4 interface increases acetylcholine efficacy and that agonists excluded from the agonist site at the α4/α4 interface behave as partial agonists, we conclude that the ability to engage all agonist sites in (α4ß2)2α4 nAChRs is a key determinant of agonist efficacy. The findings add another level of complexity to the structural mechanisms that govern agonist efficacy in heteromeric nAChRs and related ligand-gated ion channels.

Modelo experimental de lesão raquimedular em ratos com dispositivo para acesso de agentes terapêuticos locais / Experimental model of spinal cord injury in rats with a device for local therapeutic agents access

Um modelo experimental de lesão raquimedular com localização precisa e reproduzível é uma ferramenta extremamente importante para o estudo de novas terapias em lesões raquimedulares. OBJETIVOS: Desenvolver um modelo experimental de lesão raquimedular em ratos que produza lesão completa (paraplegia) com o posicionamento de um sistema que permita o acesso de agentes próximo ao local da lesão para testar agentes terapêuticos locais. MÉTODOS: Quinze ratos Wistar foram submetidos à transecção cirúrgica da medula espinhal, realizada com o uso de tesoura ao nível dos corpos vertebrais de T-13 a L-3 e, ao final do procedimento, à implantação de um cateter subcutâneo para o acesso de agentes terapêuticos locais ao local da lesão. RESULTADOS: Um modelo experimental de paraplegia foi consistentemente desenvolvido com a adição suplementar de um cateter para o acesso de agentes terapêuticos locais ao local da lesão. CONCLUSÃO: Um modelo animal de lesão raquimedular e um sistema para o acesso de agentes terapêuticos locais pode ser reproduzido para o estudo de diferentes modificadores da resposta regenerativa em um modelo de ratos com lesão raquimedular.

An experimental model of spinal cord injury at a precise and reproducible site is an extremely important tool for studying new therapies in spinal cord injuries. OBJECTIVES: To develop an experimental model of spinal cord injury in rats that is able to produce a complete injury (paraplegia) and placing a system enabling agents access close to injury site in order to test local therapeutic agents. METHODS: Fifteen Wistar rats were submitted to surgical transection of the spine, performed by using scissors at the level of T-13 to L-3 vertebral bodies, and, at the end of the procedure, to the insertion of a subdermal catheter intended to enable local therapeutic agents access to injury site. RESULTS: An experimental model of paraplegia was consistently developed by adding a supplementary catheter for local therapeutic agentsÆ access to injury site. CONCLUSION: An animal model of spinal cord injury and a system for local therapeutic agents access can be reproduced for the study of different modifiers of the regenerative response in a model of rats with spinal cord injury.