Characterization of topographical effects on macrophage behavior in a foreign body response model.

Current strategies to limit macrophage adhesion, fusion and fibrous capsule formation in the foreign body response have focused on modulating material surface properties. We hypothesize that topography close to biological scale, in the micron and nanometric range, provides a passive approach without bioactive agents to modulate macrophage behavior. In our study, topography-induced changes in macrophage behavior was examined using parallel gratings (250 nm-2 mum line width) imprinted on poly(epsilon-caprolactone) (PCL), poly(lactic acid) (PLA) and poly(dimethyl siloxane) (PDMS). RAW 264.7 cell adhesion and elongation occurred maximally on 500 nm gratings compared to planar controls over 48 h. TNF-alpha and VEGF secretion levels by RAW 264.7 cells showed greatest sensitivity to topographical effects, with reduced levels observed on larger grating sizes at 48 h. In vivo studies at 21 days showed reduced macrophage adhesion density and degree of high cell fusion on 2 mum gratings compared to planar controls. It was concluded that topography affects macrophage behavior in the foreign body response on all polymer surfaces examined. Topography-induced changes, independent of surface chemistry, did not reveal distinctive patterns but do affect cell morphology and cytokine secretion in vitro, and cell adhesion in vivo particularly on larger size topography compared to planar controls.

Nanotopography-induced changes in focal adhesions, cytoskeletal organization, and mechanical properties of human mesenchymal stem cells.

The growth of stem cells can be modulated by physical factors such as extracellular matrix nanotopography. We hypothesize that nanotopography modulates cell behavior by changing the integrin clustering and focal adhesion (FA) assembly, leading to changes in cytoskeletal organization and cell mechanical properties. Human mesenchymal stem cells (hMSCs) cultured on 350 nm gratings of tissue-culture polystyrene (TCPS) and polydimethylsiloxane (PDMS) showed decreased expression of integrin subunits alpha2, alpha , alpha V, beta2, beta 3 and beta 4 compared to the unpatterned controls. On gratings, the elongated hMSCs exhibited an aligned actin cytoskeleton, while on unpatterned controls, spreading cells showed a random but denser actin cytoskeleton network. Expression of cytoskeleton and FA components was also altered by the nanotopography as reflected in the mechanical properties measured by atomic force microscopy (AFM) indentation. On the rigid TCPS, hMSCs on gratings exhibited lower instantaneous and equilibrium Young's moduli and apparent viscosity. On the softer PDMS, the effects of nanotopography were not significant. However, hMSCs cultured on PDMS showed lower cell mechanical properties than those on TCPS, regardless of topography. These suggest that both nanotopography and substrate stiffness could be important in determining mechanical properties, while nanotopography may be more dominant in determining the organization of the cytoskeleton and FAs.

Low-dose studies of bystander cell killing with targeted soft X rays

The Gray Cancer Institute ultrasoft X-ray microprobe was used to quantify the bystander response of individual V79 cells exposed to a focused carbon K-shell (278 eV) X-ray beam. The ultrasoft X-ray microprobe is designed to precisely assess the biological response of individual cells irradiated in vitro with a very fine beam of low-energy photons. Characteristic C-K X rays are generated by a focused beam of 10 keV electrons striking a graphite target. Circular diffraction gratings (i.e. zone plates) are then employed to focus the X-ray beam into a spot with a radius of 0.25 mum at the sample position. Using this microbeam technology, the correlation between the irradiated cells and their nonirradiated neighbors can be examined critically. The survival response of V79 cells irradiated with a C-K X-ray beam was measured in the 0-2-Gy dose range. The response when all cells were irradiated was compared to that obtained when only a single cell was exposed. The cell survival data exhibit a linear-quadratic response when all cells were targeted (with evidence for hyper-sensitivity at low doses). When only a single cell was targeted within the population, 10% cell killing was measured. In contrast to the binary bystander behavior reported by many other investigations, the effect detected was initially dependent on dose (200 mGy). In the low-dose region (

Chemical Sensing Using a Polymer Coated Long-Period Fiber Grating Interrogated by Ring-Down Spectroscopy

An etched long-period grating was used as a refractive index sensor for vapours of four volatile organic compounds, i.e. m-xylene, cyclohexane, trichloroethylene and commercial gasoline. The sensitivity to the vapours was further increased by solid-phase microextraction into a coating made of polydimethylsiloxane (PDMS)/polymethyl-octylsiloxane (PMOS) co-polymer. By further amplification of the optical loss in an optical cavity made of two identical fiber-Bragg gratings and interrogation by phase-shift cavity ring-down spectroscopy we could detect and distinguish xylene (detection limit: 134ppm) from trichloroethylene (3300ppm), cyclohexane (1850ppm) and gasoline (10,500ppm).

Single-Mode Fiber Refractive Index Sensor Based on Core-Offset Attenuators

Mach-Zehnder and Michelson interferometers using core-offset attenuators were demonstrated. As the relative offset direction of the two attenuators in the Mach-Zehnder interferometer can significantly affect the extinction ratio of the interference pattern, single core-offset attenuator-based sensors appear more robust and repeatable. A novel fiber Michelson interferometer refractive index (RI) sensor was subsequently realized by a single core-offset attenuator and a layer of ~ 500-nm gold coating. The device had a minimum insertion loss of 0.01 dB and maximum extinction ratio over 9 dB. The sensitivity (0.333 nm) of the new sensor to its surrounding RI change (0.01) was found to be comparable to that (0.252 nm) of an identical long period gratings pair Mach-Zehnder interferometric sensor, and its ease of fabrication makes it a low-cost alternative to existing sensing applications.

Optical Fiber Sensing Based on Reflection Laser Spectroscopy

An overview on high-resolution and fast interrogation of optical-fiber sensors relying on laser reflection spectroscopy is given. Fiber Bragg-gratings (FBGs) and FBG resonators built in fibers of different types are used for strain, temperature and acceleration measurements using heterodyne-detection and optical frequency-locking techniques. Silica fiber-ring cavities are used for chemical sensing based on evanescent-wave spectroscopy. Various arrangements for signal recovery and noise reduction, as an extension of most typical spectroscopic techniques, are illustrated and results on detection performances are presented.

Fiber-Optic Ring-Down Spectroscopy Using a Tunable Picosecond Gain-Switched Diode Laser

Visible and near-infrared laser light pulses were coupled into two different types of optical fiber cavities. One cavity consisted of a short strand of fiber waveguide that contained two identical fiber Bragg gratings. Another cavity was made using a loop of optical fiber. In either cavity ∼ 40 ps laser pulses, which were generated using a custom-built gainswitched diode laser, circulated for a large number of round trips. The optical loss of either cavity was determined from the ring-down times. Cavity ring-down spectroscopy was performed on 200 pL volumes of liquid samples that were injected into the cavities using a 100 μm gap in the fiber loop. A detection limit of 20 ppm of methylene blue dye in aqueous solution, corresponding to a minimum absorptivity of εC < 6 cm−1, was realized.

Appearance of the frequency-doubling stimulus at threshold.

PURPOSE. It has been argued that the threshold for detecting frequency-doubling (FD) technology perimeter stimuli differs from the threshold for perceiving spatial structure (pattern) in the same targets. Thresholds for perceiving spatial structure have typically been assessed using orientation-identification experiments. The authors investigated the influence of orientation, edge profile, and psychophysical method on the origin of the reported differences in detection and orientation-identification thresholds for FD gratings.

METHODS. Detection and orientation-identification thresholds were determined in 12 observers with the use of FD stimuli (0.25 cyc/deg, 25 Hz) presented centrally and at 15° eccentricity. Edge profile (square- and Gaussian-windowed) and orientation (horizontal, vertical, and oblique) were independently modified. Detection thresholds were also measured for spatially uniform flickering targets (25 Hz). Orientation-identification thresholds using a two-alternative forced choice (2-AFC) and a two-interval forced choice (2-IFC) method were also compared in five experienced observers.

RESULTS. Orientation-identification and detection thresholds did not significantly differ under any condition tested. Orientation-identification thresholds obtained with 2-AFC were not significantly different from those obtained with 2-IFC. Thresholds for spatially uniform flicker were significantly lower than for FD stimuli.

CONCLUSIONS. The authors found that orientation-identification and detection thresholds for FD gratings did not differ and argue that recent findings to the contrary arise from the inappropriate use of spatially uniform flicker targets as alternatives in 2-IFC experiments.

Building Stone Condition Monitoring Using Specially Designed Compensated Optical Fiber Humidity Sensors

This paper presents the design and implementation of a novel optical fiber temperature compensated relative humidity (RH) sensor device, based on fiber Bragg gratings (FBGs) and developed specifically for monitoring water ingress leading to the deterioration of building stone. The performance of the sensor thus created, together with that of conventional sensors, was first assessed in the laboratory where they were characterized under experimental conditions of controlled wetting and drying cycles of limestone blocks, before being employed “in-the-field” to monitor actual building stone in a specially built wall. Although a new construction, this was built specifically using conservation methods similar to those employed in past centuries, to allow an accurate simulation of processes occurring with wetting and drying in the historic walls in the University of Oxford.

Fibre-optic strain sensor system with temperature compensation for arch bridge condition monitoring

This paper presents an innovative sensor system, created specifically for new civil engineering structural monitoring applications, allowing specially packaged fiber grating-based sensors to be used in harsh, in-the-field measurement conditions for accurate strain measurement with full temperature compensation. The sensor consists of two fiber Bragg gratings that are protected within a polypropylene package, with one of the fiber gratings isolated from the influence of strain and thus responding only to temperature variations, while the other is sensitive to both strain and temperature. To achieve this, the temperature-monitoring fiber grating is slightly bent and enclosed in a metal envelope to isolate it effectively from the strain. Through an appropriate calibration process, both the strain and temperature coefficients of each individual grating component when incorporated in the sensor system can be thus obtained. By using these calibrated coefficients in the operation of the sensor, both strain and temperature can be accurately determined. The specific application for which these sensors have been designed is seen when installed on an innovative small-scale flexi-arch bridge where they are used for real-time strain measurements during the critical installation stage (lifting) and loading. These sensors have demonstrated enhanced resilience when embedded in or surface-mounted on such concrete structures, providing accurate and consistent strain measurements not only during installation but subsequently during use. This offers an inexpensive and highly effective monitoring system tailored for the new, rapid method of the installation of small-scale bridges for a variety of civil engineering applications.

Do different 'magnocellular tasks' probe the same neural substrate?

The sensory abnormalities associated with disorders such as dyslexia, autism and schizophrenia have often been attributed to a generalized deficit in the visual magnocellular-dorsal stream and its auditory homologue. To probe magnocellular function, various psychophysical tasks are often employed that require the processing of rapidly changing stimuli. But is performance on these several tasks supported by a common substrate? To answer this question, we tested a cohort of 1060 individuals on four 'magnocellular tasks': detection of low-spatial-frequency gratings reversing in contrast at a high temporal frequency (so-called frequency-doubled gratings); detection of pulsed low-spatial-frequency gratings on a steady luminance pedestal; detection of coherent motion; and auditory discrimination of temporal order. Although all tasks showed test-retest reliability, only one pair shared more than 4 per cent of variance. Correlations within the set of 'magnocellular tasks' were similar to the correlations between those tasks and a 'non-magnocellular task', and there was little consistency between 'magnocellular deficit' groups comprising individuals with the lowest sensitivity for each task. Our results suggest that different 'magnocellular tasks' reflect different sources of variance, and thus are not general measures of 'magnocellular function'.

Mimicking the colourful wing scale structure of the Papilio blumei butterfly

The brightest and most vivid colours in nature arise from the interaction of light with surfaces that exhibit periodic structure on the micro- and nanoscale. In the wings of butterflies, for example, a combination of multilayer interference, optical gratings, photonic crystals and other optical structures gives rise to complex colour mixing. Although the physics of structural colours is well understood, it remains a challenge to create artificial replicas of natural photonic structures(1-3). Here we use a combination of layer deposition techniques, including colloidal self-assembly, sputtering and atomic layer deposition, to fabricate photonic structures that mimic the colour mixing effect found on the wings of the Indonesian butterfly Papilio blumei. We also show that a conceptual variation to the natural structure leads to enhanced optical properties. Our approach offers improved efficiency, versatility and scalability compared with previous approaches(4-6).

Variants in the 1q21 risk region are associated with a visual endophenotype of autism and schizophrenia

Deficits in sensitivity to visual stimuli of low spatial frequency and high temporal frequency (so-called frequency-doubled gratings) have been demonstrated both in schizophrenia and in autism spectrum disorder (ASD). Such basic perceptual functions are ideal candidates for molecular genetic study, because the underlying neural mechanisms are well characterized; but they have sometimes been overlooked in favor of cognitive and neurophysiological endophenotypes, for which neural substrates are often unknown. Here, we report a genome-wide association study of a basic visual endophenotype associated with psychological disorder. Sensitivity to frequency-doubled gratings was measured in 1060 healthy young adults, and analyzed for association with genotype using linear regression at 642758 single nucleotide polymorphism (SNP) markers. A significant association (P=7.9×10) was found with the SNP marker rs1797052, situated in the 5′-untranslated region of PDZK1; each additional copy of the minor allele was associated with an increase in sensitivity equivalent to more than half a standard deviation. A permutation procedure, which accounts for multiple testing, showed that the association was significant at the α=0.005 level. The region on chromosome 1q21.1 surrounding PDZK1 is an established susceptibility locus both for schizophrenia and for ASD, mirroring the common association of the visual endophenotype with the two disorders. PDZK1 interacts with N-methyl-d-aspartate receptors and neuroligins, which have been implicated in the etiologies of schizophrenia and ASD. These findings suggest that perceptual abnormalities observed in two different disorders may be linked by common genetic elements. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

OPTIMIZATION OF THE SLOW-MODE PLASMON POLARITON IN LIGHT-EMITTING TUNNEL-JUNCTIONS

Light emitted from metal/oxide/metal tunnel junctions can originate from the slow-mode surface plasmon polariton supported in the oxide interface region. The effective radiative decay of this mode is constrained by competition with heavy intrinsic damping and by the need to scatter from very small scale surface roughness; the latter requirement arises from the mode's low phase velocity and the usual momentum conservation condition in the scattering process. Computational analysis of conventional devices shows that the desirable goals of decreased intrinsic damping and increased phase velocity are influenced, in order of priority, by the thickness and dielectric function of the oxide layer, the type of metal chosen for each conducting electrode, and temperature. Realizable devices supporting an optimized slow-mode plasmon polariton are suggested. Essentially these consist of thin metal electrodes separated by a dielectric layer which acts as a very thin (a few nm) electron tunneling barrier but a relatively thick (several 10's of nm) optically lossless region. (C) 1995 American Institute of Physics.

Monitoring of a novel FlexiArchTM bridge system to investigate soil-structure interaction

Masonry arch bridges are one of the oldest forms of bridge construction and have been around for thousands of years. Brick and stone arch bridges have proven to be highly durable as most of them have remained serviceable after hundreds of years. In contrast, many bridges built of modern materials have required extensive repair and strengthening after being in service for a relatively short part of their design life. This paper describes the structural monitoring of a novel flexible concrete arch known as: FlexiArchTM. This is a bridge system that can be transported as a flat-pack system to form an arch in-situ by the use of a flexible polymeric membrane. The system has been developed under a Knowledge Transfer Partnership between Queen’s University Belfast (QUB) and Macrete Ltd. Tievenameena Bridge in Northern Ireland was a replacement bridge for the Northern Ireland Roads Service and was monitored under different axle loadings using a range of sensors including discrete fiber optic Bragg gratings to measure the change in strain in the arch ring under live loading. This paper discusses the results of a laboratory model study carried out at QUB. A scaled arch system was loaded with a simulated moving axle. Various techniques were used to monitor the arch under the moving axle load with particular emphasis on the interaction of the arch ring and engineered backfill.