Thermodynamics of Competitive Molecular Channel Transport: Application to Artificial Nuclear Pores

In an analytical model channel transport is analyzed as a function of key parameters, determining efficiency and selectivity of particle transport in a competitive molecular environment. These key parameters are the concentration of particles, solvent-channel exchange dynamics, as well as particle-in-channel- and interparticle interaction. These parameters are explicitly related to translocation dynamics and channel occupation probability. Slowing down the exchange dynamics at the channel ends, or elevating the particle concentration reduces the in-channel binding strength necessary to maintain maximum transport. Optimized in-channel interaction may even shift from binding to repulsion. A simple equation gives the interrelation of access dynamics and concentration at this transition point. The model is readily transferred to competitive transport of different species, each of them having their individual in-channel affinity. Combinations of channel affinities are determined which differentially favor selectivity of certain species on the cost of others. Selectivity for a species increases if its in-channel binding enhances the species' translocation probablity when compared to that of the other species. Selectivity increases particularly for a wide binding site, long channels, and fast access dynamics. Recent experiments on competitive transport of in-channel binding and inert molecules through artificial nuclear pores serve as a paradigm for our model. It explains qualitatively and quantitatively how binding molecules are favored for transport at the cost of the transport of inert molecules

The Personal Sequence Database: a suite of tools to create and maintain web-accessible sequence databases

Background: Large molecular sequence databases are fundamental resources for modern\ud bioscientists. Whether for project-specific purposes or sharing data with colleagues, it is often\ud advantageous to maintain smaller sequence databases. However, this is usually not an easy task for\ud the average bench scientist.\ud \ud Results: We present the Personal Sequence Database (PSD), a suite of tools to create and\ud maintain small- to medium-sized web-accessible sequence databases. All interactions with PSD\ud tools occur via the internet with a web browser. Users may define sequence groups within their\ud database that can be maintained privately or published to the web for public use. A sequence group\ud can be downloaded, browsed, searched by keyword or searched for sequence similarities using\ud BLAST. Publishing a sequence group extends these capabilities to colleagues and collaborators. In\ud addition to being able to manage their own sequence databases, users can enroll sequences in\ud BLASTAgent, a BLAST hit tracking system, to monitor NCBI databases for new entries displaying\ud a specified level of nucleotide or amino acid similarity.\ud \ud Conclusion: The PSD offers a valuable set of resources unavailable elsewhere. In addition to\ud managing sequence data and BLAST search results, it facilitates data sharing with colleagues,\ud collaborators and public users. The PSD is hosted by the authors and is available at http://\ud bioinfo.cgrb.oregonstate.edu/psd/

Analytic Markovian Rates for Generalized Protein Structure Evolution

A general understanding of the complex phenomenon of protein evolution requires the accurate description of the constraints that define the sub-space of proteins with mutations that do not appreciably reduce the fitness of the organism. Such constraints can have multiple origins, in this work we present a model for constrained evolutionary trajectories represented by a Markovian process throughout a set of protein-like structures artificially constructed to be topological intermediates between the structure of two natural occurring proteins. The number and type of intermediate steps defines how constrained the total evolutionary process is. By using a coarse-grained representation for the protein structures, we derive an analytic formulation of the transition rates between each of the intermediate structures. The results indicate that compact structures with a high number of hydrogen bonds are more probable and have a higher likelihood to arise during evolution. Knowledge of the transition rates allows for the study of complex evolutionary pathways represented by trajectories through a set of intermediate structures

Ioffe Times in DIS from a Dipole Model Fit

We present a study of Ioffe times in deep inelastic electron-proton scattering. We deduce 'experimental' Ioffe-time distributions from the small-x HERA data as described by a particular colour-dipole-model fit. We show distributions for three representative gamma*-proton c.m. energies W and various values of the photon virtuality Q^2. These distributions are rather broad for transversely and very narrow for longitudinally polarised virtual photons. The Ioffe times for W=150 GeV, for example, range from around 1000 fm for Q^2=1 GeV^2 to around 10 fm for Q^2=100 GeV^2. Based on our results we discuss consequences for the limitations of applicability of the dipole picture.Comment: 20 page

The porin and the permeating antibiotic: A selective diffusion barrier in gram-negative bacteria

Gram-negative bacteria are responsible for a large proportion of antibiotic resistant bacterial diseases. These bacteria have a complex cell envelope that comprises an outer membrane and an inner membrane that delimit the periplasm. The outer membrane contains various protein channels, called porins, which are involved in the influx of various compounds, including several classes of antibiotics. Bacterial adaptation to reduce influx through porins is an increasing problem worldwide that contributes, together with efflux systems, to the emergence and dissemination of antibiotic resistance. An exciting challenge is to decipher the genetic and molecular basis of membrane impermeability as a bacterial resistance mechanism. This Review outlines the bacterial response towards antibiotic stress on altered membrane permeability and discusses recent advances in molecular approaches that are improving our knowledge of the physico-chemical parameters that govern the translocation of antibiotics through porin channel

Projected WIMP sensitivity of the LUX-ZEPLIN dark matter experiment

LUX-ZEPLIN (LZ) is a next-generation dark matter direct detection experiment that will operate 4850 feet underground at the Sanford Underground Research Facility (SURF) in Lead, South Dakota, USA. Using a two-phase xenon detector with an active mass of 7 tonnes, LZ will search primarily for low-energy interactions with weakly interacting massive particles (WIMPs), which are hypothesized to make up the dark matter in our galactic halo. In this paper, the projected WIMP sensitivity of LZ is presented based on the latest background estimates and simulations of the detector. For a 1000 live day run using a 5.6-tonne fiducial mass, LZ is projected to exclude at 90% confidence level spin-independent WIMP-nucleon cross sections above 1.4×10-48 cm2 for a 40 GeV/c2 mass WIMP. Additionally, a 5σ discovery potential is projected, reaching cross sections below the exclusion limits of recent experiments. For spin-dependent WIMP-neutron(-proton) scattering, a sensitivity of 2.3×10-43 cm2 (7.1×10-42 cm2) for a 40 GeV/c2 mass WIMP is expected. With underground installation well underway, LZ is on track for commissioning at SURF in 2020

Boundless plains

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