Identification of critical amino acids involved in α1-β interaction in voltage-dependent Ca2+ channels

AbstractIn voltage-dependent Ca2+ channels, the α1 and β subunits interact via two cytoplasmic regions defined as the Alpha Interaction Domain (AID) and Beta Interaction Domain (BID). Several novel amino acids for that interaction have now been mapped in both domains by point mutations. It was found that three of the nine amino acids in AID and four of the eight BID amino acids tested were essential for the interaction. Whereas the important AID amino acids were clustered around five residues, the important BID residues were more widely distributed within a larger 16 amino acid sequence. The affinity of the AIDA GST fusion protein for the four interacting β1b BID mutants was not significantly altered compared with the wild-type β1b despite the close localization of mutated residues to disruptive BID amino acids. Expression of these interactive β mutants with the full-length α1A subunit only slightly modified the stimulation efficiency when compared with the wild-type β1b subunit. Our data suggest that non-disruptive BID sequence alterations do not dramatically affect the β subunit-induced current stimulation

Eyes wide shut? UK consumer perceptions on aviation climate impacts and travel decisions to New Zealand

The purview of climate change concern has implicated air travel, as evidenced in a growing body of academic literature concerned with aviation CO2 emissions. This article assesses the relevance of climate change to long haul air travel decisions to New Zealand for United Kingdom consumers. Based on 15 semi-structured open-ended interviews conducted in Bournemouth, UK during June 2009, it was found that participants were unlikely to forgo potential travel decisions to New Zealand because of concern over air travel emissions. Underpinning the interviewees’ understandings and responses to air travel’s climate impact was a spectrum of awareness and attitudes to air travel and climate change. This spectrum ranged from individuals who were unaware of air travel’s climate impact to those who were beginning to consume air travel with a ‘carbon conscience’. Within this spectrum were some who were aware of the impact but not willing to change their travel behaviours at all. Rather than implicating long haul air travel, the empirical evidence instead exemplifies changing perceptions towards frequent short haul air travel and voices calls for both government and media in the UK to deliver more concrete messages on air travel’s climate impact

Canary in the coalmine: Norwegian attitudes towards climate change and extreme long-haul air travel to Aotearoa/New Zealand

Accelerating global climate change poses considerable challenges to all societies and economies. The European Union now targets a 20% reduction in CO2 emissions by 2020. Indeed, the Labour-led Norwegian government is committed to carbon neutrality across all sectors of the economy by 2030. Aviation has been identified as a rapidly growing contributor to CO2 emissions. This article reports on a research project that explored Norwegian attitudes towards climate change, particularly as they relate to extreme long-haul air travel to Aotearoa/New Zealand. It reveals that the 'dream trip' to New Zealand for Norwegians is still largely intact. It also finds evidence of 'air travel with a carbon conscience' arising from growing concern for high frequency discretionary air travel. Evidence of denial of the climate impact of air travel that recent studies have revealed was largely absent. Interviewees expressed a greater concern for short-haul air travel emissions than for the climate impact of long-haul travel. However, intentions to adapt long-haul travel behaviours were expressed, highlighting the need to monitor consumer attitudes towards the impact of air travel on climate change. We conclude that Norway is a vanguard European tourism market in terms of climate sensitivity

Binge flying: Behavioural addiction and climate change

Recent popular press suggests that ‘binge flying’ constitutes a new site of behavioural addiction. We theoretically appraise and empirically support this proposition through interviews with consumers in Norway and the United Kingdom conducted in 2009. Consistent findings from across two national contexts evidence a growing negative discourse towards frequent short-haul tourist air travel and illustrate strategies of guilt suppression and denial used to span a cognitive dissonance between the short-term personal benefits of tourism and the air travel’s associated long-term consequences for climate change. Tensions between tourism consumption and changing social norms towards acceptable flying practice exemplify how this social group is beginning to (re)frame what constitutes ‘excessive’ holiday flying, despite concomitantly continuing their own frequent air travels

Cosmic Microwave Background Anisotropies from Scaling Seeds: Global Defect Models

We investigate the global texture model of structure formation in cosmogonies with non-zero cosmological constant for different values of the Hubble parameter. We find that the absence of significant acoustic peaks and little power on large scales are robust predictions of these models. However, from a careful comparison with data we conclude that at present we cannot safely reject the model on the grounds of present CMB data. Exclusion by means of galaxy correlation data requires assumptions on biasing and statistics. New, very stringent constraints come from peculiar velocities. Investigating the large-N limit, we argue that our main conclusions apply to all global O(N) models of structure formation.Comment: LaTeX file with RevTex, 27 pages, 23 eps figs., submitted to Phys. Rev. D. A version with higher quality images can be found at http://mykonos.unige.ch/~kunz/download/lam.tar.gz for the LaTeX archive and at http://mykonos.unige.ch/~kunz/download/lam.ps.gz for the compiled PostScript fil

Geotechnical Field Reconnaissance: Gorkha (Nepal) Earthquake of April 25, 2015 and Related Shaking Sequence

The April 25, 2015 Gorkha (Nepal) Earthquake and its related aftershocks had a devastating impact on Nepal. The earthquake sequence resulted in nearly 9,000 deaths, tens of thousands of injuries, and has left hundreds of thousands of inhabitants homeless. With economic losses estimated at several billion US dollars, the financial impact to Nepal is severe and the rebuilding phase will likely span many years. The Geotechnical Extreme Events Reconnaissance (GEER) Association assembled a reconnaissance team under the leadership of D. Scott Kieffer, Binod Tiwari and Youssef M.A. Hashash to evaluate geotechnical impacts of the April 25, 2015 Gorkha Earthquake and its related aftershocks. The focus of the reconnaissance was on time-sensitive (perishable) data, and the GEER team included a large group of experts in the areas of Geology, Engineering Geology, Seismology, Tectonics, Geotechnical Engineering, Geotechnical Earthquake Engineering, and Civil and Environmental Engineering. The GEER team worked in close collaboration with local and international organizations to document earthquake damage and identify targets for detailed follow up investigations. The overall distribution of damage relative to the April 25, 2015 epicenter indicates significant ground motion directivity, with pronounced damage to the east and comparatively little damage to the west. In the Kathmandu Basin, characteristics of recorded strong ground motion data suggest that a combination of directivity and deep basin effects resulted in significant amplification at a period of approximately five seconds. Along the margins of Kathmandu Basin structural damage and ground failures are more pronounced than in the basin interior, indicating possible basin edge motion amplification. Although modern buildings constructed within the basin generally performed well, local occurrences of heavy damage and collapse of reinforced concrete structures were observed. Ground failures in the basin included cyclic failure of silty clay, lateral spreading and liquefaction. Significant landsliding was triggered over a broad area, with concentrated activity east of the April 25, 2015 epicenter and between Kathmandu and the Nepal-China border. The distribution of concentrated landsliding partially reflects directivity in the ground motion. Several landslides have dammed rivers and many of these features have already been breached. Hydropower is a primary source of electric power in Nepal, and several facilities were damaged due to earthquake-induced landsliding. Powerhouses and penstocks experienced significant damage, and an intake structure currently under construction experienced significant dynamic settlement during the earthquake. Damage to roadways, bridges and retaining structures was also primarily related to landsliding. The greater concentration of infrastructure damage along steep hillsides, ridges and mountain peaks offers a proxy for the occurrence of topographic amplification. The lack of available strong motion records has severely limited the GEER team’s ability to understand how strong motions were distributed and how they correlate to distributions of landsliding, ground failure and infrastructure damage. It is imperative that the engineering and scientific community continues to install strong motion stations so that such data is available for future earthquake events. Such information will benefit the people of Nepal through improved approaches to earthquake resilient design

Treat-to-target strategies in rheumatoid arthritis: a systematic review and cost-effectiveness analysis

To systematically review clinical and health economic impacts of treat-to-target (TTT) strategies in patients with rheumatoid arthritis (RA) managed in specialist units, compared with routine care. Sixteen and seven electronic databases were searched for clinical RCTs and cost-effectiveness respectively. Study selection, data extraction and quality assessment (Cochrane Collaboration risk of bias criteria) were performed. Evidence was reported by (1) TTT vs. usual care; (2) comparison of different treatment protocols against each other; (3) comparison of different targets against each other. Narrative synthesis was undertaken and conclusions drawn on a trial by trial basis, due to study heterogeneity. Twenty-two RCTs were included. Sixteen were at high risk of bias, five unclear and one low risk. Three trials showed TTT to be more effective than usual care in terms of remissions, in some or all comparisons, whereas one other trial reported no significant difference. Two trials showed TTT to be more effective than usual care in terms of low disease activity (LDA), in some or all comparisons, whereas two trials reported little difference. Some evidence suggests that TTT strategies involving combination therapy can achieve more remissions than those involving monotherapy, but little impact of alternative treatment targets on remission or LDA. Overall, there is evidence that TTT increases remissions in early RA and mixed early and established RA populations, and increases LDA in established RA. Although results varied, typically TTT was estimated to be more cost-effective than usual care. No target appears more effective than others

Geotechnical Effects of the 2015 Magnitude 7.8 Gorkha, Nepal, Earthquake and Aftershocks

This article summarizes the geotechnical effects of the 25 April 2015 M 7.8 Gorkha, Nepal, earthquake and aftershocks, as documented by a reconnaissance team that undertook a broad engineering and scientific assessment of the damage and collected perishable data for future analysis. Brief descriptions are provided of ground shaking, surface fault rupture, landsliding, soil failure, and infrastructure performance. The goal of this reconnaissance effort, led by Geotechnical Extreme Events Reconnaissance, is to learn from earthquakes and mitigate hazards in future earthquakes