Different colors of light lead to different adaptation and activation as determined by high-density EEG.

Light adaptation is crucial for coping with the varying levels of ambient light. Using high-density electroencephalography (EEG), we investigated how adaptation to light of different colors affects brain responsiveness. In a within-subject design, sixteen young participants were adapted first to dim white light and then to blue, green, red, or white bright light (one color per session in a randomized order). Immediately after both dim and bright light adaptation, we presented brief light pulses and recorded event-related potentials (ERPs). We analyzed ERP response strengths and brain topographies and determined the underlying sources using electrical source imaging. Between 150 and 261ms after stimulus onset, the global field power (GFP) was higher after dim than bright light adaptation. This effect was most pronounced with red light and localized in the frontal lobe, the fusiform gyrus, the occipital lobe and the cerebellum. After bright light adaptation, within the first 100ms after light onset, stronger responses were found than after dim light adaptation for all colors except for red light. Differences between conditions were localized in the frontal lobe, the cingulate gyrus, and the cerebellum. These results indicate that very short-term EEG brain responses are influenced by prior light adaptation and the spectral quality of the light stimulus. We show that the early EEG responses are differently affected by adaptation to different colors of light which may contribute to known differences in performance and reaction times in cognitive tests.

Hyperactivation of retina by light in mice leads to photoreceptor cell death mediated by VEGF and retinal pigment epithelium permeability.

Light toxicity is suspected to enhance certain retinal degenerative processes such as age-related macular degeneration. Death of photoreceptors can be induced by their exposure to the visible light, and although cellular processes within photoreceptors have been characterized extensively, the role of the retinal pigment epithelium (RPE) in this model is less well understood. We demonstrate that exposition to intense light causes the immediate breakdown of the outer blood-retinal barrier (BRB). In a molecular level, we observed the slackening of adherens junctions tying up the RPE and massive leakage of albumin into the neural retina. Retinal pigment epithelial cells normally secrete vascular endothelial growth factor (VEGF) at their basolateral side; light damage in contrast leads to VEGF increase on the apical side - that is, in the neuroretina. Blocking VEGF, by means of lentiviral gene transfer to express an anti-VEGF antibody in RPE cells, inhibits outer BRB breakdown and retinal degeneration, as illustrated by functional, behavioral and morphometric analysis. Our data show that exposure to high levels of visible light induces hyperpermeability of the RPE, likely involving VEGF signaling. The resulting retinal edema contributes to irreversible damage to photoreceptors. These data suggest that anti-VEGF compounds are of therapeutic interest when the outer BRB is altered by retinal stresses.

Ice-Retardant Pavement, HR-290, 1991

During 1986, the City of Des Moines placed an experimental asphaltic concrete overlay containing an ice-retardant additive (Verglimit) on Euclid Avenue (U.S. Highway 6). Verglimit is a chemical multi-component deicer which is added to the surface course of an asphalt overlay. The additive was uniformly distributed through the mix at the asphalt plant, which allows exposure of the particles as the finished surface wears under traffic. During a snowfall, the exposed particles attract and absorb moisture creating a deicing solution which dampens the pavement. The Verglimit additive used on this project cost $1,180 per metric ton. The Verglimit was added at a rate of 6.3% by weight, which was 126 pounds per ton, or $66.38 per ton of hot mix asphalt. The purchase of Verglimit additive was funded by the Iowa Department of Transportation through a research project recommended by the Highway Research Advisory Board. The pavement surface experienced severe wetting due to the additive's affinity for water immediately after the project was completed and during periods of high humidity. This wetting created slippery conditions both on the project itself and where vehicles tracked the additive. The only way to remove the slipperiness was by flushing the street with water. The ice-retardant overlay appears to perform as expected in reducing the adherence of ice and snow, especially at temperatures just below freezing. It performs better in light snowfalls than in heavy ones. The ice retardant overlay is effective in eliminating thin coatings of ice due to freezing drizzle or widespread frost. The accident data showed a reduction in the number of snow and ice related accidents but due to the low number of this type of accident the results are inconclusive.

Evaluation of "FIBERMESH" Synthetic Fibers in P.C. Concrete Bridge Barrier Rail, MLR-88-17, 1988

Ten bridges were chosen to have their concrete barrier rails constructed with one rail having "Fibermesh" synthetic fibers added and the other rail without the fibers. The rails were constructed in 1985, 1986, or 1987. All the bridges were inspected in 1988 and no consistent reduction in cracking was achieved using Fibermesh fibers in the p.c. concrete bridge barrier rails.

Bond strength of orthodontic brackets using different light and self-curing cements

The purpose of the study was to evaluate the shear bond strength of stainless steel orthodontic brackets directly bonded to extracted human premolar teeth. Fifty teeth were randomly divided into ¿ve groups: (1) System One (chemically cured composite resin), (2) Light Bond (light-cured composite resin), (3) Vivaglass Cem (self-curing glass ionomer cement), (4) Fuji Ortho LC (light-cured glass ionomer cement) used after 37% orthophosphoric acid¿etching of enamel (5) Fuji Ortho LC without orthophosphoric acid¿etching. The brackets were placed on the buccal and lingual surfaces of each tooth, and the specimens were stored in distilled water (24 hours) at 378C and thermocycled. Teeth were mounted on acrylic block frames, and brackets were debonded using an Instron machine. Shear bond strength values at fracture (Nw)were recorded. ANOVA and Student-Newman-Keuls multiple comparison tests were performed (P , .05). Bonding failure site was recorded by stereomicroscope and analyzed by Chi-square test, selected specimens of each group were observed by scanning electron microscope. System One attained the highest bond strength. Light Bond and Fuji Ortho LC, when using an acid-etching technique, obtained bond strengths that were within the range of estimated bond strength values for successful clinical bonding. Fuji Ortho LC and Vivaglass Cem left an almost clean enamel surface after debracketing.

Dynamics of Highway Bridges, HR-67, 1961

The AASHO specifications for highway bridges require that in designing a bridge, the live load must be multiplied by an impact factor for which a formula is given, dependent only upon the length of the bridge. This formula is a result of August Wohler's tests on fatigue in metals, in which he determined that metals which are subjected to large alternating loads will ultimately fail at lower stresses than those which are subjected only to continuous static loads. It is felt by some investigators that this present impact factor is not realistic, and it is suggested that a consideration of the increased stress due to vibrations caused by vehicles traversing the span would result in a more realistic impact factor than now exists. Since the current highway program requires a large number of bridges to be built, the need for data on dynamic behavior of bridges is apparent. Much excellent material has already been gathered on the subject, but many questions remain unanswered. This work is designed to investigate further a specific corner of that subject, and it is hoped that some useful light may be shed on the subject. Specifically this study hopes to correlate, by experiment on a small scale test bridge, the upper limits of impact utilizing a stationary, oscillating load to represent axle loads moving past a given point. The experiments were performed on a small scale bridge which is located in the basement of the Iowa Engineering Experiment Station. The bridge is a 25 foot simply supported span, 10 feet wide, supported by four beams with a composite concrete slab. It is assumed that the magnitude of the predominant forcing function is the same as the magnitude of the dynamic force produced by a smoothly rolling load, which has a frequency determined by the passage of axles. The frequency of passage of axles is defined as the speed of the vehicle divided by the axle spacing. Factors affecting the response of the bridge to this forcing function are the bridge stiffness and mass, which determine the natural frequency, and the effects of solid damping due to internal structural energy dissipation.

Visibility and Speed Estimation of Iowa State Highway Commission Snowplows, HR-174, 1975

Many accidents involving Iowa snowplows have happened in recent years. This study investigated the influence of time of day, sex of subject, type of snowplow sign and snowplow speed on the criteria of oncoming driver reaction time and his estimate of snowplow speed. Film strips were made of a car passing a snow-Plow under various experimental conditions. These experimental movie strips were viewed in the laboratory by college student drivers who were asked to indicate their reaction time to slow down and to estimate the speed of the snowplow being passed. The generally best sign condition for the snowplow was to have a striped rear sign and a speed-proportional flashing light in addition to the standard rotating beacon on top of the truck. Several recommendations were made.

Field/Laboratory Testing of Damaged Prestressed Concrete Girder Bridges, HR-397, 1999

Due to frequent accidental damage to prestressed concrete (P/C) bridges caused by impact from overheight vehicles, a project was initiated to evaluate the strength and load distribution characteristics of damaged P/C bridges. A comprehensive literature review was conducted. It was concluded that only a few references pertain to the assessment and repair of damaged P/C beams. No reference was found that involves testing of a damaged bridge(s) as well as the damaged beams following their removal. Structural testing of two bridges was conducted in the field. The first bridge tested, damaged by accidental impact, was the westbound (WB) I-680 bridge in Beebeetown, Iowa. This bridge had significant damage to the first and second beams consisting of extensive loss of section and the exposure of numerous strands. The second bridge, the adjacent eastbound (EB) structure, was used as a baseline of the behavior of an undamaged bridge. Load testing concluded that a redistribution of load away from the damaged beams of the WB bridge was occurring. Subsequent to these tests, the damaged beams in the WB bridge were replaced and the bridge retested. The repaired WB bridge behaved, for the most part, like the undamaged EB bridge indicating that the beam replacement restored the original live load distribution patterns. A large-scale bridge model constructed for a previous project was tested to study the changes in behavior due to incrementally applied damage consisting initially of only concrete removal and then concrete removal and strand damage. A total of 180 tests were conducted with the general conclusion that for exterior beam damage, the bridge load distribution characteristics were relatively unchanged until significant portions of the bottom flange were removed along with several strands. A large amount of the total applied moment to the exterior beam was redistributed to the interior beam of the model. Four isolated P/C beams were tested, two removed from the Beebeetown bridge and two from the aforementioned bridge model. For the Beebeetown beams, the first beam, Beam 1W, was tested in an "as removed" condition to obtain the baseline characteristics of a damaged beam. The second beam, Beam 2W, was retrofit with carbon fiber reinforced polymer (CFRP) longitudinal plates and transverse stirrups to strengthen the section. The strengthened Beam was 12% stronger than Beam 1W. Beams 1 and 2 from the bridge model were also tested. Beam 1 was not damaged and served as the baseline behavior of a "new" beam while Beam 2 was damaged and repaired again using CFRP plates. Prior to debonding of the plates from the beam, the behavior of both Beams 1 and 2 was similar. The retrofit beam attained a capacity greater than a theoretically undamaged beam prior to plate debonding. Analytical models were created for the undamaged and damaged center spans of the WB bridge; stiffened plate and refined grillage models were used. Both models were accurate at predicting the deflections in the tested bridge and should be similarly accurate in modeling other P/C bridges. The moment fractions per beam were computed using both models for the undamaged and damaged bridges. The damaged model indicates a significant decrease in moment in the damaged beams and a redistribution of load to the adjacent curb and rail as well as to the undamaged beam lines.

Deleterious Actions Of Vegf On The Blood Retinal Barrier And Photoreceptor Survival In The Light-damage Model

Purpose: The retinal balance between pro- and anti-angiogenic factors is critical for angiogenesis control, but is also involved in cell survival. We previously reported upregulation of VEGF and photoreceptor (PR) cell death in the Light-damage (LD) model. Preliminary results showed that anti-VEGF can rescue PR from cell death. Thus, we investigated the role of VEGF on the retina and we herein described the effect of anti-VEGF antibody delivered by lentiviral gene transfer in this model.Methods: To characterize the action of VEGF during the LD, we exposed Balb/c mice subretinally injected with LV-anti-VEGF, or not, to 5'000 lux for 1h. We next evaluated the retinal function, PR survival and protein expression (VEGF, VEGFR1/2, Src, PEDF, p38MAPK, Akt, Peripherin, SWL-opsin) after LD. We analyzed Blood retinal barrier (BRB) integrity on flat-mounted RPE and cryosections stained with β-catenin, ZO-1, N-cadherin and albumin.Results: Results indicate that the VEGF pathway is modulated after LD. LD leads to extravascular albumin leakage and BRB breakdown: β-catenin, ZO-1 and N-cadherin translocate to the cytoplasm of RPE cells showing loss of cell cohesion. This phenomenon is in adequacy with the VEGF time-course expression. Assessment of the retinal function reveals that PR rescue correlates with the level of LV-anti-VEGF expression. Rhodopsin content was higher in the LV-anti-VEGF group than in controls and measures of the ONL thickness indicate that LV-anti-VEGF preserves by 82% the outer nuclear layer from degeneration. Outer segments (OS) appeared well organized with an appropriate length in the LV-anti-VEGF group compared to controls, and the expression of SWL-opsin is maintained in the OS without being mislocalized as in the LV-GFP group. Finally, LV-anti-VEGF treatment prevents BRB breakdown and maintained RPE cell integrity.Conclusions: This study involves VEGF in LD and highlights the prime importance of the BRB integrity for PR survival. Taken together, these results show that anti-VEGF is neuroprotective in this model and maintains functional PR layer in LD-treated mice.

Dissociation from BiP and Retrotranslocation of Unassembled Immunoglobulin Light Chains Are Tightly Coupled to Proteasome Activity

Unassembled immunoglobulin light chains expressed by the mouse plasmacytoma cell line NS1 (KNS1) are degraded in vivo with a half-life of 50-60 min in a way that closely resembles endoplasmic reticulum (ER)-associated degradation (Knittler et al., 1995). Here we show that the peptide aldehydes MG132 and PS1 and the specific proteasome inhibitor lactacystin effectively increased the half-life of KNS1, arguing for a proteasome-mediated degradation pathway. Subcellular fractionation and protease protection assays have indicated an ER localization of KNS1 upon proteasome inhibition. This was independently confirmed by the analysis of the folding state of KNS1and size fractionation experiments showing that the immunoglobulin light chain remained bound to the ER chaperone BiP when the activity of the proteasome was blocked. Moreover, kinetic studies performed in lactacystin-treated cells revealed a time-dependent increase in the physical stability of the BiP-KNS1complex, suggesting that additional proteins are present in the older complex. Together, our data support a model for ER-associated degradation in which both the release of a soluble nonglycosylated protein from BiP and its retrotranslocation out of the ER are tightly coupled with proteasome activity.

LIGHT/HVEM/LTβR interaction as a target for the modulation of the allogeneic immune response in transplantation.

The exchange of information during interactions of T cells with dendritic cells, B cells or other T cells regulates the course of T, B and DC-cell activation and their differentiation into effector cells. The tumor necrosis factor superfamily member LIGHT (homologous to lymphotoxin, exhibits inducible expression and competes with HSV glycoprotein D for binding to herpesvirus entry mediator, a receptor expressed on T lymphocytes) is transiently expressed upon T cell activation and modulates CD8 T cell-mediated alloreactive responses upon herpes virus entry mediator (HVEM) and lymphotoxin β receptor (LTβR) engagement. LIGHT-deficient mice, or WT mice treated with LIGHT-targeting decoy receptors HVEM-Ig, LTβR-Ig or sDcR3-Ig, exhibit prolonged graft survival compared to untreated controls, suggesting that LIGHT modulates the course and severity of graft rejection. Therefore, targeting the interaction of LIGHT with HVEM and/or LTβR using recombinant soluble decoy receptors or monoclonal antibodies represent an innovative therapeutic strategy for the prevention and treatment of allograft rejection and for the promotion of donor-specific tolerance.

Advanced light microscopy techniques

This article summarizes the basic principles of light microscopy, with examples of applications in biomedicine that illustrate the capabilities of thetechnique.

Phototropism: at the crossroads of light-signaling pathways.

Phototropism enables plants to orient growth towards the direction of light and thereby maximizes photosynthesis in low-light environments. In angiosperms, blue-light photoreceptors called phototropins are primarily involved in sensing the direction of light. Phytochromes and cryptochromes (sensing red/far-red and blue light, respectively) also modulate asymmetric hypocotyl growth, leading to phototropism. Interactions between different light-signaling pathways regulating phototropism occur in cryptogams and angiosperms. In this review, we focus on the molecular mechanisms underlying the co-action between photosensory systems in the regulation of hypocotyl phototropism in Arabidopsis thaliana. Recent studies have shown that phytochromes and cryptochromes enhance phototropism by controlling the expression of important regulators of phototropin signaling. In addition, phytochromes may also regulate growth towards light via direct interaction with the phototropins.

Light-regulated interactions with SPA proteins underlie cryptochrome-mediated gene expression.

Cryptochromes are a class of photosensory receptors that control important processes in animals and plants primarily by regulating gene expression. How photon absorption by cryptochromes leads to changes in gene expression has remained largely elusive. Three recent studies, including Lian and colleagues (pp. 1023-1028) and Liu and colleagues (pp. 1029-1034) in this issue of Genes & Development, demonstrate that the interaction of light-activated Arabidopsis cryptochromes with a class of regulatory components of E3 ubiquitin ligase complexes leads to environmentally controlled abundance of transcriptional regulators.