Stochastic dynamics of remote knock-on permeation in biological ion channels

Brownian dynamics simulations provide evidence for a remote knock-on mechanism facilitating the permeation of a biological ion channel by an ion that is initially trapped at the selectivity filter (SF). Unlike the case of conventional direct knock-on, the second ion that instigates permeation does not need to enter the channel. Nor does it necessarily take the place of the permeating ion at the SF, and it can even be of a different ionic species. The study is based on the simultaneous, self-consistent, solution of the coupled Poisson and Langevin equations for a simple generic model, taking account of all the charges present. The new permeation mechanism involves electrostatic amplification attributable to the permittivity mismatch between water and protein: the arrival of the instigating ion at the channel entrance reduces the exit barrier for the ion trapped at the SF, facilitating escape

Self-organized enhancement of conductivity in biological ion channels

We discuss an example of self-organization in a biological system. It arises from long-range ion–ion interactions, and it leads us to propose a new kind of enhanced conduction in ion channels. The underlying mechanism involves charge fluctuations near the channel mouth, amplified by the mismatch between the relative permittivities of water and the protein of the channel walls. We use Brownian dynamics simulations to show that, as in conventional 'knock on' permeation, these interactions can strongly enhance the channel current; but unlike the conventional mechanism, the enhancement occurs without the instigating bath ion entering the channel. The transition between these two mechanisms is clearly demonstrated, emphasizing their distinction. A simple model accurately reproduces the observed phenomena. We point out that electrolyte plus protein of low relative permittivity are universal in living systems, so that long-range ion–ion correlations of the kind considered must be common

The complex network of global cargo ship movements

Transportation networks play a crucial role in human mobility, the exchange of goods, and the spread of invasive species. With 90% of world trade carried by sea, the global network of merchant ships provides one of the most important modes of transportation. Here we use information about the itineraries of 16,363 cargo ships during the year 2007 to construct a network of links between ports. We show that the network has several features which set it apart from other transportation networks. In particular, most ships can be classified in three categories: bulk dry carriers, container ships and oil tankers. These three categories do not only differ in the ships' physical characteristics, but also in their mobility patterns and networks. Container ships follow regularly repeating paths whereas bulk dry carriers and oil tankers move less predictably between ports. The network of all ship movements possesses a heavy-tailed distribution for the connectivity of ports and for the loads transported on the links with systematic differences between ship types. The data analyzed in this paper improve current assumptions based on gravity models of ship movements, an important step towards understanding patterns of global trade and bioinvasion.Comment: 7 figures Accepted for publication by Journal of the Royal Society Interface (2010) For supplementary information, see http://www.icbm.de/~blasius/publications.htm

Spatial accessibility and social inclusion: The impact of Portugal's last health reform

Health policies seek to promote access to health care and should provide appropriate geographical accessibility to each demographical functional group. The dispersal demand of health‐careservices and the provision for such services atfixed locations contribute to the growth of inequality intheir access. Therefore, the optimal distribution of health facilities over the space/area can lead toaccessibility improvements and to the mitigation of the social exclusion of the groups considered mostvulnerable. Requiring for such, the use of planning practices joined with accessibility measures. However,the capacities of Geographic Information Systems in determining and evaluating spatial accessibility inhealth system planning have not yet been fully exploited. This paper focuses on health‐care services planningbased on accessibility measures grounded on the network analysis. The case study hinges on mainlandPortugal. Different scenarios were developed to measure and compare impact on the population'saccessibility. It distinguishes itself from other studies of accessibility measures by integrating network data ina spatial accessibility measure: the enhanced two‐stepfloating catchment area. The convenient location forhealth‐care facilities can increase the accessibility standards of the population and consequently reducethe economic and social costs incurred. Recently, the Portuguese government implemented a reform thataimed to improve, namely, the access and equity in meeting with the most urgent patients. It envisaged,in terms of equity, the allocation of 89 emergency network points that ensured more than 90% of thepopulation be within 30 min from any one point in the network. Consequently, several emergency serviceswere closed, namely, in rural areas. This reform highlighted the need to improve the quality of the emergencycare, accessibility to each care facility, and equity in their access. Hence, accessibility measures becomean efficient decision‐making tool, despite its absence in effective practice planning. According to anapplication of this type of measure, it was possible to verify which levels of accessibility were decreased,including the most disadvantaged people, with a larger time of dislocation of 12 min between 2001 and 2011

The evaluation of redundancy for road traffic networks.

This paper presents two redundancy indices for road traffic network junctions and also an aggregated network redundancy index. The proposed redundancy indices could be implemented to identify optimal design alternatives during the planning stage of the network junctions whereas the aggregated network redundancy index could assess the best control and management policies under disruptive events. Furthermore, effective measures of network redundancy are important to policy makers in understanding the current resilience and future planning to mitigate the impacts of greenhouse gases. The proposed junction indices cover the static aspect of redundancy, i.e. alternative paths, and the dynamic feature of redundancy reflected by the availability of spare capacity under different network loading and service level. The proposed redundancy indices are based on the entropy concept, due to its ability to measure the system configuration in addition to being able to model the inherent uncertainty in road transport network conditions. Various system parameters based on different combinations of link flow, relative link spare capacity and relative link speed were examined. However, the two redundancy indices developed from the combined relative link speed and relative link spare capacity showed strong correlation with junction delay and volume capacity ratio of a synthetic road transport network of Delft city. Furthermore, the developed redundancy indices responded well to demand variation under the same network conditions and supply variations. Another case study on Junction 3A in M42 motorway near Birmingham demonstrated that the developed redundancy index is able to reflect the impact of the Active Traffic Management scheme introduced in 2006

The Evolution of Transport Across World Regions

This chapter aims at providing an overview of the multiple aspects involved in passenger and freight transport, which are the base for the understanding of the energy consumption of the sector, as well as for the current trends and prospects related to digitalization and decarbonization. A brief historical discussion and some trends will be presented, followed by a description of the main modes and technologies, both for passenger and freight transport, and a final focus on the differences across world regions in mobility patterns and behaviors. The evolution of transport systems has led to very different situations worldwide, depending on different strategies related to economic development, geographical limitations and cultural, political and social aspects. Proper sustainable mobility plans need to be based on the specific characteristics of each location, and the integration between different governance levels is of utmost importance to improve the reliability, affordability, and energy performance on the entire transport system

Digital MDA for enumeration of total nucleic acid contamination

Multiple displacement amplification (MDA) is an isothermal, sequence-independent method for the amplification of high molecular weight DNA that is driven by ϕ29 DNA polymerase (DNAP). Here we report digital MDA (dMDA), an ultrasensitive method for quantifying nucleic acid fragments of unknown sequence. We use the new assay to show that our custom ϕ29 DNAP preparation is free of contamination at the limit of detection of the dMDA assay (1 contaminating molecule per assay microliter). Contamination in commercially available preparations is also investigated. The results of the dMDA assay provide strong evidence that the so-called ‘template-independent’ MDA background can be attributed to high-molecular weight contaminants and is not primer-derived in the commercial kits tested. dMDA is orders of magnitude more sensitive than PCR-based techniques for detection of microbial genomic DNA fragments and opens up new possibilities for the ultrasensitive quantification of DNA fragments in a wide variety of application areas using MDA chemistry and off-the-shelf hardware developed for digital PCR

Hybrid approach for energy aware management of multi-cloud architecture integrating user machines

International audienceThe arrival and development of remotely accessible services via the cloud has transfigured computer technology. However, its impact on personal computing remains limited to cloud-based applications. Meanwhile, acceptance and usage of telephony and smartphones have exploded. Their sparse administration needs and general user friendliness allows all people, regardless of technology literacy, to access, install and use a large variety of applications.We propose in this paper a model and a platform to offer personal computing a simple and transparent usage similar to modern telephony. In this model, user machines are integrated within the classical cloud model, consequently expanding available resources and management targets. In particular, we defined and implemented a modular architecture including resource managers at different levels that take into account energy and QoS concerns. We also propose simulation tools to design and size the underlying infrastructure to cope with the explosion of usage. Functionalities of the resulting platform are validated and demonstrated through various utilization scenarios. The internal scheduler managing resource usage is experimentally evaluated and compared with classical method-ologies, showing a significant reduction of energy consumption with almost no QoS degradation

Free-trade agreements: challenges for global health

In this study new free-trade agreements are discussed, which are based on the breaking down of tariff and technical barriers and normally exclude most of the poorest countries in the world. Considering the current context of economic globalization and its health impacts, seven controversial points of these treaties and their possible implications for global public health are presented, mainly regarding health equity and other health determinants. Finally, this research proposes a greater social and health professionals participation in the formulation and discussion of these treaties, and a deeper insertion of Brazil in this important international agenda.</p