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Global Environmental Assessments (GEAs) are in a unique position to influence environmental decision-making in the context of sustainability challenges. To do this effectively, however, new methods are needed to respond to the needs of decision-makers for a more integrated, contextualized and goal-seeking evaluation of different policies, geared for action from global to local. While scenarios are an important tool for GEAs to link short-term decisions and medium and long-term consequences, these current information needs cannot be met only through deductive approaches focused on the global level. In this paper, we argue that a more diverse set of futures tools operating at multiple scales are needed to improve GEA scenario development and analysis to meet the information needs of policymakers and other stakeholders better. Based on the literature, we highlight four challenges that GEAs need to be able to address in order to contribute to global environmental decision-making about the future: 1. anticipate unpredictable future conditions; 2. be relevant at multiple scales, 3. include diverse actors, perspectives and contexts; and 4. leverage the imagination to inspire action. We present a toolbox of future-oriented approaches and methods that can be used to effectively address the four challenges currently faced by GEAs.

Aging is a natural process that is also influenced by some factors like the food someone eats, lifestyle decisions, and impacts on general health. Despite the recognized role of nutrition in modulating the molecular and cellular mechanisms underlying aging, there is a lack of comprehensive exploration into potential interventions that can effectively mitigate these effects. In this study, we investigated the potential anti-aging properties of vitamin D by examining its interactions with key molecular targets involved in aging-related pathways. By using molecular docking and dynamics techniques, we evaluate the interactions and stability of vitamins D2 and D3 with key proteins involved in aging pathways, such as SIRT1, mTOR, AMPK, Klotho, AhR, and MAPK. Our results reveal promising binding affinities between vitamin D and SIRT1 forms, with energy values of −48.33 kJ/mol and −45.94 kJ/mol for vitamins D2 and D3, respectively, in aqueous environments. Moreover, molecular dynamics simulations revealed that the vitamin D3–SIRT1 complex exhibited greater stability compared with the vitamin D2–SIRT1 complex. The study calculated the solvation free energy to compare the solubility of vitamins D2 and D3 in water and various organic solvents. Despite their strong interactions with water, both vitamins exhibited low solubility, primarily due to the high energy cost associated with cavity formation in the aqueous environment. Compared with other solvents, water demonstrated particularly low solubility for both vitamins. This suggested that vitamins D2 and D3 preferred binding to aging receptors over dissolving in bulk aqueous environments, supporting their strong therapeutic interactions with these receptors. These findings shed light on the molecular mechanisms underlying vitamin D's potential anti-aging effects and lay the groundwork for developing nutraceuticals targeting aging and associated diseases. Understanding these mechanisms holds promise for future interventions aimed at promoting healthy aging and enhancing overall well-being. [ABSTRACT FROM AUTHOR]

The synthesis of the new bulky vinyllithium reagent (MeIPr=CH)Li, (MeIPr=[(MeCNDipp)2C]; Dipp=2,6‐iPr2C6H3) is reported. This vinyllithium precursor was found to act as a general source of the anionic 2σ, 2π‐electron donor ligand [MeIPr=CH]−. Furthermore, a high‐yielding route to the degradation‐resistant SiII precursor MeIPr⋅SiBr2 is presented. The efficacy of (MeIPr=CH)Li in synthesis was demonstrated by the generation of a complete inorganic divinyltetrelene series (MeIPrCH)2E: (E=Si to Pb). (MeIPrCH)2Si: represents the first two‐coordinate acyclic silylene not bound by heteroatom donors, with dual electrophilic and nucleophilic character at the SiII center noted. Cyclic voltammetry shows this electron‐rich silylene to be a potent reducing agent, rivalling the reducing power of the 19‐electron complex cobaltocene (Cp2Co). [ABSTRACT FROM AUTHOR]

A dinculear Re(CO)3 complex with a proton responsive phenol unit and a pyrene anchor in the ligand backbone was investigated in the electrochemical CO2/H+ conversion in solution and adsorbed on multi walled carbon nanotubes (MWCNT) on an GC electrode surface. The pyrene group unit is introduced at the end of the ligand synthesis via a coupling reaction, which allows for a versatile ligand modification in order to tune the electronic properties or to introduce various anchor groups for heterogenisation at a late stage. The redox chemistry of the pyrene-α-diimine-Re(CO)3 complex, 1, was investigated in N,N-dimethylformamide (dmf), including IR-spectroelectrochemical (IR-SEC) characterisation of the short lived, reduced species. Subsequently, the electrochemical H+/CO2-reduction catalysis in dmf/water was investigated. The complex catalyses syngas formation yielding CO and H2 with similar rates, namely in Faraday yields of 45% and 35%, respectively. Since the similar complex without the pyrene anchor in the backbone, I, prefers CO2 over H+ reduction, the formation of syngas was rationalised by the small differences in the redox properties and pKa values of the phenol-pyrene unit in regard to phenol unit as in I. Subsequently, the complex was adsorbed on multi walled carbon nanotubes (MWCNT) on a GC electrode surface. Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) confirmed coating of the electrode. The immobilised complex was utilised in the electrochemical CO2/H+ reduction in dmf/water, however, the complex quickly desorbed under reductive conditions, likely due to the good solubility of the reduced species. Water as a solvent prevents desorption as confirmed by XPS, however, then a preference for H2 formation over syngas formation was observed under electrocatalytic conditions. Thus, these experiments show, that the results obtained in aqueous organic solution are not easily transferable to the heterogeneous systems operating in water due to changes in the reaction rates for competing pathways. [ABSTRACT FROM AUTHOR]

Linamarin has been reported to have anticancer activities; however, its extraction and isolation using different solvents yield a low amount. Therefore, understanding the physical properties, such as solvents' solubility, membrane permeability and lipophilicity and how they are associated with different solvents, is a paramount topic for discussion, especially for its potential as a drug. Linamarin has a sugar moiety with many polar groups responsible for its physical properties. Following current trends, a molecular dynamics simulation is performed to investigate its physical properties and how different solvents, such as water, methanol (MeOH), dimethyl sulfoxide (DMSO) and dichloromethane (DCM), affect such properties. In this work, we have investigated the influence of intermolecular and intramolecular hydrogen bonding and the influence of polar and non-polar solvents on the physical properties of linamarin. Furthermore, solvation free-energy and electronic structure analysis are performed. The structural analysis results show that the polar groups of linamarin have strong interactions with all solvents except the etheric oxygen groups. A detailed analysis shows intermolecular hydrogen bonding between polar solvents (water, MeOH and DMSO) and the hydroxyl oxygens of linamarin. Water exhibits the strongest interaction with linamarin's functional groups among the investigated solvents. The findings show that within the first solvation shell, the number of water molecules is greatest, while MeOH has the fewest. Centrally to the structural analysis, solvation free energy confirms DMSO to be the best solvent since it prefers to interact with linamarin over itself, while water prefers to interact with itself. While the solute–solvent interactions are strongest between linamarin and water, the solvent–solvent interactions are strongest in water. As a result, the solvation free-energy calculations reveal that linamarin solvation is most favourable in DMSO. [ABSTRACT FROM AUTHOR]

This article presents the regional emission targets corresponding to different climate regimes for differentiating commitments beyond 2012 on the basis of the Multi-Stage approach. This approach assumes a gradual increase in the number of Parties involved and their level of commitment according to participation and differentiation rules. The analysis focuses on two global greenhouse gas emission profiles resulting in CO2-equivalent concentrations stabilising at 550 and 650 ppmv in 2100 and 2150, respectively. Three Multi-Stage cases have been developed in order to assess different types of thresholds. These share three consecutive stages representing different commitments: stage 1 – no quantitative commitments; stage 2 – emission–limitation targets and stage 3 – emission reduction targets. The analysis shows that by 2025 all three cases result in emission reduction objectives for all Annex I regions of at least 30–55% below their 1990 levels for 550 ppmv, whereas for 650 ppmv target they range from 0 to 20%. Furthermore, early participation is required of the major non-Annex I regions through emission limitation targets i.e. before 2025 and 2050 for the 550 and 650 ppmv targets, respectively. The first participation threshold for adopting emission–limitation targets on the basis of a capability–responsibility index (as introduced here) can provide for a balanced and timely participation of non-Annex I regions. Major strengths and weaknesses of the climate regimes are discussed and important obstacles and pre-conditions for their feasibility and acceptability are highlighted. [ABSTRACT FROM AUTHOR]

This paper describes the design, implementation, and performance characteristics of a commercial XQuery processing engine, the BEA streaming XQuery processor. This XQuery engine was designed to provide high performance for message-processing applications, i.e., for transforming XML data streams. The engine is a central component of the 8.1 release of BEA?s WebLogic Integration (WLI) product. The BEA XQuery engine is fully compliant with the August 2002 draft of the W3C XML Query Language specification and we are currently porting it to the latest version of the XQuery language (July 2004). A goal of this paper is to describe how a fully compliant yet efficient XQuery engine has been built from a few relatively simple components and well-understood technologies. [ABSTRACT FROM AUTHOR]

Neuroinflammation is thought to contribute to Alzheimer’s disease (AD) pathogenesis that is, to a large extent, mediated by microglia. Given the tight interaction between the immune system and the brain, peripheral immune challenges can profoundly affect brain function. Indeed, both preclinical and clinical studies have indicated that an aberrant inflammatory response can elicit behavioral impairments and cognitive deficits, especially when the brain is in a vulnerable state, e.g. during early development, as a result of aging, or under disease conditions like AD. However, how exactly peripheral immune challenges affect brain function and whether this is mediated by aberrant microglial functioning remains largely elusive. In this review, we hypothesize that; 1) systemic immune challenges occurring during vulnerable periods of life can increase the propensity to induce later cognitive dysfunction and accelerate AD pathology, and 2) that 'priming' of microglial cells is instrumental in mediating this vulnerability. We highlight how microglia can be primed by both neonatal infections as well as by aging, two periods of life during which microglial activity is known to be specifically upregulated. Lasting changes in (the ratios of) specific microglial phenotypes can result in an exaggerated pro-inflammatory cytokine response to subsequent inflammatory challenges. While the resulting changes in brain function are initially transient, a continued and/or excess release of such pro-inflammatory cytokines can activate various downstream cellular cascades known to be relevant for AD. Finally, we discuss microglial priming and the aberrant microglial response as potential target for treatment strategies for AD.

Aerobic exercise (AE) has been widely praised for its potential benefits to cognition and overall brain and mental health. In particular, AE has a potent impact on promoting the function of the hippocampus and stimulating neuroplasticity. As the evidence-base rapidly builds, and given most of the supporting work can be readily translated from animal models to humans, the potential for AE to be applied as a therapeutic or adjunctive intervention for a range of human conditions appears ever more promising. Notably, many psychiatric and neurological disorders have been associated with hippocampal dysfunction, which may underlie the expression of certain symptoms common to these disorders, including (aspects of) cognitive dysfunction. Augmenting existing treatment approaches using AE based interventions may promote hippocampal function and alleviate cognitive deficits in various psychiatric disorders that currently remain untreated. Incorporating non-pharmacological interventions into clinical treatment may also have a number of other benefits to patient well being, such as limiting the risk of adverse side effects. This review incorporates both animal and human literature to comprehensively detail how AE is associated with cognitive enhancements and stimulates a cascade of neuroplastic mechanisms that support improvements in hippocampal functioning. Using the examples of schizophrenia and major depressive disorder, the utility and implementation of an AE intervention to the clinical domain will be proposed, aimed to reduce cognitive deficits in these, and related disorders.

Exposure of an organism to environmental challenges activates two hormonal systems that help the organism to adapt. As part of this adaptational process, brain processes are changed such that appropriate behavioral strategies are selected that allow optimal performance at the short term, while relevant information is stored for the future. Over the past years it has become evident that chronic uncontrollable and unpredictable stress also exerts profound effects on structure and function of limbic neurons, but the impact of chronic stress is not a mere accumulation of repeated episodes of acute stress exposure. Dendritic trees are reduced in some regions but expanded in others, and cells are generally exposed to a higher calcium load upon depolarization. Synaptic strengthening is largely impaired. Neurotransmitter responses are also changed, e.g. responses to serotonin. We here discuss: a) the main cellular effects after chronic stress with emphasis on the hippocampus, b) how such effects could contribute to the development of psychopathology in genetically vulnerable individuals, and c) their normalization by brief treatment with anti-glucocorticoids.