CO2 directly modulates connexin 26 by formation of carbamate bridges between subunits

Homeostatic regulation of the partial pressure of CO2 (PCO2) is vital for life. Sensing of pH has been proposed as a sufficient proxy for determination of PCO2 and direct CO2-sensing largely discounted. Here we show that connexin 26 (Cx26) hemichannels, causally linked to respiratory chemosensitivity, are directly modulated by CO2. A ‘carbamylation motif’, present in CO2-sensitive connexins (Cx26, Cx30, Cx32) but absent from a CO2-insensitive connexin (Cx31), comprises Lys125 and four further amino acids that orient Lys125 towards Arg104 of the adjacent subunit of the connexin hexamer. Introducing the carbamylation motif into Cx31 created a mutant hemichannel (mCx31) that was opened by increases in PCO2. Mutation of the carbamylation motif in Cx26 and mCx31 destroyed CO2 sensitivity. Course-grained computational modelling of Cx26 demonstrated that the proposed carbamate bridge between Lys125 and Arg104 biases the hemichannel to the open state. Carbamylation of Cx26 introduces a new transduction principle for physiological sensing of CO2

Treatment for language comprehension processes in right hemisphere brain damage: Phase I data

This study presents preliminary, Phase I data from a novel, implicit language processing treatment for adults with right hemisphere damage (RHD). The focus of treatment is motivated by two major accounts of common language comprehension problems in adults with RHD: Coarse coding and suppression deficits. The treatment approach is novel in that it aims to facilitate coarse coding and suppression processes implicitly, through contextual prestimulation. The treatment also targets partially domain-general operations with broad implications for language comprehension, rather than specific language structures or forms. Discussion will address the promise and limitations of treatment results for three adults with RHD

Implicit Treatment of Underlying Comprehension Processes Improves Narrative Comprehension in Right Hemisphere Brain Damage

Language comprehension deficits in adults with focal right hemisphere brain damage (RHD) can cause considerable social handicap. To date, however, treatment for these deficits remains almost entirely untested. This abstract reports an investigation of whether Contextual Constraint Treatment (CCT) -- a novel, implicit, stimulation-facilitation treatment for language comprehension processes1,2 -- can yield generalized gains to measures of discourse comprehension in adults with RHD. The focus of CCT is motivated by two major accounts of typical RHD language comprehension problems: that they are due to coarse coding or suppression deficits. Coarse coding (CC) activates wide-ranging aspects of word meaning independent of surrounding context. In RHD, CC deficits impair processing of distant meanings/features of words (e.g., “rotten” as a feature of “apple”)3. A normal suppression (SUPP) process reduces mental activation of concepts that become less relevant to a current context. RHD SUPP impairment is indexed by prolonged processing interference from contextually-inappropriate interpretations (e.g., the “ink” meaning of the word “pen,” in the sentence “He built a pen”)4,5. CC and SUPP are partially domain-general language comprehension processes. For example, both predict aspects of discourse comprehension and are hypothesized to underpin figurative language comprehension; SUPP is important for resolving lexical and inferential ambiguities; and CC is involved in processing both literal lexical items and phrasal metaphors1,2,6. Thus, treatment that improves CC and SUPP processes may hold promise for improving a broad range of communicative outcomes. CCT is novel in aiming to facilitate comprehension processes implicitly, through contextual prestimulation. Adults with RHD who perform well on implicit assessments of language processing often have difficulty on metalinguistic assessments of the same operations2. Thus we implemented this approach to avoid confounding treatment of impaired processes with irrelevant, and potentially difficult, task demands

Right Hemisphere Damage and Theory of Mind Deficit: A Deficit in the Theory?

This study assessed whether right-hemisphere-damaged (RHD) adults’ deficits in processing alternative meanings of lexical ambiguities would extend to semantic feature representations of unambiguous lexical items. If so, RHD deficit was expected to affect only activation/deactivation for subordinate features that are incompatible with the most common representations of unambiguous words (e.g., ‘rotten’ for ‘apple’). Contrary to predictions, neither RHD nor control participants evidenced a change in activation over time for this type of subordinate features. Continued research on RHD adults’ communicative strengths and weaknesses will have future implications for clinical assessment and management

Generalization of a Novel, Implicit Treatment for Coarse Coding Deficit

The language comprehension deficits in adults with focal right hemisphere brain damage (RHD) can cause considerable social handicap. To date, however, treatment for language deficits in this population remains almost entirely untested. This abstract reports a single-subject experimental design study, performed to investigate whether Contextual Constraint Treatment -- a novel, implicit, stimulation-facilitation treatment for language comprehension processes -- can yield generalized gains to broader measures of language comprehension in adults with RHD. The focus of Contextual Constraint Treatment (CCT) is motivated by two major accounts of common language comprehension problems in adults with RHD: coarse coding and suppression deficits. The patient in this study had a coarse coding (CC) deficit, so we describe here only the CC version of the treatment. CC processes activate wide-ranging aspects of word meaning independent of the surrounding context, and CC deficits in adults with RHD impair the processing of distant meanings or features of words (e.g., “rotten” as a feature of “apple”)1. CC is a partially domain-general language comprehension process. That is, CC ability predicts aspects of discourse comprehension, is hypothesized to underpin figurative language comprehension, and is involved in processing phrasal metaphors2. Thus, treatment that improves CC processes has the potential to generalize to a range of communicative outcomes. CCT is novel in aiming to facilitate comprehension processes implicitly, through contextual prestimulation. This approach contrasts with the majority of treatments for neurologically-based cognitive-linguistic disorders, which are direct, explicit, and/or metalinguistic. We implemented this approach to avoid confounding treatment of impaired processes with irrelevant, and potentially difficult, task demands, as adults with RHD who can perform well on implicit assessments of language processing often have difficulty with metalinguistic assessments of the same processing operations2

The impacts of climate change on river flood risk at the global scale

This paper presents an assessment of the implications of climate change for global river flood risk. It is based on the estimation of flood frequency relationships at a grid resolution of 0.5 × 0.5°, using a global hydrological model with climate scenarios derived from 21 climate models, together with projections of future population. Four indicators of the flood hazard are calculated; change in the magnitude and return period of flood peaks, flood-prone population and cropland exposed to substantial change in flood frequency, and a generalised measure of regional flood risk based on combining frequency curves with generic flood damage functions. Under one climate model, emissions and socioeconomic scenario (HadCM3 and SRES A1b), in 2050 the current 100-year flood would occur at least twice as frequently across 40 % of the globe, approximately 450 million flood-prone people and 430 thousand km2 of flood-prone cropland would be exposed to a doubling of flood frequency, and global flood risk would increase by approximately 187 % over the risk in 2050 in the absence of climate change. There is strong regional variability (most adverse impacts would be in Asia), and considerable variability between climate models. In 2050, the range in increased exposure across 21 climate models under SRES A1b is 31–450 million people and 59 to 430 thousand km2 of cropland, and the change in risk varies between −9 and +376 %. The paper presents impacts by region, and also presents relationships between change in global mean surface temperature and impacts on the global flood hazard. There are a number of caveats with the analysis; it is based on one global hydrological model only, the climate scenarios are constructed using pattern-scaling, and the precise impacts are sensitive to some of the assumptions in the definition and application

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Modelling of the effect of ELMs on fuel retention at the bulk W divertor of JET

Effect of ELMs on fuel retention at the bulk W target of JET ITER-Like Wall was studied with multi-scale calculations. Plasma input parameters were taken from ELMy H-mode plasma experiment. The energetic intra-ELM fuel particles get implanted and create near-surface defects up to depths of few tens of nm, which act as the main fuel trapping sites during ELMs. Clustering of implantation-induced vacancies were found to take place. The incoming flux of inter-ELM plasma particles increases the different filling levels of trapped fuel in defects. The temperature increase of the W target during the pulse increases the fuel detrapping rate. The inter-ELM fuel particle flux refills the partially emptied trapping sites and fills new sites. This leads to a competing effect on the retention and release rates of the implanted particles. At high temperatures the main retention appeared in larger vacancy clusters due to increased clustering rate