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Sample records for matrix metalloproteinase-7 activity

  1. Proliferative effects of apical, but not basal, matrix metalloproteinase-7 activity in polarized MDCK cells

    International Nuclear Information System (INIS)

    Harrell, Permila C.; McCawley, Lisa J.; Fingleton, Barbara; McIntyre, J. Oliver; Matrisian, Lynn M.

    2005-01-01

    Matrix metalloproteinase-7 (MMP-7) is primarily expressed in glandular epithelium. Therefore, its mechanism of action may be influenced by its regulated vectorial release to either the apical and/or basolateral compartments, where it would act on its various substrates. To gain a better understanding of where MMP-7 is released in polarized epithelium, we have analyzed its pattern of secretion in polarized MDCK cells expressing stably transfected human MMP-7 (MDCK-MMP-7), and HCA-7 and Caco2 human colon cancer cell lines. In all cell lines, latent MMP-7 was secreted to both cellular compartments, but was 1.5- to 3-fold more abundant in the basolateral compartment as compared to the apical. However, studies in the MDCK system demonstrated that MMP-7 activity was 2-fold greater in the apical compartment of MDCK-MMP-7 HIGH -polarized monolayers, which suggests the apical co-release of an MMP-7 activator. In functional assays, MMP-7 over-expression increased cell saturation density as a result of increased cell proliferation with no effect on apoptosis. Apical MMP-7 activity was shown to be responsible for the proliferative effect, which occurred, as demonstrated by media transfer experiments, through cleavage of an apical substrate and not through the generation of a soluble factor. Taken together, our findings demonstrate the importance of MMP-7 secretion in relation to its mechanism of action when expressed in a polarized epithelium

  2. By activating matrix metalloproteinase-7, shear stress promotes chondrosarcoma cell motility, invasion and lung colonization.

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    Guan, Pei-Pei; Yu, Xin; Guo, Jian-Jun; Wang, Yue; Wang, Tao; Li, Jia-Yi; Konstantopoulos, Konstantinos; Wang, Zhan-You; Wang, Pu

    2015-04-20

    Interstitial fluid flow and associated shear stress are relevant mechanical signals in cartilage and bone (patho)physiology. However, their effects on chondrosarcoma cell motility, invasion and metastasis have yet to be delineated. Using human SW1353, HS.819.T and CH2879 chondrosarcoma cell lines as model systems, we found that fluid shear stress induces the accumulation of cyclic AMP (cAMP) and interleukin-1β (IL-1β), which in turn markedly enhance chondrosarcoma cell motility and invasion via the induction of matrix metalloproteinase-7 (MMP-7). Specifically, shear-induced cAMP and IL-1β activate PI3-K, ERK1/2 and p38 signaling pathways, which lead to the synthesis of MMP-7 via transactivating NF-κB and c-Jun in human chondrosarcoma cells. Importantly, MMP-7 upregulation in response to shear stress exposure has the ability to promote lung colonization of chondrosarcomas in vivo. These findings offer a better understanding of the mechanisms underlying MMP-7 activation in shear-stimulated chondrosarcoma cells, and provide insights on designing new therapeutic strategies to interfere with chondrosarcoma invasion and metastasis.

  3. Optical Imaging of Matrix Metalloproteinase-7 Activity in Vivo Using a Proteolytic Nanobeacon

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    Randy L. Scherer

    2008-05-01

    Full Text Available Matrix metalloproteinases (MMPs are extracellular proteolytic enzymes involved in tumor progression. We present the in vivo detection and quantitation of MMP7 activity using a specific near-infrared polymer-based proteolytic beacon, PB-M7NIR. PB-M7NIR is a pegylated polyamidoamine PAMAM-Generation 4 dendrimer core covalently coupled to a Cy5.5-labeled peptide representing a selective substrate that monitors MMP7 activity (sensor and AF750 as an internal reference to monitor relative substrate concentration (reference. In vivo imaging of tumors expressing MMP7 had a median sensor to reference ratio 2.2-fold higher than a that of a bilateral control tumor. Ex vivo imaging of intestines of multiple intestinal neoplasia (APCMin mice injected systemically with PB-M7NIR revealed a sixfold increase in the sensor to reference ratio in the adenomas of APCMin mice compared with control intestinal tissue or adenomas from MMP7-null Min mice. PB-M7NIR detected tumor sizes as small as 0.01 cm2, and the sensor to reference ratio was independent of tumor size. Histologic sectioning of xenograft tumors localized the proteolytic signal to the extracellular matrix; MMP7-overexpressing tumors displayed an approximately 300-fold enhancement in the sensor to reference ratio compared with nonexpressing tumor cells. In APCMin adenomas, the proteolytic signal colocalized with the endogenously expressed MMP7 protein, with sensor to reference ratios approximately sixfold greater than that of normal intestinal epithelium. PB-M7NIR provides a useful reagent for the in vivo and ex vivo quantitation and localization of MMP-selective proteolytic activity.

  4. The diagnostic importance of matrix metalloproteinase-7 and nestin in gastrointestinal stromal tumors

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    Peker, Kemal; Sayar, Ilyas; Gelincik, İbrahim; Bulut, Gülay; Ünal, Tuba Dilay Kökenek; Şenol, Serkan; Gökçe, Aysun; Isik, Arda

    2014-01-01

    Background The importance of the matrix metalloproteinase-7 (MMP-7) and nestin immunomarkers, C-kit proto-oncogene (CD117), and the efficiency of the Ki-67 proliferation index for gastrointestinal stromal tumors were evaluated. Material/Methods This study was conducted by examining the microscope slides of 72 patients with gastrointestinal stromal tumors that were sent to the pathology laboratory between 2007 and 2012. Immunohistochemical staining for CD117, MMP-7, nestin, and marker of proliferation Ki-67 was performed. The correlations between the positive results for Ki-67, CD117, MMP-7, and nestin were evaluated relative to the tumor characteristics of size, localization, grade, cellular type, cellularity, cytology type, growth pattern, ulceration, necrosis, hemorrhage, invasion depth, and lymph node metastasis. Results The tumor was localized in the stomach in 42 of the patients, the intestines in 19, the colon in 7, and the rectum in 4. Comparisons among the groups showed that MMP-7 was correlated with the tumor grade (p<0.001), cellularity (p<0.009), cytologic atypia (p<0.001), ulceration (p=0.002), necrosis (p<0.001), and tumor size (p=0.001). Nestin was correlated with the tumor grade (p=0.013), and tumor size (p=0.024). Correlations among CD117, MMP-7, nestin, and Ki-67 were examined. Nestin and Ki-67 were both significantly correlated with CD117 and MMP-7 [(r=0.279, p=0.018), (r=0.322, p=0.006), (r=0.386, p=0.001), (r=0.386, p=0.002)], respectively. Conclusions MMP-7 and nestin may be beneficial as markers, given their sensitivity to gastrointestinal stromal tumors. PMID:24755685

  5. Matrix metalloproteinase-7 and matrix metalloproteinase-25 in oral tongue squamous cell carcinoma.

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    Mäkinen, Laura K; Häyry, Valtteri; Hagström, Jaana; Sorsa, Timo; Passador-Santos, Fabricio; Keski-Säntti, Harri; Haukka, Jari; Mäkitie, Antti A; Haglund, Caj; Atula, Timo

    2014-12-01

    Predicting the clinical course of early-stage oral tongue squamous cell carcinoma (SCC) is challenging. As matrix metalloproteinases (MMPs) are enzymes associated with invasion, metastasis, and poor survival in many cancers, we examined MMP-7 and MMP-25 in oral tongue SCC. We used tissue microarray (TMA) technique and immunohistochemistry to study the expression of MMP-7 and MMP-25 in 73 patients with stage I to II oral tongue SCC and compared their immunoexpressions with clinical data. Immunohistochemistry revealed MMP-7 and MMP-25 expression in 90% (n = 63 of 70) and 90% (n = 64 of 71) of the tumors, respectively. MMP-7 protein expression was associated with presence of occult cervical metastases (odds ratio [OR], 3.67; p = .013), increased invasion depth (OR, 4.60; p = .005), and higher tumor grade (OR, 3.30; p = .007). MMP-7 expression was predictive for poor outcome (p = .021). Immunostaining of MMP-25 did not correlate with any clinical parameters. We conclude that MMP-7, but not MMP-25, expression may have prognostic significance in early-stage oral tongue SCC. © 2014 Wiley Periodicals, Inc.

  6. Allele-specific transactivation of matrix metalloproteinase 7 by FOXA2 and correlation with plasma levels in idiopathic pulmonary fibrosis.

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    Richards, Thomas J; Park, Chunghyun; Chen, Yiliang; Gibson, Kevin F; Peter Di, Y; Pardo, Annie; Watkins, Simon C; Choi, Augustine M K; Selman, Moises; Pilewski, Joseph; Kaminski, Naftali; Zhang, Yingze

    2012-04-15

    Idiopathic pulmonary fibrosis (IPF) is a complex disease with poorly understood etiology. Previously, we reported upregulation of matrix metalloproteinase 7 (MMP7) in both lung and peripheral blood of IPF patients. Here we report evidence for genetic correlation of plasma levels and promoter polymorphisms (rs11568818 and rs11568819) of MMP7 in a well-characterized IPF cohort. Both the AA genotype of rs11568818 and the CT genotype of rs11568819 were found to be significantly associated with higher MMP7 plasma levels. These associations were observed only in IPF patients and not in healthy controls. The G-to-A transition of rs11568818 resulted in a novel binding site for the forkhead box A2 (FOXA2) transcription factor, a key regulator of embryonic lung development and proper function of the mature lung. In vitro, this transition led to increased sensitivity of the MMP7 promoter to FOXA2. In IPF lungs, FOXA2 was localized in the nucleus of epithelial cells that expressed MMP7 in the cytoplasm. These results suggest that increased sensitivity of the polymorphic MMP7 promoter to FOXA2 provides one of the genetic bases for the upregulation of MMP7 in IPF.

  7. Expression and correlation of matrix metalloproteinase-7 and interleukin-15 in human osteoarthritis.

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    Tao, Yulei; Qiu, Xianxing; Xu, Changbo; Sun, Bo; Shi, Changxiu

    2015-01-01

    To investigate the expression and correlation of matrix metalloproteinase (MMP)-7 and interleukin (IL)-15 in human osteoarthritis (OA). From October 2013 to December 2014, 30 patients with OA were enrolled. In addition, anther 30 patients with simple meniscus injury were collected as a control group. There were no significant differences in age and gender between the two groups. Articular cartilage tissue was obtained from both OA patients and control group patients. Protein, mRNA, and serum expression levels of MMP-7 and IL-15 in the both two groups were determined by immunohistochemical (IHC), in situ hybridization, and enzyme-linked immunosorbent assay (ELISA) assay, respectively. Additionally, correlation between MMP-7 and IL-15 expression level in cartilage tissue and serum was assessed using Pearson correlation analysis. Protein, mRNA, and serum expression levels of MMP-7 and IL-15 in patients with OA were all significantly increased in OA patients compared with the control group. Besides, there were strong positive relationships between articular MMP-7 level and serum MMP-7 level (R(2) = 0.573, P = 0.018), between articular IL-15 level and serum IL-15 level (R(2) = 0.861, P = 0.023), and between serum IL-15 level and serum MMP-7 level (R(2) = 0.602, P = 0.012). These results suggest that MMP-7 and IL-15 might play important roles in the pathogenesis of OA, and IL-15 and MMP-7 has positive correlation in OA.

  8. Association of Matrix Metalloproteinase-7 Genotypes to the Risk of Oral Cancer in Taiwan.

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    Shih, Liang-Chun; Li, Ching-Hao; Sun, Kuo-Ting; Chen, Liang-Yu; Hsu, Che-Lun; Hung, Yi-Wen; Wu, Cheng-Nan; Hsia, Te-Chun; Shen, Te-Chun; Chang, Wen-Shin; Shih, Tzu-Ching; Tsai, Chia-Wen; Bau, DA-Tian

    2018-04-01

    Matrix metalloproteinases (MMPs) play a critical role in inflammation and carcinogenesis, and the expression of mRNA MMP7 in oral squamous cell carcinoma tissues was higher than in the oral lichen planus or normal oral mucosa. However, the genotypic role of MMP7 has never been examined in oral cancer. Therefore, in the current study we aimed to examine the contribution of genotypic variants in the promoter region of MMP7 (A-181G and C-153T) to oral cancer risk in Taiwan. In this hospital-based case-control study, 788 patients with oral cancer and 956 gender-and age-matched healthy controls were genotyped for MMP7 A-181G and C-153T via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. The distribution pattern of AA, AG and GG for MMP7 promoter A-181G genotype was 88.2, 10.4 and 1.4% in the oral cancer patient group and 89.0, 9.3 and 1.7% in the healthy control group, respectively (p for trend=0.6779), non-significantly differentially distributed between the two groups. There is no polymorphic genotype for MMP7 C-153T among Taiwanese. The comparisons in allelic frequency distribution also support the findings that G allele may not be the risk determinant allele for oral cancer. There is no interaction between the genotypes of MMP7 with age, gender, smoking, alcohol or betel quid consumption on oral cancer risk. Our results indicate that the MMP7 promoter genotypes only play an indirect role in determining the personal susceptibility to oral cancer in Taiwan. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  9. Levels of matrix metalloproteinase-7 and osteopontin in human gingival crevicular fluid during initial tooth movement

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    Dhaval Oswal

    2015-01-01

    Full Text Available Purpose: During orthodontic treatment, the early response of periodontal tissues to mechanical stress involves several metabolic changes that allow tooth movement. The purpose of this investigation was to evaluate osteopontin (OPN and matrix metalloproteinase (MMP-7 in the gingival crevicular fluid (GCF of human teeth exposed to orthodontic force. Materials and Methods: GCF samples were obtained from 15 healthy orthodontic patients (age, 12-22 years. In each patient, the left maxillary canine having the fixed orthodontic appliance was used as the test tooth, and its antagonist, with no appliance, was the control. Orthodontic force, 75 g was applied using a 16 × 22 beta titanium closing loop. The GCF sampling on the disto-buccal aspects of experimental and control tooth was performed at specific time interval with sterilized absorbent paper point. Processing was carried out with enzyme-linked immunosorbent assay to detect OPN and MMP-7 levels. Results: The peak level of OPN was seen after 1 h application of orthodontic force which was 1280.36 pg/ml ± 185.02. The peak level of MMP-7 was seen at 0 h which was 598.3 pg/ml ± 107.5. The levels of OPN after 1 h increased to 1280.36 pg/ml ± 185.02, and they decreased at 24 h to 1012.86 pg/ml ± 168.47 (P = 0.001. The levels of MMP-7 after 1 h decreased to 478 pg/ml ± 99.7 which increased at 24 h to 526.9 pg/ml ± 99.2. Conclusions: Orthodontic forces affect both OPN and MMP-7 protein levels on the compression side in a time-dependent fashion.

  10. Contribution of Matrix Metalloproteinase-7 Genotypes to the Risk of Non-solid Tumor, Childhood Leukemia.

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    Pei, Jen-Sheng; Chou, An-Kuo; Hsu, Pei-Chen; Tsai, Chia-Wen; Chang, Wen-Shin; Wu, Meng-Feng; Wu, Ming-Hsien; Hsia, Te-Chun; Cheng, Shun-Ping; Bau, DA-Tian

    2017-12-01

    The matrix metalloproteinases (MMPs) are important in inflammation and carcinogenesis, and the genotypic role of MMP7 has never been examined in leukemia to date. Therefore, in this study we aimed to evaluate the contribution of the genotypic variants in the promoter region of MMP7 (A-181G and C-153T) to childhood acute lymphoblastic leukemia (ALL) risk in Taiwan. In this case-control study, 266 patients with childhood ALL and 266 non-cancer controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism methodology. The distribution of AA, AG and GG for MMP7 promoter A-181G genotype was 83.5, 12.0 and 4.5% in the childhood ALL group and 89.8%, 9.4 and 0.8% in the non-cancer control group, respectively (p for trend=0.0134), significantly differentially distributed between childhood ALL and control groups. The comparisons in allelic frequency distribution also support the findings that G appears to be the risky allele in childhood ALL. In genotype and gender interaction analysis, it was found that boys carrying the MMP7 A-181G GG and AG+GG genotypes had 9.05- and 2.45-fold odds ratios (ORs) (p=0.0135 and 0.0142, respectively) for childhood ALL compared to those carrying wild-type AA genotype. But these differences were not found in girls. Analysis of genotype interaction with age of onset age showed those aged less than 3.5 years at onset carrying the GG or AG+GG genotypes also had elevated ORs of 8.79- and 2.04-fold (p=0.0150 and 0.0413, respectively) for childhood ALL, but there was no such difference for those having an age at onset of 3.5 years or more. Our results indicate that the MMP7 A-181G genotype interacts with age and gender and may serve as an early and predictive biomarker for childhood ALL. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. Fractional Excretion of Survivin, Extracellular Matrix Metalloproteinase Inducer, and Matrix Metalloproteinase 7 in Children with Chronic Kidney Disease

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    Agnieszka Bargenda

    2016-07-01

    Full Text Available Background: Epithelial–mesenchymal transition (EMT is defined as a transformation of tubular epithelial cells into mesenchymal ones. These cells migrate through the extracellular matrix and change into active myofibroblasts, which are responsible for excessive matrix deposition. Such changes may lead to tubular dysfunction and fibrosis of the renal parenchyma, characteristic of chronic kidney disease (CKD. However, there are no data on potential EMT markers in children with CKD. The aim of our study was to assess the usefulness of fractional excretion (FE of survivin, E-cadherin, extracellular matrix metalloproteinase inducer (EMMPRIN, matrix metalloproteinase (MMP7, and transforming growth factor beta 1 (TGF-β1 as potential markers of CKD-related complications such as tubular damage and fibrosis. Methods: Forty-one pre-dialysis children with CKD Stages 3–5 and 23 age-matched controls were enrolled in the study. The serum and urine concentrations of analysed parameters were assessed by an enzyme-linked immunosorbent assay test. Results: Tubular reabsorption of all analysed parameters was >99% in the control group. All FE values rose significantly in children with CKD, yet they remained 1%. Conclusions: FE of the examined markers may become a useful tool in the assessment of tubular dysfunction during the course of CKD. The FE of survivin, EMMPRIN, and MMP7 warrant further research as potential independent markers of kidney-specific EMT.

  12. Achaete-scute complex homolog-1 promotes DNA repair in the lung carcinogenesis through matrix metalloproteinase-7 and O(6-methylguanine-DNA methyltransferase.

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    Xiao-Yang Wang

    Full Text Available Lung cancer is the leading cause of cancer-related deaths in the world. Achaete-scute complex homolog-1 (Ascl1 is a member of the basic helix-loop-helix (bHLH transcription factor family that has multiple functions in the normal and neoplastic lung such as the regulation of neuroendocrine differentiation, prevention of apoptosis and promotion of tumor-initiating cells. We now show that Ascl1 directly regulates matrix metalloproteinase-7 (MMP-7 and O(6-methylguanine-DNA methyltransferase (MGMT. Loss- and gain-of-function experiments in human bronchial epithelial and lung carcinoma cell lines revealed that Ascl1, MMP-7 and MGMT are able to protect cells from the tobacco-specific nitrosamine NNK-induced DNA damage and the alkylating agent cisplatin-induced apoptosis. We also examined the role of Ascl1 in NNK-induced lung tumorigenesis in vivo. Using transgenic mice which constitutively expressed human Ascl1 in airway lining cells, we found that there was a delay in lung tumorigenesis. We conclude that Ascl1 potentially enhances DNA repair through activation of MMP-7 and MGMT which may impact lung carcinogenesis and chemoresistance. The study has uncovered a novel and unexpected function of Ascl1 which will contribute to better understanding of lung carcinogenesis and the broad implications of transcription factors in tobacco-related carcinogenesis.

  13. Implications of Isoprostanes and Matrix Metalloproteinase-7 Having Potential Role in the Development of Colorectal Cancer in Males

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    Mahmood Rasool

    2018-06-01

    Full Text Available BackgroundColorectal cancer (CRC is the third most common type of cancer and leading cause of death worldwide. Major risk factors involved in the development of CRC are increased dietary sources, genetics, and increasing age. Purpose of the study was to find the role of different variables in the progression of CRC.Methodology50 blood samples from CRC patients and 20 samples from control were collected. Serum was separated from the blood by centrifugation. This serum was assessed for several antioxidants like superoxide dismutase (SOD, glutathione, glutathione peroxidase, glutathione reductase, catalase, vitamin A, C, and E, and pro-oxidants such as malondialdehyde, advanced oxidation protein products (AOPPs, and AGEs according to their respective protocols. Matrix metalloproteinase-7 (MMP-7 and isoprostanes were assessed by ELISA kits.ResultsLower levels of GSH (4.86 ± 0.78 vs 9.65 ± 1.13 μg/dl, SOD (0.08 ± 0.012 vs 0.46 ± 0.017 μg/dl, CAT (2.45 ± 0.03 vs 4.22 ± 0.19 μmol/mol of protein, and GRx (5.16 ± 0.06 vs 7.23 ± 0.36 μmol/ml in the diseased group were recorded as compared with control. Higher levels of GPx (6.64 ± 0.19 mmol/dl were observed in the subjects in comparison with control group (1.58 ± 0.30 mmol/dl. Highly significant decreased levels of vitamin A (0.81 ± 0.07 vs 2.37 ± 0.15 mg/ml, vitamin E (15.42 ± 1.26 vs 25.96 ± 2.19 mg/ml, and vitamin C (47.67 ± 7.69 vs 80.37 ± 10.21 mg/ml were observed in the patients in contrast to control group. The reversal of antioxidants in later stages of CRC may be due to compensatory mechanisms in cancerous cells. The levels of MDA (nmol/ml were also assessed, which shows significantly increased level in CRC patients as compared with control groups (3.67 ± 0.19 vs 1.31 ± 0.27. The levels of protein oxidation products [AGEs (2.74 ± 0.16 vs 0.84 ± 0.05 IU and AOPPs (1.32

  14. Overexpression of matrix metalloproteinase-7 and -9 in NSCLC tumor and stromal cells: correlation with a favorable clinical outcome.

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    Stenvold, Helge; Donnem, Tom; Andersen, Sigve; Al-Saad, Samer; Al-Shibli, Khalid; Busund, Lill-Tove; Bremnes, Roy M

    2012-02-01

    Matrix metalloproteinases (MMPs) are considered important players in angiogenesis and cancer progression. Several drugs developed for targeting MMPs have until now been without clinical efficacy. As both malignant cells and cells of the surrounding stroma contribute to tumor growth, we have explored the impact of MMP-2, -7 and -9 expression in both the tumor and stromal compartment of non-small-cell lung cancers (NSCLC). From 335 unselected stage I to IIIA NSCLC carcinomas, duplicate tumor and tumor-associated stromal cores were collected in tissue microarrays (TMAs). Immunohistochemistry was used to detect the expression of MMP-2, -7 and -9 in tumor and stromal cells. In univariate analyses, high tumor cell MMP-7 expression (P=0.029) and high stromal MMP-9 expression (P=0.001) were positive prognostic factors. In the multivariate analysis, high tumor cell MMP-7 expression (HR 1.58, CI 1.08-2.32, P=0.020) and high stromal MMP-9 expression (HR 1.92, CI 1.25-2.96, P=0.003) were independent positive prognostic factors for disease-specific survival. High levels of MMP-7 in tumor cells and high levels of MMP-9 in tumor associated stroma were independent positive prognostic factors in NSCLC patients. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. Matrix metalloproteinase activity assays: Importance of zymography.

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    Kupai, K; Szucs, G; Cseh, S; Hajdu, I; Csonka, C; Csont, T; Ferdinandy, P

    2010-01-01

    Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases capable of degrading extracellular matrix, including the basement membrane. MMPs are associated with various physiological processes such as morphogenesis, angiogenesis, and tissue repair. Moreover, due to the novel non-matrix related intra- and extracellular targets of MMPs, dysregulation of MMP activity has been implicated in a number of acute and chronic pathological processes, such as arthritis, acute myocardial infarction, chronic heart failure, chronic obstructive pulmonary disease, inflammation, and cancer metastasis. MMPs are considered as viable drug targets in the therapy of the above diseases. For the development of selective MMP inhibitor molecules, reliable methods are necessary for target validation and lead development. Here, we discuss the major methods used for MMP assays, focusing on substrate zymography. We highlight some problems frequently encountered during sample preparations, electrophoresis, and data analysis of zymograms. Zymography is a widely used technique to study extracellular matrix-degrading enzymes, such as MMPs, from tissue extracts, cell cultures, serum or urine. This simple and sensitive technique identifies MMPs by the degradation of their substrate and by their molecular weight and therefore helps to understand the widespread role of MMPs in different pathologies and cellular pathways. Copyright 2010 Elsevier Inc. All rights reserved.

  16. The transcription factor SOX18 regulates the expression of matrix metalloproteinase 7 and guidance molecules in human endothelial cells.

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    Martina Hoeth

    Full Text Available Mutations in the transcription factor SOX18 are responsible for specific cardiovascular defects in humans and mice. In order to gain insight into the molecular basis of its action, we identified target genes of SOX18 and analyzed one, MMP7, in detail.SOX18 was expressed in HUVEC using a recombinant adenoviral vector and the altered gene expression profile was analyzed using microarrays. Expression of several regulated candidate SOX18 target genes was verified by real-time PCR. Knock-down of SOX18 using RNA interference was then used to confirm the effect of the transcription factor on selected genes that included the guidance molecules ephrin B2 and semaphorin 3G. One gene, MMP7, was chosen for further analysis, including detailed promoter studies using reporter gene assays, electrophoretic mobility shift analysis and chromatin-immunoprecipitation, revealing that it responds directly to SOX18. Immunohistochemical analysis demonstrated the co-expression of SOX18 and MMP7 in blood vessels of human skin.The identification of MMP7 as a direct SOX18 target gene as well as other potential candidates including guidance molecules provides a molecular basis for the proposed function of this transcription factor in the regulation of vessel formation.

  17. Google matrix of the world network of economic activities

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    Kandiah, Vivek; Escaith, Hubert; Shepelyansky, Dima L.

    2015-07-01

    Using the new data from the OECD-WTO world network of economic activities we construct the Google matrix G of this directed network and perform its detailed analysis. The network contains 58 countries and 37 activity sectors for years 1995 and 2008. The construction of G, based on Markov chain transitions, treats all countries on equal democratic grounds while the contribution of activity sectors is proportional to their exchange monetary volume. The Google matrix analysis allows to obtain reliable ranking of countries and activity sectors and to determine the sensitivity of CheiRank-PageRank commercial balance of countries in respect to price variations and labor cost in various countries. We demonstrate that the developed approach takes into account multiplicity of network links with economy interactions between countries and activity sectors thus being more efficient compared to the usual export-import analysis. The spectrum and eigenstates of G are also analyzed being related to specific activity communities of countries.

  18. New intracellular activities of matrix metalloproteinases shine in the moonlight.

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    Jobin, Parker G; Butler, Georgina S; Overall, Christopher M

    2017-11-01

    Adaption of a single protein to perform multiple independent functions facilitates functional plasticity of the proteome allowing a limited number of protein-coding genes to perform a multitude of cellular processes. Multifunctionality is achievable by post-translational modifications and by modulating subcellular localization. Matrix metalloproteinases (MMPs), classically viewed as degraders of the extracellular matrix (ECM) responsible for matrix protein turnover, are more recently recognized as regulators of a range of extracellular bioactive molecules including chemokines, cytokines, and their binders. However, growing evidence has convincingly identified select MMPs in intracellular compartments with unexpected physiological and pathological roles. Intracellular MMPs have both proteolytic and non-proteolytic functions, including signal transduction and transcription factor activity thereby challenging their traditional designation as extracellular proteases. This review highlights current knowledge of subcellular location and activity of these "moonlighting" MMPs. Intracellular roles herald a new era of MMP research, rejuvenating interest in targeting these proteases in therapeutic strategies. This article is part of a Special Issue entitled: Matrix Metalloproteinases edited by Rafael Fridman. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Ramiprilate inhibits functional matrix metalloproteinase activity in Crohn's disease fistulas

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    Efsen, Eva; Saermark, Torben; Hansen, Alastair

    2011-01-01

    Increased expression of matrix metalloproteinase (MMP)-2, -3 and -9 has been demonstrated in Crohn's disease fistulas, but it is unknown whether these enzymes are biologically active and represent a therapeutic target. Therefore, we investigated the proteolytic activity of MMPs in fistula tissue...... from six controls were also included. Total functional MMP activity was measured by a high-pressure liquid chromatography (HPLC)-based, fluorogenic MMP-substrate cleavage assay, and the specific activity of MMP-2, -3 and -9 by the MMP Biotrak Activity Assay. The MMP inhibitors comprised ethylene......-9.83) compared with non-Crohn's fistulas, [0.32 ng/ml, range 0-2.66, (p MMP-9 activity [0.64 ng/ml, range 0-5.66 and 0.17 ng/ml, range 0-1.1, respectively (p MMP activity level by 42% and suppressed the specific MMP-3...

  20. Risk matrix model applied to the outsourcing of logistics' activities

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    Fouad Jawab

    2015-09-01

    Full Text Available Purpose: This paper proposes the application of the risk matrix model in the field of logistics outsourcing. Such an application can serve as the basis for decision making regarding the conduct of a risk management in the logistics outsourcing process and allow its prevention. Design/methodology/approach: This study is based on the risk management of logistics outsourcing in the field of the retail sector in Morocco. The authors identify all possible risks and then classify and prioritize them using the Risk Matrix Model. Finally, we have come to four possible decisions for the identified risks. The analysis was made possible through interviews and discussions with the heads of departments and agents who are directly involved in each outsourced activity. Findings and Originality/value: It is possible to improve the risk matrix model by proposing more personalized prevention measures according to each company that operates in the mass-market retailing. Originality/value: This study is the only one made in the process of logistics outsourcing in the retail sector in Morocco through Label’vie as a case study. First, we had identified as thorough as we could all possible risks, then we applied the Risk Matrix Model to sort them out in an ascending order of importance and criticality. As a result, we could hand out to the decision-makers the mapping for an effective control of risks and a better guiding of the process of risk management.

  1. Platelet activation by extracellular matrix proteins in haemostasis and thrombosis.

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    Watson, Steve P

    2009-01-01

    The prevention of excessive blood loss to avoid fatal haemorrhage is a pivotal process for all organisms possessing a circulatory system. Increased circulating blood volume and pressure, as required in larger animals, make this process all the more important and challenging. It is essential to have a powerful and rapid system to detect damage and generate an effective seal, and which is also exquisitely regulated to prevent unwanted, excessive or systemic activation so as to avoid blockage of vessels. Thus, a highly specialised and efficient haemostatic system has evolved that consists of cellular (platelets) and protein (coagulation factors) components. Importantly, this is able to support haemostasis in both the low shear environment of the venous system and the high shear environment of the arterial system. Endothelial cells, lining the entire circulation system, play a crucial role in the delicate balance between activation and inhibition of the haemostatic system. An intact and healthy endothelium supports blood flow by preventing attachment of cells and proteins which is required for initiation of coagulation and platelet activation. Endothelial cells produce and release the two powerful soluble inhibitors of platelet activation, nitric oxide and prostacyclin, and express high levels of CD39 which rapidly metabolises the major platelet feedback agonist, ADP. This antithrombotic environment however can rapidly change following activation or removal of endothelial cells through injury or rupture of atherosclerotic plaques. Loss of endothelial cells exposes the subendothelial extracellular matrix which creates strong signals for activation of the haemostatic system including powerful platelet adhesion and activation. Quantitative and qualitative changes in the composition of the subendothelial extracellular matrix influence these prothrombotic characteristics with life threatening thrombotic and bleeding complications, as illustrated by formation of

  2. Matrix metalloproteinases with gelatinolytic activity induced by Paracoccidioides brasiliensis infection

    Science.gov (United States)

    Nishikaku, Angela Satie; Ribeiro, Luciana Cristina; Molina, Raphael Fagnani Sanchez; Albe, Bernardo Paulo; Cunha, Cláudia da Silva; Burger, Eva

    2009-01-01

    Matrix metalloproteinases (MMPs) modulate extracellular matrix turnover, inflammation and immunity. We studied MMP-9 and MMP-2 in experimental paracoccidioidomycosis. At 15 and 120 days after infection (DAI) with virulent Paracoccidioides brasiliensis, MMP-9 was positive by immunohistochemistry in multinucleated giant cells, in mononuclear cells with macrophage and lymphocyte morphologies and also in fungal cells in the lesions of susceptible and resistant mice. Using gelatin zymography, pro- and active MMP-9 and active MMP-2 were detected in all infected mice, but not in controls. Gelatinolytic activity was not observed in P. brasiliensis extracts. Semiquantitative analysis of gelatinolytic activities revealed weak or absent MMP-2 and strong MMP-9 activity in both mouse strains at 15 DAI, declining at 120 DAI. Avirulent P. brasiliensis-infected mice had residual lesions with MMP-9-positive pseudoxantomatous macrophages, but no gelatinase activity at 120 DAI. Our findings demonstrate the induction of MMPs, particularly MMP-9, in experimental paracoccidioidomycosis, suggesting a possible influence in the pattern of granulomas and in fungal dissemination. PMID:19765107

  3. Neutron activation analysis on determination of arsenic in biological matrixes

    Energy Technology Data Exchange (ETDEWEB)

    Menezes, Maria Angela de B.C.; Silva, Maria Aparecida, E-mail: menezes@cdtn.br, E-mail: cida@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2013-07-01

    Aiming at giving support to the Worker's Health Awareness Program of the Municipal Department of Health of Belo Horizonte, an assessment related arsenic was carried out in two galvanising factories by means of hair and toenail samples analysis as biomonitors. The arsenic was determined in all matrixes from the factories where gold electrodeposition process was applied. This is because arsenic salts are usually added to gold bath to improve the metal covering. The high concentration results surprised the health surveillance professionals, and alerted for the need of assessing the influence of a long-term exposure. Studies concerning galvanising process have usually been developed broaching many aspects, but so far few works has pointed out the detection and measurement of other elements like arsenic. The k{sub 0}-Instrumental Neutron Activation method was applied confirming to be a suitable technique on determination of arsenic in biological matrixes. (author)

  4. Neutron activation analysis on determination of arsenic in biological matrixes

    International Nuclear Information System (INIS)

    Menezes, Maria Angela de B.C.; Silva, Maria Aparecida

    2013-01-01

    Aiming at giving support to the Worker's Health Awareness Program of the Municipal Department of Health of Belo Horizonte, an assessment related arsenic was carried out in two galvanising factories by means of hair and toenail samples analysis as biomonitors. The arsenic was determined in all matrixes from the factories where gold electrodeposition process was applied. This is because arsenic salts are usually added to gold bath to improve the metal covering. The high concentration results surprised the health surveillance professionals, and alerted for the need of assessing the influence of a long-term exposure. Studies concerning galvanising process have usually been developed broaching many aspects, but so far few works has pointed out the detection and measurement of other elements like arsenic. The k 0 -Instrumental Neutron Activation method was applied confirming to be a suitable technique on determination of arsenic in biological matrixes. (author)

  5. DANTE, Activation Analysis Neutron Spectra Unfolding by Covariance Matrix Method

    International Nuclear Information System (INIS)

    Petilli, M.

    1981-01-01

    1 - Description of problem or function: The program evaluates activation measurements of reactor neutron spectra and unfolds the results for dosimetry purposes. Different evaluation options are foreseen: absolute or relative fluxes and different iteration algorithms. 2 - Method of solution: A least-square fit method is used. A correlation between available data and their uncertainties has been introduced by means of flux and activity variance-covariance matrices. Cross sections are assumed to be constant, i.e. with variance-covariance matrix equal to zero. The Lagrange multipliers method has been used for calculating the solution. 3 - Restrictions on the complexity of the problem: 9 activation experiments can be analyzed. 75 energy groups are accepted

  6. High matrix metalloproteinase activity is a hallmark of periapical granulomas.

    Science.gov (United States)

    de Paula-Silva, Francisco Wanderley Garcia; D'Silva, Nisha J; da Silva, Léa Assed Bezerra; Kapila, Yvonne Lorraine

    2009-09-01

    The inability to distinguish periapical cysts from granulomas before performing root canal treatment leads to uncertainty in treatment outcomes because cysts have lower healing rates. Searching for differential expression of molecules within cysts or granulomas could provide information with regard to the identity of the lesion or suggest mechanistic differences that may form the basis for future therapeutic intervention. Thus, we investigated whether granulomas and cysts exhibit differential expression of extracellular matrix (ECM) molecules. Human periapical granulomas, periapical cysts, and healthy periodontal ligament tissues were used to investigate the differential expression of ECM molecules by microarray analysis. Because matrix metalloproteinases (MMP) showed the highest differential expression in the microarray analysis, MMPs were further examined by in situ zymography and immunohistochemistry. Data were analyzed by using one-way analysis of variance followed by the Tukey test. We observed that cysts and granulomas differentially expressed several ECM molecules, especially those from the MMP family. Compared with cysts, granulomas exhibited higher MMP enzymatic activity in areas stained for MMP-9. These areas were composed of polymorphonuclear cells (PMNs) in contrast to cysts. Similarly, MMP-13 was expressed by a greater number of cells in granulomas compared with cysts. Our findings indicate that high enzymatic MMP activity in PMNs together with MMP-9 and MMP-13 stained cells could be a molecular signature of granulomas unlike periapical cysts.

  7. Calcium-Oxidant Signaling Network Regulates AMP-activated Protein Kinase (AMPK) Activation upon Matrix Deprivation*

    Science.gov (United States)

    Sundararaman, Ananthalakshmy; Amirtham, Usha; Rangarajan, Annapoorni

    2016-01-01

    The AMP-activated protein kinase (AMPK) has recently been implicated in anoikis resistance. However, the molecular mechanisms that activate AMPK upon matrix detachment remain unexplored. In this study, we show that AMPK activation is a rapid and sustained phenomenon upon matrix deprivation, whereas re-attachment to the matrix leads to its dephosphorylation and inactivation. Because matrix detachment leads to loss of integrin signaling, we investigated whether integrin signaling negatively regulates AMPK activation. However, modulation of focal adhesion kinase or Src, the major downstream components of integrin signaling, failed to cause a corresponding change in AMPK signaling. Further investigations revealed that the upstream AMPK kinases liver kinase B1 (LKB1) and Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ) contribute to AMPK activation upon detachment. In LKB1-deficient cells, we found AMPK activation to be predominantly dependent on CaMKKβ. We observed no change in ATP levels under detached conditions at early time points suggesting that rapid AMPK activation upon detachment was not triggered by energy stress. We demonstrate that matrix deprivation leads to a spike in intracellular calcium as well as oxidant signaling, and both these intracellular messengers contribute to rapid AMPK activation upon detachment. We further show that endoplasmic reticulum calcium release-induced store-operated calcium entry contributes to intracellular calcium increase, leading to reactive oxygen species production, and AMPK activation. We additionally show that the LKB1/CaMKK-AMPK axis and intracellular calcium levels play a critical role in anchorage-independent cancer sphere formation. Thus, the Ca2+/reactive oxygen species-triggered LKB1/CaMKK-AMPK signaling cascade may provide a quick, adaptable switch to promote survival of metastasizing cancer cells. PMID:27226623

  8. Matrix and Tensor Completion on a Human Activity Recognition Framework.

    Science.gov (United States)

    Savvaki, Sofia; Tsagkatakis, Grigorios; Panousopoulou, Athanasia; Tsakalides, Panagiotis

    2017-11-01

    Sensor-based activity recognition is encountered in innumerable applications of the arena of pervasive healthcare and plays a crucial role in biomedical research. Nonetheless, the frequent situation of unobserved measurements impairs the ability of machine learning algorithms to efficiently extract context from raw streams of data. In this paper, we study the problem of accurate estimation of missing multimodal inertial data and we propose a classification framework that considers the reconstruction of subsampled data during the test phase. We introduce the concept of forming the available data streams into low-rank two-dimensional (2-D) and 3-D Hankel structures, and we exploit data redundancies using sophisticated imputation techniques, namely matrix and tensor completion. Moreover, we examine the impact of reconstruction on the classification performance by experimenting with several state-of-the-art classifiers. The system is evaluated with respect to different data structuring scenarios, the volume of data available for reconstruction, and various levels of missing values per device. Finally, the tradeoff between subsampling accuracy and energy conservation in wearable platforms is examined. Our analysis relies on two public datasets containing inertial data, which extend to numerous activities, multiple sensing parameters, and body locations. The results highlight that robust classification accuracy can be achieved through recovery, even for extremely subsampled data streams.

  9. Influence of tool pin in friction stir welding on activated carbon reinforced aluminium metal matrix composite

    Science.gov (United States)

    DijuSamuel, G.; Raja Dhas, J. Edwin

    2017-10-01

    This paper focus on impact of tool pin in friction stir welding on activated carbon reinforced aluminium metal matrix composite. For fabrication of metal matrix composite AA6061 is used as matrix and activated carbon is used as reinforcement and it is casted using modified stir casting technique. After casting metal matrix composite has undergone various microstructure tests like SEM,EDAX and XRD. FSW is carried out in this metal matrix composite by choosing various tool pin profile like square,round,Threaded round, hexagon and taper. The quality of welded plates is measured in terms of ultimate tensile strength and hardness.

  10. Monolithic Active Pixel Matrix with Binary Counters (MAMBO) ASIC

    International Nuclear Information System (INIS)

    Khalid, Farah F.; Deptuch, Grzegorz; Shenai, Alpana; Yarema, Raymond J.

    2010-01-01

    Monolithic Active Matrix with Binary Counters (MAMBO) is a counting ASIC designed for detecting and measuring low energy X-rays from 6-12 keV. Each pixel contains analogue functionality implemented with a charge preamplifier, CR-RC 2 shaper and a baseline restorer. It also contains a window comparator which can be trimmed by 4 bit DACs to remove systematic offsets. The hits are registered by a 12 bit ripple counter which is reconfigured as a shift register to serially output the data from the entire ASIC. Each pixel can be tested individually. Two diverse approaches have been used to prevent coupling between the detector and electronics in MAMBO III and MAMBO IV. MAMBO III is a 3D ASIC, the bottom ASIC consists of diodes which are connected to the top ASIC using μ-bump bonds. The detector is decoupled from the electronics by physically separating them on two tiers and using several metal layers as a shield. MAMBO IV is a monolithic structure which uses a nested well approach to isolate the detector from the electronics. The ASICs are being fabricated using the SOI 0.2 (micro)m OKI process, MAMBO III is 3D bonded at T-Micro and MAMBO IV nested well structure was developed in collaboration between OKI and Fermilab.

  11. Monolithic Active Pixel Matrix with Binary Counters (MAMBO) ASIC

    Energy Technology Data Exchange (ETDEWEB)

    Khalid, Farah F.; Deptuch, Grzegorz; Shenai, Alpana; Yarema, Raymond J.; /Fermilab

    2010-11-01

    Monolithic Active Matrix with Binary Counters (MAMBO) is a counting ASIC designed for detecting and measuring low energy X-rays from 6-12 keV. Each pixel contains analogue functionality implemented with a charge preamplifier, CR-RC{sup 2} shaper and a baseline restorer. It also contains a window comparator which can be trimmed by 4 bit DACs to remove systematic offsets. The hits are registered by a 12 bit ripple counter which is reconfigured as a shift register to serially output the data from the entire ASIC. Each pixel can be tested individually. Two diverse approaches have been used to prevent coupling between the detector and electronics in MAMBO III and MAMBO IV. MAMBO III is a 3D ASIC, the bottom ASIC consists of diodes which are connected to the top ASIC using {mu}-bump bonds. The detector is decoupled from the electronics by physically separating them on two tiers and using several metal layers as a shield. MAMBO IV is a monolithic structure which uses a nested well approach to isolate the detector from the electronics. The ASICs are being fabricated using the SOI 0.2 {micro}m OKI process, MAMBO III is 3D bonded at T-Micro and MAMBO IV nested well structure was developed in collaboration between OKI and Fermilab.

  12. Collagenolytic Matrix Metalloproteinase Activities toward Peptomeric Triple-Helical Substrates.

    Science.gov (United States)

    Stawikowski, Maciej J; Stawikowska, Roma; Fields, Gregg B

    2015-05-19

    Although collagenolytic matrix metalloproteinases (MMPs) possess common domain organizations, there are subtle differences in their processing of collagenous triple-helical substrates. In this study, we have incorporated peptoid residues into collagen model triple-helical peptides and examined MMP activities toward these peptomeric chimeras. Several different peptoid residues were incorporated into triple-helical substrates at subsites P3, P1, P1', and P10' individually or in combination, and the effects of the peptoid residues were evaluated on the activities of full-length MMP-1, MMP-8, MMP-13, and MMP-14/MT1-MMP. Most peptomers showed little discrimination between MMPs. However, a peptomer containing N-methyl Gly (sarcosine) in the P1' subsite and N-isobutyl Gly (NLeu) in the P10' subsite was hydrolyzed efficiently only by MMP-13 [nomenclature relative to the α1(I)772-786 sequence]. Cleavage site analysis showed hydrolysis at the Gly-Gln bond, indicating a shifted binding of the triple helix compared to the parent sequence. Favorable hydrolysis by MMP-13 was not due to sequence specificity or instability of the substrate triple helix but rather was based on the specific interactions of the P7' peptoid residue with the MMP-13 hemopexin-like domain. A fluorescence resonance energy transfer triple-helical peptomer was constructed and found to be readily processed by MMP-13, not cleaved by MMP-1 and MMP-8, and weakly hydrolyzed by MT1-MMP. The influence of the triple-helical structure containing peptoid residues on the interaction between MMP subsites and individual substrate residues may provide additional information about the mechanism of collagenolysis, the understanding of collagen specificity, and the design of selective MMP probes.

  13. VANGL2 interacts with integrin αv to regulate matrix metalloproteinase activity and cell adhesion to the extracellular matrix.

    Science.gov (United States)

    Jessen, Tammy N; Jessen, Jason R

    2017-12-15

    Planar cell polarity (PCP) proteins are implicated in a variety of morphogenetic processes including embryonic cell migration and potentially cancer progression. During zebrafish gastrulation, the transmembrane protein Vang-like 2 (VANGL2) is required for PCP and directed cell migration. These cell behaviors occur in the context of a fibrillar extracellular matrix (ECM). While it is thought that interactions with the ECM regulate cell migration, it is unclear how PCP proteins such as VANGL2 influence these events. Using an in vitro cell culture model system, we previously showed that human VANGL2 negatively regulates membrane type-1 matrix metalloproteinase (MMP14) and activation of secreted matrix metalloproteinase 2 (MMP2). Here, we investigated the functional relationship between VANGL2, integrin αvβ3, and MMP2 activation. We provide evidence that VANGL2 regulates cell surface integrin αvβ3 expression and adhesion to fibronectin, laminin, and vitronectin. Inhibition of MMP14/MMP2 activity suppressed the cell adhesion defect in VANGL2 knockdown cells. Furthermore, our data show that MMP14 and integrin αv are required for increased proteolysis by VANGL2 knockdown cells. Lastly, we have identified integrin αvβ3 as a novel VANGL2 binding partner. Together, these findings begin to dissect the molecular underpinnings of how VANGL2 regulates MMP activity and cell adhesion to the ECM. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Matrix viscoplasticity and its shielding by active mechanics in microtissue models: experiments and mathematical modeling

    Science.gov (United States)

    Liu, Alan S.; Wang, Hailong; Copeland, Craig R.; Chen, Christopher S.; Shenoy, Vivek B.; Reich, Daniel H.

    2016-01-01

    The biomechanical behavior of tissues under mechanical stimulation is critically important to physiological function. We report a combined experimental and modeling study of bioengineered 3D smooth muscle microtissues that reveals a previously unappreciated interaction between active cell mechanics and the viscoplastic properties of the extracellular matrix. The microtissues’ response to stretch/unstretch actuations, as probed by microcantilever force sensors, was dominated by cellular actomyosin dynamics. However, cell lysis revealed a viscoplastic response of the underlying model collagen/fibrin matrix. A model coupling Hill-type actomyosin dynamics with a plastic perfectly viscoplastic description of the matrix quantitatively accounts for the microtissue dynamics, including notably the cells’ shielding of the matrix plasticity. Stretch measurements of single cells confirmed the active cell dynamics, and were well described by a single-cell version of our model. These results reveal the need for new focus on matrix plasticity and its interactions with active cell mechanics in describing tissue dynamics. PMID:27671239

  15. Matrix metalloproteinase 2 (MMP-2) levels are increased in active acromegaly patients.

    Science.gov (United States)

    Karci, Alper Cagri; Canturk, Zeynep; Tarkun, Ilhan; Cetinarslan, Berrin

    2017-07-01

    During follow-up of acromegaly patients, there is a discordance rate of 30% between the measurements of growth hormone and insulin-like growth factor-1 levels. Further tests are required to determine disease activity in patients with discordant results. This study was planned to investigate an association of serum levels of matrix metalloproteinase-2, matrix metalloproteinase-9, and cathepsin B with disease activity in acromegaly patients. In this study, 64 acromegaly patients followed in our clinic were divided into two groups according to the 2010 consensus criteria for cure of acromegaly as patients with active disease (n = 24) and patients with controlled disease (n = 40). Serum matrix metalloproteinase-2, matrix metalloproteinase-9, and cathepsin B levels were measured by the enzyme-linked immunosorbent assay method. The mean serum matrix metalloproteinase-2 level was significantly higher in the active acromegaly patients than in the controlled acromegaly patients (150.1 ± 54.5 ng/mL vs. 100.2 ± 44.6 ng/mL; p matrix metalloproteinase-9 and cathepsin B levels (p = 0.205 and p = 0.598, respectively). Serum matrix metalloproteinase-2 levels of 118.3 ng/mL and higher had a sensitivity of 75% and a specificity of 77.5% in determining active disease. The risk of active acromegaly was 3.3 fold higher in the patients with a matrix metalloproteinase-2 level of >118.3 ng/mL than in the patients with a matrix metalloproteinase-2 level of matrix metalloproteinase-2 level is increased in the active acromegaly patients and a threshold value in determining active disease was defined for serum matrix metalloproteinase-2 level. This study is the first to compare acromegaly patients having active or controlled disease in terms of matrix metalloproteinase-2 and matrix metalloproteinase-9 levels. The results need to be confirmed by a study that will be conducted in a larger patient group also including a healthy control group to demonstrate the

  16. Activity and expression of urokinase-type plasminogen activator and matrix metalloproteinases in human colorectal cancer

    International Nuclear Information System (INIS)

    Kim, Tae-Dong; Song, Kyoung-Sub; Li, Ge; Choi, Hoon; Park, Hae-Duck; Lim, Kyu; Hwang, Byung-Doo; Yoon, Wan-Hee

    2006-01-01

    Matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-type plasminogen activator (uPA) are involved in colorectal cancer invasion and metastasis. There is still debate whether the activity of MMP-2 and MMP-9 differs between tumors located in the colon and rectum. We designed this study to determine any differences in the expression of MMP-2, MMP-9 and uPA system between colon and rectal cancer tissues. Cancer tissue samples were obtained from colon carcinoma (n = 12) and rectal carcinomas (n = 10). MMP-2 and MMP-9 levels were examined using gelatin zymography and Western blotting; their endogenous inhibitors, tissue inhibitor of metalloproteinase-2 (TIMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1), were assessed by Western blotting. uPA, uPAR and PAI-1 were examined using enzyme-linked immunosorbent assay (ELISA). The activity of uPA was assessed by casein-plasminogen zymography. In both colon and rectal tumors, MMP-2, MMP-9 and TIMP-1 protein levels were higher than in corresponding paired normal mucosa, while TIMP-2 level in tumors was significantly lower than in normal mucosa. The enzyme activities or protein levels of MMP-2, MMP-9 and their endogenous inhibitors did not reach a statistically significant difference between colon and rectal cancer compared with their normal mucosa. In rectal tumors, there was an increased activity of uPA compared with the activity in colon tumors (P = 0.0266), however urokinase-type plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) showed no significant difference between colon and rectal cancer tissues. These findings suggest that uPA may be expressed differentially in colon and rectal cancers, however, the activities or protein levels of MMP-2, MMP-9, TIMP-1, TIMP-2, PAI-1 and uPAR are not affected by tumor location in the colon or the rectum

  17. Analytical Model of Water Flow in Coal with Active Matrix

    Science.gov (United States)

    Siemek, Jakub; Stopa, Jerzy

    2014-12-01

    This paper presents new analytical model of gas-water flow in coal seams in one dimension with emphasis on interactions between water flowing in cleats and coal matrix. Coal as a flowing system, can be viewed as a solid organic material consisting of two flow subsystems: a microporous matrix and a system of interconnected macropores and fractures. Most of gas is accumulated in the microporous matrix, where the primary flow mechanism is diffusion. Fractures and cleats existing in coal play an important role as a transportation system for macro scale flow of water and gas governed by Darcy's law. The coal matrix can imbibe water under capillary forces leading to exchange of mass between fractures and coal matrix. In this paper new partial differential equation for water saturation in fractures has been formulated, respecting mass exchange between coal matrix and fractures. Exact analytical solution has been obtained using the method of characteristics. The final solution has very simple form that may be useful for practical engineering calculations. It was observed that the rate of exchange of mass between the fractures and the coal matrix is governed by an expression which is analogous to the Newton cooling law known from theory of heat exchange, but in present case the mass transfer coefficient depends not only on coal and fluid properties but also on time and position. The constant term of mass transfer coefficient depends on relation between micro porosity and macro porosity of coal, capillary forces, and microporous structure of coal matrix. This term can be expressed theoretically or obtained experimentally. W artykule zaprezentowano nowy model matematyczny przepływu wody i gazu w jednowymiarowej warstwie węglowej z uwzględnieniem wymiany masy między systemem szczelin i matrycą węglową. Węgiel jako system przepływowy traktowany jest jako układ o podwójnej porowatości i przepuszczalności, składający się z mikroporowatej matrycy węglowej oraz z

  18. Pesticide-exposure Matrix helps identify active ingredients in pesticides used in past years

    Science.gov (United States)

    Pesticide-exposure Matrix was developed to help epidemiologists and other researchers identify the active ingredients to which people were likely exposed when their homes and gardens were treated for pests in past years

  19. Active matrix metalloproteases are expressed early on and are high during the Barrett's esophagus malignancy sequence

    NARCIS (Netherlands)

    Davelaar, Akueni L.; Straub, Daniëlle; Buttar, Navtej S.; Fockens, Paul; Krishnadath, Kausilia K.

    2015-01-01

    Objective. Molecular processes underlying Barrett's malignant development are poorly understood. Matrix metalloproteases (MMPs) are enzymes involved in inflammation, tissue remodeling, and malignant development. Therefore, active MMPs may have a role in early metaplasia development and Barrett's

  20. Plastic Substrate Active Matrix Displays Final Report CRADA No. TC-2011-00

    Energy Technology Data Exchange (ETDEWEB)

    Bernhardt, A. F. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Smith, P. M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2017-09-28

    This project was a collaborative effort between the University of California, Lawrence Livermore National Laboratory (LLNL) and FlexICs, Inc. to develop thin film transistor (TFT) electronics for active matrix displays.

  1. Activity of matrix metalloproteinases during antimycobacterial therapy in mice with simulated tuberculous inflammation.

    Science.gov (United States)

    Sumenkova, D V; Russkikh, G S; Poteryaeva, O N; Polyakov, L M; Panin, L E

    2013-05-01

    Matrix metalloproteinases are shown to be involved in the pathogenesis of tuberculosis inflammation. In the early stages of BCG-granuloma formation in mouse liver and lungs, the serum levels of matrix metalloproteinases 2 and 7 increased by 4.5 times and remained unchanged while the pathology developed. Antimycobacterial therapy with isoniazid reduced enzyme activity almost to the level of intact control. The decrease in activity of matrix metalloproteinases 2 and 7 that play the most prominent role in the development of destructive forms of tuberculosis is of great therapeutic importance.

  2. Ramiprilate inhibits functional matrix metalloproteinase activity in Crohn's disease fistulas

    DEFF Research Database (Denmark)

    Efsen, Eva; Saermark, Torben; Hansen, Alastair

    2011-01-01

    from six controls were also included. Total functional MMP activity was measured by a high-pressure liquid chromatography (HPLC)-based, fluorogenic MMP-substrate cleavage assay, and the specific activity of MMP-2, -3 and -9 by the MMP Biotrak Activity Assay. The MMP inhibitors comprised ethylene...

  3. ASTM and VAMAS activities in titanium matrix composites test methods development

    Science.gov (United States)

    Johnson, W. S.; Harmon, D. M.; Bartolotta, P. A.; Russ, S. M.

    1994-01-01

    Titanium matrix composites (TMC's) are being considered for a number of aerospace applications ranging from high performance engine components to airframe structures in areas that require high stiffness to weight ratios at temperatures up to 400 C. TMC's exhibit unique mechanical behavior due to fiber-matrix interface failures, matrix cracks bridged by fibers, thermo-viscoplastic behavior of the matrix at elevated temperatures, and the development of significant thermal residual stresses in the composite due to fabrication. Standard testing methodology must be developed to reflect the uniqueness of this type of material systems. The purpose of this paper is to review the current activities in ASTM and Versailles Project on Advanced Materials and Standards (VAMAS) that are directed toward the development of standard test methodology for titanium matrix composites.

  4. Immobilization of mercury and zinc in an alkali-activated slag matrix.

    Science.gov (United States)

    Qian, Guangren; Sun, Darren Delai; Tay, Joo Hwa

    2003-07-04

    The behavior of heavy metals mercury and zinc immobilized in an alkali-activated slag (AAS) matrix has been evaluated using physical property tests, pore structure analysis and XRD, TG-DTG, FTIR and TCLP analysis. Low concentrations (0.5%) of mercury and zinc ions had only a slight affect on compressive strength, pore structure and hydration of AAS matrixes. The addition of 2% Hg ions to the AAS matrix resulted in a reduction in early compressive strength but no negative effects were noticed after 28 days of hydration. Meanwhile, 2% Hg ions can be effectively immobilized in the AAS matrix with the leachate meeting the USEPA TCLP mercury limit. For a 2% Zn-doped AAS matrix, the hydration of the AAS paste was greatly retarded and the zinc concentration in the leachate from this matrix was higher than 5mg/l even at 28 days. Based on these results, we conclude that the physical encapsulation and chemical fixation mechanisms were likely to be responsible for the immobilization of Hg ions in the AAS matrix while only chemical fixation mechanisms were responsible for the immobilization of Zn ions in the AAS matrix.

  5. pH-Sensitive Microparticles with Matrix-Dispersed Active Agent

    Science.gov (United States)

    Li, Wenyan (Inventor); Buhrow, Jerry W. (Inventor); Jolley, Scott T. (Inventor); Calle, Luz M. (Inventor)

    2014-01-01

    Methods to produce pH-sensitive microparticles that have an active agent dispersed in a polymer matrix have certain advantages over microcapsules with an active agent encapsulated in an interior compartment/core inside of a polymer wall. The current invention relates to pH-sensitive microparticles that have a corrosion-detecting or corrosion-inhibiting active agent or active agents dispersed within a polymer matrix of the microparticles. The pH-sensitive microparticles can be used in various coating compositions on metal objects for corrosion detecting and/or inhibiting.

  6. Omega-3 and Omega-6 Fatty Acids Act as Inhibitors of the Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 Activity.

    Science.gov (United States)

    Nicolai, Eleonora; Sinibaldi, Federica; Sannino, Gianpaolo; Laganà, Giuseppina; Basoli, Francesco; Licoccia, Silvia; Cozza, Paola; Santucci, Roberto; Piro, Maria Cristina

    2017-08-01

    Polyunsaturated fatty acids have been reported to play a protective role in a wide range of diseases characterized by an increased metalloproteinases (MMPs) activity. The recent finding that omega-3 and omega-6 fatty acids exert an anti-inflammatory effect in periodontal diseases has stimulated the present study, designed to determine whether such properties derive from a direct inhibitory action of these compounds on the activity of MMPs. To this issue, we investigated the effect exerted by omega-3 and omega-6 fatty acids on the activity of MMP-2 and MMP-9, two enzymes that actively participate to the destruction of the organic matrix of dentin following demineralization operated by bacteria acids. Data obtained (both in vitro and on ex-vivo teeth) reveal that omega-3 and omega-6 fatty acids inhibit the proteolytic activity of MMP-2 and MMP-9, two enzymes present in dentin. This observation is of interest since it assigns to these compounds a key role as MMPs inhibitors, and stimulates further study to better define their therapeutic potentialities in carious decay.

  7. SPARC regulates extracellular matrix organization through its modulation of integrin-linked kinase activity.

    Science.gov (United States)

    Barker, Thomas H; Baneyx, Gretchen; Cardó-Vila, Marina; Workman, Gail A; Weaver, Matt; Menon, Priya M; Dedhar, Shoukat; Rempel, Sandra A; Arap, Wadih; Pasqualini, Renata; Vogel, Viola; Sage, E Helene

    2005-10-28

    SPARC, a 32-kDa matricellular glycoprotein, mediates interactions between cells and their extracellular matrix, and targeted deletion of Sparc results in compromised extracellular matrix in mice. Fibronectin matrix provides provisional tissue scaffolding during development and wound healing and is essential for the stabilization of mature extracellular matrix. Herein, we report that SPARC expression does not significantly affect fibronectin-induced cell spreading but enhances fibronectin-induced stress fiber formation and cell-mediated partial unfolding of fibronectin molecules, an essential process in fibronectin matrix assembly. By phage display, we identify integrin-linked kinase as a potential binding partner of SPARC and verify the interaction by co-immunoprecipitation and colocalization in vitro. Cells lacking SPARC exhibit diminished fibronectin-induced integrin-linked kinase activation and integrin-linked kinase-dependent cell-contractile signaling. Furthermore, induced expression of SPARC in SPARC-null fibroblasts restores fibronectin-induced integrin-linked kinase activation, downstream signaling, and fibronectin unfolding. These data further confirm the function of SPARC in extracellular matrix organization and identify a novel mechanism by which SPARC regulates extracellular matrix assembly.

  8. EMMPRIN mediates beta-adrenergic receptor-stimulated matrix metalloproteinase activity in cardiac myocytes.

    OpenAIRE

    Siwik Deborah A; Kuster Gabriela M; Brahmbhatt Jamin V; Zaidi Zaheer; Malik Julia; Ooi Henry; Ghorayeb Ghassan

    2008-01-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN) expression is increased in myocardium from patients with dilated cardiomyopathy and animal models of heart failure. However little is known about the regulated expression or functional role of EMMPRIN in the myocardium. In rat cardiac cells EMMPRIN is expressed on myocytes but not endothelial cells or fibroblasts. Therefore we tested the hypothesis that EMMPRIN expression regulates matrix metalloproteinase (MMP) activity in rat ventricu...

  9. Determination of platinum concentration in gold matrix by neutron activation

    International Nuclear Information System (INIS)

    Cojocaru, V.; Spiridon, S.

    1985-01-01

    A comparative study was made of the neutron activation technique and atomic absorption spectrometry applied for the analysis of high purity Bi 2 O 3 and PbCl 2 . The study showed that in most cases NAA is sensitive enough to give reliable results. Atomic absorption spectroscopy was preferable for some elements which cannot be determined by NAA due to high matrice activity. So the combination of the two methods proved very successful and permits the determination of more than 20 elements. Additionally this approach enabled to control the accuracy of the method by comparison of the results obtained

  10. Errors in instumental neutron activation analysis caused by matrix absorption

    International Nuclear Information System (INIS)

    Croudace, I.W.

    1979-01-01

    Instrumental neutron activation analysis of the geochemically important rare earth elements, together with Ta, Hf and U involves energies below 150 keV where absorption of radiation by the sample becomes inceasingly important. Determinations of the total mass absorption coefficients have been made. (C.F.)

  11. Conversion Matrix Analysis of GaAs HEMT Active Gilbert Cell Mixers

    DEFF Research Database (Denmark)

    Jiang, Chenhui; Johansen, Tom Keinicke; Krozer, Viktor

    2006-01-01

    In this paper, the nonlinear model of the GaAs HEMT active Gilbert cell mixer is investigated. Based on the model, the conversion gain expression of active Gilbert cell mixers is derived theoretically by using conversion matrix analysis method. The expression is verified by harmonic balance simul...

  12. PPARγ agonist pioglitazone reduces matrix metalloproteinase-9 activity and neuronal damage after focal cerebral ischemia

    International Nuclear Information System (INIS)

    Lee, Seong-Ryong; Kim, Hahn-Young; Hong, Jung-Suk; Baek, Won-Ki; Park, Jong-Wook

    2009-01-01

    Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, has shown protective effects against ischemic insult in various tissues. Pioglitazone is also reported to reduce matrix metalloproteinase (MMP) activity. MMPs can remodel extracellular matrix components in many pathological conditions. The current study was designed to investigate whether the neuroprotection of pioglitazone is related to its MMP inhibition in focal cerebral ischemia. Mice were subjected to 90 min focal ischemia and reperfusion. In gel zymography, pioglitazone reduced the upregulation of active form of MMP-9 after ischemia. In in situ zymograms, pioglitazone also reduced the gelatinase activity induced by ischemia. After co-incubation with pioglitazone, in situ gelatinase activity was directly reduced. Pioglitazone reduced the infarct volume significantly compared with controls. These results demonstrate that pioglitazone may reduce MMP-9 activity and neuronal damage following focal ischemia. The reduction of MMP-9 activity may have a possible therapeutic effect for the management of brain injury after focal ischemia.

  13. Kinematic matrix theory and universalities in self-propellers and active swimmers.

    Science.gov (United States)

    Nourhani, Amir; Lammert, Paul E; Borhan, Ali; Crespi, Vincent H

    2014-06-01

    We describe an efficient and parsimonious matrix-based theory for studying the ensemble behavior of self-propellers and active swimmers, such as nanomotors or motile bacteria, that are typically studied by differential-equation-based Langevin or Fokker-Planck formalisms. The kinematic effects for elementary processes of motion are incorporated into a matrix, called the "kinematrix," from which we immediately obtain correlators and the mean and variance of angular and position variables (and thus effective diffusivity) by simple matrix algebra. The kinematrix formalism enables us recast the behaviors of a diverse range of self-propellers into a unified form, revealing universalities in their ensemble behavior in terms of new emergent time scales. Active fluctuations and hydrodynamic interactions can be expressed as an additive composition of separate self-propellers.

  14. Superoxide activates mitochondrial uncoupling protein 2 from the matrix side. Studies using targeted antioxidants.

    Science.gov (United States)

    Echtay, Karim S; Murphy, Michael P; Smith, Robin A J; Talbot, Darren A; Brand, Martin D

    2002-12-06

    Superoxide activates nucleotide-sensitive mitochondrial proton transport through the uncoupling proteins UCP1, UCP2, and UCP3 (Echtay, K. S., et al. (2002) Nature 415, 1482-1486). Two possible mechanisms were proposed: direct activation of the UCP proton transport mechanism by superoxide or its products and a cycle of hydroperoxyl radical entry coupled to UCP-catalyzed superoxide anion export. Here we provide evidence for the first mechanism and show that superoxide activates UCP2 in rat kidney mitochondria from the matrix side of the mitochondrial inner membrane: (i) Exogenous superoxide inhibited matrix aconitase, showing that external superoxide entered the matrix. (ii) Superoxide-induced uncoupling was abolished by low concentrations of the mitochondrially targeted antioxidants 10-(6'-ubiquinonyl)decyltriphenylphosphonium (mitoQ) or 2-[2-(triphenylphosphonio)ethyl]-3,4-dihydro-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol bromide (mitoVit E), which are ubiquinone (Q) or tocopherol derivatives targeted to the matrix by covalent attachment to triphenylphosphonium cation. However, superoxide-induced uncoupling was not affected by similar concentrations of the nontargeted antioxidants Q(o), Q(1), decylubiquinone, vitamin E, or 6-hydroxy-2,5,7,8-tetramethylchroman 2-carboxylic acid (TROLOX) or of the mitochondrially targeted but redox-inactive analogs decyltriphenylphosphonium or 4-chlorobutyltriphenylphosphonium. Thus matrix superoxide appears to be necessary for activation of UCP2 by exogenous superoxide. (iii) When the reduced to oxidized ratio of mitoQ accumulated by mitochondria was increased by inhibiting cytochrome oxidase, it induced nucleotide-sensitive uncoupling that was not inhibited by external superoxide dismutase. Under these conditions quinols are known to produce superoxide, and because mitoQ is localized within the mitochondrial matrix this suggests that production of superoxide in the matrix was sufficient to activate UCP2. Furthermore, the superoxide

  15. Neutron activation of chlorine in zirconium and zirconium alloys use of the matrix as comparator

    International Nuclear Information System (INIS)

    Cohen, I.M.; Gomez, C.D.; Mila, M.I.

    1981-01-01

    A procedure is described for neutron activation analysis of chlorine in zirconium and zirconium alloys. Calculation of chlorine concentration is performed relative to zirconium concentration in the matrix in order to minimize effects of differences in irradiation and counting geometry. Principles of the method and the results obtained are discussed. (author)

  16. A hands-on activity for teaching product-process matrix: roadmap and application

    Directory of Open Access Journals (Sweden)

    Luciano Costa Santos

    2014-08-01

    Full Text Available The product-process matrix is a well-known framework proposed by Hayes and Wheelwright (1979 that is commonly used to identify processes types and to analyze the alignment of these processes with the products of a company. For didactic purposes, the matrix helps undergraduates beginners from Production Engineering to understand the logic of production systems, providing knowledge that will be essential for various course subjects. Considering the high level of abstraction of the concepts underlying the product-process matrix, this paper presents a way to facilitate the learning of them through the application of a hands-on activity which relies on the active learning philosophy. The proposed dynamic uses colored plastic sheets and PVC pipes as main materials, differing from the original proposal of Penlesky and Treleven (2005 . In addition to presenting an extremely simple exercise, which encourages its application in the classroom, another contribution of this paper is to define a complete roadmap for conducting the activity. This roadmap describes the assembly of fictitious products in customization and standardization scenarios for the comparison of two processes types of product-process matrix, job shop and assembly line. The activity revealed very successful after its application to two groups of Production Engineering undergraduates, confirmed with positive feedback from the students surveyed.

  17. CCR5 delta32, matrix metalloproteinase-9 and disease activity in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, Finn; Madsen, Hans O; Jensen, Claus V

    2000-01-01

    Chemokines and matrix metalloproteinases (MMPs) appear to be crucial in leukocyte recruitment to the central nervous system in multiple sclerosis (MS). CCR5 delta32, a truncated allele of the CC chemokine receptor CCR5 gene encoding a non-functional receptor, did not confer protection from MS. CCR5...... delta32 was, however, associated with a lower risk of recurrent clinical disease activity. High CSF levels of MMP-9 activity were also associated with recurrent disease activity. These results directly link intrathecal inflammation to disease activity in patients with MS, suggesting that treatments...... targeting CCR5 or treatment with MMP inhibitors may attenuate disease activity in MS...

  18. Analysis of Enzymatic Activity of Matrix Metalloproteinase (MMP) by Collagen Zymography in Melanoma.

    Science.gov (United States)

    Walia, Vijay; Samuels, Yardena

    2018-01-01

    Protein zymography is the most commonly used technique to study the enzymatic activity of matrix metalloproteinases (MMPs) and their inhibitors. MMPs are proteolytic enzymes that promote extracellular matrix degradation. MMPs are frequently mutated in malignant melanomas as well as other cancers and are linked to increasing incidence of tumor metastasis. Substrate zymography characterizes MMP activity by their ability to degrade preferred substrates. Here we describe the collagen zymography technique to measure the active or latent form of MMPs using MMP-8 as an example, which is a frequently mutated MMP family member in malignant melanomas. The same technique can be used with the modification of substrate to detect metalloproteinase activity of other MMPs. Both wild-type and mutated forms of MMPs can be analyzed using a single gel using this method.

  19. Oxidation modifies the structure and function of the extracellular matrix generated by human coronary artery endothelial cells.

    Science.gov (United States)

    Chuang, Christine Y; Degendorfer, Georg; Hammer, Astrid; Whitelock, John M; Malle, Ernst; Davies, Michael J

    2014-04-15

    ECM (extracellular matrix) materials, such as laminin, perlecan, type IV collagen and fibronectin, play a key role in determining the structure of the arterial wall and the properties of cells that interact with the ECM. The aim of the present study was to investigate the effect of peroxynitrous acid, an oxidant generated by activated macrophages, on the structure and function of the ECM laid down by HCAECs (human coronary artery endothelial cells) in vitro and in vivo. We show that exposure of HCAEC-derived native matrix components to peroxynitrous acid (but not decomposed oxidant) at concentrations >1 μM results in a loss of antibody recognition of perlecan, collagen IV, and cell-binding sites on laminin and fibronectin. Loss of recognition was accompanied by decreased HCAEC adhesion. Real-time PCR showed up-regulation of inflammation-associated genes, including MMP7 (matrix metalloproteinase 7) and MMP13, as well as down-regulation of the laminin α2 chain, in HCAECs cultured on peroxynitrous acid-treated matrix compared with native matrix. Immunohistochemical studies provided evidence of co-localization of laminin with 3-nitrotyrosine, a biomarker of peroxynitrous acid damage, in type II-III/IV human atherosclerotic lesions, consistent with matrix damage occurring during disease development in vivo. The results of the present study suggest a mechanism through which peroxynitrous acid modifies endothelial cell-derived native ECM proteins of the arterial basement membrane in atherosclerotic lesions. These changes to ECM and particularly perlecan and laminin may be important in inducing cellular dysfunction and contribute to atherogenesis.

  20. Matrix metalloproteinases (MMP) and cathepsin K contribute differently to osteoclastic activities

    DEFF Research Database (Denmark)

    Delaissé, Jean-Marie; Andersen, Thomas L; Engsig, Michael T

    2003-01-01

    The best established proteolytic event of osteoclasts is bone matrix solubilization by the cysteine proteinase cathepsin K. Here, however, we draw the attention on osteoclastic activities depending on matrix metalloproteinases (MMPs). We discuss the observations supporting that MMPs contribute...... significantly to bone matrix solubilization in specific areas of the skeleton and in some developmental and pathological situations. Our discussion takes into account (1) the characteristics of the bone remodeling persisting in the absence of cathepsin K, (2) the ultrastructure of the resorption zone...... in response to inactivation of MMPs and of cathepsin K in different bone types, (3) bone resorption levels in MMP knockout mice compared to wild-type mice, (4) the identification of MMPs in osteoclasts and surrounding cells, and (5) the effect of different bone pathologies on the serum concentrations...

  1. The effect of tomatine on metastasis related matrix metalloproteinase (MMP) activities in breast cancer cell model.

    Science.gov (United States)

    Yelken, Besra Özmen; Balcı, Tuğçe; Süslüer, Sunde Yılmaz; Kayabaşı, Çağla; Avcı, Çığır Biray; Kırmızıbayrak, Petek Ballar; Gündüz, Cumhur

    2017-09-05

    Breast cancer is one of the most common malignancies in women and metastasis is the cause of morbidity and mortality in patients. In the development of metastasis, the matrix metalloproteinase (MMP) family has a very important role in tumor development. MMP-2 and MMP-9 work together for extracellular matrix (ECM) cleavage to increase migration. Tomatine is a secondary metabolite that has a natural defense role against plants, fungi, viruses and bacteria that are synthesized from tomato. In additıon, tomatine is also known that it breaks down the cell membrane and is a strong inhibitor in human cancer cells. In this study, it was aimed to evaluate the effect of tomatine on cytotoxicity, apoptosis and matrix metalloproteinase inhibition in MCF-7 cell lines. Human breast cancer cell line (MCF-7) was used as a cell line. In MCF-7 cells, the IC 50 dose of tomatine was determined to be 7.07μM. According to the control cells, apoptosis increased 3.4 fold in 48thh. Activation of MMP-2, MMP-9 and MMP-9\\NGAL has been shown to decrease significantly in cells treated with tomatine by gelatin zymography compared to the control. As a result, matrix metalloproteinase activity and cell proliferation were suppressed by tomatine and this may provide support in treatment methods. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Phosphorylated hepatocyte growth factor receptor/c-Met is associated with tumor growth and prognosis in patients with bladder cancer: correlation with matrix metalloproteinase-2 and -7 and E-cadherin.

    Science.gov (United States)

    Miyata, Yasuyoshi; Sagara, Yuji; Kanda, Shigeru; Hayashi, Tomayoshi; Kanetake, Hiroshi

    2009-04-01

    Hepatocyte growth factor receptor/c-Met is associated with malignant aggressiveness and survival in various cancers including bladder cancer. Although phosphorylation of hepatocyte growth factor receptor/c-Met is essential for its function, the pathologic significance of phosphorylated hepatocyte growth factor receptor/c-Met in bladder cancer remains elusive. We investigated the clinical significance of its expression, and its correlation with cancer cell progression-related molecules. The expression levels of 2 tyrosine residues of hepatocyte growth factor receptor/c-Met (pY1234/1235 and pY1349) were examined immunohistochemically in 133 specimens with nonmetastatic bladder cancer. We also investigated their correlation with matrix metalloproteinase-1, -2, -7, and -14; urokinase-type plasminogen activator; E-cadherin; CD44 standard, variant 3, and variant 6; and vascular endothelial growth factor. Expression of phosphorylated hepatocyte growth factor receptor/c-Met was detected in cancer cells, but was rare in normal urothelial cells. Although hepatocyte growth factor receptor/c-Met, pY1234/1235 hepatocyte growth factor receptor/c-Met, and pY1349 hepatocyte growth factor receptor/c-Met were associated with pT stage, multivariate analysis identified pY1349 hepatocyte growth factor receptor/c-met expression only as a significant factor for high pT stage. Expression of pY1349 hepatocyte growth factor receptor/c-Met was a marker of metastasis and (P = .001) and cause-specific survival (P = .003). Expressions of matrix metalloproteinase-2, matrix metalloproteinase-7, and E-cadherin correlated with pY1349 hepatocyte growth factor receptor/c-Met expression. Our results demonstrated that pY1349 hepatocyte growth factor receptor/c-Met plays an important role in tumor development, and its expression is a significant predictor of metastasis and survival of patients with bladder cancer. The results suggest that these activities are mediated, at least in part, by matrix

  3. Differential in vivo zymography: a method for observing matrix metalloproteinase activity in the zebrafish embryo.

    Science.gov (United States)

    Keow, Jonathan Y; Herrmann, Kurt M; Crawford, Bryan D

    2011-04-01

    Investigations into the molecular mechanisms of, and cellular signaling pathways modulating ECM remodeling are especially challenging due to the complex post-translational regulation of the primary effectors of ECM catabolism - the matrix metalloproteinases (MMPs). Recently a variety of approaches to the detection of MMP activity have been developed, and the prospect of visualizing ECM remodeling activity in living tissues is now opening exciting avenues of research for matrix biologists. In particular the use of FRET-quenched MMP substrates, which generate a fluorescent signal upon hydrolysis, is becoming increasingly popular, especially because linkers with defined and/or restricted proteolytic sensitivity can be used to bind fluorophore-quencher pairs, making these probes useful in characterizing the activity of specific proteases. We have taken advantage of the transparency and amenability to reverse genetics of the zebrafish embryo, in combination with these fluorogenic MMP substrates, to develop a multiplex in vivo assay for MMP activity that we dub "differential in vivo zymography." Copyright © 2011 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  4. Bi-layered nanocomposite bandages for controlling microbial infections and overproduction of matrix metalloproteinase activity.

    Science.gov (United States)

    Anjana, J; Mohandas, Annapoorna; Seethalakshmy, S; Suresh, Maneesha K; Menon, Riju; Biswas, Raja; Jayakumar, R

    2018-04-15

    Chronic diabetic wounds is characterised by increased microbial contamination and overproduction of matrix metalloproteases that would degrade the extracellular matrix. A bi-layer bandage was developed, that promotes the inhibition of microbial infections and matrix metalloprotease (MMPs) activity. Bi-layer bandage containing benzalkonium chloride loaded gelatin nanoparticles (BZK GNPs) in chitosan-Hyaluronic acid (HA) as a bottom layer and sodium alendronate containing chitosan as top layer was developed. We hypothesized that the chitosan-gelatin top layer with sodium alendronate could inhibit the MMPs activity, whereas the chitosan-HA bottom layer with BZK GNPs (240±66nm) would enable the elimination of microbes. The porosity, swelling and degradation nature of the prepared Bi-layered bandage was studied. The bottom layer could degrade within 4days whereas the top layer remained upto 7days. The antimicrobial activity of the BZK NPs loaded bandage was determined using normal and clinical strains. Gelatin zymography shows that the proteolytic activity of MMP was inhibited by the bandage. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Improvement of the matrix effect compensation in active neutron measurement by simulated annealing algorithm (June 2009)

    International Nuclear Information System (INIS)

    Raoux, A. C.; Loridon, J.; Mariani, A.; Passard, C.

    2009-01-01

    Active neutron measurements such as the Differential Die-Away (DDA) technique involving pulsed neutron generator, are widely applied to determine the fissile content of waste packages. Unfortunately, the main drawback of such techniques is coming from the lack of knowledge of the waste matrix composition. Thus, the matrix effect correction for the DDA measurement is an essential improvement in the field of fissile material content determination. Different solutions have been developed to compensate the effect of the matrix on the neutron measurement interpretation. In this context, this paper describes an innovative matrix correction method we have developed with the goal of increasing the accuracy of the matrix effect correction and reducing the measurement time. The implementation of this method is based on the analysis of the raw signal with an optimisation algorithm called the simulated annealing algorithm. This algorithm needs a reference data base of Multi-Channel Scaling (MCS) spectra, to fit the raw signal. The construction of the MCS library involves a learning phase to define and acquire the DDA signals. This database has been provided by a set of active signals from experimental matrices (mock-up waste drums of 118 litres) recorded in a specific device dedicated to neutron measurement research and development of the Nuclear Measurement Laboratory of CEA-Cadarache, called PROMETHEE 6. The simulated annealing algorithm is applied to make use of the effect of the matrices on the total active signal of DDA measurement. Furthermore, as this algorithm is directly applied to the raw active signal, it is very useful when active background contributions can not be easily estimated and removed. Most of the cases tested during this work which represents the feasibility phase of the method, are within a 4% agreement interval with the expected experimental value. Moreover, one can notice that without any compensation of the matrix effect, the classical DDA prompt

  6. Improvement of the matrix effect compensation in active neutron measurement by simulated annealing algorithm (June 2009)

    Energy Technology Data Exchange (ETDEWEB)

    Raoux, A. C.; Loridon, J.; Mariani, A.; Passard, C. [French Atomic Energy Commission, DEN, Cadarache, F-3108 Saint-Paul-Lez-Durance (France)

    2009-07-01

    Active neutron measurements such as the Differential Die-Away (DDA) technique involving pulsed neutron generator, are widely applied to determine the fissile content of waste packages. Unfortunately, the main drawback of such techniques is coming from the lack of knowledge of the waste matrix composition. Thus, the matrix effect correction for the DDA measurement is an essential improvement in the field of fissile material content determination. Different solutions have been developed to compensate the effect of the matrix on the neutron measurement interpretation. In this context, this paper describes an innovative matrix correction method we have developed with the goal of increasing the accuracy of the matrix effect correction and reducing the measurement time. The implementation of this method is based on the analysis of the raw signal with an optimisation algorithm called the simulated annealing algorithm. This algorithm needs a reference data base of Multi-Channel Scaling (MCS) spectra, to fit the raw signal. The construction of the MCS library involves a learning phase to define and acquire the DDA signals. This database has been provided by a set of active signals from experimental matrices (mock-up waste drums of 118 litres) recorded in a specific device dedicated to neutron measurement research and development of the Nuclear Measurement Laboratory of CEA-Cadarache, called PROMETHEE 6. The simulated annealing algorithm is applied to make use of the effect of the matrices on the total active signal of DDA measurement. Furthermore, as this algorithm is directly applied to the raw active signal, it is very useful when active background contributions can not be easily estimated and removed. Most of the cases tested during this work which represents the feasibility phase of the method, are within a 4% agreement interval with the expected experimental value. Moreover, one can notice that without any compensation of the matrix effect, the classical DDA prompt

  7. Correlation between telomerase activity and matrix metalloproteinases 2 expression in gastric cancer.

    Science.gov (United States)

    Wang, Gang; Wang, Wenling; Zhou, Jianjiang; Yang, Xiaofeng

    2013-01-01

    To investigate the relationship between telomerase activity (TA) and matrix metallo proteinases 2 (MMP-2) on malignant behavior and prognosis predictable value in gastric cancer. Telomerase activity and MMP-2 protein expressions were tested in 40 gastric surgical resected cancer samples and the clinicopathological data of enrolled patients were obtained to get correlation analysis results. The expression of telomerase was up-regulated with infiltrating depth, lymph node metastasis and stage (P correlated with infiltrating depth (P < 0.05). Combined detections of telomerase activity and MMP2 protein could identify patients at high risk in disease recurrence and prognosis more efficiently.

  8. Development of immobilizing matrix for radioactive hearth ash of low activity level

    International Nuclear Information System (INIS)

    Greben'kov, A.J.; Kopets, Z.V.; Rytvinskaya, E.V.; Vecher, V.A.

    2004-01-01

    The incorporation of a certain quantity of the sorbing admixtures, i.e. the clay containing about 80 mas.% of montmorillonite, natural molding flask, into an ash-cement matrix allowed obtaining the hardened compounds with radioactive ash mass fraction of 40-60 mas.%, which physicochemical characteristics are significantly better that those required by regulations. This will facilitate the development of effective low active hearth ash utilization technologies. (authors)

  9. Stretchable Active Matrix Temperature Sensor Array of Polyaniline Nanofibers for Electronic Skin.

    Science.gov (United States)

    Hong, Soo Yeong; Lee, Yong Hui; Park, Heun; Jin, Sang Woo; Jeong, Yu Ra; Yun, Junyeong; You, Ilhwan; Zi, Goangseup; Ha, Jeong Sook

    2016-02-03

    A stretchable polyaniline nanofiber temperature sensor array with an active matrix consisting of single-walled carbon nanotube thin-film transistors is demonstrated. The integrated temperature sensor array gives mechanical stability under biaxial stretching of 30%, and the resultant spatial temperature mapping does not show any mechanical or electrical degradation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Distribution and activity levels of matrix metalloproteinase 2 and 9 in canine and feline osteosarcoma

    OpenAIRE

    Gebhard, Christiane; Fuchs-Baumgartinger, Andrea; Razzazi-Fazeli, Ebrahim; Miller, Ingrid; Walter, Ingrid

    2016-01-01

    Overexpression of matrix metalloproteinases (MMPs) has been associated with increased tumor aggressiveness and metastasis dissemination. We investigated whether the contrasting metastatic behavior of feline and canine osteosarcoma is related to levels and activities of MMP2 and MMP9. Zymography and immunohistochemistry were used to determine expression levels of MMP2 and MMP9 in canine and feline osteosarcoma. Using immunohistochemistry, increased MMP9 levels were identified in most canine os...

  11. Peptide-Based Selective Inhibitors of Matrix Metalloproteinase-Mediated Activities

    Directory of Open Access Journals (Sweden)

    Margaret W. Ndinguri

    2012-11-01

    Full Text Available The matrix metalloproteinases (MMPs exhibit a broad array of activities, some catalytic and some non-catalytic in nature. An overall lack of selectivity has rendered small molecule, active site targeted MMP inhibitors problematic in execution. Inhibitors that favor few or individual members of the MMP family often take advantage of interactions outside the enzyme active site. We presently focus on peptide-based MMP inhibitors and probes that do not incorporate conventional Zn2+ binding groups. In some cases, these inhibitors and probes function by binding only secondary binding sites (exosites, while others bind both exosites and the active site. A myriad of MMP mediated-activities beyond selective catalysis can be inhibited by peptides, particularly cell adhesion, proliferation, motility, and invasion. Selective MMP binding peptides comprise highly customizable, unique imaging agents. Areas of needed improvement for MMP targeting peptides include binding affinity and stability.

  12. Ulex europaeus I lectin induces activation of matrix-metalloproteinase-2 in endothelial cells.

    Science.gov (United States)

    Gomez, D E; Yoshiji, H; Kim, J C; Thorgeirsson, U P

    1995-11-02

    In this report, we show that the lectin Ulex europaeus agglutinin I (UEA I), which binds to alpha-linked fucose residues on the surface of endothelial cells, mediates activation of the 72-kDa matrix metalloproteinase-2 (MMP-2). A dose-dependent increase in the active 62-kDa form of MMP-2 was observed in conditioned medium from monkey aortic endothelial cells (MAEC) following incubation with concentrations of UEA I ranging from 2 to 100 micrograms/ml. The increase in the 62-kDa MMP-2 gelatinolytic activity was not reflected by a rise in MMP-2 gene expression. The UEA I-mediated activation of MMP-2 was blocked by L-fucose, which competes with UEA I for binding to alpha-fucose. These findings may suggest that a similar in vivo mechanism exists, whereby adhesive interactions between tumor cell lectins and endothelial cells can mediate MMP-2 activation.

  13. Matrix Metalloproteinase Activities And Some Hormones Levels During Gestation Period In Cows

    International Nuclear Information System (INIS)

    TEAMA, F.E.

    2010-01-01

    Many factors including proteases, growth factors and hormones play important role in implantation and tissue remodelling of endometrium during different stages of gestation.Matrix metalloproteinases (MMP) such as gelatinases mainly MMP-2 and MMP-9 are implicated in the degradation of extracellular matrix for tissue remodelling.The aim of the present study is to evaluate the role of matrix metalloproteinases (MMP-2 and MMP-9) and hormones including progesterone (P4) and estradiol (E2) in the gestation process. The enzyme activities of MMP-2 and MMP-9 in serum collected from 8 Brown Swiss cows during different periods of gestation using zymography technique were examined. Hormonal levels for both P4 and E2 were determined using radioimmunoassay and also total proteins were estimated. A significant increase in MMP-2 activity by about 98%, 115% and 110% in the 1 st , 2 nd and 3 rd trimester of gestation were recorded, respectively, whereas it increased to be 185% in the pre-partum period as compared to non-pregnant cows (P nd trimester was recorded where the activity elevated by about 85% of non-pregnant controls (P st and 3 rd trimesters, the enzyme activity was not detectable. P4 level was increased gradually until its maximum at the 2 nd trimester then decreased until pre-partum.E2 level recorded too little increase at the beginning of the 1 st and 2 nd trimesters then sharply increased at the 3 rd one reached its maximum at pre-partum. There were significant decreases in total protein concentrations in the 2 nd and 3 rd trimesters then reached the lowest level before parturition .It could be concluded that the high activity of MMP-2 but not MMP-9 enzyme has important role throughout the gestation period in cows and P4 has important role in the fetal growth and E2 in the placental loss.

  14. Cortisol/cortisone ratio and matrix metalloproteinase-9 activity are associated with pediatric primary hypertension.

    Science.gov (United States)

    Martinez-Aguayo, Alejandro; Campino, Carmen; Baudrand, Rene; Carvajal, Cristian A; García, Hernán; Aglony, Marlene; Bancalari, Rodrigo; García, Lorena; Loureiro, Carolina; Vecchiola, Andrea; Tapia-Castillo, Alejandra; Valdivia, Carolina; Sanhueza, Sebastian; Fuentes, Cristobal A; Lagos, Carlos F; Solari, Sandra; Allende, Fidel; Kalergis, Alexis M; Fardella, Carlos E

    2016-09-01

    To identify novel biomarkers associated with pediatric primary hypertension. We recruited 350 participants (4-16 years). Anthropometric parameters and aldosterone, plasma renin activity, cortisol, cortisone, Homeostasis Model Assessment Insulin Resistance (HOMA-IR), high-sensitivity C-reactive protein, adiponectin, IL-6, plasminogen activator inhibitor type 1 levels and matrix metalloproteinase-9 and matrix metalloproteinase-2 (MMP-9 and MMP-2) activities were measured. Genomic DNA was isolated. Patients with altered glucose metabolism, severe obesity [BMI-SD score (BMI-SDS) > 2.5], renovascular disease, primary aldosteronism and apparent mineralocorticoid excess syndrome were excluded. In selected participants (n = 320), SBP was positively correlated with BMI-SDS (r = 0.382, P cortisol/cortisone ratio (r = 0.231, P cortisol/cortisone ratio (P cortisol/cortisone ratio (OR = 3.92; 95% CI = 1.98-7.71) and increased MMP-9 activity (OR = 4.23; 95% CI = 2.15-8.32). We report that MMP-9 activity and the cortisol/cortisone ratio were higher in pediatric primary hypertensive patients, and these associations were independent of the effect of obesity. The potential role of these novel biomarkers in predicting hypertension risk and blood pressure regulation warrants further investigation.

  15. Effect of the glass transition temperature on alpha-amylase activity in a starch matrix.

    Science.gov (United States)

    Chaudhary, Vinita; Panyoyai, Naksit; Small, Darryl M; Shanks, Robert A; Kasapis, Stefan

    2017-02-10

    This study optimises a protocol for the estimation of α-amylase activity in a condensed starch matrix in the vicinity of the glass transition region. Enzymatic activity on the vitrified starch system was compared with that of a reference substrate, maltodextrin. The activity was assayed as the rate of release of reducing sugar using a dinitrosalicylic acid procedure. The condensed carbohydrate matrices served the dual purpose of acting as a substrate as well as producing a pronounced effect on the ability to enzymatic hydrolysis. Activation energies were estimated throughout the glass transition region of condensed carbohydrate preparations based on the concept of the spectroscopic shift factor. Results were used to demonstrate a considerable moderation by the mechanical glass transition temperature, beyond the expected linear effect of the temperature dependence, on the reaction rate of starch hydrolysis by α-amylase in comparison with the low-molecular weight chain of maltodextrin. Copyright © 2016. Published by Elsevier Ltd.

  16. Spontaneous and cytokine induced expression and activity of matrix metalloproteinases in human colonic epithelium

    DEFF Research Database (Denmark)

    Pedersen, G; Saermark, T; Kirkegaard, T

    2009-01-01

    levels in cells from inflamed IBD mucosa. MMP-2 and -8 mRNA were expressed inconsistently and MMP-11, -13 and -14 mRNA undetectable. Proteolytic MMP activity was detected in CEC supernatants and the level was increased significantly in inflamed IBD epithelium. The enzyme activity was inhibited strongly......Matrix metalloproteinases (MMPs) have been implicated in tissue damage associated with inflammatory bowel disease (IBD).As the role of the intestinal epithelium in this process is unknown, we determined MMP expression and enzyme activity in human colonic epithelial cells (CEC). MMP mRNA expression...... was assessed by reverse transcription-polymerase chain reaction in HT-29 and DLD-1 cells and in CEC isolated from biopsies from IBD and control patients. Total MMP activity in the cells was measured by a functional assay, based on degradation of a fluorescent synthetic peptide containing the specific bond...

  17. Distribution and activity levels of matrix metalloproteinase 2 and 9 in canine and feline osteosarcoma.

    Science.gov (United States)

    Gebhard, Christiane; Fuchs-Baumgartinger, Andrea; Razzazi-Fazeli, Ebrahim; Miller, Ingrid; Walter, Ingrid

    2016-01-01

    Overexpression of matrix metalloproteinases (MMPs) has been associated with increased tumor aggressiveness and metastasis dissemination. We investigated whether the contrasting metastatic behavior of feline and canine osteosarcoma is related to levels and activities of MMP2 and MMP9. Zymography and immunohistochemistry were used to determine expression levels of MMP2 and MMP9 in canine and feline osteosarcoma. Using immunohistochemistry, increased MMP9 levels were identified in most canine osteosarcomas, whereas cat samples more often displayed moderate levels. High levels of pro-MMP9, pro-MMP2, and active MMP2 were detected by gelatin zymography in both species, with significantly higher values for active MMP2 in canine osteosarcoma. These findings indicate that MMP2 is probably involved in canine and feline osteosarcoma and their expression and activity could be associated with the different metastatic behavior of canine and feline osteosarcoma.

  18. Relative contribution of matrix metalloprotease and cysteine protease activities to cytokine-stimulated articular cartilage degradation

    DEFF Research Database (Denmark)

    Sondergaard, B C; Henriksen, K; Wulf, H

    2006-01-01

    OBJECTIVE: Both matrix metalloprotease (MMP) activity and cathepsin K (CK) activity have been implicated in cartilage turnover. We investigated the relative contribution of MMP activity and CK activity in cartilage degradation using ex vivo and in vivo models. METHODS: Bovine articular cartilage...... explants were stimulated with oncostatin M (OSM) 10 ng/ml and tumor necrosis factor-alpha (TNF-alpha) 20 ng/ml in the presence or absence of the broad-spectrum MMP inhibitor GM6001 and the cysteine protease inhibitor, E64. Cartilage degradation was evaluated in the conditioned medium by glycosaminoglycans...... was measured from CK-deficient mice. RESULTS: OSM and TNF-alpha combined induced significant (Pcartilage degradation products measured by hydroxyproline and CTX-II compared to vehicle control. The cytokines potently induced MMP expression, assessed by zymography, and CK expression...

  19. Understanding the Relationship between Red Wine Matrix, Tannin Activity, and Sensory Properties.

    Science.gov (United States)

    Watrelot, Aude A; Byrnes, Nadia K; Heymann, Hildegarde; Kennedy, James A

    2016-11-30

    One major red wine mouthfeel characteristic, astringency, is derived from grape-extracted tannins and is considered to be a result of interaction with salivary proteins and the oral mucosa. To improve our understanding of the role that the enthalpy of interaction of tannin with a hydrophobic surface (tannin activity) has in astringency perception, a chromatographic method was used to determine the tannin concentration and activity of 34 Cabernet Sauvignon wines, as well as sensory analysis done on 13 of those wines. In addition, astringency-relevant matrix parameters (pH, titratable acidity, ethanol, glucose, and fructose) were measured across all wines. Tannin activity was not significantly correlated with any matrix variables, and the perception of drying and grippy was not correlated with tannin concentration and activity. However, ethanol content was well related to mouthfeel attributes and appeared to drive perceived drying. Although fructose and glucose content were well correlated, they did not drive the perception of sweetness, which is explained by the well-known mixture suppression effect.

  20. Chromium liquid waste inertization in an inorganic alkali activated matrix: Leaching and NMR multinuclear approach

    International Nuclear Information System (INIS)

    Ponzoni, Chiara; Lancellotti, Isabella; Barbieri, Luisa; Spinella, Alberto; Saladino, Maria Luisa; Martino, Delia Chillura; Caponetti, Eugenio; Armetta, Francesco; Leonelli, Cristina

    2015-01-01

    Highlights: • Inertization of chromium liquid waste in aluminosilicate matrix. • Water less inertization technique exploiting the waste water content. • Liquid waste inertization without drying step. • Long term stabilization study through leaching test. • SEM analysis and 29 Si and 27 Al MAS NMR in relation with long curing time. - Abstract: A class of inorganic binders, also known as geopolymers, can be obtained by alkali activation of aluminosilicate powders at room temperature. The process is affected by many parameters (curing time, curing temperature, relative humidity etc.) and leads to a resistant matrix usable for inertization of hazardous waste. In this study an industrial liquid waste containing a high amount of chromium (≈2.3 wt%) in the form of metalorganic salts is inertized into a metakaolin based geopolymer matrix. One of the innovative aspects is the exploitation of the water contained in the waste for the geopolymerization process. This avoided any drying treatment, a common step in the management of liquid hazardous waste. The evolution of the process - from the precursor dissolution to the final geopolymer matrix hardening - of different geopolymers containing a waste amount ranging from 3 to 20% wt and their capability to inertize chromium cations were studied by: i) the leaching tests, according to the EN 12,457 regulation, at different curing times (15, 28, 90 and 540 days) monitoring releases of chromium ions (Cr(III) and Cr(VI)) and the cations constituting the aluminosilicate matrix (Na, Si, Al); ii) the humidity variation for different curing times (15 and 540 days); iii) SEM characterization at different curing times (28 and 540 days); iv) the trend of the solution conductivity and pH during the leaching test; v) the characterization of the short-range ordering in terms of T−O−T bonds (where T is Al or Si) by 29 Si and 27 Al solid state magic-angle spinning nuclear magnetic resonance (ss MAS NMR) for geopolymers

  1. Chromium liquid waste inertization in an inorganic alkali activated matrix: Leaching and NMR multinuclear approach

    Energy Technology Data Exchange (ETDEWEB)

    Ponzoni, Chiara, E-mail: chiara.ponzoni@unimore.it [University of Modena and Reggio Emilia, Department of Engineering “Enzo Ferrari”, Modena (Italy); Lancellotti, Isabella; Barbieri, Luisa [University of Modena and Reggio Emilia, Department of Engineering “Enzo Ferrari”, Modena (Italy); Spinella, Alberto; Saladino, Maria Luisa [University of Palermo CGA-UniNetLab, Palermo (Italy); Martino, Delia Chillura [University of Palermo, Department STEBICEF, Palermo (Italy); Caponetti, Eugenio [University of Palermo CGA-UniNetLab, Palermo (Italy); University of Palermo, Department STEBICEF, Palermo (Italy); Armetta, Francesco [University of Palermo, Department STEBICEF, Palermo (Italy); Leonelli, Cristina [University of Modena and Reggio Emilia, Department of Engineering “Enzo Ferrari”, Modena (Italy)

    2015-04-09

    Highlights: • Inertization of chromium liquid waste in aluminosilicate matrix. • Water less inertization technique exploiting the waste water content. • Liquid waste inertization without drying step. • Long term stabilization study through leaching test. • SEM analysis and {sup 29}Si and {sup 27}Al MAS NMR in relation with long curing time. - Abstract: A class of inorganic binders, also known as geopolymers, can be obtained by alkali activation of aluminosilicate powders at room temperature. The process is affected by many parameters (curing time, curing temperature, relative humidity etc.) and leads to a resistant matrix usable for inertization of hazardous waste. In this study an industrial liquid waste containing a high amount of chromium (≈2.3 wt%) in the form of metalorganic salts is inertized into a metakaolin based geopolymer matrix. One of the innovative aspects is the exploitation of the water contained in the waste for the geopolymerization process. This avoided any drying treatment, a common step in the management of liquid hazardous waste. The evolution of the process - from the precursor dissolution to the final geopolymer matrix hardening - of different geopolymers containing a waste amount ranging from 3 to 20% wt and their capability to inertize chromium cations were studied by: i) the leaching tests, according to the EN 12,457 regulation, at different curing times (15, 28, 90 and 540 days) monitoring releases of chromium ions (Cr(III) and Cr(VI)) and the cations constituting the aluminosilicate matrix (Na, Si, Al); ii) the humidity variation for different curing times (15 and 540 days); iii) SEM characterization at different curing times (28 and 540 days); iv) the trend of the solution conductivity and pH during the leaching test; v) the characterization of the short-range ordering in terms of T−O−T bonds (where T is Al or Si) by {sup 29}Si and {sup 27}Al solid state magic-angle spinning nuclear magnetic resonance (ss MAS NMR) for

  2. Matrix Metalloproteinase Activity in Infections by an Encephalitic Virus, Mouse Adenovirus Type 1

    Science.gov (United States)

    Ashley, Shanna L.; Pretto, Carla D.; Stier, Matthew T.; Kadiyala, Padma; Castro-Jorge, Luiza; Hsu, Tien-Huei; Doherty, Robert; Carnahan, Kelly E.; Castro, Maria G.; Lowenstein, Pedro R.

    2017-01-01

    ABSTRACT Mouse adenovirus type 1 (MAV-1) infection causes encephalitis in susceptible strains of mice and alters the permeability of infected brains to small molecules, which indicates disruption of the blood-brain barrier (BBB). Under pathological conditions, matrix metalloproteinases (MMPs) can disrupt the BBB through their proteolytic activity on basement membrane and tight junction proteins. We examined whether MAV-1 infection alters MMP activity in vivo and in vitro. Infected MAV-1-susceptible SJL mice had higher MMP2 and MMP9 activity in brains, measured by gelatin zymography, than mock-infected mice. Infected MAV-1-resistant BALB/c mice had MMP activity levels equivalent to those in mock infection. Primary SJL mouse brain endothelial cells (a target of MAV-1 in vivo) infected ex vivo with MAV-1 had no difference in activities of secreted MMP2 and MMP9 from mock cells. We show for the first time that astrocytes and microglia are also infected in vivo by MAV-1. Infected mixed primary cultures of astrocytes and microglia had higher levels of MMP2 and MMP9 activity than mock-infected cells. These results indicate that increased MMP activity in the brains of MAV-1-infected susceptible mice may be due to MMP activity produced by endothelial cells, astrocytes, and microglia, which in turn may contribute to BBB disruption and encephalitis in susceptible mice. IMPORTANCE RNA and DNA viruses can cause encephalitis; in some cases, this is accompanied by MMP-mediated disruption of the BBB. Activated MMPs degrade extracellular matrix and cleave tight-junction proteins and cytokines, modulating their functions. MAV-1 infection of susceptible mice is a tractable small-animal model for encephalitis, and the virus causes disruption of the BBB. We showed that MAV-1 infection increases enzymatic activity of two key MMPs known to be secreted and activated in neuroinflammation, MMP2 and MMP9, in brains of susceptible mice. MAV-1 infects endothelial cells, astrocytes, and

  3. Tissue- and Cell-Specific Co-localization of Intracellular Gelatinolytic Activity and Matrix Metalloproteinase 2

    Science.gov (United States)

    Solli, Ann Iren; Fadnes, Bodil; Winberg, Jan-Olof; Uhlin-Hansen, Lars

    2013-01-01

    Matrix metalloproteinase 2 (MMP-2) is a proteolytic enzyme that degrades extracellular matrix proteins. Recent studies indicate that MMP-2 also has a role in intracellular proteolysis during various pathological conditions, such as ischemic injuries in heart and brain and in tumor growth. The present study was performed to map the distribution of intracellular MMP-2 activity in various mouse tissues and cells under physiological conditions. Samples from normal brain, heart, lung, liver, spleen, pancreas, kidney, adrenal gland, thyroid gland, gonads, oral mucosa, salivary glands, esophagus, intestines, and skin were subjected to high-resolution in situ gelatin zymography and immunohistochemical staining. In hepatocytes, cardiac myocytes, kidney tubuli cells, epithelial cells in the oral mucosa as well as in excretory ducts of salivary glands, and adrenal cortical cells, we found strong intracellular gelatinolytic activity that was significantly reduced by the metalloprotease inhibitor EDTA but not by the cysteine protease inhibitor E-64. Furthermore, the gelatinolytic activity was co-localized with MMP-2. Western blotting and electron microscopy combined with immunogold labeling revealed the presence of MMP-2 in different intracellular compartments of isolated hepatocytes. Our results indicate that MMP-2 takes part in intracellular proteolysis in specific tissues and cells during physiological conditions. PMID:23482328

  4. Enhanced activation of matrix metalloproteinase-9 correlates with the degree of papillary thyroid carcinoma infiltration

    Science.gov (United States)

    Marečko, Ilona; Cvejić, Dubravka; Šelemetjev, Sonja; Paskaš, Svetlana; Tatić, Svetislav; Paunović, Ivan; Savin, Svetlana

    2014-01-01

    Aim To determine whether matrix metalloproteinase-9 (MMP-9) may be a useful adjunctive tool for predicting unfavorable biological behavior of papillary thyroid carcinoma (PTC) by evaluating the expression profile and proteolytic activity of MMP-9 in PTC by different techniques and correlating the findings with clinicopathological prognostic factors. Methods Immunohistochemical localization of MMP-9 was analyzed with antibodies specific for either total or active MMP-9. Activation ratios of MMP-9 were calculated by quantifying gel zymography bands. Enzymatic activity of MMP-9 was localized by in situ zymography after inhibiting MMP-2 activity. Results Immunostaining of total and active MMP-9 was observed in tumor tissue and occasionally in non-neoplastic epithelium. Only active MMP-9 was significantly associated with extrathyroid invasion, lymph-node metastasis, and the degree of tumor infiltration (P zymography revealed a correlation between the MMP-9 activation ratio and nodal involvement, extrathyroid invasion, and the degree of tumor infiltration. In situ zymography showed that gelatinases exerted their activity in tumor parenchymal and stromal cells. Moreover, after application of MMP-2 inhibitor, the remaining gelatinase activity, corresponding to MMP-9, was highest in cancers with the most advanced degree of tumor infiltration. Conclusions This is the first report suggesting that the evaluation of active MMP-9 by immunohistochemistry and determination of its activation ratio by gelatin zymography may be a useful adjunct to the known clinicopathological factors in predicting tumor behavior. Most important, in situ zimography with an MMP-2 inhibitor for the first time demonstrated a strong impact of MMP-9 activity on the degree of tumor infiltration during PTC progression. PMID:24778099

  5. Effects of Resistance Training on Matrix Metalloproteinase Activity in Skeletal Muscles and Blood Circulation During Aging

    Directory of Open Access Journals (Sweden)

    Ivo V. de Sousa Neto

    2018-03-01

    Full Text Available Aging is a complex, multifactorial process characterized by the accumulation of deleterious effects, including biochemical adaptations of the extracellular matrix (ECM. The purpose of this study was to investigate the effects of 12 weeks of resistance training (RT on metalloproteinase 2 (MMP-2 activity in skeletal muscles and, MMP-2 and MMP-9 activity in the blood circulation of young and old rats. Twenty-eight Wistar rats were randomly divided into four groups (n = 7 per group: young sedentary (YS; young trained (YT, old sedentary (OS, and old trained (OT. The stair climbing RT consisted of one training session every 2 other day, with 8–12 dynamic movements per climb. The animals were euthanized 48 h after the end of the experimental period. MMP-2 and MMP-9 activity was measured by zymography. There was higher active MMP-2 activity in the lateral gastrocnemius and flexor digitorum profundus muscles in the OT group when compared to the OS, YS, and YT groups (p ≤ 0.001. Moreover, there was higher active MMP-2 activity in the medial gastrocnemius muscle in the OT group when compared to the YS and YT groups (p ≤ 0.001. The YS group presented lower active MMP-2 activity in the soleus muscle than the YT, OS, OT groups (p ≤ 0.001. With respect to active MMP-2/9 activity in the bloodstream, the OT group displayed significantly reduced activity (p ≤ 0.001 when compared to YS and YT groups. In conclusion, RT up-regulates MMP-2 activity in aging muscles, while down-regulating MMP-2 and MMP-9 in the blood circulation, suggesting that it may be a useful tool for the maintenance of ECM remodeling.

  6. Photorefractive keratectomy: measuring the matrix metalloproteinase activity and chondroitin sulfate concentration in tear fluid

    Directory of Open Access Journals (Sweden)

    Tetsuya Mutoh

    2010-09-01

    Full Text Available Tetsuya Mutoh, Masaya Nishio, Yukihiro Matsumoto, Kiyomi Arai, Makoto ChikudaDepartment of Ophthalmology, Dokkyo Medical University Koshigaya Hospital, Saitama, JapanAbstract: We herein report the case of a 20-year-old man who underwent a photorefractive keratectomy (PRK. We measured matrix metalloproteinase-9 (MMP-9 activity and chondroitin 4 sulfate and chondroitin 6 sulfate concentrations in tear fluid. Tear fluid was collected preoperatively via microcapillary tube, and was collected postoperatively on the first and fourth days, and after one week, one month, three months, and six months. Samples were formulated by dilution with 200 µL of saline. MMP-9 activity was analyzed by an enzyme immunocapture activity assay, and the concentrations of chondroitin sulfate were analyzed by enzyme-linked immunosorbent assay. No complications were observed after surgery, except for a minimal subepithelial haze. Although MMP-9 activity changed on the fourth postoperative day, the activity changed only minimally at this time. Chondroitin 4 sulfate concentrations in tear fluid increased dramatically from one week to one month, decreased transiently at three months, and increased by six months. The chondroitin 6 sulfate concentration did not normalize within one week, and decreased from one week to three months compared with the preoperative score, and was close to the preoperative score at six months. We conclude that corneal wound healing was still incomplete six months after PRK, and chondroitin 4 sulfate appears to be critical in this process.Keywords: matrix metalloproteinase, chondroitin sulfate, human tear fluid, photorefractive keratectomy, corneal wound healing

  7. Plasma membrane factor XIIIA transglutaminase activity regulates osteoblast matrix secretion and deposition by affecting microtubule dynamics.

    Directory of Open Access Journals (Sweden)

    Hadil F Al-Jallad

    2011-01-01

    Full Text Available Transglutaminase activity, arising potentially from transglutaminase 2 (TG2 and Factor XIIIA (FXIIIA, has been linked to osteoblast differentiation where it is required for type I collagen and fibronectin matrix deposition. In this study we have used an irreversible TG-inhibitor to 'block -and-track' enzyme(s targeted during osteoblast differentiation. We show that the irreversible TG-inhibitor is highly potent in inhibiting osteoblast differentiation and mineralization and reduces secretion of both fibronectin and type I collagen and their release from the cell surface. Tracking of the dansyl probe by Western blotting and immunofluorescence microscopy demonstrated that the inhibitor targets plasma membrane-associated FXIIIA. TG2 appears not to contribute to crosslinking activity on the osteoblast surface. Inhibition of FXIIIA with NC9 resulted in defective secretory vesicle delivery to the plasma membrane which was attributable to a disorganized microtubule network and decreased microtubule association with the plasma membrane. NC9 inhibition of FXIIIA resulted in destabilization of microtubules as assessed by cellular Glu-tubulin levels. Furthermore, NC9 blocked modification of Glu-tubulin into 150 kDa high-molecular weight Glu-tubulin form which was specifically localized to the plasma membrane. FXIIIA enzyme and its crosslinking activity were colocalized with plasma membrane-associated tubulin, and thus, it appears that FXIIIA crosslinking activity is directed towards stabilizing the interaction of microtubules with the plasma membrane. Our work provides the first mechanistic cues as to how transglutaminase activity could affect protein secretion and matrix deposition in osteoblasts and suggests a novel function for plasma membrane FXIIIA in microtubule dynamics.

  8. High resolution in situ zymography reveals matrix metalloproteinase activity at glutamatergic synapses.

    Science.gov (United States)

    Gawlak, M; Górkiewicz, T; Gorlewicz, A; Konopacki, F A; Kaczmarek, L; Wilczynski, G M

    2009-01-12

    Synaptic plasticity involves remodeling of extracellular matrix. This is mediated, in part, by enzymes of the matrix metalloproteinase (MMP) family, in particular by gelatinase MMP-9. Accordingly, there is a need of developing methods to visualize gelatinolytic activity at the level of individual synapses, especially in the context of neurotransmitters receptors. Here we present a high-resolution fluorescent in situ zymography (ISZ), performed in thin sections of the alcohol-fixed and polyester wax-embedded brain tissue of the rat (Rattus norvegicus), which is superior to the current ISZ protocols. The method allows visualization of structural details up to the resolution-limit of light microscopy, in conjunction with immunofluorescent labeling. We used this technique to visualize and quantify gelatinolytic activity at the synapses in control and seizure-affected rat brain. In particular, we demonstrated, for the first time, frequent colocalization of gelatinase(s) with synaptic N-methyl-D-aspartic acid (NMDA)- and AMPA-type glutamate receptors. We believe that our method represents a valuable tool to study extracellular proteolytic processes at the synapses, it could be used, as well, to investigate proteinase involvement in a range of physiological and pathological phenomena in the nervous system.

  9. Buddleja officinalis inhibits high glucose-induced matrix metalloproteinase activity in human umbilical vein endothelial cells.

    Science.gov (United States)

    Lee, Yun Jung; Kang, Dae Gill; Kim, Jin Sook; Lee, Ho Sub

    2008-12-01

    The aim of the present investigation was to investigate whether an aqueous extract of Buddleja officinalis (ABO), a traditional Korean herbal medicine, suppresses the endothelial extracellular matrix degradation under high glucose condition. The incubation with high concentration of glucose (25 mM) increased significantly matrix metalloproteinase (MMP)-2/-9 expressions and activities in primary cultured human umbilical vein endothelial cells (HUVEC). Pretreatment with ABO decreased high glucose-induced increase of MMP-2/-9 activities in a dose-dependent manner. Real time qRT-PCR revealed that high glucose-induced MMP-2/-9 mRNA expression levels were attenuated by pretreatment with ABO. High glucose-induced MCP-1 and IL-8 mRNA expression levels also decreased by ABO. ABO decreased high glucose-induced hydrogen peroxide production, oxidative stress marker. These results provide new insights into the pathophysiological mechanisms for anti-inflammatory properties of ABO in vascular diseases associated with diabetes mellitus. (c) 2008 John Wiley & Sons, Ltd.

  10. Ultrasound-responsive gene-activated matrices for osteogenic gene therapy using matrix-assisted sonoporation.

    Science.gov (United States)

    Nomikou, N; Feichtinger, G A; Saha, S; Nuernberger, S; Heimel, P; Redl, H; McHale, A P

    2018-01-01

    Gene-activated matrix (GAM)-based therapeutics for tissue regeneration are limited by efficacy, the lack of spatiotemporal control and availability of target cells, all of which impact negatively on their translation to the clinic. Here, an advanced ultrasound-responsive GAM is described containing target cells that facilitates matrix-assisted sonoporation (MAS) to induce osteogenic differentiation. Ultrasound-responsive GAMs consisting of fibrin/collagen hybrid-matrices containing microbubbles, bone morphogenetic protein BMP2/7 coexpression plasmids together with C2C12 cells were treated with ultrasound either in vitro or following parenteral intramuscular implantation in vivo. Using direct measurement for alkaline phosphatase activity, von Kossa staining and immunohistochemical analysis for osteocalcin expression, MAS-stimulated osteogenic differentiation was confirmed in the GAMs in vitro 7 days after treatment with ultrasound. At day 30 post-treatment with ultrasound, ectopic osteogenic differentiation was confirmed in vivo using X-ray microcomputed tomography and histological analysis. Osteogenic differentiation was indicated by the presence of ectopic bone structures in all animals treated with MAS. In addition, bone volumes in this group were statistically greater than those in the control groups. This novel approach of incorporating a MAS capability into GAMs could be exploited to facilitate ex vivo gene transfer with subsequent surgical implantation or alternatively provide a minimally invasive means of stimulating in situ transgene delivery for osteoinductive gene-based therapies. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  11. Cytokine Response to Diet and Exercise Affects Atheromatous Matrix Metalloproteinase-2/9 Activity in Mice.

    Science.gov (United States)

    Shon, Soo-Min; Jang, Hee Jeong; Schellingerhout, Dawid; Kim, Jeong-Yeon; Ryu, Wi-Sun; Lee, Su-Kyoung; Kim, Jiwon; Park, Jin-Yong; Oh, Ji Hye; Kang, Jeong Wook; Je, Kang-Hoon; Park, Jung E; Kim, Kwangmeyung; Kwon, Ick Chan; Lee, Juneyoung; Nahrendorf, Matthias; Park, Jong-Ho; Kim, Dong-Eog

    2017-09-25

    The aim of this study is to identify the principal circulating factors that modulate atheromatous matrix metalloproteinase (MMP) activity in response to diet and exercise.Methods and Results:Apolipoprotein-E knock-out (ApoE -/- ) mice (n=56) with pre-existing plaque, fed either a Western diet (WD) or normal diet (ND), underwent either 10 weeks of treadmill exercise or had no treatment. Atheromatous MMP activity was visualized using molecular imaging with a MMP-2/9 activatable near-infrared fluorescent (NIRF) probe. Exercise did not significantly reduce body weight, visceral fat, and plaque size in either WD-fed animals or ND-fed animals. However, atheromatous MMP-activity was different; ND animals that did or did not exercise had similarly low MMP activities, WD animals that did not exercise had high MMP activity, and WD animals that did exercise had reduced levels of MMP activity, close to the levels of ND animals. Factor analysis and path analysis showed that soluble vascular cell adhesion molecule (sVCAM)-1 was directly positively correlated to atheromatous MMP activity. Adiponectin was indirectly negatively related to atheromatous MMP activity by way of sVCAM-1. Resistin was indirectly positively related to atheromatous MMP activity by way of sVCAM-1. Visceral fat amount was indirectly positively associated with atheromatous MMP activity, by way of adiponectin reduction and resistin elevation. MMP-2/9 imaging of additional mice (n=18) supported the diet/exercise-related anti-atherosclerotic roles for sVCAM-1. Diet and exercise affect atheromatous MMP activity by modulating the systemic inflammatory milieu, with sVCAM-1, resistin, and adiponectin closely interacting with each other and with visceral fat.

  12. Activation of matrix metalloproteinases following anti-Aβ immunotherapy; implications for microhemorrhage occurrence

    Directory of Open Access Journals (Sweden)

    Ridnour Lisa A

    2011-09-01

    Full Text Available Abstract Background Anti-Aβ immunotherapy is a promising approach to the prevention and treatment of Alzheimer's disease (AD currently in clinical trials. There is extensive evidence, both in mice and humans that a significant adverse event is the occurrence of microhemorrhages. Also, vasogenic edema was reported in phase 2 of a passive immunization clinical trial. In order to overcome these vascular adverse effects it is critical that we understand the mechanism(s by which they occur. Methods We have examined the matrix metalloproteinase (MMP protein degradation system in two previously published anti-Aβ immunotherapy studies. The first was a passive immunization study in which we examined 22 month old APPSw mice that had received anti-Aβ antibodies for 1, 2 or 3 months. The second is an active vaccination study in which we examined 16 month old APPSw/NOS2-/- mice treated with Aβ vaccination for 4 months. Results There is a significant activation of the MMP2 and MMP9 proteinase degradation systems by anti-Aβ immunotherapy, regardless of whether this is delivered through active vaccination or passive immunization. We have characterized this activation by gene expression, protein expression and zymography assessment of MMP activity. Conclusions Since the MMP2 and MMP9 systems are heavily implicated in the pathophysiology of intracerbral hemorrhage, these data may provide a potential mechanism of microhemorrhage due to immunotherapy. Increased activity of the MMP system, therefore, is likely to be a major factor in increased microhemorrhage occurrence.

  13. MMP-9 directed shRNAs as relevant inhibitors of matrix metalloproteinase 9 activity and signaling

    Directory of Open Access Journals (Sweden)

    Ewa Nowak

    2013-08-01

    Full Text Available Introduction: The main function of matrix metalloproteinases is the degradation of extracellular matrix components, which is related to changes in the proliferation of cells, their differentiation, motility, and death. MMPs play an important role in physiological processes such as embryogenesis, angiogenesis and tissue remodeling. The increase of MMPs activity is also observed in pathological conditions including tumorigenesis where MMP-2 (gelatinase A and MMP-9 (gelatinase B show the ability to degrade the basement membrane of vessels and they are involved in metastasis. The aim of our study was to verify the changes of MMP-9 enzymatic activity and the mobility of cells after inhibition of MMP-9 gene expression.Material and Methods: The oligonucleotide shRNA insert had been designed to silence MMP-9 gene expression and was cloned into the pSUPER.neo expression vector. The construct was introduced into the HeLa (CCL-2 cervical cancer cells by lipotransfection. Simultaneously in control cells MMP-9 were inhibited by doxycycline. Changes in activity of MMP-9 were analyzed by gelatin zymography and wound-healing assay.Results/Conclusions: Gelatin zymography allowed us to confirm that activity of MMP-9 in cells transfected by shRNA-MMP-9 and treated by doxycycline were similar and significantly lower in comparison with control cells. Phenotypic tests of migration in vitro confirm statistically significant (P<0.05 changes in cell migration – control cells healed 3 to 5 times faster in comparison with transfected or doxycycline treated cells. Our studies show the significant role of MMP-9 in mobility and invasiveness of tumor cells, thus indicating a potential target point of interest for gene therapy.

  14. Positive correlation between disease activity index and matrix metalloproteinases activity in a rat model of colitis.

    Science.gov (United States)

    Oliveira, Luiz Gustavo de; Cunha, André Luiz da; Duarte, Amaury Caiafa; Castañon, Maria Christina Marques Nogueira; Chebli, Júlio Maria Fonseca; Aguiar, Jair Adriano Kopke de

    2014-01-01

    Inflammatory bowel disease, including ulcerative colitis and Crohn's disease, comprising a broad spectrum of diseases those have in common chronic inflammation of the gastrointestinal tract, histological alterations and an increased activity levels of certain enzymes, such as, metalloproteinases. Evaluate a possible correlation of disease activity index with the severity of colonic mucosal damage and increased activity of metalloproteinases in a model of ulcerative colitis induced by dextran sulfate sodium. Colitis was induced by oral administration of 5% dextran sulfate sodium for seven days in this group (n=10), whereas control group (n=16) received water. Effects were analyzed daily by disease activity index. In the seventh day, animals were euthanized and hematological measurements, histological changes (hematoxylin and eosin and Alcian Blue staining), myeloperoxidase and metalloproteinase activities (MMP-2 and MMP-9) were determined. Dextran sulfate sodium group showed elevated disease activity index and reduced hematological parameters. Induction of colitis caused tissue injury with loss of mucin and increased myeloperoxidase (Pcorrelation with the degree of histopathological changes after induction of colitis, and this result may be related mainly to the increased activity of MMP-9 and mieloperoxidase.

  15. Monolithic Active Pixel Matrix with Binary Counters ASIC with nested wells

    International Nuclear Information System (INIS)

    Fahim, F; Deptuch, G; Holm, S; Shenai, A; Lipton, R

    2013-01-01

    Monolithic Active Matrix with Binary Counters (MAMBO) V ASIC has been designed for detecting and measuring low energy X-rays. A nested well structure with a buried n-well (BNW) and a deeper buried p-well (BPW) is used to electrically isolate the detector from the electronics. BNW acts as an AC ground to electrical signals and behaves as a shield. BPW allows for a homogenous electric field in the entire detector volume. The ASIC consists of a matrix of 50 × 52 pixels, each of 105x105μm 2 . Each pixel contains analog functionality accomplished by a charge preamplifier, CR-RC 2 shaper and a baseline restorer. It also contains a window comparator with Upper and Lower thresholds which can be individually trimmed by 4 bit DACs to remove systematic offsets. The hits are registered by a 12 bit counter which is reconfigured as a shift register to serially output the data from the entire ASIC.

  16. Histone Deacetylase 3 Suppresses Erk Phosphorylation and Matrix Metalloproteinase (Mmp)-13 Activity in Chondrocytes

    Science.gov (United States)

    Carpio, Lomeli R.; Bradley, Elizabeth W.; Westendorf, Jennifer J.

    2017-01-01

    Histone deacetylase inhibitors are emerging therapies for many diseases including cancers and neurological disorders; however, these drugs are teratogens to the developing skeleton. Hdac3 is essential for proper endochondral ossification as its deletion in chondrocytes increases cytokine signaling and the expression of matrix remodeling enzymes. Here we explored the mechanism by which Hdac3 controls Mmp13 expression in chondrocytes. In Hdac3-depleted chondrocytes, Erk1/2 as well as its downstream substrate, Runx2, were hyperphosphorylated as a result of decreased expression and activity of the Erk1/2 specific phosphatase, Dusp6. Erk1/2 kinase inhibitors and Dusp6 adenoviruses reduced Mmp13 expression and partially rescued matrix production in Hdac3-deficient chondrocytes. Postnatal chondrocyte-specific deletion of Hdac3 with an inducible Col2a1-Cre caused premature production of pErk1/2 and Mmp13 in the growth plate. Thus, Hdac3 controls the temporal and spatial expression of tissue-remodeling genes in chondrocytes to ensure proper endochondral ossification during development. PMID:27662443

  17. On the influence of matrix's heterogeneity on uncertainty of gamma-spectrometry at activity assay of radioactive waste

    Directory of Open Access Journals (Sweden)

    V. S. Prokopenko

    2009-09-01

    Full Text Available The influence of the waste matrix heterogeneity on the flux density value of initial gamma quanta at the transport of quanta in the matrix was considered. It is shown that the waste heterogeneity leads to the positive shift of the average flux density value comparing with corresponding value for homogeneous waste if average value of the attenuation factor in heterogeneous matrix is equal to the attenuation factor of homogeneous matrix. Due to this the activity assay of heterogeneous waste by a technique which was calibrated by using a homogeneous standard (surrogate container the measurement results will be positively shifted, or, in other words, conservative estimation of the waste activity will be obtained.

  18. Extracellular matrix of collagen modulates arrhythmogenic activity of pulmonary veins through p38 MAPK activation.

    Science.gov (United States)

    Lu, Yen-Yu; Chen, Yao-Chang; Kao, Yu-Hsun; Chen, Shih-Ann; Chen, Yi-Jen

    2013-06-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia. Cardiac fibrosis with enhanced extracellular collagen plays a critical role in the pathophysiology of AF through structural and electrical remodeling. Pulmonary veins (PVs) are important foci for AF genesis. The purpose of this study was to evaluate whether collagen can directly modulate PV arrhythmogenesis. Action potentials and ionic currents were investigated in isolated male New Zealand rabbit PV cardiomyocytes with and without collagen incubation (10μg/ml, 5-7h) using the whole-cell patch-clamp technique. Compared to control PV cardiomyocytes (n=25), collagen-treated PV cardiomyocytes (n=22) had a faster beating rate (3.2±04 vs. 1.9±0.2Hz, pcollagen-treated PV cardiomyocytes showed a larger transient outward potassium current, small-conductance Ca(2+)-activated K(+) current, inward rectifier potassium current, pacemaker current, and late sodium current than control PV cardiomyocytes, but amplitudes of the sodium current, sustained outward potassium current, and L-type calcium current were similar. Collagen increased the p38 MAPK phosphorylation in PV cardiomyocytes as compared to control. The change of the spontaneous activity and action potential morphology were ameliorated by SB203580 (the p38 MAPK catalytic activity inhibitor), indicating that collagen can directly increase PV cardiomyocyte arrhythmogenesis through p38 MAPK activation, which may contribute to the pathogenesis of AF. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Acrolein activates matrix metalloproteinases by increasing reactive oxygen species in macrophages.

    Science.gov (United States)

    O'Toole, Timothy E; Zheng, Yu-Ting; Hellmann, Jason; Conklin, Daniel J; Barski, Oleg; Bhatnagar, Aruni

    2009-04-15

    Acrolein is a ubiquitous component of environmental pollutants such as automobile exhaust, cigarette, wood, and coal smoke. It is also a natural constituent of several foods and is generated endogenously during inflammation or oxidation of unsaturated lipids. Because increased inflammation and episodic exposure to acrolein-rich pollutants such as traffic emissions or cigarette smoke have been linked to acute myocardial infarction, we examined the effects of acrolein on matrix metalloproteinases (MMPs), which destabilize atherosclerotic plaques. Our studies show that exposure to acrolein resulted in the secretion of MMP-9 from differentiated THP-1 macrophages. Acrolein-treatment of macrophages also led to an increase in reactive oxygen species (ROS), free intracellular calcium ([Ca2+](i)), and xanthine oxidase (XO) activity. ROS production was prevented by allopurinol, but not by rotenone or apocynin and by buffering changes in [Ca2+](I) with BAPTA-AM. The increase in MMP production was abolished by pre-treatment with the antioxidants Tiron and N-acetyl cysteine (NAC) or with the xanthine oxidase inhibitors allopurinol or oxypurinol. Finally, MMP activity was significantly stimulated in aortic sections from apoE-null mice containing advanced atherosclerotic lesions after exposure to acrolein ex vivo. These observations suggest that acrolein exposure results in MMP secretion from macrophages via a mechanism that involves an increase in [Ca2+](I), leading to xanthine oxidase activation and an increase in ROS production. ROS-dependent activation of MMPs by acrolein could destabilize atherosclerotic lesions during brief episodes of inflammation or pollutant exposure.

  20. Acrolein-activated matrix metalloproteinase 9 contributes to persistent mucin production.

    Science.gov (United States)

    Deshmukh, Hitesh S; Shaver, Colleen; Case, Lisa M; Dietsch, Maggie; Wesselkamper, Scott C; Hardie, William D; Korfhagen, Thomas R; Corradi, Massimo; Nadel, Jay A; Borchers, Michael T; Leikauf, George D

    2008-04-01

    Chronic obstructive pulmonary disease (COPD), a global public health problem, is characterized by progressive difficulty in breathing, with increased mucin production, especially in the small airways. Acrolein, a constituent of cigarette smoke and an endogenous mediator of oxidative stress, increases airway mucin 5, subtypes A and C (MUC5AC) production; however, the mechanism remains unclear. In this study, increased mMUC5AC transcripts and protein were associated with increased lung matrix metalloproteinase 9 (mMMP9) transcripts, protein, and activity in acrolein-exposed mice. Increased mMUC5AC transcripts and mucin protein were diminished in gene-targeted Mmp9 mice [Mmp9((-/-))] or in mice treated with an epidermal growth factor receptor (EGFR) inhibitor, erlotinib. Acrolein also decreased mTissue inhibitor of metalloproteinase protein 3 (an MMP9 inhibitor) transcript levels. In a cell-free system, acrolein increased pro-hMMP9 cleavage and activity in concentrations (100-300 nM) found in sputum from subjects with COPD. Acrolein increased hMMP9 transcripts in human airway cells, which was inhibited by an MMP inhibitor, EGFR-neutralizing antibody, or a mitogen-activated protein kinase (MAPK) 3/2 inhibitor. Together these findings indicate that acrolein can initiate cleavage of pro-hMMP9 and EGFR/MAPK signaling that leads to additional MMP9 formation. Augmentation of hMMP9 activity, in turn, could contribute to persistent excessive mucin production.

  1. Acrolein activates matrix metalloproteinases by increasing reactive oxygen species in macrophages

    International Nuclear Information System (INIS)

    O'Toole, Timothy E.; Zheng Yuting; Hellmann, Jason; Conklin, Daniel J.; Barski, Oleg; Bhatnagar, Aruni

    2009-01-01

    Acrolein is a ubiquitous component of environmental pollutants such as automobile exhaust, cigarette, wood, and coal smoke. It is also a natural constituent of several foods and is generated endogenously during inflammation or oxidation of unsaturated lipids. Because increased inflammation and episodic exposure to acrolein-rich pollutants such as traffic emissions or cigarette smoke have been linked to acute myocardial infarction, we examined the effects of acrolein on matrix metalloproteinases (MMPs), which destabilize atherosclerotic plaques. Our studies show that exposure to acrolein resulted in the secretion of MMP-9 from differentiated THP-1 macrophages. Acrolein-treatment of macrophages also led to an increase in reactive oxygen species (ROS), free intracellular calcium ([Ca 2+ ] i ), and xanthine oxidase (XO) activity. ROS production was prevented by allopurinol, but not by rotenone or apocynin and by buffering changes in [Ca 2+ ] I with BAPTA-AM. The increase in MMP production was abolished by pre-treatment with the antioxidants Tiron and N-acetyl cysteine (NAC) or with the xanthine oxidase inhibitors allopurinol or oxypurinol. Finally, MMP activity was significantly stimulated in aortic sections from apoE-null mice containing advanced atherosclerotic lesions after exposure to acrolein ex vivo. These observations suggest that acrolein exposure results in MMP secretion from macrophages via a mechanism that involves an increase in [Ca 2+ ] I , leading to xanthine oxidase activation and an increase in ROS production. ROS-dependent activation of MMPs by acrolein could destabilize atherosclerotic lesions during brief episodes of inflammation or pollutant exposure.

  2. Effect of eosinophils activated with Alternaria on the production of extracellular matrix from nasal fibroblasts.

    Science.gov (United States)

    Shin, Seung-Heon; Ye, Mi-Kyung; Choi, Sung-Yong; Kim, Yee-Hyuk

    2016-06-01

    Eosinophils and fibroblasts are known to play major roles in the pathogenesis of nasal polyps. Fungi are commonly found in nasal secretion and are associated with airway inflammation. To investigate whether activated eosinophils by airborne fungi can influence the production of extracellular matrix (ECM) from nasal fibroblasts. Inferior turbinate and nasal polyp fibroblasts were stimulated with Alternaria or Aspergillus, respectively, for 24 hours and ECM messenger RNA (mRNA) and protein expressions were measured. Eosinophils isolated from healthy volunteers were stimulated with Alternaria or Aspergillus for 4 hours then superoxide, eosinophil peroxidase, and transforming growth factor β1 were measured. Then activated eosinophils were cocultured with nasal fibroblasts for 24 hours, and ECM mRNA expressions were measured. Alternaria strongly enhanced ECM mRNA expression and protein production from nasal fibroblasts. Alternaria also induced the production of superoxide, eosinophil peroxidase, and transforming growth factor β1 from eosinophils, and activated eosinophils enhanced ECM mRNA expression when they were cocultured without the Transwell insert system. Eosinophils activated with Alternaria enhanced ECM mRNA expression from nasal polyp fibroblasts. Alternaria plays an important role in tissue fibrosis in the pathogenesis of nasal polyps by directly or indirectly influencing the production of ECM from nasal fibroblasts. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  3. An asynchronous, pipelined, electronic acquisition system for Active Matrix Flat-Panel Imagers (AMFPIs)

    CERN Document Server

    Huang, W; Berry, J; Maolinbay, M; Martelli, C; Mody, P; Nassif, S; Yeakey, M

    1999-01-01

    The development of a full-custom electronic acquisition system designed for readout of large-area active matrix flat-panel imaging arrays is reported. The arrays, which comprise two-dimensional matrices of pixels utilizing amorphous silicon thin-film transistors, are themselves under development for a wide variety of X-ray imaging applications. The acquisition system was specifically designed to facilitate detailed, quantitative investigations of the properties of these novel imaging arrays and contains significant enhancements compared to a previously developed acquisition system. These enhancements include pipelined preamplifier circuits to allow faster readout speed, expanded addressing capabilities allowing a maximum of 4096 array data lines, and on-board summing of image frames. The values of many acquisition system parameters, including timings and voltages, may be specified and downloaded from a host computer. Once acquisition is enabled, the system operates asynchronously of its host computer. The sys...

  4. Matrix mechanics controls FHL2 movement to the nucleus to activate p21 expression

    Science.gov (United States)

    Nakazawa, Naotaka; Sathe, Aneesh R.; Shivashankar, G. V.; Sheetz, Michael P.

    2016-01-01

    Substrate rigidity affects many physiological processes through mechanochemical signals from focal adhesion (FA) complexes that subsequently modulate gene expression. We find that shuttling of the LIM domain (domain discovered in the proteins, Lin11, Isl-1, and Mec-3) protein four-and-a-half LIM domains 2 (FHL2) between FAs and the nucleus depends on matrix mechanics. In particular, on soft surfaces or after the loss of force, FHL2 moves from FAs into the nucleus and concentrates at RNA polymerase (Pol) II sites, where it acts as a transcriptional cofactor, causing an increase in p21 gene expression that will inhibit growth on soft surfaces. At the molecular level, shuttling requires a specific tyrosine in FHL2, as well as phosphorylation by active FA kinase (FAK). Thus, we suggest that FHL2 phosphorylation by FAK is a critical, mechanically dependent step in signaling from soft matrices to the nucleus to inhibit cell proliferation by increasing p21 expression. PMID:27742790

  5. Cartilage oligomeric matrix protein in patients with juvenile idiopathic arthritis: relation to growth and disease activity

    DEFF Research Database (Denmark)

    Bjørnhart, Birgitte; Juul, Anders; Nielsen, Susan

    2009-01-01

    OBJECTIVE: Cartilage oligomeric matrix protein (COMP) has been identified as a prognostic marker of progressive joint destruction in rheumatoid arthritis. In this population based study we evaluated associations between plasma concentrations of COMP, disease activity, and growth velocity...... in patients with recent-onset juvenile idiopathic arthritis (JIA). COMP levels in JIA and healthy children were compared with those in healthy adults. Plasma levels of insulin-like growth factor I (IGF-1), which has been associated with COMP expression and growth velocity, were studied in parallel. METHODS......: 87 patients with JIA entered the study, including oligoarticular JIA (n = 34), enthesitis-related arthritis (n = 8), polyarticular rheumatoid factor (RF)-positive JIA (n = 2), polyarticular RF-negative JIA (n = 27), systemic JIA (n = 6), and undifferentiated JIA (n = 10). Plasma levels of COMP were...

  6. High performance organic transistor active-matrix driver developed on paper substrate

    Science.gov (United States)

    Peng, Boyu; Ren, Xiaochen; Wang, Zongrong; Wang, Xinyu; Roberts, Robert C.; Chan, Paddy K. L.

    2014-09-01

    The fabrication of electronic circuits on unconventional substrates largely broadens their application areas. For example, green electronics achieved through utilization of biodegradable or recyclable substrates, can mitigate the solid waste problems that arise at the end of their lifespan. Here, we combine screen-printing, high precision laser drilling and thermal evaporation, to fabricate organic field effect transistor (OFET) active-matrix (AM) arrays onto standard printer paper. The devices show a mobility and on/off ratio as high as 0.56 cm2V-1s-1 and 109 respectively. Small electrode overlap gives rise to a cut-off frequency of 39 kHz, which supports that our AM array is suitable for novel practical applications. We demonstrate an 8 × 8 AM light emitting diode (LED) driver with programmable scanning and information display functions. The AM array structure has excellent potential for scaling up.

  7. Matrix metalloproteinase-2 of human carotid atherosclerotic plaques promotes platelet activation. Correlation with ischaemic events.

    Science.gov (United States)

    Lenti, Massimo; Falcinelli, Emanuela; Pompili, Marcella; de Rango, Paola; Conti, Valentina; Guglielmini, Giuseppe; Momi, Stefania; Corazzi, Teresa; Giordano, Giuseppe; Gresele, Paolo

    2014-06-01

    Purified active matrix metalloproteinase-2 (MMP-2) is able to promote platelet aggregation. We aimed to assess the role of MMP-2 expressed in atherosclerotic plaques in the platelet-activating potential of human carotid plaques and its correlation with ischaemic events. Carotid plaques from 81 patients undergoing endarterectomy were tested for pro-MMP-2 and TIMP-2 content by zymography and ELISA. Plaque extracts were incubated with gel-filtered platelets from healthy volunteers for 2 minutes before the addition of a subthreshold concentration of thrombin receptor activating peptide-6 (TRAP-6) and aggregation was assessed. Moreover, platelet deposition on plaque extracts immobilised on plastic coverslips under high shear-rate flow conditions was measured. Forty-three plaque extracts (53%) potentiated platelet aggregation (+233 ± 26.8%), an effect prevented by three different specific MMP-2 inhibitors (inhibitor II, TIMP-2, moAb anti-MMP-2). The pro-MMP-2/TIMP-2 ratio of plaques potentiating platelet aggregation was significantly higher than that of plaques not potentiating it (3.67 ± 1.21 vs 1.01 ± 0.43, p<0.05). Moreover, the platelet aggregation-potentiating effect, the active-MMP-2 content and the active MMP-2/pro-MMP-2 ratio of plaque extracts were significantly higher in plaques from patients who developed a subsequent major cardiovascular event. In conclusion, atherosclerotic plaques exert a prothrombotic effect by potentiating platelet activation due to their content of MMP-2; an elevated MMP-2 activity in plaques is associated with a higher rate of subsequent ischaemic cerebrovascular events.

  8. Evaluation of matrix metalloproteinase and cysteine cathepsin activity in dentin hybrid layer by gelatin zymography.

    Science.gov (United States)

    Mahalaxmi, Sekar; Madhubala, Manavalan Madhana; Jayaraman, Mahendran; Sathyakumar, Shanmugasundaram

    2016-01-01

    The aim of this study was to comparatively assess the gelatinolytic activity of matrix metalloproteinases(MMPs) and Cysteine Cathepsins (CCs) in the adhesive interface using etch and rinse adhesive at different time intervals using zymographic technique. Twenty freshly extracted non-carious human third molars were used in this study. Occlusal surfaces were ground flat and 1mm thick horizontal dentin slabs were obtained from each tooth using a diamond disc. The dentin surface was polished with 600-grit silicon-carbide paper. Five out of 20 samples were directly pulverized. In the remaining fifteen samples, the dentin was etched and adhesive was applied and light cured according to the manufacturer's instructions. A 1mm thick flowable composite was build up and light cured. Bonded specimens were cut vertically into 3 to 4 dentin slabs by means of diamond disc to expose the adhesive/dentin interfaces. These were then ground down to 500 µm thick resin-dentin interface using a hard tissue microtome. These sections were then pulverised into powder. Following this, every five samples were subjected to zymographic analysis after 1 day, 7 days and 21 days. Zymograms showed clear, thicker bands on all three isoforms in the etched samples compared to control samples at 1st and 7th day intervals and became inactive at 21st day for all three isoforms. MMP 9 activity was relatively higher when compared to CCs and MMP 2. Etch and rinse adhesive activated MMPs and CCs within the hybrid layer that remained active till 7th day and no gelatinolytic activity was found on 21st day and MMPs are more active compared to CCs and MMP-2.

  9. Prospective Effects of Statin in Repression of Matrix Metalloproteinases Activities in Irradiated Rats

    International Nuclear Information System (INIS)

    Zahran, A.M.; Sallam, M.H.

    2009-01-01

    Several studies had been committed that HMG-CoA (3-Hydroxy-3 methylglutaryl coenzyme A) reductase inhibitors (statins) may exert a pleotropic effects attributed to mechanisms independent of their conventional hypolipidaemic effects. Meantime, inadequate studies have been sustained these independence mechanisms in regard to regulation and signal transduction of matrix metalloproteinases (MMPs). Sprague Dawley male albino rats were given by gavage atorvastatin; a synthetic form of statins, at a dose of I mg/kg body weight/day for 7 successive days before starting irradiation and 15 successive days during and along the exposure to γ-radiation. Rats were exposed to fractionated whole body gamma radiation, delivered as 1 Gy every other day up to total dose of 8 Gy. Quantitative assay of gelatinolytic zymographic analysis of serum and hepatic tissues showed that exposure to γ rays yields a marked significant increase in the activities of both pro-MMP-9 and active MMP-9 (92 and 86 kDa), as well as pro-MMP-2 and active MMP-2 (72 and 66 kDa), respectively. Administration of atorvastatin has significantly lowered the MMP-2 and MMP-9 enzymatic activity in y-irradiated rats, Conclusion: the present study demonstrated that irradiation of rats led to up regulation of enzymatic activities of MMP-2 and MMP-9 in their pro- and active forms. Administration of atorvastatin exerted defensive effects on γ irradiated rats via down regulation of MMP-2 and MMP-9. Moreover, atorvastatin may be applied to minimize radiation-induced oxidative damage and attenuate the side effects of radiotherapy. However, these results observed in rats need to be confirmed in other experimental models

  10. Prospective Effects of Statin in Repression of Matrix Metalloproteinases Activities in Irradiated Rats

    International Nuclear Information System (INIS)

    Zahran, A.M.; Sallam, M.H.

    2008-01-01

    Several studies had been committed that HMG-CoA (3-Hydroxy-3 methylglutaryl coenzyme A) reductase inhibitors (statins) may exert a pleotropic effects attributed to mechanisms independent of their conventional hypolipidaemic effects. Meantime, inadequate studies have been sustained these independence mechanisms in regard to regulation and signal transduction of matrix metalloproteinases (MMPs). Sprague Dawley male albino rats were given by gavage atorvastatin; a synthetic form of statins, at a dose of I mg/kg body weight/day for 7 successive days before starting irradiation and 15 successive days during and along the exposure to γ-radiation. Rats were exposed to fractionated whole body gamma radiation, delivered as 1 Gy every other day up to total dose of 8 Gy. Quantitative assay of gelatinolytic zymographic analysis of serum and hepatic tissues showed that exposure to γ rays yields a marked significant increase in the activities of both pro-MMP-9 and active MMP-9 (92 and 86 kDa), as well as pro-MMP-2 and active MMP-2 (72 and 66 kDa), respectively. Administration of atorvastatin has significantly lowered the MMP-2 and MMP-9 enzymatic activity in y-irradiated rats, Conclusion: the present study demonstrated that irradiation of rats led to up regulation of enzymatic activities of MMP-2 and MMP-9 in their pro- and active forms. Administration of atorvastatin exerted defensive effects on γ irradiated rats via down regulation of MMP-2 and MMP-9. Moreover, atorvastatin may be applied to minimize radiation-induced oxidative damage and attenuate the side effects of radiotherapy. However, these results observed in rats need to be confirmed in other experimental models

  11. Prospective Effects of Statin in Repression of Matrix Metalloproteinases Activities in Irradiated Rats

    Energy Technology Data Exchange (ETDEWEB)

    Zahran, A M [Radiation Biology Department, National Centre/or Radiation Research and Technology (NCRRT), Atomic Energy Authority, Cairo (Egypt); Sallam, M H [Health Radiation Research Department, Radiation Research and Technology (NCRRT), Atomic Energy Authority, Cairo (Egypt)

    2008-07-01

    Several studies had been committed that HMG-CoA (3-Hydroxy-3 methylglutaryl coenzyme A) reductase inhibitors (statins) may exert a pleotropic effects attributed to mechanisms independent of their conventional hypolipidaemic effects. Meantime, inadequate studies have been sustained these independence mechanisms in regard to regulation and signal transduction of matrix metalloproteinases (MMPs). Sprague Dawley male albino rats were given by gavage atorvastatin; a synthetic form of statins, at a dose of I mg/kg body weight/day for 7 successive days before starting irradiation and 15 successive days during and along the exposure to {gamma}-radiation. Rats were exposed to fractionated whole body gamma radiation, delivered as 1 Gy every other day up to total dose of 8 Gy. Quantitative assay of gelatinolytic zymographic analysis of serum and hepatic tissues showed that exposure to {gamma} rays yields a marked significant increase in the activities of both pro-MMP-9 and active MMP-9 (92 and 86 kDa), as well as pro-MMP-2 and active MMP-2 (72 and 66 kDa), respectively. Administration of atorvastatin has significantly lowered the MMP-2 and MMP-9 enzymatic activity in y-irradiated rats, Conclusion: the present study demonstrated that irradiation of rats led to up regulation of enzymatic activities of MMP-2 and MMP-9 in their pro- and active forms. Administration of atorvastatin exerted defensive effects on {gamma} irradiated rats via down regulation of MMP-2 and MMP-9. Moreover, atorvastatin may be applied to minimize radiation-induced oxidative damage and attenuate the side effects of radiotherapy. However, these results observed in rats need to be confirmed in other experimental models.

  12. Prospective Effects of Statin in Repression of Matrix Metalloproteinases Activities in Irradiated Rats

    Energy Technology Data Exchange (ETDEWEB)

    Zahran, A M [Radiation Biology Department, National Centre/or Radiation Research and Technology (NCRRT), Atomic Energy Authority, Cairo (Egypt); Sallam, M H [Health Radiation Research Department, Radiation Research and Technology (NCRRT), Atomic Energy Authority, Cairo (Egypt)

    2009-07-01

    Several studies had been committed that HMG-CoA (3-Hydroxy-3 methylglutaryl coenzyme A) reductase inhibitors (statins) may exert a pleotropic effects attributed to mechanisms independent of their conventional hypolipidaemic effects. Meantime, inadequate studies have been sustained these independence mechanisms in regard to regulation and signal transduction of matrix metalloproteinases (MMPs). Sprague Dawley male albino rats were given by gavage atorvastatin; a synthetic form of statins, at a dose of I mg/kg body weight/day for 7 successive days before starting irradiation and 15 successive days during and along the exposure to {gamma}-radiation. Rats were exposed to fractionated whole body gamma radiation, delivered as 1 Gy every other day up to total dose of 8 Gy. Quantitative assay of gelatinolytic zymographic analysis of serum and hepatic tissues showed that exposure to {gamma} rays yields a marked significant increase in the activities of both pro-MMP-9 and active MMP-9 (92 and 86 kDa), as well as pro-MMP-2 and active MMP-2 (72 and 66 kDa), respectively. Administration of atorvastatin has significantly lowered the MMP-2 and MMP-9 enzymatic activity in y-irradiated rats, Conclusion: the present study demonstrated that irradiation of rats led to up regulation of enzymatic activities of MMP-2 and MMP-9 in their pro- and active forms. Administration of atorvastatin exerted defensive effects on {gamma} irradiated rats via down regulation of MMP-2 and MMP-9. Moreover, atorvastatin may be applied to minimize radiation-induced oxidative damage and attenuate the side effects of radiotherapy. However, these results observed in rats need to be confirmed in other experimental models.

  13. Lysophosphatidic acid (LPA) effects on endometrial carcinoma in vitro proliferation, invasion, and matrix metalloproteinase activity.

    Science.gov (United States)

    Wang, Feng-qiang; Ariztia, Edgardo V; Boyd, Leslie R; Horton, Faith R; Smicun, Yoel; Hetherington, Jessica A; Smith, Phillip J; Fishman, David A

    2010-04-01

    Lysophosphatidic acid (LPA) has potent growth-regulatory effect in many cell types and has been linked to the in vivo tumor growth and metastasis in several malignancies. The goal of this study was to assess the regulation of (EC) microenvironment by LPA through the examination of its effect on cell proliferation, migration, invasion, uPA activity, and matrix metalloproteinase (MMP) secretion/activation. All experiments were performed in vitro using an EC cell line, HEC-1A. Cell proliferation was determined using the Promega MTS proliferation assay following 48 h of exposures to different concentrations of LPA (0.1, 1.0 and 10.0 microM). Cell invasion was assessed using a modified Boyden chamber assay with collagen I coated on the membrane. HEC-1A motility was examined by Boyden chamber migration assay as well as the scratch wound closure assay on type I collagen. MMP secretion/activation in HEC-1A conditioned medium was detected by gelatin zymography. MMP-7 mRNA expression was determined using real-time PCR. uPA activity was measured using a coupled colorimetric assay. LPA, at the concentrations of 0.1 and 1.0 microM, significantly induced the proliferation of HEC-1A cells (p0.05). Gelatin zymogram showed that HEC-1A cells secreted high levels of MMP-7, while MMP-2 and MMP-9 are barely detectable. In addition, LPA significantly enhanced uPA activity in HEC-1A conditioned medium in a concentration-dependent manner. LPA is a potent modulator of cellular proliferation and invasion for EC cells. It also has the capacity to stimulate the secretion/activity of uPA and MMP-7. Those results suggest that LPA is a bioactive modulator of EC microenvironment and may have a distinct regulation mechanism as observed in epithelial ovarian cancer. Copyright 2009. Published by Elsevier Inc.

  14. Aqueous zymography screening of matrix metalloproteinase activity and inhibition based on colorimetric gold nanoparticles.

    Science.gov (United States)

    Chuang, Yao-Chen; Huang, Wei-Ting; Chiang, Pin-Hsuan; Tang, Meng-Che; Lin, Chih-Sheng

    2012-02-15

    An optical gold nanoparticles (AuNPs)-based method was fabricated for the rapid detection of matrix metalloproteinase (MMP) activity and screening potential MMP inhibitors without sophisticated instruments. The diagnosis platform was composed of AuNPs, particular MMP substrates and 6-mercapto-1-hexanol (MCH). The functionalized AuNPs were subjected to specific MMP digestion, and the MMP found the substrate on AuNPs, such that the AuNPs lost shelter and MCH increased the attraction force between AuNPs. Consequently, AuNPs aggregation and a color change from red to purple with increasing MMP concentration were observed. The surface plasmon resonance (SPR) of the formed AuNPs allowed for the quantitative detection of MMP activity. A sensitive linear correlation existed between the absorbance and the activity of the MMPs, which ranged from 10 ng/mL to 700 ng/mL in NTTC buffer and plasma samples. The proposed colorimetric method could be accomplished in a homogeneous solution with one-step operation in 30 min and has been successfully applied to the determination of particular MMP activity in plasma samples, in which the results are consistent with substrate zymography. This technology may become a simple platform for parallel screening a number of inhibitors and offer an alternative method to studying the efficiency of inhibitors for suppressing MMP activity. The absorbance ratio at 625 nm and 525 nm (A(625)/A(525)) confirmed the efficiency of the inhibitors as observed in substrate zymography. The IC(50) of ONO-4817 and galardin for MMP-1, MMP-2 and MMP-7 determined by the proposed colorimetric method was similar to the results of substrate zymography. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  15. Spermidine promotes Bacillus subtilis biofilm formation by activating expression of the matrix regulator slrR.

    Science.gov (United States)

    Hobley, Laura; Li, Bin; Wood, Jennifer L; Kim, Sok Ho; Naidoo, Jacinth; Ferreira, Ana Sofia; Khomutov, Maxim; Khomutov, Alexey; Stanley-Wall, Nicola R; Michael, Anthony J

    2017-07-21

    Ubiquitous polyamine spermidine is not required for normal planktonic growth of Bacillus subtilis but is essential for robust biofilm formation. However, the structural features of spermidine required for B. subtilis biofilm formation are unknown and so are the molecular mechanisms of spermidine-stimulated biofilm development. We report here that in a spermidine-deficient B. subtilis mutant, the structural analogue norspermidine, but not homospermidine, restored biofilm formation. Intracellular biosynthesis of another spermidine analogue, aminopropylcadaverine, from exogenously supplied homoagmatine also restored biofilm formation. The differential ability of C-methylated spermidine analogues to functionally replace spermidine in biofilm formation indicated that the aminopropyl moiety of spermidine is more sensitive to C -methylation, which it is essential for biofilm formation, but that the length and symmetry of the molecule is not critical. Transcriptomic analysis of a spermidine-depleted B. subtilis speD mutant uncovered a nitrogen-, methionine-, and S -adenosylmethionine-sufficiency response, resulting in repression of gene expression related to purine catabolism, methionine and S -adenosylmethionine biosynthesis and methionine salvage, and signs of altered membrane status. Consistent with the spermidine requirement in biofilm formation, single-cell analysis of this mutant indicated reduced expression of the operons for production of the exopolysaccharide and TasA protein biofilm matrix components and SinR antagonist slrR Deletion of sinR or ectopic expression of slrR in the spermidine-deficient Δ speD background restored biofilm formation, indicating that spermidine is required for expression of the biofilm regulator slrR Our results indicate that spermidine functions in biofilm development by activating transcription of the biofilm matrix exopolysaccharide and TasA operons through the regulator slrR . © 2017 by The American Society for Biochemistry and

  16. Effect Of Neutron Activation Factor On The Physico-Chemical Properties Of Hydrophilic And Hydrophobic Polymer Formulation Of Matrix Tablets

    International Nuclear Information System (INIS)

    Ibrahim Ijang; Bohari Yaacob; Nordiana, N.R.

    2011-01-01

    This study was to investigate effect of neutron activation on the physicochemical properties and in vitro dissolution of sustained-release matrix tablets. The tablets incorporation of Samarium oxide (Sm 2 O 3 ) and were compared before and after irradiation with thermal neutron for 5 minutes at 1.2 x 10 12 neutron cm -2 s -1 . The neutron activation factor did not influence the compression properties of the tablets. The dissolution tests showed that irradiation increased the release of the model drug ketoprofen from the tablets. This effect might be explained by polymer degradation. Incorporation of Sm 2 O 3 in the matrix tablets did not influence the release. (author)

  17. Atmospheric-Pressure Cold Plasmas Used to Embed Bioactive Compounds in Matrix Material for Active Packaging of Fruits and Vegetables

    Science.gov (United States)

    Fernandez, Sulmer; Pedrow, Patrick; Powers, Joseph; Pitts, Marvin

    2009-10-01

    Active thin film packaging is a technology with the potential to provide consumers with new fruit and vegetable products-if the film can be applied without deactivating bioactive compounds.Atmospheric pressure cold plasma (APCP) processing can be used to activate monomer with concomitant deposition of an organic plasma polymerized matrix material and to immobilize a bioactive compound all at or below room temperature.Aims of this work include: 1) immobilize an antimicrobial in the matrix; 2) determine if the antimicrobial retains its functionality and 3) optimize the reactor design.The plasma zone will be obtained by increasing the voltage on an electrode structure until the electric field in the feed material (argon + monomer) yields electron avalanches. Results will be described using Red Delicious apples.Prospective matrix precursors are vanillin and cinnamic acid.A prospective bioactive compound is benzoic acid.

  18. Increased matrix metalloproteinase-8 and -9 activity in patients with infarct rupture after myocardial infarction

    NARCIS (Netherlands)

    Borne, S.W.M. van den; Cleutjens, J.P.M.; Hanemaaijer, R.; Creemers, E.E.; Smits, J.F.M.; Daemen, M.J.A.P.; Blankesteijn, W.M.

    2009-01-01

    Background: Infarct rupture is a usually fatal complication of myocardial infarction (MI), for which no molecular mechanism has been described in humans. Experimental evidence in mouse models suggests that the degradation of the extracellular matrix by matrix metalloproteinases (MMPs) plays an

  19. Production of active lysozyme films by matrix assisted pulsed laser evaporation at 355 nm

    DEFF Research Database (Denmark)

    Purice, Andreea; Schou, Jørgen; Kingshott, P.

    2007-01-01

    Thin lysozyme films have been produced in a dry environment by MAPLE (matrix assisted pulsed laser evaporation) from a water ice matrix irradiated by laser light at 355 nm above the absorption threshold of the protein. A significant part of the lysozyme molecules are transferred to the film without...

  20. Development of an integrated system for activity-based profiling of matrix metallo-proteases

    NARCIS (Netherlands)

    Freije, Jan Robert

    2006-01-01

    Matrix metallo-proteases constitute a family of extracellular zinc-dependent endopeptidases that are involved in degradation of extracellular matrix (ECM) components and other bioactive non-ECM molecules. A plethora of studies have implicated important roles for MMPs in many diseases (including

  1. Increasing extracellular matrix collagen level and MMP activity induces cyst development in polycystic kidney disease.

    Science.gov (United States)

    Liu, Bin; Li, Chenghai; Liu, Zijuan; Dai, Zonghan; Tao, Yunxia

    2012-09-11

    Polycystic Kidney Disease (PKD) kidneys exhibit increased extracellular matrix (ECM) collagen expression and metalloproteinases (MMPs) activity. We investigated the role of these increases on cystic disease progression in PKD kidneys. We examined the role of type I collagen (collagen I) and membrane bound type 1 MMP (MT1-MMP) on cyst development using both in vitro 3 dimensional (3D) collagen gel culture and in vivo PCK rat model of PKD. We found that collagen concentration is critical in controlling the morphogenesis of MDCK cells cultured in 3D gels. MDCK cells did not form 3D structures at collagen I concentrations lower than 1 mg/ml but began forming tubules when the concentration reaches 1 mg/ml. Significantly, these cells began to form cyst when collagen I concentration reached to 1.2 mg/ml, and the ratios of cyst to tubule structures increased as the collagen I concentration increased. These cells exclusively formed cyst structures at a collagen I concentration of 1.8 mg/ml or higher. Overexpression of MT1-MMP in MDCK cells significantly induced cyst growth in 3D collagen gel culture. Conversely, inhibition of MMPs activity with doxycycline, a FDA approved pan-MMPs inhibitor, dramatically slowed cyst growth. More importantly, the treatment of PCK rats with doxycycline significantly decreased renal tubule cell proliferation and markedly inhibited the cystic disease progression. Our data suggest that increased collagen expression and MMP activity in PKD kidneys may induce cyst formation and expansion. Our findings also suggest that MMPs may serve as a therapeutic target for the treatment of human PKD.

  2. Increasing extracellular matrix collagen level and MMP activity induces cyst development in polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    Liu Bin

    2012-09-01

    Full Text Available Abstract Background Polycystic Kidney Disease (PKD kidneys exhibit increased extracellular matrix (ECM collagen expression and metalloproteinases (MMPs activity. We investigated the role of these increases on cystic disease progression in PKD kidneys. Methods We examined the role of type I collagen (collagen I and membrane bound type 1 MMP (MT1-MMP on cyst development using both in vitro 3 dimensional (3D collagen gel culture and in vivo PCK rat model of PKD. Results We found that collagen concentration is critical in controlling the morphogenesis of MDCK cells cultured in 3D gels. MDCK cells did not form 3D structures at collagen I concentrations lower than 1 mg/ml but began forming tubules when the concentration reaches 1 mg/ml. Significantly, these cells began to form cyst when collagen I concentration reached to 1.2 mg/ml, and the ratios of cyst to tubule structures increased as the collagen I concentration increased. These cells exclusively formed cyst structures at a collagen I concentration of 1.8 mg/ml or higher. Overexpression of MT1-MMP in MDCK cells significantly induced cyst growth in 3D collagen gel culture. Conversely, inhibition of MMPs activity with doxycycline, a FDA approved pan-MMPs inhibitor, dramatically slowed cyst growth. More importantly, the treatment of PCK rats with doxycycline significantly decreased renal tubule cell proliferation and markedly inhibited the cystic disease progression. Conclusions Our data suggest that increased collagen expression and MMP activity in PKD kidneys may induce cyst formation and expansion. Our findings also suggest that MMPs may serve as a therapeutic target for the treatment of human PKD.

  3. AMP-activated protein kinase activation mediates CCL3-induced cell migration and matrix metalloproteinase-2 expression in human chondrosarcoma

    Science.gov (United States)

    2013-01-01

    Chemokine (C-C motif) ligand 3 (CCL3), also known as macrophage inflammatory protein-1α, is a cytokine involved in inflammation and activation of polymorphonuclear leukocytes. CCL3 has been detected in infiltrating cells and tumor cells. Chondrosarcoma is a highly malignant tumor that causes distant metastasis. However, the effect of CCL3 on human chondrosarcoma metastasis is still unknown. Here, we found that CCL3 increased cellular migration and expression of matrix metalloproteinase (MMP)-2 in human chondrosarcoma cells. Pre-treatment of cells with the MMP-2 inhibitor or transfection with MMP-2 specific siRNA abolished CCL3-induced cell migration. CCL3 has been reported to exert its effects through activation of its specific receptor, CC chemokine receptor 5 (CCR5). The CCR5 and AMP-activated protein kinase (AMPK) inhibitor or siRNA also attenuated CCL3-upregulated cell motility and MMP-2 expression. CCL3-induced expression of MMP-2 and migration were also inhibited by specific inhibitors, and inactive mutants of AMPK, p38 mitogen activated protein kinase (p38 or p38-MAPK), and nuclear factor κB (NF-κB) cascades. On the other hand, CCL3 treatment demonstrably activated AMPK, p38, and NF-κB signaling pathways. Furthermore, the expression levels of CCL3, CCR5, and MMP-2 were correlated in human chondrosarcoma specimens. Taken together, our results indicate that CCL3 enhances the migratory ability of human chondrosarcoma cells by increasing MMP-2 expression via the CCR5, AMPK, p38, and NF-κB pathways. PMID:24047437

  4. An asynchronous, pipelined, electronic acquisition system for Active Matrix Flat-Panel Imagers (AMFPIs)

    Energy Technology Data Exchange (ETDEWEB)

    Huang, W.; Antonuk, L.E. E-mail: antonuk@umich.edu; Berry, J.; Maolinbay, M.; Martelli, C.; Mody, P.; Nassif, S.; Yeakey, M

    1999-07-11

    The development of a full-custom electronic acquisition system designed for readout of large-area active matrix flat-panel imaging arrays is reported. The arrays, which comprise two-dimensional matrices of pixels utilizing amorphous silicon thin-film transistors, are themselves under development for a wide variety of X-ray imaging applications. The acquisition system was specifically designed to facilitate detailed, quantitative investigations of the properties of these novel imaging arrays and contains significant enhancements compared to a previously developed acquisition system. These enhancements include pipelined preamplifier circuits to allow faster readout speed, expanded addressing capabilities allowing a maximum of 4096 array data lines, and on-board summing of image frames. The values of many acquisition system parameters, including timings and voltages, may be specified and downloaded from a host computer. Once acquisition is enabled, the system operates asynchronously of its host computer. The system allows image capture in both radiographic mode (corresponding to the capture of individual X-ray images), and fluoroscopic mode (corresponding to the capture of a continual series of X-ray images). A detailed description of the system architecture and the underlying motivations for the design is reported in this paper. (author)

  5. Beyond the limits of present active matrix flat-panel imagers (AMFPIs) for diagnostic radiology

    Science.gov (United States)

    Antonuk, Larry E.; El-Mohri, Youcef; Jee, Kyung-Wook; Maolinbay, Manat; Nassif, Samer C.; Rong, Xiujiang; Siewerdsen, Jeffrey H.; Zhao, Qihua; Street, Robert A.

    1999-05-01

    A theoretical cascaded systems analysis of the performance limits of x-ray imagers based on thin-film, active matrix flat-panel technology is presented. This analysis specifically focuses upon an examination of the functional dependence of the detective quantum efficiency on exposure. While the DQE of AMFPI systems is relatively high at the large exposure levels associated with radiographic x-ray imaging, there is a significant decline in DQE with decreasing exposure over the medium and lower end of the exposure range associated with fluoroscopic imaging. This fall-off in DQE originates from the relatively large size of the additive noise of AMFPI systems compared to their overall system gain. Therefore, strategies to diminish additive noise and increase system gain should significantly improve performance. Potential strategies for noise reduction include the use of charge compensation lines while strategies for gain enhancement include continuous photodiodes, pixel amplification structures, or higher gain converters. The effect of the implementation of such strategies is examined for a variety for hypothetical imager configurations. Through the modeling of these configurations, such enhancements are shown to hold the potential of making low frequency DQE response large and essentially independent of exposure while greatly reducing the fall-off in DQE at higher spatial frequencies.

  6. Matrix Effects on the Stability and Antioxidant Activity of Red Cabbage Anthocyanins under Simulated Gastrointestinal Digestion

    Directory of Open Access Journals (Sweden)

    Anna Podsędek

    2014-01-01

    Full Text Available Red cabbage is, among different vegetables, one of the major sources of anthocyanins. In the present study an in vitro digestion method has been used to assay the influence of the physiological conditions in the stomach and small intestine, as well as faecal microflora on anthocyanins stability in red cabbage and anthocyanin-rich extract. The recovery of anthocyanins during in vitro gastrointestinal digestion was strongly influenced by food matrix. The results showed that other constituents present in cabbage enhanced the stability of anthocyanins during the digestion. The amount of anthocyanins (HPLC method and antioxidant capacity (ABTS and FRAP assays strongly decreased after pancreatic-bile digestion in both matrices but total phenolics content (Folin-Ciocalteu assay in these digestions was higher than in initial samples. Incubation with human faecal microflora caused further decline in anthocyanins content. The results obtained suggest that intact anthocyanins in gastric and products of their decomposition in small and large intestine may be mainly responsible for the antioxidant activity and other physiological effects after consumption of red cabbage.

  7. Probing matrix and tumor mechanics with in situ calibrated optical trap based active microrheology

    Science.gov (United States)

    Staunton, Jack Rory; Vieira, Wilfred; Tanner, Kandice; Tissue Morphodynamics Unit Team

    Aberrant extracellular matrix deposition and vascularization, concomitant with proliferation and phenotypic changes undergone by cancer cells, alter mechanical properties in the tumor microenvironment during cancer progression. Tumor mechanics conversely influence progression, and the identification of physical biomarkers promise improved diagnostic and prognostic power. Optical trap based active microrheology enables measurement of forces up to 0.5 mm within a sample, allowing interrogation of in vitro biomaterials, ex vivo tissue sections, and small organisms in vivo. We fabricated collagen I hydrogels exhibiting distinct structural properties by tuning polymerization temperature Tp, and measured their shear storage and loss moduli at frequencies 1-15k Hz at multiple amplitudes. Lower Tp gels, with larger pore size but thicker, longer fibers, were stiffer than higher Tp gels; decreasing strain increased loss moduli and decreased storage moduli at low frequencies. We subcutanously injected probes with metastatic murine melanoma cells into mice. The excised tumors displayed storage and loss moduli 40 Pa and 10 Pa at 1 Hz, increasing to 500 Pa and 1 kPa at 15 kHz, respectively.

  8. Matrix Effects on the Stability and Antioxidant Activity of Red Cabbage Anthocyanins under Simulated Gastrointestinal Digestion

    Science.gov (United States)

    Podsędek, Anna; Koziołkiewicz, Maria

    2014-01-01

    Red cabbage is, among different vegetables, one of the major sources of anthocyanins. In the present study an in vitro digestion method has been used to assay the influence of the physiological conditions in the stomach and small intestine, as well as faecal microflora on anthocyanins stability in red cabbage and anthocyanin-rich extract. The recovery of anthocyanins during in vitro gastrointestinal digestion was strongly influenced by food matrix. The results showed that other constituents present in cabbage enhanced the stability of anthocyanins during the digestion. The amount of anthocyanins (HPLC method) and antioxidant capacity (ABTS and FRAP assays) strongly decreased after pancreatic-bile digestion in both matrices but total phenolics content (Folin-Ciocalteu assay) in these digestions was higher than in initial samples. Incubation with human faecal microflora caused further decline in anthocyanins content. The results obtained suggest that intact anthocyanins in gastric and products of their decomposition in small and large intestine may be mainly responsible for the antioxidant activity and other physiological effects after consumption of red cabbage. PMID:24575407

  9. Biosensing of matrix metalloproteinase activity with Cd-free quantum dots

    Science.gov (United States)

    Plumley, John Bryan

    Quantum dots (QDs) have become attractive in the biomedical field on account of their superior optical properties and stability, in comparison to traditional fluorophores. QDs also have properties which make them ideal for complex in vivo conditions. However, toxicity has been a chief concern in the eventual implementation of QDs for in vivo applications such as biosensing and tumor imaging. Commercially available QDs contain a notoriously noxious Cd component and therefore continuous research has gone into developing QDs without toxic heavy metals, generally Cd, that would still yield comparable performance in terms of their optical properties. Nonetheless, even in the case of Cd-free QDs, toxicity should be evaluated on a case by case basis, as other properties such as size, coating, stability, and charge can affect toxicity of nanomaterials as well, making it a very complex issue. With the high promise of QDs in the field of biomedical development as a motivation, this work strives to develop the efficient and repeatable synthesis of Cd-free QDs with high stability and luminescence, with proven low toxicity, and the ability to detect active matrix metalloproteinase (MMP) in a biosensing system, designed to identify direct biomarkers for pathological conditions, which in turn would enable early disease diagnosis and better treatment development. In this work, highly luminescent ZnSe:Mn/ZnS QDs have been synthesized, characterized, and modified with peptides with a bioconjugation procedure that utilized thiol-metal affinity. Experiments aiming at MMP detection were conducted using the peptide/QD conjugates. In addition, the ApoTox-Glo(TM) Triplex assay was utilized to evaluate cytotoxicity, and a safe concentration below 0.125 microM was identified for peptide-coated ZnSe:Mn/ZnS QDs in water. Finally, in contribution to developing an in vivo fiberoptic system for sensing MMP activity, the QDs were successfully tethered to silica and MMP detection was demonstrated

  10. Inhibition of Matrix Metalloproteinase Activity Prevents Increases in Myocardial Tumor Necrosis Factor-α

    Science.gov (United States)

    Murray, David B.; Levick, Scott P; Brower, Gregory L.; Janicki, Joseph S.

    2010-01-01

    Aim TNF-α is known to cause adverse myocardial remodeling. While we have previously shown a role for cardiac mast cells in mediating myocardial TNF-α, matrix metalloproteinases (MMP) activation of TNF-α may also be contributory. We sought to determine the relative roles of MMPs and cardiac mast cells in the activation of TNF-α in the hearts of rats subjected to chronic volume overload. Methods Interventions with the broad spectrum MMP inhibitor, GM6001, or the mast cell stabilizer, nedocromil, were performed in the rat aortocaval fistula (ACF) model of volume overload. Results Myocardial TNF-α levels were significantly increased in the ACF. This increase was prevented by MMP inhibition with GM6001 (p ≤ 0.001 vs. ACF). Conversely, myocardial TNF-α levels were increased in the ACF + nedocromil treated fistula groups (p ≤ 0.001 vs. sham). The degradation of interstitial collagen volume fraction seen in the untreated ACF group was prevented in both the GM6001 and nedocromil treated hearts. Significant increases in LV myocardial ET-1 levels also occurred in the ACF group at 3 days post-fistula. Whereas administration of GM6001 significantly attenuated this increase, mast cell stabilization with nedocromil markedly exacerbated the increase, producing ET-1 levels 6.5 fold and 2 fold greater than that in the sham-operated control and ACF group, respectively. Conclusion The efficacy of the MMP inhibitor, GM6001, to prevent increased levels of myocardial TNF-α is indicative of MMP-mediated cleavage of latent extracellular membrane bound TNF-α protein as the primary source of bioactive TNF-α in the myocardium of the volume-overload heart. PMID:20403361

  11. Dimerization Efficiency of Canine Distemper Virus Matrix Protein Regulates Membrane-Budding Activity.

    Science.gov (United States)

    Bringolf, Fanny; Herren, Michael; Wyss, Marianne; Vidondo, Beatriz; Langedijk, Johannes P; Zurbriggen, Andreas; Plattet, Philippe

    2017-08-15

    Paramyxoviruses rely on the matrix (M) protein to orchestrate viral assembly and budding at the plasma membrane. Although the mechanistic details remain largely unknown, structural data suggested that M dimers and/or higher-order oligomers may facilitate membrane budding. To gain functional insights, we employed a structure-guided mutagenesis approach to investigate the role of canine distemper virus (CDV) M protein self-assembly in membrane-budding activity. Three six-alanine-block (6A-block) mutants with mutations located at strategic oligomeric positions were initially designed. While the first one includes residues potentially residing at the protomer-protomer interface, the other two display amino acids located within two distal surface-exposed α-helices proposed to be involved in dimer-dimer contacts. We further focused on the core of the dimeric interface by mutating asparagine 138 (N138) to several nonconservative amino acids. Cellular localization combined with dimerization and coimmunopurification assays, performed under various denaturing conditions, revealed that all 6A-block mutants were impaired in self-assembly and cell periphery accumulation. These phenotypes correlated with deficiencies in relocating CDV nucleocapsid proteins to the cell periphery and in virus-like particle (VLP) production. Conversely, all M-N138 mutants remained capable of self-assembly, though to various extents, which correlated with proper accumulation and redistribution of nucleocapsid proteins at the plasma membrane. However, membrane deformation and VLP assays indicated that the M-N138 variants exhibiting the most reduced dimerization propensity were also defective in triggering membrane remodeling and budding, despite proper plasma membrane accumulation. Overall, our data provide mechanistic evidence that the efficiency of CDV M dimerization/oligomerization governs both cell periphery localization and membrane-budding activity. IMPORTANCE Despite the availability of

  12. Matrix metalloproteinase 2 and 9 activity in patients with colorectal cancer liver metastasis.

    NARCIS (Netherlands)

    Waas, E.T.; Wobbes, Th.; Lomme, R.M.L.M.; Groot, J.H. de; Ruers, T.J.M.; Hendriks, T.

    2003-01-01

    BACKGROUND: Matrix metalloproteinases (MMPs) have been reported to play an important role in tumour cell invasion and metastasis. The bioactivity of MMPs in liver metastasis from colorectal cancer was investigated and correlated with clinicopathological variables. METHOD: Thirty-two patients

  13. Levels of Matrix Metalloproteinases in Arthroplasty Patients and Their Correlation With Inflammatory and Thrombotic Activation Processes.

    Science.gov (United States)

    Alexander, Kyle; Banos, Andrew; Abro, Schuharazad; Hoppensteadt, Debra; Fareed, Jawed; Rees, Harold; Hopkinson, William

    2016-07-01

    An imbalance of matrix metalloproteinases (MMPs) and their inhibitors is thought to play a major role in the pathophysiology of joint diseases. The aim of this study is to provide additional insights into the relevance of MMP levels in arthroplasty patients in relation to inflammation and thrombosis. Deidentified plasma samples from 100 patients undergoing total hip arthroplasty or total knee arthroplasty were collected preoperatively, on postoperative day 1, and on postoperative day 3. Tissue inhibitor of MMP 4, tumor necrosis factor α (TNF-α), pro-MMP1, MMP3, MMP9, MMP13, and d-dimer were measured using enzyme-linked immunosorbent assay kits. A biochip array was used to profile interleukin (IL) 2, IL-4, IL-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), interferon gamma, TNF-α, IL-1α, IL-1β, monocyte chemoattractant protein 1, and endothelial growth factor (EGF) levels. The levels of MMP1, MMP9, MMP13, and TNF-α were elevated preoperatively in arthroplasty patients when compared to healthy individuals. The concentrations of MMP1 and MMP9 increased slightly in postsurgical samples. d-Dimer levels were elevated preoperatively, increased postoperatively, and started decreasing on postoperative day 3. Significant correlations between MMP9 with TNF-α, IL-6, IL-8, VEGF, and EGF were identified. Elevated preoperative MMP1, MMP9, and MMP13 concentrations suggest that they may play a role in the pathogenesis of arthritis. There is also evidence of increased coagulation activity and possible upregulation of several MMPs postsurgically. Correlation analysis indicates that MMP9 levels may potentially be related to inflammation and thrombosis in arthroplasty patients. © The Author(s) 2016.

  14. Piezoelectric properties of the new generation active matrix hybrid (micro-nano) composites

    Energy Technology Data Exchange (ETDEWEB)

    Parali, Levent, E-mail: levent.parali@cbu.edu.tr [Department of Electronics and Automation, Celal Bayar University, Manisa (Turkey); Şabikoğlu, İsrafil [Department of Physics, Celal Bayar University, Manisa (Turkey); Kurbanov, Mirza A. [Institute of Physics, Academy of Sciences of Azerbaijan, Baku (Azerbaijan)

    2014-11-01

    Highlights: • We prepared hybrid structured piezocomposites. • We examine thermostimulated depolarization of piezocomposites. • We examine frequency characteristic of piezocomposites with SiO{sub 2} and BaTiO{sub 3}. • The piezocomposites can be used in acoustic applications at 5 Hz–40 kHz. - Abstract: A hybrid piezoelectric composite structure is obtained by addition of nano-sized BaTiO{sub 3}, SiO{sub 2} to the micro-sized PZT and polymers composition. Although the PZT material itself has excellent piezoelectric properties, PZT-based composite variety is limited. Piezoelectric properties of PZT materials can be varied with an acceptor or a donor added to the material. In addition, varieties of PZT-based sensors can be increased with doping polymers which have physical-mechanical, electrophysical, thermophysical and photoelectrical properties. The active matrix hybrid structure occurs when bringing together the unique piezoelectric properties of micro-sized PZT with electron trapping properties of nano-sized insulators (BaTiO{sub 3} or SiO{sub 2}), and their piezoelectric, mechanic and electromechanic properties significantly change. In this study, the relationship between the piezoelectric constant and the coupling factor values of microstructure (PZT–PVDF) and the hybrid structure (PZT–PVDF–BaTiO{sub 3}) composite are compared. The d{sub 33} value and the coupling factor of the hybrid structure have shown an average of 54 and 62% increase according to microstructure composite, respectively. In addition, the d{sub 33} value and the coupling factor of the hybrid structure (PZT–HDPE–SiO{sub 2}) have exhibited about 68 and 52% increase according to microstructure composite (PZT–HDPE), respectively.

  15. Active matrix metalloproteinase-8 and periodontal bacteria depending on periodontal status in patients with rheumatoid arthritis.

    Science.gov (United States)

    Kirchner, A; Jäger, J; Krohn-Grimberghe, B; Patschan, S; Kottmann, T; Schmalz, G; Mausberg, R F; Haak, R; Ziebolz, D

    2017-08-01

    The aim of this clinical cross-sectional study was to determine the level of active matrix metalloproteinase-8 (aMMP-8) and periodontal pathogenic bacteria in gingival crevicular fluid in patients with rheumatoid arthritis (RA) with varying periodontal conditions. In total, 103 patients with RA and 104 healthy controls (HC) were included. The assessment of periodontal status included periodontal probing depth, bleeding on probing and clinical attachment loss. Periodontal disease was classified as healthy/mild, moderate or severe. For the determination of aMMP-8 levels using enzyme-linked immunosorbent assay and periodontal pathogenic bacteria using polymerase chain reaction, samples of gingival crevicular fluid were taken from the deepest gingival pockets. The statistical analyses used included a Mann-Whitney U-test, a chi-squared test or a Fisher's exact test, and the significance level was set at α = 5%. We found that 65% of patients with RA and 79% of HC had moderate to severe periodontal disease (p = 0.02). The prevalence of periodontal pathogens was almost equal (p > 0.05). Furthermore, depending on periodontal disease severity only minor differences in bacterial prevalence were detected. With increasing severity of periodontal disease, higher aMMP-8 levels were observed. Accordingly, a significant difference in patients with moderate periodontal disease (RA: 15.3 ± 13.8; HC: 9.1 ± 9.1; p ≤ 0.01) and severe periodontal disease (RA: 21.7 ± 13.3; HC: 13.1 ± 8.6; p = 0.07) was detected, with a greater tendency in the latter group. The increased aMMP-8 levels in the RA group indicate that the presence of RA appears to have an influence on the host response at a comparable level of bacterial load and periodontal disease severity. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Pilot Study on the Genetic Background of an Active Matrix Metalloproteinase-8 Test in Finnish Adolescents.

    Science.gov (United States)

    Heikkinen, Anna Maria; Raivisto, Teija; Kettunen, Kaisa; Kovanen, Leena; Haukka, Jari; Pakbaznejad Esmaeili, Elmira; Elg, Jessica; Gieselmann, Dirk-Rolf; Rathnayake, Nilminie; Ruokonen, Hellevi; Tervahartiala, Taina; Sorsa, Timo

    2017-05-01

    In periodontitis, genetics and smoking play important roles in host immune system response. The aim of this study is to determine whether the genetic background of initial periodontitis and caries could be detected using an active matrix metalloproteinase (aMMP)-8 chairside test in Finnish adolescents. Forty-seven participants gave approval for analysis of both oral fluid collection and DNA. An aMMP-8 chairside test was performed on participants (adolescents aged 15 to 17 years), and full-mouth clinical parameters of oral health were assessed including periodontal, oral mucosal, and caries status in Eastern Finland from 2014 to 2015. DNA was extracted from oral fluid samples and genotyped for 71 polymorphisms in 29 candidate genes for periodontitis. Results were analyzed using a logistic regression model. P values were corrected for multiple testing using false discovery rate (<0.05). aMMP-8 chairside test positivity and three or more ≥4 mm pockets were associated with vitamin D receptor (VDR) (rs2228570, P = 0.002, q = 0.04) and MMP3 (rs520540, rs639752, rs679620, P = 0.0009, 0.003, 0.003, q = 0.04, respectively). None of the other single-nucleotide polymorphisms studied showed a significant association with the aMMP-8 chairside test and at least one caries lesion positivity. Genetic polymorphisms of MMP3 and VDR are linked to initial periodontitis in Finnish adolescents, and the aMMP-8 chairside test can eventually detect initial periodontitis in young patients with predisposing genetic background.

  17. Food matrix and processing influence on carotenoid bioaccessibility and lipophilic antioxidant activity of fruit juice-based beverages.

    Science.gov (United States)

    Rodríguez-Roque, María Janeth; de Ancos, Begoña; Sánchez-Vega, Rogelio; Sánchez-Moreno, Concepción; Cano, M Pilar; Elez-Martínez, Pedro; Martín-Belloso, Olga

    2016-01-01

    The biological activity of carotenoids depends on their bioaccessibility and solubilization in the gastrointestinal tract. These compounds are poorly dispersed in the aqueous media of the digestive tract due to their lipophilic nature. Thus, it is important to analyze the extent to which some factors, such as the food matrix and food processing, may improve their bioaccessibility. Beverages formulated with a blend of fruit juices and water (WB), milk (MB) or soymilk (SB) were treated by high-intensity pulsed electric fields (HIPEF) (35 kV cm(-1) with 4 μs bipolar pulses at 200 Hz for 1800 μs), high-pressure processing (HPP) (400 MPa at 40 °C for 5 min) or thermal treatment (TT) (90 °C for 1 min) in order to evaluate the influence of food matrix and processing on the bioaccessibility of carotenoids and on the lipophilic antioxidant activity (LAA). The bioaccessibility of these compounds diminished after applying any treatment (HIPEF, HPP and TT), with the exception of cis-violaxanthin + neoxanthin, which increased by 79% in HIPEF and HPP beverages. The lowest carotenoid bioaccessibility was always obtained in TT beverages (losses up to 63%). MB was the best food matrix for improving the bioaccessibility of carotenoids, as well as the LAA. The results demonstrate that treatment and food matrix modulated the bioaccessibility of carotenoids as well as the lipophilic antioxidant potential of beverages. Additionally, HIPEF and HPP could be considered as promising technologies to obtain highly nutritional and functional beverages.

  18. Chromosomal loop/nuclear matrix organization of transcriptionally active and inactive RNA polymerases in HeLa nuclei.

    Science.gov (United States)

    Roberge, M; Dahmus, M E; Bradbury, E M

    1988-06-05

    The relative distribution of transcriptionally active and inactive RNA polymerases I and II between the nuclear matrix/scaffold and chromosomal loops of HeLa cells was determined. Total RNA polymerase was assessed by immunoblotting and transcribing RNA polymerase by a photoaffinity labeling technique in isolated nuclei. Nuclear matrix/scaffold was isolated by three methods using high-salt, intermediate-salt or low-salt extraction. The distribution of RNA polymerases I and II were very similar within each of the methods, but considerable differences in distributions were found between the different preparation methods. Either intermediate-salt or high-salt treatment of DNase I-digested nuclei showed significant association of RNA polymerases with the nuclear matrix. However, intermediate-salt followed by high-salt treatment released all transcribing and non-transcribing RNA polymerases. Nuclear scaffolds isolated with lithium diiodosalicylate (low-salt) contained very little of the RNA polymerases. This treatment, however, caused the dissociation of RNA polymerase II transcription complexes. These results show unambiguously that RNA polymerases, both in their active and inactive forms, are not nuclear matrix proteins. The data support models in which the transcriptional machinery moves around DNA loops during transcription.

  19. ASH1L Suppresses Matrix Metalloproteinase through Mitogen-activated Protein Kinase Signaling Pathway in Pulpitis.

    Science.gov (United States)

    Bei, Yin; Tianqian, Hui; Fanyuan, Yu; Haiyun, Luo; Xueyang, Liao; Jing, Yang; Chenglin, Wang; Ling, Ye

    2017-02-01

    Pulpitis is an inflammation of dental pulp produced by a response to external stimuli. The response entails substantial cellular and molecular activities. Both genetic and epigenetic regulators contribute to the occurrence of pulpitis. However, the epigenetic mechanisms are still poorly understood. In this research, we studied the role of the absent, small, or homeotic-like (ASH1L) gene in the process of pulpitis. Human dental pulp cells (HDPCs) were stimulated with proinflammatory cytokine tumor necrosis factor alpha (TNF-α). Gene expression profiling was performed to assess the occurrence of epigenetic regulators. Pulp tissue from rat experimental pulpitis was subjected to immunofluorescence to detect the occurrence of ASH1L and trimethylation of lysine 4 histone 3 (H3K4me3). The presence of ASH1L in HDPCs that had been generated by TNF-α stimulation was analyzed by Western blot procedures and cellular immunofluorescence. Once detected, ASH1L was silenced through the use of specific small interfering RNA. The effects of ASH1L on the occurrence and operation of matrix metalloproteinases (MMPs) were then tested by analysis of quantitative polymerase chain reactions, Western blotting, and zymography. Chromatin immunoprecipitation was performed to detect whether ASH1L and H3K4me3 were present in the promoter regions of MMPs. We then used Western blot procedures to examine the nuclear factor kappa B and the mitogen-activated protein kinase (MAPK) responses to the silencing of ASH1L. We also examined the specific pathway involved in ASH1L regulation of the MMPs. After stimulating HDPCs with TNF-α, ASH1L emerged as 1 of the most strongly induced epigenetic mediators. We found that TNF-α treatment induced the expression of ASH1L through the nuclear factor kappa B and MAPK signal pathways. ASH1L was found in both the nucleus and the cytoplasm. TNF-α treatment was particularly active in inducing the accumulation of ASH1L in cellular cytoplasm. As is also consistent

  20. Correcting the effects of the matrix using capture gamma-ray spectrometry: Application to measurement by Active Neutron Interrogation

    International Nuclear Information System (INIS)

    Baudry, G.

    2003-11-01

    In the field of the measurement of low masses of fissile material ( 235 U, 239 Pu, 241 Pu) in radioactive waste drums, the Active Neutron Interrogation is a non-destructive method achieving good results. It does however remain reliant upon uncertainties related to the matrix effects on interrogation and fission neutrons. The aim of this thesis is to develop a correction method able to take into account these matrix effects by quantifying the amount of absorbent materials (chlorine and hydrogen) in a 118- liter homogeneous matrix. The main idea is to use the gamma-ray spectrometry of gamma emitted by neutron captures to identify and quantify the composition of the matrix. An indicator from its chlorine content is then deduced in order to choose the calibration coefficient which best represents the real composition of the matrix. This document firstly presents the needs of control and characterization of radioactive objects, and the means used in the field of nuclear measurement. Emphases is put in particular on the Active Neutron Interrogation method. The matrices of interest are those made of light technological waste (density ≤ 0,4 g/cm 3 ) containing hydrogenated and chlorinated materials. The advantages of gamma-rays emitted by neutron captures for the determination of a chlorine content indicator of the matrices and the principles of the correction method are then explained. Measurements have been firstly realized with an existing Neutron Interrogation device (PROMETHEE 6). Such measurements have proven its inadequacy: no signal from the matrix hydrogen was detected, due to an intense signal from the polyethylene contained in some cell elements. Moreover, the matrix chlorine content appeared difficult to be measured. A new and specific device, named REGAIN and dedicated to active gamma-rays spectrometry, was defined with the Monte-Carlo N-Particle (MCNP) code. The experiments conducted with this new device made it possible to detect the hydrogen from the

  1. Role of matrix metalloprotease-2 in oxidant activation of Ca ATPase ...

    Indian Academy of Sciences (India)

    Unknown

    We sought to determine the role of matrix metalloprotease-2 (MMP-2) ... Ca2+ overload in cells and tissues (Bennet and Williams. 1993; Ghosh et ..... tease balance in favour of the protease. ... This work was partly supported by the Life Science.

  2. X-RAY ACTIVE MATRIX PIXEL SENSORS BASEDON J-FET TECHNOLOGY DEVELOPED FOR THE LINAC COHERENT LIGHT SOURCE.

    Energy Technology Data Exchange (ETDEWEB)

    CARINI,G.A.; CHEN, W.; LI, Z.; REHAK, P.; SIDDONS, D.P.

    2007-10-29

    An X-ray Active Matrix Pixel Sensor (XAMPS) is being developed for recording data for the X-ray Pump Probe experiment at the Linac Coherent Light Source (LCLS). Special attention has to be paid to some technological challenges that this design presents. New processes were developed and refined to address problems encountered during previous productions of XAMPS. The development of these critical steps and corresponding tests results are reported here.

  3. Matrix Metalloproteinase-9/Neutrophil Gelatinase-Associated Lipocalin Complex Activity in Human Glioma Samples Predicts Tumor Presence and Clinical Prognosis

    Directory of Open Access Journals (Sweden)

    Ming-Fa Liu

    2015-01-01

    Full Text Available Matrix metalloproteinase-9/neutrophil gelatinase-associated lipocalin (MMP-9/NGAL complex activity is elevated in brain tumors and may serve as a molecular marker for brain tumors. However, the relationship between MMP-9/NGAL activity in brain tumors and patient prognosis and treatment response remains unclear. Here, we compared the clinical characteristics of glioma patients with the MMP-9/NGAL activity measured in their respective tumor and urine samples. Using gelatin zymography assays, we found that MMP-9/NGAL activity was significantly increased in tumor tissues (TT and preoperative urine samples (Preop-1d urine. Activity was reduced by seven days after surgery (Postop-1w urine and elevated again in cases of tumor recurrence. The MMP-9/NGAL status correlated well with MRI-based tumor assessments. These findings suggest that MMP-9/NGAL activity could be a novel marker to detect gliomas and predict the clinical outcome of patients.

  4. Atypical protein kinase C activity is required for extracellular matrix degradation and invasion by Src-transformed cells.

    Science.gov (United States)

    Rodriguez, Elena M; Dunham, Elizabeth E; Martin, G Steven

    2009-10-01

    Atypical protein kinase C (aPKC) isoforms have been shown to mediate Src-dependent signaling in response to growth factor stimulation. To determine if aPKC activity contributes to the transformed phenotype of cells expressing oncogenic Src, we have examined the activity and function of aPKCs in 3T3 cells expressing viral Src (v-Src). aPKC activity and tyrosine phosphorylation were found to be elevated in some but not all clones of mouse fibroblasts expressing v-Src. aPKC activity was inhibited either by addition of a membrane-permeable pseudosubstrate, by expression of a dominant-negative aPKC, or by RNAi-mediated knockdown of specific aPKC isoforms. aPKC activity contributes to morphological transformation and stress fiber disruption, and is required for migration of Src-transformed cells and for their ability to polarize at the edge of a monolayer. The lambda isoform of aPKC is specifically required for invasion through extracellular matrix in Boyden chamber assays and for degradation of the extracellular matrix in in situ zymography assays. Tyrosine phosphorylation of aPKClambda is required for its ability to promote cell invasion. The defect in invasion upon aPKC inhibition appears to result from a defect in the assembly and/or function of podosomes, invasive adhesions on the ventral surface of the cell that are sites of protease secretion. aPKC was also found to localize to podosomes of v-Src transformed cells, suggesting a direct role for aPKC in podosome assembly and/or function. We conclude that basal or elevated aPKC activity is required for the ability of Src-transformed cells to degrade and invade the extracellular matrix. Copyright 2009 Wiley-Liss, Inc.

  5. Epithermal neutron activation analysis of blue-green algae Spirulina Platensis as a matrix for selenium-containing pharmaceuticals

    International Nuclear Information System (INIS)

    Mosulishvili, L.M.; Kirkesali, E.I.; Belokobyl'skij, A.I.; Khizanishvili, A.I.; Frontas'eva, M.V.; Gundorina, S.F.; Oprea, C.D.

    2000-01-01

    To evaluate the potentiality of the blue-green algae Spirulina Platensis as a matrix for the production of Se-containing pharmaceuticals, the background levels of 31 major, minor and trace elements (Na, Mg, Al, Cl, K, Ca, Sc, V, Cr, Mn, Fe, Co, Ni (using (n,p)-reaction), As, Br, Zn, Rb, Mo, Ag, Sb, I, Ba, Sm, Tb, Tm, Hf, Ta, W, Au, Hg, Th) in Spirulina Platensis biomass were determined by means of epithermal neutron activation analysis. The possibility of the purpose-oriented incorporation of Se into Spirulina Platensis biomass was demonstrated. The polynomial dependence of the Se accumulation on nutritional medium loading was revealed. The employed analytical technique allows one to reliably control the amount of toxic elements in algae Spirulina Platensis. Based on this study, a conclusion of the possibility to use Spirulina Platensis as a matrix for the production of Se-containing pharmaceuticals was drawn

  6. Correlation of expression and activity of matrix metalloproteinase-9 and -2 in human gingival cells of periodontitis patients.

    Science.gov (United States)

    Kim, Kyung-A; Chung, Soo-Bong; Hawng, Eun-Young; Noh, Seung-Hyun; Song, Kwon-Ho; Kim, Hanna-Hyun; Kim, Cheorl-Ho; Park, Young-Guk

    2013-02-01

    Matrix metalloproteinases (MMPs) are capable of degrading extracellular matrix, and they are inducible enzymes depending on an inflammatory environment such as periodontitis and bacterial infection in periodontal tissue. Gingival inflammation has been postulated to be correlated with the production of MMP-2 and MMP-9. The objective of this study was to quantify the expression and activity of MMP-9 and -2, and to determine the correlation between activity and expression of these MMPs in human gingival tissues with periodontitis. The gingival tissues of 13 patients were homogenized in 500 µL of phosphate buffered saline with a protease inhibitor cocktail. The expression and activity of MMP-2 and -9 were measured by enzyme-linked immunosorbent assay and Western blot analysis, and quantified by a densitometer. For the correlation line, statistical analysis was performed using the Systat software package. MMP-9 was highly expressed in all gingival tissue samples, whereas MMP-2 was underexpressed compared with MMP-9. MMP-9 activity increased together with the MMP-9 expression level, with a positive correlation (r=0.793, P=0.01). The correlation was not observed in MMP-2. The expression of MMP-2 and -9 might contribute to periodontal physiological and pathological processes, and the degree of MMP-9 expression and activity are predictive indicators relevant to the progression of periodontitis.

  7. How, with whom and when: an overview of CD147-mediated regulatory networks influencing matrix metalloproteinase activity.

    Science.gov (United States)

    Grass, G Daniel; Toole, Bryan P

    2015-11-24

    Matrix metalloproteinases (MMPs) comprise a family of 23 zinc-dependent enzymes involved in various pathologic and physiologic processes. In cancer, MMPs contribute to processes from tumour initiation to establishment of distant metastases. Complex signalling and protein transport networks regulate MMP synthesis, cell surface presentation and release. Earlier attempts to disrupt MMP activity in patients have proven to be intolerable and with underwhelming clinical efficacy; thus targeting ancillary proteins that regulate MMP activity may be a useful therapeutic approach. Extracellular matrix metalloproteinase inducer (EMMPRIN) was originally characterized as a factor present on lung cancer cells, which stimulated collagenase (MMP-1) production in fibroblasts. Subsequent studies demonstrated that EMMPRIN was identical with several other protein factors, including basigin (Bsg), all of which are now commonly termed CD147. CD147 modulates the synthesis and activity of soluble and membrane-bound [membrane-type MMPs (MT-MMPs)] in various contexts via homophilic/heterophilic cell interactions, vesicular shedding or cell-autonomous processes. CD147 also participates in inflammation, nutrient and drug transporter activity, microbial pathology and developmental processes. Despite the hundreds of manuscripts demonstrating CD147-mediated MMP regulation, the molecular underpinnings governing this process have not been fully elucidated. The present review summarizes our present knowledge of the complex regulatory systems influencing CD147 biology and provides a framework to understand how CD147 may influence MMP activity. © 2016 Authors.

  8. How, with whom and when: an overview of CD147-mediated regulatory networks influencing matrix metalloproteinase activity

    Science.gov (United States)

    Grass, G. Daniel; Toole, Bryan P.

    2015-01-01

    Matrix metalloproteinases (MMPs) comprise a family of 23 zinc-dependent enzymes involved in various pathologic and physiologic processes. In cancer, MMPs contribute to processes from tumour initiation to establishment of distant metastases. Complex signalling and protein transport networks regulate MMP synthesis, cell surface presentation and release. Earlier attempts to disrupt MMP activity in patients have proven to be intolerable and with underwhelming clinical efficacy; thus targeting ancillary proteins that regulate MMP activity may be a useful therapeutic approach. Extracellular matrix metalloproteinase inducer (EMMPRIN) was originally characterized as a factor present on lung cancer cells, which stimulated collagenase (MMP-1) production in fibroblasts. Subsequent studies demonstrated that EMMPRIN was identical with several other protein factors, including basigin (Bsg), all of which are now commonly termed CD147. CD147 modulates the synthesis and activity of soluble and membrane-bound [membrane-type MMPs (MT-MMPs)] in various contexts via homophilic/heterophilic cell interactions, vesicular shedding or cell-autonomous processes. CD147 also participates in inflammation, nutrient and drug transporter activity, microbial pathology and developmental processes. Despite the hundreds of manuscripts demonstrating CD147-mediated MMP regulation, the molecular underpinnings governing this process have not been fully elucidated. The present review summarizes our present knowledge of the complex regulatory systems influencing CD147 biology and provides a framework to understand how CD147 may influence MMP activity. PMID:26604323

  9. Supplemental Immobilization of Hanford Low-Activity Waste: Cast Stone Augmented Formulation Matrix Tests

    International Nuclear Information System (INIS)

    Cozzi, A.; Crawford, C.; Fox, K.; Hansen, E.; Roberts, K.

    2015-01-01

    More than 56 million gallons of radioactive and hazardous waste are stored in 177 underground storage tanks at the U.S. Department of Energy's (DOE's) Hanford Site in Washington State. The HLW will be vitrified in the HLW facility for ultimate disposal at an offsite federal repository. A portion (~35%) of the LAW will be vitrified in the LAW vitrification facility for disposal onsite at the Integrated Disposal Facility (IDF). The pretreatment and HLW vitrification facilities will have the capacity to treat and immobilize all of the wastes destined for those facilities. However, a second facility will be needed for the expected volume of LAW requiring immobilization. Cast Stone, a cementitious waste form, is being considered to provide the required additional LAW immobilization capacity. The Cast Stone waste form must be acceptable for disposal in the IDF. The Cast Stone waste form and immobilization process must be tested to demonstrate that the final Cast Stone waste form can comply with the waste acceptance criteria for the disposal facility and that the immobilization processes can be controlled to consistently provide an acceptable waste form product. A testing program was developed in fiscal year (FY) 2012 describing in detail the work needed to develop and qualify Cast Stone as a waste form for the solidification of Hanford LAW. A statistically designed test matrix was used to evaluate the effects of key parameters on the properties of the Cast Stone as it is initially prepared and after curing. For the processing properties, the water-to-dry-blend mix ratio was the most significant parameter in affecting the range of values observed for each property. The single shell tank (SST) Blend simulant also showed differences in measured properties compared to the other three simulants tested. A review of the testing matrix and results indicated that an additional set of tests would be beneficial to improve the understanding of the impacts noted in the

  10. Supplemental Immobilization of Hanford Low-Activity Waste: Cast Stone Augmented Formulation Matrix Tests

    Energy Technology Data Exchange (ETDEWEB)

    Cozzi, A. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Crawford, C. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Fox, K. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Hansen, E. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Roberts, K. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2015-07-20

    More than 56 million gallons of radioactive and hazardous waste are stored in 177 underground storage tanks at the U.S. Department of Energy’s (DOE’s) Hanford Site in Washington State. The HLW will be vitrified in the HLW facility for ultimate disposal at an offsite federal repository. A portion (~35%) of the LAW will be vitrified in the LAW vitrification facility for disposal onsite at the Integrated Disposal Facility (IDF). The pretreatment and HLW vitrification facilities will have the capacity to treat and immobilize all of the wastes destined for those facilities. However, a second facility will be needed for the expected volume of LAW requiring immobilization. Cast Stone, a cementitious waste form, is being considered to provide the required additional LAW immobilization capacity. The Cast Stone waste form must be acceptable for disposal in the IDF. The Cast Stone waste form and immobilization process must be tested to demonstrate that the final Cast Stone waste form can comply with the waste acceptance criteria for the disposal facility and that the immobilization processes can be controlled to consistently provide an acceptable waste form product. A testing program was developed in fiscal year (FY) 2012 describing in detail the work needed to develop and qualify Cast Stone as a waste form for the solidification of Hanford LAW. A statistically designed test matrix was used to evaluate the effects of key parameters on the properties of the Cast Stone as it is initially prepared and after curing. For the processing properties, the water-to-dry-blend mix ratio was the most significant parameter in affecting the range of values observed for each property. The single shell tank (SST) Blend simulant also showed differences in measured properties compared to the other three simulants tested. A review of the testing matrix and results indicated that an additional set of tests would be beneficial to improve the understanding of the impacts noted in the Screening

  11. Peroxisome proliferator-activated receptor δ inhibits Porphyromonas gingivalis lipopolysaccharide-induced activation of matrix metalloproteinase-2 by downregulating NADPH oxidase 4 in human gingival fibroblasts.

    Science.gov (United States)

    Yoo, T; Ham, S A; Hwang, J S; Lee, W J; Paek, K S; Oh, J W; Kim, J H; Do, J T; Han, C W; Kim, J H; Seo, H G

    2016-10-01

    We investigated the roles of peroxisome proliferator-activated receptor δ (PPARδ) in Porphyromonas gingivalis-derived lipopolysaccharide (Pg-LPS)-induced activation of matrix metalloproteinase 2 (MMP-2). In human gingival fibroblasts (HGFs), activation of PPARδ by GW501516, a specific ligand of PPARδ, inhibited Pg-LPS-induced activation of MMP-2 and generation of reactive oxygen species (ROS), which was associated with reduced expression of NADPH oxidase 4 (Nox4). These effects were significantly smaller in the presence of small interfering RNA targeting PPARδ or the specific PPARδ inhibitor GSK0660, indicating that PPARδ is involved in these events. In addition, modulation of Nox4 expression by small interfering RNA influenced the effect of PPARδ on MMP-2 activity, suggesting a mechanism in which Nox4-derived ROS modulates MMP-2 activity. Furthermore, c-Jun N-terminal kinase and p38, but not extracellular signal-regulated kinase, mediated PPARδ-dependent inhibition of MMP-2 activity in HGFs treated with Pg-LPS. Concomitantly, PPARδ-mediated inhibition of MMP-2 activity was associated with the restoration of types I and III collagen to levels approaching those in HGFs not treated with Pg-LPS. These results indicate that PPARδ-mediated downregulation of Nox4 modulates cellular redox status, which in turn plays a critical role in extracellular matrix homeostasis through ROS-dependent regulation of MMP-2 activity. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Resveratrol increases nucleus pulposus matrix synthesis through activating the PI3K/Akt signaling pathway under mechanical compression in a disc organ culture.

    Science.gov (United States)

    Han, Xiaorui; Leng, Xiaoming; Zhao, Man; Wu, Mei; Chen, Amei; Hong, Guoju; Sun, Ping

    2017-12-22

    Disc nucleus pulposus (NP) matrix homeostasis is important for normal disc function. Mechanical overloading seriously decreases matrix synthesis and increases matrix degradation. The present study aims to investigate the effects of resveratrol on disc NP matrix homeostasis under a relatively high-magnitude mechanical compression and the potential mechanism underlying this process. Porcine discs were perfusion-cultured and subjected to a relatively high-magnitude mechanical compression (1.3 MPa at a frequency of 1.0 Hz for 2 h once per day) for 7 days in a mechanically active bioreactor. The non-compressed discs were used as controls. Resveratrol was added along with culture medium to observe the effects of resveratrol on NP matrix synthesis under mechanical load respectively. NP matrix synthesis was evaluated by histology, biochemical content (glycosaminoglycan (GAG) and hydroxyproline (HYP)), and expression of matrix macromolecules (aggrecan and collagen II). Results showed that this high-magnitude mechanical compression significantly decreased NP matrix content, indicated by the decreased staining intensity of Alcian Blue and biochemical content (GAG and HYP), and the down-regulated expression of NP matrix macromolecules (aggrecan and collagen II). Further analysis indicated that resveratrol partly stimulated NP matrix synthesis and increased activity of the PI3K/Akt pathway in a dose-dependent manner under mechanical compression. Together, resveratrol is beneficial for disc NP matrix synthesis under mechanical overloading, and the activation of the PI3K/Akt pathway may participate in this regulatory process. Resveratrol may be promising to regenerate mechanical overloading-induced disc degeneration. © 2017 The Author(s).

  13. Developpement of a photoaffinity probe for the sensitive detection of matrix metallo-protease active forms from complex biological systems

    International Nuclear Information System (INIS)

    Nury, Catherine

    2012-01-01

    A new activity-based probe able to covalently modify the active site of proteases belonging to the matrix metallo-protease family (MMPs) has been developed in this thesis project. The probe was shown to behave as potent inhibitor of several MMPs, with nanomolar Ki values. This probe was also able to modify specifically only the free active site of MMPs, with particular high yields of cross-linking varying from 50 % to 11 %, depending of the MMPs tested. Using radioactivity as means of detection, this probe was able to detect active form of MMPs with a threshold of 1 femto-mole. Applied to the study of bronchoalveolar fluids (BAL) from mice exposed to nanoparticles by a lung aspiration protocol, this probe revealed the presence of the catalytic domain of MMP-12 under its active form, but not in control animals. When used to detect active form of MMPs from extracts obtained from human arteries of patient suffering from atherosclerosis, the probe was not able to detect such MMP active forms. Despite this negative result, the detection of active form of MMP in pathological fluid like BAL has never been reported before this work. Having validated this novel MMP activity-based probe, it will be possible to use it now for detecting MMPs from other pathological fluids or tissues extracts in which MMPs can be good markers of the pathology. (author) [fr

  14. Broccoli and watercress suppress matrix metalloproteinase-9 activity and invasiveness of human MDA-MB-231 breast cancer cells

    International Nuclear Information System (INIS)

    Rose, Peter; Huang, Qing; Ong, Choon Nam; Whiteman, Matt

    2005-01-01

    A high dietary intake of cruciferous vegetables has been associated with a reduction in numerous human pathologies particularly cancer. In the current study, we examined the inhibitory effects of broccoli (Brassica oleracea var. italica) and watercress (Rorripa nasturtium aquaticum) extracts on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cancer cell invasion and matrix metalloproteinase-9 activity using human MDA-MB-231 breast cancer cells. Aberrant overexpression of matrix metalloproteinases, including metalloproteinase-9, is associated with increased invasive potential in cancer cell lines. Our results demonstrate that extracts of broccoli and Rorripa suppressed TPA-induced MMP-9 activity and invasiveness in a concentration dependant manner as determined by zymographic analysis. Furthermore, fractionation of individual extracts followed by liquid chromatography mass spectroscopy analysis (LC-MS) revealed that the inhibitory effects of each vegetable were associated with the presence of 4-methysulfinylbutyl (sulforaphane) and 7-methylsulphinylheptyl isothiocyanates. Taken together, our data indicate that isothiocyanates derived form broccoli and Rorripa inhibit metalloproteinase 9 activities and also suppress the invasive potential of human MDA-MB-231 breast cancer cells in vitro. The inhibitory effects observed in the current study may contribute to the suppression of carcinogenesis by diets high in cruciferous vegetables

  15. Identification of matrix metalloproteinase-2 and -9 activities within the intestinal mucosa of dogs with chronic enteropathies.

    Science.gov (United States)

    Hanifeh, Mohsen; Rajamäki, Minna Marjaana; Syrjä, Pernilla; Mäkitalo, Laura; Kilpinen, Susanne; Spillmann, Thomas

    2018-03-12

    Matrix metalloproteinases (MMPs) 2 and 9 are zinc- and calcium-dependent endopeptidases involved in the breakdown and reconstitution of extracellular matrix under both physiological and pathological conditions. Mucosal MMP-2 and -9 activities have been reported to be upregulated in the intestine of humans with inflammatory bowel disease (IBD), and in animal models of IBD. However, their involvement in the pathogenesis of canine chronic enteropathies (CE) is unknown. This study investigated mucosal pro- and active MMP-2 and -9 activities in dogs with CE and healthy dogs using gelatin zymography, and also to determine the association of their activities in dogs with CE with the canine IBD activity index (CIBDAI), histopathologic findings, the clinical outcome, and hypoalbuminemia. Intestinal mucosal samples from duodenum, ileum, colon, and cecum were collected from 40 dogs with CE and 18 healthy Beagle dogs. In dogs with CE, the number of samples positive for mucosal pro- and active MMP-2 was significantly higher in the duodenum (P < 0.0001 and P = 0.011, respectively), ileum (P = 0.002 and P = 0.018, respectively), and colon (P < 0.0001 and P = 0.002, respectively), compared with healthy controls. Mucosal pro-MMP-9-positive samples in the duodenum and colon were significantly more frequent in dogs with CE than in healthy dogs (P = 0.0004 and P = 0.001, respectively). Despite the presence of mucosal samples positive for active MMP-9 in the intestinal segments of dogs with CE, the difference compared to healthy controls did not reach statistical significance. None of the intestinal mucosal samples in healthy dogs showed gelatinolytic activity corresponding to the control bands of active MMP-2 and -9. Mucosal active MMP-9 activities displayed a significant positive association with the severity of neutrophil infiltration in the duodenum (P = 00.040), eosinophils in the cecum (P = 00.037), and the CIBDAI score for ileum samples

  16. AMP-Activated Protein Kinase Alleviates Extracellular Matrix Accumulation in High Glucose-Induced Renal Fibroblasts through mTOR Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Xia Luo

    2015-01-01

    Full Text Available Background/Aims: Extracellular matrix accumulation contributes significantly to the pathogenesis of diabetic nephropathy. Although AMP-activated protein kinase (AMPK has been found to inhibit extracellular matrix synthesis by experiments in vivo and vitro, its role in alleviating the deposition of extracellular matrix in renal interstitial fibroblasts has not been well defined. Methods: Currently, we conducted this study to investigate the effects of AMPK on high glucose-induced extracellular matrix synthesis and involved intracellular signaling pathway by using western blot in the kidney fibroblast cell line (NRK-49f. Results: Collagen IV protein levels were significantly increased by high glucose in a time-dependent manner. This was associated with a decrease in Thr72 phosphorylation of AMPK and an increase in phosphorylation of mTOR on Ser2448. High glucose-induced extracellular matrix accumulation and mTOR activation were significantly inhibited by the co-treatment of rAAV-AMPKα1312 (encoding constitutively active AMPKα1 whereas activated by r-AAV-AMPKα1D157A (encoding dominant negative AMPKα1. In cultured renal fibroblasts, overexpression of AMPKα1D157A upregulated mTOR signaling and matrix synthesis, which were ameliorated by co-treatment with the inhibitor of mTOR, rapamycin. Conclusion: Collectively, these findings indicate that AMPK exerts renoprotective effects by inhibiting the accumulation of extracellular matrix through mTOR signaling pathway.

  17. Matrix pencil method-based reference current generation for shunt active power filters

    DEFF Research Database (Denmark)

    Terriche, Yacine; Golestan, Saeed; Guerrero, Josep M.

    2018-01-01

    response and works well under distorted and unbalanced voltage. Moreover, the proposed method can estimate the voltage phase accurately; this property enables the algorithm to compensate for both power factor and current unbalance. The effectiveness of the proposed method is verified using simulation...... are using the discrete Fourier transform (DFT) in the frequency domain or the instantaneous p–q theory and the synchronous reference frame in the time domain. The DFT, however, suffers from the picket-fence effect and spectral leakage. On the other hand, the DFT takes at least one cycle of the nominal...... frequency. The time-domain methods show a weakness under voltage distortion, which requires prior filtering techniques. The aim of this study is to present a fast yet effective method for generating the RCC for SAPFs. The proposed method, which is based on the matrix pencil method, has a fast dynamic...

  18. Effect of flavones on rat brain and lung matrix metalloproteinase activity measured by film in-situ zymography.

    Science.gov (United States)

    Sasaki, K; Tateoka, N; Ando, H; Yoshizaki, F

    2005-04-01

    We have evaluated the inhibitory activity of flavone, nobiletin, and heptamethoxyflavone on matrix metalloproteinase (MMP) activity in the rat. MMP in 9000-g supernatant fraction of lung homogenate was activated by p-aminophenyl mercuric acetate (APMA), and gelatinolytic activity was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) followed by Coomassie staining. This activity should be related to MMP-2 and/or MMP-9 and was confirmed by gelatin zymography. Fluorescent-conjugated collagen used as a substrate for collagenolytic activity wasinvestigated by SDS-PAGE also. The film in-situ zymography method was applied to rat brain and lung tissue in the same manner. Flavone and nobiletin inhibited the APMA-stimulated gelatinolytic activity and also the collagenolytic activity by more than 75%. The film in-situ zymography method indicated that these compounds might be potent inhibitors of MMP, suggesting the specific inhibition of localized MMP in brain hippocampus and/or lung terminal bronchioles, which may contribute to the prevention of some types of brain disease or cancer invasion and metastasis.

  19. Mueller-matrix ellipsometry studies of optically active structures in scarab beetles

    Directory of Open Access Journals (Sweden)

    Arwin H.

    2010-06-01

    Full Text Available The complexity of multilayers, photonic crystals, metamaterials and other artificial materials has promoted the use of spectroscopic, variable angle, generalized and Mueller-matrix ellipsometry. Naturally occurring structures may show even higher complexity than artificial structures but with a more narrow range of constituent materials. Fascinating reflection properties result from intricate photonic structures in, for instance, the wing scales and cuticles of insects. Currently there is a large interest to explore such functional supramolecular architectures for exploitation in nanotechnology. In this study, Mueller-matrix spectroscopic ellipsometry is applied in the spectral range of 250 to 1000 nm to investigate optical response and structures of the cuticle of Scarab beetles of the Cetoniinae subfamily. The cuticle of Cetonia aurata (the rose chafer, la cétoine dorée is green with a metallic appearance and reflects left-handed circular/elliptically polarized light. It has been suggested that the polarization of this metallic gloss is caused by a helical structure in the chitinous cuticle. We find that the polarization effect is limited to the narrow spectral range 470-550 nm whereas for shorter or longer wavelengths the reflection properties are similar to those from a near-dielectric material. Model calculations and parameterization of the nanostructure employing a heliocoidal structure are discussed. As a comparison the polarization effects from light reflected from two other beetles will be presented. Coptomia laevis has a similar appearance as Cetonia aurata but has very different polarization properties. The golden Plusiotis argentiola has very interesting properties showing both left and right-handed polarization depending on incidence angle and wavelength.

  20. Treatment of active unicameral bone cysts with percutaneous injection of demineralized bone matrix and autogenous bone marrow.

    Science.gov (United States)

    Rougraff, Bruce T; Kling, Thomas J

    2002-06-01

    The treatment of unicameral bone cysts varies from open bone-grafting procedures to percutaneous injection of corticosteroids or bone marrow. The purpose of this study was to evaluate the feasibility and effectiveness of percutaneous injection of a mixture of demineralized bone matrix and autogenous bone marrow for the treatment of simple bone cysts. Twenty-three patients with an active unicameral bone cyst were treated with trephination and injection of allogeneic demineralized bone matrix and autogenous bone marrow. The patients were followed for an average of fifty months (range, thirty to eighty-one months), at which time pain, function, and radiographic signs of resolution of the cyst were assessed. The average time until the patients had pain relief was five weeks, and the average time until the patients returned to full, unrestricted activities was six weeks. Bone-healing at the site of the injection was first seen radiographically at three to six months. No patient had a pathologic fracture during this early bone-healing stage. Cortical remodeling was seen radiographically by six to nine months, and after one year the response was usually complete, changing very little from then on. Five patients required a second injection because of recurrence of the cyst, and all five had a clinically and radiographically quiescent cyst after an average of thirty-six additional months of follow-up. Seven of the twenty-three patients had incomplete healing manifested by small, persistent radiolucent areas within the original cyst. None of these cysts increased in size or resulted in pain or fracture. Percutaneous injection of allogeneic demineralized bone matrix and autogenous bone marrow is an effective treatment for unicameral bone cysts.

  1. CAPN 7 promotes the migration and invasion of human endometrial stromal cell by regulating matrix metalloproteinase 2 activity.

    Science.gov (United States)

    Liu, Hongyu; Jiang, Yue; Jin, Xiaoyan; Zhu, Lihua; Shen, Xiaoyue; Zhang, Qun; Wang, Bin; Wang, Junxia; Hu, Yali; Yan, Guijun; Sun, Haixiang

    2013-07-15

    Matrix metalloproteinase 2 (MMP-2) has been reported to be an important regulator of cell migration and invasion through degradation of the extracellular matrix (ECM) in many diseases, such as cancer and endometriosis. Here, we found calcium-activated neutral protease 7 (CAPN 7) expression was markedly upregulated in the eutopic endometrium and endometrial stromal cells of women diagnosed with endometriosis. Our studies were carried out to detect the effects of CAPN 7 on human endometrial stromal cell (hESC) migration and invasion. Western blotting and quantitative real-time PCR were used to detect the expression of CAPN 7 in endometriosis patients and normal fertile women. Scratch-wound-healing and invasion chamber assay were used to investigate the role of CAPN 7 in hESC migration and invasion. Western blotting, quantitative real-time PCR and zymography were carried out to detect the effect of CAPN 7 on the expressions and activity of MMP-2. CAPN 7 was markedly up-regulated in endometriosis, thereby promoting the migration and invasion of hESC. CAPN 7 overexpression led to increased expression of MMP-2 and tissue inhibitor of metalloproteinases 2 (TIMP-2); CAPN 7 knockdown reversed these changes. CAPN 7 increased MMP-2 activity by increasing the ratio of MMP-2 to TIMP-2. We also found that OA-Hy (an MMP-2 inhibitor) decreased the effects of CAPN 7 overexpression on hESC migration and invasion by approximately 50% and 55%, respectively. Additionally, a coimmunoprecipitation assay demonstrated that CAPN 7 interacted with activator protein 2α (AP-2α): an important transcription factor of MMP-2. CAPN 7 promotes hESC migration and invasion by increasing the activity of MMP-2 via an increased ratio of MMP-2 to TIMP-2.

  2. Pentagalloyl glucose increases elastin deposition, decreases reactive oxygen species and matrix metalloproteinase activity in pulmonary fibroblasts under inflammatory conditions.

    Science.gov (United States)

    Parasaram, Vaideesh; Nosoudi, Nasim; Chowdhury, Aniqa; Vyavahare, Naren

    2018-04-30

    Emphysema is characterized by degradation of lung alveoli that leads to poor airflow in lungs. Irreversible elastic fiber degradation by matrix metalloproteinases (MMPs) and reactive oxygen species (ROS) activity leads to loss of elasticity and drives the progression of this disease. We investigated if a polyphenol, pentagalloyl glucose (PGG) can increase elastin production in pulmonary fibroblasts. We also studied the effect of PGG treatment in reducing MMP activity and ROS levels in cells. We exposed rat pulmonary fibroblasts to two different types of inflammatory environments i.e., tumor necrosis factor-α (TNF-α) and cigarette smoke extract (CSE) to mimic the disease. Parameters like lysyl oxidase (LOX) and elastin gene expression, MMP-9 activity in the medium, lysyl oxidase (LOX) activity and ROS levels were studied to assess the effect of PGG on pulmonary fibroblasts. CSE inhibited lysyl oxidase (LOX) enzyme activity that resulted in a decreased elastin formation. Similarly, TNF-α treated cells showed less elastin in the cell layers. Both these agents caused increase in MMP activity and ROS levels in cells. However, when supplemented with PGG treatment along with these two inflammatory agents, we saw a significant increase in elastin deposition, reduction in both MMP activity and ROS levels. Thus PGG, which has anti-inflammatory, anti-oxidant properties coupled with its ability to aid in elastic fiber formation, can be a multifunctional drug to potentially arrest the progression of emphysema. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Large-Area High-Performance Flexible Pressure Sensor with Carbon Nanotube Active Matrix for Electronic Skin.

    Science.gov (United States)

    Nela, Luca; Tang, Jianshi; Cao, Qing; Tulevski, George; Han, Shu-Jen

    2018-03-14

    Artificial "electronic skin" is of great interest for mimicking the functionality of human skin, such as tactile pressure sensing. Several important performance metrics include mechanical flexibility, operation voltage, sensitivity, and accuracy, as well as response speed. In this Letter, we demonstrate a large-area high-performance flexible pressure sensor built on an active matrix of 16 × 16 carbon nanotube thin-film transistors (CNT TFTs). Made from highly purified solution tubes, the active matrix exhibits superior flexible TFT performance with high mobility and large current density, along with a high device yield of nearly 99% over 4 inch sample area. The fully integrated flexible pressure sensor operates within a small voltage range of 3 V and shows superb performance featuring high spatial resolution of 4 mm, faster response than human skin (<30 ms), and excellent accuracy in sensing complex objects on both flat and curved surfaces. This work may pave the road for future integration of high-performance electronic skin in smart robotics and prosthetic solutions.

  4. TIMP-1 resistant matrix metalloproteinase-9 is the predominant serum active isoform associated with MRI activity in patients with multiple sclerosis.

    Science.gov (United States)

    Trentini, Alessandro; Manfrinato, Maria C; Castellazzi, Massimiliano; Tamborino, Carmine; Roversi, Gloria; Volta, Carlo A; Baldi, Eleonora; Tola, Maria R; Granieri, Enrico; Dallocchio, Franco; Bellini, Tiziana; Fainardi, Enrico

    2015-08-01

    The activity of matrix metalloproteinase-9 (MMP-9) depends on two isoforms, an 82 kDa active MMP-9 modulated by its specific tissue inhibitor (TIMP-1), and a 65 kDa TIMP-1 resistant active MMP-9. The relevance of these two enzymatic isoforms in multiple sclerosis (MS) is still unknown. To investigate the contribution of the TIMP-1 modulated and resistant active MMP-9 isoforms to MS pathogenesis. We measured the serum levels of the 82 kDa and TIMP-1 resistant active MMP-9 isoforms by activity assay systems in 86 relapsing-remitting MS (RRMS) patients, categorized according to clinical and magnetic resonance imaging (MRI) evidence of disease activity, and in 70 inflammatory (OIND) and 69 non-inflammatory (NIND) controls. Serum levels of TIMP-1 resistant MMP-9 were more elevated in MS patients than in OIND and NIND (p < 0.05, p < 0.02, respectively). Conversely, 82 kDa active MMP-9 was higher in NIND than in the OIND and MS patients (p < 0.01 and p < 0.00001, respectively). MRI-active patients had higher levels of TIMP-1 resistant MMP-9 and 82 kDa active MMP-9, than did those with MRI inactive MS (p < 0.01 and p < 0.05, respectively). Our findings suggested that the TIMP-1 resistant MMP-9 seem to be the predominantly active isoform contributing to MS disease activity. © The Author(s), 2015.

  5. Exogenous L-arginine reduces matrix metalloproteinase-2 and -9 activities and oxidative stress in patients with hypertension

    DEFF Research Database (Denmark)

    Garcia, Vinicius P; Rocha, Helena N M; Silva, Gustavo M.

    2016-01-01

    Aims Increased matrix metalloproteinases activity and reduced nitric oxide (NO) bioavailability contributes to development of hypertension and this may be associated with a defective L-arginine-NO pathway. Exogenous L-arginine improves endothelial function to prevent the onset of cardiovascular...... disease, but the mechanism by which this is accomplished remains unclear. We determined the effects of exogenous L-arginine infusion on vascular biomarkers in patients with hypertension. Main methods Venous blood samples were obtained from seven patients with hypertension (45 ± 5 yrs., HT group...... biomarkers between groups during the saline infusion (P > 0.05). Significance Exogenous L-arginine diminished metalloproteinase-2 and -9 activities and MMP-9/TIMP-1 ratio along with restoring the oxidative stress balance in patients with hypertension....

  6. A matrix-focused structure-activity and binding site flexibility study of quinolinol inhibitors of botulinum neurotoxin serotype A.

    Science.gov (United States)

    Harrell, William A; Vieira, Rebecca C; Ensel, Susan M; Montgomery, Vicki; Guernieri, Rebecca; Eccard, Vanessa S; Campbell, Yvette; Roxas-Duncan, Virginia; Cardellina, John H; Webb, Robert P; Smith, Leonard A

    2017-02-01

    Our initial discovery of 8-hydroxyquinoline inhibitors of BoNT/A and separation/testing of enantiomers of one of the more active leads indicated considerable flexibility in the binding site. We designed a limited study to investigate this flexibility and probe structure-activity relationships; utilizing the Betti reaction, a 36 compound matrix of quinolinol BoNT/A LC inhibitors was developed using three 8-hydroxyquinolines, three heteroaromatic amines, and four substituted benzaldehydes. This study has revealed some of the most effective quinolinol-based BoNT/A inhibitors to date, with 7 compounds displaying IC 50 values ⩽1μM and 11 effective at ⩽2μM in an ex vivo assay. Published by Elsevier Ltd.

  7. Matrix suites applying when making the commercial-company-activity-andfinancial-risks-express-diagnostics

    Directory of Open Access Journals (Sweden)

    Valentina Petrovn Neganova

    2011-09-01

    Full Text Available This paper describes an original technique and peculiarities of its use for the express diagnostics of a company and analysis of financial risks. The feature of this technique is potential Russian reality accountance of optimizational transformations of statements in order to minimize taxation and refract the information field of a business system for the apperception. It is based on the conceptual principle of studies of the University of Ghent, according to which, these three cycles affect stability of the companies to the important risk - the risk of bankruptcy. It is noted that the use of matrix analysis can become an additional powerful tool for solving the conceptual verification problem of financial permanence of business systems operation in the marketplace because it allows to determine the internal nature of the underlying processes that occur within an atomic business system and to make every effort to minimize potential and actual manifestations of instability of the external and internal environment of the business system. This method satisfies the multiple set of conditions-equations: apperceptive, asymptotic and simplificational functions that form the basis of calculations for model creation. The technique can be applied by commercial banks in the analysis of the elements of their loan portfolio. Application of this technique allows analyzing the performance of a commercial company in the features of Russian life with minimal iterations.

  8. In Vivo Molecular Imaging of Cathepsin and Matrix Metalloproteinase Activity Discriminates between Arthritic and Osteoarthritic Processes in Mice

    Directory of Open Access Journals (Sweden)

    Eline A. Vermeij

    2014-01-01

    Full Text Available Rheumatoid arthritis (RA and osteoarthritis (OA are serologically and clinically distinctive, but at the local level, both diseases have many molecular pathways in common. In vivo molecular imaging can unravel the local pathologic processes involved in both diseases. In this study, we investigated matrix metalloproteinase (MMP and cathepsin activity during cartilage destruction, in an RA and an OA mouse model, using biophotonic imaging of substrate-based probes. Mice with collagen-induced arthritis (CIA or destabilization of the medial meniscus (DMM were imaged using near-infrared fluorescent probes, activated by several cathepsins or MMPs. Fluorescence signal intensity was compared to synovial gene expression, histology, and cartilage staining of a neoepitope of aggrecan cleaved by MMPs with the amino acids DIPEN. Increased cathepsin and MMP activity was seen during CIA, whereas the DMM model only showed increased MMP activity. DIPEN expression was seen only during CIA. A possible explanation can be differences in gene expressions; MMP3 and -13, known to produce DIPEN neoepitopes, were upregulated in the CIA model, whereas MMP12, known to be involved in elastin degradation and chemokine inhibition, was upregulated in the DMM model. Thus, molecular imaging showed no cathepsin activity at the time of cartilage damage in the DMM model, whereas both cathepsins and MMPs are active in the CIA model during disease progression.

  9. Molecular Structures and Dynamics of the Stepwise Activation Mechanism of a Matrix Metalloproteinase Zymogen: Challenging the Cysteine Switch Dogma

    International Nuclear Information System (INIS)

    Rosenblum, G.; Meroueh, S.; Toth, M.; Fisher, J.; Fridman, R.; Mobashery, S.; Sagi, I.

    2007-01-01

    Activation of matrix metalloproteinase zymogen (pro-MMP) is a vital homeostatic process, yet its molecular basis remains unresolved. Using stopped-flow X-ray spectroscopy of the active site zinc ion, we determined the temporal sequence of pro-MMP-9 activation catalyzed by tissue kallikrein protease in milliseconds to several minutes. The identity of three intermediates seen by X-ray spectroscopy was corroborated by molecular dynamics simulations and quantum mechanics/molecular mechanics calculations. The cysteine-zinc interaction that maintains enzyme latency is disrupted via active-site proton transfers that mediate transient metal-protein coordination events and eventual binding of water. Unexpectedly, these events ensue as a direct result of complexation of pro-MMP-9 and kallikrein and occur before proteolysis and eventual dissociation of the pro-peptide from the catalytic site. Here we demonstrate the synergism among long-range protein conformational transitions, local structural rearrangements, and fine atomic events in the process of zymogen activation.

  10. Matrix metalloproteinases (MMP-2 and MMP-9) activity in corneal ulcer and ocular surface disorders determined by gelatin zymography.

    Science.gov (United States)

    Singh, Arti; Maurya, O P S; Jagannadhan, M V; Patel, Ashok

    2012-01-01

    The purpose of this paper is to determine the active form of matrix metalloproteinases (MMP-2 and MMP-9) in corneal ulcer and ocular surface disorder patients. A total of 35 patients of corneal ulcer, 20 patients of ocular surface disorders and 10 control subjects were included in this study and estimation of active form of MMP-2 and MMP-9 was done by gelatin zymography. Tear samples were collected by capillary tube method. Both pro- and active forms of MMP-9 were detected in 24 out of 35 patients with corneal ulcer and 15 out of 20 patients with ocular surface disorders. None of the patients were showing MMP-2 activity. Neither MMP-2 nor MMP-9 was detected in the control group. Active forms of MMP-9 are present in tears of severe ulcerative and ocular surface disorder patients. Thus, proteinase inhibitors have been recommended for the treatment of corneal ulcer and ocular surface disorders to reduced the progression of stromal ulcer and to minimize corneal scarring.

  11. Haloperidol Abrogates Matrix Metalloproteinase-9 Expression by Inhibition of NF-κB Activation in Stimulated Human Monocytic Cells

    Directory of Open Access Journals (Sweden)

    Yueh-Lun Lee

    2018-01-01

    Full Text Available Much evidence has indicated that matrix metalloproteinases (MMPs participate in the progression of neuroinflammatory disorders. The present study was undertaken to investigate the inhibitory effect and mechanism of the antipsychotic haloperidol on MMP activation in the stimulated THP-1 monocytic cells. Haloperidol exerted a strong inhibition on tumor necrosis factor- (TNF- α-induced MMP-9 gelatinolysis of THP-1 cells. A concentration-dependent inhibitory effect of haloperidol was observed in TNF-α-induced protein and mRNA expression of MMP-9. On the other hand, haloperidol slightly affected cell viability and tissue inhibition of metalloproteinase-1 levels. It significantly inhibited the degradation of inhibitor-κB-α (IκBα in activated cells. Moreover, it suppressed activated nuclear factor-κB (NF-κB detected by a mobility shift assay, NF-κB reporter gene, and chromatin immunoprecipitation analyses. Consistent with NF-κB inhibition, haloperidol exerted a strong inhibition of lipopolysaccharide- (LPS- induced MMP-9 gelatinolysis but not of transforming growth factor-β1-induced MMP-2. In in vivo studies, administration of haloperidol significantly attenuated LPS-induced intracerebral MMP-9 activation of the brain homogenate and the in situ in C57BL/6 mice. In conclusion, the selective anti-MMP-9 activation of haloperidol could possibly involve the inhibition of the NF-κB signal pathway. Hence, it was found that haloperidol treatment may represent a bystander of anti-MMP actions for its conventional psychotherapy.

  12. Wogonin Suppresses the Activity of Matrix Metalloproteinase-9 and Inhibits Migration and Invasion in Human Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Ming Hong

    2018-02-01

    Full Text Available As one of the major active ingredients in Radix Scutellariae, wogonin has been shown to be associated with various pharmacological activities on cancer cell growth, apoptosis, and cell invasion and migration. Here, we demonstrated that wogonin may harbor potential anti-metastatic activities in hepatocarcinoma (HCC. The anti-metastasis potential of wogonin and its underlying mechanisms were evaluated by ligand–protein docking approach, surface plasmon resonance assay, and in vitro gelatin zymography studies. Our results showed that wogonin (100 μM, 50 μM suppressed MHCC97L and PLC/PRF/5 cells migration and invasion in vitro. The docking approach and surface plasmon resonance assay indicated that the potential binding affinity between wogonin and matrix metalloproteinase-9 (MMP-9 may lead to inhibition of MMP-9 activity and further leads to suppression of tumor metastasis. This conclusion was further verified by Western blot results and gelatin zymography analysis. Wogonin might be a potent treatment option for disrupting the tumor metastasis that favors HCC development. The potential active targets from computational screening integrated with biomedical study may help us to explore the molecular mechanism of herbal medicines.

  13. Valsartan attenuates pulmonary hypertension via suppression of mitogen activated protein kinase signaling and matrix metalloproteinase expression in rodents.

    Science.gov (United States)

    Lu, Yuyan; Guo, Haipeng; Sun, Yuxi; Pan, Xin; Dong, Jia; Gao, Di; Chen, Wei; Xu, Yawei; Xu, Dachun

    2017-08-01

    It has previously been demonstrated that the renin-angiotensin system is involved in the pathogenesis and development of pulmonary hypertension (PH). However, the efficacy of angiotensin II type I (AT1) receptor blockers in the treatment of PH is variable. The present study examined the effects of the AT1 receptor blocker valsartan on monocrotaline (MCT)‑induced PH in rats and chronic hypoxia‑induced PH in mice. The results demonstrated that valsartan markedly attenuated development of PH in rats and mice, as indicated by reduced right ventricular systolic pressure, diminished lung vascular remodeling and decreased right ventricular hypertrophy, compared with vehicle treated animals. Immunohistochemical analyses of proliferating cell nuclear antigen expression revealed that valsartan suppressed smooth muscle cell proliferation. Western blot analysis demonstrated that valsartan limited activation of p38, c‑Jun N‑terminal kinase 1/2 and extracellular signal‑regulated kinase 1/2 signaling pathways and significantly reduced MCT‑induced upregulation of pulmonary matrix metalloproteinases‑2 and ‑9, and transforming growth factor‑β1 expression. The results suggested that valsartan attenuates development of PH in rodents by reducing expression of extracellular matrix remodeling factors and limiting smooth muscle cell proliferation to decrease pathological vascular remodeling. Therefore, valsartan may be a valuable future therapeutic approach for the treatment of PH.

  14. Potential Effects of Caffeic Acid in Suppression of Matrix Metalloproteinases Activities in Irradiated Rats

    International Nuclear Information System (INIS)

    Zahran, A.M.

    2008-01-01

    Great Number of researches on the potential role of antioxidant nutrients and phenolic compounds in the prevention of chronic diseases has been accumulated over the past several decades. Despite this effort, there is much that remains uncertain. Bio markers research in this field has the potential to help fill the gaps in current knowledge. The present study was designed to evaluate, in one aspect, the probable direction expression of proteolytic enzymes as indices for gamma-irradiation-induced oxidative stress and their relationship, in other aspect with one antioxidant micro nutrient phenolic compound: caffeic acid (CA). Sprague Dawley male albino rats were administrated CA intraperitoneally (i.p.) 10 μmol/ kg body wt/ day for 8 consecutive days pre irradiation exposure (fractionated doses, instalment as 1 Gy every day up to total dose of 8 Gy). The treatment was continued for 15 successive days following irradiation processing. Quantitative assay of gelatinolytic zymo graphic analysis of serum and hepatic tissues showed that exposure to gamma-rays yields a marked significant increase in the activities of both latent and active MMP-9 (92 and 86 kDa), respectively, and both latent and active MMP-2 (72 and 66 kDa), respectively. Administration of CA significantly decreased the activities of MMP-2 and MMP-9 in gamma-irradiated rats. Conclusion: the present findings demonstrated that irradiation-exposure leads to enhancement of enzymatic activities of MMP-2 and MMP-9 in their inactive and active forms in the serum and liver. Meanwhile, administration of CA exhibits protective effects in gamma-irradiated rats through down-regulation of MMP-2 and MMP-9 activities

  15. Regulation of Matrix Metalloproteinase-2 Activity by COX-2-PGE2-pAKT Axis Promotes Angiogenesis in Endometriosis

    Science.gov (United States)

    Ray, Amlan K.; DasMahapatra, Pramathes; Swarnakar, Snehasikta

    2016-01-01

    Endometriosis is characterized by the ectopic development of the endometrium which relies on angiogenesis. Although studies have identified the involvement of different matrix metalloproteinases (MMPs) in endometriosis, no study has yet investigated the role of MMP-2 in endometriosis-associated angiogenesis. The present study aims to understand the regulation of MMP-2 activity in endothelial cells and on angiogenesis during progression of ovarian endometriosis. Histological and biochemical data showed increased expressions of vascular endothelial growth factor (VEGF), VEGF receptor-2, cycloxygenase (COX)-2, von Willebrand factor along with angiogenesis during endometriosis progression. Women with endometriosis showed decreased MMP-2 activity in eutopic endometrium as compared to women without endometriosis. However, ectopic ovarian endometrioma showed significantly elevated MMP-2 activity with disease severity. In addition, increased MT1MMP and decreased tissue inhibitors of metalloproteinases (TIMP)-2 expressions were found in the late stages of endometriosis indicating more MMP-2 activation with disease progression. In vitro study using human endothelial cells showed that prostaglandin E2 (PGE2) significantly increased MMP-2 activity as well as tube formation. Inhibition of COX-2 and/or phosphorylated AKT suppressed MMP-2 activity and endothelial tube formation suggesting involvement of PGE2 in regulation of MMP-2 activity during angiogenesis. Moreover, specific inhibition of MMP-2 by chemical inhibitor significantly reduced cellular migration, invasion and tube formation. In ovo assay showed decreased angiogenic branching upon MMP-2 inhibition. Furthermore, a significant reduction of lesion numbers was observed upon inhibition of MMP-2 and COX-2 in mouse model of endometriosis. In conclusion, our study establishes the involvement of MMP-2 activity via COX-2-PGE2-pAKT axis in promoting angiogenesis during endometriosis progression. PMID:27695098

  16. 3-Phosphoinositide-dependent Protein Kinase-1 (PDK1) promotes invasion and activation of matrix metalloproteinases

    International Nuclear Information System (INIS)

    Xie, Zhihui; Yuan, Hongyan; Yin, Yuzhi; Zeng, Xiao; Bai, Renkui; Glazer, Robert I

    2006-01-01

    Metastasis is a major cause of morbidity and mortality in breast cancer with tumor cell invasion playing a crucial role in the metastatic process. PDK1 is a key molecule that couples PI3K to cell proliferation and survival signals in response to growth factor receptor activation, and is oncogenic when expressed in mouse mammary epithelial cells. We now present evidence showing that PDK1-expressing cells exhibit enhanced anchorage-dependent and -independent cell growth and are highly invasive when grown on Matrigel. These properties correlate with induction of MMP-2 activity, increased MT1-MMP expression and a unique gene expression profile. Invasion assays in Matrigel, MMP-2 zymogram analysis, gene microarray analysis and mammary isografts were used to characterize the invasive and proliferative function of cells expressing PDK1. Tissue microarray analysis of human breast cancers was used to measure PDK1 expression in invasive tumors by IHC. Enhanced invasion on Matrigel in PDK1-expressing cells was accompanied by increased MMP-2 activity resulting from stabilization against proteasomal degradation. Increased MMP-2 activity was accompanied by elevated levels of MT1-MMP, which is involved in generating active MMP-2. Gene microarray analysis identified increased expression of the ECM-associated genes decorin and type I procollagen, whose gene products are substrates of MT1-MMP. Mammary fat pad isografts of PDK1-expressing cells produced invasive adenocarcinomas. Tissue microarray analysis of human invasive breast cancer indicated that PDK1pSer241 was strongly expressed in 90% of samples. These results indicate that PDK1 serves as an important effector of mammary epithelial cell growth and invasion in the transformed phenotype. PDK1 mediates its effect in part by MT1-MMP induction, which in turn activates MMP-2 and modulates the ECM proteins decorin and collagen. The presence of increased PDK1 expression in the majority of invasive breast cancers suggests its

  17. Active cell-matrix coupling regulates cellular force landscapes of cohesive epithelial monolayers

    Science.gov (United States)

    Zhao, Tiankai; Zhang, Yao; Wei, Qiong; Shi, Xuechen; Zhao, Peng; Chen, Long-Qing; Zhang, Sulin

    2018-03-01

    Epithelial cells can assemble into cohesive monolayers with rich morphologies on substrates due to competition between elastic, edge, and interfacial effects. Here we present a molecularly based thermodynamic model, integrating monolayer and substrate elasticity, and force-mediated focal adhesion formation, to elucidate the active biochemical regulation over the cellular force landscapes in cohesive epithelial monolayers, corroborated by microscopy and immunofluorescence studies. The predicted extracellular traction and intercellular tension are both monolayer size and substrate stiffness dependent, suggestive of cross-talks between intercellular and extracellular activities. Our model sets a firm ground toward a versatile computational framework to uncover the molecular origins of morphogenesis and disease in multicellular epithelia.

  18. Altered association of transcriptionally active DNA with the nuclear-matrix after heat shock

    NARCIS (Netherlands)

    Sakkers, RJ; Brunsting, JF; Filon, AR; Kampinga, HH; Konings, AWT; Mullenders, LHF

    Purpose: Exposure of human cells to heat leads to denaturation and aggregation of proteins. Within the nucleus, it has been suggested that protein aggregation is linked to the: selective inhibition by hyperthermia of nucleotide excision repair in transcriptionally active genes. Tn this study it was

  19. Matrix theory

    CERN Document Server

    Franklin, Joel N

    2003-01-01

    Mathematically rigorous introduction covers vector and matrix norms, the condition-number of a matrix, positive and irreducible matrices, much more. Only elementary algebra and calculus required. Includes problem-solving exercises. 1968 edition.

  20. Separating DDTs in edible animal fats using matrix solid-phase dispersion extraction with activated carbon filter, Toyobo-KF.

    Science.gov (United States)

    Furusawa, Naoto

    2006-09-01

    A technique is presented for the economical, routine, and quantitative analysis of contamination by dichloro-diphenyl-trichloroethanes (DDTs) [pp'-DDT, pp'-dichlorodiphenyl dichloroethylene, and pp'-dichlorodiphenyl dichloreothane in beef tallow and chicken fat samples, based on their separation using matrix solid-phase dispersion (MSPD) extraction with Toyobo-KF, an activated carbon fiber. Toyobo-KF is a newly applied MSPD sorbent, and it is followed by reversed-phase high-performance liquid chromatography (HPLC) with a photodiode array detector. The resulting analytical performance parameters [recoveries of spiked DDTs (0.1, 0.2, and 0.4 microg/g) > or = 81%, with relative standard deviations of < or = 8% (n = 5), and quantitation limits < or = 0.03 microg/g], with minimal handling and cost-efficiency, indicate that the present MSPD-HPLC method may be a useful tool for routine monitoring of DDT contamination in meat.

  1. Discovery of a highly selective chemical inhibitor of matrix metalloproteinase-9 (MMP-9) that allosterically inhibits zymogen activation.

    Science.gov (United States)

    Scannevin, Robert H; Alexander, Richard; Haarlander, Tara Mezzasalma; Burke, Sharon L; Singer, Monica; Huo, Cuifen; Zhang, Yue-Mei; Maguire, Diane; Spurlino, John; Deckman, Ingrid; Carroll, Karen I; Lewandowski, Frank; Devine, Eric; Dzordzorme, Keli; Tounge, Brett; Milligan, Cindy; Bayoumy, Shariff; Williams, Robyn; Schalk-Hihi, Celine; Leonard, Kristi; Jackson, Paul; Todd, Matthew; Kuo, Lawrence C; Rhodes, Kenneth J

    2017-10-27

    Aberrant activation of matrix metalloproteinases (MMPs) is a common feature of pathological cascades observed in diverse disorders, such as cancer, fibrosis, immune dysregulation, and neurodegenerative diseases. MMP-9, in particular, is highly dynamically regulated in several pathological processes. Development of MMP inhibitors has therefore been an attractive strategy for therapeutic intervention. However, a long history of failed clinical trials has demonstrated that broad-spectrum MMP inhibitors have limited clinical utility, which has spurred the development of inhibitors selective for individual MMPs. Attaining selectivity has been technically challenging because of sequence and structural conservation across the various MMPs. Here, through a biochemical and structural screening paradigm, we have identified JNJ0966, a highly selective compound that inhibited activation of MMP-9 zymogen and subsequent generation of catalytically active enzyme. JNJ0966 had no effect on MMP-1, MMP-2, MMP-3, MMP-9, or MMP-14 catalytic activity and did not inhibit activation of the highly related MMP-2 zymogen. The molecular basis for this activity was characterized as an interaction of JNJ0966 with a structural pocket in proximity to the MMP-9 zymogen cleavage site near Arg-106, which is distinct from the catalytic domain. JNJ0966 was efficacious in reducing disease severity in a mouse experimental autoimmune encephalomyelitis model, demonstrating the viability of this therapeutic approach. This discovery reveals an unprecedented pharmacological approach to MMP inhibition, providing an opportunity to improve selectivity of future clinical drug candidates. Targeting zymogen activation in this manner may also allow for pharmaceutical exploration of other enzymes previously viewed as intractable drug targets. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Nanofibrous matrixes with biologically active hydroxybenzophenazine pyrazolone compound for cancer theranostics

    Energy Technology Data Exchange (ETDEWEB)

    Kandhasamy, Subramani [Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar, Chennai 600020, Tamilnadu (India); Ramanathan, Giriprasath [Bioproducts Lab, CSIR-Central Leather Research Institute, Chennai 600020, Tamilnadu (India); Muthukumar, Thangavelu [Department of Clinical and Experimental Medicine (IKE), Division of Neuro and Inflammation Sciences (NIV), Linkoping University (Sweden); Thyagarajan, SitaLakshmi [Bioproducts Lab, CSIR-Central Leather Research Institute, Chennai 600020, Tamilnadu (India); Umamaheshwari, Narayanan [Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar, Chennai 600020, Tamilnadu (India); Santhanakrishnan, V P [Department of Plant Biotechnology, TNAU, Coimbatore, Tamilnadu (India); Sivagnanam, Uma Tiruchirapalli, E-mail: suma67@gmail.com [Bioproducts Lab, CSIR-Central Leather Research Institute, Chennai 600020, Tamilnadu (India); Perumal, Paramasivan Thirumalai, E-mail: ptperumal@gmail.com [Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar, Chennai 600020, Tamilnadu (India)

    2017-05-01

    The nanomaterial with the novel biologically active compounds has been actively investigated for application in cancer research. Substantial use of nanofibrous scaffold for cancer research with potentially bioactive compounds through electrospinning has not been fully explored. Here, we describe the series of fabrication of nanofibrous scaffold loaded with novel potential biologically active hydroxybenzo[a]phenazine pyrazol-5(4H)-one derivatives were designed, synthesized by a simple one-pot, two step four component condensation based on Michael type addition reaction of lawsone, benzene-1,2-diamine, aromatic aldehydes and 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one as the substrates. The heterogeneous solid state catalyst (Fe (III) Y-Zeolite) could effectively catalyze the reaction to obtain the product with high yield and short reaction time. The synthesized compounds (5a–5p) were analyzed by NMR, FTIR and HRMS analysis. Compound 5c was confirmed by single crystal XRD studies. All the compounds were biologically evaluated for their potential inhibitory effect on anticancer (MCF-7, Hep-2) and microbial (MRSA, MTCC 201 and FRCA) activities. Among the compounds 5i exhibited the highest levels of inhibitory activity against both MCF-7, Hep-2 cell lines. Furthermore, the compound 5i (BPP) was evaluated for DNA fragmentation, flow cytometry studies and cytotoxicity against MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. In addition, molecular docking (PDB ID: (1T46)) studies were performed to predict the binding affinity of ligand with receptor. Moreover, the synthesized BPP compound was loaded in to the PHB-PCL nanofibrous scaffold to check the cytotoxicity against the MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. The in vitro apoptotic potential of the PHB-PCL-BPP nanofibrous scaffold was assessed against MCF-7, Hep-2 cancerous cells and fibroblast cells at 12, 24 and 48 h respectively. The nanofibrous scaffold with BPP can induce apoptosis and also suppress the

  3. Nanofibrous matrixes with biologically active hydroxybenzophenazine pyrazolone compound for cancer theranostics

    International Nuclear Information System (INIS)

    Kandhasamy, Subramani; Ramanathan, Giriprasath; Muthukumar, Thangavelu; Thyagarajan, SitaLakshmi; Umamaheshwari, Narayanan; Santhanakrishnan, V P; Sivagnanam, Uma Tiruchirapalli; Perumal, Paramasivan Thirumalai

    2017-01-01

    The nanomaterial with the novel biologically active compounds has been actively investigated for application in cancer research. Substantial use of nanofibrous scaffold for cancer research with potentially bioactive compounds through electrospinning has not been fully explored. Here, we describe the series of fabrication of nanofibrous scaffold loaded with novel potential biologically active hydroxybenzo[a]phenazine pyrazol-5(4H)-one derivatives were designed, synthesized by a simple one-pot, two step four component condensation based on Michael type addition reaction of lawsone, benzene-1,2-diamine, aromatic aldehydes and 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one as the substrates. The heterogeneous solid state catalyst (Fe (III) Y-Zeolite) could effectively catalyze the reaction to obtain the product with high yield and short reaction time. The synthesized compounds (5a–5p) were analyzed by NMR, FTIR and HRMS analysis. Compound 5c was confirmed by single crystal XRD studies. All the compounds were biologically evaluated for their potential inhibitory effect on anticancer (MCF-7, Hep-2) and microbial (MRSA, MTCC 201 and FRCA) activities. Among the compounds 5i exhibited the highest levels of inhibitory activity against both MCF-7, Hep-2 cell lines. Furthermore, the compound 5i (BPP) was evaluated for DNA fragmentation, flow cytometry studies and cytotoxicity against MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. In addition, molecular docking (PDB ID: (1T46)) studies were performed to predict the binding affinity of ligand with receptor. Moreover, the synthesized BPP compound was loaded in to the PHB-PCL nanofibrous scaffold to check the cytotoxicity against the MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. The in vitro apoptotic potential of the PHB-PCL-BPP nanofibrous scaffold was assessed against MCF-7, Hep-2 cancerous cells and fibroblast cells at 12, 24 and 48 h respectively. The nanofibrous scaffold with BPP can induce apoptosis and also suppress the

  4. Gel-Based Gelatin Zymography to Examine Matrix Metalloproteinase Activity in Cell Culture.

    Science.gov (United States)

    Chhabra, Aastha; Rani, Vibha

    2018-01-01

    Gelatin zymography, first described by Heussen and Dowdle in the 1980s, is a widely used valuable tool in research and diagnostics. The technique identifies gelatinases by the degradation of their preferential substrate as well as by their molecular weight (kDa). We here describe detailed methodology for the detection of pro- and active- forms of both MMP-2 (gelatinase A) and MMP-9 (gelatinase B) in cells using norepinephrine-stimulated H9c2 cardiomyoblasts as model. An easy to follow step-by-step protocol has been carefully written for reliable results. We also suggest an acceptable method for quantification of gelatin zymograms.

  5. Generation of biologically active endostatin fragments from human collagen XVIII by distinct matrix metalloproteases

    International Nuclear Information System (INIS)

    Heljasvaara, Ritva; Nyberg, Pia; Luostarinen, Jani; Parikka, Mataleena; Heikkilae, Pia; Rehn, Marko; Sorsa, Timo; Salo, Tuula; Pihlajaniemi, Taina

    2005-01-01

    Endostatin, a potent inhibitor of endothelial cell proliferation, migration, angiogenesis and tumor growth, is proteolytically cleaved from the C-terminal noncollagenous NC1 domain of type XVIII collagen. We investigated the endostatin formation from human collagen XVIII by several MMPs in vitro. The generation of endostatin fragments differing in molecular size (24-30 kDa) and in N-terminal sequences was identified in the cases of MMP-3, -7, -9, -13 and -20. The cleavage sites were located in the protease-sensitive hinge region between the trimerization and endostatin domains of NC1. MMP-1, -2, -8 and -12 did not show any significant activity against the C-terminus of collagen XVIII. The anti-proliferative effect of the 20-kDa endostatin, three longer endostatin-containing fragments generated in vitro by distinct MMPs and the entire NC1 domain, on bFGF-stimulated human umbilical vein endothelial cells was established. The anti-migratory potential of some of these fragments was also studied. In addition, production of endostatin fragments between 24-30 kDa by human hepatoblastoma cells was shown to be due to MMP action on type XVIII collagen. Our results indicate that certain, especially cancer-related, MMP family members can generate biologically active endostatin-containing polypeptides from collagen XVIII and thus, by releasing endostatin fragments, may participate in the inhibition of endothelial cell proliferation, migration and angiogenesis

  6. Structure-activity relationships between sterols and their thermal stability in oil matrix.

    Science.gov (United States)

    Hu, Yinzhou; Xu, Junli; Huang, Weisu; Zhao, Yajing; Li, Maiquan; Wang, Mengmeng; Zheng, Lufei; Lu, Baiyi

    2018-08-30

    Structure-activity relationships between 20 sterols and their thermal stabilities were studied in a model oil system. All sterol degradations were found to be consistent with a first-order kinetic model with determination of coefficient (R 2 ) higher than 0.9444. The number of double bonds in the sterol structure was negatively correlated with the thermal stability of sterol, whereas the length of the branch chain was positively correlated with the thermal stability of sterol. A quantitative structure-activity relationship (QSAR) model to predict thermal stability of sterol was developed by using partial least squares regression (PLSR) combined with genetic algorithm (GA). A regression model was built with R 2 of 0.806. Almost all sterol degradation constants can be predicted accurately with R 2 of cross-validation equals to 0.680. Four important variables were selected in optimal QSAR model and the selected variables were observed to be related with information indices, RDF descriptors, and 3D-MoRSE descriptors. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Anti-photoaging activity and inhibition of matrix metalloproteinase (MMP) by marine red alga, Corallina pilulifera methanol extract

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Bo Mi [Department of Chemistry, Pukyoung National University, Busan 608-737 (Korea, Republic of); Qian Zhongji [Marine Bioprocess Research Center, Pukyong National University, Busan 608-737 (Korea, Republic of); Kim, Moon-Moo [Department of Chemistry, Dong-Eui University, Busan 614-714 (Korea, Republic of); Nam, Ki Wan [Department of Marine Biology, Pukyong National University, Busan 608-737 (Korea, Republic of); Kim, Se-Kwon [Department of Chemistry, Pukyoung National University, Busan 608-737 (Korea, Republic of); Marine Bioprocess Research Center, Pukyong National University, Busan 608-737 (Korea, Republic of)], E-mail: sknkim@pknu.ac.kr

    2009-02-15

    Matrix metalloproteinases (MMPs), a key component in photoaging of the skin due to exposure to ultraviolet A, appear to be increased by UV-irradiation-associated generation of reactive oxygen species (ROS). In this study, the alga Corallina pilulifera methanol (CPM) extract has been shown to exert a potent antioxidant activity and protective effect on UVA-induced oxidative stress of human dermal fibroblast (HDF) cell. Antioxidant evaluated by various antioxidant assays. These include reducing power, total antioxidant, DPPH radical scavenging, hydroxyl radical scavenging and protective effect on DNA damage caused by hydroxyl radicals generated. Further, the ROS level was detected using a fluorescence probe, 2',7'-dichlorofluorescein diacetate (DCFH-DA), which could be converted to highly fluorescent dichlorofluorescein (DCF) with the presence of intracellular ROS on HT-1080 cells. Those various antioxidant activities were compared to standard antioxidants such as {alpha}-tocopherol. In addition, the in vitro activities of MMP-2 and MMP-9 in HDF cell were inhibited by C. pilulifera methanol extract dose dependently by using gelatin zymography method. The results obtained in the present study suggested that the C. pilulifera methanol extract may be a potential source of natural anti-photoaging.

  8. Fluid shear promotes chondrosarcoma cell invasion by activating matrix metalloproteinase 12 via IGF-2 and VEGF signaling pathways

    Science.gov (United States)

    Wang, P; Chen, S-H; Hung, W-C; Paul, C; Zhu, F; Guan, P-P; Huso, DL; Kontrogianni-Konstantopoulos, A; Konstantopoulos, K

    2015-01-01

    Interstitial fluid flow in and around the tumor tissue is a physiologically relevant mechanical signal that regulates intracellular signaling pathways throughout the tumor. Yet, the effects of interstitial flow and associated fluid shear stress on the tumor cell function have been largely overlooked. Using in vitro bioengineering models in conjunction with molecular cell biology tools, we found that fluid shear (2 dyn/cm2) markedly upregulates matrix metalloproteinase 12 (MMP-12) expression and its activity in human chondrosarcoma cells. MMP-12 expression is induced in human chondrocytes during malignant transformation. However, the signaling pathway regulating MMP-12 expression and its potential role in human chondrosarcoma cell invasion and metastasis have yet to be delineated. We discovered that fluid shear stress induces the synthesis of insulin growth factor-2 (IGF-2) and vascular endothelial growth factor (VEGF) B and D, which in turn transactivate MMP-12 via PI3-K, p38 and JNK signaling pathways. IGF-2-, VEGF-B- or VEGF-D-stimulated chondrosarcoma cells display markedly higher migratory and invasive potentials in vitro, which are blocked by inhibiting MMP-12, PI3-K, p38 or JNK activity. Moreover, recombinant human MMP-12 or MMP-12 overexpression can potentiate chondrosarcoma cell invasion in vitro and the lung colonization in vivo. By reconstructing and delineating the signaling pathway regulating MMP-12 activation, potential therapeutic strategies that interfere with chondrosarcoma cell invasion may be identified. PMID:25435370

  9. Anti-photoaging activity and inhibition of matrix metalloproteinase (MMP) by marine red alga, Corallina pilulifera methanol extract

    Science.gov (United States)

    Ryu, BoMi; Qian, Zhong-Ji; Kim, Moon-Moo; Nam, Ki Wan; Kim, Se-Kwon

    2009-02-01

    Matrix metalloproteinases (MMPs), a key component in photoaging of the skin due to exposure to ultraviolet A, appear to be increased by UV-irradiation-associated generation of reactive oxygen species (ROS). In this study, the alga Corallina pilulifera methanol (CPM) extract has been shown to exert a potent antioxidant activity and protective effect on UVA-induced oxidative stress of human dermal fibroblast (HDF) cell. Antioxidant evaluated by various antioxidant assays. These include reducing power, total antioxidant, DPPH radical scavenging, hydroxyl radical scavenging and protective effect on DNA damage caused by hydroxyl radicals generated. Further, the ROS level was detected using a fluorescence probe, 2',7'-dichlorofluorescein diacetate (DCFH-DA), which could be converted to highly fluorescent dichlorofluorescein (DCF) with the presence of intracellular ROS on HT-1080 cells. Those various antioxidant activities were compared to standard antioxidants such as α-tocopherol. In addition, the in vitro activities of MMP-2 and MMP-9 in HDF cell were inhibited by C. pilulifera methanol extract dose dependently by using gelatin zymography method. The results obtained in the present study suggested that the C. pilulifera methanol extract may be a potential source of natural anti-photoaging.

  10. Anti-photoaging activity and inhibition of matrix metalloproteinase (MMP) by marine red alga, Corallina pilulifera methanol extract

    International Nuclear Information System (INIS)

    Ryu, Bo Mi; Qian Zhongji; Kim, Moon-Moo; Nam, Ki Wan; Kim, Se-Kwon

    2009-01-01

    Matrix metalloproteinases (MMPs), a key component in photoaging of the skin due to exposure to ultraviolet A, appear to be increased by UV-irradiation-associated generation of reactive oxygen species (ROS). In this study, the alga Corallina pilulifera methanol (CPM) extract has been shown to exert a potent antioxidant activity and protective effect on UVA-induced oxidative stress of human dermal fibroblast (HDF) cell. Antioxidant evaluated by various antioxidant assays. These include reducing power, total antioxidant, DPPH radical scavenging, hydroxyl radical scavenging and protective effect on DNA damage caused by hydroxyl radicals generated. Further, the ROS level was detected using a fluorescence probe, 2',7'-dichlorofluorescein diacetate (DCFH-DA), which could be converted to highly fluorescent dichlorofluorescein (DCF) with the presence of intracellular ROS on HT-1080 cells. Those various antioxidant activities were compared to standard antioxidants such as α-tocopherol. In addition, the in vitro activities of MMP-2 and MMP-9 in HDF cell were inhibited by C. pilulifera methanol extract dose dependently by using gelatin zymography method. The results obtained in the present study suggested that the C. pilulifera methanol extract may be a potential source of natural anti-photoaging

  11. Minocycline Attenuates Neonatal Germinal-Matrix-Hemorrhage-Induced Neuroinflammation and Brain Edema by Activating Cannabinoid Receptor 2.

    Science.gov (United States)

    Tang, Jun; Chen, Qianwei; Guo, Jing; Yang, Liming; Tao, Yihao; Li, Lin; Miao, Hongping; Feng, Hua; Chen, Zhi; Zhu, Gang

    2016-04-01

    Germinal matrix hemorrhage (GMH) is the most common neurological disease of premature newborns leading to detrimental neurological sequelae. Minocycline has been reported to play a key role in neurological inflammatory diseases by controlling some mechanisms that involve cannabinoid receptor 2 (CB2R). The current study investigated whether minocycline reduces neuroinflammation and protects the brain from injury in a rat model of collagenase-induced GMH by regulating CB2R activity. To test this hypothesis, the effects of minocycline and a CB2R antagonist (AM630) were evaluated in male rat pups that were post-natal day 7 (P7) after GMH. We found that minocycline can lead to increased CB2R mRNA expression and protein expression in microglia. Minocycline significantly reduced GMH-induced brain edema, microglial activation, and lateral ventricular volume. Additionally, minocycline enhanced cortical thickness after injury. All of these neuroprotective effects of minocycline were prevented by AM630. A cannabinoid CB2 agonist (JWH133) was used to strengthen the hypothesis, which showed the identical neuroprotective effects of minocycline. Our study demonstrates, for the first time, that minocycline attenuates neuroinflammation and brain injury in a rat model of GMH, and activation of CBR2 was partially involved in these processes.

  12. Functional proteomic of Matrix Metallo-proteinases (MMP) dedicated to the detection of active forms of MMP in complex proteome

    International Nuclear Information System (INIS)

    David, A.

    2007-07-01

    The Matrix Metallo-proteinases (M.M.P.) represent a family of Zinc dependent extracellular proteinases able to cleave collectively all the proteins constituting the extracellular matrix. Currently, 23 human M.M.P. have been identified and are characterized by their sequence in amino-acids and their highly conserved 3 D structure. These enzymes are expressed constitutively during the tissue remodeling process. Their over-expression in various diseases tightly related to inflammatory processes (arthritis, emphysema, cancer) described M.M.P. as choice therapeutic targets. However, as the tissue remodeling implicates modification of cellular contacts, M.M.P. appear currently as proteins involved in signalling pathways. Recent works demonstrating that M.M.P. are able to cleave substrates, which are different than proteins constituting the extracellular matrix, reinforce this vision. In order to identify the individual role and the protein expression level of M.M.P. in pathological context, we developed a new technique of functional proteomics dedicated to the detection of active forms of M.M.P. in tumour samples. This technique relied on the development of a new photoaffinity probe, based on the structure of a potent phosphinic inhibitor of M.M.P., allowing targeting and isolating active forms of M.M.P. by photoaffinity labelling. Furthermore, as the new developed probe incorporated a radioactive element, photoaffinity labelling permitted to radiolabel the targeted proteins. This probe demonstrated in vitro its remarkable ability to covalently modify the h M.M.P.-12, with a singular cross-linking yield, determined at 42 %, displaying an extremely sensitive detection (2.5 fmoles of h M.M.P.-12). When added to complex proteome, the photoaffinity probe presents the same sensibility of detection for the h M.M.P.-12 (5 fmoles); importantly, in this case, h M.M.P.-12 represents only 0.001 % of the totality of the proteins present in the sample. Moreover, this technique allows

  13. In vivo imaging of matrix metalloprotease 12 and matrix metalloprotease 13 activities in the mouse model of collagen-induced arthritis

    DEFF Research Database (Denmark)

    Lim, Ngee Han; Meinjohanns, Ernst; Bou-Gharios, George

    2014-01-01

    inhibitor GM6001 and specific synthetic inhibitors of MMP-12 and MMP-13. The probes were used to follow these enzyme activities in the collagen-induced arthritis (CIA) model in vivo. Results. The MMP-12- and MMP-13-activity probes (MMP12ap and MMP13ap, respectively) discriminated between the two enzymatic...... activities. The in vivo activation of these probes was inhibited by GM6001 and by their respective specific inhibitors. In the CIA model, MMP12ap activation peaked 5 days after disease onset and showed strong correlation with disease severity during this time (r = 0.85; p...

  14. Cartilage oligomeric matrix protein (COMP) in rheumatoid arthritis and its correlation with sonographic knee cartilage thickness and disease activity.

    Science.gov (United States)

    Sakthiswary, Rajalingham; Rajalingam, Shamala; Hussein, Heselynn; Sridharan, Radhika; Asrul, Abdul Wahab

    2017-12-01

    The aim of the study is to investigate the correlation of serum cartilage oligomeric matrix protein (COMP) levels with articular cartilage damage based on sonographic knee cartilage thickness (KCT) and disease activity in rheumatoid arthritis (RA). A total of 61 RA patients and 27 healthy controls were recruited in this study. Serum samples were obtained from all subjects to determine the serum COMP levels. All subjects had bilateral ultrasound scan of their knees. The KCT was based on the mean of measurements at three sites: the medial condyle, lateral condyle and intercondylar notch. Besides, the RA patients were assessed for their disease activity based on 28-joint-based Disease Activity Score (DAS 28). Serum COMP concentrations were significantly elevated in the RA patients compared to the controls (p = 0.001). The serum COMP levels had an inverse relationship with bilateral KCT in RA subjects and the healthy controls. COMP correlated significantly with disease activity based on DAS 28 (r = 0.299, p = 0.010), disease duration (r = 0.439, p = correlation between serum COMP and DAS 28 scores was comparable to the traditional markers of inflammation: erythrocyte sedimentation rate (ESR) (r = 0.372, p = 0.003) and C-reactive protein (CRP) (r = 0.305, p = 0.017). The serum COMP is a promising biomarker in RA which reflects disease activity and damage to the articular cartilage.

  15. Applications of snake venom components to modulate integrin activities in cell-matrix interactions

    Science.gov (United States)

    Marcinkiewicz, Cezary

    2013-01-01

    Snake venom proteins are broadly investigated in the different areas of life science. Direct interaction of these compounds with cells may involve a variety of mechanisms that result in diverse cellular responses leading to the activation or blocking of physiological functions of the cell. In this review, the snake venom components interacting with integrins will be characterized in context of their effect on cellular response. Currently, two major families of snake venom proteins are considered as integrin-binding molecules. The most attention has been devoted to the disintegrin family, which binds certain types of integrins through specific motifs recognized as a tri-peptide structurally localized on an integrin-binding loop. Other snake venom integrin-binding proteins belong to the C-type lectin family. Snake venom molecules bind to the cellular integrins resulting in a modulation of cell signaling and in consequence, the regulation of cell proliferation, migration and apoptosis. Therefore, snake venom research on the integrin-binding molecules may have significance in biomedicine and basic cell biology. PMID:23811033

  16. Inhibiting Invasion into Human Bladder Carcinoma 5637 Cells with Diallyl Trisulfide by Inhibiting Matrix Metalloproteinase Activities and Tightening Tight Junctions

    Directory of Open Access Journals (Sweden)

    Yung Hyun Choi

    2013-10-01

    Full Text Available Diallyl trisulfide (DATS, an organosulfur compound in garlic, possesses pronounced anti-cancer potential. However, the anti-invasive mechanism of this compound in human bladder carcinoma is not fully understood. In this study, we evaluated the anti-invasive effects of DATS on a human bladder carcinoma (5637 cell line and investigated the underlying mechanism. The results indicated that DATS suppressed migration and invasion of 5637 cells by reducing the activities and expression of matrix metalloproteinase (MMP-2 and MMP-9 at both the protein and mRNA levels. DATS treatment up-regulated expression of tissue inhibitor of metalloproteinase (TIMP-1 and TIMP-2 in 5637 cells. The inhibitory effects of DATS on invasiveness were associated with an increase in transepithelial electrical resistance and repression of the levels of claudin family members. Although further studies are needed, our data demonstrate that DATS exhibits anti-invasive effects in 5637 cells by down-regulating the activity of tight junctions and MMPs. DATS may have future utility in clinical applications for treating bladder cancer.

  17. Matrix metalloproteinase-1 inhibitory activities of Morinda citrifolia seed extract and its constituents in UVA-irradiated human dermal fibroblasts.

    Science.gov (United States)

    Masuda, Megumi; Murata, Kazuya; Naruto, Shunsuke; Uwaya, Akemi; Isami, Fumiyuki; Matsuda, Hideaki

    2012-01-01

    The objective of this study was to examine whether a 50% ethanolic extract (MCS-ext) of the seeds of Morinda citrifolia (noni) and its constituents have matrix metalloproteinase-1 (MMP-1) inhibitory activity in UVA-irradiated normal human dermal fibroblasts (NHDFs). The MCS-ext (10 μg/mL) inhibited MMP-1 secretion from UVA-irradiated NHDFs, without cytotoxic effects, at 48 h after UV exposure. The ethyl acetate-soluble fraction of MCS-ext was the most potent inhibitor of MMP-1 secretion. Among the constituents of the fraction, a lignan, 3,3'-bisdemethylpinoresinol (1), inhibited the MMP-1 secretion at a concentration of 0.3 μM without cytotoxic effects. Furthermore, 1 (0.3 μM) reduced the level of intracellular MMP-1 expression. Other constituents, namely americanin A (2), quercetin (3) and ursolic acid (4), were inactive. To elucidate inhibition mechanisms of MMP-1 expression and secretion, the effect of 1 on mitogen-activated protein kinases (MAPKs) phosphorylation was examined. Western blot analysis revealed that 1 (0.3 μM) reduced the phosphorylations of p38 and c-Jun-N-terminal kinase (JNK). These results suggested that 1 suppresses intracellular MMP-1 expression, and consequent secretion from UVA-irradiated NHDFs, by down-regulation of MAPKs phosphorylation.

  18. Matrix metalloproteinase activity and prostaglandin E2 are elevated in the synovial fluid of meniscus tear patients.

    Science.gov (United States)

    Liu, Betty; Goode, Adam P; Carter, Teralyn E; Utturkar, Gangadhar M; Huebner, Janet L; Taylor, Dean C; Moorman, Claude T; Garrett, William E; Kraus, Virginia B; Guilak, Farshid; DeFrate, Louis E; McNulty, Amy L

    Meniscus tears are a common knee injury and are associated with the development of post-traumatic osteoarthritis (OA). The purpose of this study is to evaluate potential OA mediators in the synovial fluid and serum of meniscus tear subjects compared to those in the synovial fluid of radiographic non-OA control knees. Sixteen subjects with an isolated unilateral meniscus injury and six subjects who served as reference controls (knee Kellgren-Lawrence grade 0-1) were recruited. Twenty-one biomarkers were measured in serum from meniscus tear subjects and in synovial fluid from both groups. Meniscus tear subjects were further stratified by tear type to assess differences in biomarker levels. Synovial fluid total matrix metalloproteinase (MMP) activity and prostaglandin E2 (PGE2) were increased 25-fold and 290-fold, respectively, in meniscus tear subjects as compared to reference controls (p meniscus tear subjects (R = 0.83, p meniscus tear subjects, synovial fluid levels of MMP activity, MMP-2, MMP-3, sGAG, COMP, IL-6, and PGE2 were higher than serum levels (p meniscus tears had higher synovial fluid MMP-10 (p meniscus injury may be targets to promote meniscus repair and prevent OA development.

  19. Activity concentration measurements of 137Cs, 90Sr and 40K in a wild food matrix reference material (Wild Berries) CCRI(II)-S8

    International Nuclear Information System (INIS)

    Watjen, U.; Altzitzogloa, T.; Spasova, Y.; Ceccatelli, A.; Kis-Benedek, G.; Dikmen, H.; Gundogdu, G.; Yucel, U.; Ferreux, L.; Frechou, C.; Pierre, S.; Garcia, L.; Moreno, Y.; Oropesa, P.; La Rosa, J.; Luca, A.; Schmiedel, M.; Wershofen, H.; Szucs, L.; Vasile, M.

    2014-01-01

    In 2009, the CCRI approved a supplementary comparison to be organized by the IRMM as pilot laboratory for the activity concentrations of 137 Cs, 90 Sr and 40 K in a matrix material of dried bilberries. The organization of this comparison and the material and measurement methods used are described. The supplementary comparison reference values (SCRV) for each of the three radionuclides are given together with the degrees of equivalence of each participating laboratory with the SCRV for the specific radionuclide. The results of this supplementary comparison allow the participating NMIs/designated institutes to declare calibration and measurement capabilities (CMCs) for the given radionuclides in a similar type of food matrix, an important aspect given the relatively few supplementary comparisons for activity in matrix materials organized so far. (authors)

  20. Interleukin-1β regulates cell proliferation and activity of extracellular matrix remodelling enzymes in cultured primary pig heart cells

    International Nuclear Information System (INIS)

    Zitta, Karina; Brandt, Berenice; Wuensch, Annegret; Meybohm, Patrick; Bein, Berthold; Steinfath, Markus; Scholz, Jens; Albrecht, Martin

    2010-01-01

    Research highlights: → Levels of IL-1β are increased in the pig myocardium after infarction. → Cultured pig heart cells possess IL-1 receptors. → IL-1β increases cell proliferation of pig heart cells in-vitro. → IL-1β increases MMP-2 and MMP-9 activity in pig heart cells in-vitro. → IL-1β may be important for tissue remodelling events after myocardial infarction. -- Abstract: After myocardial infarction, elevated levels of interleukins (ILs) are found within the myocardial tissue and IL-1β is considered to play a major role in tissue remodelling events throughout the body. In the study presented, we have established a cell culture model of primary pig heart cells to evaluate the effects of different concentrations of IL-1β on cell proliferation as well as expression and activity of enzymes typically involved in tissue remodelling. Primary pig heart cell cultures were derived from three different animals and stimulated with recombinant pig IL-1β. RNA expression was detected by RT-PCR, protein levels were evaluated by Western blotting, activity of matrix metalloproteinases (MMPs) was quantified by gelatine zymography and cell proliferation was measured using colorimetric MTS assays. Pig heart cells express receptors for IL-1 and application of IL-1β resulted in a dose-dependent increase of cell proliferation (P < 0.05 vs. control; 100 ng/ml; 24 h). Gene expression of caspase-3 was increased by IL-1β (P < 0.05 vs. control; 100 ng/ml; 3 h), and pro-caspase-3 but not active caspase was detected in lysates of pig heart cells by Western blotting. MMP-2 gene expression as well as enzymatic activities of MMP-2 and MMP-9 were increased by IL-1β (P < 0.05 vs. control; 100 ng/ml; 3 h for gene expression, 48 and 72 h for enzymatic activities of MMP-2 and MMP-9, respectively). Our in vitro data suggest that IL-1β plays a major role in the events of tissue remodelling in the heart. Combined with our recently published in vivo data (Meybohm et al., PLoS One

  1. Interleukin-1{beta} regulates cell proliferation and activity of extracellular matrix remodelling enzymes in cultured primary pig heart cells

    Energy Technology Data Exchange (ETDEWEB)

    Zitta, Karina; Brandt, Berenice [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany); Wuensch, Annegret [Institute of Molecular Animal Breeding and Biotechnology, Ludwig Maximilians University, Munich (Germany); Meybohm, Patrick; Bein, Berthold; Steinfath, Markus; Scholz, Jens [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany); Albrecht, Martin, E-mail: Albrecht@anaesthesie.uni-kiel.de [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany)

    2010-09-03

    Research highlights: {yields} Levels of IL-1{beta} are increased in the pig myocardium after infarction. {yields} Cultured pig heart cells possess IL-1 receptors. {yields} IL-1{beta} increases cell proliferation of pig heart cells in-vitro. {yields} IL-1{beta} increases MMP-2 and MMP-9 activity in pig heart cells in-vitro. {yields} IL-1{beta} may be important for tissue remodelling events after myocardial infarction. -- Abstract: After myocardial infarction, elevated levels of interleukins (ILs) are found within the myocardial tissue and IL-1{beta} is considered to play a major role in tissue remodelling events throughout the body. In the study presented, we have established a cell culture model of primary pig heart cells to evaluate the effects of different concentrations of IL-1{beta} on cell proliferation as well as expression and activity of enzymes typically involved in tissue remodelling. Primary pig heart cell cultures were derived from three different animals and stimulated with recombinant pig IL-1{beta}. RNA expression was detected by RT-PCR, protein levels were evaluated by Western blotting, activity of matrix metalloproteinases (MMPs) was quantified by gelatine zymography and cell proliferation was measured using colorimetric MTS assays. Pig heart cells express receptors for IL-1 and application of IL-1{beta} resulted in a dose-dependent increase of cell proliferation (P < 0.05 vs. control; 100 ng/ml; 24 h). Gene expression of caspase-3 was increased by IL-1{beta} (P < 0.05 vs. control; 100 ng/ml; 3 h), and pro-caspase-3 but not active caspase was detected in lysates of pig heart cells by Western blotting. MMP-2 gene expression as well as enzymatic activities of MMP-2 and MMP-9 were increased by IL-1{beta} (P < 0.05 vs. control; 100 ng/ml; 3 h for gene expression, 48 and 72 h for enzymatic activities of MMP-2 and MMP-9, respectively). Our in vitro data suggest that IL-1{beta} plays a major role in the events of tissue remodelling in the heart. Combined

  2. Alteration of matrix metalloproteinase-3 O-glycan structure as a biomarker for disease activity of rheumatoid arthritis.

    Science.gov (United States)

    Takeshita, Masaru; Kuno, Atsushi; Suzuki, Katsuya; Matsuda, Atsushi; Shimazaki, Hiroko; Nakagawa, Tomomi; Otomo, Yuki; Kabe, Yasuaki; Suematsu, Makoto; Narimatsu, Hisashi; Takeuchi, Tsutomu

    2016-05-21

    Nearly all secreted proteins are glycosylated, and serum glycoproteins that exhibit disease-associated glycosylation changes have potential to be biomarkers. In rheumatoid arthritis (RA), C-reactive protein (CRP), and matrix metalloproteinase-3 (MMP-3) are widely used as serologic biomarkers, but they lack sufficient specificity or precision. We performed comparative glycosylation profiling of MMP-3 using a recently developed antibody-overlay lectin microarray technology that allows semicomprehensive and quantitative analysis of specific protein glycosylation to develop an RA-specific disease activity biomarker. Serum was taken from patients with RA (n = 24) whose disease activity was scored using composite measures, and MMP-3 was immunoprecipitated and subjected to lectin microarray analysis. A disease activity index (DAI) based on lectin signal was developed and validated using another cohort (n = 60). Synovial fluid MMP-3 in patients with RA and patients with osteoarthritis (OA) was also analyzed. Intense signals were observed on a sialic acid-binding lectin (Agrocybe cylindracea galectin [ACG]) and O-glycan-binding lectins (Jacalin, Agaricus bisporus agglutinin [ABA], and Amaranthus caudatus agglutinin [ACA]) by applying subnanogram levels of serum MMP-3. ACG, ABA, and ACA revealed differences in MMP-3 quantity, and Jacalin revealed differences in MMP-3 quality. The resultant index, ACG/Jacalin, correlated well with disease activity. Further validation using another cohort confirmed that this index correlated well with several DAIs and their components, and reflected DAI changes following RA treatment, with correlations greater than those for MMP-3 and CRP. Furthermore, MMP-3, which generated a high ACG/Jacalin score, accumulated in synovial fluid of patients with RA but not in that of patients with OA. Sialidase digestion revealed that the difference in quality was derived from O-glycan α-2,6-sialylation. This is the first report of a glycoprotein

  3. Red Grape Skin Polyphenols Blunt Matrix Metalloproteinase-2 and -9 Activity and Expression in Cell Models of Vascular Inflammation: Protective Role in Degenerative and Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Nadia Calabriso

    2016-08-01

    Full Text Available Matrix metalloproteinases (MMPs are endopeptidases responsible for the hydrolysis of various components of extracellular matrix. MMPs, namely gelatinases MMP-2 and MMP-9, contribute to the progression of chronic and degenerative diseases. Since gelatinases’ activity and expression are regulated by oxidative stress, we sought to evaluate whether supplementation with polyphenol-rich red grape skin extracts modulated the matrix-degrading capacity in cell models of vascular inflammation. Human endothelial and monocytic cells were incubated with increasing concentrations (0.5–25 μg/mL of Negroamaro and Primitivo red grape skin polyphenolic extracts (NSPE and PSPE, respectively or their specific components (0.5–25 μmol/L, before stimulation with inflammatory challenge. NSPE and PSPE inhibited, in a concentration-dependent manner, endothelial invasion as well as the MMP-9 and MMP-2 release in stimulated endothelial cells, and MMP-9 production in inflamed monocytes, without affecting tissue inhibitor of metalloproteinases (TIMP-1 and TIMP-2. The matrix degrading inhibitory capacity was the same for both NSPE and PSPE, despite their different polyphenolic profiles. Among the main polyphenols of grape skin extracts, trans-resveratrol, trans-piceid, kaempferol and quercetin exhibited the most significant inhibitory effects on matrix-degrading enzyme activities. Our findings appreciate the grape skins as rich source of polyphenols able to prevent the dysregulation of vascular remodelling affecting degenerative and inflammatory diseases.

  4. Integrated arrays of air-dielectric graphene transistors as transparent active-matrix pressure sensors for wide pressure ranges.

    Science.gov (United States)

    Shin, Sung-Ho; Ji, Sangyoon; Choi, Seiho; Pyo, Kyoung-Hee; Wan An, Byeong; Park, Jihun; Kim, Joohee; Kim, Ju-Young; Lee, Ki-Suk; Kwon, Soon-Yong; Heo, Jaeyeong; Park, Byong-Guk; Park, Jang-Ung

    2017-03-31

    Integrated electronic circuitries with pressure sensors have been extensively researched as a key component for emerging electronics applications such as electronic skins and health-monitoring devices. Although existing pressure sensors display high sensitivities, they can only be used for specific purposes due to the narrow range of detectable pressure (under tens of kPa) and the difficulty of forming highly integrated arrays. However, it is essential to develop tactile pressure sensors with a wide pressure range in order to use them for diverse application areas including medical diagnosis, robotics or automotive electronics. Here we report an unconventional approach for fabricating fully integrated active-matrix arrays of pressure-sensitive graphene transistors with air-dielectric layers simply formed by folding two opposing panels. Furthermore, this realizes a wide tactile pressure sensing range from 250 Pa to ∼3 MPa. Additionally, fabrication of pressure sensor arrays and transparent pressure sensors are demonstrated, suggesting their substantial promise as next-generation electronics.

  5. Optimal Topology and Experimental Evaluation of Piezoelectric Materials for Actively Shunted General Electric Polymer Matrix Fiber Composite Blades

    Science.gov (United States)

    Choi, Benjamin B.; Duffy, Kirsten; Kauffman, Jeffrey L.; Kray, Nicholas

    2012-01-01

    NASA Glenn Research Center, in collaboration with GE Aviation, has begun the development of a smart adaptive structure system with piezoelectric (PE) transducers to improve composite fan blade damping at resonances. Traditional resonant damping approaches may not be realistic for rotating frame applications such as engine blades. The limited space in which the blades reside in the engine makes it impossible to accommodate the circuit size required to implement passive resonant damping. Thus, a novel digital shunt scheme has been developed to replace the conventional electric passive shunt circuits. The digital shunt dissipates strain energy through the load resistor on a power amplifier. General Electric (GE) designed and fabricated a variety of polymer matrix fiber composite (PMFC) test specimens. Investigating the optimal topology of PE sensors and actuators for each test specimen has revealed the best PE transducer location for each target mode. Also a variety of flexible patches, which can conform to the blade surface, have been tested to identify the best performing PE patch. The active damping control achieved significant performance at target modes. This work has been highlighted by successful spin testing up to 5000 rpm of subscale GEnx composite blades in Glenn s Dynamic Spin Rig.

  6. Active site specificity profiling datasets of matrix metalloproteinases (MMPs 1, 2, 3, 7, 8, 9, 12, 13 and 14

    Directory of Open Access Journals (Sweden)

    Ulrich Eckhard

    2016-06-01

    Full Text Available The data described provide a comprehensive resource for the family-wide active site specificity portrayal of the human matrix metalloproteinase family. We used the high-throughput proteomic technique PICS (Proteomic Identification of protease Cleavage Sites to comprehensively assay 9 different MMPs. We identified more than 4300 peptide cleavage sites, spanning both the prime and non-prime sides of the scissile peptide bond allowing detailed subsite cooperativity analysis. The proteomic cleavage data were expanded by kinetic analysis using a set of 6 quenched-fluorescent peptide substrates designed using these results. These datasets represent one of the largest specificity profiling efforts with subsequent structural follow up for any protease family and put the spotlight on the specificity similarities and differences of the MMP family. A detailed analysis of this data may be found in Eckhard et al. (2015 [1]. The raw mass spectrometry data and the corresponding metadata have been deposited in PRIDE/ProteomeXchange with the accession number http://www.ebi.ac.uk/pride/archive/projects/PXD002265.

  7. Image quality affected by diffraction of aperture structure arrangement in transparent active-matrix organic light-emitting diode displays.

    Science.gov (United States)

    Tsai, Yu-Hsiang; Huang, Mao-Hsiu; Jeng, Wei-de; Huang, Ting-Wei; Lo, Kuo-Lung; Ou-Yang, Mang

    2015-10-01

    Transparent display is one of the main technologies in next-generation displays, especially for augmented reality applications. An aperture structure is attached on each display pixel to partition them into transparent and black regions. However, diffraction blurs caused by the aperture structure typically degrade the transparent image when the light from a background object passes through finite aperture window. In this paper, the diffraction effect of an active-matrix organic light-emitting diode display (AMOLED) is studied. Several aperture structures have been proposed and implemented. Based on theoretical analysis and simulation, the appropriate aperture structure will effectively reduce the blur. The analysis data are also consistent with the experimental results. Compared with the various transparent aperture structure on AMOLED, diffraction width (zero energy position of diffraction pattern) of the optimize aperture structure can be reduced 63% and 31% in the x and y directions in CASE 3. Associated with a lenticular lens on the aperture structure, the improvement could reach to 77% and 54% of diffraction width in the x and y directions. Modulation transfer function and practical images are provided to evaluate the improvement of image blurs.

  8. An Antifungal Combination Matrix Identifies a Rich Pool of Adjuvant Molecules that Enhance Drug Activity against Diverse Fungal Pathogens

    Directory of Open Access Journals (Sweden)

    Nicole Robbins

    2015-11-01

    Full Text Available There is an urgent need to identify new treatments for fungal infections. By combining sub-lethal concentrations of the known antifungals fluconazole, caspofungin, amphotericin B, terbinafine, benomyl, and cyprodinil with ∼3,600 compounds in diverse fungal species, we generated a deep reservoir of chemical-chemical interactions termed the Antifungal Combinations Matrix (ACM. Follow-up susceptibility testing against a fluconazole-resistant isolate of C. albicans unveiled ACM combinations capable of potentiating fluconazole in this clinical strain. We used chemical genetics to elucidate the mode of action of the antimycobacterial drug clofazimine, a compound with unreported antifungal activity that synergized with several antifungals. Clofazimine induces a cell membrane stress for which the Pkc1 signaling pathway is required for tolerance. Additional tests against additional fungal pathogens, including Aspergillus fumigatus, highlighted that clofazimine exhibits efficacy as a combination agent against multiple fungi. Thus, the ACM is a rich reservoir of chemical combinations with therapeutic potential against diverse fungal pathogens.

  9. A flexible organic active matrix circuit fabricated using novel organic thin film transistors and organic light-emitting diodes

    KAUST Repository

    Gutiérrez-Heredia, Gerardo

    2010-10-04

    We present an active matrix circuit fabricated on plastic (polyethylene naphthalene, PEN) and glass substrates using organic thin film transistors and organic capacitors to control organic light-emitting diodes (OLEDs). The basic circuit is fabricated using two pentacene-based transistors and a capacitor using a novel aluminum oxide/parylene stack (Al2O3/ parylene) as the dielectric for both the transistor and the capacitor. We report that our circuit can deliver up to 15 μA to each OLED pixel. To achieve 200 cd m-2 of brightness a 10 μA current is needed; therefore, our approach can initially deliver 1.5× the required current to drive a single pixel. In contrast to parylene-only devices, the Al2O 3/parylene stack does not fail after stressing at a field of 1.7 MV cm-1 for >10 000 s, whereas \\'parylene only\\' devices show breakdown at approximately 1000 s. Details of the integration scheme are presented. © 2010 IOP Publishing Ltd.

  10. A flexible organic active matrix circuit fabricated using novel organic thin film transistors and organic light-emitting diodes

    KAUST Repository

    Gutié rrez-Heredia, Gerardo; Gonzá lez, Luis A.; Alshareef, Husam N.; Gnade, Bruce E.; Quevedo-Ló pez, Manuel Angel Quevedo

    2010-01-01

    We present an active matrix circuit fabricated on plastic (polyethylene naphthalene, PEN) and glass substrates using organic thin film transistors and organic capacitors to control organic light-emitting diodes (OLEDs). The basic circuit is fabricated using two pentacene-based transistors and a capacitor using a novel aluminum oxide/parylene stack (Al2O3/ parylene) as the dielectric for both the transistor and the capacitor. We report that our circuit can deliver up to 15 μA to each OLED pixel. To achieve 200 cd m-2 of brightness a 10 μA current is needed; therefore, our approach can initially deliver 1.5× the required current to drive a single pixel. In contrast to parylene-only devices, the Al2O 3/parylene stack does not fail after stressing at a field of 1.7 MV cm-1 for >10 000 s, whereas 'parylene only' devices show breakdown at approximately 1000 s. Details of the integration scheme are presented. © 2010 IOP Publishing Ltd.

  11. 3.4-Inch Quarter High Definition Flexible Active Matrix Organic Light Emitting Display with Oxide Thin Film Transistor

    Science.gov (United States)

    Hatano, Kaoru; Chida, Akihiro; Okano, Tatsuya; Sugisawa, Nozomu; Inoue, Tatsunori; Seo, Satoshi; Suzuki, Kunihiko; Oikawa, Yoshiaki; Miyake, Hiroyuki; Koyama, Jun; Yamazaki, Shunpei; Eguchi, Shingo; Katayama, Masahiro; Sakakura, Masayuki

    2011-03-01

    In this paper, we report a 3.4-in. flexible active matrix organic light emitting display (AMOLED) display with remarkably high definition (quarter high definition: QHD) in which oxide thin film transistors (TFTs) are used. We have developed a transfer technology in which a TFT array formed on a glass substrate is separated from the substrate by physical force and then attached to a flexible plastic substrate. Unlike a normal process in which a TFT array is directly fabricated on a thin plastic substrate, our transfer technology permits a high integration of high performance TFTs, such as low-temperature polycrystalline silicon TFTs (LTPS TFTs) and oxide TFTs, on a plastic substrate, because a flat, rigid, and thermally-stable glass substrate can be used in the TFT fabrication process in our transfer technology. As a result, this technology realized an oxide TFT array for an AMOLED on a plastic substrate. Furthermore, in order to achieve a high-definition AMOLED, color filters were incorporated in the TFT array and a white organic light-emitting diode (OLED) was combined. One of the features of this device is that the whole body of the device can be bent freely because a source driver and a gate driver can be integrated on the substrate due to the high mobility of an oxide TFT. This feature means “true” flexibility.

  12. Leflunomide and methotrexate reduce levels of activated matrix metalloproteinases in complexes with α2 macroglobulin in serum of rheumatoid arthritis patients

    NARCIS (Netherlands)

    Tchetverikov, I.; Kraan, M.C.; El, B. van; Hanemaaijer, R.; Groot, J. de; Huizinga, T.W.J.

    2008-01-01

    Objective: To analyse the effects of leflunomide and methotrexate treatment on matrix metalloproteinase (MMP) activity levels in a2 macroglobulin/MMP (α2M/MMP) complexes in the systemic circulation of rheumatoid arthritis (RA) patients. Methods: A total of 102 RA patients from a prospective,

  13. IKKα/CHUK regulates extracellular matrix remodeling independent of its kinase activity to facilitate articular chondrocyte differentiation.

    Directory of Open Access Journals (Sweden)

    Eleonora Olivotto

    Full Text Available BACKGROUND: The non-canonical NF-κB activating kinase IKKα, encoded by CHUK (conserved-helix-loop-helix-ubiquitous-kinase, has been reported to modulate pro- or anti- inflammatory responses, cellular survival and cellular differentiation. Here, we have investigated the mechanism of action of IKKα as a novel effector of human and murine chondrocyte extracellular matrix (ECM homeostasis and differentiation towards hypertrophy. METHODOLOGY/PRINCIPAL FINDINGS: IKKα expression was ablated in primary human osteoarthritic (OA chondrocytes and in immature murine articular chondrocytes (iMACs derived from IKKα(f/f:CreERT2 mice by retroviral-mediated stable shRNA transduction and Cre recombinase-dependent Lox P site recombination, respectively. MMP-10 was identified as a major target of IKKα in chondrocytes by mRNA profiling, quantitative RT-PCR analysis, immunohistochemistry and immunoblotting. ECM integrity, as assessed by type II collagen (COL2 deposition and the lack of MMP-dependent COL2 degradation products, was enhanced by IKKα ablation in mice. MMP-13 and total collagenase activities were significantly reduced, while TIMP-3 (tissue inhibitor of metalloproteinase-3 protein levels were enhanced in IKKα-deficient chondrocytes. IKKα deficiency suppressed chondrocyte differentiation, as shown by the quantitative inhibition of.Alizarin red staining and the reduced expression of multiple chondrocyte differentiation effectors, including Runx2, Col10a1 and Vegfa,. Importantly, the differentiation of IKKα-deficient chondrocytes was rescued by a kinase-dead IKKα protein mutant. CONCLUSIONS/SIGNIFICANCE: IKKα acts independent of its kinase activity to help drive chondrocyte differentiation towards a hypertrophic-like state. IKKα positively modulates ECM remodeling via multiple downstream targets (including MMP-10 and TIMP-3 at the mRNA and post-transcriptional levels, respectively to maintain maximal MMP-13 activity, which is required for ECM

  14. Salivary matrix metalloproteinase (MMP-8) levels and gelatinase (MMP-9) activities in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Collin, H L; Sorsa, T; Meurman, J H; Niskanen, L; Salo, T; Rönkä, H; Konttinen, Y T; Koivisto, A M; Uusitupa, M

    2000-10-01

    We studied the salivary levels and activities of the matrix metalloproteinases (MMP) -8 and -9 in 45 type 2 diabetic patients and 77 control subjects. The patients' mean glycosylated haemoglobin (HbA1c) was 8.7%, indicating an unsatisfactory metabolic control of the disease. The MMP levels were further related to the clinical and microbiological periodontal findings as well as to salivary flow rate and other factors. The salivary flow rate, albumin and amylase concentrations were similar in type 2 diabetic patients to those in the control group. The mean gingival and periodontal pocket indexes were higher in the diabetes group. The number of potential periodontopathogenic bacteria was lower, however, in the diabetic than in the control group. Zymography and immunoblotting revealed that the major MMPs in the type 2 diabetic patients' saliva were MMP-8 and MMP-9. Salivary MMP levels and activities in type 2 diabetic patients were in general similar to those in the control group. However, the correlation coefficients using multiple regression analysis revealed that gingival bleeding, pocket depths and HbA1c were associated with increased MMP-8 levels which, in turn, were negatively predicted by elevated plasma lipid peroxide levels in the diabetic group. Our data on salivary MMP-8 and -9 do not support the concept of generalized neutrophil dysfunction in unbalanced diabetes. Moreover, plasma lipid peroxidation levels reflecting the increased oxidative burden, which is generated mainly by triggered neutrophils, do not indicate neutrophil dysfunction due to diabetes, but may rather be related to the increased tissue damage in an uncontrolled disease. However. advanced periodontitis in type 2 diabetes seems to be related to elevated salivary MMP-8 levels which might be useful in monitoring periodontal disease in diabetes.

  15. Matrix calculus

    CERN Document Server

    Bodewig, E

    1959-01-01

    Matrix Calculus, Second Revised and Enlarged Edition focuses on systematic calculation with the building blocks of a matrix and rows and columns, shunning the use of individual elements. The publication first offers information on vectors, matrices, further applications, measures of the magnitude of a matrix, and forms. The text then examines eigenvalues and exact solutions, including the characteristic equation, eigenrows, extremum properties of the eigenvalues, bounds for the eigenvalues, elementary divisors, and bounds for the determinant. The text ponders on approximate solutions, as well

  16. The theoretical study of passive and active optical devices via planewave based transfer (scattering) matrix method and other approaches

    Energy Technology Data Exchange (ETDEWEB)

    Zhuo, Ye [Iowa State Univ., Ames, IA (United States)

    2011-01-01

    In this thesis, we theoretically study the electromagnetic wave propagation in several passive and active optical components and devices including 2-D photonic crystals, straight and curved waveguides, organic light emitting diodes (OLEDs), and etc. Several optical designs are also presented like organic photovoltaic (OPV) cells and solar concentrators. The first part of the thesis focuses on theoretical investigation. First, the plane-wave-based transfer (scattering) matrix method (TMM) is briefly described with a short review of photonic crystals and other numerical methods to study them (Chapter 1 and 2). Next TMM, the numerical method itself is investigated in details and developed in advance to deal with more complex optical systems. In chapter 3, TMM is extended in curvilinear coordinates to study curved nanoribbon waveguides. The problem of a curved structure is transformed into an equivalent one of a straight structure with spatially dependent tensors of dielectric constant and magnetic permeability. In chapter 4, a new set of localized basis orbitals are introduced to locally represent electromagnetic field in photonic crystals as alternative to planewave basis. The second part of the thesis focuses on the design of optical devices. First, two examples of TMM applications are given. The first example is the design of metal grating structures as replacements of ITO to enhance the optical absorption in OPV cells (chapter 6). The second one is the design of the same structure as above to enhance the light extraction of OLEDs (chapter 7). Next, two design examples by ray tracing method are given, including applying a microlens array to enhance the light extraction of OLEDs (chapter 5) and an all-angle wide-wavelength design of solar concentrator (chapter 8). In summary, this dissertation has extended TMM which makes it capable of treating complex optical systems. Several optical designs by TMM and ray tracing method are also given as a full complement of this

  17. Matrix Metalloproteinase Enzyme Family

    Directory of Open Access Journals (Sweden)

    Ozlem Goruroglu Ozturk

    2013-04-01

    Full Text Available Matrix metalloproteinases play an important role in many biological processes such as embriogenesis, tissue remodeling, wound healing, and angiogenesis, and in some pathological conditions such as atherosclerosis, arthritis and cancer. Currently, 24 genes have been identified in humans that encode different groups of matrix metalloproteinase enzymes. This review discuss the members of the matrix metalloproteinase family and their substrate specificity, structure, function and the regulation of their enzyme activity by tissue inhibitors. [Archives Medical Review Journal 2013; 22(2.000: 209-220

  18. [Fabrication of porous poly lactic acid-bone matrix gelatin composite bioactive material and its osteoinductive activity].

    Science.gov (United States)

    Zhang, Yumin; Li, Baoxing; Li, Ji

    2007-02-01

    To fabricate a novel porous bioactive composite biomaterial consisting of poly lactic acid (PLA)-bone matrix gelatin (BMG) by using the supercritical carbon dioxide fluid technique (SC-CO2) and to evaluate its osteoinductive activity. The cortical bones selected from healthy adult donors were processed into BMG by the defatting, demineralizing, and deproteinizing processes. PLA and BMG were mixed at a volume radio of 3 : 1; then, the PLA-BMG mixed material and the pure PLA material were respectively placed in the supercritical carbon dioxide reaction kettles, and were respectively added by the NaCl particles 100-200 microm in diameter for the porosity of the materials so that the porous PLA-BMG composite material and the porous PLA composite material could be formed. The mouse osteoblast-like MC3T3-E1 cells were cultured in the dulbecco's modified eagle medium (DMEM) supplemented with 10% fetal bovine serum. Then, 20 microl of the MC3T3-E1 cell suspensions containing 2 X 10(6) cells /ml were delivered into the culturing plate (24 wells/plate) made of the different materials, which were co-cultured for 2 weeks. In the PLA-BMG group, 100 microg of the crushed PLA-BMG material was contained in each well; in the PLA group, 100 microg of the crushed PLA material was contained in each well; and in the DMEM group, only DMEM was contained, which served as the control group. There were 6 wells in each group. The quantitative analysis on the calcification area was performed by the staining of the alizarin red S. The co-cultured cells were harvested and lysated in 1 ml of 0. 2% Nonidet P-40 by the ultrasonic lysating technique. Then, the ALP activity and the Ca content were measured according to the illuminations of the reagent kits. The porous PLA-BMG composite material showed a good homological porosity with a pore diameter of 50-150 microm and a good connectivity between the pores. The ALP activity, the Ca content, and the calcification area were significantly greater in

  19. Matrix thermalization

    International Nuclear Information System (INIS)

    Craps, Ben; Evnin, Oleg; Nguyen, Kévin

    2017-01-01

    Matrix quantum mechanics offers an attractive environment for discussing gravitational holography, in which both sides of the holographic duality are well-defined. Similarly to higher-dimensional implementations of holography, collapsing shell solutions in the gravitational bulk correspond in this setting to thermalization processes in the dual quantum mechanical theory. We construct an explicit, fully nonlinear supergravity solution describing a generic collapsing dilaton shell, specify the holographic renormalization prescriptions necessary for computing the relevant boundary observables, and apply them to evaluating thermalizing two-point correlation functions in the dual matrix theory.

  20. Matrix thermalization

    Science.gov (United States)

    Craps, Ben; Evnin, Oleg; Nguyen, Kévin

    2017-02-01

    Matrix quantum mechanics offers an attractive environment for discussing gravitational holography, in which both sides of the holographic duality are well-defined. Similarly to higher-dimensional implementations of holography, collapsing shell solutions in the gravitational bulk correspond in this setting to thermalization processes in the dual quantum mechanical theory. We construct an explicit, fully nonlinear supergravity solution describing a generic collapsing dilaton shell, specify the holographic renormalization prescriptions necessary for computing the relevant boundary observables, and apply them to evaluating thermalizing two-point correlation functions in the dual matrix theory.

  1. Matrix thermalization

    Energy Technology Data Exchange (ETDEWEB)

    Craps, Ben [Theoretische Natuurkunde, Vrije Universiteit Brussel (VUB), and International Solvay Institutes, Pleinlaan 2, B-1050 Brussels (Belgium); Evnin, Oleg [Department of Physics, Faculty of Science, Chulalongkorn University, Thanon Phayathai, Pathumwan, Bangkok 10330 (Thailand); Theoretische Natuurkunde, Vrije Universiteit Brussel (VUB), and International Solvay Institutes, Pleinlaan 2, B-1050 Brussels (Belgium); Nguyen, Kévin [Theoretische Natuurkunde, Vrije Universiteit Brussel (VUB), and International Solvay Institutes, Pleinlaan 2, B-1050 Brussels (Belgium)

    2017-02-08

    Matrix quantum mechanics offers an attractive environment for discussing gravitational holography, in which both sides of the holographic duality are well-defined. Similarly to higher-dimensional implementations of holography, collapsing shell solutions in the gravitational bulk correspond in this setting to thermalization processes in the dual quantum mechanical theory. We construct an explicit, fully nonlinear supergravity solution describing a generic collapsing dilaton shell, specify the holographic renormalization prescriptions necessary for computing the relevant boundary observables, and apply them to evaluating thermalizing two-point correlation functions in the dual matrix theory.

  2. The Exopolysaccharide Matrix

    Science.gov (United States)

    Koo, H.; Falsetta, M.L.; Klein, M.I.

    2013-01-01

    Many infectious diseases in humans are caused or exacerbated by biofilms. Dental caries is a prime example of a biofilm-dependent disease, resulting from interactions of microorganisms, host factors, and diet (sugars), which modulate the dynamic formation of biofilms on tooth surfaces. All biofilms have a microbial-derived extracellular matrix as an essential constituent. The exopolysaccharides formed through interactions between sucrose- (and starch-) and Streptococcus mutans-derived exoenzymes present in the pellicle and on microbial surfaces (including non-mutans) provide binding sites for cariogenic and other organisms. The polymers formed in situ enmesh the microorganisms while forming a matrix facilitating the assembly of three-dimensional (3D) multicellular structures that encompass a series of microenvironments and are firmly attached to teeth. The metabolic activity of microbes embedded in this exopolysaccharide-rich and diffusion-limiting matrix leads to acidification of the milieu and, eventually, acid-dissolution of enamel. Here, we discuss recent advances concerning spatio-temporal development of the exopolysaccharide matrix and its essential role in the pathogenesis of dental caries. We focus on how the matrix serves as a 3D scaffold for biofilm assembly while creating spatial heterogeneities and low-pH microenvironments/niches. Further understanding on how the matrix modulates microbial activity and virulence expression could lead to new approaches to control cariogenic biofilms. PMID:24045647

  3. Fully Screen-Printed, Large-Area, and Flexible Active-Matrix Electrochromic Displays Using Carbon Nanotube Thin-Film Transistors.

    Science.gov (United States)

    Cao, Xuan; Lau, Christian; Liu, Yihang; Wu, Fanqi; Gui, Hui; Liu, Qingzhou; Ma, Yuqiang; Wan, Haochuan; Amer, Moh R; Zhou, Chongwu

    2016-11-22

    Semiconducting single-wall carbon nanotubes are ideal semiconductors for printed electronics due to their advantageous electrical and mechanical properties, intrinsic printability in solution, and desirable stability in air. However, fully printed, large-area, high-performance, and flexible carbon nanotube active-matrix backplanes are still difficult to realize for future displays and sensing applications. Here, we report fully screen-printed active-matrix electrochromic displays employing carbon nanotube thin-film transistors. Our fully printed backplane shows high electrical performance with mobility of 3.92 ± 1.08 cm 2 V -1 s -1 , on-off current ratio I on /I off ∼ 10 4 , and good uniformity. The printed backplane was then monolithically integrated with an array of printed electrochromic pixels, resulting in an entirely screen-printed active-matrix electrochromic display (AMECD) with good switching characteristics, facile manufacturing, and long-term stability. Overall, our fully screen-printed AMECD is promising for the mass production of large-area and low-cost flexible displays for applications such as disposable tags, medical electronics, and smart home appliances.

  4. MT1-MMP promotes cell growth and ERK activation through c-Src and paxillin in three-dimensional collagen matrix

    International Nuclear Information System (INIS)

    Takino, Takahisa; Tsuge, Hisashi; Ozawa, Terumasa; Sato, Hiroshi

    2010-01-01

    Membrane-type 1 matrix metalloproteinase (MT1-MMP) is essential for tumor invasion and growth. We show here that MT1-MMP induces extracellular signal-regulated kinase (ERK) activation in cancer cells cultured in collagen gel, which is indispensable for their proliferation. Inhibition of MT1-MMP by MMP inhibitor or small interfering RNA suppressed activation of focal adhesion kinase (FAK) and ERK in MT1-MMP-expressing cancer cells, which resulted in up-regulation of p21 WAF1 and suppression of cell growth in collagen gel. Cell proliferation was also abrogated by the inhibitor against ERK pathway without affecting FAK phosphorylation. MT1-MMP and integrin α v β 3 were shown to be involved in c-Src activation, which induced FAK and ERK activation in collagen gel. These MT1-MMP-mediated signal transductions were paxillin dependent, as knockdown of paxillin reduced cell growth and ERK activation, and co-expression of MT1-MMP with paxillin induced ERK activation. The results suggest that MT1-MMP contributes to proliferation of cancer cells in the extracellular matrix by activating ERK through c-Src and paxillin.

  5. Characterization of silica particles prepared via urease-catalyzed urea hydrolysis and activity of urease in sol–gel silica matrix

    International Nuclear Information System (INIS)

    Kato, Katsuya; Nishida, Masakazu; Ito, Kimiyasu; Tomita, Masahiro

    2012-01-01

    Highlights: ► Silica precipitation occurred via urease-catalytic reactions. ► Higher urease activity for silica synthesis enables mesostructure of silica–urease composites. ► Urease encapsulating in silica matrix retained high activity. - Abstract: Urease templated precipitation of silica synthesized by sol–gel chemistry produces a composite material allowing high urease activity. This study investigates the structural properties of the composite material that allow for the retention of the urease hydrolysis activity. Scanning (SEM) and transmission (TEM) electron microscopy reveal that the composite has a mesoporous structure composed of closely packed spherical structures ∼20–50 nm in diameter. Brunauer–Emmett–Teller (BET) analysis revealed that the surface area and pore volume of the composite prepared under the conditions of 50 mM urea and 25 °C is relatively high (324 m 2 /g and 1.0 cm 3 /g). These values are equivalent to those of usual mesoporous silica materials synthesized from the self-assembly of triblock copolymers as organic templates. In addition, after encapsulating in a sol–gel silica matrix, urease retained high activity (∼90% of the activity compared with native urease). Our results suggest a new method for synthesizing mesoporous silica materials with highly tunable pore sizes and shapes under mild conditions.

  6. Extracellular S100A4(mts1) stimulates invasive growth of mouse endothelial cells and modulates MMP-13 matrix metalloproteinase activity

    DEFF Research Database (Denmark)

    Schmidt-Hansen, Birgitte; Ornås, Dorte; Grigorian, Mariam

    2004-01-01

    with the transcriptional modulation of genes involved in the proteolytic degradation of extracellular matrix (ECM). Treatment of SVEC 4-10 with the S100A4 protein leads to the transcriptional activation of collagenase 3 (MMP-13) mRNA followed by subsequent release of the protein from the cells. Beta-casein zymography...... demonstrates enhancement of proteolytic activity associated with MMP-13. This observation indicates that extracellular S100A4 stimulates the production of ECM degrading enzymes from endothelial cells, thereby stimulating the remodeling of ECM. This could explain the angiogenic and metastasis...

  7. Doxycycline reduces the expression and activity of matrix metalloproteinase-2 in the periodontal ligament of the rat incisor without altering the eruption process.

    Science.gov (United States)

    Gomes, J R; Omar, N F; Neves, J D S; Novaes, P D

    2017-06-01

    Doxycycline is an antibiotic agent that inhibits the activity of matrix metalloproteinases (MMPs) present in the extracellular matrix. In this study, the rat incisor was submitted to a hypofunctional condition, and the effects of doxycycline (80 mg/kg/d) on the expression and activity of MMP-2, as well as on eruption rate, were determined in the odontogenic region and in the periodontal ligament for 14 d. Rats were distributed into four groups: normofunctional (NF); doxycyline normofunctional (DNF); hypofunctional (HP); and doxycyline hypofunctional (DHP). The left lower incisors of 10 rats were shortened every 2 d, using a high-rotation drill, to produce the HP and DHP groups, after starting doxycycline treatment (80 mg/kg) by gavage. Eruption was measured using a millimeter ocular, from the gingival margin to the top of the tooth in the HP and DHP groups, and also by a mark made in the tooth previously, in the NF and DNF groups. The hemimandibles were removed and the teeth were extracted to collect the periodontal and odontogenic tissues for immunohistochemical analyses and zymography. The eruption rates were higher in the HP and the DHP groups than in the NF and DNF groups, respectively (p matrix of the periodontal ligament during the tooth-eruption process. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Electrical features of an amorphous indium-gallium-zinc-oxide film transistor using a double active matrix with different oxygen contents

    International Nuclear Information System (INIS)

    Koo, Ja Hyun; Kang, Tae Sung; Hong, Jin Pyo

    2012-01-01

    The electrical characteristics of amorphous indium-gallium-zinc-oxide (a-IGZO) thin film transistor (TFTs) are systematically studied using a double a-IGZO active layer that is composed of a-IGZO x (oxygen-ion-poor region) and a-IGZO y (oxygen-ion-rich-region). An active layer is designed to have a serially-stacked bi-layer matrix with different oxygen contents, providing the formation of different electron conduction channels. Two different oxygen contents in the active layer are obtained by varying the O 2 partial pressure during sputtering. The a-IGZO TFT based on a double active layer exhibits a high mobility of 9.1 cm 2 /Vsec, a threshold voltage (V T ) of 16.5 V, and ΔV T shifts of less than 1.5 V under gate voltage stress. A possible electrical sketch for the double active layer channel is also discussed.

  9. Matrix inequalities

    CERN Document Server

    Zhan, Xingzhi

    2002-01-01

    The main purpose of this monograph is to report on recent developments in the field of matrix inequalities, with emphasis on useful techniques and ingenious ideas. Among other results this book contains the affirmative solutions of eight conjectures. Many theorems unify or sharpen previous inequalities. The author's aim is to streamline the ideas in the literature. The book can be read by research workers, graduate students and advanced undergraduates.

  10. Superior integrin activating capacity and higher adhesion to fibrinogen matrix in buffy coat-derived platelet concentrates (PCs) compared to PRP-PCs.

    Science.gov (United States)

    Beshkar, Pezhman; Hosseini, Ehteramolsadat; Ghasemzadeh, Mehran

    2018-02-01

    Regardless of different sources, methods or devices which are applied for preparation of therapeutic platelets, these products are generally isolated from whole blood by the sedimentation techniques which are based on PRP or buffy coat (BC) separation. As a general fact, platelet preparation and storage are also associated with some deleterious changes that known as platelet storage lesion (PSL). Although these alternations in platelet functional activity are aggravated during storage, whether technical issues within preparation can affect integrin activation and platelet adhesion to fibrinogen were investigated in this study. PRP- and BC-platelet concentrates (PCs) were subjected to flowcytometry analysis to examine the expression of platelet activation marker, P-selectin as well as active confirmation of the GPIIb/IIIa (α IIb β 3 ) on day 0, 1, 3 and 5 post-storage. Platelet adhesion to fibrinogen matrix was evaluated by fluorescence microscopy. Glucose concentration and LDH activity were also measured by colorimetric methods. The increasing P-selectin expression during storage was in a reverse correlation with PAC-1 binding (r = -0.67; p = .001). PRP-PCs showed the higher level of P-selectin expression than BC-PCs, whereas the levels of PAC-1 binding and platelet adhesion to fibrinogen matrix were significantly lower in PRP-PCs. Higher levels of active confirmation of the GPIIb/IIIa in BC-PCs were also associated with greater concentration of glucose in these products. We demonstrated the superior capacities of integrin activation and adhesion to fibrinogen for BC-PCs compared to those of PRP-PCs. These findings may provide more advantages for BC method of platelet preparation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Effect of cannabidiol on human gingival fibroblast extracellular matrix metabolism: MMP production and activity, and production of fibronectin and transforming growth factor β.

    Science.gov (United States)

    Rawal, S Y; Dabbous, M Kh; Tipton, D A

    2012-06-01

    Marijuana (Cannabis sativa) use may be associated with gingival enlargement, resembling that caused by phenytoin. Cannabidiol (CBD), a nonpsychotropic Cannabis derivative, is structurally similar to phenytoin. While there are many reports on effects of phenytoin on human gingival fibroblasts, there is no information on effects of Cannabis components on these cells. The objective of this study was to determine effects of CBD on human gingival fibroblast fibrogenic and matrix-degrading activities. Fibroblasts were incubated with CBD in serum-free medium for 1-6 d. The effect of CBD on cell viability was determined by measuring activity of a mitochondrial enzyme. The fibrogenic molecule transforming growth factor β and the extracellular matrix molecule fibronectin were measured by ELISA. Pro-MMP-1 and total MMP-2 were measured by ELISA. Activity of MMP-2 was determined via a colorimetric assay in which a detection enzyme is activated by active MMP-2. Data were analysed using ANOVA and Scheffe's F procedure for post hoc comparisons. Cannabidiol had little or no significant effect on cell viability. Low CBD concentrations increased transforming growth factor β production by as much as 40% (p Cannabidiol increased fibronectin production by as much as approximately 100% (p < 0.001). Lower CBD concentrations increased MMP production, but the highest concentrations decreased production of both MMPs (p < 0.05) and decreased MMP-2 activity (p < 0.02). The data suggest that the CBD may promote fibrotic gingival enlargement by increasing gingival fibroblast production of transforming growth factor β and fibronectin, while decreasing MMP production and activity. © 2011 John Wiley & Sons A/S.

  12. Protective Effects of LSGYGP from Fish Skin Gelatin Hydrolysates on UVB-Induced MEFs by Regulation of Oxidative Stress and Matrix Metalloproteinase Activity.

    Science.gov (United States)

    Ma, Qingyu; Liu, Qiuming; Yuan, Ling; Zhuang, Yongliang

    2018-03-28

    A previous study has shown that tilapia fish skin gelatin hydrolysates inhibited photoaging in vivo, and that, Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP) identified in the hydrolysate had a high hydroxyl radical scavenging activity. In this study, activities of LSGYGP were further evaluated using ultraviolet B (UVB)-induced mouse embryonic fibroblasts (MEFs). UVB irradiation significantly increased the intercellular reactive oxygen species (ROS) production and matrix metalloproteinases (MMPs) activities and decreased the content of collagen in MEFs. LSGYGP reduced the intercellular ROS generation in UVB-induced MEFs. Meanwhile, the decrease of superoxide dismutase (SOD) activity and the increase of malondiaidehyde (MDA) content were inhibited by LSGYGP. LSGYGP reduced MMP-1 and MMP-9 activities in a dose-dependent manner. Molecular docking simulation indicated that LSGYGP inhibited MMPs activities by docking the active sites of MMP-1 and MMP-9. Furthermore, LSGYGP also affected the intercellular phosphorylation of UVB-induced the mitogen-activated protein kinase pathway. LSGYGP could protect collagen synthesis in MEFs under UVB irradiation by inhibiting oxidative stress and regulating MMPs activities.

  13. Protective Effects of LSGYGP from Fish Skin Gelatin Hydrolysates on UVB-Induced MEFs by Regulation of Oxidative Stress and Matrix Metalloproteinase Activity

    Directory of Open Access Journals (Sweden)

    Qingyu Ma

    2018-03-01

    Full Text Available A previous study has shown that tilapia fish skin gelatin hydrolysates inhibited photoaging in vivo, and that, Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP identified in the hydrolysate had a high hydroxyl radical scavenging activity. In this study, activities of LSGYGP were further evaluated using ultraviolet B (UVB-induced mouse embryonic fibroblasts (MEFs. UVB irradiation significantly increased the intercellular reactive oxygen species (ROS production and matrix metalloproteinases (MMPs activities and decreased the content of collagen in MEFs. LSGYGP reduced the intercellular ROS generation in UVB-induced MEFs. Meanwhile, the decrease of superoxide dismutase (SOD activity and the increase of malondiaidehyde (MDA content were inhibited by LSGYGP. LSGYGP reduced MMP-1 and MMP-9 activities in a dose-dependent manner. Molecular docking simulation indicated that LSGYGP inhibited MMPs activities by docking the active sites of MMP-1 and MMP-9. Furthermore, LSGYGP also affected the intercellular phosphorylation of UVB-induced the mitogen-activated protein kinase pathway. LSGYGP could protect collagen synthesis in MEFs under UVB irradiation by inhibiting oxidative stress and regulating MMPs activities.

  14. Global Matrix 2.0: Report Card Grades on the Physical Activity of Children and Youth Comparing 38 Countries

    DEFF Research Database (Denmark)

    Tremblay, Mark S.; Barnes, Joel; Gonzales, Silvia

    2016-01-01

    The Active Healthy Kids Global Alliance organized the concurrent preparation of Report Cards on the physical activity of children and youth in 38 countries from 6 continents (representing 60% of the world’s population). Nine common indicators were used (Overall Physical Activity, Organized Sport ...... reporting better infrastructure, suggests that autonomy to play, travel, or chore requirements and/or fewer attractive sedentary pursuits, rather than infrastructure and structured activities, may facilitate higher levels of physical activity....

  15. Global Matrix 2.0: Report Card Grades on the Physical Activity of Children and Youth Comparing 38 Countries

    DEFF Research Database (Denmark)

    Tremblay, Mark S.; Barnes, Joel; Gonzales, Silvia

    2016-01-01

    The Active Healthy Kids Global Alliance organized the concurrent preparation of Report Cards on the physical activity of children and youth in 38 countries from 6 continents (representing 60% of the world’s population). Nine common indicators were used (Overall Physical Activity, Organized Sport...... reporting better infrastructure, suggests that autonomy to play, travel, or chore requirements and/or fewer attractive sedentary pursuits, rather than infrastructure and structured activities, may facilitate higher levels of physical activity....

  16. Active and Reactive Power Control Strategy for Grid-Connected Six-Phase Generator by Using Multi-Modular Matrix Converters

    Directory of Open Access Journals (Sweden)

    David Caballero

    2016-12-01

    Full Text Available This paper proposes an active and reactive power control strategy based on predictive control approaches applied to gridconnected renewable energy systems. To accomplish this a multi-modular matrix converter topologies are used in combination with a simple but efficient grid synchronization strategy. The theoretical performance analysis is performed considering a six-phase wind energy generator system interconnected with the grid. Results based on a MATLAB/Simulink simulation environment are discussed and the most relevant characteristics of the proposed control technique are highlighted considering the total harmonic distortion and the mean squared error as a parameters of performance.

  17. High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells

    Directory of Open Access Journals (Sweden)

    Xiaofei Cheng

    2016-01-01

    Full Text Available Objectives. To investigate whether high glucose-induced oxidative stress is implicated in apoptosis of rat nucleus pulposus cells (NPCs and abnormal expression of critical genes involved in the metabolic balance of extracellular matrix (ECM. Methods. NPCs were cultured with various concentrations of glucose to detect cell viability and apoptosis. Cells cultured with high glucose (25 mM were untreated or pretreated with N-acetylcysteine or a p38 MAPK inhibitor SB 202190. Reactive oxygen species (ROS production was evaluated. Activation of p38 MAPK was measured by Western blot. The expression of ECM metabolism-related genes, including type II collagen, aggrecan, SRY-related high-mobility-group box 9 (Sox-9, matrix metalloproteinase 3 (MMP-3, and tissue inhibitor of metalloproteinase 1 (TIMP-1, was analyzed by semiquantitative RT-PCR. Results. High glucose reduced viability of NPCs and induced apoptosis. High glucose resulted in increased ROS generation and p38 MAPK activation. In addition, it negatively regulated the expression of type II collagen, aggrecan, Sox-9, and TIMP-1 and positively regulated MMP-3 expression. These results were changed by pretreatment with N-acetylcysteine or SB 202190. Conclusions. High glucose might promote apoptosis of NPCs, trigger ECM catabolic pathways, and inhibit its anabolic activities, possibly through a p38 MAPK-dependent oxidative stress mechanism.

  18. Matrix analysis

    CERN Document Server

    Bhatia, Rajendra

    1997-01-01

    A good part of matrix theory is functional analytic in spirit. This statement can be turned around. There are many problems in operator theory, where most of the complexities and subtleties are present in the finite-dimensional case. My purpose in writing this book is to present a systematic treatment of methods that are useful in the study of such problems. This book is intended for use as a text for upper division and gradu­ ate courses. Courses based on parts of the material have been given by me at the Indian Statistical Institute and at the University of Toronto (in collaboration with Chandler Davis). The book should also be useful as a reference for research workers in linear algebra, operator theory, mathe­ matical physics and numerical analysis. A possible subtitle of this book could be Matrix Inequalities. A reader who works through the book should expect to become proficient in the art of deriving such inequalities. Other authors have compared this art to that of cutting diamonds. One first has to...

  19. Zymographic analysis using gelatin-coated film of the effect of etanercept on the extracellular matrix-degrading activity in synovial fluids of rheumatoid arthritis patients.

    Science.gov (United States)

    Kamataki, Akihisa; Ishida, Mutsuko; Komagamine, Masataka; Yoshida, Masaaki; Ando, Takanobu; Sawai, Takashi

    2016-04-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease. Most RA patients develop cartilage and bone destruction, and various proteinases are involved in the destruction of extracellular matrix of cartilage and bone. The aim of this study is to evaluate the utility of our newly developed method to measure total gelatinolytic activity. We adopted this method for measurement in synovial fluid from RA patients treated by the anti-rheumatic drug etanercept (ETN), a recombinant human soluble tumor necrosis factor receptor fusion protein, and compared the findings with clinical and laboratory data. Enzymatic activity of synovial fluid was analyzed by zymography using gelatin-coated film, and compared with the index of Disease Activity Score of 28 joints - C-reactive protein (DAS28-CRP), CRP and matrix metalloproteinase (MMP)-3 level before and after ETN therapy. Synovial fluids of 19 patients were collected before and after administration of ETN therapy. In nine of 19 patients, who showed a decrease in gelatin-degrading activity in synovial fluid, the index of DAS28-CRP (4.85-2.85, ΔDAS = -2.00) and CRP (3.30-0.94 mg/dL, ΔCRP = -2.36) was alleviated after ETN therapy, while cases with no change or an increase in gelatin-degrading activity showed a modest improvement in clinical data: DAS28-CRP (4.23-3.38, ΔDAS = -0.85) and CRP (1.70-0.74 mg/dL, ΔCRP = -0.96). Our newly developed method for measurement of gelatin-degrading activity in synovial fluid from RA patients is highly practicable and useful for predicting the effect of ETN therapy. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  20. Matrix Metalloproteinase-3 (MMP-3) Is an Endogenous Activator of the MMP-9 Secreted by Placental Leukocytes: Implication in Human Labor.

    Science.gov (United States)

    Flores-Pliego, Arturo; Espejel-Nuñez, Aurora; Castillo-Castrejon, Marisol; Meraz-Cruz, Noemi; Beltran-Montoya, Jorge; Zaga-Clavellina, Veronica; Nava-Salazar, Sonia; Sanchez-Martinez, Maribel; Vadillo-Ortega, Felipe; Estrada-Gutierrez, Guadalupe

    2015-01-01

    The activity of matrix degrading enzymes plays a leading role in the rupture of the fetal membranes under normal and pathological human labor, and matrix metalloproteinase-9 (MMP-9) it is considered a biomarker of this event. To gain further insight into local MMP-9 origin and activation, in this study we analyzed the contribution of human placental leukocytes to MMP-9 secretion and explored the local mechanisms of the pro-enzyme activation. Placental blood leukocytes were obtained from women at term gestation without labor and maintained in culture up to 72 h. MMP-9 activity in the culture supernatants was determined by zymography and using a specific substrate. The presence of a potential pro-MMP-9 activator in the culture supernatants was monitored using a recombinant biotin-labeled human pro-MMP-9. To characterize the endogenous pro-MMP-9 activator, MMP-1, -3, -7 and -9 were measured by multiplex assay in the supernatants, and an inhibition assay of MMP-9 activation was performed using an anti-human MMP-3 and a specific MMP-3 inhibitor. Finally, production of MMP-9 and MMP-3 in placental leukocytes obtained from term pregnancies with and without labor was assessed by immunofluorescence. Placental leukocytes spontaneously secreted pro-MMP-9 after 24 h of culture, increasing significantly at 48 h (P≤0.05), when the active form of MMP-9 was detected. Culture supernatants activated the recombinant pro-MMP-9 showing that placental leukocytes secrete the activator. A significant increase in MMP-3 secretion by placental leukocytes was observed since 48 h in culture (P≤0.05) and up to 72 h (P≤0.001), when concentration reached its maximum value. Specific activity of MMP-9 decreased significantly (P≤0.005) when an anti-MMP-3 antibody or a specific MMP-3 inhibitor were added to the culture media. Placental leukocytes from term labor produced more MMP-9 and MMP-3 compared to term non-labor cells. In this work we confirm that placental leukocytes from human term

  1. Global Matrix 2.0 : Report Card Grades on the Physical Activity of Children and Youth Comparing 38 Countries

    NARCIS (Netherlands)

    Tremblay, Mark S; Barnes, Joel D; González, Silvia A; Katzmarzyk, Peter T; Onywera, Vincent O; Reilly, John J; Tomkinson, Grant R; Takken, T

    2016-01-01

    The Active Healthy Kids Global Alliance organized the concurrent preparation of Report Cards on the physical activity of children and youth in 38 countries from 6 continents (representing 60% of the world's population). Nine common indicators were used (Overall Physical Activity, Organized Sport

  2. Streaming Potential Modeling to Understand the Identification of Hydraulically Active Fractures and Fracture-Matrix Fluid Interactions Using the Self-Potential Method

    Science.gov (United States)

    Jougnot, D.; Roubinet, D.; Linde, N.; Irving, J.

    2016-12-01

    Quantifying fluid flow in fractured media is a critical challenge in a wide variety of research fields and applications. To this end, geophysics offers a variety of tools that can provide important information on subsurface physical properties in a noninvasive manner. Most geophysical techniques infer fluid flow by data or model differencing in time or space (i.e., they are not directly sensitive to flow occurring at the time of the measurements). An exception is the self-potential (SP) method. When water flows in the subsurface, an excess of charge in the pore water that counterbalances electric charges at the mineral-pore water interface gives rise to a streaming current and an associated streaming potential. The latter can be measured with the SP technique, meaning that the method is directly sensitive to fluid flow. Whereas numerous field experiments suggest that the SP method may allow for the detection of hydraulically active fractures, suitable tools for numerically modeling streaming potentials in fractured media do not exist. Here, we present a highly efficient two-dimensional discrete-dual-porosity approach for solving the fluid-flow and associated self-potential problems in fractured domains. Our approach is specifically designed for complex fracture networks that cannot be investigated using standard numerical methods due to computational limitations. We then simulate SP signals associated with pumping conditions for a number of examples to show that (i) accounting for matrix fluid flow is essential for accurate SP modeling and (ii) the sensitivity of SP to hydraulically active fractures is intimately linked with fracture-matrix fluid interactions. This implies that fractures associated with strong SP amplitudes are likely to be hydraulically conductive, attracting fluid flow from the surrounding matrix.

  3. Gel structure has an impact on pericellular and extracellular matrix deposition, which subsequently alters metabolic activities in chondrocyte-laden PEG hydrogels.

    Science.gov (United States)

    Nicodemus, G D; Skaalure, S C; Bryant, S J

    2011-02-01

    While designing poly(ethylene glycol) hydrogels with high moduli suitable for in situ placement is attractive for cartilage regeneration, the impact of a tighter crosslinked structure on the organization and deposition of the matrix is not fully understood. The objectives of this study were to characterize the composition and spatial organization of new matrix as a function of gel crosslinking and study its impact on chondrocytes in terms of anabolic and catabolic gene expression and catabolic activity. Bovine articular chondrocytes were encapsulated in hydrogels with three crosslinking densities (compressive moduli 60, 320 and 590 kPa) and cultured for 25 days. Glycosaminoglycan production increased with culture time and was greatest in the gels with lowest crosslinking. Collagens II and VI, aggrecan, link protein and decorin were localized to pericellular regions in all gels, but their presence decreased with increasing gel crosslinking. Collagen II and aggrecan expression were initially up-regulated in gels with higher crosslinking, but increased similarly up to day 15. Matrix metalloproteinase (MMP)-1 and MMP-13 expression were elevated (∼25-fold) in gels with higher crosslinking throughout the study, while MMP-3 was unaffected by gel crosslinking. The presence of aggrecan and collagen degradation products confirmed MMP activity. These findings indicate that chondrocytes synthesized the major cartilage components within PEG hydrogels, however, gel structure had a significant impact on the composition and spatial organization of the new tissue and on how chondrocytes responded to their environment, particularly with respect to their catabolic expression. Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  4. Oleuropein potentiates anti-tumor activity of cisplatin against HepG2 through affecting proNGF/NGF balance.

    Science.gov (United States)

    Sherif, Iman O; Al-Gayyar, Mohammed M H

    2018-04-01

    Oleuropein is considered as a new chemotherapeutic agent in human hepatocellular carcinoma (HCC) while, its exact underlying molecular mechanism still not yet explored. In addition, cisplatin is a standard anticancer drug against solid tumors with toxic side effects. Therefore, we conducted this study to assess antitumor activity of oleuropein either alone or in combination with cisplatin against HepG2, human HCC cell lines, via targeting pro-NGF/NGF signaling pathway. HepG2 cells were treated with cisplatin (20, 50, 100 μM) and oleuropein (100, 200, 300 and 400 μM) as well as some of the cells were treated with 50 μM cisplatin and different concentrations of oleuropein. Gene expressions of nerve growth factor (NGF), matrix metalloproteinase-7 (MMP-7) and caspase-3 were evaluated by real time-PCR. In addition, protein levels of NGF and pro-form of NGF (pro-NGF) were measured by ELISA while, nitric oxide (NO) content was determined colorimetrically. Cisplatin treatment showed a significant elevation of NO content and pro-NGF protein level with a marked reduction of NGF protein level in addition to the upregulation of caspase-3 along with downregulation of MMP-7 gene expressions in a dose-dependent manner. However, the combination of 50 μM cisplatin and 200 μM oleuropein showed the most potent effect on the molecular level when compared with oleuropein or cisplatin alone. Our results showed for the first time that the anti-tumor activity of oleuropein against HCC could be attributed to influencing the pro-NGF/NGF balance via affecting MMP-7 activity without affecting the gene expression of NGF. Concurrent treatment with both oleuropein and cisplatin could lead to more effective chemotherapeutic combination against HCC. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Plastic substrates for active matrix liquid crystal display incapable of withstanding processing temperature of over 200 C and method of fabrication

    Energy Technology Data Exchange (ETDEWEB)

    Carey, P.G.; Smith, P.M.; Havens, J.H.; Jones, P.

    1999-01-05

    Bright-polarizer-free, active-matrix liquid crystal displays (AMLCDs) are formed on plastic substrates. The primary components of the display are a pixel circuit fabricated on one plastic substrate, an intervening liquid-crystal material, and a counter electrode on a second plastic substrate. The-pixel circuit contains one or more thin-film transistors (TFTs) and either a transparent or reflective pixel electrode manufactured at sufficiently low temperatures to avoid damage to the plastic substrate. Fabrication of the TFTs can be carried out at temperatures less than 100 C. The liquid crystal material is a commercially made nematic curvilinear aligned phase (NCAP) film. The counter electrode is comprised of a plastic substrate coated with a transparent conductor, such as indium-doped tin oxide (ITO). By coupling the active matrix with NCAP, a high-information content can be provided in a bright, fully plastic package. Applications include any low cost portable electronics containing flat displays where ruggedization of the display is desired. 12 figs.

  6. Plastic substrates for active matrix liquid crystal display incapable of withstanding processing temperature of over 200.degree. C and method of fabrication

    Energy Technology Data Exchange (ETDEWEB)

    Carey, Paul G. (Mountain View, CA); Smith, Patrick M. (San Ramon, CA); Havens, John (San Diego, CA); Jones, Phil (Marlborough, GB)

    1999-01-01

    Bright-polarizer-free, active-matrix liquid crystal displays (AMLCDs) are formed on plastic substrates. The primary components of the display are a pixel circuit fabricated on one plastic substrate, an intervening liquid-crystal material, and a counter electrode on a second plastic substrate. The-pixel circuit contains one or more thin-film transistors (TFTs) and either a transparent or reflective pixel electrode manufactured at sufficiently low temperatures to avoid damage to the plastic substrate. Fabrication of the TFTs can be carried out at temperatures less than 100.degree. C. The liquid crystal material is a commercially made nematic curvilinear aligned phase (NCAP) film. The counter electrode is comprised of a plastic substrate coated with a transparent conductor, such as indium-doped tin oxide (ITO). By coupling the active matrix with NCAP, a high-information content can be provided in a bright, fully plastic package. Applications include any low cost portable electronics containing flat displays where ruggedization of the display is desired.

  7. Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2

    International Nuclear Information System (INIS)

    Peng, P.-L.; Hsieh, Y.-S.; Wang, C.-J.; Hsu, J.-L.; Chou, F.-P.

    2006-01-01

    Berberine, a compound isolated from medicinal herbs, has been reported with many pharmacological effects related to anti-cancer and anti-inflammation capabilities. In this study, we observed that berberine exerted a dose- and time-dependent inhibitory effect on the motility and invasion ability of a highly metastatic A549 cells under non-cytotoxic concentrations. In cancer cell migration and invasion process, matrix-degrading proteinases are required. A549 cell treated with berberine at various concentrations showed reduced ECM proteinases including matrix metalloproteinase-2 (MMP2) and urokinase-plasminogen activator (u-PA) by gelatin and casein zymography analysis. The inhibitory effect is likely to be at the transcriptional level, since the reduction in the transcripts levels was corresponding to the proteins. Moreover, berberine also exerted its action via regulating tissue inhibitor of metalloproteinase-2 (TIMP-2) and urokinase-plasminogen activator inhibitor (PAI). The upstream mediators of the effect involved c-jun, c-fos and NF-κB, as evidenced by reduced phosphorylation of the proteins. These findings suggest that berberine possesses an anti-metastatic effect in non-small lung cancer cell and may, therefore, be helpful in clinical treatment

  8. Matrix pentagons

    Science.gov (United States)

    Belitsky, A. V.

    2017-10-01

    The Operator Product Expansion for null polygonal Wilson loop in planar maximally supersymmetric Yang-Mills theory runs systematically in terms of multi-particle pentagon transitions which encode the physics of excitations propagating on the color flux tube ending on the sides of the four-dimensional contour. Their dynamics was unraveled in the past several years and culminated in a complete description of pentagons as an exact function of the 't Hooft coupling. In this paper we provide a solution for the last building block in this program, the SU(4) matrix structure arising from internal symmetry indices of scalars and fermions. This is achieved by a recursive solution of the Mirror and Watson equations obeyed by the so-called singlet pentagons and fixing the form of the twisted component in their tensor decomposition. The non-singlet, or charged, pentagons are deduced from these by a limiting procedure.

  9. Matrix pentagons

    Directory of Open Access Journals (Sweden)

    A.V. Belitsky

    2017-10-01

    Full Text Available The Operator Product Expansion for null polygonal Wilson loop in planar maximally supersymmetric Yang–Mills theory runs systematically in terms of multi-particle pentagon transitions which encode the physics of excitations propagating on the color flux tube ending on the sides of the four-dimensional contour. Their dynamics was unraveled in the past several years and culminated in a complete description of pentagons as an exact function of the 't Hooft coupling. In this paper we provide a solution for the last building block in this program, the SU(4 matrix structure arising from internal symmetry indices of scalars and fermions. This is achieved by a recursive solution of the Mirror and Watson equations obeyed by the so-called singlet pentagons and fixing the form of the twisted component in their tensor decomposition. The non-singlet, or charged, pentagons are deduced from these by a limiting procedure.

  10. The use of a diode matrix in commissioning activities for electron energies ≥9 MeV: A feasibility study

    International Nuclear Information System (INIS)

    Casanova Borca, Valeria; Pasquino, Massimo; Ozzello, Franca; Tofani, Santi

    2009-01-01

    The contribution of a commercially available diode matrix (MapCHECK trade mark sign , provided by Sun Nuclear, Melbourne, FL) for the commissioning procedures of the voxel based Monte Carlo (VMC++) algorithm for electron beams of MasterPlan treatment planning system was investigated. The attention is mainly focused on the calculation in homogeneous and heterogeneous phantoms. With this aim, following a data set similar to that proposed by Electron Collaborative Working Group (ECWG), the dose profiles and two-dimensional (2D) dose distributions measured by the diode matrix were compared with the calculated ones using the gamma analysis method with acceptance criteria for the dose difference and the distance to agreement equal to 4% and 4 mm, respectively. The average and standard deviation of the percentage of points satisfying the constraint γ≤1 are 98.3±4.1% and 99.3±1.7% for the 9 and 12 MeV electron beam, respectively, showing that the accuracy of MasterPlan electron beam algorithm is good for simple two-dimensional geometries as well as for more complicated three-dimensional ones. The results are in agreement with those reported in literature by Cygler et al. [''Evaluation of the first commercial Monte Carlo dose calculation engine for electron beam treatment planning,'' Med. Phys. 31, 142-153 (2004)]. In addition, the authors have also analyzed the response of the 2D array in terms of dose profiles at different depths, comparing the results with those obtained in water phantom using an electron diode. The results show that in the low gradient regions there were no deviations larger than the criteria of acceptability set by Van Dyk et al. [''Commissioning and quality assurance of treatment planning computers,'' Int. J. Radiat. Oncol. Biol. Phys. 26, 261-273 (1993)]; in the high gradient region, the maximum deviations are less than 2 mm with most of the values less than 1 mm. The present article shows that MapCHECK trade mark sign can play a useful role in

  11. 18F-Fluorodeoxyglucose positron emission tomography and serum cytokines and matrix metalloproteinases in the assessment of disease activity in Takayasu's arteritis

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    Anne E.D. Arraes

    Full Text Available ABSTRACT Objective: To evaluate 18F-fluorodeoxyglucose (18F-FDG uptake on positron emission tomography–computed tomography (PET–CT and serum levels of different cytokines and matrix metalloproteinases (MMPs in patients with Takayasu arteritis (TA and associations with disease activity. Methods: Serum levels of tumor necrosis factor-α (TNF-α, interleukin (IL-2, IL-6, IL-8, IL-12, IL-18, MMP-3 and MMP-9 were measured in 36 TA patients and 36 controls. Maximum standard uptake value (SUVmax of 18F-FDG in arterial walls was determined by PET–CT scans. TA patients were classified as active disease, inactive disease and possible active disease. Results: Serum IL-6 and MMP-3 levels were higher in TA patients than in controls (p < 0.001. Serum IL-6 was higher in patients with active disease and in patients with possible active disease than in inactive disease (p < 0.0001. Patients with active disease had higher serum TNFα levels than patients with inactive disease (p = 0.049 while patients with possible active disease presented higher IL-18 levels than patients with inactive disease (p = 0.046. Patients with active disease had higher SUVmax values than those with inactive disease (p = 0.042. By receiver operating characteristic (ROC curve SUVmax was predictive of active disease in TA and values ≥1.3 were associated with disease activity (p = 0.039. Serum TNF-α levels were higher in patients with SUVmax ≥ 1.3 than <1.3 (p = 0.045 and controls (p = 0.012. Serum IL-6 levels were higher in patients with SUVmax ≥ 1.3 than in controls (p < 0.001. No differences regarding other biomarkers were found between TA patients and controls. Conclusions: Higher serum IL-6 and TNFα levels as well as higher 18F-FDG uptake in arterial wall are associated with active TA.

  12. Identification of Proteins with Potential Osteogenic Activity Present in the Water-Soluble Matrix Proteins from Crassostrea gigas Nacre Using a Proteomic Approach

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    Daniel V. Oliveira

    2012-01-01

    Full Text Available Nacre, when implanted in vivo in bones of dogs, sheep, mice, and humans, induces a biological response that includes integration and osteogenic activity on the host tissue that seems to be activated by a set of proteins present in the nacre water-soluble matrix (WSM. We describe here an experimental approach that can accurately identify the proteins present in the WSM of shell mollusk nacre. Four proteins (three gigasin-2 isoforms and a cystatin A2 were for the first time identified in WSM of Crassostrea gigas nacre using 2DE and LC-MS/MS for protein identification. These proteins are thought to be involved in bone remodeling processes and could be responsible for the biocompatibility shown between bone and nacre grafts. These results represent a contribution to the study of shell biomineralization process and opens new perspectives for the development of new nacre biomaterials for orthopedic applications.

  13. (60)Co in cast steel matrix: A European interlaboratory comparison for the characterisation of new activity standards for calibration of gamma-ray spectrometers in metallurgy.

    Science.gov (United States)

    Tzika, Faidra; Burda, Oleksiy; Hult, Mikael; Arnold, Dirk; Marroyo, Belén Caro; Dryák, Pavel; Fazio, Aldo; Ferreux, Laurent; García-Toraño, Eduardo; Javornik, Andrej; Klemola, Seppo; Luca, Aurelian; Moser, Hannah; Nečemer, Marijan; Peyrés, Virginia; Reis, Mario; Silva, Lidia; Šolc, Jaroslav; Svec, Anton; Tyminski, Zbigniew; Vodenik, Branko; Wätjen, Uwe

    2016-08-01

    Two series of activity standards of (60)Co in cast steel matrix, developed for the calibration of gamma-ray spectrometry systems in the metallurgical sector, were characterised using a European interlaboratory comparison among twelve National Metrology Institutes and one international organisation. The first standard, consisting of 14 disc shaped samples, was cast from steel contaminated during production ("originally"), and the second, consisting of 15 similar discs, from artificially-contaminated ("spiked") steel. The reference activity concentrations of (60)Co in the cast steel standards were (1.077±0.019) Bqg(-1) on 1 January 2013 12h00 UT and (1.483±0.022) Bqg(-1) on 1 June 2013 12h00 UT, respectively. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Influence of Polyphenol Extract from Evening Primrose (Oenothera Paradoxa Seeds on Proliferation of Caco-2 Cells and on Expression, Synthesis and Activity of Matrix Metalloproteinases and Their Inhibitors

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    Szewczyk Karolina

    2014-09-01

    Full Text Available Evening primrose (Oenothera paradoxa Hudziok seeds are a rich source of not only a valuable oil containing an essential fatty acid - ᵧ-linolenic acid (GLA - but also polyphenols which can be obtained from the biomass remaining after oil pressing. The aim of our studies was to evaluate the influence of a polyphenol extract from defatted seeds of evening primrose on human colorectal adenocarcinoma Caco-2 cell proliferation and matrix metalloproteinases (MMPs synthesis and activity. To assess the effect of evening primrose extract on Caco-2 cell proliferation, crystal violet staining and sulforhodamine B (SRB assays were used whereas mRNA expression and activity of MMPs were evaluated by RT-PCR and gelatin zymography.

  15. Calcium alginate gels as stem cell matrix-making paracrine stem cell activity available for enhanced healing after surgery.

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    Andreas Schmitt

    Full Text Available Regeneration after surgery can be improved by the administration of anabolic growth factors. However, to locally maintain these factors at the site of regeneration is problematic. The aim of this study was to develop a matrix system containing human mesenchymal stem cells (MSCs which can be applied to the surgical site and allows the secretion of endogenous healing factors from the cells. Calcium alginate gels were prepared by a combination of internal and external gelation. The gelling behaviour, mechanical stability, surface adhesive properties and injectability of the gels were investigated. The permeability of the gels for growth factors was analysed using bovine serum albumin and lysozyme as model proteins. Human MSCs were isolated, cultivated and seeded into the alginate gels. Cell viability was determined by AlamarBlue assay and fluorescence microscopy. The release of human VEGF and bFGF from the cells was determined using an enzyme-linked immunoassay. Gels with sufficient mechanical properties were prepared which remained injectable through a syringe and solidified in a sufficient time frame after application. Surface adhesion was improved by the addition of polyethylene glycol 300,000 and hyaluronic acid. Humans MSCs remained viable for the duration of 6 weeks within the gels. Human VEGF and bFGF was found in quantifiable concentrations in cell culture supernatants of gels loaded with MSCs and incubated for a period of 6 weeks. This work shows that calcium alginate gels can function as immobilization matrices for human MSCs.

  16. Terminalia catappa Exerts Antimetastatic Effects on Hepatocellular Carcinoma through Transcriptional Inhibition of Matrix Metalloproteinase-9 by Modulating NF-κB and AP-1 Activity

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    Chao-Bin Yeh

    2012-01-01

    Full Text Available High mortality and morbidity rates for hepatocellular carcinoma (HCC in Taiwan primarily result from uncontrolled tumor metastasis. Previous studies have identified that Terminalia catappa leaf extracts (TCE exert hepatoprotective, antioxidative, antiinflammatory, anticancer, and antimetastatic activities. However, the effects of TCE on HCC and the underlying molecular mechanisms of its activities have yet to be fully elucidated. The present study's findings demonstrate that TCE concentration dependently inhibits human HCC migration/invasion. Zymographic and western blot analyses revealed that TCE inhibited the activities and expression of matrix metalloproteinase-9 (MMP-9. Assessment of mRNA levels, using reverse transcriptase polymerase chain reaction (PCR and real-time PCR, and promoter assays confirmed the inhibitory effects of TCE on MMP-9 expression in HCC cells. The inhibitory effects of TCE on MMP-9 proceeded by upregulating tissue inhibitor of metalloproteinase-1 (TIMP-1, as well as suppressing nuclear translocation and DNA binding activity of nuclear factor-kappa B (NF-κB and activating protein-1 (AP-1 on the MMP-9 promoter in Huh7 cells. In conclusion, TCE inhibits MMP-9 expression and HCC cell metastasis and, thus, has potential use as a chemopreventive agent. Its inhibitory effects are associated with downregulation of the binding activities of the transcription factors NF-κB and AP-1.

  17. Phosphodiesterase inhibition mediates matrix metalloproteinase activity and the level of collagen degradation fragments in a liver fibrosis ex vivo rat model

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    Veidal Sanne Skovgård

    2012-12-01

    Full Text Available Abstract Background Accumulation of extracellular matrix (ECM and increased matrix metalloproteinase (MMP activity are hallmarks of liver fibrosis. The aim of the present study was to develop a model of liver fibrosis combining ex vivo tissue culture of livers from CCl4 treated animals with an ELISA detecting a fragment of type III collagen generated in vitro by MMP-9 (C3M, known to be associated with liver fibrosis and to investigate cAMP modulation of MMP activity and liver tissue turnover in this model. Findings In vivo: Rats were treated for 8 weeks with CCl4/Intralipid. Liver slices were cultured for 48 hours. Levels of C3M were determined in the supernatants of slices cultured without treatment, treated with GM6001 (positive control or treated with IBMX (phosphodiesterase inhibitor. Enzymatic activity of MMP-2 and MMP-9 were studied by gelatin zymography. Ex vivo: The levels of serum C3M increased 77% in the CCl4-treated rats at week 8 (p 4-treated animals had highly increased MMP-9, but not MMP-2 activity, compared to slices derived from control animals. Conclusions We have combined an ex vivo model of liver fibrosis with measurement of a biochemical marker of collagen degradation in the condition medium. This technology may be used to evaluate the molecular process leading to structural fibrotic changes, as collagen species are the predominant structural part of fibrosis. These data suggest that modulation of cAMP may play a role in regulation of collagen degradation associated with liver fibrosis.

  18. Pericellular activation of proMMP-7 (promatrilysin-1) through interaction with CD151.

    Science.gov (United States)

    Shiomi, Takayuki; Inoki, Isao; Kataoka, Fumio; Ohtsuka, Takashi; Hashimoto, Gakuji; Nemori, Ryoichi; Okada, Yasunori

    2005-12-01

    Matrix metalloproteinase-7 (MMP-7) (also known as matrilysin-1) is secreted as a proenzyme (proMMP-7) and plays a key role in the degradation of various extracellular matrix (ECM) and non-ECM molecules after activation. To identify the binding proteins related to proMMP-7 activation, a human lung cDNA library was screened by yeast two-hybrid system using proMMP-7 as bait. We identified a candidate molecule CD151, which is a member of the transmembrane 4 superfamily. Complex formation of proMMP-7 with CD151 was demonstrated by immunoprecipitation of the molecules from CaR-1 cells, a human rectal carcinoma cell line, expressing both proMMP-7 and CD151, and CD151 stable transfectants incubated with proMMP-7. Yeast two-hybrid assays using deletion mutants of proMMP-7 and CD151 suggested an interaction between the propeptide of proMMP-7 and the COOH-terminal extracellular loop of CD151. The binding activity of (125)I-labeled proMMP-7 to CD151 on the cell membranes was shown with CD151 stable transfectants. Laser-scanning confocal microscopy demonstrated that proMMP-7 colocalizes with CD151 on the cell membranes of CD151 stable transfectants and CaR-1 cells. In situ zymography using crosslinked carboxymethylated transferrin, a substrate of MMP-7, demonstrated proteinase activity on and around CD151 stable transfectants and CaR-1 cells, while the activity was abolished by their treatment with MMP inhibitors, anti-MMP-7 antibody or anti-CD151 antibody. In human lung adenocarcinoma tissues, colocalization of MMP-7 and CD151 was demonstrated on the carcinoma cells. Metalloproteinase activity was present in these tissues and could be inhibited by antibodies to MMP-7 or CD151. These data demonstrate for the first time that proMMP-7 is captured and activated on the cell membranes through interaction with CD151, and suggest the possibility that similar to the MT1-MMP/MMP-2 system, MMP-7 is involved in the pericellular activation mechanism mediated by CD151, a crucial step in

  19. A composite demineralized bone matrix--self assembling peptide scaffold for enhancing cell and growth factor activity in bone marrow.

    Science.gov (United States)

    Hou, Tianyong; Li, Zhiqiang; Luo, Fei; Xie, Zhao; Wu, Xuehui; Xing, Junchao; Dong, Shiwu; Xu, Jianzhong

    2014-07-01

    The need for suitable bone grafts is high; however, there are limitations to all current graft sources, such as limited availability, the invasive harvest procedure, insufficient osteoinductive properties, poor biocompatibility, ethical problems, and degradation properties. The lack of osteoinductive properties is a common problem. As an allogenic bone graft, demineralized bone matrix (DBM) can overcome issues such as limited sources and comorbidities caused by invasive harvest; however, DBM is not sufficiently osteoinductive. Bone marrow has been known to magnify osteoinductive components for bone reconstruction because it contains osteogenic cells and factors. Mesenchymal stem cells (MSCs) derived from bone marrow are the gold standard for cell seeding in tissue-engineered biomaterials for bone repair, and these cells have demonstrated beneficial effects. However, the associated high cost and the complicated procedures limit the use of tissue-engineered bone constructs. To easily enrich more osteogenic cells and factors to DBM by selective cell retention technology, DBM is modified by a nanoscale self-assembling peptide (SAP) to form a composite DBM/SAP scaffold. By decreasing the pore size and increasing the charge interaction, DBM/SAP scaffolds possess a much higher enriching yield for osteogenic cells and factors compared with DBM alone scaffolds. At the same time, SAP can build a cellular microenvironment for cell adhesion, proliferation, and differentiation that promotes bone reconstruction. As a result, a suitable bone graft fabricated by DBM/SAP scaffolds and bone marrow represents a new strategy and product for bone transplantation in the clinic. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. The changes in amount and activity of matrix metalloproteinases in rat's serum irradiated by γ-rays

    International Nuclear Information System (INIS)

    Le Chen; Li Haijun; Cheng Ying; Min Rui

    2009-01-01

    Rats were whole body irradiated by γ-rays with different doses. A commercial ELISA kit was used to analyze the concentration of MMP-2 and MMP-9 in rat's serum. And Gelatin zymography electrophoresis was used to test the activity of serum MMPs at 24 h after irradiation. The results show that the amount and the activity of MMP-2 in rat's serum increase with increment of irradiation doses. Compared with 1∼4 Gy exposed groups a significant rising of MMP-2 has been found in 5 Gy and 6 Gy exposed groups (p<0.01). On the contrast, the amount and activity of MMP-9 in rat's serum have a little change at 24 hours after irradiation in all of exposed groups. It can be deduced that the changes with amount and activity of MMP-2 may be used as a potential indicator of exposed dose in organisms. (authors)

  1. Inhibition of matrix metalloproteinase-9 activity by doxycycline ameliorates RANK ligand-induced osteoclast differentiation in vitro and in vivo

    International Nuclear Information System (INIS)

    Franco, Gilson C.N.; Kajiya, Mikihito; Nakanishi, Tadashi; Ohta, Kouji; Rosalen, Pedro L.; Groppo, Francisco C.; Ernst, Cory W.O.; Boyesen, Janie L.; Bartlett, John D.; Stashenko, Philip; Taubman, Martin A.; Kawai, Toshihisa

    2011-01-01

    Tetracycline antibiotics, including doxycycli/e (DOX), have been used to treat bone resorptive diseases, partially because of their activity to suppress osteoclastogenesis induced by receptor activator of nuclear factor kappa B ligand (RANKL). However, their precise inhibitory mechanism remains unclear. Therefore, the present study examined the effect of Dox on osteoclastogenesis signaling induced by RANKL, both in vitro and in vivo. Although Dox inhibited RANKL-induced osteoclastogenesis and down-modulated the mRNA expression of functional osteoclast markers, including tartrate-resistant acid phosphatase (TRAP) and cathepsin K, Dox neither affected RANKL-induced MAPKs phosphorylation nor NFATc1 gene expression in RAW264.7 murine monocytic cells. Gelatin zymography and Western blot analyses showed that Dox down-regulated the enzyme activity of RANKL-induced MMP-9, but without affecting its protein expression. Furthermore, MMP-9 enzyme inhibitor also attenuated both RANKL-induced osteoclastogenesis and up-regulation of TRAP and cathepsin K mRNA expression, indicating that MMP-9 enzyme action is engaged in the promotion of RANKL-induced osteoclastogenesis. Finally, Dox treatment abrogated RANKL-induced osteoclastogenesis and TRAP activity in mouse calvaria along with the suppression of MMP9 enzyme activity, again without affecting the expression of MMP9 protein. These findings suggested that Dox inhibits RANKL-induced osteoclastogenesis by its inhibitory effect on MMP-9 enzyme activity independent of the MAPK-NFATc1 signaling cascade.

  2. Inhibition of matrix metalloproteinase-9 activity by doxycycline ameliorates RANK ligand-induced osteoclast differentiation in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Franco, Gilson C.N. [Department of Immunology, Forsyth Institute, Cambridge, MA (United States); Department of Pharmacology, FOP/UNICAMP, Piracicaba, SP (Brazil); Kajiya, Mikihito [Department of Immunology, Forsyth Institute, Cambridge, MA (United States); Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA (United States); Nakanishi, Tadashi [Department of Immunology, Forsyth Institute, Cambridge, MA (United States); Ohta, Kouji [Department of Immunology, Forsyth Institute, Cambridge, MA (United States); Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA (United States); Rosalen, Pedro L.; Groppo, Francisco C. [Department of Pharmacology, FOP/UNICAMP, Piracicaba, SP (Brazil); Ernst, Cory W.O.; Boyesen, Janie L. [Department of Immunology, Forsyth Institute, Cambridge, MA (United States); Bartlett, John D.; Stashenko, Philip [Department of Cytokine Biology, Forsyth Institute, Cambridge, MA (United States); Taubman, Martin A. [Department of Immunology, Forsyth Institute, Cambridge, MA (United States); Kawai, Toshihisa, E-mail: tkawai@forsyth.org [Department of Immunology, Forsyth Institute, Cambridge, MA (United States); Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA (United States)

    2011-06-10

    Tetracycline antibiotics, including doxycycli/e (DOX), have been used to treat bone resorptive diseases, partially because of their activity to suppress osteoclastogenesis induced by receptor activator of nuclear factor kappa B ligand (RANKL). However, their precise inhibitory mechanism remains unclear. Therefore, the present study examined the effect of Dox on osteoclastogenesis signaling induced by RANKL, both in vitro and in vivo. Although Dox inhibited RANKL-induced osteoclastogenesis and down-modulated the mRNA expression of functional osteoclast markers, including tartrate-resistant acid phosphatase (TRAP) and cathepsin K, Dox neither affected RANKL-induced MAPKs phosphorylation nor NFATc1 gene expression in RAW264.7 murine monocytic cells. Gelatin zymography and Western blot analyses showed that Dox down-regulated the enzyme activity of RANKL-induced MMP-9, but without affecting its protein expression. Furthermore, MMP-9 enzyme inhibitor also attenuated both RANKL-induced osteoclastogenesis and up-regulation of TRAP and cathepsin K mRNA expression, indicating that MMP-9 enzyme action is engaged in the promotion of RANKL-induced osteoclastogenesis. Finally, Dox treatment abrogated RANKL-induced osteoclastogenesis and TRAP activity in mouse calvaria along with the suppression of MMP9 enzyme activity, again without affecting the expression of MMP9 protein. These findings suggested that Dox inhibits RANKL-induced osteoclastogenesis by its inhibitory effect on MMP-9 enzyme activity independent of the MAPK-NFATc1 signaling cascade.

  3. Caffeic Acid Phenethyl Ester Inhibits Oral Cancer Cell Metastasis by Regulating Matrix Metalloproteinase-2 and the Mitogen-Activated Protein Kinase Pathway

    Directory of Open Access Journals (Sweden)

    Chih-Yu Peng

    2012-01-01

    Full Text Available Caffeic acid phenethyl ester (CAPE, an active component extracted from honeybee hives, exhibits anti-inflammatory and anticancer activities. However, the molecular mechanism by which CAPE affects oral cancer cell metastasis has yet to be elucidated. In this study, we investigated the potential mechanisms underlying the effects of CAPE on the invasive ability of SCC-9 oral cancer cells. Results showed that CAPE attenuated SCC-9 cell migration and invasion at noncytotoxic concentrations (0 μM to 40 μM. Western blot and gelatin zymography analysis findings further indicated that CAPE downregulated matrix metalloproteinase-2 (MMP-2 protein expression and inhibited its enzymatic activity. CAPE exerted its inhibitory effects on MMP-2 expression and activity by upregulating tissue inhibitor of metalloproteinase-2 (TIMP-2 and potently decreased migration by reducing focal adhesion kinase (FAK phosphorylation and the activation of its downstream signaling molecules p38/MAPK and JNK. These data indicate that CAPE could potentially be used as a chemoagent to prevent oral cancer metastasis.

  4. Inhibitory effects of kaempferol on the invasion of human breast carcinoma cells by downregulating the expression and activity of matrix metalloproteinase-9.

    Science.gov (United States)

    Li, Chenglin; Zhao, Yuanwei; Yang, Dan; Yu, Yanyan; Guo, Hao; Zhao, Ziming; Zhang, Bei; Yin, Xiaoxing

    2015-02-01

    Matrix metalloproteinases (MMPs) have been regarded as major critical molecules assisting tumor cells during metastasis, for excessive ECM (ECM) degradation, and cancer cell invasion. In the present study, in vitro and in vivo assays were employed to examine the inhibitory effects of kaempferol, a natural polyphenol of flavonoid family, on tumor metastasis. Data showed that kaempferol could inhibit adhesion, migration, and invasion of MDA-MB-231 human breast carcinoma cells. Moreover, kaempferol led to the reduced activity and expression of MMP-2 and MMP-9, which were detected by gelatin zymography, real-time PCR, and western blot analysis, respectively. Further elucidation of the mechanism revealed that kaempferol treatment inhibited the activation of transcription factor activator protein-1 (AP-1) and MAPK signaling pathway. Moreover, kaempferol repressed phorbol-12-myristate-13-acetate (PMA)-induced MMP-9 expression and activity through suppressing the translocation of protein kinase Cδ (PKCδ) and MAPK signaling pathway. Our results also indicated that kaempferol could block the lung metastasis of B16F10 murine melanoma cells as well as the expression of MMP-9 in vivo. Taken together, these results demonstrated that kaempferol could inhibit cancer cell invasion through blocking the PKCδ/MAPK/AP-1 cascade and subsequent MMP-9 expression and its activity. Therefore, kaempferol might act as a therapeutic potential candidate for cancer metastasis.

  5. Mast cell-restricted, tetramer-forming tryptases induce aggrecanolysis in articular cartilage by activating matrix metalloproteinase-3 and -13 zymogens.

    Science.gov (United States)

    Magarinos, Natalia J; Bryant, Katherine J; Fosang, Amanda J; Adachi, Roberto; Stevens, Richard L; McNeil, H Patrick

    2013-08-01

    Mouse mast cell protease (mMCP)-6-null C57BL/6 mice lost less aggrecan proteoglycan from the extracellular matrix of their articular cartilage during inflammatory arthritis than wild-type (WT) C57BL/6 mice, suggesting that this mast cell (MC)-specific mouse tryptase plays prominent roles in articular cartilage catabolism. We used ex vivo mouse femoral head explants to determine how mMCP-6 and its human ortholog hTryptase-β mediate aggrecanolysis. Exposure of the explants to recombinant hTryptase-β, recombinant mMCP-6, or lysates harvested from WT mouse peritoneal MCs (PMCs) significantly increased the levels of enzymatically active matrix metalloproteinases (MMP) in cartilage and significantly induced aggrecan loss into the conditioned media, relative to replicate explants exposed to medium alone or lysates collected from mMCP-6-null PMCs. Treatment of cartilage explants with tetramer-forming tryptases generated aggrecan fragments that contained C-terminal DIPEN and N-terminal FFGVG neoepitopes, consistent with MMP-dependent aggrecanolysis. In support of these data, hTryptase-β was unable to induce aggrecan release from the femoral head explants obtained from Chloe mice that resist MMP cleavage at the DIPEN↓FFGVG site in the interglobular domain of aggrecan. In addition, the abilities of mMCP-6-containing lysates from WT PMCs to induce aggrecanolysis were prevented by inhibitors of MMP-3 and MMP-13. Finally, recombinant hTryptase-β was able to activate latent pro-MMP-3 and pro-MMP-13 in vitro. The accumulated data suggest that human and mouse tetramer-forming tryptases are MMP convertases that mediate cartilage damage and the proteolytic loss of aggrecan proteoglycans in arthritis, in part, by activating the zymogen forms of MMP-3 and MMP-13, which are constitutively present in articular cartilage.

  6. Real-time zymography and reverse zymography: a method for detecting activities of matrix metalloproteinases and their inhibitors using FITC-labeled collagen and casein as substrates.

    Science.gov (United States)

    Hattori, Shunji; Fujisaki, Hitomi; Kiriyama, Tomomi; Yokoyama, Tsukao; Irie, Shinkichi

    2002-02-01

    Zymography and reverse zymography are widely used techniques for identifying the proteolytic activity of enzymes and the presence of protease inhibitors in polyacrylamide gels. In the current studies, we utilized a fluorescein-isothiocyanate-labeled substrate to develop novel zymographic and reverse zymographic methods for detecting matrix metalloproteinases and tissue inhibitors of the metalloproteinases, respectively. Using a transilluminator, the results can be observed visually without stopping the enzymatic reaction. For this reason, we have named these methods real-time zymography and real-time reverse zymography. These methods have the following advantages compared with conventional protocols: (1) because the reaction can be repeatedly monitored on the polyacrylamide gels, optimization of the incubation time can be achieved without preliminary analyses; (2) higher sensitivity is achieved with a lower amount of substrate than with conventional methods; (3) a semi-quantitative analysis of matrix metalloproteinases is possible. An additional advantage of the real-time reverse zymography is that, because the fluorescence detection is specific for substrate digestion, the inhibitor bands can be easily distinguished from contaminating proteins.

  7. Mixed-matrix membranes with enhanced antifouling activity: probing the surface-tailoring potential of Tiron and chromotropic acid for nano-TiO2

    Science.gov (United States)

    Pal, Avishek; Dey, T. K.; Debnath, A. K.; Bhushan, Bharat; Sahu, A. K.; Bindal, R. C.; Kar, Soumitra

    2017-09-01

    Mixed-matrix membranes (MMMs) were developed by impregnating organofunctionalized nanoadditives within fouling-susceptible polysulfone matrix following the non-solvent induced phase separation (NIPS) method. The facile functionalization of nanoparticles of anatase TiO2 (nano-TiO2) by using two different organoligands, viz. Tiron and chromotropic acid, was carried out to obtain organofunctionalized nanoadditives, FT-nano-TiO2 and FC-nano-TiO2, respectively. The structural features of nanoadditives were evaluated by X-ray diffraction, X-ray photoelectron spectroscopy, Raman and Fourier transform infrared spectroscopy, which established that Tiron leads to the blending of chelating and bridging bidentate geometries for FT-nano-TiO2, whereas chromotropic acid produces bridging bidentate as well as monodentate geometries for FC-nano-TiO2. The surface chemistry of the studied membranes, polysulfone (Psf): FT-nano-TiO2 UF and Psf: FC-nano-TiO2 UF, was profoundly influenced by the benign distributions of the nanoadditives enriched with distinctly charged sites (-SO3 -H+ ), as evidenced by superior morphology, improved topography, enhanced surface hydrophilicity and altered electrokinetic features. The membranes exhibited enhanced solvent throughputs, viz. 3500-4000 and 3400-4300 LMD at 1 bar of transmembrane pressure, without significant compromise in their rejection attributes. The flux recovery ratios and fouling resistive behaviours of MMMs towards bovine serum albumin indicated that the nanoadditives could impart stable and appreciable antifouling activity, potentially aiding in a sustainable ultrafiltration performance.

  8. Acute morphine activates satellite glial cells and up-regulates IL-1β in dorsal root ganglia in mice via matrix metalloprotease-9

    Directory of Open Access Journals (Sweden)

    Berta Temugin

    2012-03-01

    Full Text Available Abstract Background Activation of spinal cord glial cells such as microglia and astrocytes has been shown to regulate chronic opioid-induced antinociceptive tolerance and hyperalgesia, due to spinal up-regulation of the proinflammatory cytokines such as interleukin-1 beta (IL-1β. Matrix metalloprotease-9 (MMP-9 has been implicated in IL-1β activation in neuropathic pain. However, it is unclear whether acute opioid treatment can activate glial cells in the peripheral nervous system. We examined acute morphine-induced activation of satellite glial cells (SGCs and up-regulation of IL-1β in dorsal root ganglia (DRGs, and further investigated the involvement of MMP-9 in these opioid-induced peripheral changes. Results Subcutaneous morphine injection (10 mg/kg induced robust peripheral glial responses, as evidenced by increased GFAP expression in DRGs but not in spinal cords. The acute morphine-induced GFAP expression is transient, peaking at 2 h and declining after 3 h. Acute morphine treatment also increased IL-1β immunoreactivity in SGCs and IL-1β activation in DRGs. MMP-9 and GFAP are expressed in DRG neurons and SGCs, respectively. Confocal analysis revealed a close proximity of MMP-9 and GFAP immunostaining. Importantly, morphine-induced DRG up-regulation of GFAP expression and IL-1β activation was abolished after Mmp9 deletion or naloxone pre-treatment. Finally, intrathecal injections of IL-1β-selective siRNA not only reduced DRG IL-1β expression but also prolonged acute morphine-induced analgesia. Conclusions Acute morphine induces opioid receptors- and MMP-9-dependent up-regulation of GFAP expression and IL-1β activation in SGCs of DRGs. MMP-9 could mask and shorten morphine analgesia via peripheral neuron-glial interactions. Targeting peripheral glial activation might prolong acute opioid analgesia.

  9. Immobilization of cellulase using porous polymer matrix

    International Nuclear Information System (INIS)

    Kumakura, M.; Kaetsu, I.

    1984-01-01

    A new method is discussed for the immobilization of cellulase using porous polymer matrices, which were obtained by radiation polymerization of hydrophilic monomers. In this method, the immobilized enzyme matrix was prepared by enzyme absorbtion in the porous polymer matrix and drying treatment. The enzyme activity of the immobilized enzyme matrix varied with monomer concentration, cooling rate of the monomer solution, and hydrophilicity of the polymer matrix, takinn the change of the nature of the porous structure in the polymer matrix. The leakage of the enzymes from the polymer matrix was not observed in the repeated batch enzyme reactions

  10. Effect of the activation of a clay-base paper industry by-product on cement matrix behaviour

    Directory of Open Access Journals (Sweden)

    García, R.

    2008-12-01

    Full Text Available The present study addresses variations in the calcination temperature (600-750 ºC and kiln time (two to five hours applied to activate coated paper waste and their effect on the rheological, physical and mechanical behaviour of cement matrices containing these active additions.The results obtained showed that the conditions under which kaolinite was activated had a direct effect on the subsequent behaviour of the calcined products. At activating temperatures of over 700 ºC, pozzolanic activity and mechanical strength were observed to be lower, setting time shorter and the mortar less workable.El presente trabajo de investigación aborda la influencia de las condiciones de activación (600-750 ºC y 2-5 horas de permanencia en el horno de los lodos de papel procedente de la fabricación de papel estucado en el comportamiento reológico, físico y mecánico de las matrices de cementos elaboradas con este tipo de adiciones activas.Los resultados obtenidos muestran una influencia directa entre las condiciones de activación de la caolinita y el comportamiento posterior de los productos calcinados. Así, en condiciones de activación superiores a 700 ºC se observa una menor actividad puzolánica, tiempo de fraguado más corto, disminución de la trabajabilidad de los morteros mezcla y resistencia mecánica más baja.

  11. Ulcerative colitis, Crohn's disease, and irritable bowel syndrome have different profiles of extracellular matrix turnover, which also reflects disease activity in Crohn's disease

    DEFF Research Database (Denmark)

    Mortensen, Joachim Høg; Manon-Jensen, Tina; Jensen, Michael Dam

    2017-01-01

    Increased protease activity is a key pathological feature of inflammatory bowel disease (IBD). However, the differences in extracellular matrix remodelling (ECM) in Crohn's disease (CD) and ulcerative colitis (UC) are not well described. An increased understanding of the inflammatory processes may...... provide optimized disease monitoring and diagnostics. We investigated the tissue remodelling in IBD and IBS patients by using novel blood-based biomarkers reflecting ECM remodelling. Five ECM biomarkers (VICM, BGM, EL-NE, C5M, Pro-C5) were measured by competitive ELISAs in serum from 72 CD patients, 60 UC...... patients, 22 patients with irritable bowel syndrome (IBS), and 24 healthy donors. One-way analysis of variance, Mann-Whitney U-test, logistic regression models, and receiver operator characteristics (ROC) curve analysis was carried out to evaluate the diagnostic accuracy of the biomarkers. The ECM...

  12. Mangiferin exerts antitumor activity in breast cancer cells by regulating matrix metalloproteinases, epithelial to mesenchymal transition, and β-catenin signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hongzhong; Huang, Jing; Yang, Bing; Xiang, Tingxiu; Yin, Xuedong; Peng, Weiyan; Cheng, Wei [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Wan, Jingyuan; Luo, Fuling [Department of Pharmacology, Chongqing Medical University, Chongqing (China); Li, Hongyuan [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Ren, Guosheng, E-mail: rgs726@163.com [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China)

    2013-10-01

    Although mangiferin which is a naturally occurring glucosylxanthone has exhibited promising anticancer activities, the detailed molecular mechanism of mangiferin on cancers still remains enigmatic. In this study, the anticancer activity of mangiferin was evaluated in breast cancer cell line-based in vitro and in vivo models. We showed that mangiferin treatment resulted in decreased cell viability and suppression of metastatic potential in breast cancer cells. Further mechanistic investigation revealed that mangiferin induced decreased matrix metalloproteinase (MMP)-7 and -9, and reversal of epithelial–mesenchymal transition (EMT). Moreover, it was demonstrated that mangiferin significantly inhibited the activation of β-catenin pathway. Subsequent experiments showed that inhibiting β-catenin pathway might play a central role in mangiferin-induced anticancer activity through modulation of MMP-7 and -9, and EMT. Consistent with these findings in vitro, the antitumor potential was also verified in mangiferin-treated MDA-MB-231 xenograft mice where significantly decreased tumor volume, weight and proliferation, and increased apoptosis were obtained, with lower expression of MMP-7 and -9, vimentin and active β-catenin, and higher expression of E-cadherin. Taken together, our study suggests that mangiferin might be used as an effective chemopreventive agent against breast cancer. - Highlights: • Mangiferin inhibits growth and metastatic potential in breast cancer cells. • Mangiferin down-regulates MMP-7 and -9 in breast cancer cells. • Mangiferin induces the reversal of EMT in metastatic breast cancer cells. • Mangiferin inhibits the activation of β-catenin pathway in breast cancer cells. • Inhibiting β-catenin is responsible for the antitumor activity of mangiferin.

  13. Indirect flat-panel detector with avalanche gain: Fundamental feasibility investigation for SHARP-AMFPI (scintillator HARP active matrix flat panel imager)

    International Nuclear Information System (INIS)

    Zhao Wei; Li Dan; Reznik, Alla; Lui, B.J.M.; Hunt, D.C.; Rowlands, J.A.; Ohkawa, Yuji; Tanioka, Kenkichi

    2005-01-01

    An indirect flat-panel imager (FPI) with avalanche gain is being investigated for low-dose x-ray imaging. It is made by optically coupling a structured x-ray scintillator CsI(Tl) to an amorphous selenium (a-Se) avalanche photoconductor called HARP (high-gain avalanche rushing photoconductor). The final electronic image is read out using an active matrix array of thin film transistors (TFT). We call the proposed detector SHARP-AMFPI (scintillator HARP active matrix flat panel imager). The advantage of the SHARP-AMFPI is its programmable gain, which can be turned on during low dose fluoroscopy to overcome electronic noise, and turned off during high dose radiography to avoid pixel saturation. The purpose of this paper is to investigate the important design considerations for SHARP-AMFPI such as avalanche gain, which depends on both the thickness d Se and the applied electric field E Se of the HARP layer. To determine the optimal design parameter and operational conditions for HARP, we measured the E Se dependence of both avalanche gain and optical quantum efficiency of an 8 μm HARP layer. The results were used in a physical model of HARP as well as a linear cascaded model of the FPI to determine the following x-ray imaging properties in both the avalanche and nonavalanche modes as a function of E Se : (1) total gain (which is the product of avalanche gain and optical quantum efficiency); (2) linearity; (3) dynamic range; (4) gain nonuniformity resulting from thickness nonuniformity; and (5) effects of direct x-ray interaction in HARP. Our results showed that a HARP layer thickness of 8 μm can provide adequate avalanche gain and sufficient dynamic range for x-ray imaging applications to permit quantum limited operation over the range of exposures needed for radiography and fluoroscopy

  14. Effects of parathyroid hormone and calcitonin on alkaline phosphatase activity and matrix calcification in rabbit growth-plate chondrocyte cultures

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Y.; Shimazu, A.; Nakashima, K.; Suzuki, F.; Jikko, A.; Iwamoto, M. (Osaka Univ. (Japan))

    1990-07-01

    The effects of PTH and calcitonin (CT) on the expression of mineralization-related phenotypes by chondrocytes were examined. In cultures of pelleted growth-plate chondrocytes. PTH caused 60-90% decreases in alkaline phosphatase activity, the incorporation of {sup 45}Ca into insoluble material, and the calcium content during the post-mitotic stage. These effects of PTH were dose-dependent and reversible. In contrast, CT increased alkaline phosphatase activity, {sup 45}Ca incorporation into insoluble material, and the calcium content by 1.4- to 1.8-fold. These observations suggest that PTH directly inhibits the expression of the mineralization-related phenotypes by growth-plate chondrocytes, and that CT has the opposite effects.

  15. A Low-Operating-Power and Flexible Active-Matrix Organic-Transistor Temperature-Sensor Array.

    Science.gov (United States)

    Ren, Xiaochen; Pei, Ke; Peng, Boyu; Zhang, Zhichao; Wang, Zongrong; Wang, Xinyu; Chan, Paddy K L

    2016-06-01

    An organic flexible temperature-sensor array exhibits great potential in health monitoring and other biomedical applications. The actively addressed 16 × 16 temperature sensor array reaches 100% yield rate and provides 2D temperature information of the objects placed in contact, even if the object has an irregular shape. The current device allows defect predictions of electronic devices, remote sensing of harsh environments, and e-skin applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. TNF-α promotes human retinal pigment epithelial (RPE) cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression through activation of Akt/mTORC1 signaling

    International Nuclear Information System (INIS)

    Wang, Cheng-hu; Cao, Guo-Fan; Jiang, Qin; Yao, Jin

    2012-01-01

    Highlights: ► TNF-α induces MMP-9 expression and secretion to promote RPE cell migration. ► MAPK activation is not critical for TNF-α-induced MMP-9 expression. ► Akt and mTORC1 signaling mediate TNF-α-induced MMP-9 expression. ► SIN1 knockdown showed no significant effect on MMP-9 expression by TNF-α. -- Abstract: Tumor necrosis factor-alpha (TNF-α) promotes in vitro retinal pigment epithelial (RPE) cell migration to initiate proliferative vitreoretinopathy (PVR). Here we report that TNF-α promotes human RPE cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression. Inhibition of MMP-9 by its inhibitor or its neutralizing antibody inhibited TNF-α-induced in vitro RPE cell migration. Reversely, exogenously-added active MMP-9 promoted RPE cell migration. Suppression Akt/mTOR complex 1(mTORC1) activation by LY 294002 and rapamycin inhibited TNF-α-mediated MMP-9 expression. To introduce a constitutively active Akt (CA-Akt) in cultured RPE cells increased MMP-9 expression, and to block mTORC1 activation by rapamycin inhibited its effect. RNA interference (RNAi)-mediated silencing of SIN1, a key component of mTOR complex 2 (mTORC2), had no effect on MMP-9 expression or secretion. In conclusion, this study suggest that TNF-α promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1, but not mTORC2 signaling.

  17. TNF-{alpha} promotes human retinal pigment epithelial (RPE) cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression through activation of Akt/mTORC1 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Cheng-hu; Cao, Guo-Fan [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Jiang, Qin, E-mail: Jqin710@vip.sina.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Yao, Jin, E-mail: dryaojin@yahoo.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China)

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer TNF-{alpha} induces MMP-9 expression and secretion to promote RPE cell migration. Black-Right-Pointing-Pointer MAPK activation is not critical for TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer Akt and mTORC1 signaling mediate TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer SIN1 knockdown showed no significant effect on MMP-9 expression by TNF-{alpha}. -- Abstract: Tumor necrosis factor-alpha (TNF-{alpha}) promotes in vitro retinal pigment epithelial (RPE) cell migration to initiate proliferative vitreoretinopathy (PVR). Here we report that TNF-{alpha} promotes human RPE cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression. Inhibition of MMP-9 by its inhibitor or its neutralizing antibody inhibited TNF-{alpha}-induced in vitro RPE cell migration. Reversely, exogenously-added active MMP-9 promoted RPE cell migration. Suppression Akt/mTOR complex 1(mTORC1) activation by LY 294002 and rapamycin inhibited TNF-{alpha}-mediated MMP-9 expression. To introduce a constitutively active Akt (CA-Akt) in cultured RPE cells increased MMP-9 expression, and to block mTORC1 activation by rapamycin inhibited its effect. RNA interference (RNAi)-mediated silencing of SIN1, a key component of mTOR complex 2 (mTORC2), had no effect on MMP-9 expression or secretion. In conclusion, this study suggest that TNF-{alpha} promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1, but not mTORC2 signaling.

  18. Neutron activation determination of impurities in high-purity bismuth with separation of matrix in form of hydroxide

    International Nuclear Information System (INIS)

    Artyukhin, P.I.; Shavinskij, B.M.; Mityakin, Yu.L.

    1979-01-01

    The technique of neutron activation determination of 15 impurity elements (Au, Ag, Ba, Cd, Co, Cs, Cu, Hg, K, Na, Ni, Se, Sr, Te, Zn) in high-purity bismuth (impurity content is approximately 10 -6 -10 -10 %) is presented. Bismuth hydroxide precipitation by ammonia from nitric acid solutions was used to separate bismuth from alkali, alkaline earth metals and elements forming stable ammines. Gold, selenium and tellurium are isolated in the form of metals at reduction by muriatic hydrazine. Results of analyzing two samples of special purity bismuth are presented. Neutron flux comprised 0.8-1x10 13 n/cm 2 xs. Radiation time was equal to 90 hours

  19. Progesterone receptor membrane component 1 as the mediator of the inhibitory effect of progestins on cytokine-induced matrix metalloproteinase 9 activity in vitro.

    Science.gov (United States)

    Allen, Terrence K; Feng, Liping; Grotegut, Chad A; Murtha, Amy P

    2014-02-01

    Progesterone (P4) and the progestin, 17α-hydroxyprogesterone caproate, are clinically used to prevent preterm births (PTBs); however, their mechanism of action remains unclear. Cytokine-induced matrix metalloproteinase 9 (MMP-9) activity plays a key role in preterm premature rupture of the membranes and PTB. We demonstrated that the primary chorion cells and the HTR8/SVneo cells (cytotrophoblast cell line) do not express the classical progesterone receptor (PGR) but instead a novel progesterone receptor, progesterone receptor membrane component 1 (PGRMC1), whose role remains unclear. Using HTR8/SVneo cells in culture, we further demonstrated that 6 hours pretreatment with medroxyprogesterone acetate (MPA) and dexamethasone (Dex) but not P4 or 17α-hydroxyprogesterone hexanoate significantly attenuated tumor necrosis factor α-induced MMP-9 activity after a 24-hour incubation period. The inhibitory effect of MPA, but not Dex, was attenuated when PGRMC1 expression was successfully reduced by PGRMC1 small interfering RNA. Our findings highlight a possible novel role of PGRMC1 in mediating the effects of MPA and in modulating cytokine-induced MMP-9 activity in cytotrophoblast cells in vitro.

  20. Buddleja officinalis suppresses high glucose-induced vascular smooth muscle cell proliferation: role of mitogen-activated protein kinases, nuclear factor-kappaB and matrix metalloproteinases.

    Science.gov (United States)

    Lee, Yun Jung; Kim, Jin Sook; Kang, Dae Gill; Lee, Ho Sub

    2010-02-01

    Diabetes mellitus is a well-established risk factor for vascular diseases caused by atherosclerosis. In the development of diabetic atherogenesis, vascular smooth muscle cell proliferation is recognized as a key event. Thus, we aimed to investigate whether an ethanol extract of Buddleja officinalis (EBO) suppresses high glucose-induced proliferation in primary cultured human aortic smooth muscle cells (HASMC). [(3)H]-thymidine incorporation revealed that incubation of HASMC with a high concentration of glucose (25 mmol/L) increased cell proliferation. The expression levels of cell cycle protein were also increased by treatment with high glucose concentration. Pretreatment of HASMC with EBO significantly attenuated the increase of high glucose-induced cell proliferation as well as p38 mitogen-activated protein kinases (MAPK) and JNK phosphorylation. EBO suppressed high glucose-induced matrix metalloproteinase (MMP)-9 activity in a dose-dependent manner. In addition, EBO suppressed nuclear factor-kappaB (NF-kappaB) nuclear translocation and transcriptional activity in high glucose conditions. Taken together, the present data suggest that EBO could suppress high glucose-induced atherosclerotic processes through inhibition of p38, JNK, NF-kappaB and MMP signal pathways in HASMC.

  1. Membrane Type 1–Matrix Metalloproteinase/Akt Signaling Axis Modulates TNF-α-Induced Procoagulant Activity and Apoptosis in Endothelial Cells

    Science.gov (United States)

    Ohkawara, Hiroshi; Ishibashi, Toshiyuki; Sugimoto, Koichi; Ikeda, Kazuhiko; Ogawa, Kazuei; Takeishi, Yasuchika

    2014-01-01

    Membrane type 1–matrix metalloproteinase (MT1-MMP) functions as a signaling molecule in addition to a proteolytic enzyme. Our hypothesis was that MT1-MMP cooperates with protein kinase B (Akt) in tumor necrosis factor (TNF)-α-induced signaling pathways of vascular responses, including tissue factor (TF) procoagulant activity and endothelial apoptosis, in cultured human aortic endothelial cells (ECs). TNF-α (10 ng/mL) induced a decrease in Akt phosphorylation within 60 minutes in ECs. A chemical inhibitor of MMP, TIMP-2 and selective small interfering RNA (siRNA)-mediated suppression of MT1-MMP reversed TNF-α-triggered transient decrease of Akt phosphorylation within 60 minutes, suggesting that MT1-MMP may be a key regulator of Akt phosphorylation in TNF-α-stimulated ECs. In the downstream events, TNF-α increased TF antigen and activity, and suppressed the expression of thrombomodulin (TM) antigen. Inhibition of Akt markedly enhanced TNF-α-induced expression of TF antigen and activity, and further reduced the expression of TM antigen. Silencing of MT1-MMP by siRNA also reversed the changed expression of TF and TM induced by TNF-α. Moreover, TNF-α induced apoptosis of ECs through Akt- and forkhead box protein O1 (FoxO1)-dependent signaling pathway and nuclear factor-kB (NF-kB) activation. Knockdown of MT1-MMP by siRNA reversed apoptosis of ECs by inhibiting TNF-α-induced Akt-dependent regulation of FoxO1 in TNF-α-stimulated ECs. Immunoprecipitation demonstrated that TNF-α induced the changes in the associations between the cytoplasmic fraction of MT1-MMP and Akt in ECs. In conclusion, we show new evidence that MT1-MMP/Akt signaling axis is a key modifier for TNF-α-induced signaling pathways for modulation of procoagulant activity and apoptosis of ECs. PMID:25162582

  2. Fisetin regulates TPA-induced breast cell invasion by suppressing matrix metalloproteinase-9 activation via the PKC/ROS/MAPK pathways.

    Science.gov (United States)

    Noh, Eun-Mi; Park, Yeon-Ju; Kim, Jeong-Mi; Kim, Mi-Seong; Kim, Ha-Rim; Song, Hyun-Kyung; Hong, On-Yu; So, Hong-Seob; Yang, Sei-Hoon; Kim, Jong-Suk; Park, Samg Hyun; Youn, Hyun-Jo; You, Yong-Ouk; Choi, Ki-Bang; Kwon, Kang-Beom; Lee, Young-Rae

    2015-10-05

    Invasion and metastasis are among the main causes of death in patients with malignant tumors. Fisetin (3,3',4',7-tetrahydroxyflavone), a natural flavonoid found in the smoke tree (Cotinus coggygria), is known to have antimetastatic effects on prostate and lung cancers; however, the effect of fisetin on breast cancer metastasis is unknown. The aim of this study was to determine the anti-invasive activity of fisetin in human breast cancer cells. Matrix metalloproteinase (MMP)-9 is a major component facilitating the invasion of many cancer tumor cell types, and thus the inhibitory effect of fisetin on MMP-9 expression in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated human breast cancer cells was investigated in this study. Fisetin significantly attenuated TPA-induced cell invasion in MCF-7 human breast cancer cells, and was found to inhibit the activation of the PKCα/ROS/ERK1/2 and p38 MAPK signaling pathways. This effect was furthermore associated with reduced NF-κB activation, suggesting that the anti-invasive effect of fisetin on MCF-7 cells may result from inhibited TPA activation of NF-κB and reduced TPA activation of PKCα/ROS/ERK1/2 and p38 MAPK signals, ultimately leading to the downregulation of MMP-9 expression. Our findings indicate the role of fisetin in MCF-7 cell invasion, and clarify the underlying molecular mechanisms of this role, suggesting fisetin as a potential chemopreventive agent for breast cancer metastasis. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Membrane type 1-matrix metalloproteinase/Akt signaling axis modulates TNF-α-induced procoagulant activity and apoptosis in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Hiroshi Ohkawara

    Full Text Available Membrane type 1-matrix metalloproteinase (MT1-MMP functions as a signaling molecule in addition to a proteolytic enzyme. Our hypothesis was that MT1-MMP cooperates with protein kinase B (Akt in tumor necrosis factor (TNF-α-induced signaling pathways of vascular responses, including tissue factor (TF procoagulant activity and endothelial apoptosis, in cultured human aortic endothelial cells (ECs. TNF-α (10 ng/mL induced a decrease in Akt phosphorylation within 60 minutes in ECs. A chemical inhibitor of MMP, TIMP-2 and selective small interfering RNA (siRNA-mediated suppression of MT1-MMP reversed TNF-α-triggered transient decrease of Akt phosphorylation within 60 minutes, suggesting that MT1-MMP may be a key regulator of Akt phosphorylation in TNF-α-stimulated ECs. In the downstream events, TNF-α increased TF antigen and activity, and suppressed the expression of thrombomodulin (TM antigen. Inhibition of Akt markedly enhanced TNF-α-induced expression of TF antigen and activity, and further reduced the expression of TM antigen. Silencing of MT1-MMP by siRNA also reversed the changed expression of TF and TM induced by TNF-α. Moreover, TNF-α induced apoptosis of ECs through Akt- and forkhead box protein O1 (FoxO1-dependent signaling pathway and nuclear factor-kB (NF-kB activation. Knockdown of MT1-MMP by siRNA reversed apoptosis of ECs by inhibiting TNF-α-induced Akt-dependent regulation of FoxO1 in TNF-α-stimulated ECs. Immunoprecipitation demonstrated that TNF-α induced the changes in the associations between the cytoplasmic fraction of MT1-MMP and Akt in ECs. In conclusion, we show new evidence that MT1-MMP/Akt signaling axis is a key modifier for TNF-α-induced signaling pathways for modulation of procoagulant activity and apoptosis of ECs.

  4. Strong correlation in acene sheets from the active-space variational two-electron reduced density matrix method: effects of symmetry and size.

    Science.gov (United States)

    Pelzer, Kenley; Greenman, Loren; Gidofalvi, Gergely; Mazziotti, David A

    2011-06-09

    Polyaromatic hydrocarbons (PAHs) are a class of organic molecules with importance in several branches of science, including medicine, combustion chemistry, and materials science. The delocalized π-orbital systems in PAHs require highly accurate electronic structure methods to capture strong electron correlation. Treating correlation in PAHs has been challenging because (i) traditional wave function methods for strong correlation have not been applicable since they scale exponentially in the number of strongly correlated orbitals, and (ii) alternative methods such as the density-matrix renormalization group and variational two-electron reduced density matrix (2-RDM) methods have not been applied beyond linear acene chains. In this paper we extend the earlier results from active-space variational 2-RDM theory [Gidofalvi, G.; Mazziotti, D. A. J. Chem. Phys. 2008, 129, 134108] to the more general two-dimensional arrangement of rings--acene sheets--to study the relationship between geometry and electron correlation in PAHs. The acene-sheet calculations, if performed with conventional wave function methods, would require wave function expansions with as many as 1.5 × 10(17) configuration state functions. To measure electron correlation, we employ several RDM-based metrics: (i) natural-orbital occupation numbers, (ii) the 1-RDM von Neumann entropy, (iii) the correlation energy per carbon atom, and (iv) the squared Frobenius norm of the cumulant 2-RDM. The results confirm a trend of increasing polyradical character with increasing molecular size previously observed in linear PAHs and reveal a corresponding trend in two-dimensional (arch-shaped) PAHs. Furthermore, in PAHs of similar size they show significant variations in correlation with geometry. PAHs with the strictly linear geometry (chains) exhibit more electron correlation than PAHs with nonlinear geometries (sheets).

  5. Mixed-matrix membranes with enhanced antifouling activity: probing the surface-tailoring potential of Tiron and chromotropic acid for nano-TiO2.

    Science.gov (United States)

    Pal, Avishek; Dey, T K; Debnath, A K; Bhushan, Bharat; Sahu, A K; Bindal, R C; Kar, Soumitra

    2017-09-01

    Mixed-matrix membranes (MMMs) were developed by impregnating organofunctionalized nanoadditives within fouling-susceptible polysulfone matrix following the non-solvent induced phase separation (NIPS) method. The facile functionalization of nanoparticles of anatase TiO 2 (nano-TiO 2 ) by using two different organoligands, viz . Tiron and chromotropic acid, was carried out to obtain organofunctionalized nanoadditives, F T -nano-TiO 2 and F C -nano-TiO 2 , respectively. The structural features of nanoadditives were evaluated by X-ray diffraction, X-ray photoelectron spectroscopy, Raman and Fourier transform infrared spectroscopy, which established that Tiron leads to the blending of chelating and bridging bidentate geometries for F T -nano-TiO 2 , whereas chromotropic acid produces bridging bidentate as well as monodentate geometries for F C -nano-TiO 2 . The surface chemistry of the studied membranes, polysulfone (Psf): F T -nano-TiO 2 UF and Psf: F C -nano-TiO 2 UF, was profoundly influenced by the benign distributions of the nanoadditives enriched with distinctly charged sites ([Formula: see text]), as evidenced by superior morphology, improved topography, enhanced surface hydrophilicity and altered electrokinetic features. The membranes exhibited enhanced solvent throughputs, viz . 3500-4000 and 3400-4300 LMD at 1 bar of transmembrane pressure, without significant compromise in their rejection attributes. The flux recovery ratios and fouling resistive behaviours of MMMs towards bovine serum albumin indicated that the nanoadditives could impart stable and appreciable antifouling activity, potentially aiding in a sustainable ultrafiltration performance.

  6. Fragility Fracture Incidence in Chronic Obstructive Pulmonary Disease (COPD) Patients Associates With Nanoporosity, Mineral/Matrix Ratio, and Pyridinoline Content at Actively Bone-Forming Trabecular Surfaces.

    Science.gov (United States)

    Paschalis, Eleftherios P; Gamsjaeger, Sonja; Dempster, David; Jorgetti, Vanda; Borba, Victoria; Boguszewski, Cesar L; Klaushofer, Klaus; Moreira, Carolina A

    2017-01-01

    Chronic obstructive pulmonary disease (COPD) is associated with low areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) and altered microstructure by bone histomorphometry and micro-computed tomography. Nevertheless, not all COPD patients sustain fragility fractures. In the present study, we used Raman microspectroscopic analysis to determine bone compositional properties at actively forming trabecular surfaces (based on double fluorescent labels) in iliac crest biopsies from 19 postmenopausal COPD patients (aged 62.1 ± 7.3 years). Additionally, we analyzed trabecular geometrical centers, representing tissue much older than the forming surfaces. Eight of the patients had sustained fragility fractures, and 13 had received treatment with inhaled glucocorticoids. None of the patients had taken oral glucocorticoids. The monitored parameters were mineral/matrix ratio (MM), nanoporosity, and relative glycosaminoglycan (GAG), lipid, and pyridinoline contents (PYD). There were no significant differences between the glucocorticoid-treated patients and those who did not receive any. On the other hand, COPD patients sustaining fragility fractures had significantly lower nanoporosity and higher MM and PYD values compared with COPD patients without fragility fractures. To the best of our knowledge, this is the first study to discriminate between fracture and non-fracture COPD patients based on differences in the material properties of bone matrix. Given that these bone material compositional differences are evident close to the cement line (a major bone interface), they may contribute to the inferior bone toughness and coupled with the lower lumbar spine bone mineral density values result in the fragility fractures prevalent in these patients. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

  7. Determination of Methylmercury Traces in Biological Matrix: Chemical Extraction and Nuclear Quantification with the Neutron Activation Analysis Technique

    International Nuclear Information System (INIS)

    Soldati, A.L.

    2002-01-01

    Mercury is present in the environment as a result of the human and natural activities.The total amount of Hg present in the biosphere has been incremented three times since the industrial era, and now it is affecting in a global sense all the ecosystem.One of the main entrance of Hg in the human diet is the consumption of fish and other marine creatures.Most of the ingested Hg is mono methylmercury (MeHg), which is one of the most toxic forms in which this element could be found because it crosses membranes.Since the toxicity levels are low, the determination of concentrations of total Hg and Me Hg require very careful sampling, sample conditioning and analytical procedures to prevent either losses or contamination, or the degradation of the Hg species.In this work, we implemented a chemical Me Hg extraction procedure, using a ionic exchange resin, with three different types of fish tissue: muscle, liver and hepato pancreas.After Me Hg extraction, the determination and quantification was made by Instrumental Neutron Activation Analysis, by measuring the 197 Au, y el 203 Tl deexcitation s, created through the radioactive decay of the isotopes 197 Hg y 203 Hg.The influence of several parameters on the overall extraction process, such as velocity of passage through the ionic exchange column and the acid concentration used in the extraction was evaluated.Regarding the INAA determinations, a choice was made for the irradiation, decay and counting times, neutron and gamma doses, and the counting geometry The detection limit found for this technique (dry weight) is 140 pg MeHg/g. The Hg contents of the muscle samples were measured with the 279 keV emission of the product of the 202 Hg(n,g) 203 Hg reaction, with a recovery of (100 ± 13)%. Liver and Hepato pancreas samples were measured with the 77 keV gamma emission of the 197 Hg, checking this result with the 67 y 69 keV X emissions from the same isotope.The liver samples needed an extra vacuum filtering process during

  8. Bio-inspired crosslinking and matrix-drug interactions for advanced wound dressings with long-term antimicrobial activity.

    Science.gov (United States)

    Dhand, Chetna; Venkatesh, Mayandi; Barathi, Veluchami Amutha; Harini, Sriram; Bairagi, Samiran; Goh Tze Leng, Eunice; Muruganandham, Nandhakumar; Low, Kenny Zhi Wei; Fazil, Mobashar Hussain Urf Turabe; Loh, Xian Jun; Srinivasan, Dinesh Kumar; Liu, Shou Ping; Beuerman, Roger W; Verma, Navin Kumar; Ramakrishna, Seeram; Lakshminarayanan, Rajamani

    2017-09-01

    There is a growing demand for durable advanced wound dressings for the management of persistent infections after deep burn injuries. Herein, we demonstrated the preparation of durable antimicrobial nanofiber mats, by taking advantage of strong interfacial interactions between polyhydroxy antibiotics (with varying number of OH groups) and gelatin and their in-situ crosslinking with polydopamine (pDA) using ammonium carbonate diffusion method. Polydopamine crosslinking did not interfere with the antimicrobial efficacy of the loaded antibiotics. Interestingly, incorporation of antibiotics containing more number of alcoholic OH groups (N OH  ≥ 5) delayed the release kinetics with complete retention of antimicrobial activity for an extended period of time (20 days). The antimicrobials-loaded mats displayed superior mechanical and thermal properties than gelatin or pDA-crosslinked gelatin mats. Mats containing polyhydroxy antifungals showed enhanced aqueous stability and retained nanofibrous morphology under aqueous environment for more than 4 weeks. This approach can be expanded to produce mats with broad spectrum antimicrobial properties by incorporating the combination of antibacterial and antifungal drugs. Direct electrospinning of vancomycin-loaded electrospun nanofibers onto a bandage gauze and subsequent crosslinking produced non-adherent durable advanced wound dressings that could be easily applied to the injured sites and readily detached after treatment. In a partial thickness burn injury model in piglets, the drug-loaded mats displayed comparable wound closure to commercially available silver-based dressings. This prototype wound dressing designed for easy handling and with long-lasting antimicrobial properties represents an effective option for treating life-threatening microbial infections due to thermal injuries. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Evaluation of synthase and hemisynthase activities of glucosamine-6-phosphate synthase by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

    Science.gov (United States)

    Gaucher-Wieczorek, Florence; Guérineau, Vincent; Touboul, David; Thétiot-Laurent, Sophie; Pelissier, Franck; Badet-Denisot, Marie-Ange; Badet, Bernard; Durand, Philippe

    2014-08-01

    Glucosamine-6-phosphate synthase (GlmS, EC 2.6.1.16) catalyzes the first and rate-limiting step in the hexosamine biosynthetic pathway, leading to the synthesis of uridine-5'-diphospho-N-acetyl-D-glucosamine, the major building block for the edification of peptidoglycan in bacteria, chitin in fungi, and glycoproteins in mammals. This bisubstrate enzyme converts D-fructose-6-phosphate (Fru-6P) and L-glutamine (Gln) into D-glucosamine-6-phosphate (GlcN-6P) and L-glutamate (Glu), respectively. We previously demonstrated that matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) allows determination of the kinetic parameters of the synthase activity. We propose here to refine the experimental protocol to quantify Glu and GlcN-6P, allowing determination of both hemisynthase and synthase parameters from a single assay kinetic experiment, while avoiding interferences encountered in other assays. It is the first time that MALDI-MS is used to survey the activity of a bisubstrate enzyme. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Activity-dependent shedding of the NMDA receptor glycine binding site by matrix metalloproteinase 3: a PUTATIVE mechanism of postsynaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Thorsten Pauly

    Full Text Available Functional and structural alterations of clustered postsynaptic ligand gated ion channels in neuronal cells are thought to contribute to synaptic plasticity and memory formation in the human brain. Here, we describe a novel molecular mechanism for structural alterations of NR1 subunits of the NMDA receptor. In cultured rat spinal cord neurons, chronic NMDA receptor stimulation induces disappearance of extracellular epitopes of NMDA receptor NR1 subunits, which was prevented by inhibiting matrix metalloproteinases (MMPs. Immunoblotting revealed the digestion of solubilized NR1 subunits by MMP-3 and identified a fragment of about 60 kDa as MMPs-activity-dependent cleavage product of the NR1 subunit in cultured neurons. The expression of MMP-3 in the spinal cord culture was shown by immunoblotting and immunofluorescence microscopy. Recombinant NR1 glycine binding protein was used to identify MMP-3 cleavage sites within the extracellular S1 and S2-domains. N-terminal sequencing and site-directed mutagenesis revealed S542 and L790 as two putative major MMP-3 cleavage sites of the NR1 subunit. In conclusion, our data indicate that MMPs, and in particular MMP-3, are involved in the activity dependent alteration of NMDA receptor structure at postsynaptic membrane specializations in the CNS.

  11. Activity-dependent shedding of the NMDA receptor glycine binding site by matrix metalloproteinase 3: a PUTATIVE mechanism of postsynaptic plasticity.

    Science.gov (United States)

    Pauly, Thorsten; Ratliff, Miriam; Pietrowski, Eweline; Neugebauer, Rainer; Schlicksupp, Andrea; Kirsch, Joachim; Kuhse, Jochen

    2008-07-16

    Functional and structural alterations of clustered postsynaptic ligand gated ion channels in neuronal cells are thought to contribute to synaptic plasticity and memory formation in the human brain. Here, we describe a novel molecular mechanism for structural alterations of NR1 subunits of the NMDA receptor. In cultured rat spinal cord neurons, chronic NMDA receptor stimulation induces disappearance of extracellular epitopes of NMDA receptor NR1 subunits, which was prevented by inhibiting matrix metalloproteinases (MMPs). Immunoblotting revealed the digestion of solubilized NR1 subunits by MMP-3 and identified a fragment of about 60 kDa as MMPs-activity-dependent cleavage product of the NR1 subunit in cultured neurons. The expression of MMP-3 in the spinal cord culture was shown by immunoblotting and immunofluorescence microscopy. Recombinant NR1 glycine binding protein was used to identify MMP-3 cleavage sites within the extracellular S1 and S2-domains. N-terminal sequencing and site-directed mutagenesis revealed S542 and L790 as two putative major MMP-3 cleavage sites of the NR1 subunit. In conclusion, our data indicate that MMPs, and in particular MMP-3, are involved in the activity dependent alteration of NMDA receptor structure at postsynaptic membrane specializations in the CNS.

  12. Fisetin Ameliorated Photodamage by Suppressing the Mitogen-Activated Protein Kinase/Matrix Metalloproteinase Pathway and Nuclear Factor-κB Pathways.

    Science.gov (United States)

    Chiang, Hsiu-Mei; Chan, Shih-Yun; Chu, Yin; Wen, Kuo-Ching

    2015-05-13

    Ultraviolet (UV) irradiation is one of the most important extrinsic factors contributing to skin photodamage. After UV irradiation, a series of signal transductions in the skin will be activated, leading to inflammatory response and photoaged skin. In this study, fisetin, a flavonol that exists in fruits and vegetables, was investigated for its photoprotective effects. The results revealed that 5-25 μM fisetin inhibits cyclooxygenase-2 (COX-2) and matrix metalloproteinase (MMP)-1, MMP-3, MMP-9 expression induced by ultraviolet B (UVB) irradiation in human skin fibroblasts. In addition, fisetin suppressed UVB-induced collagen degradation. With regard to its effect on upper-stream signal transduction, we found that fisetin reduced the expression of ultraviolet (UV)-induced ERK, JNK, and p38 phosphorylation in the mitogen-activated protein kinase (MAP kinase) pathway. Furthermore, fisetin reduced inhibitor κB (IκB) degradation and increased the amount of p65, which is a major subunit of nuclear factor-κB (NF-κB), in cytoplasm. It also suppressed NF-κB translocated to the nucleus and inhibited cAMP response element-binding protein (CREB) Ser-133 phosphorylation level in the phosphoinositide 3-kinase/protein kinase B/CREB (PI3K/AKT/CREB) pathway. Finally, fisetin inhibited UV-induced intracellular reactive oxygen species (ROS), prostaglandin E2 (PGE2), and nitric oxide (NO) generation. The mentioned effects and mechanisms suggest that fisetin can be used in the development of photoprotective agents.

  13. Influence of polymer matrix and adsorption onto silica materials on the migration of alpha-tocopherol into 95% ethanol from active packaging.

    Science.gov (United States)

    Heirlings, L; Siró, I; Devlieghere, F; Van Bavel, E; Cool, P; De Meulenaer, B; Vansant, E F; Debevere, J

    2004-11-01

    In this study, the effect of polymer materials with different polarity, namely low density polyethylene (LDPE) and ethylene vinyl acetate (EVA), on the migration behaviour of alpha-tocopherol from active packaging was investigated. The antioxidant was also adsorbed onto silica materials, namely SBA-15 (Santa Barbara-15) and Syloblock, in order to protect the antioxidant during extrusion and to ensure a controlled and sufficient release during the shelf-life of the food product. Migration experiments were performed at 7.0 +/- 0.5 degrees C and 95% ethanol was used as fatty food simulant. All films contained a high concentration of alpha-tocopherol, approximately 2000 mg kg(-1), to obtain an active packaging. Polymer matrix had a small influence on the migration profile. The migration of 80% of total migrated amount of antioxidant was retarded for 2.4 days by using LDPE instead of EVA. When alpha-tocopherol was adsorbed onto both silica materials, the migration of 80% of total migrated amount of antioxidant was retarded for 3.4 days in comparison to pure alpha-tocopherol. No difference was seen between the migration profiles of alpha-tocopherol adsorbed onto both silica materials. In the case of pure alpha-tocopherol, 82% of the initial amount of alpha-tocopherol in the film migrated into the food simulant at a rather fast migration rate. In the case of adsorption on silica materials, a total migration was observed. These antioxidative films can have positive food applications.

  14. New bio-active, antimicrobial and adherent coatings of nanostructured carbon double-reinforced with silver and silicon by Matrix-Assisted Pulsed Laser Evaporation for medical applications

    Science.gov (United States)

    Duta, L.; Ristoscu, C.; Stan, G. E.; Husanu, M. A.; Besleaga, C.; Chifiriuc, M. C.; Lazar, V.; Bleotu, C.; Miculescu, F.; Mihailescu, N.; Axente, E.; Badiceanu, M.; Bociaga, D.; Mihailescu, Ion N.

    2018-05-01

    We report on Matrix-Assisted Pulsed Laser Evaporation (MAPLE) deposition of Carbon thin films, simple or reinforced with intended concentrations of Ag and Si. A KrF∗ (λ = 248 nm, τFWHM ≤ 25 ns, ν = 10 Hz) excimer laser was used for irradiation. The effect of a post-deposition thermal treatment in vacuum was studied. Besides detailed morphological, compositional, structural and pull-out adherence characterizations, the potential of the carbonaceous films for medical applications was investigated in vitro by anti-biofilm and cytocompatibility assays. The microscopic images evidenced no delaminations. Micro-Raman spectroscopy revealed a graphitization tendency depending on preparation conditions, thermal treatment and reinforcing agents' presence. Adherence values improved considerably after thermal treatment. In vitro biological evaluation showed that the films containing ∼1.85 at.% Ag were non-cytotoxic for MG63 cells, while eliciting a limited antimicrobial activity. The increase of Ag content to 3.6 at.% results in a significant enhancement of antimicrobial activity, whilst maintaining the cytotoxic action and adherence characteristics at acceptable levels. We propose a new class of metamaterials based on C reinforced with Ag and Si obtained by MAPLE for medical applications, i.e. the prevention and treatment of various infections associated with biofilms developed on implants and other medical equipments.

  15. Endothelial-monocyte activating polypeptide II alters fibronectin based endothelial cell adhesion and matrix assembly via alpha5 beta1 integrin

    International Nuclear Information System (INIS)

    Schwarz, Margaret A.; Zheng, Hiahua; Liu, Jie; Corbett, Siobhan; Schwarz, Roderich E.

    2005-01-01

    Mature Endothelial-Monocyte Activating Polypeptide (mEMAP) II functions as a potent antiangiogenic peptide. Although the anti-tumor effect of mEMAP II has been described, little is known regarding its mechanism of action. Observations that mEMAP II induced apoptosis only in a subset of migrating and proliferating endothelial cells (EC) suggests a targeted effect on cells engaged in angiogenic activities which are known to rely upon cell adhesion and migration. Indeed, we demonstrate that mEMAP II inhibited fibronectin (FN) dependent microvascular EC (MEC) adhesion and spreading and we show that this depends upon the alpha5 beta1 integrin. Immunofluorescence analysis demonstrated that mEMAP II-dependent blockade of FN-alpha5 beta1 interactions was associated with disassembly of both actin stress fiber networks and FN matrix. These findings suggest that mEMAP II blocks MEC adhesion and spreading on fibronectin, via a direct interaction with the integrin alpha5 beta1, thus implicating that alpha5 integrin may be a mediator of mEMAP II's antiangiogenic function

  16. Platelet-derived growth factor-D modulates extracellular matrix homeostasis and remodeling through TIMP-1 induction and attenuation of MMP-2 and MMP-9 gelatinase activities

    International Nuclear Information System (INIS)

    Borkham-Kamphorst, Erawan; Alexi, Pascal; Tihaa, Lidia; Haas, Ute; Weiskirchen, Ralf

    2015-01-01

    Platelet-derived growth factor-D (PDGF-D) is a more recent recognized growth factor involved in the regulation of several cellular processes, including cell proliferation, transformation, invasion, and angiogenesis by binding to and activating its cognate receptor PDGFR-β. After bile duct ligation or in the carbon tetrachloride-induced hepatic fibrosis model , PDGF-D showed upregulation comparable to PDGF-B. Moreover, adenoviral PDGF-D gene transfer induced hepatic stellate cell proliferation and liver fibrosis. We here investigated the molecular mechanism of PDGF-D involvement in liver fibrogenesis. Therefore, the GRX mouse cell line was stimulated with PDGF-D and evaluated for fibrotic markers and PDGF-D signaling pathways in comparison to the other PDGF isoforms. We found that PDGF-D failed to enhance Col I and α-smooth muscle actin (α-SMA) production but has capacity to upregulate expression of the tissue inhibitor of metalloprotease 1 (TIMP-1) resulting in attenuation of MMP-2 and MMP-9 gelatinase activity as indicated by gelatinase zymography. This phenomenon was restored through application of a PDGF-D neutralizing antibody. Unexpectedly, PDGF-D incubation decreased both PDGFR-α and -β in mRNA and protein levels, and PDGF-D phosphorylated typrosines specific for PDGFR-α and -β. We conclude that PDGF-D intensifies fibrogenesis by interfering with the fibrolytic activity of the TIMP-1/MMP system and that PDGF-D signaling is mediated through both PDGF-α and -β receptors. - Highlights: • PDGF-D signals through PDGF receptor type α and β. • PDGF-D modulates extracellular matrix homeostasis and remodeling. • Like PDGF-B, PDGF-D triggers phosphorylation of PLC-γ, Akt/PKB, JNK, ERK1/2, and p38. • PDGF-D induces TIMP-1 expression through ERK and p38 MAPK. • PDGF-D attenuates MMP-2 and MMP-9 gelatinase activities

  17. Matrix Metalloproteinase-2 Activity is Associated with Divergent Regulation of Calponin-1 in Conductance and Resistance Arteries in Hypertension-induced Early Vascular Dysfunction and Remodelling.

    Science.gov (United States)

    Parente, Juliana M; Pereira, Camila A; Oliveira-Paula, Gustavo H; Tanus-Santos, José E; Tostes, Rita C; Castro, Michele M

    2017-10-01

    Matrix metalloproteinase (MMP)-2 participates in hypertension-induced maladaptive vascular remodelling by degrading extra- and intracellular proteins. The consequent extracellular matrix rearrangement and phenotype switch of vascular smooth muscle cells (VSMCs) lead to increased cellular migration and proliferation. As calponin-1 degradation by MMP-2 may lead to VSMC proliferation during hypertension, the hypothesis of this study is that increased MMP-2 activity contributes to early hypertension-induced maladaptive remodelling in conductance and resistance arteries via regulation of calponin-1. The main objective was to analyse whether MMP-2 exerts similar effects on the structure and function of the resistance and conductance arteries during early hypertension. Two-kidney, one-clip (2K-1C) hypertensive male rats and corresponding controls were treated with doxycycline (30 mg/kg/day) or water until reaching one week of hypertension. Systolic blood pressure was increased in 2K-1C rats, and doxycycline did not reduce it. Aortas and mesenteric arteries were analysed. MMP-2 activity and expression were increased in both arteries, and doxycycline reduced it. Significant hypertrophic remodelling and VSMC proliferation were observed in aortas but not in mesenteric arteries of 2K-1C rats. The contractility of mesenteric arteries to phenylephrine was increased in 2K-1C rats, and doxycycline prevented this alteration. The potency of phenylephrine to contract aortas of 2K-1C rats was increased, and doxycycline decreased it. Whereas calponin-1 expression was increased in 2K-1C mesenteric arteries, calponin-1 was reduced in aortas. Doxycycline treatment reverted changes in calponin-1 expression. MMP-2 contributes to hypertrophic remodelling in aortas by decreasing calponin-1 levels, which may result in VSMC proliferation. On the other hand, MMP-2-dependent increased calponin-1 in mesenteric arteries may contribute to vascular hypercontractility in 2K-1C rats. Divergent

  18. The study of electromagnetic wave propagation in photonic crystals via planewave based transfer (scattering) matrix method with active gain material applications

    Science.gov (United States)

    Li, Ming

    In this dissertation, a set of numerical simulation tools are developed under previous work to efficiently and accurately study one-dimensional (1D), two-dimensional (2D), 2D slab and three-dimensional (3D) photonic crystal structures and their defects effects by means of spectrum (transmission, reflection, absorption), band structure (dispersion relation), and electric and/or magnetic fields distribution (mode profiles). Further more, the lasing property and spontaneous emission behaviors are studied when active gain materials are presented in the photonic crystal structures. First, the planewave based transfer (scattering) matrix method (TMM) is described in every detail along with a brief review of photonic crystal history (Chapter 1 and 2). As a frequency domain method, TMM has the following major advantages over other numerical methods: (1) the planewave basis makes Maxwell's Equations a linear algebra problem and there are mature numerical package to solve linear algebra problem such as Lapack and Scalapack (for parallel computation). (2) Transfer (scattering) matrix method make 3D problem into 2D slices and link all slices together via the scattering matrix (S matrix) which reduces computation time and memory usage dramatically and makes 3D real photonic crystal devices design possible; and this also makes the simulated domain no length limitation along the propagation direction (ideal for waveguide simulation). (3) It is a frequency domain method and calculation results are all for steady state, without the influences of finite time span convolution effects and/or transient effects. (4) TMM can treat dispersive material (such as metal at visible light) naturally without introducing any additional computation; and meanwhile TMM can also deal with anisotropic material and magnetic material (such as perfectly matched layer) naturally from its algorithms. (5) Extension of TMM to deal with active gain material can be done through an iteration procedure with gain

  19. Inhibitory effect of Daesungki-Tang on the invasiveness potential of hepatocellular carcinoma through inhibition of matrix metalloproteinase-2 and -9 activities

    International Nuclear Information System (INIS)

    Ha, Ki-Tae; Kim, June-Ki; Lee, Young-Choon; Kim, Cheorl-Ho

    2004-01-01

    Daesungki-Tang (DST), a drug preparation consisting of four herbs, that is, Rhei radix et rhizoma (RR; the roots of Rheum coreanum Nakai, Daehwang in Korean), Aurantiii frutus immaturus (AFI; immature fruits of Poncirus trifolita Rafin., Jisil in Korean), Magnoliae cortex (MC; the stem bark of Magnolia officinalis Rehd. Et Wils., Hubak in Korean), and Mirabilite (MS; Matrii sulfas, Mangcho in Korean), is a traditional Korean herbal medicine that is widely used in the treatment of cancer metastasis, gastrointestinal complaints, vascular disorders, and atherosclerosis-related disorders. In this study, water extracts of DST and each of the four ingredient herbs were prepared. The extracts were tested for cytotoxic activity on human hepatocellular carcinoma cells, Hep3B cells using the XTT assay method. The inhibitory effect of the extracts on the invasion of Hep3B cells was also tested using matrigel precoated transwell chambers. DST effectively inhibited the invasion of Hep3B cells, compared with the control groups in a dose-dependent manner. In addition, a gelatin zymography assay showed that DST decreased the gelatinolytic activity of matrix metalloproteinases-2 (MMP-2; IC 50 = 87 μg/ml) and -9 (MMP-9; IC 50 = 75 μg/ml) that are secreted from Hep3B cells, respectively. Among the four herbal ingredients of DST, only MC has been shown to significantly inhibit the invasion of Hep3B cells and MMP-2 and -9 activities. From these results, it can be concluded that DST has some potential for use as an antitumor agent

  20. Ubiquitin-specific peptidase 22 inhibits colon cancer cell invasion by suppressing the signal transducer and activator of transcription 3/matrix metalloproteinase 9 pathway.

    Science.gov (United States)

    Ao, Ning; Liu, Yanyan; Bian, Xiaocui; Feng, Hailiang; Liu, Yuqin

    2015-08-01

    Colon cancer is associated with increased cell migration and invasion. In the present study, the role of ubiquitin-specific peptidase 22 (USP22) in signal transducer and activator of transcription 3 (STAT3)-mediated colon cancer cell invasion was investigated. The messenger RNA levels of STAT3 target genes were measured by reverse transcription-quantitative polymerase chain reaction, following USP22 knockdown by RNA interference in SW480 colon cancer cells. The matrix metalloproteinase 9 (MMP9) proteolytic activity and invasion potential of SW480 cells were measured by zymography and Transwell assay, respectively, following combined USP22 and STAT3 short interfering (si)RNA treatment or STAT3 siRNA treatment alone. Similarly, a cell counting kit-8 assay was used to detect the proliferation potential of SW480 cells. The protein expression levels of USP22, STAT3 and MMP9 were detected by immunohistochemistry in colon cancer tissue microarrays (TMAs) and the correlation between USP22, STAT3 and MMP9 was analyzed. USP22/STAT3 co-depletion partly rescued the MMP9 proteolytic activity and invasion of SW480 cells, compared with that of STAT3 depletion alone. However, the proliferation of USP22/STAT3si-SW480 cells was decreased compared with that of STAT3si-SW480 cells. USP22 expression was positively correlated with STAT3 and MMP9 expression in colon cancer TMAs. In conclusion, USP22 attenuated the invasion capacity of colon cancer cells by inhibiting the STAT3/MMP9 signaling pathway.

  1. Extracellular matrix glycation and receptor for advanced glycation end-products activation: a missing piece in the puzzle of the association between diabetes and cancer.

    Science.gov (United States)

    Rojas, Armando; Añazco, Carolina; González, Ileana; Araya, Paulina

    2018-04-05

    A growing body of epidemiologic evidence suggests that people with diabetes are at a significantly higher risk of many forms of cancer. However, the molecular mechanisms underlying this association are not fully understood. Cancer cells are surrounded by a complex milieu, also known as tumor microenvironment, which contributes to the development and metastasis of tumors. Of note, one of the major components of this niche is the extracellular matrix (ECM), which becomes highly disorganized during neoplastic progression, thereby stimulating cancer cell transformation, growth and spread. One of the consequences of chronic hyperglycemia, the most frequently observed sign of diabetes and the etiological source of diabetes complications, is the irreversible glycation and oxidation of proteins and lipids leading to the formation of the advanced glycation end-products (AGEs). These compounds may covalently crosslink and biochemically modify structure and functions of many proteins, and AGEs accumulation is particularly high in long-living proteins with low biological turnover, features that are shared by most, if not all, ECM proteins. AGEs-modified proteins are recognized by AGE-binding proteins, and thus glycated ECM components have the potential to trigger Receptor for advanced glycation end-products-dependent mechanisms. The biological consequence of receptor for advanced glycation end-products activation mechanisms seems to be connected, in different ways, to drive some hallmarks of cancer onset and tumor growth. The present review intends to highlight the potential impact of ECM glycation on tumor progression by triggering receptor for advanced glycation end-products-mediated mechanisms.

  2. Development and Characterization of Defect-Free Matrimid® Mixed-Matrix Membranes Containing Activated Carbon Particles for Gas Separation

    Directory of Open Access Journals (Sweden)

    Fynn Weigelt

    2018-01-01

    Full Text Available In this work, mixed-matrix membranes (MMMs for gas separation in the form of thick films were prepared via the combination of the polymer Matrimid® 5218 and activated carbons (AC. The AC particles had a mean particle size of 1.5 μm and a mean pore diameter of 1.9 nm. The films were prepared by slow solvent evaporation from casting solutions in chloroform, which had a varying polymer–AC ratio. It was possible to produce stable films with up to a content of 50 vol % of AC. Thorough characterization experiments were accomplished via differential scanning calorimetry and thermogravimetric analysis, while the morphology of the MMMs was also investigated via scanning electron microscopy. The gas transport properties were revealed by employing time-lag measurements for different pure gases as well as sorption balance experiments for the filler particles. It was found that defect free Matrimid® MMMs with AC were prepared and the increase of the filler content led to a higher effective permeability for different gases. The single gas selectivity αij of different gas pairs maintained stable values with the increase of AC content, regardless of the steep increase in the effective permeability of the pure gases. Estimation of the solubilities and the diffusivities of the Matrimid®, AC, and MMMs allowed for the explanation of the increasing permeabilities of the MMMs, with the increase of AC content by modelling.

  3. Interrelations between blood-brain barrier permeability and matrix metalloproteinases are differently affected by tissue plasminogen activator and hyperoxia in a rat model of embolic stroke

    Directory of Open Access Journals (Sweden)

    Michalski Dominik

    2012-01-01

    Full Text Available Abstract Background In ischemic stroke, blood-brain barrier (BBB regulations, typically involving matrix metalloproteinases (MMPs and inhibitors (TIMPs as mediators, became interesting since tissue plasminogen activator (tPA-related BBB breakdown with risk of secondary hemorrhage was considered to involve these mediators too. Despite high clinical relevance, detailed interactions are purely understood. After a pilot study addressing hyperoxia as potential neuroprotective co-treatment to tPA, we analyzed interrelations between BBB permeability (BBB-P, MMPs and TIMPs. Findings Rats underwent embolic middle cerebral artery occlusion (eMCAO and treatment with normobaric (NBO or hyperbaric oxygen (HBO, tPA, tPA+HBO, or no treatment. BBB-P was assessed by intravenously applied FITC-albumin at 4 or 24 hours. MMP-2/-9 and TIMP-1/-2 serum levels were determined at 5 or 25 hours. Time point-corrected partial correlations were used to explore interrelations of BBB-P in ischemic regions (extra-/intravasal FITC-albumin ratio and related serum markers. BBB-P correlated positively with MMP-2 and MMP-9 in controls, whereas hyperoxia led to an inverse association, most pronounced for HBO/MMP-9 (r = -0.606; P Conclusions HBO was found to reverse the positively directed interrelation of BBB-P and MMPs after eMCAO, but this effect failed to sustain in the expected amount when HBO and tPA were given simultaneously.

  4. A Novel LTPS-TFT Pixel Circuit to Compensate the Electronic Degradation for Active-Matrix Organic Light-Emitting Diode Displays

    Directory of Open Access Journals (Sweden)

    Ching-Lin Fan

    2013-01-01

    Full Text Available A novel pixel driving circuit for active-matrix organic light-emitting diode (AMOLED displays with low-temperature polycrystalline-silicon thin-film transistors (LTPS-TFTs is studied. The proposed compensation pixel circuit is driven by voltage programming scheme, which is composed of five TFTs and one capacitor, and has been certified to provide uniform output current by the Automatic Integrated Circuit Modeling Simulation Program with Integrated Circuit Emphasis (AIM-SPICE simulator. The results of simulation show excellent performance, such as the low average error rate of OLED current variation (<0.5% and the low average nonuniformity of OLED current variation (<0.8% while the shift of threshold voltage of the driving poly-Si TFT and the OLED are both in the worst case ( V for TFT and  V for OLED. The proposed pixel circuit shows high immunity to the threshold voltage deviation of both the driving poly-Si TFT and the OLED.

  5. Membrane-Type 1 Matrix Metal loproteinase Is Regulated by Sp1 through the Differential Activation of AKT, JNK, and ERK Pathways in Human Prostate Tumor Cells

    Directory of Open Access Journals (Sweden)

    Isis C. Sroka

    2007-05-01

    Full Text Available We and other investigators have previously shown that membrane-type 1 matrix metalloproteinase (MT1-MMP is overexpressed in invasive prostate cancer cells. However, the mechanism for this expression is not known. Here, we show that MT1-MMP is minimally expressed in nonmalignant primary prostate cells, moderately expressed in DU-145 cells, and highly expressed in invasive PC-3 and PC-3N cells. Using human MT1-MMP promoter reporter plasmids and mobility shift assays, we show that Spi regulates MT1-MMP expression in DU-145, PC-3, and PC-3N cells and in PC3-N cells using chromatin immunoprecipitation analysis and silencing RNA. Investigation of signaling pathway showed that DU-145 cells express constitutively phosphorylated extracellular stress-regulated kinase (ERK, whereas PC-3 and PC-3N cells express constitutively phosphorylated AKT/PKB and c-Jun NH2 terminal kinase (JNK. We show that MT1-MMP and Spi levels are decreased in PC-3 and PC-3N cells when phosphatidylinositol-3 kinase and JNK are inhibited, and that MT1-MMP levels are decreased in DU-145 cells when MEK is inhibited. Transient transfection of PC-3 and PC-3N cells with a dominant-negative JNK or p85, and of DU-145 cells with a dominant negative ERK, reduces MT1-MMP promoter activity. These results indicate differential signaling control of Spi-mediated transcriptional regulation of MT1-MMP in prostate cancer cell lines.

  6. Heterogeneous adsorption behavior of landfill leachate on granular activated carbon revealed by fluorescence excitation emission matrix (EEM)-parallel factor analysis (PARAFAC).

    Science.gov (United States)

    Lee, Sonmin; Hur, Jin

    2016-04-01

    Heterogeneous adsorption behavior of landfill leachate on granular activated carbon (GAC) was investigated by fluorescence excitation-emission matrix (EEM) combined with parallel factor analysis (PARAFAC). The equilibrium adsorption of two leachates on GAC was well described by simple Langmuir and Freundlich isotherm models. More nonlinear isotherm and a slower adsorption rate were found for the leachate with the higher values of specific UV absorbance and humification index, suggesting that the leachate containing more aromatic content and condensed structures might have less accessible sites of GAC surface and a lower degree of diffusive adsorption. Such differences in the adsorption behavior were found even within the bulk leachate as revealed by the dissimilarity in the isotherm and kinetic model parameters between two identified PARAFAC components. For both leachates, terrestrial humic-like fluorescence (C1) component, which is likely associated with relatively large sized and condensed aromatic structures, exhibited a higher isotherm nonlinearity and a slower kinetic rate for GAC adsorption than microbial humic-like (C2) component. Our results were consistent with size exclusion effects, a well-known GAC adsorption mechanism. This study demonstrated the promising benefit of using EEM-PARAFAC for GAC adsorption processes of landfill leachate through fast monitoring of the influent and treated leachate, which can provide valuable information on optimizing treatment processes and predicting further environmental impacts of the treated effluent. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Source apportionment for indoor PM2.5 and elemental concentrations using by a positive matrix factorization and an instrumental neutron activation analysis

    International Nuclear Information System (INIS)

    Lim, Jong Myoung; Moon, Jong Hwa; Chung, Yong Sam; Jung, Byoung Won; Lee, Jin Hong

    2009-01-01

    Airborne particulate matters, especially the PM2.5 (aerodynamic equivalent diameter, AED, less than 2.5 μm) fraction has been important. This is because of their potential for deposition on to the human respiratory system being accompanied by many harmful trace metals (such as As, Cd, Cr, Cu, Mn, Pb, Se, and Zn). The indoor air quality has become a great concern since late 1980s, because the population spends a majority of their time in various indoor environments. The indoor particulate matter may be influenced from outdoor environment and indoor sources such as environmental tobacco smoke (ETS), combustion devices, cooking, etc. In this study, we undertake the measurements of about 26 elements using instrumental neutron activation analysis (INAA). Based on our measurement data, we characterize concentration status and mutual relationship between indoor and adjacent outdoor air quality. Next, sources at indoor/outdoor environment were identified and the contributions of each source were quantified by positive matrix factorization (PMF)

  8. Effects of neutral particle beam on nano-crystalline silicon thin films, with application to thin film transistor backplane for flexible active matrix organic light emitting diodes

    International Nuclear Information System (INIS)

    Jang, Jin Nyoung; Song, Byoung Chul; Lee, Dong Hyeok; Yoo, Suk Jae; Lee, Bonju; Hong, MunPyo

    2011-01-01

    A novel deposition process for nano-crystalline silicon (nc-Si) thin films was developed using neutral beam assisted chemical vapor deposition (NBaCVD) technology for the application of the thin film transistor (TFT) backplane of flexible active matrix organic light emitting diode (AMOLED). During the formation of a nc-Si thin film, the energetic particles enhance nano-sized crystalline rather microcrystalline Si in thin films. Neutral Particle Beam (NPB) affects the crystallinity in two ways: (1) NPB energy enhances nano-crystallinity through kinetic energy transfer and chemical annealing, and (2) heavier NPB (such as Ar) induces damage and amorphization through energetic particle impinging. Nc-Si thin film properties effectively can be changed by the reflector bias. As increase of NPB energy limits growing the crystalline, the performance of TFT supports this NPB behavior. The results of nc-Si TFT by NBaCVD demonstrate the technical potentials of neutral beam based processes for achieving high stability and reduced leakage in TFT backplanes for AMOLEDs.

  9. TISSUE INHIBITOR OF METALLOPROTEINASE 1, MATRIX METALLOPROTEINASE 9, ALPHA-1 ANTITRYPSIN, METALLOTHIONEIN AND UROKINASE TYPE PLASMINOGEN ACTIVATOR RECEPTOR IN SKIN BIOPSIES FROM PATIENTS AFFECTED BY AUTOIMMUNE BLISTERING DISEASES

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2013-07-01

    Full Text Available Introduction: Proteinases and proteinase inhibitors have been described to play a role in autoimmune skin blistering diseases. We studied skin lesional biopsies from patients affected by several autoimmune skin blistering diseases for proteinases and proteinase inhibitors. Methods: We utilized immunohistochemistry to evaluate biopsies for alpha-1-antitrypsin, human matrix metalloproteinase 9 (MMP9, human tissue inhibitor of metalloproteinases 1 (TIMP-1, metallothionein and urokinase type plasminogen activator receptor (uPAR. We tested 30 patients affected by endemic pemphigus, 30 controls from the endemic area, and 15 normal controls. We also tested 30 biopsies from patients with bullous pemphigoid (BP, 20 with pemphigus vulgaris (PV, 8 with pemphigus foliaceus, and 14 with dermatitis herpetiformis (DH. Results: Contrary to findings in the current literature, most autoimmune skin blistering disease biopsies were negative for uPAR and MMP9. Only some chronic patients with El Bagre-EPF were positive to MMP9 in the dermis, in proximity to telocytes. TIMP-1 and metallothionein were positive in half of the biopsies from BP patients at the basement membrane of the skin, within several skin appendices, in areas of dermal blood vessel inflammation and within dermal mesenchymal-epithelial cell junctions.

  10. Preparation of clinical-scale 99Mo/99mTc column generator using neutron activated low specific activity 99Mo and nanocrystalline γ-Al2O3 as column matrix.

    Science.gov (United States)

    Chakravarty, Rubel; Ram, Ramu; Dash, Ashutosh; Pillai, M R A

    2012-10-01

    Preparation of clinical-scale (99)Mo/(99m)Tc generator using (n,γ) activated low specific activity (99)Mo and nanocrystalline γ-Al(2)O(3) as a high capacity sorbent matrix is attempted. Nanocrystalline γ-Al(2)O(3) was synthesized by 'solid state mechanochemical' reaction of aluminum nitrate with ammonium bicarbonate. Experimental parameters were optimized to effectively separate (99m)Tc from (99)Mo using this sorbent as the column matrix. The performance features of a 13 GBq (350 mCi) (99)Mo/(99m)Tc generator using this sorbent and (99)Mo produced by (n,γ) route having specific activity 12.9-18.5 GBq/g were evaluated for 10 days. The sorbent possessed the requisite selectivity for (99)Mo and demonstrated a maximum sorption capacity of 200 ± 5mg Mo/g, which is ~10 times higher than that of ordinary acidic alumina. The overall yield of (99m)Tc was >80%, with radionuclidic purity >99.99% and radiochemical purity >99%. The yield of (99m)Tc varied from 7.8 to 2.1 GBq in the eluate for the six days of operation of the generator. The radioactive concentration of (99m)Tc eluted was adequate for the formulation of radiopharmaceuticals. The performance of the generator remained consistent over an extended period of 10 days. The eluted (99m)Tc was suitable for the formulation of (99m)Tc-DMSA and (99m)Tc-EC resulting in high radiolabeling yields (>98%). The effectiveness of γ-Al(2)O(3) as a new generation sorbent in the development of clinically useful (99)Mo/(99m)Tc generator using low specific activity (99)Mo and yielding (99m)Tc with adequate radioactive concentration and high purity suitable for formulation of radiopharmaceuticals is demonstrated. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Inhibitory activities of selected Sudanese medicinal plants on Porphyromonas gingivalis and matrix metalloproteinase-9 and isolation of bioactive compounds from Combretum hartmannianum (Schweinf) bark.

    Science.gov (United States)

    Mohieldin, Ebtihal Abdalla M; Muddathir, Ali Mahmoud; Mitsunaga, Tohru

    2017-04-20

    Periodontal diseases are one of the major health problems and among the most important preventable global infectious diseases. Porphyromonas gingivalis is an anaerobic Gram-negative bacterium which has been strongly implicated in the etiology of periodontitis. Additionally, matrix metalloproteinases-9 (MMP-9) is an important factor contributing to periodontal tissue destruction by a variety of mechanisms. The purpose of this study was to evaluate the selected Sudanese medicinal plants against P. gingivalis bacteria and their inhibitory activities on MMP-9. Sixty two methanolic and 50% ethanolic extracts from 24 plants species were tested for antibacterial activity against P. gingivalis using microplate dilution assay method to determine the minimum inhibitory concentration (MIC). The inhibitory activity of seven methanol extracts selected from the 62 extracts against MMP-9 was determined by Colorimetric Drug Discovery Kit. In search of bioactive lead compounds, Combretum hartmannianum bark which was found to be within the most active plant extracts was subjected to various chromatographic (medium pressure liquid chromatography, column chromatography on a Sephadex LH-20, preparative high performance liquid chromatography) and spectroscopic methods (liquid chromatography-mass spectrometry, Nuclear Magnetic Resonance (NMR)) to isolate and characterize flavogalonic acid dilactone and terchebulin as bioactive compounds. About 80% of the crude extracts provided a MIC value ≤4 mg/ml against bacteria. The extracts which revealed the highest potency were: methanolic extracts of Terminalia laxiflora (wood; MIC = 0.25 mg/ml) followed by Acacia totrtilis (bark), Ambrosia maritima (aerial part), Argemone mexicana (seed), C. hartmannianum (bark), Terminalia brownii (wood) and 50% ethanolic extract of T. brownii (bark) with MIC values of 0.5 mg/ml. T. laxiflora (wood) and C. hartmannianum (bark) which belong to combretaceae family showed an inhibitory activity over 50% at

  12. Integrins and extracellular matrix in mechanotransduction

    Directory of Open Access Journals (Sweden)

    Ramage L

    2011-12-01

    Full Text Available Lindsay RamageQueen’s Medical Research Institute, University of Edinburgh, Edinburgh, UKAbstract: Integrins are a family of cell surface receptors which mediate cell–matrix and cell–cell adhesions. Among other functions they provide an important mechanical link between the cells external and intracellular environments while the adhesions that they form also have critical roles in cellular signal-transduction. Cell–matrix contacts occur at zones in the cell surface where adhesion receptors cluster and when activated the receptors bind to ligands in the extracellular matrix. The extracellular matrix surrounds the cells of tissues and forms the structural support of tissue which is particularly important in connective tissues. Cells attach to the extracellular matrix through specific cell-surface receptors and molecules including integrins and transmembrane proteoglycans. Integrins work alongside other proteins such as cadherins, immunoglobulin superfamily cell adhesion molecules, selectins, and syndecans to mediate cell–cell and cell–matrix interactions and communication. Activation of adhesion receptors triggers the formation of matrix contacts in which bound matrix components, adhesion receptors, and associated intracellular cytoskeletal and signaling molecules form large functional, localized multiprotein complexes. Cell–matrix contacts are important in a variety of different cell and tissue properties including embryonic development, inflammatory responses, wound healing, and adult tissue homeostasis. This review summarizes the roles and functions of integrins and extracellular matrix proteins in mechanotransduction.Keywords: ligand binding, α subunit, ß subunit, focal adhesion, cell differentiation, mechanical loading, cell–matrix interaction

  13. Interaction with extracellular matrix proteins influences Lsh/Ity/Bcg (candidate Nramp) gene regulation of macrophage priming/activation for tumour necrosis factor-alpha and nitrite release.

    Science.gov (United States)

    Formica, S; Roach, T I; Blackwell, J M

    1994-05-01

    The murine resistance gene Lsh/Ity/Bcg regulates activation of macrophages for tumour necrosis factor-alpha (TNF-alpha)-dependent production of nitric oxide mediating antimicrobial activity against Leishmania, Salmonella and Mycobacterium. As Lsh is differentially expressed in macrophages from different tissue sites, experiments were performed to determine whether interaction with extracellular matrix (ECM) proteins would influence the macrophage TNF-alpha response. Plating of bone marrow-derived macrophages onto purified fibrinogen or fibronectin-rich L929 cell-derived matrices, but not onto mannan, was itself sufficient to stimulate TNF-alpha release, with significantly higher levels released from congenic B10.L-Lshr compared to C57BL/10ScSn (Lshs) macrophages. Only macrophages plated onto fibrinogen also released measurable levels of nitrites, again higher in Lshr compared to Lshs macrophages. Addition of interferon-gamma (IFN-gamma), but not bacterial lipopolysaccharide or mycobacterial lipoarabinomannan, as a second signal enhanced the TNF-alpha and nitrite responses of macrophages plated onto fibrinogen, particularly in the Lshr macrophages. Interaction with fibrinogen and fibronectin also primed macrophages for an enhanced TNF-alpha response to leishmanial parasites, but this was only translated into enhanced nitrite responses in the presence of IFN-gamma. In these experiments, Lshr macrophages remained superior in their TNF-alpha responses throughout, but to a degree which reflected the magnitude of the difference observed on ECM alone. Hence, the specificity for the enhanced TNF-alpha responses of Lshr macrophages lay in their interaction with fibrinogen and fibronectin ECM, while a differential nitrite response was only observed with fibrinogen and/or IFN-gamma. The results are discussed in relation to the possible function of the recently cloned candidate gene Nramp, which has structural identity to eukaryote transporters and an N-terminal cytoplasmic

  14. Ulcerative colitis, Crohn's disease, and irritable bowel syndrome have different profiles of extracellular matrix turnover, which also reflects disease activity in Crohn's disease.

    Directory of Open Access Journals (Sweden)

    Joachim Høg Mortensen

    Full Text Available Increased protease activity is a key pathological feature of inflammatory bowel disease (IBD. However, the differences in extracellular matrix remodelling (ECM in Crohn's disease (CD and ulcerative colitis (UC are not well described. An increased understanding of the inflammatory processes may provide optimized disease monitoring and diagnostics. We investigated the tissue remodelling in IBD and IBS patients by using novel blood-based biomarkers reflecting ECM remodelling.Five ECM biomarkers (VICM, BGM, EL-NE, C5M, Pro-C5 were measured by competitive ELISAs in serum from 72 CD patients, 60 UC patients, 22 patients with irritable bowel syndrome (IBS, and 24 healthy donors. One-way analysis of variance, Mann-Whitney U-test, logistic regression models, and receiver operator characteristics (ROC curve analysis was carried out to evaluate the diagnostic accuracy of the biomarkers.The ECM remodelling was significantly different in UC compared to CD. The best biomarker combination to differentiate UC from CD and colonic CD was BGM and VICM (AUC = 0.98, P5mg/mL, correlation of Pro-C5 (r = 0.36 with CDAI was slightly improved compared to CRP (r = 0.27 corrected for the use of immunosuppressant. Furthermore, BGM and EL-NE biomarkers were highly associated with colon inflammation in CD patients.ECM fragments of tissue remodelling in IBD affect UC and CD differently, and may aid in differentiating IBD from IBS (EL-NE, BGM, Pro-C5, and UC from CD patients (BGM, VICM. Formation of type V collagen is related to the level of inflammation in CD and may reflect disease activity in CD.

  15. Galectin-3 facilitates cell motility in gastric cancer by up-regulating protease-activated receptor-1 (PAR-1 and matrix metalloproteinase-1 (MMP-1.

    Directory of Open Access Journals (Sweden)

    Seok-Jun Kim

    Full Text Available BACKGROUND: Galectin-3 is known to regulate cancer metastasis. However, the underlying mechanism has not been defined. Through the DNA microarray studies after galectin-3 silencing, we demonstrated here that galectin-3 plays a key role in up-regulating the expressions of protease-activated receptor-1 (PAR-1 and matrix metalloproteinase-1 (MMP-1 PAR-1 thereby promoting gastric cancer metastasis. METHODOLOGY/PRINCIPAL FINDINGS: We examined the expression levels of Galectin-3, PAR-1, and MMP-1 in gastric cancer patient tissues and also the effects of silencing these proteins with specific siRNAs and of over-expressing them using specific lenti-viral constructs. We also employed zebrafish embryo model for analysis of in vivo gastric cancer cell invasion. These studies demonstrated that: a galectin-3 silencing decreases the expression of PAR-1. b galectin-3 over-expression increases cell migration and invasion and this increase can be reversed by PAR-1 silencing, indicating that galectin-3 increases cell migration and invasion via PAR-1 up-regulation. c galectin-3 directly interacts with AP-1 transcriptional factor, and this complex binds to PAR-1 promoter and drives PAR-1 transcription. d galectin-3 also amplifies phospho-paxillin, a PAR-1 downstream target, by increasing MMP-1 expression. MMP-1 silencing blocks phospho-paxillin amplification and cell invasion caused by galectin-3 over-expression. e Silencing of either galectin-3, PAR-1 or MMP-1 significantly reduced cell migration into the vessels in zebrafish embryo model. f Galectin-3, PAR-1, and MMP-1 are highly expressed and co-localized in malignant tissues from gastric cancer patients. CONCLUSIONS/SIGNIFICANCE: Galectin-3 plays the key role of activating cell surface receptor through production of protease and boosts gastric cancer metastasis. Galectin-3 has the potential to serve as a useful pharmacological target for prevention of gastric cancer metastasis.

  16. Efficiency criterion for teleportation via channel matrix, measurement matrix and collapsed matrix

    Directory of Open Access Journals (Sweden)

    Xin-Wei Zha

    Full Text Available In this paper, three kinds of coefficient matrixes (channel matrix, measurement matrix, collapsed matrix associated with the pure state for teleportation are presented, the general relation among channel matrix, measurement matrix and collapsed matrix is obtained. In addition, a criterion for judging whether a state can be teleported successfully is given, depending on the relation between the number of parameter of an unknown state and the rank of the collapsed matrix. Keywords: Channel matrix, Measurement matrix, Collapsed matrix, Teleportation

  17. Extended biorthogonal matrix polynomials

    Directory of Open Access Journals (Sweden)

    Ayman Shehata

    2017-01-01

    Full Text Available The pair of biorthogonal matrix polynomials for commutative matrices were first introduced by Varma and Tasdelen in [22]. The main aim of this paper is to extend the properties of the pair of biorthogonal matrix polynomials of Varma and Tasdelen and certain generating matrix functions, finite series, some matrix recurrence relations, several important properties of matrix differential recurrence relations, biorthogonality relations and matrix differential equation for the pair of biorthogonal matrix polynomials J(A,B n (x, k and K(A,B n (x, k are discussed. For the matrix polynomials J(A,B n (x, k, various families of bilinear and bilateral generating matrix functions are constructed in the sequel.

  18. Platelet-derived growth factor-D modulates extracellular matrix homeostasis and remodeling through TIMP-1 induction and attenuation of MMP-2 and MMP-9 gelatinase activities

    Energy Technology Data Exchange (ETDEWEB)

    Borkham-Kamphorst, Erawan, E-mail: ekamphorst@ukaachen.de; Alexi, Pascal; Tihaa, Lidia; Haas, Ute; Weiskirchen, Ralf, E-mail: rweiskirchen@ukaachen.de

    2015-02-13

    Platelet-derived growth factor-D (PDGF-D) is a more recent recognized growth factor involved in the regulation of several cellular processes, including cell proliferation, transformation, invasion, and angiogenesis by binding to and activating its cognate receptor PDGFR-β. After bile duct ligation or in the carbon tetrachloride-induced hepatic fibrosis model{sub ,} PDGF-D showed upregulation comparable to PDGF-B. Moreover, adenoviral PDGF-D gene transfer induced hepatic stellate cell proliferation and liver fibrosis. We here investigated the molecular mechanism of PDGF-D involvement in liver fibrogenesis. Therefore, the GRX mouse cell line was stimulated with PDGF-D and evaluated for fibrotic markers and PDGF-D signaling pathways in comparison to the other PDGF isoforms. We found that PDGF-D failed to enhance Col I and α-smooth muscle actin (α-SMA) production but has capacity to upregulate expression of the tissue inhibitor of metalloprotease 1 (TIMP-1) resulting in attenuation of MMP-2 and MMP-9 gelatinase activity as indicated by gelatinase zymography. This phenomenon was restored through application of a PDGF-D neutralizing antibody. Unexpectedly, PDGF-D incubation decreased both PDGFR-α and -β in mRNA and protein levels, and PDGF-D phosphorylated typrosines specific for PDGFR-α and -β. We conclude that PDGF-D intensifies fibrogenesis by interfering with the fibrolytic activity of the TIMP-1/MMP system and that PDGF-D signaling is mediated through both PDGF-α and -β receptors. - Highlights: • PDGF-D signals through PDGF receptor type α and β. • PDGF-D modulates extracellular matrix homeostasis and remodeling. • Like PDGF-B, PDGF-D triggers phosphorylation of PLC-γ, Akt/PKB, JNK, ERK1/2, and p38. • PDGF-D induces TIMP-1 expression through ERK and p38 MAPK. • PDGF-D attenuates MMP-2 and MMP-9 gelatinase activities.

  19. Matrix completion by deep matrix factorization.

    Science.gov (United States)

    Fan, Jicong; Cheng, Jieyu

    2018-02-01

    Conventional methods of matrix completion are linear methods that are not effective in handling data of nonlinear structures. Recently a few researchers attempted to incorporate nonlinear techniques into matrix completion but there still exists considerable limitations. In this paper, a novel method called deep matrix factorization (DMF) is proposed for nonlinear matrix completion. Different from conventional matrix completion methods that are based on linear latent variable models, DMF is on the basis of a nonlinear latent variable model. DMF is formulated as a deep-structure neural network, in which the inputs are the low-dimensional unknown latent variables and the outputs are the partially observed variables. In DMF, the inputs and the parameters of the multilayer neural network are simultaneously optimized to minimize the reconstruction errors for the observed entries. Then the missing entries can be readily recovered by propagating the latent variables to the output layer. DMF is compared with state-of-the-art methods of linear and nonlinear matrix completion in the tasks of toy matrix completion, image inpainting and collaborative filtering. The experimental results verify that DMF is able to provide higher matrix completion accuracy than existing methods do and DMF is applicable to large matrices. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. An approach to the structural features of the socio-economic activity of a country based on a Social Accounting Matrix.Evidences and multiplier effects on distribution of income.

    OpenAIRE

    Santos, Susana

    2017-01-01

    Abstract A Social Accounting Matrix (SAM) is presented as a tool to study the socio-economic activity of a country. This activity involves the monetary or nominal flows that are measured by the National Accounts, as well as production (organized in factors, industries and goods and services) and institutions (organized in households, general government, non-financial and financial corporations, non-profit institutions serving households, and rest of the world). In order to contribute t...

  1. IL-1β-induced matrix metalloproteinase-13 is activated by a disintegrin and metalloprotease-28-regulated proliferation of human osteoblast-like cells

    International Nuclear Information System (INIS)

    Ozeki, Nobuaki; Kawai, Rie; Yamaguchi, Hideyuki; Hiyama, Taiki; Kinoshita, Katsue; Hase, Naoko; Nakata, Kazuhiko; Kondo, Ayami; Mogi, Makio; Nakamura, Hiroshi

    2014-01-01

    We reported previously that matrix metalloproteinase (MMP)-13 accelerates bone remodeling in oral periradicular lesions, and indicated a potentially unique role for MMP-13 in wound healing and regeneration of alveolar bone. The ADAM (a disintegrin and metalloprotease) family is a set of multifunctional cell surface and secreted glycoproteins, of which ADAM-28 has been localized in bone and bone-like tissues. In this study, we show that interleukin (IL)-1β induces the expression of MMP-13 and ADAM-28 in homogeneous α7 integrin-positive human skeletal muscle stem cell (α7 + hSMSC)-derived osteoblast-like (α7 + hSMSC-OB) cells, and promotes proliferation while inhibiting apoptosis in these cells. At higher concentrations, however, IL-1β failed to induce the expression of these genes and caused an increase in apoptosis. We further employed ADAM-28 small interfering RNA (siRNA) to investigate whether IL-1β-induced MMP-13 expression is linked to this IL-1β-mediated changes in cell proliferation and apoptosis. Silencing ADAM-28 expression potently suppressed IL-1β-induced MMP-13 expression and activity, decreased cell proliferation and increased apoptosis in α7 + hSMSC-OB cells. In contrast, MMP-13 siRNA had no effect on ADAM-28 expression, suggesting ADAM-28 regulates MMP-13. Exogenous MMP-13 induced α7 + hSMSC-OB cell proliferation and could rescue ADAM-28 siRNA-induced apoptosis, and we found that proMMP-13 is partially cleaved into its active form by ADAM-28 in vitro. Overall, our results suggest that IL-1β-induced MMP-13 expression and changes in cell proliferation and apoptosis in α7 + hSMSC-OB cells are regulated by ADAM-28. - Highlights: • IL-1β induces the MMP-13 and ADAM-28 expression in human osteoblast-like cells. • IL-1β-induced MMP-13 expression increases proliferation and decreased apoptosis. • MMP-13 expression induced by IL-1β is regulated by ADAM-28. • proMMP-13 appears to be cleaved into its active form via ADAM-28

  2. IL-1β-induced matrix metalloproteinase-13 is activated by a disintegrin and metalloprotease-28-regulated proliferation of human osteoblast-like cells

    Energy Technology Data Exchange (ETDEWEB)

    Ozeki, Nobuaki; Kawai, Rie; Yamaguchi, Hideyuki; Hiyama, Taiki; Kinoshita, Katsue; Hase, Naoko; Nakata, Kazuhiko [Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi 464-8651 (Japan); Kondo, Ayami [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya, Aichi 464-8650 (Japan); Mogi, Makio, E-mail: makio@dpc.agu.ac.jp [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya, Aichi 464-8650 (Japan); Nakamura, Hiroshi [Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi 464-8651 (Japan)

    2014-04-15

    We reported previously that matrix metalloproteinase (MMP)-13 accelerates bone remodeling in oral periradicular lesions, and indicated a potentially unique role for MMP-13 in wound healing and regeneration of alveolar bone. The ADAM (a disintegrin and metalloprotease) family is a set of multifunctional cell surface and secreted glycoproteins, of which ADAM-28 has been localized in bone and bone-like tissues. In this study, we show that interleukin (IL)-1β induces the expression of MMP-13 and ADAM-28 in homogeneous α7 integrin-positive human skeletal muscle stem cell (α7{sup +}hSMSC)-derived osteoblast-like (α7{sup +}hSMSC-OB) cells, and promotes proliferation while inhibiting apoptosis in these cells. At higher concentrations, however, IL-1β failed to induce the expression of these genes and caused an increase in apoptosis. We further employed ADAM-28 small interfering RNA (siRNA) to investigate whether IL-1β-induced MMP-13 expression is linked to this IL-1β-mediated changes in cell proliferation and apoptosis. Silencing ADAM-28 expression potently suppressed IL-1β-induced MMP-13 expression and activity, decreased cell proliferation and increased apoptosis in α7{sup +}hSMSC-OB cells. In contrast, MMP-13 siRNA had no effect on ADAM-28 expression, suggesting ADAM-28 regulates MMP-13. Exogenous MMP-13 induced α7{sup +}hSMSC-OB cell proliferation and could rescue ADAM-28 siRNA-induced apoptosis, and we found that proMMP-13 is partially cleaved into its active form by ADAM-28 in vitro. Overall, our results suggest that IL-1β-induced MMP-13 expression and changes in cell proliferation and apoptosis in α7{sup +}hSMSC-OB cells are regulated by ADAM-28. - Highlights: • IL-1β induces the MMP-13 and ADAM-28 expression in human osteoblast-like cells. • IL-1β-induced MMP-13 expression increases proliferation and decreased apoptosis. • MMP-13 expression induced by IL-1β is regulated by ADAM-28. • proMMP-13 appears to be cleaved into its active form via

  3. Matrix metalloproteinase-2 and -9 are induced differently by metal nanoparticles in human monocytes: The role of oxidative stress and protein tyrosine kinase activation

    International Nuclear Information System (INIS)

    Wan Rong; Mo Yiqun; Zhang Xing; Chien Sufan; Tollerud, David J.; Zhang Qunwei

    2008-01-01

    Recently, many studies have shown that nanoparticles can translocate from the lungs to the circulatory system. As a particulate foreign body, nanoparticles could induce host responses such as reactive oxygen species (ROS) generation, inflammatory cytokine and matrix metalloproteinase (MMP) release which play a major role in tissue destruction and remodeling. However, the direct effects of nanoparticles on leukocytes, especially monocytes, are still unclear. The objective of the present study was to compare the ability of Nano-Co and Nano-TiO 2 to cause alteration of transcription and activity of MMPs and to explore possible mechanisms. We hypothesized that non-toxic doses of some transition metal nanoparticles stimulate an imbalance of MMP/TIMP that cause MMP production that may contribute to their health effects. To test this hypothesis, U937 cells were treated with Nano-Co and Nano-TiO 2 and cytotoxic effects and ROS generation were measured. The alteration of MMP-2 and MMP-9 expression and activity of MMP-2 and MMP-9 after exposure to these metal nanoparticles were subsequently determined. To investigate the potential signaling pathways involved in the Nano-Co-induced MMP activation, the ROS scavengers or inhibitors, AP-1 inhibitor, and protein tyrosine kinase (PTK) inhibitors were also used to pre-treat U937 cells. Our results demonstrated that exposure of U937 cells to Nano-Co, but not to Nano-TiO 2 , at a dose that does not cause cytotoxicity, resulted in ROS generation and up-regulation of MMP-2 and MMP-9 mRNA expression .. Our results also showed dose- and time-related increases in pro-MMP-2 and pro-MMP-9 gelatinolytic activities in conditioned media after exposure of U937 cells to Nano-Co, but not to Nano-TiO 2 . Nano-Co-induced pro-MMP-2 and pro-MMP-9 activity increases were inhibited by pre-treatment with ROS scavengers or inhibitors. We also demonstrated dose- and time-related decreases in tissue inhibitors of metalloproteinases 2 (TIMP-2) in U937 cells

  4. Measurement of laser activated electron tunneling from semiconductor zinc oxide to adsorbed organic molecules by a matrix assisted laser desorption ionization mass spectrometer

    International Nuclear Information System (INIS)

    Zhong Hongying; Fu Jieying; Wang Xiaoli; Zheng Shi

    2012-01-01

    Highlights: ► Irradiation of photons with energies more than the band gap generates electron–hole pairs. ► Electron tunneling probability is dependent on the electron mobility. ► Tunneling electrons are captured by charge deficient atoms. ► Unpaired electrons induce cleavages of chemical bonds. - Abstract: Measurement of light induced heterogeneous electron transfer is important for understanding of fundamental processes involved in chemistry, physics and biology, which is still challenging by current techniques. Laser activated electron tunneling (LAET) from semiconductor metal oxides was observed and characterized by a MALDI (matrix assisted laser desorption ionization) mass spectrometer in this work. Nanoparticles of ZnO were placed on a MALDI sample plate. Free fatty acids and derivatives were used as models of organic compounds and directly deposited on the surface of ZnO nanoparticles. Irradiation of UV laser (λ = 355 nm) with energy more than the band gap of ZnO produces ions that can be detected in negative mode. When TiO 2 nanoparticles with similar band gap but much lower electron mobility were used, these ions were not observed unless the voltage on the sample plate was increased. The experimental results indicate that laser induced electron tunneling is dependent on the electron mobility and the strength of the electric field. Capture of low energy electrons by charge-deficient atoms of adsorbed organic molecules causes unpaired electron-directed cleavages of chemical bonds in a nonergodic pathway. In positive detection mode, electron tunneling cannot be observed due to the reverse moving direction of electrons. It should be able to expect that laser desorption ionization mass spectrometry is a new technique capable of probing the dynamics of electron tunneling. LAET offers advantages as a new ionization dissociation method for mass spectrometry.

  5. Pollution sources for indoor PM2.5 at the platform in subway station using a positive matrix factorization and an instrumental neutron activation analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Jong Myoung; Moon, Jong Hwa; Chung, Yong Sam [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Lee, Jin Hong [Chungnam National University, Daejeon (Korea, Republic of)

    2010-05-15

    Airborne particulate matters, especially the PM2.5 (aerodynamic equivalent diameter, AED, less than 2.5 )m) fraction has been important. This is because of their potential for deposition on to the human respiratory system being accompanied by many harmful trace metals (such as As, Cd, Cr, Cu, Mn, Pb, Se, and Zn). As most people spend more than 80% of their time indoors, indoor air quality (IAQ) can exert a considerable impact on the inhalation condition of toxic substances. Therefore, assessment of the absolute concentration levels and elemental composition of PM in an indoor environment such as subway station can be used as a practical barometer of IAQ. The contaminants originated from the indoor pollution sources as well as various outdoor sources are easily accumulated in indoor environment dissimilar to the outdoor. Especially, since the natural ventilation is nearly impossible in the subway station, its pollution status can be worsened under the circumstance that contaminants are constantly originated and circulated inside of station by the repetitive action of subway trains. In this study, a total of 60 PM2.5 samples were collected for 4 seasonal campaigns in 2009 with a low-volume air sampler at one subway station in Daejeon, Korea. We undertook the measurements of up to 25 elements in PM2.5 using an instrumental neutron activation analysis (INAA) and X-ray fluorescence (XRF). And inorganic ion species (SO{sub 4}{sup 2-}, NO{sub 3}{sup -}, NH{sub 4}{sup +}) also were determined by ion chromatography (IC). Next, sources at indoor/outdoor environment were identified and the contributions of each source were quantified by positive matrix factorization (PMF).

  6. Pollution sources for indoor PM2.5 at the platform in subway station using a positive matrix factorization and an instrumental neutron activation analysis

    International Nuclear Information System (INIS)

    Lim, Jong Myoung; Moon, Jong Hwa; Chung, Yong Sam; Lee, Jin Hong

    2010-01-01

    Airborne particulate matters, especially the PM2.5 (aerodynamic equivalent diameter, AED, less than 2.5 )m) fraction has been important. This is because of their potential for deposition on to the human respiratory system being accompanied by many harmful trace metals (such as As, Cd, Cr, Cu, Mn, Pb, Se, and Zn). As most people spend more than 80% of their time indoors, indoor air quality (IAQ) can exert a considerable impact on the inhalation condition of toxic substances. Therefore, assessment of the absolute concentration levels and elemental composition of PM in an indoor environment such as subway station can be used as a practical barometer of IAQ. The contaminants originated from the indoor pollution sources as well as various outdoor sources are easily accumulated in indoor environment dissimilar to the outdoor. Especially, since the natural ventilation is nearly impossible in the subway station, its pollution status can be worsened under the circumstance that contaminants are constantly originated and circulated inside of station by the repetitive action of subway trains. In this study, a total of 60 PM2.5 samples were collected for 4 seasonal campaigns in 2009 with a low-volume air sampler at one subway station in Daejeon, Korea. We undertook the measurements of up to 25 elements in PM2.5 using an instrumental neutron activation analysis (INAA) and X-ray fluorescence (XRF). And inorganic ion species (SO 4 2- , NO 3 - , NH 4 + ) also were determined by ion chromatography (IC). Next, sources at indoor/outdoor environment were identified and the contributions of each source were quantified by positive matrix factorization (PMF).

  7. The Matrix Cookbook

    DEFF Research Database (Denmark)

    Petersen, Kaare Brandt; Pedersen, Michael Syskind

    Matrix identities, relations and approximations. A desktop reference for quick overview of mathematics of matrices.......Matrix identities, relations and approximations. A desktop reference for quick overview of mathematics of matrices....

  8. Carbonate fuel cell matrix

    Science.gov (United States)

    Farooque, Mohammad; Yuh, Chao-Yi

    1996-01-01

    A carbonate fuel cell matrix comprising support particles and crack attenuator particles which are made platelet in shape to increase the resistance of the matrix to through cracking. Also disclosed is a matrix having porous crack attenuator particles and a matrix whose crack attenuator particles have a thermal coefficient of expansion which is significantly different from that of the support particles, and a method of making platelet-shaped crack attenuator particles.

  9. Matrix with Prescribed Eigenvectors

    Science.gov (United States)

    Ahmad, Faiz

    2011-01-01

    It is a routine matter for undergraduates to find eigenvalues and eigenvectors of a given matrix. But the converse problem of finding a matrix with prescribed eigenvalues and eigenvectors is rarely discussed in elementary texts on linear algebra. This problem is related to the "spectral" decomposition of a matrix and has important technical…

  10. Triangularization of a Matrix

    Indian Academy of Sciences (India)

    Much of linear algebra is devoted to reducing a matrix (via similarity or unitary similarity) to another that has lots of zeros. The simplest such theorem is the Schur triangularization theorem. This says that every matrix is unitarily similar to an upper triangular matrix. Our aim here is to show that though it is very easy to prove it ...

  11. Diurnal and seasonal trends and source apportionment of redox-active metals in Los Angeles using a novel online metal monitor and Positive Matrix Factorization (PMF)

    Science.gov (United States)

    Mousavi, Amirhosein; Sowlat, Mohammad H.; Sioutas, Constantinos

    2018-02-01

    In the present study, we identified the sources of four redox-active metals, including Iron (Fe), Chromium (Cr), Cupper (Cu), and Manganese (Mn) and quantified the contribution of these sources to PM2.5 concentrations in central Los Angeles, California, by employing time-resolved measurements (i.e., a time resolution of 2 h) with a recently developed online metal monitor and Positive Matrix Factorization (PMF). Size distribution of ambient PM (14 nm-10 μm) was measured using the Scanning Mobility Particle Sizer (SMPS) and Optical Particle Sizer (OPS). Auxiliary variables were also collected, including elemental (EC) and organic carbon (OC), gaseous pollutants (NO2 and O3), meteorological parameters (including relative humidity (RH) and temperature), and traffic data (for heavy- (HDVs) and light-duty vehicles (LDVs)). A 4-factor solution was found to be optimum for the chemically-speciated dataset, whereas a 5-factor solution appeared to be most plausible for the size distribution data. The factors included fresh traffic, soil/road dust, urban background aerosol, secondary aerosol, and nucleation (only resolved for the size distribution data). Fresh traffic was the major contributor to Fe and Cu concentrations, whereas Cr was mostly found in the urban background aerosol (reflecting a mixture of small local sources as well as aged traffic emissions), and Mn mostly came from both soil/road dust and was to a lesser degree found in urban background aerosol. Secondary aerosol did not contribute to the concentrations of any of these metals, but was associated with very high loading of OC, as expected. Even though the urban background aerosol and secondary aerosol appeared to be characterized by "aged" particles and have a rather homogeneous spatial distribution, the reactions and processes involved in their formation are entirely different. Our results provide insights into the sources of redox-active metals in central Los Angeles. They also underscore the benefits of

  12. How to get the Matrix Organization to Work

    DEFF Research Database (Denmark)

    Burton, Richard M.; Obel, Børge; Håkonsson, Dorthe Døjbak

    2015-01-01

    a matrix to work, taking a multi-contingency perspective. We translate the matrix concept for designers and managers who are considering a matrix organization and argue that three factors are critical for its success: (1) Strong purpose: Only choose the matrix structure if there are strong reasons...... for doing so, (2) Alignment among contingencies: A matrix can only be successful if key contingencies are aligned with the matrix’s purpose, and (3) Management of junctions: The success of a matrix depends on how well activities at the junctions of the matrix are managed....

  13. A marketing matrix for health care organizations.

    Science.gov (United States)

    Weaver, F J; Gombeski, W R; Fay, G W; Eversman, J J; Cowan-Gascoigne, C

    1986-06-01

    Irrespective of the formal marketing structure successful marketing for health care organizations requires the input on many people. Detailed here is the Marketing Matrix used at the Cleveland Clinic Foundation in Cleveland, Ohio. This Matrix is both a philosophy and a tool for clarifying and focusing the organization's marketing activities.

  14. An investigation of signal performance enhancements achieved through innovative pixel design across several generations of indirect detection, active matrix, flat-panel arrays

    International Nuclear Information System (INIS)

    Antonuk, Larry E.; Zhao Qihua; El-Mohri, Youcef; Du Hong; Wang Yi; Street, Robert A.; Ho, Jackson; Weisfield, Richard; Yao, William

    2009-01-01

    Active matrix flat-panel imager (AMFPI) technology is being employed for an increasing variety of imaging applications. An important element in the adoption of this technology has been significant ongoing improvements in optical signal collection achieved through innovations in indirect detection array pixel design. Such improvements have a particularly beneficial effect on performance in applications involving low exposures and/or high spatial frequencies, where detective quantum efficiency is strongly reduced due to the relatively high level of additive electronic noise compared to signal levels of AMFPI devices. In this article, an examination of various signal properties, as determined through measurements and calculations related to novel array designs, is reported in the context of the evolution of AMFPI pixel design. For these studies, dark, optical, and radiation signal measurements were performed on prototype imagers incorporating a variety of increasingly sophisticated array designs, with pixel pitches ranging from 75 to 127 μm. For each design, detailed measurements of fundamental pixel-level properties conducted under radiographic and fluoroscopic operating conditions are reported and the results are compared. A series of 127 μm pitch arrays employing discrete photodiodes culminated in a novel design providing an optical fill factor of ∼80% (thereby assuring improved x-ray sensitivity), and demonstrating low dark current, very low charge trapping and charge release, and a large range of linear signal response. In two of the designs having 75 and 90 μm pitches, a novel continuous photodiode structure was found to provide fill factors that approach the theoretical maximum of 100%. Both sets of novel designs achieved large fill factors by employing architectures in which some, or all of the photodiode structure was elevated above the plane of the pixel addressing transistor. Generally, enhancement of the fill factor in either discrete or continuous

  15. In situ localization of gelatinolytic activity in the extracellular matrix of metastases of colon cancer in rat liver using quenched fluorogenic DQ-gelatin

    NARCIS (Netherlands)

    Mook, Olaf R. F.; van Overbeek, Claudia; Ackema, Eleonora G.; van Maldegem, Febe; Frederiks, Wilma M.

    2003-01-01

    Matrix metalloproteinases (MMPs) such as gelatinases are believed to play an important role in invasion and metastasis of cancer. In this study we investigated the possible role of MMP-2 and MMP-9 in an experimental model of colon cancer metastasis in rat liver. We demonstrated with gelatin

  16. Cytokine-induced endogenous procollagenase stored in the extracellular matrix of soft connective tissue results in a burst of collagen breakdown following its activation

    NARCIS (Netherlands)

    van der Zee, E.; Everts, V.; Beertsen, W.

    1996-01-01

    Numerous data strongly suggest the involvement of cytokines and the matrix metalloproteinase collagenase (MMP-1) in the pathogenesis of periodontitis. Recently, we have demonstrated that, upon culturing under the influence of IL-1 alpha + EGF, a large amount of inactive procollagenase (MMP-1) is

  17. Adenoviral vectors expressing fusogenic membrane glycoproteins activated via matrix metalloproteinase cleavable linkers have significant antitumor potential in the gene therapy of gliomas.

    Science.gov (United States)

    Allen, Cory; McDonald, Cari; Giannini, Caterina; Peng, Kah Whye; Rosales, Gabriela; Russell, Stephen J; Galanis, Evanthia

    2004-11-01

    Fusogenic membrane glycoproteins (FMG) such as the gibbon ape leukemia virus envelope (GALV) glycoprotein are potent therapeutic transgenes with potential utility in the gene therapy of gliomas. Transfection of glioma cell lines with FMG expression constructs results in fusion with massive syncytia formation followed by cytotoxic cell death. Nevertheless, ubiquitous expression of the GALV receptor, Pit-1, makes targeting desirable in order to increase the specificity of the observed cytopathic effect. Here we report on use of matrix metalloproteinase (MMP)-cleavable linkers to target the cytotoxicity of FMG-expressing adenoviral vectors against gliomas. Replication-defective adenoviruses (Ad) were constructed expressing the hyperfusogenic version of the GALV glycoprotein linked to a blocking ligand (C-terminal extracellular domain of CD40 ligand) through either an MMP-cleavable linker (AdM40) or a non-cleavable linker (AdN40). Both viruses also co-expressed the green fluorescent protein (GFP) via an internal ribosomal entry site. The glioma cell lines U87, U118, and U251 characterized by zymography and MMP-2 activity assay as high, medium and low MMP expressors, respectively, the MMP-poor cell lines TE671 and normal human astrocytes were infected with AdM40 and AdN40 at different multiplicities of infection (MOIs) from 1-30. Fusion was quantitated by counting both number and size of syncytia. Infection of these cell lines with AdN40 did not result in fusion or cytotoxic cell death, despite the presence of infection, as demonstrated by GFP positivity, therefore indicating that the displayed CD40 ligand blocked GALV-induced fusion. Fusion was restored after infection of glioma cells with AdM40 at an MOI as low as 1 to an extent dependent on MMP expression and coxsackie adenovirus receptor (CAR) expression in the specific cell line. Western immunoblotting demonstrated the presence of the cleaved CD40 ligand in the supernatant of fused glioma cells. Use of the MMP

  18. Parallelism in matrix computations

    CERN Document Server

    Gallopoulos, Efstratios; Sameh, Ahmed H

    2016-01-01

    This book is primarily intended as a research monograph that could also be used in graduate courses for the design of parallel algorithms in matrix computations. It assumes general but not extensive knowledge of numerical linear algebra, parallel architectures, and parallel programming paradigms. The book consists of four parts: (I) Basics; (II) Dense and Special Matrix Computations; (III) Sparse Matrix Computations; and (IV) Matrix functions and characteristics. Part I deals with parallel programming paradigms and fundamental kernels, including reordering schemes for sparse matrices. Part II is devoted to dense matrix computations such as parallel algorithms for solving linear systems, linear least squares, the symmetric algebraic eigenvalue problem, and the singular-value decomposition. It also deals with the development of parallel algorithms for special linear systems such as banded ,Vandermonde ,Toeplitz ,and block Toeplitz systems. Part III addresses sparse matrix computations: (a) the development of pa...

  19. Neutrino mass matrix

    International Nuclear Information System (INIS)

    Strobel, E.L.

    1985-01-01

    Given the many conflicting experimental results, examination is made of the neutrino mass matrix in order to determine possible masses and mixings. It is assumed that the Dirac mass matrix for the electron, muon, and tau neutrinos is similar in form to those of the quarks and charged leptons, and that the smallness of the observed neutrino masses results from the Gell-Mann-Ramond-Slansky mechanism. Analysis of masses and mixings for the neutrinos is performed using general structures for the Majorana mass matrix. It is shown that if certain tentative experimental results concerning the neutrino masses and mixing angles are confirmed, significant limitations may be placed on the Majorana mass matrix. The most satisfactory simple assumption concerning the Majorana mass matrix is that it is approximately proportional to the Dirac mass matrix. A very recent experimental neutrino mass result and its implications are discussed. Some general properties of matrices with structure similar to the Dirac mass matrices are discussed

  20. A simple method for correcting the neutron self-shielding effect of matrix and improving the analytical response in prompt gamma-ray neutron activation analysis

    International Nuclear Information System (INIS)

    Sudarshan, K.; Tripathi, R.; Nair, A.G.C.; Acharya, R.; Reddy, A.V.R.; Goswami, A.

    2005-01-01

    A simple method using an internal standard is proposed to correct for the self-shielding effect of B, Cd and Gd in a matrix. This would increase the linear dynamic range of PGNAA in analyzing samples containing these elements. The method is validated by analyzing synthetic samples containing large amounts of B, Cd, Hg and Gd, the elements having high neutron absorption cross-section, in aqueous solutions and solid forms. A simple Monte-Carlo simulation to find the extent of self-shielding in the matrix is presented. The method is applied to the analysis of titanium boride alloy containing large amount of boron. The satisfactory results obtained showed the efficacy of the method of correcting for the self-shielding effects in the sample

  1. Data set for the proteomic inventory and quantitative analysis of chicken eggshell matrix proteins during the primary events of eggshell mineralization and the active growth phase of calcification.

    Science.gov (United States)

    Marie, Pauline; Labas, Valérie; Brionne, Aurélien; Harichaux, Grégoire; Hennequet-Antier, Christelle; Rodriguez-Navarro, Alejandro B; Nys, Yves; Gautron, Joël

    2015-09-01

    Chicken eggshell is a biomineral composed of 95% calcite calcium carbonate mineral and of 3.5% organic matrix proteins. The assembly of mineral and its structural organization is controlled by its organic matrix. In a recent study [1], we have used quantitative proteomic, bioinformatic and functional analyses to explore the distribution of 216 eggshell matrix proteins at four key stages of shell mineralization defined as: (1) widespread deposition of amorphous calcium carbonate (ACC), (2) ACC transformation into crystalline calcite aggregates, (3) formation of larger calcite crystal units and (4) rapid growth of calcite as columnar structure with preferential crystal orientation. The current article detailed the quantitative analysis performed at the four stages of shell mineralization to determine the proteins which are the most abundant. Additionally, we reported the enriched GO terms and described the presence of 35 antimicrobial proteins equally distributed at all stages to keep the egg free of bacteria and of 81 proteins, the function of which could not be ascribed.

  2. Data set for the proteomic inventory and quantitative analysis of chicken eggshell matrix proteins during the primary events of eggshell mineralization and the active growth phase of calcification

    Directory of Open Access Journals (Sweden)

    Pauline Marie

    2015-09-01

    Full Text Available Chicken eggshell is a biomineral composed of 95% calcite calcium carbonate mineral and of 3.5% organic matrix proteins. The assembly of mineral and its structural organization is controlled by its organic matrix. In a recent study [1], we have used quantitative proteomic, bioinformatic and functional analyses to explore the distribution of 216 eggshell matrix proteins at four key stages of shell mineralization defined as: (1 widespread deposition of amorphous calcium carbonate (ACC, (2 ACC transformation into crystalline calcite aggregates, (3 formation of larger calcite crystal units and (4 rapid growth of calcite as columnar structure with preferential crystal orientation. The current article detailed the quantitative analysis performed at the four stages of shell mineralization to determine the proteins which are the most abundant. Additionally, we reported the enriched GO terms and described the presence of 35 antimicrobial proteins equally distributed at all stages to keep the egg free of bacteria and of 81 proteins, the function of which could not be ascribed.

  3. Matrix metalloproteinases in lung biology

    Directory of Open Access Journals (Sweden)

    Parks William C

    2000-12-01

    Full Text Available Abstract Despite much information on their catalytic properties and gene regulation, we actually know very little of what matrix metalloproteinases (MMPs do in tissues. The catalytic activity of these enzymes has been implicated to function in normal lung biology by participating in branching morphogenesis, homeostasis, and repair, among other events. Overexpression of MMPs, however, has also been blamed for much of the tissue destruction associated with lung inflammation and disease. Beyond their role in the turnover and degradation of extracellular matrix proteins, MMPs also process, activate, and deactivate a variety of soluble factors, and seldom is it readily apparent by presence alone if a specific proteinase in an inflammatory setting is contributing to a reparative or disease process. An important goal of MMP research will be to identify the actual substrates upon which specific enzymes act. This information, in turn, will lead to a clearer understanding of how these extracellular proteinases function in lung development, repair, and disease.

  4. Patience of matrix games

    DEFF Research Database (Denmark)

    Hansen, Kristoffer Arnsfelt; Ibsen-Jensen, Rasmus; Podolskii, Vladimir V.

    2013-01-01

    For matrix games we study how small nonzero probability must be used in optimal strategies. We show that for image win–lose–draw games (i.e. image matrix games) nonzero probabilities smaller than image are never needed. We also construct an explicit image win–lose game such that the unique optimal...

  5. Matrix comparison, Part 2

    DEFF Research Database (Denmark)

    Schneider, Jesper Wiborg; Borlund, Pia

    2007-01-01

    The present two-part article introduces matrix comparison as a formal means for evaluation purposes in informetric studies such as cocitation analysis. In the first part, the motivation behind introducing matrix comparison to informetric studies, as well as two important issues influencing such c...

  6. Unitarity of CKM Matrix

    CERN Document Server

    Saleem, M

    2002-01-01

    The Unitarity of the CKM matrix is examined in the light of the latest available accurate data. The analysis shows that a conclusive result cannot be derived at present. Only more precise data can determine whether the CKM matrix opens new vistas beyond the standard model or not.

  7. Fuzzy risk matrix

    International Nuclear Information System (INIS)

    Markowski, Adam S.; Mannan, M. Sam

    2008-01-01

    A risk matrix is a mechanism to characterize and rank process risks that are typically identified through one or more multifunctional reviews (e.g., process hazard analysis, audits, or incident investigation). This paper describes a procedure for developing a fuzzy risk matrix that may be used for emerging fuzzy logic applications in different safety analyses (e.g., LOPA). The fuzzification of frequency and severity of the consequences of the incident scenario are described which are basic inputs for fuzzy risk matrix. Subsequently using different design of risk matrix, fuzzy rules are established enabling the development of fuzzy risk matrices. Three types of fuzzy risk matrix have been developed (low-cost, standard, and high-cost), and using a distillation column case study, the effect of the design on final defuzzified risk index is demonstrated

  8. Fuzzy vulnerability matrix

    International Nuclear Information System (INIS)

    Baron, Jorge H.; Rivera, S.S.

    2000-01-01

    The so-called vulnerability matrix is used in the evaluation part of the probabilistic safety assessment for a nuclear power plant, during the containment event trees calculations. This matrix is established from what is knows as Numerical Categories for Engineering Judgement. This matrix is usually established with numerical values obtained with traditional arithmetic using the set theory. The representation of this matrix with fuzzy numbers is much more adequate, due to the fact that the Numerical Categories for Engineering Judgement are better represented with linguistic variables, such as 'highly probable', 'probable', 'impossible', etc. In the present paper a methodology to obtain a Fuzzy Vulnerability Matrix is presented, starting from the recommendations on the Numerical Categories for Engineering Judgement. (author)

  9. Transcriptional Inhibition of Matrix Metal loproteinase 9 (MMP-9 Activity by a c-fos/Estrogen Receptor Fusion Protein is Mediated by the Proximal AP-1 Site of the MMP-9 Promoter and Correlates with Reduced Tumor Cell Invasion

    Directory of Open Access Journals (Sweden)

    David L. Crowe

    1999-10-01

    Full Text Available Tumor cell invasion of basement membranes is one of the hallmarks of malignant transformation. Tumor cells secrete proteolytic enzymes known as matrix metalloproteinases (MMPs which degrade extracellular matrix molecules. Increased expression of MMP-9 has been associated with acquisition of invasive phenotype in many tumors. However, multiple mechanisms for regulation of MMP-9 gene expression by tumor cell lines have been proposed. A number of transcription factor binding sites have been characterized in the upstream regulatory region of the MMP-9 gene, including those for AP-1. To determine how a specific AP-1 family member, c-fos, regulates MMP-9 promoter activity through these sites, we used an expression vector containing the c-fos coding region fused to the estrogen receptor (ER ligand binding domain. This construct is activated upon binding estradiol. Stable expression of this construct in ER negative squamous cell carcinoma (SCC lines produced an estradiol dependent decrease in the number of cells that migrated through a reconstituted basement membrane. This decreased invasiveness was accompanied by estradiol dependent downregulation of MMP-9 activity as determined by gelatin zymography. Estradiol also produced transcriptional downregulation of an MMP-9 promoter construct in cells transiently transfected with the c-fosER expression vector. This downregulation was mediated by the AP-1 site at —79 by in the MMP-9 promoter. We concluded that the proximal AP-1 site mediated the transcriptional downregulation of the MMP-9 promoter by a conditionally activated c-fos fusion protein.

  10. cAMP-response Element-binding Protein (CREB) and NF-κB Transcription Factors Are Activated during Prolonged Hypoxia and Cooperatively Regulate the Induction of Matrix Metalloproteinase MMP1*

    Science.gov (United States)

    Nakayama, Koh

    2013-01-01

    Responses to low levels of oxygen (hypoxia) are essential to maintain homeostasis. During the hypoxic response, gene expression is altered by various transcription factors. The transcription factor, hypoxia-inducible factor (HIF), plays a central role in the hypoxic response. The α subunit of HIF, which is actively degraded during normoxia, becomes stabilized during hypoxia, which leads to HIF activation. A microarray analysis of HeLa cells showed that expression of matrix metalloproteinase 1 (MMP1) was markedly induced during prolonged hypoxia. CREB and NF-κB binding sites were identified in the MMP1 promoter region between 1945 and 1896 nucleotides upstream of the transcription start site. Assays with luciferase reporters demonstrated that HIF activity was induced during the early phase of hypoxia, whereas CREB and NF-κB were activated during the later (prolonged) phase. Depletion of CREB and/or NF-κB reduced MMP1 induction during prolonged hypoxia both at the mRNA and protein levels. A chromatin immunoprecipitation assay demonstrated binding of CREB and NF-κB to the MMP1 promoter. Finally, cell migration and invasion on a collagen matrix and pulmonary metastasis in nude mice were inhibited after depletion of CREB and NF-κB in MDA-MB-231 cells. Taken together, these results suggest that the cooperative action of CREB and NF-κB plays an important role to induce MMP1 expression during prolonged hypoxia and regulates cell migration and invasion in cancer cells. PMID:23775082

  11. The nuclear reaction matrix

    International Nuclear Information System (INIS)

    Krenciglowa, E.M.; Kung, C.L.; Kuo, T.T.S.; Osnes, E.; and Department of Physics, State University of New York at Stony Brook, Stony Brook, New York 11794)

    1976-01-01

    Different definitions of the reaction matrix G appropriate to the calculation of nuclear structure are reviewed and discussed. Qualitative physical arguments are presented in support of a two-step calculation of the G-matrix for finite nuclei. In the first step the high-energy excitations are included using orthogonalized plane-wave intermediate states, and in the second step the low-energy excitations are added in, using harmonic oscillator intermediate states. Accurate calculations of G-matrix elements for nuclear structure calculations in the Aapprox. =18 region are performed following this procedure and treating the Pauli exclusion operator Q 2 /sub p/ by the method of Tsai and Kuo. The treatment of Q 2 /sub p/, the effect of the intermediate-state spectrum and the energy dependence of the reaction matrix are investigated in detail. The present matrix elements are compared with various matrix elements given in the literature. In particular, close agreement is obtained with the matrix elements calculated by Kuo and Brown using approximate methods

  12. Clay matrix voltammetry

    International Nuclear Information System (INIS)

    Perdicakis, Michel

    2012-01-01

    Document available in extended abstract form only. In many countries, it is planned that the long life highly radioactive nuclear spent fuel will be stored in deep argillaceous rocks. The sites selected for this purpose are anoxic and satisfy several recommendations as mechanical stability, low permeability and low redox potential. Pyrite (FeS 2 ), iron(II) carbonate, iron(II) bearing clays and organic matter that are present in very small amounts (about 1% w:w) in soils play a major role in their reactivity and are considered today as responsible for the low redox potential values of these sites. In this communication, we describe an electrochemical technique derived from 'Salt matrix voltammetry' and allowing the almost in-situ voltammetric characterization of air-sensitive samples of soils after the only addition of the minimum humidity required for electrolytic conduction. Figure 1 shows the principle of the developed technique. It consists in the entrapment of the clay sample between a graphite working electrode and a silver counter/quasi-reference electrode. The sample was previously humidified by passing a water saturated inert gas through the electrochemical cell. The technique leads to well-defined voltammetric responses of the electro-active components of the clays. Figure 2 shows a typical voltammogram relative to a Callovo-Oxfordian argillite sample from Bure, the French place planned for the underground nuclear waste disposal. During the direct scan, one can clearly distinguish the anodic voltammetric signals for the oxidation of the iron (II) species associated with the clay and the oxidation of pyrite. The reverse scan displays a small cathodic signal for the reduction of iron (III) associated with the clay that demonstrates that the majority of the previously oxidized iron (II) species were transformed into iron (III) oxides reducible at lower potentials. When a second voltammetric cycle is performed, one can notice that the signal for iron (II

  13. Matrix groups for undergraduates

    CERN Document Server

    Tapp, Kristopher

    2005-01-01

    Matrix groups touch an enormous spectrum of the mathematical arena. This textbook brings them into the undergraduate curriculum. It makes an excellent one-semester course for students familiar with linear and abstract algebra and prepares them for a graduate course on Lie groups. Matrix Groups for Undergraduates is concrete and example-driven, with geometric motivation and rigorous proofs. The story begins and ends with the rotations of a globe. In between, the author combines rigor and intuition to describe basic objects of Lie theory: Lie algebras, matrix exponentiation, Lie brackets, and maximal tori.

  14. Elementary matrix theory

    CERN Document Server

    Eves, Howard

    1980-01-01

    The usefulness of matrix theory as a tool in disciplines ranging from quantum mechanics to psychometrics is widely recognized, and courses in matrix theory are increasingly a standard part of the undergraduate curriculum.This outstanding text offers an unusual introduction to matrix theory at the undergraduate level. Unlike most texts dealing with the topic, which tend to remain on an abstract level, Dr. Eves' book employs a concrete elementary approach, avoiding abstraction until the final chapter. This practical method renders the text especially accessible to students of physics, engineeri

  15. Structural properties of matrix metalloproteinases.

    Science.gov (United States)

    Bode, W; Fernandez-Catalan, C; Tschesche, H; Grams, F; Nagase, H; Maskos, K

    1999-04-01

    Matrix metalloproteinases (MMPs) are involved in extracellular matrix degradation. Their proteolytic activity must be precisely regulated by their endogenous protein inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). Disruption of this balance results in serious diseases such as arthritis, tumour growth and metastasis. Knowledge of the tertiary structures of the proteins involved is crucial for understanding their functional properties and interference with associated dysfunctions. Within the last few years, several three-dimensional MMP and MMP-TIMP structures became available, showing the domain organization, polypeptide fold and main specificity determinants. Complexes of the catalytic MMP domains with various synthetic inhibitors enabled the structure-based design and improvement of high-affinity ligands, which might be elaborated into drugs. A multitude of reviews surveying work done on all aspects of MMPs have appeared in recent years, but none of them has focused on the three-dimensional structures. This review was written to close the gap.

  16. Hacking the Matrix.

    Science.gov (United States)

    Czerwinski, Michael; Spence, Jason R

    2017-01-05

    Recently in Nature, Gjorevski et al. (2016) describe a fully defined synthetic hydrogel that mimics the extracellular matrix to support in vitro growth of intestinal stem cells and organoids. The hydrogel allows exquisite control over the chemical and physical in vitro niche and enables identification of regulatory properties of the matrix. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. The Matrix Organization Revisited

    DEFF Research Database (Denmark)

    Gattiker, Urs E.; Ulhøi, John Parm

    1999-01-01

    This paper gives a short overview of matrix structure and technology management. It outlines some of the characteristics and also points out that many organizations may actualy be hybrids (i.e. mix several ways of organizing to allocate resorces effectively).......This paper gives a short overview of matrix structure and technology management. It outlines some of the characteristics and also points out that many organizations may actualy be hybrids (i.e. mix several ways of organizing to allocate resorces effectively)....

  18. Modulation of extracellular matrix proteins and hepatate stellate cell activation following gadolinium chloride induced Kuffer cell blockade in an experimental model of liver fibrosis/cirrhosis

    Directory of Open Access Journals (Sweden)

    Nilgün Tekkesin

    2013-06-01

    Full Text Available Hepatic fibrosis is now regarded as a common response to chronic liver injury; regardless of its nature (viral infections, alcohol abuse and metal overload. It is also characterized by excessive deposition of extracellular matrix (ECM components. The ECM is a dynamic complex of macromolecules that includes collagens, glycoproteins, and proteoglycans, such as laminin and fibronectin; it has been shown that it does not only support the tissue structure, but also plays a major role in cell adhesion, proliferation, and differentiation. Remodelling of the ECM may be the signal that facilitates lobular reorganization during liver regeneration after a liver injury. Much work has been done concerning the ECM synthesis and protein contents.

  19. Multifaceted role of matrix metalloproteinases (MMPs)

    OpenAIRE

    Singh, Divya; Srivastava, Sanjeev K.; Chaudhuri, Tapas K.; Upadhyay, Ghanshyam

    2015-01-01

    Matrix metalloproteinases (MMPs), a large family of calcium-dependent zinc-containing endopeptidases, are involved in the tissue remodeling and degradation of the extracellular matrix. MMPs are widely distributed in the brain and regulate various processes including microglial activation, inflammation, dopaminergic apoptosis, blood-brain barrier disruption, and modulation of ?-synuclein pathology. High expression of MMPs is well documented in various neurological disorders including Parkinson...

  20. Matrix metalloproteinases in exercise and obesity

    OpenAIRE

    Jaoude, Jonathan; Koh, Yunsuk

    2016-01-01

    Jonathan Jaoude,1 Yunsuk Koh2 1Department of Biology, 2Department of Health, Human Performance, and Recreation, Baylor University, Waco, TX, USA Abstract: Matrix metalloproteinases (MMPs) are zinc- and calcium-dependent endoproteinases that have the ability to break down extracellular matrix. The large range of MMPs’ functions widens their spectrum of potential role as activators or inhibitors in tissue remodeling, cardiovascular diseases, and obesity. In particular, MMP-1, -2, and ...

  1. Matrix Information Geometry

    CERN Document Server

    Bhatia, Rajendra

    2013-01-01

    This book is an outcome of the Indo-French Workshop on Matrix Information Geometries (MIG): Applications in Sensor and Cognitive Systems Engineering, which was held in Ecole Polytechnique and Thales Research and Technology Center, Palaiseau, France, in February 23-25, 2011. The workshop was generously funded by the Indo-French Centre for the Promotion of Advanced Research (IFCPAR).  During the event, 22 renowned invited french or indian speakers gave lectures on their areas of expertise within the field of matrix analysis or processing. From these talks, a total of 17 original contribution or state-of-the-art chapters have been assembled in this volume. All articles were thoroughly peer-reviewed and improved, according to the suggestions of the international referees. The 17 contributions presented  are organized in three parts: (1) State-of-the-art surveys & original matrix theory work, (2) Advanced matrix theory for radar processing, and (3) Matrix-based signal processing applications.  

  2. Preferential binding of DNA primase to the nuclear matrix

    International Nuclear Information System (INIS)

    Wood, S.H.; Collins, J.M.

    1986-01-01

    Several lines of research have stimulated interest in the nuclear matrix as the subcellular site of DNA replication. The authors have recently reported a relationship between rates of DNA synthesis and the differential binding of polymerase α to the nuclear matrix. They now report the detection of DNA primase bound to the HeLa nuclear matrix. Matrix-bound primase can be measured either indirectly, by the incorporation of [ 32 P] dAMP into an unprimed single-stranded template, or directly, by the incorporation of [ 3 H] AMP into matrix DNA. Characteristics of this system include a requirement for ATP, inhibition by adenosine-5'-0-(3'-thiotriphosphate), a primase inhibitor, and insensitivity to aphidicolin and α-amanitine, inhibitors of polymerase α and RNA polymerase, respectively. Subcellular quantification of primase and polymerase α activity revealed that while a majority of primase activity is bound to the matrix (72%), only 32% of polymerase α activity is matrix-bound. Treatment of the nuclear matrix with β-D-Octylglucoside allowed the solubilization of 54% of primase activity and 39% of polymerase α activity. This data provides further evidence of a structural and functional role for the nuclear matrix in DNA replication. The ability to solubilize matrix-bound replicative enzymes may prove to be an important tool in the elucidation of the spatial organization of DNA replication

  3. Extracellular matrix metalloproteinase inducer (EMMPRIN) expression correlates positively with active angiogenesis and negatively with basic fibroblast growth factor expression in epithelial ovarian cancer.

    Science.gov (United States)

    Szubert, Sebastian; Szpurek, Dariusz; Moszynski, Rafal; Nowicki, Michal; Frankowski, Andrzej; Sajdak, Stefan; Michalak, Slawomir

    2014-03-01

    The primary aim of this paper was to evaluate the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and its relationship with proangiogenic factors and microvessel density (MVD) in ovarian cancer. The study group included 58 epithelial ovarian cancers (EOCs), 35 benign ovarian tumors, and 21 normal ovaries. The expression of EMMPRIN, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) was assessed by ELISA of tissue homogenates. Antibodies against CD105, CD31, and CD34 were used to immunohistochemically assess MVD. We have found significantly higher EMMPRIN expression in EOC than in benign ovarian tumors and normal ovaries. Similarly, the VEGF expression was higher in EOC than in benign ovarian tumors and normal ovaries. By contrast, bFGF expression was lower in EOC than in benign ovarian tumors and ovary samples. EMMPRIN expression in EOC was directly correlated with VEGF expression and CD105-MVD, but inversely correlated with bFGF expression. Grade 2/3 ovarian cancers had increased expression of EMMPRIN and VEGF, increased CD105-MVD, and lowered expression of bFGF compared to grade 1 ovarian cancers. Moreover, EMMPRIN expression was higher in advanced (FIGO III and IV) ovarian cancer. The upregulation of EMMPRIN and VEGF expression is correlated with increased CD105-MVD and silenced bFGF, which suggests early and/or reactivated angiogenesis in ovarian cancer. Aggressive EOC is characterized by the following: high expression of EMMPRIN and VEGF, high CD105-MVD, and low expression of bFGF.

  4. A novel interaction between calcium-modulating cyclophilin ligand and Basigin regulates calcium signaling and matrix metalloproteinase activities in human melanoma cells.

    Science.gov (United States)

    Long, Tingting; Su, Juan; Tang, Wen; Luo, Zhongling; Liu, Shuang; Liu, Zhaoqian; Zhou, Honghao; Qi, Min; Zeng, Weiqi; Zhang, Jianglin; Chen, Xiang

    2013-10-01

    Intracellular free calcium is a ubiquitous second messenger regulating a multitude of normal and pathogenic cellular responses, including the development of melanoma. Upstream signaling pathways regulating the intracellular free calcium concentration ([Ca2+]i) may therefore have a significant impact on melanoma growth and metastasis. In this study, we demonstrate that the endoplasmic reticulum (ER)-associated protein calcium-modulating cyclophilin ligand (CAML) is bound to Basigin, a widely expressed integral plasma membrane glycoprotein and extracellular matrix metalloproteinase inducer (EMMPRIN, or CD147) implicated in melanoma proliferation, invasiveness, and metastasis. This interaction between CAML and Basigin was first identified using yeast two-hybrid screening and further confirmed by co-immunoprecipitation. In human A375 melanoma cells, CAML and Basigin were co-localized to the ER. Knockdown of Basigin in melanoma cells by siRNA significantly decreased resting [Ca2+]i and the [Ca2+]i increase induced by the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) inhibitor thapsigargin (TG), indicating that the interaction between CAML and Basigin regulates ER-dependent [Ca2+]i signaling. Meanwhile upregulating the [Ca2+]i either by TG or phorbol myristate acetate (PMA) could stimulate the production of MMP-9 in A375 cells with the expression of Basigin. Our study has revealed a previously uncharacterized [Ca2+]i signaling pathway that may control melanoma invasion, and metastasis. Disruption of this pathway may be a novel therapeutic strategy for melanoma treatment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Insulin Promotes the Proliferation of Human Umbilical Cord Matrix-Derived Mesenchymal Stem Cells by Activating the Akt-Cyclin D1 Axis

    Directory of Open Access Journals (Sweden)

    Peng Li

    2017-01-01

    Full Text Available Background. The functions of insulin in mesenchymal stem cells (MSC remain poorly understood. Methods. MSC from human umbilical cord matrix (UCM cultured in serum-free media (SFM with or without insulin were subjected to various molecular biological analyses to determine their proliferation and growth states, expression levels of Akt-cyclin D1 signaling molecules, and in vitro differentiation capacities. Results. Insulin accelerated the G1-S cell cycle progression of UCM-MSC and significantly stimulated their proliferation and growth in SFM. The pro-proliferative action of insulin was associated with augmented cyclin D1 and phosphorylated Akt expression levels. Akt inactivation remarkably abrogated insulin-induced increases in cyclin D1 expression and cell proliferation, indicating that insulin enhances the proliferation of UCM-MSC via acceleration of the G1-S transition mediated by the Akt-cyclin D1 pathway. Additionally, the UCM-MSC propagated in SFM supplemented with insulin exhibited similar specific surface antigen profiles and differentiation capacities as those generated in conventional media containing fetal bovine serum. Conclusions. These findings suggest that insulin acts solely to promote UCM-MSC proliferation without affecting their immunophenotype and differentiation potentials and thus have important implications for utilizing insulin to expand clinical-grade MSC in vitro.

  6. Instant screening and verification of carbapenemase activity in Bacteroides fragilis in positive blood culture, using matrix-assisted laser desorption ionization--time of flight mass spectrometry.

    Science.gov (United States)

    Johansson, Åsa; Nagy, Elisabeth; Sóki, József

    2014-08-01

    Rapid identification of isolates in positive blood cultures are of great importance to secure correct treatment of septicaemic patients. As antimicrobial resistance is increasing, rapid detection of resistance is crucial. Carbapenem resistance in Bacteroides fragilis associated with cfiA-encoded class B metallo-beta-lactamase is emerging. In our study we spiked blood culture bottles with 26 B. fragilis strains with various cfiA-status and ertapenem MICs. By using main spectra specific for cfiA-positive and cfiA-negative B. fragilis strains, isolates could be screened for resistance. To verify strains that were positive in the screening, a carbapenemase assay was performed where the specific peaks of intact and hydrolysed ertapenem were analysed with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). We show here that it is possible to correctly identify B. fragilis and to screen for enzymic carbapenem resistance directly from the pellet of positive blood cultures. The carbapenemase assay to verify the presence of the enzyme was successfully performed on the pellet from the direct identification despite the presence of blood components. The result of the procedure was achieved in 3 h. Also the Bruker mass spectrometric β-lactamase assay (MSBL assay) prototype software was proven not only to be based on an algorithm that correlated with the manual inspection of the spectra, but also to improve the interpretation by showing the variation in the dataset. © 2014 The Authors.

  7. Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry rapid detection of carbapenamase activity in Acinetobacter baumannii isolates

    Directory of Open Access Journals (Sweden)

    Noha Abouseada

    2017-01-01

    Full Text Available Introduction: Carbapenamase-producing Acinetobacter baumannii are an increasing threat in hospitals and Intensive Care Units. Accurate and rapid detection of carbapenamase producers has a great impact on patient improvement and aids in implementation of infection control measures. Aim: In this study, we describe the use of matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI TOF MS to identify carbapenamase-producing A. baumannii isolates in up to 3 h. Isolates and Methods: A total of 50 A. baumannii isolates (of which 39 were carabapenamase producers were tested using MALDI TOF MS. Isolates were incubated for 3 h with 0.25 mg/ml up to 2 mg/ml of imipenem (IMP at 37°C. Supernatants were analysed by MALDI TOF to analyse peaks corresponding to IMP (300 Da and an IMP metabolite (254 Da using UltrafleXtreme (Bruker Daltonics, Bremen, Germany. Results: All carbapenamase-producing isolates were evidenced by the disappearance or reduction in intensity of the 300 Da peak of IPM and the appearance of a 254 Da peak of the IPM metabolite. In isolates that did not produce carbapenamase, the IPM 300 Da peak remained intact. Conclusion: MALDI TOF is a promising tool in the field of diagnostic microbiology that has the ability to transfer identification and antimicrobial susceptibility testing time from days to hours.

  8. Physiology and pathophysiology of matrix metalloproteases

    NARCIS (Netherlands)

    Klein, T.; Bischoff, R.

    Matrix metalloproteases (MMPs) comprise a family of enzymes that cleave protein substrates based on a conserved mechanism involving activation of an active site-bound water molecule by a Zn(2+) ion. Although the catalytic domain of MMPs is structurally highly similar, there are many differences with

  9. Physiology and pathophysiology of matrix metalloproteases

    NARCIS (Netherlands)

    Klein, T; Bischoff, Rainer

    2010-01-01

    Matrix metalloproteases (MMPs) comprise a family of enzymes that cleave protein substrates based on a conserved mechanism involving activation of an active site-bound water molecule by a Zn(2+) ion. Although the catalytic domain of MMPs is structurally highly similar, there are many differences with

  10. Elimination of matrix effects in the determination of oxygen in some non-ferrous metals by activation with 14 MeV neutrons

    International Nuclear Information System (INIS)

    Szopa, Z.; Sterlinski, S.; Tetteh, G.

    1981-01-01

    It is shown that the lower limit of detection and specificity of oxygen determination in strongly activated non-ferrous metals can be improved by means of the optimization of Pb-absorber thickness, cooling time and cyclic activation analysis. Some mathematical predictions are verified by oxygen determination in copper and yttrium. (author)

  11. Downregulation of Extracellular Matrix Metalloproteinase Inducer by scFv-M6-1B9 Intrabody Suppresses Cervical Cancer Invasion Through Inhibition of Urokinase-Type Plasminogen Activator.

    Science.gov (United States)

    Panich, Tipattaraporn; Tragoolpua, Khajornsak; Pata, Supansa; Tayapiwatana, Chatchai; Intasai, Nutjeera

    2017-02-01

    Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN) accelerates tumor invasion and metastasis via activation of matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA) expression. The authors were interested in whether the scFv-M6-1B9 intrabody against EMMPRIN that retains EMMPRIN in endoplasmic reticulum could be a potential tool to suppress cervical cancer invasion through inhibition of uPA. The chimeric adenoviral vector Ad5/F35-scFv-M6-1B9 was transferred into human cervical carcinoma HeLa cells to produce the scFv-M6-1B9 intrabody against EMMPRIN. Cell surface expression of EMMPRIN, the membrane-bound uPA, the enzymatic activity of secreted uPA, and the invasion ability were analyzed. The scFv-M6-1B9 intrabody successfully diminished the cell surface expression of EMMPRIN and the membrane-bound uPA on HeLa cells. uPA activity from tissue culture media of EMMPRIN-downregulated HeLa cells was decreased. The invasion ability of HeLa cells harboring scFv-M6-1B9 intrabody was also suppressed. These results suggested that the scFv-M6-1B9 intrabody might represent a potential approach for invasive cervical cancer treatment. The application of scFv-M6-1B9 intrabody in animal experiments and preclinical studies would be investigated further.

  12. Aryl hydrocarbon receptor pathway activation enhances gastric cancer cell invasiveness likely through a c-Jun-dependent induction of matrix metalloproteinase-9

    Directory of Open Access Journals (Sweden)

    Song Xin

    2009-04-01

    Full Text Available Abstract Background Abberant aryl hydrocarbon receptor (AhR expression and AhR pathway activation are involved in gastric carcinogenesis. However, the relationship between AhR pathway activation and gastric cancer progression is still unclear. In present study, we used 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD, a classic and most potent ligand of AhR, to activate AhR pathway and investigated the effect of AhR pathway activation on human gastric cancer AGS cell invasion and explored the corresponding mechanism. Results To determine whether AhR pathway can be activated in AGS cells, we examined the expression of CYP1A1, a classic target gene of AhR pathway, following TCDD exposure. RT-PCR and western blot analysis showed that both CYP1A1 mRNA and protein expression were increased in a dose-dependent manner following TCDD treatment and AhR antagonist resveratrol (RSV could reverse this TCDD-induced CYP1A1 expression. To determine whether TCDD treatment of AGS cells results in an induction of MMP-9 expression, we detected MMP-9 mRNA using RT-PCR and detected MMP-9 enzymatic activity using gelatin zymography. The results showed that both MMP-9 mRNA expression and enzymatic activity were gradually increased with the concentration increase of TCDD in media and these changes could be reversed by RSV treatment in a dose-dependent manner. To examine whether AhR activation-induced MMP-9 expression and activity in AGS cells results in increased migration and invasion, we performed wound healing migration assay and transwell migration and invasion assay. After TCDD treatment, the migration distance and the migration and invasion abilities of AGS cells were increased with a dose-dependent manner. To demonstrate AhR activation-induced MMP-9 expression is mediated by c-Jun, siRNA transfection was performed to silence c-Jun mRNA in AGS cells. The results showed that MMP-9 mRNA expression and activity in untreated control AGS cells were very weak; After TCDD

  13. 2016 MATRIX annals

    CERN Document Server

    Praeger, Cheryl; Tao, Terence

    2018-01-01

    MATRIX is Australia’s international, residential mathematical research institute. It facilitates new collaborations and mathematical advances through intensive residential research programs, each lasting 1-4 weeks. This book is a scientific record of the five programs held at MATRIX in its first year, 2016: Higher Structures in Geometry and Physics (Chapters 1-5 and 18-21); Winter of Disconnectedness (Chapter 6 and 22-26); Approximation and Optimisation (Chapters 7-8); Refining C*-Algebraic Invariants for Dynamics using KK-theory (Chapters 9-13); Interactions between Topological Recursion, Modularity, Quantum Invariants and Low-dimensional Topology (Chapters 14-17 and 27). The MATRIX Scientific Committee selected these programs based on their scientific excellence and the participation rate of high-profile international participants. Each program included ample unstructured time to encourage collaborative research; some of the longer programs also included an embedded conference or lecture series. The artic...

  14. Matrix interdiction problem

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Feng [Los Alamos National Laboratory; Kasiviswanathan, Shiva [Los Alamos National Laboratory

    2010-01-01

    In the matrix interdiction problem, a real-valued matrix and an integer k is given. The objective is to remove k columns such that the sum over all rows of the maximum entry in each row is minimized. This combinatorial problem is closely related to bipartite network interdiction problem which can be applied to prioritize the border checkpoints in order to minimize the probability that an adversary can successfully cross the border. After introducing the matrix interdiction problem, we will prove the problem is NP-hard, and even NP-hard to approximate with an additive n{gamma} factor for a fixed constant {gamma}. We also present an algorithm for this problem that achieves a factor of (n-k) mUltiplicative approximation ratio.

  15. Dynamic Matrix Rank

    DEFF Research Database (Denmark)

    Frandsen, Gudmund Skovbjerg; Frandsen, Peter Frands

    2009-01-01

    We consider maintaining information about the rank of a matrix under changes of the entries. For n×n matrices, we show an upper bound of O(n1.575) arithmetic operations and a lower bound of Ω(n) arithmetic operations per element change. The upper bound is valid when changing up to O(n0.575) entries...... in a single column of the matrix. We also give an algorithm that maintains the rank using O(n2) arithmetic operations per rank one update. These bounds appear to be the first nontrivial bounds for the problem. The upper bounds are valid for arbitrary fields, whereas the lower bound is valid for algebraically...... closed fields. The upper bound for element updates uses fast rectangular matrix multiplication, and the lower bound involves further development of an earlier technique for proving lower bounds for dynamic computation of rational functions....

  16. MATLAB matrix algebra

    CERN Document Server

    Pérez López, César

    2014-01-01

    MATLAB is a high-level language and environment for numerical computation, visualization, and programming. Using MATLAB, you can analyze data, develop algorithms, and create models and applications. The language, tools, and built-in math functions enable you to explore multiple approaches and reach a solution faster than with spreadsheets or traditional programming languages, such as C/C++ or Java. MATLAB Matrix Algebra introduces you to the MATLAB language with practical hands-on instructions and results, allowing you to quickly achieve your goals. Starting with a look at symbolic and numeric variables, with an emphasis on vector and matrix variables, you will go on to examine functions and operations that support vectors and matrices as arguments, including those based on analytic parent functions. Computational methods for finding eigenvalues and eigenvectors of matrices are detailed, leading to various matrix decompositions. Applications such as change of bases, the classification of quadratic forms and ...

  17. Elementary matrix algebra

    CERN Document Server

    Hohn, Franz E

    2012-01-01

    This complete and coherent exposition, complemented by numerous illustrative examples, offers readers a text that can teach by itself. Fully rigorous in its treatment, it offers a mathematically sound sequencing of topics. The work starts with the most basic laws of matrix algebra and progresses to the sweep-out process for obtaining the complete solution of any given system of linear equations - homogeneous or nonhomogeneous - and the role of matrix algebra in the presentation of useful geometric ideas, techniques, and terminology.Other subjects include the complete treatment of the structur

  18. Complex matrix model duality

    International Nuclear Information System (INIS)

    Brown, T.W.

    2010-11-01

    The same complex matrix model calculates both tachyon scattering for the c=1 non-critical string at the self-dual radius and certain correlation functions of half-BPS operators in N=4 super- Yang-Mills. It is dual to another complex matrix model where the couplings of the first model are encoded in the Kontsevich-like variables of the second. The duality between the theories is mirrored by the duality of their Feynman diagrams. Analogously to the Hermitian Kontsevich- Penner model, the correlation functions of the second model can be written as sums over discrete points in subspaces of the moduli space of punctured Riemann surfaces. (orig.)

  19. Complex matrix model duality

    Energy Technology Data Exchange (ETDEWEB)

    Brown, T.W.

    2010-11-15

    The same complex matrix model calculates both tachyon scattering for the c=1 non-critical string at the self-dual radius and certain correlation functions of half-BPS operators in N=4 super- Yang-Mills. It is dual to another complex matrix model where the couplings of the first model are encoded in the Kontsevich-like variables of the second. The duality between the theories is mirrored by the duality of their Feynman diagrams. Analogously to the Hermitian Kontsevich- Penner model, the correlation functions of the second model can be written as sums over discrete points in subspaces of the moduli space of punctured Riemann surfaces. (orig.)

  20. Anti–elastase, anti–tyrosinase and matrix metalloproteinase–1 inhibitory activity of earthworm extracts as potential new anti–aging agent

    Directory of Open Access Journals (Sweden)

    Nurhazirah Azmi

    2014-05-01

    Conclusions: Earthworms extract showed effective inhibition of tyrosinase, elastase and MMP-1 activities. Therefore, this experiment further rationalizes the traditional use of this worm extracts which may be useful as an anti-wrinkle agent.

  1. Correcting the effects of the matrix using capture gamma-ray spectrometry: Application to measurement by Active Neutron Interrogation; Correction des effets de matrice par spectrometrie des rayonnements gamma de capture: Application a la mesure par Interrogation Neutronique Active (I.N.A.)

    Energy Technology Data Exchange (ETDEWEB)

    Baudry, G.

    2003-11-15

    In the field of the measurement of low masses of fissile material ({sup 235}U, {sup 239}Pu, {sup 241}Pu) in radioactive waste drums, the Active Neutron Interrogation is a non-destructive method achieving good results. It does however remain reliant upon uncertainties related to the matrix effects on interrogation and fission neutrons. The aim of this thesis is to develop a correction method able to take into account these matrix effects by quantifying the amount of absorbent materials (chlorine and hydrogen) in a 118- liter homogeneous matrix. The main idea is to use the gamma-ray spectrometry of gamma emitted by neutron captures to identify and quantify the composition of the matrix. An indicator from its chlorine content is then deduced in order to choose the calibration coefficient which best represents the real composition of the matrix. This document firstly presents the needs of control and characterization of radioactive objects, and the means used in the field of nuclear measurement. Emphases is put in particular on the Active Neutron Interrogation method. The matrices of interest are those made of light technological waste (density {<=} 0,4 g/cm{sup 3}) containing hydrogenated and chlorinated materials. The advantages of gamma-rays emitted by neutron captures for the determination of a chlorine content indicator of the matrices and the principles of the correction method are then explained. Measurements have been firstly realized with an existing Neutron Interrogation device (PROMETHEE 6). Such measurements have proven its inadequacy: no signal from the matrix hydrogen was detected, due to an intense signal from the polyethylene contained in some cell elements. Moreover, the matrix chlorine content appeared difficult to be measured. A new and specific device, named REGAIN and dedicated to active gamma-rays spectrometry, was defined with the Monte-Carlo N-Particle (MCNP) code. The experiments conducted with this new device made it possible to detect the

  2. Ethical Matrix Manual

    NARCIS (Netherlands)

    Mepham, B.; Kaiser, M.; Thorstensen, E.; Tomkins, S.; Millar, K.

    2006-01-01

    The ethical matrix is a conceptual tool designed to help decision-makers (as individuals or working in groups) reach sound judgements or decisions about the ethical acceptability and/or optimal regulatory controls for existing or prospective technologies in the field of food and agriculture.

  3. Combinatorial matrix theory

    CERN Document Server

    Mitjana, Margarida

    2018-01-01

    This book contains the notes of the lectures delivered at an Advanced Course on Combinatorial Matrix Theory held at Centre de Recerca Matemàtica (CRM) in Barcelona. These notes correspond to five series of lectures. The first series is dedicated to the study of several matrix classes defined combinatorially, and was delivered by Richard A. Brualdi. The second one, given by Pauline van den Driessche, is concerned with the study of spectral properties of matrices with a given sign pattern. Dragan Stevanović delivered the third one, devoted to describing the spectral radius of a graph as a tool to provide bounds of parameters related with properties of a graph. The fourth lecture was delivered by Stephen Kirkland and is dedicated to the applications of the Group Inverse of the Laplacian matrix. The last one, given by Ángeles Carmona, focuses on boundary value problems on finite networks with special in-depth on the M-matrix inverse problem.

  4. Visualizing Matrix Multiplication

    Science.gov (United States)

    Daugulis, Peteris; Sondore, Anita

    2018-01-01

    Efficient visualizations of computational algorithms are important tools for students, educators, and researchers. In this article, we point out an innovative visualization technique for matrix multiplication. This method differs from the standard, formal approach by using block matrices to make computations more visual. We find this method a…

  5. Challenging the CSCW matrix

    DEFF Research Database (Denmark)

    Jørnø, Rasmus Leth Vergmann; Gynther, Karsten; Christensen, Ove

    2014-01-01

    useful information, we question whether the axis of time and space comprising the matrix pertains to relevant defining properties of the tools, technology or learning environments to which they are applied. Subsequently we offer an example of an Adobe Connect e-learning session as an illustration...

  6. Matrix metalloproteinase-12 (MMP-12) in osteoclasts

    DEFF Research Database (Denmark)

    Hou, Peng; Troen, Tine; Ovejero, Maria C

    2004-01-01

    Osteoclasts require matrix metalloproteinase (MMP) activity and cathepsin K to resorb bone, but the critical MMP has not been identified. Osteoclasts express MMP-9 and MMP-14, which do not appear limiting for resorption, and the expression of additional MMPs is not clear. MMP-12, also called...... bone show MMP-12 expression in osteoclasts in calvariae and long bones. We also demonstrate that recombinant MMP-12 cleaves the putative functional domains of osteopontin and bone sialoprotein, two bone matrix proteins that strongly influence osteoclast activities, such as attachment, spreading...

  7. Activation of the Wnt/β-catenin signaling pathway by mechanical ventilation is associated with ventilator-induced pulmonary fibrosis in healthy lungs.

    Directory of Open Access Journals (Sweden)

    Jesús Villar

    Full Text Available BACKGROUND: Mechanical ventilation (MV with high tidal volumes (V(T can cause or aggravate lung damage, so-called ventilator induced lung injury (VILI. The relationship between specific mechanical events in the lung and the cellular responses that result in VILI remains incomplete. Since activation of Wnt/β-catenin signaling has been suggested to be central to mechanisms of lung healing and fibrosis, we hypothesized that the Wnt/β-catenin signaling plays a role during VILI. METHODOLOGY/PRINCIPAL FINDINGS: Prospective, randomized, controlled animal study using adult, healthy, male Sprague-Dawley rats. Animals (n = 6/group were randomized to spontaneous breathing or two strategies of MV for 4 hours: low tidal volume (V(T (6 mL/kg or high V(T (20 mL/kg. Histological evaluation of lung tissue, measurements of WNT5A, total β-catenin, non-phospho (Ser33/37/Thr41 β-catenin, matrix metalloproteinase-7 (MMP-7, cyclin D1, vascular endothelial growth factor (VEGF, and axis inhibition protein 2 (AXIN2 protein levels by Western blot, and WNT5A, non-phospho (Ser33/37/Thr41 β-catenin, MMP-7, and AXIN2 immunohistochemical localization in the lungs were analyzed. High-V(T MV caused lung inflammation and perivascular edema with cellular infiltrates and collagen deposition. Protein levels of WNT5A, non-phospho (Ser33/37/Thr41 β-catenin, MMP-7, cyclin D1, VEGF, and AXIN2 in the lungs were increased in all ventilated animals although high-V(T MV was associated with significantly higher levels of WNT5A, non-phospho (Ser33/37/Thr41 β-catenin, MMP-7, cyclin D1, VEGF, and AXIN2 levels. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that the Wnt/β-catenin signaling pathway is modulated very early by MV in lungs without preexistent lung disease, suggesting that activation of this pathway could play an important role in both VILI and lung repair. Modulation of this pathway might represent a therapeutic option for prevention and/or management of VILI.

  8. THE ACTIVATION OF MATRIX METALLOPROTEINASES AND CHONDROCYTE DIFFERENTIATION, WHICH ACCOMPANIES THE INDUCTION OF COLLAGEN DECOMPOSITION UNDER THE ACTION OF COLLAGEN PEPTIDE IN THE CARTILAGE OFHEALTHY INDIVIDUALS

    Directory of Open Access Journals (Sweden)

    Elena Vasil'evna Chetina

    2010-01-01

    Conclusion. This study has shown that the induction of collagenase activity by CB12-2 in the human articular cartilage chondrocytes is attended by terminal differentiation/hypertrophy of these cells. The terminal differentiation of chondrocytes may be one of the mechanisms of chondrolysis in osteoarthrosis since it naturally occurs not only in endochondrial ossification, but also in the development of pathology.

  9. Solvent Stability Study with Thermodynamic Analysis and Superior Biocatalytic Activity of Burkholderia cepacia Lipase Immobilized on Biocompatible Hybrid Matrix of Poly(vinyl alcohol) and Hypromellose.

    Science.gov (United States)

    Badgujar, Kirtikumar C; Bhanage, Bhalchandra M

    2014-12-26

    In the present study, we have synthesized a biocompatible hybrid carrier of hypromellose (HY) and poly(vinyl alcohol) (PVA) for immobilization of Burkholderia cepacia lipase (BCL). The immobilized biocatalyst HY:PVA:BCL was subjected to determination of half-life time (τ) and deactivation rate constant (K(D)) in various organic solvents. Biocatalyst showed higher τ-value in a nonpolar solvent like cyclohexane (822 h) as compared to that of a polar solvent such as acetone (347 h), which signifies better compatibility of biocatalyst in the nonpolar solvents. Furthermore, the K(D)-value was found to be less in cyclohexane (0.843 × 10(-3)) as compared to acetone (1.997 × 10(-3)), indicating better stability in the nonpolar solvents. Immobilized-BCL (35 mg) was sufficient to achieve 99% conversion of phenethyl butyrate (natural constituent of essential oils and has wide industrial applications) using phenethyl alcohol (2 mmol) and vinyl butyrate (6 mmol) at 44 °C in 3 h. The activation energy (E(a)) was found to be lower for immobilized-BCL than crude-BCL, indicating better catalytic efficiency of immobilized lipase BCL. The immobilized-BCL reported 6-fold superior biocatalytic activity and 8 times recyclability as compared to crude-BCL. Improved catalytic activity of immobilized enzyme in nonpolar media was also supported by thermodynamic activation parameters such as enthalpy (ΔH(⧧)), entropy (ΔS(⧧)) and Gibb's free energy (ΔG(⧧)) study, which showed that phenethyl butyrate synthesis catalyzed by immobilized-BCL was feasible as compared to crude-BCL. The present work explains a thermodynamic investigation and superior biocatalytic activity for phenethyl butyrate synthesis using biocompatible immobilized HY:PVA:BCL in nonaqueous media for the first time.

  10. Helicobacter pylori-elicited induction in gastric mucosal matrix metalloproteinase-9 (MMP-9) release involves ERK-dependent cPLA2 activation and its recruitment to the membrane-localized Rac1/p38 complex.

    Science.gov (United States)

    Slomiany, B L; Slomiany, A

    2016-06-01

    Matrix metalloproteinases (MMPs) are a family of endopeptidases implicated in a wide rage of degenerative and inflammatory diseases, including Helicobacter pylori-associated gastritis, and gastric and duodenal ulcer. As gastric mucosal inflammatory responses to H. pylori are characterized by the rise in MMP-9 production, as well as the induction in mitogen-activated protein kinase (MAPK) and Rac1 activation, we investigated the role of Rac1/MAPK in the processes associated with the release of MMP-9. We show that H. pylori LPS-elicited induction in gastric mucosal MMP-9 release is associated with MAPK, ERK and p38 activation, and occurs with the involvement of Rac1 and cytosolic phospholipase A2 (cPLA2). Further, we demonstrate that the LPS-induced MMP-9 release requires ERK-mediated phosphorylation of cPLA2 on Ser(505) that is essential for its membrane localization with Rac1, and that this process necessitates p38 participation. Moreover, we reveal that the activation and membrane translocation of p38 to the Rac1-GTP complex plays a pivotal role in cPLA2-dependent enhancement in MMP-9 release. Hence, our findings provide a strong evidence for the role of ERK/cPLA2 and Rac1/p38/cPLA2 cascade in H. pylori LPS-induced up-regulation in gastric mucosal MMP-9 release.

  11. Receptor for advanced glycation end products - membrane type1 matrix metalloproteinase axis regulates tissue factor expression via RhoA and Rac1 activation in high-mobility group box-1 stimulated endothelial cells.

    Directory of Open Access Journals (Sweden)

    Koichi Sugimoto

    Full Text Available BACKGROUND: Atherosclerosis is understood to be a blood vessel inflammation. High-mobility group box-1 (HMGB-1 plays a key role in the systemic inflammation. Tissue factor (TF is known to lead to inflammation which promotes thrombus formation. Membrane type1 matrix metalloprotease (MT1-MMP associates with advanced glycation endproducts (AGE triggered-TF protein expression and phosphorylation of NF-κB. However, it is still unclear about the correlation of MT1-MMP and HMBG-1-mediated TF expression. In this study, we investigated the molecular mechanisms of TF expression in response to HMGB-1 stimulation and the involvement of MT1-MMP in endothelial cells. METHODS AND RESULTS: Pull-down assays and Western blotting revealed that HMGB-1 induced RhoA/Rac1 activation and NF-kB phosphorylation in cultured human aortic endothelial cells. HMGB-1 increased the activity of MT1-MMP, and inhibition of RAGE or MT1-MMP by siRNA suppressed HMGB-1-induced TF upregulation as well as HMGB-1-triggered RhoA/Rac1 activation and NF-kB phosphorylation. CONCLUSIONS: The present study showed that RAGE/MT1-MMP axis modified HMBG-1-mediated TF expression through RhoA and Rac1 activation and NF-κB phosphorylation in endothelial cells. These results suggested that MT1-MMP was involved in vascular inflammation and might be a good target for treating atherosclerosis.

  12. Control of radioactive wastes and coupling of neutron/gamma measurements: use of radiative capture for the correction of matrix effects that penalize the fissile mass measurement by active neutron interrogation

    International Nuclear Information System (INIS)

    Loche, F.

    2006-10-01

    In the framework of radioactive waste drums control, difficulties arise in the nondestructive measurement of fissile mass ( 235 U, 239 Pu..) by Active Neutron Interrogation (ANI), when dealing with matrices containing materials (Cl, H...) influencing the neutron flux. The idea is to use the neutron capture reaction (n,γ) to determine the matrix composition to adjust the ANI calibration coefficient value. This study, dealing with 118 litres, homogeneous drums of density less than 0,4 and composed of chlorinated and/or hydrogenated materials, leads to build abacus linking the γ ray peak areas to the ANI calibration coefficient. Validation assays of these abacus show a very good agreement between the corrected and true fissile masses for hydrogenated matrices (max. relative standard deviation: 23 %) and quite good for chlorinated and hydrogenated matrices (58 %). The developed correction method improves the measured values. It may be extended to 0,45 density, heterogeneous drums. (author)

  13. Matrix Management Structures in Higher Education. Coombe Lodge Working Paper. Information Bank Number 1394.

    Science.gov (United States)

    Cuthbert, Rob

    The matrix structure as an alternative to the departmental structure for colleges and universities is discussed, and the matrix system at Middlesex Polytechnic in England is used as illustration. The major impact of the introduction of a matrix structure is its effect on teaching activities within the institution. The matrix structure formally…

  14. Comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, LXR/RXR, activation that influence the status of the extracellular matrix.

    Science.gov (United States)

    Ali, Neserin; Ljunggren, Stefan; Karlsson, Helen M; Wierzbicka, Aneta; Pagels, Joakim; Isaxon, Christina; Gudmundsson, Anders; Rissler, Jenny; Nielsen, Jörn; Lindh, Christian H; Kåredal, Monica

    2018-01-01

    Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind observed symptoms is still partly lacking, although inflammation is suggested to play a central role. The aim of this study was to investigate the effects of welding fume particle exposure on the proteome expression level in welders suffering from respiratory symptoms, and changes in protein mediators in nasal lavage samples were analyzed. Such mediators will be helpful to clarify the pathomechanisms behind welding fume particle-induced effects. In an exposure chamber, 11 welders with work-related symptoms in the lower airways during the last month were exposed to mild-steel welding fume particles (1 mg/m 3 ) and to filtered air, respectively, in a double-blind manner. Nasal lavage samples were collected before, immediately after, and the day after exposure. The proteins in the nasal lavage were analyzed with two different mass spectrometry approaches, label-free discovery shotgun LC-MS/MS and a targeted selected reaction monitoring LC-MS/MS analyzing 130 proteins and four in vivo peptide degradation products. The analysis revealed 30 significantly changed proteins that were associated with two main pathways; activation of acute phase response signaling and activation of LXR/RXR, which is a nuclear receptor family involved in lipid signaling. Connective tissue proteins and proteins controlling the degradation of such tissues, including two different matrix metalloprotease proteins, MMP8 and MMP9, were among the significantly changed enzymes and were identified as important key players in the pathways. Exposure to mild-steel welding fume particles causes measurable changes on the proteome level in nasal lavage matrix in exposed welders, although no clinical symptoms were manifested. The

  15. Paths correlation matrix.

    Science.gov (United States)

    Qian, Weixian; Zhou, Xiaojun; Lu, Yingcheng; Xu, Jiang

    2015-09-15

    Both the Jones and Mueller matrices encounter difficulties when physically modeling mixed materials or rough surfaces due to the complexity of light-matter interactions. To address these issues, we derived a matrix called the paths correlation matrix (PCM), which is a probabilistic mixture of Jones matrices of every light propagation path. Because PCM is related to actual light propagation paths, it is well suited for physical modeling. Experiments were performed, and the reflection PCM of a mixture of polypropylene and graphite was measured. The PCM of the mixed sample was accurately decomposed into pure polypropylene's single reflection, pure graphite's single reflection, and depolarization caused by multiple reflections, which is consistent with the theoretical derivation. Reflection parameters of rough surface can be calculated from PCM decomposition, and the results fit well with the theoretical calculations provided by the Fresnel equations. These theoretical and experimental analyses verify that PCM is an efficient way to physically model light-matter interactions.

  16. Partially separable t matrix

    International Nuclear Information System (INIS)

    Sasakawa, T.; Okuno, H.; Ishikawa, S.; Sawada, T.

    1982-01-01

    The off-shell t matrix is expressed as a sum of one nonseparable and one separable terms so that it is useful for applications to more-than-two body problems. All poles are involved in this one separable term. Both the nonseparable and the separable terms of the kernel G 0 t are regular at the origin. The nonseparable term of this kernel vanishes at large distances, while the separable term behaves asymptotically as the spherical Hankel function. These properties make our expression free from defects inherent in the Jost or the K-matrix expressions, and many applications are anticipated. As the application, a compact expression of the many-level formula is presented. Also the application is suggested to the breakup threebody problem based on the Faddeev equation. It is demonstrated that the breakup amplitude is expressed in a simple and physically interesting form and we can calculate it in coordinate space

  17. Exactly soluble matrix models

    International Nuclear Information System (INIS)

    Raju Viswanathan, R.

    1991-09-01

    We study examples of one dimensional matrix models whose potentials possess an energy spectrum that can be explicitly determined. This allows for an exact solution in the continuum limit. Specifically, step-like potentials and the Morse potential are considered. The step-like potentials show no scaling behaviour and the Morse potential (which corresponds to a γ = -1 model) has the interesting feature that there are no quantum corrections to the scaling behaviour in the continuum limit. (author). 5 refs

  18. Inside the NIKE matrix

    OpenAIRE

    Brenner, Barbara; Schlegelmilch, Bodo B.; Ambos, Björn

    2013-01-01

    This case describes how Nike, a consumer goods company with an ever expanding portfolio and a tremendous brand value, manages the tradeoff between local responsiveness and global integration. In particular, the case highlights Nike's organizational structure that consists of a global matrix organization that is replicated at a regional level for the European market. While this organizational structure allows Nike to respond to local consumer tastes it also ensures that the company benefits f...

  19. A matrix contraction process

    Science.gov (United States)

    Wilkinson, Michael; Grant, John

    2018-03-01

    We consider a stochastic process in which independent identically distributed random matrices are multiplied and where the Lyapunov exponent of the product is positive. We continue multiplying the random matrices as long as the norm, ɛ, of the product is less than unity. If the norm is greater than unity we reset the matrix to a multiple of the identity and then continue the multiplication. We address the problem of determining the probability density function of the norm, \

  20. Matrix String Theory

    CERN Document Server

    Dijkgraaf, R; Verlinde, Herman L

    1997-01-01

    Via compactification on a circle, the matrix model of M-theory proposed by Banks et al suggests a concrete identification between the large N limit of two-dimensional N=8 supersymmetric Yang-Mills theory and type IIA string theory. In this paper we collect evidence that supports this identification. We explicitly identify the perturbative string states and their interactions, and describe the appearance of D-particle and D-membrane states.

  1. Matrix groups for undergraduates

    CERN Document Server

    Tapp, Kristopher

    2016-01-01

    Matrix groups touch an enormous spectrum of the mathematical arena. This textbook brings them into the undergraduate curriculum. It makes an excellent one-semester course for students familiar with linear and abstract algebra and prepares them for a graduate course on Lie groups. Matrix Groups for Undergraduates is concrete and example-driven, with geometric motivation and rigorous proofs. The story begins and ends with the rotations of a globe. In between, the author combines rigor and intuition to describe the basic objects of Lie theory: Lie algebras, matrix exponentiation, Lie brackets, maximal tori, homogeneous spaces, and roots. This second edition includes two new chapters that allow for an easier transition to the general theory of Lie groups. From reviews of the First Edition: This book could be used as an excellent textbook for a one semester course at university and it will prepare students for a graduate course on Lie groups, Lie algebras, etc. … The book combines an intuitive style of writing w...

  2. Extracellular matrix structure.

    Science.gov (United States)

    Theocharis, Achilleas D; Skandalis, Spyros S; Gialeli, Chrysostomi; Karamanos, Nikos K

    2016-02-01

    Extracellular matrix (ECM) is a non-cellular three-dimensional macromolecular network composed of collagens, proteoglycans/glycosaminoglycans, elastin, fibronectin, laminins, and several other glycoproteins. Matrix components bind each other as well as cell adhesion receptors forming a complex network into which cells reside in all tissues and organs. Cell surface receptors transduce signals into cells from ECM, which regulate diverse cellular functions, such as survival, growth, migration, and differentiation, and are vital for maintaining normal homeostasis. ECM is a highly dynamic structural network that continuously undergoes remodeling mediated by several matrix-degrading enzymes during normal and pathological conditions. Deregulation of ECM composition and structure is associated with the development and progression of several pathologic conditions. This article emphasizes in the complex ECM structure as to provide a better understanding of its dynamic structural and functional multipotency. Where relevant, the implication of the various families of ECM macromolecules in health and disease is also presented. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Activation of phagocytic cells by Staphylococcus epidermidis biofilms: effects of extracellular matrix proteins and the bacterial stress protein GroEL on netosis and MRP-14 release.

    Science.gov (United States)

    Dapunt, Ulrike; Gaida, Matthias M; Meyle, Eva; Prior, Birgit; Hänsch, Gertrud M

    2016-07-01

    The recognition and phagocytosis of free-swimming (planktonic) bacteria by polymorphonuclear neutrophils have been investigated in depth. However, less is known about the neutrophil response towards bacterial biofilms. Our previous work demonstrated that neutrophils recognize activating entities within the extracellular polymeric substance (EPS) of biofilms (the bacterial heat shock protein GroEL) and that this process does not require opsonization. Aim of this study was to evaluate the release of DNA by neutrophils in response to biofilms, as well as the release of the inflammatory cytokine MRP-14. Neutrophils were stimulated with Staphylococcus epidermidis biofilms, planktonic bacteria, extracted EPS and GroEL. Release of DNA and of MRP-14 was evaluated. Furthermore, tissue samples from patients suffering from biofilm infections were collected and evaluated by histology. MRP-14 concentration in blood samples was measured. We were able to show that biofilms, the EPS and GroEL induce DNA release. MRP-14 was only released after stimulation with EPS, not GroEL. Histology of tissue samples revealed MRP-14 positive cells in association with neutrophil infiltration and MRP-14 concentration was elevated in blood samples of patients suffering from biofilm infections. Our data demonstrate that neutrophil-activating entities are present in the EPS and that GroEL induces DNA release by neutrophils. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. From undefined red smear cheese consortia to minimal model communities both exhibiting similar anti-listerial activity on a cheese-like matrix.

    Science.gov (United States)

    Imran, M; Desmasures, N; Vernoux, J-P

    2010-12-01

    Starting from one undefined cheese smear consortium exhibiting anti-listerial activity (signal) at 15 °C, 50 yeasts and 39 bacteria were identified by partial rDNA sequencing. Construction of microbial communities was done either by addition or by erosion approach with the aim to obtain minimal communities having similar signal to that of the initial smear. The signal of these microbial communities was monitored in cheese microcosm for 14 days under ripening conditions. In the addition scheme, strains having significant signals were mixed step by step. Five-member communities, obtained by addition of a Gram negative bacterium to two yeasts and two Gram positive bacteria, enhanced the signal dramatically contrary to six-member communities including two Gram negative bacteria. In the erosion approach, a progressive reduction of 89 initial strains was performed. While intermediate communities (89, 44 and 22 members) exhibited a lower signal than initial smear consortium, eleven- and six-member communities gave a signal almost as efficient. It was noteworthy that the final minimal model communities obtained by erosion and addition approaches both had anti-listerial activity while consisting of different strains. In conclusion, some minimal model communities can have higher anti-listerial effectiveness than individual strains or the initial 89 micro-organisms from smear. Thus, microbial interactions are involved in the production and modulation of anti-listerial signals in cheese surface communities. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. Synthesis, spectroscopic characterization of palladium(II)-orthohydroxyacetophenone azine nano-optical sensor doped in sol–gel matrix and its use as probe for assessment of α-amylase activity in human saliva

    Energy Technology Data Exchange (ETDEWEB)

    El-Sayed, B.A. [Chemistry department, Faculty of Science, al Azhr University, Cairo (Egypt); Abo-Aly, M.M., E-mail: aboalymoh@hotmail.com [Chemistry department, Faculty of Science, Ain Shams University, Cairo (Egypt); Attia, M.S.; Gamal, S. [Chemistry department, Faculty of Science, Ain Shams University, Cairo (Egypt)

    2016-01-15

    PdAPA (palladium(II)-orthohydroxyacetophenone azine) complex doped in sol–gel matrix is synthesized. It is characterized using UV-visible, infrared spectra and TEM image. A novel, simple, sensitive spectrofluorometric method was developed for measuring the activity of the α-amylase enzyme in human saliva for smokers and non-smokers with age range (17–64 years) based on the quenching of the luminescence intensity at 450 nm of the new synthesized complex characterized by various concentrations of the maltose released from the hydrolysis of starch by α-amylase enzyme and was successfully used as nano-optical sensor. The calibration plot was achieved over the concentration range 4.7×10{sup −6}–9.3×10{sup −10} mol L{sup −1} maltose with a correlation coefficient of 0.996 and a detection minimum limit value of 7.55×10{sup −10} mol L{sup −1}. The method was satisfactorily used for the assessment of the α-amylase activity in a number of human saliva samples for various smokers and non-smoker's volunteers. - Highlights: • The (palladium(II)-orthohydroxyacetophenone azine) complex doped in sol–gel was prepared. • It was used for the assessment of of α-amylase enzyme activity. • By maltose resulting from the reaction of α-amylase enzyme with starch. • A novel, simple, sensitive and precise spectrofluorometric method was developed.

  6. Synthesis, spectroscopic characterization of palladium(II)-orthohydroxyacetophenone azine nano-optical sensor doped in sol–gel matrix and its use as probe for assessment of α-amylase activity in human saliva

    International Nuclear Information System (INIS)

    El-Sayed, B.A.; Abo-Aly, M.M.; Attia, M.S.; Gamal, S.

    2016-01-01

    PdAPA (palladium(II)-orthohydroxyacetophenone azine) complex doped in sol–gel matrix is synthesized. It is characterized using UV-visible, infrared spectra and TEM image. A novel, simple, sensitive spectrofluorometric method was developed for measuring the activity of the α-amylase enzyme in human saliva for smokers and non-smokers with age range (17–64 years) based on the quenching of the luminescence intensity at 450 nm of the new synthesized complex characterized by various concentrations of the maltose released from the hydrolysis of starch by α-amylase enzyme and was successfully used as nano-optical sensor. The calibration plot was achieved over the concentration range 4.7×10 −6 –9.3×10 −10 mol L −1 maltose with a correlation coefficient of 0.996 and a detection minimum limit value of 7.55×10 −10 mol L −1 . The method was satisfactorily used for the assessment of the α-amylase activity in a number of human saliva samples for various smokers and non-smoker's volunteers. - Highlights: • The (palladium(II)-orthohydroxyacetophenone azine) complex doped in sol–gel was prepared. • It was used for the assessment of of α-amylase enzyme activity. • By maltose resulting from the reaction of α-amylase enzyme with starch. • A novel, simple, sensitive and precise spectrofluorometric method was developed.

  7. A standardized extract of Butea monosperma (Lam.) flowers suppresses the IL-1β-induced expression of IL-6 and matrix-metalloproteases by activating autophagy in human osteoarthritis chondrocytes.

    Science.gov (United States)

    Ansari, Mohammad Y; Khan, Nazir M; Haqqi, Tariq M

    2017-12-01

    Osteoarthritis (OA) is a leading cause of joint dysfunction, disability and poor quality of life in the affected population. The underlying mechanism of joint dysfunction involves increased oxidative stress, inflammation, high levels of cartilage extracellular matrix degrading proteases and decline in autophagy-a mechanism of cellular defense. There is no disease modifying therapies currently available for OA. Different parts of the Butea monosperma (Lam.) plant have widely been used in the traditional Indian Ayurvedic medicine system for the treatment of various human diseases including inflammatory conditions. Here we studied the chondroprotective effect of hydromethanolic extract of Butea monosperma (Lam.) flowers (BME) standardized to the concentration of Butein on human OA chondrocytes stimulated with IL-1β. The hydromethanolic extract of Butea monosperma (Lam.) (BME) was prepared with 70% methanol-water mixer using Soxhlet. Chondrocytes viability after BME treatment was measured by MTT assay. Gene expression levels were determined by quantitative polymerase chain reaction (qPCR) using TaqMan assays and immunoblotting with specific antibodies. Autophagy activation was determined by measuring the levels of microtubule associated protein 1 light chain 3-II (LC3-II) by immunoblotting and visualization of autophagosomes by transmission electron and confocal microscopy. BME was non-toxic to the OA chondrocytes at the doses employed and suppressed the IL-1β induced expression of inerleukin-6 (IL-6) and matrix metalloprotease-3 (MMP-3), MMP-9 and MMP-13. BME enhanced autophagy in chondrocytes as determined by measuring the levels of LC3-II by immunoblotting and increased number of autophagosomes in BME treated chondrocytes by transmission electron microscopy and confocal microscopy. BME upregulated the expression of several autophagy related genes and increased the autophagy flux in human OA chondrocytes under pathological conditions. Further analysis revealed that

  8. Standard Errors for Matrix Correlations.

    Science.gov (United States)

    Ogasawara, Haruhiko

    1999-01-01

    Derives the asymptotic standard errors and intercorrelations for several matrix correlations assuming multivariate normality for manifest variables and derives the asymptotic standard errors of the matrix correlations for two factor-loading matrices. (SLD)

  9. The Study of Electromagnetic Wave Propogation in Photonic Crystals Via Planewave Based Transfer (Scattering) Matrix Method with Active Gain Material Applications

    Energy Technology Data Exchange (ETDEWEB)

    LI, Ming [Iowa State Univ., Ames, IA (United States)

    2007-01-01

    In this dissertation, a set of numerical simulation tools are developed under previous work to efficiently and accurately study one-dimensional (1D), two-dimensional(2D), 2D slab and three-dimensional (3D) photonic crystal structures and their defects effects by means of spectrum (transmission, reflection, absorption), band structure (dispersion relation), and electric and/or magnetic fields distribution (mode profiles). Furthermore, the lasing property and spontaneous emission behaviors are studied when active gain materials are presented in the photonic crystal structures. Various physical properties such as resonant cavity quality factor, waveguide loss, propagation group velocity of electromagnetic wave and light-current curve (for lasing devices) can be obtained from the developed software package.

  10. IGD motifs, which are required for migration stimulatory activity of fibronectin type I modules, do not mediate binding in matrix assembly.

    Directory of Open Access Journals (Sweden)

    Lisa M Maurer

    Full Text Available Picomolar concentrations of proteins comprising only the N-terminal 70-kDa region (70K of fibronectin (FN stimulate cell migration into collagen gels. The Ile-Gly-Asp (IGD motifs in four of the nine FN type 1 (FNI modules in 70K are important for such migratory stimulating activity. The 70K region mediates binding of nanomolar concentrations of intact FN to cell-surface sites where FN is assembled. Using baculovirus, we expressed wildtype 70K and 70K with Ile-to-Ala mutations in (3FNI and (5FNI; (7FNI and (9FNI; or (3FNI, (5FNI, (7FNI, and (9FNI. Wildtype 70K and 70K with Ile-to-Ala mutations were equally active in binding to assembly sites of FN-null fibroblasts. This finding indicates that IGD motifs do not mediate the interaction between 70K and the cell-surface that is important for FN assembly. Further, FN fragment N-(3FNIII, which does not stimulate migration, binds to assembly sites on FN-null fibroblast. The Ile-to-Ala mutations had effects on the structure of FNI modules as evidenced by decreases in abilities of 70K with Ile-to-Ala mutations to bind to monoclonal antibody 5C3, which recognizes an epitope in (9FNI, or to bind to FUD, a polypeptide based on the F1 adhesin of Streptococcus pyogenes that interacts with 70K by the β-zipper mechanism. These results suggest that the picomolar interactions of 70K with cells that stimulate cell migration require different conformations of FNI modules than the nanomolar interactions required for assembly.

  11. Baicalein, unlike 4-hydroxytamoxifen but similar to G15, suppresses 17β-estradiol-induced cell invasion, and matrix metalloproteinase-9 expression and activation in MCF-7 human breast cancer cells.

    Science.gov (United States)

    Chen, Yan; Hong, Duan-Yang; Wang, Jing; Ling-Hu, Jun; Zhang, Yan-Yan; Pan, Di; Xu, Yi-Ni; Tao, Ling; Luo, Hong; Shen, Xiang-Chun

    2017-08-01

    Estrogen performs an important role in the growth and development of breast cancer. There are at least three major receptors, including estrogen receptor (ER)α and β, and G protein-coupled receptor 30 (GPR30), which mediate the actions of estrogen through using transcriptional and rapid non-genomic signaling pathways. Flavonoids have been considered candidates for chemopreventive agents in breast cancer. Baicalein, the primary flavonoid derived from the root of Scutellaria baicalensis Georgi, has been reported to exert an anti-estrogenic effect. In the present study, the effects of baicalein on 17β-estradiol (E2)-induced cell invasion, and matrix metalloproteinase-9 (MMP-9) expression and activation were investigated. Furthermore, its effects were compared with that of the active form of the ER modulator tamoxifen 4-hydroxytamoxifen (OHT) and the GPR30 antagonist G15 in ERα- and GPR30-positive MCF-7 breast cancer cells. The results demonstrated that OHT failed to prevent E2-induced cell invasion, upregulation and proteolytic activity of MMP-9. However, baicalein was able to significantly suppress these E2-induced effects. Furthermore, E2-stimulated invasion, and MMP-9 expression and activation were significantly attenuated following G15 treatment. In addition, baicalein significantly inhibited G-1, a specific GPR30 agonist, induced invasion, and reduced G-1 promoted expression and activity of MMP-9, consistent with effects of G15. The results of the present study suggest that baicalein is a therapeutic candidate for GPR30-positive breast cancer treatment, and besides ERα targeting the GPR30 receptor it may achieve additional therapeutic benefits in breast cancer.

  12. Integrating porphyrin nanoparticles into a 2D graphene matrix for free-standing nanohybrid films with enhanced visible-light photocatalytic activity.

    Science.gov (United States)

    Chen, Yingzhi; Huang, Zheng-Hong; Yue, Mengbin; Kang, Feiyu

    2014-01-21

    Organic nanostructures in terms of porphyrin building blocks have shown great potential in visible-light photocatalytic applications because of their optical, electrical, and catalytic properties. Graphenes are known to provide a high-quality two-dimensional (2D) support for inorganic semiconductor nanostructures to increase the adsorption capability of the photocatalysts and an electron-transfer medium with attractive potential to enhance photogenerated charge separation. A combination of porphyrin nanostructures with graphene sheets, particularly in the form of free-standing films, is highly desirable due to its photocatalysing feasibility and convenience. Toward this aim, we demonstrate a facile method to integrate porphyrin (meso-tetra(p-hydroxyphenyl)porphyrin, p-THPP) nanoparticles (NPs) into macroscopic graphene (reduced graphene oxide, rGO) films through vacuum filtration of the co-colloids of graphene oxide (GO) and p-THPP nanoparticles (NPs) followed by gaseous reduction. The obtained p-THPP/rGO nanohybrid film exhibits enhanced visible-light photocatalytic activity compared to each moiety of the hybrid, and this photocatalyst can be easily separated and recycled for successive use with excellent stability. The results show that this facile fabrication of the p-THPP/rGO nanohybrid film makes it available for high-performance optoelectronic applications, as well as for device integration.

  13. Kaempferol Reduces Matrix Metalloproteinase-2 Expression by Down-Regulating ERK1/2 and the Activator Protein-1 Signaling Pathways in Oral Cancer Cells

    Science.gov (United States)

    Lin, Chiao-Wen; Chen, Pei-Ni; Chen, Mu-Kuan; Yang, Wei-En; Tang, Chih-Hsin; Yang, Shun-Fa; Hsieh, Yih-Shou

    2013-01-01

    Background Kaempferol has been proposed as a potential drug for cancer chemoprevention and treatment because it is a natural polyphenol contained in plant-based foods. Recent studies have demonstrated that kaempferol protects against cardiovascular disease and cancer. Based on this finding, we investigated the mechanisms by which kaempferol produces the anti-metastatic effect in human tongue squamous cell carcinoma SCC4 cells. Methodology/Principal Findings In this study, we provided molecular evidence associated with the anti-metastatic effect of kaempferol by demonstrating a substantial suppression of SCC4 cell migration and invasion. This effect was associated with reduced expressions of MMP-2 and TIMP-2 mRNA and protein levels. Analysis of the transcriptional regulation indicated that kaempferol inhibited MMP-2 transcription by suppressing c-Jun activity. Kaempferol also produced an inhibitory effect on the phosphorylation of ERK1/2. Conclusions These findings provide new insights into the molecular mechanisms involved in the anti-metastatic effect of kaempferol, and are valuable in the prevention of oral cancer metastasis. PMID:24278338

  14. [Acetyl-11-keto-beta-boswellic acid and arsenic trioxide regulate the productions and activities of matrix metalloproteinases in human skin fibroblasts and human leukemia cell line THP-1].

    Science.gov (United States)

    Liang, Ya-hui; Li, Ping; Zhao, Jing-xia; Liu, Xin; Huang, Qi-fu

    2010-11-01

    In order to reveal the treatment mechanism of Chinese medicine with the effect of activating blood and resolving putridity, we selected acetyl-11-keto-beta-boswellic acid (AKBA) and arsenic trioxide (ATO), the main monomeric components of frankincense and arsenolite which are two most commonly used Chinese medicine with effect of activating blood and resolving putridity. We combined AKBA and ATO as a compound, and explored its regulatory role in productions and activities of matrix metalloproteinase (MMP)-1, MMP-2 and MMP-9 in human skin fibroblasts (HSFbs) and human acute monocytic leukemia cell line THP-1 in inflammatory state. In order to simulate the inflammatory micro-environment of chronic wounds, we established 3 cell models: HSFb model activated by tumor necrosis factor-alpha (TNF-α), THP-1 cell model activated by phorbol-12-myristate-13-acetate (PMA) and HSFb-THP-1 cell coculture system. AKBA and ATO were cocultured with these cell models. Enzyme-linked immunosorbent assay (ELISA), gelatin zymography assay and reverse transcription-polymerase chain reaction (RT-PCR) were used to test the secretions, activities and mRNA expressions of MMP-1, MMP-2 and MMP-9. In the study of the regulatory mechanism of AKBA and ATO on MMPs, AKBA and ATO were cocultured with the cell models. ELISA was used to test the secretions of TNF-α and interleukin-1beta (IL-β) and Western blot was used to test the phosphorylation levels of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated proteinkinase (p38MAPK). Compound of AKBA and ATO inhibited MMP-1, MMP-2 and MMP-9 mRNA expressions, secretions and activities respectively in HSFbs and THP-1 cells in inflammatory state (PTHP-1 cells and cell coculture system (PTHP-1 cells (P<0.05, P<0.01). The combined use of AKBA and ATO which in line with the rule of activating blood and resolving putridity inhibits fibroblasts and inflammatory cells in producing MMPs in inflammatory state through inhibiting the

  15. The cellulose resource matrix.

    Science.gov (United States)

    Keijsers, Edwin R P; Yılmaz, Gülden; van Dam, Jan E G

    2013-03-01

    The emerging biobased economy is causing shifts from mineral fossil oil based resources towards renewable resources. Because of market mechanisms, current and new industries utilising renewable commodities, will attempt to secure their supply of resources. Cellulose is among these commodities, where large scale competition can be expected and already is observed for the traditional industries such as the paper industry. Cellulose and lignocellulosic raw materials (like wood and non-wood fibre crops) are being utilised in many industrial sectors. Due to the initiated transition towards biobased economy, these raw materials are intensively investigated also for new applications such as 2nd generation biofuels and 'green' chemicals and materials production (Clark, 2007; Lange, 2007; Petrus & Noordermeer, 2006; Ragauskas et al., 2006; Regalbuto, 2009). As lignocellulosic raw materials are available in variable quantities and qualities, unnecessary competition can be avoided via the choice of suitable raw materials for a target application. For example, utilisation of cellulose as carbohydrate source for ethanol production (Kabir Kazi et al., 2010) avoids the discussed competition with easier digestible carbohydrates (sugars, starch) deprived from the food supply chain. Also for cellulose use as a biopolymer several different competing markets can be distinguished. It is clear that these applications and markets will be influenced by large volume shifts. The world will have to reckon with the increase of competition and feedstock shortage (land use/biodiversity) (van Dam, de Klerk-Engels, Struik, & Rabbinge, 2005). It is of interest - in the context of sustainable development of the bioeconomy - to categorize the already available and emerging lignocellulosic resources in a matrix structure. When composing such "cellulose resource matrix" attention should be given to the quality aspects as well as to the available quantities and practical possibilities of processing the

  16. Assessment of Matrix Metalloproteinases by Gelatin Zymography.

    Science.gov (United States)

    Cathcart, Jillian

    2016-01-01

    Matrix metalloproteinases are endopeptidases responsible for remodeling of the extracellular matrix and have been identified as critical contributors to breast cancer progression. Gelatin zymography is a valuable tool which allows the analysis of MMP expression. In this approach, enzymes are resolved electrophoretically on a sodium dodecyl sulfate-polyacrylamide gel copolymerized with the substrate for the MMP of interest. Post electrophoresis, the enzymes are refolded in order for proteolysis of the incorporated substrate to occur. This assay yields valuable information about MMP isoforms or changes in activation and can be used to analyze the role of MMPs in normal versus pathological conditions.

  17. New PLGA-P188-PLGA matrix enhances TGF-β3 release from pharmacologically active microcarriers and promotes chondrogenesis of mesenchymal stem cells.

    Science.gov (United States)

    Morille, Marie; Van-Thanh, Tran; Garric, Xavier; Cayon, Jérôme; Coudane, Jean; Noël, Danièle; Venier-Julienne, Marie-Claire; Montero-Menei, Claudia N

    2013-08-28

    The use of injectable scaffolding materials for in vivo tissue regeneration has raised great interest in various clinical applications because it allows cell implantation through minimally invasive surgical procedures. In case of cartilage repair, a tissue engineered construct should provide a support for the cell and allow sustained in situ delivery of bioactive factors capable of inducing cell differentiation into chondrocytes. Pharmacologically active microcarriers (PAMs), made of biodegradable poly(d,l-lactide-co-glycolide acid) (PLGA), are a unique system, which combines these properties in an adaptable and simple microdevice. However, a limitation of such scaffold is low and incomplete protein release that occurs using the hydrophobic PLGA based microspheres. To circumvent this problem, we developed a novel formulation of polymeric PAMs containing a P188 poloxamer, which protects the protein from denaturation and may positively affect chondrogenesis. This poloxamer was added as a free additive for protein complexation and as a component of the scaffold covalently linked to PLGA. This procedure allows getting a more hydrophilic scaffold but also retaining the protective polymer inside the microcarriers during their degradation. The novel PLGA-P188-PLGA PAMs presenting a fibronectin-covered surface allowed enhanced MSC survival and proliferation. When engineered with TGFβ3, they allowed the sustained release of 70% of the incorporated TGF-β3 over time. Importantly, they exerted superior chondrogenic differentiation potential compared to previous FN-PAM-PLGA-TGF-β3, as shown by an increased expression of specific cartilage markers such as cartilage type II, aggrecan and COMP. Therefore, this microdevice represents an efficient easy-to-handle and injectable tool for cartilage repair. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Oxidation of Tris (2-chloroethyl) phosphate in aqueous solution by UV-activated peroxymonosulfate: Kinetics, water matrix effects, degradation products and reaction pathways.

    Science.gov (United States)

    Xu, Xinxin; Chen, Jing; Qu, Ruijuan; Wang, Zunyao

    2017-10-01

    The feasibility of UV-activated peroxymonosulfate (PMS) technology for the degradation of Tris (2-chloroethyl) phosphate (TCEP) in an aqueous solution was investigated in this study. The conditions of [PMS] 0 : [TCEP] 0  = 20:1, T = 25 ± 2 °C and pH = 5.5 ± 0.5 cause a 94.6% removal of TCEP (1 mg L -1 ) after 30 min of Hg lamp irradiation. The effects of operating parameters (the oxidant doses, pH and presence of typical cations (Fe 3+ , Cu 2+ , Ni 2+ , NH 4 + ), anions (Cl - , HCO 3 - , NO 3 - , HPO 4 2- ) and humic acid (HA)) were evaluated. It was found that an increase of the PMS dose and the presence of Fe 3+ could accelerate the reaction, while the anions and HA inhibited the reaction. Meanwhile, TCEP removal in various water matrices was compared, and the order for TCEP removal was as follows: ultrapure water > tap water > synthetic water > secondary clarifier effluent > Jiuxiang river water. Twenty-two oxidation products were identified using an electrospray time-of-flight mass spectrometer, and the degradation pathways mainly involved radicals' addition and CO bond cleavage. Furthermore, ECOSAR analysis revealed that the intermediate products during the TCEP oxidation process were generally not harmful to three typical aquatic species. Hence, UV/PMS can be used as an efficient technology to treat TCEP-containing water and wastewaters. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Random matrix theory

    CERN Document Server

    Deift, Percy

    2009-01-01

    This book features a unified derivation of the mathematical theory of the three classical types of invariant random matrix ensembles-orthogonal, unitary, and symplectic. The authors follow the approach of Tracy and Widom, but the exposition here contains a substantial amount of additional material, in particular, facts from functional analysis and the theory of Pfaffians. The main result in the book is a proof of universality for orthogonal and symplectic ensembles corresponding to generalized Gaussian type weights following the authors' prior work. New, quantitative error estimates are derive

  20. Matrix vector analysis

    CERN Document Server

    Eisenman, Richard L

    2005-01-01

    This outstanding text and reference applies matrix ideas to vector methods, using physical ideas to illustrate and motivate mathematical concepts but employing a mathematical continuity of development rather than a physical approach. The author, who taught at the U.S. Air Force Academy, dispenses with the artificial barrier between vectors and matrices--and more generally, between pure and applied mathematics.Motivated examples introduce each idea, with interpretations of physical, algebraic, and geometric contexts, in addition to generalizations to theorems that reflect the essential structur

  1. Matrix Encryption Scheme

    Directory of Open Access Journals (Sweden)

    Abdelhakim Chillali

    2017-05-01

    Full Text Available In classical cryptography, the Hill cipher is a polygraphic substitution cipher based on linear algebra. In this work, we proposed a new problem applicable to the public key cryptography, based on the Matrices, called “Matrix discrete logarithm problem”, it uses certain elements formed by matrices whose coefficients are elements in a finite field. We have constructed an abelian group and, for the cryptographic part in this unreliable group, we then perform the computation corresponding to the algebraic equations, Returning the encrypted result to a receiver. Upon receipt of the result, the receiver can retrieve the sender’s clear message by performing the inverse calculation.

  2. Matrix string partition function

    CERN Document Server

    Kostov, Ivan K; Kostov, Ivan K.; Vanhove, Pierre

    1998-01-01

    We evaluate quasiclassically the Ramond partition function of Euclidean D=10 U(N) super Yang-Mills theory reduced to a two-dimensional torus. The result can be interpreted in terms of free strings wrapping the space-time torus, as expected from the point of view of Matrix string theory. We demonstrate that, when extrapolated to the ultraviolet limit (small area of the torus), the quasiclassical expressions reproduce exactly the recently obtained expression for the partition of the completely reduced SYM theory, including the overall numerical factor. This is an evidence that our quasiclassical calculation might be exact.

  3. Matrix algebra for linear models

    CERN Document Server

    Gruber, Marvin H J

    2013-01-01

    Matrix methods have evolved from a tool for expressing statistical problems to an indispensable part of the development, understanding, and use of various types of complex statistical analyses. This evolution has made matrix methods a vital part of statistical education. Traditionally, matrix methods are taught in courses on everything from regression analysis to stochastic processes, thus creating a fractured view of the topic. Matrix Algebra for Linear Models offers readers a unique, unified view of matrix analysis theory (where and when necessary), methods, and their applications. Written f

  4. Antioxidative activity of 3,4-dihydroxyplienylacetic acid and α-tocopherol on the triglyceride matrix of olive oil. Effect of acidity.

    Directory of Open Access Journals (Sweden)

    Blekas, Georgios

    1998-02-01

    Full Text Available Minor constituents of virgin olive oil are important for the remarkable stability of the oil in autoxidation, but the exact role and the extent to which each antioxidant factor contributes to the total antioxidant effect has not been thoroughly Investigated. In this study the role of α-tocopherol is explored at various acidity levels and at low concentrations of ortho-diphenols. A substrate of olive oil triacylglycerols devoid of prooxidant or antioxidant constituents was prepared from refined olive oil by column chromatography To tills substrate, slightly oxidized, the additives (oleic acid, 3,4-dihydroxyphenylacetic acid and α-tocopherol were added and the stability was assessed by periodical measurements of peroxide values. It was found that free fatty adds reduce mainly the protective activity of the ortho-diphenol. It is also concluded that α-tocopherol has a synergistic effect with the ortho-diphenols and contributes significantly to the retardation of peroxide formation. This is Important for oils poor in ortho-diphenols.

    Los constituyentes menores del aceite de oliva virgen son importantes para la notable estabilidad del aceite en la autooxidación, pero el papel exacto y el alcance con que cada factor antioxidante contribuye al efecto antioxidante total no ha sido investigado a fondo. En este estudio el papel del α-tocoferol es examinado a varios niveles de acidez y a baja concentraciones de o-difenoles. Un sustrato de triacilgliceroles de aceite de oliva desprovisto de constituyentes prooxidantes o antioxidantes fue preparado a partir de aceite de oliva refinado mediante cromatografía en columna. A este sustrato, un poco oxidado, los aditivos (ácido oleico, ácido 3,4-dihidroxifenilacético y α-tocoferol fueron añadidos y la estabilidad fue calculada mediante medidas periódicas del índice de peróxido. Se encontró que los ácidos grasos libres reducen principalmente la actividad protectora de los orto-difenoles. Se

  5. Suppression of Heregulin-β1/HER2-Modulated Invasive and Aggressive Phenotype of Breast Carcinoma by Pterostilbene via Inhibition of Matrix Metalloproteinase-9, p38 Kinase Cascade and Akt Activation

    Directory of Open Access Journals (Sweden)

    Min-Hsiung Pan

    2011-01-01

    Full Text Available Invasive breast cancer is the major cause of death among females and its incidence is closely linked to HER2 (human epidermal growth factor receptor 2 overexpression. Pterostilbene, a natural analog of resveratrol, exerts its cancer chemopreventive activity similar to resveratrol by inhibiting cancer cell proliferation and inducing apoptosis. However, the anti-invasive effect of pterostilbene on HER2-bearing breast cancer has not been evaluated. Here, we used heregulin-β1 (HRG-β1, a ligand for HER3, to transactivate HER2 signaling. We found that pterostilbene was able to suppress HRG-β1-mediated cell invasion, motility and cell transformation of MCF-7 human breast carcinoma through down-regulation of matrix metalloproteinase-9 (MMP-9 activity and growth inhibition. In parallel, pterostilbene also inhibited protein and mRNA expression of MMP-9 driven by HRG-β1, suggesting that pterostilbene decreased HRG-β1-mediated MMP-9 induction via transcriptional regulation. Examining the signaling pathways responsible for HRG-β1-associated MMP-9 induction and growth inhibition, we observed that pterostilbene, as well as SB203580 (p38 kinase inhibitor, can abolish the phosphorylation of p38 mitogen-activated protein kinase (p38 kinase, a downstream HRG-β1-responsive kinase responsible for MMP-9 induction. In addition, HRG-β1-driven Akt phosphorylation required for cell proliferation was also suppressed by pterostilbene. Taken together, our present results suggest that pterostilbene may serve as a chemopreventive agent to inhibit HRG-β1/HER2-mediated aggressive and invasive phenotype of breast carcinoma through down-regulation of MMP-9, p38 kinase and Akt activation.

  6. The NAD-Dependent Deacetylase Sirtuin-1 Regulates the Expression of Osteogenic Transcriptional Activator Runt-Related Transcription Factor 2 (Runx2 and Production of Matrix Metalloproteinase (MMP-13 in Chondrocytes in Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Koh Terauchi

    2016-06-01

    Full Text Available Aging is one of the major pathologic factors associated with osteoarthritis (OA. Recently, numerous reports have demonstrated the impact of sirtuin-1 (Sirt1, which is the NAD-dependent deacetylase, on human aging. It has been demonstrated that Sirt1 induces osteogenic and chondrogenic differentiation of mesenchymal stem cells. However, the role of Sirt1 in the OA chondrocytes still remains unknown. We postulated that Sirt1 regulates a hypertrophic chondrocyte lineage and degeneration of articular cartilage through the activation of osteogenic transcriptional activator Runx2 and matrix metalloproteinase (MMP-13 in OA chondrocytes. To verify whether sirtuin-1 (Sirt1 regulates chondrocyte activity in OA, we studied expressions of Sirt1, Runx2 and production of MMP-13, and their associations in human OA chondrocytes. The expression of Sirt1 was ubiquitously observed in osteoarthritic chondrocytes; in contrast, Runx2 expressed in the osteophyte region in patients with OA and OA model mice. OA relating catabolic factor IL-1βincreased the expression of Runx2 in OA chondrocytes. OA chondrocytes, which were pretreated with Sirt1 inhibitor, inhibited the IL-1β-induced expression of Runx2 compared to the control. Since the Runx2 is a promotor of MMP-13 expression, Sirt1 inactivation may inhibit the Runx2 expression and the resultant down-regulation of MMP-13 production in chondrocytes. Our findings suggest thatSirt1 may regulate the expression of Runx2, which is the osteogenic transcription factor, and the production of MMP-13 from chondrocytes in OA. Since Sirt1 activity is known to be affected by several stresses, including inflammation and oxidative stress, as well as aging, SIRT may be involved in the development of OA.

  7. CELLULAR CONTROL OF CONNECTIVE TISSUE MATRIX TENSION†

    OpenAIRE

    Langevin, Helene M.; Nedergaard, Maiken; Howe, Alan

    2013-01-01

    The biomechanical behavior of connective tissue in response to stretching is generally attributed to the molecular composition and organization of its extracellular matrix. It also is becoming apparent that fibroblasts play an active role in regulating connective tissue tension. In response to static stretching of the tissue, fibroblasts expand within minutes by actively remodeling their cytoskeleton. This dynamic change in fibroblast shape contributes to the drop in tissue tension that occur...

  8. ACORNS, Covariance and Correlation Matrix Diagonalization

    International Nuclear Information System (INIS)

    Szondi, E.J.

    1990-01-01

    1 - Description of program or function: The program allows the user to verify the different types of covariance/correlation matrices used in the activation neutron spectrometry. 2 - Method of solution: The program performs the diagonalization of the input covariance/relative covariance/correlation matrices. The Eigen values are then analyzed to determine the rank of the matrices. If the Eigen vectors of the pertinent correlation matrix have also been calculated, the program can perform a complete factor analysis (generation of the factor matrix and its rotation in Kaiser's 'varimax' sense to select the origin of the correlations). 3 - Restrictions on the complexity of the problem: Matrix size is limited to 60 on PDP and to 100 on IBM PC/AT

  9. Characterization of supercapacitors matrix

    Energy Technology Data Exchange (ETDEWEB)

    Sakka, Monzer Al, E-mail: Monzer.Al.Sakka@vub.ac.b [Vrije Universiteit Brussel, pleinlaan 2, B-1050 Brussels (Belgium); FEMTO-ST Institute, ENISYS Department, FCLAB, UFC-UTBM, bat.F, 90010 Belfort (France); Gualous, Hamid, E-mail: Hamid.Gualous@unicaen.f [Laboratoire LUSAC, Universite de Caen Basse Normandie, Rue Louis Aragon - BP 78, 50130 Cherbourg-Octeville (France); Van Mierlo, Joeri [Vrije Universiteit Brussel, pleinlaan 2, B-1050 Brussels (Belgium)

    2010-10-30

    This paper treats supercapacitors matrix characterization. In order to cut off transient power peaks and to compensate for the intrinsic limitations in embedded sources, the use of supercapacitors as a storage system is quite suitable, because of their appropriate electrical characteristics (huge capacitance, small series resistance, high specific energy, high specific power), direct storage (energy ready for use), and easy control by power electronic conversion. This use requires supercapacitors modules where several cells connected in serial and/or in parallel, thus a bypass system to balance the charging or the discharging of supercapacitors is required. In the matrix of supercapacitors, six elements of three parallel BCAP0350 supercapacitors in serial connections have been considered. This topology permits to reduce the number of the bypass circuits and it can work in degraded mode. Actually, it allows the system to have more reliability by providing power continually to the load even when there are one or more cells failed. Simulation and experimental results are presented and discussed.

  10. Characterization of supercapacitors matrix

    International Nuclear Information System (INIS)

    Sakka, Monzer Al; Gualous, Hamid; Van Mierlo, Joeri

    2010-01-01

    This paper treats supercapacitors matrix characterization. In order to cut off transient power peaks and to compensate for the intrinsic limitations in embedded sources, the use of supercapacitors as a storage system is quite suitable, because of their appropriate electrical characteristics (huge capacitance, small series resistance, high specific energy, high specific power), direct storage (energy ready for use), and easy control by power electronic conversion. This use requires supercapacitors modules where several cells connected in serial and/or in parallel, thus a bypass system to balance the charging or the discharging of supercapacitors is required. In the matrix of supercapacitors, six elements of three parallel BCAP0350 supercapacitors in serial connections have been considered. This topology permits to reduce the number of the bypass circuits and it can work in degraded mode. Actually, it allows the system to have more reliability by providing power continually to the load even when there are one or more cells failed. Simulation and experimental results are presented and discussed.

  11. The effect of chronic periodontitis on serum levels of matrix ...

    African Journals Online (AJOL)

    A complex network of chemokines and pro- and anti-inflammatory mediators is involved in the initiation and progression of chronic periodontitis. Matrix metalloproteinases (MMPs), the main enzymes responsible for matrix degradation, are important for periodontal tissue destruction, but their activity can be inhibited by tissue ...

  12. Ceramic matrix and resin matrix composites - A comparison

    Science.gov (United States)

    Hurwitz, Frances I.

    1987-01-01

    The underlying theory of continuous fiber reinforcement of ceramic matrix and resin matrix composites, their fabrication, microstructure, physical and mechanical properties are contrasted. The growing use of organometallic polymers as precursors to ceramic matrices is discussed as a means of providing low temperature processing capability without the fiber degradation encountered with more conventional ceramic processing techniques. Examples of ceramic matrix composites derived from particulate-filled, high char yield polymers and silsesquioxane precursors are provided.

  13. Ceramic matrix and resin matrix composites: A comparison

    Science.gov (United States)

    Hurwitz, Frances I.

    1987-01-01

    The underlying theory of continuous fiber reinforcement of ceramic matrix and resin matrix composites, their fabrication, microstructure, physical and mechanical properties are contrasted. The growing use of organometallic polymers as precursors to ceramic matrices is discussed as a means of providing low temperature processing capability without the fiber degradation encountered with more conventional ceramic processing techniques. Examples of ceramic matrix composites derived from particulate-filled, high char yield polymers and silsesquioxane precursors are provided.

  14. A matrix big bang

    International Nuclear Information System (INIS)

    Craps, Ben; Sethi, Savdeep; Verlinde, Erik

    2005-01-01

    The light-like linear dilaton background represents a particularly simple time-dependent 1/2 BPS solution of critical type-IIA superstring theory in ten dimensions. Its lift to M-theory, as well as its Einstein frame metric, are singular in the sense that the geometry is geodesically incomplete and the Riemann tensor diverges along a light-like subspace of codimension one. We study this background as a model for a big bang type singularity in string theory/M-theory. We construct the dual Matrix theory description in terms of a (1+1)-d supersymmetric Yang-Mills theory on a time-dependent world-sheet given by the Milne orbifold of (1+1)-d Minkowski space. Our model provides a framework in which the physics of the singularity appears to be under control

  15. A matrix big bang

    Energy Technology Data Exchange (ETDEWEB)

    Craps, Ben [Instituut voor Theoretische Fysica, Universiteit van Amsterdam, Valckenierstraat 65, 1018 XE Amsterdam (Netherlands); Sethi, Savdeep [Enrico Fermi Institute, University of Chicago, Chicago, IL 60637 (United States); Verlinde, Erik [Instituut voor Theoretische Fysica, Universiteit van Amsterdam, Valckenierstraat 65, 1018 XE Amsterdam (Netherlands)

    2005-10-15

    The light-like linear dilaton background represents a particularly simple time-dependent 1/2 BPS solution of critical type-IIA superstring theory in ten dimensions. Its lift to M-theory, as well as its Einstein frame metric, are singular in the sense that the geometry is geodesically incomplete and the Riemann tensor diverges along a light-like subspace of codimension one. We study this background as a model for a big bang type singularity in string theory/M-theory. We construct the dual Matrix theory description in terms of a (1+1)-d supersymmetric Yang-Mills theory on a time-dependent world-sheet given by the Milne orbifold of (1+1)-d Minkowski space. Our model provides a framework in which the physics of the singularity appears to be under control.

  16. Matrix metalloproteinases outside vertebrates.

    Science.gov (United States)

    Marino-Puertas, Laura; Goulas, Theodoros; Gomis-Rüth, F Xavier

    2017-11-01

    The matrix metalloproteinase (MMP) family belongs to the metzincin clan of zinc-dependent metallopeptidases. Due to their enormous implications in physiology and disease, MMPs have mainly been studied in vertebrates. They are engaged in extracellular protein processing and degradation, and present extensive paralogy, with 23 forms in humans. One characteristic of MMPs is a ~165-residue catalytic domain (CD), which has been structurally studied for 14 MMPs from human, mouse, rat, pig and the oral-microbiome bacterium Tannerella forsythia. These studies revealed close overall coincidence and characteristic structural features, which distinguish MMPs from other metzincins and give rise to a sequence pattern for their identification. Here, we reviewed the literature available on MMPs outside vertebrates and performed database searches for potential MMP CDs in invertebrates, plants, fungi, viruses, protists, archaea and bacteria. These and previous results revealed that MMPs are widely present in several copies in Eumetazoa and higher plants (Tracheophyta), but have just token presence in eukaryotic algae. A few dozen sequences were found in Ascomycota (within fungi) and in double-stranded DNA viruses infecting invertebrates (within viruses). In contrast, a few hundred sequences were found in archaea and >1000 in bacteria, with several copies for some species. Most of the archaeal and bacterial phyla containing potential MMPs are present in human oral and gut microbiomes. Overall, MMP-like sequences are present across all kingdoms of life, but their asymmetric distribution contradicts the vertical descent model from a eubacterial or archaeal ancestor. This article is part of a Special Issue entitled: Matrix Metalloproteinases edited by Rafael Fridman. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Benzoxime inhibits matrix metalloproteinase-13 activation and ...

    African Journals Online (AJOL)

    admin

    Rats in the treatment group were given benzoxime (5 mg/kg) daily for 21 days through ... reproduction in any medium, provided the original work is properly credited. ... joints has adverse impact on socio-economic ... lifestyle, physiotherapy, chemotherapy and ..... chondroprotective effects of curcumin and resveratrol in.

  18. Imipenem-avibactam: a novel combination for the rapid detection of carbapenemase activity in Enterobacteriaceae and Acinetobacter baumannii by matrix-assisted laser desorption ionization-time of flight mass spectrometry.

    Science.gov (United States)

    Oviaño, Marina; Bou, Germán

    2017-02-01

    In the present study, we propose a novel matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS)-based method for detecting carbapenemase-producing Enterobacteriaceae and Acinetobacter baumannii. For this, we analyzed a series of 131 isolates. Among them, a total of 115 Enterobacteriaceae: 79 of them carrying a carbapenemase enzyme (15bla KPC , 7bla NDM , 11bla IMP , 12bla VIM , and 34bla OXA-48 ) and 16 A. baumannii isolates: 15 of them carrying carbapenemases (10bla OXA-23, 2bla OXA-58, 2bla OXA-24 , and 1bla OXA-237 ). The rest of the isolates were noncarbapenemase producers and used as negative controls. The isolates were submitted to susceptibility testing using a combination of imipenem-avibactam and analysis by the MALDI-TOF Biotyper Compass software (Bruker Daltonik, Germany). The assay showed an overall sensitivity and specificity for carbapenemase detection of 98% and 100%, respectively. The combination of imipenem and avibactam displayed activity against KPC and OXA-48-producing Enterobacteriaceae and thus represents a new strategy for identifying and confirming these carbapenemases. However, the combination did not provide any benefit over A. baumannii. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Improvement in Brightness Uniformity by Compensating for the Threshold Voltages of Both the Driving Thin-Film Transistor and the Organic Light-Emitting Diode for Active-Matrix Organic Light-Emitting Diode Displays

    Directory of Open Access Journals (Sweden)

    Ching-Lin Fan

    2014-01-01

    Full Text Available This paper proposes a novel pixel circuit design and driving method for active-matrix organic light-emitting diode (AM-OLED displays that use low-temperature polycrystalline-silicon thin-film transistors (LTPS-TFTs as driving element. The automatic integrated circuit modeling simulation program with integrated circuit emphasis (AIM-SPICE simulator was used to verify that the proposed pixel circuit, which comprises five transistors and one capacitor, can supply uniform output current. The voltage programming method of the proposed pixel circuit comprises three periods: reset, compensation with data input, and emission periods. The simulated results reflected excellent performance. For instance, when ΔVTH=±0.33 V, the average error rate of the OLED current variation was low (<0.8%, and when ΔVTH_OLED=+0.33 V, the error rate of the OLED current variation was 4.7%. Moreover, when the I×R (current × resistance drop voltage of a power line was 0.3 V, the error rate of the OLED current variation was 5.8%. The simulated results indicated that the proposed pixel circuit exhibits high immunity to the threshold voltage deviation of both the driving poly-Si TFTs and OLEDs, and simultaneously compensates for the I×R drop voltage of a power line.

  20. A novel assay for extracellular matrix remodeling associated with liver fibrosis

    DEFF Research Database (Denmark)

    Barascuk, N; Veidal, S S; Larsen, L

    2010-01-01

    Accumulation of extracellular matrix (ECM) components and increased matrix-metalloprotease (MMPs) activity are hallmarks of fibrosis. We developed an ELISA for quantification of MMP-9 derived collagen type III (CO3) degradation.......Accumulation of extracellular matrix (ECM) components and increased matrix-metalloprotease (MMPs) activity are hallmarks of fibrosis. We developed an ELISA for quantification of MMP-9 derived collagen type III (CO3) degradation....

  1. Phenomenology of the CKM matrix

    International Nuclear Information System (INIS)

    Nir, Y.

    1989-01-01

    The way in which an exact determination of the CKM matrix elements tests the standard Model is demonstrated by a two-generation example. The determination of matrix elements from meson semileptonic decays is explained, with an emphasis on the respective reliability of quark level and meson level calculations. The assumptions involved in the use of loop processes are described. Finally, the state of the art of the knowledge of the CKM matrix is presented. 19 refs., 2 figs

  2. On matrix fractional differential equations

    OpenAIRE

    Adem Kılıçman; Wasan Ajeel Ahmood

    2017-01-01

    The aim of this article is to study the matrix fractional differential equations and to find the exact solution for system of matrix fractional differential equations in terms of Riemann–Liouville using Laplace transform method and convolution product to the Riemann–Liouville fractional of matrices. Also, we show the theorem of non-homogeneous matrix fractional partial differential equation with some illustrative examples to demonstrate the effectiveness of the new methodology. The main objec...

  3. Matrix transformations and sequence spaces

    International Nuclear Information System (INIS)

    Nanda, S.

    1983-06-01

    In most cases the most general linear operator from one sequence space into another is actually given by an infinite matrix and therefore the theory of matrix transformations has always been of great interest in the study of sequence spaces. The study of general theory of matrix transformations was motivated by the special results in summability theory. This paper is a review article which gives almost all known results on matrix transformations. This also suggests a number of open problems for further study and will be very useful for research workers. (author)

  4. Multivariate Matrix-Exponential Distributions

    DEFF Research Database (Denmark)

    Bladt, Mogens; Nielsen, Bo Friis

    2010-01-01

    be written as linear combinations of the elements in the exponential of a matrix. For this reason we shall refer to multivariate distributions with rational Laplace transform as multivariate matrix-exponential distributions (MVME). The marginal distributions of an MVME are univariate matrix......-exponential distributions. We prove a characterization that states that a distribution is an MVME distribution if and only if all non-negative, non-null linear combinations of the coordinates have a univariate matrix-exponential distribution. This theorem is analog to a well-known characterization theorem...

  5. A matrix model for WZW

    International Nuclear Information System (INIS)

    Dorey, Nick; Tong, David; Turner, Carl

    2016-01-01

    We study a U(N) gauged matrix quantum mechanics which, in the large N limit, is closely related to the chiral WZW conformal field theory. This manifests itself in two ways. First, we construct the left-moving Kac-Moody algebra from matrix degrees of freedom. Secondly, we compute the partition function of the matrix model in terms of Schur and Kostka polynomials and show that, in the large N limit, it coincides with the partition function of the WZW model. This same matrix model was recently shown to describe non-Abelian quantum Hall states and the relationship to the WZW model can be understood in this framework.

  6. Simulation of sparse matrix array designs

    Science.gov (United States)

    Boehm, Rainer; Heckel, Thomas

    2018-04-01

    Matrix phased array probes are becoming more prominently used in industrial applications. The main drawbacks, using probes incorporating a very large number of transducer elements, are needed for an appropriate cabling and an ultrasonic device offering many parallel channels. Matrix arrays designed for extended functionality feature at least 64 or more elements. Typical arrangements are square matrices, e.g., 8 by 8 or 11 by 11 or rectangular matrixes, e.g., 8 by 16 or 10 by 12 to fit a 128-channel phased array system. In some phased array systems, the number of simultaneous active elements is limited to a certain number, e.g., 32 or 64. Those setups do not allow running the probe with all elements active, which may cause a significant change in the directivity pattern of the resulting sound beam. When only a subset of elements can be used during a single acquisition, different strategies may be applied to collect enough data for rebuilding the missing information from the echo signal. Omission of certain elements may be one approach, overlay of subsequent shots with different active areas may be another one. This paper presents the influence of a decreased number of active elements on the sound field and their distribution on the array. Solutions using subsets with different element activity patterns on matrix arrays and their advantages and disadvantages concerning the sound field are evaluated using semi-analytical simulation tools. Sound field criteria are discussed, which are significant for non-destructive testing results and for the system setup.

  7. Cartilage oligomeric matrix protein in patients with juvenile idiopathic arthritis

    DEFF Research Database (Denmark)

    Bjørnhart, Birgitte; Juul, Anders; Nielsen, Susan

    2009-01-01

    Cartilage oligomeric matrix protein (COMP) has been identified as a prognostic marker of progressive joint destruction in rheumatoid arthritis. In this population based study we evaluated associations between plasma concentrations of COMP, disease activity, and growth velocity in patients...

  8. Matrix Metalloproteinases in Non-Neoplastic Disorders

    Science.gov (United States)

    Tokito, Akinori; Jougasaki, Michihisa

    2016-01-01

    The matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases belonging to the metzincin superfamily. There are at least 23 members of MMPs ever reported in human, and they and their substrates are widely expressed in many tissues. Recent growing evidence has established that MMP not only can degrade a variety of components of extracellular matrix, but also can cleave and activate various non-matrix proteins, including cytokines, chemokines and growth factors, contributing to both physiological and pathological processes. In normal conditions, MMP expression and activity are tightly regulated via interactions between their activators and inhibitors. Imbalance among these factors, however, results in dysregulated MMP activity, which causes tissue destruction and functional alteration or local inflammation, leading to the development of diverse diseases, such as cardiovascular disease, arthritis, neurodegenerative disease, as well as cancer. This article focuses on the accumulated evidence supporting a wide range of roles of MMPs in various non-neoplastic diseases and provides an outlook on the therapeutic potential of inhibiting MMP action. PMID:27455234

  9. Matrix metalloproteinase content and activity in low-platelet, low-leukocyte and high-platelet, high-leukocyte platelet rich plasma (PRP) and the biologic response to PRP by human ligament fibroblasts.

    Science.gov (United States)

    Pifer, Matthew A; Maerz, Tristan; Baker, Kevin C; Anderson, Kyle

    2014-05-01

    Recent work has shown the presence of catabolic cytokines in platelet-rich plasma (PRP), but little is known about endogenous catabolic proteases such as matrix metalloproteinases (MMPs). Hypothesis/ To quantify MMP content in 2 commercially available PRP preparation systems: Arthrex Double Syringe System autologous conditioned plasma (ACP) and Biomet GPS (GPS). The hypothesis was that MMPs are actively secreted from PRP immediately after preparation. Controlled laboratory study. PRP was prepared using either ACP (low platelet, low leukocyte) or GPS (high platelet, high leukocyte). MMP-2, MMP-3, and MMP-9 concentrations were measured using multiplex enzyme-linked immunosorbent assays for up to 6 days in 2 donors, and MMP activity was measured in 3 donors using kinetic activity kits able to detect the enzymatic cleavage of a fluorogenic peptide. Human ligament fibroblasts were cultured and exposed to both ACP and GPS from 1 donor each. MMP-2, -3, and -9 concentrations were assayed in culture media at 24 and 48 hours after exposure. GPS exhibited higher total MMP-2, -3, and -9 concentrations for up to 144 hours of release, while ACP had higher platelet-normalized MMP-2 and MMP-3 concentrations. GPS had significantly higher total and endogenous MMP-2 activity (P = .004 and .014, respectively), MMP-3 activity (P = .020 and .015, respectively), and MMP-9 activity (P = .004 and .002, respectively) compared with ACP. Once normalized to platelet count, differences in MMP activity were not significant between ACP and GPS. Compared with controls, cells stimulated with interleukin-1 beta (IL-1β) and treated with ACP showed significantly higher fold changes of MMP-2 (P = .001) and MMP-3 (P = .003) concentrations at 24 hours than did cells treated with GPS. Total MMP-9 content was higher in the media of GPS-treated, IL-1β-stimulated cells compared with ACP-treated cells (P = .001). At 48 hours, IL-1β-stimulated cells treated with GPS exhibited higher fold changes of MMP-2

  10. NADPH oxidase/ROS-dependent PYK2 activation is involved in TNF-α-induced matrix metalloproteinase-9 expression in rat heart-derived H9c2 cells

    International Nuclear Information System (INIS)

    Yang, Chuen-Mao; Lee, I-Ta; Hsu, Ru-Chun; Chi, Pei-Ling; Hsiao, Li-Der

    2013-01-01

    TNF-α plays a mediator role in the pathogenesis of chronic heart failure contributing to cardiac remodeling and peripheral vascular disturbances. The implication of TNF-α in inflammatory responses has been shown to be mediated through up-regulation of matrix metalloproteinase-9 (MMP-9). However, the detailed mechanisms of TNF-α-induced MMP-9 expression in rat embryonic-heart derived H9c2 cells are largely not defined. We demonstrated that in H9c2 cells, TNF-α induced MMP-9 mRNA and protein expression associated with an increase in the secretion of pro-MMP-9. TNF-α-mediated responses were attenuated by pretreatment with the inhibitor of ROS (N-acetyl-L-cysteine, NAC), NADPH oxidase [apocynin (APO) or diphenyleneiodonium chloride (DPI)], MEK1/2 (U0126), p38 MAPK (SB202190), JNK1/2 (SP600125), NF-κB (Bay11-7082), or PYK2 (PF-431396) and transfection with siRNA of TNFR1, p47 phox , p42, p38, JNK1, p65, or PYK2. Moreover, TNF-α markedly induced NADPH oxidase-derived ROS generation in these cells. TNF-α-enhanced p42/p44 MAPK, p38 MAPK, JNK1/2, and NF-κB (p65) phosphorylation and in vivo binding of p65 to the MMP-9 promoter were inhibited by U0126, SB202190, SP600125, NAC, DPI, or APO. In addition, TNF-α-mediated PYK2 phosphorylation was inhibited by NAC, DPI, or APO. PYK2 inhibition could reduce TNF-α-stimulated MAPKs and NF-κB activation. Thus, in H9c2 cells, we are the first to show that TNF-α-induced MMP-9 expression is mediated through a TNFR1/NADPH oxidase/ROS/PYK2/MAPKs/NF-κB cascade. We demonstrated that NADPH oxidase-derived ROS generation is involved in TNF-α-induced PYK2 activation in these cells. Understanding the regulation of MMP-9 expression and NADPH oxidase activation by TNF-α on H9c2 cells may provide potential therapeutic targets of chronic heart failure. - Highlights: • TNF-α induces MMP-9 secretion and expression via a TNFR1-dependent pathway. • TNF-α induces ROS/PYK2-dependent MMP-9 expression in H9c2 cells. • TNF-α induces

  11. Ceramic matrix composite article and process of fabricating a ceramic matrix composite article

    Science.gov (United States)

    Cairo, Ronald Robert; DiMascio, Paul Stephen; Parolini, Jason Robert

    2016-01-12

    A ceramic matrix composite article and a process of fabricating a ceramic matrix composite are disclosed. The ceramic matrix composite article includes a matrix distribution pattern formed by a manifold and ceramic matrix composite plies laid up on the matrix distribution pattern, includes the manifold, or a combination thereof. The manifold includes one or more matrix distribution channels operably connected to a delivery interface, the delivery interface configured for providing matrix material to one or more of the ceramic matrix composite plies. The process includes providing the manifold, forming the matrix distribution pattern by transporting the matrix material through the manifold, and contacting the ceramic matrix composite plies with the matrix material.

  12. CELLULAR CONTROL OF CONNECTIVE TISSUE MATRIX TENSION†

    Science.gov (United States)

    Langevin, Helene M.; Nedergaard, Maiken; Howe, Alan

    2013-01-01

    The biomechanical behavior of connective tissue in response to stretching is generally attributed to the molecular composition and organization of its extracellular matrix. It also is becoming apparent that fibroblasts play an active role in regulating connective tissue tension. In response to static stretching of the tissue, fibroblasts expand within minutes by actively remodeling their cytoskeleton. This dynamic change in fibroblast shape contributes to the drop in tissue tension that occurs during viscoelastic relaxation. We propose that this response of fibroblasts plays a role in regulating extracellular fluid flow into the tissue, and protects against swelling when the matrix is stretched. This article reviews the evidence supporting possible mechanisms underlying this response including autocrine purinergic signaling. We also discuss fibroblast regulation of connective tissue tension with respect to lymphatic flow, immune function and cancer. PMID:23444198

  13. Cellular control of connective tissue matrix tension.

    Science.gov (United States)

    Langevin, Helene M; Nedergaard, Maiken; Howe, Alan K

    2013-08-01

    The biomechanical behavior of connective tissue in response to stretching is generally attributed to the molecular composition and organization of its extracellular matrix. It also is becoming apparent that fibroblasts play an active role in regulating connective tissue tension. In response to static stretching of the tissue, fibroblasts expand within minutes by actively remodeling their cytoskeleton. This dynamic change in fibroblast shape contributes to the drop in tissue tension that occurs during viscoelastic relaxation. We propose that this response of fibroblasts plays a role in regulating extracellular fluid flow into the tissue, and protects against swelling when the matrix is stretched. This article reviews the evidence supporting possible mechanisms underlying this response including autocrine purinergic signaling. We also discuss fibroblast regulation of connective tissue tension with respect to lymphatic flow, immune function, and cancer. Copyright © 2013 Wiley Periodicals, Inc.

  14. Strategy BMT Al-Ittihad Using Matrix IE, Matrix SWOT 8K, Matrix SPACE and Matrix TWOS

    Directory of Open Access Journals (Sweden)

    Nofrizal Nofrizal

    2018-03-01

    Full Text Available This research aims to formulate and select BMT Al-Ittihad Rumbai strategy to face the changing of business environment both from internal environment such as organization resources, finance, member and external business such as competitor, economy, politics and others. This research method used Analysis of EFAS, IFAS, IE Matrix, SWOT-8K Matrix, SPACE Matrix and TWOS Matrix. our hope from this research it can assist BMT Al-Ittihad in formulating and selecting strategies for the sustainability of BMT Al-Ittihad in the future. The sample in this research is using purposive sampling technique that is the manager and leader of BMT Al-IttihadRumbaiPekanbaru. The result of this research shows that the position of BMT Al-Ittihad using IE Matrix, SWOT-8K Matrix and SPACE Matrix is in growth position, stabilization and aggressive. The choice of strategy after using TWOS Matrix is market penetration, market development, vertical integration, horizontal integration, and stabilization (careful.

  15. How to Study a Matrix

    Science.gov (United States)

    Jairam, Dharmananda; Kiewra, Kenneth A.; Kauffman, Douglas F.; Zhao, Ruomeng

    2012-01-01

    This study investigated how best to study a matrix. Fifty-three participants studied a matrix topically (1 column at a time), categorically (1 row at a time), or in a unified way (all at once). Results revealed that categorical and unified study produced higher: (a) performance on relationship and fact tests, (b) study material satisfaction, and…

  16. An Analysis on BCG Growth Sharing Matrix

    OpenAIRE

    Mohajan, Haradhan

    2017-01-01

    In the 21st century, sustainable improvement of business faces various challenges for the global economic competition. But, these challenges can be overcome by the efficient business strategies. The Boston Consulting Group (BCG) helps the business organizations to develop their efficiency for the successful operation of their business activities. To develop the efficiency of marketing decision making, the BCG Matrix plays an effective tool for strategic planning of product performance in indu...

  17. Bulk metallic glass matrix composites

    International Nuclear Information System (INIS)

    Choi-Yim, H.; Johnson, W.L.

    1997-01-01

    Composites with a bulk metallic glass matrix were synthesized and characterized. This was made possible by the recent development of bulk metallic glasses that exhibit high resistance to crystallization in the undercooled liquid state. In this letter, experimental methods for processing metallic glass composites are introduced. Three different bulk metallic glass forming alloys were used as the matrix materials. Both ceramics and metals were introduced as reinforcement into the metallic glass. The metallic glass matrix remained amorphous after adding up to a 30 vol% fraction of particles or short wires. X-ray diffraction patterns of the composites show only peaks from the second phase particles superimposed on the broad diffuse maxima from the amorphous phase. Optical micrographs reveal uniformly distributed particles in the matrix. The glass transition of the amorphous matrix and the crystallization behavior of the composites were studied by calorimetric methods. copyright 1997 American Institute of Physics

  18. Machining of Metal Matrix Composites

    CERN Document Server

    2012-01-01

    Machining of Metal Matrix Composites provides the fundamentals and recent advances in the study of machining of metal matrix composites (MMCs). Each chapter is written by an international expert in this important field of research. Machining of Metal Matrix Composites gives the reader information on machining of MMCs with a special emphasis on aluminium matrix composites. Chapter 1 provides the mechanics and modelling of chip formation for traditional machining processes. Chapter 2 is dedicated to surface integrity when machining MMCs. Chapter 3 describes the machinability aspects of MMCs. Chapter 4 contains information on traditional machining processes and Chapter 5 is dedicated to the grinding of MMCs. Chapter 6 describes the dry cutting of MMCs with SiC particulate reinforcement. Finally, Chapter 7 is dedicated to computational methods and optimization in the machining of MMCs. Machining of Metal Matrix Composites can serve as a useful reference for academics, manufacturing and materials researchers, manu...

  19. Quantum mechanics in matrix form

    CERN Document Server

    Ludyk, Günter

    2018-01-01

    This book gives an introduction to quantum mechanics with the matrix method. Heisenberg's matrix mechanics is described in detail. The fundamental equations are derived by algebraic methods using matrix calculus. Only a brief description of Schrödinger's wave mechanics is given (in most books exclusively treated), to show their equivalence to Heisenberg's matrix  method. In the first part the historical development of Quantum theory by Planck, Bohr and Sommerfeld is sketched, followed by the ideas and methods of Heisenberg, Born and Jordan. Then Pauli's spin and exclusion principles are treated. Pauli's exclusion principle leads to the structure of atoms. Finally, Dirac´s relativistic quantum mechanics is shortly presented. Matrices and matrix equations are today easy to handle when implementing numerical algorithms using standard software as MAPLE and Mathematica.

  20. Mid-temperature deep removal of hydrogen sulfide on rare earth (RE = Ce, La, Sm, Gd) doped ZnO supported on KIT-6: Effect of RE dopants and interaction between active phase and support matrix

    Science.gov (United States)

    Li, Lu; Zhou, Pin; Zhang, Hongbo; Meng, Xianglong; Li, Juexiu; Sun, Tonghua

    2017-06-01

    Rare earth oxides (RE = Ce, La, Sm and Gd) doped ZnO supported on KIT-6 sorbents (RE-ZnO/KIT-6) were synthesized by sol-gel method and their performance for deep removal of H2S (bellow 0.1 ppmv) from gas stream at medium temperature was tested. The RE dopants (except Ce) significantly enhance the deep desulfurization capacity of ZnO/KIT-6 sorbent and maintained higher sulfur uptake capacities upon multiple cycles of regeneration by a simple thermal oxidation in 10 v% of O2 in N2 atmosphere. The results of SAXS, XRD, N2 physisorption, TEM, FIIR, and XPS implied that the KIT-6 structure of loading metal oxides remained intact. It was found that RE could hinder the ZnO crystal ripening during calcination resulted in smaller ZnO particles, enhance the interaction of ZnO and silica matrix to improve the dispersion of active phase on KIT-6. Furthermore, by increasing the outlayer electron density of Zn atom and oxygen transfer ability, the synergistic effect considered to be favorable for RE-ZnO/KIT-6 sulfidation. Even though the performance of improving ZnO dispersion was weaker than that of Sm and Gd, La-ZnO/KIT-6 performs the best deep desulfurizers by changing the surface chemical atmosphere for ZnO. Steam in the gas stream inhibited the capture of H2S by ZnO in the sorbents, in the case of La-ZnO/KIT-6, the steam content should control as lower as 5 v% to ensure the desulfurization efficiency and precision.

  1. Mixed Fibronectin-Derived Peptides Conjugated to a Chitosan Matrix Effectively Promotes Biological Activities through Integrins, α4β1, α5β1, αvβ3, and Syndecan

    Directory of Open Access Journals (Sweden)

    Hozumi Kentaro

    2016-11-01

    Full Text Available Mimicking the biological function of the extracellular matrix is an approach to developing cell adhesive biomaterials. The RGD peptide, derived from fibronectin (Fn, mainly binds to integrin αvβ3 and has been widely used as a cell adhesive peptide on various biomaterials. However, cell adhesion to Fn is thought to be mediated by several integrin subtypes and syndecans. In this study, we synthesized an RGD-containing peptide (FIB1 and four integrin α4β1-binding-related motif-containing peptides (LDV, IDAPS, KLDAPT, and PRARI and constructed peptide-chitosan matrices. The FIB1-chitosan matrix promoted human dermal fibroblast (HDF attachment, and the C-terminal elongated PRARI (ePRARI-C-conjugated chitosan matrix significantly promoted HDF attachment through integrin α4β1 and syndecan binding. Next, we constructed a mixed ePRARI-C- and FIB1-chitosan matrix to develop a Fn mimetic biomaterial. The mixed ePRARI-C/FIB1-chitosan matrix promoted significantly better cell attachment and neurite outgrowth compared to those of either ePRARI-C- or FIB1-chitosan matrices. HDF adhesion to the ePRARI-C/FIB1-chitosan matrix was mediated by integrin, α4β1, α5β1, and αvβ3, similar to HDF adhesion to Fn. These data suggest that an ePRARI-C/FIB1-chitosan matrix can be used as a tool to analyze the multiple functions of Fn and can serve as a Fn-mimetic biomaterial.

  2. The provisional matrix: setting the stage for tissue repair outcomes.

    Science.gov (United States)

    Barker, Thomas H; Engler, Adam J

    2017-07-01

    Since its conceptualization in the 1980s, the provisional matrix has often been characterized as a simple fibrin-containing scaffold for wound healing that supports the nascent blood clot and is functionally distinct from the basement membrane. However subsequent advances have shown that this matrix is far from passive, with distinct compositional differences as the wound matures, and providing an active role for wound remodeling. Here we review the stages of this matrix, provide an update on the state of our understanding of provisional matrix, and present some of the outstanding issues related to the provisional matrix, its components, and their assembly and use in vivo. Copyright © 2017. Published by Elsevier B.V.

  3. Containment Code Validation Matrix

    International Nuclear Information System (INIS)

    Chin, Yu-Shan; Mathew, P.M.; Glowa, Glenn; Dickson, Ray; Liang, Zhe; Leitch, Brian; Barber, Duncan; Vasic, Aleks; Bentaib, Ahmed; Journeau, Christophe; Malet, Jeanne; Studer, Etienne; Meynet, Nicolas; Piluso, Pascal; Gelain, Thomas; Michielsen, Nathalie; Peillon, Samuel; Porcheron, Emmanuel; Albiol, Thierry; Clement, Bernard; Sonnenkalb, Martin; Klein-Hessling, Walter; Arndt, Siegfried; Weber, Gunter; Yanez, Jorge; Kotchourko, Alexei; Kuznetsov, Mike; Sangiorgi, Marco; Fontanet, Joan; Herranz, Luis; Garcia De La Rua, Carmen; Santiago, Aleza Enciso; Andreani, Michele; Paladino, Domenico; Dreier, Joerg; Lee, Richard; Amri, Abdallah

    2014-01-01

    The Committee on the Safety of Nuclear Installations (CSNI) formed the CCVM (Containment Code Validation Matrix) task group in 2002. The objective of this group was to define a basic set of available experiments for code validation, covering the range of containment (ex-vessel) phenomena expected in the course of light and heavy water reactor design basis accidents and beyond design basis accidents/severe accidents. It was to consider phenomena relevant to pressurised heavy water reactor (PHWR), pressurised water reactor (PWR) and boiling water reactor (BWR) designs of Western origin as well as of Eastern European VVER types. This work would complement the two existing CSNI validation matrices for thermal hydraulic code validation (NEA/CSNI/R(1993)14) and In-vessel core degradation (NEA/CSNI/R(2001)21). The report initially provides a brief overview of the main features of a PWR, BWR, CANDU and VVER reactors. It also provides an overview of the ex-vessel corium retention (core catcher). It then provides a general overview of the accident progression for light water and heavy water reactors. The main focus is to capture most of the phenomena and safety systems employed in these reactor types and to highlight the differences. This CCVM contains a description of 127 phenomena, broken down into 6 categories: - Containment Thermal-hydraulics Phenomena; - Hydrogen Behaviour (Combustion, Mitigation and Generation) Phenomena; - Aerosol and Fission Product Behaviour Phenomena; - Iodine Chemistry Phenomena; - Core Melt Distribution and Behaviour in Containment Phenomena; - Systems Phenomena. A synopsis is provided for each phenomenon, including a description, references for further information, significance for DBA and SA/BDBA and a list of experiments that may be used for code validation. The report identified 213 experiments, broken down into the same six categories (as done for the phenomena). An experiment synopsis is provided for each test. Along with a test description

  4. The matrix of inspiration

    Science.gov (United States)

    Oehlmann, Dietmar; Ohlmann, Odile M.; Danzebrink, Hans U.

    2005-04-01

    perform this exchange, as a matrix, understood as source, of new ideas.

  5. Mid-temperature deep removal of hydrogen sulfide on rare earth (RE = Ce, La, Sm, Gd) doped ZnO supported on KIT-6: Effect of RE dopants and interaction between active phase and support matrix

    Energy Technology Data Exchange (ETDEWEB)

    Li, Lu; Zhou, Pin; Zhang, Hongbo; Meng, Xianglong; Li, Juexiu; Sun, Tonghua, E-mail: sunth@sjtu.edu.cn

    2017-06-15

    Highlights: • Various rare earth (RE)-doped ZnO/KIT-6 sorbents were prepared via sol-gel method. • La showed the highest efficiency on promoting ZnO/KIT-6 desulfurization activity. • The morphology of ZnO on KIT-6 played a crucial role for the reactivity. • The most initial factor of improving reactivity by RE was surface chemical property. • Crystallinity, host-guest interaction were also important to ZnO state on support. - Abstract: Rare earth oxides (RE = Ce, La, Sm and Gd) doped ZnO supported on KIT-6 sorbents (RE-ZnO/KIT-6) were synthesized by sol-gel method and their performance for deep removal of H{sub 2}S (bellow 0.1 ppmv) from gas stream at medium temperature was tested. The RE dopants (except Ce) significantly enhance the deep desulfurization capacity of ZnO/KIT-6 sorbent and maintained higher sulfur uptake capacities upon multiple cycles of regeneration by a simple thermal oxidation in 10 v% of O{sub 2} in N{sub 2} atmosphere. The results of SAXS, XRD, N{sub 2} physisorption, TEM, FIIR, and XPS implied that the KIT-6 structure of loading metal oxides remained intact. It was found that RE could hinder the ZnO crystal ripening during calcination resulted in smaller ZnO particles, enhance the interaction of ZnO and silica matrix to improve the dispersion of active phase on KIT-6. Furthermore, by increasing the outlayer electron density of Zn atom and oxygen transfer ability, the synergistic effect considered to be favorable for RE-ZnO/KIT-6 sulfidation. Even though the performance of improving ZnO dispersion was weaker than that of Sm and Gd, La-ZnO/KIT-6 performs the best deep desulfurizers by changing the surface chemical atmosphere for ZnO. Steam in the gas stream inhibited the capture of H{sub 2}S by ZnO in the sorbents, in the case of La-ZnO/KIT-6, the steam content should control as lower as 5 v% to ensure the desulfurization efficiency and precision.

  6. Mid-temperature deep removal of hydrogen sulfide on rare earth (RE = Ce, La, Sm, Gd) doped ZnO supported on KIT-6: Effect of RE dopants and interaction between active phase and support matrix

    International Nuclear Information System (INIS)

    Li, Lu; Zhou, Pin; Zhang, Hongbo; Meng, Xianglong; Li, Juexiu; Sun, Tonghua

    2017-01-01

    Highlights: • Various rare earth (RE)-doped ZnO/KIT-6 sorbents were prepared via sol-gel method. • La showed the highest efficiency on promoting ZnO/KIT-6 desulfurization activity. • The morphology of ZnO on KIT-6 played a crucial role for the reactivity. • The most initial factor of improving reactivity by RE was surface chemical property. • Crystallinity, host-guest interaction were also important to ZnO state on support. - Abstract: Rare earth oxides (RE = Ce, La, Sm and Gd) doped ZnO supported on KIT-6 sorbents (RE-ZnO/KIT-6) were synthesized by sol-gel method and their performance for deep removal of H 2 S (bellow 0.1 ppmv) from gas stream at medium temperature was tested. The RE dopants (except Ce) significantly enhance the deep desulfurization capacity of ZnO/KIT-6 sorbent and maintained higher sulfur uptake capacities upon multiple cycles of regeneration by a simple thermal oxidation in 10 v% of O 2 in N 2 atmosphere. The results of SAXS, XRD, N 2 physisorption, TEM, FIIR, and XPS implied that the KIT-6 structure of loading metal oxides remained intact. It was found that RE could hinder the ZnO crystal ripening during calcination resulted in smaller ZnO particles, enhance the interaction of ZnO and silica matrix to improve the dispersion of active phase on KIT-6. Furthermore, by increasing the outlayer electron density of Zn atom and oxygen transfer ability, the synergistic effect considered to be favorable for RE-ZnO/KIT-6 sulfidation. Even though the performance of improving ZnO dispersion was weaker than that of Sm and Gd, La-ZnO/KIT-6 performs the best deep desulfurizers by changing the surface chemical atmosphere for ZnO. Steam in the gas stream inhibited the capture of H 2 S by ZnO in the sorbents, in the case of La-ZnO/KIT-6, the steam content should control as lower as 5 v% to ensure the desulfurization efficiency and precision.

  7. Measuring methods of matrix diffusion

    International Nuclear Information System (INIS)

    Muurinen, A.; Valkiainen, M.

    1988-03-01

    In Finland the spent nuclear fuel is planned to be disposed of at large depths in crystalline bedrock. The radionuclides which are dissolved in the groundwater may be able to diffuse into the micropores of the porous rock matrix and thus be withdrawn from the flowing water in the fractures. This phenomenon is called matrix diffusion. A review over matrix diffusion is presented in the study. The main interest is directed to the diffusion of non-sorbing species. The review covers diffusion experiments and measurements of porosity, pore size, specific surface area and water permeability

  8. Maximal quantum Fisher information matrix

    International Nuclear Information System (INIS)

    Chen, Yu; Yuan, Haidong

    2017-01-01

    We study the existence of the maximal quantum Fisher information matrix in the multi-parameter quantum estimation, which bounds the ultimate precision limit. We show that when the maximal quantum Fisher information matrix exists, it can be directly obtained from the underlying dynamics. Examples are then provided to demonstrate the usefulness of the maximal quantum Fisher information matrix by deriving various trade-off relations in multi-parameter quantum estimation and obtaining the bounds for the scalings of the precision limit. (paper)

  9. Removal of phenolic endocrine disrupting compounds from waste activated sludge using UV, H2O2, and UV/H2O2 oxidation processes: Effects of reaction conditions and sludge matrix

    International Nuclear Information System (INIS)

    Zhang, Ai; Li, Yongmei

    2014-01-01

    Removal of six phenolic endocrine disrupting compounds (EDCs) (estrone, 17β-estradiol, 17α-ethinylestradiol, estriol, bisphenol A, and 4-nonylphenols) from waste activated sludge (WAS) was investigated using ultraviolet light (UV), hydrogen peroxide (H 2 O 2 ), and the combined UV/H 2 O 2 processes. Effects of initial EDC concentration, H 2 O 2 dosage, and pH value were investigated. Particularly, the effects of 11 metal ions and humic acid (HA) contained in a sludge matrix on EDC degradation were evaluated. A pseudo-first-order kinetic model was used to describe the EDC degradation during UV, H 2 O 2 , and UV/H 2 O 2 treatments of WAS. The results showed that the degradation of the 6 EDCs during all the three oxidation processes fitted well with pseudo-first-order kinetics. Compared with the sole UV irradiation or H 2 O 2 oxidation process, UV/H 2 O 2 treatment was much more effective for both EDC degradation and WAS solubilization. Under their optimal conditions, the EDC degradation rate constants during UV/H 2 O 2 oxidation were 45–197 times greater than those during UV irradiation and 11–53 times greater than those during H 2 O 2 oxidation. High dosage of H 2 O 2 and low pH were favorable for the degradation of EDCs. Under the conditions of pH = 3, UV wavelength = 253.7 nm, UV fluence rate = 0.069 mW cm −2 , and H 2 O 2 dosage = 0.5 mol L −1 , the removal efficiencies of E1, E2, EE2, E3, BPA, and NP in 2 min were 97%, 92%, 95%, 94%, 89%, and 67%, respectively. The hydroxyl radical (·OH) was proved to take the most important role for the removal of EDCs. Metal ions in sludge could facilitate the removal of EDCs during UV/H 2 O 2 oxidation. Fe, Ag, and Cu ions had more obvious effects compared with other metal ions. The overall role of HA was dependent on the balance between its competition as organics and its catalysis/photosensitization effects. These indicate that the sludge matrix plays an important role in the degradation of EDCs. - Highlights:

  10. A random matrix analysis

    Indian Academy of Sciences (India)

    in a wide variety of disciplines ranging from physics to psychology to economics and attempts to draw the .... ferences, differences in internal environment, biological activities, modes of functioning in those species .... tra of the gene coexpression network of Zebrafish generated for different environmental perturbations, is ...

  11. Gonadotropin-releasing hormone type II (GnRH-II) agonist regulates the invasiveness of endometrial cancer cells through the GnRH-I receptor and mitogen-activated protein kinase (MAPK)-dependent activation of matrix metalloproteinase (MMP)-2

    International Nuclear Information System (INIS)

    Wu, Hsien-Ming; Wang, Hsin-Shih; Huang, Hong-Yuan; Lai, Chyong-Huey; Lee, Chyi-Long; Soong, Yung-Kuei; Leung, Peter CK

    2013-01-01

    More than 25% of patients diagnosed with endometrial carcinoma have an invasive primary cancer accompanied by metastases. Gonadotropin-releasing hormone (GnRH) plays an important role in reproduction. In mammals, expression of GnRH-II is higher than GnRH-I in reproductive tissues. Here, we examined the effect of a GnRH-II agonist on the motility of endometrial cancer cells and its mechanism of action in endometrial cancer therapy. Immunoblotting and immunohistochemistry (IHC) were used to determine the expression of the GnRH-I receptor protein in human endometrial cancer. The activity of MMP-2 in the conditioned medium was determined by gelatin zymography. Cell motility was assessed by invasion and migration assay. GnRH-I receptor si-RNA was applied to knockdown GnRH-I receptor. The GnRH-I receptor was expressed in the endometrial cancer cells. The GnRH-II agonist promoted cell motility in a dose-dependent manner. The GnRH-II agonist induced the phosphorylation of ERK1/2 and JNK, and the phosphorylation was abolished by ERK1/2 inhibitor (U0126) and the JNK inhibitor (SP600125). Cell motility promoted by GnRH-II agonist was suppressed in cells that were pretreated with U0126 and SP600125. Moreover, U0126 and SP600125 abolished the GnRH-II agonist-induced activation of MMP-2. The inhibition of MMP-2 with MMP-2 inhibitor (OA-Hy) suppressed the increase in cell motility in response to the GnRH-II agonist. Enhanced cell motility mediated by GnRH-II agonist was also suppressed by the knockdown of the endogenous GnRH-I receptor using siRNA. Our study indicates that GnRH-II agonist promoted cell motility of endometrial cancer cells through the GnRH-I receptor via the phosphorylation of ERK1/2 and JNK, and the subsequent, MAPK-dependent activation of MMP-2. Our findings represent a new concept regarding the mechanism of GnRH-II-induced cell motility in endometrial cancer cells and suggest the possibility of exploring GnRH-II as a potential therapeutic target for the

  12. Matrix product operators, matrix product states, and ab initio density matrix renormalization group algorithms

    Science.gov (United States)

    Chan, Garnet Kin-Lic; Keselman, Anna; Nakatani, Naoki; Li, Zhendong; White, Steven R.

    2016-07-01

    Current descriptions of the ab initio density matrix renormalization group (DMRG) algorithm use two superficially different languages: an older language of the renormalization group and renormalized operators, and a more recent language of matrix product states and matrix product operators. The same algorithm can appear dramatically different when written in the two different vocabularies. In this work, we carefully describe the translation between the two languages in several contexts. First, we describe how to efficiently implement the ab initio DMRG sweep using a matrix product operator based code, and the equivalence to the original renormalized operator implementation. Next we describe how to implement the general matrix product operator/matrix product state algebra within a pure renormalized operator-based DMRG code. Finally, we discuss two improvements of the ab initio DMRG sweep algorithm motivated by matrix product operator language: Hamiltonian compression, and a sum over operators representation that allows for perfect computational parallelism. The connections and correspondences described here serve to link the future developments with the past and are important in the efficient implementation of continuing advances in ab initio DMRG and related algorithms.

  13. GoM Diet Matrix

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set was taken from CRD 08-18 at the NEFSC. Specifically, the Gulf of Maine diet matrix was developed for the EMAX exercise described in that center...

  14. On matrix fractional differential equations

    Directory of Open Access Journals (Sweden)

    Adem Kılıçman

    2017-01-01

    Full Text Available The aim of this article is to study the matrix fractional differential equations and to find the exact solution for system of matrix fractional differential equations in terms of Riemann–Liouville using Laplace transform method and convolution product to the Riemann–Liouville fractional of matrices. Also, we show the theorem of non-homogeneous matrix fractional partial differential equation with some illustrative examples to demonstrate the effectiveness of the new methodology. The main objective of this article is to discuss the Laplace transform method based on operational matrices of fractional derivatives for solving several kinds of linear fractional differential equations. Moreover, we present the operational matrices of fractional derivatives with Laplace transform in many applications of various engineering systems as control system. We present the analytical technique for solving fractional-order, multi-term fractional differential equation. In other words, we propose an efficient algorithm for solving fractional matrix equation.

  15. Electromagnetic matrix elements in baryons

    International Nuclear Information System (INIS)

    Lipkin, H.J.; Moinester, M.A.

    1992-01-01

    Some simple symmetry relations between matrix elements of electromagnetic operators are investigated. The implications are discussed for experiments to study hyperon radiative transitions and polarizabilities and form factors. (orig.)

  16. The R-matrix theory

    International Nuclear Information System (INIS)

    Descouvemont, P; Baye, D

    2010-01-01

    The different facets of the R-matrix method are presented pedagogically in a general framework. Two variants have been developed over the years: (i) The 'calculable' R-matrix method is a calculational tool to derive scattering properties from the Schroedinger equation in a large variety of physical problems. It was developed rather independently in atomic and nuclear physics with too little mutual influence. (ii) The 'phenomenological' R-matrix method is a technique to parametrize various types of cross sections. It was mainly (or uniquely) used in nuclear physics. Both directions are explained by starting from the simple problem of scattering by a potential. They are illustrated by simple examples in nuclear and atomic physics. In addition to elastic scattering, the R-matrix formalism is applied to inelastic and radiative-capture reactions. We also present more recent and more ambitious applications of the theory in nuclear physics.

  17. Random matrix improved subspace clustering

    KAUST Repository

    Couillet, Romain; Kammoun, Abla

    2017-01-01

    This article introduces a spectral method for statistical subspace clustering. The method is built upon standard kernel spectral clustering techniques, however carefully tuned by theoretical understanding arising from random matrix findings. We show

  18. Matrix Effects in XRF Measurements

    International Nuclear Information System (INIS)

    Kandil, A.T.; Gabr, N.A.; El-Aryan, S.M.

    2015-01-01

    This research treats the matrix effect on XRF measurements. The problem is treated by preparing general oxide program, which contains many samples that represent all materials in cement factories, then by using T rail Lachance m ethod to correct errors of matrix effect. This work compares the effect of using lithium tetraborate or sodium tetraborate as a fluxing agent in terms of accuracy and economic cost

  19. Matrix analysis of electrical machinery

    CERN Document Server

    Hancock, N N

    2013-01-01

    Matrix Analysis of Electrical Machinery, Second Edition is a 14-chapter edition that covers the systematic analysis of electrical machinery performance. This edition discusses the principles of various mathematical operations and their application to electrical machinery performance calculations. The introductory chapters deal with the matrix representation of algebraic equations and their application to static electrical networks. The following chapters describe the fundamentals of different transformers and rotating machines and present torque analysis in terms of the currents based on the p

  20. Staggered chiral random matrix theory

    International Nuclear Information System (INIS)

    Osborn, James C.

    2011-01-01

    We present a random matrix theory for the staggered lattice QCD Dirac operator. The staggered random matrix theory is equivalent to the zero-momentum limit of the staggered chiral Lagrangian and includes all taste breaking terms at their leading order. This is an extension of previous work which only included some of the taste breaking terms. We will also present some results for the taste breaking contributions to the partition function and the Dirac eigenvalues.

  1. Control of extracellular matrix assembly by syndecan-2 proteoglycan

    DEFF Research Database (Denmark)

    Klass, C M; Couchman, J R; Woods, A

    2000-01-01

    Extracellular matrix (ECM) deposition and organization is maintained by transmembrane signaling and integrins play major roles. We now show that a second transmembrane component, syndecan-2 heparan sulfate proteoglycan, is pivotal in matrix assembly. Chinese Hamster Ovary (CHO) cells were stably...... to rearrange laminin or fibronectin substrates into fibrils and to bind exogenous fibronectin. Transfection of activated alphaIIbalphaLdeltabeta3 integrin into alpha(5)-deficient CHO B2 cells resulted in reestablishment of the previously lost fibronectin matrix. However, cotransfection of this cell line with S...

  2. Control of radioactive wastes and coupling of neutron/gamma measurements: use of radiative capture for the correction of matrix effects that penalize the fissile mass measurement by active neutron interrogation; Controle des dechets radioactifs et couplage de mesures neutron/gamma: exploitation de la capture radiative pour corriger les effets de matrice penalisant la mesure de la masse fissile par interrogation neutronique active

    Energy Technology Data Exchange (ETDEWEB)

    Loche, F

    2006-10-15

    In the framework of radioactive waste drums control, difficulties arise in the nondestructive measurement of fissile mass ({sup 235}U, {sup 239}Pu..) by Active Neutron Interrogation (ANI), when dealing with matrices containing materials (Cl, H...) influencing the neutron flux. The idea is to use the neutron capture reaction (n,{gamma}) to determine the matrix composition to adjust the ANI calibration coefficient value. This study, dealing with 118 litres, homogeneous drums of density less than 0,4 and composed of chlorinated and/or hydrogenated materials, leads to build abacus linking the {gamma} ray peak areas to the ANI calibration coefficient. Validation assays of these abacus show a very good agreement between the corrected and true fissile masses for hydrogenated matrices (max. relative standard deviation: 23 %) and quite good for chlorinated and hydrogenated matrices (58 %). The developed correction method improves the measured values. It may be extended to 0,45 density, heterogeneous drums. (author)

  3. Scintillator high-gain avalanche rushing photoconductor active-matrix flat panel imager: zero-spatial frequency x-ray imaging properties of the solid-state SHARP sensor structure.

    Science.gov (United States)

    Wronski, M; Zhao, W; Tanioka, K; Decrescenzo, G; Rowlands, J A

    2012-11-01

    The authors are investigating the feasibility of a new type of solid-state x-ray imaging sensor with programmable avalanche gain: scintillator high-gain avalanche rushing photoconductor active matrix flat panel imager (SHARP-AMFPI). The purpose of the present work is to investigate the inherent x-ray detection properties of SHARP and demonstrate its wide dynamic range through programmable gain. A distributed resistive layer (DRL) was developed to maintain stable avalanche gain operation in a solid-state HARP. The signal and noise properties of the HARP-DRL for optical photon detection were investigated as a function of avalanche gain both theoretically and experimentally, and the results were compared with HARP tube (with electron beam readout) used in previous investigations of zero spatial frequency performance of SHARP. For this new investigation, a solid-state SHARP x-ray image sensor was formed by direct optical coupling of the HARP-DRL with a structured cesium iodide (CsI) scintillator. The x-ray sensitivity of this sensor was measured as a function of avalanche gain and the results were compared with the sensitivity of HARP-DRL measured optically. The dynamic range of HARP-DRL with variable avalanche gain was investigated for the entire exposure range encountered in radiography∕fluoroscopy (R∕F) applications. The signal from HARP-DRL as a function of electric field showed stable avalanche gain, and the noise associated with the avalanche process agrees well with theory and previous measurements from a HARP tube. This result indicates that when coupled with CsI for x-ray detection, the additional noise associated with avalanche gain in HARP-DRL is negligible. The x-ray sensitivity measurements using the SHARP sensor produced identical avalanche gain dependence on electric field as the optical measurements with HARP-DRL. Adjusting the avalanche multiplication gain in HARP-DRL enabled a very wide dynamic range which encompassed all clinicall