Ultrafast adaptive optics for imaging the living human eye.

Adaptive optics (AO) is a powerful method for correcting dynamic aberrations in numerous applications. When applied to the eye, it enables cellular-resolution retinal imaging and enhanced visual performance and stimulation. Most ophthalmic AO systems correct dynamic aberrations up to 1-2 Hz, the commonly-known cutoff frequency for correcting ocular aberrations.

Cone photoreceptor dysfunction in retinitis pigmentosa revealed by optoretinography.

Retinitis pigmentosa (RP) is the most common group of inherited retinal degenerative diseases, whose most debilitating phase is cone photoreceptor death. Perimetric and electroretinographic methods are the gold standards for diagnosing and monitoring RP and assessing cone function. However, these methods lack the spatial resolution and sensitivity to assess disease progression at the level of individual photoreceptor cells, where the disease originates and whose degradation causes vision loss.

Revealing How Color Vision Phenotype and Genotype Manifest in Individual Cone Cells.

Purpose: Psychophysical and genetic testing provide substantial information about color vision phenotype and genotype. However, neither reveals how color vision phenotypes and genotypes manifest themselves in individual cones, where color vision and its anomalies are thought to originate. Here, we use adaptive-optics phase-sensitive optical coherence tomography (AO-PSOCT) to investigate these relationships.

Multi-reference global registration of individual A-lines in adaptive optics optical coherence tomography retinal images (Publisher's Note).

The note corrects an error that appeared in Equation 14 of the originally published article.

Multi-reference global registration of individual A-lines in adaptive optics optical coherence tomography retinal images.

Significance: Adaptive optics optical coherence tomography (AO-OCT) technology enables non-invasive, high-resolution three-dimensional (3D) imaging of the retina and promises earlier detection of ocular disease. However, AO-OCT data are corrupted by eye-movement artifacts that must be removed in post-processing, a process rendered time-consuming by the immense quantity of data.

Aim: To efficiently remove eye-movement artifacts at the level of individual A-lines, including those present in any individual reference volume.

Suite of methods for assessing inner retinal temporal dynamics across spatial and temporal scales in the living human eye.

There are no label-free imaging descriptors related to physiological activity of inner retinal cells in the living human eye. A major reason is that inner retinal neurons are highly transparent and reflect little light, making them extremely difficult to visualize and quantify. To measure physiologically-induced optical changes of inner retinal cells despite their challenging optical properties.

Association of Exercise and Swimming Goggles With Modulation of Cerebro-ocular Hemodynamics and Pressures in a Model of Spaceflight-Associated Neuro-ocular Syndrome.

Importance: Astronauts on International Space Station missions demonstrate adverse neuro-ocular changes. Reversing a negative translaminar pressure gradient (TLPG) by modulating cerebral blood flow, decreasing intracranial pressure, or increasing intraocular pressure (IOP) has been proposed as potential intervention for spaceflight-associated neuro-ocular syndrome (SANS).

Objective: To examine whether exercise (resistance, moderate-intensity aerobic, and high-intensity aerobic) or artificially increasing IOP is associated with modulated cerebro-ocular hemodynamic and pressure changes during head-down tilt (HDT), an analogue of spaceflight, in healthy adults.

Cone photoreceptor classification in the living human eye from photostimulation-induced phase dynamics.

Human color vision is achieved by mixing neural signals from cone photoreceptors sensitive to different wavelengths of light. The spatial arrangement and proportion of these spectral types in the retina set fundamental limits on color perception, and abnormal or missing types are responsible for color vision loss. Imaging provides the most direct and quantitative means to study these photoreceptor properties at the cellular scale in the living human retina, but remains challenging.

Global gene expression of histologically normal primary skin cells from BCNS subjects reveals "single-hit" effects that are influenced by rapamycin.

Studies of dominantly heritable cancers enabled insights about tumor progression. BCNS is a dominantly inherited disorder that is characterized by developmental abnormalities and postnatal neoplasms, principally BCCs. We performed an exploratory gene expression profiling of primary cell cultures derived from clinically unaffected skin biopsies of BCNS gene-carriers ( ) and normal individuals.

Older Adult Multitasking Performance Using a Gaze-Contingent Useful Field of View.

Objective We implemented a gaze-contingent useful field of view paradigm to examine older adult multitasking performance in a simulated driving environment. Background Multitasking refers to the ability to manage multiple simultaneous streams of information. Recent work suggests that multitasking declines with age, yet the mechanisms supporting these declines are still debated.

The National Cancer Institute ALMANAC: A Comprehensive Screening Resource for the Detection of Anticancer Drug Pairs with Enhanced Therapeutic Activity.

To date, over 100 small-molecule oncology drugs have been approved by the FDA. Because of the inherent heterogeneity of tumors, these small molecules are often administered in combination to prevent emergence of resistant cell subpopulations. Therefore, new combination strategies to overcome drug resistance in patients with advanced cancer are needed.

Haploinsufficiency in tumor predisposition syndromes: altered genomic transcription in morphologically normal cells heterozygous for VHL or TSC mutation.

Tumor suppressor genes and their effector pathways have been identified for many dominantly heritable cancers, enabling efforts to intervene early in the course of disease. Our approach on the subject of early intervention was to investigate gene expression patterns of morphologically normal "one-hit" cells before they become hemizygous or homozygous for the inherited mutant gene which is usually required for tumor formation. Here, we studied histologically non-transformed renal epithelial cells from patients with inherited disorders that predispose to renal tumors, including von Hippel-Lindau (VHL) disease and Tuberous Sclerosis (TSC).

Measuring the Useful Field of View During Simulated Driving With Gaze-Contingent Displays.

Objective: We aimed to develop and test a new dynamic measure of transient changes to the useful field of view (UFOV), utilizing a gaze-contingent paradigm for use in realistic simulated environments.

Background: The UFOV, the area from which an observer can extract visual information during a single fixation, has been correlated with driving performance and crash risk. However, some existing measures of the UFOV cannot be used dynamically in realistic simulators, and other UFOV measures involve constant stimuli at fixed locations.

The Effects of Cell Phone and Text Message Conversations on Simulated Street Crossing.

Objective: A fully immersive, high-fidelity street-crossing simulator was used to examine the effects of texting on pedestrian street-crossing performance.

Background: Research suggests that street-crossing performance is impaired when pedestrians engage in cell phone conversations. Less is known about the impact of texting on street-crossing performance.

Are gamers better crossers? An examination of action video game experience and dual task effects in a simulated street crossing task.

Objective: A high-fidelity street crossing simulator was used to test the hypothesis that experienced action video game players are less vulnerable than non-gamers to dual task costs in complex tasks.

Background: Previous research has shown that action video game players outperform nonplayers on many single task measures of perception and attention. It is unclear, however, whether action video game players outperform nonplayers in complex, divided attention tasks.

The effect of landmarks in human path integration.

The effect of landmarks in human path integration was investigated using virtual hallway-mazes. Participants traveled along random 5-segment paths either with or without distinctive landmarks at some segment intersections. They were required to directly return to the origin or to one of the landmark locations from the end of the path.

Synthesis and biological activity of acetyl-protected hydroxybenzyl diethyl phosphates (EHBP) as potential chemotherapeutic agents.

Several acetyl-protected hydroxybenzyl diethyl phosphates (EHBPs) that are capable of forming quinone methide intermediates were synthesized and their cell growth inhibitory properties were evaluated in four different human cancer cell lines. Compounds 1, 1a, and 1b, corresponding to (4-acetyloxybenzyl diethylphosphate), (3-methyl-4-acetyloxybenzyl diethylphosphate), and (3-chloro-4-acetyloxybenzyl diethylphosphate), were significantly more potent than compounds 2 and 3, (2-acetyloxybenzyl diethylphosphate) and (3-acetyloxybenzyl diethylphosphate), respectively. Using HT-29 human colon cancer cells, compounds 1 and 3 increased apoptosis, inhibited proliferation, and caused a G(2)/M block in the cell cycle.

Methyl selenocysteine: single-dose pharmacokinetics in men.

The recently published report of the SELECT evaluation of selenium and vitamin E provided strong evidence that selenium 200 μg per day in the form of selenomethionine does not protect selenium-replete men against prostate or any other cancer. This seems to refute the result of the much smaller Nutritional Prevention of Cancer (NPC) trial of selenium. Because SELECT did not test the NPC agent, it is possible that the difference between the two trials stems partly from the use of different agents: selenomethionine in SELECT, and selenized yeast in the NPC trial.

Effects of 5,6-benzoflavone, indole-3-carbinol (I3C) and diindolylmethane (DIM) on chemically-induced mammary carcinogenesis: is DIM a substitute for I3C?

The abilities of 5,6-benzoflavone (5,6-BF, a synthetic flavonoid), indole-3-carbinol (I3C, a plant derived product) or diindolylmethane (DIM, a condensation product of I3C) to alter the induction of mammary cancers induced by the carcinogens 7,12-dimethylbenzanthracene (DMBA) or N-methyl-N-nitrosourea (MNU) were evaluated. Interestingly, the first two agents act as aryl hydrocarbon receptor (AhR) agonists, while DIM does not. The agents were initially examined for their ability to inhibit DMBA-induced mammary carcinogenesis.

APC +/- alters colonic fibroblast proteome in FAP.

Here we compared the proteomes of primary fibroblast cultures derived from morphologically normal colonic mucosa of familial adenomatous polyposis (FAP) patients with those obtained from unaffected controls. The expression signature of about 19% of total fibroblast proteins separates FAP mutation carriers from unaffected controls (P < 0.01).

Walking and talking: dual-task effects on street crossing behavior in older adults.

The ability to perform multiple tasks simultaneously has become increasingly important as technologies such as cell phones and portable music players have become more common. In the current study, we examined dual-task costs in older and younger adults using a simulated street crossing task constructed in an immersive virtual environment with an integrated treadmill so that participants could walk as they would in the real world. Participants were asked to cross simulated streets of varying difficulty while either undistracted, listening to music, or conversing on a cell phone.

Phase 0 clinical chemoprevention trial of the Akt inhibitor SR13668.

SR13668, an orally active Akt pathway inhibitor, has demonstrated cancer chemopreventive potential in preclinical studies. To accelerate the clinical development of this promising agent, we designed and conducted the first-ever phase 0 chemoprevention trial to evaluate and compare the effects of food and formulation on SR13668 bioavailability. Healthy adult volunteers were randomly assigned to receive a single, 38-mg oral dose of SR13668 in one of five different formulations, with or without food.

Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis.

Resveratrol, a naturally occurring polyphenol, has cancer chemopreventive properties in preclinical models. It has been shown to downregulate the levels of insulin-like growth factor-1 (IGF-I) in rodents. The purpose of the study was to assess its safety, pharmacokinetics, and effects on circulating levels of IGF-I and IGF-binding protein-3 (IGFBP-3) after repeated dosing.

The effect of active selection in human path integration.

Path integration refers to the ability to integrate self-motion information to estimate one's current position and orientation relative to the origin. To investigate the effect of active selection in path integration, we used a virtual homing task in which participants traveled along hallways and attempted to directly return to the origin. Two groups of participants differed in the voluntary selection of the path structure, but received the same perceptual and motor information.

Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients.

Resveratrol is a phytochemical with chemopreventive activity in preclinical rodent models of colorectal carcinogenesis. Antiproliferation is one of the many chemopreventive modes of action it has been shown to engage in. Concentrations of resveratrol, which can be achieved in human tissues after p.