Climate change and the long-term viability of the World’s busiest heavy haul ice road

Climate models project that the northern high latitudes will warm at a rate in excess of the global mean. This will pose severe problems for Arctic and sub-Arctic infrastructure dependent on maintaining low temperatures for structural integrity. This is the case for the economically important Tibbitt to Contwoyto Winter Road (TCWR)—the world’s busiest heavy haul ice road, spanning 400 km across mostly frozen lakes within the Northwest Territories of Canada. In this study, future climate scenarios are developed for the region using statistical downscaling methods. In addition, changes in lake ice thickness are projected based on historical relationships between measured ice thickness and air temperatures. These projections are used to infer the theoretical operational dates of the TCWR based on weight limits for trucks on the ice. Results across three climate models driven by four RCPs reveal a considerable warming trend over the coming decades. Projected changes in ice thickness reveal a trend towards thinner lake ice and a reduced time window when lake ice is at sufficient thickness to support trucks on the ice road, driven by increasing future temperatures. Given the uncertainties inherent in climate modelling and the resultant projections, caution should be exercised in interpreting the magnitude of these scenarios. More certain is the direction of change, with a clear trend towards winter warming that will reduce the operation time window of the TCWR. This illustrates the need for planners and policymakers to consider future changes in climate when planning annual haulage along the TCWR

Gene duplications and evolution of vertebrate voltage-gated sodium channels

Author Posting. © The Author(s), 2006. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Journal of Molecular Evolution 63 (2006): 208-221, doi:10.1007/s00239-005-0287-9.Voltage-gated sodium channels underlie action potential generation in excitable tissue. To establish the evolutionary mechanisms that shaped the vertebrate sodium channel a-subunit (SCNA) gene family and their encoded Nav1 proteins, we identified all SCNA genes in several teleost species. Molecular cloning revealed that teleosts have eight SCNA genes, comparable to the number in another vertebrate lineage, mammals. Prior phylogenetic analyses had indicated that teleosts and tetrapods share four monophyletic groups of SCNA genes and that tandem duplications selectively expanded the number of genes in two of the four mammalian groups. However, the number of genes in each group varies between teleosts and tetrapods suggesting different evolutionary histories in the two vertebrate lineages. Our findings from phylogenetic analysis and chromosomal mapping of Danio rerio genes indicate that tandem duplications are an unlikely mechanism for generation of the extant teleost SCNA genes. Instead, analysis of other closely mapped genes in D. rerio supports the hypothesis that a whole genome duplication was involved in expansion of the SCNA gene family in teleosts. Interestingly, despite their different evolutionary histories, mRNA analyses demonstrated a conservation of expression patterns for SCNA orthologues in teleosts and tetrapods, suggesting functional conservation.The authors’ work was supported by NIH grants (NS 38937; AEN, ADT and ABR, NS 25513; HHZ and YL and NSF IBN 0236147; MCJ)

Survivors of intensive care with type 2 diabetes and the effect of shared care follow-up clinics: study protocol for the SWEET-AS randomised controlled feasibility study

Published online: 13 October 2016Background: Many patients who survive the intensive care unit (ICU) experience long-term complications such as peripheral neuropathy and nephropathy which represent a major source of morbidity and affect quality of life adversely. Similar pathophysiological processes occur frequently in ambulant patients with diabetes mellitus who have never been critically ill. Some 25 % of all adult ICU patients have diabetes, and it is plausible that ICU survivors with co-existing diabetes are at heightened risk of sequelae from their critical illness. ICU follow-up clinics are being progressively implemented based on the concept that interventions provided in these clinics will alleviate the burdens of survivorship. However, there is only limited information about their outcomes. The few existing studies have utilised the expertise of healthcare professionals primarily trained in intensive care and evaluated heterogenous cohorts. A shared care model with an intensivist- and diabetologist-led clinic for ICU survivors with type 2 diabetes represents a novel targeted approach that has not been evaluated previously. Prior to undertaking any definitive study, it is essential to establish the feasibility of this intervention. Methods: This will be a prospective, randomised, parallel, open-label feasibility study. Eligible patients will be approached before ICU discharge and randomised to the intervention (attending a shared care follow-up clinic 1 month after hospital discharge) or standard care. At each clinic visit, patients will be assessed independently by both an intensivist and a diabetologist who will provide screening and targeted interventions. Six months after discharge, all patients will be assessed by blinded assessors for glycated haemoglobin, peripheral neuropathy, cardiovascular autonomic neuropathy, nephropathy, quality of life, frailty, employment and healthcare utilisation. The primary outcome of this study will be the recruitment and retention at 6 months of all eligible patients. Discussion: This study will provide preliminary data about the potential effects of critical illness on chronic glucose metabolism, the prevalence of microvascular complications, and the impact on healthcare utilisation and quality of life in intensive care survivors with type 2 diabetes. If feasibility is established and point estimates are indicative of benefit, funding will be sought for a larger, multi-centre study. Trial registration: ANZCTR ACTRN12616000206426Yasmine Ali Abdelhamid, Liza Phillips, Michael Horowitz and Adam Dean

Outer membrane protein folding from an energy landscape perspective

The cell envelope is essential for the survival of Gram-negative bacteria. This specialised membrane is densely packed with outer membrane proteins (OMPs), which perform a variety of functions. How OMPs fold into this crowded environment remains an open question. Here, we review current knowledge about OFMP folding mechanisms in vitro and discuss how the need to fold to a stable native state has shaped their folding energy landscapes. We also highlight the role of chaperones and the β-barrel assembly machinery (BAM) in assisting OMP folding in vivo and discuss proposed mechanisms by which this fascinating machinery may catalyse OMP folding

Dark Matter in the Milky Way's Dwarf Spheroidal Satellites

The Milky Way's dwarf spheroidal satellites include the nearest, smallest and least luminous galaxies known. They also exhibit the largest discrepancies between dynamical and luminous masses. This article reviews the development of empirical constraints on the structure and kinematics of dSph stellar populations and discusses how this phenomenology translates into constraints on the amount and distribution of dark matter within dSphs. Some implications for cosmology and the particle nature of dark matter are discussed, and some topics/questions for future study are identified.Comment: A version with full-resolution figures is available at http://www.cfa.harvard.edu/~mwalker/mwdsph_review.pdf; 70 pages, 22 figures; invited review article to be published in Vol. 5 of the book "Planets, Stars, and Stellar Systems", published by Springe

Genetic modifiers affecting severity of epilepsy caused by mutation of sodium channel Scn2a

Mutations in the voltage-gated sodium channels SCN1A and SCN2A are responsible for several types of human epilepsy. Variable expressivity among family members is a common feature of these inherited epilepsies, suggesting that genetic modifiers may influence the clinical manifestation of epilepsy. The transgenic mouse model Scn2a Q54 has an epilepsy phenotype as a result of a mutation in Scn2a that slows channel inactivation. The mice display progressive epilepsy that begins with short-duration partial seizures that appear to originate in the hippocampus. The partial seizures become more frequent and of longer duration with age and often induce secondary generalized seizures. Clinical severity of the Scn2a Q54 phenotype is influenced by genetic background. Congenic C57BL/6J.Q54 mice exhibit decreased incidence of spontaneous seizures, delayed seizure onset, and longer survival in comparison with [C57BL/6J × SJL/J]F 1 .Q54 mice. This observation indicates that strain SJL/J carries dominant modifier alleles at one or more loci that determine the severity of the epilepsy phenotype. Genome-wide interval mapping in an N 2 backcross revealed two modifier loci on Chromosomes 11 and 19 that influence the clinical severity of of this sodium channel-induced epilepsy. Modifier genes affecting clinical severity in the Scn2a Q54 mouse model may contribute to the variable expressivity seen in epilepsy patients with sodium channel mutations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46986/1/335_2005_Article_49.pd

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion