Biomedical subjects

M A Webster

Publications and source records attributed to M A Webster.

At least 19 recordsLinked to original sources

PubMed2005

Modeling a tethered polymer in Poiseuille flow.

We investigate the behavior of a tethered polymer in Poiseuille flow using a multiscale algorithm. The polymer, treated using molecular dynamics, is coupled to a solvent modeled by the stochastic rotation algorithm, a particle-based Navier-Stokes integrator. The expected series of morphological transitions of the polymer: sphere to distorted sphere to trumpet to stem and flower to rod are recovered, and we discuss how the polymer extension depends on the flow velocity. Backflow effects cause an effective increase in viscosity, which appears to be primarily due to the fluctuations of the free end of the polymer.

Algorithms↗

PubMed2004

Spectral and temporal speckle field measurements of a random medium.

The zero-mean circular complex Gaussian field statistics of a random medium are experimentally demonstrated in the optical domain, thus verifying this key assumption of statistical optics. Using a frequency-tunable laser source in a fixed-path-length interferometer, we obtain optical field fluctuations in the time and frequency domains that clearly show that the ensemble-averaged temporal intensity converges to the photon transit time distribution, which for the samples used is in excellent agreement with a diffusion model.

Journal Article↗

PubMed2002

Temporal response of a random medium from third-order laser speckle frequency correlations.

We demonstrate for the first time that the temporal response of a random medium can be obtained from optical intensity fluctuations. Our method uses third-order intensity correlations of measured speckle patterns from a multiple scattering random medium as a function of optical frequency. In particular, our experimental results for the temporal response extracted from third-order intensity correlations are in good agreement with the predictions of a diffusion model. Our results are valid for waves in random media where the scattered field is described by circular complex Gaussian statistics.

Journal Article↗

PubMed2000

Interactions between chromatic adaptation and contrast adaptation in color appearance.

Color appearance depends on adaptation processes that adjust sensitivity both to the average color in the stimulus (through light or chromatic adaptation) and to the variations in color (through contrast adaptation). We explored how these different forms of adaptation interact, by examining how the state of chromatic adaptation depends on the time-varying color contrasts in the stimulus, and conversely, how adaptation to the mean determines the stimulus contrasts underlying contrast adaptation. Light adaptation levels remain very similar whether observers adapt to a static chromaticity or to large temporal modulations in cone excitation that vary at rates of 0.5 Hz or higher. This suggests that up to the sites of light adaptation, the response to moderate contrasts is effectively linear and that the adaptation effectively averages over several seconds of the stimulus. For slower flicker rates color is differentially biased by the last half-cycle of the flicker, and perceived contrast may be altered by response polarization. This polarization selectively saturates responses to moderate (but not low) contrasts along the color direction complementary to the mean color bias, implying that the response changes occur within multiple mechanisms tuned to different chromatic axes. Chromatic adaptation often adjusts only partially to the mean color of the stimulus, and thus leaves a residual bias in the color appearance of the field. Contrast adaptation reduces perceived contrast relative to this residual color, and not relative to the stimulus that appears achromatic. Similarly, contrast discrimination thresholds appear lower around the residual color than around the achromatic point. Thus under biased states of chromatic adaptation alternative measures of 'zero contrast' can be dissociated, suggesting that they do not depend on a common null point within the channels encoding chromatic contrast.

Adaptation, Ocular↗

PubMed2000

Variations in normal color vision. I. Cone-opponent axes.

Early postreceptoral color vision is thought to be organized in terms of two principal axes corresponding to opposing L- and M-cone signals (LvsM) or to S-cone signals opposed by a combination of L- and M-cone signals (SvsLM). These cone-opponent axes are now widely used in studies of color vision, but in most cases the corresponding stimulus variations are defined only theoretically, based on a standard observer. We examined the range and implications of interobserver variations in the cone-opponent axes. We used chromatic adaptation to empirically define the LvsM and SvsLM axes and used both thresholds and color contrast adaptation to determine sensitivity to the axes. We also examined the axis variations implied by individual differences in the color matching data of Stiles and Burch [Opt. Acta 6, 1 (1959)]. The axes estimated for individuals can differ measurably from the nominal standard-observer axes and can influence the interpretation of postreceptoral color organization (e.g., regarding interactions between the two axes). Thus, like luminance sensitivity, individual differences in chromatic sensitivity may be important to consider in studies of the cone-opponent axes.

Color Perception↗

PubMed2000

Variations in normal color vision. II. Unique hues.

We examined individual differences in the color appearance of nonspectral lights and asked how they might be related to individual differences in sensitivity to chromatic stimuli. Observers set unique hues for moderately saturated equiluminant stimuli by varying their hue angle within a plane defined by the LvsM and SvsLM cone-opponent axes that are thought to characterize early postreceptoral color coding. Unique red settings were close to the +L pole of the LvsM axis, while green, blue, and yellow settings clustered along directions intermediate to the LvsM and SvsLM axes and thus corresponded to particular ratios of LvsM to SvsLM activity. Interobserver differences in the unique hues were substantial. However, no relationship was found between hue settings and relative sensitivity to the LvsM and SvsLM axes. Moreover, interobserver variations in different unique hues were uncorrelated and were thus inconsistent with a common underlying factor such as relative sensitivity or changes in the spectral sensitivities of the cones. Thus for the moderately saturated lights we tested, the unique hues appear largely unconstrained by normal individual differences in the cone-opponent axes. In turn, this suggests that the perceived hue for these stimuli does not depend on fixed (common) physiological weightings of the cone-opponent axes or on fixed (common) color signals in the environment.

Color↗

PubMed2000

Color-luminance relationships and the McCollough effect.

The McCollough effect is an orientation-specific color aftereffect induced by adapting to colored gratings. We examined how the McCollough effect depends on the relationships between color and luminance within the inducing and test gratings and compared the aftereffects to the color changes predicted from selective adaptation to different color-luminance combinations. Our results suggest that the important contingency underlying the McCollough effect is between orientation and color-luminance direction and are consistent with sensitivity changes within mechanisms tuned to specific color-luminance directions. Aftereffects are similar in magnitude for adapting color pairs that differ only in S cone excitation or L and M cone excitation, and they have a similar dependence on spatial frequency. In particular, orientation-specific aftereffects are induced for S cone colors even when the grating frequencies are above the S cone resolution limit. Thus, the McCollough effect persists even when different cone classes encode the orientation and color of the gratings.

Color Perception↗

PubMed1999

Figural aftereffects in the perception of faces.

We examined figural aftereffects in images of human faces, for which changes in configuration are highly discriminable. Observers either matched or rated faces before or after viewing distorted images of faces. Prior adaptation strongly biases face perception by causing the original face to appear distorted in a direction opposite to the adapting distortion. Aftereffects transferred across different faces and were similar for upright or inverted faces, but were weaker when the adapting and test faces had different orientations (e.g., adapt inverted and test upright). Thus the aftereffects depend on which images are distorted, and not simply on the type of distortion introduced. We further show that the aftereffects are asymmetric, for adapting to the original face has little effect on the perception of a distorted face. This asymmetry suggests that adaptation may play an important normalizing role in face perception. Our results suggest that in normal viewing, figural aftereffects may strongly influence form perception and could provide a novel method for probing properties of human face perception.

Discrimination Learning↗

PubMed1998

The induction of uterine leiomyomas and mammary tumors in transgenic mice expressing polyomavirus (PyV) large T (LT) antigen is associated with the ability of PyV LT antigen to form specific complexes with retinoblastoma and CUTL1 family members.

The inactivation of certain tumor suppressor genes is thought to play an important role in the genesis of a number of tumor types. For example, inactivation of the Retinoblastoma (Rb) tumor suppressor is frequently observed in a proportion of sporadic human breast cancers. While these studies suggest that inactivation of key tumor suppressor genes may play an important role in the induction of mammary cancers, direct evidence supporting this contention is lacking. Because polyomavirus (PyV) Large T (LT) antigen is known to associate with and inactivate certain members of the Rb family (p105Rb, p107, p130), we have derived transgenic mice which express PyV LT antigen in the mammary epithelium. As expected mammary epithelial-specific expression of PyV LT antigen resulted in the induction of mammary tumors which correlated with their capacity to associate with Rb family members. In addition to mammary carcinomas, female transgenic mice expressing the PyV LT transgene frequently develop uterine leiomyomas. Because loss of heterozygosity involving the human CUTL1 (Cut like 1) gene located at chromosomal position 7q22 has been recently implicated in sporadic human uterine leiomyomas, we tested the hypothesis that PyV LT antigen may also form specific complexes with CUTL1. The results of these analyses revealed that specific complexes of CUTL1 and PyV LT antigen could be detected in both leiomyomas and mammary tumors. Taken together, these observations suggest that PyV LT antigen may be involved in inducing these tumors by sequestering both CUTL1 and Rb growth regulatory proteins.

Animals↗

PubMed1998

Bleeding pattern and endometrial changes during continuous combined hormone replacement therapy. The Ogen/Provera Study Group.

OBJECTIVE: To establish the optimum oral daily dose of micronized medroxyprogesterone acetate, given in combination with a fixed oral dose of estrone (E1) sulfate as hormone replacement therapy, that provides endometrial protection and induces cessation of vaginal bleeding. METHODS: This multicenter, randomized, double-blind study was conducted for 2 years. Five hundred sixty-eight postmenopausal women were randomized to take E1 sulfate 1.25 mg daily and one of three doses of medroxyprogesterone acetate (2.5, 5, or 10 mg) daily. Any vaginal bleeding was recorded by patients in a daily diary, and endometrial biopsies were performed at entry into the study and at 3, 12, and 24 months. RESULTS: Forty-two percent of all women reported some bleeding at month 3 of therapy. However, by month 6, 76.5, 80.1, and 80.9% of women were amenorrheic in the 2.5-, 5-, and 10-mg medroxyprogesterone acetate groups, respectively. Over time, the percentage of women with no bleeding increased in each group, and by 24 months 91.5, 89.9, and 94.3% were amenorrheic in the 2.5- and 10-mg medroxyprogesterone acetate groups, respectively. Approximately 10% of women continue to have some bleeding, regardless of the dose of medroxyprogesterone acetate. There were no statistically significant differences in the number of women with bleeding at any time point between the three groups. There were no cases of endometrial hyperplasia reported in the study population over the 2 years. CONCLUSION: All three studied doses of medroxyprogesterone acetate, given in combination with 1.25 mg of E1 sulfate, provide adequate endometrial protection and render approximately 80% of women amenorrheic by 6 months of therapy.

Adult↗

PubMed1998

Requirement for both Shc and phosphatidylinositol 3' kinase signaling pathways in polyomavirus middle T-mediated mammary tumorigenesis.

Transgenic mice expressing the polyomavirus (PyV) middle T antigen (MT) develop multifocal mammary tumors which frequently metastasize to the lung. The potent transforming activity of PyV MT is correlated with its capacity to activate and associate with a number of signaling molecules, including the Src family tyrosine kinases, the 85-kDa Src homology 2 subunit of the phosphatidylinositol 3' (PI-3') kinase, and the Shc adapter protein. To uncover the role of these signaling proteins in MT-mediated mammary tumorigenesis, we have generated transgenic mice that express mutant PyV MT antigens decoupled from either the Shc or the PI-3' kinase signaling pathway. In contrast to the rapid induction of metastatic mammary tumors observed in the strains expressing wild-type PyV MT, mammary epithelial cell-specific expression of either mutant PyV MT resulted in the induction of extensive mammary epithelial hyperplasias. The mammary epithelial hyperplasias expressing the mutant PyV MT defective in recruiting the PI-3' kinase were highly apoptotic, suggesting that recruitment of PI-3' kinase by MT affects cell survival. Whereas the initial phenotypes observed in both strains were global mammary epithelial hyperplasias, focal mammary tumors eventually arose in all female transgenic mice. Genetic and biochemical analyses of tumorigenesis in the transgenic strains expressing the PyV MT mutant lacking the Shc binding site revealed that a proportion of the metastatic tumors arising in these mice displayed evidence of reversion of the mutant Shc binding site. In contrast, no evidence of reversion of the PI-3' kinase binding site was noted in tumors derived from the strains expressing the PI-3' kinase binding site MT mutant. Tumor progression in both mutant strains was further correlated with upregulation of the epidermal growth factor receptor family members which are known to couple to the PI-3' kinase and Shc signaling pathways. Taken together, these observations suggest that PyV MT-mediated tumorigenesis requires activation of both Shc and PI-3' kinase, which appear to be required for stimulation of cell proliferation and survival signaling pathways, respectively.

Adaptor Proteins, Signal Transducing↗

PubMed1998

Menopausal symptom control and side-effects on continuous estrone sulfate and three doses of medroxyprogesterone acetate. Ogen/Provera Study Group.

OBJECTIVES: To establish the optimum oral daily dose of micronized medroxyprogesterone acetate (MPA), given in combination with 1.25 mg of estrone sulfate for menopausal symptom control. METHODS: This multicenter, randomized, double-blind study was conducted on 568 postmenopausal women who were randomized to take estrone sulfate 1.25 mg daily with 2.5, 5.0 or 10 mg of MPA daily for 2 years. The number of vasomotor symptoms and the severity of mood swings, lethargy, vaginal dryness and loss of libido as well as side-effects were recorded in a diary. Blood pressure and weight were recorded at each 3-month visit. RESULTS: Vasomotor symptoms were reported by approximately 80% of subjects at month 1, 23% at month 3 but only 9% by month 24. Mood swings, lethargy and vaginal dryness improved rapidly in the initial 3 months of therapy. Decrease in libido had a slower response to therapy in all three treatment groups. Breast tenderness was the commonest side-effect with 22% of subjects complaining of this in the first 3 months of therapy, dropping to 13% by 6 months. Headache, depression, nausea, bloating and irritability showed a similar pattern of decline. There was no significant difference in the rate of decrease in menopausal symptoms or reported side-effects between the three treatment groups. There was a small but significant (p < 0.001) decrease in systolic and diastolic blood pressure over the study period. CONCLUSIONS: All three treatment regimens provide adequate symptom control. Side-effects decreased markedly after the first 3 months, with no significant difference between the treatment groups.

Adult↗

PubMed1997

Motion minima for different directions in color space.

We have used the minimum-motion stimulus of Cavanagh, MacLeod & Anstis [(1987) Journal of the Optical Society of America A, 4, 1428-1438] to examine how signals along different directions in color space interact in motion perception. Stimuli were pairs of counterphasing gratings combined 90 deg out of phase in both space and time and modulated along different color-luminance axes. The axis for one of the gratings was fixed, while the axis for the second was varied so as to null perceived motion in the stimulus. The motion nulls show that observers are sensitive to motion signals carried by each of the cardinal directions of color space [an achromatic axis and L-M and S-(L+M) chromatic axes], but that signals along different cardinal axes are not combined to yield a net direction of motion. Pairing an achromatic and chromatic grating resulted in a motion null regardless of the relative or overall contrast of the two gratings, while the null directions for intermediate axes shifted depending on contrast. This result points to the special status of the luminance and chromatic axes. However, our results do not reveal a special pair of axes within the equiluminant plane. When contrasts along the cardinal axes are scaled for equal multiples of their respective detection thresholds, the L-M and S chromatic contrasts contribute roughly equally to the perceived motion, but are many times weaker than luminance contrast. Moreover, sensitivity to luminance motion is little affected by the presence of chromatic contrast, whereas sensitivity to chromatic motion is strongly masked by either luminance or chromatic contrast. These asymmetric interactions suggest that the motion of the luminance and chromatic components is encoded in qualitatively different ways.

Color Perception↗

PubMed1997

Adaptation and the color statistics of natural images.

Color perception depends profoundly on adaptation processes that adjust sensitivity in response to the prevailing pattern of stimulation. We examined how color sensitivity and appearance might be influenced by adaptation to the color distributions characteristic of natural images. Color distributions were measured for natural scenes by sampling an array of locations within each scene with a spectroradiometer, or by recording each scene with a digital camera successively through 31 interference filters. The images were used to reconstruct the L, M and S cone excitation at each spatial location, and the contrasts along three post-receptoral axes [L + M, L - M or S - (L + M)]. Individual scenes varied substantially in their mean chromaticity and luminance, in the principal color-luminance axes of their distributions, and in the range of contrasts in their distributions. Chromatic contrasts were biased along a relatively narrow range of bluish to yellowish-green angles, lying roughly between the S - (L + M) axis (which was more characteristic of scenes with lush vegetation and little sky) and a unique blue-yellow axis (which was more typical of arid scenes). For many scenes L - M and S - (L + M) signals were highly correlated, with weaker correlations between luminance and chromaticity. We use a two-stage model (von Kries scaling followed by decorrelation) to show how the appearance of colors may be altered by light adaptation to the mean of the distributions and by contrast adaptation to the contrast range and principal axes of the distributions; and we show that such adjustments are qualitatively consistent with empirical measurements of asymmetric color matches obtained after adaptation to successive random samples drawn from natural distributions of chromaticities and lightnesses. Such adaptation effects define the natural range of operating states of the visual system.

Adaptation, Ocular↗

PubMed1997

Contrast adaptation and the spatial structure of natural images.

Natural images have a characteristic spatial structure, with amplitude spectra that decrease with frequency roughly as 1/f. We have examined how contrast (pattern-selective) adaptation to this structure influences the spatial sensitivity of the visual system. Contrast thresholds and suprathreshold contrast and frequency matches were measured after adaptation to random samples from an ensemble of images of outdoor scenes or of synthetic images formed by filtering the amplitude spectra of noise over a range of spectral slopes. Adaptation selectively reduced sensitivity at low-to-medium frequencies, biasing contrast sensitivity toward higher frequencies. The pattern of aftereffects was similar for different natural image ensembles but varied with large changes in the slope of the noise spectra. Our results suggest that adaptation to the spatial structure in natural scenes may exert strong and selective influences on perception that are important in characterizing the normal operating states of the visual system.

Adaptation, Physiological↗

PubMed1996

Synergistic interaction of the Neu proto-oncogene product and transforming growth factor alpha in the mammary epithelium of transgenic mice.

Transgenic mice expressing either the neu proto-oncogene or transforming growth factor (TGF-alpha) in the mammary epithelium develop spontaneous focal mammary tumors that occur after a long latency. Since the epidermal growth factor receptor (EGFR) and Neu are capable of forming heterodimers that are responsive to EGFR ligands such as TGF-alpha, we examined whether coexpression of TGF-alpha and Neu in mammary epithelium could cooperate to accelerate the onset of mammary tumors. To test this hypothesis, we interbred separate transgenic strains harboring either a mouse mammary tumor virus/TGF-alpha or a mouse mammary tumor virus/neu transgene to generate bitransgenic mice that coexpress TGF-alpha and neu in the mammary epithelium. Female mice coexpressing TGF-alpha and neu developed multifocal mammary tumors which arose after a significantly shorter latency period than either parental strain alone. The development of these mammary tumors was correlated with the tyrosine phosphorylation of Neu and the recruitment of c-Src to the Neu complex. Immunoprecipitation and immunoblot analyses with EGFR- and Neu-specific antisera, however, failed to detect physical complexes of these two receptors. Taken together, these observations suggest that Neu and TGF-alpha cooperate in mammary tumorigenesis through a mechanism involving Neu and EGFR transactivation.

Aging↗

PubMed1995

Induction of mammary epithelial hyperplasias and mammary tumors in transgenic mice expressing a murine mammary tumor virus/activated c-src fusion gene.

Activation of the c-Src tyrosine kinase has been implicated as an important step in the induction of mammary tumors in both mice and humans. To directly assess the effect of mammary gland-specific expression of activated c-Src, we established transgenic mice that carry a constitutively activated form of c-src under transcriptional control of the murine mammary tumor virus long terminal repeat. Female mice derived from several independent transgenic lines lactate poorly as a consequence of an impairment in normal mammary epithelial development. In addition to this lactation defect, female mice frequently develop mammary epithelial hyperplasias, which occasionally progress to frank neoplasias. Taken together, these observations suggest that expression of activated c-Src in the mammary epithelium of transgenic mice is not sufficient for induction of mammary tumors.

Aging↗

PubMed1995

Colour constancy influenced by contrast adaptation.

Visual sensitivity is controlled by at least two distinct types of adaptation: light adaptation adjusts sensitivity to the mean luminance and colour in the stimulus, and contrast adaptation adjusts sensitivity to the variations in luminance and colour. Light adaptation is thought to be important in maintaining the perceived colour of objects despite changes in illumination ('colour constancy'), compensating for the mean changes in the light reflected from scenes under different illuminants. But for naturalistic colour signals, we show here that changes in an illuminant can also alter colour contrasts in images (how colours are distributed around the mean) enough to alter the state of contrast adaptation. Thus perceived colour under different illuminants may also be noticeably influenced by contrast adaptation.

Adaptation, Ocular↗