In Vitro and In Vivo Analysis of Ochratoxin A-Derived Glucuronides and Mercapturic Acids as Biomarkers of Exposure.

Ochratoxin A (OTA) is a widespread food contaminant, with exposure estimated to range from 0.64 to 17.79 ng/kg body weight (bw) for average consumers and from 2.40 to 51.69 ng/kg bw per day for high consumers. Current exposure estimates are, however, associated with considerable uncertainty. While biomarker-based approaches may contribute to improved exposure assessment, there is yet insufficient data on urinary metabolites of OTA and their relation to external dose to allow reliable estimates of daily intake. This study was designed to assess potential species differences in phase II biotransformation in vitro and to establish a correlation between urinary OTA-derived glucuronides and mercapturic acids and external exposure in rats in vivo. In vitro analyses of OTA metabolism using the liver S9 of rats, humans, rabbits and minipigs confirmed formation of an OTA glucuronide but provided no evidence for the formation of OTA-derived mercapturic acids to support their use as biomarkers. Similarly, OTA-derived mercapturic acids were not detected in urine of rats repeatedly dosed with OTA, while indirect analysis using enzymatic hydrolysis of the urine samples prior to LC-MS/MS established a linear relationship between urinary glucuronide excretion and OTA exposure. These results support OTA-derived glucuronides but not mercapturic acids as metabolites suitable for biomonitoring.

Perception of a Black Room Seen Through a Veiling Luminance.

When a black room (a room painted black and filled with objects painted black) is viewed through a veiling luminance, how does it appear? Prior work on black rooms and white rooms suggests the room will appear white because mutual illumination in the high-reflectance white room lowers image contrast, and the veil also lowers image contrast. Other work reporting high lightness constancy for three-dimensional scenes viewed through a veil suggests the veil will not make the room appear lighter. Because mutual illumination also modifies the pattern of luminance gradients across the room while the veil does not, we were able to tease apart local luminance gradients from overall luminance contrast by presenting observers with a black room viewed through a veiling luminance. The room appeared white, and no veil was perceived. This suggests that lightness judgments in a room of one reflectance depend on overall luminance contrast only.

The quality of COPD care in German general practice-A cross-sectional study.

OBJECTIVES: Chronic Obstructive Pulmonary Disease (COPD) is a common health problem to be dealt with in primary care. Little is known about the quality of care provided for patients with COPD in Germany. Therefore, we wanted to assess the current quality of care delivered by a primary care network (PCN) for patients with COPD. METHODS: A cross-sectional study was conducted in collaboration with a primary care network (PCN). All patients of the PCN aged 40 years and older with a diagnosis of COPD were identified through electronic health records (EHR). A set of quality indicators (QIs) developed in accordance with current COPD-guidelines were appraised through numerical data retrieved from the EHR. RESULTS: In total, 2,568 patients with COPD were identified. Their mean age was 67 (SD±12) years, 49% were male. Thirty-five percent had a parallel diagnosis of asthma. There was no documentation of any spirometry for 54% of patients; 29% had a spirometry within the previous year. An influenza vaccination was documented for 37% within the preceding 12 months; 12% received a pneumococcal vaccination in the last 6 years. Smoking status was documented for 44% within the last year. CONCLUSION: The quality of care for patients with COPD in the PCN seemed suboptimal, despite the presence of a Disease Management Program (DMP). This finding is likely to apply widely to German general practice. Quality assessment through currently available EHR data was challenging due to non-standardized and insufficient documentation.

Density discrimination with occlusions in 3D clutter.

We examined how well human observers can discriminate the density of surfaces in two halves of a rotating three-dimensional cluttered sphere. The observer's task was to compare the density of the front versus back half or the left versus right half. We measured how the bias and sensitivity in judging the denser half depended on the level of occlusion and on the area and density of the surfaces in the clutter. When occlusion level was low, observers in the front-back task were biased to judge the back as denser, and when occlusion level was high they were biased to judge the front as denser. Weber fractions decreased as density increased for both the front-back and left-right tasks, consistent with previous findings for two-dimensional density discrimination. Weber fractions did not vary significantly with area for the front-back task, but increased with area for the left-right task, and we attribute this difference to occlusions that have different effects in the two tasks. We also ran model observers that compared the image occupancies of the two halves against a known expected difference. As the occlusion level increased, this expected difference followed a similar trend as the biases of the human observers, with a roughly constant offset between them. Weber fractions for human and model observers followed some similar trends, but there were discrepancies as well that can be partly explained by the information available to human versus model observers in carrying out their respective tasks.

A Psychophysical Evaluation of Texture Compression Masking Effects.

Lossy texture compression is increasingly used to reduce GPU memory and bandwidth consumption. However, as raised by recent studies, evaluating the quality of compressed textures is a difficult problem. Indeed using Peak Signal-to-Noise Ratio (PSNR) on texture images, like done in most applications, may not be a correct way to proceed. In particular, there is evidence that masking effects apply when the texture image is mapped on a surface and combined with other textures (e.g., affecting geometry or normal). These masking effects have to be taken into account when compressing a set of texture maps, in order to have a real understanding of the visual impact of the compression artifacts on the rendered images. In this work, we present the first psychophysical experiment investigating the perceptual impact of texture compression on rendered images. We explore the influence of compression bit rate, light direction, and diffuse and normal map content on the visual impact of artifacts. The collected data reveal huge masking effects from normal map to diffuse map artifacts and vice versa, and reveal the weakness of PSNR applied on individual textures for evaluating compression quality. The results allow us to also analyze the performance and failures of image quality metrics for predicting the visibility of these artifacts. We finally provide some recommendations for evaluating the quality of texture compression and show a practical application to approximating the distortion measured on a rendered 3D shape.

Signs of depth-luminance covariance in 3-D cluttered scenes.

In three-dimensional (3-D) cluttered scenes such as foliage, deeper surfaces often are more shadowed and hence darker, and so depth and luminance often have negative covariance. We examined whether the sign of depth-luminance covariance plays a role in depth perception in 3-D clutter. We compared scenes rendered with negative and positive depth-luminance covariance where positive covariance means that deeper surfaces are brighter and negative covariance means deeper surfaces are darker. For each scene, the sign of the depth-luminance covariance was given by occlusion cues. We tested whether subjects could use this sign information to judge the depth order of two target surfaces embedded in 3-D clutter. The clutter consisted of distractor surfaces that were randomly distributed in a 3-D volume. We tested three independent variables: the sign of the depth-luminance covariance, the colors of the targets and distractors, and the background luminance. An analysis of variance showed two main effects: Subjects performed better when the deeper surfaces were darker and when the color of the target surfaces was the same as the color of the distractors. There was also a strong interaction: Subjects performed better under a negative depth-luminance covariance condition when targets and distractors had different colors than when they had the same color. Our results are consistent with a "dark means deep" rule, but the use of this rule depends on the similarity between the color of the targets and color of the 3-D clutter.

Defocus Discrimination in Video: Motion in Depth.

We perform two psychophysics experiments to investigate a viewer's ability to detect defocus in video; in particular, the defocus that arises in video during motion in depth when the camera does not maintain sharp focus throughout the motion. The first experiment demonstrates that blur sensitivity during viewing is affected by the speed at which the target moves towards the camera. The second experiment measures a viewer's ability to notice momentary defocus and shows that the threshold of blur detection in arc minutes decreases significantly as the duration of the blur increases. Our results suggest that it is important to have good control of focus while recording video and that momentary defocus should be kept as short as possible so it goes unnoticed.

Depth discrimination from occlusions in 3D clutter.

Objects such as trees, shrubs, and tall grass consist of thousands of small surfaces that are distributed over a three-dimensional (3D) volume. To perceive the depth of surfaces within 3D clutter, a visual system can use binocular stereo and motion parallax. However, such parallax cues are less reliable in 3D clutter because surfaces tend to be partly occluded. Occlusions provide depth information, but it is unknown whether visual systems use occlusion cues to aid depth perception in 3D clutter, as previous studies have addressed occlusions for simple scene geometries only. Here, we present a set of depth discrimination experiments that examine depth from occlusion cues in 3D clutter, and how these cues interact with stereo and motion parallax. We identify two probabilistic occlusion cues. The first is based on the fraction of an object that is visible. The second is based on the depth range of the occluders. We show that human observers use both of these occlusion cues. We also define ideal observers that are based on these occlusion cues. Human observer performance is close to ideal using the visibility cue but far from ideal using the range cue. A key reason for the latter is that the range cue depends on depth estimation of the clutter itself which is unreliable. Our results provide new fundamental constraints on the depth information that is available from occlusions in 3D clutter, and how the occlusion cues are combined with binocular stereo and motion parallax cues.

Examination of Substance Use, Risk Factors, and Protective Factors on Student Academic Test Score Performance.

BACKGROUND: School administrators and teachers face difficult decisions about how best to use school resources to meet academic achievement goals. Many are hesitant to adopt prevention curricula that are not focused directly on academic achievement. Yet, some have hypothesized that prevention curricula can remove barriers to learning and, thus, promote achievement. We examined relationships among school levels of student substance use and risk and protective factors that predict adolescent problem behaviors and achievement test performance. METHODS: Hierarchical generalized linear models were used to predict associations involving school-averaged levels of substance use and risk and protective factors and students' likelihood of meeting achievement test standards on the Washington Assessment of Student Learning, statistically controlling for demographic and economic factors known to be associated with achievement. RESULTS: Levels of substance use and risk/protective factors predicted the academic test score performance of students. Many of these effects remained significant even after controlling for model covariates. CONCLUSIONS: Implementing prevention programs that target empirically identified risk and protective factors has the potential to have a favorable effect on students' academic achievement.

Are blur and disparity complementary cues to depth?

The image blur and binocular disparity of a 3D scene point both increase with distance in depth away from fixation. Perceived depth from disparity has been studied extensively and is known to be most precise near fixation. Perceived depth from blur is much less well understood. A recent experiment (Held, R. T, Cooper, E. A., & Banks, M. S. (2012). Current Biology, 22, 426-431) which used a volumetric stereo display found evidence that blur and disparity are complementary cues to depth, namely the disparity cue dominates over the blur cue near the fixation depth and blur dominates over disparity at depths that are far from fixation. Here we present a similar experiment but which used a traditional 3D display so that blur was produced by image processing rather than by the subjects' optics. Contrary to Held et al., we found that subjects did not rely more on blur to discriminate depth at distances far from fixation, even though a sufficient level of blur was available to do so. The discrepancy between the findings of the two studies can be explained in at least two ways. First, Held et al.'s subjects received trial-to-trial feedback in a training phase and may have learned how to perform the task using blur discrimination. Second, Held et al.'s volumetric stereo display may have provided other optical cues that indicated that the blur was real rather than rendered. The latter possibility would have significant implications about how depth is perceived from blur under different viewing conditions.

Qualitative shape from shading, highlights, and mirror reflections.

The human visual system has a remarkable ability to perceive three-dimensional (3-D) surface shape from shading and specular reflections. This paper presents two experiments that examined the perception of local qualitative shape under various conditions. Surfaces were rendered using standard computer graphics models of matte, glossy, and mirror reflectance and were viewed from a small oblique angle to avoid occluding contour shape cues. The subjects' task was to judge whether a marked point on each surface lay on a local hill or valley. In the first experiment, performance was lower for glossy surfaces than matte surfaces, which is contrary to findings in previous studies of quantitative shape. For mirror surfaces, performance was high despite the absence of occluding contours, and performance was increased when the environment map was brighter in the upper hemisphere as in a natural environment. The second experiment examined how subjects resolve a depth-reversal shape ambiguity where surfaces can be either upward or downward facing. An upward-facing surface prior that is known to exist for matte surfaces was also found to exist for glossy and mirror surfaces. Subjects relied entirely on this prior to resolve the depth-reversal ambiguity for matte and glossy surfaces, but relied on perspective cues as well for mirror surfaces.

Visibility in three-dimensional cluttered scenes.

Three-dimensional (3D) cluttered scenes consist of a large number of small surfaces distributed randomly in a 3D view volume. The canonical example is the foliage of a tree or bush. 3D cluttered scenes are challenging for vision tasks such as object recognition and depth perception because most surfaces or objects are only partly visible. This paper examines the probabilities of surface visibility in 3D cluttered scenes. We model how the probabilities of visible gaps, depth discontinuities, and binocular and half-occluded points depend on scene parameters such as the size and density of the surfaces that make up the clutter, as well as on depth and inverse depth. Inverse depth is of particular interest since both binocular disparity and motion parallax depend directly on it. The probability models are verified using data from synthetic 3D cluttered scenes, which are generated using computer graphics.

Removal of partial occlusion from single images.

This paper examines large partial occlusions in an image which occur near depth discontinuities when the foreground object is severely out of focus. We model these partial occlusions using matting, with the alpha value determined by the convolution of the blur kernel with a pinhole projection of the occluder. The main contribution is a method for removing the image contribution of the foreground occluder in regions of partial occlusion, which improves the visibility of the background scene. The method consists of three steps. First, the region of complete occlusion is estimated using a curve evolution method. Second, the alpha value at each pixel in the partly occluded region is estimated. Third, the intensity contribution of the foreground occluder is removed in regions of partial occlusion. Experiments demonstrate the method's ability to remove the effects of partial occlusion in single images with minimal user input.

Learning illumination- and orientation-invariant representations of objects through temporal association.

As the orientation or illumination of an object changes so does its appearance. This paper considers how observers are nonetheless able to recognize objects that have undergone such changes. In particular the paper tests the hypothesis that observers rely on temporal correlations between different object views to decide whether they are views of the same object or not. In a series of experiments subjects were shown a sequence of views representing a slowly transforming object. Testing revealed that subjects had formed object representations which were directly influenced by the temporal characteristics of the training views. In particular, introducing spurious correlations between views of different people's heads caused subjects to regard those views as being of a single person. This rapid and robust overriding of basic generalization processes supports the view that our recognition system tracks the correlated appearance of views of objects across time. Such view associations appear to allow the visual system to solve the view invariance problem without recourse to complex illumination models for extracting 3D form, or the use of the image plane transformations required to make appearance-based comparisons.

Palladium-catalyzed annulation of haloanilines and halobenzamides using norbornadiene as an acetylene synthon: a route to functionalized indolines, isoquinolinones, and indoles.

A general procedure for the palladium-catalyzed annulation of substituted haloanilines with norbornadiene gives functionalized indolines in 51-98% yield. These indolines can be rapidly converted to benzenoid-substituted indoles and tricyclic indolines. Extension to the use of substituted halobenzamides gives functionalized isoquinolinones in up to 86% yield.

Electrical conductance of conjugated oligomers at the single molecule level.

We determine and compare, at the single molecule level and under identical environmental conditions, the electrical conductance of four conjugated phenylene oligomers comprising terminal sulfur anchor groups with simple structural and conjugation variations. The comparison shows that the conductance of oligo(phenylene vinylene) (OPV) is slightly higher than that of oligo(phenylene ethynylene) (OPE). We find that solubilizing side groups do neither prevent the molecules from being anchored within a break junction nor noticeably influence the conductance value.

Spectrum analysis of motion parallax in a 3D cluttered scene and application to egomotion.

Previous methods for estimating observer motion in a rigid 3D scene assume that image velocities can be measured at isolated points. When the observer is moving through a cluttered 3D scene such as a forest, however, pointwise measurements of image velocity are more challenging to obtain because multiple depths, and hence multiple velocities, are present in most local image regions. We introduce a method for estimating egomotion that avoids pointwise image velocity estimation as a first step. In its place, the direction of motion parallax in local image regions is estimated, using a spectrum-based method, and these directions are then combined to directly estimate 3D observer motion. There are two advantages to this approach. First, the method can be applied to a wide range of 3D cluttered scenes, including those for which pointwise image velocities cannot be measured because only normal velocity information is available. Second, the egomotion estimates can be used as a posterior constraint on estimating pointwise image velocities, since known egomotion parameters constrain the candidate image velocities at each point to a one-dimensional rather than a two-dimensional space.

Probenecid interacts with the pharmacokinetics of morphine-6-glucuronide in humans.

BACKGROUND: Evidence obtained from porcine cell cultures and experiments in laboratory animals indicates that transmembrane transporters may play a role in the distribution of the active morphine metabolite morphine-6-glucuronide (M6G). This was evaluated in a study in healthy volunteers. METHODS: Ten subjects received an intravenous M6G infusion for 30 min at a dosage of 0.5 mg/kg body weight, leading to M6G plasma concentrations approximately two to three times higher than those observed with analgesic morphine doses in subjects with normal kidney function. In a randomized, double-blind, three-way crossover fashion, subjects received 800 mg quinidine for inhibition of P-glycoprotein; 500 mg probenecid for inhibition of other transporters, including organic anion transporter peptide, multidrug resistance-related protein, and organic anion transporter families; or placebo 1 h before the start of M6G administration. Plasma concentrations of M6G and pupil size were measured for 7 h. RESULTS: Probenecid pretreatment resulted in a decrease in the clearance of M6G from 8.3 +/- 1 l/h to 6.7 +/- 1.3 l/h (factor of 0.8; P < 0.05 vs. placebo cotreatment). This was paralleled by an increase by a factor of 1.2 of the area under the miotic effect-versus-time curves (P < 0.05 vs. placebo). In contrast, quinidine pretreatment had no influence on the pharmacokinetics of M6G. CONCLUSIONS: The active morphine metabolite is subject to transmembrane transport by transporters inhibited by probenecid in humans.

Substrate specificity and kinetic mechanism of the Sir2 family of NAD+-dependent histone/protein deacetylases.

The Silent information regulator 2 (Sir2) family of enzymes consists of NAD(+)-dependent histone/protein deacetylases that tightly couple the hydrolysis of NAD(+) and the deacetylation of an acetylated substrate to form nicotinamide, the deacetylated product, and the novel metabolite O-acetyl-ADP-ribose (OAADPR). In this paper, we analyzed the substrate specificity of the yeast Sir2 (ySir2), the yeast HST2, and the human SIRT2 homologues toward various monoacetylated histone H3 and H4 peptides, determined the basic kinetic mechanism, and resolved individual chemical steps of the Sir2 reaction. Using steady-state kinetic analysis, we have shown that ySir2, HST2, and SIRT2 exhibit varying catalytic efficiencies and display a preference among the monoacetylated peptide substrates. Bisubstrate kinetic analysis indicates that Sir2 enzymes follow a sequential mechanism, where both the acetylated substrate and NAD(+) must bind to form a ternary complex, prior to any catalytic step. Using rapid-kinetic analysis, we have shown that after ternary complex formation, nicotinamide cleavage occurs first, followed by the transfer of the acetyl group from the donor substrate to the ADP-ribose portion of NAD(+) to form OAADPr and the deacetylated product. Product and dead-end inhibition analyses revealed that nicotinamide is the first product released followed by random release of OAADPr and the deacetylated product.