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

Evaluating the performance of ionic liquid coatings for mitigation of spacecraft surface charges

To reduce the impact of charging effects on satellites, cheap and lightweight conductive coatings are desirable. We mimic space-like charging environments in ultra-high vacuum (UHV) chambers during deposition of charges via the electron beam of a scanning electron microscope (SEM). We use the charge induced signatures in SEM images of a thin ionic liquid (IL) film on insulating surfaces such as glass, to assess the general performance of such coatings. In order to get a reference structure in SEM, the samples were structured by nanosphere lithography and coated with IL. The IL film (we choose BMP DCA, due to its beneficial physical properties) was applied ex situ and a thickness of 10 to 30 nm was determined by reflectometry. Such an IL film is stable under vacuum conditions. It would also only lead to additional mass of below 20 mg/m$^2$. At about 5 A/m$^2 \approx 3\cdot10^{19}$ e/(s$\cdot$m$^2$), a typical sample charging rate in SEM, imaging is possible with no noticeable contrast changes over many hours; this electron current density is already 6 orders of magnitudes higher than "worst case geosynchronous environments" of $3\cdot10^{-6}$ A/m$^2$. Measurements of the surface potential are used for further insights in the reaction of IL films to the electron beam of a SEM. Participating mechanisms such as polarization or reorientation will are discussed.Comment: Submitted to Proceedings of the 14th IAA Symposium on Small Satellites for Earth System Observatio

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

Optimisation of pulse shape discrimination using EJ299-33 for high energy neutron detection in proton beam therapy

It is widely understood that proton beam therapy has considerable clinical benefits over photon therapy for treating certain types of tumours. Protons deposit most of their energy in a very localised area, the so-called Bragg peak, sparing surrounding healthy tissue and critical organs from radiation. However, secondary neutrons and gamma rays are generated in the beam nozzle and inside the patient. Clinically, it is highly desirable to monitor the neutron dose the patient is exposed to, and this requires a neutron detector sensitive to high energies. EJ299-33 is a solid plastic scintillator capable of discriminating neutrons from gamma rays using pulse shape analysis of scintillation light. EJ299-33 has the potential to detect neutrons with energies up to 100 MeV and does not present leakage and flammability hazards generally associated with liquid scintillators. Experimental measurements with 60Co, 137Cs and 241AmBe sources were performed to calibrate and optimise pulse shape discrimination parameters. We also performed experimental measurements at the Clatterbridge Cancer Centre in a 60 MeV passive scattered beam to detect high energy neutrons

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

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

Microstructural analysis of phase separation in iron chalcogenide superconductors

The interplay between superconductivity, magnetism and crystal structure in iron-based superconductors is a topic of great interest amongst the condensed matter physics community as it is thought to be the key to understanding the mechanisms responsible for high temperature superconductivity. Alkali metal doped iron chalcogenide superconductors exhibit several unique characteristics which are not found in other iron-based superconducting materials such as antiferromagnetic ordering at room temperature, the presence of ordered iron vacancies and high resistivity normal state properties. Detailed microstructural analysis is essential in order to understand the origin of these unusual properties. Here we have used a range of complementary scanning electron microscope based techniques, including high-resolution electron backscatter di raction mapping, to assess local variations in composition and lattice parameter with high precision and sub-micron spatial resolution. Phase separation is observed in the Csx Fe2-ySe2 crystals, with the minor phase distributed in a plate-like morphology throughout the crystal. Our results are consistent with superconductivity occurring only in the minority phase.Comment: Accepted for publication in a special edition of Supercond. Sci. Techno