Chaperone-assisted translocation of a polymer through a nanopore

Using Langevin dynamics simulations, we investigate the dynamics of chaperone-assisted translocation of a flexible polymer through a nanopore. We find that increasing the binding energy $\epsilon$ between the chaperone and the chain and the chaperone concentration $N_c$ can greatly improve the translocation probability. Particularly, with increasing the chaperone concentration a maximum translocation probability is observed for weak binding. For a fixed chaperone concentration, the histogram of translocation time $\tau$ has a transition from long-tailed distribution to Gaussian distribution with increasing $\epsilon$. $\tau$ rapidly decreases and then almost saturates with increasing binding energy for short chain, however, it has a minimum for longer chains at lower chaperone concentration. We also show that $\tau$ has a minimum as a function of the chaperone concentration. For different $\epsilon$, a nonuniversal dependence of $\tau$ on the chain length $N$ is also observed. These results can be interpreted by characteristic entropic effects for flexible polymers induced by either crowding effect from high chaperone concentration or the intersegmental binding for the high binding energy.Comment: 10 pages, to appear in J. Am. Chem. So

Reduction of aldehydes and hydrogen cyanide yields in mainstream cigarette smoke using an amine functionalised ion exchange resin

<p>Abstract</p> <p>Background</p> <p>Cigarette smoking is a well recognized cause of diseases such as lung cancer, chronic obstructive pulmonary disease and cardiovascular disease. Of the more than 5000 identified species in cigarette smoke, at least 150 have toxicological activity. For example, formaldehyde and acetaldehyde have been assigned as Group 1 and Group 2B carcinogens by IARC, and hydrogen cyanide has been identified as a respiratory and cardiovascular toxicant. Active carbon has been shown to be an effective material for the physical adsorption of many of the smoke volatile species. However, physical adsorption of acetaldehyde, formaldehyde and also hydrogen cyanide from smoke is less effective using carbon. Alternative methods for the removal of these species from cigarette smoke are therefore of interest. A macroporous, polystyrene based ion-exchange resin (Diaion^®CR20) with surface amine group functionality has been investigated for its ability to react with aldehydes and HCN in an aerosol stream, and thus selectively reduce the yields of these compounds (in particular formaldehyde) in mainstream cigarette smoke.</p> <p>Results</p> <p>Resin surface chemistry was characterized using vapour sorption, XPS, TOF-SIMS and ¹⁵N NMR. Diaion^®CR20 was found to have structural characteristics indicating weak physisorption properties, but sufficient surface functionalities to selectively remove aldehydes and HCN from cigarette smoke. Using 60 mg of Diaion^®CR20 in a cigarette cavity filter gave reductions in smoke formaldehyde greater than 50% (estimated to be equivalent to >80% of the formaldehyde present in the smoke vapour phase) independent of a range of flow rates. Substantial removal of HCN (>80%) and acetaldehyde (>60%) was also observed. The performance of Diaion^®CR20 was found to be consistent over a test period of 6 months. The overall adsorption for the majority of smoke compounds measured appeared to follow a pseudo-first order approximation to second order kinetics.</p> <p>Conclusions</p> <p>This study has shown that Diaion^®CR20 is a highly selective and efficient adsorbent for formaldehyde, acetaldehyde and HCN in cigarette smoke. The reductions for these compounds were greater than those achieved using an active carbon. The results also demonstrate that chemisorption can be an effective mechanism for the removal of certain vapour phase toxicants from cigarette smoke.</p

Transverse Electronic Transport through DNA Nucleotides with Functionalized Graphene Electrodes

Graphene nanogaps and nanopores show potential for the purpose of electrical DNA sequencing, in particular because single-base resolution appears to be readily achievable. Here, we evaluated from first principles the advantages of a nanogap setup with functionalized graphene edges. To this end, we employed density functional theory and the non-equilibrium Green's function method to investigate the transverse conductance properties of the four nucleotides occurring in DNA when located between the opposing functionalized graphene electrodes. In particular, we determined the electrical tunneling current variation as a function of the applied bias and the associated differential conductance at a voltage which appears suitable to distinguish between the four nucleotides. Intriguingly, we observe for one of the nucleotides a negative differential resistance effect.Comment: 19 pages, 7 figure

Nanopore surface coating delivers nanopore size and shape through conductance-based sizing

The performance of nanopore single-molecule sensing elements depends intimately on their physical dimensions and surface chemical properties. These factors underpin the dependence of the nanopore ionic conductance on electrolyte concentration, yet the measured, or modeled, dependence only partially illuminates the details of geometry and surface chemistry. Using the electrolyte-dependent conductance data before and after selective surface functionalization of solid-state nanopores, however, introduces more degrees of freedom and improves the performance of conductance-based nanopore characterizations. Sets of representative nanopore profiles were used to generate conductance data, and the nanopore shape and exact dimensions were identified, through conductance alone, by orders-of-magnitude 3 reductions in the geometry optimization metrics. The optimization framework could similarly be used to evaluate the nanopore surface coating thickness

Microscopic annealing process and its impact on superconductivity in T'-structure electron-doped copper oxides

High-transition-temperature superconductivity arises in copper oxides when holes or electrons are doped into the CuO2 planes of their insulating parent compounds. While hole-doping quickly induces metallic behavior and superconductivity in many cuprates, electron-doping alone is insufficient in materials such as R2CuO4 (R is Nd, Pr, La, Ce, etc.), where it is necessary to anneal an as-grown sample in a low-oxygen environment to remove a tiny amount of oxygen in order to induce superconductivity. Here we show that the microscopic process of oxygen reduction repairs Cu deficiencies in the as-grown materials and creates oxygen vacancies in the stoichiometric CuO2 planes, effectively reducing disorder and providing itinerant carriers for superconductivity. The resolution of this long-standing materials issue suggests that the fundamental mechanism for superconductivity is the same for electron- and hole-doped copper oxides.Comment: 23 pages, 3 figures, accepted for publication in Nature Material

A novel, fast, HMM-with-Duration implementation – for application with a new, pattern recognition informed, nanopore detector

<p>Abstract</p> <p>Background</p> <p>Hidden Markov Models (HMMs) provide an excellent means for structure identification and feature extraction on stochastic sequential data. An HMM-with-Duration (HMMwD) is an HMM that can also exactly model the hidden-label length (recurrence) distributions – while the regular HMM will impose a best-fit geometric distribution in its modeling/representation.</p> <p>Results</p> <p>A Novel, Fast, HMM-with-Duration (HMMwD) Implementation is presented, and experimental results are shown that demonstrate its performance on two-state synthetic data designed to model Nanopore Detector Data. The HMMwD experimental results are compared to (i) the ideal model and to (ii) the conventional HMM. Its accuracy is clearly an improvement over the standard HMM, and matches that of the ideal solution in many cases where the standard HMM does not. Computationally, the new HMMwD has all the speed advantages of the conventional (simpler) HMM implementation. In preliminary work shown here, HMM feature extraction is then used to establish the first pattern recognition-informed (PRI) sampling control of a Nanopore Detector Device (on a "live" data-stream).</p> <p>Conclusion</p> <p>The improved accuracy of the new HMMwD implementation, at the same order of computational cost as the standard HMM, is an important augmentation for applications in gene structure identification and channel current analysis, especially PRI sampling control, for example, where speed is essential. The PRI experiment was designed to inherit the high accuracy of the well characterized and distinctive blockades of the DNA hairpin molecules used as controls (or blockade "test-probes"). For this test set, the accuracy inherited is 99.9%.</p

Nanopore-based kinetics analysis of individual antibody-channel and antibody-antigen interactions

<p>Abstract</p> <p>Background</p> <p>The UNO/RIC Nanopore Detector provides a new way to study the binding and conformational changes of individual antibodies. Many critical questions regarding antibody function are still unresolved, questions that can be approached in a new way with the nanopore detector.</p> <p>Results</p> <p>We present evidence that different forms of channel blockade can be associated with the same antibody, we associate these different blockades with different orientations of "capture" of an antibody in the detector's nanometer-scale channel. We directly detect the presence of antibodies via reductions in channel current. Changes to blockade patterns upon addition of antigen suggest indirect detection of antibody/antigen binding. Similarly, DNA-hairpin anchored antibodies have been studied, where the DNA linkage is to the carboxy-terminus at the base of the antibody's Fc region, with significantly fewer types of (lengthy) capture blockades than was observed for free (un-bound) IgG antibody. The introduction of chaotropic agents and its effects on protein-protein interactions have also been observed.</p> <p>Conclusion</p> <p>Nanopore-based approaches may eventually provide a direct analysis of the complex conformational "negotiations" that occur upon binding between proteins.</p