A copper-hydrogen peroxide redox system induces dityrosine cross-links and chemokine oligomerisation

The activity of the chemoattractant cytokines, the chemokines, in vivo is enhanced by oligomerisation and aggregation on glycosaminoglycan (GAG), particularly heparan sulphate, side chains of proteoglycans. The chemokine RANTES (CCL5) is a T-lymphocyte and monocyte chemoattractant, which has a minimum tetrameric structure for in vivo activity and a propensity to form higher order oligomers. RANTES is unusual among the chemokines in having five tyrosine residues, an amino acid susceptible to oxidative cross-linking. Using fluorescence emission spectroscopy, Western blot analysis and LCMS-MS, we show that a copper/H2O2 redox system induces the formation of covalent dityrosine cross-links and RANTES oligomerisation with the formation of tetramers, as well as higher order oligomers. Amongst the transition metals tested, namely copper, nickel, mercury, iron and zinc, copper appeared unique in this respect. At high (400 µM) concentrations of H2O2, RANTES monomers, dimers and oligomers are destroyed, but heparan sulphate protects the chemokine from oxidative damage, promoting dityrosine cross-links and multimer formation under oxidative conditions. Low levels of dityrosine cross-links were detected in copper/H2O2-treated IL-8 (CXCL8), which has one tyrosine residue, and none were detected in ENA-78 (CXCL5), which has none. Redox-treated RANTES was fully functional in Boyden chamber assays of T-cell migration and receptor usage on activated T-cells following RANTES oligomerisation was not altered. Our results point to a protective, anti-oxidant, role for heparan sulphate and a previously unrecognised role for copper in chemokine oligomerisation that may offer an explanation for the known anti-inflammatory effect of copper-chelators such as penicillamine and tobramycin.

Childhood auditory processing disorder as a developmental disorder:the case for a multi-professional approach to diagnosis and management

Auditory processing disorder (APD) is diagnosed when a patient presents with listening difficulties which can not be explained by a peripheral hearing impairment or higher-order cognitive or language problems. This review explores the association between auditory processing disorder (APD) and other specific developmental disorders such as dyslexia and attention-deficit hyperactivity disorder. The diagnosis and aetiology of APD are similar to those of other developmental disorders and it is well established that APD often co-occurs with impairments of language, literacy, and attention. The genetic and neurological causes of APD are poorly understood, but developmental and behavioural genetic research with other disorders suggests that clinicians should expect APD to co-occur with other symptoms frequently. The clinical implications of co-occurring symptoms of other developmental disorders are considered and the review concludes that a multi-professional approach to the diagnosis and management of APD, involving speech and language therapy and psychology as well as audiology, is essential to ensure that children have access to the most appropriate range of support and interventions.

Effective electromagnetic noise cancellation with beamformers and synthetic gradiometry in shielded and partly shielded environments

The major challenge of MEG, the inverse problem, is to estimate the very weak primary neuronal currents from the measurements of extracranial magnetic fields. The non-uniqueness of this inverse solution is compounded by the fact that MEG signals contain large environmental and physiological noise that further complicates the problem. In this paper, we evaluate the effectiveness of magnetic noise cancellation by synthetic gradiometers and the beamformer analysis method of synthetic aperture magnetometry (SAM) for source localisation in the presence of large stimulus-generated noise. We demonstrate that activation of primary somatosensory cortex can be accurately identified using SAM despite the presence of significant stimulus-related magnetic interference. This interference was generated by a contact heat evoked potential stimulator (CHEPS), recently developed for thermal pain research, but which to date has not been used in a MEG environment. We also show that in a reduced shielding environment the use of higher order synthetic gradiometry is sufficient to obtain signal-to-noise ratios (SNRs) that allow for accurate localisation of cortical sensory function.

Nonlinear and ROADM induced penalties in 28 Gbaud dynamic optical mesh networks employing electronic signal processing

We report the impact of cascaded reconfigurable optical add-drop multiplexer induced penalties on coherently-detected 28 Gbaud polarization multiplexed m-ary quadrature amplitude modulation (PM m-ary QAM) WDM channels. We investigate the interplay between different higher-order modulation channels and the effect of filter shapes and bandwidth of (de)multiplexers on the transmission performance, in a segment of pan-European optical network with a maximum optical path of 4,560 km (80km x 57 spans). We verify that if the link capacities are assigned assuming that digital back propagation is available, 25% of the network connections fail using electronic dispersion compensation alone. However, majority of such links can indeed be restored by employing single-channel digital back-propagation employing less than 15 steps for the whole link, facilitating practical application of DBP. We report that higher-order channels are most sensitive to nonlinear fiber impairments and filtering effects, however these formats are less prone to ROADM induced penalties due to the reduced maximum number of hops. Furthermore, it has been demonstrated that a minimum filter Gaussian order of 3 and bandwidth of 35 GHz enable negligible excess penalty for any modulation order.

Digital back-propagation for spectrally efficient WDM 112 Gbit/s PM m-ary QAM transmission

We report the performance of coherently-detected nine-channel WDM transmission over high dispersion fibers, using polarization multiplexed m-ary quadrature amplitude modulation (m = 4, 16, 64, 256) at 112 Gbit/s. Compensation of fiber nonlinearities via digital back-propagation enables up to 10 dB improvement in maximum transmittable power and similar to 8 dB Q(eff) improvement which translates to a nine-fold enhancement in transmission reach for PM-256QAM, where the largest improvements are associated with higher-order modulation formats. We further demonstrate that even under strong nonlinear distortion the transmission reach only reduces by a factor of similar to 2.5 for a 2 unit increase in capacity (log(2)m) when full band DBP is employed, in proportion to the required back-to-back OSNR.

Nonlinear soliton propagation in a few mode optical fibre

We experimentally demonstrate adiabatic soliton propagation in the fundamental mode of a few mode optical fibre and more complex behaviour in a higher order mode, indicating that the impact of nonlinearities differs for each mode.

A common rule for integration and suppression of luminance contrast across eyes, space, time, and pattern

Visual perception begins by dissecting the retinal image into millions of small patches for local analyses by local receptive fields. However, image structures extend well beyond these receptive fields and so further processes must be involved in sewing the image fragments back together to derive representations of higher order (more global) structures. To investigate the integration process, we also need to understand the opposite process of suppression. To investigate both processes together, we measured triplets of dipper functions for targets and pedestals involving interdigitated stimulus pairs (A, B). Previous work has shown that summation and suppression operate over the full contrast range for the domains of ocularity and space. Here, we extend that work to include orientation and time domains. Temporal stimuli were 15-Hz counter-phase sine-wave gratings, where A and B were the positive and negative phases of the oscillation, respectively. For orientation, we used orthogonally oriented contrast patches (A, B) whose sum was an isotropic difference of Gaussians. Results from all four domains could be understood within a common framework in which summation operates separately within the numerator and denominator of a contrast gain control equation. This simple arrangement of summation and counter-suppression achieves integration of various stimulus attributes without distorting the underlying contrast code.

Design and validity of a miniaturized open-field aberrometer

PURPOSE: To validate a new miniaturised, open-field wavefront device which has been developed with the capacity to be attached to an ophthalmic surgical microscope or slit-lamp. SETTING: Solihull Hospital and Aston University, Birmingham, UK DESIGN: Comparative non-interventional study. METHODS: The dynamic range of the Aston Aberrometer was assessed using a calibrated model eye. The validity of the Aston Aberrometer was compared to a conventional desk mounted Shack-Hartmann aberrometer (Topcon KR1W) by measuring the refractive error and higher order aberrations of 75 dilated eyes with both instruments in random order. The Aston Aberrometer measurements were repeated five times to assess intra-session repeatability. Data was converted to vector form for analysis. RESULTS: The Aston Aberrometer had a large dynamic range of at least +21.0 D to -25.0 D. It gave similar measurements to a conventional aberrometer for mean spherical equivalent (mean difference ± 95% confidence interval: 0.02 ± 0.49D; correlation: r=0.995, p<0.001), astigmatic components (J0: 0.02 ± 0.15D; r=0.977, p<0.001; J45: 0.03 ± 0.28; r=0.666, p<0.001) and higher order aberrations RMS (0.02 ± 0.20D; r=0.620, p<0.001). Intraclass correlation coefficient assessments of intra-sessional repeatability for the Aston Aberrometer were excellent (spherical equivalent =1.000, p<0.001; astigmatic components J0 =0.998, p<0.001, J45=0.980, p<0.01; higher order aberrations RMS =0.961, p<0.001). CONCLUSIONS: The Aston Aberrometer gives valid and repeatable measures of refractive error and higher order aberrations over a large range. As it is able to measure continuously, it can provide direct feedback to surgeons during intraocular lens implantations and corneal surgery as to the optical status of the visual system.

Anterior segment anomalies and effects on visual quality

The tear film, cornea and lens dictate the refractive power of the eye and the retinal image quality is principally defined by diffraction, whole eye wavefront error, scatter, and chromatic aberration. Diffraction and wave aberration are fundamentally pupil diameter dependent; however scatter can be induced by refractive surgery and in the normal ageing eye becomes an increasingly important factor defining retinal image quality. The component of visual quality most affected by the tear film, refractive surgery and multifocal contact and intraocular lenses is the wave aberration of the eye. This body of work demonstrates the effects of each of these anomalies on the visual quality of the eye. When assessing normal or borderline self-diagnosed dry eye subjects using aberrometry, combining lubricating eye drops and spray does not offer any benefit over individual products. However, subjects perceive a difference in comfort for all interventions after one hour. Total higher order aberrations increase after laser assisted sub-epithelial keratectomy performed using a solid-state laser on myopes, but this causes no significant decrease in contrast sensitivity or increase in glare disability. Mean sensitivity and reliability indices for perimetry were comparable to pre-surgery results. Multifocal contact lenses and intraocular lenses are designed to maximise vision when the patient is binocular, so any evaluation of the eyes individually is confounded by reduced individual visual acuity and visual quality. Different designs of aspheric multifocal contact lenses do not provide the same level of visual quality. Multifocal contact lenses adversely affect mean deviation values for perimetry and this should be considered when screening individuals with multifocal contact or intraocular lenses. Photographic image quality obtained through a multifocal contact or intraocular lens appears to be unchanged. Future work should evaluate the effect of these anomalies in combination; with the aim of providing the best visual quality possible and supplying normative data for screening purposes.

Performance-based vs socially supportive culture:a cross-national study of descriptive norms and entrepreneurship

This paper is a cross-national study testing a framework relating cultural descriptive norms to entrepreneurship in a sample of 40 nations. Based on data from the Global Leadership and Organizational Behavior Effectiveness project, we identify two higher-order dimensions of culture – socially supportive culture (SSC) and performance-based culture (PBC) – and relate them to entrepreneurship rates and associated supply-side and demand-side variables available from the Global Entrepreneurship Monitor. Findings provide strong support for a social capital/SSC and supply-side variable explanation of entrepreneurship rate. PBC predicts demand-side variables, such as opportunity existence and the quality of formal institutions to support entrepreneurship.

Organisational receptivity for change:combining context and capability to explain competitive advantage

This thesis explores efforts to conjoin organisational contexts and capabilities in explaining sustainable competitive advantage. Oliver (1997) argued organisations need to balance the need to conform to industry’s requirements to attain legitimization (e.g. DiMaggio & Powell, 1983), and the need for resource optimization (e.g. Barney, 1991). The author hypothesized that such balance can be viewed as movements along the homogeneity-heterogeneity continuum. An organisation in a homogenous industry possesses similar characteristics as its competitors, as opposed to a heterogeneous industry in which organisations within are differentiated and competitively positioned (Oliver, 1997). The movement is influenced by the dynamic environmental conditions that an organisation is experiencing. The author extended Oliver’s (1997) propositions of combining RBV’s focus on capabilities with institutional theory’s focus on organisational context, as well as redefining organisational receptivity towards change (ORC) factors from Butler and Allen’s (2008) findings. The authors contributed to the theoretical development of ORC theory to explain the attainment of sustainable competitive advantage. ORC adopts the assumptions from both institutional and RBV theories, where the receptivity factors include both organisational contexts and capabilities. The thesis employed a mixed method approach in which sequential qualitative quantitative studies were deployed to establish a robust, reliable, and valid ORC scale. The adoption of Hinkin’s (1995) three-phase scale development process was updated, thus items generated from interviews and literature reviews went through numerous exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to achieve convergent, discriminant, and nomological validities. Samples in the first phase (semi structured interviews) were hotel owners and managers. In the second phase, samples were MBA students, and employees of private and public sectors. In the third phase, samples were hotel managers. The final ORC scale is a parsimonious second higher-order latent construct. The first-order constructs comprises four latent receptivity factors which are ideological vision (4 items), leading change (4 items), implementation capacity (4 items), and change orientation (7 items). Hypotheses testing revealed that high levels of perceived environmental uncertainty leads to high levels of receptivity factor. Furthermore, the study found a strong positive correlation between receptivity factors and competitive advantage, and between receptivity factors and organisation performance. Mediation analyses revealed that receptivity factors partially mediate the relationship between perceived environmental uncertainty, competitive advantage and organisational performance.

Subjective and objective performance of the Lenstec KH-3500 "accommodative" intraocular lens

Aim: To determine whether eyes implanted with the Lenstec KH-3500 "accommodative" intraocular lenses (IOLs) have improved subjective and objective focusing performance compared to a standard monofocal IOLs. Methods: 28 participants were implanted monocularly with a KH-3500 " accommodative" IOL and 20 controls with a Softec1 IOL. Outcome measures of refraction, visual acuity, subjective amplitude of accommodation, objective accommodative stimulus response curve, aberrometry, and Scheimpflug imaging were taken at ∼3 weeks and repeated after 6 months. Results: Best corrected acuity with the KH-3500 was 0.06 (SD 0.13) logMAR at distance and 0.58 (0.20) logMAR at near. Accommodation was 0.39 (0.53) D measured objectively and 3.1 (1.6) D subjectively. Higher order aberrations were 0.87 (0.85) μm and lower order were 0.24 (0.39) μm. Posterior subcapsular light scatter was 0.95% (1.37%) greater than IOL clarity. In comparison, all control group measures were similar except objective (0.17 (0.13) D; p = 0.032) and subjective (2.0 (0.9) D; p = 0.009) amplitude of accommodation. Six months following surgery, posterior subcapsular scatter had increased (p<0.01) in the KH-3500 implanted subjects and near word acuity had decreased (p<0.05). Conclusions: The objective accommodating effects of the KH-3500 IOL appear to be limited, although the subjective and objective accommodative range is significantly increased compared to control subjects implanted with conventional IOLs. However, this "accommodative" ability of the lens appears to have decreased by 6 months post-surgery.

Fundamental Pd0/PdII redox steps in cross-coupling reactions:homogeneous, hybrid homogeneous-heterogeneous to heterogeneous mechanistic pathways for C-C couplings

C–C bond-forming, cross-coupling reactions of organohalides with nucleophilic compounds, catalysed by palladium, are amongst the most important chemical reactions available to the synthetic chemist. The intimate mechanisms of these reactions, involving Pd0/PdII redox steps, have been of great historical interest and continue to be so. The myriad of possible mechanisms is reviewed in this chapter. The interplay of mononuclear Pd species with higher order Pd species, e.g. nanoclusters/nanoparticles are considered as being equally important in cross-coupling reaction mechanisms. A focus is placed on trichotomic behaviour of cross-coupling catalytic manifolds, from homogeneous to hybrid homogeneous–heterogeneous to truly heterogeneous behaviour. For the latter, surface chemistry and metal atom leaching (and various experimental techniques) are broadly discussed. It is now clear that mechanism for general cross‐coupling reactions, that is as presented to undergraduate students studying Chemistry degrees across the world, is undoubtedly more complex than first thought. New opportunities for catalyst design have therefore emerged in the area of Pd nanoparticles and nanocatalysis, with some wonderful applications especially in chemical biology, providing a snapshot of what the future might hold.

Design of a genetic algorithm for bi-objective flow shop scheduling problems with re-entrant jobs

This paper presents a simulated genetic algorithm (GA) model of scheduling the flow shop problem with re-entrant jobs. The objective of this research is to minimize the weighted tardiness and makespan. The proposed model considers that the jobs with non-identical due dates are processed on the machines in the same order. Furthermore, the re-entrant jobs are stochastic as only some jobs are required to reenter to the flow shop. The tardiness weight is adjusted once the jobs reenter to the shop. The performance of the proposed GA model is verified by a number of numerical experiments where the data come from the case company. The results show the proposed method has a higher order satisfaction rate than the current industrial practices.

Femtosecond laser inscribed phase masks for fibre Bragg grating sensor inscription

We present femtosecond laser inscribed phase masks for the inscription of Bragg gratings in optical fibres. The principal advantage is the flexibility afforded by the femtosecond laser inscription, where sub-surface structures define the phase mask period and mask properties. The masks are used to produce fibre Bragg gratings having different orders according to the phase mask period. The work demonstrates the incredible flexibility of femtosecond lasers for the rapid prototyping of complex and reproducible mask structures. We also consider three-beam interference effects, a consequence of the zeroth-order component present in addition to higher-order diffraction components. © 2012 SPIE.