[2.2]Paracyclophane-Based TCN-201 Analogs as GluN2A-Selective NMDA Receptor Antagonists

Recent studies have shown the involvement of GluN2A subunit-containing NMDA receptors in various neurological and pathological disorders. In the X-ray crystal structure, TCN-201 ( 1 ) and analogous pyrazine derivatives 2 and 3 adopt a U-shape (hairpin) conformation within the binding site formed by the ligand binding domains of the GluN1 and GluN2A subunits. In order to mimic the resulting π/π-interactions of two aromatic rings in the binding site, a [2.2]paracyclophane system was designed to lock these aromatic rings in a parallel orientation. Acylation of [2.2]paracyclophane ( 5 ) with oxalyl chloride and chloroacetyl chloride and subsequent transformations led to the oxalamide 7 , triazole 10 and benzamides 12 . The GluN2A inhibitory activities of the paracyclophane derivatives were tested with two-electrode voltage clamp electrophysiology using Xenopus laevis oocytes expressing selectively functional NMDA receptors with GluN2A subunit. The o-iodobenzamide 12 b with the highest similarity to TCN-201 showed the highest GuN2A inhibitory activity of this series of compounds. At a concentration of 10 μM, 12 b reached 36 % of the inhibitory activity of TCN-201 ( 1 ). This result indicates that the [2.2]paracyclophane system is well accepted by the TCN-201 binding site.     

Microstructured Fischer‐Tropsch Reactor Scale‐up and Opportunities for Decentralized Application

Current projects focusing on the energy transition in traffic will rely on a high‐level technology mix for their commissioning. One of those technologies is the Fischer‐Tropsch synthesis (FTS) that converts synthesis gas into hydrocarbons of different chain lengths. A microstructured packed‐bed reactor for low‐temperature FTS is tested towards its versatility for biomass‐based syngas with a high inert gas dilution. Investigations include overall productivity, conversion, and product selectivity. A 60‐times larger pilot‐scale reactor is further tested. Evaporation cooling is introduced which allows to increase the available energy extraction from the system. From that scale on, an autothermal operation at elevated conversion levels is applicable.     

Spurenstoffabtrennung mit keramischen Nanofiltrationsmembranen als Rotationsscheibenfilter

Reducing micropollutant pollution of water bodies is an important objective of water management and an integral part of environmental policy. Ceramic nanofiltration membranes were developed as multichannel membranes of increased membrane area and rotating disk filters. The membranes developed show retention of over 80 % for PEG 400. The membranes are currently being tested for the separation of micropollutants from wastewater contaminated with pharmaceuticals. With the help of a downstream oxidative process, the trace substances remaining in the permeate are degraded.     

‘Breaking’ news: uncovering sense-breaking patterns in social media crisis communication during the 2017 Manchester bombing

ABSTRACT

Individuals, (media-) organisations, and crisis responders who are involved in ad hoc crisis communication steadily deploy social media to contribute to collective sense-making as an endeavour to create meaning in highly uncertain situations. Exerting sense-giving in order to shape others’ conceptions is causally preceded by an initial breakup of existing understanding. This study aims to explore patterns of sense-breaking in social media crisis communication and its impact on collective sense-making and sense-giving. To this end, we conducted a case study of the Manchester bombing in 2017, including a social network analysis of 708,147 Twitter postings and a content analysis of 2006 original tweets. We found individual role types to be initiators of sense-breaking in early crisis stages when uncertainty is at its height. Exerting successive sense-giving becomes more challenging if the collective sense-making has progressed along with the sequence of events. This understanding aims to encourage emergency management organisations to move their sense-giving actions closer to the point in time when sense-breaking occurs.     

The Pathophysiological Role of CoA

The importance of coenzyme A (CoA) as a carrier of acyl residues in cell metabolism is well understood. Coenzyme A participates in more than 100 different catabolic and anabolic reactions, including those involved in the metabolism of lipids, carbohydrates, proteins, ethanol, bile acids, and xenobiotics. However, much less is known about the importance of the concentration of this cofactor in various cell compartments and the role of altered CoA concentration in various pathologies. Despite continuous research on these issues, the molecular mechanisms in the regulation of the intracellular level of CoA under pathological conditions are still not well understood. This review summarizes the current knowledge of (a) CoA subcellular concentrations; (b) the roles of CoA synthesis and degradation processes; and (c) protein modification by reversible CoA binding to proteins (CoAlation). Particular attention is paid to (a) the roles of changes in the level of CoA under pathological conditions, such as in neurodegenerative diseases, cancer, myopathies, and infectious diseases; and (b) the beneficial effect of CoA and pantethine (which like CoA is finally converted to Pan and cysteamine), used at pharmacological doses for the treatment of hyperlipidemia.     

Drivers of change in groundwater resources: a case study of the Indian Punjab

Indian Punjab, a strategically important region from India’s national food security standpoint, is increasingly the focus of attention for academics and policymakers because of serious concerns about over-exploitation of its groundwater resources. Currently, policy makers and agricultural researchers/scientists in India are in a fix to prescribe an alternative, probably more sustainable, crop-mix to farmers that can save water while maintaining farm incomes. Using primary data from 120 farmers, this paper evaluates the current situation of groundwater resources in Punjab, and outlines the major socio-economic factors that have a significant association with the change in the groundwater depth in this region. General ANOVA regression results suggest that groundwater depth varied significantly with respect to agro-climatic regions, crop diversity, and farmer education. Crop diversity had an inverse relationship with groundwater depth whereas the association between farmer education and groundwater depth was non-linear although in the case of Gurdaspur, they showed a direct relationship. In the central zone of Indian Punjab, groundwater level on 92% of the farms had depleted by more than 0.60 m annually between 2000 and 2010, while the current state of groundwater resources in the other two regions was not so serious and are manageable for the time being. However, if the existing policy framework for groundwater resources in the state, which allows the state government to release 0.11 million more connections to farmers, putting much pressure not only on the groundwater resources but also burdening the state exchequer, continues, Punjab may end up losing all its groundwater resources for ever. Considering this alarming situation, one-fifth of the farmers surveyd agreed to delay the sowing of rice by another 2 weeks i.e. up to 30 June which could save the fast depleting groundwater resources in Punjab.     

Intravital FRET: Probing Cellular and Tissue Function in Vivo

The development of intravital Förster Resonance Energy Transfer (FRET) is required to probe cellular and tissue function in the natural context: the living organism. Only in this way can biomedicine truly comprehend pathogenesis and develop effective therapeutic strategies. Here we demonstrate and discuss the advantages and pitfalls of two strategies to quantify FRET in vivo—ratiometrically and time-resolved by fluorescence lifetime imaging—and show their concrete application in the context of neuroinflammation in adult mice.     

Coil‐Type Asymmetric Supercapacitor Electrical Cables

Cable‐shaped supercapacitors (SCs) have recently aroused significant attention due to their attractive properties such as small size, lightweight, and bendability. Current cable‐shaped SCs have symmetric device configuration. However, if an asymmetric design is used in cable‐shaped supercapacitors, they would become more attractive due to broader cell operation voltages, which results in higher energy densities. Here, a novel coil‐type asymmetric supercapacitor electrical cable (CASEC) is reported with enhanced cell operation voltage and extraordinary mechanical‐electrochemical stability. The CASECs show excellent charge–discharge profiles, extraordinary rate capability (95.4%), high energy density (0.85 mWh cm⁻³), remarkable flexibility and bendability, and superior bending cycle stability (≈93.0% after 4000 cycles at different bending states). In addition, the CASECs not only exhibit the capability to store energy but also to transmit electricity simultaneously and independently. The integrated electrical conduction and storage capability of CASECS offer many potential applications in solar energy storage and electronic gadgets.     

Analytical Model to Characterize the Efficiency of Disk Stack Separators

Up to now the prediction of separation efficiency for disk stack separators is largely based on the concept of equivalent clarification area, short Σ-theory, firstly published in 1949. An improved analytical model with a closed-form solution is presented in which the assumptions of uniform flow and unhindered solids transport are dropped. The contributions of distributor and solids holding space to the total separation efficiency are considered. The model is validated by comprehensive experiments with different geometry parameters and particle systems. The results are presented in a universal form for a combination of dimensionless numbers.