Network theory approach for data evaluation in the dynamic force spectroscopy of biomolecular interactions

Investigations of molecular bonds between single molecules and molecular complexes by the dynamic force spectroscopy are subject to large fluctuations at nanoscale and possible other aspecific binding, which mask the experimental output. Big efforts are devoted to develop methods for effective selection of the relevant experimental data, before taking the quantitative analysis of bond parameters. Here we present a methodology which is based on the application of graph theory. The force-distance curves corresponding to repeated pulling events are mapped onto their correlation network (mathematical graph). On these graphs the groups of similar curves appear as topological modules, which are identified using the spectral analysis of graphs. We demonstrate the approach by analyzing a large ensemble of the force-distance curves measured on: ssDNA-ssDNA, peptide-RNA (system from HIV1), and peptide-Au surface. Within our data sets the methodology systematically separates subgroups of curves which are related to different intermolecular interactions and to spatial arrangements in which the molecules are brought together and/or pulling speeds. This demonstrates the sensitivity of the method to the spatial degrees of freedom, suggesting potential applications in the case of large molecular complexes and situations with multiple binding sites

Strain in epitaxial MnSi films on Si(111) in the thick film limit studied by polarization-dependent extended x-ray absorption fine structure

We report a study of the strain state of epitaxial MnSi films on Si(111) substrates in the thick film limit (100-500~\AA) as a function of film thickness using polarization-dependent extended x-ray absorption fine structure (EXAFS). All films investigated are phase-pure and of high quality with a sharp interface between MnSi and Si. The investigated MnSi films are in a thickness regime where the magnetic transition temperature $T_\mathrm{c}$ assumes a thickness-independent enhanced value of $\geq$43~K as compared with that of bulk MnSi, where $T_\mathrm{c} \approx 29~{\rm K}$. A detailed refinement of the EXAFS data reveals that the Mn positions are unchanged, whereas the Si positions vary along the out-of-plane [111]-direction, alternating in orientation from unit cell to unit cell. Thus, for thick MnSi films, the unit cell volume is essentially that of bulk MnSi --- except in the vicinity of the interface with the Si substrate (thin film limit). In view of the enhanced magnetic transition temperature we conclude that the mere presence of the interface, and its specific characteristics, strongly affects the magnetic properties of the entire MnSi film, even far from the interface. Our analysis provides invaluable information about the local strain at the MnSi/Si(111) interface. The presented methodology of polarization dependent EXAFS can also be employed to investigate the local structure of other interesting interfaces.Comment: 11 pages, 10 figure

High resolution characterisation of microstructural evolution in Rbx_{x}Fe2−y_{2-y}Se2_{2} crystals on annealing

The superconducting and magnetic properties of phase-separated A$_x$Fe$_{2-y}$Se$_2$ compounds are known to depend on post-growth heat treatments and cooling profiles. This paper focusses on the evolution of microstructure on annealing, and how this influences the superconducting properties of Rb$_x$Fe$_2-y$Se$_2$ crystals. We find that the minority phase in the as-grown crystal has increased unit cell anisotropy (c/a ratio), reduced Rb content and increased Fe content compared to the matrix. The microstructure is rather complex, with two-phase mesoscopic plate-shaped features aligned along {113} habit planes. The minority phase are strongly facetted on the {113} planes, which we have shown to be driven by minimising the volume strain energy introduced as a result of the phase transformation. Annealing at 488K results in coarsening of the mesoscopic plate-shaped features and the formation of a third distinct phase. The subtle differences in structure and chemistry of the minority phase(s) in the crystals are thought to be responsible for changes in the superconducting transition temperature. In addition, scanning photoemission microscopy has clearly shown that the electronic structure of the minority phase has a higher occupied density of states of the low binding energy Fe3d orbitals, characteristic of crystals that exhibit superconductivity. This demonstrates a clear correlation between the Fe-vacancy-free phase with high c/a ratio and the electronic structure characteristics of the superconducting phase.Comment: 6 figures v2 is exactly the same as v1. The typesetting errors in the abstract have been correcte

Individual grain boundary properties and overall performance of metal-organic deposition coated conductors

have investigated single grain boundaries (GBs) isolated in coated conductors produced by metal-organic deposition. When a magnetic field is swept in the film plane, an angle-dependent crossover from boundary to grain limited critical current density J(c) is found. In the force-free orientation, even at fields as high as 8 T, the GBs still limit Jc. We deduce that this effect is a direct consequence of GB meandering. We have employed these single GB results to explain the dependence of Jc of polycrystalline tracks on their width: in-plane measurements become flatter as the tracks are narrowed down. This result is consistent with the stronger GB limitation at field configurations close to force-free found from the isolated boundaries. Our study shows that for certain geometries even at high fields the effect of GBs cannot be neglected.This work was supported by the Engineering and Physical Sciences Research Council [grant numbers EP/C011546/1 and EP/C011554/1

Fluctuations, line tensions, and correlation times of nanoscale islands on surfaces

We analyze in detail the fluctuations and correlations of the (spatial) Fourier modes of nano-scale single-layer islands on (111) fcc crystal surfaces. We analytically show that the Fourier modes of the fluctuations couple due to the anisotropy of the crystal, changing the power spectrum of the fluctuations, and that the actual eigenmodes of the fluctuations are the appropriate linear combinations of the Fourier modes. Using kinetic Monte Carlo simulations with bond-counting parameters that best match realistic energy barriers for hopping rates, we deduce absolute line tensions as a function of azimuthal orientation from the analyses of the fluctuation of each individual mode. The autocorrelation functions of these modes give the scaling of the correlation times with wavelength, providing us with the rate-limiting kinetics driving the fluctuations, here step-edge diffusion. The results for the energetic parameters are in reasonable agreement with available experimental data for Pb(111) surfaces, and we compare the correlation times of island-edge fluctuations to relaxation times of quenched Pb crystallites.Comment: 11 pages, 8 figures; to appear in PRB 70, xxx (15 Dec 2004), changes in MC and its implication

Correlations in nano-scale step fluctuations: comparison of simulation and experiments

We analyze correlations in step-edge fluctuations using the Bortz-Kalos-Lebowitz kinetic Monte Carlo algorithm, with a 2-parameter expression for energy barriers, and compare with our VT-STM line-scan experiments on spiral steps on Pb(111). The scaling of the correlation times gives a dynamic exponent confirming the expected step-edge-diffusion rate-limiting kinetics both in the MC and in the experiments. We both calculate and measure the temperature dependence of (mass) transport properties via the characteristic hopping times and deduce therefrom the notoriously-elusive effective energy barrier for the edge fluctuations. With a careful analysis we point out the necessity of a more complex model to mimic the kinetics of a Pb(111) surface for certain parameter ranges.Comment: 10 pages, 9 figures, submitted to Physical Review

Initiation of dendritic failure of LLZTO via sub-surface lithium deposition

The occurrence of lithium deposition in occluded spaces within ceramic electrolytes due to electronic leakage currents can jeopardise the commercialization of power-dense solid-state batteries. Here, we utilize plasma-FIB serial sectioning to visualize the surface and sub-surface of a garnet solid electrolyte (LLZTO) after lithium plating. We study the morphology of surface spallation cracks, which represent the initial stage of dendrite formation. Employing a LiMg anode, we track the magnesium diffusion around these surface cracks with EDS. The absence of magnesium in early-stage cracks suggests they form due to the pressure build-up from the deposition of pure lithium in occluded pores near the electrolyte surface. These spallation cracks act as current focusing and stress concentration hot spots. Electron beam induced current imaging demonstrates that short-circuiting lithium dendrites grow from the spallations during plating. Thus, the sub-surface deposition of lithium is a possible explanation for the initiation of lithium dendrites in LLZTO

A novel methodology for in vivo endoscopic phenotyping of colorectal cancer based on real-time analysis of the mucosal lipidome: a prospective observational study of the iKnife

Background: This pilot study assessed the diagnostic accuracy of rapid evaporative ionization mass spectrometry (REIMS) in colorectal cancer (CRC) and colonic adenomas. Methods: Patients undergoing elective surgical resection for CRC were recruited at St. Mary’s Hospital London and The Royal Marsden Hospital, UK. Ex vivo analysis was performed using a standard electrosurgery handpiece with aspiration of the electrosurgical aerosol to a Xevo G2-S iKnife QTof mass spectrometer (Waters Corporation). Histological examination was performed for validation purposes. Multivariate analysis was performed using principal component analysis and linear discriminant analysis in Matlab 2015a (Mathworks, Natick, MA). A modified REIMS endoscopic snare was developed (Medwork) and used prospectively in five patients to assess its feasibility during hot snare polypectomy. Results: Twenty-eight patients were recruited (12 males, median age 71, range 35–89). REIMS was able to reliably distinguish between cancer and normal adjacent mucosa (NAM) (AUC 0.96) and between NAM and adenoma (AUC 0.99). It had an overall accuracy of 94.4 % for the detection of cancer versus adenoma and an adenoma sensitivity of 78.6 % and specificity of 97.3 % (AUC 0.99) versus cancer. Long-chain phosphatidylserines (e.g., PS 22:0) and bacterial phosphatidylglycerols were over-expressed on cancer samples, while NAM was defined by raised plasmalogens and triacylglycerols expression and adenomas demonstrated an over-expression of ceramides. REIMS was able to classify samples according to tumor differentiation, tumor budding, lymphovascular invasion, extramural vascular invasion and lymph node micrometastases (AUC’s 0.88, 0.87, 0.83, 0.81 and 0.81, respectively). During endoscopic deployment, colonoscopic REIMS was able to detect target lipid species such as ceramides during hot snare polypectomy. Conclusion: REIMS demonstrates high diagnostic accuracy for tumor type and for established histological features of poor prognostic outcome in CRC based on a multivariate analysis of the mucosal lipidome. REIMS could augment endoscopic and imaging technologies for precision phenotyping of colorectal cancer

Quantum interference structures in the conductance plateaus of gold nanojunctions

The conductance of breaking metallic nanojunctions shows plateaus alternated with sudden jumps, corresponding to the stretching of stable atomic configurations and atomic rearrangements, respectively. We investigate the structure of the conductance plateaus both by measuring the voltage dependence of the plateaus' slope on individual junctions and by a detailed statistical analysis on a large amount of contacts. Though the atomic discreteness of the junction plays a fundamental role in the evolution of the conductance, we find that the fine structure of the conductance plateaus is determined by quantum interference phenomenon to a great extent.Comment: 4 pages, 4 figure