Inactivation defects caused by myotonia-associated mutations in the sodium channel III-IV linker.

Missense mutations in the skeletal muscle Na+ channel alpha subunit occur in several heritable forms of myotonia and periodic paralysis. Distinct phenotypes arise from mutations at two sites within the III-IV cytoplasmic loop: myotonia without weakness due to substitutions at glycine 1306, and myotonia plus weakness caused by a mutation at threonine 1313. Heterologous expression in HEK cells showed that substitutions at either site disrupted inactivation, as reflected by slower inactivation rates, shifts in steady-state inactivation, and larger persistent Na+ currents. For T1313M, however, the changes were an order of magnitude larger than any of three substitutions at G1306, and recovery from inactivation was hastened as well. Model simulations demonstrate that these functional difference have distinct phenotypic consequences. In particular, a large persistent Na+ current predisposes to paralysis due to depolarization-induced block of action potential generation

A multi-commodity discrete/continuum model for a traffic equilibrium system

We consider a city with several highly compact central business districts (CBDs). The commuters’ origins are continuously dispersed. The travel demand to each CBD, which is considered to be a distinct commodity of traffic movements, is dependent on the total travel cost to that CBD. The transportation system is divided into two layers: major freeways and a dense network of surface streets. Whereas the major freeway network is modelled according to the conventional discrete-network approach, the dense surface streets are approximated as a continuum. Travellers to each CBD can either travel within the continuum (surface streets) and then transfer to the discrete network (freeways) at an interchange (ramp) before moving to the CBD on the discrete network, or they can travel directly to the CBD within the continuum. Specific travel cost-flow relationships for the two layers of transportation facilities are considered. We develop a traffic equilibrium model for this discrete/continuum transportation system in which, for each origin–destination pair, no traveller can reduce his or her individual travel cost by unilaterally changing routes. The problem is formulated as a simultaneous optimisation programme with two sub-problems. One sub-problem is a traffic assignment problem from the interchanges to the CBD in the discrete network, and the other is a traffic assignment problem within a continuum system with multiple centres (i.e. the interchange points and the CBDs). A Newtonian algorithm based on sensitivity analyses of the two sub-problems is proposed to solve the resultant simultaneous optimisation programme. A numerical example is given to demonstrate the effectiveness of the proposed method.postprin

Implementing bridge model updating for operation and maintenance purposes: examination based on UK practitioners’ views

There has been a vision of creating bridge digital twins as virtual simulation models of bridge assets to facilitate remote management. Bridge model updating is one digital twin technology which can enable the continuous updating of the structural model as new monitoring data is collected. This paper examines why there is currently little industry uptake of monitoring, modelling and model updating for the operation and maintenance of bridges despite over two decades of research in these fields. The study analyses the findings from a series of semi-structured industry interviews with expert bridge professionals in the U.K. and from an extensive literature survey of bridge model updating studies to examine the disconnects between research and practice and the practical issues of implementing bridge model updating. In particular, the study found that localised damage resulting in local reduction in structural stiffness, a key assumption made in the majority of research, is subject to question by practitioners as many common types of bridge damage may not induce noticeable change in structural stiffness that existing model updating techniques would identify. Key recommendations for future research are proposed to drive adoption of bridge monitoring, modelling and model updating and thus realise their industrial value

Carbonated Drinks Impact Follicle Development, Expression of Ovarian FSHR and Serum Caspase-3 in Mice

Objectives: The present study aimed to assess the effects of Coca-Cola and Pepsi-Cola on the development of ovaries and follicles, and on the reproduction of animals

Precise Complexity of the Core in Dichotomous and Additive Hedonic Games

Hedonic games provide a general model of coalition formation, in which a set of agents is partitioned into coalitions, with each agent having preferences over which other players are in her coalition. We prove that with additively separable preferences, it is $\Sigma_2^p$-complete to decide whether a core- or strict-core-stable partition exists, extending a result of Woeginger (2013). Our result holds even if valuations are symmetric and non-zero only for a constant number of other agents. We also establish $\Sigma_2^p$-completeness of deciding non-emptiness of the strict core for hedonic games with dichotomous preferences. Such results establish that the core is much less tractable than solution concepts such as individual stability.Comment: ADT-2017, 15 pages in LNCS styl

Negative pressure characteristics of an evaporating meniscus at nanoscale

This study aims at understanding the characteristics of negative liquid pressures at the nanoscale using molecular dynamics simulation. A nano-meniscus is formed by placing liquid argon on a platinum wall between two nano-channels filled with the same liquid. Evaporation is simulated in the meniscus by increasing the temperature of the platinum wall for two different cases. Non-evaporating films are obtained at the center of the meniscus. The liquid film in the non-evaporating and adjacent regions is found to be under high absolute negative pressures. Cavitation cannot occur in these regions as the capillary height is smaller than the critical cavitation radius. Factors which determine the critical film thickness for rupture are discussed. Thus, high negative liquid pressures can be stable at the nanoscale, and utilized to create passive pumping devices as well as significantly enhance heat transfer rates