Activation of Both MAP Kinase and Phosphatidylinositide 3-Kinase by Ras Is Required for Hepatocyte Growth Factor/Scatter Factor–induced Adherens Junction Disassembly

Hepatocyte growth factor/scatter factor (HGF/SF) stimulates the motility of epithelial cells, initially inducing centrifugal spreading of colonies followed by disruption of cell–cell junctions and subsequent cell scattering. In Madin–Darby canine kidney cells, HGF/SF-induced motility involves actin reorganization mediated by Ras, but whether Ras and downstream signals regulate the breakdown of intercellular adhesions has not been established. Both HGF/SF and V12Ras induced the loss of the adherens junction proteins E-cadherin and β-catenin from intercellular junctions during cell spreading, and the HGF/SF response was blocked by dominant-negative N17Ras. Desmosomes and tight junctions were regulated separately from adherens junctions, because they were not disrupted by V12Ras. MAP kinase, phosphatidylinositide 3-kinase (PI 3-kinase), and Rac were required downstream of Ras, because loss of adherens junctions was blocked by the inhibitors PD098059 and LY294002 or by dominant-inhibitory mutants of MAP kinase kinase 1 or Rac1. All of these inhibitors also prevented HGF/SF-induced cell scattering. Interestingly, activated Raf or the activated p110α subunit of PI 3-kinase alone did not induce disruption of adherens junctions. These results indicate that activation of both MAP kinase and PI 3-kinase by Ras is required for adherens junction disassembly and that this is essential for the motile response to HGF/SF.

Neutralizing monoclonal antibodies to hepatocyte growth factor/scatter factor (HGF/SF) display antitumor activity in animal models

The hepatocyte growth factor (HGF/SF) receptor, Met, regulates mitogenesis, motility, and morphogenesis in a cell type-dependent fashion. Activation of Met via autocrine, paracrine, or mutational mechanisms can lead to tumorigenesis and metastasis and numerous studies have linked inappropriate expression of this ligand-receptor pair to most types of human solid tumors. To prepare mAbs to human HGF/SF, mice were immunized with native and denatured preparations of the ligand. Recloned mAbs were tested in vitro for blocking activity against scattering and branching morphogenesis. Our results show that no single mAb was capable of neutralizing the in vitro activity of HGF/SF, and that the ligand possesses a minimum of three epitopes that must be blocked to prevent Met tyrosine kinase activation. In vivo, the neutralizing mAb combination inhibited s.c. growth in athymic nu/nu mice of tumors dependent on an autocrine Met-HGF/SF loop. Importantly, growth of human glioblastoma multiforme xenografts expressing Met and HGF/SF were markedly reduced in the presence of HGF/SF-neutralizing mAbs. These results suggest interrupting autocrine and/or paracrine Met-HGF/SF signaling in tumors dependent on this pathway is a possible intervention strategy.

Scatter factor/hepatocyte growth factor as a regulator of skeletal muscle and neural crest development.

Factors that regulate cellular migration during embryonic development are essential for tissue and organ morphogenesis. Scatter factor/hepatocyte growth factor (SF/HGF) can stimulate motogenic and morphogenetic activities in cultured epithelial cells expressing the Met tyrosine kinase receptor and is essential for development; however, the precise physiological role of SF/HGF is incompletely understood. Here we provide functional evidence that inappropriate expression of SF/HGF in transgenic mice influences the development of two distinct migratory cell lineages, resulting in ectopic skeletal muscle formation and melanosis in the central nervous system, and patterned hyperpigmentation of the skin. Committed TRP-2 positive melanoblasts were found to be situated aberrantly within defined regions of the transgenic embryo, including the neural tube, which overproduced SF/RGF. Our data strongly suggest that SF/HGF possesses physiologically relevant scatter activity, and functions as a true morphogenetic factor by regulating migration and/or differentiation of select populations of premyogenic and neural crest cells during normal mammalian embryogenesis.

Tropospheric scatter propagation investigation; final report.

"Contract no. AF 19(604)-1835."

Operator's, organizational, direct support, and general support maintenance manual : tropospheric scatter tactical radio relay system.

"October 1975."

Optical scatter imaging using digital Fourier microscopy

An approach reported recently by Alexandrov et al (2005 Int. J Imag. Syst. Technol. 14 253-8) on optical scatter imaging, termed digital Fourier microscopy (DFM), represents an adaptation of digital Fourier holography to selective imaging of biological matter. The holographic mode of the recording of the sample optical scatter enables reconstruction of the sample image. The form-factor of the sample constituents provides a basis for discrimination of these constituents implemented via flexible digital Fourier filtering at the post-processing stage. As in dark-field microscopy, the DFM image contrast appears to improve due to the suppressed optical scatter from extended sample structures. In this paper, we present the theoretical and experimental study of DFM using a biological phantom that contains polymorphic scatterers.

Effects of yellow filters on visual acuity, contrast sensitivity and reading under conditions of forward light scatter

Background Yellow filters are sometimes recommended to people with low vision. Our aim was investigate the effects of three commercial yellow filters on visual acuity and contrast sensitivity (with and without glare) and reading (without glare) under conditions of forward light scatter (FLS). Method Fifty-five healthy subjects were assessed with Corning Photochromic Filters (CPFs) 450, 511 and 527 and a filter producing FLS. The effects on log MAR visual acuity, Pelli–Robson contrast sensitivity with and without glare, and reading (measured with MNRead charts) without glare were determined. Results Statistically significant differences were found between the overall effect of glare and between CPFs for visual acuity and contrast sensitivity. A gradual decline in visual acuity, contrast sensitivity and reading with increasing CPF absorption was noted. Conclusion Effects of CPF450, 511, 527 on visual acuity, contrast sensitivity and reading under conditions of FLS were negative but not clinically significant.

Inherited labour hoarding, insiders and employment growth:panel data results : Poland, 1996-2002

Using panel data pertaining to large Polish (non-financial) firms this paper examines the determinants of employment change during the period 1996-2002. Paying particular attention to the asymmetry hypothesis we investigate the impact of own wages, outside wages, output growth, regional characteristics and sectoral affiliation on the evolution of employment. In keeping with the 'right to manage' model we find that employment dynamics are not affected negatively by alternative wages. Furthermore, in contrast to the early transition period, we find evidence that employment levels respond to positive sales growth (in all but state firms). The early literature, (e.g. Kollo, 1998) found that labour hoarding lowered employment elasticities in the presence of positive demand shocks. Our findings suggest that inherited labour hoarding may no longer be a factor. We argue that the present pattern of employment adjustment is better explained by the role of insiders. This tentative conclusion is hinged on the contrasting behaviour of state and privatised companies and the similar behaviour of privatised and new private companies. We conclude that lower responsiveness of employment to both positive and negative changes in revenue in state firms is consistent with the proposition that rent sharing by insiders is stronger in the state sector.

The effect of simulated cataract light scatter on retinal vessel oximetry

To assess the impact of light scatter, similar to that introduced by cataract on retinal vessel blood oxygen saturation measurements using poly-bead solutions of varying concentrations. Eight healthy, young, non-smoking individuals were enrolled for this study. All subjects underwent digital blood pressure measurements, assessment of non-contact intraocular pressure, pupil dilation and retinal vessel oximetry using dual wavelength photography (Oximetry Module, Imedos Systems, Germany). To simulate light scatter, cells comprising a plastic collar and two plano lenses were filled with solutions of differing concentrations (0.001, 0.002 and 0.004%) of polystyrene microspheres (Polysciences Inc., USA). The adopted light scatter model showed an artifactual increase in venous optical density ratio (p=0.036), with the 0.004% condition producing significantly higher venous optical density ratio values when compared to images without a cell in place. Spectrophotometric analysis, and thus retinal vessel oximetry of the retinal vessels, is altered by artificial light scatter. © 2013 Elsevier Ltd.

Tissue Equivalent Phantom Design for Optimization of a Coherent Scatter Imaging System

Scatter in medical imaging is typically cast off as image-related noise that detracts from meaningful diagnosis. It is therefore typically rejected or removed from medical images. However, it has been found that every material, including cancerous tissue, has a unique X-ray coherent scatter signature that can be used to identify the material or tissue. Such scatter-based tissue-identification provides the advantage of locating and identifying particular materials over conventional anatomical imaging through X-ray radiography. A coded aperture X-ray coherent scatter spectral imaging system has been developed in our group to classify different tissue types based on their unique scatter signatures. Previous experiments using our prototype have demonstrated that the depth-resolved coherent scatter spectral imaging system (CACSSI) can discriminate healthy and cancerous tissue present in the path of a non-destructive x-ray beam. A key to the successful optimization of CACSSI as a clinical imaging method is to obtain anatomically accurate phantoms of the human body. This thesis describes the development and fabrication of 3D printed anatomical scatter phantoms of the breast and lung.

The purpose of this work is to accurately model different breast geometries using a tissue equivalent phantom, and to classify these tissues in a coherent x-ray scatter imaging system. Tissue-equivalent anatomical phantoms were designed to assess the capability of the CACSSI system to classify different types of breast tissue (adipose, fibroglandular, malignant). These phantoms were 3D printed based on DICOM data obtained from CT scans of prone breasts. The phantoms were tested through comparison of measured scatter signatures with those of adipose and fibroglandular tissue from literature. Tumors in the phantom were modeled using a variety of biological tissue including actual surgically excised benign and malignant tissue specimens. Lung based phantoms have also been printed for future testing. Our imaging system has been able to define the location and composition of the various materials in the phantom. These phantoms were used to characterize the CACSSI system in terms of beam width and imaging technique. The result of this work showed accurate modeling and characterization of the phantoms through comparison of the tissue-equivalent form factors to those from literature. The physical construction of the phantoms, based on actual patient anatomy, was validated using mammography and computed tomography to visually compare the clinical images to those of actual patient anatomy.

Validation of Coded Aperture Coherent Scatter Spectral Imaging for Differentiation of Normal and Neoplastic Breast Tissues via Surgical Pathology

This study intends to validate the sensitivity and specificity of coded aperture coherent scatter spectral imaging (CACSSI) by comparison to clinical histological preparation and pathologic analysis methods currently used for the differentiation of normal and neoplastic breast tissues. A composite overlay of the CACSSI rendered image and pathologist interpreted, stained sections validate the ability of coherent scatter imaging to differentiate cancerous tissues from normal, healthy breast structures ex-vivo. Via comparison to the pathologist annotated slides, the CACSSI system may be further optimized to maximized sensitivity and specificity for differentiation of breast carcinomas.

Navigating 3d Scatter Plots in Immersive Virtual Reality

Thesis (Master's)--University of Washington, 2016-01

Characterising creativity : a holistic methodology for the assessment of creative works

This paper reports on the early stages of a design experiment in educational assessment that challenges the dichotomous legacy evident in many assessment activities. Combining social networking technologies with the sociology of education the paper proposes that assessment activities are best understood as a negotiable field of exchange. In this design experiment students, peers and experts engage in explicit, "front-end" assessment (Wyatt-Smith, 2008) to translate holistic judgments into institutional, and potentiality economic capital without adhering to long lists of pre-set criteria. This approach invites participants to use social networking technologies to judge creative works using scatter graphs, keywords and tag clouds. In doing so assessors will refine their evaluative expertise and negotiate the characteristics of creative works from which criteria will emerge (Sadler, 2008). The real-time advantages of web-based technologies will aggregate, externalise and democratise this transparent method of assessment for most, if not all, creative works that can be represented in a digital format.