Voltage-induced modulation of interfacial ionic liquids measured using surface plasmon resonant grating nanostructures.

We have used surface plasmon resonant metal gratings to induce and probe the dielectric response (i.e., electro-optic modulation) of ionic liquids (ILs) at electrode interfaces. Here, the cross-plane electric field at the electrode surface modulates the refractive index of the IL due to the Pockels effect. This is observed as a shift in the resonant angle of the grating (i.e., Δϕ), which can be related to the change in the local index of refraction of the electrolyte (i.e., Δnlocal). The reflection modulation of the IL is compared against a polar (D2O) and a non-polar solvent (benzene) to confirm the electro-optic origin of resonance shift. The electrostatic accumulation of ions from the IL induces local index changes to the gratings over the extent of electrical double layer (EDL) thickness. Finite difference time domain simulations are used to relate the observed shifts in the plasmon resonance and change in reflection to the change in the local index of refraction of the electrolyte and the thickness of the EDL. Simultaneously using the wavelength and intensity shift of the resonance enables us to determine both the effective thickness and Δn of the double layer. We believe that this technique can be used more broadly, allowing the dynamics associated with the potential-induced ordering and rearrangement of ionic species in electrode-solution interfaces.

Molecular alignment-assisted spectral broadening and shifting in the near-infrared with a recycled depleted pump from an optical parametric amplifier.

We demonstrate how the depleted pump of an optical parametric amplifier can be recycled for impulsive alignment of a molecular gas inside a hollow-core fiber and use such alignment for the broadening and frequency shift of the signal pulse at a center wavelength of ∼1300 nm. Our results combine non-adiabatic molecular alignment, self-phase modulation, and Raman non-linearities. We demonstrate spectral shifts of up to 204 nm and a spectral broadening of more than one octave. We also report on the time delays at which broadening occurs, which do not coincide with any of the molecular rotational constants. Further, we encounter that maximum frequency shifts occur when the signal and pump have perpendicular polarization instead of parallel.

Five point initiative: a community-informed bundled implementation strategy to address HIV in Black communities.

BACKGROUND: Black individuals in the U.S. remain the most disproportionately impacted by new HIV diagnoses, represent the highest portion of individuals living with HIV, and have the highest morbidity rates. Structural inequities and historical oppression are the primary drivers. Such drivers limit access to HIV prevention tools that need to be delivered with culturally congruent and community-informed approaches. METHODS: The Five Point Initiative (FPI) is a community-informed bundled implementation strategy developed and piloted between September 2019 and March 2020 in Miami, Florida in communities heavily impacted by HIV. Key components of the strategy included community consultants/experts, five categories (hence the "Five Point") of community businesses (e.g., corner stores, beauty supply stores, laundromats, mechanics, barbershops), local health organizations, an academic research program engrossed in community engaged research, and community residents who provided ongoing feedback throughout. Outcomes of FPI included (a) survey information (e.g., knowledge of and access to PrEP, barriers to care) and pilot data (acceptability and feasibility), (b) expansion of reach to Black individuals in HIV high impact zip codes in Miami, (c) insights on our bundled implementation strategy, (d) condom distribution, and (e) HIV testing. RESULTS: Over the course of six months FPI carried out 10 outreach events, partnered with 13 community businesses and 5 health organizations, engaged 677 community residents, collected health information via a survey, distributed 12,434 condoms, provided information on PrEP, and offered voluntary HIV testing (131 completed). FPI's ability to reach residents who are not being reached (e.g., 68.8% never heard of PrEP, 8% no HIV testing ever, 65.9% no primary care provider), positive feedback from residents (e.g., 70% very satisfied, 21% satisfied; 62% strongly agree and 25% agree they would participate again) and qualitative interviews with businesses provide evidence of acceptability and feasibility. Further, survey data provided insights on factors such as socio-demographics, discrimination experiences, barriers to care, social-structural factors, physical and sexual health, and mental health and substance use. CONCLUSIONS: The FPI bundled implementation strategy shows promise to deliver health prevention/intervention for HIV and other health conditions to communities facing health inequities and for whom the current system for delivering care is insufficient.

A plano-convex thick-lens velocity map imaging apparatus for direct, high resolution 3D momentum measurements of photoelectrons with ion time-of-flight coincidence.

Since their inception, velocity map imaging (VMI) techniques have received continued interest in their expansion from 2D to 3D momentum measurements through either reconstructive or direct methods. Recently, much work has been devoted to the latter of these by relating electron time-of-flight (TOF) to the third momentum component. The challenge is having a timing resolution sufficient to resolve the structure in the narrow (<10 ns) electron TOF spread. Here, we build upon the work in VMI lens design and 3D VMI measurement by using a plano-convex thick-lens (PCTL) VMI in conjunction with an event-driven camera (TPX3CAM) providing TOF information for high resolution 3D electron momentum measurements. We perform simulations to show that, with the addition of a mesh electrode to the thick-lens geometry, the resulting plano-convex electrostatic field extends the detectable electron cutoff energy range while retaining the high resolution. This design also extends the electron TOF range, allowing for a better momentum resolution along this axis. We experimentally demonstrate these capabilities by examining above-threshold ionization in xenon, where the apparatus is shown to collect electrons of energy up to ∼7 eV with a TOF spread of ∼30 ns, both of which are improved compared to a previous work by factors of ∼1.4 and ∼3.75, respectively. Finally, the PCTL-VMI is equipped with a coincident ion TOF spectrometer, which is shown to effectively extract unique 3D momentum distributions for different ionic species in a gas mixture. These techniques have the potential to lend themselves to more advanced measurements involving systems where the electron momentum distributions possess non-trivial symmetries.

An endogenous inhibitor of angiogenesis downregulated by hypoxia in human aortic valve stenosis promotes disease pathogenesis.

Aortic valve stenosis is the most common valve disease in the western world. Central to the pathogenesis of this disease is the growth of new blood vessels (angiogenesis) within the aortic valve allowing infiltration of immune cells and development of intra-valve inflammation. Identifying the cellular mediators involved in this angiogenesis is important as this may reveal new therapeutic targets which could ultimately prevent the progression of aortic valve stenosis. Aortic valves from patients undergoing surgery for aortic valve replacement or dilation of the aortic arch were examined both ex vivo and in vitro. We now demonstrate that the anti-angiogenic protein, soluble fms-like tyrosine kinase 1 (sFlt1), a non-signalling soluble receptor for vascular endothelial growth factor, is constitutively expressed in non-diseased valves. sFlt-1 expression was, however, significantly reduced in aortic valve tissue from patients with aortic valve stenosis while protein markers of hypoxia were simultaneously increased. Exposure of primary-cultured valve interstitial cells to hypoxia resulted in a decrease in the expression of sFlt-1. We further reveal using a bioassay that siRNA knock-down of sFlt1 in valve interstitial cells directly results in a pro-angiogenic environment. Finally, incubation of aortic valves with sphingosine 1-phosphate, a bioactive lipid-mediator, increased sFlt-1 expression and inhibited angiogenesis within valve tissue. In conclusion, this study demonstrates that sFlt1 expression is directly correlated with angiogenesis in aortic valves and the observed decrease in sFlt-1 expression in aortic valve stenosis could increase valve inflammation, promoting disease progression. This could be a viable therapeutic target in treating this disease.

Multiplexed detection and quantification of human antibody response to COVID-19 infection using a plasmon enhanced biosensor platform.

The 2019 SARS CoV-2 (COVID-19) pandemic has illustrated the need for rapid and accurate diagnostic tests. In this work, a multiplexed grating-coupled fluorescent plasmonics (GC-FP) biosensor platform was used to rapidly and accurately measure antibodies against COVID-19 in human blood serum and dried blood spot samples. The GC-FP platform measures antibody-antigen binding interactions for multiple targets in a single sample, and has 100% selectivity and sensitivity (n = 23) when measuring serum IgG levels against three COVID-19 antigens (spike S1, spike S1S2, and the nucleocapsid protein). The GC-FP platform yielded a quantitative, linear response for serum samples diluted to as low as 1:1600 dilution. Test results were highly correlated with two commercial COVID-19 antibody tests, including an enzyme linked immunosorbent assay (ELISA) and a Luminex-based microsphere immunoassay. To demonstrate test efficacy with other sample matrices, dried blood spot samples (n = 63) were obtained and evaluated with GC-FP, yielding 100% selectivity and 86.7% sensitivity for diagnosing prior COVID-19 infection. The test was also evaluated for detection of multiple immunoglobulin isotypes, with successful detection of IgM, IgG and IgA antibody-antigen interactions. Last, a machine learning approach was developed to accurately score patient samples for prior COVID-19 infection, using antibody binding data for all three COVID-19 antigens used in the test.

Hot Electron Driven Photocatalysis on Plasmon-Resonant Grating Nanostructures.

We demonstrate the hot electron injection of photoexcited carriers in an Ag-based plasmon resonant grating structure. By varying the incident angle of irradiation, sharp dips are observed in the reflectance with p-polarized light (electric field perpendicular to grating lines) when there is wavevector matching between the incident light and the plasmon resonant modes of the grating and no angle dependence is observed with s-polarized light. This configuration enables us to compare photoelectrochemical current produced by plasmon resonant excitation with that of bulk metal interband absorption simply by rotating the polarization of the incident light while keeping all other parameters of the measurement fixed. With 633 nm light, we observed a 12-fold enhancement in the photocurrent (i.e., reaction rate) between resonant and nonresonant polarizations at incident angles of ±7.6° from normal. At 785 nm irradiation, we observed similar resonant profiles to those obtained with 633 nm wavelength light but with a 44-fold enhancement factor. Using 532 nm light, we observed two resonant peaks (with approximately 10× enhancement) in the photocurrent at 19.4° and 28.0° incident angles, each corresponding to higher order modes in the grating with more nodes per period. The lower enhancement factors observed at shorter wavelengths are attributed to interband transitions, which provide a damping mechanism for the plasmon resonance. Finite difference time domain (FDTD) simulations of these grating structures confirm the resonant profiles observed in the angle-dependent spectra of these gratings and provide a detailed picture of the electric field profiles on and off resonance.

Hot electron-driven photocatalysis and transient absorption spectroscopy in plasmon resonant grating structures.

Plasmon resonant grating structures provide an effective platform for distinguishing between the effects of plasmon resonant excitation and bulk metal absorption via interband transitions. By simply rotating the polarization of the incident light, we can switch between resonant excitation and non-resonant excitation, while keeping all other parameters of the measurement constant. With light polarized perpendicular to the lines in the grating (i.e., TE-polarization), the photocatalytic reaction rate (i.e., photocurrent) is measured as the angle of the incident laser light is tuned through the resonance with the grating. Here, hot holes photoexcited in the metal are used to drive the oxygen evolution reaction (OER), producing a measurable photocurrent. Using TE-polarized light, we observe sharp peaks in the photocurrent and sharp dips in the photoreflectance at approximately 9° from normal incidence, which corresponds to the conditions under which there is good wavevector matching between the incident light and the lines in the grating. With light polarized parallel to the grating (i.e., TM), we excite the grating structure non-resonantly and there is no angular dependence in the photocurrent or photoreflectance. In order to quantify the lifetime of these hot carriers, we performed transient absorption spectroscopy of these plasmon resonant grating structures. Here, we observe one feature in the spectra corresponding to interband transitions and another feature associated with the plasmon resonant mode in the grating. Both features decay over a time scale of 1-2 ps. The spectral responses of grating structures fabricated with Ag, Al, and Cu are also presented.

Addition of a Carbonyl End Group Increases the Rate of Excited-State Decay in a Carotenoid via Conjugation Extension and Symmetry Breaking.

Steady-state absorption, transient absorption, and transient grating spectroscopies were employed to elucidate the role of a conjugated carbonyl group in the photophysics of carotenoids. Spheroidenone and spheroidene have similar molecular structures and differ only in an additional carbonyl group in spheroidenone. Comparison of the optical responses of these two molecules under similar experimental conditions was used to understand the role of this carbonyl group in the structure. It was found that the carbonyl group has two main effects: first, it dramatically increases the depopulation rate of the excited states of the molecule. The lifetimes of all the excited states of spheroidenone were found to be almost half of the ones for spheroidene. Second, the presence of the carbonyl group in the chain alters the decay mechanism to the symmetry-forbidden S1 state of the molecule, so that the higher vibrational levels of the S1 state are populated much more effectively. It was also revealed that for both molecules, the S2/S x → S1(hot) → S1 decay process is not purely sequential and follows a branched model.

Development and validation of diagnostic triage criteria for liver disease from a minimum data set enabling the 'intelligent LFT' pathway for the automated assessment of deranged liver enzymes.

BACKGROUND: Liver function tests (LFTs) are commonly abnormal; most patients with 'incidental' abnormal LFTs are not investigated appropriately and for those who are, current care pathways are geared to find an explanation for the abnormality by a lengthy process of investigation and exclusion, with costs to the patient and to the health service. OBJECTIVE: To validate an intelligent automatable analysis tool (iLFT) for abnormal liver enzymes, which diagnoses common liver conditions, provides fibrosis stage and recommends management. DESIGN: A retrospective case note review from three tertiary referral liver centres, with application of the iLFT algorithm and comparison with the clinician's final opinion as gold standard. RESULTS: The iLFT algorithm in 91.3% of cases would have correctly recommended referral or management in primary care. In the majority of the rest of the cases, iLFT failed safe and recommended referral even when the final clinical diagnosis could have been managed in primary care. Diagnostic accuracy was achieved in 82.4% of cases, consistent with the fail-safe design of the algorithm. Two cases would have remained in primary care as per the algorithm outcome, however on clinical review had features of advanced fibrosis. CONCLUSION: iLFT analysis of abnormal liver enzymes offers a safe and robust method of risk stratifying patients to the most appropriate care pathway as well as providing reliable diagnostic information based on a single blood draw, without repeated contacts with health services. Offers the possibility of high quality investigation and diagnosis to all patients rather than a tiny minority.

Optical Coherence Tomography Reveals Sigmoidal Crystalline Lens Changes during Accommodation.

This study aimed to quantify biometric modifications of the anterior segment (AS) during accommodation and to compare them against changes in both accommodative demand and response. Thirty adults, aged 18-25 years were rendered functionally emmetropic with contact lenses. AS optical coherence tomography (AS-OCT) images were captured along the 180° meridian (Visante, Zeiss Meditec, Jena, Germany) under stimulated accommodative demands (0-4 D). Images were analysed and lens thickness (LT) was measured, applying a refractive index correction of 1.00. Accommodative responses were also measured sequentially through a Badal optical system fitted to an autorefractor (Shin Nippon NVision-K 5001, Rexxam, Japan). Data were compared with Dubbelman schematic eye calculations. Significant changes occurred in LT, anterior chamber depth (ACD), lens centroid (i.e., ACD + LT/2), and AS length (ASL = ACD + LT) with accommodation (all p < 0.01). There was no significant change in CT with accommodation (p = 0.81). Measured CT, ACD, and lens centroid values were similar to Dubbelman modelled parameters, however AS-OCT overestimated LT and ASL. As expected, the accommodative response was less than the demand. Interestingly, up until approximately 1.5 D of response (2.0 D demand), the anterior crystalline lens surface appears to be the primary correlate. Beyond this point, the posterior lens surface moves posteriorly resulting in an over-all sigmoidal trajectory. he posterior crystalline lens surface demonstrates a sigmoidal response with increasing accommodative effort.

PEA-15 (Phosphoprotein Enriched in Astrocytes 15) Is a Protective Mediator in the Vasculature and Is Regulated During Neointimal Hyperplasia.

BACKGROUND: Neointimal hyperplasia following angioplasty occurs via vascular smooth muscle cell proliferation. The mechanisms involved are not fully understood but include mitogen-activated protein kinases ERK1/2 (extracellular signal-regulated kinases 1 and 2). We recently identified the intracellular mediator PEA-15 (phosphoprotein enriched in astrocytes 15) in vascular smooth muscle cells as a regulator of ERK1/2-dependent proliferation in vitro. PEA-15 acts as a cytoplasmic anchor for ERK1/2, preventing nuclear localization and thereby reducing ERK1/2-dependent gene expression. The aim of the current study was to examine the role of PEA-15 in neointimal hyperplasia in vivo. METHOD AND RESULTS: Mice deficient in PEA-15 or wild-type mice were subjected to wire injury of the carotid artery. In uninjured arteries from PEA-15-deficient mice, ERK1/2 had increased nuclear translocation and increased basal ERK1/2-dependent transcription. Following wire injury, arteries from PEA-15-deficient mice developed neointimal hyperplasia at an increased rate compared with wild-type mice. This occurred in parallel with an increase in a proliferative marker and vascular smooth muscle cell proliferation. In wild-type mice, PEA-15 expression was decreased in vascular smooth muscle cells at an early stage before any increase in intima:media ratio. This regulation of PEA-15 expression following injury was also observed in an ex vivo human model of hyperplasia. CONCLUSIONS: These results indicate, for the first time, a novel protective role for PEA-15 against inappropriate vascular proliferation. PEA-15 expression may also be repressed during vascular injury, suggesting that maintenance of PEA-15 expression is a novel therapeutic target in vascular disease.

Fullerene-Assisted Photoinduced Charge Transfer of Single-Walled Carbon Nanotubes through a Flavin Helix.

One of the greatest challenges with single-walled carbon nanotube (SWNT) photovoltaics and nanostructured devices is maintaining the nanotubes in their pristine state (i.e., devoid of aggregation and inhomogeneous doping) so that their unique spectroscopic and transport characteristics are preserved. To this effect, we report on the synthesis and self-assembly of a C60-functionalized flavin (FC60), composed of PCBM and isoalloxazine moieties attached on either ends of a linear, C-12 aliphatic spacer. Small amounts of FC60 (up to 3 molar %) were shown to coassembly with an organic soluble derivative of flavin (FC12) around SWNTs and impart effective dispersion and individualization. A key annealing step was necessary to perfect the isoalloxazine helix and expel the C60 moiety away from the nanotubes. Steady-state and transient absorption spectroscopy illustrate that 1% or higher incorporation of FC60 allows for an effective photoinduced charge transfer quenching of the encased SWNTs through the seamless helical encase. This is enabled via the direct π-π overlap between the graphene sidewalls, isoalloxazine helix, and the C60 cage that facilitates SWNT exciton dissociation and electron transfer to the PCBM moiety. Atomistic molecular simulations indicate that the stability of the complex originates from enhanced van der Waals interactions of the flexible spacer wrapped around the fullerene that brings the C60 in π-π overlap with the isoalloxazine helix. The remarkable spectral purity (in terms of narrow E(S)ii line widths) for the resulting ground-state complex signals a new class of highly organized supramolecular nanotube architecture with profound importance for advanced nanostructured devices.

Spectral heterogeneity and carotenoid-to-bacteriochlorophyll energy transfer in LH2 light-harvesting complexes from Allochromatium vinosum.

Photosynthetic organisms produce a vast array of spectral forms of antenna pigment-protein complexes to harvest solar energy and also to adapt to growth under the variable environmental conditions of light intensity, temperature, and nutrient availability. This behavior is exemplified by Allochromatium (Alc.) vinosum, a photosynthetic purple sulfur bacterium that produces different types of LH2 light-harvesting complexes in response to variations in growth conditions. In the present work, three different spectral forms of LH2 from Alc. vinosum, B800-820, B800-840, and B800-850, were isolated, purified, and examined using steady-state absorption and fluorescence spectroscopy, and ultrafast time-resolved absorption spectroscopy. The pigment composition of the LH2 complexes was analyzed by high-performance liquid chromatography, and all were found to contain five carotenoids: lycopene, anhydrorhodovibrin, spirilloxanthin, rhodopin, and rhodovibrin. Spectral reconstructions of the absorption and fluorescence excitation spectra based on the pigment composition revealed significantly more spectral heterogeneity in these systems compared to LH2 complexes isolated from other species of purple bacteria. The data also revealed the individual carotenoid-to-bacteriochlorophyll energy transfer efficiencies which were correlated with the kinetic data from the ultrafast transient absorption spectroscopic experiments. This series of LH2 complexes allows a systematic exploration of the factors that determine the spectral properties of the bound pigments and control the rate and efficiency of carotenoid-to-bacteriochlorophyll energy transfer.

The cAMP-producing agonist beraprost inhibits human vascular smooth muscle cell migration via exchange protein directly activated by cAMP.

AIMS: During restenosis, vascular smooth muscle cells (VSMCs) migrate from the vascular media to the developing neointima. Preventing VSMC migration is therefore a therapeutic target for restenosis. Drugs, such as prostacyclin analogues, that increase the intracellular concentration of cyclic adenosine monophosphate (cAMP) can inhibit VSMC migration, but the mechanisms via which this occurs are unknown. Two main downstream mediators of cAMP are protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac). This study has examined the effects of the prostacyclin analogue beraprost on VSMC migration and investigated the intracellular pathways involved. METHODS AND RESULTS: In a chemotaxis chamber, human saphenous vein VSMC migrated towards a platelet-derived growth-factor-BB (PDGF) chemogradient. Incubation with therapeutically relevant concentrations of cAMP-producing agonist beraprost significantly decreased PDGF-induced migration. Direct activation of either PKA or Epac inhibited migration whereas inhibition of PKA did not prevent the anti-migratory effect of beraprost. Direct activation of Epac also prevented hyperplasia in ex vivo serum-treated human veins. Using fluorescence resonance energy transfer, we demonstrated that beraprost activated Epac but not PKA. The mechanisms of this Epac-mediated effect involved activation of Rap1 with subsequent inhibition of RhoA. Cytoskeletal rearrangement at the leading edge of the cell was consequently inhibited. Interestingly, Epac1 was localized to the leading edge of migrating VSMC. CONCLUSIONS: These results indicate that therapeutically relevant concentrations of beraprost can inhibit VSMC migration via a previously unknown mechanism involving the cAMP mediator Epac. This may provide a novel target that could blunt neointimal formation.

High efficiency light harvesting by carotenoids in the LH2 complex from photosynthetic bacteria: unique adaptation to growth under low-light conditions.

Rhodopin, rhodopinal, and their glucoside derivatives are carotenoids that accumulate in different amounts in the photosynthetic bacterium, Rhodoblastus (Rbl.) acidophilus strain 7050, depending on the intensity of the light under which the organism is grown. The different growth conditions also have a profound effect on the spectra of the bacteriochlorophyll (BChl) pigments that assemble in the major LH2 light-harvesting pigment-protein complex. Under high-light conditions the well-characterized B800-850 LH2 complex is formed and accumulates rhodopin and rhodopin glucoside as the primary carotenoids. Under low-light conditions, a variant LH2, denoted B800-820, is formed, and rhodopinal and rhodopinal glucoside are the most abundant carotenoids. The present investigation compares and contrasts the spectral properties and dynamics of the excited states of rhodopin and rhodopinal in solution. In addition, the systematic differences in pigment composition and structure of the chromophores in the LH2 complexes provide an opportunity to explore the effect of these factors on the rate and efficiency of carotenoid-to-BChl energy transfer. It is found that the enzymatic conversion of rhodopin to rhodopinal by Rbl. acidophilus 7050 grown under low-light conditions results in nearly 100% carotenoid-to-BChl energy transfer efficiency in the LH2 complex. This comparative analysis provides insight into how photosynthetic systems are able to adapt and survive under challenging environmental conditions.

Analysis of immunoarrays using a gold grating-based dual mode surface plasmon-coupled emission (SPCE) sensor chip.

We have developed a novel dual mode immunoassay platform that combines the advantages of real-time, label free measurement of surface plasmon resonance (SPR) and the highly directional surface plasmon-coupled emission (SPCE) using a gold grating-based sensor chip. Since only fluorophore-labeled analyte molecules that are close to the metal surface of the sensor chip will couple to the surface plasmon, SPCE detection is highly surface-specific leading to background suppression and increased sensitivity. Theoretical calculations were done to find SPR and SPCE angles for a sensor chip optimized for Alexa Fluor 647. We have confirmed the SPR and SPCE responses on the dual mode sensor chip using Alexa Fluor 647 labeled anti-mouse IgG. Signal fluctuation of the dual mode sensor chip reader was below 1.2% and 0.8% for SPR and SPCE, respectively. The SPR response in this configuration showed a minimum detection level of 1 µg ml(-1), and the SPCE response showed a minimum detection level of 1 ng ml(-1) for the same sample. A range of human IgG concentrations in human serum was also analyzed with the dual mode sensor chip. The SPCE measurement is more sensitive than the SPR real-time measurement, and substantially extends the dynamic range of the assay platform, as well as enabling independent measurements of co-localized analytes on the same sensor chip region of interest. Since this assay platform is capable of measuring more than 1000 spatially encoded regions of interest on a 1 cm(2) sensor chip, it has the potential for high-content analyses of biological samples with both research and clinical applications.

Sphingosine-1-phosphate-induced release of TIMP-2 from vascular smooth muscle cells inhibits angiogenesis.

Following myocardial infarction, angiogenesis occurs as a result of thrombus formation, which permits reperfusion of damaged myocardium. Sphingosine 1-phosphate (S1P) is a naturally occurring lipid mediator released from platelets and is found in high concentrations at sites of thrombosis. S1P might therefore be involved in regulating angiogenesis following myocardial infarction and might influence reperfusion. The aims of this study were to determine the effects of S1P in human coronary arterial cell angiogenesis and delineate the subsequent mechanisms. An in vitro model of angiogenesis was developed using a co-culture of human coronary artery endothelial cells, human coronary smooth muscle cells and human fibroblasts. In this model, S1P inhibited angiogenesis and this was dependent on the presence of smooth muscle cells. The mechanism of the inhibitory effect was through S1P-induced release of a soluble mediator from smooth muscle cells. This mediator was identified as tissue inhibitor of metalloproteinase-2 (TIMP-2). Release of TIMP-2 was dependent on S1P-induced activation of Rho kinase and directly contributed to incomplete formation of endothelial cell adherens junctions. This was observed as a diffuse localisation of VE-cadherin, leading to decreased tubulogenesis. A similar inhibitory response to S1P was demonstrated in an ex vivo human arterial model of angiogenesis. In summary, S1P-induced inhibition of angiogenesis in human artery endothelial cells is mediated by TIMP-2 from vascular smooth muscle cells. This reduces the integrity of intercellular junctions between nascent endothelial cells. S1P might therefore inhibit the angiogenic response following myocardial infarction.

Evaluation of an open-field autorefractor's ability to measure refraction and hence potential to assess objective accommodation in pseudophakes.

BACKGROUND: To evaluate the accuracy of an open-field autorefractor compared with subjective refraction in pseudophakes and hence its ability to assess objective eye focus with intraocular lenses (IOLs). METHODS: Objective refraction was measured at 6 m using the Shin-Nippon NVision-K 5001/Grand Seiko WR-5100K open-field autorefractor (five repeats) and by subjective refraction on 141 eyes implanted with a spherical (Softec1 n=53), aspherical (SoftecHD n=37) or accommodating (1CU n=22; Tetraflex n=29) IOL. Autorefraction was repeated 2 months later. RESULTS: The autorefractor prescription was similar (average difference: 0.09 ± 0.53 D; p=0.19) to that found by subjective refraction, with ∼71% within ± 0.50 D. The horizontal cylindrical components were similar (difference: 0.00 ± 0.39 D; p=0.96), although the oblique (J(45)) autorefractor cylindrical vector was slightly more negative (by -0.06 ± 0.25 D; p=0.06) than the subjective refraction. The results were similar for each of the IOL designs except for the spherical IOL, where the mean spherical equivalent difference between autorefraction and subjective was more hypermetropic than the Tetraflex accommodating IOL (F=2.77, p=0.04). The intrasession repeatability was <0.55 D (95% CI) and intersession repeatability <0.50 D in ≥ 85%. CONCLUSIONS: The autorefractor gives valid and repeatable measures of pseudophakic eye refraction and hence objective accommodation.

Vergence analysis reveals the influence of axial distances on accommodation with age and axial ametropia.

Despite numerous investigations, the aetiology and mechanism of accommodation and presbyopia remains equivocal. Using Gaussian first-order ray tracing calculations, we examine the contribution that ocular axial distances make to the accommodation response. Further, the influence of age and ametropia are also considered. The data show that all changes in axial distances during accommodation reduce the accommodation response, with the reduction in anterior chamber depth contributing most to this overall attenuation. Although the total power loss due to the changes in axial distances remained constant with increasing age, hyperopes exhibited less accommodation than myopes. The study, therefore, enhances our understanding of biometric accommodative changes and demonstrates the utility of vergence analysis in the assessment of accommodation.