Retinoid regulation of heparin-binding EGF-like growth factor gene expression in human keratinocytes and skin *

Retinoic acid (RA) has profound effects on epidermal homeostasis; however, the molecular mechanisms by which retinoids regulate keratinocyte cell proliferation and differentiation are not well understood. Here we report that mRNA expression of heparin-binding EGF-like growth factor (HB-EGF), a member of the EGF family of growth factors, is induced by RA in human keratinocytes and skin, and is overexpressed in the context of epidermal hyperplasia in vivo. Treatment of normal adult human keratinocytes with micromolar concentrations of RA significantly induced the expression of HB-EGF. The response was efficiently blocked by specific inhibitors of ErbB tyrosine kinase activity, MAP kinase kinase (MEK), or p38 stress-activated protein kinase. RA also enhanced the induction of HB-EGF mRNA in human skin organ culture, an ex vivo model system displaying many similarities to wound healing in vivo. HB- EGF transcripts were markedly increased in human skin by topical treat- ment with RA under conditions known to provoke epidermal hyperplasia. HB-EGF transcripts were also markedly overexpressed in the hyperplas- tic epidermis of psoriatic lesions, relative to normal skin. These results support the hypothesis that the effects of RA on epidermal hyperplasia are mediated at least in part by HB-EGF, and suggest that signal transduction mechanisms other than or in addition to nuclear RA receptors contribute to this effect.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72809/1/j.1600-0625.1998.tb00339.x.pd

Evaluation of early and late presentation of patients with ocular mucous membrane pemphigoid to two major tertiary referral hospitals in the United Kingdom

PURPOSE: Ocular mucous membrane pemphigoid (OcMMP) is a sight-threatening autoimmune disease in which referral to specialists units for further management is a common practise. This study aims to describe referral patterns, disease phenotype and management strategies in patients who present with either early or established disease to two large tertiary care hospitals in the United Kingdom.\ud \ud PATIENTS AND METHODS: In all, 54 consecutive patients with a documented history of OcMMP were followed for 24 months. Two groups were defined: (i) early-onset disease (EOD:<3 years, n=26, 51 eyes) and (ii) established disease (EstD:>5 years, n=24, 48 eyes). Data were captured at first clinic visit, and at 12 and 24 months follow-up. Information regarding duration, activity and stage of disease, visual acuity (VA), therapeutic strategies and clinical outcome were analysed.\ud \ud RESULTS: Patients with EOD were younger and had more severe conjunctival inflammation (76% of inflamed eyes) than the EstD group, who had poorer VA (26.7%=VA<3/60, P<0.01) and more advanced disease. Although 40% of patients were on existing immunosuppression, 48% required initiation or switch to more potent immunotherapy. In all, 28% (14) were referred back to the originating hospitals for continued care. Although inflammation had resolved in 78% (60/77) at 12 months, persistence of inflammation and progression did not differ between the two phenotypes. Importantly, 42% demonstrated disease progression in the absence of clinically detectable inflammation.\ud \ud CONCLUSIONS: These data highlight that irrespective of OcMMP phenotype, initiation or escalation of potent immunosuppression is required at tertiary hospitals. Moreover, the conjunctival scarring progresses even when the eye remains clinically quiescent. Early referral to tertiary centres is recommended to optimise immunosuppression and limit long-term ocular damage.\ud \u

Noise and dynamical pattern selection

In pattern forming systems such as Rayleigh-Benard convection or directional solidification, a large number of linearly stable, patterned steady states exist when the basic, simple steady state is unstable. Which of these steady states will be realized in a given experiment appears to depend on unobservable details of the system's initial conditions. We show, however, that weak, Gaussian white noise drives such a system toward a preferred wave number which depends only on the system parameters and is independent of initial conditions. We give a prescription for calculating this wave number, analytically near the onset of instability and numerically otherwise.Comment: 12 pages, REVTEX, no figures. Submitted to Phys. Rev. Let

Properties of pattern formation and selection processes in nonequilibrium systems with external fluctuations

We extend the phase field crystal method for nonequilibrium patterning to stochastic systems with external source where transient dynamics is essential. It was shown that at short time scales the system manifests pattern selection processes. These processes are studied by means of the structure function dynamics analysis. Nonequilibrium pattern-forming transitions are analyzed by means of numerical simulations.Comment: 15 poages, 8 figure

Phase-field modeling of microstructural pattern formation during directional solidification of peritectic alloys without morphological instability

During the directional solidification of peritectic alloys, two stable solid phases (parent and peritectic) grow competitively into a metastable liquid phase of larger impurity content than either solid phase. When the parent or both solid phases are morphologically unstable, i.e., for a small temperature gradient/growth rate ratio ($G/v_p$), one solid phase usually outgrows and covers the other phase, leading to a cellular-dendritic array structure closely analogous to the one formed during monophase solidification of a dilute binary alloy. In contrast, when $G/v_p$ is large enough for both phases to be morphologically stable, the formation of the microstructurebecomes controlled by a subtle interplay between the nucleation and growth of the two solid phases. The structures that have been observed in this regime (in small samples where convection effect are suppressed) include alternate layers (bands) of the parent and peritectic phases perpendicular to the growth direction, which are formed by alternate nucleation and lateral spreading of one phase onto the other as proposed in a recent model [R. Trivedi, Metall. Mater. Trans. A 26, 1 (1995)], as well as partially filled bands (islands), where the peritectic phase does not fully cover the parent phase which grows continuously. We develop a phase-field model of peritectic solidification that incorporates nucleation processes in order to explore the formation of these structures. Simulations of this model shed light on the morphology transition from islands to bands, the dynamics of spreading of the peritectic phase on the parent phase following nucleation, which turns out to be characterized by a remarkably constant acceleration, and the types of growth morphology that one might expect to observe in large samples under purely diffusive growth conditions.Comment: Final version, minor revisions, 16 pages, 14 EPS figures, RevTe

Interviewing suspects: examining the association between skills, questioning, evidence disclosure, and interview outcomes

The interviewing of suspects is an important element in the investigation of crime. However, studies concerning actual performance of investigators when undertaking such interviews remain sparse. Nevertheless, in England and Wales, since the introduction of a prescribed framework over 20 years ago, field studies have generally shown an improvement in interviewing performance, notwithstanding ongoing concerns largely relating to the more demanding aspects (such as building/maintaining rapport, intermittent summarising and the logical development of topics). Using a sample of 70 real-life interviews, the present study examined questioning and various evidence disclosure strategies (which have also been found demanding), examining their relationships between interview skills and interview outcomes. It was found that when evidence was disclosed gradually (but revealed later), interviews were generally both more skilled and involved the gaining of comprehensive accounts, whereas when evidence was disclosed either early or very late, interviews were found to be both less skilled and less likely to involve this outcome. These findings contribute towards an increased research base for the prescribed framework

Use of Local Image Information in Depth Edge Classification by Humans and Neural Networks

Humans can use local cues to distinguish image edges caused by a depth change from other types of edges (Vilankar et al., 2014). But which local cues? Here we use the SYNS database (Adams et al., 2016) to automatically label edges in images of natural scenes as depth or non-depth. We use this ground truth to identify the cues used by human observers and convolutional neural networks (CNNs) for edge classification. Eight observers viewed square image patches, each centered on an image edge, ranging in width from 0.6 to 2.4 degrees (8 to 32 pixels). Human judgments (depth/non-depth) were compared to responses of a CNN trained on the same task. Human performance improved with patch size (65%-74% correct) but remained well below CNN accuracy (82-86% correct). Agreement between humans and the CNN was above chance but lower than human-human agreement. Decision Variable Correlation (Sebastian & Geisler, in press) was used to evaluate the relationships between depth responses and local edge cues. Humans seem to rely primarily on contrast cues, specifically luminance contrast and red-green contrast across the edge. The CNN also relies on luminance contrast, but unlike humans it seems to make use of mean luminance and red-green intensity as well. These local luminance and color features provide valid cues for depth edge discrimination in natural scenes

Surface reconstruction of wear in carpets by using a wavelet edge detector

Carpet manufacturers have wear labels assigned to their products by human experts who evaluate carpet samples subjected to accelerated wear in a test device. There is considerable industrial and academic interest in going from human to automated evaluation, which should be less cumbersome and more objective. In this paper, we present image analysis research on videos of carpet surfaces scanned with a 3D laser. The purpose is obtaining good depth Images for an automated system that should have a high percentage of correct assessments for a wide variety of carpets. The innovation is the use of a wavelet edge detector to obtain a more continuously defined surface shape. The evaluation is based on how well the algorithms allow a good linear ranking and a good discriminance of consecutive wear labels. The results show an improved linear ranking for most carpet types, for two carpet types the results are quite significant

Ultra-short silicon-organic hybrid (SOH) modulator for bidirectional polarization-independent operation

We propose a bidirectional, polarization-independent, recirculating IQ-modulator scheme based on the silicon-organic hybrid (SOH) platform. We demonstrate the viability of the concept by using an SOH Mach-Zehnder modulator, operated at 10 GBd BPSK and 2ASK-2PSK