14 research outputs found

    Integrin-Blocking Antibodies Delay Keratinocyte Re-Epithelialization in a Human Three-Dimensional Wound Healing Model

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    The α6β4 integrin plays a significant role in tumor growth, angiogenesis and metastasis through modulation of growth factor signaling, and is a potentially important therapeutic target. However, α6β4-mediated cell-matrix adhesion is critical in normal keratinocyte attachment, signaling and anchorage to the basement membrane through its interaction with laminin-5, raising potential risks for targeted therapy. Bioengineered Human Skin Equivalent (HSE), which have been shown to mimic their normal and wounded counterparts, have been used here to investigate the consequences of targeting β4 to establish toxic effects on normal tissue homeostasis and epithelial wound repair. We tested two antibodies directed to different β4 epitopes, one adhesion-blocking (ASC-8) and one non-adhesion blocking (ASC-3), and determined that these antibodies were appropriately localized to the basal surface of keratinocytes at the basement membrane interface where β4 is expressed. While normal tissue architecture was not altered, ASC-8 induced a sub-basal split at the basement membrane in non-wounded tissue. In addition, wound closure was significantly inhibited by ASC-8, but not by ASC-3, as the epithelial tongue only covered 40 percent of the wound area at 120 hours post-wounding. These results demonstrate β4 adhesion-blocking antibodies may have adverse effects on normal tissue, whereas antibodies directed to other epitopes may provide safer alternatives for therapy. Taken together, we conclude that these three-dimensional tissue models provide a biologically relevant platform to identify toxic effects induced by candidate therapeutics, which will allow generation of findings that are more predictive of in vivo responses early in the drug development process

    Local Site Effects in the Town of Benevento (Italy) from Noise Measurements

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    The study of ground motion amplification produced by surface geology is extremely interesting in the Benevento area, Southern Italy, as it is characterized by high seismic hazard. The present moderate-to-low seismicity makes the noise method appropriate to estimate the seismic site response in the area. The three components of seismic noise have been recorded in five sites in the Benevento metropolitan area characterized by different surface geology, in order to estimate the seismic site response. In evaluating site amplification effects we used the direct interpretation of amplitude spectra and standard spectral ratio techniques, evaluating sediment-to-bedrock, sediment-to-average and H/V spectral ratios. The temporal evolution of the noise spectra is analysed within one day, in order to assess the stationarity of the noise signal. The noise wavefield properties have been studied through polarization analyses in selected bands of frequency, where spectral peaks are observed to dominate, to better understand the real nature of those peaks. Results give evidence of low amplification levels, missing any correlation between spectral amplitudes and sediment thickness over the basement. We interpret this result as due to the poor impedance contrast between sediments and basement, which is characterized by low values of shear waves velocity. Moreover, sharp amplitude peaks are observed in the raw spectra of the sediment-sites, in the 2–4 Hz frequency band; a numerical simulation interprets this effect as possibly associated with a wide-scale structure, invoking the presence of a sharper impedance contrast at greater depth. At high frequencies the action of ambient noise sources, mainly active on horizontal components of motion, is retained dominant to generate the prominent peaks observed in the H/V spectral ratios; in some cases the presence of a nearsurface low-velocity layer can contribute to amplify the seismic motion generated at these frequencies

    Confronto di differenti tecniche per la valutazione dell'amplificazione di sito nella cittĂ  di Benevento

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    In the textRegione Campania Provincia di Benevento Comune di Benevento C.C.I.A.A. Benevento ESRI Italia Delisa S.p.a., Trento Infotel S.r.l., TarantoPublishedBenevento, Italy4.1. Metodologie sismologiche per l'ingegneria sismicaope

    Local Site Effects in the Town of Benevento (Italy) from Noise Measurements

    No full text
    The study of ground motion amplification produced by surface geology is extremely interesting in the Benevento area, Southern Italy, as it is characterized by high seismic hazard. The present moderate-to-low seismicity makes the noise method appropriate to estimate the seismic site response in the area. The three components of seismic noise have been recorded in five sites in the Benevento metropolitan area characterized by different surface geology, in order to estimate the seismic site response. In evaluating site amplification effects we used the direct interpretation of amplitude spectra and standard spectral ratio techniques, evaluating sediment-to-bedrock, sediment-to-average and H/V spectral ratios. The temporal evolution of the noise spectra is analysed within one day, in order to assess the stationarity of the noise signal. The noise wavefield properties have been studied through polarization analyses in selected bands of frequency, where spectral peaks are observed to dominate, to better understand the real nature of those peaks. Results give evidence of low amplification levels, missing any correlation between spectral amplitudes and sediment thickness over the basement. We interpret this result as due to the poor impedance contrast between sediments and basement, which is characterized by low values of shear waves velocity. Moreover, sharp amplitude peaks are observed in the raw spectra of the sediment-sites, in the 2–4 Hz frequency band; a numerical simulation interprets this effect as possibly associated with a wide-scale structure, invoking the presence of a sharper impedance contrast at greater depth. At high frequencies the action of ambient noise sources, mainly active on horizontal components of motion, is retained dominant to generate the prominent peaks observed in the H/V spectral ratios; in some cases the presence of a nearsurface low-velocity layer can contribute to amplify the seismic motion generated at these frequencies.Published1745-17644.1. Metodologie sismologiche per l'ingegneria sismicaJCR Journalreserve
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