Design of multi-frequency acoustic kinoforms

Complex diffraction limited acoustic fields can be generated from a single element transducer using inexpensive 3-D printable acoustic kinoforms. This is extremely promising for a number of applications. However, the lack of ability to vary the field limits the potential use of this technology. In this work, this limitation is circumvented using multi-frequency acoustic kinoforms for which different acoustic fields are encoded onto different driving frequencies. An optimisation approach based on random downhill binary search is introduced for the design of the multi-frequency kinoforms. This is applied to two test cases to demonstrate the technique: a kinoform designed to generate the numerals “1,” “2,” and “3” in the same plane but at different driving frequencies, and a kinoform designed to generate 3 sets of eight foci lying on a circle with a driving-frequency-dependent radius. Field measurements from these samples confirmed that multi-frequency acoustic kinoforms can be designed that switch between different arbitrary, pre-designed, acoustic field patterns in the target plane by changing the driving frequenc

Generating arbitrary ultrasound fields with tailored optoacoustic surface profiles

Acoustic fields with multiple foci have many applications in physical acoustics ranging from particle manipulation to neural modulation. However, the generation of multiple foci at arbitrary locations in three-dimensional is challenging using conventional transducer technology. In this work, the optical generation of acoustic fields focused at multiple points using a single optical pulse is demonstrated. This is achieved using optically absorbing surface profiles designed to generate specific, user-defined, wavefields. An optimisation approach for the design of these tailored surface profiles is developed. This searches for a smoothly varying surface that will generate a high peak pressure at a set of target focal points. The designed surface profiles are then realised via a combination of additive manufacturing and absorber deposition techniques. Acoustic field measurements from a sample designed to generate the numeral “7” are used to demonstrate the design method

Control of broadband optically generated ultrasound pulses using binary amplitude holograms

In this work, the use of binary amplitude holography is investigated as a mechanism to focus broadband acoustic pulses generated by high peak-power pulsed lasers. Two algorithms are described for the calculation of the binary holograms; one using ray-tracing, and one using an optimization based on direct binary search. It is shown using numerical simulations that when a binary amplitude hologram is excited by a train of laser pulses at its design frequency, the acoustic field can be focused at a pre-determined distribution of points, including single and multiple focal points, and line and square foci. The numerical results are validated by acoustic field measurements from binary amplitude holograms, excited by a high peak-power laser

Preliminary evaluation of a variable compliance joystick for people with multiple sclerosis

Upper-limb fatigue is a common problem that may restrict people with multiple sclerosis (MS) from using their electric powered wheelchair effectively and for a long period of time. The objective of this research is to evaluate whether participants with MS can drive better with a variable compliance joystick (VCJ) and customizable algorithms than with a conventional wheelchair joystick. Eleven participants were randomly assigned to one of two groups. The groups used the VCJ in either compliant or noncompliant isometric mode and a standard algorithm, personally fitted algorithm, or personally fitted algorithm with fatigue adaptation running in the background in order to complete virtual wheelchair driving tasks. Participants with MS showed better driving performance metrics while using the customized algorithms than while using the standard algorithm with the VCJ. Fatigue adaptation algorithms are especially beneficial in improving overall task performance while using the VCJ in isometric mode. The VCJ, along with the personally fitted algorithms and fatigue adaptation algorithms, has the potential to be an effective input interface for wheelchairs

Single Pulse Illumination of Multi-Layer Photoacoustic Holograms for Patterned Ultrasound Field Generation

A new method for the creation of patterned, focused, optically generated acoustic fields using a single optical pulse is introduced. This utilises multi-layer `holograms' composed of several spatially separate absorbing layers. Each layer is individually patterned so as to focus at a set of targeted points. To create the patterns, a ray-tracing model was implemented to calculate the impulse response of pixels within each absorbing layer to a set of targeted points. An optimisation approach was then used to find the optimal pattern for each layer to create a field evenly focused at each of the target points. The method was validated using both numerical simulations and acoustic field measurements. It was demonstrated that a 3×3 array of acoustic foci could be generated from a 3-layer hologram using a single laser pulse

Hydrazine compounds inhibit glycation of low-density lipoproteins and prevent the in vitro formation of model foam cells from glycolaldehyde-modified low-density lipoproteins

Aims/hypothesis: Previous studies have shown that glycation of LDL by methylglyoxal and glycolaldehyde, in the absence of significant oxidation, results in lipid accumulation in macrophage cells. Such 'foam cells' are a hallmark of atherosclerosis. In this study we examined whether LDL glycation by methylglyoxal or glycolaldehyde, and subsequent lipid loading of cells, can be inhibited by agents that scavenge reactive carbonyls. Such compounds may have therapeutic potential in diabetes-associated atherosclerosis. Materials and methods: LDL was glycated with methylglyoxal or glycolaldehyde in the absence or presence of metformin, aminoguanidine, Girard's reagents P and T, or hydralazine. LDL modification was characterised by changes in mobility (agarose gel electrophoresis), cross-linking (SDS-PAGE) and loss of amino acid residues (HPLC). Accumulation of cholesterol and cholesteryl esters in murine macrophages was assessed by HPLC. Results: Inhibition of LDL glycation was detected with equimolar or greater concentrations of the scavengers over the reactive carbonyl. This inhibition was structure-dependent and accompanied by a modulation of cholesterol and cholesteryl ester accumulation. With aminoguanidine, Girard's reagent P and hydralazine, cellular sterol levels returned to control levels despite incomplete inhibition of LDL modification. Conclusions/ interpretation: Inhibition of LDL glycation by interception of the reactive aldehydes that induce LDL modification prevents lipid loading and model foam cell formation in murine macrophage cells. Carbonyl-scavenging reagents, such as hydrazines, may therefore help inhibit LDL glycation in vivo and prevent diabetes-induced atherosclerosis. © Springer-Verlag 2006

Comparative reactivity of the myeloperoxidase-derived oxidants HOCl and HOSCN with low-density lipoprotein (LDL): Implications for foam cell formation in atherosclerosis

© 2015 Elsevier Inc. All rights reserved. Abstract Atherosclerosis is characterised by the accumulation of lipids within macrophages in the artery wall. Low-density lipoprotein (LDL) is the source of this lipid, owing to the uptake of oxidised LDL by scavenger receptors. Myeloperoxidase (MPO) released by leukocytes during inflammation produces oxidants that are implicated in atherosclerosis. Modification of LDL by the MPO oxidant hypochlorous acid (HOCl), results in extensive lipid accumulation by macrophages. However, the reactivity of the other major MPO oxidant, hypothiocyanous acid (HOSCN) with LDL is poorly characterised, which is significant given that thiocyanate is the favoured substrate for MPO. In this study, we comprehensively compare the reactivity of HOCl and HOSCN with LDL, and show key differences in the profile of oxidative damage observed. HOSCN selectively modifies Cys residues on apolipoprotein B100, and oxidises cholesteryl esters resulting in formation of lipid hydroperoxides, 9-hydroxy-10,12-octadecadienoic acid (9-HODE) and F2-isoprostanes. The modification of LDL by HOSCN results macrophage lipid accumulation, though generally to a lesser extent than HOCl-modified LDL. This suggests that a change in the ratio of HOSCN:HOCl formation by MPO from variations in plasma thiocyanate levels, will influence the nature of LDL oxidation in vivo, and has implications for the progression of atherosclerosis

A Dynamic Model of Interactions of Ca^(2+), Calmodulin, and Catalytic Subunits of Ca^(2+)/Calmodulin-Dependent Protein Kinase II

During the acquisition of memories, influx of Ca^(2+) into the postsynaptic spine through the pores of activated N-methyl-D-aspartate-type glutamate receptors triggers processes that change the strength of excitatory synapses. The pattern of Ca^(2+) influx during the first few seconds of activity is interpreted within the Ca^(2+)-dependent signaling network such that synaptic strength is eventually either potentiated or depressed. Many of the critical signaling enzymes that control synaptic plasticity, including Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII), are regulated by calmodulin, a small protein that can bind up to 4 Ca^(2+) ions. As a first step toward clarifying how the Ca^(2+)-signaling network decides between potentiation or depression, we have created a kinetic model of the interactions of Ca^(2+), calmodulin, and CaMKII that represents our best understanding of the dynamics of these interactions under conditions that resemble those in a postsynaptic spine. We constrained parameters of the model from data in the literature, or from our own measurements, and then predicted time courses of activation and autophosphorylation of CaMKII under a variety of conditions. Simulations showed that species of calmodulin with fewer than four bound Ca^(2+) play a significant role in activation of CaMKII in the physiological regime, supporting the notion that processing ofCa^(2+) signals in a spine involves competition among target enzymes for binding to unsaturated species of CaM in an environment in which the concentration of Ca^(2+) is fluctuating rapidly. Indeed, we showed that dependence of activation on the frequency of Ca^(2+) transients arises from the kinetics of interaction of fluctuating Ca^(2+) with calmodulin/CaMKII complexes. We used parameter sensitivity analysis to identify which parameters will be most beneficial to measure more carefully to improve the accuracy of predictions. This model provides a quantitative base from which to build more complex dynamic models of postsynaptic signal transduction during learning

Gene Function Classification Using Bayesian Models with Hierarchy-Based Priors

We investigate the application of hierarchical classification schemes to the annotation of gene function based on several characteristics of protein sequences including phylogenic descriptors, sequence based attributes, and predicted secondary structure. We discuss three Bayesian models and compare their performance in terms of predictive accuracy. These models are the ordinary multinomial logit (MNL) model, a hierarchical model based on a set of nested MNL models, and a MNL model with a prior that introduces correlations between the parameters for classes that are nearby in the hierarchy. We also provide a new scheme for combining different sources of information. We use these models to predict the functional class of Open Reading Frames (ORFs) from the E. coli genome. The results from all three models show substantial improvement over previous methods, which were based on the C5 algorithm. The MNL model using a prior based on the hierarchy outperforms both the non-hierarchical MNL model and the nested MNL model. In contrast to previous attempts at combining these sources of information, our approach results in a higher accuracy rate when compared to models that use each data source alone. Together, these results show that gene function can be predicted with higher accuracy than previously achieved, using Bayesian models that incorporate suitable prior information