Trusty URIs: Verifiable, Immutable, and Permanent Digital Artifacts for Linked Data

To make digital resources on the web verifiable, immutable, and permanent, we propose a technique to include cryptographic hash values in URIs. We call them trusty URIs and we show how they can be used for approaches like nanopublications to make not only specific resources but their entire reference trees verifiable. Digital artifacts can be identified not only on the byte level but on more abstract levels such as RDF graphs, which means that resources keep their hash values even when presented in a different format. Our approach sticks to the core principles of the web, namely openness and decentralized architecture, is fully compatible with existing standards and protocols, and can therefore be used right away. Evaluation of our reference implementations shows that these desired properties are indeed accomplished by our approach, and that it remains practical even for very large files.Comment: Small error corrected in the text (table data was correct) on page 13: "All average values are below 0.8s (0.03s for batch mode). Using Java in batch mode even requires only 1ms per file.

Molecular dynamics of ion transport through the open conformation of a bacterial voltage-gated sodium channel

The crystal structure of the open conformation of a bacterial voltage-gated sodium channel pore from Magnetococcus sp. (NaVMs) has provided the basis for a molecular dynamics study defining the channel’s full ion translocation pathway and conductance process, selectivity, electrophysiological characteristics, and ion-binding sites. Microsecond molecular dynamics simulations permitted a complete time-course characterization of the protein in a membrane system, capturing the plethora of conductance events and revealing a complex mixture of single and multi-ion phenomena with decoupled rapid bidirectional water transport. The simulations suggest specific localization sites for the sodium ions, which correspond with experimentally determined electron density found in the selectivity filter of the crystal structure. These studies have also allowed us to identify the ion conductance mechanism and its relation to water movement for the NavMs channel pore and to make realistic predictions of its conductance properties. The calculated single-channel conductance and selectivity ratio correspond closely with the electrophysiology measurements of the NavMs channel expressed in HEK 293 cells. The ion translocation process seen in this voltage-gated sodium channel is clearly different from that exhibited by members of the closely related family of voltage-gated potassium channels and also differs considerably from existing proposals for the conductance process in sodium channels. These studies simulate sodium channel conductance based on an experimentally determined structure of a sodium channel pore that has a completely open transmembrane pathway and activation gate

Microsecond molecular dynamics simulations of the open state structure of a bacterial voltage-gated sodium channel reveal mechanisms of ion selectivity and conduction

Microsecond atomic detail equilibrium molecular dynamics simulations based on the open-state crystal structure (McCusker et al, 2012, Nature Comm) of a bacterial voltage-gated sodium channel (NavMs) have been employed to characterize the mechanisms underlying ion selectivity and conductance of the channel embedded in a lipid bilayer membrane. This approach captured the full plethora of conduction events, revealing a complex mixture of single and multi-ion phenomena, with decoupled rapid bi-directional water transport. Channel selectivity for Na over K ions was found to increase with decreasing applied membrane potential. In marked difference to K-channel simulations, no voltage lag was observed for Na+. Unlike in K+ channels, the ions are fully hydrated at all times, even when bound. The ion positions were correlated with electron density in selectivity filter of the crystal structure. Remarkably, and in stark contrast to K-channels, ionic conduction was found to be independent of net water flux, which was zero for all applied voltages and ionic species. This zero water transport was found to result from the balance of two large and opposing water fluxes of equal magnitude