An adaptive non-raster scanning method in atomic force microscopy for simple sample shapes

It is a significant challenge to reduce the scanning time in atomic force microscopy while retaining imaging quality. In this paper, a novel non-raster scanning method for high-speed imaging is presented. The method proposed here is developed for a specimen with the simple shape of a cell. The image is obtained by scanning the boundary of the specimen at successively increasing heights, creating a set of contours. The scanning speed is increased by employing a combined prediction algorithm, using a weighted prediction from the contours scanned earlier, and from the currently scanned contour. In addition, an adaptive change in the height step after each contour scan is suggested. A rigorous simulation test bed recreates the x-y specimen stage dynamics and the cantilever height control dynamics, so that a detailed parametric comparison of the scanning algorithms is possible. The data from different scanning algorithms are compared after the application of an image interpolation algorithm (the Delaunay interpolation algorithm), which can also run on-line.We would like to acknowledge the support of the Engineering and Physical Sciences Research Council (EPSRC) (grant nos. EP/I034882/1 & EP/I034831/1)

A Multi-mode Transverse Dynamic Force Microscope - Design, Identification and Control

This is the author accepted manuscript. The final version is available from IEEE via the DOI in this record.The transverse dynamic force microscope (TDFM) and its shear force sensing principle permit true non-contact force detection in contrast to typical atomic force microscopes. The two TDFM measurement signals for the cantilever allow, in principle, two different scanning modes of which, in particular, the second presented here permits a full-scale non-contact scan. Previous research mainly focused on developing the sensing mechanism, whereas this work investigates the vertical axis dynamics for advanced robust closed-loop control. This paper presents a new TDFM digital control solution, built on field-programmable gate array (FPGA) equipment running at high implementation frequencies. The integrated control system allows the implementation of online customizable controllers, and raster-scans in two modes at very high detection bandwidth and nano-precision. Robust control algorithms are designed, implemented, and practically assessed. The two realized scanning modes are experimentally evaluated by imaging nano-spheres with known dimensions in wet conditions.Engineering and Physical Sciences Research Council (EPSRC

Optimisation of a nano-positioning stage for a Transverse Dynamic Force Microscope

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.This paper describes the optimisation of a nano-positioning stage for a Transverse Dynamic Force Microscope (TDFM). The nano-precision stage is required to move a specimen dish within a horizontal region of 1 μm × 1 μm and with a resolution of 0.3 nm. The design objective was to maximise positional accuracy during high speed actuation. This was achieved by minimising out-of-plane distortions and vibrations during actuation. Optimal performance was achieved through maximising out-of-plane stiffness through shape and material selection as well optimisation of the anchoring system. Several shape parameters were optimised including the shape of flexural beams and the shape of the dish holder. Physical prototype testing was an essential part of the design process to confirm the accuracy of modelling and also to reveal issues with manufacturing tolerances. An overall resonant frequency of 6 kHz was achieved allowing for a closed loop-control frequency of 1.73 kHz for precise horizontal motion control. This resonance represented a 12-fold increase from the original 500 Hz of a commercially available positioning stage. Experimental maximum out-of-plane distortions below the first resonance frequency were reduced from 0.3 μm for the first prototype to less than 0.05 μm for the final practical prototype

Real-time sliding mode observer scheme for shear force estimation in a transverse dynamic force microscope

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.This paper describes a sliding mode observer scheme for estimation of the shear force affecting the cantilever in a Transverse Dynamic Force Microscope (TDFM). The vertically oriented cantilever is oscillated in proximity to the specimen under investigation. The amplitude of oscillation of the cantilever tip is affected by these shear forces. They are created by the ordered-water layer above the specimen. The oscillation amplitude is therefore a measure of distance between the tip and the surface of the specimen. Consequently, the estimation of the shear forces provides useful information about the specimen characteristics. For estimating the shear forces, an approximate finite dimensional model of the cantilever is created using the method of lines. This model is subsequently reduced for its model order. An unknown input sliding mode observer has been used to reconstruct the unknown shear forces using only tip position measurements and the cantilever excitation. This paper describes the development of the sliding mode scheme and presents experimental results from the TDFM set up at the Centre for Nanoscience and Quantum Information (NSQI) at Bristol University

SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer

Pancreatic cancer has a devastating prognosis, with an overall 5-year survival rate of ~8%, restricted treatment options and characteristic molecular heterogeneity. SerpinB2 expression, particularly in the stromal compartment, is associated with reduced metastasis and prolonged survival in pancreatic ductal adenocarcinoma (PDAC) and our genomic analysis revealed that SERPINB2 is frequently deleted in PDAC. We show that SerpinB2 is required by stromal cells for normal collagen remodelling in vitro, regulating fibroblast interaction and engagement with collagen in the contracting matrix. In a pancreatic cancer allograft model, co-injection of PDAC cancer cells and SerpinB2(-/-) mouse embryonic fibroblasts (MEFs) resulted in increased tumour growth, aberrant remodelling of the extracellular matrix (ECM) and increased local invasion from the primary tumour. These tumours also displayed elevated proteolytic activity of the primary biochemical target of SerpinB2-urokinase plasminogen activator (uPA). In a large cohort of patients with resected PDAC, we show that increasing uPA mRNA expression was significantly associated with poorer survival following pancreatectomy. This study establishes a novel role for SerpinB2 in the stromal compartment in PDAC invasion through regulation of stromal remodelling and highlights the SerpinB2/uPA axis for further investigation as a potential therapeutic target in pancreatic cancer

Robust, Integrated Computational Control of NMR Experiments to Achieve Optimal Assignment by ADAPT-NMR

ADAPT-NMR (Assignment-directed Data collection Algorithm utilizing a Probabilistic Toolkit in NMR) represents a groundbreaking prototype for automated protein structure determination by nuclear magnetic resonance (NMR) spectroscopy. With a [13C,15N]-labeled protein sample loaded into the NMR spectrometer, ADAPT-NMR delivers complete backbone resonance assignments and secondary structure in an optimal fashion without human intervention. ADAPT-NMR achieves this by implementing a strategy in which the goal of optimal assignment in each step determines the subsequent step by analyzing the current sum of available data. ADAPT-NMR is the first iterative and fully automated approach designed specifically for the optimal assignment of proteins with fast data collection as a byproduct of this goal. ADAPT-NMR evaluates the current spectral information, and uses a goal-directed objective function to select the optimal next data collection step(s) and then directs the NMR spectrometer to collect the selected data set. ADAPT-NMR extracts peak positions from the newly collected data and uses this information in updating the analysis resonance assignments and secondary structure. The goal-directed objective function then defines the next data collection step. The procedure continues until the collected data support comprehensive peak identification, resonance assignments at the desired level of completeness, and protein secondary structure. We present test cases in which ADAPT-NMR achieved results in two days or less that would have taken two months or more by manual approaches

Age-related changes in global motion coherence: conflicting haemodynamic and perceptual responses

Our aim was to use both behavioural and neuroimaging data to identify indicators of perceptual decline in motion processing. We employed a global motion coherence task and functional Near Infrared Spectroscopy (fNIRS). Healthy adults (n = 72, 18-85) were recruited into the following groups: young (n = 28, mean age = 28), middle-aged (n = 22, mean age = 50), and older adults (n = 23, mean age = 70). Participants were assessed on their motion coherence thresholds at 3 different speeds using a psychophysical design. As expected, we report age group differences in motion processing as demonstrated by higher motion coherence thresholds in older adults. Crucially, we add correlational data showing that global motion perception declines linearly as a function of age. The associated fNIRS recordings provide a clear physiological correlate of global motion perception. The crux of this study lies in the robust linear correlation between age and haemodynamic response for both measures of oxygenation. We hypothesise that there is an increase in neural recruitment, necessitating an increase in metabolic need and blood flow, which presents as a higher oxygenated haemoglobin response. We report age-related changes in motion perception with poorer behavioural performance (high motion coherence thresholds) associated with an increased haemodynamic response

Boolean Dynamics with Random Couplings

This paper reviews a class of generic dissipative dynamical systems called N-K models. In these models, the dynamics of N elements, defined as Boolean variables, develop step by step, clocked by a discrete time variable. Each of the N Boolean elements at a given time is given a value which depends upon K elements in the previous time step. We review the work of many authors on the behavior of the models, looking particularly at the structure and lengths of their cycles, the sizes of their basins of attraction, and the flow of information through the systems. In the limit of infinite N, there is a phase transition between a chaotic and an ordered phase, with a critical phase in between. We argue that the behavior of this system depends significantly on the topology of the network connections. If the elements are placed upon a lattice with dimension d, the system shows correlations related to the standard percolation or directed percolation phase transition on such a lattice. On the other hand, a very different behavior is seen in the Kauffman net in which all spins are equally likely to be coupled to a given spin. In this situation, coupling loops are mostly suppressed, and the behavior of the system is much more like that of a mean field theory. We also describe possible applications of the models to, for example, genetic networks, cell differentiation, evolution, democracy in social systems and neural networks.Comment: 69 pages, 16 figures, Submitted to Springer Applied Mathematical Sciences Serie