The clinical and cellular basis of contact lens-related corneal infections

Microbial keratitis (MK) is the most visually devastating complication associated with contact lens wear. Pseudomonas aeruginosa (PA) is highly invasive in the corneal epithelium and is responsible for more than half of the reported cases of contact lens-related MK. To protect against Pseudomonas-mediated MK, the corneal epithelium has evolved overlapping defense mechanisms that function to protect the ocular surface from microbial invasion. Research has shown that contact lens wear disrupts these protective mechanisms through breakdown of normal homeostatic surface renewal as well as damaging the corneal surface, exposing underlying cell membrane receptors that bind and internalize PA through the formation of lipid rafts. Human clinical trials have shown that initial adherence of PA with resulting increased risk for microbial infection is mediated in part by contact lens oxygen transmissibility. Recently, chemical preserved multipurpose solutions (MPS) have been implicated in increasing PA adherence to corneal epithelial cells, in addition to inducing significant levels of toxic staining when used in conjunction with specific silicone hydrogel lenses. This review summarizes what is currently known about the relationship between contact lenses, the corneal epithelium, MPS, and infection

Lattice simulation method to model diffusion and NMR spectra in porous materials.

A coarse-grained simulation method to predict nuclear magnetic resonance (NMR) spectra of ions diffusing in porous carbons is proposed. The coarse-grained model uses input from molecular dynamics simulations such as the free-energy profile for ionic adsorption, and density-functional theory calculations are used to predict the NMR chemical shift of the diffusing ions. The approach is used to compute NMR spectra of ions in slit pores with pore widths ranging from 2 to 10 nm. As diffusion inside pores is fast, the NMR spectrum of an ion trapped in a single mesopore will be a sharp peak with a pore size dependent chemical shift. To account for the experimentally observed NMR line shapes, our simulations must model the relatively slow exchange between different pores. We show that the computed NMR line shapes depend on both the pore size distribution and the spatial arrangement of the pores. The technique presented in this work provides a tool to extract information about the spatial distribution of pore sizes from NMR spectra. Such information is difficult to obtain from other characterisation techniques.C.M. acknowledges the School of the Physical Sciences of the University of Cambridge for funding through an Oppenheimer Research Fellowship. C.M., A.C.F., J.M.G., and C.P.G. acknowledge the Sims Scholarship (A.C.F.), EPSRC (via the Supergen consortium, J.M.G.), and the EU ERC (via an Advanced Fellowship to C.P.G.) for funding. A.C.F. and J.M.G. thank the NanoDTC Cambridge for travel funding. D.F. acknowledges EPSRC Grant No. EP/I000844/1.This is the final published version. It first appeared at http://scitation.aip.org/content/aip/journal/jcp/142/9/10.1063/1.4913368

Geodesics for Efficient Creation and Propagation of Order along Ising Spin Chains

Experiments in coherent nuclear and electron magnetic resonance, and optical spectroscopy correspond to control of quantum mechanical ensembles, guiding them from initial to final target states by unitary transformations. The control inputs (pulse sequences) that accomplish these unitary transformations should take as little time as possible so as to minimize the effects of relaxation and decoherence and to optimize the sensitivity of the experiments. Here we give efficient syntheses of various unitary transformations on Ising spin chains of arbitrary length. The efficient realization of the unitary transformations presented here is obtained by computing geodesics on a sphere under a special metric. We show that contrary to the conventional belief, it is possible to propagate a spin order along an Ising spin chain with coupling strength J (in units of Hz), significantly faster than 1/(2J) per step. The methods presented here are expected to be useful for immediate and future applications involving control of spin dynamics in coherent spectroscopy and quantum information processing

Motion and position shifts induced by the double-drift stimulus are unaffected by attentional load.

The double-drift stimulus produces a strong shift in apparent motion direction that generates large errors of perceived position. In this study, we tested the effect of attentional load on the perceptual estimates of motion direction and position for double-drift stimuli. In each trial, four objects appeared, one in each quadrant of a large screen, and they moved upward or downward on an angled trajectory. The target object whose direction or position was to be judged was either cued with a small arrow prior to object motion (low attentional load condition) or cued after the objects stopped moving and disappeared (high attentional load condition). In Experiment 1, these objects appeared 10° from the central fixation, and participants reported the perceived direction of the target's trajectory after the stimulus disappeared by adjusting the direction of an arrow at the center of the response screen. In Experiment 2, the four double-drift objects could appear between 6 ° and 14° from the central fixation, and participants reported the location of the target object after its disappearance by moving the position of a small circle on the response screen. The errors in direction and position judgments showed little effect of the attentional manipulation-similar errors were seen in both experiments whether or not the participant knew which double-drift object would be tested. This suggests that orienting endogenous attention (i.e., by only attending to one object in the precued trials) does not interact with the strength of the motion or position shifts for the double-drift stimulus

Electron wavepacket propagation and entanglement in a chain of coupled quantum dots

We study the coherent dynamics of one- and two-electron transport in a linear array of tunnel-coupled quantum dots. We find that this system exhibits a rich variety of coherent phenomena, ranging from electron wavepacket propagation and interference to two-particle bonding and entanglement. Our studies, apart from their relevance to the exploration of quantum dynamics and transport in periodic structures, are also aimed at possible applications in future quantum computation schemes.Comment: 10 pages, 8 figure

The Effect of Nonpreserved Care Solutions on 12 Months of Daily and Extended Silicone Hydrogel Contact Lens Wear

PURPOSE. To determine the effects of nonpreserved care solutions on human corneal epithelium in long-term daily wear (DW) compared with overnight (extended) wear (EW) of hyper-oxygen-permeable silicone hydrogel contact lenses. METHODS. This was a prospective, randomized, double-masked, single-center, parallel treatment group clinical trial (NCT 00344643). One hundred twenty-one patients completed the 13 month study: (1) Lotrafilcon A (30 night EW, n ϭ 29; DW, n ϭ 32); (2) Galyfilcon A (DW, n ϭ 20); and (3) Lotrafilcon B (6 night EW, n ϭ 20; DW, n ϭ 21). Irrigation chamber collection of corneal surface cells (OD) and confocal microscopy (OS) were performed at baseline, 1 week; and 1, 3, 6, 9, and 12 months of EW. The main outcome measures were: (1) Pseudomonas aeruginosa (PA) binding to exfoliated corneal surface cells; (2) central epithelial thickness (CET); and (3) epithelial surface cell exfoliation rate (desquamation). RESULTS. DW had no significant effect on CET; there was a decrease in CET with EW that recovered (adapted) over 1 year (Lotrafilcon B, P Ͻ 0.05). All lens wear (DW, EW) decreased desquamation with adaptive effects over 1 year (P Ͻ 0.001). There was no significant difference in PA binding between lenses or modality of wear. CONCLUSIONS. PA binding to corneal epithelial cells is a prerequisite for infection, and no binding indicates no lensenhanced risk of infection. In contrast to prior studies of preserved lens-care products, the absence of a change in the PA binding data results predict that the risk for PA CTLkeratitis should be similar for daily and extended silicone hydrogel lens wear over 1 year when preservative-free care solutions are used. (ClinicalTrials.gov number, NCT00344643.) (Invest Ophthalmol Vis Sci. 2008;49:7-15

Perceptual Context in Cognitive Hierarchies

Cognition does not only depend on bottom-up sensor feature abstraction, but also relies on contextual information being passed top-down. Context is higher level information that helps to predict belief states at lower levels. The main contribution of this paper is to provide a formalisation of perceptual context and its integration into a new process model for cognitive hierarchies. Several simple instantiations of a cognitive hierarchy are used to illustrate the role of context. Notably, we demonstrate the use context in a novel approach to visually track the pose of rigid objects with just a 2D camera

A peptide mimic of the chemotaxis inhibitory protein of Staphylococcus aureus: towards the development of novel anti-inflammatory compounds

Complement factor C5a is one of the most powerful pro-inflammatory agents involved in recruitment of leukocytes, activation of phagocytes and other inflammatory responses. C5a triggers inflammatory responses by binding to its G-protein-coupled C5a-receptor (C5aR). Excessive or erroneous activation of the C5aR has been implicated in numerous inflammatory diseases. The C5aR is therefore a key target in the development of specific anti-inflammatory compounds. A very potent natural inhibitor of the C5aR is the 121-residue chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS). Although CHIPS effectively blocks C5aR activation by binding tightly to its extra-cellular N terminus, it is not suitable as a potential anti-inflammatory drug due to its immunogenic properties. As a first step in the development of an improved CHIPS mimic, we designed and synthesized a substantially shorter 50-residue adapted peptide, designated CHOPS. This peptide included all residues important for receptor binding as based on the recent structure of CHIPS in complex with the C5aR N terminus. Using isothermal titration calorimetry we demonstrate that CHOPS has micromolar affinity for a model peptide comprising residues 7–28 of the C5aR N terminus including two O-sulfated tyrosine residues at positions 11 and 14. CD and NMR spectroscopy showed that CHOPS is unstructured free in solution. Upon addition of the doubly sulfated model peptide, however, the NMR and CD spectra reveal the formation of structural elements in CHOPS reminiscent of native CHIPS