signaling pathways in elastic tissues

Abstract For many years elastin was considered as the matrix component structurally required to provide tissue elasticity. However, the expanded knowledge on the regulation of connective tissue homeostasis has revealed that elastic fibers also represent a source of elastokines and are the target of a number of signaling pathways mainly involving the TGF-β/BMP axis. A better understanding of these complex regulatory networks may pave the way for targeted therapeutic strategies in a number of genetic as well as acquired diseases and for the development of new functionalized biomaterials

Image Thresholding Technique Based On Fuzzy Partition And Entropy Maximization

Thresholding is a commonly used technique in image segmentation because of its fast and easy application. For this reason threshold selection is an important issue. There are two general approaches to threshold selection. One approach is based on the histogram of the image while the other is based on the gray scale information located in the local small areas. The histogram of an image contains some statistical data of the grayscale or color ingredients. In this thesis, an adaptive logical thresholding method is proposed for the binarization of blueprint images first. The new method exploits the geometric features of blueprint images. This is implemented by utilizing a robust windows operation, which is based on the assumption that the objects have "e;C"e; shape in a small area. We make use of multiple window sizes in the windows operation. This not only reduces computation time but also separates effectively thin lines from wide lines. Our method can automatically determine the threshold of images. Experiments show that our method is effective for blueprint images and achieves good results over a wide range of images. Second, the fuzzy set theory, along with probability partition and maximum entropy theory, is explored to compute the threshold based on the histogram of the image. Fuzzy set theory has been widely used in many fields where the ambiguous phenomena exist since it was proposed by Zadeh in 1965. And many thresholding methods have also been developed by using this theory. The concept we are using here is called fuzzy partition. Fuzzy partition means that a histogram is parted into several groups by some fuzzy sets which represent the fuzzy membership of each group because our method is based on histogram of the image . Probability partition is associated with fuzzy partition. The probability distribution of each group is derived from the fuzzy partition. Entropy which originates from thermodynamic theory is introduced into communications theory as a commonly used criteria to measure the information transmitted through a channel. It is adopted by image processing as a measurement of the information contained in the processed images. Thus it is applied in our method as a criterion for selecting the optimal fuzzy sets which partition the histogram. To find the threshold, the histogram of the image is partitioned by fuzzy sets which satisfy a certain entropy restriction. The search for the best possible fuzzy sets becomes an important issue. There is no efficient method for the searching procedure. Therefore, expansion to multiple level thresholding with fuzzy partition becomes extremely time consuming or even impossible. In this thesis, the relationship between a probability partition (PP) and a fuzzy C-partition (FP) is studied. This relationship and the entropy approach are used to derive a thresholding technique to select the optimal fuzzy C-partition. The measure of the selection quality is the entropy function defined by the PP and FP. A necessary condition of the entropy function arriving at a maximum is derived. Based on this condition, an efficient search procedure for two-level thresholding is derived, which makes the search so efficient that extension to multilevel thresholding becomes possible. A novel fuzzy membership function is proposed in three-level thresholding which produces a better result because a new relationship among the fuzzy membership functions is presented. This new relationship gives more flexibility in the search for the optimal fuzzy sets, although it also increases the complication in the search for the fuzzy sets in multi-level thresholding. This complication is solved by a new method called the "e;Onion-Peeling"e; method. Because the relationship between the fuzzy membership functions is so complicated it is impossible to obtain the membership functions all at once. The search procedure is decomposed into several layers of three-level partitions except for the last layer which may be a two-level one. So the big problem is simplified to three-level partitions such that we can obtain the two outmost membership functions without worrying too much about the complicated intersections among the membership functions. The method is further revised for images with a dominant area of background or an object which affects the appearance of the histogram of the image. The histogram is the basis of our method as well as of many other methods. A "e;bad"e; shape of the histogram will result in a bad thresholded image. A quadtree scheme is adopted to decompose the image into homogeneous areas and heterogeneous areas. And a multi-resolution thresholding method based on quadtree and fuzzy partition is then devised to deal with these images. Extension of fuzzy partition methods to color images is also examined. An adaptive thresholding method for color images based on fuzzy partition is proposed which can determine the number of thresholding levels automatically. This thesis concludes that the "e;C"e; shape assumption and varying sizes of windows for windows operation contribute to a better segmentation of the blueprint images. The efficient search procedure for the optimal fuzzy sets in the fuzzy-2 partition of the histogram of the image accelerates the process so much that it enables the extension of it to multilevel thresholding. In three-level fuzzy partition the new relationship presentation among the three fuzzy membership functions makes more sense than the conventional assumption and, as a result, performs better. A novel method, the "e;Onion-Peeling"e; method, is devised for dealing with the complexity at the intersection among the multiple membership functions in the multilevel fuzzy partition. It decomposes the multilevel partition into the fuzzy-3 partitions and the fuzzy-2 partitions by transposing the partition space in the histogram. Thus it is efficient in multilevel thresholding. A multi-resolution method which applies the quadtree scheme to distinguish the heterogeneous areas from the homogeneous areas is designed for the images with large homogeneous areas which usually distorts the histogram of the image. The new histogram based on only the heterogeneous area is adopted for partition and outperforms the old one. While validity checks filter out the fragmented points which are only a small portion of the whole image. Thus it gives good thresholded images for human face images

Matrisomal components involved in regenerative wound healing in axolotl and acomys: implications for biomaterial development

Achieving regeneration in humans has been a long-standing goal of many researchers. Whereas amphibians like the axolotl (Ambystoma mexicanum) are capable of regenerating whole organs and even limbs, most mammals heal their wounds via fibrotic scarring. Recently, the African spiny mouse (Acomys sp.) has been shown to be injury resistant and capable of regenerating several tissue types. A major focal point of research with Acomys has been the identification of drivers of regeneration. In this search, the matrisome components related to the extracellular matrix (ECM) are often overlooked. In this review, we compare Acomys and axolotl skin wound healing and blastema-mediated regeneration by examining their wound healing responses and comparing the expression pattern of matrisome genes, including glycosaminoglycan (GAG) related genes. The goal of this review is to identify matrisome genes that are upregulated during regeneration and could be potential candidates for inclusion in pro-regenerative biomaterials. Research papers describing transcriptomic or proteomic coverage of either skin regeneration or blastema formation in Acomys and axolotl were selected. Matrisome and GAG related genes were extracted from each dataset and the resulting lists of genes were compared. In our analysis, we found several genes that were consistently upregulated, suggesting possible involvement in regenerative processes. Most of the components have been implicated in regulation of cell behavior, extracellular matrix remodeling and wound healing. Incorporation of such pro-regenerative factors into biomaterials may help to shift pro-fibrotic processes to regenerative responses in treated wounds.European Union’s Horizon 2020 ;Grant Agreement No. 955722info:eu-repo/semantics/publishedVersio

Spectral analysis and resolving spatial ambiguities in human sound localization

This dissertation provides an overview of my research over the last five years into the spectral analysis involved in human sound localization. The work involved conducting psychophysical tests of human auditory localization performance and then applying analytical techniques to analyze and explain the data. It is a fundamental thesis of this work that human auditory localization response directions are primarily driven by the auditory localization cues associated with the acoustic filtering properties of the external auditory periphery, i.e., the head, torso, shoulder, neck, and external ears. This work can be considered as composed of three parts. In the first part of this work, I compared the auditory localization performance of a human subject and a time-delay neural network model under three sound conditions: broadband, high-pass, and low-pass. A “black-box” modeling paradigm was applied. The modeling results indicated that training the network to localize sounds of varying center-frequency and bandwidth could degrade localization performance results in a manner demonstrating some similarity to human auditory localization performance. As the data collected during the network modeling showed that humans demonstrate striking localization errors when tested using bandlimited sound stimuli, the second part of this work focused on human sound localization of bandpass filtered noise stimuli. Localization data was collected from 5 subjects and for 7 sound conditions: 300 Hz to 5 kHz, 300 Hz to 7 kHz, 300 Hz to 10 kHz, 300 Hz to 14 kHz, 3 to 8 kHz, 4 to 9 kHz, and 7 to 14 kHz. The localization results were analyzed using the method of cue similarity indices developed by Middlebrooks (1992). The data indicated that the energy level in relatively wide frequency bands could be driving the localization response directions, just as in Butler’s covert peak area model (see Butler and Musicant, 1993). The question was then raised as to whether the energy levels in the various frequency bands, as described above, are most likely analyzed by the human auditory localization system on a monaural or an interaural basis. In the third part of this work, an experiment was conducted using virtual auditory space sound stimuli in which the monaural spectral cues for auditory localization were disrupted, but the interaural spectral difference cue was preserved. The results from this work showed that the human auditory localization system relies primarily on a monaural analysis of spectral shape information for its discrimination of directions on the cone of confusion. The work described in the three parts lead to the suggestion that a spectral contrast model based on overlapping frequency bands of varying bandwidth and perhaps multiple frequency scales can provide a reasonable algorithm for explaining much of the current psychophysical and neurophysiological data related to human auditory localization

Copper-Heparin Inhalation Therapy To Repair Emphysema:A Scientific Rationale

Current pharmacotherapy of chronic obstructive pulmonary disease (COPD) aims at reducing respiratory symptoms and exacerbation frequency. Effective therapies to reduce disease progression, however, are still lacking. Furthermore, COPD medications showed less favorable effects in emphysema than in other COPD phenotypes. Elastin fibers are reduced and disrupted, whereas collagen levels are increased in emphysematous lungs. Protease/antiprotease imbalance has historically been regarded as the sole cause of emphysema. However, it is nowadays appreciated that emphysema may also be provoked by perturbations in the sequential repair steps following elastolysis. Essentiality of fibulin-5 and lysyl oxidase-like 1 in the elastin restoration process is discussed, and it is argued that copper deficiency is a plausible reason for failing elastin repair in emphysema patients. Since copper-dependent lysyl oxidases crosslink elastin as well as collagen fibers, copper supplementation stimulates accumulation of both proteins in the extracellular matrix. Restoration of abnormal elastin fibers in emphysematous lungs is favorable, whereas stimulating pulmonary fibrosis formation by further increasing collagen concentrations and organization is detrimental. Heparin inhibits collagen crosslinking while stimulating elastin repair and might therefore be the ideal companion of copper for emphysema patients. Efficacy and safety considerations may lead to a preference of pulmonary administration of copper-heparin over systemic administration

Abnormalities in reparative function of lung-derived mesenchymal stromal cells in emphysema

Mesenchymal stromal cells (MSCs) may provide crucial support in the regeneration of destructed alveolar tissue (emphysema) in COPD. We hypothesized that lung-derived MSCs (LMSCs) from emphysema patients are hampered in their repair capacity, either intrinsically or due to their interaction with the damaged micro-environment. LMSCs were isolated from lung tissue of controls and severe emphysema patients, and characterized at baseline. Additionally, LMSCs were seeded onto control and emphysematous decellularized lung tissue scaffolds and assessed for deposition of extracellular matrix (ECM). We observed no differences in surface markers, differentiation/proliferation potential and expression of ECM genes between control- and COPD-derived LMSCs. Notably, COPD-derived LMSCs displayed lower expression of FGF10 and HGF mRNA, and HGF and decorin protein. When seeded on control decellularized lung tissue scaffolds, control and COPD-derived LMSCs showed no differences in engraftment, proliferation or survival within 2 weeks, with similar ability to deposit new matrix on the scaffolds. Moreover, LMSC numbers and ability to deposit new matrix was not compromised on emphysematous scaffolds. Collectively, our data show that LMSCs from COPD patients compared to controls show less expression of FGF10 mRNA, HGF mRNA and protein and decorin protein, while other features including the mRNA expression of various ECM molecules are unaffected. Furthermore, COPD-derived LMSCs are capable of engraftment, proliferation and functioning on native lung tissue scaffolds. The damaged, emphysematous micro-environment as such does not hamper the potential of LMSCs. Thus, specific intrinsic deficiencies in growth factor production by diseased LMSCs may contribute to impaired alveolar repair in emphysema

Copper-heparin inhalation therapy to repair emphysema: A scientific rationale

Current pharmacotherapy of chronic obstructive pulmonary disease (COPD) aims at reducing respiratory symptoms and exacerbation frequency. Effective therapies to reduce disease progression, however, are still lacking. Furthermore, COPD medications showed less favorable effects in emphysema than in other COPD phenotypes. Elastin fibers are reduced and disrupted, whereas collagen levels are increased in emphysematous lungs. Protease/antiprotease imbalance has historically been regarded as the sole cause of emphysema. However, it is nowadays appreciated that emphysema may also be provoked by perturbations in the sequential repair steps following elastolysis. Essentiality of fibulin-5 an

Isolation of intact elastin fibers devoid of microfibrils.

Contains fulltext : 48622.pdf (publisher's version ) (Open Access)Purification protocols for elastin generally result in greatly damaged elastin fibers and this likely influences the biological response. We here describe a novel protocol for the isolation of elastin whereby the fibers stay intact, and introduce the term "elastin fiber" for intact elastic fibers with elastin as their sole component. As opposed to elastic fibers, elastin fibers do not contain any microfibrils or associated molecules. Elastin fibers were isolated from equine elastic ligaments according to various protocols and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, amino acid quantification, immunofluorescence assay, transmission/scanning electron microscopy, and cellular reactivity in vivo. The optimal protocol comprised several extraction steps and trypsin digestion. Elastin fibers were free of contaminants and had a smooth, regular appearance. The cellular response to purified, intact elastin fibers was different in comparison with purified, but affected, fibers and to contaminated fibers. Intact fibers consisting only of elastin may be important for both fundamental and applied research, for example, tissue engineering, which need well-defined preparations to study the cellular biological effect of individual components

Properties of different poultry skins sources in relation to co-extruded sausage casings

Casings are an essential component in the transformation of comminuted meat into a finished sausage. Their strength and the texture of the ground meat determine the “bite” perception when eating a sausage. Traditionally, meat has been stuffed into natural casings, but alternatives, such as cellulose and co-extruded collagen casings are emerging. Bovine hide split collagen is the primary source for co-extruded casings. However, an increase in meat products consumption puts pressure on the supply of collagen casings, and therefore producers are searching for alternatives. In this study, the properties of chicken skin collagen preparations from four types of birds [fast-growing broilers (42 d), slower-growing broilers (56 d), broiler breeders (52 wk), and laying hens (100 wk)] were investigated by biochemical, and physical analyses to obtain properties important in designing new dispersions for co-extrusion. SDS-PAGE, rheology, DSC and TNBS showed little difference in parameters between the different chicken types. However, after salt precipitation, creating strong films from the broiler breeder and laying hen skins’ dispersions was not possible. Creating films was possible with the dispersions of fast and slower-growing broiler skins, particularly after precipitation with saturated NaCl. In conclusion, chicken skin collagen from slower and fast growing broilers have the potential of being a suitable collagen source for the co-extrusion process. Overall, it was feasible to form stronger films with broiler skins than with skins of broiler breeder and laying hens. This is important as the casings’ strength dictates the initial sensory perception when eating a sausage