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Sample records for cartilage gap model

  1. Cartilage.

    Science.gov (United States)

    Caplan, Arnold I.

    1984-01-01

    Cartilage is a fundamental biological material that helps to shape the body and then helps to support it. Its fundamental properties of strength and resilience are explained in terms of the tissue's molecular structure. (JN)

  2. Modeling the development of tissue engineered cartilage

    NARCIS (Netherlands)

    Sengers, B.G.

    2005-01-01

    The limited healing capacity of articular cartilage forms a major clinical problem. In general, current treatments of cartilage damage temporarily reliefs symptoms, but fail in the long term. Tissue engineering (TE) has been proposed as a more permanent repair strategy. Cartilage TE aims at

  3. An ex vivo human cartilage repair model to evaluate the potency of a cartilage cell transplant.

    Science.gov (United States)

    Bartz, Christoph; Meixner, Miriam; Giesemann, Petra; Roël, Giulietta; Bulwin, Grit-Carsta; Smink, Jeske J

    2016-11-15

    Cell-based therapies such as autologous chondrocyte implantation are promising therapeutic approaches to treat cartilage defects to prevent further cartilage degeneration. To assure consistent quality of cell-based therapeutics, it is important to be able to predict the biological activity of such products. This requires the development of a potency assay, which assesses a characteristic of the cell transplant before implantation that can predict its cartilage regeneration capacity after implantation. In this study, an ex vivo human cartilage repair model was developed as quality assessment tool for potency and applied to co.don's chondrosphere product, a matrix-associated autologous chondrocyte implant (chondrocyte spheroids) that is in clinical use in Germany. Chondrocyte spheroids were generated from 14 donors, and implanted into a subchondral cartilage defect that was manually generated in human articular cartilage tissue. Implanted spheroids and cartilage tissue were co-cultured ex vivo for 12 weeks to allow regeneration processes to form new tissue within the cartilage defect. Before implantation, spheroid characteristics like glycosaminoglycan production and gene and protein expression of chondrogenic markers were assessed for each donor sample and compared to determine donor-dependent variation. After the co-cultivation, histological analyses showed the formation of repair tissue within the cartilage defect, which varied in amount for the different donors. In the repair tissue, aggrecan protein was expressed and extra-cellular matrix cartilage fibers were present, both indicative for a cartilage hyaline-like character of the repair tissue. The amount of formed repair tissue was used as a read-out for regeneration capacity and was correlated with the spheroid characteristics determined before implantation. A positive correlation was found between high level of aggrecan protein expression in spheroids before implantation and a higher regeneration potential

  4. An ex vivo human cartilage repair model to evaluate the potency of a cartilage cell transplant

    Directory of Open Access Journals (Sweden)

    Christoph Bartz

    2016-11-01

    Full Text Available Abstract Background Cell-based therapies such as autologous chondrocyte implantation are promising therapeutic approaches to treat cartilage defects to prevent further cartilage degeneration. To assure consistent quality of cell-based therapeutics, it is important to be able to predict the biological activity of such products. This requires the development of a potency assay, which assesses a characteristic of the cell transplant before implantation that can predict its cartilage regeneration capacity after implantation. In this study, an ex vivo human cartilage repair model was developed as quality assessment tool for potency and applied to co.don’s chondrosphere product, a matrix-associated autologous chondrocyte implant (chondrocyte spheroids that is in clinical use in Germany. Methods Chondrocyte spheroids were generated from 14 donors, and implanted into a subchondral cartilage defect that was manually generated in human articular cartilage tissue. Implanted spheroids and cartilage tissue were co-cultured ex vivo for 12 weeks to allow regeneration processes to form new tissue within the cartilage defect. Before implantation, spheroid characteristics like glycosaminoglycan production and gene and protein expression of chondrogenic markers were assessed for each donor sample and compared to determine donor-dependent variation. Results After the co-cultivation, histological analyses showed the formation of repair tissue within the cartilage defect, which varied in amount for the different donors. In the repair tissue, aggrecan protein was expressed and extra-cellular matrix cartilage fibers were present, both indicative for a cartilage hyaline-like character of the repair tissue. The amount of formed repair tissue was used as a read-out for regeneration capacity and was correlated with the spheroid characteristics determined before implantation. A positive correlation was found between high level of aggrecan protein expression in spheroids

  5. Animal models used for testing hydrogels in cartilage regeneration.

    Science.gov (United States)

    Zhu, Chuntie; Wu, Qiong; Zhang, Xu; Chen, Fubo; Liu, Xiyang; Yang, Qixiang; Zhu, Lei

    2018-05-14

    Focal cartilage or osteochondral lesions can be painful and detrimental. Besides pain and limited function of joints, cartilage defect is considered as one of the leading extrinsic risk factors for osteoarthritis (OA). Thus, clinicians and scientists have paid great attention to regenerative therapeutic methods for the early treatment of cartilaginous defects. Regenerative medicine, showing great hope for regenerating cartilage tissue, rely on the combination of biodegradable scaffolds and specific biological cues, such as growth factors, adhesive factors and genetic materials. Among all biomaterials, hydrogels have emerged as promising cartilage tissue engineering scaffolds for simultaneous cell growth and drug delivery. A wide range of animal models have been applied in testing repair with hydrogels in cartilage defects. This review summarized the current animal models used to test hydrogels technologies for the regeneration of cartilage. Advantages and disadvantages in the establishment of the cartilage defect animal models among different species were emphasized, as well as feasibility of replication of diseases in animals. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Articular chondrocyte network mediated by gap junctions: role in metabolic cartilage homeostasis

    Science.gov (United States)

    Mayan, Maria D; Gago-Fuentes, Raquel; Carpintero-Fernandez, Paula; Fernandez-Puente, Patricia; Filgueira-Fernandez, Purificacion; Goyanes, Noa; Valiunas, Virginijus; Brink, Peter R; Goldberg, Gary S; Blanco, Francisco J

    2017-01-01

    Objective This study investigated whether chondrocytes within the cartilage matrix have the capacity to communicate through intercellular connections mediated by voltage-gated gap junction (GJ) channels. Methods Frozen cartilage samples were used for immunofluorescence and immunohistochemistry assays. Samples were embedded in cacodylate buffer before dehydration for scanning electron microscopy. Co-immunoprecipitation experiments and mass spectrometry (MS) were performed to identify proteins that interact with the C-terminal end of Cx43. GJ communication was studied through in situ electroporation, electrophysiology and dye injection experiments. A transwell layered culture system and MS were used to identify and quantify transferred amino acids. Results Microscopic images revealed the presence of multiple cellular projections connecting chondrocytes within the matrix. These projections were between 5 and 150 μm in length. MS data analysis indicated that the C-terminus of Cx43 interacts with several cytoskeletal proteins implicated in Cx trafficking and GJ assembly, including α-tubulin and β-tubulin, actin, and vinculin. Electrophysiology experiments demonstrated that 12-mer oligonucleotides could be transferred between chondrocytes within 12 min after injection. Glucose was homogeneously distributed within 22 and 35 min. No transfer was detected when glucose was electroporated into A549 cells, which have no GJs. Transwell layered culture systems coupled with MS analysis revealed connexins can mediate the transfer of L-lysine and L-arginine between chondrocytes. Conclusions This study reveals that intercellular connections between chondrocytes contain GJs that play a key role in cell-cell communication and a metabolic function by exchange of nutrients including glucose and essential amino acids. A three-dimensional cellular network mediated through GJs might mediate metabolic and physiological homeostasis to maintain cartilage tissue. PMID:24225059

  7. Comparative digital cartilage histology for human and common osteoarthritis models

    Directory of Open Access Journals (Sweden)

    Pedersen DR

    2013-02-01

    Full Text Available Douglas R Pedersen, Jessica E Goetz, Gail L Kurriger, James A MartinDepartment of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA, USAPurpose: This study addresses the species-specific and site-specific details of weight-bearing articular cartilage zone depths and chondrocyte distributions among humans and common osteoarthritis (OA animal models using contemporary digital imaging tools. Histological analysis is the gold-standard research tool for evaluating cartilage health, OA severity, and treatment efficacy. Historically, evaluations were made by expert analysts. However, state-of-the-art tools have been developed that allow for digitization of entire histological sections for computer-aided analysis. Large volumes of common digital cartilage metrics directly complement elucidation of trends in OA inducement and concomitant potential treatments.Materials and methods: Sixteen fresh human knees, 26 adult New Zealand rabbit stifles, and 104 bovine lateral plateaus were measured for four cartilage zones and the cell densities within each zone. Each knee was divided into four weight-bearing sites: the medial and lateral plateaus and femoral condyles.Results: One-way analysis of variance followed by pairwise multiple comparisons (Holm–Sidak method at a significance of 0.05 clearly confirmed the variability between cartilage depths at each site, between sites in the same species, and between weight-bearing articular cartilage definitions in different species.Conclusion: The present study clearly demonstrates multisite, multispecies differences in normal weight-bearing articular cartilage, which can be objectively quantified by a common digital histology imaging technique. The clear site-specific differences in normal cartilage must be taken into consideration when characterizing the pathoetiology of OA models. Together, these provide a path to consistently analyze the volume and variety of histologic slides necessarily generated

  8. Repair of articular cartilage defects in the knee with autologous iliac crest cartilage in a rabbit model.

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    Jing, Lizhong; Zhang, Jiying; Leng, Huijie; Guo, Qinwei; Hu, Yuelin

    2015-04-01

    To demonstrate that iliac crest cartilage may be used to repair articular cartilage defects in the knees of rabbits. Full-thickness cartilage defects were created in the medial femoral condyle on both knees of 36 New Zealand white rabbits. The 72 defects were randomly assigned to be repaired with ipsilateral iliac crest cartilage (Group I), osteochondral tissues removed at defect creation (Group II), or no treatment (negative control, Group III). Animals were killed at 6, 12, and 24 weeks post-operatively. The repaired tissues were harvested for magnetic resonance imaging (MRI), histological studies (haematoxylin and eosin and immunohistochemical staining), and mechanical testing. At 6 weeks, the iliac crest cartilage graft was not yet well integrated with the surrounding articular cartilage, but at 12 weeks, the graft deep zone had partial ossification. By 24 weeks, the hyaline cartilage-like tissue was completely integrated with the surrounding articular cartilage. Osteochondral autografts showed more rapid healing than Group I at 6 weeks and complete healing at 12 weeks. Untreated defects were concave or partly filled with fibrous tissue throughout the study. MRI showed that Group I had slower integration with surrounding normal cartilage compared with Group II. The mechanical properties of Group I were significantly lower than those of Group II at 12 weeks, but this difference was not significant at 24 weeks. Iliac crest cartilage autografts were able to repair knee cartilage defects with hyaline cartilage and showed comparable results with osteochondral autografts in the rabbit model.

  9. A retinaculum-sparing surgical approach preserves porcine stifle joint cartilage in an experimental animal model of cartilage repair.

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    Bonadio, Marcelo B; Friedman, James M; Sennett, Mackenzie L; Mauck, Robert L; Dodge, George R; Madry, Henning

    2017-12-01

    This study compares a traditional parapatellar retinaculum-sacrificing arthrotomy to a retinaculum-sparing arthrotomy in a porcine stifle joint as a cartilage repair model. Surgical exposure of the femoral trochlea of ten Yucatan pigs stifle joint was performed using either a traditional medial parapatellar approach with retinaculum incision and luxation of the patella (n = 5) or a minimally invasive (MIS) approach which spared the patellar retinaculum (n = 5). Both classical and MIS approaches provided adequate access to the trochlea, enabling the creation of cartilage defects without difficulties. Four full thickness, 4 mm circular full-thickness cartilage defects were created in each trochlea. There were no intraoperative complications observed in either surgical approach. All pigs were allowed full weight-bearing and full range of motion immediately postoperatively and were euthanized between 2 and 3 weeks. The traditional approach was associated with increased cartilage wear compared to the MIS approach. Two blinded raters performed gross evaluation of the trochlea cartilage surrounding the defects according to the modified ICRS cartilage injury classification. The traditional approach cartilage received a significantly worse score than the MIS approach group from both scorers (3.2 vs 0.8, p = 0.01 and 2.8 vs 0, p = 0.005 respectively). The MIS approach results in less damage to the trochlear cartilage and faster return to load bearing activities. As an arthrotomy approach in the porcine model, MIS is superior to the traditional approach.

  10. The fluctuating gap model

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Xiaobin

    2011-01-15

    The quasi-one-dimensional systems exhibit some unusual phenomenon, such as the Peierls instability, the pseudogap phenomena and the absence of a Fermi-Dirac distribution function line shape in the photoemission spectroscopy. Ever since the discovery of materials with highly anisotropic properties, it has been recognized that fluctuations play an important role above the three-dimensional phase transition. This regime where the precursor fluctuations are presented can be described by the so called fluctuating gap model (FGM) which was derived from the Froehlich Hamiltonian to study the low energy physics of the one-dimensional electron-phonon system. Not only is the FGM of great interest in the context of quasi-one-dimensional materials, liquid metal and spin waves above T{sub c} in ferromagnets, but also in the semiclassical approximation of superconductivity, it is possible to replace the original three-dimensional problem by a directional average over effectively one-dimensional problem which in the weak coupling limit is described by the FGM. In this work, we investigate the FGM in a wide temperature range with different statistics of the order parameter fluctuations. We derive a formally exact solution to this problem and calculate the density of states, the spectral function and the optical conductivity. In our calculation, we show that a Dyson singularity appears in the low energy density of states for Gaussian fluctuations in the commensurate case. In the incommensurate case, there is no such kind of singularity, and the zero frequency density of states varies differently as a function of the correlation lengths for different statistics of the order parameter fluctuations. Using the density of states we calculated with non-Gaussian order parameter fluctuations, we are able to calculate the static spin susceptibility which agrees with the experimental data very well. In the calculation of the spectral functions, we show that as the correlation increases, the

  11. The fluctuating gap model

    International Nuclear Information System (INIS)

    Cao, Xiaobin

    2011-01-01

    The quasi-one-dimensional systems exhibit some unusual phenomenon, such as the Peierls instability, the pseudogap phenomena and the absence of a Fermi-Dirac distribution function line shape in the photoemission spectroscopy. Ever since the discovery of materials with highly anisotropic properties, it has been recognized that fluctuations play an important role above the three-dimensional phase transition. This regime where the precursor fluctuations are presented can be described by the so called fluctuating gap model (FGM) which was derived from the Froehlich Hamiltonian to study the low energy physics of the one-dimensional electron-phonon system. Not only is the FGM of great interest in the context of quasi-one-dimensional materials, liquid metal and spin waves above T c in ferromagnets, but also in the semiclassical approximation of superconductivity, it is possible to replace the original three-dimensional problem by a directional average over effectively one-dimensional problem which in the weak coupling limit is described by the FGM. In this work, we investigate the FGM in a wide temperature range with different statistics of the order parameter fluctuations. We derive a formally exact solution to this problem and calculate the density of states, the spectral function and the optical conductivity. In our calculation, we show that a Dyson singularity appears in the low energy density of states for Gaussian fluctuations in the commensurate case. In the incommensurate case, there is no such kind of singularity, and the zero frequency density of states varies differently as a function of the correlation lengths for different statistics of the order parameter fluctuations. Using the density of states we calculated with non-Gaussian order parameter fluctuations, we are able to calculate the static spin susceptibility which agrees with the experimental data very well. In the calculation of the spectral functions, we show that as the correlation increases, the quasi

  12. A novel in vitro bovine cartilage punch model for assessing the regeneration of focal cartilage defects with biocompatible bacterial nanocellulose

    Science.gov (United States)

    2013-01-01

    Introduction Current therapies for articular cartilage defects fail to achieve qualitatively sufficient tissue regeneration, possibly because of a mismatch between the speed of cartilage rebuilding and the resorption of degradable implant polymers. The present study focused on the self-healing capacity of resident cartilage cells in conjunction with cell-free and biocompatible (but non-resorbable) bacterial nanocellulose (BNC). This was tested in a novel in vitro bovine cartilage punch model. Methods Standardized bovine cartilage discs with a central defect filled with BNC were cultured for up to eight weeks with/without stimulation with transforming growth factor-β1 (TGF-β1. Cartilage formation and integrity were analyzed by histology, immunohistochemistry and electron microscopy. Content, release and neosynthesis of the matrix molecules proteoglycan/aggrecan, collagen II and collagen I were also quantified. Finally, gene expression of these molecules was profiled in resident chondrocytes and chondrocytes migrated onto the cartilage surface or the implant material. Results Non-stimulated and especially TGF-β1-stimulated cartilage discs displayed a preserved structural and functional integrity of the chondrocytes and surrounding matrix, remained vital in long-term culture (eight weeks) without signs of degeneration and showed substantial synthesis of cartilage-specific molecules at the protein and mRNA level. Whereas mobilization of chondrocytes from the matrix onto the surface of cartilage and implant was pivotal for successful seeding of cell-free BNC, chondrocytes did not immigrate into the central BNC area, possibly due to the relatively small diameter of its pores (2 to 5 μm). Chondrocytes on the BNC surface showed signs of successful redifferentiation over time, including increase of aggrecan/collagen type II mRNA, decrease of collagen type I mRNA and initial deposition of proteoglycan and collagen type II in long-term high-density pellet cultures

  13. Anomalous NMR Relaxation in Cartilage Matrix Components and Native Cartilage: Fractional-Order Models

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    Magin, Richard L.; Li, Weiguo; Velasco, M. Pilar; Trujillo, Juan; Reiter, David A.; Morgenstern, Ashley; Spencer, Richard G.

    2011-01-01

    We present a fractional-order extension of the Bloch equations to describe anomalous NMR relaxation phenomena (T1 and T2). The model has solutions in the form of Mittag-Leffler and stretched exponential functions that generalize conventional exponential relaxation. Such functions have been shown by others to be useful for describing dielectric and viscoelastic relaxation in complex, heterogeneous materials. Here, we apply these fractional-order T1 and T2 relaxation models to experiments performed at 9.4 and 11.7 Tesla on type I collagen gels, chondroitin sulfate mixtures, and to bovine nasal cartilage (BNC), a largely isotropic and homogeneous form of cartilage. The results show that the fractional-order analysis captures important features of NMR relaxation that are typically described by multi-exponential decay models. We find that the T2 relaxation of BNC can be described in a unique way by a single fractional-order parameter (α), in contrast to the lack of uniqueness of multi-exponential fits in the realistic setting of a finite signal-to-noise ratio. No anomalous behavior of T1 was observed in BNC. In the single-component gels, for T2 measurements, increasing the concentration of the largest components of cartilage matrix, collagen and chondroitin sulfate, results in a decrease in α, reflecting a more restricted aqueous environment. The quality of the curve fits obtained using Mittag-Leffler and stretched exponential functions are in some cases superior to those obtained using mono- and bi-exponential models. In both gels and BNC, α appears to account for microstructural complexity in the setting of an altered distribution of relaxation times. This work suggests the utility of fractional-order models to describe T2 NMR relaxation processes in biological tissues. PMID:21498095

  14. Multiparametric MRI of Epiphyseal Cartilage Necrosis (Osteochondrosis with Histological Validation in a Goat Model.

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    Luning Wang

    Full Text Available To evaluate multiple MRI parameters in a surgical model of osteochondrosis (OC in goats.Focal ischemic lesions of two different sizes were induced in the epiphyseal cartilage of the medial femoral condyles of goats at 4 days of age by surgical transection of cartilage canal blood vessels. Goats were euthanized and specimens harvested 3, 4, 5, 6, 9 and 10 weeks post-op. Ex vivo MRI scans were conducted at 9.4 Tesla for mapping the T1, T2, T1ρ, adiabatic T1ρ and TRAFF relaxation times of articular cartilage, unaffected epiphyseal cartilage, and epiphyseal cartilage within the area of the induced lesion. After MRI scans, safranin O staining was conducted to validate areas of ischemic necrosis induced in the medial femoral condyles of six goats, and to allow comparison of MRI findings with the semi-quantitative proteoglycan assessment in corresponding safranin O-stained histological sections.All relaxation time constants differentiated normal epiphyseal cartilage from lesions of ischemic cartilage necrosis, and the histological staining results confirmed the proteoglycan (PG loss in the areas of ischemia. In the scanned specimens, all of the measured relaxation time constants were higher in the articular than in the normal epiphyseal cartilage, consistently allowing differentiation between these two tissues.Multiparametric MRI provided a sensitive approach to discriminate between necrotic and viable epiphyseal cartilage and between articular and epiphyseal cartilage, which may be useful for diagnosing and monitoring OC lesions and, potentially, for assessing effectiveness of treatment interventions.

  15. Application of a semi-automatic cartilage segmentation method for biomechanical modeling of the knee joint.

    Science.gov (United States)

    Liukkonen, Mimmi K; Mononen, Mika E; Tanska, Petri; Saarakkala, Simo; Nieminen, Miika T; Korhonen, Rami K

    2017-10-01

    Manual segmentation of articular cartilage from knee joint 3D magnetic resonance images (MRI) is a time consuming and laborious task. Thus, automatic methods are needed for faster and reproducible segmentations. In the present study, we developed a semi-automatic segmentation method based on radial intensity profiles to generate 3D geometries of knee joint cartilage which were then used in computational biomechanical models of the knee joint. Six healthy volunteers were imaged with a 3T MRI device and their knee cartilages were segmented both manually and semi-automatically. The values of cartilage thicknesses and volumes produced by these two methods were compared. Furthermore, the influences of possible geometrical differences on cartilage stresses and strains in the knee were evaluated with finite element modeling. The semi-automatic segmentation and 3D geometry construction of one knee joint (menisci, femoral and tibial cartilages) was approximately two times faster than with manual segmentation. Differences in cartilage thicknesses, volumes, contact pressures, stresses, and strains between segmentation methods in femoral and tibial cartilage were mostly insignificant (p > 0.05) and random, i.e. there were no systematic differences between the methods. In conclusion, the devised semi-automatic segmentation method is a quick and accurate way to determine cartilage geometries; it may become a valuable tool for biomechanical modeling applications with large patient groups.

  16. In Vitro Analysis of Cartilage Regeneration Using a Collagen Type I Hydrogel (CaReS) in the Bovine Cartilage Punch Model.

    Science.gov (United States)

    Horbert, Victoria; Xin, Long; Foehr, Peter; Brinkmann, Olaf; Bungartz, Matthias; Burgkart, Rainer H; Graeve, T; Kinne, Raimund W

    2018-02-01

    Objective Limitations of matrix-assisted autologous chondrocyte implantation to regenerate functional hyaline cartilage demand a better understanding of the underlying cellular/molecular processes. Thus, the regenerative capacity of a clinically approved hydrogel collagen type I implant was tested in a standardized bovine cartilage punch model. Methods Cartilage rings (outer diameter 6 mm; inner defect diameter 2 mm) were prepared from the bovine trochlear groove. Collagen implants (± bovine chondrocytes) were placed inside the cartilage rings and cultured up to 12 weeks. Cartilage-implant constructs were analyzed by histology (hematoxylin/eosin; safranin O), immunohistology (aggrecan, collagens 1 and 2), and for protein content, RNA expression, and implant push-out force. Results Cartilage-implant constructs revealed vital morphology, preserved matrix integrity throughout culture, progressive, but slight proteoglycan loss from the "host" cartilage or its surface and decreasing proteoglycan release into the culture supernatant. In contrast, collagen 2 and 1 content of cartilage and cartilage-implant interface was approximately constant over time. Cell-free and cell-loaded implants showed (1) cell migration onto/into the implant, (2) progressive deposition of aggrecan and constant levels of collagens 1 and 2, (3) progressively increased mRNA levels for aggrecan and collagen 2, and (4) significantly augmented push-out forces over time. Cell-loaded implants displayed a significantly earlier and more long-lasting deposition of aggrecan, as well as tendentially higher push-out forces. Conclusion Preserved tissue integrity and progressively increasing cartilage differentiation and push-out forces for up to 12 weeks of cultivation suggest initial cartilage regeneration and lateral bonding of the implant in this in vitro model for cartilage replacement materials.

  17. Science and animal models of marrow stimulation for cartilage repair.

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    Fortier, Lisa A; Cole, Brian J; McIlwraith, C Wayne

    2012-03-01

    Microfracture of subchondral bone to enhance cartilage repair is a popular surgical technique used in human and animal patients. Clinical results with resolution or improvement in pain are promising and last on average for 2 to 3 years. Animal studies aimed at understanding microfracture indicate that the repair tissue continues to remodel toward chondrogenesis for at least a year, but longer term results are not available to gain insight into the mechanism of microfracture function or failure over time. Subchondral bone sclerosis and central lesional osteophyte formation following subchondral bone microfracture have been observed in animal models of microfracture, but studies do not provide any insight into the etiology of these pathologies. The continued maturation of microfracture repair tissue over time supports further investigation of microfracture or microfracture-augmented cartilage repair procedures with caution for the investigator and clinician to be observant for conditions that lead to subchondral bone sclerosis or central osteophyte formation, and what affect these boney reactions have on clinical outcome.

  18. Contact mechanics of articular cartilage layers asymptotic models

    CERN Document Server

    Argatov, Ivan

    2015-01-01

    This book presents a comprehensive and unifying approach to articular contact mechanics with an emphasis on frictionless contact interaction of thin cartilage layers. The first part of the book (Chapters 1–4) reviews the results of asymptotic analysis of the deformational behavior of thin elastic and viscoelastic layers. A comprehensive review of the literature is combined with the authors’ original contributions. The compressible and incompressible cases are treated separately with a focus on exact solutions for asymptotic models of frictionless contact for thin transversely isotropic layers bonded to rigid substrates shaped like elliptic paraboloids. The second part (Chapters 5, 6, and 7) deals with the non-axisymmetric contact of thin transversely isotropic biphasic layers and presents the asymptotic modelling methodology for tibio-femoral contact. The third part of the book consists of Chapter 8, which covers contact problems for thin bonded inhomogeneous transversely isotropic elastic layers, and Cha...

  19. Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures

    Directory of Open Access Journals (Sweden)

    Melissa Lo Monaco

    2018-01-01

    Full Text Available Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs or induced pluripotent stem cells (iPSCs have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles. But before novel cell-based therapies for cartilage repair can be introduced into the clinic, rigorous testing in preclinical animal models is required. Preclinical models used in regenerative cartilage studies include murine, lapine, caprine, ovine, porcine, canine, and equine models, each associated with its specific advantages and limitations. This review presents a summary of recent in vitro data and from in vivo preclinical studies justifying the use of MSCs and iPSCs in cartilage tissue engineering. Moreover, the advantages and disadvantages of utilizing small and large animals will be discussed, while also describing suitable outcome measures for evaluating cartilage repair.

  20. Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures.

    Science.gov (United States)

    Lo Monaco, Melissa; Merckx, Greet; Ratajczak, Jessica; Gervois, Pascal; Hilkens, Petra; Clegg, Peter; Bronckaers, Annelies; Vandeweerd, Jean-Michel; Lambrichts, Ivo

    2018-01-01

    Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles. But before novel cell-based therapies for cartilage repair can be introduced into the clinic, rigorous testing in preclinical animal models is required. Preclinical models used in regenerative cartilage studies include murine, lapine, caprine, ovine, porcine, canine, and equine models, each associated with its specific advantages and limitations. This review presents a summary of recent in vitro data and from in vivo preclinical studies justifying the use of MSCs and iPSCs in cartilage tissue engineering. Moreover, the advantages and disadvantages of utilizing small and large animals will be discussed, while also describing suitable outcome measures for evaluating cartilage repair.

  1. Model-based cartilage thickness measurement in the submillimeter range

    International Nuclear Information System (INIS)

    Streekstra, G. J.; Strackee, S. D.; Maas, M.; Wee, R. ter; Venema, H. W.

    2007-01-01

    Current methods of image-based thickness measurement in thin sheet structures utilize second derivative zero crossings to locate the layer boundaries. It is generally acknowledged that the nonzero width of the point spread function (PSF) limits the accuracy of this measurement procedure. We propose a model-based method that strongly reduces PSF-induced bias by incorporating the PSF into the thickness estimation method. We estimated the bias in thickness measurements in simulated thin sheet images as obtained from second derivative zero crossings. To gain insight into the range of sheet thickness where our method is expected to yield improved results, sheet thickness was varied between 0.15 and 1.2 mm with an assumed PSF as present in the high-resolution modes of current computed tomography (CT) scanners [full width at half maximum (FWHM) 0.5-0.8 mm]. Our model-based method was evaluated in practice by measuring layer thickness from CT images of a phantom mimicking two parallel cartilage layers in an arthrography procedure. CT arthrography images of cadaver wrists were also evaluated, and thickness estimates were compared to those obtained from high-resolution anatomical sections that served as a reference. The thickness estimates from the simulated images reveal that the method based on second derivative zero crossings shows considerable bias for layers in the submillimeter range. This bias is negligible for sheet thickness larger than 1 mm, where the size of the sheet is more than twice the FWHM of the PSF but can be as large as 0.2 mm for a 0.5 mm sheet. The results of the phantom experiments show that the bias is effectively reduced by our method. The deviations from the true thickness, due to random fluctuations induced by quantum noise in the CT images, are of the order of 3% for a standard wrist imaging protocol. In the wrist the submillimeter thickness estimates from the CT arthrography images correspond within 10% to those estimated from the anatomical

  2. Application of multiphysics models to efficient design of experiments of solute transport across articular cartilage.

    Science.gov (United States)

    Pouran, Behdad; Arbabi, Vahid; Weinans, Harrie; Zadpoor, Amir A

    2016-11-01

    Transport of solutes helps to regulate normal physiology and proper function of cartilage in diarthrodial joints. Multiple studies have shown the effects of characteristic parameters such as concentration of proteoglycans and collagens and the orientation of collagen fibrils on the diffusion process. However, not much quantitative information and accurate models are available to help understand how the characteristics of the fluid surrounding articular cartilage influence the diffusion process. In this study, we used a combination of micro-computed tomography experiments and biphasic-solute finite element models to study the effects of three parameters of the overlying bath on the diffusion of neutral solutes across cartilage zones. Those parameters include bath size, degree of stirring of the bath, and the size and concentration of the stagnant layer that forms at the interface of cartilage and bath. Parametric studies determined the minimum of the finite bath size for which the diffusion behavior reduces to that of an infinite bath. Stirring of the bath proved to remarkably influence neutral solute transport across cartilage zones. The well-stirred condition was achieved only when the ratio of the diffusivity of bath to that of cartilage was greater than ≈1000. While the thickness of the stagnant layer at the cartilage-bath interface did not significantly influence the diffusion behavior, increase in its concentration substantially elevated solute concentration in cartilage. Sufficient stirring attenuated the effects of the stagnant layer. Our findings could be used for efficient design of experimental protocols aimed at understanding the transport of molecules across articular cartilage. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Platelet-Rich Fibrin Improves the Viability of Diced Cartilage Grafts in a Rabbit Model.

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    Göral, Ali; Aslan, Cem; Bolat Küçükzeybek, Betül; Işık, Dağhan; Hoşnuter, Mübin; Durgun, Mustafa

    2016-04-01

    Diced cartilage may be wrapped with synthetic or biological materials before grafting to a recipient site. These materials have unique advantages and disadvantages, and a gold standard is not available. The authors investigated the effects of platelet-rich fibrin (PRF) on the survival of cartilage grafts in a rabbit model. In this experimental study, diced cartilage pieces from the ears of 9 male rabbits were left unwrapped or were wrapped with PRF, oxidized regenerated cellulose, or fascia. Specimens then were placed into subcutaneous pockets prepared on the backs of the rabbits. The animals were sacrificed 2 months after the procedure, and the grafts were excised for macroscopic and histopathologic examination. The cartilage graft wrapped with PRF showed superior viability compared with the cartilage graft wrapped with oxidized regenerated cellulose. No significant differences were found among the other groups. The groups were not significantly different in terms of rates of inflammation, fibrosis, or vascularization. PRF enhances the viability of diced cartilage grafts and should be considered an appropriate biological wrapping material for cartilage grafting. © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

  4. Passaged adult chondrocytes can form engineered cartilage with functional mechanical properties: a canine model.

    Science.gov (United States)

    Ng, Kenneth W; Lima, Eric G; Bian, Liming; O'Conor, Christopher J; Jayabalan, Prakash S; Stoker, Aaron M; Kuroki, Keiichi; Cook, Cristi R; Ateshian, Gerard A; Cook, James L; Hung, Clark T

    2010-03-01

    It was hypothesized that previously optimized serum-free culture conditions for juvenile bovine chondrocytes could be adapted to generate engineered cartilage with physiologic mechanical properties in a preclinical, adult canine model. Primary or passaged (using growth factors) adult chondrocytes from three adult dogs were encapsulated in agarose, and cultured in serum-free media with transforming growth factor-beta3. After 28 days in culture, engineered cartilage formed by primary chondrocytes exhibited only small increases in glycosaminoglycan content. However, all passaged chondrocytes on day 28 elaborated a cartilage matrix with compressive properties and glycosaminoglycan content in the range of native adult canine cartilage values. A preliminary biocompatibility study utilizing chondral and osteochondral constructs showed no gross or histological signs of rejection, with all implanted constructs showing excellent integration with surrounding cartilage and subchondral bone. This study demonstrates that adult canine chondrocytes can form a mechanically functional, biocompatible engineered cartilage tissue under optimized culture conditions. The encouraging findings of this work highlight the potential for tissue engineering strategies using adult chondrocytes in the clinical treatment of cartilage defects.

  5. Multiscale Mechanics of Articular Cartilage: Potentials and Challenges of Coupling Musculoskeletal, Joint, and Microscale Computational Models

    Science.gov (United States)

    Halloran, J. P.; Sibole, S.; van Donkelaar, C. C.; van Turnhout, M. C.; Oomens, C. W. J.; Weiss, J. A.; Guilak, F.; Erdemir, A.

    2012-01-01

    Articular cartilage experiences significant mechanical loads during daily activities. Healthy cartilage provides the capacity for load bearing and regulates the mechanobiological processes for tissue development, maintenance, and repair. Experimental studies at multiple scales have provided a fundamental understanding of macroscopic mechanical function, evaluation of the micromechanical environment of chondrocytes, and the foundations for mechanobiological response. In addition, computational models of cartilage have offered a concise description of experimental data at many spatial levels under healthy and diseased conditions, and have served to generate hypotheses for the mechanical and biological function. Further, modeling and simulation provides a platform for predictive risk assessment, management of dysfunction, as well as a means to relate multiple spatial scales. Simulation-based investigation of cartilage comes with many challenges including both the computational burden and often insufficient availability of data for model development and validation. This review outlines recent modeling and simulation approaches to understand cartilage function from a mechanical systems perspective, and illustrates pathways to associate mechanics with biological function. Computational representations at single scales are provided from the body down to the microstructure, along with attempts to explore multiscale mechanisms of load sharing that dictate the mechanical environment of the cartilage and chondrocytes. PMID:22648577

  6. Early Changes of Articular Cartilage and Subchondral Bone in The DMM Mouse Model of Osteoarthritis

    OpenAIRE

    Fang, Hang; Huang, Lisi; Welch, Ian; Norley, Chris; Holdsworth, David W.; Beier, Frank; Cai, Daozhang

    2018-01-01

    To examine the early changes of articular cartilage and subchondral bone in the DMM mouse model of osteoarthritis, mice were subjected to DMM or SHAM surgery and sacrificed at 2-, 5- and 10-week post-surgery. Catwalk gait analyses, Micro-Computed Tomography, Toluidine Blue, Picrosirius Red and Tartrate-Resistant Acid Phosphatase (TRAP) staining were used to investigate gait patterns, joint morphology, subchondral bone, cartilage, collagen organization and osteoclasts activity, respectively. R...

  7. International Cartilage Repair Society (ICRS) Recommended Guidelines for Histological Endpoints for Cartilage Repair Studies in Animal Models and Clinical Trials

    Science.gov (United States)

    Hoemann, Caroline; Kandel, Rita; Roberts, Sally; Saris, Daniel B.F.; Creemers, Laura; Mainil-Varlet, Pierre; Méthot, Stephane; Hollander, Anthony P.; Buschmann, Michael D.

    2011-01-01

    Cartilage repair strategies aim to resurface a lesion with osteochondral tissue resembling native cartilage, but a variety of repair tissues are usually observed. Histology is an important structural outcome that could serve as an interim measure of efficacy in randomized controlled clinical studies. The purpose of this article is to propose guidelines for standardized histoprocessing and unbiased evaluation of animal tissues and human biopsies. Methods were compiled from a literature review, and illustrative data were added. In animal models, treatments are usually administered to acute defects created in healthy tissues, and the entire joint can be analyzed at multiple postoperative time points. In human clinical therapy, treatments are applied to developed lesions, and biopsies are obtained, usually from a subset of patients, at a specific time point. In striving to standardize evaluation of structural endpoints in cartilage repair studies, 5 variables should be controlled: 1) location of biopsy/sample section, 2) timing of biopsy/sample recovery, 3) histoprocessing, 4) staining, and 5) blinded evaluation with a proper control group. Histological scores, quantitative histomorphometry of repair tissue thickness, percentage of tissue staining for collagens and glycosaminoglycan, polarized light microscopy for collagen fibril organization, and subchondral bone integration/structure are all relevant outcome measures that can be collected and used to assess the efficacy of novel therapeutics. Standardized histology methods could improve statistical analyses, help interpret and validate noninvasive imaging outcomes, and permit cross-comparison between studies. Currently, there are no suitable substitutes for histology in evaluating repair tissue quality and cartilaginous character. PMID:26069577

  8. A High Throughput Model of Post-Traumatic Osteoarthritis using Engineered Cartilage Tissue Analogs

    Science.gov (United States)

    Mohanraj, Bhavana; Meloni, Gregory R.; Mauck, Robert L.; Dodge, George R.

    2014-01-01

    (1) Objective A number of in vitro models of post-traumatic osteoarthritis (PTOA) have been developed to study the effect of mechanical overload on the processes that regulate cartilage degeneration. While such frameworks are critical for the identification therapeutic targets, existing technologies are limited in their throughput capacity. Here, we validate a test platform for high-throughput mechanical injury incorporating engineered cartilage. (2) Method We utilized a high throughput mechanical testing platform to apply injurious compression to engineered cartilage and determined their strain and strain rate dependent responses to injury. Next, we validated this response by applying the same injury conditions to cartilage explants. Finally, we conducted a pilot screen of putative PTOA therapeutic compounds. (3) Results Engineered cartilage response to injury was strain dependent, with a 2-fold increase in GAG loss at 75% compared to 50% strain. Extensive cell death was observed adjacent to fissures, with membrane rupture corroborated by marked increases in LDH release. Testing of established PTOA therapeutics showed that pan-caspase inhibitor (ZVF) was effective at reducing cell death, while the amphiphilic polymer (P188) and the free-radical scavenger (NAC) reduced GAG loss as compared to injury alone. (4) Conclusions The injury response in this engineered cartilage model replicated key features of the response from cartilage explants, validating this system for application of physiologically relevant injurious compression. This study establishes a novel tool for the discovery of mechanisms governing cartilage injury, as well as a screening platform for the identification of new molecules for the treatment of PTOA. PMID:24999113

  9. Fractional calculus model of articular cartilage based on experimental stress-relaxation

    Science.gov (United States)

    Smyth, P. A.; Green, I.

    2015-05-01

    Articular cartilage is a unique substance that protects joints from damage and wear. Many decades of research have led to detailed biphasic and triphasic models for the intricate structure and behavior of cartilage. However, the models contain many assumptions on boundary conditions, permeability, viscosity, model size, loading, etc., that complicate the description of cartilage. For impact studies or biomimetic applications, cartilage can be studied phenomenologically to reduce modeling complexity. This work reports experimental results on the stress-relaxation of equine articular cartilage in unconfined loading. The response is described by a fractional calculus viscoelastic model, which gives storage and loss moduli as functions of frequency, rendering multiple advantages: (1) the fractional calculus model is robust, meaning that fewer constants are needed to accurately capture a wide spectrum of viscoelastic behavior compared to other viscoelastic models (e.g., Prony series), (2) in the special case where the fractional derivative is 1/2, it is shown that there is a straightforward time-domain representation, (3) the eigenvalue problem is simplified in subsequent dynamic studies, and (4) cartilage stress-relaxation can be described with as few as three constants, giving an advantage for large-scale dynamic studies that account for joint motion or impact. Moreover, the resulting storage and loss moduli can quantify healthy, damaged, or cultured cartilage, as well as artificial joints. The proposed characterization is suited for high-level analysis of multiphase materials, where the separate contribution of each phase is not desired. Potential uses of this analysis include biomimetic dampers and bearings, or artificial joints where the effective stiffness and damping are fundamental parameters.

  10. Multiphasic modeling of charged solute transport across articular cartilage: Application of multi-zone finite-bath model.

    Science.gov (United States)

    Arbabi, Vahid; Pouran, Behdad; Weinans, Harrie; Zadpoor, Amir A

    2016-06-14

    Charged and uncharged solutes penetrate through cartilage to maintain the metabolic function of chondrocytes and to possibly restore or further breakdown the cartilage tissue in different stages of osteoarthritis. In this study the transport of charged solutes across the various zones of cartilage was quantified, taken into account the physicochemical interactions between the solute and the cartilage constituents. A multiphasic finite-bath finite element (FE) model was developed to simulate equine cartilage diffusion experiments that used a negatively charged contrast agent (ioxaglate) in combination with serial micro-computed tomography (micro-CT) to measure the diffusion. By comparing the FE model with the experimental data both the diffusion coefficient of ioxaglate and the fixed charge density (FCD) were obtained. In the multiphasic model, cartilage was divided into multiple (three) zones to help understand how diffusion coefficient and FCD vary across cartilage thickness. The direct effects of charged solute-FCD interaction on diffusion were investigated by comparing the diffusion coefficients derived from the multiphasic and biphasic-solute models. We found a relationship between the FCD obtained by the multiphasic model and ioxaglate partitioning obtained from micro-CT experiments. Using our multi-zone multiphasic model, diffusion coefficient of the superficial zone was up to ten-fold higher than that of the middle zone, while the FCD of the middle zone was up to almost two-fold higher than that of the superficial zone. In conclusion, the developed finite-bath multiphasic model provides us with a non-destructive method by which we could obtain both diffusion coefficient and FCD of different cartilage zones. The outcomes of the current work will also help understand how charge of the bath affects the diffusion of a charged molecule and also predict the diffusion behavior of a charged solute across articular cartilage. Copyright © 2016 Elsevier Ltd. All

  11. Cartilage regeneration by chondrogenic induced adult stem cells in osteoarthritic sheep model.

    Science.gov (United States)

    Ude, Chinedu C; Sulaiman, Shamsul B; Min-Hwei, Ng; Hui-Cheng, Chen; Ahmad, Johan; Yahaya, Norhamdan M; Saim, Aminuddin B; Idrus, Ruszymah B H

    2014-01-01

    In this study, Adipose stem cells (ADSC) and bone marrow stem cells (BMSC), multipotent adult cells with the potentials for cartilage regenerations were induced to chondrogenic lineage and used for cartilage regenerations in surgically induced osteoarthritis in sheep model. Osteoarthritis was induced at the right knee of sheep by complete resection of the anterior cruciate ligament and medial meniscus following a 3-weeks exercise regimen. Stem cells from experimental sheep were culture expanded and induced to chondrogenic lineage. Test sheep received a single dose of 2 × 10(7) autologous PKH26-labelled, chondrogenically induced ADSCs or BMSCs as 5 mls injection, while controls received 5 mls culture medium. The proliferation rate of ADSCs 34.4 ± 1.6 hr was significantly higher than that of the BMSCs 48.8 ± 5.3 hr (P = 0.008). Chondrogenic induced BMSCs had significantly higher expressions of chondrogenic specific genes (Collagen II, SOX9 and Aggrecan) compared to chondrogenic ADSCs (P = 0.031, 0.010 and 0.013). Grossly, the treated knee joints showed regenerated de novo cartilages within 6 weeks post-treatment. On the International Cartilage Repair Society grade scores, chondrogenically induced ADSCs and BMSCs groups had significantly lower scores than controls (P = 0.0001 and 0.0001). Fluorescence of the tracking dye (PKH26) in the injected cells showed that they had populated the damaged area of cartilage. Histological staining revealed loosely packed matrixes of de novo cartilages and immunostaining demonstrated the presence of cartilage specific proteins, Collagen II and SOX9. Autologous chondrogenically induced ADSCs and BMSCs could be promising cell sources for cartilage regeneration in osteoarthritis.

  12. Cartilage regeneration by chondrogenic induced adult stem cells in osteoarthritic sheep model.

    Directory of Open Access Journals (Sweden)

    Chinedu C Ude

    Full Text Available OBJECTIVES: In this study, Adipose stem cells (ADSC and bone marrow stem cells (BMSC, multipotent adult cells with the potentials for cartilage regenerations were induced to chondrogenic lineage and used for cartilage regenerations in surgically induced osteoarthritis in sheep model. METHODS: Osteoarthritis was induced at the right knee of sheep by complete resection of the anterior cruciate ligament and medial meniscus following a 3-weeks exercise regimen. Stem cells from experimental sheep were culture expanded and induced to chondrogenic lineage. Test sheep received a single dose of 2 × 10(7 autologous PKH26-labelled, chondrogenically induced ADSCs or BMSCs as 5 mls injection, while controls received 5 mls culture medium. RESULTS: The proliferation rate of ADSCs 34.4 ± 1.6 hr was significantly higher than that of the BMSCs 48.8 ± 5.3 hr (P = 0.008. Chondrogenic induced BMSCs had significantly higher expressions of chondrogenic specific genes (Collagen II, SOX9 and Aggrecan compared to chondrogenic ADSCs (P = 0.031, 0.010 and 0.013. Grossly, the treated knee joints showed regenerated de novo cartilages within 6 weeks post-treatment. On the International Cartilage Repair Society grade scores, chondrogenically induced ADSCs and BMSCs groups had significantly lower scores than controls (P = 0.0001 and 0.0001. Fluorescence of the tracking dye (PKH26 in the injected cells showed that they had populated the damaged area of cartilage. Histological staining revealed loosely packed matrixes of de novo cartilages and immunostaining demonstrated the presence of cartilage specific proteins, Collagen II and SOX9. CONCLUSION: Autologous chondrogenically induced ADSCs and BMSCs could be promising cell sources for cartilage regeneration in osteoarthritis.

  13. Kalman filter-based gap conductance modeling

    International Nuclear Information System (INIS)

    Tylee, J.L.

    1983-01-01

    Geometric and thermal property uncertainties contribute greatly to the problem of determining conductance within the fuel-clad gas gap of a nuclear fuel pin. Accurate conductance values are needed for power plant licensing transient analysis and for test analyses at research facilities. Recent work by Meek, Doerner, and Adams has shown that use of Kalman filters to estimate gap conductance is a promising approach. A Kalman filter is simply a mathematical algorithm that employs available system measurements and assumed dynamic models to generate optimal system state vector estimates. This summary addresses another Kalman filter approach to gap conductance estimation and subsequent identification of an empirical conductance model

  14. Characterization of an Ex vivo Femoral Head Model Assessed by Markers of Bone and Cartilage Turnover

    Science.gov (United States)

    Madsen, Suzi Hoegh; Goettrup, Anne Sofie; Thomsen, Gedske; Christensen, Søren Tvorup; Schultz, Nikolaj; Henriksen, Kim; Bay-Jensen, Anne-Christine; Karsdal, Morten Asser

    2011-01-01

    Objective: The pathophysiology of osteoarthritis involves the whole joint and is characterized by cartilage degradation and altered subchondral bone turnover. At present, there is a need for biological models that allow investigation of the interactions between the key cellular players in bone/cartilage: osteoblasts, osteoclasts, and chondrocytes. Methods: Femoral heads from 3-, 6-, 9-, and 12-week-old female mice were isolated and cultured for 10 days in serum-free media in the absence or presence of IGF-I (100 nM) (anabolic stimulation) or OSM (10 ng/mL) + TNF-α (20 ng/mL) (catabolic stimulation). Histology on femoral heads before and after culture was performed, and the growth plate size was examined to evaluate the effects on cell metabolism. The conditioned medium was examined for biochemical markers of bone and cartilage degradation/formation. Results: Each age group represented a unique system regarding the interest of bone or cartilage metabolism. Stimulation over 10 days with OSM + TNF-α resulted in depletion of proteoglycans from the cartilage surface in all ages. Furthermore, OSM + TNF-α decreased growth plate size, whereas IGF-I increased the size. Measurements from the conditioned media showed that OSM + TNF-α increased the number of osteoclasts by approximately 80% and induced bone and cartilage degradation by approximately 1200% and approximately 2600%, respectively. Stimulation with IGF-I decreased the osteoclast number and increased cartilage formation by approximately 30%. Conclusion: Biochemical markers and histology together showed that the catabolic stimulation induced degradation and the anabolic stimulation induced formation in the femoral heads. We propose that we have established an explant whole-tissue model for investigating cell-cell interactions, reflecting parts of the processes in the pathogenesis of joint degenerative diseases. PMID:26069585

  15. Tenascin-C Prevents Articular Cartilage Degeneration in Murine Osteoarthritis Models.

    Science.gov (United States)

    Matsui, Yuriyo; Hasegawa, Masahiro; Iino, Takahiro; Imanaka-Yoshida, Kyoko; Yoshida, Toshimichi; Sudo, Akihiro

    2018-01-01

    Objective The objective of this study was to determine whether intra-articular injections of tenascin-C (TNC) could prevent cartilage damage in murine models of osteoarthritis (OA). Design Fluorescently labeled TNC was injected into knee joints and its distribution was examined at 1 day, 4 days, 1 week, 2 weeks, and 4 weeks postinjection. To investigate the effects of TNC on cartilage degeneration after surgery to knee joints, articular spaces were filled with 100 μg/mL (group I), 10 μg/mL (group II) of TNC solution, or control (group III). TNC solution of 10 μg/mL was additionally injected twice after 3 weeks (group IV) or weekly after 1 week, 2 weeks, and 3 weeks (group V). Joint tissues were histologically assessed using the Mankin score and the modified Chambers system at 2 to 8 weeks after surgery. Results Exogenous TNC was maintained in the cartilage and synovium for 1 week after administration. Histological scores in groups I and II were better than scores in group III at 4 and 6 weeks, but progressive cartilage damage was seen in all groups 8 weeks postoperatively. Sequential TNC injections (groups IV and V) showed significantly better Mankin score than single injection (group II) at 8 weeks. Conclusion TNC administered exogenously remained in the cartilage of knee joints for 1 week, and could decelerate articular cartilage degeneration in murine models of OA. We also showed that sequential administration of TNC was more effective than a single injection. TNC could be an important molecule for prevention of articular cartilage damage.

  16. Iodoacetate and allogenous cartilage particles as models for arthritis induction in equine

    Directory of Open Access Journals (Sweden)

    Ahmed Elmesiry

    2014-12-01

    Full Text Available Experimental models of osteoarthritis (OA have been widely developed in different animal species, because of the high incidence of osteoarthritis diseases in humans and animals. To date, no ideal OA animal model has been reported. The present study compare different osteoarthritis models to determine which one is suitable for inducing experimental equine OA. Fifteen donkeys were divided into three equal groups (n = 5. The radio carpal joints of the right forelimb of 15 donkeys were injected with 25 mg monoiodoacetate (MIA (group A, 50 mg allogenous cartilage particles (ACP (group B, or vehicle solution (group C over a period of 70 days. Osteoarthritis induction was evaluated weekly through lameness score, carpal circumference, joint flexion angel, synovial fluid analysis (total protein and WBC count, and radiology. Animal were euthanized and joints histopathology were performed at 70 days. Lameness score and joint circumference was increased in both group A and B however joint flexion angel was decreased compared to group C (p < 0.05. Osteophytes were observed in MIA injected joints only accompanied with subchondral bone sclerosis. Cartilage damage was observed grossly and histologically in Group A together with synovial membrane fibrosis. Group B had on cartilage damage grossly however histological examination revealed some cartilage surface discontinuity with synovial membrane edema. Injection of monoiodoacetate in the donkey is a successful model to create the acute clinical signs of joint disease as well as cartilage damage. However, allogenous cartilage particles injection need more investigation to be applied.

  17. Subchondral Bone Plate Thickening Precedes Chondrocyte Apoptosis and Cartilage Degradation in Spontaneous Animal Models of Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Zaitunnatakhin Zamli

    2014-01-01

    Full Text Available Osteoarthritis (OA is the most common joint disorder characterised by bone remodelling and cartilage degradation and associated with chondrocyte apoptosis. These processes were investigated at 10, 16, 24, and 30 weeks in Dunkin Hartley (DH and Bristol Strain 2 (BS2 guinea pigs that develop OA spontaneously. Both strains had a more pronounced chondrocyte apoptosis, cartilage degradation, and subchondral bone changes in the medial than the lateral side of the tibia, and between strains, the changes were always greater and faster in DH than BS2. In the medial side, a significant increase of chondrocyte apoptosis and cartilage degradation was observed in DH between 24 and 30 weeks of age preceded by a progressive thickening and stiffening of subchondral bone plate (Sbp. The Sbp thickness consistently increased over the 30-week study period but the bone mineral density (BMD of the Sbp gradually decreased after 16 weeks. The absence of these changes in the medial side of BS2 may indicate that the Sbp of DH was undergoing remodelling. Chondrocyte apoptosis was largely confined to the deep zone of articular cartilage and correlated with thickness of the subchondral bone plate suggesting that cartilage degradation and chondrocyte apoptosis may be a consequence of continuous bone remodelling during the development of OA in these animal models of OA.

  18. Chicken collagen type II reduces articular cartilage destruction in a model of osteoarthritis in rats.

    Science.gov (United States)

    Xu, D; Shen, W

    2007-06-01

    To evaluate the therapeutic effects of domestic chicken collagen type II (CCII) on rat osteoarthritis (OA) and analyze concomitant changes in the level of Matrix metalloproteinase (MMP)-13, MMP-9, Cathepsin K and their mRNA as well as the tissue inhibitor of matrix metalloproteinase (TIMP)-1 mRNA in articular cartilage of osteoarthritic rats. Osteoarthritis models were surgically induced. Morphology of articular cartilage was done by haematoxylin and eosin staining and Mankin score was calculated, immunohistochemistry of MMP-13, MMP-9 and Cathepsin K was done by ABC method while the mRNA level for MMP-13, MMP-9, cathepsin K as well as TIMP-1 was evaluated by RT-PCR method. Oral administration of CCII reduced the morphological changes of osteoarthritic cartilage (shown by Mankin score), decreased levels of MMP-13, MMP-9, cathepsin K as well as their mRNA in articular cartilage from osteoarthritic rats while it exhibited no effect on TIMP-1 mRNA. Oral CCII reduced articular cartilage degradation of osteoarthritic rats and may probably be a potent drug candidate for OA treatment.

  19. Small-Diameter Awls Improve Articular Cartilage Repair After Microfracture Treatment in a Translational Animal Model.

    Science.gov (United States)

    Orth, Patrick; Duffner, Julia; Zurakowski, David; Cucchiarini, Magali; Madry, Henning

    2016-01-01

    Microfracture is the most commonly applied arthroscopic marrow stimulation procedure. Articular cartilage repair is improved when the subchondral bone is perforated by small-diameter microfracture awls compared with larger awls. Controlled laboratory study. Standardized rectangular (4 × 8 mm) full-thickness chondral defects (N = 24) were created in the medial femoral condyle of 16 adult sheep and debrided down to the subchondral bone plate. Three treatment groups (n = 8 defects each) were tested: 6 microfracture perforations using small-diameter awls (1.0 mm; group 1), large-diameter awls (1.2 mm; group 2), or without perforations (debridement control; group 3). Osteochondral repair was assessed at 6 months in vivo using established macroscopic, histological, immunohistochemical, biochemical, and micro-computed tomography analyses. Compared with control defects, histological cartilage repair was always improved after both microfracture techniques (P Subchondral bone cysts and intralesional osteophytes were frequently observed after either microfracture treatment. Macroscopic grading, DNA, proteoglycan, and type I and type II collagen contents as well as degenerative changes within the adjacent cartilage remained unaffected by the awl diameter. Small-diameter microfracture awls improve articular cartilage repair in the translational sheep model more effectively than do larger awls. These data support the use of small microfracture instruments for the surgical treatment of cartilage defects and warrant prolonged clinical investigations. © 2015 The Author(s).

  20. Osteochondral Allograft Transplantation in Cartilage Repair: Graft Storage Paradigm, Translational Models, and Clinical Applications

    Science.gov (United States)

    Bugbee, William D.; Pallante-Kichura, Andrea L.; Görtz, Simon; Amiel, David; Sah, Robert

    2016-01-01

    The treatment of articular cartilage injury and disease has become an increasingly relevant part of orthopaedic care. Articular cartilage transplantation, in the form of osteochondral allografting, is one of the most established techniques for restoration of articular cartilage. Our research efforts over the last two decades have supported the transformation of this procedure from experimental “niche” status to a cornerstone of orthopaedic practice. In this Kappa Delta paper, we describe our translational and clinical science contributions to this transformation: (1) to enhance the ability of tissue banks to process and deliver viable tissue to surgeons and patients, (2) to improve the biological understanding of in vivo cartilage and bone remodeling following osteochondral allograft (OCA) transplantation in an animal model system, (3) to define effective surgical techniques and pitfalls, and (4) to identify and clarify clinical indications and outcomes. The combination of coordinated basic and clinical studies is part of our continuing comprehensive academic OCA transplant program. Taken together, the results have led to the current standards for OCA processing and storage prior to implantation and also novel observations and mechanisms of the biological and clinical behavior of OCA transplants in vivo. Thus, OCA transplantation is now a successful and increasingly available treatment for patients with disabling osteoarticular cartilage pathology. PMID:26234194

  1. Knee cartilage segmentation using active shape models and local binary patterns

    Science.gov (United States)

    González, Germán.; Escalante-Ramírez, Boris

    2014-05-01

    Segmentation of knee cartilage has been useful for opportune diagnosis and treatment of osteoarthritis (OA). This paper presents a semiautomatic segmentation technique based on Active Shape Models (ASM) combined with Local Binary Patterns (LBP) and its approaches to describe the surrounding texture of femoral cartilage. The proposed technique is tested on a 16-image database of different patients and it is validated through Leave- One-Out method. We compare different segmentation techniques: ASM-LBP, ASM-medianLBP, and ASM proposed by Cootes. The ASM-LBP approaches are tested with different ratios to decide which of them describes the cartilage texture better. The results show that ASM-medianLBP has better performance than ASM-LBP and ASM. Furthermore, we add a routine which improves the robustness versus two principal problems: oversegmentation and initialization.

  2. Species-Independent Modeling of High-Frequency Ultrasound Backscatter in Hyaline Cartilage.

    Science.gov (United States)

    Männicke, Nils; Schöne, Martin; Liukkonen, Jukka; Fachet, Dominik; Inkinen, Satu; Malo, Markus K; Oelze, Michael L; Töyräs, Juha; Jurvelin, Jukka S; Raum, Kay

    2016-06-01

    Apparent integrated backscatter (AIB) is a common ultrasound parameter used to assess cartilage matrix degeneration. However, the specific contributions of chondrocytes, proteoglycan and collagen to AIB remain unknown. To reveal these relationships, this work examined biopsies and cross sections of human, ovine and bovine cartilage with 40-MHz ultrasound biomicroscopy. Site-matched estimates of collagen concentration, proteoglycan concentration, collagen orientation and cell number density were employed in quasi-least-squares linear regression analyses to model AIB. A positive correlation (R(2) = 0.51, p 70°) to the sound beam direction. These findings indicate causal relationships between AIB and cartilage structural parameters and could aid in more sophisticated future interpretations of ultrasound backscatter. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  3. Structural and in vivo mechanical characterization of canine patellar cartilage: a closed chondromalacia patellae model.

    Science.gov (United States)

    LaBerge, M; Audet, J; Drouin, G; Rivard, C H

    1993-01-01

    The purpose of this project was to study the relationship between the structure of the patellar cartilage and its response to static compressive loading with a closed chondromalacia patellae model. An animal model was used to induce degeneration of the patella that was monitored quantitatively and qualitatively as a function of time. Ten adult mongrel dogs had their left patellofemoral groove replaced by a customized metallic implant covered with a thin film of polyethylene for periods of 3 months (five dogs) and 6 months (five dogs). An indenter was designed to perform mechanical indentation testing on the patellar cartilage in situ. The animals were anesthetized and the response of patellar cartilage to a static compressive load of 4.5 MPa was monitored for 20 min and its relaxation after load removal for 20 min. Indentation tests were performed every 3 months of the implantation period. At the end of the implantation period, the patellae were processed for histology, and sections were stained with Safranin-O indicative of the proteoglycans content. Macroscopically, no apparent degeneration or fibrillation of the patellar surfaces was observed after 3 or 6 months of implantation. However, the patellar surface showed a change in coloration after 6 months. A 17 +/- 3% and 37 +/- 8% deformation of the cartilage were calculated for the 3-month and 6-month specimens, respectively. Histologically, a progressive loss of proteoglycans was observed in the matrix as a function of implantation time. These results indicated that an increase in cartilage compliance is associated with an intrinsic remodeling of the cartilage matrix and that these changes might occur without external signs of degeneration and can be quantified.

  4. In Vitro Mimetic Models for the Bone-Cartilage Interface Regeneration.

    Science.gov (United States)

    Bicho, Diana; Pina, Sandra; Oliveira, J Miguel; Reis, Rui L

    2018-01-01

    In embryonic development, pure cartilage structures are in the basis of bone-cartilage interfaces. Despite this fact, the mature bone and cartilage structures can vary greatly in composition and function. Nevertheless, they collaborate in the osteochondral region to create a smooth transition zone that supports the movements and forces resulting from the daily activities. In this sense, all the hierarchical organization is involved in the maintenance and reestablishment of the equilibrium in case of damage. Therefore, this interface has attracted a great deal of interest in order to understand the mechanisms of regeneration or disease progression in osteoarthritis. With that purpose, in vitro tissue models (either static or dynamic) have been studied. Static in vitro tissue models include monocultures, co-cultures, 3D cultures, and ex vivo cultures, mostly cultivated in flat surfaces, while dynamic models involve the use of bioreactors and microfluidic systems. The latter have emerged as alternatives to study the cellular interactions in a more authentic manner over some disadvantages of the static models. The current alternatives of in vitro mimetic models for bone-cartilage interface regeneration are overviewed and discussed herein.

  5. Mesenchymal Stem Cells in Oriented PLGA/ACECM Composite Scaffolds Enhance Structure-Specific Regeneration of Hyaline Cartilage in a Rabbit Model.

    Science.gov (United States)

    Guo, Weimin; Zheng, Xifu; Zhang, Weiguo; Chen, Mingxue; Wang, Zhenyong; Hao, Chunxiang; Huang, Jingxiang; Yuan, Zhiguo; Zhang, Yu; Wang, Mingjie; Peng, Jiang; Wang, Aiyuan; Wang, Yu; Sui, Xiang; Xu, Wenjing; Liu, Shuyun; Lu, Shibi; Guo, Quanyi

    2018-01-01

    Articular cartilage lacks a blood supply and nerves. Hence, articular cartilage regeneration remains a major challenge in orthopedics. Decellularized extracellular matrix- (ECM-) based strategies have recently received particular attention. The structure of native cartilage exhibits complex zonal heterogeneity. Specifically, the development of a tissue-engineered scaffold mimicking the aligned structure of native cartilage would be of great utility in terms of cartilage regeneration. Previously, we fabricated oriented PLGA/ACECM (natural, nanofibrous, articular cartilage ECM) composite scaffolds. In vitro, we found that the scaffolds not only guided seeded cells to proliferate in an aligned manner but also exhibited high biomechanical strength. To detect whether oriented cartilage regeneration was possible in vivo, we used mesenchymal stem cell (MSC)/scaffold constructs to repair cartilage defects. The results showed that cartilage defects could be completely regenerated. Histologically, these became filled with hyaline cartilage and subchondral bone. Moreover, the aligned structure of cartilage was regenerated and was similar to that of native tissue. In conclusion, the MSC/scaffold constructs enhanced the structure-specific regeneration of hyaline cartilage in a rabbit model and may be a promising treatment strategy for the repair of human cartilage defects.

  6. Characterization of articular cartilage and subchondral bone changes in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis.

    Science.gov (United States)

    Hayami, Tadashi; Pickarski, Maureen; Zhuo, Ya; Wesolowski, Gregg A; Rodan, Gideon A; Duong, Le T

    2006-02-01

    Osteoarthritis (OA) is a chronic joint disease characterized by cartilage destruction, subchondral bone sclerosis, and osteophyte formation. Subchondral bone stiffness has been proposed to initiate and/or contribute to cartilage deterioration in OA. The purpose of this study was to characterize subchondral bone remodeling, cartilage damage, and osteophytosis during the disease progression in two models of surgically induced OA. Rat knee joints were subjected either to anterior cruciate ligament transection (ACLT) alone or in combination with resection of medial menisci (ACLT + MMx). Histopathological changes in the surgical joints were compared with sham at 1, 2, 4, 6, and 10 weeks post-surgery. Using a modified Mankin scoring system, we demonstrate that articular cartilage damage occurs within 2 weeks post-surgery in both surgical models. Detectable cartilage surface damage and proteoglycan loss were observed as early as 1 week post-surgery. These were followed by the increases in vascular invasion into cartilage, in loss of chondrocyte number and in cell clustering. Histomorphometric analysis revealed subchondral bone loss in both models within 2 weeks post-surgery followed by significant increases in subchondral bone volume relative to sham up to 10 weeks post-surgery. Incidence of osteophyte formation was optimally observed in ACLT joints at 10 weeks and in ACLT + MMx joints at 6 weeks post-surgery. In summary, the two surgically induced rat OA models share many characteristics seen in human and other animal models of OA, including progressive articular cartilage degradation, subchondral bone sclerosis, and osteophyte formation. Moreover, increased subchondral bone resorption is associated with early development of cartilage lesions, which precedes significant cartilage thinning and subchondral bone sclerosis. Together, these findings support a role for bone remodeling in OA pathogenesis and suggest that these rat models are suitable for evaluating bone

  7. An experimental model to mimic the mechanical behavior of a scaffold in a cartilage defect

    OpenAIRE

    VIKINGSSON, LINE KARINA ALVA

    2015-01-01

    [EN] Abstract The main purpose of this thesis is the design and characterization of an experimental articular cartilage model. The in vitro model is composed of a macro and micro- porous Polycaprolactone scaffold with a Poly(Vinyl Alcohol) filling. The scaffold/hydrogel construct has been subjected to repeating number of freezing and thawing cycles in order to crosslink the hydrogel inside the scaffold's pores. The Poly(Vinyl Alcohol) resembles the growing cartilaginous tissue inside the ...

  8. A composition-based cartilage model for the assessment of compositional changes during cartilage damage and adaptation

    NARCIS (Netherlands)

    Wilson, W.; Huyghe, J.M.R.J.; Donkelaar, van C.C.

    2006-01-01

    The composition of articular cartilage changes with progression of osteoarthritis. Since compositional changes are associated with changes in the mechanical properties of the tissue, they are relevant for understanding how mechanical loading induces progression. The objective of this study is to

  9. Gap timing and the spectral timing model.

    Science.gov (United States)

    Hopson, J W

    1999-04-01

    A hypothesized mechanism underlying gap timing was implemented in the Spectral Timing Model [Grossberg, S., Schmajuk, N., 1989. Neural dynamics of adaptive timing and temporal discrimination during associative learning. Neural Netw. 2, 79-102] , a neural network timing model. The activation of the network nodes was made to decay in the absence of the timed signal, causing the model to shift its peak response time in a fashion similar to that shown in animal subjects. The model was then able to accurately simulate a parametric study of gap timing [Cabeza de Vaca, S., Brown, B., Hemmes, N., 1994. Internal clock and memory processes in aminal timing. J. Exp. Psychol.: Anim. Behav. Process. 20 (2), 184-198]. The addition of a memory decay process appears to produce the correct pattern of results in both Scalar Expectancy Theory models and in the Spectral Timing Model, and the fact that the same process should be effective in two such disparate models argues strongly that process reflects a true aspect of animal cognition.

  10. Modeling the effect of blunt impact on mitochondrial function in cartilage: implications for development of osteoarthritis

    Directory of Open Access Journals (Sweden)

    Georgi I. Kapitanov

    2017-07-01

    Full Text Available Objective Osteoarthritis (OA is a disease characterized by degeneration of joint cartilage. It is associated with pain and disability and is the result of either age and activity related joint wear or an injury. Non-invasive treatment options are scarce and prevention and early intervention methods are practically non-existent. The modeling effort presented in this article is constructed based on an emerging biological hypothesis—post-impact oxidative stress leads to cartilage cell apoptosis and hence the degeneration observed with the disease. The objective is to quantitatively describe the loss of cell viability and function in cartilage after an injurious impact and identify the key parameters and variables that contribute to this phenomenon. Methods We constructed a system of differential equations that tracks cell viability, mitochondrial function, and concentrations of reactive oxygen species (ROS, adenosine triphosphate (ATP, and glycosaminoglycans (GAG. The system was solved using MATLAB and the equations’ parameters were fit to existing data using a particle swarm algorithm. Results The model fits well the available data for cell viability, ATP production, and GAG content. Local sensitivity analysis shows that the initial amount of ROS is the most important parameter. Discussion The model we constructed is a viable method for producing in silico studies and with a few modifications, and data calibration and validation, may be a powerful predictive tool in the search for a non-invasive treatment for post-traumatic osteoarthritis.

  11. Gap Acceptance Behavior Model for Non-signalized

    OpenAIRE

    Fajaruddin Bin Mustakim

    2015-01-01

    The paper proposes field studies that were performed to determine the critical gap on the multiple rural roadways Malaysia, at non-signalized T-intersection by using The Raff and Logic Method. Critical gap between passenger car and motorcycle have been determined.   There are quite number of studied doing gap acceptance behavior model for passenger car however still few research on gap acceptance behavior model for motorcycle. Thus in this paper, logistic regression models were developed to p...

  12. Development of Multidimensional Gap Conductance model using Virtual Link Gap Element

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyo Chan; Yang, Yong Sik; Kim, Dae Ho; Bang, Je Geon; Kim, Sun Ki; Koo, Yang Hyun [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2013-10-15

    The gap conductance that determines temperature gradient between pellet and cladding can be quite sensitive to gap thickness. For instance, once the gap size increases up to several micrometers in certain region, difference of pellet surface temperatures increases up to 100 Kelvin. Therefore, iterative thermo-mechanical coupled analysis is required to solve temperature distribution throughout pellet and cladding. Recently, multidimensional fuel performance codes have been being developed in the advanced countries to evaluate thermal behavior of fuel for off normal conditions and DBA(design based accident) conditions using the Finite Element Method (FEM). FRAPCON-FRAPTRAN code system, which is well known as the verified and reliable code, incorporates 1D thermal module and multidimensional mechanical module. In this code, multidimensional gap conductance model is not applied. ALCYONE developed by CEA introduces equivalent heat convection coefficient that represents multidimensional gap conductance as a function of gap thickness. BISON, which is multidimensional fuel performance code developed by INL, owns multidimensional gap conductance model using projected thermal contact. In general, thermal contact algorithm is nonlinear calculation which is expensive approach numerically. The gap conductance model for multi-dimension is difficult issue in terms of convergence and nonlinearity because gap conductance is function of gap thickness which depends on mechanical analysis at each iteration step. In this paper, virtual link gap (VLG) element has been proposed to resolve convergence issue and nonlinear characteristic of multidimensional gap conductance. In terms of calculation accuracy and convergence efficiency, the proposed VLG model was evaluated. LWR fuel performance codes should incorporate thermo-mechanical loop to solve gap conductance problem, iteratively. However, gap conductance in multidimensional model is difficult issue owing to its nonlinearity and

  13. Biphasic Finite Element Modeling Reconciles Mechanical Properties of Tissue-Engineered Cartilage Constructs Across Testing Platforms.

    Science.gov (United States)

    Meloni, Gregory R; Fisher, Matthew B; Stoeckl, Brendan D; Dodge, George R; Mauck, Robert L

    2017-07-01

    Cartilage tissue engineering is emerging as a promising treatment for osteoarthritis, and the field has progressed toward utilizing large animal models for proof of concept and preclinical studies. Mechanical testing of the regenerative tissue is an essential outcome for functional evaluation. However, testing modalities and constitutive frameworks used to evaluate in vitro grown samples differ substantially from those used to evaluate in vivo derived samples. To address this, we developed finite element (FE) models (using FEBio) of unconfined compression and indentation testing, modalities commonly used for such samples. We determined the model sensitivity to tissue radius and subchondral bone modulus, as well as its ability to estimate material parameters using the built-in parameter optimization tool in FEBio. We then sequentially tested agarose gels of 4%, 6%, 8%, and 10% weight/weight using a custom indentation platform, followed by unconfined compression. Similarly, we evaluated the ability of the model to generate material parameters for living constructs by evaluating engineered cartilage. Juvenile bovine mesenchymal stem cells were seeded (2 × 10 7 cells/mL) in 1% weight/volume hyaluronic acid hydrogels and cultured in a chondrogenic medium for 3, 6, and 9 weeks. Samples were planed and tested sequentially in indentation and unconfined compression. The model successfully completed parameter optimization routines for each testing modality for both acellular and cell-based constructs. Traditional outcome measures and the FE-derived outcomes showed significant changes in material properties during the maturation of engineered cartilage tissue, capturing dynamic changes in functional tissue mechanics. These outcomes were significantly correlated with one another, establishing this FE modeling approach as a singular method for the evaluation of functional engineered and native tissue regeneration, both in vitro and in vivo.

  14. Experimental articular cartilage repair in the Göttingen minipig

    DEFF Research Database (Denmark)

    Christensen, Bjørn Borsøe; Foldager, Casper Bindzus; Olesen, Morten Lykke

    2015-01-01

    BACKGROUND: A gold standard treatment for articular cartilage injuries is yet to be found, and a cost-effective and predictable large animal model is needed to bridge the gap between in vitro studies and clinical studies. Ideally, the animal model should allow for testing of clinically relevant...

  15. Engineering Cartilage

    Science.gov (United States)

    ... Research Matters NIH Research Matters March 3, 2014 Engineering Cartilage Artistic rendering of human stem cells on ... situations has been a major goal in tissue engineering. Cartilage contains water, collagen, proteoglycans, and chondrocytes. Collagens ...

  16. Shark Cartilage

    Science.gov (United States)

    Shark cartilage (tough elastic tissue that provides support, much as bone does) used for medicine comes primarily from sharks ... Several types of extracts are made from shark cartilage including squalamine lactate, AE-941, and U-995. ...

  17. Robust and general method for determining surface fluid flow boundary conditions in articular cartilage contact mechanics modeling.

    Science.gov (United States)

    Pawaskar, Sainath Shrikant; Fisher, John; Jin, Zhongmin

    2010-03-01

    Contact detection in cartilage contact mechanics is an important feature of any analytical or computational modeling investigation when the biphasic nature of cartilage and the corresponding tribology are taken into account. The fluid flow boundary conditions will change based on whether the surface is in contact or not, which will affect the interstitial fluid pressurization. This in turn will increase or decrease the load sustained by the fluid phase, with a direct effect on friction, wear, and lubrication. In laboratory experiments or clinical hemiarthroplasty, when a rigid indenter or metallic prosthesis is used to apply load to the cartilage, there will not be any fluid flow normal to the surface in the contact region due to the impermeable nature of the indenter/prosthesis. In the natural joint, on the other hand, where two cartilage surfaces interact, flow will depend on the pressure difference across the interface. Furthermore, in both these cases, the fluid would flow freely in non-contacting regions. However, it should be pointed out that the contact area is generally unknown in advance in both cases and can only be determined as part of the solution. In the present finite element study, a general and robust algorithm was proposed to decide nodes in contact on the cartilage surface and, accordingly, impose the fluid flow boundary conditions. The algorithm was first tested for a rigid indenter against cartilage model. The algorithm worked well for two-dimensional four-noded and eight-noded axisymmetric element models as well as three-dimensional models. It was then extended to include two cartilages in contact. The results were in excellent agreement with the previous studies reported in the literature.

  18. Interleukin-6 is elevated in synovial fluid of patients with focal cartilage defects and stimulates cartilage matrix production in an in vitro regeneration model

    NARCIS (Netherlands)

    Tsuchida, Anika I.; Beekhuizen, Michiel; Rutgers, Marijn; van Osch, Gerjo J.V.M.; Bekkers, Joris E.J.; Bot, Arjan G.J.; Geurts, Bernd; Dhert, Wouter J.A.; Saris, Daniël B.F.; Creemers, Laura B.

    2012-01-01

    Introduction This study aimed to determine whether, as in osteoarthritis, increased levels of interleukin-6 (IL-6) are present in the synovial fluid of patients with symptomatic cartilage defects and whether this IL-6 affects cartilage regeneration as well as the cartilage in the degenerated knee.

  19. Brief report: reconstruction of joint hyaline cartilage by autologous progenitor cells derived from ear elastic cartilage.

    Science.gov (United States)

    Mizuno, Mitsuru; Kobayashi, Shinji; Takebe, Takanori; Kan, Hiroomi; Yabuki, Yuichiro; Matsuzaki, Takahisa; Yoshikawa, Hiroshi Y; Nakabayashi, Seiichiro; Ik, Lee Jeong; Maegawa, Jiro; Taniguchi, Hideki

    2014-03-01

    In healthy joints, hyaline cartilage covering the joint surfaces of bones provides cushioning due to its unique mechanical properties. However, because of its limited regenerative capacity, age- and sports-related injuries to this tissue may lead to degenerative arthropathies, prompting researchers to investigate a variety of cell sources. We recently succeeded in isolating human cartilage progenitor cells from ear elastic cartilage. Human cartilage progenitor cells have high chondrogenic and proliferative potential to form elastic cartilage with long-term tissue maintenance. However, it is unknown whether ear-derived cartilage progenitor cells can be used to reconstruct hyaline cartilage, which has different mechanical and histological properties from elastic cartilage. In our efforts to develop foundational technologies for joint hyaline cartilage repair and reconstruction, we conducted this study to obtain an answer to this question. We created an experimental canine model of knee joint cartilage damage, transplanted ear-derived autologous cartilage progenitor cells. The reconstructed cartilage was rich in proteoglycans and showed unique histological characteristics similar to joint hyaline cartilage. In addition, mechanical properties of the reconstructed tissues were higher than those of ear cartilage and equal to those of joint hyaline cartilage. This study suggested that joint hyaline cartilage was reconstructed from ear-derived cartilage progenitor cells. It also demonstrated that ear-derived cartilage progenitor cells, which can be harvested by a minimally invasive method, would be useful for reconstructing joint hyaline cartilage in patients with degenerative arthropathies. © AlphaMed Press.

  20. Analysis of the cartilage proteome from three different mouse models of genetic skeletal diseases reveals common and discrete disease signatures

    Directory of Open Access Journals (Sweden)

    Peter A. Bell

    2013-06-01

    Pseudoachondroplasia and multiple epiphyseal dysplasia are genetic skeletal diseases resulting from mutations in cartilage structural proteins. Electron microscopy and immunohistochemistry previously showed that the appearance of the cartilage extracellular matrix (ECM in targeted mouse models of these diseases is disrupted; however, the precise changes in ECM organization and the pathological consequences remain unknown. Our aim was to determine the effects of matrilin-3 and COMP mutations on the composition and extractability of ECM components to inform how these detrimental changes might influence cartilage organization and degeneration. Cartilage was sequentially extracted using increasing denaturants and the extraction profiles of specific proteins determined using SDS-PAGE/Western blotting. Furthermore, the relative composition of protein pools was determined using mass spectrometry for a non-biased semi-quantitative analysis. Western blotting revealed changes in the extraction of matrilins, COMP and collagen IX in mutant cartilage. Mass spectrometry confirmed quantitative changes in the extraction of structural and non-structural ECM proteins, including proteins with roles in cellular processes such as protein folding and trafficking. In particular, genotype-specific differences in the extraction of collagens XII and XIV and tenascins C and X were identified; interestingly, increased expression of several of these genes has recently been implicated in susceptibility and/or progression of murine osteoarthritis. We demonstrated that mutation of matrilin-3 and COMP caused changes in the extractability of other cartilage proteins and that proteomic analyses of Matn3 V194D, Comp T585M and Comp DelD469 mouse models revealed both common and discrete disease signatures that provide novel insight into skeletal disease mechanisms and cartilage degradation.

  1. HIF-2α-induced chemokines stimulate motility of fibroblast-like synoviocytes and chondrocytes into the cartilage-pannus interface in experimental rheumatoid arthritis mouse models.

    Science.gov (United States)

    Huh, Yun Hyun; Lee, Gyuseok; Lee, Keun-Bae; Koh, Jeong-Tae; Chun, Jang-Soo; Ryu, Je-Hwang

    2015-10-29

    Pannus formation and resulting cartilage destruction during rheumatoid arthritis (RA) depends on the migration of synoviocytes to cartilage tissue. Here, we focused on the role of hypoxia-inducible factor (HIF)-2α-induced chemokines by chondrocytes in the regulation of fibroblast-like synoviocyte (FLS) migration into the cartilage-pannus interface and cartilage erosion. Collagen-induced arthritis (CIA), K/BxN serum transfer, and tumor necrosis factor-α transgenic mice were used as experimental RA models. Expression patterns of HIF-2α and chemokines were determined via immunostaining, Western blotting and RT-PCR. FLS motility was evaluated using transwell migration and invasion assays. The specific role of HIF-2α was determined via local deletion of HIF-2α in joint tissues or using conditional knockout (KO) mice. Cartilage destruction, synovitis and pannus formation were assessed via histological analysis. HIF-2α and various chemokines were markedly upregulated in degenerating cartilage and pannus of RA joints. HIF-2α induced chemokine expression by chondrocytes in both primary culture and cartilage tissue. HIF-2α -induced chemokines by chondrocytes regulated the migration and invasion of FLS. Local deletion of HIF-2α in joint tissues inhibited pannus formation adjacent to cartilage tissue and cartilage destruction caused by K/BxN serum transfer. Furthermore, conditional knockout of HIF-2α in cartilage blocked pannus formation in adjacent cartilage but not bone tissue, along with inhibition of cartilage erosion caused by K/BxN serum transfer. Our findings suggest that chemokines induced by IL-1β or HIF-2α in chondrocytes regulate pannus expansion by stimulating FLS migration and invasion, leading to cartilage erosion during RA pathogenesis.

  2. Laser-induced cartilage damage: an ex-vivo model using confocal microscopy

    Science.gov (United States)

    Frenz, Martin; Zueger, Benno J.; Monin, D.; Weiler, C.; Mainil-Varlet, P. M.; Weber, Heinz P.; Schaffner, Thomas

    1999-06-01

    Although there is an increasing popularity of lasers in orthopedic surgery, there is a growing concern about negative side effects of this therapy e.g. prolonged restitution time, radiation damage to adjacent cartilage or depth effects like bone necrosis. Despite case reports and experimental investigations over the last few years little is known about the extent of acute cartilage damage induced by different lasers types and energies. Histological examination offers only limited insights in cell viability and metabolism. Ho:YAG and Er:YAG lasers emitting at 2.1 micrometer and 2.94 micrometer, respectively, are ideally suited for tissue treatment because these wavelengths are strongly absorbed in water. The Purpose of the present study is to evaluate the effect of laser type and energy on chondrocyte viability in an ex vivo model. Free running Er:YAG (E equals 100 and 150 mJ) and Ho:YAG (E equals 500 and 800 mJ) lasers were used at different energy levels using a fixed pulse length of 400 microseconds. The energy was delivered at 8 Hz through optical fibers. Fresh bovine hyaline cartilage samples were mounted in a water bath at room temperature and the fiber was positioned at 30 degree and 180 degree angles relative to the tissue surface. After laser irradiation the samples were assessed by a life-dead cell viability test using a confocal microscope and by standard histology. Thermal damage was much deeper with Ho:YAG (up to 1800 micrometer) than with the Er:YAG laser (up to 70 micrometer). The cell viability test revealed a damage zone about twice the one determined by standard histology. Confocal microscopy is a powerful tool for assessing changes in tissue structure after laser treatment. In addition this technique allows to quantify these alterations without necessitating time consuming and expensive animal experiments.

  3. CARTILAGE CONSTRUCTS ENGINEERED FROM CHONDROCYTES OVEREXPRESSING IGF-I IMPROVE THE REPAIR OF OSTEOCHONDRAL DEFECTS IN A RABBIT MODEL

    Science.gov (United States)

    Madry, Henning; Kaul, Gunter; Zurakowski, David; Vunjak-Novakovic, Gordana; Cucchiarini, Magali

    2015-01-01

    Tissue engineering combined with gene therapy is a promising approach for promoting articular cartilage repair. Here, we tested the hypothesis that engineered cartilage with chondrocytes over expressing a human insulin-like growth factor I (IGF-I) gene can enhance the repair of osteochondral defects, in a manner dependent on the duration of cultivation. Genetically modified chondrocytes were cultured on biodegradable polyglycolic acid scaffolds in dynamic flow rotating bioreactors for either 10 or 28 d. The resulting cartilaginous constructs were implanted into osteochondral defects in rabbit knee joints. After 28 weeks of in vivo implantation, immunoreactivity to ß-gal was detectable in the repair tissue of defects that received lacZ constructs. Engineered cartilaginous constructs based on IGF-I-over expressing chondrocytes markedly improved osteochondral repair compared with control (lacZ) constructs. Moreover, IGF-I constructs cultivated for 28 d in vitro significantly promoted osteochondral repair vis-à-vis similar constructs cultivated for 10 d, leading to significantly decreased osteoarthritic changes in the cartilage adjacent to the defects. Hence, the combination of spatially defined overexpression of human IGF-I within a tissue-engineered construct and prolonged bioreactor cultivation resulted in most enhanced articular cartilage repair and reduction of osteoarthritic changes in the cartilage adjacent to the defect. Such genetically enhanced tissue engineering provides a versatile tool to evaluate potential therapeutic genes in vivo and to improve our comprehension of the development of the repair tissue within articular cartilage defects. Insights gained with additional exploration using this model may lead to more effective treatment options for acute cartilage defects. PMID:23588785

  4. Cartilage constructs engineered from chondrocytes overexpressing IGF-I improve the repair of osteochondral defects in a rabbit model

    Directory of Open Access Journals (Sweden)

    H Madry

    2013-04-01

    Full Text Available Tissue engineering combined with gene therapy is a promising approach for promoting articular cartilage repair. Here, we tested the hypothesis that engineered cartilage with chondrocytes overexpressing a human insulin-like growth factor I (IGF-I gene can enhance the repair of osteochondral defects, in a manner dependent on the duration of cultivation. Genetically modified chondrocytes were cultured on biodegradable polyglycolic acid scaffolds in dynamic flow rotating bioreactors for either 10 or 28 d. The resulting cartilaginous constructs were implanted into osteochondral defects in rabbit knee joints. After 28 weeks of in vivo implantation, immunoreactivity to ß-gal was detectable in the repair tissue of defects that received lacZ constructs. Engineered cartilaginous constructs based on IGF-I-overexpressing chondrocytes markedly improved osteochondral repair compared with control (lacZ constructs. Moreover, IGF-I constructs cultivated for 28 d in vitro significantly promoted osteochondral repair vis-à-vis similar constructs cultivated for 10 d, leading to significantly decreased osteoarthritic changes in the cartilage adjacent to the defects. Hence, the combination of spatially defined overexpression of human IGF-I within a tissue-engineered construct and prolonged bioreactor cultivation resulted in most enhanced articular cartilage repair and reduction of osteoarthritic changes in the cartilage adjacent to the defect. Such genetically enhanced tissue engineering provides a versatile tool to evaluate potential therapeutic genes in vivo and to improve our comprehension of the development of the repair tissue within articular cartilage defects. Insights gained with additional exploration using this model may lead to more effective treatment options for acute cartilage defects.

  5. Early Changes of Articular Cartilage and Subchondral Bone in The DMM Mouse Model of Osteoarthritis.

    Science.gov (United States)

    Fang, Hang; Huang, Lisi; Welch, Ian; Norley, Chris; Holdsworth, David W; Beier, Frank; Cai, Daozhang

    2018-02-12

    To examine the early changes of articular cartilage and subchondral bone in the DMM mouse model of osteoarthritis, mice were subjected to DMM or SHAM surgery and sacrificed at 2-, 5- and 10-week post-surgery. Catwalk gait analyses, Micro-Computed Tomography, Toluidine Blue, Picrosirius Red and Tartrate-Resistant Acid Phosphatase (TRAP) staining were used to investigate gait patterns, joint morphology, subchondral bone, cartilage, collagen organization and osteoclasts activity, respectively. Results showed OA progressed over 10-week time-course. Gait disparity occurred only at 10-week post-surgery. Osteophyte formed at 2-week post-surgery. BMDs of DMM showed no statistical differences comparing to SHAM at 2 weeks, but BV/TV is much higher in DMM mice. Increased BMD was clearly found at 5- and 10-week post-surgery in DMM mice. TRAP staining showed increased osteoclast activity at the site of osteophyte formation of DMM joints at 5- and 10-week time points. These results showed that subchondral bone turnover might occurred earlier than 2 weeks in this mouse DMM model. Gait disparity only occurred at later stage of OA in DMM mice. Notably, patella dislocation could occur in some of the DMM mice and cause a different pattern of OA in affected knee.

  6. Mechanics and crack formation in the extracellular matrix with articular cartilage as a model system

    Science.gov (United States)

    Kearns, Sarah; Silverberg, Jesse; Bonassar, Lawrence; Cohen, Itai; Das, Moumita

    We investigate the mechanical structure-function relations in the extracellular matrix (ECM) with focus on crack formation and failure. As a model system, our study focuses on the ECM in articular cartilage (AC), the tissue that covers the ends of bones, and distributes load in joints including in the knees, shoulders, and hips. The strength, toughness, and crack resistance of native articular cartilage is unparalleled in materials made by humankind. This mechanical response is mainly due to its ECM. The ECM in AC has two major mechanobiological components: a network of the biopolymer collagen and a flexible aggrecan gel. We model this system as a biopolymer network embedded in a swelling gel, and investigate the conditions for the formation and propagation of cracks using a combination of rigidity percolation theory and energy minimization approaches. Our results may provide useful insights into the design principles of the ECM as well as of biomimetic hydrogels that are mechanically robust and can, at the same time, easily adapt to cues in their surroundings. This work was partially supported by a Cottrell College Science Award.

  7. Joint distraction and movement for repair of articular cartilage in a rabbit model with subsequent weight-bearing.

    Science.gov (United States)

    Nishino, T; Chang, F; Ishii, T; Yanai, T; Mishima, H; Ochiai, N

    2010-07-01

    We have previously shown that joint distraction and movement with a hinged external fixation device for 12 weeks was useful for repairing a large articular cartilage defect in a rabbit model. We have now investigated the results after six months and one year. The device was applied to 16 rabbits who underwent resection of the articular cartilage and subchondral bone from the entire tibial plateau. In group A (nine rabbits) the device was applied for six months. In group B (seven rabbits) it was in place for six months, after which it was removed and the animals were allowed to move freely for an additional six months. The cartilage remained sound in all rabbits. The areas of type II collagen-positive staining and repaired soft tissue were larger in group B than in group A. These findings provide evidence of long-term persistence of repaired cartilage with this technique and that weight-bearing has a positive effect on the quality of the cartilage.

  8. Glucosamine sulfate effect on the degenerated patellar cartilage: preliminary findings by pharmacokinetic magnetic resonance modeling

    Energy Technology Data Exchange (ETDEWEB)

    Marti-Bonmati, Luis [Dr Peset University Hospital, Radiology Department, Valencia (Spain); Hospital Quiron Valencia, Radiology Department, Valencia (Spain); Sanz-Requena, Roberto; Alberich-Bayarri, Angel [Hospital Quiron Valencia, Radiology Department, Valencia (Spain); Rodrigo, Jose Luis [Dr Peset University Hospital, Traumatology and Orthopedics Surgery Department, Valencia (Spain); Carot, Jose Miguel [Universidad Politecnica de Valencia, EIO Department, Valencia (Spain)

    2009-06-15

    Normal and degenerated cartilages have different magnetic resonance (MR) capillary permeability (K{sup trans}) and interstitial interchangeable volume (v{sub e}). Our hypothesis was that glucosamine sulfate treatment modifies these neovascularity abnormalities in osteoarthritis. Sixteen patients with patella degeneration, randomly distributed into glucosamine or control groups, underwent two 1.5-Tesla dynamic contrast-enhanced MR imaging studies (treatment initiation and after 6 months). The pain visual analog scale (VAS) and American Knee Society (AKS) score were used. A two-compartment pharmacokinetic model was used. Percentages of variations (postreatment-pretreatment/pretreatment) were compared (t-test for independent data). In the glucosamine group, pain and functional outcomes statistically improved (VAS: 7.3 {+-} 1.1 to 3.6 {+-} 1.3, p < 0.001; AKS: 18.6 {+-} 6.9 to 42.9 {+-} 2.7, p < 0.01). Glucosamine significantly increased K{sup trans} at 6 months (-54.4 {+-} 21.2% vs 126.7 {+-} 56.9%, p < 0.001, control vs glucosamine). In conclusion, glucosamine sulfate decreases pain while improving functional outcome in patients with cartilage degeneration. Glucosamine sulfate increases K{sup trans}, allowing its proposal as a surrogate imaging biomarker after 6 months of treatment. (orig.)

  9. Study on biphasic material model and mechanical analysis of knee joint cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Nakatani, A; Sakashita, A [Department of Adaptive Machine Systems, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871 (Japan)], E-mail: nakatani@ams.eng.osaka-u.ac.jp

    2008-02-15

    A material model of articular cartilage is formulated, and fundamental problems are analyzed. The soft tissue is assumed to comprise two phases: solid and fluid. The biphasic theory proposed by Spilker and Suh (1990) to deal with such materials is reviewed, and some new additional analyses are carried out on the basis of this theory. Assuming the elasticity for the solid phase and introducing the pressure, which is defined by the product of the volume change and penalty coefficient, it is shown that the viscoelastic property of the soft tissue can be reproduced. A preferable solution is obtained for the solid phase by using the reduction integral, even if a high-order interpolation function is used. However, the high-order element cannot satisfactorily capture the velocity distribution of fluids. The pressure distribution is studied by assuming the change in the surface characteristics of the cartilage tissue with the progress of osteoarthritis. The pressure is strongly related to the lubrication conditions, i.e., perfect lubrication, perfect adhesion, and partial adhesion.

  10. Effects of collagen matrix and bioreactor cultivation on cartilage regeneration of a full-thickness critical-size knee joint cartilage defects with subchondral bone damage in a rabbit model.

    Directory of Open Access Journals (Sweden)

    Kuo-Hwa Wang

    Full Text Available Cartilage has limited self-repair ability. The purpose of this study was to investigate the effects of different species of collagen-engineered neocartilage for the treatment of critical-size defects in the articular joint in a rabbit model. Type II and I collagen obtained from rabbits and rats was mixed to form a scaffold. The type II/I collagen scaffold was then mixed with rabbit chondrocytes to biofabricate neocartilage constructs using a rotating cell culture system [three-dimensional (3D-bioreactor]. The rabbit chondrocytes were mixed with rabbit collagen scaffold and rat collagen scaffold to form neoRBT (neo-rabbit cartilage and neoRAT (neo-rat cartilage constructs, respectively. The neocartilage matrix constructs were implanted into surgically created defects in rabbit knee chondyles, and histological examinations were performed after 2 and 3 months. Cartilage-like lacunae formation surrounding the chondrocytes was noted in the cell cultures. After 3 months, both the neoRBT and neoRAT groups showed cartilage-like repair tissue covering the 5-mm circular, 4-mm-deep defects that were created in the rabbit condyle and filled with neocartilage plugs. Reparative chondrocytes were aligned as apparent clusters in both the neoRAT and neoRBT groups. Both neoRBT and neoRAT cartilage repair demonstrated integration with healthy adjacent tissue; however, more integration was obtained using the neoRAT cartilage. Our data indicate that different species of type II/I collagen matrix and 3D bioreactor cultivation can facilitate cartilage engineering in vitro for the repair of critical-size defect.

  11. Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures

    OpenAIRE

    Lo Monaco, Melissa; Merckx, Greet; Ratajczak, Jessica; Gervois, Pascal; Hilkens, Petra; Clegg, Peter; Bronckaers, Annelies; Vandeweerd, Jean-Michel; Lambrichts, Ivo

    2018-01-01

    Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain...

  12. Quantitative T2 mapping evaluation for articular cartilage lesions in a rabbit model of anterior cruciate ligament transection osteoarthritis.

    Science.gov (United States)

    Wei, Zheng-mao; Du, Xiang-ke; Huo, Tian-long; Li, Xu-bin; Quan, Guang-nan; Li, Tian-ran; Cheng, Jin; Zhang, Wei-tao

    2012-03-01

    Quantitative T2 mapping has been a widely used method for the evaluation of pathological cartilage properties, and the histological assessment system of osteoarthritis in the rabbit has been published recently. The aim of the study was to investigate the effectiveness of quantitative T2 mapping evaluation for articular cartilage lesions of a rabbit model of anterior cruciate ligament transection (ACLT) osteoarthritis. Twenty New Zealand White (NZW) rabbits were divided into ACLT surgical group and sham operated group equally. The anterior cruciate ligaments of the rabbits in ACLT group were transected, while the joints were closed intactly in sham operated group. Magnetic resonance (MR) examinations were performed on 3.0T MR unit at week 0, week 6, and week 12. T2 values were computed on GE ADW4.3 workstation. All rabbits were killed at week 13, and left knees were stained with Haematoxylin and Eosin. Semiquantitative histological grading was obtained according to the osteoarthritis cartilage histopathology assessment system. Computerized image analysis was performed to quantitate the immunostained collagen type II. The average MR T2 value of whole left knee cartilage in ACLT surgical group ((29.05±12.01) ms) was significantly higher than that in sham operated group ((24.52±7.97) ms) (P=0.024) at week 6. The average T2 value increased to (32.18±12.79) ms in ACLT group at week 12, but remained near the baseline level ((27.66±8.08) ms) in the sham operated group (P=0.03). The cartilage lesion level of left knee in ACLT group was significantly increased at week 6 (P=0.005) and week 12 (PT2 values had positive correlation with histological grading scores, but inverse correlation with optical densities (OD) of type II collagen. This study demonstrated the reliability and practicability of quantitative T2 mapping for the cartilage injury of rabbit ACLT osteoarthritis model.

  13. Quantitative magnetic resonance imaging (MRI) evaluation of cartilage repair after microfracture treatment for full-thickness cartilage defect models in rabbit knee joints: correlations with histological findings

    International Nuclear Information System (INIS)

    Tao, Hongyue; Feng, Xiaoyuan; Chen, Shuang; Li, Hong; Hua, Yinghui; Chen, Zhongqing

    2015-01-01

    To evaluate repair tissue (RT) after microfracture treatment for full-thickness cartilage defect models using quantitative MRI and investigate the correlations between MRI and histological findings. The animal experiment was approved by the Animal Care and Use Committee of our college. Thirty-six full-thickness cartilage defect models in rabbit knee joints were assigned to the microfracture or joint debridement group (as control). Each group consisted of 3-week, 5-week, and 7-week subgroups. MR imaging, including a three-dimensional double-echo steady-state sequence (3D-DESS), and T2 mapping were performed at 3, 5, and 7 weeks postoperatively. The thickness and T2 indices of RT were calculated. After MRI scans at each time point, operation sites were removed to make hematoxylin-eosin (H and E)-stained sections. Histological results were evaluated using the modified O'Driscoll score system. Comparisons were made between the two groups with respect to the MRI and histological findings, and correlation analysis was performed within each group. The thickness index and histological O'Driscoll score of RT in the two groups increased over time, while the T2 index decreased. The thickness index and histological O'Driscoll score of the microfracture group were higher than in the joint debridement group at each time point. The T2 index of the microfracture group was lower than in the joint debridement group at 3 weeks (P = 0.006), while it was higher than in the joint debridement group at 5 and 7 weeks (P = 0.025 and 0.025). The thickness index was positively correlated with the histological O'Driscoll score in both groups (microfracture: r s = 0.745, P s = 0.680, P = 0.002). The T2 index was negatively correlated with the histological O'Driscoll score in both groups (microfracture: r s = -0.715, P = 0.002; joint debridement: r s = -0.826, P < 0.001). Significant improvement over time after microfracture can be expected on the basis of the quantitative MRI finding and

  14. Quantitative magnetic resonance imaging (MRI) evaluation of cartilage repair after microfracture treatment for full-thickness cartilage defect models in rabbit knee joints: correlations with histological findings

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Hongyue; Feng, Xiaoyuan; Chen, Shuang [Fudan University, Department of Radiology, Huashan Hospital, Shanghai (China); Li, Hong; Hua, Yinghui [Fudan University, Department of Sports Medicine, Huashan Hospital, Shanghai (China); Chen, Zhongqing [Fudan University, Department of Pathology, Huashan Hospital, Shanghai (China)

    2014-11-26

    To evaluate repair tissue (RT) after microfracture treatment for full-thickness cartilage defect models using quantitative MRI and investigate the correlations between MRI and histological findings. The animal experiment was approved by the Animal Care and Use Committee of our college. Thirty-six full-thickness cartilage defect models in rabbit knee joints were assigned to the microfracture or joint debridement group (as control). Each group consisted of 3-week, 5-week, and 7-week subgroups. MR imaging, including a three-dimensional double-echo steady-state sequence (3D-DESS), and T2 mapping were performed at 3, 5, and 7 weeks postoperatively. The thickness and T2 indices of RT were calculated. After MRI scans at each time point, operation sites were removed to make hematoxylin-eosin (H and E)-stained sections. Histological results were evaluated using the modified O'Driscoll score system. Comparisons were made between the two groups with respect to the MRI and histological findings, and correlation analysis was performed within each group. The thickness index and histological O'Driscoll score of RT in the two groups increased over time, while the T2 index decreased. The thickness index and histological O'Driscoll score of the microfracture group were higher than in the joint debridement group at each time point. The T2 index of the microfracture group was lower than in the joint debridement group at 3 weeks (P = 0.006), while it was higher than in the joint debridement group at 5 and 7 weeks (P = 0.025 and 0.025). The thickness index was positively correlated with the histological O'Driscoll score in both groups (microfracture: r{sub s} = 0.745, P < 0.001; joint debridement: r{sub s} = 0.680, P = 0.002). The T2 index was negatively correlated with the histological O'Driscoll score in both groups (microfracture: r{sub s} = -0.715, P = 0.002; joint debridement: r{sub s} = -0.826, P < 0.001). Significant improvement over time after

  15. Theoretical modeling of heating and structure alterations in cartilage under laser radiation with regard to water evaporation and diffusion dominance

    Science.gov (United States)

    Sobol, Emil N.; Kitai, Moishe S.; Jones, Nicholas; Sviridov, Alexander P.; Milner, Thomas E.; Wong, Brian

    1998-05-01

    We develop a theoretical model to calculate the temperature field and the size of modified structure area in cartilaginous tissue. The model incorporates both thermal and mass transfer in a tissue regarding bulk absorption of laser radiation, water evaporation from a surface and temperature dependence of diffusion coefficient. It is proposed that due to bound- to free-phase transition of water in cartilage heated to about 70 degrees Celsius, some parts of cartilage matrix (proteoglycan units) became more mobile. The movement of these units takes place only when temperature exceed 70 degrees Celsius and results in alteration of tissue structure (denaturation). It is shown that (1) the maximal temperature is reached not on the surface irradiated at some distance from the surface; (2) surface temperature reaches a plateau quicker that the maximal temperature; (3) the depth of denatured area strongly depends on laser fluence and wavelength, exposure time and thickness of cartilage. The model allows to predict and control temperature and depth of structure alterations in the course of laser reshaping and treatment of cartilage.

  16. Cell compaction influences the regenerative potential of passaged bovine articular chondrocytes in an ex vivo cartilage defect model.

    Science.gov (United States)

    Schmutzer, Michael; Aszodi, Attila

    2017-04-01

    The loss and degradation of articular cartilage tissue matrix play central roles in the process of osteoarthritis (OA). New models for evaluating cartilage repair/regeneration are thus of great value for transferring various culture systems into clinically relevant situations. The repair process can be better monitored in ex vivo systems than in in vitro cell cultures. I have therefore established an ex vivo defect model prepared from bovine femoral condyles for evaluating cartilage repair by the implantation of cells cultured in various ways, e.g., monolayer-cultured cells or suspension or pellet cultures of articular bovine chondrocytes representing different cell compactions with variable densities of chondrocytes. I report that the integrin subunit α10 was significantly upregulated in suspension-cultured bovine chondrocytes at passage P2 compared with monolayer-cultured cells at P1 (p = 0.0083) and P2 (p innovation of this system over in vitro differentiation (e.g., micromass, pellet) assays is the possibility of examining and evaluating cartilage regeneration in an environment in which implanted cells are embedded within native surrounding tissue at the defect site. Such ex vivo explants might serve as a better model system to mimic clinical situations. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  17. Cartilage extracellular matrix as a biomaterial for cartilage regeneration.

    Science.gov (United States)

    Kiyotake, Emi A; Beck, Emily C; Detamore, Michael S

    2016-11-01

    The extracellular matrix (ECM) of various tissues possesses the model characteristics that biomaterials for tissue engineering strive to mimic; however, owing to the intricate hierarchical nature of the ECM, it has yet to be fully characterized and synthetically fabricated. Cartilage repair remains a challenge because the intrinsic properties that enable its durability and long-lasting function also impede regeneration. In the last decade, cartilage ECM has emerged as a promising biomaterial for regenerating cartilage, partly because of its potentially chondroinductive nature. As this research area of cartilage matrix-based biomaterials emerged, investigators facing similar challenges consequently developed convergent solutions in constructing robust and bioactive scaffolds. This review discusses the challenges, emerging trends, and future directions of cartilage ECM scaffolds, including a comparison between two different forms of cartilage matrix: decellularized cartilage (DCC) and devitalized cartilage (DVC). To overcome the low permeability of cartilage matrix, physical fragmentation greatly enhances decellularization, although the process itself may reduce the chondroinductivity of fabricated scaffolds. The less complex processing of a scaffold composed of DVC, which has not been decellularized, appears to have translational advantages and potential chondroinductive and mechanical advantages over DCC, without detrimental immunogenicity, to ultimately enhance cartilage repair in a clinically relevant way. © 2016 New York Academy of Sciences.

  18. Use of magnetic forces to promote stem cell aggregation during differentiation, and cartilage tissue modeling.

    Science.gov (United States)

    Fayol, D; Frasca, G; Le Visage, C; Gazeau, F; Luciani, N; Wilhelm, C

    2013-05-14

    Magnetic forces induce cell condensation necessary for stem cell differentiation into cartilage and elicit the formation of a tissue-like structure: Magnetically driven fusion of aggregates assembled by micromagnets results in the formation of a continuous tissue layer containing abundant cartilage matrix. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Development of a Novel Large Animal Model to Evaluate Human Dental Pulp Stem Cells for Articular Cartilage Treatment.

    Science.gov (United States)

    Fernandes, Tiago Lazzaretti; Shimomura, Kazunori; Asperti, Andre; Pinheiro, Carla Cristina Gomes; Caetano, Heloísa Vasconcellos Amaral; Oliveira, Claudia Regina G C M; Nakamura, Norimasa; Hernandez, Arnaldo José; Bueno, Daniela Franco

    2018-05-04

    Chondral lesion is a pathology with high prevalence, reaching as much as 63% of general population and 36% among athletes. The ability of human Dental Pulp Stem Cells (DPSCs) to differentiate into chondroblasts in vitro suggests that this stem cell type may be useful for tissue bioengineering. However, we have yet to identify a study of large animal models in which DPSCs were used to repair articular cartilage. Therefore, this study aimed to describe a novel treatment for cartilage lesion with DPSCs on a large animal model. Mesenchymal stem cells (MSC) were obtained from deciduous teeth and characterized by flow cytometry. DPSCs were cultured and added to a collagen type I/III biomaterial composite scaffold. Brazilian miniature pig (BR-1) was used. A 6-mm diameter, full-thickness chondral defect was created in each posterior medial condyle. The defects were covered with scaffold alone or scaffold + DPSCs on the contralateral side. Animals were euthanized 6 weeks post-surgery. Cartilage defects were analyzed macroscopically and histology according to modified O'Driscoll scoring system. Flow cytometry confirmed characterization of DPSCs as MSCs. Macroscopic and histological findings suggested that this time period was reasonable for evaluating cartilage repair. To our knowledge, this study provides the first description of an animal model using DPSCs to study the differentiation of hyaline articular cartilage in vivo. The animals tolerated the procedure well and did not show clinical or histological rejection of the DPSCs, reinforcing the feasibility of this descriptive miniature pig model for pre-clinical studies.

  20. A CHF Model in Narrow Gaps under Saturated Boiling

    International Nuclear Information System (INIS)

    Park, Suki; Kim, Hyeonil; Park, Cheol

    2014-01-01

    Many researchers have paid a great attention to the CHF in narrow gaps due to enormous industrial applications. Especially, a great number of researches on the CHF have been carried out in relation to nuclear safety issues such as in-vessel retention for nuclear power plants during a severe accident. Analytical studies to predict the CHF in narrow gaps have been also reported. Yu et al. (2012) developed an analytical model to predict the CHF on downward facing and inclined heaters based on the model of Kandlikar et al. (2001) for an upward facing heater. A new theoretical model is developed to predict the CHF in narrow gaps under saturated pool boiling. This model is applicable when one side of coolant channels or both sides are heated including the effects of heater orientation. The present model is compared with the experimental CHF data obtained in narrow gaps. A new analytical CHF model is proposed to predict CHF for narrow gaps under saturated pool boiling. This model can be applied to one-side or two-sides heating surface and also consider the effects of heater orientation on CHF. The present model is compared with the experimental data obtained in narrow gaps with one heater. The comparisons indicate that the present model shows a good agreement with the experimental CHF data in the horizontal annular tubes. However, it generally under-predicts the experimental data in the narrow rectangular gaps except the data obtained in the gap thickness of 10 mm and the horizontal downward facing heater

  1. A model for gap conductance in nuclear fuel rods

    International Nuclear Information System (INIS)

    Loyalka, S.K.

    1982-01-01

    Computation of nuclear reactor fuel behavior under normal and off-normal conditions is influenced by gap conductance models. These models should provide accurate results for heat transfer for arbitrary gap widths and gas mixtures and should be based on considerations of the kinetic theory of gases. There has been considerable progress in the study of heat transfer in a simple gas for arbitrary Knudsen numbers (Kn = l/similar to d, where l is a meanfree-path and similar d is the gap width) in recent years. Using these recent results, a simple expression for heat transfer in a gas mixture (enclosed between parallel plates) for an arbitrary Knudsen number has been constructed, and a new model for gap conductance has been proposed. The latter reproduces the free molecular (small gap, Kn >> 1) and the jump limits (large gaps, Kn << 1) correctly, and it provides fairly accurate results for arbitrary gap widths. The new model is suitable for use in large fuel behavior computer programs

  2. Modeling pedestrian gap crossing index under mixed traffic condition.

    Science.gov (United States)

    Naser, Mohamed M; Zulkiple, Adnan; Al Bargi, Walid A; Khalifa, Nasradeen A; Daniel, Basil David

    2017-12-01

    There are a variety of challenges faced by pedestrians when they walk along and attempt to cross a road, as the most recorded accidents occur during this time. Pedestrians of all types, including both sexes with numerous aging groups, are always subjected to risk and are characterized as the most exposed road users. The increased demand for better traffic management strategies to reduce the risks at intersections, improve quality traffic management, traffic volume, and longer cycle time has further increased concerns over the past decade. This paper aims to develop a sustainable pedestrian gap crossing index model based on traffic flow density. It focusses on the gaps accepted by pedestrians and their decision for street crossing, where (Log-Gap) logarithm of accepted gaps was used to optimize the result of a model for gap crossing behavior. Through a review of extant literature, 15 influential variables were extracted for further empirical analysis. Subsequently, data from the observation at an uncontrolled mid-block in Jalan Ampang in Kuala Lumpur, Malaysia was gathered and Multiple Linear Regression (MLR) and Binary Logit Model (BLM) techniques were employed to analyze the results. From the results, different pedestrian behavioral characteristics were considered for a minimum gap size model, out of which only a few (four) variables could explain the pedestrian road crossing behavior while the remaining variables have an insignificant effect. Among the different variables, age, rolling gap, vehicle type, and crossing were the most influential variables. The study concludes that pedestrians' decision to cross the street depends on the pedestrian age, rolling gap, vehicle type, and size of traffic gap before crossing. The inferences from these models will be useful to increase pedestrian safety and performance evaluation of uncontrolled midblock road crossings in developing countries. Copyright © 2017 National Safety Council and Elsevier Ltd. All rights reserved.

  3. Towards Finite-Gap Integration of the Inozemtsev Model

    Directory of Open Access Journals (Sweden)

    Kouichi Takemura

    2007-03-01

    Full Text Available The Inozemtsev model is considered to be a multivaluable generalization of Heun's equation. We review results on Heun's equation, the elliptic Calogero-Moser-Sutherland model and the Inozemtsev model, and discuss some approaches to the finite-gap integration for multivariable models.

  4. Yougui Pills Attenuate Cartilage Degeneration via Activation of TGF-β/Smad Signaling in Chondrocyte of Osteoarthritic Mouse Model.

    Science.gov (United States)

    Zhang, Lei; Wang, Ping-Er; Ying, Jun; Jin, Xing; Luo, Cheng; Xu, Taotao; Xu, Shibing; Dong, Rui; Xiao, Luwei; Tong, Peijian; Jin, Hongting

    2017-01-01

    Yougui pills (YGPs) have been used for centuries in the treatment of Chinese patients with Kidney-Yang Deficiency Syndrome. Despite the fact that the efficiency of YGPs on treating osteoarthritis has been verified in clinic, the underlying mechanisms are not totally understood. The present study observes the therapeutic role of YGPs and mechanisms underlying its chondroprotective action in osteoarthritic cartilage. To evaluate the chondroprotective effects of YGPs, we examined the impact of orally administered YGPs in a model of destabilization of the medial meniscus (DMM). Male C57BL/6J mice were provided a daily treatment of YGPs and a DMM surgery was performed on the right knee. At 12 weeks post-surgery, the joints were harvested for tissue analyses, including histomorphometry, OARSI scoring, micro-CT and immunohistochemistry for COL-2, MMP-13 and pSMAD-2. We also performed the relative experiments mentioned above in mice with Tgfbr2 conditional knockout ( TGF-βRII Col2ER mice) in articular cartilage. To evaluate the safety of YGPs, hematology was determined in each group. Amelioration of cartilage degradation was observed in the YGPs group, with increases in cartilage area and thickness, proteoglycan matrix, and decreases in OARSI score at 12 weeks post surgery. In addition, reduced BV/TV and Tb. Th, and elevated Tb. Sp were observed in DMM-induced mice followed by YGPs treatment. Moreover, the preservation of cartilage correlated with reduced MMP-13, and elevated COL-2 and pSMAD-2 protein expressional levels were also revealed in DMM-induced mice treated with YGPs. Similarly, TGF-βRII Col2ER mice exhibited significant OA-like phenotype. However, no significant difference in cartilage structure was observed in TGF-βRII Col2ER mice after YGPs treatment. Interestingly, no obvious adverse effects were observed in mice from each group based on the hematologic analyses. These findings suggested that YGPs could inhibit cartilage degradation through enhancing TGF

  5. Bone compaction enhances implant fixation in a canine gap model

    DEFF Research Database (Denmark)

    Kold, Søren; Rahbek, Ole; Toft, Marianne

    2005-01-01

    A new bone preparation technique, compaction, has increased fixation of implants inserted with exact-fit or press-fit to bone. Furthermore, a demonstrated spring-back effect of compacted bone might be of potential value in reducing the initial gaps that often exist between clinical inserted...... implants and bone. However, it is unknown whether the compression and breakage of trabeculae during the compaction procedure results in impaired gap-healing of compacted bone. Therefore, we compared compaction with conventional drilling in a canine gap model. Grit-blasted titanium implants (diameter 6 mm...... that the beneficial effect of reduced gap size, as compacted bone springs back, is not eliminated by an impaired gap-healing of compacted bone....

  6. Sequential change in T2* values of cartilage, meniscus, and subchondral bone marrow in a rat model of knee osteoarthritis.

    Directory of Open Access Journals (Sweden)

    Ping-Huei Tsai

    Full Text Available BACKGROUND: There is an emerging interest in using magnetic resonance imaging (MRI T2* measurement for the evaluation of degenerative cartilage in osteoarthritis (OA. However, relatively few studies have addressed OA-related changes in adjacent knee structures. This study used MRI T2* measurement to investigate sequential changes in knee cartilage, meniscus, and subchondral bone marrow in a rat OA model induced by anterior cruciate ligament transection (ACLX. MATERIALS AND METHODS: Eighteen male Sprague Dawley rats were randomly separated into three groups (n = 6 each group. Group 1 was the normal control group. Groups 2 and 3 received ACLX and sham-ACLX, respectively, of the right knee. T2* values were measured in the knee cartilage, the meniscus, and femoral subchondral bone marrow of all rats at 0, 4, 13, and 18 weeks after surgery. RESULTS: Cartilage T2* values were significantly higher at 4, 13, and 18 weeks postoperatively in rats of the ACLX group than in rats of the control and sham groups (p<0.001. In the ACLX group (compared to the sham and control groups, T2* values increased significantly first in the posterior horn of the medial meniscus at 4 weeks (p = 0.001, then in the anterior horn of the medial meniscus at 13 weeks (p<0.001, and began to increase significantly in the femoral subchondral bone marrow at 13 weeks (p = 0.043. CONCLUSION: Quantitative MR T2* measurements of OA-related tissues are feasible. Sequential change in T2* over time in cartilage, meniscus, and subchondral bone marrow were documented. This information could be potentially useful for in vivo monitoring of disease progression.

  7. Production of hyaline-like cartilage by bone marrow mesenchymal stem cells in a self-assembly model.

    Science.gov (United States)

    Elder, Steven H; Cooley, Avery J; Borazjani, Ali; Sowell, Brittany L; To, Harrison; Tran, Scott C

    2009-10-01

    A scaffoldless or self-assembly approach to cartilage tissue engineering has been used to produce hyaline cartilage from bone marrow-derived mesenchymal stem cells (bMSCs), but the mechanical properties of such engineered cartilage and the effects the transforming growth factor (TGF) isoform have not been fully explored. This study employs a cell culture insert model to produce tissue-engineered cartilage using bMSCs. Neonatal pig bMSCs were isolated by plastic adherence and expanded in monolayer before being seeded into porous transwell inserts and cultured for 4 or 8 weeks in defined chondrogenic media containing either TGF-beta1 or TGF-beta3. Following biomechanical evaluation in confined compression, colorimetric dimethyl methylene blue and Sircol dye-binding assays were used to analyze glycosaminoglycan (GAG) and collagen contents, respectively. Histological sections were stained with toluidine blue for proteoglycans and with picrosirius red to reveal collagen orientation, and immunostained for detection of collagen types I and II. Neocartilage increased in thickness, collagen, and GAG content between 4 and 8 weeks. Proteoglycan concentration increased with depth from the top surface. The tissue contained much more collagen type II than type I, and there was a consistent pattern of collagen alignment. TGF-beta1-treated and TGF-beta3-treated constructs were similar at 4 weeks, but 8-week TGF-beta1 constructs had a higher aggregate modulus and GAG content compared to TGF-beta3. These results demonstrate that bMSCs can generate functional hyaline-like cartilage through a self-assembling process.

  8. Subchondral Bone Plate Thickening Precedes Chondrocyte Apoptosis and Cartilage Degradation in Spontaneous Animal Models of Osteoarthritis

    OpenAIRE

    Zamli, Zaitunnatakhin; Robson Brown, Kate; Tarlton, John F.; Adams, Mike A.; Torlot, Georgina E.; Cartwright, Charlie; Cook, William A.; Vassilevskaja, Kristiina; Sharif, Mohammed

    2014-01-01

    Osteoarthritis (OA) is the most common joint disorder characterised by bone remodelling and cartilage degradation and associated with chondrocyte apoptosis. These processes were investigated at 10, 16, 24, and 30 weeks in Dunkin Hartley (DH) and Bristol Strain 2 (BS2) guinea pigs that develop OA spontaneously. Both strains had a more pronounced chondrocyte apoptosis, cartilage degradation, and subchondral bone changes in the medial than the lateral side of the tibia, and between strains, the ...

  9. Genetic modification of chondrocytes with insulin-like growth factor-1 enhances cartilage healing in an equine model.

    Science.gov (United States)

    Goodrich, L R; Hidaka, C; Robbins, P D; Evans, C H; Nixon, A J

    2007-05-01

    Gene therapy with insulin-like growth factor-1 (IGF-1) increases matrix production and enhances chondrocyte proliferation and survival in vitro. The purpose of this study was to determine whether arthroscopically-grafted chondrocytes genetically modified by an adenovirus vector encoding equine IGF-1 (AdIGF-1) would have a beneficial effect on cartilage healing in an equine femoropatellar joint model. A total of 16 horses underwent arthroscopic repair of a single 15 mm cartilage defect in each femoropatellar joint. One joint received 2 x 10(7) AdIGF-1 modified chondrocytes and the contralateral joint received 2 x 10(7) naive (unmodified) chondrocytes. Repairs were analysed at four weeks, nine weeks and eight months after surgery. Morphological and histological appearance, IGF-1 and collagen type II gene expression (polymerase chain reaction, in situ hybridisation and immunohistochemistry), collagen type II content (cyanogen bromide and sodium dodecyl sulphate-polyacrylamide gel electrophoresis), proteoglycan content (dimethylmethylene blue assay), and gene expression for collagen type I, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, aggrecanase-1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-3 were evaluated. Genetic modification of chondrocytes significantly increased IGF-1 mRNA and ligand production in repair tissue for up to nine weeks following transplantation. The gross and histological appearance of IGF-1 modified repair tissue was improved over control defects. Gross filling of defects was significantly improved at four weeks, and a more hyaline-like tissue covered the lesions at eight months. Histological outcome at four and nine weeks post-transplantation revealed greater tissue filling of defects transplanted with genetically modified chondrocytes, whereas repair tissue in control defects was thin and irregular and more fibrous. Collagen type II expression in IGF-1 gene-transduced defects was increased 100-fold at four weeks and

  10. Constrained convex minimization via model-based excessive gap

    OpenAIRE

    Tran Dinh, Quoc; Cevher, Volkan

    2014-01-01

    We introduce a model-based excessive gap technique to analyze first-order primal- dual methods for constrained convex minimization. As a result, we construct new primal-dual methods with optimal convergence rates on the objective residual and the primal feasibility gap of their iterates separately. Through a dual smoothing and prox-function selection strategy, our framework subsumes the augmented Lagrangian, and alternating methods as special cases, where our rates apply.

  11. Molecular changes in articular cartilage and subchondral bone in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis

    OpenAIRE

    Zhuo Ya; Hayami Tadashi; Pickarski Maureen; Duong Le T

    2011-01-01

    Abstract Background Osteoarthritis (OA) is a debilitating, progressive joint disease. Methods Similar to the disease progression in humans, sequential events of early cartilage degradation, subchondral osteopenia followed by sclerosis, and late osteophyte formation were demonstrated in the anterior cruciate ligament transection (ACLT) or ACLT with partial medial meniscectomy (ACLT + MMx) rat OA models. We describe a reliable and consistent method to examine the time dependent changes in the g...

  12. Utility of a mouse model of osteoarthritis to demonstrate cartilage protection by IFNγ-primed equine mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Marie Maumus

    2016-09-01

    Full Text Available Objective. Mesenchymal stem cells isolated from adipose tissue (ASC have been shown to influence the course of osteoarthritis (OA in different animal models and are promising in veterinary medicine for horses involved in competitive sport. The aim of this study was to characterize equine ASCs (eASC and investigate the role of interferon-gamma (IFNγ-priming on their therapeutic effect in a murine model of OA, which could be relevant to equine OA.Methods. ASC were isolated from subcutaneous fat. Expression of specific markers was tested by cytometry and RT-qPCR. Differentiation potential was evaluated by histology and RT-qPCR. For functional assays, naïve or IFNγ-primed eASCs were cocultured with PBMC or articular cartilage explants. Finally, the therapeutic effect of eASCs was tested in the model of collagenase-induced OA in mice (CIOA.Results. The immunosuppressive function of eASCs on equine T cell proliferation and their chondroprotective effect on equine cartilage explants were demonstrated in vitro. Both cartilage degradation and T cell activation were reduced by naïve and IFNγ-primed eASCs but IFNγ-priming enhanced these functions. In CIOA, intra-articular injection of eASCs prevented articular cartilage from degradation and IFNγ-primed eASCs were more potent than naïve cells. This effect was related to the modulation of eASC secretome by IFNγ-priming.Conclusion. IFNγ-priming of eASCs potentiated their antiproliferative and chondroprotective functions. We demonstrated that the immunocompetent mouse model of CIOA was relevant to test the therapeutic efficacy of xenogeneic eASCs for OA and confirmed that IFNγ-primed eASCs may have a therapeutic value for musculoskeletal diseases in veterinary medicine.

  13. Spatial distance in a technology gap model

    NARCIS (Netherlands)

    Verspagen, B.; Caniëls, M.C.J.

    1999-01-01

    This paper analyses the effect of locally bounded knowledge spillovers on regional differences in growth. A model will be developed that allows spillovers to take place across regions. Certain conditions determine the amount of spillovers a region receives. By use of simulations (with randomised

  14. Applying revised gap analysis model in measuring hotel service quality.

    Science.gov (United States)

    Lee, Yu-Cheng; Wang, Yu-Che; Chien, Chih-Hung; Wu, Chia-Huei; Lu, Shu-Chiung; Tsai, Sang-Bing; Dong, Weiwei

    2016-01-01

    With the number of tourists coming to Taiwan growing by 10-20 % since 2010, the number has increased due to an increasing number of foreign tourists, particularly after deregulation allowed admitting tourist groups, followed later on by foreign individual tourists, from mainland China. The purpose of this study is to propose a revised gap model to evaluate and improve service quality in Taiwanese hotel industry. Thus, service quality could be clearly measured through gap analysis, which was more effective for offering direction in developing and improving service quality. The HOLSERV instrument was used to identify and analyze service gaps from the perceptions of internal and external customers. The sample for this study included three main categories of respondents: tourists, employees, and managers. The results show that five gaps influenced tourists' evaluations of service quality. In particular, the study revealed that Gap 1 (management perceptions vs. customer expectations) and Gap 9 (service provider perceptions of management perceptions vs. service delivery) were more critical than the others in affecting perceived service quality, making service delivery the main area of improvement. This study contributes toward an evaluation of the service quality of the Taiwanese hotel industry from the perspectives of customers, service providers, and managers, which is considerably valuable for hotel managers. It was the aim of this study to explore all of these together in order to better understand the possible gaps in the hotel industry in Taiwan.

  15. The effects of orally administered diacerein on cartilage and subchondral bone in an ovine model of osteoarthritis.

    Science.gov (United States)

    Hwa, S Y; Burkhardt, D; Little, C; Ghosh, P

    2001-04-01

    An ovine model of osteoarthritis (OA) induced by bilateral lateral meniscectomy (BLM) was used to evaluate in vivo effects of the slow acting antiarthritic drug diacerein (DIA) on degenerative changes in cartilage and subchondral bone of the operated joints. Twenty of 30 adult age matched Merino wethers were subjected to BLM in the knee joints and the remainder served as non-operated controls (NOC). Half of the BLM group (n = 10) were given DIA (25 mg/kg orally) daily for 3 mo, then 50 mg/kg daily for a further 6 mo. The remainder of the meniscectomized (MEN) group served as OA controls. Five DIA, 5 MEN, and 5 NOC animals were sacrificed at 3 mo and the remainder at 9 mo postsurgery. One knee joint of each animal was used for bone mineral density (BMD) studies. Osteochondral slabs from the lateral femoral condyle and lateral tibial plateau were cut from the contralateral joint and were processed for histological and histomorphometric examination to assess the cartilage and subchondral bone changes. No significant difference was observed in the modified Mankin scores for cartilage from the DIA and MEN groups at 3 or 9 mo. However, in animals treated with DIA, the thickness of cartilage (p = 0.05) and subchondral bone (p = 0.05) in the lesion (middle) zone of the lateral tibial plateau were decreased relative to the corresponding zone of the MEN group at 3 mo (p = 0.05). At 9 mo subchondral bone thickness in this zone remained the same as NOC but BMD, which included both subchondral and trabecular bone, was significantly increased relative to the NOC group (p = 0.01). In contrast, the subchondral bone thickness of the outer zone of lateral tibial plateau and lateral femoral condyle of both MEN and DIA groups increased after 9 mo, while BMD remained the same as in the NOC. DIA treatment of meniscectomized animals mediated selective responses of cartilage and subchondral bone to the altered mechanical stresses induced across the joints by this procedure. While

  16. Perivascular Mesenchymal Stem Cells in Sheep: Characterization and Autologous Transplantation in a Model of Articular Cartilage Repair.

    Science.gov (United States)

    Hindle, Paul; Baily, James; Khan, Nusrat; Biant, Leela C; Simpson, A Hamish R; Péault, Bruno

    2016-11-01

    Previous research has indicated that purified perivascular stem cells (PSCs) have increased chondrogenic potential compared to conventional mesenchymal stem cells (MSCs) derived in culture. This study aimed to develop an autologous large animal model for PSC transplantation and to specifically determine if implanted cells are retained in articular cartilage defects. Immunohistochemistry and fluorescence-activated cell sorting were used to ascertain the reactivity of anti-human and anti-ovine antibodies, which were combined and used to identify and isolate pericytes (CD34 - CD45 - CD146 + ) and adventitial cells (CD34 + CD45 - CD146 - ). The purified cells demonstrated osteogenic, adipogenic, and chondrogenic potential in culture. Autologous ovine PSCs (oPSCs) were isolated, cultured, and efficiently transfected using a green fluorescence protein (GFP) encoding lentivirus. The cells were implanted into articular cartilage defects on the medial femoral condyle using hydrogel and collagen membranes. Four weeks following implantation, the condyle was explanted and confocal laser scanning microscopy demonstrated the presence of oPSCs in the defect repaired with the hydrogel. These data suggest the testability in a large animal of native MSC autologous grafting, thus avoiding possible biases associated with xenotransplantation. Such a setting will be used in priority for indications in orthopedics, at first to model articular cartilage repair.

  17. Microstructural changes in cartilage and bone related to repetitive overloading in an equine athlete model.

    Science.gov (United States)

    Turley, Sean M; Thambyah, Ashvin; Riggs, Christopher M; Firth, Elwyn C; Broom, Neil D

    2014-06-01

    The palmar aspect of the third metacarpal (MC3) condyle of equine athletes is known to be subjected to repetitive overloading that can lead to the accumulation of joint tissue damage, degeneration, and stress fractures, some of which result in catastrophic failure. However, there is still a need to understand at a detailed microstructural level how this damage progresses in the context of the wider joint tissue complex, i.e. the articular surface, the hyaline and calcified cartilage, and the subchondral bone. MC3 bones from non-fractured joints were obtained from the right forelimbs of 16 Thoroughbred racehorses varying in age between 3 and 8 years, with documented histories of active race training. Detailed microstructural analysis of two clinically important sites, the parasagittal grooves and the mid-condylar regions, identified extensive levels of microdamage in the calcified cartilage and subchondral bone concealed beneath outwardly intact hyaline cartilage. The study shows a progression in microdamage severity, commencing with mild hard-tissue microcracking in younger animals and escalating to severe subchondral bone collapse and lesion formation in the hyaline cartilage with increasing age and thus athletic activity. The presence of a clearly distinguishable fibrous tissue layer at the articular surface immediately above sites of severe subchondral collapse suggested a limited reparative response in the hyaline cartilage. © 2014 Anatomical Society.

  18. Microstructural changes in cartilage and bone related to repetitive overloading in an equine athlete model

    Science.gov (United States)

    Turley, Sean M; Thambyah, Ashvin; Riggs, Christopher M; Firth, Elwyn C; Broom, Neil D

    2014-01-01

    The palmar aspect of the third metacarpal (MC3) condyle of equine athletes is known to be subjected to repetitive overloading that can lead to the accumulation of joint tissue damage, degeneration, and stress fractures, some of which result in catastrophic failure. However, there is still a need to understand at a detailed microstructural level how this damage progresses in the context of the wider joint tissue complex, i.e. the articular surface, the hyaline and calcified cartilage, and the subchondral bone. MC3 bones from non-fractured joints were obtained from the right forelimbs of 16 Thoroughbred racehorses varying in age between 3 and 8 years, with documented histories of active race training. Detailed microstructural analysis of two clinically important sites, the parasagittal grooves and the mid-condylar regions, identified extensive levels of microdamage in the calcified cartilage and subchondral bone concealed beneath outwardly intact hyaline cartilage. The study shows a progression in microdamage severity, commencing with mild hard-tissue microcracking in younger animals and escalating to severe subchondral bone collapse and lesion formation in the hyaline cartilage with increasing age and thus athletic activity. The presence of a clearly distinguishable fibrous tissue layer at the articular surface immediately above sites of severe subchondral collapse suggested a limited reparative response in the hyaline cartilage. PMID:24689513

  19. Transplantation of dedifferentiated fat cell-derived micromass pellets contributed to cartilage repair in the rat osteochondral defect model.

    Science.gov (United States)

    Shimizu, Manabu; Matsumoto, Taro; Kikuta, Shinsuke; Ohtaki, Munenori; Kano, Koichiro; Taniguchi, Hiroaki; Saito, Shu; Nagaoka, Masahiro; Tokuhashi, Yasuaki

    2018-03-20

    Mature adipocyte-derived dedifferentiated fat (DFAT) cells possesses the ability to proliferate effectively and the potential to differentiate into multiple linages of mesenchymal tissue; similar to adipose-derived stem cells (ASCs). The purpose of this study is to examine the effects of DFAT cell transplantation on cartilage repair in a rat model of osteochondral defects. Full-thickness osteochondral defects were created in the knees of Sprague-Dawley rats bilaterally. Cartilage-like micromass pellets were prepared from green fluorescent protein (GFP)-labeled rat DFAT cells and subsequently transplanted into the affected right knee of these rats. Defects in the left knee were used as a control. Macroscopic and microscopic changes of treated and control defects were evaluated up to 12 weeks post-treatment with DFAT cells. To observe the transplanted cells, sectioned femurs were immunostained for GFP and type II collagen. DFAT cells formed micromass pellets expressing characteristics of immature cartilage in vitro. In the DFAT cell-transplanted limbs, the defects were completely filled with white micromass pellets as early as 2 weeks post-treatment. These limbs became smooth at 4 weeks. Conversely, the defects in the control limbs were still not repaired by 4 weeks. Macroscopic ICRS scores at 2 and 4 weeks were significantly higher in the DFAT cells-transplanted limbs compared to those of the control limbs. The modified O'Driscol histological scores for the DFAT cell-transplanted limbs were significantly higher than those of the control limbs at corresponding time points. GFP-positive DAFT cells were detected in the transplanted area at 2 weeks but hardly visible at 12 weeks post-operation. Transplantation of DFAT cell-derived micromass pellets contribute to cartilage repair in a rat osteochondral defect model. DFAT cell transplantation may be a viable therapeutic strategy for the repair of osteochondral injuries. Copyright © 2018 The Authors. Published by

  20. Molecular changes in articular cartilage and subchondral bone in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis.

    Science.gov (United States)

    Pickarski, Maureen; Hayami, Tadashi; Zhuo, Ya; Duong, Le T

    2011-08-24

    Osteoarthritis (OA) is a debilitating, progressive joint disease. Similar to the disease progression in humans, sequential events of early cartilage degradation, subchondral osteopenia followed by sclerosis, and late osteophyte formation were demonstrated in the anterior cruciate ligament transection (ACLT) or ACLT with partial medial meniscectomy (ACLT + MMx) rat OA models. We describe a reliable and consistent method to examine the time dependent changes in the gene expression profiles in articular cartilage and subchondral bone. Local regulation of matrix degradation markers was demonstrated by a significant increase in mRNA levels of aggrecanase-1 and MMP-13 as early as the first week post-surgery, and expression remained elevated throughout the 10 week study. Immunohistochemistry confirmed MMP-13 expression in differentiated chondrocytes and synovial fibroblasts at week-2 and cells within osteophytes at week-10 in the surgically-modified-joints. Concomitant increases in chondrocyte differentiation markers, Col IIA and Sox 9, and vascular invasion markers, VEGF and CD31, peaked around week-2 to -4, and returned to Sham levels at later time points in both models. Indeed, VEGF-positive cells were found in the deep articular chondrocytes adjacent to subchondral bone. Osteoclastic bone resorption markers, cathepsin K and TRAP, were also elevated at week-2. Confirming bone resorption is an early local event in OA progression, cathepsin K positive osteoclasts were found invading the articular cartilage from the subchondral region at week 2. This was followed by late disease events, including subchondral sclerosis and osteophyte formation, as demonstrated by the upregulation of the osteoanabolic markers runx2 and osterix, toward week-4 to 6 post-surgery. In summary, this study demonstrated the temporal and cohesive gene expression changes in articular cartilage and subchondral bone using known markers of OA progression. The findings here support genome-wide profiling

  1. Molecular changes in articular cartilage and subchondral bone in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis

    Directory of Open Access Journals (Sweden)

    Zhuo Ya

    2011-08-01

    Full Text Available Abstract Background Osteoarthritis (OA is a debilitating, progressive joint disease. Methods Similar to the disease progression in humans, sequential events of early cartilage degradation, subchondral osteopenia followed by sclerosis, and late osteophyte formation were demonstrated in the anterior cruciate ligament transection (ACLT or ACLT with partial medial meniscectomy (ACLT + MMx rat OA models. We describe a reliable and consistent method to examine the time dependent changes in the gene expression profiles in articular cartilage and subchondral bone. Results Local regulation of matrix degradation markers was demonstrated by a significant increase in mRNA levels of aggrecanase-1 and MMP-13 as early as the first week post-surgery, and expression remained elevated throughout the 10 week study. Immunohistochemistry confirmed MMP-13 expression in differentiated chondrocytes and synovial fibroblasts at week-2 and cells within osteophytes at week-10 in the surgically-modified-joints. Concomitant increases in chondrocyte differentiation markers, Col IIA and Sox 9, and vascular invasion markers, VEGF and CD31, peaked around week-2 to -4, and returned to Sham levels at later time points in both models. Indeed, VEGF-positive cells were found in the deep articular chondrocytes adjacent to subchondral bone. Osteoclastic bone resorption markers, cathepsin K and TRAP, were also elevated at week-2. Confirming bone resorption is an early local event in OA progression, cathepsin K positive osteoclasts were found invading the articular cartilage from the subchondral region at week 2. This was followed by late disease events, including subchondral sclerosis and osteophyte formation, as demonstrated by the upregulation of the osteoanabolic markers runx2 and osterix, toward week-4 to 6 post-surgery. Conclusions In summary, this study demonstrated the temporal and cohesive gene expression changes in articular cartilage and subchondral bone using known markers of

  2. Inhibition of cathepsin K reduces cartilage degeneration in the anterior cruciate ligament transection rabbit and murine models of osteoarthritis.

    Science.gov (United States)

    Hayami, Tadashi; Zhuo, Ya; Wesolowski, Gregg A; Pickarski, Maureen; Duong, Le T

    2012-06-01

    To investigate the disease modifying effects of cathepsin K (CatK) inhibitor L-006235 compared to alendronate (ALN) in two preclinical models of osteoarthritis (OA). Skeletally mature rabbits underwent sham or anterior cruciate ligament transection (ACLT)-surgery and were treated with L-006235 (L-235, 10 mg/kg or 50 mg/kg, p.o., daily) or ALN (0.6 mg/kg, s.c., weekly) for 8-weeks. ACLT joint instability was also induced in CatK(-/-) versus wild type (wt) mice and treated for 16-weeks. Changes in cartilage degeneration, subchondral bone volume and osteophyte area were determined by histology and μ-CT. Collagen type I helical peptide (HP-I), a bone resorption marker and collagen type II C-telopeptide (CTX-II), a cartilage degradation marker were measured. L-235 (50 mg/kg) and ALN treatment resulted in significant chondroprotective effects, reducing CTX-II by 60% and the histological Mankin score for cartilage damage by 46% in the ACLT-rabbits. Both doses of L-235 were more potent than ALN in protecting against focal subchondral bone loss, and reducing HP-I by 70% compared to vehicle. L-235 (50 mg/kg) and ALN significantly reduced osteophyte formation in histomorphometric analysis by 55%. The Mankin score in ACLT-CatK(-/-) mice was ~2.5-fold lower than the ACLT-wt mice and was not different from sham-CatK(-/-). Osteophyte development was not different among the groups. Inhibition of CatK provides significant benefits in ACLT-model of OA, including: 1) protection of subchondral bone integrity, 2) protection against cartilage degradation and 3) reduced osteophytosis. Preclinical evidence supports the role of CatK as a potential therapeutic target for the treatment of OA. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Excessive activity of cathepsin K is associated with cartilage defects in a zebrafish model of mucolipidosis II

    Directory of Open Access Journals (Sweden)

    Aaron C. Petrey

    2012-03-01

    The severe pediatric disorder mucolipidosis II (ML-II; also known as I-cell disease is caused by defects in mannose 6-phosphate (Man-6-P biosynthesis. Patients with ML-II exhibit multiple developmental defects, including skeletal, craniofacial and joint abnormalities. To date, the molecular mechanisms that underlie these clinical manifestations are poorly understood. Taking advantage of a zebrafish model of ML-II, we previously showed that the cartilage morphogenesis defects in this model are associated with altered chondrocyte differentiation and excessive deposition of type II collagen, indicating that aspects of development that rely on proper extracellular matrix homeostasis are sensitive to decreases in Man-6-P biosynthesis. To further investigate the molecular bases for the cartilage phenotypes, we analyzed the transcript abundance of several genes in chondrocyte-enriched cell populations isolated from wild-type and ML-II zebrafish embryos. Increased levels of cathepsin and matrix metalloproteinase (MMP transcripts were noted in ML-II cell populations. This increase in transcript abundance corresponded with elevated and sustained activity of several cathepsins (K, L and S and MMP-13 during early development. Unlike MMP-13, for which higher levels of protein were detected, the sustained activity of cathepsin K at later stages seemed to result from its abnormal processing and activation. Inhibition of cathepsin K activity by pharmacological or genetic means not only reduced the activity of this enzyme but led to a broad reduction in additional protease activity, significant correction of the cartilage morphogenesis phenotype and reduced type II collagen staining in ML-II embryos. Our findings suggest a central role for excessive cathepsin K activity in the developmental aspects of ML-II cartilage pathogenesis and highlight the utility of the zebrafish system to address the biochemical underpinnings of metabolic disease.

  4. URGAP: A gap conductance model for transient conditions

    International Nuclear Information System (INIS)

    Lassmann, K.; Pazdera, F.

    1983-01-01

    A gap conductance model, URGAP, has been developed with contributions from solid, fluid and radiation heat transfer components. Model parameters are easily available, independent of different combinations of material surfaces. The model parameters were fitted to 388 data points under reactor conditions. For model verification, another 274 data points of steel-steel and aluminium-aluminium interfaces, respectively, were used. For minor surface roughnesses normally prevailing in reactor fuel elements the model asymptotically yields Ross' and Stoute's model for the open gap, which is thus confirmed. Materials data were carefully checked over a wide range of temperatures. Special attention was paid to the contact term for high temperatures. Thus, the model can be applied to transients. The URGAP model is being used successfully in several codes (e.g. URANUS, SSYST). (author)

  5. Effect of distraction arthroplasty on osteoarthritic goat models of the articular cartilage

    Directory of Open Access Journals (Sweden)

    Rizky N.H. Putro

    2013-05-01

    Full Text Available Background: Osteoarthritis (OA is the most common knee degenerative disease, the number of OA patients increases along with the increase of life expectancy. Distraction arthroplasty is a less invasive alternatif for OA management by releaving mechanical stress while maintaining intermitten joint fluid pressure changes, thus halting the OA destructive cycle and inducing repair. This study aims to evaluate the anatomical and histopathological changes after distraction arthroplasty on osteoarthritic animal models.Methods: The study was performed on 32 goat stiffle joint (16 goats with mechanically induced OA by lateral meniscectomy. During the study 6 goats were decreased. Distraction arthroplasty was performed using external fixation on 10 knees for 4 weeks, and the contralateral knees left untreated. The knees were anatomically and histopathologically examined using International Cartilage Repair Society (ICRS staging and Osteoarthritis Research Society International (OARSI scoring. The differences of the anatomical and histopathological changes are tested for significance using the Wilcoxon test.Results: There was anatomical and histopathological worsening of the OA on treated knees. The anatomical difference assessed using ICRS stage gave median values of 1.5 and 2.5 respectively (p < 0.002. The histopathological difference assessed using OARSI scoring was significant (6 vs 10; p < 0.002.Conclusion: Distraction arthroplasty in OA goat models in this study, worsens the OA instead of inducing repair. Further studies are required to find out a convincing biological basis of distraction arthroplasty as an alternative treatment for OA. (Med J Indones. 2013;22:64-9Keywords: Animal model, distraction arthroplasty, osteoarthritis

  6. Gap probability - Measurements and models of a pecan orchard

    Science.gov (United States)

    Strahler, Alan H.; Li, Xiaowen; Moody, Aaron; Liu, YI

    1992-01-01

    Measurements and models are compared for gap probability in a pecan orchard. Measurements are based on panoramic photographs of 50* by 135 view angle made under the canopy looking upwards at regular positions along transects between orchard trees. The gap probability model is driven by geometric parameters at two levels-crown and leaf. Crown level parameters include the shape of the crown envelope and spacing of crowns; leaf level parameters include leaf size and shape, leaf area index, and leaf angle, all as functions of canopy position.

  7. Computational fluid dynamics modeling of momentum transport in rotating wall perfused bioreactor for cartilage tissue engineering.

    Science.gov (United States)

    Cinbiz, Mahmut N; Tığli, R Seda; Beşkardeş, Işil Gerçek; Gümüşderelioğlu, Menemşe; Colak, Uner

    2010-11-01

    In this study, computational fluid dynamics (CFD) analysis of a rotating-wall perfused-vessel (RWPV) bioreactor is performed to characterize the complex hydrodynamic environment for the simulation of cartilage development in RWPV bioreactor in the presence of tissue-engineered cartilage constructs, i.e., cell-chitosan scaffolds. Shear stress exerted on chitosan scaffolds in bioreactor was calculated for different rotational velocities in the range of 33-38 rpm. According to the calculations, the lateral and lower surfaces were exposed to 0.07926-0.11069 dyne/cm(2) and 0.05974-0.08345 dyne/cm(2), respectively, while upper surfaces of constructs were exposed to 0.09196-0.12847 dyne/cm(2). Results validate adequate hydrodynamic environment for scaffolds in RWPV bioreactor for cartilage tissue development which concludes the suitability of operational conditions of RWPV bioreactor. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Cartilage Protective and Chondrogenic Capacity of WIN-34B, a New Herbal Agent, in the Collagenase-Induced Osteoarthritis Rabbit Model and in Progenitor Cells from Subchondral Bone

    Directory of Open Access Journals (Sweden)

    Jeong-Eun Huh

    2013-01-01

    Full Text Available We sought to determine the cartilage repair capacity of WIN-34B in the collagenase-induced osteoarthritis rabbit model and in progenitor cells from subchondral bone. The cartilage protective effect of WIN-34B was measured by clinical and histological scores, cartilage area, and proteoglycan and collagen contents in the collagenase-induced osteoarthritis rabbit model. The efficacy of chondrogenic differentiation of WIN-34B was assessed by expression of CD105, CD73, type II collagen, and aggrecan in vivo and was analyzed by the surface markers of progenitor cells, the mRNA levels of chondrogenic marker genes, and the level of proteoglycan, GAG, and type II collagen in vitro. Oral administration of WIN-34B significantly increased cartilage area, and this was associated with the recovery of proteoglycan and collagen content. Moreover, WIN-34B at 200 mg/kg significantly increased the expression of CD105, CD73, type II collagen, and aggrecan compared to the vehicle group. WIN-34B markedly enhanced the chondrogenic differentiation of CD105 and type II collagen in the progenitor cells from subchondral bone. Also, we confirmed that treatment with WIN-34B strongly increased the number of SH-2(CD105 cells and expression type II collagen in subchondral progenitor cells. Moreover, WIN-34B significantly increased proteoglycan, as measured by alcian blue staining; the mRNA level of type II α1 collagen, cartilage link protein, and aggrecan; and the inhibition of cartilage matrix molecules, such as GAG and type II collagen, in IL-1β-treated progenitor cells. These findings suggest that WIN-34B could be a potential candidate for effective anti-osteoarthritic therapy with cartilage repair as well as cartilage protection via enhancement of chondrogenic differentiation in the collagenase-induced osteoarthritis rabbit model and progenitor cells from subchondral bone.

  9. Optimizing a gap conductance model applicable to VVER-1000 thermal–hydraulic model

    International Nuclear Information System (INIS)

    Rahgoshay, M.; Hashemi-Tilehnoee, M.

    2012-01-01

    Highlights: ► Two known conductance models for application in VVER-1000 thermal–hydraulic code are examined. ► An optimized gap conductance model is developed which can predict the gap conductance in good agreement with FSAR data. ► The licensed thermal–hydraulic code is coupled with the gap conductance model predictor externally. -- Abstract: The modeling of gap conductance for application in VVER-1000 thermal–hydraulic codes is addressed. Two known models, namely CALZA-BINI and RELAP5 gap conductance models, are examined. By externally linking of gap conductance models and COBRA-EN thermal hydraulic code, the acceptable range of each model is specified. The result of each gap conductance model versus linear heat rate has been compared with FSAR data. A linear heat rate of about 9 kW/m is the boundary for optimization process. Since each gap conductance model has its advantages and limitation, the optimized gap conductance model can predict the gap conductance better than each of the two other models individually.

  10. Sequence-based model of gap gene regulatory network.

    Science.gov (United States)

    Kozlov, Konstantin; Gursky, Vitaly; Kulakovskiy, Ivan; Samsonova, Maria

    2014-01-01

    The detailed analysis of transcriptional regulation is crucially important for understanding biological processes. The gap gene network in Drosophila attracts large interest among researches studying mechanisms of transcriptional regulation. It implements the most upstream regulatory layer of the segmentation gene network. The knowledge of molecular mechanisms involved in gap gene regulation is far less complete than that of genetics of the system. Mathematical modeling goes beyond insights gained by genetics and molecular approaches. It allows us to reconstruct wild-type gene expression patterns in silico, infer underlying regulatory mechanism and prove its sufficiency. We developed a new model that provides a dynamical description of gap gene regulatory systems, using detailed DNA-based information, as well as spatial transcription factor concentration data at varying time points. We showed that this model correctly reproduces gap gene expression patterns in wild type embryos and is able to predict gap expression patterns in Kr mutants and four reporter constructs. We used four-fold cross validation test and fitting to random dataset to validate the model and proof its sufficiency in data description. The identifiability analysis showed that most model parameters are well identifiable. We reconstructed the gap gene network topology and studied the impact of individual transcription factor binding sites on the model output. We measured this impact by calculating the site regulatory weight as a normalized difference between the residual sum of squares error for the set of all annotated sites and for the set with the site of interest excluded. The reconstructed topology of the gap gene network is in agreement with previous modeling results and data from literature. We showed that 1) the regulatory weights of transcription factor binding sites show very weak correlation with their PWM score; 2) sites with low regulatory weight are important for the model output; 3

  11. Cartilage Repair Using Composites of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells and Hyaluronic Acid Hydrogel in a Minipig Model.

    Science.gov (United States)

    Ha, Chul-Won; Park, Yong-Beom; Chung, Jun-Young; Park, Yong-Geun

    2015-09-01

    The cartilage regeneration potential of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) with a hyaluronic acid (HA) hydrogel composite has shown remarkable results in rat and rabbit models. The purpose of the present study was to confirm the consistent regenerative potential in a pig model using three different cell lines. A full-thickness chondral injury was intentionally created in the trochlear groove of each knee in 6 minipigs. Three weeks later, an osteochondral defect, 5 mm wide by 10 mm deep, was created, followed by an 8-mm-wide and 5-mm-deep reaming. A mixture (1.5 ml) of hUCB-MSCs (0.5×10(7) cells per milliliter) and 4% HA hydrogel composite was then transplanted into the defect on the right knee. Each cell line was used in two minipigs. The osteochondral defect created in the same manner on the left knee was untreated to act as the control. At 12 weeks postoperatively, the pigs were sacrificed, and the degree of subsequent cartilage regeneration was evaluated by gross and histological analysis. The transplanted knee resulted in superior and more complete hyaline cartilage regeneration compared with the control knee. The cellular characteristics (e.g., cellular proliferation and chondrogenic differentiation capacity) of the hUCB-MSCs influenced the degree of cartilage regeneration potential. This evidence of consistent cartilage regeneration using composites of hUCB-MSCs and HA hydrogel in a large animal model could be a stepping stone to a human clinical trial in the future. To date, several studies have investigated the chondrogenic potential of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs); however, the preclinical studies are still limited in numbers with various results. In parallel, in the past several years, the cartilage regeneration potential of hUCB-MSCs with a hyaluronic acid (HA) hydrogel composite have been investigated and remarkable results in rat and rabbit models have been attained. (These

  12. Evaluation of Cost Models and Needs & Gaps Analysis

    DEFF Research Database (Denmark)

    Kejser, Ulla Bøgvad

    2014-01-01

    they breakdown costs. This is followed by an in depth analysis of stakeholders’ needs for financial information derived from the 4C project stakeholder consultation.The stakeholders’ needs analysis indicated that models should:• support accounting, but more importantly they should enable budgeting• be able......his report ’D3.1—Evaluation of Cost Models and Needs & Gaps Analysis’ provides an analysis of existing research related to the economics of digital curation and cost & benefit modelling. It reports upon the investigation of how well current models and tools meet stakeholders’ needs for calculating...... andcomparing financial information. Based on this evaluation, it aims to point out gaps that need to be bridged in order to increase the uptake of cost & benefit modelling and good practices that will enable costing and comparison of the costs of alternative scenarios—which in turn provides a starting point...

  13. On the problem of model reduction in the gap metric

    NARCIS (Netherlands)

    Mutsaers, M.E.C.; Weiland, S.

    2010-01-01

    This paper deals with the model reduction problem where, for a given linear time-invariant dynamical system of complexity n, a simpler system of complexity r gap between their respective behaviors is minimized. We describe dynamical systems as closed, shift invariant

  14. Ex vivo model unravelling cell distribution effect in hydrogels for cartilage repair

    NARCIS (Netherlands)

    Mouser, Vivian H M; Dautzenberg, Noël M M; Levato, Riccardo; van Rijen, Mattie H P; Dhert, Wouter J A; Malda, Jos; Gawlitta, Debby

    2018-01-01

    The implantation of chondrocyte-laden hydrogels is a promising cartilage repair strategy. Chondrocytes can be spatially positioned in hydrogels and thus in defects, while current clinical cell-therapies introduce chondrocytes in the defect depth. The main aim of this study was to evaluate the effect

  15. High throughput proteomic analysis of the secretome in an explant model of articular cartilage inflammation

    Science.gov (United States)

    Clutterbuck, Abigail L.; Smith, Julia R.; Allaway, David; Harris, Pat; Liddell, Susan; Mobasheri, Ali

    2011-01-01

    This study employed a targeted high-throughput proteomic approach to identify the major proteins present in the secretome of articular cartilage. Explants from equine metacarpophalangeal joints were incubated alone or with interleukin-1beta (IL-1β, 10 ng/ml), with or without carprofen, a non-steroidal anti-inflammatory drug, for six days. After tryptic digestion of culture medium supernatants, resulting peptides were separated by HPLC and detected in a Bruker amaZon ion trap instrument. The five most abundant peptides in each MS scan were fragmented and the fragmentation patterns compared to mammalian entries in the Swiss-Prot database, using the Mascot search engine. Tryptic peptides originating from aggrecan core protein, cartilage oligomeric matrix protein (COMP), fibronectin, fibromodulin, thrombospondin-1 (TSP-1), clusterin (CLU), cartilage intermediate layer protein-1 (CILP-1), chondroadherin (CHAD) and matrix metalloproteinases MMP-1 and MMP-3 were detected. Quantitative western blotting confirmed the presence of CILP-1, CLU, MMP-1, MMP-3 and TSP-1. Treatment with IL-1β increased MMP-1, MMP-3 and TSP-1 and decreased the CLU precursor but did not affect CILP-1 and CLU levels. Many of the proteins identified have well-established extracellular matrix functions and are involved in early repair/stress responses in cartilage. This high throughput approach may be used to study the changes that occur in the early stages of osteoarthritis. PMID:21354348

  16. Transglutaminase-2 differently regulates cartilage destruction and osteophyte formation in a surgical model of osteoarthritis.

    Science.gov (United States)

    Orlandi, A; Oliva, F; Taurisano, G; Candi, E; Di Lascio, A; Melino, G; Spagnoli, L G; Tarantino, U

    2009-04-01

    Osteoarthritis is a progressive joint disease characterized by cartilage degradation and bone remodeling. Transglutaminases catalyze a calcium-dependent transamidation reaction that produces covalent cross-linking of available substrate glutamine residues and modifies the extracellular matrix. Increased transglutaminases-mediated activity is reported in osteoarthritis, but the relative contribution of transglutaminases-2 (TG2) is uncertain. We describe TG2 expression in human femoral osteoarthritis and in wild-type and homozygous TG2 knockout mice after surgically-induced knee joint instability. Increased TG2 levels were observed in human and wild-type murine osteoarthritic cartilage compared to the respective controls. Histomorphometrical but not X-ray investigation documented in osteoarthritic TG2 knockout mice reduced cartilage destruction and an increased osteophyte formation compared to wild-type mice. These differences were associated with increased TGFbeta-1 expression. In addition to confirming its important role in osteoarthritis development, our results demonstrated that TG2 expression differently influences cartilage destruction and bone remodeling, suggesting new targeted TG2-related therapeutic strategies.

  17. Modulation of Cartilage Degradation Biomarkers Reflect the Activation and Inhibition of Pro-Inflammatory Cytokine Signaling in an Ex Vivo Model of Bovine Cartilage

    DEFF Research Database (Denmark)

    Kjelgaard-Petersen, Cecilie Freja; Sharma, Neha; Kayed, Ashref

    2017-01-01

    -inflammatory treatments for inflammatory arthritis. The aim of this study was to investigate the effect of small molecule inhibitors targeting 4 main pro-inflammatory signaling pathways (p38, Syk, IκBα, and STAT) on Oncostatin M (OSM) and Tumor Necrosis Factor α (TNFα) stimulated cartilage....

  18. Gap junction modulation by extracellular signaling molecules: the thymus model

    Directory of Open Access Journals (Sweden)

    Alves L.A.

    2000-01-01

    Full Text Available Gap junctions are intercellular channels which connect adjacent cells and allow direct exchange of molecules of low molecular weight between them. Such a communication has been described as fundamental in many systems due to its importance in coordination, proliferation and differentiation. Recently, it has been shown that gap junctional intercellular communication (GJIC can be modulated by several extracellular soluble factors such as classical hormones, neurotransmitters, interleukins, growth factors and some paracrine substances. Herein, we discuss some aspects of the general modulation of GJIC by extracellular messenger molecules and more particularly the regulation of such communication in the thymus gland. Additionally, we discuss recent data concerning the study of different neuropeptides and hormones in the modulation of GJIC in thymic epithelial cells. We also suggest that the thymus may be viewed as a model to study the modulation of gap junction communication by different extracellular messengers involved in non-classical circuits, since this organ is under bidirectional neuroimmunoendocrine control.

  19. Oral administration of undenatured native chicken type II collagen (UC-II) diminished deterioration of articular cartilage in a rat model of osteoarthritis (OA).

    Science.gov (United States)

    Bagi, C M; Berryman, E R; Teo, S; Lane, N E

    2017-12-01

    The aim of this study was to determine the ability of undenatured native chicken type II collagen (UC-II) to prevent excessive articular cartilage deterioration in a rat model of osteoarthritis (OA). Twenty male rats were subjected to partial medial meniscectomy tear (PMMT) surgery to induce OA. Immediately after the surgery 10 rats received vehicle and another 10 rats oral daily dose of UC-II at 0.66 mg/kg for a period of 8 weeks. In addition 10 naïve rats were used as an intact control and another 10 rats received sham surgery. Study endpoints included a weight-bearing capacity of front and hind legs, serum biomarkers of bone and cartilage metabolism, analyses of subchondral and cancellous bone at the tibial epiphysis and metaphysis, and cartilage pathology at the medial tibial plateau using histological methods. PMMT surgery produced moderate OA at the medial tibial plateau. Specifically, the deterioration of articular cartilage negatively impacted the weight bearing capacity of the operated limb. Immediate treatment with the UC-II preserved the weight-bearing capacity of the injured leg, preserved integrity of the cancellous bone at tibial metaphysis and limited the excessive osteophyte formation and deterioration of articular cartilage. Study results demonstrate that a clinically relevant daily dose of UC-II when applied immediately after injury can improve the mechanical function of the injured knee and prevent excessive deterioration of articular cartilage. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  20. Pairing gaps from nuclear mean-field models

    International Nuclear Information System (INIS)

    Bender, M.; Rutz, K.; Maruhn, J.A.

    2000-01-01

    We discuss the pairing gap, a measure for nuclear pairing correlations, in chains of spherical, semi-magic nuclei in the framework of self-consistent nuclear mean-field models. The equations for the conventional BCS model and the approximate projection-before-variation Lipkin-Nogami method are formulated in terms of local density functionals for the effective interaction. We calculate the Lipkin-Nogami corrections of both the mean-field energy and the pairing energy. Various definitions of the pairing gap are discussed as three-point, four-point and five-point mass-difference formulae, averaged matrix elements of the pairing potential, and single-quasiparticle energies. Experimental values for the pairing gap are compared with calculations employing both a delta pairing force and a density-dependent delta interaction in the BCS and Lipkin-Nogami model. Odd-mass nuclei are calculated in the spherical blocking approximation which neglects part of the the core polarization in the odd nucleus. We find that the five-point mass difference formula gives a very robust description of the odd-even staggering, other approximations for the gap may differ from that up to 30% for certain nuclei. (orig.)

  1. Determination of the mechanical and physical properties of cartilage by coupling poroelastic-based finite element models of indentation with artificial neural networks.

    Science.gov (United States)

    Arbabi, Vahid; Pouran, Behdad; Campoli, Gianni; Weinans, Harrie; Zadpoor, Amir A

    2016-03-21

    One of the most widely used techniques to determine the mechanical properties of cartilage is based on indentation tests and interpretation of the obtained force-time or displacement-time data. In the current computational approaches, one needs to simulate the indentation test with finite element models and use an optimization algorithm to estimate the mechanical properties of cartilage. The modeling procedure is cumbersome, and the simulations need to be repeated for every new experiment. For the first time, we propose a method for fast and accurate estimation of the mechanical and physical properties of cartilage as a poroelastic material with the aid of artificial neural networks. In our study, we used finite element models to simulate the indentation for poroelastic materials with wide combinations of mechanical and physical properties. The obtained force-time curves are then divided into three parts: the first two parts of the data is used for training and validation of an artificial neural network, while the third part is used for testing the trained network. The trained neural network receives the force-time curves as the input and provides the properties of cartilage as the output. We observed that the trained network could accurately predict the properties of cartilage within the range of properties for which it was trained. The mechanical and physical properties of cartilage could therefore be estimated very fast, since no additional finite element modeling is required once the neural network is trained. The robustness of the trained artificial neural network in determining the properties of cartilage based on noisy force-time data was assessed by introducing noise to the simulated force-time data. We found that the training procedure could be optimized so as to maximize the robustness of the neural network against noisy force-time data. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Study of gap conductance model for thermo mechanical fully coupled finite element model

    International Nuclear Information System (INIS)

    Kim, Hyo Cha; Yang, Yong Sik; Kim, Dae Ho; Bang, Je Geon; Kim, Sun Ki; Koo, Yang Hyun

    2012-01-01

    A light water reactor (LWR) fuel rod consists of zirconium alloy cladding and uranium dioxide pellets, with a slight gap between them. Therefore, the mechanical integrity of zirconium alloy cladding is the most critical issue, as it is an important barrier for fission products released into the environment. To evaluate the stress and strain of the cladding during operation, fuel performance codes with a one-dimensional (1D) approach have been reported since the 1970s. However, it is difficult for a 1D model to simulate the stress and strain of the cladding accurately owing to a lack of degree of freedom. A LWR fuel performance code should include thermo-mechanical coupled model owing to the existence of the fuel-cladding gap. Generally, the gap that is filled with helium gas results in temperature drop along radius direction. The gap conductance that determines temperature gradient within the gap is very sensitive to gap thickness. For instance, once the gap size increases up to several microns in certain region, difference of surface temperatures increases up to 100 Kelvin. Therefore, iterative thermo-mechanical coupled analysis is required to solve temperature distribution throughout pellet and cladding. Consequently, the Finite Element (FE) module, which can simulate a higher degree of freedom numerically, is an indispensable requirement to understand the thermomechanical behavior of cladding. FRAPCON-3, which is reliable performance code, has iterative loop for thermo-mechanical coupled calculation to solve 1D gap conductance model. In FEMAXI-III, 1D thermal analysis module and FE module for stress-strain analysis were separated. 1D thermal module includes iterative analysis between them. DIONISIO code focused on thermal contact model as function of surface roughness and contact pressure when the gap is closed. In previous works, gap conductance model has been developed only for 1D model or hybrid model (1D and FE). To simulate temperature, stress and strain

  3. Application of a Three-Dimensional Poroelastic BEM to Modeling the Biphasic Mechanics of Cell-Matrix Interactions in Articular Cartilage (REVISION).

    Science.gov (United States)

    Haider, Mansoor A; Guilak, Farshid

    2007-06-15

    Articular cartilage exhibits viscoelasticity in response to mechanical loading that is well described using biphasic or poroelastic continuum models. To date, boundary element methods (BEMs) have not been employed in modeling biphasic tissue mechanics. A three dimensional direct poroelastic BEM, formulated in the Laplace transform domain, is applied to modeling stress relaxation in cartilage. Macroscopic stress relaxation of a poroelastic cylinder in uni-axial confined compression is simulated and validated against a theoretical solution. Microscopic cell deformation due to poroelastic stress relaxation is also modeled. An extended Laplace inversion method is employed to accurately represent mechanical responses in the time domain.

  4. Systematized water content calculation in cartilage using T1-mapping MR estimations: design and validation of a mathematical model.

    Science.gov (United States)

    Shiguetomi-Medina, J M; Ramirez-Gl, J L; Stødkilde-Jørgensen, H; Møller-Madsen, B

    2017-09-01

    Up to 80 % of cartilage is water; the rest is collagen fibers and proteoglycans. Magnetic resonance (MR) T1-weighted measurements can be employed to calculate the water content of a tissue using T1 mapping. In this study, a method that translates T1 values into water content data was tested statistically. To develop a predictive equation, T1 values were obtained for tissue-mimicking gelatin samples. 1.5 T MRI was performed using inverse angle phase and an inverse sequence at 37 (±0.5) °C. Regions of interest were manually delineated and the mean T1 value was estimated in arbitrary units. Data were collected and modeled using linear regression. To validate the method, articular cartilage from six healthy pigs was used. The experiment was conducted in accordance with the Danish Animal Experiment Committee. Double measurements were performed for each animal. Ex vivo, all water in the tissue was extracted by lyophilization, thus allowing the volume of water to be measured. This was then compared with the predicted water content via Lin's concordance correlation coefficient at the 95 % confidence level. The mathematical model was highly significant when compared to a null model (p < 0.0001). 97.3 % of the variation in water content can be explained by absolute T1 values. Percentage water content could be predicted as 0.476 + (T1 value) × 0.000193 × 100 %. We found that there was 98 % concordance between the actual and predicted water contents. The results of this study demonstrate that MR data can be used to predict percentage water contents of cartilage samples. 3 (case-control study).

  5. Development of heat transfer models for gap cooling

    Energy Technology Data Exchange (ETDEWEB)

    Kohriyama, Tamio; Murase, Michio; Tamaki, Tomohiko [Institute of Nuclear Safety System Inc., Mihama, Fukui (Japan)

    2001-09-01

    In a severe accident of a light water reactor (LWR), heat transfer models in a narrow annular gap between superheated core debris and a reactor pressure vessel (RPV) are important to evaluate the integrity of RPV and emergency procedures. This paper discusses the effects of superheat on the heat flux based on existing data. In low superheat conditions, the heat flux in the narrow gap is higher than the heat flux in pool nucleate boiling due to restricted flow area. It approaches the nucleate boiling heat flux as superheat increasing and reaches a critical value subject to the counter-current flow limiting (CCFL) at the top end of the gap. A heat transfer correlation was derived as a function of dimensionless superheat and a Kutateladze-type CCFL correlation was deduced for critical heat flux (CHF) restricted by CCFL, which gave good prediction for a wide range of the CHF data. Effect of an angle of inclination of the gap could also be incorporated in the CCFL correlation. In high superheat conditions, the heat flux in the narrow gap maintains a similar shape to the pool boiling curve but shifts the position to a higher superheated side than the pool boiling except film boiling, which could be expressed by the typical pool film boiling correlation. Incorporating quench test data, the heat flux correlation was derived as a function of dimensionless superheat using the same formula for the low superheat and the Kutateladze-type CCFL correlation was deduced for CHF. The CHF at the high superheat was 3-4 times as large as CHF at the low superheat and this difference was well predicted by different flow patterns in the gap and the balance of pressure gradients between gas and liquid phases. (author)

  6. Mechanics of Fluid-Filled Interstitial Gaps. I. Modeling Gaps in a Compact Tissue.

    Science.gov (United States)

    Parent, Serge E; Barua, Debanjan; Winklbauer, Rudolf

    2017-08-22

    Fluid-filled interstitial gaps are a common feature of compact tissues held together by cell-cell adhesion. Although such gaps can in principle be the result of weak, incomplete cell attachment, adhesion is usually too strong for this to occur. Using a mechanical model of tissue cohesion, we show that, instead, a combination of local prevention of cell adhesion at three-cell junctions by fluidlike extracellular material and a reduction of cortical tension at the gap surface are sufficient to generate stable gaps. The size and shape of these interstitial gaps depends on the mechanical tensions between cells and at gap surfaces, and on the difference between intracellular and interstitial pressures that is related to the volume of the interstitial fluid. As a consequence of the dependence on tension/tension ratios, the presence of gaps does not depend on the absolute strength of cell adhesion, and similar gaps are predicted to occur in tissues of widely differing cohesion. Tissue mechanical parameters can also vary within and between cells of a given tissue, generating asymmetrical gaps. Within limits, these can be approximated by symmetrical gaps. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  7. Autologous Bone Marrow Concentrate in a Sheep Model of Osteoarthritis: New Perspectives for Cartilage and Meniscus Repair.

    Science.gov (United States)

    Desando, Giovanna; Giavaresi, Gianluca; Cavallo, Carola; Bartolotti, Isabella; Sartoni, Federica; Nicoli Aldini, Nicolò; Martini, Lucia; Parrilli, Annapaola; Mariani, Erminia; Fini, Milena; Grigolo, Brunella

    2016-06-01

    Cell-based therapies are becoming a valuable tool to treat osteoarthritis (OA). This study investigated and compared the regenerative potential of bone marrow concentrate (BMC) and mesenchymal stem cells (MSC), both engineered with Hyaff(®)-11 (HA) for OA treatment in a sheep model. OA was induced via unilateral medial meniscectomy. Bone marrow was aspirated from the iliac crest, followed by concentration processes or cell isolation and expansion to obtain BMC and MSC, respectively. Treatments consisted of autologous BMC and MSC seeded onto HA. The regenerative potential of bone, cartilage, menisci, and synovia was monitored using macroscopy, histology, immunohistochemistry, and micro-computed tomography at 12 weeks post-op. Data were analyzed using the general linear model with adjusted Sidak's multiple comparison and Spearman's tests. BMC-HA treatment showed a greater repair ability in inhibiting OA progression compared to MSC-HA, leading to a reduction of inflammation in cartilage, meniscus, and synovium. Indeed, the decrease of inflammation positively contributed to counteract the progression of fibrotic and hypertrophic processes, known to be involved in tissue failure. Moreover, the treatment with BMC-HA showed the best results in allowing meniscus regeneration. Minor healing effects were noticed at bone level for both cell strategies; however, a downregulation of subchondral bone thickness (Cs.Th) was found in both cell treatments compared to the OA group in the femur. The transplantation of BMC-HA provided the best effects in supporting regenerative processes in cartilage, meniscus, and synovium and at less extent in bone. On the whole, both MSC and BMC combined with HA reduced inflammation and contributed to switch off fibrotic and hypertrophic processes. The observed regenerative potential by BMC-HA on meniscus could open new perspectives, suggesting its use not only for OA care but also for the treatment of meniscal lesions, even if further analyses are

  8. Validation of heat transfer models for gap cooling

    International Nuclear Information System (INIS)

    Okano, Yukimitsu; Nagae, Takashi; Murase, Michio

    2004-01-01

    For severe accident assessment of a light water reactor, models of heat transfer in a narrow annular gap between overheated core debris and a reactor pressure vessel are important for evaluating vessel integrity and accident management. The authors developed and improved the models of heat transfer. However, validation was not sufficient for applicability of the gap heat flux correlation to the debris cooling in the vessel lower head and applicability of the local boiling heat flux correlations to the high-pressure conditions. Therefore, in this paper, we evaluated the validity of the heat transfer models and correlations by analyses for ALPHA and LAVA experiments where molten aluminum oxide (Al 2 O 3 ) at about 2700 K was poured into the high pressure water pool in a small-scale simulated vessel lower head. In the heating process of the vessel wall, the calculated heating rate and peak temperature agreed well with the measured values, and the validity of the heat transfer models and gap heat flux correlation was confirmed. In the cooling process of the vessel wall, the calculated cooling rate was compared with the measured value, and the validity of the nucleate boiling heat flux correlation was confirmed. The peak temperatures of the vessel wall in ALPHA and LAVA experiments were lower than the temperature at the minimum heat flux point between film boiling and transition boiling, so the minimum heat flux correlation could not be validated. (author)

  9. A Three-Component Model for Magnetization Transfer. Solution by Projection-Operator Technique, and Application to Cartilage

    Science.gov (United States)

    Adler, Ronald S.; Swanson, Scott D.; Yeung, Hong N.

    1996-01-01

    A projection-operator technique is applied to a general three-component model for magnetization transfer, extending our previous two-component model [R. S. Adler and H. N. Yeung,J. Magn. Reson. A104,321 (1993), and H. N. Yeung, R. S. Adler, and S. D. Swanson,J. Magn. Reson. A106,37 (1994)]. The PO technique provides an elegant means of deriving a simple, effective rate equation in which there is natural separation of relaxation and source terms and allows incorporation of Redfield-Provotorov theory without any additional assumptions or restrictive conditions. The PO technique is extended to incorporate more general, multicomponent models. The three-component model is used to fit experimental data from samples of human hyaline cartilage and fibrocartilage. The fits of the three-component model are compared to the fits of the two-component model.

  10. Effects of phototherapy on cartilage structure and inflammatory markers in an experimental model of osteoarthritis

    Science.gov (United States)

    Oliveira, Poliani; Santos, Anderson Amaro; Rodrigues, Tamara; Tim, Carla Roberta; Pinto, Karina Zambone; Magri, Angela Maria Paiva; Fernandes, Kelly Rossetti; Mattiello, Stela M.; Parizotto, Nivaldo Antonio; Anibal, Fernanda Freitas; Rennó, Ana Claudia Muniz

    2013-12-01

    The aim of this study was to evaluate the effects of laser phototherapy on the degenerative modifications on the articular cartilage after the anterior cruciate ligament transection (ACLT) in the knee of rats. Eighty male rats (Wistar) were distributed into four groups: intact control group (IG), injured control group (CG), injured laser treated group at 10 J/cm2 (L10), and injured laser treated group at 50 J/cm2 (L50). Animals were distributed into two subgroups, sacrificed in 5 and 8 weeks postsurgery. The ACLT was used to induce knee osteoarthritis in rats. After 2 weeks postsurgery, laser phototherapy initiated and it was performed for 15 and 30 sessions. The histological findings revealed that laser irradiation, especially at 10 J/cm2, modulated the progression of the degenerative process, showing a better cartilage structure and lower number of condrocytes compared to the other groups. Laser phototherapy was not able to decrease the degenerative process measured by Mankin score and prevent the increase of cartilage thickness related to the degenerative process. Moreover, it did not have any effect in the biomodulation of the expression of markers IL1β, tumor necrosis factor-α, and metalloprotein-13. Furthermore, laser irradiated animals, at 50 J/cm2 showed a lower amount of collagen type 1.

  11. Modeling of the Inductance of a Blumlein Circuit Spark Gap

    International Nuclear Information System (INIS)

    Aboites, V; Rendón, L; Hernández, A I; Valdés, E

    2015-01-01

    In this paper we present an analysis of the time-varying inductance in the spark gap of a Blumlein circuit. We assume several mathematical expressions to describe the inductance and compare theoretical and computational calculations with experimental results. The time-varying inductance is approximated by a constant, a straight line and two parables which differ in their concavity. This is the first time to our knowledge, in which the time-varying ignition inductance of a nitrogen laser is modeled

  12. Pulsar Polar Cap and Slot Gap Models: Confronting Fermi Data

    Science.gov (United States)

    Harding, Alice K.

    2012-01-01

    Rotation-powered pulsars are excellent laboratories for studying particle acceleration as well as fundamental physics of strong gravity, strong magnetic fields and relativity. I will review acceleration and gamma-ray emission from the pulsar polar cap and slot gap. Predictions of these models can be tested with the data set on pulsars collected by the Large Area Telescope on the Fermi Gamma-Ray Telescope over the last four years, using both detailed light curve fitting and population synthesis.

  13. Efficacy of platelet-rich fibrin matrix on viability of diced cartilage grafts in a rabbit model.

    Science.gov (United States)

    Güler, İsmail; Billur, Deniz; Aydin, Sevim; Kocatürk, Sinan

    2015-03-01

    The objective of this study was to compare the viability of cartilage grafts embedded in platelet-rich fibrin matrix (PRFM) wrapped with no material (bare diced cartilage grafts), oxidized methylcellulose (Surgicel), or acellular dermal tissue (AlloDerm). Experimental study. In this study, six New Zealand rabbits were used. Cartilage grafts including perichondrium were excised from each ear and diced into 2-mm-by 2-mm pieces. There were four comparison groups: 1) group A, diced cartilage (not wrapped with any material); 2) group B, diced cartilage wrapped with AlloDerm; 3) group C, diced cartilage grafts wrapped with Surgicel; and 4) group D, diced cartilage wrapped with PRFM. Four cartilage grafts were implanted under the skin at the back of each rabbit. All rabbits were sacrificed at the end of 10 weeks. The cartilages were stained with hematoxylin-eosin, Masson's Trichrome, and Orcein. After that, they were evaluated for the viability of chondrocytes, collagen content, fibrillar structure of matrix, and changes in peripheral tissues. When the viability of chondrocytes, the content of fiber in matrix, and changes in peripheral tissues were compared, the cartilage embedded in the PRFM group was statistically significantly higher than in the other groups (P < 0.05). We concluded that PRFM has significant advantages in ensuring the chondrocyte viability of diced cartilage grafts. It is also biocompatible, with relatively lesser inflammation and fibrosis. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  14. Experimental model to evaluate in vivo and in vitro cartilage MR imaging by means of histological analyses

    International Nuclear Information System (INIS)

    Bittersohl, B.; Mamisch, T.C.; Welsch, G.H.; Stratmann, J.; Forst, R.; Swoboda, B.; Bautz, W.; Rechenberg, B. von; Cavallaro, A.

    2009-01-01

    Objectives: Implementation of an experimental model to compare cartilage MR imaging by means of histological analyses. Material and methods: MRI was obtained from 4 patients expecting total knee replacement at 1.5 and/or 3 T prior surgery. The timeframe between pre-op MRI and knee replacement was within two days. Resected cartilage-bone samples were tagged with Ethi-pins to reproduce the histological cutting course. Pre-operative scanning at 1.5 T included following parameters for fast low angle shot (FLASH: TR/TE/FA = 33 ms/6 ms/30 deg., BW = 110 kHz, 120 mm x 120 mm FOV, 256 x 256 matrix, 0.65 mm slice-thickness) and double echo steady state (DESS: TR/TE/FA = 23.7 ms/6.9 ms/40 deg., BW = 130 kHz, 120 x 120 mm FOV, 256 x 256 matrix, 0.65 mm slice-thickness). At 3 T, scan parameters were: FLASH (TR/TE/FA = 12.2 ms/5.1 ms/10 deg., BW = 130 kHz, 170 x 170 mm FOV, 320 x 320, 0.5 mm slice-thickness) and DESS (TR/TE/FA = 15.6 ms/4.5 ms/25 deg., BW = 200 kHz, 135 mm x 150 mm FOV, 288 x 320 matrix, 0.5 mm slice-thickness). Imaging of the specimens was done the same day at 1.5 T. MRI (Noyes) and histological (Mankin) score scales were correlated using the paired t-test. Sensitivity and specificity for the detection of different grades of cartilage degeneration were assessed. Inter-reader and intra-reader reliability was determined using Kappa analysis. Results: Low correlation (sensitivity, specificity) was found for both sequences in normal to mild Mankin grades. Only moderate to severe changes were diagnosed with higher significance and specificity. The use of higher field-strengths was advantageous for both protocols with sensitivity values ranging from 13.6% to 93.3% (FLASH) and 20.5% to 96.2% (DESS). Kappa values ranged from 0.488 to 0.944. Conclusions: Correlating MR images with continuous histological slices was feasible by using three-dimensional imaging, multi-planar-reformat and marker pins. The capability of diagnosing early cartilage changes with high accuracy

  15. Soya-cerebroside, an extract of Cordyceps militaris, suppresses monocyte migration and prevents cartilage degradation in inflammatory animal models

    Science.gov (United States)

    Liu, Shan-Chi; Chiu, Ching-Peng; Tsai, Chun-Hao; Hung, Chun-Yin; Li, Te-Mao; Wu, Yang-Chang; Tang, Chih-Hsin

    2017-01-01

    Pathophysiological events that modulate the progression of structural changes in osteoarthritis (OA) include the secretion of inflammatory molecules, such as proinflammatory cytokines. Interleukin-1beta (IL-1β) is the prototypical inflammatory cytokine that activates OA synovial cells to release cytokines and chemokines in support of the inflammatory response. The monocyte chemoattractant protein-1 (MCP-1/CCL2) is one of the key chemokines that regulate migration and infiltration of monocytes in response to inflammation. We show in this study that IL-1β-induced MCP-1 expression and monocyte migration in OA synovial fibroblasts (OASFs) is effectively inhibited by soya-cerebroside, an extract of Cordyceps militaris. We found that soya-cerebroside up-regulated of microRNA (miR)-432 expression via inhibiting AMPK and AKT signaling pathways in OASFs. Soya-cerebroside also effectively decreased monocyte infiltration and prevented cartilage degradation in a rat inflammatory model. Our findings are the first to demonstrate that soya-cerebroside inhibits monocyte/macrophage infiltration into synoviocytes, attenuating synovial inflammation and preventing cartilage damage by reducing MCP-1 expression in vitro and in vivo. Taken together, we suggest a novel therapeutic strategy based on the use of soya-cerebroside for the management of OA. PMID:28225075

  16. Effectiveness of photobiomodulation therapy and aerobic exercise training on articular cartilage in an experimental model of osteoarthritis in rats

    Science.gov (United States)

    Assis, Lívia; Tim, Carla; Martignago, Cintia; Gonçalves, Silma Rodrigues; Renno, Ana Claudia Muniz

    2018-02-01

    Osteoarthritis (OA) is the most common disease of the knee joints in adults throughout the world. Photobiomodulation (PBM) and physical exercise have been studied for clinical treatment of OA, even though the effects and action mechanisms have not yet been clarified. The aim of this study was to evaluate the effects of PBM and aerobic exercise (associated or not) on degenerative modifications and inflammatory mediators in articular cartilage using an experimental model of knee OA. Forty male Wistar rats were randomly divided into 4 groups: OA animals without treatment (OAC); OA plus aerobic exercise training (OAT); OA animals plus PBM treatment (OAP); OA plus aerobic exercise training and PBM treatment (OATP). The exercise training (treadmill; 16m/min; 50 min/day) and the PBM treatment started 4 weeks after the surgery, 3 days/week for 8 weeks. The results showed that all treated groups showed a lower degenerative process measured by OARSI system and higher thickness values. Moreover, aerobic exercise and PBM (associated or not) decreased iNOS expression and increased IL-10 expression in OAT and OATL compared to OAC. Furthermore, a lower TGF-β expression was observed in associated therapies. These results suggest that PBM and aerobic exercise training were effective in modulating inflammatory process and preventing cartilage degeneration in knees in OA rats.

  17. Intra-articular TSG-6 delivery from heparin-based microparticles reduces cartilage damage in a rat model of osteoarthritis.

    Science.gov (United States)

    Tellier, Liane E; Treviño, Elda A; Brimeyer, Alexandra L; Reece, David S; Willett, Nick J; Guldberg, Robert E; Temenoff, Johnna S

    2018-05-01

    As a potential treatment for osteoarthritis (OA), we have developed injectable and hydrolytically degradable heparin-based biomaterials with tunable sulfation for the intra-articular delivery of tumor necrosis factor-alpha stimulated gene-6 (TSG-6), a protein known to inhibit plasmin which may degrade extracellular matrix within OA joints. We first assessed the effect of heparin sulfation on TSG-6 anti-plasmin activity and found that while fully sulfated (Hep) and heparin desulfated at only the N position (Hep-N) significantly enhanced TSG-6 bioactivity in vitro, fully desulfated heparin (Hep-) had no effect, indicating that heparin sulfation plays a significant role in modulating TSG-6 bioactivity. Next, TSG-6 loaded, degradable 10 wt% Hep-N microparticles (MPs) were delivered via intra-articular injection into the knee at 1, 7, and 15 days following medial meniscal transection (MMT) injury in a rat model. After 21 days, cartilage thickness, volume, and attenuation were significantly increased with soluble TSG-6, indicating degenerative changes. In contrast, no significant differences were observed with TSG-6 loaded MP treatment, demonstrating that TSG-6 loaded MPs reduced cartilage damage following MMT injury. Ultimately, our results indicate that Hep-N can enhance TSG-6 anti-plasmin activity and that Hep-N-based biomaterials may be an effective method for TSG-6 delivery to treat OA.

  18. A fast quadrature-based numerical method for the continuous spectrum biphasic poroviscoelastic model of articular cartilage.

    Science.gov (United States)

    Stuebner, Michael; Haider, Mansoor A

    2010-06-18

    A new and efficient method for numerical solution of the continuous spectrum biphasic poroviscoelastic (BPVE) model of articular cartilage is presented. Development of the method is based on a composite Gauss-Legendre quadrature approximation of the continuous spectrum relaxation function that leads to an exponential series representation. The separability property of the exponential terms in the series is exploited to develop a numerical scheme that can be reduced to an update rule requiring retention of the strain history at only the previous time step. The cost of the resulting temporal discretization scheme is O(N) for N time steps. Application and calibration of the method is illustrated in the context of a finite difference solution of the one-dimensional confined compression BPVE stress-relaxation problem. Accuracy of the numerical method is demonstrated by comparison to a theoretical Laplace transform solution for a range of viscoelastic relaxation times that are representative of articular cartilage. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  19. Ablation of Perlecan Domain 1 Heparan Sulfate Reduces Progressive Cartilage Degradation, Synovitis, and Osteophyte Size in a Preclinical Model of Posttraumatic Osteoarthritis.

    Science.gov (United States)

    Shu, Cindy C; Jackson, Miriam T; Smith, Margaret M; Smith, Susan M; Penm, Steven; Lord, Megan S; Whitelock, John M; Little, Christopher B; Melrose, James

    2016-04-01

    To investigate the role of the heparan sulfate (HS) proteoglycan perlecan (HSPG-2) in regulating fibroblast growth factor (FGF) activity, bone and joint growth, and the onset and progression of posttraumatic osteoarthritis (OA) in a mouse gene-knockout model. Maturational changes were evaluated histologically in the knees of 3-, 6-, and 12-week-old wild-type (WT) mice and Hspg2(Δ3-/Δ3-) mice (Hspg2 lacking domain 1 HS, generated by ablation of exon 3 of perlecan). Cartilage damage, subchondral bone sclerosis, osteophytosis, and synovial inflammation were scored at 4 and 8 weeks after surgical induction of OA in WT and Hspg2(Δ3-/Δ3-) mice. Changes in cartilage expression of FGF-2, FGF-18, HSPG-2, FGF receptor 1 (FGFR-1), and FGFR-3 were examined immunohistochemically. Femoral head cartilage from both mouse genotypes was cultured in the presence or absence of interleukin-1α (IL-1α), FGF-2, and FGF-18, and the content and release of glycosaminoglycan (GAG) and expression of messenger RNA (mRNA) for key matrix molecules, enzymes, and inhibitors were quantified. No effect of perlecan HS ablation on growth plate or joint development was detected. After induction of OA, Hspg2(Δ3-/Δ3-) mice had significantly reduced cartilage erosion, osteophytosis, and synovitis. OA-induced loss of chondrocyte expression of FGF-2, FGF-18, and HSPG-2 occurred in both genotypes. Expression of FGFR-1 after OA induction was maintained in WT mice, while FGFR-3 loss after OA induction was significantly reduced in Hspg2(Δ3-/Δ3-) mice. There were no genotypic differences in GAG content or release between unstimulated control cartilage and IL-1α-stimulated cartilage. However, IL-1α-induced cartilage expression of Mmp3 mRNA was significantly reduced in Hspg2(Δ3-/Δ3-) mice. Cartilage GAG release in either the presence or absence of IL-1α was unaltered by FGF-2 in both genotypes. In cartilage cultures with FGF-18, IL-1α-stimulated GAG loss was significantly reduced only in Hspg2(Δ3

  20. In Vivo Tibial Cartilage Strains in Regions of Cartilage-to-Cartilage Contact and Cartilage-to-Meniscus Contact in Response to Walking.

    Science.gov (United States)

    Liu, Betty; Lad, Nimit K; Collins, Amber T; Ganapathy, Pramodh K; Utturkar, Gangadhar M; McNulty, Amy L; Spritzer, Charles E; Moorman, Claude T; Sutter, E Grant; Garrett, William E; DeFrate, Louis E

    2017-10-01

    There are currently limited human in vivo data characterizing the role of the meniscus in load distribution within the tibiofemoral joint. Purpose/Hypothesis: The purpose was to compare the strains experienced in regions of articular cartilage covered by the meniscus to regions of cartilage not covered by the meniscus. It was hypothesized that in response to walking, tibial cartilage covered by the meniscus would experience lower strains than uncovered tibial cartilage. Descriptive laboratory study. Magnetic resonance imaging (MRI) of the knees of 8 healthy volunteers was performed before and after walking on a treadmill. Using MRI-generated 3-dimensional models of the tibia, cartilage, and menisci, cartilage thickness was measured in 4 different regions based on meniscal coverage and compartment: covered medial, uncovered medial, covered lateral, and uncovered lateral. Strain was defined as the normalized change in cartilage thickness before and after activity. Within each compartment, covered cartilage before activity was significantly thinner than uncovered cartilage before activity ( P meniscus experiences lower strains than uncovered cartilage in the medial compartment. These findings provide important baseline information on the relationship between in vivo tibial compressive strain responses and meniscal coverage, which is critical to understanding normal meniscal function.

  1. Injectable perlecan domain 1-hyaluronan microgels potentiate the cartilage repair effect of BMP2 in a murine model of early osteoarthritis

    International Nuclear Information System (INIS)

    Srinivasan, Padma P; McCoy, Sarah Y; Yang Weidong; Farach-Carson, Mary C; Kirn-Safran, Catherine B; Jha, Amit K; Jia Xinqiao

    2012-01-01

    The goal of this study was to use bioengineered injectable microgels to enhance the action of bone morphogenetic protein 2 (BMP2) and stimulate cartilage matrix repair in a reversible animal model of osteoarthritis (OA). A module of perlecan (PlnD1) bearing heparan sulfate (HS) chains was covalently immobilized to hyaluronic acid (HA) microgels for the controlled release of BMP2 in vivo. Articular cartilage damage was induced in mice using a reversible model of experimental OA and was treated by intra-articular injection of PlnD1-HA particles with BMP2 bound to HS. Control injections consisted of BMP2-free PlnD1-HA particles, HA particles, free BMP2 or saline. Knees dissected following these injections were analyzed using histological, immunostaining and gene expression approaches. Our results show that knees treated with PlnD1-HA/BMP2 had lesser OA-like damage compared to control knees. In addition, the PlnD1-HA/BMP2-treated knees had higher mRNA levels encoding for type II collagen, proteoglycans and xylosyltransferase 1, a rate-limiting anabolic enzyme involved in the biosynthesis of glycosaminoglycan chains, relative to control knees (PlnD1-HA). This finding was paralleled by enhanced levels of aggrecan in the articular cartilage of PlnD1-HA/BMP2-treated knees. Additionally, decreases in the mRNA levels encoding for cartilage-degrading enzymes and type X collagen were seen relative to controls. In conclusion, PlnD1-HA microgels constitute a formulation improvement compared to HA for efficient in vivo delivery and stimulation of proteoglycan and cartilage matrix synthesis in mouse articular cartilage. Ultimately, PlnD1-HA/BMP2 may serve as an injectable therapeutic agent for slowing or inhibiting the onset of OA after knee injury.

  2. The exact mass-gaps of the principal chiral models

    CERN Document Server

    Hollowood, Timothy J

    1994-01-01

    An exact expression for the mass-gap, the ratio of the physical particle mass to the $\\Lambda$-parameter, is found for the principal chiral sigma models associated to all the classical Lie algebras. The calculation is based on a comparison of the free-energy in the presence of a source coupling to a conserved charge of the theory computed in two ways: via the thermodynamic Bethe Ansatz from the exact scattering matrix and directly in perturbation theory. The calculation provides a non-trivial test of the form of the exact scattering matrix.

  3. Pulsar Polar Cap and Slot Gap Models: Confronting Fermi Data

    Directory of Open Access Journals (Sweden)

    Alice K. Harding

    2013-09-01

    Full Text Available Rotation-powered pulsars are excellent laboratories for studying particle acceleration as well as fundamental physics of strong gravity, strong magnetic fields and relativity. Particle acceleration and high-energy emission from the polar caps is expected to occur in connection with electron-positron pair cascades. I will review acceleration and gamma-ray emission from the pulsar polar cap and associated slot gap. Predictions of these models can be tested with the data set on pulsars collected by the Large Area Telescope on the Fermi Gamma-Ray Telescope over the last four years, using both detailed light curve fitting, population synthesis and phase-resolved spectroscopy.

  4. A three-dimensional model of a gap junction

    International Nuclear Information System (INIS)

    Xylouris, K.; Wittum, G.

    2009-01-01

    Gap junctions are effective electric couplings between neurons and form a very important way of communication between them. Since they can be considered as the points on the neuron's membrane on which for example dendrites of different cells become one piece, in three dimensions they can be modelled by observing this property in the created geometry. Thus they can be easily made part in an already existing 3-dimensional model for signal propagation on the neuron's membrane, if the geometries are chosen in such a way respect the blending of the membranes. A small network of two cells was created, which blend in their dendrites and a simulation of the three-dimensional model was carried out which reveals the fast transmission of the signal from one cell to the other.

  5. Which cartilage is regenerated, hyaline cartilage or fibrocartilage? Non-invasive ultrasonic evaluation of tissue-engineered cartilage.

    Science.gov (United States)

    Hattori, K; Takakura, Y; Ohgushi, H; Habata, T; Uematsu, K; Takenaka, M; Ikeuchi, K

    2004-09-01

    To investigate ultrasonic evaluation methods for detecting whether the repair tissue is hyaline cartilage or fibrocartilage in new cartilage regeneration therapy. We examined four experimental rabbit models: a spontaneous repair model (group S), a large cartilage defect model (group L), a periosteal graft model (group P) and a tissue-engineered cartilage regeneration model (group T). From the resulting ultrasonic evaluation, we used %MM (the maximum magnitude of the measurement area divided by that of the intact cartilage) as a quantitative index of cartilage regeneration. The results of the ultrasonic evaluation were compared with the histological findings and histological score. The %MM values were 61.1 +/- 16.5% in group S, 29.8 +/- 15.1% in group L, 36.3 +/- 18.3% in group P and 76.5 +/- 18.7% in group T. The results showed a strong similarity to the histological scoring. The ultrasonic examination showed that all the hyaline-like cartilage in groups S and T had a high %MM (more than 60%). Therefore, we could define the borderline between the two types of regenerated cartilage by the %MM.

  6. Structure modeling and mutational analysis of gap junction beta 2 ...

    African Journals Online (AJOL)

    Yomi

    2012-04-03

    Apr 3, 2012 ... Three dimensional (3 D) structure is very useful for understanding biological functions. Gap junction beta 2 (GJB2), human gene encoding for gap junction beta 2 protein is involved in ... Research in deafness became real.

  7. Imaging of articular cartilage

    Directory of Open Access Journals (Sweden)

    Bhawan K Paunipagar

    2014-01-01

    Full Text Available We tried to review the role of magnetic resonance imaging (MRI in understanding microscopic and morphologic structure of the articular cartilage. The optimal protocols and available spin-echo sequences in present day practice are reviewed in context of common pathologies of articular cartilage. The future trends of articular cartilage imaging have been discussed with their appropriateness. In diarthrodial joints of the body, articular cartilage is functionally very important. It is frequently exposed to trauma, degeneration, and repetitive wear and tear. MRI has played a vital role in evaluation of articular cartilage. With the availability of advanced repair surgeries for cartilage lesions, there has been an increased demand for improved cartilage imaging techniques. Recent advances in imaging strategies for native and postoperative articular cartilage open up an entirely new approach in management of cartilage-related pathologies.

  8. Berberine attenuates CCN2-induced IL-1β expression and prevents cartilage degradation in a rat model of osteoarthritis

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Shan-Chi [Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China); Lee, Hsiang-Ping [Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan (China); Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan (China); Hung, Chun-Yin [Department of Orthopaedic Surgery, China Medical University Beigang Hospital, Yun-Lin County, Taiwan (China); Tsai, Chun-Hao [Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan (China); Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan (China); Li, Te-Mao [School of Chinese Medicine, China Medical University, Taichung, Taiwan (China); Tang, Chih-Hsin, E-mail: chtang@mail.cmu.edu.tw [Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China); Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan (China); Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan (China)

    2015-11-15

    Connective tissue growth factor (CTGF; also known as CCN2) is an inflammatory mediator that is abundantly expressed in osteoarthritis (OA). Interleukin-1β (IL-1β) plays a pivotal role in OA pathogenesis. Berberine exhibits an anti-inflammatory effect, but the mechanisms by which it modulates CCN2-induced IL-1β expression in OA synovial fibroblasts (OASFs) remain unknown. We showed that CCN2-induced IL-1β expression is mediated by the activation of α{sub v}β{sub 3}/α{sub v}β{sub 5} integrin-dependent reactive oxygen species (ROS) generation, and subsequent activation of apoptosis signal-regulating kinase 1 (ASK1), p38/JNK, and nuclear factor-κB (NF-κB) signaling pathways. This IL-1β expression in OASFs is attenuated by N-acetylcysteine (NAC), inhibitors of ASK1, p38, or JNK, or treatment with berberine. Furthermore, berberine also reverses cartilage damage in an experimental model of collagenase-induced OA (CIOA). We observed that CCN2 increased IL-1β expression via α{sub v}β{sub 3}/α{sub v}β{sub 5} integrins, ROS, and ASK1, p38/JNK, and NF-κB signaling pathways. Berberine was found to inhibit these signaling components in OASFs in vitro and prevent cartilage degradation in vivo. We suggest a novel therapeutic strategy of using berberine for managing OA. - Highlights: • CCN2 induce IL-1β production via αvβ3/αvβ5 integrin, ROS, ASK1, p38/JNK, and NF-κB. • Berberine attenuates CCN2-induced IL-1β expression in vitro and in OA rat model. • Berberine as natural drug of choice for anti-inflammatory effect to ameliorates OA.

  9. Expanding the Acculturation Gap-Distress Model: An Integrative Review of Research

    Science.gov (United States)

    Telzer, Eva H.

    2010-01-01

    The acculturation gap-distress model purports that immigrant children acculturate to their new culture at a quicker pace than their parents, leading to family conflict and youth maladjustment. This article reviews literature on the acculturation gap-distress model, showing that acculturation gaps function in unique ways depending on many social…

  10. Immunological gap in the infectious animal model for biliary atresia.

    Science.gov (United States)

    Czech-Schmidt, G; Verhagen, W; Szavay, P; Leonhardt, J; Petersen, C

    2001-11-01

    Extrahepatic biliary atresia (EHBA), the etiology of which still remains unclear, occurs exclusively in newborns and has recently been simulated in an animal model. It is possible to trigger an EHBA corresponding to the human disease by means of intraperitoneal infection of newborn Balb/c mice with rhesus rotavirus (RRV). The aim of the present study was to determine the conditions and circumstances for inducing biliary atresia in this model focusing on first-line immunological aspects. Newborn as well as pregnant Balb/c mice were intraperitoneally infected with RRV. The highest incidence of cholestasis (86%) was achieved by infection with 10(6) PFU/ml RRV within the first 12 h postpartum, resulting in EHBA with a lethality of 100%. However, the later the newborn mouse is infected, the less likelihood there is that EHBA is triggered. Additionally, the incidence of biliary atresia in this model depends on the quantity of the virus that is given intraperitoneally. However, the development of biliary atresia is not correlated to the virus in the liver. The antepartum infection of pregnant mice does not induce EHBA in the offspring. Female mice that are immunized against RRV protect their newborns from developing RRV-induced cholestasis and EHBA. This protection is transmitted transplacentally and not by breast milk. It is obvious that a temporary immunological gap is essential for virally induced EHBA. Further studies should focus on specific parameters of the immune system of newborn mice in this biliary atresia model. Copyright 2001 Academic Press.

  11. Modeling charged defects inside density functional theory band gaps

    International Nuclear Information System (INIS)

    Schultz, Peter A.; Edwards, Arthur H.

    2014-01-01

    Density functional theory (DFT) has emerged as an important tool to probe microscopic behavior in materials. The fundamental band gap defines the energy scale for charge transition energy levels of point defects in ionic and covalent materials. The eigenvalue gap between occupied and unoccupied states in conventional DFT, the Kohn–Sham gap, is often half or less of the experimental band gap, seemingly precluding quantitative studies of charged defects. Applying explicit and rigorous control of charge boundary conditions in supercells, we find that calculations of defect energy levels derived from total energy differences give accurate predictions of charge transition energy levels in Si and GaAs, unhampered by a band gap problem. The GaAs system provides a good theoretical laboratory for investigating band gap effects in defect level calculations: depending on the functional and pseudopotential, the Kohn–Sham gap can be as large as 1.1 eV or as small as 0.1 eV. We find that the effective defect band gap, the computed range in defect levels, is mostly insensitive to the Kohn–Sham gap, demonstrating it is often possible to use conventional DFT for quantitative studies of defect chemistry governing interesting materials behavior in semiconductors and oxides despite a band gap problem

  12. Attenuation of the progression of articular cartilage degeneration by inhibition of TGF-β1 signaling in a mouse model of osteoarthritis.

    Science.gov (United States)

    Chen, Rebecca; Mian, Michelle; Fu, Martin; Zhao, Jing Ying; Yang, Liang; Li, Yefu; Xu, Lin

    2015-11-01

    Transforming growth factor beta 1 (TGF-β1) is implicated in osteoarthritis. We therefore studied the role of TGF-β1 signaling in the development of osteoarthritis in a developmental stage-dependent manner. Three different mouse models were investigated. First, the Tgf-β receptor II (Tgfbr2) was specifically removed from the mature cartilage of joints. Tgfbr2-deficient mice were grown to 12 months of age and were then euthanized for collection of knee and temporomandibular joints. Second, Tgfbr2-deficient mice were subjected to destabilization of the medial meniscus (DMM) surgery. Knee joints were then collected from the mice at 8 and 16 weeks after the surgery. Third, wild-type mice were subjected to DMM at the age of 8 weeks. Immediately after the surgery, these mice were treated with the Tgfbr2 inhibitor losartan for 8 weeks and then euthanized for collection of knee joints. All joints were characterized for evidences of articular cartilage degeneration. Initiation or acceleration of articular cartilage degeneration was not observed by the genetic inactivation of Tgfbr2 in the joints at the age of 12 months. In fact, the removal of Tgfbr2 and treatment with losartan both delayed the progression of articular cartilage degeneration induced by DMM compared with control littermates. Therefore, we conclude that inhibition of Tgf-β1 signaling protects adult knee joints in mice against the development of osteoarthritis. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  13. Gap Conductance model Validation in the TASS/SMR-S code using MARS code

    International Nuclear Information System (INIS)

    Ahn, Sang Jun; Yang, Soo Hyung; Chung, Young Jong; Lee, Won Jae

    2010-01-01

    Korea Atomic Energy Research Institute (KAERI) has been developing the TASS/SMR-S (Transient and Setpoint Simulation/Small and Medium Reactor) code, which is a thermal hydraulic code for the safety analysis of the advanced integral reactor. An appropriate work to validate the applicability of the thermal hydraulic models within the code should be demanded. Among the models, the gap conductance model which is describes the thermal gap conductivity between fuel and cladding was validated through the comparison with MARS code. The validation of the gap conductance model was performed by evaluating the variation of the gap temperature and gap width as the changed with the power fraction. In this paper, a brief description of the gap conductance model in the TASS/SMR-S code is presented. In addition, calculated results to validate the gap conductance model are demonstrated by comparing with the results of the MARS code with the test case

  14. Evaluation of gap heat transfer model in ELESTRES for CANDU fuel element under normal operating conditions

    International Nuclear Information System (INIS)

    Lee, Kang Moon; Ohn, Myung Ryong; Im, Hong Sik; Choi, Jong Hoh; Hwang, Soon Taek

    1995-01-01

    The gap conductance between the fuel and the sheath depends strongly on the gap width and has a significant influence on the amount of initial stored energy. The modified Ross and Stoute gap conductance model in ELESTRES is based on a simplified thermal deformation model for steady-state fuel temperature calculations. A review on a series of experiments reveals that fuel pellets crack, relocate, and are eccentrically positioned within the sheath rather than solid concentric cylinders. In this paper, the two recently-proposed gap conductance models (offset gap model and relocated gap model) are described and are applied to calculate the fuel-sheath gap conductances under experimental conditions and normal operating conditions in CANDU reactors. The good agreement between the experimentally-inferred and calculated gap conductance values demonstrates that the modified Ross and Stoute model was implemented correctly in ELESTRES. The predictions of the modified Ross and Stoute model provide conservative values for gap heat transfer and fuel surface temperature compared to the offset gap and relocated gap models for a limiting power envelope. 13 figs., 3 tabs., 16 refs. (Author)

  15. Study on models for gap conductance between fuel and sheath for CANDU reactors

    International Nuclear Information System (INIS)

    Lee, K.M.; Ohn, M.Y.; Lim, H.S.; Choi, J.H.; Hwang, S.T.

    1995-01-01

    The gap conductance between the fuel and the sheath depends strongly on the gap width and has a significant influence on the amount of initial stored energy. The modified Ross and Stoute gap conductance model in ELESTRES is based on a simplified thermal deformation model for steady-state fuel temperature calculations. A review on a series of experiments reveals that fuel pellets crack, relocate, and are eccentrically positioned within the sheath rather than solid concentric cylinders. In this paper, the two recently-proposed gap conductance models (offset gap model and relocated gap model) are described and are applied to calculate the fuel-sheath gap conductances under experimental conditions and normal operating conditions in CANDU reactors. The good agreement between the experimentally-inferred and calculated gap conductance values demonstrates that the modified Ross and Stoute model was implemented correctly in ELESTRES. The predictions of the modified Ross and Stoute model provide conservative values for gap heat transfer and fuel surface temperature compared to the offset gap and relocated gap models for a limiting power envelope. (author)

  16. Mechano growth factor (MGF) and transforming growth factor (TGF)-β3 functionalized silk scaffolds enhance articular hyaline cartilage regeneration in rabbit model.

    Science.gov (United States)

    Luo, Ziwei; Jiang, Li; Xu, Yan; Li, Haibin; Xu, Wei; Wu, Shuangchi; Wang, Yuanliang; Tang, Zhenyu; Lv, Yonggang; Yang, Li

    2015-06-01

    Damaged cartilage has poor self-healing ability and usually progresses to scar or fibrocartilaginous tissue, and finally degenerates to osteoarthritis (OA). Here we demonstrated that one of alternative isoforms of IGF-1, mechano growth factor (MGF) acted synergistically with transforming growth factor β3 (TGF-β3) embedded in silk fibroin scaffolds to induce chemotactic homing and chondrogenic differentiation of mesenchymal stem cells (MSCs). Combination of MGF and TGF-β3 significantly increased cell recruitment up to 1.8 times and 2 times higher than TGF-β3 did in vitro and in vivo. Moreover, MGF increased Collagen II and aggrecan secretion of TGF-β3 induced hMSCs chondrogenesis, but decreased Collagen I in vitro. Silk fibroin (SF) scaffolds have been widely used for tissue engineering, and we showed that methanol treated pured SF scaffolds were porous, similar to compressive module of native cartilage, slow degradation rate and excellent drug released curves. At 7 days after subcutaneous implantation, TGF-β3 and MGF functionalized silk fibroin scaffolds (STM) recruited more CD29+/CD44+cells (Pcartilage-like extracellular matrix and less fibrillar collagen were detected in STM scaffolds than that in TGF-β3 modified scaffolds (ST) at 2 months after subcutaneous implantation. When implanted into articular joints in a rabbit osteochondral defect model, STM scaffolds showed the best integration into host tissues, similar architecture and collagen organization to native hyaline cartilage, as evidenced by immunostaining of aggrecan, collagen II and collagen I, as well as Safranin O and Masson's trichrome staining, and histological evalution based on the modified O'Driscoll histological scoring system (Pcartilage regeneration. This study demonstrated that TGF-β3 and MGF functionalized silk fibroin scaffolds enhanced endogenous stem cell recruitment and facilitated in situ articular cartilage regeneration, thus providing a novel strategy for cartilage repair

  17. Transcriptomic signatures in cartilage ageing

    Science.gov (United States)

    2013-01-01

    Introduction Age is an important factor in the development of osteoarthritis. Microarray studies provide insight into cartilage aging but do not reveal the full transcriptomic phenotype of chondrocytes such as small noncoding RNAs, pseudogenes, and microRNAs. RNA-Seq is a powerful technique for the interrogation of large numbers of transcripts including nonprotein coding RNAs. The aim of the study was to characterise molecular mechanisms associated with age-related changes in gene signatures. Methods RNA for gene expression analysis using RNA-Seq and real-time PCR analysis was isolated from macroscopically normal cartilage of the metacarpophalangeal joints of eight horses; four young donors (4 years old) and four old donors (>15 years old). RNA sequence libraries were prepared following ribosomal RNA depletion and sequencing was undertaken using the Illumina HiSeq 2000 platform. Differentially expressed genes were defined using Benjamini-Hochberg false discovery rate correction with a generalised linear model likelihood ratio test (P ageing cartilage. Conclusion There was an age-related dysregulation of matrix, anabolic and catabolic cartilage factors. This study has increased our knowledge of transcriptional networks in cartilage ageing by providing a global view of the transcriptome. PMID:23971731

  18. Reducing Excellence Gaps: A Research-Based Model

    Science.gov (United States)

    Plucker, Jonathan A.; Peters, Scott J.; Schmalensee, Stephanie

    2017-01-01

    As the awareness of the existence and negative effects of excellence gaps has grown among educators and policy makers, so too has a desire for research-supported interventions to reduce these gaps. A recent review of research related to promoting equitable outcomes for all gifted students identified six specific strategies for reducing excellence…

  19. A PC microsimulation of a gap acceptance model for turning left at a T-junction

    NARCIS (Netherlands)

    Schaap, Nina; Dijck, T.; van Arem, Bart; Morsink, Peter L.J.

    2009-01-01

    Vehicles are controlled by sub-behavioral models in a microsimulation model, this includes the gap acceptance model where the decision about how to cross a junction is made. The critical gap in these models must serve as a threshold value to accept or reject the space between two successive vehicles

  20. Prefabrication of 3D cartilage contructs: towards a tissue engineered auricle--a model tested in rabbits.

    Directory of Open Access Journals (Sweden)

    Achim von Bomhard

    Full Text Available The reconstruction of an auricle for congenital deformity or following trauma remains one of the greatest challenges in reconstructive surgery. Tissue-engineered (TE three-dimensional (3D cartilage constructs have proven to be a promising option, but problems remain with regard to cell vitality in large cell constructs. The supply of nutrients and oxygen is limited because cultured cartilage is not vascular integrated due to missing perichondrium. The consequence is necrosis and thus a loss of form stability. The micro-surgical implantation of an arteriovenous loop represents a reliable technology for neovascularization, and thus vascular integration, of three-dimensional (3D cultivated cell constructs. Auricular cartilage biopsies were obtained from 15 rabbits and seeded in 3D scaffolds made from polycaprolactone-based polyurethane in the shape and size of a human auricle. These cartilage cell constructs were implanted subcutaneously into a skin flap (15 × 8 cm and neovascularized by means of vascular loops implanted micro-surgically. They were then totally enhanced as 3D tissue and freely re-implanted in-situ through microsurgery. Neovascularization in the prefabricated flap and cultured cartilage construct was analyzed by microangiography. After explantation, the specimens were examined by histological and immunohistochemical methods. Cultivated 3D cartilage cell constructs with implanted vascular pedicle promoted the formation of engineered cartilaginous tissue within the scaffold in vivo. The auricles contained cartilage-specific extracellular matrix (ECM components, such as GAGs and collagen even in the center oft the constructs. In contrast, in cultivated 3D cartilage cell constructs without vascular pedicle, ECM distribution was only detectable on the surface compared to constructs with vascular pedicle. We demonstrated, that the 3D flaps could be freely transplanted. On a microangiographic level it was evident that all the skin flaps

  1. Electrical and Thermal Modulation of Protein Synthesis in Cartilage: A Model for Field Effects on Biological Tissues.

    Science.gov (United States)

    1988-01-15

    76] under physiological conditions. Oscillatory streaming currents of 1-5 pA/cm’ were recently demonstrated in bovine knee articular cartilage...in cellular metabolism or cellular acidosis ). In general, these agents are lethal in high enough doses. The stress proteins are highly conserved...which under reducing conditions subdivides into subunits of 35 kD (on SDS-PAGE) in bovine fetal epiphyseal and articular cartilage [170]. The tissue

  2. Release of transgenic progranulin from a living hyaline cartilage graft model: An in vitro evaluation on anti-inflammation.

    Science.gov (United States)

    Lau, Ting Ting; Zhang, Feng; Tang, Wei; Wang, Dong-An

    2016-12-01

    Osteoarthritis (OA) is a prevalent condition that compromises and even jeopardizes the life quality of millions of people. Common symptoms in OA includes joint stiffness and soreness, and they are often associated with inflammations to various extend. Due to the avascular and aneural nature of articular hyaline cartilage, it has limited self-repair capabilities; especially under inflammatory conditions, damages inflicted on cartilage are often irreversible. Hence, treatment approaches focus on anti-inflammation or articular cartilage replacement. In this study, an engineered, dual-functional living hyaline cartilage graft (LhCG), capable of releasing transgenic anti-inflammatory cytokine-progranulin (PGRN) is developed and envisioned to simultaneously fulfil both requirements. The therapeutic functionality of PGRN releasing LhCG is evaluated by co-culturing the constructs with tumor necrosis factor-alpha (TNFα) secreting THP-1 cells to simulate the inflammatory condition in arthritis. Non-transgenic LhCG constructs and non-coculture sample groups were set up as controls. Gene expression and ECM composition changes across samples were assessed to understand the effects of PGRN as well as inflammatory environment on the cartilage graft. Collectively, the results in this study suggest that in situ release of transgenic recombinant PGRN protects LhCG from induced inflammation in vitro; contrastively, in the absence of PGRN, cartilage grafts are at risk of being degraded and mineralized under exposure to TNFα signaling. This shows that cartilage graft itself can be at risk of degradation or calcification when implanted in arthritic microenvironment. Hence, the inflammatory microenvironment has to be considered in cartilage replacement therapy to increase chances of successful joint mobility restoration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2968-2977, 2016. © 2016 Wiley Periodicals, Inc.

  3. Comparing Novel Multi-Gap Resistive Plate Chamber Models

    Science.gov (United States)

    Stien, Haley; EIC PID Consortium Collaboration

    2016-09-01

    Investigating nuclear structure has led to the fundamental theory of Quantum Chromodynamics. An Electron Ion Collider (EIC) is a proposed accelerator that would further these investigations. In order to prepare for the EIC, there is an active detector research and development effort. One specific goal is to achieve better particle identification via improved Time of Flight (TOF) detectors. A promising option is the Multi-Gap Resistive Plate Chamber (mRPC). These detectors are similar to the more traditional RPCs, but their active gas gaps have dividers to form several thinner gas gaps. These very thin and accurately defined gas gaps improve the timing resolution of the chamber, so the goal is to build an mRPC with the thinnest gaps to achieve the best possible timing resolution. Two different construction techniques have been employed to make two mRPCs. The first technique is to physically separate the gas gaps with sheets of glass that are .2mm thick. The second technique is to 3D print the layered gas gaps. A comparison of these mRPCs and their performances will be discussed and the latest data presented. This research was supported by US DOE MENP Grant DE-FG02-03ER41243.

  4. Hyaline cartilage degenerates after autologous osteochondral transplantation.

    Science.gov (United States)

    Tibesku, C O; Szuwart, T; Kleffner, T O; Schlegel, P M; Jahn, U R; Van Aken, H; Fuchs, S

    2004-11-01

    Autologous osteochondral grafting is a well-established clinical procedure to treat focal cartilage defects in patients, although basic research on this topic remains sparse. The aim of the current study was to evaluate (1) histological changes of transplanted hyaline cartilage of osteochondral grafts and (2) the tissue that connects the transplanted cartilage with the adjacent cartilage in a sheep model. Both knee joints of four sheep were opened surgically and osteochondral grafts were harvested and simultaneously transplanted to the contralateral femoral condyle. The animals were sacrificed after three months and the received knee joints were evaluated histologically. Histological evaluation showed a complete ingrowth of the osseous part of the osteochondral grafts. A healing or ingrowth at the level of the cartilage could not be observed. Histological evaluation of the transplanted grafts according to Mankin revealed significantly more and more severe signs of degeneration than the adjacent cartilage, such as cloning of chondrocytes and irregularities of the articular surface. We found no connecting tissue between the transplanted and the adjacent cartilage and histological signs of degeneration of the transplanted hyaline cartilage. In the light of these findings, long-term results of autologous osteochondral grafts in human beings have to be followed critically.

  5. The Influence of Oblique Angle Forced Exercise in Surgically Destabilized Stifle Joints Is Synergistic with Bone, but Antagonistic with Cartilage in an Ovine Model of Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Rachel J. Hill

    2017-01-01

    Full Text Available Large animal models of osteoarthritis are a necessary testing ground for FDA approval of human medicine applications. Sheep models have advantages over other available large animals, but development and progression of osteoarthritis in sheep is exceedingly slow, which handicaps progress in development of potential treatments. We combined oblique angle forced exercise to increase stress on the stifle, with surgical destabilization to hasten the development of osteoarthritis in ewes. Methods for early detection of clinical signs included radiography, urine, and serum biomarker assays and gait analysis and ex vivo we used microcomputed tomography and macroscopic joint analysis. Our model was able to produce clinically detectable signs of osteoarthritis in a relatively short period (14 weeks. Changes in bone were highly correlated between microcomputed tomography and radiographic analysis and changes in cartilage correlated well between urinary glycosaminoglycan levels and serum aggrecanase analyses. Exercise improved the negative effects of destabilization in bone but exacerbated the negative effects of destabilization in cartilage. These observations suggest that we may need to consider treatments for bone and cartilage separately. These results represent an improved large animal model of osteoarthritis with rapid onset of disease and superior detection of bone and soft tissue changes.

  6. Spectrocolorimetric evaluation of repaired articular cartilage after a microfracture

    Directory of Open Access Journals (Sweden)

    Dohi Yoshihiro

    2008-09-01

    Full Text Available Abstract Background In clinical practice, surgeons differentiate color changes in repaired cartilage compared with surrounding intact cartilage, but cannot quantify these color changes. Objective assessments are required. A spectrocolorimeter was used to evaluate whether intact and repaired cartilage can be quantified. Findings We investigated the use of a spectrocolorimeter and the application of two color models (L* a* b* colorimetric system and spectral reflectance distribution to describe and quantify articular cartilage. In this study, we measured the colors of intact and repaired cartilage after a microfracture. Histologically, the repaired cartilage was a mixture of fibrocartilage and hyaline cartilage. In the L* a* b* colorimetric system, the L* and a* values recovered to close to the values of intact cartilage, whereas the b* value decreased over time after the operation. Regarding the spectral reflectance distribution at 12 weeks after the operation, the repaired cartilage had a higher spectral reflectance ratio than intact cartilage between wavelengths of 400 to 470 nm. Conclusion This study reports the first results regarding the relationship between spectrocolorimetric evaluation and the histological findings of repair cartilage after a microfracture. Our findings demonstrate the ability of spectrocolorimetric measurement to judge the repair cartilage after treatment on the basis of objective data such as the L*, a* and b* values and the SRP as a coincidence index of the spectral reflectance curve.

  7. Modeling of Photonic Band Gap Crystals and Applications

    Energy Technology Data Exchange (ETDEWEB)

    El-Kady, Ihab Fathy [Iowa State Univ., Ames, IA (United States)

    2002-01-01

    In this work, the authors have undertaken a theoretical approach to the complex problem of modeling the flow of electromagnetic waves in photonic crystals. The focus is to address the feasibility of using the exciting phenomena of photonic gaps (PBG) in actual applications. The authors start by providing analytical derivations of the computational electromagnetic methods used in their work. They also present a detailed explanation of the physics underlying each approach, as well as a comparative study of the strengths and weaknesses of each method. The Plane Wave expansion, Transfer Matrix, and Finite Difference time Domain Methods are addressed. They also introduce a new theoretical approach, the Modal Expansion Method. They then shift the attention to actual applications. They begin with a discussion of 2D photonic crystal wave guides. The structure addressed consists of a 2D hexagonal structure of air cylinders in a layered dielectric background. Comparison with the performance of a conventional guide is made, as well as suggestions for enhancing it. The studies provide an upper theoretical limit on the performance of such guides, as they assumed no crystal imperfections and non-absorbing media. Next, they study 3D metallic PBG materials at near infrared and optical wavelengths. The main objective is to study the importance of absorption in the metal and the suitability of observing photonic band gaps in such structures. They study simple cubic structures where the metallic scatters are either cubes or interconnected metallic rods. Several metals are studied (aluminum, gold, copper, and silver). The effect of topology is addressed and isolated metallic cubes are found to be less lossy than the connected rod structures. The results reveal that the best performance is obtained by choosing metals with a large negative real part of the dielectric function, together with a relatively small imaginary part. Finally, they point out a new direction in photonic crystal

  8. Modelling and design of complete photonic band gaps in two ...

    Indian Academy of Sciences (India)

    Photonic crystal; complete photonic band gap; plane-wave expansion method. ... lies in the possibility of the substantial control of the radiation field by means of ... research. To prevent the propagation of the waves, whatever its direction is, the.

  9. Hydrogeologic Model for the Gable Gap Area, Hanford Site

    Energy Technology Data Exchange (ETDEWEB)

    Bjornstad, Bruce N.; Thorne, Paul D.; Williams, Bruce A.; Last, George V.; Thomas, Gregory S.; Thompson, Michael D.; Ludwig, Jami L.; Lanigan, David C.

    2010-09-30

    Gable Gap is a structural and topographic depression between Gable Mountain and Gable Butte within the central Hanford Site. It has a long and complex geologic history, which includes tectonic uplift synchronous with erosional downcutting associated with the ancestral Columbia River during both Ringold and Cold Creek periods, and by the later Ice Age (mostly glacial Lake Missoula) floods. The gap was subsequently buried and partially backfilled by mostly coarse-grained, Ice Age flood deposits (Hanford formation). Erosional remnants of both the Ringold Formation and Cold Creek unit locally underlie the high-energy flood deposits. A large window exists in the gap where confined basalt aquifers are in contact with the unconfined suprabasalt aquifer. Several paleochannels, of both Hanford and Ringold Formation age, were eroded into the basalt bedrock across Gable Gap. Groundwater from the Central Plateau presently moves through Gable Gap via one or more of these shallow paleochannels. As groundwater levels continue to decline in the region, groundwater flow may eventually be cut off through Gable Gap.

  10. Platelet-rich plasma enhances the integration of bioengineered cartilage with native tissue in an in vitro model.

    Science.gov (United States)

    Sermer, Corey; Kandel, Rita; Anderson, Jesse; Hurtig, Mark; Theodoropoulos, John

    2018-02-01

    Current therapies for cartilage repair can be limited by an inability of the repair tissue to integrate with host tissue. Thus, there is interest in developing approaches to enhance integration. We have previously shown that platelet-rich plasma (PRP) improves cartilage tissue formation. This raised the question as to whether PRP could promote cartilage integration. Chondrocytes were isolated from cartilage harvested from bovine joints, seeded on a porous bone substitute and grown in vitro to form an osteochondral-like implant. After 7 days, the biphasic construct was soaked in PRP for 30 min before implantation into the core of a donut-shaped biphasic explant of native cartilage and bone. Controls were not soaked in PRP. The implant-explant construct was cultured for 2-4 weeks. PRP-soaked bioengineered implants integrated with host tissue in 73% of samples, whereas controls only integrated in 19% of samples. The integration strength, as determined by a push-out test, was significantly increased in the PRP-soaked implant group (219 ± 35.4 kPa) compared with controls (72.0 ± 28.5 kPa). This correlated with an increase in glycosaminoglycan and collagen accumulation in the region of integration in the PRP-treated implant group, compared with untreated controls. Immunohistochemical studies revealed that the integration zone contained collagen type II and aggrecan. The cells at the zone of integration in the PRP-soaked group had a 3.5-fold increase in matrix metalloproteinase-13 gene expression compared with controls. These results suggest that PRP-soaked bioengineered cartilage implants may be a better approach for cartilage repair due to enhanced integration. Copyright © 2017 John Wiley & Sons, Ltd.

  11. Increasing the Dose of Autologous Chondrocytes Improves Articular Cartilage Repair: Histological and Molecular Study in the Sheep Animal Model.

    Science.gov (United States)

    Guillén-García, Pedro; Rodríguez-Iñigo, Elena; Guillén-Vicente, Isabel; Caballero-Santos, Rosa; Guillén-Vicente, Marta; Abelow, Stephen; Giménez-Gallego, Guillermo; López-Alcorocho, Juan Manuel

    2014-04-01

    We hypothesized that implanting cells in a chondral defect at a density more similar to that of the intact cartilage could induce them to synthesize matrix with the features more similar to that of the uninjured one. We compared the implantation of different doses of chondrocytes: 1 million (n = 5), 5 million (n = 5), or 5 million mesenchymal cells (n = 5) in the femoral condyle of 15 sheep. Tissue generated by microfracture at the trochlea, and normal cartilage from a nearby region, processed as the tissues resulting from the implantation, were used as references. Histological and molecular (expression of type I and II collagens and aggrecan) studies were performed. The features of the cartilage generated by implantation of mesenchymal cells and elicited by microfractures were similar and typical of a poor repair of the articular cartilage (presence of fibrocartilage, high expression of type I collagen and a low mRNA levels of type II collagen and aggrecan). Nevertheless, in the samples obtained from tissues generated by implantation of chondrocytes, hyaline-like cartilage, cell organization, low expression rates of type I collagen and high levels of mRNA corresponding to type II collagen and aggrecan were observed. These histological features, show less variability and are more similar to those of the normal cartilage used as control in the case of 5 million cells implantation than when 1 million cells were used. The implantation of autologous chondrocytes in type I/III collagen membranes at high density could be a promising tool to repair articular cartilage.

  12. Treadmill Running Ameliorates Destruction of Articular Cartilage and Subchondral Bone, Not Only Synovitis, in a Rheumatoid Arthritis Rat Model

    Directory of Open Access Journals (Sweden)

    Seiji Shimomura

    2018-06-01

    Full Text Available We analyzed the influence of treadmill running on rheumatoid arthritis (RA joints using a collagen-induced arthritis (CIA rat model. Eight-week-old male Dark Agouti rats were randomly divided into four groups: The control group, treadmill group (30 min/day for 4 weeks from 10-weeks-old, CIA group (induced CIA at 8-weeks-old, and CIA + treadmill group. Destruction of the ankle joint was evaluated by histological analyses. Morphological changes of subchondral bone were analyzed by μ-CT. CIA treatment-induced synovial membrane invasion, articular cartilage destruction, and bone erosion. Treadmill running improved these changes. The synovial membrane in CIA rats produced a large amount of tumor necrosis factor-α and Connexin 43; production was significantly suppressed by treadmill running. On μ-CT of the talus, bone volume fraction (BV/TV was significantly decreased in the CIA group. Marrow star volume (MSV, an index of bone loss, was significantly increased. These changes were significantly improved by treadmill running. Bone destruction in the talus was significantly increased with CIA and was suppressed by treadmill running. On tartrate-resistant acid phosphate and alkaline phosphatase (TRAP/ALP staining, the number of osteoclasts around the pannus was decreased by treadmill running. These findings indicate that treadmill running in CIA rats inhibited synovial hyperplasia and joint destruction.

  13. Berberine prevents nitric oxide-induced rat chondrocyte apoptosis and cartilage degeneration in a rat osteoarthritis model via AMPK and p38 MAPK signaling.

    Science.gov (United States)

    Zhou, Yan; Liu, Shi-Qing; Yu, Ling; He, Bin; Wu, Shi-Hao; Zhao, Qi; Xia, Shao-Qiang; Mei, Hong-Jun

    2015-09-01

    Chondrocyte apoptosis is an important mechanism involved in osteoarthritis (OA). Berberine (BBR), a plant alkaloid derived from Chinese medicine, is characterized by multiple pharmacological effects, such as anti-inflammatory and anti-apoptotic activities. This study aimed to evaluate the chondroprotective effect and underlying mechanisms of BBR on sodium nitroprusside (SNP)-stimulated chondrocyte apoptosis and surgically-induced rat OA model. The in vitro results revealed that BBR suppressed SNP-stimulated chondrocyte apoptosis as well as cytoskeletal remodeling, down-regulated expressions of inducible nitric oxide synthase (iNOS) and caspase-3, and up-regulated Bcl-2/Bax ratio and Type II collagen (Col II) at protein levels, which were accompanied by increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and decreased phosphorylation of p38 mitogen-activated protein kinase (MAPK). Furthermore, the anti-apoptotic effect of BBR was blocked by AMPK inhibitor Compound C (CC) and adenosine-9-β-D-arabino-furanoside (Ara A), and enhanced by p38 MAPK inhibitor SB203580. In vivo experiment suggested that BBR ameliorated cartilage degeneration and exhibited an anti-apoptotic effect on articular cartilage in a rat OA model, as demonstrated by histological analyses, TUNEL assay and immunohistochemical analyses of caspase-3, Bcl-2 and Bax expressions. These findings suggest that BBR suppresses SNP-stimulated chondrocyte apoptosis and ameliorates cartilage degeneration via activating AMPK signaling and suppressing p38 MAPK activity.

  14. Morus alba L. Stem Extract Attenuates Pain and Articular Cartilage Damage in the Anterior Cruciate Ligament Transection-Induced Rat Model of Osteoarthritis.

    Science.gov (United States)

    Khunakornvichaya, Arada; Lekmeechai, Sujinna; Pham, Phi Phuong; Himakoun, Wanwisa; Pitaksuteepong, Tasana; Morales, Noppawan Phumala; Hemstapat, Warinkarn

    2016-01-01

    This study was designed to investigate the anti-nociceptive effect of Morus alba stem extract as well as its cartilage protective effect in the anterior cruciate ligament transection (ACLT)-induced rat model of osteoarthritis (OA). The anti-nociceptive effect of this plant extract was determined by measuring hind limb weight bearing, while the severity of cartilage damage to the knee joints was evaluated using the modified Mankin grading system. Oral administration of M. alba stem extract (56 and 560 mg/kg) significantly attenuated joint pain as indicated by a significant (p alba stem extract at 56 and 560 mg/kg when compared to those of the vehicle-treated OA-induced group. In addition, a significant improvement in the Mankin score was also observed in rats treated with 560 mg/kg M. alba stem extract, which was in agreement with its pain-relieving effect. The results showed that M. alba stem extract exhibited an anti-nociceptive effect as well as cartilage protection in the ACLT-induced rat model of OA, supporting its potential use as a therapeutic treatment for OA. © 2016 S. Karger AG, Basel.

  15. Comparison of Regenerative Tissue Quality following Matrix-Associated Cell Implantation Using Amplified Chondrocytes Compared to Synovium-Derived Stem Cells in a Rabbit Model for Cartilage Lesions

    DEFF Research Database (Denmark)

    Schmal, Hagen; Kowal, Justyna M; Kassem, Moustapha

    2018-01-01

    Known problems of the autologous chondrocyte implantation motivate the search for cellular alternatives. The aim of the study was to test the potential of synovium-derived stem cells (SMSC) to regenerate cartilage using a matrix-associated implantation. In an osteochondral defect model of the med......Known problems of the autologous chondrocyte implantation motivate the search for cellular alternatives. The aim of the study was to test the potential of synovium-derived stem cells (SMSC) to regenerate cartilage using a matrix-associated implantation. In an osteochondral defect model...... of the medial femoral condyle in a rabbit, a collagen membrane was seeded with either culture-expanded allogenic chondrocytes or SMSC and then transplanted into the lesion. A tailored piece synovium served as a control. Rabbit SMSC formed typical cartilage in vitro. Macroscopic evaluation of defect healing...... and the thickness of the regenerated tissue did not reveal a significant difference between the intervention groups. However, instantaneous and shear modulus, reflecting the biomechanical strength of the repair tissue, was superior in the implantation group using allogenic chondrocytes (p

  16. Chemical changes demonstrated in cartilage by synchrotron infrared microspectroscopy in an antibody-induced murine model of rheumatoid arthritis

    Science.gov (United States)

    Croxford, Allyson M.; Selva Nandakumar, Kutty; Holmdahl, Rikard; Tobin, Mark J.; McNaughton, Don; Rowley, Merrill J.

    2011-06-01

    Collagen antibody-induced arthritis develops in mice following passive transfer of monoclonal antibodies (mAbs) to type II collagen (CII) and is attributed to effects of proinflammatory immune complexes, but transferred mAbs may react directly and damagingly with CII. To determine whether such mAbs cause cartilage damage in vivo in the absence of inflammation, mice lacking complement factor 5 that do not develop joint inflammation were injected intravenously with two arthritogenic mAbs to CII, M2139 and CIIC1. Paws were collected at day 3, decalcified, paraffin embedded, and 5-μm sections were examined using standard histology and synchrotron Fourier-transform infrared microspectroscopy (FTIRM). None of the mice injected with mAb showed visual or histological evidence of inflammation but there were histological changes in the articular cartilage including loss of proteoglycan and altered chondrocyte morphology. Findings using FTIRM at high lateral resolution revealed loss of collagen and the appearance of a new peak at 1635 cm-1 at the surface of the cartilage interpreted as cellular activation. Thus, we demonstrate the utility of synchrotron FTIRM for examining chemical changes in diseased cartilage at the microscopic level and establish that arthritogenic mAbs to CII do cause cartilage damage in vivo in the absence of inflammation.

  17. Induction of mesenchymal stem cell chondrogenic differentiation and functional cartilage microtissue formation for in vivo cartilage regeneration by cartilage extracellular matrix-derived particles.

    Science.gov (United States)

    Yin, Heyong; Wang, Yu; Sun, Zhen; Sun, Xun; Xu, Yichi; Li, Pan; Meng, Haoye; Yu, Xiaoming; Xiao, Bo; Fan, Tian; Wang, Yiguo; Xu, Wenjing; Wang, Aiyuan; Guo, Quanyi; Peng, Jiang; Lu, Shibi

    2016-03-01

    We propose a method of preparing a novel cell carrier derived from natural cartilage extracellular matrix (ECM), designated cartilage ECM-derived particles (CEDPs). Through a series of processes involving pulverization, sieving, and decellularization, fresh cartilage was made into CEDPs with a median diameter of 263 ± 48 μm. Under microgravity culture conditions in a rotary cell culture system (RCCS), bone marrow stromal cells (BMSCs) can proliferate rapidly on the surface of CEDPs with high viability. Histological evaluation and gene expression analysis indicated that BMSCs were differentiated into mature chondrocytes after 21 days of culture without the use of exogenous growth factors. Functional cartilage microtissue aggregates of BMSC-laden CEDPs formed as time in culture increased. Further, the microtissue aggregates were directly implanted into trochlear cartilage defects in a rat model (CEDP+MSC group). Gait analysis and histological results indicated that the CEDP+MSC group obtained better and more rapid joint function recovery and superior cartilage repair compared to the control groups, in which defects were treated with CEDPs alone or only fibrin glue, at both 6 and 12 weeks after surgery. In conclusion, the innovative cell carrier derived from cartilage ECM could promote chondrogenic differentiation of BMSCs, and the direct use of functional cartilage microtissue facilitated cartilage regeneration. This strategy for cell culture, stem cell differentiation and one-step surgery using cartilage microtissue for cartilage repair provides novel prospects for cartilage tissue engineering and may have further broad clinical applications. We proposed a method to prepare a novel cell carrier derived from natural cartilage ECM, termed cartilage ECM-derived particles (CEDPs), which can support proliferation of MSCs and facilitate their chondrogenic differentiation. Further, the direct use of functional cartilage microtissue of MSC-laden CEDP aggregates for

  18. Degeneration of osteoarthritis cartilage

    DEFF Research Database (Denmark)

    Jørgensen, Dan Richter

    of sensitive biomarkers for monitoring disease progression. This thesis investigates how subregional measures of cartilage thickness can be used to improve upon current imaging biomarkers. The first part of this investigation aims to discover discriminative areas in the cartilage using machine......-learning techniques specifically developed to take advantage of the spatial nature of the problem. The methods were evaluated on data from a longitudinal study where detailed cartilage thickness maps were quantified from magnetic resonance images. The results showed that focal differences in cartilage thickness may...... be relevant for both OA diagnosis and for prediction of future cartilage loss. The second part of the thesis investigates spatial patterns of longitudinal cartilage thickness changes in healthy and OA knees. Based on our findings, we propose a new, conceptually simple biomarker that embraces the heterogeneous...

  19. Modelling and design of complete photonic band gaps in two ...

    Indian Academy of Sciences (India)

    In this paper, we investigate the existence and variation of complete photonic band gap size with the introduction of asymmetry in the constituent dielectric rods with honeycomb lattices in two-dimensional photonic crystals (PhC) using the plane-wave expansion (PWE) method. Two examples, one consisting of elliptical rods ...

  20. Assessing Emphasis Gaps among MBA Alumni: A Model Framework

    Science.gov (United States)

    Van Auken, Stuart; Chrysler, Earl; Wells, Ludmilla Gricenko

    2016-01-01

    Purpose: This paper aims to focus on Master of Business Administration (MBA) alumni and their ability to provide institution-specific insights into MBA program delivery. Given desired MBA positioning dimensions, a case exemplar is used to reveal gaps between "should have" program emphases and "actual" emphases. Departures from…

  1. Does Loading Influence the Severity of Cartilage Degeneration in the Canine Groove-Model of OA?

    NARCIS (Netherlands)

    Vos, Petra; Intema, Femke; van El, Benno; DeGroot, Jeroen; Bijlsma, J. W. J.; Lafeber, Floris; Mastbergen, Simon

    2009-01-01

    Many animal models are used to study osteoarthritis (OA). In these models the role of joint loading in the development of CA is not fully understood. We studied the effect of loading on the development of CIA in the canine Groove-model. In ten female beagle dogs OA was induced in one knee according

  2. Bone Marrow Mesenchymal Stem Cell-Based Engineered Cartilage Ameliorates Polyglycolic Acid/Polylactic Acid Scaffold-Induced Inflammation Through M2 Polarization of Macrophages in a Pig Model.

    Science.gov (United States)

    Ding, Jinping; Chen, Bo; Lv, Tao; Liu, Xia; Fu, Xin; Wang, Qian; Yan, Li; Kang, Ning; Cao, Yilin; Xiao, Ran

    2016-08-01

    in better tissue survival in a pig model. Additionally, the effect of BMSC-based cartilage on the phenotype conversion of macrophages was further studied through an in vitro coculture system. This study could provide further support for the regeneration of cartilage engineering in immunocompetent animal models and provide new insight into the interaction of tissue-engineered cartilage and macrophages. ©AlphaMed Press.

  3. A New Model of Tracheostomy Care: Closing the Research-Practice Gap

    Science.gov (United States)

    2003-01-01

    521 A New Model of Tracheostomy Care: Closing the Research –Practice Gap Joel St. Clair Abstract Performance improvements have brought about...and it continues to close the research - practice gap . The WRAMC Department of Nursing is presently developing similar evidence-based procedures for... Research -Practice Gap 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK

  4. Modelling of deep gaps created by giant planets in protoplanetary disks

    Science.gov (United States)

    Kanagawa, Kazuhiro D.; Tanaka, Hidekazu; Muto, Takayuki; Tanigawa, Takayuki

    2017-12-01

    A giant planet embedded in a protoplanetary disk creates a gap. This process is important for both theory and observation. Using results of a survey for a wide parameter range with two-dimensional hydrodynamic simulations, we constructed an empirical formula for the gap structure (i.e., the radial surface density distribution), which can reproduce the gap width and depth obtained by two-dimensional simulations. This formula enables us to judge whether an observed gap is likely to be caused by an embedded planet or not. The propagation of waves launched by the planet is closely connected to the gap structure. It makes the gap wider and shallower as compared with the case where an instantaneous wave damping is assumed. The hydrodynamic simulations show that the waves do not decay immediately at the launching point of waves, even when the planet is as massive as Jupiter. Based on the results of hydrodynamic simulations, we also obtained an empirical model of wave propagation and damping in cases of deep gaps. The one-dimensional gap model with our wave propagation model is able to reproduce the gap structures in hydrodynamic simulations well. In the case of a Jupiter-mass planet, we also found that the waves with a smaller wavenumber (e.g., m = 2) are excited and transport the angular momentum to a location far away from the planet. The wave with m = 2 is closely related with a secondary wave launched by a site opposite from the planet.

  5. Development of a computational technique to measure cartilage contact area.

    Science.gov (United States)

    Willing, Ryan; Lapner, Michael; Lalone, Emily A; King, Graham J W; Johnson, James A

    2014-03-21

    Computational measurement of joint contact distributions offers the benefit of non-invasive measurements of joint contact without the use of interpositional sensors or casting materials. This paper describes a technique for indirectly measuring joint contact based on overlapping of articular cartilage computer models derived from CT images and positioned using in vitro motion capture data. The accuracy of this technique when using the physiological nonuniform cartilage thickness distribution, or simplified uniform cartilage thickness distributions, is quantified through comparison with direct measurements of contact area made using a casting technique. The efficacy of using indirect contact measurement techniques for measuring the changes in contact area resulting from hemiarthroplasty at the elbow is also quantified. Using the physiological nonuniform cartilage thickness distribution reliably measured contact area (ICC=0.727), but not better than the assumed bone specific uniform cartilage thicknesses (ICC=0.673). When a contact pattern agreement score (s(agree)) was used to assess the accuracy of cartilage contact measurements made using physiological nonuniform or simplified uniform cartilage thickness distributions in terms of size, shape and location, their accuracies were not significantly different (p>0.05). The results of this study demonstrate that cartilage contact can be measured indirectly based on the overlapping of cartilage contact models. However, the results also suggest that in some situations, inter-bone distance measurement and an assumed cartilage thickness may suffice for predicting joint contact patterns. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Modeling the radiation transfer of discontinuous canopies: results for gap probability and single-scattering contribution

    Science.gov (United States)

    Zhao, Feng; Zou, Kai; Shang, Hong; Ji, Zheng; Zhao, Huijie; Huang, Wenjiang; Li, Cunjun

    2010-10-01

    In this paper we present an analytical model for the computation of radiation transfer of discontinuous vegetation canopies. Some initial results of gap probability and bidirectional gap probability of discontinuous vegetation canopies, which are important parameters determining the radiative environment of the canopies, are given and compared with a 3- D computer simulation model. In the model, negative exponential attenuation of light within individual plant canopies is assumed. Then the computation of gap probability is resolved by determining the entry points and exiting points of the ray with the individual plants via their equations in space. For the bidirectional gap probability, which determines the single-scattering contribution of the canopy, a gap statistical analysis based model was adopted to correct the dependence of gap probabilities for both solar and viewing directions. The model incorporates the structural characteristics, such as plant sizes, leaf size, row spacing, foliage density, planting density, leaf inclination distribution. Available experimental data are inadequate for a complete validation of the model. So it was evaluated with a three dimensional computer simulation model for 3D vegetative scenes, which shows good agreement between these two models' results. This model should be useful to the quantification of light interception and the modeling of bidirectional reflectance distributions of discontinuous canopies.

  7. In Vivo Evaluation of a Novel Oriented Scaffold-BMSC Construct for Enhancing Full-Thickness Articular Cartilage Repair in a Rabbit Model.

    Directory of Open Access Journals (Sweden)

    Shuaijun Jia

    Full Text Available Tissue engineering (TE has been proven usefulness in cartilage defect repair. For effective cartilage repair, the structural orientation of the cartilage scaffold should mimic that of native articular cartilage, as this orientation is closely linked to cartilage mechanical functions. Using thermal-induced phase separation (TIPS technology, we have fabricated an oriented cartilage extracellular matrix (ECM-derived scaffold with a Young's modulus value 3 times higher than that of a random scaffold. In this study, we test the effectiveness of bone mesenchymal stem cell (BMSC-scaffold constructs (cell-oriented and random in repairing full-thickness articular cartilage defects in rabbits. While histological and immunohistochemical analyses revealed efficient cartilage regeneration and cartilaginous matrix secretion at 6 and 12 weeks after transplantation in both groups, the biochemical properties (levels of DNA, GAG, and collagen and biomechanical values in the oriented scaffold group were higher than that in random group at early time points after implantation. While these differences were not evident at 24 weeks, the biochemical and biomechanical properties of the regenerated cartilage in the oriented scaffold-BMSC construct group were similar to that of native cartilage. These results demonstrate that an oriented scaffold, in combination with differentiated BMSCs can successfully repair full-thickness articular cartilage defects in rabbits, and produce cartilage enhanced biomechanical properties.

  8. Capacity Prediction Model Based on Limited Priority Gap-Acceptance Theory at Multilane Roundabouts

    Directory of Open Access Journals (Sweden)

    Zhaowei Qu

    2014-01-01

    Full Text Available Capacity is an important design parameter for roundabouts, and it is the premise of computing their delay and queue. Roundabout capacity has been studied for decades, and empirical regression model and gap-acceptance model are the two main methods to predict it. Based on gap-acceptance theory, by considering the effect of limited priority, especially the relationship between limited priority factor and critical gap, a modified model was built to predict the roundabout capacity. We then compare the results between Raff’s method and maximum likelihood estimation (MLE method, and the MLE method was used to predict the critical gaps. Finally, the predicted capacities from different models were compared, with the observed capacity by field surveys, which verifies the performance of the proposed model.

  9. Efficient Computation of Info-Gap Robustness for Finite Element Models

    International Nuclear Information System (INIS)

    Stull, Christopher J.; Hemez, Francois M.; Williams, Brian J.

    2012-01-01

    A recent research effort at LANL proposed info-gap decision theory as a framework by which to measure the predictive maturity of numerical models. Info-gap theory explores the trade-offs between accuracy, that is, the extent to which predictions reproduce the physical measurements, and robustness, that is, the extent to which predictions are insensitive to modeling assumptions. Both accuracy and robustness are necessary to demonstrate predictive maturity. However, conducting an info-gap analysis can present a formidable challenge, from the standpoint of the required computational resources. This is because a robustness function requires the resolution of multiple optimization problems. This report offers an alternative, adjoint methodology to assess the info-gap robustness of Ax = b-like numerical models solved for a solution x. Two situations that can arise in structural analysis and design are briefly described and contextualized within the info-gap decision theory framework. The treatments of the info-gap problems, using the adjoint methodology are outlined in detail, and the latter problem is solved for four separate finite element models. As compared to statistical sampling, the proposed methodology offers highly accurate approximations of info-gap robustness functions for the finite element models considered in the report, at a small fraction of the computational cost. It is noted that this report considers only linear systems; a natural follow-on study would extend the methodologies described herein to include nonlinear systems.

  10. Comparable Senescence Induction in Three-dimensional Human Cartilage Model by Exposure to Therapeutic Doses of X-rays or C-ions.

    Science.gov (United States)

    Hamdi, Dounia Houria; Chevalier, François; Groetz, Jean-Emmanuel; Durantel, Florent; Thuret, Jean-Yves; Mann, Carl; Saintigny, Yannick

    2016-05-01

    Particle therapy using carbon ions (C-ions) has been successfully used in the treatment of tumors resistant to conventional radiation therapy. However, the potential side effects to healthy cartilage exposed to lower linear energy transfer (LET) ions in the beam track before the tumor have not been evaluated. The aim of the present study was to assess the extent of damage after C-ion irradiation in a 3-dimensional (3D) cartilage model close to human homeostasis. Primary human articular chondrocytes from a healthy donor were cultured in a collagen scaffold to construct a physioxic 3D cartilage model. A 2-dimensional (2D) culture was used as a reference. The cells were irradiated with a single dose of a monoenergetic C-ion beam with a LET of approximatively 30 keV/μm. This LET corresponds to the entrance channel of C-ions in the shallow healthy tissues before the spread-out Bragg peak (∼100 keV/μm) during hadron therapy protocols. The same dose of X-rays was used as a reference. Survival, cell death, and senescence assays were performed. As expected, in the 2D culture, C-ions were more efficient than X-rays in reducing cell survival with a relative biological effectiveness of 2.6. This correlated with stronger radiation-induced senescence (two-fold) but not with higher cell death induction. This differential effect was not reflected in the 3D culture. Both ionizing radiation types induced a comparable rate of senescence induction in the 3D model. The greater biological effectiveness of C-ions compared with low LET radiation when evaluated in treatment planning systems might be misevaluated using 2D culture experiments. Radiation-induced senescence is an important factor of potential cartilage attrition. The present data should encourage the scientific community to use relevant models and beams to improve the use of charged particles with better safety for patients. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Comparable Senescence Induction in Three-dimensional Human Cartilage Model by Exposure to Therapeutic Doses of X-rays or C-ions

    Energy Technology Data Exchange (ETDEWEB)

    Hamdi, Dounia Houria; Chevalier, François [Laboratoire d' Accueil et de Recherche avec les Ions Accélérés (LARIA), Institut de Radiobiologie Cellulaire et Moléculaire (IRCM), Direction de la Recherche Fondamentale - DRF, Commissariat à l' Energie Atomique et aux Energies Alternatives, Caen (France); Groetz, Jean-Emmanuel [UMR6249, Université de Franche-Comté, Besançon (France); Durantel, Florent [UMR6252, Centre de Recherche sur les Ions, les Matériaux et la Photonique (CIMAP), Direction de la Recherche Fondamentale (DRF), Commissariat à l' Energie Atomique et aux Energies Alternatives, Caen (France); Thuret, Jean-Yves; Mann, Carl [FRE3377, Service de Biologie Intégrative et Génétique Moléculaire SBIGeM, Institut de Biologie et de Technologies de Saclay (iBiTec-S), Direction de la Recherche Fondamentale (DRF), Commissariat à l' Energie Atomique et aux Energies Alternatives, Gif-sur-Yvette (France); Institut de Biologie Intégrative de la Cellule I2BC / Université Paris Saclay, Gif-sur-Yvette (France); and others

    2016-05-01

    Purpose: Particle therapy using carbon ions (C-ions) has been successfully used in the treatment of tumors resistant to conventional radiation therapy. However, the potential side effects to healthy cartilage exposed to lower linear energy transfer (LET) ions in the beam track before the tumor have not been evaluated. The aim of the present study was to assess the extent of damage after C-ion irradiation in a 3-dimensional (3D) cartilage model close to human homeostasis. Methods and Materials: Primary human articular chondrocytes from a healthy donor were cultured in a collagen scaffold to construct a physioxic 3D cartilage model. A 2-dimensional (2D) culture was used as a reference. The cells were irradiated with a single dose of a monoenergetic C-ion beam with a LET of approximatively 30 keV/μm. This LET corresponds to the entrance channel of C-ions in the shallow healthy tissues before the spread-out Bragg peak (∼100 keV/μm) during hadron therapy protocols. The same dose of X-rays was used as a reference. Survival, cell death, and senescence assays were performed. Results: As expected, in the 2D culture, C-ions were more efficient than X-rays in reducing cell survival with a relative biological effectiveness of 2.6. This correlated with stronger radiation-induced senescence (two-fold) but not with higher cell death induction. This differential effect was not reflected in the 3D culture. Both ionizing radiation types induced a comparable rate of senescence induction in the 3D model. Conclusions: The greater biological effectiveness of C-ions compared with low LET radiation when evaluated in treatment planning systems might be misevaluated using 2D culture experiments. Radiation-induced senescence is an important factor of potential cartilage attrition. The present data should encourage the scientific community to use relevant models and beams to improve the use of charged particles with better safety for patients.

  12. NONLINEAR SPECTRAL IMAGING OF ELASTIC CARTILAGE IN RABBIT EARS

    Directory of Open Access Journals (Sweden)

    JING CHEN

    2013-07-01

    Full Text Available Elastic cartilage in the rabbit external ear is an important animal model with attractive potential value for researching the physiological and pathological states of cartilages especially during wound healing. In this work, nonlinear optical microscopy based on two-photon excited fluorescence and second harmonic generation were employed for imaging and quantifying the intact elastic cartilage. The morphology and distribution of main components in elastic cartilage including cartilage cells, collagen and elastic fibers were clearly observed from the high-resolution two-dimensional nonlinear optical images. The areas of cell nuclei, a parameter related to the pathological changes of normal or abnormal elastic cartilage, can be easily quantified. Moreover, the three-dimensional structure of chondrocytes and matrix were displayed by constructing three-dimensional image of cartilage tissue. At last, the emission spectra from cartilage were obtained and analyzed. We found that the different ratio of collagen over elastic fibers can be used to locate the observed position in the elastic cartilage. The redox ratio based on the ratio of nicotinamide adenine dinucleotide (NADH over flavin adenine dinucleotide (FAD fluorescence can also be calculated to analyze the metabolic state of chondrocytes in different regions. Our results demonstrated that this technique has the potential to provide more accurate and comprehensive information for the physiological states of elastic cartilage.

  13. Preclinical Studies for Cartilage Repair

    Science.gov (United States)

    Hurtig, Mark B.; Buschmann, Michael D.; Fortier, Lisa A.; Hoemann, Caroline D.; Hunziker, Ernst B.; Jurvelin, Jukka S.; Mainil-Varlet, Pierre; McIlwraith, C. Wayne; Sah, Robert L.; Whiteside, Robert A.

    2011-01-01

    Investigational devices for articular cartilage repair or replacement are considered to be significant risk devices by regulatory bodies. Therefore animal models are needed to provide proof of efficacy and safety prior to clinical testing. The financial commitment and regulatory steps needed to bring a new technology to clinical use can be major obstacles, so the implementation of highly predictive animal models is a pressing issue. Until recently, a reductionist approach using acute chondral defects in immature laboratory species, particularly the rabbit, was considered adequate; however, if successful and timely translation from animal models to regulatory approval and clinical use is the goal, a step-wise development using laboratory animals for screening and early development work followed by larger species such as the goat, sheep and horse for late development and pivotal studies is recommended. Such animals must have fully organized and mature cartilage. Both acute and chronic chondral defects can be used but the later are more like the lesions found in patients and may be more predictive. Quantitative and qualitative outcome measures such as macroscopic appearance, histology, biochemistry, functional imaging, and biomechanical testing of cartilage, provide reliable data to support investment decisions and subsequent applications to regulatory bodies for clinical trials. No one model or species can be considered ideal for pivotal studies, but the larger animal species are recommended for pivotal studies. Larger species such as the horse, goat and pig also allow arthroscopic delivery, and press-fit or sutured implant fixation in thick cartilage as well as second look arthroscopies and biopsy procedures. PMID:26069576

  14. Magnetic resonance imaging of hyaline cartilage regeneration in neocartilage graft implantation.

    Science.gov (United States)

    Tan, C F; Ng, K K; Ng, S H; Cheung, Y C

    2003-12-01

    The purpose of this study was to investigate the regenerative potential of hyaline cartilage in a neocartilage graft implant with the aid of MR cartilage imaging using a rabbit model. Surgical osteochondral defects were created in the femoral condyles of 30 mature New Zealand rabbits. The findings of neocartilage in autologous cartilage grafts packed into osteochondral defects were compared with control group of no implant to the osteochondral defect. The outcome of the implantations was correlated with histologic and MR cartilage imaging findings over a 3-month interval. Neocartilage grafts packed into osteochondral defects showed regeneration of hyaline cartilage at the outer layer of the implant using MR cartilage imaging. Fibrosis of fibrocartilage developed at the outer layer of the autologous cartilage graft together with an inflammatory reaction within the osteochondral defect. This animal study provides evidence of the regenerative ability of hyaline cartilage in neocartilage transplants to repair articular cartilage.

  15. A Thin Lens Model for Charged-Particle RF Accelerating Gaps

    Energy Technology Data Exchange (ETDEWEB)

    Allen, Christopher K. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2017-07-01

    Presented is a thin-lens model for an RF accelerating gap that considers general axial fields without energy dependence or other a priori assumptions. Both the cosine and sine transit time factors (i.e., Fourier transforms) are required plus two additional functions; the Hilbert transforms the transit-time factors. The combination yields a complex-valued Hamiltonian rotating in the complex plane with synchronous phase. Using Hamiltonians the phase and energy gains are computed independently in the pre-gap and post-gap regions then aligned using the asymptotic values of wave number. Derivations of these results are outlined, examples are shown, and simulations with the model are presented.

  16. Effect of gradual weight-bearing on regenerated articular cartilage after joint distraction and motion in a rabbit model.

    Science.gov (United States)

    Nishino, Tomofumi; Ishii, Tomoo; Chang, Fei; Yanai, Takaji; Watanabe, Arata; Ogawa, Takeshi; Mishima, Hajime; Nakai, Kenjiro; Ochiai, Naoyuki

    2010-05-01

    The purpose of this study was to clarify the effect of gradual weight bearing (GWB) on regenerating cartilage. We developed a novel external fixation device (EFD) with a controllable weight-bearing system and continuous passive motion (CPM). A full-thickness defect was created by resection of the entire articular surface of the tibial plateau after the EFD was fixed in the rabbit's left knee. In the GWB group (n=6), GWB was started 6 weeks after surgery. In the CPM group (n=6), CPM with EFD was applied in the same manner without GWB. The control group (n=5) received only joint distraction. All rabbits were sacrificed 9 weeks after surgery. The central one-third of the regenerated tissue was assessed and scored blindly using a grading scale modified from the International Cartilage Repair Society visual histological assessment scale. The areas stained by Safranin-O and type II collagen antibody were measured, and the percentage of each area was calculated. There was no significant difference in the histological assessment scale among the groups. The percentage of the type II collagen-positive area was significantly larger in the GWB group than in the CPM group. The present study suggests that optimal mechanical stress, such as GWB, may affect regeneration of cartilage, in vivo. Copyright (c) 2009 Orthopaedic Research Society.

  17. MRI of the cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Imhof, H.; Noebauer-Huhmann, I.-M.; Krestan, C.; Gahleitner, A.; Marlovits, S.; Trattnig, S. [Department of Osteology, Universitaetklinik fuer Radiodiagnostik, AKH-Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Sulzbacher, I. [Universitaetsklinik fuer Pathologie Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria)

    2002-11-01

    With the introduction of fat-suppressed gradient-echo and fast spin-echo (FSE) sequences in clinical routine MR visualization of the hyaline articular cartilage is routinely possible in the larger joints. While 3D gradient-echo with fat suppression allows exact depiction of the thickness and surface of cartilage, FSE outlines the normal and abnormal internal structures of the hyaline cartilage; therefore, both sequences seem to be necessary in a standard MRI protocol for cartilage visualization. In diagnostically ambiguous cases, in which important therapeutic decisions are required, direct MR arthrography is the established imaging standard as an add-on procedure. Despite the social impact and prevalence, until recent years there was a paucity of knowledge about the pathogenesis of cartilage damage. With the introduction of high-resolution MRI with powerful surface coils and fat-suppression techniques, visualization of the articular cartilage is now routinely possible in many joints. After a short summary of the anatomy and physiology of the hyaline cartilage, the different MR imaging methods are discussed and recommended standards are suggested. (orig.)

  18. Application of Gap Model in the Researches of Hotel Services Quality

    Directory of Open Access Journals (Sweden)

    Ivana Blešić

    2011-01-01

    Full Text Available This work presents the research results of the hotel services quality by applying Gap model and SERVQUAL questionnaire. The research was conducted in five health spa centers in the West Morava river valley region during August and September 2008. The reach is aimed at testing of Gap model, i.e. identification of exceptions when the hotel services quality in the observed sample is concerned.

  19. Carprofen inhibits the release of matrix metalloproteinases 1, 3, and 13 in the secretome of an explant model of articular cartilage stimulated with interleukin 1β.

    Science.gov (United States)

    Williams, Adam; Smith, Julia R; Allaway, David; Harris, Pat; Liddell, Susan; Mobasheri, Ali

    2013-01-01

    Arthritic diseases are characterized by the degradation of collagenous and noncollagenous extracellular matrix (ECM) components in articular cartilage. The increased expression and activity of matrix metalloproteinases (MMPs) is partly responsible for cartilage degradation. This study used proteomics to identify inflammatory proteins and catabolic enzymes released in a serum-free explant model of articular cartilage stimulated with the pro-inflammatory cytokine interleukin 1β (IL-1β). Western blotting was used to quantify the release of selected proteins in the presence or absence of the cyclooxygenase-2 specific nonsteroidal pro-inflammatory drug carprofen. Cartilage explant cultures were established by using metacarpophalangeal joints from horses euthanized for purposes other than research. Samples were treated as follows: no treatment (control), IL-1β (10 ng/ml), carprofen (100 μg/ml), and carprofen (100 μg/ml) + IL-1β (10 ng/ml). Explants were incubated (37°C, 5% CO2) over twelve day time courses. High-throughput nano liquid chromatography/mass spectrometry/mass spectrometry uncovered candidate proteins for quantitative western blot analysis. Proteoglycan loss was assessed by using the dimethylmethylene blue (DMMB) assay, which measures the release of sulfated glycosaminoglycans (GAGs). Mass spectrometry identified MMP-1, -3, -13, and the ECM constituents thrombospondin-1 (TSP-1) and fibronectin-1 (FN1). IL-1β stimulation increased the release of all three MMPs. IL-1β also stimulated the fragmentation of FN1 and increased chondrocyte cell death (as assessed by β-actin release). Addition of carprofen significantly decreased MMP release and the appearance of a 60 kDa fragment of FN1 without causing any detectable cytotoxicity to chondrocytes. DMMB assays suggested that carprofen initially inhibited IL-1β-induced GAG release, but this effect was transient. Overall, during the two time courses, GAG release was 58.67% ± 10.91% (SD) for IL-1

  20. Modeling and analysis of mover gaps in tubular moving-magnet linear oscillating motors

    Directory of Open Access Journals (Sweden)

    Xuesong LUO

    2018-05-01

    Full Text Available A tubular moving-magnet linear oscillating motor (TMMLOM has merits of high efficiency and excellent dynamic capability. To enhance the thrust performance, quasi-Halbach permanent magnet (PM arrays are arranged on its mover in the application of a linear electro-hydrostatic actuator in more electric aircraft. The arrays are assembled by several individual segments, which lead to gaps between them inevitably. To investigate the effects of the gaps on the radial magnetic flux density and the machine thrust in this paper, an analytical model is built considering both axial and radial gaps. The model is validated by finite element simulations and experimental results. Distributions of the magnetic flux are described in condition of different sizes of radial and axial gaps. Besides, the output force is also discussed in normal and end windings. Finally, the model has demonstrated that both kinds of gaps have a negative effect on the thrust, and the linear motor is more sensitive to radial ones. Keywords: Air-gap flux density, Linear motor, Mover gaps, Quasi-Halbach array, Thrust output, Tubular moving-magnet linear oscillating motor (TMMLOM

  1. The role of subchondral bone remodeling in osteoarthritis: reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection model.

    Science.gov (United States)

    Hayami, Tadashi; Pickarski, Maureen; Wesolowski, Gregg A; McLane, Julia; Bone, Ashleigh; Destefano, James; Rodan, Gideon A; Duong, Le T

    2004-04-01

    It has been suggested that subchondral bone remodeling plays a role in the progression of osteoarthritis (OA). To test this hypothesis, we characterized the changes in the rat anterior cruciate ligament transection (ACLT) model of OA and evaluated the effects of alendronate (ALN), a potent inhibitor of bone resorption, on cartilage degradation and on osteophyte formation. Male Sprague-Dawley rats underwent ACLT or sham operation of the right knee. Animals were then treated with ALN (0.03 and 0.24 microg/kg/week subcutaneously) and necropsied at 2 or 10 weeks postsurgery. OA changes were evaluated. Subchondral bone volume and osteophyte area were measured by histomorphometric analysis. Coimmunostaining for transforming growth factor beta (TGF beta), matrix metalloproteinase 9 (MMP-9), and MMP-13 was performed to investigate the effect of ALN on local activation of TGF beta. ALN was chondroprotective at both dosages, as determined by histologic criteria and collagen degradation markers. ALN suppressed subchondral bone resorption, which was markedly increased 2 weeks postsurgery, and prevented the subsequent increase in bone formation 10 weeks postsurgery, in the untreated tibial plateau of ACLT joints. Furthermore, ALN reduced the incidence and area of osteophytes in a dose-dependent manner. ALN also inhibited vascular invasion into the calcified cartilage in rats with OA and blocked osteoclast recruitment to subchondral bone and osteophytes. ALN treatment reduced the local release of active TGF beta, possibly via inhibition of MMP-13 expression in articular cartilage and MMP-9 expression in subchondral bone. Subchondral bone remodeling plays an important role in the pathogenesis of OA. ALN or other inhibitors of bone resorption could potentially be used as disease-modifying agents in the treatment of OA.

  2. Increased cartilage type II collagen degradation in patients with osteogenesis imperfecta used as a human model of bone type I collagen alterations.

    Science.gov (United States)

    Rousseau, Jean-Charles; Chevrel, Guillaume; Schott, Anne-Marie; Garnero, Patrick

    2010-04-01

    We investigated whether cartilage degradation is altered in adult patients with mild osteogenesis imperfecta (OI) used as a human model of bone type I collagen-related osteoarthritis (OA). Sixty-four adult patients with OI (39% women, mean age+/-SD: 37+/-12 years) and 64 healthy age-matched controls (54% women, 39+/-7 years) were included. We also compared data in 87 patients with knee OA (73% women, 63+/-8 years, mean disease duration: 6 years) and 291 age-matched controls (80% women, 62+/-10 years). Urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II), a marker of cartilage degradation, urinary helical peptide of type I collagen (Helix-I), a marker of bone resorption, and the urinary ratio between non-isomerised/isomerised (alpha/beta CTX-I) type I collagen C-telopeptide, a marker of type I collagen maturation, were measured. Patients with OI had CTX-II levels similar to those of subjects with knee OA (p=0.89; mean+/-SEM; 460+/-57 ng/mmol Cr for OI group and 547+/-32 ng/mmol Cr for OA group) and significantly higher than both young (144+/-7.8 ng/mmol Cr, p<0.0001) and old controls (247+/-7 ng/mmol Cr, p<0.0001). In patients with OI, increased Helix-I (p<0.0001) and alpha/beta CTX-I (p=0.0067) were independently associated with increased CTX-II and together explained 26% of its variance (p< 0.0001). In patients with knee OA, increased levels of alpha/beta CTX-I ratio were also associated with higher CTX-II levels. Adult patients with OI or knee OA are characterized by increased cartilage type II collagen degradation, which is associated with increased type I collagen degradation for OI and lower type I collagen maturation for both OI and OA. These data suggest that both quantitative and qualitative alterations of bone type I collagen metabolism are involved in increased cartilage degradation in patients with OI or knee OA. Copyright 2009 Elsevier Inc. All rights reserved.

  3. City Logistics Modeling Efforts : Trends and Gaps - A Review

    NARCIS (Netherlands)

    Anand, N.R.; Quak, H.J.; Van Duin, J.H.R.; Tavasszy, L.A.

    2012-01-01

    In this paper, we present a review of city logistics modeling efforts reported in the literature for urban freight analysis. The review framework takes into account the diversity and complexity found in the present-day city logistics practice. Next, it covers the different aspects in the modeling

  4. Storm Water Management Model (SWMM): Performance Review and Gap Analysis

    Science.gov (United States)

    The Storm Water Management Model (SWMM) is a widely used tool for urban drainage design and planning. Hundreds of peer-reviewed articles and conference proceedings have been written describing applications of SWMM. This review focused on collecting information on model performanc...

  5. SAR Observation and Modeling of Gap Winds in the Prince William Sound of Alaska.

    Science.gov (United States)

    Liu, Haibo; Olsson, Peter Q; Volz, Karl

    2008-08-22

    Alaska's Prince William Sound (PWS) is a unique locale tending to have strong gap winds, especially in the winter season. To characterize and understand these strong surface winds, which have great impacts on the local marine and aviation activities, the surface wind retrieval from the Synthetic Aperture Radar data (SAR-wind) is combined with a numerical mesoscale model. Helped with the SAR-wind observations, the mesoscale model is used to study cases of strong winds and relatively weak winds to depict the nature of these winds, including the area of extent and possible causes of the wind regimes. The gap winds from the Wells Passage and the Valdez Arm are the most dominant gap winds in PWS. Though the Valdez Arm is north-south trending and Wells Passage is east-west oriented, gap winds often develop simultaneously in these two places when a low pressure system is present in the Northern Gulf of Alaska. These two gap winds often converge at the center of PWS and extend further out of the Sound through the Hinchinbrook Entrance. The pressure gradients imposed over these areas are the main driving forces for these gap winds. Additionally, the drainage from the upper stream glaciers and the blocking effect of the banks of the Valdez Arm probably play an important role in enhancing the gap wind.

  6. SAR Observation and Modeling of Gap Winds in the Prince William Sound of Alaska

    Directory of Open Access Journals (Sweden)

    Karl Volz

    2008-08-01

    Full Text Available Alaska’s Prince William Sound (PWS is a unique locale tending to have strong gap winds, especially in the winter season. To characterize and understand these strong surface winds, which have great impacts on the local marine and aviation activities, the surface wind retrieval from the Synthetic Aperture Radar data (SAR-wind is combined with a numerical mesoscale model. Helped with the SAR-wind observations, the mesoscale model is used to study cases of strong winds and relatively weak winds to depict the nature of these winds, including the area of extent and possible causes of the wind regimes. The gap winds from the Wells Passage and the Valdez Arm are the most dominant gap winds in PWS. Though the Valdez Arm is north-south trending and Wells Passage is east-west oriented, gap winds often develop simultaneously in these two places when a low pressure system is present in the Northern Gulf of Alaska. These two gap winds often converge at the center of PWS and extend further out of the Sound through the Hinchinbrook Entrance. The pressure gradients imposed over these areas are the main driving forces for these gap winds. Additionally, the drainage from the upper stream glaciers and the blocking effect of the banks of the Valdez Arm probably play an important role in enhancing the gap wind.

  7. Model based optimization of driver-pickup separation for eddy current measurement of gap

    Science.gov (United States)

    Klein, G.; Morelli, J.; Krause, T. W.

    2018-04-01

    The fuel channels in CANDU® (CANada Deuterium Uranium) nuclear reactors consist of a pressure tube (PT) contained within a larger diameter calandria tube (CT). The separation between the tubes, known as the PT-CT gap, ensures PT hydride blisters, which could lead to potential cracking of the PT, do not develop. Therefore, accurate measurements are required to confirm that contact between PT and CT is not imminent. Gap measurement uses an eddy current probe. However this probe is sensitive to lift-off variations, which can adversely affect estimated gap. A validated analytical flat plate model of eddy current response to gap was used to examine the effect of driver-pickup spacing on lift-off and response to gap at a frequency of 4 kHz, which is used for in-reactor measurements. This model was compared against, and shown to have good agreement with, a COMSOL® finite element method (FEM) model. The optimum coil separation, which included the constraint of coil size, was found to be 11 mm, resulting in a phase response between lift-off and response to change in gap of 66°. This work demonstrates the advantages of using analytical models for optimizing coil designs for measurement of parameters that may negatively influence the outcome of an inspection measurement.

  8. Magnetic resonance imaging of cartilage and cartilage repair

    International Nuclear Information System (INIS)

    Verstraete, K.L.; Almqvist, F.; Verdonk, P.; Vanderschueren, G.; Huysse, W.; Verdonk, R.; Verbrugge, G.

    2004-01-01

    Magnetic resonance (MR) imaging of articular cartilage has assumed increased importance because of the prevalence of cartilage injury and degeneration, as well as the development of new surgical and pharmacological techniques to treat damaged cartilage. This article will review relevant aspects of the structure and biochemistry of cartilage that are important for understanding MR imaging of cartilage, describe optimal MR pulse sequences for its evaluation, and review the role of experimental quantitative MR techniques. These MR aspects are applied to clinical scenarios, including traumatic chondral injury, osteoarthritis, inflammatory arthritis, and cartilage repair procedures

  9. Magnetic resonance imaging of cartilage and cartilage repair

    Energy Technology Data Exchange (ETDEWEB)

    Verstraete, K.L. E-mail: koenraad.verstraete@ugent.be; Almqvist, F.; Verdonk, P.; Vanderschueren, G.; Huysse, W.; Verdonk, R.; Verbrugge, G

    2004-08-01

    Magnetic resonance (MR) imaging of articular cartilage has assumed increased importance because of the prevalence of cartilage injury and degeneration, as well as the development of new surgical and pharmacological techniques to treat damaged cartilage. This article will review relevant aspects of the structure and biochemistry of cartilage that are important for understanding MR imaging of cartilage, describe optimal MR pulse sequences for its evaluation, and review the role of experimental quantitative MR techniques. These MR aspects are applied to clinical scenarios, including traumatic chondral injury, osteoarthritis, inflammatory arthritis, and cartilage repair procedures.

  10. Modeling Plasma Formation in a Micro-gap at Microwave Frequency

    Science.gov (United States)

    Bowman, Arthur; Remillard, Stephen

    2013-03-01

    In the presence of a strong electric field, gas molecules become ionized, forming a plasma. The study of this dielectric breakdown at microwave frequency has important applications in improving the operation of radio frequency (RF) devices, where the high electric fields present in small gaps can easily ionize gases like air. A cone and tuner resonant structure was used to induce breakdown of diatomic Nitrogen in adjustable micro-gaps ranging from 13 to 1,156 μm. The electric field for plasma formation exhibited strong pressure dependence in the larger gap sizes, as predicted by previous theoretical and experimental work. Pressure is proportional to the frequency of collision between electrons and molecules, which increases with pressure when the gap is large, but levels off in the micro-gap region. A separate model of the breakdown electric field based on the characteristic diffusion length of the plasma also fit the data poorly for these smaller gap sizes. This may be explained by a hypothesis that dielectric breakdown at and below the 100 μm gap size occurs outside the gap, an argument that is supported by the observation of very high breakdown threshold electric fields in this region. Optical emissions revealed that vibrational and rotational molecular transitions of the first positive electronic system are suppressed in micro-gaps, indicating that transitions into the molecular ground state do not occur in micro-gap plasmas. Acknowledgements: National Science Foundation under NSF-REU Grant No. PHY/DMR-1004811, the Provost's Office of Hope College, and the Hope College Division of Natural and Applied Sciences.

  11. Improved gap conductance model for the TRAC code

    International Nuclear Information System (INIS)

    Hatch, S.W.; Mandell, D.A.

    1980-01-01

    The purpose of the present work, as indicated earlier, is to improve the present constant fuel clad spacing in TRAC-P1A without significantly increasing the computer costs. It is realized that the simple model proposed may not be accurate enough for some cases, but for the initial calculations made the DELTAR model improves the predictions over the constant Δr results of TRAC-P1A and the additional computing costs are negligible

  12. Narrowing the gap between network models and real complex systems

    OpenAIRE

    Viamontes Esquivel, Alcides

    2014-01-01

    Simple network models that focus only on graph topology or, at best, basic interactions are often insufficient to capture all the aspects of a dynamic complex system. In this thesis, I explore those limitations, and some concrete methods of resolving them. I argue that, in order to succeed at interpreting and influencing complex systems, we need to take into account  slightly more complex parts, interactions and information flows in our models.This thesis supports that affirmation with five a...

  13. Modeling impact damper in building frames using GAP element

    Directory of Open Access Journals (Sweden)

    Seyed Mehdi Zahrai

    2017-05-01

    Full Text Available Main effective factor in impact dampers to control vibration is to create disruption in structural oscillation amplitude using small forces induced by auxiliary masses to reduce strong vibrations. So far, modeling of the impact damper has been conducted solely through MATLAB software. Naturally, the functional aspects of this software are limited in research and development aspects compared to the common programs such as SAP2000 and ETABS. In this paper, a Single Degree of Freedom System, SDOF, is first modeled under harmonic loading with maximum amplitude of 0.4g in SAP2000 program. Then, the results are compared with numerical model. In this way, the proposed model is validated and the SDOF system equipped with an impact damper is investigated under the Kobe and Northridge earthquake records using SAP2000 model. Based on obtained results, the system equipped with an impact damper under the Kobe and Northridge earthquakes for structures considered in this study would have better seismic performance in which maximum displacements are reduced 6% and 33% respectively. Finally, impact dampers are modeled in a 4-story building structure with concentric bracing leading to 12% reduction in story drifts.

  14. An alternative model for the origin of gaps in circumstellar disks

    OpenAIRE

    Vorobyov, Eduard I.; Regaly, Zsolt; Guedel, Manuel; Lin, D. N. C.

    2016-01-01

    Motivated by recent observational and numerical studies suggesting that collapsing protostellar cores may be replenished from the local environment, we explore the evolution of protostellar cores submerged in the external counter-rotating environment. These models predict the formation of counter-rotating disks with a deep gap in the gas surface density separating the inner disk (corotating with the star) and the outer counter-rotating disk. The properties of these gaps are compared to those ...

  15. Automatic segmentation of the glenohumeral cartilages from magnetic resonance images

    International Nuclear Information System (INIS)

    Neubert, A.; Yang, Z.; Engstrom, C.; Xia, Y.; Strudwick, M. W.; Chandra, S. S.; Crozier, S.; Fripp, J.

    2016-01-01

    Purpose: Magnetic resonance (MR) imaging plays a key role in investigating early degenerative disorders and traumatic injuries of the glenohumeral cartilages. Subtle morphometric and biochemical changes of potential relevance to clinical diagnosis, treatment planning, and evaluation can be assessed from measurements derived from in vivo MR segmentation of the cartilages. However, segmentation of the glenohumeral cartilages, using approaches spanning manual to automated methods, is technically challenging, due to their thin, curved structure and overlapping intensities of surrounding tissues. Automatic segmentation of the glenohumeral cartilages from MR imaging is not at the same level compared to the weight-bearing knee and hip joint cartilages despite the potential applications with respect to clinical investigation of shoulder disorders. In this work, the authors present a fully automated segmentation method for the glenohumeral cartilages using MR images of healthy shoulders. Methods: The method involves automated segmentation of the humerus and scapula bones using 3D active shape models, the extraction of the expected bone–cartilage interface, and cartilage segmentation using a graph-based method. The cartilage segmentation uses localization, patient specific tissue estimation, and a model of the cartilage thickness variation. The accuracy of this method was experimentally validated using a leave-one-out scheme on a database of MR images acquired from 44 asymptomatic subjects with a true fast imaging with steady state precession sequence on a 3 T scanner (Siemens Trio) using a dedicated shoulder coil. The automated results were compared to manual segmentations from two experts (an experienced radiographer and an experienced musculoskeletal anatomist) using the Dice similarity coefficient (DSC) and mean absolute surface distance (MASD) metrics. Results: Accurate and precise bone segmentations were achieved with mean DSC of 0.98 and 0.93 for the humeral head

  16. Automatic segmentation of the glenohumeral cartilages from magnetic resonance images

    Energy Technology Data Exchange (ETDEWEB)

    Neubert, A., E-mail: ales.neubert@csiro.au [School of Information Technology and Electrical Engineering, University of Queensland, Brisbane 4072, Australia and The Australian E-Health Research Centre, CSIRO Health and Biosecurity, Brisbane 4029 (Australia); Yang, Z. [School of Information Technology and Electrical Engineering, University of Queensland, Brisbane 4072, Australia and Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190 (China); Engstrom, C. [School of Human Movement Studies, University of Queensland, Brisbane 4072 (Australia); Xia, Y.; Strudwick, M. W.; Chandra, S. S.; Crozier, S. [School of Information Technology and Electrical Engineering, University of Queensland, Brisbane 4072 (Australia); Fripp, J. [The Australian E-Health Research Centre, CSIRO Health and Biosecurity, Brisbane, 4029 (Australia)

    2016-10-15

    Purpose: Magnetic resonance (MR) imaging plays a key role in investigating early degenerative disorders and traumatic injuries of the glenohumeral cartilages. Subtle morphometric and biochemical changes of potential relevance to clinical diagnosis, treatment planning, and evaluation can be assessed from measurements derived from in vivo MR segmentation of the cartilages. However, segmentation of the glenohumeral cartilages, using approaches spanning manual to automated methods, is technically challenging, due to their thin, curved structure and overlapping intensities of surrounding tissues. Automatic segmentation of the glenohumeral cartilages from MR imaging is not at the same level compared to the weight-bearing knee and hip joint cartilages despite the potential applications with respect to clinical investigation of shoulder disorders. In this work, the authors present a fully automated segmentation method for the glenohumeral cartilages using MR images of healthy shoulders. Methods: The method involves automated segmentation of the humerus and scapula bones using 3D active shape models, the extraction of the expected bone–cartilage interface, and cartilage segmentation using a graph-based method. The cartilage segmentation uses localization, patient specific tissue estimation, and a model of the cartilage thickness variation. The accuracy of this method was experimentally validated using a leave-one-out scheme on a database of MR images acquired from 44 asymptomatic subjects with a true fast imaging with steady state precession sequence on a 3 T scanner (Siemens Trio) using a dedicated shoulder coil. The automated results were compared to manual segmentations from two experts (an experienced radiographer and an experienced musculoskeletal anatomist) using the Dice similarity coefficient (DSC) and mean absolute surface distance (MASD) metrics. Results: Accurate and precise bone segmentations were achieved with mean DSC of 0.98 and 0.93 for the humeral head

  17. Effect of Transplanting Various Concentrations of a Composite of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells and Hyaluronic Acid Hydrogel on Articular Cartilage Repair in a Rabbit Model.

    Directory of Open Access Journals (Sweden)

    Yong-Beom Park

    Full Text Available Mesenchymal stem cells (MSCs are known to have therapeutic potential for cartilage repair. However, the optimal concentration of MSCs for cartilage repair remains unclear. Therefore, we aimed to explore the feasibility of cartilage repair by human umbilical cord blood-derived MSCs (hUCB-MSCs and to determine the optimal concentrations of the MSCs in a rabbit model.Osteochondral defects were created in the trochlear groove of femur in 55 rabbits. Four experimental groups (11 rabbits/group were treated by transplanting the composite of hUCB-MSCs and HA with various MSCs concentrations (0.1, 0.5, 1.0, and 1.5 x 107 cells/ml. One control group was left untreated. At 4, 8, and 16 weeks post-transplantation, the degree of cartilage repair was evaluated grossly and histologically.Overall, transplanting hUCB-MSCs and HA hydrogel resulted in cartilage repair tissue with better quality than the control without transplantation (P = 0.015 in 0.1, P = 0.004 in 0.5, P = 0.004 in 1.0, P = 0.132 in 1.5 x 107 cells/ml. Interestingly, high cell concentration of hUCB-MSCs (1.5×107 cells/ml was inferior to low cell concentrations (0.1, 0.5, and 1.0 x 107 cells/ml in cartilage repair (P = 0.394,P = 0.041, P = 0.699, respectively. The 0.5 x 107 cells/ml group showed the highest cartilage repair score at 4, 8 and 16 weeks post transplantation, and followed by 0.1x107 cells/ml group or 1.0 x 107 cell/ml group.The results of this study suggest that transplantation of the composite of hUCB-MSCs and HA is beneficial for cartilage repair. In addition, this study shows that optimal MSC concentration needs to be determined for better cartilage repair.

  18. The Extended Parallel Process Model: Illuminating the Gaps in Research

    Science.gov (United States)

    Popova, Lucy

    2012-01-01

    This article examines constructs, propositions, and assumptions of the extended parallel process model (EPPM). Review of the EPPM literature reveals that its theoretical concepts are thoroughly developed, but the theory lacks consistency in operational definitions of some of its constructs. Out of the 12 propositions of the EPPM, a few have not…

  19. Modeling of Wide-Band-Gap Semiconductor Alloys

    National Research Council Canada - National Science Library

    Lambrecht, W

    1998-01-01

    .... The band structure and the total energy properties of LiGaO2 were studied in relation to its possible role as a substrate for GaN growth and as a model system for cation ordering on wurtzite based lattices...

  20. Gap conductance model validation in the TASS/SMR-S code

    International Nuclear Information System (INIS)

    Ahn, Sang-Jun; Yang, Soo-Hyung; Chung, Young-Jong; Bae, Kyoo-Hwan; Lee, Won-Jae

    2011-01-01

    An advanced integral pressurized water reactor, SMART (System-Integrated Modular Advanced ReacTor) has been developed by KAERI (Korea Atomic Energy Research and Institute). The purposes of the SMART are sea water desalination and an electricity generation. For the safety evaluation and performance analysis of the SMART, TASS/SMR-S (Transient And Setpoint Simulation/System-integrated Modular Reactor) code, has been developed. In this paper, the gap conductance model for the calculation of gap conductance has been validated by using another system code, MARS code, and experimental results. In the validation, the behaviors of fuel temperature and gap width are selected as the major parameters. According to the evaluation results, the TASS/SMR-S code predicts well the behaviors of fuel temperatures and gap width variation, compared to the MARS calculation results and experimental data. (author)

  1. Modeling of air-gap membrane distillation process: A theoretical and experimental study

    KAUST Repository

    Alsaadi, Ahmad Salem; Ghaffour, NorEddine; Li, Junde; Gray, Stephen R.; Francis, Lijo; Maab, Husnul; Amy, Gary L.

    2013-01-01

    A one dimensional (1-D) air gap membrane distillation (AGMD) model for flat sheet type modules has been developed. This model is based on mathematical equations that describe the heat and mass transfer mechanisms of a single-stage AGMD process

  2. Filling Landsat ETM+ SLC-off gaps using a segmentation model approach

    Science.gov (United States)

    Maxwell, Susan

    2004-01-01

    The purpose of this article is to present a methodology for filling Landsat Scan Line Corrector (SLC)-off gaps with same-scene spectral data guided by a segmentation model. Failure of the SLC on the Landsat 7 Enhanced Thematic Mapper Plus (ETM+) instrument resulted in a loss of approximately 25 percent of the spectral data. The missing data span across most of the image with scan gaps varying in size from two pixels near the center of the image to 14 pixels along the east and west edges. Even with the scan gaps, the radiometric and geometric qualities of the remaining portions of the image still meet design specifications and therefore contain useful information (see http:// landsat7.usgs.gov for additional information). The U.S. Geological Survey EROS Data Center (EDC) is evaluating several techniques to fill the gaps in SLC-off data to enhance the usability of the imagery (Howard and Lacasse 2004) (PE&RS, August 2004). The method presented here uses a segmentation model approach that allows for same-scene spectral data to be used to fill the gaps. The segment model is generated from a complete satellite image with no missing spectral data (e.g., Landsat 5, Landsat 7 SLCon, SPOT). The model is overlaid on the Landsat SLC-off image, and the missing data within the gaps are then estimated using SLC-off spectral data that intersect the segment boundary. A major advantage of this approach is that the gaps are filled using spectral data derived from the same SLC-off satellite image.

  3. Exponential model normalization for electrical capacitance tomography with external electrodes under gap permittivity conditions

    International Nuclear Information System (INIS)

    Baidillah, Marlin R; Takei, Masahiro

    2017-01-01

    A nonlinear normalization model which is called exponential model for electrical capacitance tomography (ECT) with external electrodes under gap permittivity conditions has been developed. The exponential model normalization is proposed based on the inherently nonlinear relationship characteristic between the mixture permittivity and the measured capacitance due to the gap permittivity of inner wall. The parameters of exponential equation are derived by using an exponential fitting curve based on the simulation and a scaling function is added to adjust the experiment system condition. The exponential model normalization was applied to two dimensional low and high contrast dielectric distribution phantoms by using simulation and experimental studies. The proposed normalization model has been compared with other normalization models i.e. Parallel, Series, Maxwell and Böttcher models. Based on the comparison of image reconstruction results, the exponential model is reliable to predict the nonlinear normalization of measured capacitance in term of low and high contrast dielectric distribution. (paper)

  4. Constraining Gamma-Ray Pulsar Gap Models with a Simulated Pulsar Population

    Science.gov (United States)

    Pierbattista, Marco; Grenier, I. A.; Harding, A. K.; Gonthier, P. L.

    2012-01-01

    With the large sample of young gamma-ray pulsars discovered by the Fermi Large Area Telescope (LAT), population synthesis has become a powerful tool for comparing their collective properties with model predictions. We synthesised a pulsar population based on a radio emission model and four gamma-ray gap models (Polar Cap, Slot Gap, Outer Gap, and One Pole Caustic). Applying gamma-ray and radio visibility criteria, we normalise the simulation to the number of detected radio pulsars by a select group of ten radio surveys. The luminosity and the wide beams from the outer gaps can easily account for the number of Fermi detections in 2 years of observations. The wide slot-gap beam requires an increase by a factor of 10 of the predicted luminosity to produce a reasonable number of gamma-ray pulsars. Such large increases in the luminosity may be accommodated by implementing offset polar caps. The narrow polar-cap beams contribute at most only a handful of LAT pulsars. Using standard distributions in birth location and pulsar spin-down power (E), we skew the initial magnetic field and period distributions in a an attempt to account for the high E Fermi pulsars. While we compromise the agreement between simulated and detected distributions of radio pulsars, the simulations fail to reproduce the LAT findings: all models under-predict the number of LAT pulsars with high E , and they cannot explain the high probability of detecting both the radio and gamma-ray beams at high E. The beaming factor remains close to 1.0 over 4 decades in E evolution for the slot gap whereas it significantly decreases with increasing age for the outer gaps. The evolution of the enhanced slot-gap luminosity with E is compatible with the large dispersion of gamma-ray luminosity seen in the LAT data. The stronger evolution predicted for the outer gap, which is linked to the polar cap heating by the return current, is apparently not supported by the LAT data. The LAT sample of gamma-ray pulsars

  5. Comparison of CPI and GAP models in patients with idiopathic pulmonary fibrosis: a nationwide cohort study.

    Science.gov (United States)

    Lee, Sang Hoon; Park, Jong Sun; Kim, Song Yee; Kim, Dong Soon; Kim, Young Whan; Chung, Man Pyo; Uh, Soo Taek; Park, Choon Sik; Park, Sung Woo; Jeong, Sung Hwan; Park, Yong Bum; Lee, Hong Lyeol; Shin, Jong Wook; Lee, Eun Joo; Lee, Jin Hwa; Jegal, Yangin; Lee, Hyun Kyung; Kim, Yong Hyun; Song, Jin Woo; Park, Moo Suk

    2018-03-19

    The clinical course of idiopathic pulmonary fibrosis (IPF) is difficult to predict, partly owing to its heterogeneity. Composite physiologic index (CPI) and gender-age-physiology (GAP) models are easy-to-use predictors of IPF progression. This study aimed to compare the predictive values of these two models. From 2003 to 2007, the Korean Interstitial Lung Disease (ILD) Study Group surveyed ILD patients using the 2002 ATS/ERS criteria. A total of 832 patients with IPF were enrolled in this study. CPI was calculated as follows: 91.0 - (0.65 × %DL CO ) - [0.53 × %FVC + [0.34 × %FEV 1 . GAP stage was calculated based on gender (0-1 points), age (0-2 points), and two physiologic lung function parameters (0-5 points). The two models had similar significant predictive values for patients with IPF (p GAP for prediction of 1-, 2-, and 3-year mortality in this study. The AUC was higher for surgically diagnosed IPF patients than for clinically diagnosed patients. However, neither CPI nor GAP yielded good predictions of outcomes; the AUC was approximately 0.61~0.65. Although both CPI and GAP stage are significantly useful predictors for IPF, they have limited capability to accurately predict outcomes.

  6. The Influence of Articular Cartilage Thickness Reduction on Meniscus Biomechanics.

    Science.gov (United States)

    Łuczkiewicz, Piotr; Daszkiewicz, Karol; Chróścielewski, Jacek; Witkowski, Wojciech; Winklewski, Pawel J

    2016-01-01

    Evaluation of the biomechanical interaction between meniscus and cartilage in medial compartment knee osteoarthritis. The finite element method was used to simulate knee joint contact mechanics. Three knee models were created on the basis of knee geometry from the Open Knee project. We reduced the thickness of medial cartilages in the intact knee model by approximately 50% to obtain a medial knee osteoarthritis (OA) model. Two variants of medial knee OA model with congruent and incongruent contact surfaces were analysed to investigate the influence of congruency. A nonlinear static analysis for one compressive load case was performed. The focus of the study was the influence of cartilage degeneration on meniscal extrusion and the values of the contact forces and contact areas. In the model with incongruent contact surfaces, we observed maximal compressive stress on the tibial plateau. In this model, the value of medial meniscus external shift was 95.3% greater, while the contact area between the tibial cartilage and medial meniscus was 50% lower than in the congruent contact surfaces model. After the non-uniform reduction of cartilage thickness, the medial meniscus carried only 48.4% of load in the medial compartment in comparison to 71.2% in the healthy knee model. We have shown that the change in articular cartilage geometry may significantly reduce the role of meniscus in load transmission and the contact area between the meniscus and cartilage. Additionally, medial knee OA may increase the risk of meniscal extrusion in the medial compartment of the knee joint.

  7. Development of CHF models for inner and outer RPV gaps in a meltdown severe accident

    International Nuclear Information System (INIS)

    Wang, J.; Tian, W.X.; Feng, K.; Yu, H.X.; Zhang, Y.P.; Su, G.H.; Qiu, S.Z.

    2013-01-01

    Highlights: • A CHF model was developed to predict the CHF in hemispherical narrow gap. • The computed result was validated by the test data of Park and Köhler. • An analytical CHF model was developed to predict the CHF on the outer surface of the lower head. • The predicted CHF was compared with the experimental data of ULPU-V. • Two CHF models developed for the inner and outer CHF predict the CHF well. - Abstract: During a severe accident, the core melt relocates in the lower head and a hemispherical narrow gap may appear between the crust and the lower head because of the different material expansion ratio. The existence of this gap is very important to the integrity of the lower head. Based on the counter current flow limitation (CCFL) between the vapor phase and the liquid phase, a CHF model was developed to predict the CHF in hemispherical narrow gap. The CHF model developed was validated by the test data of Park and Köhler. The effect of key parameters, including the system pressure, radius of melt, and gap size, on the CHF were investigated. And the TMI-2 accident was also calculated by using the CHF formula. Moreover, based on the interface separation model, an analytical CHF model was developed to predict the CHF on the outer surface of the lower head. The predicted CHF was compared with the experimental data of ULPU-V. It indicated that the CHF models developed for the inner and outer CHF could predict the CHF well

  8. Degenerated human articular cartilage at autopsy represents preclinical osteoarthritic cartilage: comparison with clinically defined osteoarthritic cartilage

    NARCIS (Netherlands)

    van Valburg, A. A.; Wenting, M. J.; Beekman, B.; te Koppele, J. M.; Lafeber, F. P.; Bijlsma, J. W.

    1997-01-01

    To investigate whether macroscopically fibrillated human articular knee cartilage observed at autopsy can be considered an early, preclinical phase of osteoarthritis (OA). Histological and biochemical characteristics of 3 types of articular knee cartilage were compared: macroscopically degenerated

  9. Reducing the number of laboratory animals used in tissue engineering research by restricting the variety of animal models. Articular cartilage tissue engineering as a case study.

    Science.gov (United States)

    de Vries, Rob B M; Buma, Pieter; Leenaars, Marlies; Ritskes-Hoitinga, Merel; Gordijn, Bert

    2012-12-01

    The use of laboratory animals in tissue engineering research is an important underexposed ethical issue. Several ethical questions may be raised about this use of animals. This article focuses on the possibilities of reducing the number of animals used. Given that there is considerable debate about the adequacy of the current animal models in tissue engineering research, we investigate whether it is possible to reduce the number of laboratory animals by selecting and using only those models that have greatest predictive value for future clinical application of the tissue engineered product. The field of articular cartilage tissue engineering is used as a case study. Based on a study of the scientific literature and interviews with leading experts in the field, an overview is provided of the animal models used and the advantages and disadvantages of each model, particularly in terms of extrapolation to the human situation. Starting from this overview, it is shown that, by skipping the small models and using only one large preclinical model, it is indeed possible to restrict the number of animal models, thereby reducing the number of laboratory animals used. Moreover, it is argued that the selection of animal models should become more evidence based and that researchers should seize more opportunities to choose or create characteristics in the animal models that increase their predictive value.

  10. Principles of cartilage repair

    CERN Document Server

    Erggelet, Christoph; Mandelbaum, Bert R

    2008-01-01

    Cartilage defects affect patients of all age groups. Surgeons, teamdoctors, general practitioners and physiotherapists alike are expected to provide adequate care. Only individual treatment plans combining a well balanced choice of various options will be successful. Background knowledge, operative and non-operative therapies are described in concise chapters: Articular cartilage biology - Diagnostics - Surgical techniques - Symptomatic and alternative medications - Physiotherapy. Diagnostic findings and surgical procedures are generously illustrated by aquarelles and colour photographs. Recommendations for additional reading, description of important clinical scoring systems and a listing of analytic tools are added for further information.

  11. The junction between hyaline cartilage and engineered cartilage in rabbits.

    Science.gov (United States)

    Komura, Makoto; Komura, Hiroko; Otani, Yushi; Kanamori, Yutaka; Iwanaka, Tadashi; Hoshi, Kazuto; Tsuyoshi, Takato; Tabata, Yasuhiko

    2013-06-01

    Tracheoplasty using costal cartilage grafts to enlarge the tracheal lumen was performed to treat congenital tracheal stenosis. Fibrotic granulomatous tissue was observed at the edge of grafted costal cartilage. We investigated the junction between the native hyaline cartilage and the engineered cartilage plates that were generated by auricular chondrocytes for fabricating the airway. Controlled, prospecive study. In group 1, costal cartilage from New Zealand white rabbits was collected and implanted into a space created in the cervical trachea. In group 2, chondrocytes from auricular cartilages were seeded on absorbable scaffolds. These constructs were implanted in the subcutaneous space. Engineered cartilage plates were then implanted into the trachea after 3 weeks of implantation of the constructs. The grafts in group 1 and 2 were retrieved after 4 weeks. In group 1, histological studies of the junction between the native hyaline cartilage and the implanted costal cartilage demonstrated chondrogenic tissue in four anastomoses sides out of the 10 examined. In group 2, the junction between the native trachea and the engineered cartilage showed neocartilage tissue in nine anastomoses sides out of 10. Engineered cartilage may be beneficial for engineered airways, based on the findings of the junction between the native and engineered grafts. Copyright © 2012 The American Laryngological, Rhinological and Otological Society, Inc.

  12. Mechanical testing of hydrogels in cartilage tissue engineering: beyond the compressive modulus.

    Science.gov (United States)

    Xiao, Yinghua; Friis, Elizabeth A; Gehrke, Stevin H; Detamore, Michael S

    2013-10-01

    Injuries to articular cartilage result in significant pain to patients and high medical costs. Unfortunately, cartilage repair strategies have been notoriously unreliable and/or complex. Biomaterial-based tissue-engineering strategies offer great promise, including the use of hydrogels to regenerate articular cartilage. Mechanical integrity is arguably the most important functional outcome of engineered cartilage, although mechanical testing of hydrogel-based constructs to date has focused primarily on deformation rather than failure properties. In addition to deformation testing, as the field of cartilage tissue engineering matures, this community will benefit from the addition of mechanical failure testing to outcome analyses, given the crucial clinical importance of the success of engineered constructs. However, there is a tremendous disparity in the methods used to evaluate mechanical failure of hydrogels and articular cartilage. In an effort to bridge the gap in mechanical testing methods of articular cartilage and hydrogels in cartilage regeneration, this review classifies the different toughness measurements for each. The urgency for identifying the common ground between these two disparate fields is high, as mechanical failure is ready to stand alongside stiffness as a functional design requirement. In comparing toughness measurement methods between hydrogels and cartilage, we recommend that the best option for evaluating mechanical failure of hydrogel-based constructs for cartilage tissue engineering may be tensile testing based on the single edge notch test, in part because specimen preparation is more straightforward and a related American Society for Testing and Materials (ASTM) standard can be adopted in a fracture mechanics context.

  13. Contact mechanics for poroelastic, fluid-filled media, with application to cartilage.

    Science.gov (United States)

    Persson, B N J

    2016-12-21

    I study a simple contact mechanics model for a poroelastic, fluid-filled solid squeezed against a rigid, randomly rough substrate. I study how the fluid is squeezed out from the interface, and how the area of contact, and the average interfacial separation, change with time. I present numerical results relevant for a human cartilage. I show that for a fluid filled poroelastic solid the probability of cavitation (and the related wear as the cavities implode), and dynamical scraping (defined below and in Hutt and Persson, J. Chem. Phys. 144, 124903 (2016)), may be suppressed by fluid flow from the poroelastic solid into the (roughness induced) interfacial gap between the solids.

  14. Follistatin Alleviates Synovitis and Articular Cartilage Degeneration Induced by Carrageenan

    Directory of Open Access Journals (Sweden)

    Jun Yamada

    2014-01-01

    Full Text Available Activins are proinflammatory cytokines which belong to the TGFβ superfamily. Follistatin is an extracellular decoy receptor for activins. Since both activins and follistatin are expressed in articular cartilage, we hypothesized that activin-follistatin signaling participates in the process of joint inflammation and cartilage degeneration. To test this hypothesis, we examined the effects of follistatin in a carrageenan-induced mouse arthritis model. Synovitis induced by intra-articular injection of carrageenan was significantly alleviated by preinjection with follistatin. Macrophage infiltration into the synovial membrane was significantly reduced in the presence of follistatin. In addition, follistatin inhibited proteoglycan erosion induced by carrageenan in articular cartilage. These data indicate that activin-follistatin signaling is involved in joint inflammation and cartilage homeostasis. Our data suggest that follistatin can be a new therapeutic target for inflammation-induced articular cartilage degeneration.

  15. Interacting gaps model, dynamics of order book, and stock-market fluctuations

    Czech Academy of Sciences Publication Activity Database

    Svorenčík, A.; Slanina, František

    2007-01-01

    Roč. 57, - (2007), s. 453-462 ISSN 1434-6028 R&D Projects: GA MŠk 1P04OCP10.001 Institutional research plan: CEZ:AV0Z10100520 Keywords : interacting gaps model * dynamics of order book * stock - market fluctuations Subject RIV: BE - Theoretical Physics Impact factor: 1.356, year: 2007

  16. Improved variational estimates for the mass gap in the 2-dimensional XY-model

    International Nuclear Information System (INIS)

    Patkos, A.; Hari Dass, N.D.

    1982-07-01

    The variational estimate obtained recently for the mass gap of the 2-dimensional XY-model is improved by extending the treatment to higher powers of the transfer operator. The relativistic dispersion relation for single particle states of low momentum is also verified. (Auth.)

  17. Air gap membrane distillation. 2. Model validation and hollow fibre module performance analysis

    NARCIS (Netherlands)

    Guijt, C.M.; Meindersma, G.W.; Reith, T.; de Haan, A.B.

    2005-01-01

    In this paper the experimental results of counter current flow air gap membrane distillation experiments are presented and compared with predictive model calculations. Measurements were carried out with a cylindrical test module containing a single hollow fibre membrane in the centre and a

  18. A model for the direct-to-indirect band-gap transition in monolayer ...

    Indian Academy of Sciences (India)

    Abstract. A monolayer of MoSe2 is found to be a direct band-gap semiconductor. We show, ... In order to determine appropriate basis for the tight-binding model, the Mo and Se ..... RD thanks the Council of Scientific and Industrial Research.

  19. Fit Gap Analysis – The Role of Business Process Reference Models

    Directory of Open Access Journals (Sweden)

    Dejan Pajk

    2013-12-01

    Full Text Available Enterprise resource planning (ERP systems support solutions for standard business processes such as financial, sales, procurement and warehouse. In order to improve the understandability and efficiency of their implementation, ERP vendors have introduced reference models that describe the processes and underlying structure of an ERP system. To select and successfully implement an ERP system, the capabilities of that system have to be compared with a company’s business needs. Based on a comparison, all of the fits and gaps must be identified and further analysed. This step usually forms part of ERP implementation methodologies and is called fit gap analysis. The paper theoretically overviews methods for applying reference models and describes fit gap analysis processes in detail. The paper’s first contribution is its presentation of a fit gap analysis using standard business process modelling notation. The second contribution is the demonstration of a process-based comparison approach between a supply chain process and an ERP system process reference model. In addition to its theoretical contributions, the results can also be practically applied to projects involving the selection and implementation of ERP systems.

  20. Assessment of hyaline cartilage matrix composition using near infrared spectroscopy.

    Science.gov (United States)

    Palukuru, Uday P; McGoverin, Cushla M; Pleshko, Nancy

    2014-09-01

    Changes in the composition of the extracellular matrix (ECM) are characteristic of injury or disease in cartilage tissue. Various imaging modalities and biochemical techniques have been used to assess the changes in cartilage tissue but lack adequate sensitivity, or in the case of biochemical techniques, result in destruction of the sample. Fourier transform near infrared (FT-NIR) spectroscopy has shown promise for the study of cartilage composition. In the current study NIR spectroscopy was used to identify the contributions of individual components of cartilage in the NIR spectra by assessment of the major cartilage components, collagen and chondroitin sulfate, in pure component mixtures. The NIR spectra were obtained using homogenous pellets made by dilution with potassium bromide. A partial least squares (PLS) model was calculated to predict composition in bovine cartilage samples. Characteristic absorbance peaks between 4000 and 5000 cm(-1) could be attributed to components of cartilage, i.e. collagen and chondroitin sulfate. Prediction of the amount of collagen and chondroitin sulfate in tissues was possible within 8% (w/dw) of values obtained by gold standard biochemical assessment. These results support the use of NIR spectroscopy for in vitro and in vivo applications to assess matrix composition of cartilage tissues, especially when tissue destruction should be avoided. Copyright © 2014. Published by Elsevier B.V.

  1. Development of a simplified fuel-cladding gap conductance model for nuclear feedback calculation in 16x16 FA

    International Nuclear Information System (INIS)

    Yoo, Jong Sung; Park, Chan Oh; Park, Yong Soo

    1995-01-01

    The accurate determination of the fuel-cladding gap conductance as functions of rod burnup and power level may be a key to the design and safety analysis of a reactor. The incorporation of a sophisticated gap conductance model into nuclear design code for computing thermal hydraulic feedback effect has not been implemented mainly because of computational inefficiency due to complicated behavior of gap conductance. To avoid the time-consuming iteration scheme, simplification of the gap conductance model is done for the current design model. The simplified model considers only the heat conductance contribution to the gap conductance. The simplification is made possible by direct consideration of the gap conductivity depending on the composition of constituent gases in the gap and the fuel-cladding gap size from computer simulation of representative power histories. The simplified gap conductance model is applied to the various fuel power histories and the predicted gap conductances are found to agree well with the results of the design model

  2. When is cartilage repair successful?

    International Nuclear Information System (INIS)

    Raudner, M.; Roehrich, S.; Zalaudek, M.; Trattnig, S.; Schreiner, M.M.

    2017-01-01

    Focal cartilage lesions are a cause of long-term disability and morbidity. After cartilage repair, it is crucial to evaluate long-term progression or failure in a reproducible, standardized manner. This article provides an overview of the different cartilage repair procedures and important characteristics to look for in cartilage repair imaging. Specifics and pitfalls are pointed out alongside general aspects. After successful cartilage repair, a complete, but not hypertrophic filling of the defect is the primary criterion of treatment success. The repair tissue should also be completely integrated to the surrounding native cartilage. After some months, the transplants signal should be isointense compared to native cartilage. Complications like osteophytes, subchondral defects, cysts, adhesion and chronic bone marrow edema or joint effusion are common and have to be observed via follow-up. Radiological evaluation and interpretation of postoperative changes should always take the repair method into account. (orig.) [de

  3. MR imaging of articular cartilage

    International Nuclear Information System (INIS)

    Schaefer, F.K.W.; Muhle, C.; Heller, M.; Brossmann, J.

    2001-01-01

    MR imaging has evolved to the best non-invasive method for the evaluation of articular cartilage. MR imaging helps to understand the structure and physiology of cartilage, and to diagnose cartilage lesions. Numerous studies have shown high accuracy and reliability concerning detection of cartilage lesions and early changes in both structure and biochemistry. High contrast-to-noise ratio and high spatial resolution are essential for analysis of articular cartilage. Fat-suppressed 3D-T 1 weighted gradient echo and T 2 -weighted fast spin echo sequences with or without fat suppression are recommended for clinical routine. In this article the anatomy and pathology of hyaline articular cartilage and the complex imaging characteristics of hyaline cartilage will be discussed. (orig.) [de

  4. Behaviour of the energy gap in a model of Josephson coupled Bose-Einstein condensates

    International Nuclear Information System (INIS)

    Tonel, A P; Links, J; Foerster, A

    2005-01-01

    In this work we investigate the energy gap between the ground state and the first excited state in a model of two single-mode Bose-Einstein condensates coupled via Josephson tunnelling. The energy gap is never zero when the tunnelling interaction is non-zero. The gap exhibits no local minimum below a threshold coupling which separates a delocalized phase from a self-trapping phase that occurs in the absence of the external potential. Above this threshold point one minimum occurs close to the Josephson regime, and a set of minima and maxima appear in the Fock regime. Expressions for the position of these minima and maxima are obtained. The connection between these minima and maxima and the dynamics for the expectation value of the relative number of particles is analysed in detail. We find that the dynamics of the system changes as the coupling crosses these points

  5. Lubrication and cartilage.

    Science.gov (United States)

    Wright, V; Dowson, D

    1976-02-01

    Mechanisms of lubrication of human synovial joints have been analysed in terms of the operating conditions of the joint, the synovial fluid and articular cartilage. In the hip and knee during a walking cycle the load may rise up to four times body weight. In the knee on dropping one metre the load may go up to 25 time body weight. The elastic modulus of cartilage is similar to that of the synthetic rubber of a car tyre. The cartilage surface is rough and in elderly specimens the centre line average is 2-75 mum. The friction force generated in reciprocating tests shows that both cartilage and synovial fluid are important in lubrication. The viscosity-shear rate relationships of normal synovial fluid show that it is non-Newtonian. Osteoarthrosic fluid is less so and rheumatoid fluid is more nearly Newtonian. Experiments with hip joints in a pendulum machine show that fluid film lubrication obtains at some phases of joint action. Boundary lubrication prevails under certain conditions and has been examined with a reciprocating friction machine. Digestion of hyaluronate does not alter the boundary lubrication, but trypsin digestion does. Surface active substances (lauryl sulphate and cetyl 3-ammonium bromide) give a lubricating ability similar to that of synovial fluid. The effectiveness of the two substances varies with pH.

  6. Chondroptosis in Alkaptonuric Cartilage

    Science.gov (United States)

    Millucci, Lia; Giorgetti, Giovanna; Viti, Cecilia; Ghezzi, Lorenzo; Gambassi, Silvia; Braconi, Daniela; Marzocchi, Barbara; Paffetti, Alessandro; Lupetti, Pietro; Bernardini, Giulia; Orlandini, Maurizio

    2015-01-01

    Alkaptonuria (AKU) is a rare genetic disease that affects the entire joint. Current standard of treatment is palliative and little is known about AKU physiopathology. Chondroptosis, a peculiar type of cell death in cartilage, has been so far reported to occur in osteoarthritis, a rheumatic disease that shares some features with AKU. In the present work, we wanted to assess if chondroptosis might also occur in AKU. Electron microscopy was used to detect the morphological changes of chondrocytes in damaged cartilage distinguishing apoptosis from its variant termed chondroptosis. We adopted histological observation together with Scanning Electron Microscopy and Transmission Electron Microscopy to evaluate morphological cell changes in AKU chondrocytes. Lipid peroxidation in AKU cartilage was detected by fluorescence microscopy. Using the above‐mentioned techniques, we performed a morphological analysis and assessed that AKU chondrocytes undergo phenotypic changes and lipid oxidation, resulting in a progressive loss of articular cartilage structure and function, showing typical features of chondroptosis. To the best of our knowledge, AKU is the second chronic pathology, following osteoarthritis, where chondroptosis has been documented. Our results indicate that Golgi complex plays an important role in the apoptotic process of AKU chondrocytes and suggest a contribution of chondroptosis in AKU pathogenesis. These findings also confirm a similarity between osteoarthritis and AKU. J. Cell. Physiol. 230: 1148–1157, 2015. © 2014 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. PMID:25336110

  7. INJURED ARTICULAR CARTILAGE REPAIR

    Directory of Open Access Journals (Sweden)

    Ariana Barlič

    2008-02-01

    Surveys show that the most frequently used surgical methods are mosaicplasty and bonemarrow stimulation with microfracturing. The efficacy of the autologous chondrocyte implantationmethod should be superior to microfracturing on a long run. Especially when(regeneration of the hyaline cartilage instead of fibrous tissue (fibrocartilage is concerned.However, it has not been scientifically proved yet

  8. A survey of quality gap of Khoramabad medical emergency services using SERVQUAL model

    Directory of Open Access Journals (Sweden)

    gholamreza Toushmal

    2015-05-01

    Full Text Available Background : Awareness of perceptions and expectations of receivers of health centers services, as well as determination of gap between these two subjects can play an important role in better services rendering of these centers. Thise survey was conducted to evaluate quality of emergency centers of Khorramabad city by use of SERVQUAL model in 2012. Materials and Methods: This analytic-descriptive research was carried out on 400 people receiving services of Khorramabad emergency centers, selected using continuous sampling method. Data was gathered using standard SERVQUAL questionnaire and then analyzed by SPSS software, descriptive and inferential statistics such as Kruskal-wallis, paired T test And ANOVA. Results: The results showed that there was negative gap of quality in all five dimensions of services (sensible thing, guarantee and trust, responsibility, and empathy. The most quality gap was in empathy aspect and the least belonged to politeness and trust, and this gap among all dimensions, exception for trust, was statistically significant. But no significant statistical relation was found between age, sex and educational level and quality gap score. Conclusion: Expectation of customers in all dimensions was higher than their perceptions, and it should promote the quality of all dimensions, specially empathy. It is suggested to evaluate services quality in these centers and other centers periodically to promote their quality of services.

  9. Inhibition of cartilage degradation and suppression of PGE2 and MMPs expression by pomegranate fruit extract in a model of posttraumatic osteoarthritis.

    Science.gov (United States)

    Akhtar, Nahid; Khan, Nazir M; Ashruf, Omer S; Haqqi, Tariq M

    2017-01-01

    Osteoarthritis (OA) is characterized by cartilage degradation in the affected joints. Pomegranate fruit extract (PFE) inhibits cartilage degradation in vitro. The aim of this study was to determine whether oral consumption of PFE inhibits disease progression in rabbits with surgically induced OA. OA was surgically induced in the tibiofemoral joints of adult New Zealand White rabbits. In one group, animals were fed PFE in water for 8 wk postsurgery. In the second group, animals were fed PFE for 2 wk before surgery and for 8 wk postsurgery. Histologic assessment and scoring of the cartilage was per Osteoarthritis Research Society International guidelines. Gene expression and matrix metalloproteinases (MMP) activity were determined using quantitative reverse transcriptase polymerase chain reaction and fluorometric assay, respectively. Interleukin (IL)-1 β, MMP-13, IL-6, prostaglandin (PG)E 2 , and type II collagen (COL2A1) levels in synovial fluid/plasma/culture media were quantified using enzyme-linked immunosorbent assay. Expression of active caspase-3 and poly (ADP-ribose) polymerase p85 was determined by immunohistochemistry. Effect of PFE and inhibitors of MMP-13, mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB was studied in IL-1 β-stimulated rabbit articular chondrocytes. Safranin-O-staining and chondrocyte cluster formation was significantly reduced in the anterior cruciate ligament transaction plus PFE fed groups. Expression of MMP-3, MMP-9, and MMP-13 mRNA was higher in the cartilage of rabbits given water alone but was significantly lower in the animals fed PFE. PFE-fed rabbits had lower IL-6, MMP-13, and PGE 2 levels in the synovial fluid and plasma, respectively, and showed higher expression of aggrecan and COL2A1 mRNA. Significantly higher numbers of chondrocytes were positive for markers of apoptosis in the joints of rabbits with OA given water only compared with those in the PFE-fed groups. PFE pretreatment significantly

  10. The Three-Dimensional Velocity Distribution of Wide Gap Taylor-Couette Flow Modelled by CFD

    Directory of Open Access Journals (Sweden)

    David Shina Adebayo

    2016-01-01

    Full Text Available A numerical investigation is conducted for the flow between two concentric cylinders with a wide gap, relevant to bearing chamber applications. This wide gap configuration has received comparatively less attention than narrow gap journal bearing type geometries. The flow in the gap between an inner rotating cylinder and an outer stationary cylinder has been modelled as an incompressible flow using an implicit finite volume RANS scheme with the realisable k-ε model. The model flow is above the critical Taylor number at which axisymmetric counterrotating Taylor vortices are formed. The tangential velocity profiles at all axial locations are different from typical journal bearing applications, where the velocity profiles are quasilinear. The predicted results led to two significant findings of impact in rotating machinery operations. Firstly, the axial variation of the tangential velocity gradient induces an axially varying shear stress, resulting in local bands of enhanced work input to the working fluid. This is likely to cause unwanted heat transfer on the surface in high torque turbomachinery applications. Secondly, the radial inflow at the axial end-wall boundaries is likely to promote the transport of debris to the junction between the end-collar and the rotating cylinder, causing the build-up of fouling in the seal.

  11. Prediction of the fuel failure following a large LOCA using modified gap heat transfer model

    International Nuclear Information System (INIS)

    Lee, K.M.; Lee, N.H.; Huh, J.Y.; Seo, S.K.; Choi, J.H.

    1995-01-01

    The modified Ross and Stoute gap heat transfer model in the ELOCA.Mk5 code for CANDU safety analysis is based on a simplified thermal deformation model. A review on a series of recent experiments reveals that fuel pellets crack, relocate, and are eccentrically positioned within the sheath rather than solid concentric cylinders. In this study, more realistic offset crap conductance model is implemented in the code to estimate the fuel failure thresholds usincr the transient conditions of a 100% Reactor Outlet Header (ROH) break LOCA. Based on the offset gap conductance model, the total release of I-131 from the failed fuel elements in the core is reduced from 3876 TBq to 3283 TBq to increase margin for dose limit. (author)

  12. Technical Report: Correlation Between the Repair of Cartilage and Subchondral Bone in an Osteochondral Defect Using Bilayered, Biodegradable Hydrogel Composites

    NARCIS (Netherlands)

    Lu, S.; Lam, J.; Trachtenberg, J.E.; Lee, E.J.; Seyednejad, H.; Beucken, J.J.J.P van den; Tabata, Y.; Kasper, F.K.; Scott, D.W.; Wong, M.E.; Jansen, J.A.; Mikos, A.G.

    2015-01-01

    The present work investigated correlations between cartilage and subchondral bone repair, facilitated by a growth factor-delivering scaffold, in a rabbit osteochondral defect model. Histological scoring indices and microcomputed tomography morphological parameters were used to evaluate cartilage and

  13. Equivalence and precision of knee cartilage morphometry between different segmentation teams, cartilage regions, and MR acquisitions

    Science.gov (United States)

    Schneider, E; Nevitt, M; McCulloch, C; Cicuttini, FM; Duryea, J; Eckstein, F; Tamez-Pena, J

    2012-01-01

    Objective To compare precision and evaluate equivalence of femorotibial cartilage volume (VC) and mean cartilage thickness (ThCtAB.Me) from independent segmentation teams using identical MR images from three series: sagittal 3D Dual Echo in the Steady State (DESS), coronal multi-planar reformat (DESS-MPR) of DESS and coronal 3D Fast Low Angle SHot (FLASH). Design 19 subjects underwent test-retest MR imaging at 3 Tesla. Four teams segmented the cartilage using prospectively defined plate regions and rules. Mixed models analysis of the pooled data were used to evaluate the effect of acquisition, team and plate on precision and Pearson correlations and mixed models to evaluate equivalence. Results Segmentation team differences dominated measurement variability in most cartilage regions for all image series. Precision of VC and ThCtAB.Me differed significantly by team and cartilage plate, but not between FLASH and DESS. Mean values of VC and ThCtAB.Me differed by team (P<0.05) for DESS, FLASH and DESS-MPR, FLASH VC was 4–6% larger than DESS in the medial tibia and lateral central femur, and FLASH ThCtAB.Me was 5–6% larger in the medial tibia, but 4–8% smaller in the medial central femur. Correlations betweenDESS and FLASH for VC and ThCtAB.Me were high (r=0.90–0.97), except for DESS versus FLASH medial central femur ThCtAB.Me (r=0.81–0.83). Conclusions Cartilage morphology metrics from different image contrasts had similar precision, were generally equivalent, and may be combined for cross-sectional analyses if potential systematic offsets are accounted for. Data from different teams should not be pooled unless equivalence is demonstrated for cartilage metrics of interest. PMID:22521758

  14. Photoactivated methods for enabling cartilage-to-cartilage tissue fixation

    Science.gov (United States)

    Sitterle, Valerie B.; Roberts, David W.

    2003-06-01

    The present study investigates whether photoactivated attachment of cartilage can provide a viable method for more effective repair of damaged articular surfaces by providing an alternative to sutures, barbs, or fibrin glues for initial fixation. Unlike artificial materials, biological constructs do not possess the initial strength for press-fitting and are instead sutured or pinned in place, typically inducing even more tissue trauma. A possible alternative involves the application of a photosensitive material, which is then photoactivated with a laser source to attach the implant and host tissues together in either a photothermal or photochemical process. The photothermal version of this method shows potential, but has been almost entirely applied to vascularized tissues. Cartilage, however, exhibits several characteristics that produce appreciable differences between applying and refining these techniques when compared to previous efforts involving vascularized tissues. Preliminary investigations involving photochemical photosensitizers based on singlet oxygen and electron transfer mechanisms are discussed, and characterization of the photodynamic effects on bulk collagen gels as a simplified model system using FTIR is performed. Previous efforts using photothermal welding applied to cartilaginous tissues are reviewed.

  15. High fat diet accelerates cartilage repair in DBA/1 mice.

    Science.gov (United States)

    Wei, Wu; Bastiaansen-Jenniskens, Yvonne M; Suijkerbuijk, Mathijs; Kops, Nicole; Bos, Pieter K; Verhaar, Jan A N; Zuurmond, Anne-Marie; Dell'Accio, Francesco; van Osch, Gerjo J V M

    2017-06-01

    Obesity is a well-known risk factor for osteoarthritis, but it is unknown what it does on cartilage repair. Here we investigated whether a high fat diet (HFD) influences cartilage repair in a mouse model of cartilage repair. We fed DBA/1 mice control or HFD (60% energy from fat). After 2 weeks, a full thickness cartilage defect was made in the trochlear groove. Mice were sacrificed, 1, 8, and 24 weeks after operation. Cartilage repair was evaluated on histology. Serum glucose, insulin and amyloid A were measured 24 h before operation and at endpoints. Immunohistochemical staining was performed on synovium and adipose tissue to evaluate macrophage infiltration and phenotype. One week after operation, mice on HFD had defect filling with fibroblast-like cells and more cartilage repair as indicated by a lower Pineda score. After 8 weeks, mice on a HFD still had a lower Pineda score. After 24 weeks, no mice had complete cartilage repair and we did not detect a significant difference in cartilage repair between diets. Bodyweight was increased by HFD, whereas serum glucose, amyloid A and insulin were not influenced. Macrophage infiltration and phenotype in adipose tissue and synovium were not influenced by HFD. In contrast to common wisdom, HFD accelerated intrinsic cartilage repair in DBA/1 mice on the short term. Resistance to HFD induced inflammatory and metabolic changes could be associated with accelerated cartilage repair. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1258-1264, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  16. Advances in cartilage tissue engineering : in vitro

    NARCIS (Netherlands)

    E.W. Mandl (Erik)

    2004-01-01

    textabstractWithin the body three subtypes of cartilage can be distinguished: hyaline cartilage, elastic cartilage and fibrocartilage. Hyaline cartilage is the predominant subtype and is mainly located in articular joints and in less extent in the nasal septum and cricoid. Elastic cartilage can be

  17. Assessing climate change effects on long-term forest development: adjusting growth, phenology, and seed production in a gap model

    NARCIS (Netherlands)

    Meer, van der P.J.; Jorritsma, I.T.M.; Kramer, K.

    2002-01-01

    The sensitivity of forest development to climate change is assessed using a gap model. Process descriptions in the gap model of growth, phenology, and seed production were adjusted for climate change effects using a detailed process-based growth modeland a regression analysis. Simulation runs over

  18. Overview of existing cartilage repair technology.

    Science.gov (United States)

    McNickle, Allison G; Provencher, Matthew T; Cole, Brian J

    2008-12-01

    Currently, autologous chondrocyte implantation and osteochondral grafting bridge the gap between palliation of cartilage injury and resurfacing via arthroplasty. Emerging technologies seek to advance first generation techniques and accomplish several goals including predictable outcomes, cost-effective technology, single-stage procedures, and creation of durable repair tissue. The biologic pipeline represents a variety of technologies including synthetics, scaffolds, cell therapy, and cell-infused matrices. Synthetic constructs, an alternative to biologic repair, resurface a focal chondral defect rather than the entire joint surface. Scaffolds are cell-free constructs designed as a biologic "net" to augment marrow stimulation techniques. Minced cartilage technology uses stabilized autologous or allogeneic fragments in 1-stage transplantation. Second and third generation cell-based methods include alternative membranes, chondrocyte seeding, and culturing onto scaffolds. Despite the promising early results of these products, significant technical obstacles remain along with unknown long-term durability. The vast array of developing technologies has exceptional promise and the potential to revolutionize the cartilage treatment algorithm within the next decade.

  19. A mathematical model of a three-gap thyratron simulating turn-on

    International Nuclear Information System (INIS)

    Barnes, M. J.; Wait, G.D.

    1993-06-01

    Kicker magnets are required for all ring-to-ring transfers in the 5 rings of the proposed KAON factory synchrotron. The kick must rise/fall from 1% to 99% of full strength during the time interval of gaps created in the beam (80 ns to 160 ns) so that the beam can be extracted with minimum losses. Approximately one-third of the injection and extraction kicker magnets will operate continuously at a rate of 50 pulses per second: the others operate at 10 pulses per second. The kicker magnet PFN voltages will be in the range 50kV to 80kV, hence multi-gap thyratrons will be used for the injection and extraction kicker systems. Displacement current arising from turn-on of a multi-gap thyratron flows in the external circuit and can thus increase the effective rise-time of the kick. A mathematical model of a three-gap thyratron, which includes the drift spaces, has been developed for simulating turn-on, and is described in this paper. The thyratron model has been used to investigate ways to suppress the effects of displacement current on the kick, and to reduce thyratron switching loss. A ferrite saturating inductor may be connected adjacent to each thyratron to reduce switching loss, so that thyratron life can be extended and the kick rise-time improved. This inductor can also be used to reduce the effect of anode displacement current during turn-on of a multi-gap thyratron. The research has culminated in a predicted kick rise time (1% to 99%) of less than 50 ns for a TRIUMF 10 cell prototype kicker magnet. The proposed improvements are currently being implemented on our prototype kicker system. (author). 15 refs., 11 figs

  20. Confocal arthroscopy-based patient-specific constitutive models of cartilaginous tissues - II: prediction of reaction force history of meniscal cartilage specimens.

    Science.gov (United States)

    Taylor, Zeike A; Kirk, Thomas B; Miller, Karol

    2007-10-01

    The theoretical framework developed in a companion paper (Part I) is used to derive estimates of mechanical response of two meniscal cartilage specimens. The previously developed framework consisted of a constitutive model capable of incorporating confocal image-derived tissue microstructural data. In the present paper (Part II) fibre and matrix constitutive parameters are first estimated from mechanical testing of a batch of specimens similar to, but independent from those under consideration. Image analysis techniques which allow estimation of tissue microstructural parameters form confocal images are presented. The constitutive model and image-derived structural parameters are then used to predict the reaction force history of the two meniscal specimens subjected to partially confined compression. The predictions are made on the basis of the specimens' individual structural condition as assessed by confocal microscopy and involve no tuning of material parameters. Although the model does not reproduce all features of the experimental curves, as an unfitted estimate of mechanical response the prediction is quite accurate. In light of the obtained results it is judged that more general non-invasive estimation of tissue mechanical properties is possible using the developed framework.

  1. Surgical induction, histological evaluation, and MRI identification of cartilage necrosis in the distal femur in goats to model early lesions of osteochondrosis.

    Science.gov (United States)

    Tóth, F; Nissi, M J; Wang, L; Ellermann, J M; Carlson, C S

    2015-02-01

    Identify and interrupt the vascular supply to portions of the distal femoral articular-epiphyseal cartilage complex (AECC) in goat kids to induce cartilage necrosis, characteristic of early lesions of osteochondrosis (OC); then utilize magnetic resonance imaging (MRI) to identify necrotic areas of cartilage. Distal femora were perfused and cleared in goat kids of various ages to visualize the vascular supply to the distal femoral AECC. Vessels located on the axial aspect of the medial femoral condyle (MFC) and on the abaxial side of the lateral trochlear ridge were transected in eight 4- to 5-day-old goats to induce cartilage necrosis. Goats were euthanized 1, 2, 3, 4, 5, 6, 9, and 10 weeks post operatively and operated stifles were harvested. Adiabatic T1ρ relaxation time maps of the harvested distal femora were generated using a 9.4 T MR scanner, after which samples were evaluated histologically. Interruption of the vascular supply to the MFC caused lesions of cartilage necrosis in 6/8 goat kids that were demonstrated histologically. Adiabatic T1ρ relaxation time mapping identified these areas of cartilage necrosis in 5/6 cases. No significant findings were detected after transection of perichondrial vessels supplying the lateral trochlear ridge. Cartilage necrosis, characteristic of early OC, can be induced by interrupting the vascular supply to the distal femoral AECC in goat kids. The ability of high field MRI to identify these areas of cartilage necrosis in the AECC using the adiabatic T1ρ sequence suggests that this technique may be useful in the future for the early diagnosis of OC. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  2. Modeling imperfectly repaired system data via grey differential equations with unequal-gapped times

    International Nuclear Information System (INIS)

    Guo Renkuan

    2007-01-01

    In this paper, we argue that grey differential equation models are useful in repairable system modeling. The arguments starts with the review on GM(1,1) model with equal- and unequal-spaced stopping time sequence. In terms of two-stage GM(1,1) filtering, system stopping time can be partitioned into system intrinsic function and repair effect. Furthermore, we propose an approach to use grey differential equation to specify a semi-statistical membership function for system intrinsic function times. Also, we engage an effort to use GM(1,N) model to model system stopping times and the associated operating covariates and propose an unequal-gapped GM(1,N) model for such analysis. Finally, we investigate the GM(1,1)-embed systematic grey equation system modeling of imperfectly repaired system operating data. Practical examples are given in step-by-step manner to illustrate the grey differential equation modeling of repairable system data

  3. The effect of fixed charge density and cartilage swelling on mechanics of knee joint cartilage during simulated gait.

    Science.gov (United States)

    Räsänen, Lasse P; Tanska, Petri; Zbýň, Štefan; van Donkelaar, Corrinus C; Trattnig, Siegfried; Nieminen, Miika T; Korhonen, Rami K

    2017-08-16

    The effect of swelling of articular cartilage, caused by the fixed charge density (FCD) of proteoglycans, has not been demonstrated on knee joint mechanics during simulated walking before. In this study, the influence of the depth-wise variation of FCD was investigated on the internal collagen fibril strains and the mechanical response of the knee joint cartilage during gait using finite element (FE) analysis. The FCD distribution of tibial cartilage was implemented from sodium ( 23 Na) MRI into a 3-D FE-model of the knee joint ("Healthy model"). For comparison, models with decreased FCD values were created according to the decrease in FCD associated with the progression of osteoarthritis (OA) ("Early OA" and "Advanced OA" models). In addition, a model without FCD was created ("No FCD" model). The effect of FCD was studied with five different collagen fibril network moduli of cartilage. Using the reference fibril network moduli, the decrease in FCD from "Healthy model" to "Early OA" and "Advanced OA" models resulted in increased axial strains (by +2 and +6%) and decreased fibril strains (by -3 and -13%) throughout the stance, respectively, calculated as mean values through cartilage depth in the tibiofemoral contact regions. Correspondingly, compared to the "Healthy model", the removal of the FCD altogether in "NoFCD model" resulted in increased mean axial strains by +16% and decreased mean fibril strains by -24%. This effect was amplified as the fibril network moduli were decreased by 80% from the reference. Then mean axial strains increased by +6, +19 and +49% and mean fibril strains decreased by -9, -20 and -32%, respectively. Our results suggest that the FCD in articular cartilage has influence on cartilage responses in the knee during walking. Furthermore, the FCD is suggested to have larger impact on cartilage function as the collagen network degenerates e.g. in OA. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Cracked pellet gap conductance model: comparison of FRAP-S calculations with measured fuel centerline temperatures

    International Nuclear Information System (INIS)

    MacDonald, P.E.; Broughton, J.M.

    1975-03-01

    Fuel pellets crack extensively upon irradiation due both to thermal stresses induced by power changes and at high burnup, to accumulation of gaseous fission products at grain boundaries. Therefore, the distance between the fuel and cladding will be circumferentially nonuniform; varying between that calculated for intact operating fuel pellets and essentially zero (fuel segments in contact with the cladding wall). A model for calculation of temperatures in cracked pellets is proposed wherein the effective fuel to cladding gap conductance is calculated by taking a zero pressure contact conductance in series with an annular gap conductance. Comparisons of predicted and measured fuel centerline temperatures at beginning of life and at extended burnup are presented in support of the model. 13 references

  5. Lattice Hamiltonian approach to the massless Schwinger model. Precise extraction of the mass gap

    International Nuclear Information System (INIS)

    Cichy, Krzysztof; Poznan Univ.; Kujawa-Cichy, Agnieszka; Szyniszewski, Marcin; Manchester Univ.

    2012-12-01

    We present results of applying the Hamiltonian approach to the massless Schwinger model. A finite basis is constructed using the strong coupling expansion to a very high order. Using exact diagonalization, the continuum limit can be reliably approached. This allows to reproduce the analytical results for the ground state energy, as well as the vector and scalar mass gaps to an outstanding precision better than 10 -6 %.

  6. Lattice Hamiltonian approach to the massless Schwinger model. Precise extraction of the mass gap

    Energy Technology Data Exchange (ETDEWEB)

    Cichy, Krzysztof [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany). John von Neumann-Inst. fuer Computing NIC; Poznan Univ. (Poland). Faculty of Physics; Kujawa-Cichy, Agnieszka [Poznan Univ. (Poland). Faculty of Physics; Szyniszewski, Marcin [Poznan Univ. (Poland). Faculty of Physics; Manchester Univ. (United Kingdom). NOWNano DTC

    2012-12-15

    We present results of applying the Hamiltonian approach to the massless Schwinger model. A finite basis is constructed using the strong coupling expansion to a very high order. Using exact diagonalization, the continuum limit can be reliably approached. This allows to reproduce the analytical results for the ground state energy, as well as the vector and scalar mass gaps to an outstanding precision better than 10{sup -6} %.

  7. Optical response in Weyl semimetal in model with gapped Dirac phase

    Science.gov (United States)

    Mukherjee, S. P.; Carbotte, J. P.

    2017-10-01

    We study the optical properties of Weyl semimetal (WSM) in a model which features, in addition to the usual term describing isolated Dirac cones proportional to the Fermi velocity v F, a gap term m and a Zeeman spin-splitting term b with broken time reversal symmetry. Transport is treated within Kubo formalism and particular attention is payed to the modifications that result from a finite m and b. We consider how these modifications change when a finite residual scattering rate \

  8. Towards Regeneration of Articular Cartilage

    Science.gov (United States)

    Iwamoto, Masahiro; Ohta, Yoichi; Larmour, Colleen; Enomoto-Iwamoto, Motomi

    2014-01-01

    Articular cartilage is classified into permanent hyaline cartilage and has significant differences in structure, extracelluar matrix components, gene expression profile, and mechanical property from transient hyaline cartilage found in growth plate. In the process of synovial joint development, articular cartilage is originated from the interzone, developing at the edge of the cartilaginous anlagen, it establishes zonal structure over time and supports smooth movement of the synovial joint through life. The cascade actions of key regulators such as Wnts, GDF5, Erg, and PTHLH coordinate sequential steps of articular cartilage formation. Articular chondrocytes are restrictedly controlled not to differentiate into a hypertrophic stage by autocrine and paracrine factors and extracerllular matrix microenvironment, but retain potential to undergo hypertrophy. The basal calcified zone of articular cartilage is connected with subchondral bone, but not invaded by blood vessels nor replaced by bone, which is highly contrasted with the growth plate. Articular cartilage has limited regenerative capacity, but likely possesses and potentially uses intrinsic stem cell source in the superficial layer, Ranvier’s groove, the intra-articular tissues such as synovium and fat pad, and marrow below the subchondral bone. Considering the biological views on articular cartilage, several important points are raised for regeneration of articular cartilage. We should evaluate the nature of regenerated cartilage as permanent hyaline cartilage and not just hyaline cartilage. We should study how a hypertrophic phenotype of transplanted cells can be lastingly suppressed in regenerating tissue. Further, we should develop the methods and reagents to activate recruitment of intrinsic stem/progenitor cells into the damaged site. PMID:24078496

  9. Peculiarities in Ankle Cartilage.

    Science.gov (United States)

    Kraeutler, Matthew J; Kaenkumchorn, Tanyaporn; Pascual-Garrido, Cecilia; Wimmer, Markus A; Chubinskaya, Susanna

    2017-01-01

    Posttraumatic osteoarthritis (PTOA) is the most common form of osteoarthritis (OA) of the ankle joint. PTOA occurs as a result of several factors, including the poor regenerative capacity of hyaline articular cartilage as well as increased contact stresses following trauma. The purpose of this article is to review the epidemiology, pathogenesis, and potential targets for treatment of PTOA in the ankle joint. Previous reviews primarily addressed clinical approaches to ankle PTOA, while the focus of the current article will be specifically on the newly acquired knowledge of the cellular mechanisms that drive PTOA in the ankle joint and means for potential targeted therapeutics that might halt the progression of cartilage degeneration and/or improve the outcome of surgical interventions. Three experimental treatment strategies are discussed in this review: (1) increasing the anabolic potential of chondrocytes through treatment with growth factors such as bone morphogenetic protein-7; (2) limiting chondrocyte cell death either through the protection of cell membrane with poloxamer 188 or inhibiting activity of intracellular proteases, caspases, which are responsible for cell death by apoptosis; and (3) inhibiting catabolic/inflammatory responses of chondrocytes by treating them with anti-inflammatory agents such as tumor necrosis factor-α antagonists. Future studies should focus on identifying the appropriate timing for treatment and an appropriate combination of anti-inflammatory, chondro- and matrix-protective biologics to limit the progression of trauma-induced cartilage degeneration and prevent the development of PTOA in the ankle joint.

  10. Incorporating shrub and snag specific LiDAR data into GAP wildlife models

    Science.gov (United States)

    Teresa J Lorenz; Kerri T Vierling; Jody Vogeler; Jeffrey Lonneker; Jocelyn Aycrigg

    2015-01-01

    The U.S. Geological Survey’s Gap Analysis Program (hereafter, GAP) is a nationally based program that uses land cover, vertebrate distributions, and land ownership to identify locations where gaps in conservation coverage exist, and GAP products are commonly used by government agencies, nongovernmental organizations, and private citizens. The GAP land-cover...

  11. Cartilage damage involving extrusion of mineralisable matrix from the articular calcified cartilage and subchondral bone

    Directory of Open Access Journals (Sweden)

    A Boyde

    2011-05-01

    Full Text Available Arthropathy of the distal articular surfaces of the third metacarpal (Mc3 and metatarsal (Mt3 bones in the Thoroughbred racehorse (Tb is a natural model of repetitive overload arthrosis. We describe a novel pathology that affects the articular calcified cartilage (ACC and subchondral bone (SCB and which is associated with hyaline articular cartilage degeneration. Parasagittal slices cut from the palmar quadrant of the distal condyles of the left Mc3/Mt3 of 39 trained Tbs euthanased for welfare reasons were imaged by point projection microradiography, and backscattered electron (BSE scanning electron microscopy (SEM, light microscopy, and confocal scanning light microscopy. Mechanical properties were studied by nanoindentation. Data on the horses' training and racing career were also collected. Highly mineralised projections were observed extending from cracks in the ACC mineralising front into the hyaline articular cartilage (HAC up to two-thirds the thickness of the HAC, and were associated with focal HAC surface fibrillation directly overlying their site. Nanoindentation identified this extruded matrix to be stiffer than any other mineralised phase in the specimen by a factor of two. The presence of projections was associated with a higher cartilage Mankin histology score (P < 0.02 and increased amounts of gross cartilage loss pathologically on the condyle (P < 0.02. Presence of projections was not significantly associated with: total number of racing seasons, age of horse, amount of earnings, number of days in training, total distance galloped in career, or presence of wear lines.

  12. Cartilage grafting in nasal reconstruction.

    Science.gov (United States)

    Immerman, Sara; White, W Matthew; Constantinides, Minas

    2011-02-01

    Nasal reconstruction after resection for cutaneous malignancies poses a unique challenge to facial plastic surgeons. The nose, a unique 3-D structure, not only must remain functional but also be aesthetically pleasing to patients. A complete understanding of all the layers of the nose and knowledge of available cartilage grafting material is necessary. Autogenous material, namely septal, auricular, and costal cartilage, is the most favored material in a free cartilage graft or a composite cartilage graft. All types of material have advantages and disadvantages that should guide the most appropriate selection to maximize the functional and cosmetic outcomes for patients. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Modeling of air-gap membrane distillation process: A theoretical and experimental study

    KAUST Repository

    Alsaadi, Ahmad Salem

    2013-06-03

    A one dimensional (1-D) air gap membrane distillation (AGMD) model for flat sheet type modules has been developed. This model is based on mathematical equations that describe the heat and mass transfer mechanisms of a single-stage AGMD process. It can simulate AGMD modules in both co-current and counter-current flow regimes. The theoretical model was validated using AGMD experimental data obtained under different operating conditions and parameters. The predicted water vapor flux was compared to the flux measured at five different feed water temperatures, two different feed water salinities, three different air gap widths and two MD membranes with different average pore sizes. This comparison showed that the model flux predictions are strongly correlated with the experimental data, with model predictions being within +10% of the experimentally determined values. The model was then used to study and analyze the parameters that have significant effect on scaling-up the AGMD process such as the effect of increasing the membrane length, and feed and coolant flow rates. The model was also used to analyze the maximum thermal efficiency of the AGMD process by tracing changes in water production rate and the heat input to the process along the membrane length. This was used to understand the gain in both process production and thermal efficiency for different membrane surface areas and the resultant increases in process capital and water unit cost. © 2013 Elsevier B.V.

  14. Endogenous implementation of technology gap in energy optimization models-a systematic analysis within TIMES G5 model

    International Nuclear Information System (INIS)

    Rout, Ullash K.; Fahl, Ulrich; Remme, Uwe; Blesl, Markus; Voss, Alfred

    2009-01-01

    Evaluation of global diffusion potential of learning technologies and their timely specific cost development across regions is always a challenging issue for the future technology policy preparation. Further the process of evaluation gains interest especially by endogenous treatment of energy technologies under uncertainty in learning rates with technology gap across the regions in global regional cluster learning approach. This work devised, implemented, and examined new methodologies on technology gaps (a practical problem), using two broad concepts of knowledge deficit and time lag approaches in global learning, applying the floor cost approach methodology. The study was executed in a multi-regional, technology-rich and long horizon bottom-up linear energy system model on The Integrated MARKAL EFOM System (TIMES) framework. Global learning selects highest learning technologies in maximum uncertainty of learning rate scenario, whereas any form of technology gap retards the global learning process and discourages the technologies deployment. Time lag notions of technology gaps prefer heavy utilization of learning technologies in developed economies for early reduction of specific cost. Technology gaps of any kind should be reduced among economies through the promotion and enactment of various policies by governments, in order to utilize the technological resources by mass deployment to combat ongoing climate change.

  15. THE SAVINGS-TRADE-FISCAL GAP MODEL: APPLICATION IN SELECTED WEST AFRICAN STATES

    Directory of Open Access Journals (Sweden)

    Efayena Oba Obukohwo

    2017-07-01

    Full Text Available With most African economies experiencing adverse economic misalignment in recent times, the need of enhancing the growth process cannot be overemphasized. Using a typical Savings-Trade-Fiscal Gap Model, the paper employed panel data estimation method to examine the impact of savings, trade and fiscal gap on economic growth of 15 West African countries. The paper finds a negative relationship between net trade and economic growth, while savings and government expenditure impacts positively on economic performance. The paper thus, among recommended that it is appropriate for all countries to eliminate fiscal dominance from monetary policy-making, reduce public debt and establish institutions that promote and encourage counter-cyclical fiscal policy, develop their financial systems, establish credibility in fiscal and monetary policy-making as well as encourage trade.

  16. Characterization of a cartilage-like engineered biomass using a self-aggregating suspension culture model: molecular composition using FT-IRIS.

    Science.gov (United States)

    Kim, Minwook; Kraft, Jeffrey J; Volk, Andrew C; Pugarelli, Joan; Pleshko, Nancy; Dodge, George R

    2011-12-01

    Maintenance of chondrocyte phenotype and robust expression and organization of macromolecular components with suitable cartilaginous properties is an ultimate goal in cartilage tissue engineering. We used a self-aggregating suspension culture (SASC) method to produce an engineered cartilage, "cartilage tissue analog" (CTA). With an objective of understanding the stability of phenotype of the CTA over long periods, we cultured chondrocytes up to 4 years and analyzed the matrix. Both early (eCTAs) (6 months) and aged (aCTAs) (4 years) showed type II collagen throughout with higher concentrations near the edge. Using Fourier transform-infrared imaging spectroscopy (FT-IRIS), proteoglycan/collagen ratio of eCTA was 2.8 times greater than native cartilage at 1 week, but the ratio was balanced to native level (p = 0.017) by 36 weeks. Surprisingly, aCTAs maintained the hyaline characteristics, but there was evidence of calcification within the tissue with a distinct range of intensities. Mineral/matrix ratio of those aCTA with "intensive" calcification was significantly higher (p = 0.017) than the "partial," but when compared to native bone the ratio of "intensive" aCTAs was 2.4 times lower. In this study we utilized the imaging approach of FT-IRIS and have shown that a biomaterial formed is compositionally closely related to natural cartilage for long periods in culture. We show that this culture platform can maintain a CTA for extended periods of time (4 years) and under those conditions signs of mineralization can be found. This method of cartilage tissue engineering is a promising method to generate cartilaginous biomaterial and may have potential to be utilized in both cartilage and boney repairs. Copyright © 2011 Orthopaedic Research Society.

  17. How the Human Capital Model Explains Why the Gender Wage Gap Narrowed

    OpenAIRE

    Polachek, Solomon W.

    2004-01-01

    This paper explores secular changes in women?s pay relative to men?s pay. It shows how the human capital model predicts a smaller gender wage gap as male-female lifetime work expectations become more similar. The model explains why relative female wages rose almost unabated from 1890 to the early-1990s in the United States (with the exception of about 1940-1980), and why this relative wage growth tapered off since 1993. In addition to the US, the paper presents evidence from nine other countr...

  18. The relation between mass-gap amplitudes and critical exponents in the Heisenberg model

    International Nuclear Information System (INIS)

    Alcaraz, F.C.; Felicio, J.R.D. de

    1985-01-01

    A recent result concerning the universality of the ratio of mass-gap amplitudes using the well known 1-D Heisenberg model which is the quantum version of the two-dimensional eight-vertex model is discussed. The believed extended scaling relation (x sub(p) = x sub(is an element of)/4) relating the polarization and energy anomalous dimensions is confirmed. The exponent, α, ν, γ sub(m) and γ sub(p) is also obtained by usual phenomenological renormalization group methods. (Author) [pt

  19. Analysis of functional importance of binding sites in the Drosophila gap gene network model.

    Science.gov (United States)

    Kozlov, Konstantin; Gursky, Vitaly V; Kulakovskiy, Ivan V; Dymova, Arina; Samsonova, Maria

    2015-01-01

    The statistical thermodynamics based approach provides a promising framework for construction of the genotype-phenotype map in many biological systems. Among important aspects of a good model connecting the DNA sequence information with that of a molecular phenotype (gene expression) is the selection of regulatory interactions and relevant transcription factor bindings sites. As the model may predict different levels of the functional importance of specific binding sites in different genomic and regulatory contexts, it is essential to formulate and study such models under different modeling assumptions. We elaborate a two-layer model for the Drosophila gap gene network and include in the model a combined set of transcription factor binding sites and concentration dependent regulatory interaction between gap genes hunchback and Kruppel. We show that the new variants of the model are more consistent in terms of gene expression predictions for various genetic constructs in comparison to previous work. We quantify the functional importance of binding sites by calculating their impact on gene expression in the model and calculate how these impacts correlate across all sites under different modeling assumptions. The assumption about the dual interaction between hb and Kr leads to the most consistent modeling results, but, on the other hand, may obscure existence of indirect interactions between binding sites in regulatory regions of distinct genes. The analysis confirms the previously formulated regulation concept of many weak binding sites working in concert. The model predicts a more or less uniform distribution of functionally important binding sites over the sets of experimentally characterized regulatory modules and other open chromatin domains.

  20. Multi-linear model set design based on the nonlinearity measure and H-gap metric.

    Science.gov (United States)

    Shaghaghi, Davood; Fatehi, Alireza; Khaki-Sedigh, Ali

    2017-05-01

    This paper proposes a model bank selection method for a large class of nonlinear systems with wide operating ranges. In particular, nonlinearity measure and H-gap metric are used to provide an effective algorithm to design a model bank for the system. Then, the proposed model bank is accompanied with model predictive controllers to design a high performance advanced process controller. The advantage of this method is the reduction of excessive switch between models and also decrement of the computational complexity in the controller bank that can lead to performance improvement of the control system. The effectiveness of the method is verified by simulations as well as experimental studies on a pH neutralization laboratory apparatus which confirms the efficiency of the proposed algorithm. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

  1. Numerical modeling of the thermoelectric cooler with a complementary equation for heat circulation in air gaps

    Science.gov (United States)

    Fang, En; Wu, Xiaojie; Yu, Yuesen; Xiu, Junrui

    2017-03-01

    In this paper, a numerical model is developed by combining thermodynamics with heat transfer theory. Taking inner and external multi-irreversibility into account, it is with a complementary equation for heat circulation in air gaps of a steady cooling system with commercial thermoelectric modules operating in refrigeration mode. With two modes concerned, the equation presents the heat flowing through air gaps which forms heat circulations between both sides of thermoelectric coolers (TECs). In numerical modelling, a TEC is separated as two temperature controlled constant heat flux reservoirs in a thermal resistance network. In order to obtain the parameter values, an experimental apparatus with a commercial thermoelectric cooler was built to characterize the performance of a TEC with heat source and sink assembly. At constant power dissipation, steady temperatures of heat source and both sides of the thermoelectric cooler were compared with those in a standard numerical model. The method displayed that the relationship between Φf and the ratio Φ_{c}'/Φ_{c} was linear as expected. Then, for verifying the accuracy of proposed numerical model, the data in another system were recorded. It is evident that the experimental results are in good agreement with simulation(proposed model) data at different heat transfer rates. The error is small and mainly results from the instabilities of thermal resistances with temperature change and heat flux, heat loss of the device vertical surfaces and measurements.

  2. Xiphoid Process-Derived Chondrocytes: A Novel Cell Source for Elastic Cartilage Regeneration

    Science.gov (United States)

    Nam, Seungwoo; Cho, Wheemoon; Cho, Hyunji; Lee, Jungsun

    2014-01-01

    Reconstruction of elastic cartilage requires a source of chondrocytes that display a reliable differentiation tendency. Predetermined tissue progenitor cells are ideal candidates for meeting this need; however, it is difficult to obtain donor elastic cartilage tissue because most elastic cartilage serves important functions or forms external structures, making these tissues indispensable. We found vestigial cartilage tissue in xiphoid processes and characterized it as hyaline cartilage in the proximal region and elastic cartilage in the distal region. Xiphoid process-derived chondrocytes (XCs) showed superb in vitro expansion ability based on colony-forming unit fibroblast assays, cell yield, and cumulative cell growth. On induction of differentiation into mesenchymal lineages, XCs showed a strong tendency toward chondrogenic differentiation. An examination of the tissue-specific regeneration capacity of XCs in a subcutaneous-transplantation model and autologous chondrocyte implantation model confirmed reliable regeneration of elastic cartilage regardless of the implantation environment. On the basis of these observations, we conclude that xiphoid process cartilage, the only elastic cartilage tissue source that can be obtained without destroying external shape or function, is a source of elastic chondrocytes that show superb in vitro expansion and reliable differentiation capacity. These findings indicate that XCs could be a valuable cell source for reconstruction of elastic cartilage. PMID:25205841

  3. Regulators of articular cartilage homeostasis

    NARCIS (Netherlands)

    Leijten, Jeroen Christianus Hermanus

    2012-01-01

    Prevention of hypertrophic differentiation is essential for successful cartilage repair strategies. Although this process is essential for longitudinal growth, it also is part of degenerative cartilage diseases such as osteoarthiritis. Moreover, it limits the use of cell types prone to this process

  4. A vision on the future of articular cartilage repair

    Directory of Open Access Journals (Sweden)

    M Cucchiarini

    2014-05-01

    Full Text Available An AO Foundation (Davos, Switzerland sponsored workshop "Cell Therapy in Cartilage Repair" from the Symposium "Where Science meets Clinics" (September 5-7, 2013, Davos gathered leaders from medicine, science, industry, and regulatory organisations to debate the vision of cell therapy in articular cartilage repair and the measures that could be taken to narrow the gap between vision and current practice. Cell-based therapy is already in clinical use to enhance the repair of cartilage lesions, with procedures such as microfracture and articular chondrocyte implantation. However, even though long term follow up is good from a clinical perspective and some of the most rigorous randomised controlled trials in the regenerative medicine/orthopaedics field show beneficial effect, none of these options have proved successful in restoring the original articular cartilage structure and functionality in patients so far. With the remarkable recent advances in experimental research in cell biology (new sources for chondrocytes, stem cells, molecular biology (growth factors, genes, biomaterials, biomechanics, and translational science, a combined effort between scientists and clinicians with broad expertise may allow development of an improved cell therapy for cartilage repair. This position paper describes the current state of the art in the field to help define a procedure adapted to the clinical situation for upcoming translation in the patient.

  5. A vorticity transport model to restore spatial gaps in velocity data

    Science.gov (United States)

    Ameli, Siavash; Shadden, Shawn

    2017-11-01

    Often measurements of velocity data do not have full spatial coverage in the probed domain or near boundaries. These gaps can be due to missing measurements or masked regions of corrupted data. These gaps confound interpretation, and are problematic when the data is used to compute Lagrangian or trajectory-based analyses. Various techniques have been proposed to overcome coverage limitations in velocity data such as unweighted least square fitting, empirical orthogonal function analysis, variational interpolation as well as boundary modal analysis. In this talk, we present a vorticity transport PDE to reconstruct regions of missing velocity vectors. The transport model involves both nonlinear anisotropic diffusion and advection. This approach is shown to preserve the main features of the flow even in cases of large gaps, and the reconstructed regions are continuous up to second order. We illustrate results for high-frequency radar (HFR) measurements of the ocean surface currents as this is a common application of limited coverage. We demonstrate that the error of the method is on the same order of the error of the original velocity data. In addition, we have developed a web-based gateway for data restoration, and we will demonstrate a practical application using available data. This work is supported by the NSF Grant No. 1520825.

  6. Trends in Education Excellence Gaps: A 12-Year International Perspective via the Multilevel Model for Change

    Science.gov (United States)

    Rutkowski, David; Rutkowski, Leslie; Plucker, Jonathan A.

    2012-01-01

    A recent study in the USA documented the existence and growth of "excellence gaps" among students. These gaps are similar to the minimum competency achievement gaps that proliferate in policy discussions in many Western countries, but excellence gaps focus on the highest level of achievement rather than minimum competency. We extend this…

  7. The Role of Cartilage Stress in Patellofemoral Pain

    Science.gov (United States)

    Besier, Thor F.; Pal, Saikat; Draper, Christine E.; Fredericson, Michael; Gold, Garry E.; Delp, Scott L.; Beaupré, Gary S.

    2015-01-01

    Purpose Elevated cartilage stress has been identified as a potential mechanism for retropatellar pain; however, there are limited data in the literature to support this mechanism. Females are more likely to develop patellofemoral pain than males, yet the causes of this dimorphism are unclear. We used experimental data and computational modeling to determine whether patients with patellofemoral pain had elevated cartilage stress compared to pain-free controls and test the hypothesis that females exhibit greater cartilage stress than males. Methods We created finite element models of 24 patients with patellofemoral pain (11 males; 13 females) and 16 pain-free controls (8 males; 8 females) to estimate peak patellar cartilage stress (strain energy density) during a stair climb activity. Simulations took into account cartilage morphology from MRI, joint posture from weight-bearing MRI, and muscle forces from an EMG-driven model. Results We found no difference in peak patellar strain energy density between patellofemoral pain (1.9 ± 1.23 J/m3) and control subjects (1.66 ± 0.75 J/m3, p=0.52). Females exhibited greater cartilage stress compared to males (2.2 vs 1.3 J/m3, respectively, p=0.0075), with large quadriceps muscle forces (3.7BW females vs 3.3BW males) and 23% smaller joint contact area (females: 467 ± 59 mm2 vs males: 608 ± 95mm2). Conclusion Patellofemoral pain patients did not display significantly greater patellar cartilage stress compared to pain-free controls; however, there was a great deal of subject variation. Females exhibited greater peak cartilage stress compared to males, which might explain the greater prevalence of patellofemoral pain in females compared to males but other mechanical and biological factors are clearly involved in this complex pathway to pain. PMID:25899103

  8. Extra-virgin olive oil diet and mild physical activity prevent cartilage degeneration in an osteoarthritis model: an in vivo and in vitro study on lubricin expression.

    Science.gov (United States)

    Musumeci, Giuseppe; Trovato, Francesca Maria; Pichler, Karin; Weinberg, Annelie Martina; Loreto, Carla; Castrogiovanni, Paola

    2013-12-01

    Mediterranean diet includes a relatively high fat consumption mostly from monounsaturated fatty acids mainly provided by olive oil, the principal source of culinary and dressing fat. The beneficial effects of olive oil have been widely studied and could be due to its phytochemicals, which have been shown to possess anti-inflammatory properties. Lubricin is a chondroprotective glycoprotein and it serves as a critical boundary lubricant between opposing cartilage surfaces. A joint injury causes an initial flare of cytokines, which decreases lubricin expression and predisposes to cartilage degeneration such as osteoarthritis. The aim of this study was to evaluate the role of extra-virgin olive oil diet and physical activity on inflammation and expression of lubricin in articular cartilage of rats after injury. In this study we used histomorphometric, histological, immunocytochemical, immunohistochemical, western blot and biochemical analysis for lubricin and interleukin-1 evaluations in the cartilage and in the synovial fluid. We report the beneficial effect of physical activity (treadmill training) and extra-virgin olive oil supplementation, on the articular cartilage. The effects of anterior cruciate ligament transection decrease drastically the expression of lubricin and increase the expression of interleukin-1 in rats, while after physical activity and extra-virgin olive oil supplemented diet, the values return to a normal level compared to the control group. With our results we can confirm the importance of the physical activity in conjunction with extra-virgin olive oil diet in medical therapy to prevent osteoarthritis disease in order to preserve the articular cartilage and then the entire joint.

  9. Modelling Marine Sediment Biogeochemistry: Current Knowledge Gaps, Challenges, and Some Methodological Advice for Advancement

    Directory of Open Access Journals (Sweden)

    Gennadi Lessin

    2018-02-01

    Full Text Available The benthic environment is a crucial component of marine systems in the provision of ecosystem services, sustaining biodiversity and in climate regulation, and therefore important to human society. With the contemporary increase in computational power, model resolution and technological improvements in quality and quantity of benthic data, it is necessary to ensure that benthic systems are appropriately represented in coupled benthic-pelagic biogeochemical and ecological modelling studies. In this paper we focus on five topical challenges related to various aspects of modelling benthic environments: organic matter reactivity, dynamics of benthic-pelagic boundary layer, microphytobenthos, biological transport and small-scale heterogeneity, and impacts of episodic events. We discuss current gaps in their understanding and indicate plausible ways ahead. Further, we propose a three-pronged approach for the advancement of benthic and benthic-pelagic modelling, essential for improved understanding, management and prediction of the marine environment. This includes: (A development of a traceable and hierarchical framework for benthic-pelagic models, which will facilitate integration among models, reduce risk of bias, and clarify model limitations; (B extended cross-disciplinary approach to promote effective collaboration between modelling and empirical scientists of various backgrounds and better involvement of stakeholders and end-users; (C a common vocabulary for terminology used in benthic modelling, to promote model development and integration, and also to enhance mutual understanding.

  10. Effects of Hydrostatic Loading on a Self-Aggregating, Suspension Culture–Derived Cartilage Tissue Analog

    Science.gov (United States)

    Kraft, Jeffrey J.; Jeong, Changhoon; Novotny, John E.; Seacrist, Thomas; Chan, Gilbert; Domzalski, Marcin; Turka, Christina M.; Richardson, Dean W.; Dodge, George R.

    2011-01-01

    Objective: Many approaches are being taken to generate cartilage replacement materials. The goal of this study was to use a self-aggregating suspension culture model of chondrocytes with mechanical preconditioning. Design: Our model differs from others in that it is based on a scaffold-less, self-aggregating culture model that produces a cartilage tissue analog that has been shown to share many similarities with the natural cartilage phenotype. Owing to the known loaded environment under which chondrocytes function in vivo, we hypothesized that applying force to the suspension culture–derived chondrocyte biomass would improve its cartilage-like characteristics and provide a new model for engineering cartilage tissue analogs. Results: In this study, we used a specialized hydrostatic pressure bioreactor system to apply mechanical forces during the growth phase to improve biochemical and biophysical properties of the biomaterial formed. We demonstrated that using this high-density suspension culture, a biomaterial more consistent with the hyaline cartilage phenotype was produced without any foreign material added. Unpassaged chondrocytes responded to a physiologically relevant hydrostatic load by significantly increasing gene expression of critical cartilage molecule collagen and aggrecan along with other cartilage relevant genes, CD44, perlecan, decorin, COMP, and iNOS. Conclusions: This study describes a self-aggregating bioreactor model without foreign material or scaffold in which chondrocytes form a cartilage tissue analog with many features similar to native cartilage. This study represents a promising scaffold-less, methodological advancement in cartilage tissue engineering with potential translational applications to cartilage repair. PMID:26069584

  11. Modelling of the negative discharge in long air gaps under impulse voltages

    International Nuclear Information System (INIS)

    Rakotonandrasana, J H; Beroual, A; Fofana, I

    2008-01-01

    This paper presents a self-consistent model enabling the description of the whole negative discharge sequence, initiated in long air gaps under impulse voltage waves. This sequence includes the different phases of the propagation such as the initiation of the first corona, the pilot leader, the electrode and space leaders, and their junction. The model consists of using a RLC equivalent electrical network, the parameters of which vary with time according to the discharge characteristics and geometry (R, L and C being, respectively, the resistance, the inductance and the capacitance). This model provides the spatial and temporal evolution of the entire discharge, the current and the corresponding electrical charge, the power and energy injected into the gap and the velocity. It also allows us to simulate an image converter working in streak or frame mode and the leader propagation velocities as well as the trajectory of the discharge obtained from a probabilistic distribution. The computed results are compared with experimental data. Good agreement between computed and experimental results was obtained for various test configurations

  12. Modeling and validation of multiple joint reflections for ultra- narrow gap laser welding

    Energy Technology Data Exchange (ETDEWEB)

    Milewski, J.; Keel, G. [Los Alamos National Lab., NM (United States); Sklar, E. [Opticad Corp., Santa Fe, New Mexico (United States)

    1995-12-01

    The effects of multiple internal reflections within a laser weld joint as a function of joint geometry and processing conditions have been characterized. A computer model utilizing optical ray tracing is used to predict the reflective propagation of laser beam energy focused into the narrow gap of a metal joint for the purpose of predicting the location of melting and coalescence which form the weld. The model allows quantitative analysis of the effects of changes to joint geometry, laser design, materials and processing variables. This analysis method is proposed as a way to enhance process efficiency and design laser welds which display deep penetration and high depth to width aspect ratios, reduced occurrence of defects and enhanced melting. Of particular interest to laser welding is the enhancement of energy coupling to highly reflective materials. The weld joint is designed to act as an optical element which propagates and concentrates the laser energy deep within the joint to be welded. Experimentation has shown that it is possible to produce welds using multiple passes to achieve deep penetration and high depth to width aspect ratios without the use of filler material. The enhanced laser melting and welding of aluminum has been demonstrated. Optimization through modeling and experimental validation has resulted in the development of a laser welding process variant we refer to as Ultra-Narrow Gap Laser Welding.

  13. Some Comparative Anatomical and Histological Studies on the Laryngeal Cartilages of Buffaloes, Camels and Donkeys

    Directory of Open Access Journals (Sweden)

    Eman A. Eshra

    2016-01-01

    Full Text Available Comparative studies concerned the upper air ways of domestic animals are few. So this study was carried out to compare between the larynx of buffaloes, camels and donkeys. The present investigation was carried out on 39 larynxes, 13 larynxes (7 males, 6 females of each species. Ten heads from each species were used for gross anatomical study; the remained three heads were used for the histological study. Results revealed that, the laryngeal cartilages of the three species were consisted of three single cartilages; the thyroid, the cricoid and the epiglottis, and two paired cartilages; the arytenoid and the corniculate. The cuneiform cartilages were paired cartilages present only in the larynx of the donkey. Thyroid, arytenoid and cricoid cartilages were of hyaline type, while the epiglottis, cuniform and corniculate cartilages and the vocal process of the arytenoid cartilage were of elastic type. The laryngeal epithelium of aditus laryngis, greater part of epiglottis and vocal folds was lined by non-keratinized stratified squamous epithelium. The remained parts of laryngeal epithelium from base of epiglottis and entire parts caudal to vocal folds were lined by pseudostratified columnar ciliated epithelium with goblet cells. The laryngeal glands of lamina propria were of mixed types in buffaloes and donkeys but in camels it was pure mucous glands. This study will fill a gap in the field of comparative anatomy and help other clinical investigation applied on these animals.

  14. The technology gap and efficiency measure in WEC countries: Application of the hybrid meta frontier model

    International Nuclear Information System (INIS)

    Chiu, Yung-Ho; Lee, Jen-Hui; Lu, Ching-Cheng; Shyu, Ming-Kuang; Luo, Zhengying

    2012-01-01

    This study develops the hybrid meta frontier DEA model for which inputs are distinguished into radial inputs that change proportionally and non-radial inputs that change non-proportionally, in order to measure the technical efficiency and technology gap ratios (TGR) of four different regions: Asia, Africa, America, and Europe. This paper selects 87 countries that are members of the World Energy Council from 2005 to 2007. The input variables are industry and population, while the output variances are gross domestic product (GDP) and the amount of fossil-fuel CO 2 emissions. The result shows that countries’ efficiency ranking among their own region presents more implied volatility. In view of the Technology Gap Ratio, Europe is the most efficient of any region, but during the same period, Asia has a lower efficiency than other regions. Finally, regions with higher industry (or GDP) might not have higher efficiency from 2005 to 2007. And higher CO 2 emissions or population also might not mean lower efficiency for other regions. In addition, Brazil is not OECD member, but it is higher efficiency than other OECD members in emerging countries case. OECD countries are better efficiency than non-OECD countries and Europe is higher than Asia to control CO 2 emissions. If non-OECD countries or Asia countries could reach the best efficiency score, they should try to control CO 2 emissions. - Highlights: ► The new meta frontier Model for evaluating the efficiency and technology gap ratios. ► Higher CO 2 emissions might not lower efficiency than any other regions, like Europe. ► Asia’s output and CO 2 emissions simultaneously increased and lower of its efficiency. ► Non-OECD or Asia countries should control CO 2 emissions to reach best efficiency score.

  15. Gap Models as Tools for Sustainable Development under Environmental Changes in Northern Eurasia

    Science.gov (United States)

    Shugart, H. H., Jr.; Wang, B.; Brazhnik, K.; Armstrong, A. H.; Foster, A.

    2017-12-01

    Agent-based models of complex systems or as used in this review, Individual-based Models (IBMs), emerged in the 1960s and early 1970s, across diverse disciplines from astronomy to zoology. IBMs arose from a deeply embedded ecological tradition of understanding the dynamics of ecosystems from a "bottom-up" accounting of the interactions of the parts. In this case, individual trees are principal among the parts. Because they are computationally demanding, these models have prospered as the power of digital computers has increased exponentially over the decades following the 1970s. Forest IBMs are no longer computationally bound from developing continental- or global-scale simulations of responses of forests to climate and other changes. Gap models simulate the changes in forests by simulating the birth, growth and death of each individual tree on small plots of land that in summation comprise a forest (or set of sample plots on a forested landscape or region). Currently, gap models have grown from continental-scale and even global-scale applications to assess the potential consequences of climate change on natural forests. These predictions are valuable in the planning and anticipatory decision-making needed to sustainably manage a vast region such as Northern Eurasia. Modifications to the models have enabled simulation of disturbances including fire, insect outbreak and harvest. These disturbances have significant exogenous drivers, notably weather variables, but their effects are also a function of the endogenous conditions involving the structure of forest itself. This feedback between the forest and its environment can in some cases produce hysteresis and multiple-stable operating-regimes for forests. Such responses, often characterized as "tipping points" could play a significant role in increasing risk under environmental change, notably global warming. Such dynamics in a management context imply regional systems that could be "unforgiving" of management

  16. Magnetically targeted delivery through cartilage

    Science.gov (United States)

    Jafari, Sahar; Mair, Lamar O.; Chowdhury, Sagar; Nacev, Alek; Hilaman, Ryan; Stepanov, Pavel; Baker-McKee, James; Ijanaten, Said; Koudelka, Christian; English, Bradley; Malik, Pulkit; Weinberg, Irving N.

    2018-05-01

    In this study, we have invented a method of delivering drugs deep into articular cartilage with shaped dynamic magnetic fields acting on small metallic magnetic nanoparticles with polyethylene glycol coating and average diameter of 30 nm. It was shown that transport of magnetic nanoparticles through the entire thickness of bovine articular cartilage can be controlled by a combined alternating magnetic field at 100 Hz frequency and static magnetic field of 0.8 tesla (T) generated by 1" dia. x 2" thick permanent magnet. Magnetic nanoparticles transport through bovine articular cartilage samples was investigated at various settings of magnetic field and time durations. Combined application of an alternating magnetic field and the static field gradient resulted in a nearly 50 times increase in magnetic nanoparticles transport in bovine articular cartilage tissue as compared with static field conditions. This method can be applied to locally deliver therapeutic-loaded magnetic nanoparticles deep into articular cartilage to prevent cartilage degeneration and promote cartilage repair in osteoarthritis.

  17. Magnetically targeted delivery through cartilage

    Directory of Open Access Journals (Sweden)

    Sahar Jafari

    2018-05-01

    Full Text Available In this study, we have invented a method of delivering drugs deep into articular cartilage with shaped dynamic magnetic fields acting on small metallic magnetic nanoparticles with polyethylene glycol coating and average diameter of 30 nm. It was shown that transport of magnetic nanoparticles through the entire thickness of bovine articular cartilage can be controlled by a combined alternating magnetic field at 100 Hz frequency and static magnetic field of 0.8 tesla (T generated by 1" dia. x 2" thick permanent magnet. Magnetic nanoparticles transport through bovine articular cartilage samples was investigated at various settings of magnetic field and time durations. Combined application of an alternating magnetic field and the static field gradient resulted in a nearly 50 times increase in magnetic nanoparticles transport in bovine articular cartilage tissue as compared with static field conditions. This method can be applied to locally deliver therapeutic-loaded magnetic nanoparticles deep into articular cartilage to prevent cartilage degeneration and promote cartilage repair in osteoarthritis.

  18. GAP Analysis Program (GAP)

    Data.gov (United States)

    Kansas Data Access and Support Center — The Kansas GAP Analysis Land Cover database depicts 43 land cover classes for the state of Kansas. The database was generated using a two-stage hybrid classification...

  19. Stochastic model prediction of the Kovacs' ``expansion gap'' effect for volume relaxation in glassy polymers

    Science.gov (United States)

    Medvedev, Grigori; Caruthers, James

    2015-03-01

    The classic series of experiments by A. Kovacs on volume relaxation following temperature jumps for poly(vinyl acetate), PVAc, in the Tg region revealed the richness and complexity of the viscoelastic behavior of glassy materials. Over the years no theoretical model has been able to predict all the features of the Kovacs data, where the so-called ``expansion gap'' effect proved to be particularly challenging. Specifically, for a series of up-jump experiments with different initial temperatures, Ti, but with the same final temperature, as the relaxation approaches equilibrium it would be expected that the effective relaxation time would be the same regardless of Ti; however, Kovacs observed that the dependence on Ti persisted seemingly all the way to equilibrium. In this communication we will show that a recently developed Stochastic Constitutive Model (SCM) that explicitly acknowledges the nano-scale dynamic heterogeneity of glasses can capture the ``expansion gap'' as well as the rest of the Kovacs data set for PVAc. It will be shown that the success of the SCM is due to its inherent thermo-rheological complexity.

  20. The bio in the ink: cartilage regeneration with bioprintable hydrogels and articular cartilage-derived progenitor cells.

    Science.gov (United States)

    Levato, Riccardo; Webb, William R; Otto, Iris A; Mensinga, Anneloes; Zhang, Yadan; van Rijen, Mattie; van Weeren, René; Khan, Ilyas M; Malda, Jos

    2017-10-01

    Cell-laden hydrogels are the primary building blocks for bioprinting, and, also termed bioinks, are the foundations for creating structures that can potentially recapitulate the architecture of articular cartilage. To be functional, hydrogel constructs need to unlock the regenerative capacity of encapsulated cells. The recent identification of multipotent articular cartilage-resident chondroprogenitor cells (ACPCs), which share important traits with adult stem cells, represents a new opportunity for cartilage regeneration. However, little is known about the suitability of ACPCs for tissue engineering, especially in combination with biomaterials. This study aimed to investigate the potential of ACPCs in hydrogels for cartilage regeneration and biofabrication, and to evaluate their ability for zone-specific matrix production. Gelatin methacryloyl (gelMA)-based hydrogels were used to culture ACPCs, bone marrow mesenchymal stromal cells (MSCs) and chondrocytes, and as bioinks for printing. Our data shows ACPCs outperformed chondrocytes in terms of neo-cartilage production and unlike MSCs, ACPCs had the lowest gene expression levels of hypertrophy marker collagen type X, and the highest expression of PRG4, a key factor in joint lubrication. Co-cultures of the cell types in multi-compartment hydrogels allowed generating constructs with a layered distribution of collagens and glycosaminoglycans. By combining ACPC- and MSC-laden bioinks, a bioprinted model of articular cartilage was generated, consisting of defined superficial and deep regions, each with distinct cellular and extracellular matrix composition. Taken together, these results provide important information for the use of ACPC-laden hydrogels in regenerative medicine, and pave the way to the biofabrication of 3D constructs with multiple cell types for cartilage regeneration or in vitro tissue models. Despite its limited ability to repair, articular cartilage harbors an endogenous population of progenitor cells

  1. Toward understanding the role of cartilage particulates in synovial inflammation.

    Science.gov (United States)

    Silverstein, A M; Stefani, R M; Sobczak, E; Tong, E L; Attur, M G; Shah, R P; Bulinski, J C; Ateshian, G A; Hung, C T

    2017-08-01

    Arthroscopy with lavage and synovectomy can remove tissue debris from the joint space and the synovial lining to provide pain relief to patients with osteoarthritis (OA). Here, we developed an in vitro model to study the interaction of cartilage wear particles with fibroblast-like synoviocytes (FLS) to better understand the interplay of cartilage particulates with cytokines on cells of the synovium. In this study sub-10 μm cartilage particles or 1 μm latex particles were co-cultured with FLS ±10 ng/mL interleukin-1α (IL-1α) or tumor necrosis factor-α (TNF-α). Samples were analyzed for DNA, glycosaminoglycan (GAG), and collagen, and media samples were analyzed for media GAG, nitric oxide (NO) and prostaglandin-E2 (PGE2). The nature of the physical interaction between the particles and FLS was determined by microscopy. Both latex and cartilage particles could be phagocytosed by FLS. Cartilage particles were internalized and attached to the surface of both dense monolayers and individual cells. Co-culture of FLS with cartilage particulates resulted in a significant increase in cell sheet DNA and collagen content as well as NO and PGE2 synthesis compared to control and latex treated groups. The proliferative response of FLS to cartilage wear particles resulted in an overall increase in extracellular matrix (ECM) content, analogous to the thickening of the synovial lining observed in OA patients. Understanding how cartilage particles interface with the synovium may provide insight into how this interaction contributes to OA progression and may guide the role of lavage and synovectomy for degenerative disease. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  2. Determination of the mechanical and physical properties of cartilage by coupling poroelastic-based finite element models of indentation with artificial neural networks

    NARCIS (Netherlands)

    Arbabi, Vahid; Pouran, B; Campoli, Gianni; Weinans, Harrie; Zadpoor, Amir A

    2016-01-01

    One of the most widely used techniques to determine the mechanical properties of cartilage is based on indentation tests and interpretation of the obtained force-time or displacement-time data. In the current computational approaches, one needs to simulate the indentation test with finite element

  3. Synovial Fluid Filtration by Articular Cartilage with a Worn-out Surface Zone in the Human Ankle Joint during Walking- I.A Mathematical Mixture Model

    Czech Academy of Sciences Publication Activity Database

    Hlaváček, Miroslav

    2000-01-01

    Roč. 45, č. 3 (2000), s. 295-321 ISSN 0001-7043 R&D Projects: GA ČR GA103/00/0008 Keywords : asymptotic solution * biphasic articular cartilage * biphasic synovial fluid * human ankle joint Subject RIV: BK - Fluid Dynamics

  4. Laser-induced micropore formation and modification of cartilage structure in osteoarthritis healing

    Energy Technology Data Exchange (ETDEWEB)

    Sobol, Emil [Institute of Applied Physics of the Russian Academy of Sciences, Nizhny Novgorod, RussiabFederal Scientific Research Centre “Crystallography and Photonics” of the Russian Academy of Sciences, Institute of Photonic Technologies, Moscow, Russia; Baum, Olga [Federal Scientific Research Centre “Crystallography and Photonics” of the Russian Academy of Sciences, Institute of Photonic Technologies, Moscow, Russia; Shekhter, Anatoly [Sechenov First Medical University of Moscow, Institute of Regenerative Medicine, Moscow, Russia; Wachsmann-Hogiu, Sebastian [University of California, Center for Biophotonics, Department of Pathology and Laboratory Medicine, Sacramento, California, United StateseMcGill University, Department of Bioengineering, Montreal, Canada; Shnirelman, Alexander [Concordia University, Department of Mathematics and Statistics, Montreal, Canada; Alexandrovskaya, Yulia [Institute of Applied Physics of the Russian Academy of Sciences, Nizhny Novgorod, RussiabFederal Scientific Research Centre “Crystallography and Photonics” of the Russian Academy of Sciences, Institute of Photonic Technologies, Moscow, Russia; Sadovskyy, Ivan [Argonne National Laboratory, Materials Science Division, Argonne, Illinois, United States; Vinokur, Valerii [Argonne National Laboratory, Materials Science Division, Argonne, Illinois, United States

    2017-05-31

    Pores are vital for functioning of avascular tissues. Laser-induced pores play an important role in the process of cartilage regeneration. The aim of any treatment for osteoarthritis is to repair hyaline-type cartilage. The aims of this study are to answer two questions: (1) How do laser-assisted pores affect the cartilaginous cells to synthesize hyaline cartilage (HC)? and (2) How can the size distribution of pores arising in the course of laser radiation be controlled? We have shown that in cartilage, the pores arise predominately near chondrocytes, which promote nutrition of cells and signal molecular transfer that activates regeneration of cartilage. In vivo laser treatment of damaged cartilage of miniature pig joints provides cellular transformation and formation of HC. We propose a simple model of pore formation in biopolymers that paves the way for going beyond the trial-anderror approach when choosing an optimal laser treatment regime. Our findings support the approach toward laser healing of osteoarthritis.

  5. Physical activity is associated with changes in knee cartilage microstructure.

    Science.gov (United States)

    Halilaj, E; Hastie, T J; Gold, G E; Delp, S L

    2018-06-01

    The purpose of this study was to determine if there is an association between objectively measured physical activity and longitudinal changes in knee cartilage microstructure. We used accelerometry and T 2 -weighted magnetic resonance imaging (MRI) data from the Osteoarthritis Initiative, restricting the analysis to men aged 45-60 years, with a body mass index (BMI) of 25-27 kg/m 2 and no radiographic evidence of knee osteoarthritis. After computing 4-year changes in mean T 2 relaxation time for six femoral cartilage regions and mean daily times spent in the sedentary, light, moderate, and vigorous activity ranges, we performed canonical correlation analysis (CCA) to find a linear combination of times spent in different activity intensity ranges (Activity Index) that was maximally correlated with a linear combination of regional changes in cartilage microstructure (Cartilage Microstructure Index). We used leave-one-out pre-validation to test the robustness of the model on new data. Nineteen subjects satisfied the inclusion criteria. CCA identified an Activity Index and a Cartilage Microstructure Index that were significantly correlated (r = .82, P microstructural changes in different cartilage regions than it is with univariate or cumulative changes, likely because this index separates the effect of activity, which is greater in the medial loadbearing region, from that of patient-specific natural aging. Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  6. Particulated articular cartilage: CAIS and DeNovo NT.

    Science.gov (United States)

    Farr, Jack; Cole, Brian J; Sherman, Seth; Karas, Vasili

    2012-03-01

    Cartilage Autograft Implantation System (CAIS; DePuy/Mitek, Raynham, MA) and DeNovo Natural Tissue (NT; ISTO, St. Louis, MO) are novel treatment options for focal articular cartilage defects in the knee. These methods involve the implantation of particulated articular cartilage from either autograft or juvenile allograft donor, respectively. In the laboratory and in animal models, both CAIS and DeNovo NT have demonstrated the ability of the transplanted cartilage cells to "escape" from the extracellular matrix, migrate, multiply, and form a new hyaline-like cartilage tissue matrix that integrates with the surrounding host tissue. In clinical practice, the technique for both CAIS and DeNovo NT is straightforward, requiring only a single surgery to affect cartilage repair. Clinical experience is limited, with short-term studies demonstrating both procedures to be safe, feasible, and effective, with improvements in subjective patient scores, and with magnetic resonance imaging evidence of good defect fill. While these treatment options appear promising, prospective randomized controlled studies are necessary to refine the indications and contraindications for both CAIS and DeNovo NT.

  7. Conceptualizing Telehealth in Nursing Practice: Advancing a Conceptual Model to Fill a Virtual Gap.

    Science.gov (United States)

    Nagel, Daniel A; Penner, Jamie L

    2016-03-01

    Increasingly nurses use various telehealth technologies to deliver health care services; however, there has been a lag in research and generation of empirical knowledge to support nursing practice in this expanding field. One challenge to generating knowledge is a gap in development of a comprehensive conceptual model or theoretical framework to illustrate relationships of concepts and phenomena inherent to adoption of a broad range of telehealth technologies to holistic nursing practice. A review of the literature revealed eight published conceptual models, theoretical frameworks, or similar entities applicable to nursing practice. Many of these models focus exclusively on use of telephones and four were generated from qualitative studies, but none comprehensively reflect complexities of bridging nursing process and elements of nursing practice into use of telehealth. The purpose of this article is to present a review of existing conceptual models and frameworks, discuss predominant themes and features of these models, and present a comprehensive conceptual model for telehealth nursing practice synthesized from this literature for consideration and further development. This conceptual model illustrates characteristics of, and relationships between, dimensions of telehealth practice to guide research and knowledge development in provision of holistic person-centered care delivery to individuals by nurses through telehealth technologies. © The Author(s) 2015.

  8. Sodium fast reactor gaps analysis of computer codes and models for accident analysis and reactor safety.

    Energy Technology Data Exchange (ETDEWEB)

    Carbajo, Juan (Oak Ridge National Laboratory, Oak Ridge, TN); Jeong, Hae-Yong (Korea Atomic Energy Research Institute, Daejeon, Korea); Wigeland, Roald (Idaho National Laboratory, Idaho Falls, ID); Corradini, Michael (University of Wisconsin, Madison, WI); Schmidt, Rodney Cannon; Thomas, Justin (Argonne National Laboratory, Argonne, IL); Wei, Tom (Argonne National Laboratory, Argonne, IL); Sofu, Tanju (Argonne National Laboratory, Argonne, IL); Ludewig, Hans (Brookhaven National Laboratory, Upton, NY); Tobita, Yoshiharu (Japan Atomic Energy Agency, Ibaraki-ken, Japan); Ohshima, Hiroyuki (Japan Atomic Energy Agency, Ibaraki-ken, Japan); Serre, Frederic (Centre d' %C3%94etudes nucl%C3%94eaires de Cadarache %3CU%2B2013%3E CEA, France)

    2011-06-01

    This report summarizes the results of an expert-opinion elicitation activity designed to qualitatively assess the status and capabilities of currently available computer codes and models for accident analysis and reactor safety calculations of advanced sodium fast reactors, and identify important gaps. The twelve-member panel consisted of representatives from five U.S. National Laboratories (SNL, ANL, INL, ORNL, and BNL), the University of Wisconsin, the KAERI, the JAEA, and the CEA. The major portion of this elicitation activity occurred during a two-day meeting held on Aug. 10-11, 2010 at Argonne National Laboratory. There were two primary objectives of this work: (1) Identify computer codes currently available for SFR accident analysis and reactor safety calculations; and (2) Assess the status and capability of current US computer codes to adequately model the required accident scenarios and associated phenomena, and identify important gaps. During the review, panel members identified over 60 computer codes that are currently available in the international community to perform different aspects of SFR safety analysis for various event scenarios and accident categories. A brief description of each of these codes together with references (when available) is provided. An adaptation of the Predictive Capability Maturity Model (PCMM) for computational modeling and simulation is described for use in this work. The panel's assessment of the available US codes is presented in the form of nine tables, organized into groups of three for each of three risk categories considered: anticipated operational occurrences (AOOs), design basis accidents (DBA), and beyond design basis accidents (BDBA). A set of summary conclusions are drawn from the results obtained. At the highest level, the panel judged that current US code capabilities are adequate for licensing given reasonable margins, but expressed concern that US code development activities had stagnated and that the

  9. Effect of a Rapidly Degrading Presolidified 10 kDa Chitosan/Blood Implant and Subchondral Marrow Stimulation Surgical Approach on Cartilage Resurfacing in a Sheep Model

    Science.gov (United States)

    Bell, Angela D.; Hurtig, Mark B.; Quenneville, Eric; Rivard, Georges-Étienne; Hoemann, Caroline D.

    2016-01-01

    Objective This study tested the hypothesis that presolidified chitosan-blood implants are retained in subchondral bone channels perforated in critical-size sheep cartilage defects, and promote bone repair and hyaline-like cartilage resurfacing versus blood implant. Design Cartilage defects (10 × 10 mm) with 3 bone channels (1 drill, 2 Jamshidi biopsy, 2 mm diameter), and 6 small microfracture holes were created bilaterally in n = 11 sheep knee medial condyles. In one knee, 10 kDa chitosan–NaCl/blood implant (presolidified using recombinant factor VIIa or tissue factor), was inserted into each drill and Jamshidi hole. Contralateral knee defects received presolidified whole blood clot. Repair tissues were assessed histologically, biochemically, biomechanically, and by micro–computed tomography after 1 day (n = 1) and 6 months (n = 10). Results Day 1 defects showed a 60% loss of subchondral bone plate volume fraction along with extensive subchondral hematoma. Chitosan implant was resident at day 1, but had no effect on any subsequent repair parameter compared with blood implant controls. At 6 months, bone defects exhibited remodeling and hypomineralized bone repair and were partly resurfaced with tissues containing collagen type II and scant collagen type I, 2-fold lower glycosaminoglycan and fibril modulus, and 4.5-fold higher permeability compared with intact cartilage. Microdrill holes elicited higher histological ICRS-II overall assessment scores than Jamshidi holes (50% vs. 30%, P = 0.041). Jamshidi biopsy holes provoked sporadic osteonecrosis in n = 3 debrided condyles. Conclusions Ten kilodalton chitosan was insufficient to improve repair. Microdrilling is a feasible subchondral marrow stimulation surgical approach with the potential to elicit poroelastic tissues with at least half the compressive modulus as intact articular cartilage. PMID:28934884

  10. Effect of a Rapidly Degrading Presolidified 10 kDa Chitosan/Blood Implant and Subchondral Marrow Stimulation Surgical Approach on Cartilage Resurfacing in a Sheep Model.

    Science.gov (United States)

    Bell, Angela D; Hurtig, Mark B; Quenneville, Eric; Rivard, Georges-Étienne; Hoemann, Caroline D

    2017-10-01

    Objective This study tested the hypothesis that presolidified chitosan-blood implants are retained in subchondral bone channels perforated in critical-size sheep cartilage defects, and promote bone repair and hyaline-like cartilage resurfacing versus blood implant. Design Cartilage defects (10 × 10 mm) with 3 bone channels (1 drill, 2 Jamshidi biopsy, 2 mm diameter), and 6 small microfracture holes were created bilaterally in n = 11 sheep knee medial condyles. In one knee, 10 kDa chitosan-NaCl/blood implant (presolidified using recombinant factor VIIa or tissue factor), was inserted into each drill and Jamshidi hole. Contralateral knee defects received presolidified whole blood clot. Repair tissues were assessed histologically, biochemically, biomechanically, and by micro-computed tomography after 1 day ( n = 1) and 6 months ( n = 10). Results Day 1 defects showed a 60% loss of subchondral bone plate volume fraction along with extensive subchondral hematoma. Chitosan implant was resident at day 1, but had no effect on any subsequent repair parameter compared with blood implant controls. At 6 months, bone defects exhibited remodeling and hypomineralized bone repair and were partly resurfaced with tissues containing collagen type II and scant collagen type I, 2-fold lower glycosaminoglycan and fibril modulus, and 4.5-fold higher permeability compared with intact cartilage. Microdrill holes elicited higher histological ICRS-II overall assessment scores than Jamshidi holes (50% vs. 30%, P = 0.041). Jamshidi biopsy holes provoked sporadic osteonecrosis in n = 3 debrided condyles. Conclusions Ten kilodalton chitosan was insufficient to improve repair. Microdrilling is a feasible subchondral marrow stimulation surgical approach with the potential to elicit poroelastic tissues with at least half the compressive modulus as intact articular cartilage.

  11. The Role of Inorganic Polyphosphates in the Formation of Bioengineered Cartilage Incorporating a Zone of Calcified Cartilage In Vitro

    Science.gov (United States)

    St-Pierre, Jean-Philippe

    The development of bioengineered cartilage for replacement of damaged articular cartilage has gained momentum in recent years. One such approach has been developed in the Kandel lab, whereby cartilage is formed by seeding primary articular chondrocytes on the top surface of a porous biodegradable calcium polyphosphate (CPP) bone substitute, permitting anchorage of the tissue within the pores of the substrate; however, the interfacial shear properties of the tissue-substrate interface of these biphasic constructs are 1 to 2 orders of magnitude lower than the native cartilage-subchondral bone interface. To overcome this limitation, a strategy was devised to generate a zone of calcified cartilage (ZCC), thereby mimicking the native architecture of the osteochondral junction; however, the ZCC was located slightly above the cartilage-CPP interface. Thus, it was hypothesized that polyphosphate released from the CPP substrate and accumulating in the tissue inhibits the formation of the ZCC at the tissue-substrate interface. Based on this information, a strategy was devised to generate biphasic constructs incorporating a properly located ZCC. This approach involved the application of a thin calcium phosphate film to the surfaces of porous CPP via a sol-gel procedure, thereby limiting the accumulation of polyphosphate in the cartilaginous tissue. This modification to the substrate surface did not negatively impact the quality of the in vitro-formed cartilage tissue or the ZCC. Interfacial shear testing of biphasic constructs demonstrated significantly improved interfacial shear properties in the presence of a properly located ZCC. These studies also led to the observation that chondrocytes produce endogenous polyphosphate and that its levels in deep zone cartilage appear inversely related to mineral deposition within the tissue. Using an in vitro model of cartilage calcification, it was demonstrated that polyphosphate levels are modulated in part by the inhibitory effects

  12. Cell motility in models of wounded human skin is improved by Gap27 despite raised glucose, insulin and IGFBP-5

    Energy Technology Data Exchange (ETDEWEB)

    Wright, Catherine S.; Berends, Rebecca F. [Department of Life Sciences, School of Health and Life Sciences, Glasgow Caledonian University, 70 Cowcaddens Road, Glasgow G4 0BA (United Kingdom); Flint, David J. [Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE (United Kingdom); Martin, Patricia E.M., E-mail: Patricia.Martin@gcu.ac.uk [Department of Life Sciences, School of Health and Life Sciences, Glasgow Caledonian University, 70 Cowcaddens Road, Glasgow G4 0BA (United Kingdom)

    2013-02-15

    Reducing Cx43 expression stimulates skin wound healing. This is mimicked in models when Cx43 function is blocked by the connexin mimetic peptide Gap27. IGF-I also stimulates wound healing with IGFBP-5 attenuating its actions. Further, the IGF-I to IGFBP-5 ratio is altered in diabetic skin, where wound closure is impaired. We investigated whether Gap27 remains effective in augmenting scrape-wound closure in human skin wound models simulating diabetes-induced changes, using culture conditions with raised glucose, insulin and IGFBP-5. Gap27 increased scrape-wound closure in normal glucose and insulin (NGI) and to a lesser extent in high glucose and insulin (HGI). IGF-I enhanced scrape-wound closure in keratinocytes whereas IGFBP-5 inhibited this response. Gap27 overcame the inhibitory effects of IGFBP-5 on IGF-I activity. Connexin-mediated communication (CMC) was reduced in HGI, despite raised Cx43, and Gap27 significantly decreased CMC in NGI and HGI. IGF-I and IGFBP-5 did not affect CMC. IGF-I increased keratinocyte proliferation in NGI, and Gap27 increased proliferation in NGI to a greater extent than in HGI. We conclude that IGF-I and Gap27 stimulate scrape-wound closure by independent mechanisms with Gap27 inhibiting Cx43 function. Gap27 can enhance wound closure in diabetic conditions, irrespective of the IGF-I:IGFBP-5 balance. - Highlights: ► Human organotypic and keratinocyte ‘diabetic’ skin models were used to demonstrate the ability of Gap27 to improve scrape-wound closure. ► Gap27 enhanced scrape-wound closure by reducing Cx43-mediated communication, whereas IGFBP-5 retarded cell migration. ► IGF-I and IGFBP-5 did not affect connexin-mediated pathways. ► Gap27 can override altered glucose, insulin, IGF-I, and IGFBP-5 in ‘diabetic’ skin models and thus has therapeutic potential.

  13. Moderate forest disturbance as a stringent test for gap and big-leaf models

    Science.gov (United States)

    Bond-Lamberty, B.; Fisk, J. P.; Holm, J. A.; Bailey, V.; Bohrer, G.; Gough, C. M.

    2015-01-01

    Disturbance-induced tree mortality is a key factor regulating the carbon balance of a forest, but tree mortality and its subsequent effects are poorly represented processes in terrestrial ecosystem models. It is thus unclear whether models can robustly simulate moderate (non-catastrophic) disturbances, which tend to increase biological and structural complexity and are increasingly common in aging US forests. We tested whether three forest ecosystem models - Biome-BGC (BioGeochemical Cycles), a classic big-leaf model, and the ZELIG and ED (Ecosystem Demography) gap-oriented models - could reproduce the resilience to moderate disturbance observed in an experimentally manipulated forest (the Forest Accelerated Succession Experiment in northern Michigan, USA, in which 38% of canopy dominants were stem girdled and compared to control plots). Each model was parameterized, spun up, and disturbed following similar protocols and run for 5 years post-disturbance. The models replicated observed declines in aboveground biomass well. Biome-BGC captured the timing and rebound of observed leaf area index (LAI), while ZELIG and ED correctly estimated the magnitude of LAI decline. None of the models fully captured the observed post-disturbance C fluxes, in particular gross primary production or net primary production (NPP). Biome-BGC NPP was correctly resilient but for the wrong reasons, and could not match the absolute observational values. ZELIG and ED, in contrast, exhibited large, unobserved drops in NPP and net ecosystem production. The biological mechanisms proposed to explain the observed rapid resilience of the C cycle are typically not incorporated by these or other models. It is thus an open question whether most ecosystem models will simulate correctly the gradual and less extensive tree mortality characteristic of moderate disturbances.

  14. Calibrating and testing a gap model for simulating forest management in the Oregon Coast Range

    Science.gov (United States)

    Pabst, R.J.; Goslin, M.N.; Garman, S.L.; Spies, T.A.

    2008-01-01

    The complex mix of economic and ecological objectives facing today's forest managers necessitates the development of growth models with a capacity for simulating a wide range of forest conditions while producing outputs useful for economic analyses. We calibrated the gap model ZELIG to simulate stand-level forest development in the Oregon Coast Range as part of a landscape-scale assessment of different forest management strategies. Our goal was to incorporate the predictive ability of an empirical model with the flexibility of a forest succession model. We emphasized the development of commercial-aged stands of Douglas-fir, the dominant tree species in the study area and primary source of timber. In addition, we judged that the ecological approach of ZELIG would be robust to the variety of other forest conditions and practices encountered in the Coast Range, including mixed-species stands, small-scale gap formation, innovative silvicultural methods, and reserve areas where forests grow unmanaged for long periods of time. We parameterized the model to distinguish forest development among two ecoregions, three forest types and two site productivity classes using three data sources: chronosequences of forest inventory data, long-term research data, and simulations from an empirical growth-and-yield model. The calibrated model was tested with independent, long-term measurements from 11 Douglas-fir plots (6 unthinned, 5 thinned), 3 spruce-hemlock plots, and 1 red alder plot. ZELIG closely approximated developmental trajectories of basal area and large trees in the Douglas-fir plots. Differences between simulated and observed conifer basal area for these plots ranged from -2.6 to 2.4 m2/ha; differences in the number of trees/ha ???50 cm dbh ranged from -8.8 to 7.3 tph. Achieving these results required the use of a diameter-growth multiplier, suggesting some underlying constraints on tree growth such as the temperature response function. ZELIG also tended to overestimate

  15. Polymer Formulations for Cartilage Repair

    Energy Technology Data Exchange (ETDEWEB)

    Gutowska, Anna; Jasionowski, Marek; Morris, J. E.; Chrisler, William B.; An, Yuehuei H.; Mironov, V.

    2001-05-15

    Regeneration of destroyed articular cartilage can be induced by transplantation of cartilage cells into a defect. The best results are obtained with the use of autologus cells. However, obtaining large amounts of autologus cartilage cells causes a problem of creating a large cartilage defect in a donor site. Techniques are currently being developed to harvest a small number of cells and propagate them in vitro. It is a challenging task, however, due to the fact that ordinarily, in a cell culture on flat surfaces, chondrocytes do not maintain their in vivo phenotype and irreversibly diminish or cease the synthesis of aggregating proteoglycans. Therefore, the research is continuing to develop culture conditions for chondrocytes with the preserved phenotype.

  16. Procedure to Solve Network DEA Based on a Virtual Gap Measurement Model

    Directory of Open Access Journals (Sweden)

    Fuh-hwa Franklin Liu

    2017-01-01

    Full Text Available Network DEA models assess production systems that contain a set of network-structured subsystems. Each subsystem has input and output measures from and to the external network and has intermediate measures that link to other subsystems. Most published studies demonstrate how to employ DEA models to establish network DEA models. Neither static nor dynamic network DEA models adjust the links. This paper applies the virtual gap measurement (VGM model to construct a mixed integer program to solve dynamic network DEA problems. The mixed integer program sets the total numbers of “as-input” and “as-output” equal to the total number of links in the objective function. To obtain the best-practice efficiency, each DMU determines a set of weights for inputs, outputs, and links. The links are played either “as-input” or “as-output.” Input and as-input measures reduce slack, whereas output and as-output measures increase slacks to attain their target on the production frontier.

  17. Modeling the Daly Gap: The Influence of Latent Heat Production in Controlling Magma Extraction and Eruption

    Science.gov (United States)

    Nelson, B. K.; Ghiorso, M. S.; Bachmann, O.; Dufek, J.

    2011-12-01

    A century-old issue in volcanology is the origin of the gap in chemical compositions observed in magmatic series on ocean islands and arcs - the "Daly Gap". If the gap forms during differentiation from a mafic parent, models that predict the dynamics of magma extraction as a function of chemical composition must simulate a process that results in volumetrically biased, bimodal compositions of erupted magmas. The probability of magma extraction is controlled by magma dynamical processes, which have a complex response to magmatic heat evolution. Heat loss from the magmatic system is far from a simple, monotonic function of time. It is modified by the crystallization sequence, chamber margin heat flux, and is buffered by latent heat production. We use chemical and thermal calculations of MELTS (Ghiorso & Sack, 1995) as input to the physical model of QUANTUM (Dufek & Bachmann, 2010) to predict crystallinity windows of most probable magma extraction. We modeled two case studies: volcanism on Tenerife, Canary Islands, and the Campanian Ignimbrite (CI) of Campi Flegrei, Italy. Both preserve a basanitic to phonolitic lineage and have comparable total alkali concentrations; however, CI has high and Tenerife has low K2O/Na2O. Modeled thermal histories of differentiation for the two sequences contrast strongly. In Tenerife, the rate of latent heat production is almost always greater than sensible heat production, with spikes in the ratio of latent to sensible heats of up to 40 associated with the appearance of Fe-Ti oxides at near 50% crystallization. This punctuated heat production must cause magma temperature change to stall or slow in time. The extended time spent at ≈50% crystallinity, associated with dynamical processes that enhance melt extraction near 50% crystallinity, suggests the magma composition at this interval should be common. In Tenerife, the modeled composition coincides with that of the first peak in the bimodal frequency-composition distribution. In our

  18. Bridging the Gap between RF and Optical Patch Antenna Analysis via the Cavity Model.

    Science.gov (United States)

    Unal, G S; Aksun, M I

    2015-11-02

    Although optical antennas with a variety of shapes and for a variety of applications have been proposed and studied, they are still in their infancy compared to their radio frequency (rf) counterparts. Optical antennas have mainly utilized the geometrical attributes of rf antennas rather than the analysis tools that have been the source of intuition for antenna engineers in rf. This study intends to narrow the gap of experience and intuition in the design of optical patch antennas by introducing an easy-to-understand and easy-to-implement analysis tool in rf, namely, the cavity model, into the optical regime. The importance of this approach is not only its simplicity in understanding and implementation but also its applicability to a broad class of patch antennas and, more importantly, its ability to provide the intuition needed to predict the outcome without going through the trial-and-error simulations with no or little intuitive guidance by the user.

  19. The exact mass-gap of the supersymmetric CP$^{N-1}$ sigma model

    CERN Document Server

    Evans, J M; Evans, Jonathan M; Hollowood, Timothy J

    1995-01-01

    A formula for the mass-gap of the supersymmetric \\CP^{n-1} sigma model (n > 1) in two dimensions is derived: m/\\Lambda_{\\overline{\\rm MS}}=\\sin(\\pi\\Delta)/(\\pi\\Delta) where \\Delta=1/n and m is the mass of the fundamental particle multiplet. This result is obtained by comparing two expressions for the free-energy density in the presence of a coupling to a conserved charge; one expression is computed from the exact S-matrix of K\\"oberle and Kurak via the thermodynamic Bethe ansatz and the other is computed using conventional perturbation theory. These calculations provide a stringent test of the S-matrix, showing that it correctly reproduces the universal part of the beta-function and resolving the problem of CDD ambiguities.

  20. The exact mass-gap of the supersymmetric O(N) sigma model

    CERN Document Server

    Evans, J M; Evans, Jonathan M; Hollowood, Timothy J

    1995-01-01

    A formula for the mass-gap of the supersymmetric O(N) sigma model (N>4) in two dimensions is derived: m/\\Lambda_{\\overline{\\rm MS}}=2^{2\\Delta}\\sin(\\pi\\Delta)/(\\pi\\Delta), where \\Delta=1/(N-2) and m is the mass of the fundamental vector particle in the theory. This result is obtained by comparing two expressions for the free-energy density in the presence of a coupling to a conserved charge; one expression is computed from the exact S-matrix of Shankar and Witten via the the thermodynamic Bethe ansatz and the other is computed using conventional perturbation theory. These calculations provide a stringent test of the S-matrix, showing that it correctly reproduces the universal part of the beta-function and resolving the problem of CDD ambiguities.

  1. Filling Terrorism Gaps: VEOs, Evaluating Databases, and Applying Risk Terrain Modeling to Terrorism

    Energy Technology Data Exchange (ETDEWEB)

    Hagan, Ross F. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-08-29

    This paper aims to address three issues: the lack of literature differentiating terrorism and violent extremist organizations (VEOs), terrorism incident databases, and the applicability of Risk Terrain Modeling (RTM) to terrorism. Current open source literature and publicly available government sources do not differentiate between terrorism and VEOs; furthermore, they fail to define them. Addressing the lack of a comprehensive comparison of existing terrorism data sources, a matrix comparing a dozen terrorism databases is constructed, providing insight toward the array of data available. RTM, a method for spatial risk analysis at a micro level, has some applicability to terrorism research, particularly for studies looking at risk indicators of terrorism. Leveraging attack data from multiple databases, combined with RTM, offers one avenue for closing existing research gaps in terrorism literature.

  2. Study of MR sequence in detecting hyaline cartilage defects of the knee joint

    International Nuclear Information System (INIS)

    Li Songbai; He Cuiju; Sun Wenge; Li Chunkui; Qi Xixun; Li Yanliang; Xu Ke; Bai Xizhuang; Wu Zhenhua

    2003-01-01

    Objective: To evaluate the value of various MR imaging sequences for detecting hyaline cartilage defects. Methods: Ten animal models of cartilage defect were established in 5 pig knees. 5 knees were examined with nine different MR sequences. The signal noise ratio of cartilage and contrast noise ratio were calculated and compared between cartilage and adjacent tissue. Measurement of the defect depth and width on the imaging was correlated with the actual measurement before imaging. 23 patients with hyaline cartilage defects of the knee were evaluated with MR imaging. All these patients underwent subsequent arthroscopy. MR imaging protocol included the selected sequences in the experimental study. Results: The cartilage SNR was better in FSE PD, FS 3D FSPGR, and FS FSE PD sequences. CNR between cartilage and subcartilaginous bone was best in FS 3D FSPGR and FS FSE PD sequences. CNR between cartilage and joint fluid was best in FS 3D FSPGR and FS FSE T 2 WI sequences. CNR between cartilage and meniscus and ligament was best in FS 3D FSPGR, FS FSE PD, SE T 1 WI, and IR TI700 sequences. CNR between cartilage and fat was best in FS 3D FSPGR and SE T 1 WI sequences. The width and depth correlation was best in IR TI700 sequence, which showed the statistical significance (P 2 WI sequence, 68%, 99%, and 0.74, respectively with IR TI700 sequence. Conclusion: The sensitivity of FS 3D FSPGR sequence in detecting hyaline cartilage defect is the highest. T 1 WI of spin echo sequence and T 2 WI/PDWI of fast spin-echo with fat saturation should be the standard sequence in the examination of knee joint. T 1 WI of IR sequence has potential clinical value for cartilage examination

  3. Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage.

    Directory of Open Access Journals (Sweden)

    Rebecca Williams

    Full Text Available BACKGROUND: Articular cartilage displays a poor repair capacity. The aim of cell-based therapies for cartilage defects is to repair damaged joint surfaces with a functional replacement tissue. Currently, chondrocytes removed from a healthy region of the cartilage are used but they are unable to retain their phenotype in expanded culture. The resulting repair tissue is fibrocartilaginous rather than hyaline, potentially compromising long-term repair. Mesenchymal stem cells, particularly bone marrow stromal cells (BMSC, are of interest for cartilage repair due to their inherent replicative potential. However, chondrocyte differentiated BMSCs display an endochondral phenotype, that is, can terminally differentiate and form a calcified matrix, leading to failure in long-term defect repair. Here, we investigate the isolation and characterisation of a human cartilage progenitor population that is resident within permanent adult articular cartilage. METHODS AND FINDINGS: Human articular cartilage samples were digested and clonal populations isolated using a differential adhesion assay to fibronectin. Clonal cell lines were expanded in growth media to high population doublings and karyotype analysis performed. We present data to show that this cell population demonstrates a restricted differential potential during chondrogenic induction in a 3D pellet culture system. Furthermore, evidence of high telomerase activity and maintenance of telomere length, characteristic of a mesenchymal stem cell population, were observed in this clonal cell population. Lastly, as proof of principle, we carried out a pilot repair study in a goat in vivo model demonstrating the ability of goat cartilage progenitors to form a cartilage-like repair tissue in a chondral defect. CONCLUSIONS: In conclusion, we propose that we have identified and characterised a novel cartilage progenitor population resident in human articular cartilage which will greatly benefit future cell

  4. Modelling marine sediment biogeochemistry: Current knowledge gaps, challenges, and some methodological advice for advancement

    DEFF Research Database (Denmark)

    Lessin, Gennadi; Artioli, Yuri; Almroth-Rosell, Elin

    2018-01-01

    The benthic environment is a crucial component of marine systems in the provision of ecosystem services, sustaining biodiversity and in climate regulation, and therefore important to human society. With the contemporary increase in computational power, model resolution and technological improveme......The benthic environment is a crucial component of marine systems in the provision of ecosystem services, sustaining biodiversity and in climate regulation, and therefore important to human society. With the contemporary increase in computational power, model resolution and technological...... improvements in quality and quantity of benthic data, it is necessary to ensure that benthic systems are appropriately represented in coupled benthic-pelagic biogeochemical and ecological modelling studies. In this paper we focus on five topical challenges related to various aspects of modelling benthic...... environments: organic matter reactivity, dynamics of benthic-pelagic boundary layer, microphytobenthos, biological transport and small-scale heterogeneity, and impacts of episodic events. We discuss current gaps in their understanding and indicate plausible ways ahead. Further, we propose a three...

  5. Mixture regression models for the gap time distributions and illness-death processes.

    Science.gov (United States)

    Huang, Chia-Hui

    2018-01-27

    The aim of this study is to provide an analysis of gap event times under the illness-death model, where some subjects experience "illness" before "death" and others experience only "death." Which event is more likely to occur first and how the duration of the "illness" influences the "death" event are of interest. Because the occurrence of the second event is subject to dependent censoring, it can lead to bias in the estimation of model parameters. In this work, we generalize the semiparametric mixture models for competing risks data to accommodate the subsequent event and use a copula function to model the dependent structure between the successive events. Under the proposed method, the survival function of the censoring time does not need to be estimated when developing the inference procedure. We incorporate the cause-specific hazard functions with the counting process approach and derive a consistent estimation using the nonparametric maximum likelihood method. Simulations are conducted to demonstrate the performance of the proposed analysis, and its application in a clinical study on chronic myeloid leukemia is reported to illustrate its utility.

  6. Autologous Cartilage Chip Transplantation Improves Repair Tissue Composition Compared With Marrow Stimulation.

    Science.gov (United States)

    Christensen, Bjørn Borsøe; Olesen, Morten Lykke; Lind, Martin; Foldager, Casper Bindzus

    2017-06-01

    Repair of chondral injuries by use of cartilage chips has recently demonstrated clinical feasibility. To investigate in vivo cartilage repair outcome of autologous cartilage chips compared with marrow stimulation in full-thickness cartilage defects in a minipig model. Controlled laboratory study. Six Göttingen minipigs received two 6-mm chondral defects in the medial and lateral trochlea of each knee. The two treatment groups were (1) autologous cartilage chips embedded in fibrin glue (ACC) (n = 12) and (2) marrow stimulation (MST) (n = 12). The animals were euthanized after 6 months, and the composition of repair tissue was quantitatively determined using histomorphometry. Semiquantitative evaluation was performed by means of the International Cartilage Repair Society (ICRS) II score. Collagen type II staining was used to further evaluate the repair tissue composition. Significantly more hyaline cartilage was found in the ACC (17.1%) compared with MST (2.9%) group ( P cartilage repair tissue compared with MST at 6 months postoperatively. Further studies are needed to investigate ACC as a possible alternative first-line treatment for focal cartilage injuries in the knee.

  7. Tissue engineering of cartilages using biomatrices

    DEFF Research Database (Denmark)

    Melrose, J.; Chuang, C.; Whitelock, J.

    2008-01-01

    and age-related degenerative diseases can all lead to cartilage loss; however, the low cell density and very limited self-renewal capacity of cartilage necessitate the development of effective therapeutic repair strategies for this tissue. The ontogeny of the chondrocyte, which is the cell that provides...... the biosynthetic machinery for all the component parts of cartilage, is discussed, since an understanding of cartilage development is central to the maintenance of a chondrocytic phenotype in any strategy aiming to produce a replacement cartilage. A plethora of matrices have been developed for cartilage...

  8. Closing the contrast gap between testbed and model prediction with WFIRST-CGI shaped pupil coronagraph

    Science.gov (United States)

    Zhou, Hanying; Nemati, Bijan; Krist, John; Cady, Eric; Prada, Camilo M.; Kern, Brian; Poberezhskiy, Ilya

    2016-07-01

    JPL has recently passed an important milestone in its technology development for a proposed NASA WFIRST mission coronagraph: demonstration of better than 1x10-8 contrast over broad bandwidth (10%) on both shaped pupil coronagraph (SPC) and hybrid Lyot coronagraph (HLC) testbeds with the WFIRST obscuration pattern. Challenges remain, however, in the technology readiness for the proposed mission. One is the discrepancies between the achieved contrasts on the testbeds and their corresponding model predictions. A series of testbed diagnoses and modeling activities were planned and carried out on the SPC testbed in order to close the gap. A very useful tool we developed was a derived "measured" testbed wavefront control Jacobian matrix that could be compared with the model-predicted "control" version that was used to generate the high contrast dark hole region in the image plane. The difference between these two is an estimate of the error in the control Jacobian. When the control matrix, which includes both amplitude and phase, was modified to reproduce the error, the simulated performance closely matched the SPC testbed behavior in both contrast floor and contrast convergence speed. This is a step closer toward model validation for high contrast coronagraphs. Further Jacobian analysis and modeling provided clues to the possible sources for the mismatch: DM misregistration and testbed optical wavefront error (WFE) and the deformable mirror (DM) setting for correcting this WFE. These analyses suggested that a high contrast coronagraph has a tight tolerance in the accuracy of its control Jacobian. Modifications to both testbed control model as well as prediction model are being implemented, and future works are discussed.

  9. Gap models and their individual-based relatives in the assessment of the consequences of global change

    Science.gov (United States)

    Shugart, Herman H.; Wang, Bin; Fischer, Rico; Ma, Jianyong; Fang, Jing; Yan, Xiaodong; Huth, Andreas; Armstrong, Amanda H.

    2018-03-01

    Individual-based models (IBMs) of complex systems emerged in the 1960s and early 1970s, across diverse disciplines from astronomy to zoology. Ecological IBMs arose with seemingly independent origins out of the tradition of understanding the ecosystems dynamics of ecosystems from a ‘bottom-up’ accounting of the interactions of the parts. Individual trees are principal among the parts of forests. Because these models are computationally demanding, they have prospered as the power of digital computers has increased exponentially over the decades following the 1970s. This review will focus on a class of forest IBMs called gap models. Gap models simulate the changes in forests by simulating the birth, growth and death of each individual tree on a small plot of land. The summation of these plots comprise a forest (or set of sample plots on a forested landscape or region). Other, more aggregated forest IBMs have been used in global applications including cohort-based models, ecosystem demography models, etc. Gap models have been used to provide the parameters for these bulk models. Currently, gap models have grown from local-scale to continental-scale and even global-scale applications to assess the potential consequences of climate change on natural forests. Modifications to the models have enabled simulation of disturbances including fire, insect outbreak and harvest. Our objective in this review is to provide the reader with an overview of the history, motivation and applications, including theoretical applications, of these models. In a time of concern over global changes, gap models are essential tools to understand forest responses to climate change, modified disturbance regimes and other change agents. Development of forest surveys to provide the starting points for simulations and better estimates of the behavior of the diversity of tree species in response to the environment are continuing needs for improvement for these and other IBMs.

  10. A decreased subchondral trabecular bone tissue elastic modulus is associated with pre-arthritic cartilage damage

    DEFF Research Database (Denmark)

    Day, J; Ding, Ming; van der Linden, JC

    2001-01-01

    determined using a combination of finite element models and mechanical testing. The bone tissue modulus was reduced by 60% in the medial condyle of the cases with cartilage damage compared to the control specimens. Neither the presence of cartilage damage nor the anatomic site (medial vs. lateral) affected...

  11. Socio-demographic Model of Gender Gap in Expected and Actual Wages in Estonia

    OpenAIRE

    Vassil, Kristjan; Eamets, Raul; Mõtsmees, Pille

    2014-01-01

    Estonia ranks consistently on top of the list of countries with the largest gender pay gap. However, irrespective of abundant aggregate level evidence, little is known what motivates the gap at the individual level. In this paper we precisely address the issue of gender pay gap at the individual level. We examine how large is the gender pay gap in actual and expected wages and how it can be explained. We use a rich dataset from Estonian Labour Force Survey on actual wages, and the data from C...

  12. A novel therapeutic strategy for cartilage diseases based on lipid nanoparticle-RNAi delivery system

    Science.gov (United States)

    Wang, Shaowei; Wei, Xiaochun; Sun, Xiaojuan; Chen, Chongwei; Zhou, Jingming; Zhang, Ge; Wu, Heng; Guo, Baosheng

    2018-01-01

    Background Cartilage degeneration affects millions of people but preventing its degeneration is a big challenge. Although RNA interference (RNAi) has been used in human trials via silencing specific genes, the cartilage RNAi has not been possible to date because the cartilage is an avascular and very dense tissue with very low permeability. Purpose The objective of this study was to develop and validate a novel lipid nanoparticle (LNP)-siRNA delivery system that can prevent cartilage degeneration by knocking down specific genes. Methods LNP transfection efficiency was evaluated in vitro and ex vivo. Indian Hedgehog (Ihh) has been correlated with cartilage degeneration. The in vivo effects of LNP-Ihh siRNA complexes on cartilage degeneration were evaluated in a rat model of surgery-induced osteoarthritis (OA). Results In vitro, 100% of chondrocytes were transfected with siRNA in the LNP-siRNA group. In accordance with the cell culture results, red positive signals could be detected even in the deep layer of cartilage tissue cultures treated by LNP-beacon. In vivo data showed that LNP is specific for cartilage, since positive signals were detected by fluorescence molecular tomography and confocal microscopy in joint cartilage injected with LNP-beacon, but not on the surface of the synovium. In the rat model of OA, intraarticular injection of LNP-Ihh siRNA attenuated OA progression, and PCR results showed LNP-Ihh siRNA exerted a positive impact on anabolic metabolism and negative impact on catabolic metabolism. Conclusion This study demonstrates that our LNP-RNAi delivery system has a significantly chondroprotective effect that attenuates cartilage degeneration and holds great promise as a powerful tool for treatment of cartilage diseases by knocking down specific genes. PMID:29440889

  13. A novel therapeutic strategy for cartilage diseases based on lipid nanoparticle-RNAi delivery system.

    Science.gov (United States)

    Wang, Shaowei; Wei, Xiaochun; Sun, Xiaojuan; Chen, Chongwei; Zhou, Jingming; Zhang, Ge; Wu, Heng; Guo, Baosheng; Wei, Lei

    2018-01-01

    Cartilage degeneration affects millions of people but preventing its degeneration is a big challenge. Although RNA interference (RNAi) has been used in human trials via silencing specific genes, the cartilage RNAi has not been possible to date because the cartilage is an avascular and very dense tissue with very low permeability. The objective of this study was to develop and validate a novel lipid nanoparticle (LNP)-siRNA delivery system that can prevent cartilage degeneration by knocking down specific genes. LNP transfection efficiency was evaluated in vitro and ex vivo. Indian Hedgehog ( Ihh ) has been correlated with cartilage degeneration. The in vivo effects of LNP-Ihh siRNA complexes on cartilage degeneration were evaluated in a rat model of surgery-induced osteoarthritis (OA). In vitro, 100% of chondrocytes were transfected with siRNA in the LNP-siRNA group. In accordance with the cell culture results, red positive signals could be detected even in the deep layer of cartilage tissue cultures treated by LNP-beacon. In vivo data showed that LNP is specific for cartilage, since positive signals were detected by fluorescence molecular tomography and confocal microscopy in joint cartilage injected with LNP-beacon, but not on the surface of the synovium. In the rat model of OA, intraarticular injection of LNP-Ihh siRNA attenuated OA progression, and PCR results showed LNP-Ihh siRNA exerted a positive impact on anabolic metabolism and negative impact on catabolic metabolism. This study demonstrates that our LNP-RNAi delivery system has a significantly chondroprotective effect that attenuates cartilage degeneration and holds great promise as a powerful tool for treatment of cartilage diseases by knocking down specific genes.

  14. Conceptual Model-based Systems Biology: mapping knowledge and discovering gaps in the mRNA transcription cycle.

    Directory of Open Access Journals (Sweden)

    Judith Somekh

    2012-12-01

    Full Text Available We propose a Conceptual Model-based Systems Biology framework for qualitative modeling, executing, and eliciting knowledge gaps in molecular biology systems. The framework is an adaptation of Object-Process Methodology (OPM, a graphical and textual executable modeling language. OPM enables concurrent representation of the system's structure-the objects that comprise the system, and behavior-how processes transform objects over time. Applying a top-down approach of recursively zooming into processes, we model a case in point-the mRNA transcription cycle. Starting with this high level cell function, we model increasingly detailed processes along with participating objects. Our modeling approach is capable of modeling molecular processes such as complex formation, localization and trafficking, molecular binding, enzymatic stimulation, and environmental intervention. At the lowest level, similar to the Gene Ontology, all biological processes boil down to three basic molecular functions: catalysis, binding/dissociation, and transporting. During modeling and execution of the mRNA transcription model, we discovered knowledge gaps, which we present and classify into various types. We also show how model execution enhances a coherent model construction. Identification and pinpointing knowledge gaps is an important feature of the framework, as it suggests where research should focus and whether conjectures about uncertain mechanisms fit into the already verified model.

  15. Osteoarthritic cartilage is more homogeneous than healthy cartilage

    DEFF Research Database (Denmark)

    Qazi, Arish A; Dam, Erik B; Nielsen, Mads

    2007-01-01

    it evolves as a consequence to disease and thereby can be used as a progression biomarker. MATERIALS AND METHODS: A total of 283 right and left knees from 159 subjects aged 21 to 81 years were scanned using a Turbo 3D T1 sequence on a 0.18-T MRI Esaote scanner. The medial compartment of the tibial cartilage...... sheet was segmented using a fully automatic voxel classification scheme based on supervised learning. From the segmented cartilage sheet, homogeneity was quantified by measuring entropy from the distribution of signal intensities inside the compartment. Each knee was examined by radiography...... of the region was evaluated by testing for overfitting. Three different regularization techniques were evaluated for reducing overfitting errors. RESULTS: The P values for separating the different groups based on cartilage homogeneity were 2 x 10(-5) (KL 0 versus KL 1) and 1 x 10(-7) (KL 0 versus KL >0). Using...

  16. Knowledge Gaps

    DEFF Research Database (Denmark)

    Lyles, Marjorie; Pedersen, Torben; Petersen, Bent

    2003-01-01

    The study explores what factors influence the reduction of managers' perceivedknowledge gaps in the context of the environments of foreign markets. Potentialdeterminants are derived from traditional internationalization theory as well asorganizational learning theory, including the concept...... of absorptive capacity. Building onthese literature streams a conceptual model is developed and tested on a set of primarydata of Danish firms and their foreign market operations. The empirical study suggeststhat the factors that pertain to the absorptive capacity concept - capabilities ofrecognizing......, assimilating, and utilizing knowledge - are crucial determinants ofknowledge gap elimination. In contrast, the two factors deemed essential in traditionalinternationalization process theory - elapsed time of operations and experientiallearning - are found to have no or limited effect.Key words...

  17. Animating Research with Counseling Values: A Training Model to Address the Research-to-Practice Gap

    Science.gov (United States)

    Lee, Kristi A.; Dewell, John A.; Holmes, Courtney M.

    2014-01-01

    The persistent research-to-practice gap poses a problem for counselor education. The gap may be caused by conflicts between the humanistic values that guide much of counseling and the values that guide research training. In this article, the authors address historical concerns regarding research training for students and the conducting of research…

  18. Imaging of cartilage repair procedures

    International Nuclear Information System (INIS)

    Sanghvi, Darshana; Munshi, Mihir; Pardiwala, Dinshaw

    2014-01-01

    The rationale for cartilage repair is to prevent precocious osteoarthritis in untreated focal cartilage injuries in the young and middle-aged population. The gamut of surgical techniques, normal postoperative radiological appearances, and possible complications have been described. An objective method of recording the quality of repair tissue is with the magnetic resonance observation of cartilage repair tissue (MOCART) score. This scoring system evaluates nine parameters that include the extent of defect filling, border zone integration, signal intensity, quality of structure and surface, subchondral bone, subchondral lamina, and records presence or absence of synovitis and adhesions. The five common techniques of cartilage repair currently offered include bone marrow stimulation (microfracture or drilling), mosaicplasty, synthetic resorbable scaffold grafts, osteochondral allograft transplants, and autologous chondrocyte implantation (ACI). Complications of cartilage repair procedures that may be demonstrated on magnetic resonance imaging (MRI) include plug loosening, graft protuberance, graft depression, and collapse in mosaicplasty, graft hypertrophy in ACI, and immune response leading to graft rejection, which is more common with synthetic grafts and cadaveric allografts

  19. Strategy and gaps for modeling, simulation, and control of hybrid systems

    Energy Technology Data Exchange (ETDEWEB)

    Rabiti, Cristian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Garcia, Humberto E. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Hovsapian, Rob [Idaho National Lab. (INL), Idaho Falls, ID (United States); Kinoshita, Robert [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mesina, George L. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Bragg-Sitton, Shannon M. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Boardman, Richard D. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-04-01

    , dynamic energy systems requires multiple simulation tools, potentially developed in several programming languages and resolved on separate time scales. Whereas further investigation and development of hybrid concepts will provide a more complete understanding of the joint computational and physical modeling needs, this report highlights areas in which co-simulation capabilities are warranted. The current development status, quality assurance, availability and maintainability of simulation tools that are currently available for hybrid systems modeling is presented. Existing gaps in the modeling and simulation toolsets and development needs are subsequently discussed. This effort will feed into a broader Roadmap activity for designing, developing, and demonstrating hybrid energy systems.

  20. Preserved irradiated homologous cartilage for orbital reconstruction

    International Nuclear Information System (INIS)

    Linberg, J.V.; Anderson, R.L.; Edwards, J.J.; Panje, W.R.; Bardach, J.

    1980-01-01

    Human costal cartilage is an excellent implant material for orbital and periorbital reconstruction because of its light weight, strength, homogeneous consistency and the ease with which it can be carved. Its use has been limited by the necessity of a separate surgical procedure to obtain the material. Preserved irradiated homologous cartilage has been shown to have almost all the autogenous cartilage and is convenient to use. Preserved irradiated homologous cartilage transplants do not elicit rejection reactions, resist infection and rarely undergo absorption

  1. MR Imaging of Articular Hyaline Cartilage

    OpenAIRE

    Uetani, Masataka

    2005-01-01

    MR imaging is still an evolving technique for the diagnosis of joint cartilage lesions. Early morphologic changes in the degenerative cartilage are not reliably diagnosed even with use of tailored MR imaging techniques. The detection of the biochemical changes of cartilage or high-resolution MRI will serve as an important tool for the early diagnosis of cartilage degeneration in near future. Further prospective studies are needed to establish the role of MR imaging in clinical use.

  2. Development of Model for Pedestrian Gap Based on Land Use Pattern at Midblock Location and Estimation of Delay at Intersections

    Science.gov (United States)

    Ramesh, Adepu; Ashritha, Kilari; Kumar, Molugaram

    2018-04-01

    Walking has always been a prime source of human mobility for short distance travel. Traffic congestion has become a major problem for safe pedestrian crossing in most of the metropolitan cities. This has emphasized for providing a sufficient pedestrian gap for safe crossing on urban road. The present works aims in understanding factors that influence pedestrian crossing behaviour. Four locations were chosen for identification of pedestrian crossing behaviour, gap characteristics, waiting time etc., in Hyderabad city. From the study it was observed that pedestrian behaviour and crossing patterns are different and is influenced by land use pattern. A gap acceptance model was developed from the data for improving pedestrian safety at mid-block location; the model was validated using the existing data. Pedestrian delay was estimated at intersection using Highway Capacity Manual (HCM). It was observed that field delays are less when compared to delay arrived from HCM method.

  3. Biomaterial and Cell Based Cartilage Repair

    NARCIS (Netherlands)

    Zhao, X

    2015-01-01

    Injuries to human native cartilage tissue are particularly troublesome because cartilage has little ability to heal or regenerate itself. The reconstruction, repair, and regeneration of cartilage tissue continue to be one of the greatest clinical challenges, especially in orthopaedic and plastic

  4. Experimental study on in-vessel debris coolability during severe accident - Experimental and analytical model study on gap cooling in gap

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Soon Heung; Baek, Won Pil; Yang, Soo Hyung; Kim, Soo Hyoung; Lee, Yong Ho; Chung, Yong Hun [Korea Advanced Institute of Science and Technology, Taejon (Korea)

    1999-04-01

    To understand the flooding and mechanism in gap geometry, research was conducted. Final objectives of research are as follows: 1) Literature survey of the flooding and heat transfer mechanism in gap geometry 2) Performing CHF experiments using bottom closed rectangular channels test section 3) Development of flooding correlation using flooding data 4) Derive instability wave length in narrow gap. The major results of research are as follows: 1) Gap size and span of channel are important parameter for flooding. 2) Kutateladze number used for analysing flooding data, is appropriate to the analysis of the flooding using non-circular narrow gap channel. 3) Flooding correlation was developed using collected flooding data and it predicts flooding data lower than 10%. 4) CHF correlation derived from developed flooding collreation overpredict CHF. 5) Instability wave length is increased as gap size is decreased. 26 refs., 46 figs., 2 tabs. (Author)

  5. Cartilage oligomeric matrix protein enhances matrix assembly during chondrogenesis of human mesenchymal stem cells.

    Science.gov (United States)

    Haleem-Smith, Hana; Calderon, Raul; Song, Yingjie; Tuan, Rocky S; Chen, Faye H

    2012-04-01

    Cartilage oligomeric matrix protein/thrombospondin-5 (COMP/TSP5) is an abundant cartilage extracellular matrix (ECM) protein that interacts with major cartilage ECM components, including aggrecan and collagens. To test our hypothesis that COMP/TSP5 functions in the assembly of the ECM during cartilage morphogenesis, we have employed mesenchymal stem cell (MSC) chondrogenesis in vitro as a model to examine the effects of COMP over-expression on neo-cartilage formation. Human bone marrow-derived MSCs were transfected with either full-length COMP cDNA or control plasmid, followed by chondrogenic induction in three-dimensional pellet or alginate hydrogel culture. MSC chondrogenesis and ECM production was estimated based on quantitation of sulfated glycosaminoglycan (sGAG) accumulation, immunohistochemistry of the presence and distribution of cartilage ECM proteins, and real-time RT-PCR analyis of mRNA expression of cartilage markers. Our results showed that COMP over-expression resulted in increased total sGAG content during the early phase of MSC chondrogenesis, and increased immuno-detectable levels of aggrecan and collagen type II in the ECM of COMP-transfected pellet and alginate cultures, indicating more abundant cartilaginous matrix. COMP transfection did not significantly increase the transcript levels of the early chondrogenic marker, Sox9, or aggrecan, suggesting that enhancement of MSC cartilage ECM was effected at post-transcriptional levels. These findings strongly suggest that COMP functions in mesenchymal chondrogenesis by enhancing cartilage ECM organization and assembly. The action of COMP is most likely mediated not via direct changes in cartilage matrix gene expression but via interactions of COMP with other cartilage ECM proteins, such as aggrecan and collagens, that result in enhanced assembly and retention.

  6. CARTILAGE OLIGOMERIC MATRIX PROTEIN ENHANCES MATRIX ASSEMBLY DURING CHONDROGENESIS OF HUMAN MESENCHYMAL STEM CELLS

    Science.gov (United States)

    Haleem-Smith, Hana; Calderon, Raul; Song, Yingjie; Tuan, Rocky S.; Chen, Faye H.

    2011-01-01

    Cartilage oligomeric matrix protein/thrombospondin-5 (COMP/TSP5) is an abundant cartilage extracellular matrix (ECM) protein that interacts with major cartilage ECM components, including aggrecan and collagens. To test our hypothesis that COMP/TSP5 functions in the assembly of the ECM during cartilage morphogenesis, we have employed mesenchymal stem cell (MSC) chondrogenesis in vitro as a model to examine the effects of COMP over-expression on neo-cartilage formation. Human bone marrow-derived MSCs were transfected with either full-length COMP cDNA or control plasmid, followed by chondrogenic induction in three-dimensional pellet or alginate-hydrogel culture. MSC chondrogenesis and ECM production was estimated based on quantitation of sulfated glycosaminoglycan (sGAG) accumulation, immunohistochemistry of the presence and distribution of cartilage ECM proteins, and real-time RT-PCR analyis of mRNA expression of cartilage markers. Our results showed that COMP over-expression resulted in increased total sGAG content during the early phase of MSC chondrogenesis, and increased immuno-detectable levels of aggrecan and collagen type II in the ECM of COMP-transfected pellet and alginate cultures, indicating more abundant cartilaginous matrix. COMP transfection did not significantly increase the transcript levels of the early chondrogenic marker, Sox9, or aggrecan, suggesting that enhancement of MSC cartilage ECM was effected at post-transcriptional levels. These findings strongly suggest that COMP functions in mesenchymal chondrogenesis by enhancing cartilage ECM organization and assembly. The action of COMP is most likely mediated not via direct changes in cartilage matrix gene expression but via interactions of COMP with other cartilage ECM proteins, such as aggrecan and collagens, that result in enhanced assembly and retention. PMID:22095699

  7. Transcriptomic profiling of cartilage ageing

    Directory of Open Access Journals (Sweden)

    Mandy Jayne Peffers

    2014-12-01

    Full Text Available The musculoskeletal system is severely affected by the ageing process, with many tissues undergoing changes that lead to loss of function and frailty. Articular cartilage is susceptible to age related diseases, such as osteoarthritis. Applying RNA-Seq to young and old equine cartilage, we identified an over-representation of genes with reduced expression relating to extracellular matrix, degradative proteases, matrix synthetic enzymes, cytokines and growth factors in cartilage from older donors. Here we describe the contents and quality controls in detail for the gene expression and related results published by Peffers and colleagues in Arthritis Research and Therapy 2013 associated with the data uploaded to ArrayExpress (E-MTAB-1386.

  8. Toward bridging the gap between biological, psychobiological and psychosocial models of alcohol craving.

    Science.gov (United States)

    Monti, P M; Rohsenow, D J; Hutchison, K E

    2000-08-01

    Urge to drink ("craving") has been a central focus of many theories and treatments, but some researchers question the importance of urges during recovery. Several studies assessed reactions to the presence of beverage alcohol (cue-reactivity) or to simulated high-risk situations (role plays). Higher urges in response to role plays predicted more drinking during the 6 months after treatment. However, urges in response to beverage cues were inconsistently predictive of outcome while measures of awareness or attention to cues predicted less drinking. Urge to drink might reflect a conflict between motivation to drink and awareness of danger. Whether urges predict increased risk of drinking should be a function of factors that affect motivation to drink, awareness of risk and effectiveness of coping. Cue-reactivity assessment has recently been used to bridge the gap between psychosocial and biomedical approaches in several ways: (1) salivation to cues predicts increased drinking independent of urge or attention, showing the value of including both physiological and psychosocial measures; (2) naltrexone has been shown to decrease cue-elicited urge to drink, illustrating the value of this assessment methodology for medications evaluation and (3) pre-pulse inhibition of startle response is being used to investigate the role of dopaminergic pathways in cue-elicited urge. Thus, this laboratory based program of research has the potential to add to knowledge of both biomedical and psychosocial mechanisms involved in urge and relapse, leading to greater integration of models.

  9. A preliminary study of the T1rho values of normal knee cartilage using 3 T-MRI

    International Nuclear Information System (INIS)

    Goto, Hajimu; Iwama, Yuki; Fujii, Masahiko; Aoyama, Nobukazu; Kubo, Seiji; Kuroda, Ryosuke; Ohno, Yoshiharu; Sugimura, Kazuro

    2012-01-01

    Introduction: To investigate the degree of the effect of aging and weight-bearing on T1rho values in normal cartilage. Materials and methods: Thirty-two asymptomatic patients were examined using 3.0-T magnetic resonance imaging (MRI) to determine knee cartilage T1rho values and T2 values. The femoral and tibial cartilage was divided into weight-bearing (WB-Rs) and less-weight-bearing (LWB-Rs) regions. Single regression analysis was used to assess the relationship between cartilage T1rho values and age and between T2 values and age. Analysis of variance and post hoc-testing were used to evaluate differences in WB-Rs and LWB-Rs cartilage T1rho values and T2 values. Multiple linear regression modeling was performed to predict cartilage T1rho values. Results: Cartilage T1rho values correlated positively with age for all cartilage regions tested (p < 0.001). There were no significant correlations between cartilage T2 values and age. In both the medial femoral and tibial cartilage, T1rho values were significantly higher in WB-Rs than in LWB-Rs (p < 0.05). There were no significant differences in T2 values between WB-Rs and LWB-Rs. Multiple linear regression analysis showed that both age and weight-bearing were significant predictors of increased medial knee cartilage T1rho values (p < 0.001). Conclusions: Aging and the degree of weight-bearing correlate with the change in cartilage T1rho values. Based on multiple regression modeling, aging may be a more important factor than weight-bearing for cartilage T1rho values.

  10. Designing a Qualitative Data Collection Strategy (QDCS) for Africa - Phase 1: A Gap Analysis of Existing Models, Simulations, and Tools Relating to Africa

    Science.gov (United States)

    2012-06-01

    QDCS) for Africa – Phase I: A Gap Analysis of Existing Models, Simulations, and Tools Relating to Africa Ashley N. Bybee , Project Leader Dominick E...Strategy (QDCS) for Africa – Phase I: A Gap Analysis of Existing Models, Simulations, and Tools Relating to Africa Ashley N. Bybee , Project Leader...Africa Phase I: A Gap Analysis of Existing Models, Simulations, and Tools Relating to Africa June 2012 Authors: Dr. Ashley Bybee , Project Lead Dr

  11. Bridging the Gap between Physiology and Behavior: Evidence from the sSoTS Model of Human Visual Attention

    Science.gov (United States)

    Mavritsaki, Eirini; Heinke, Dietmar; Allen, Harriet; Deco, Gustavo; Humphreys, Glyn W.

    2011-01-01

    We present the case for a role of biologically plausible neural network modeling in bridging the gap between physiology and behavior. We argue that spiking-level networks can allow "vertical" translation between physiological properties of neural systems and emergent "whole-system" performance--enabling psychological results to be simulated from…

  12. Early detection and monitoring of cartilage alteration in the experimental meniscectomised guinea pig model of osteoarthritis by 99mTc-NTP 15-5 scintigraphy

    International Nuclear Information System (INIS)

    Miot-Noirault, Elisabeth; Vidal, Aurelien; Bonafous, Jacques; Audin, Laurent; Madelmont, Jean-Claude; Moins, Nicole; Pastoureau, Philippe; Chomel, Agnes; Sarry, Laurent

    2007-01-01

    This study in the meniscectomised guinea pig aimed to demonstrate that the radiotracer 99m Tc-NTP 15-5 would have pathophysiological validity for in vivo osteoarthritis imaging. The specificity of 99m Tc-NTP 15-5 for cartilage was determined in healthy animals (n = 13), by tissue radioactivity counting, joint autoradiography and scintigraphy. 99m Tc-NTP 15-5 scintigraphy was performed at 20, 50, 80, 115, 130, 150 and 180 days after medial meniscectomy (n = 10 MNX) or sham operation (n = 5), and scintigraphic ratios (operated/contralateral) were calculated for femoral (F) and tibial (T) areas. F and T ratios were compared with those of 99m Tc-MDP bone scintigraphy. At the study end-point, autoradiographic analysis of joint 99m Tc-NTP 15-5 distribution and macroscopic scoring of cartilage integrity were performed. The high and specific accumulation of 99m Tc-NTP 15-5 in normal cartilage (about 5.5 ± 1.7 % of injected dose/g of tissue), which permitted joint imaging with high contrast, was affected by osteoarthritis. In the MNX group, 99m Tc-NTP 15-5 accumulation in cartilage within the operated joint, relative to the contralateral joint, was observed to change in the same animals as pathology progressed. Although F and T ratios were significantly higher in MNX (F = 1.7 ± 0.2; T = 1.6 ± 0.1) than in shams (F = 1.0 ± 0.1; T = 1.0 ± 0.1) at day 50, they were significantly lower in MNX (F = 0.6 ± 0.1; T = 0.7 ± 0.1) than in shams (F = 1.0 ± 0.1; T = 0.9 ± 0.1) at day 180. No change in 99m Tc-MDP uptake was observed over 6 months. Macroscopic analysis confirmed features of osteoarthritis only in MNX knees. These results in MNX guinea pigs provide additional support for the use of 99m Tc-NTP 15-5 for in vivo imaging of osteoarthritis. (orig.)

  13. Early detection and monitoring of cartilage alteration in the experimental meniscectomised guinea pig model of osteoarthritis by {sup 99m}Tc-NTP 15-5 scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Miot-Noirault, Elisabeth; Vidal, Aurelien; Bonafous, Jacques; Audin, Laurent; Madelmont, Jean-Claude; Moins, Nicole [UMR 484 INSERM, Rue Montalembert, BP 184, Clermont-Ferrand Cedex (France); Pastoureau, Philippe; Chomel, Agnes [Institut de Recherches Servier, Suresnes (France); Sarry, Laurent [ERI 14 INSERM - Faculte de Medecine, Clermont-Ferrand (France)

    2007-08-15

    This study in the meniscectomised guinea pig aimed to demonstrate that the radiotracer {sup 99m}Tc-NTP 15-5 would have pathophysiological validity for in vivo osteoarthritis imaging. The specificity of {sup 99m}Tc-NTP 15-5 for cartilage was determined in healthy animals (n = 13), by tissue radioactivity counting, joint autoradiography and scintigraphy. {sup 99m}Tc-NTP 15-5 scintigraphy was performed at 20, 50, 80, 115, 130, 150 and 180 days after medial meniscectomy (n = 10 MNX) or sham operation (n = 5), and scintigraphic ratios (operated/contralateral) were calculated for femoral (F) and tibial (T) areas. F and T ratios were compared with those of {sup 99m}Tc-MDP bone scintigraphy. At the study end-point, autoradiographic analysis of joint {sup 99m}Tc-NTP 15-5 distribution and macroscopic scoring of cartilage integrity were performed. The high and specific accumulation of {sup 99m}Tc-NTP 15-5 in normal cartilage (about 5.5 {+-} 1.7 % of injected dose/g of tissue), which permitted joint imaging with high contrast, was affected by osteoarthritis. In the MNX group, {sup 99m}Tc-NTP 15-5 accumulation in cartilage within the operated joint, relative to the contralateral joint, was observed to change in the same animals as pathology progressed. Although F and T ratios were significantly higher in MNX (F = 1.7 {+-} 0.2; T = 1.6 {+-} 0.1) than in shams (F = 1.0 {+-} 0.1; T = 1.0 {+-} 0.1) at day 50, they were significantly lower in MNX (F = 0.6 {+-} 0.1; T = 0.7 {+-} 0.1) than in shams (F = 1.0 {+-} 0.1; T = 0.9 {+-} 0.1) at day 180. No change in {sup 99m}Tc-MDP uptake was observed over 6 months. Macroscopic analysis confirmed features of osteoarthritis only in MNX knees. These results in MNX guinea pigs provide additional support for the use of {sup 99m}Tc-NTP 15-5 for in vivo imaging of osteoarthritis. (orig.)

  14. UP3005, a Botanical Composition Containing Two Standardized Extracts of Uncaria gambir and Morus alba, Improves Pain Sensitivity and Cartilage Degradations in Monosodium Iodoacetate-Induced Rat OA Disease Model

    Directory of Open Access Journals (Sweden)

    Mesfin Yimam

    2015-01-01

    Full Text Available Osteoarthritis (OA is a multifactorial disease primarily noted by cartilage degradation in association with inflammation that causes significant morbidity, joint pain, stiffness, and limited mobility. Present-day management of OA is inadequate due to the lack of principal therapies proven to be effective in hindering disease progression where symptomatic therapy focused approach masks the actual etiology leading to irreversible damage. Here, we describe the effect of UP3005, a composition containing a proprietary blend of two standardized extracts from the leaf of Uncaria gambir and the root bark of Morus alba, in maintaining joint structural integrity and alleviating OA associated symptoms in monosodium-iodoacetate- (MIA- induced rat OA disease model. Pain sensitivity, micro-CT, histopathology, and glycosaminoglycans (GAGs level analysis were conducted. Diclofenac at 10 mg/kg was used as a reference compound. UP3005 resulted in almost a complete inhibition in proteoglycans degradation, reductions of 16.6% (week 4, 40.5% (week 5, and 22.0% (week 6 in pain sensitivity, statistically significant improvements in articular cartilage matrix integrity, minimal visual subchondral bone damage, and statistically significant increase in bone mineral density when compared to the vehicle control with MIA. Therefore, UP3005 could potentially be considered as an alternative therapy from natural sources for the treatment of OA and/or its associated symptoms.

  15. A biomechanical triphasic approach to the transport of nondilute solutions in articular cartilage.

    Science.gov (United States)

    Abazari, Alireza; Elliott, Janet A W; Law, Garson K; McGann, Locksley E; Jomha, Nadr M

    2009-12-16

    Biomechanical models for biological tissues such as articular cartilage generally contain an ideal, dilute solution assumption. In this article, a biomechanical triphasic model of cartilage is described that includes nondilute treatment of concentrated solutions such as those applied in vitrification of biological tissues. The chemical potential equations of the triphasic model are modified and the transport equations are adjusted for the volume fraction and frictional coefficients of the solutes that are not negligible in such solutions. Four transport parameters, i.e., water permeability, solute permeability, diffusion coefficient of solute in solvent within the cartilage, and the cartilage stiffness modulus, are defined as four degrees of freedom for the model. Water and solute transport in cartilage were simulated using the model and predictions of average concentration increase and cartilage weight were fit to experimental data to obtain the values of the four transport parameters. As far as we know, this is the first study to formulate the solvent and solute transport equations of nondilute solutions in the cartilage matrix. It is shown that the values obtained for the transport parameters are within the ranges reported in the available literature, which confirms the proposed model approach.

  16. Cartilage oligomeric matrix protein enhances the vascularization of acellular nerves

    Directory of Open Access Journals (Sweden)

    Wei-ling Cui

    2016-01-01

    Full Text Available Vascularization of acellular nerves has been shown to contribute to nerve bridging. In this study, we used a 10-mm sciatic nerve defect model in rats to determine whether cartilage oligomeric matrix protein enhances the vascularization of injured acellular nerves. The rat nerve defects were treated with acellular nerve grafting (control group alone or acellular nerve grafting combined with intraperitoneal injection of cartilage oligomeric matrix protein (experimental group. As shown through two-dimensional imaging, the vessels began to invade into the acellular nerve graft from both anastomotic ends at day 7 post-operation, and gradually covered the entire graft at day 21. The vascular density, vascular area, and the velocity of revascularization in the experimental group were all higher than those in the control group. These results indicate that cartilage oligomeric matrix protein enhances the vascularization of acellular nerves.

  17. Model predictions for atmospheric air breakdown by radio-frequency excitation in large gaps

    Science.gov (United States)

    Nguyen, H. K.; Mankowski, J.; Dickens, J. C.; Neuber, A. A.; Joshi, R. P.

    2017-07-01

    The behavior of the breakdown electric field versus frequency (DC to 100 MHz) for different gap lengths has been studied numerically at atmospheric pressure. Unlike previous reports, the focus here is on much larger gap lengths in the 1-5 cm range. A numerical analysis, with transport coefficients obtained from Monte Carlo calculations, is used to ascertain the electric field thresholds at which the growth and extinction of the electron population over time are balanced. Our analysis is indicative of a U-shaped frequency dependence, lower breakdown fields with increasing gap lengths, and trends qualitatively similar to the frequency-dependent field behavior for microgaps. The low frequency value of ˜34 kV/cm for a 1 cm gap approaches the reported DC Paschen limit.

  18. The Gap-Startle Paradigm for Tinnitus Screening in Animal Models: Limitations and Optimization

    Science.gov (United States)

    Lobarinas, Edward; Hayes, Sarah H.; Allman, Brian L.

    2012-01-01

    In 2006, Turner and colleagues (Behav Neurosci, 120:188–195) introduced the gap-startle paradigm as a high-throughput method for tinnitus screening in rats. Under this paradigm, gap detection ability was assessed by determining the level of inhibition of the acoustic startle reflex produced by a short silent gap inserted in an otherwise continuous background sound prior to a loud startling stimulus. Animals with tinnitus were expected to show impaired gap detection ability (i.e., lack of inhibition of the acoustic startle reflex) if the background sound containing the gap was qualitatively similar to the tinnitus pitch. Thus, for the gap-startle paradigm to be a valid tool to screen for tinnitus, a robust startle response from which to inhibit must be present. Because recent studies have demonstrated that the acoustic startle reflex could be dramatically reduced following noise exposure, we endeavored to 1) modify the gap-startle paradigm to be more resilient in the presence of hearing loss, and 2) evaluate whether a reduction in startle reactivity could confound the interpretation of gap prepulse inhibition and lead to errors in screening for tinnitus. In the first experiment, the traditional broadband noise (BBN) startle stimulus was replaced by a bandpass noise in which the sound energy was concentrated in the lower frequencies (5–10 kHz) in order to maintain audibility of the startle stimulus after unilateral high frequency noise exposure (16 kHz). However, rats still showed a 57% reduction in startle amplitude to the bandpass noise post-noise exposure. A follow-up experiment on a separate group of rats with transiently-induced conductive hearing loss revealed that startle reactivity was better preserved when the BBN startle stimulus was replaced by a rapid airpuff to the back of the rats neck. Furthermore, it was found that transient unilateral conductive hearing loss, which was not likely to induce tinnitus, caused an impairment in gap prepulse inhibition

  19. Exponential vanishing of the ground-state gap of the quantum random energy model via adiabatic quantum computing

    Science.gov (United States)

    Adame, J.; Warzel, S.

    2015-11-01

    In this note, we use ideas of Farhi et al. [Int. J. Quantum. Inf. 6, 503 (2008) and Quantum Inf. Comput. 11, 840 (2011)] who link a lower bound on the run time of their quantum adiabatic search algorithm to an upper bound on the energy gap above the ground-state of the generators of this algorithm. We apply these ideas to the quantum random energy model (QREM). Our main result is a simple proof of the conjectured exponential vanishing of the energy gap of the QREM.

  20. Exponential vanishing of the ground-state gap of the quantum random energy model via adiabatic quantum computing

    International Nuclear Information System (INIS)

    Adame, J.; Warzel, S.

    2015-01-01

    In this note, we use ideas of Farhi et al. [Int. J. Quantum. Inf. 6, 503 (2008) and Quantum Inf. Comput. 11, 840 (2011)] who link a lower bound on the run time of their quantum adiabatic search algorithm to an upper bound on the energy gap above the ground-state of the generators of this algorithm. We apply these ideas to the quantum random energy model (QREM). Our main result is a simple proof of the conjectured exponential vanishing of the energy gap of the QREM

  1. Regeneration of hyaline-like cartilage in situ with SOX9 stimulation of bone marrow-derived mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Xiaowei Zhang

    Full Text Available Microfracture, a common procedure for treatment of cartilage injury, induces fibrocartilage repair by recruiting bone marrow derived mesenchymal stem cells (MSC to the site of cartilage injury. However, fibrocartilage is inferior biomechanically to hyaline cartilage. SRY-type high-mobility group box-9 (SOX9 is a master regulator of chondrogenesis by promoting proliferation and differentiation of MSC into chondrocytes. In this study we aimed to test the therapeutic potential of cell penetrating recombinant SOX9 protein in regeneration of hyaline cartilage in situ at the site of cartilage injury. We generated a recombinant SOX9 protein which was fused with super positively charged green fluorescence protein (GFP (scSOX9 to facilitate cell penetration. scSOX9 was able to induce chondrogenesis of bone marrow derived MSC in vitro. In a rabbit cartilage injury model, scSOX9 in combination with microfracture significantly improved quality of repaired cartilage as shown by macroscopic appearance. Histological analysis revealed that the reparative tissue induced by microfracture with scSOX9 had features of hyaline cartilage; and collagen type II to type I ratio was similar to that in normal cartilage. This short term in vivo study demonstrated that when administered at the site of microfracture, scSOX9 was able to induce reparative tissue with features of hyaline cartilage.

  2. Regeneration of hyaline-like cartilage in situ with SOX9 stimulation of bone marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Zhang, Xiaowei; Wu, Shili; Naccarato, Ty; Prakash-Damani, Manan; Chou, Yuan; Chu, Cong-Qiu; Zhu, Yong

    2017-01-01

    Microfracture, a common procedure for treatment of cartilage injury, induces fibrocartilage repair by recruiting bone marrow derived mesenchymal stem cells (MSC) to the site of cartilage injury. However, fibrocartilage is inferior biomechanically to hyaline cartilage. SRY-type high-mobility group box-9 (SOX9) is a master regulator of chondrogenesis by promoting proliferation and differentiation of MSC into chondrocytes. In this study we aimed to test the therapeutic potential of cell penetrating recombinant SOX9 protein in regeneration of hyaline cartilage in situ at the site of cartilage injury. We generated a recombinant SOX9 protein which was fused with super positively charged green fluorescence protein (GFP) (scSOX9) to facilitate cell penetration. scSOX9 was able to induce chondrogenesis of bone marrow derived MSC in vitro. In a rabbit cartilage injury model, scSOX9 in combination with microfracture significantly improved quality of repaired cartilage as shown by macroscopic appearance. Histological analysis revealed that the reparative tissue induced by microfracture with scSOX9 had features of hyaline cartilage; and collagen type II to type I ratio was similar to that in normal cartilage. This short term in vivo study demonstrated that when administered at the site of microfracture, scSOX9 was able to induce reparative tissue with features of hyaline cartilage.

  3. Mechanism of laser-induced stress relaxation in cartilage

    Science.gov (United States)

    Sobol, Emil N.; Sviridov, Alexander P.; Omelchenko, Alexander I.; Bagratashvili, Victor N.; Bagratashvili, Nodar V.; Popov, Vladimir K.

    1997-06-01

    The paper presents theoretical and experimental results allowing to discuss and understand the mechanism of stress relaxation and reshaping of cartilage under laser radiation. A carbon dioxide and a Holmium laser was used for treatment of rabbits and human cartilage. We measured temperature, stress, amplitude of oscillation by free and forced vibration, internal friction, and light scattering in the course of laser irradiation. Using experimental data and theoretical modeling of heat and mass transfer in cartilaginous tissue we estimated the values of transformation heat, diffusion coefficients and energy activation for water movement.

  4. Cartilage oligomeric matrix protein specific antibodies are pathogenic

    DEFF Research Database (Denmark)

    Geng, Hui; Nandakumar, Kutty Selva; Pramhed, Anna

    2012-01-01

    -specific monoclonal antibodies (mAbs). METHODS: B cell immunodominant regions on the COMP molecule were measured with a novel enzyme-linked immunosorbent assay using mammalian expressed full-length mouse COMP as well as a panel of recombinant mouse COMP fragments. 18 mAbs specific to COMP were generated......ABSTRACT: INTRODUCTION: Cartilage oligomeric matrix protein (COMP) is a major non-collagenous component of cartilage. Earlier, we developed a new mouse model for rheumatoid arthritis using COMP. This study was undertaken to investigate the epitope specificity and immunopathogenicity of COMP...

  5. Current status of imaging of articular cartilage

    International Nuclear Information System (INIS)

    Hodler, J.; Resnick, D.

    1996-01-01

    Various imaging methods have been applied to assessment of articular cartilage. These include standard radiography, arthrography, CT, CT arthrography, ultrasonography, and MR imaging. Radiography remains the initial musculoskeletal imaging method. However, it is insensitive to early stages of cartilage abnormalities. MR imaging has great potential in the assessment of articular cartilage, although high-quality scans are required because imaging signs of cartilage abnormalities may be subtle. The potential and limitations of various sequences and techniques are discussed, including MR arthrography. The role of the other imaging methods in assessment of articular cartilage appears to be limited. (orig.). With 8 figs., 6 tabs

  6. A Capstone Project Using the Gap Analysis Model: Closing the College Readiness Gap for Latino English Language Learners with a Focus on School Support and School Counseling Resources

    Science.gov (United States)

    Jimenez, Evelyn

    2013-01-01

    This capstone project applied Clark and Estes' (2008) gap analysis framework to identify performance gaps, develop perceived root causes, validate the causes, and formulate research-based solutions to present to Trojan High School. The purpose was to examine ways to increase the academic achievement of ELL students, specifically Latinos, by…

  7. Non-invasive monitoring of in vivo hydrogel degradation and cartilage regeneration by multiparametric MR imaging

    Science.gov (United States)

    Chen, Zelong; Yan, Chenggong; Yan, Shina; Liu, Qin; Hou, Meirong; Xu, Yikai; Guo, Rui

    2018-01-01

    Numerous biodegradable hydrogels for cartilage regeneration have been widely used in the field of tissue engineering. However, to non-invasively monitor hydrogel degradation and efficiently evaluate cartilage restoration in situ is still challenging. Methods: A ultrasmall superparamagnetic iron oxide (USPIO)-labeled cellulose nanocrystal (CNC)/silk fibroin (SF)-blended hydrogel system was developed to monitor hydrogel degradation during cartilage regeneration. The physicochemical characterization and biocompatibility of the hydrogel were evaluated in vitro. The in vivo hydrogel degradation and cartilage regeneration of different implants were assessed using multiparametric magnetic resonance imaging (MRI) and further confirmed by histological analysis in a rabbit cartilage defect model for 3 months. Results: USPIO-labeled hydrogels showed sufficient MR contrast enhancement and retained stability without loss of the relaxation rate. Neither the mechanical properties of the hydrogels nor the proliferation of bone-marrow mesenchymal stem cells (BMSCs) were affected by USPIO labeling in vitro. CNC/SF hydrogels with BMSCs degraded more quickly than the acellular hydrogels as reflected by the MR relaxation rate trends in vivo. The morphology of neocartilage was noninvasively visualized by the three-dimensional water-selective cartilage MRI scan sequence, and the cartilage repair was further demonstrated by macroscopic and histological observations. Conclusion: This USPIO-labeled CNC/SF hydrogel system provides a new perspective on image-guided tissue engineering for cartilage regeneration. PMID:29464005

  8. Valence bond solids for SU(n) spin chains: Exact models, spinon confinement, and the Haldane gap

    International Nuclear Information System (INIS)

    Greiter, Martin; Rachel, Stephan

    2007-01-01

    To begin with, we introduce several exact models for SU(3) spin chains: First is a translationally invariant parent Hamiltonian involving four-site interactions for the trimer chain, with a threefold degenerate ground state. We provide numerical evidence that the elementary excitations of this model transform under representation 3 of SU(3) if the original spins of the model transform under representation 3. Second is a family of parent Hamiltonians for valence bond solids of SU(3) chains with spin representations 6, 10, and 8 on each lattice site. We argue that of these three models, only the latter two exhibit spinon confinement and, hence, a Haldane gap in the excitation spectrum. We generalize some of our models to SU(n). Finally, we use the emerging rules for the construction of valence bond solid states to argue that models of antiferromagnetic chains of SU(n) spins, in general, possess a Haldane gap if the spins transform under a representation corresponding to a Young tableau consisting of a number of boxes λ which is divisible by n. If λ and n have no common divisor, the spin chain will support deconfined spinons and not exhibit a Haldane gap. If λ and n have a common divisor different from n, it will depend on the specifics of the model including the range of the interaction

  9. Bridging the Gap Between Science and Clinical Efficacy: Physiology, Imaging, and Modeling of Aerosols in the Lung.

    Science.gov (United States)

    Darquenne, Chantal; Fleming, John S; Katz, Ira; Martin, Andrew R; Schroeter, Jeffry; Usmani, Omar S; Venegas, Jose; Schmid, Otmar

    2016-04-01

    Development of a new drug for the treatment of lung disease is a complex and time consuming process involving numerous disciplines of basic and applied sciences. During the 2015 Congress of the International Society for Aerosols in Medicine, a group of experts including aerosol scientists, physiologists, modelers, imagers, and clinicians participated in a workshop aiming at bridging the gap between basic research and clinical efficacy of inhaled drugs. This publication summarizes the current consensus on the topic. It begins with a short description of basic concepts of aerosol transport and a discussion on targeting strategies of inhaled aerosols to the lungs. It is followed by a description of both computational and biological lung models, and the use of imaging techniques to determine aerosol deposition distribution (ADD) in the lung. Finally, the importance of ADD to clinical efficacy is discussed. Several gaps were identified between basic science and clinical efficacy. One gap between scientific research aimed at predicting, controlling, and measuring ADD and the clinical use of inhaled aerosols is the considerable challenge of obtaining, in a single study, accurate information describing the optimal lung regions to be targeted, the effectiveness of targeting determined from ADD, and some measure of the drug's effectiveness. Other identified gaps were the language and methodology barriers that exist among disciplines, along with the significant regulatory hurdles that need to be overcome for novel drugs and/or therapies to reach the marketplace and benefit the patient. Despite these gaps, much progress has been made in recent years to improve clinical efficacy of inhaled drugs. Also, the recent efforts by many funding agencies and industry to support multidisciplinary networks including basic science researchers, R&D scientists, and clinicians will go a long way to further reduce the gap between science and clinical efficacy.

  10. [Current overview of cartilage regeneration procedures].

    Science.gov (United States)

    Schenker, H; Wild, M; Rath, B; Tingart, M; Driessen, A; Quack, V; Betsch, M

    2017-11-01

    Cartilage is an avascular, alymphatic and non-innervated tissue with limited intrinsic repair potential. The high prevalence of cartilage defects and their tremendous clinical importance are a challenge for all treating physicians. This article provides the reader with an overview about current cartilage treatment options and their clinical outcome. Microfracture is still considered the gold standard in the treatment of small cartilage lesions. Small osteochondral defects can be effectively treated with the autologous osteochondral transplantation system. Larger cartilage defects are successfully treated by autologous membrane-induced chondrogenesis (AMIC) or by membrane-assisted autologous chondrocyte implantation (MACI). Despite limitations of current cartilage repair strategies, such procedures can result in short- and mid-term clinical improvement of the patients. Further developments and clinical studies are necessary to improve the long-term outcome following cartilage repair.

  11. Development of artificial articular cartilage

    Indian Academy of Sciences (India)

    Mechanical strength of Poly(vinyl alcohol), PVA is improved up to 35 MPa. Manufacturing method is adopted considering colloidal stability of nano silica particle in PVA sol at specific pH = 1. An adhesive is also prepared from PVA/Si nanocomposite containing 40% TEOS for firm attachment of artificial articular cartilage on ...

  12. Postnatal development of articular cartilage

    NARCIS (Netherlands)

    Turnhout, van M.C.

    2010-01-01

    Articular cartilage (AC) is the thin layer of tissue that covers the ends of the bones in the synovial joints in mammals. Functional adult AC has depth-dependent mechanical properties that are not yet present at birth. These depth-dependent mechanical properties in adult life are the result of a

  13. Strategies for Stratified Cartilage Bioprinting

    NARCIS (Netherlands)

    Schuurman, W.|info:eu-repo/dai/nl/313939322

    2012-01-01

    Multiple materials, cells and growth factors can be combined into one construct by the use of a state–of-the-art bioprinter. This technique may in the future make the fabrication of complete tissues or organs possible. In this thesis the feasibility of the bioprinting of cartilage and the

  14. Chondroma of the cricoid cartilage

    Directory of Open Access Journals (Sweden)

    Melo, Giulianno Molina de

    2008-12-01

    Full Text Available Introduction: The larynx cartilaginous tumors are uncommon and comprise 1% of all cartilaginous tumors. The chondroma is the most common benign tumor affecting the larynx cricoid cartilage (75%, and manifests normally in the male gender with dysphonia, progressive dyspnea and dysphagy in some cases. Objective: The objective of this study is to report a case of cricoid cartilage chondroma, in a patient with the symptom of a nodular lesion in the frontal cervical region of slow and progressive growth. Case Report: The treatment was the modified partial laryngectomy with resection of the lower hemisegment of the thyroid cartilage, cricoid hemicartilage and the first tracheal ring with free margins and reconstruction with a pericondrium and muscular prethyroidean piece. The anatomopathological exam showed a chondroma of 1.1 cm, of atypical low cellularity and low figures of mitosis in the frontal region of the cricoid cartilage. Conclusion: In this report we agreed with the literature for the primarily extensive surgical treatment depending on the location and the size of the cricoid chondroma; however, other modalities of treatment may be adopted in cases where the tumor extension appoints a total laryngectomy or when this is not possible to carry out, aiming at the preservation of the larynx. For the suitable treatment of cricoid chondromas, the understanding of the disease natural evolution and more case reports are still necessary.

  15. The energy trilogy: An integrated sustainability model to bridge wastewater treatment plant energy and emissions gaps

    Science.gov (United States)

    Al-Talibi, A. Adhim

    An estimated 4% of national energy consumption is used for drinking water and wastewater services. Despite the awareness and optimization initiatives for energy conservation, energy consumption is on the rise owing to population and urbanization expansion and to commercial and industrial business advancement. The principal concern is since energy consumption grows, the higher will be the energy production demand, leading to an increase in CO2 footprints and the contribution to global warming potential. This research is in the area of energy-water nexus, focusing on wastewater treatment plant (WWTP) energy trilogy -- the group of three related entities, which includes processes: (1) consuming energy, (2) producing energy, and (3) the resulting -- CO2 equivalents. Detailed and measurable energy information is not readily obtained for wastewater facilities, specifically during facility preliminary design phases. These limitations call for data-intensive research approach on GHG emissions quantification, plant efficiencies and source reduction techniques. To achieve these goals, this research introduced a model integrating all plant processes and their pertinent energy sources. In a comprehensive and "Energy Source-to-Effluent Discharge" pattern, this model is capable of bridging the gaps of WWTP energy, facilitating plant designers' decision-making for meeting energy assessment, sustainability and the environmental regulatory compliance. Protocols for estimating common emissions sources are available such as for fuels, whereas, site-specific emissions for other sources have to be developed and are captured in this research. The dissertation objectives were met through an extensive study of the relevant literature, models and tools, originating comprehensive lists of processes and energy sources for WWTPs, locating estimation formulas for each source, identifying site specific emissions factors, and linking the sources in a mathematical model for site specific CO2 e

  16. An efficient modeling of fine air-gaps in tokamak in-vessel components for electromagnetic analyses

    International Nuclear Information System (INIS)

    Oh, Dong Keun; Pak, Sunil; Jhang, Hogun

    2012-01-01

    Highlights: ► A simple and efficient modeling technique is introduced to avoid undesirable massive air mesh which is usually encountered at the modeling of fine structures in tokamak in-vessel component. ► This modeling method is based on the decoupled nodes at the boundary element mocking the air gaps. ► We demonstrated the viability and efficacy, comparing this method with brute force modeling of air-gaps and effective resistivity approximation instead of detail modeling. ► Application of the method to the ITER machine was successfully carried out without sacrificing computational resources and speed. - Abstract: A simple and efficient modeling technique is presented for a proper analysis of complicated eddy current flows in conducting structures with fine air gaps. It is based on the idea of replacing a slit with the decoupled boundary of finite elements. The viability and efficacy of the technique is demonstrated in a simple problem. Application of the method to electromagnetic load analyses during plasma disruptions in ITER has been successfully carried out without sacrificing computational resources and speed. This shows the proposed method is applicable to a practical system with complicated geometrical structures.

  17. Effect of histone deacetylase inhibitor, trichostatin A, on cartilage ...

    African Journals Online (AJOL)

    Purpose: To evaluate the effect of histone deacetylase (HDAC) inhibitor, trichostatin A (TCA), on cartilage regeneration in a rabbit perichondrial graft model. Methods: Perichondrial grafts (20 × 20 mm2) were derived from the ears of New Zealand rabbits and transplanted onto the paravertebral muscle of the face of each ...

  18. Transport of neutral solute across articular cartilage: the role of zonal diffusivities.

    Science.gov (United States)

    Arbabi, V; Pouran, B; Weinans, H; Zadpoor, A A

    2015-07-01

    Transport of solutes through diffusion is an important metabolic mechanism for the avascular cartilage tissue. Three types of interconnected physical phenomena, namely mechanical, electrical, and chemical, are all involved in the physics of transport in cartilage. In this study, we use a carefully designed experimental-computational setup to separate the effects of mechanical and chemical factors from those of electrical charges. Axial diffusion of a neutral solute Iodixanol into cartilage was monitored using calibrated microcomputed tomography micro-CT images for up to 48 hr. A biphasic-solute computational model was fitted to the experimental data to determine the diffusion coefficients of cartilage. Cartilage was modeled either using one single diffusion coefficient (single-zone model) or using three diffusion coefficients corresponding to superficial, middle, and deep cartilage zones (multizone model). It was observed that the single-zone model cannot capture the entire concentration-time curve and under-predicts the near-equilibrium concentration values, whereas the multizone model could very well match the experimental data. The diffusion coefficient of the superficial zone was found to be at least one order of magnitude larger than that of the middle zone. Since neutral solutes were used, glycosaminoglycan (GAG) content cannot be the primary reason behind such large differences between the diffusion coefficients of the different cartilage zones. It is therefore concluded that other features of the different cartilage zones such as water content and the organization (orientation) of collagen fibers may be enough to cause large differences in diffusion coefficients through the cartilage thickness.

  19. Modeling of Particle Transport on Channels and Gaps Exposed to Plasma Fluxes

    International Nuclear Information System (INIS)

    Nieto-Perez, Martin

    2008-01-01

    Many problems in particle transport in fusion devices involve the transport of plasma or eroded particles through channels or gaps, such as in the case of trying to assess damage to delicate optical diagnostics collecting light through a slit or determining the deposition and codeposition on the gaps between tiles of plasma-facing components. A dynamic-composition Monte Carlo code in the spirit of TRIDYN, previously developed to study composition changes on optical mirrors subject to ion bombardment, has been upgraded to include motion of particles through a volume defined by sets of plane surfaces. Particles sputtered or reflected from the walls of the channel/gap can be tracked as well, allowing the calculation of wall impurity transport, either back to the plasma (for the case of a gap) or to components separated from the plasma by a channel/slit (for the case of optical diagnostics). Two examples of the code application to particle transport in fusion devices will be presented in this work: one will evaluate the erosion/impurity deposition rate on a mirror separated from a plasma source by a slit; the other case will look at the enhanced emission of tile material in the region of the gap between two tiles

  20. Effect of Climate and Management Factors on Potential and Gap of Wheat Yield in Iran with Using WOFOST Model

    Directory of Open Access Journals (Sweden)

    A Koocheki

    2017-10-01

    intensification. We estimated a stochastic frontier production function to calculate global datasets of maximum attainable grain yields, yield gaps, and efficiencies of grain production at. Applying a stochastic frontier production function facilitates estimating the yield gap based on the actual grain yield data only, instead of using actual and potential grain yield data from different sources. Therefore, the method allows for a robust and consistent analysis of the yield gap. The factors determining the yield gap are quantified at both global and regional scales. For this purpose, climatic information and wheat yield of different provinces were obtained from Iran meteorological organization and Agriculture Jahade organization, respectively. Wheat potential yield in different provinces was simulated by WOFOST model. Wheat gap was gained by difference between actual and potential yield in different provinces. Relative share of climatic variables in potential yield and also relative share of management variables included irrigation, fertilizer application, mechanization, pesticide application and manure in wheat yield gap was calculated by frontier production function. Results and Discussion The results showed that the effect of precipitation and radiation on wheat potential yield was positive and the impact of temperature was negative. Precipitation had the highest impact on wheat potential yield among other climatic variables. The range of wheat yield gap was from 1646 to 4470 kg ha-1 and 29 to 58% in Iran. Generally, the effect of all management variables on wheat yield gap was negative so that wheat yield gap was reduced by improving of these variables. Among studied management variables, irrigation had the highest effect on yield gap reduction, especially in dry-warm climate and fertilizer application was the second factor which had high effect on yield gap reduction. Therefore, to reduce wheat yield gap in Iran, irrigation management and fertilizer application should be

  1. Cartilage-selective genes identified in genome-scale analysis of non-cartilage and cartilage gene expression

    Directory of Open Access Journals (Sweden)

    Cohn Zachary A

    2007-06-01

    Full Text Available Abstract Background Cartilage plays a fundamental role in the development of the human skeleton. Early in embryogenesis, mesenchymal cells condense and differentiate into chondrocytes to shape the early skeleton. Subsequently, the cartilage anlagen differentiate to form the growth plates, which are responsible for linear bone growth, and the articular chondrocytes, which facilitate joint function. However, despite the multiplicity of roles of cartilage during human fetal life, surprisingly little is known about its transcriptome. To address this, a whole genome microarray expression profile was generated using RNA isolated from 18–22 week human distal femur fetal cartilage and compared with a database of control normal human tissues aggregated at UCLA, termed Celsius. Results 161 cartilage-selective genes were identified, defined as genes significantly expressed in cartilage with low expression and little variation across a panel of 34 non-cartilage tissues. Among these 161 genes were cartilage-specific genes such as cartilage collagen genes and 25 genes which have been associated with skeletal phenotypes in humans and/or mice. Many of the other cartilage-selective genes do not have established roles in cartilage or are novel, unannotated genes. Quantitative RT-PCR confirmed the unique pattern of gene expression observed by microarray analysis. Conclusion Defining the gene expression pattern for cartilage has identified new genes that may contribute to human skeletogenesis as well as provided further candidate genes for skeletal dysplasias. The data suggest that fetal cartilage is a complex and transcriptionally active tissue and demonstrate that the set of genes selectively expressed in the tissue has been greatly underestimated.

  2. Patellofemoral instability in children: T2 relaxation times of the patellar cartilage in patients with and without patellofemoral instability and correlation with morphological grading of cartilage damage

    International Nuclear Information System (INIS)

    Kang, Chang Ho; Kim, Hee Kyung; Shiraj, Sahar; Anton, Christopher; Kim, Dong Hoon; Horn, Paul S.

    2016-01-01

    Patellofemoral instability is one of the most common causes of cartilage damage in teenagers. To quantitatively evaluate the patellar cartilage in patients with patellofemoral instability using T2 relaxation time maps (T2 maps), compare the values to those in patients without patellofemoral instability and correlate them with morphological grades in patients with patellofemoral instability. Fifty-three patients with patellofemoral instability (mean age: 15.9 ± 2.4 years) and 53 age- and gender-matched patients without patellofemoral instability were included. Knee MR with axial T2 map was performed. Mean T2 relaxation times were obtained at the medial, central and lateral zones of the patellar cartilage and compared between the two groups. In the patellofemoral instability group, morphological grading of the patellar cartilage (0-4) was performed and correlated with T2 relaxation times. Mean T2 relaxation times were significantly longer in the group with patellofemoral instability as compared to those of the control group across the patellar cartilage (Student's t-test, P<0.05) with the longest time at the central area. Positive correlation was seen between mean T2 relaxation time and morphological grading (Pearson correlation coefficiency, P<0.001). T2 increased with severity of morphological grading from 0 to 3 (mixed model, P<0.001), but no statistical difference was seen between grades 3 and 4. In patellofemoral instability, patellar cartilage damage occurs across the entire cartilage with the highest T2 values at the apex. T2 relaxation times directly reflect the severity in low-grade cartilage damage, which implies an important role for T2 maps in differentiating between normal and low-grade cartilage damage. (orig.)

  3. Local air gap thickness and contact area models for realistic simulation of human thermo-physiological response

    Science.gov (United States)

    Psikuta, Agnes; Mert, Emel; Annaheim, Simon; Rossi, René M.

    2018-02-01

    To evaluate the quality of new energy-saving and performance-supporting building and urban settings, the thermal sensation and comfort models are often used. The accuracy of these models is related to accurate prediction of the human thermo-physiological response that, in turn, is highly sensitive to the local effect of clothing. This study aimed at the development of an empirical regression model of the air gap thickness and the contact area in clothing to accurately simulate human thermal and perceptual response. The statistical model predicted reliably both parameters for 14 body regions based on the clothing ease allowances. The effect of the standard error in air gap prediction on the thermo-physiological response was lower than the differences between healthy humans. It was demonstrated that currently used assumptions and methods for determination of the air gap thickness can produce a substantial error for all global, mean, and local physiological parameters, and hence, lead to false estimation of the resultant physiological state of the human body, thermal sensation, and comfort. Thus, this model may help researchers to strive for improvement of human thermal comfort, health, productivity, safety, and overall sense of well-being with simultaneous reduction of energy consumption and costs in built environment.

  4. Astrocytic gap junctional networks suppress cellular damage in an in vitro model of ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Shinotsuka, Takanori; Yasui, Masato; Nuriya, Mutsuo, E-mail: mnuriya@z2.keio.jp

    2014-02-07

    Highlights: • Astrocytes exhibit characteristic changes in [Ca{sup 2+}]{sub i} under OGD. • Astrocytic [Ca{sup 2+}]{sub i} increase is synchronized with a neuronal anoxic depolarization. • Gap junctional couplings protect neurons as well as astrocytes during OGD. - Abstract: Astrocytes play pivotal roles in both the physiology and the pathophysiology of the brain. They communicate with each other via extracellular messengers as well as through gap junctions, which may exacerbate or protect against pathological processes in the brain. However, their roles during the acute phase of ischemia and the underlying cellular mechanisms remain largely unknown. To address this issue, we imaged changes in the intracellular calcium concentration ([Ca{sup 2+}]{sub i}) in astrocytes in mouse cortical slices under oxygen/glucose deprivation (OGD) condition using two-photon microscopy. Under OGD, astrocytes showed [Ca{sup 2+}]{sub i} oscillations followed by larger and sustained [Ca{sup 2+}]{sub i} increases. While the pharmacological blockades of astrocytic receptors for glutamate and ATP had no effect, the inhibitions of gap junctional intercellular coupling between astrocytes significantly advanced the onset of the sustained [Ca{sup 2+}]{sub i} increase after OGD exposure. Interestingly, the simultaneous recording of the neuronal membrane potential revealed that the onset of the sustained [Ca{sup 2+}]{sub i} increase in astrocytes was synchronized with the appearance of neuronal anoxic depolarization. Furthermore, the blockade of gap junctional coupling resulted in a concurrent faster appearance of neuronal depolarizations, which remain synchronized with the sustained [Ca{sup 2+}]{sub i} increase in astrocytes. These results indicate that astrocytes delay the appearance of the pathological responses of astrocytes and neurons through their gap junction-mediated intercellular network under OGD. Thus, astrocytic gap junctional networks provide protection against tissue damage

  5. Astrocytic gap junctional networks suppress cellular damage in an in vitro model of ischemia

    International Nuclear Information System (INIS)

    Shinotsuka, Takanori; Yasui, Masato; Nuriya, Mutsuo

    2014-01-01

    Highlights: • Astrocytes exhibit characteristic changes in [Ca 2+ ] i under OGD. • Astrocytic [Ca 2+ ] i increase is synchronized with a neuronal anoxic depolarization. • Gap junctional couplings protect neurons as well as astrocytes during OGD. - Abstract: Astrocytes play pivotal roles in both the physiology and the pathophysiology of the brain. They communicate with each other via extracellular messengers as well as through gap junctions, which may exacerbate or protect against pathological processes in the brain. However, their roles during the acute phase of ischemia and the underlying cellular mechanisms remain largely unknown. To address this issue, we imaged changes in the intracellular calcium concentration ([Ca 2+ ] i ) in astrocytes in mouse cortical slices under oxygen/glucose deprivation (OGD) condition using two-photon microscopy. Under OGD, astrocytes showed [Ca 2+ ] i oscillations followed by larger and sustained [Ca 2+ ] i increases. While the pharmacological blockades of astrocytic receptors for glutamate and ATP had no effect, the inhibitions of gap junctional intercellular coupling between astrocytes significantly advanced the onset of the sustained [Ca 2+ ] i increase after OGD exposure. Interestingly, the simultaneous recording of the neuronal membrane potential revealed that the onset of the sustained [Ca 2+ ] i increase in astrocytes was synchronized with the appearance of neuronal anoxic depolarization. Furthermore, the blockade of gap junctional coupling resulted in a concurrent faster appearance of neuronal depolarizations, which remain synchronized with the sustained [Ca 2+ ] i increase in astrocytes. These results indicate that astrocytes delay the appearance of the pathological responses of astrocytes and neurons through their gap junction-mediated intercellular network under OGD. Thus, astrocytic gap junctional networks provide protection against tissue damage during the acute phase of ischemia

  6. Model Evidence of a Superconducting State with a Full Energy Gap in Small Cuprate Islands

    Science.gov (United States)

    Black-Schaffer, Annica M.; Golubev, Dmitri S.; Bauch, Thilo; Lombardi, Floriana; Fogelström, Mikael

    2013-05-01

    We investigate subdominant order parameters stabilizing at low temperatures in nanoscale high-Tc cuprate islands, motivated by the recent observation of a fully gapped state in nanosized YBa2Cu3O7-δ [D. Gustafsson et al., Nature Nanotech. 8, 25 (2013)]. Using complementary quasiclassical and tight-binding Bogoliubov-de Gennes methods, we show on distinctly different properties dependent on the symmetry being dx2-y2+is or dx2-y2+idxy. We find that a surface-induced dx2-y2+is phase creates a global spectroscopic gap which increases with an applied magnetic field, consistent with experimental observation.

  7. Multinuclear nuclear magnetic resonance spectroscopic study of cartilage proteoglycans

    Energy Technology Data Exchange (ETDEWEB)

    Lerner, L.

    1985-01-01

    Hyaline cartilage is a composite material whose major function is to withstand compression while retaining flexibility. Its mechanical properties are affected by tissue hydration and ionic composition. Models of the mechanical behavior of cartilage have incorporated certain assumptions about the interactions of the major components of cartilage: collagen, proteoglycans, water, and cations. To determine the validity of these assumption, the authors have used nuclear magnetic resonance spectroscopy (NMR). Two approaches have been used: (a) natural abundance carbon-13 NMR; and (b) NMR of sodium-23, potassium-39, magnesium-25, and calcium-43. Evidence from studies in intact tissues are reinforced by extensive measurements on solutions of proteoglycans and other relevant macromolecules. Based on the measurements of NMR relaxation rates and lineshapes reported here, it is concluded that neither sodium nor potassium interact strongly with bovine nasal proteoglycan aggregates or their substituent glycosaminoglycan chains in solution. Proteoglycans do bind magnesium and calcium. Therefore there is a qualitative difference between monovalent and divalent cations, which is not taken into account by polyelectrolyte models or models for the ionic dependence of mechanical properties. Cation binding to heparin, which has a higher charge density than cartilage proteoglycans, was also studied. The results presented here establish that heparin binds sodium, magnesium, and calcium.

  8. Systems Based Study of the Therapeutic Potential of Small Charged Molecules for the Inhibition of IL-1 Mediated Cartilage Degradation

    Science.gov (United States)

    Kar, Saptarshi; Smith, David W.; Gardiner, Bruce S.; Grodzinsky, Alan J.

    2016-01-01

    Inflammatory cytokines are key drivers of cartilage degradation in post-traumatic osteoarthritis. Cartilage degradation mediated by these inflammatory cytokines has been extensively investigated using in vitro experimental systems. Based on one such study, we have developed a computational model to quantitatively assess the impact of charged small molecules intended to inhibit IL-1 mediated cartilage degradation. We primarily focus on the simplest possible computational model of small molecular interaction with the IL-1 system—direct binding of the small molecule to the active site on the IL-1 molecule itself. We first use the model to explore the uptake and release kinetics of the small molecule inhibitor by cartilage tissue. Our results show that negatively charged small molecules are excluded from the negatively charged cartilage tissue and have uptake kinetics in the order of hours. In contrast, the positively charged small molecules are drawn into the cartilage with uptake and release timescales ranging from hours to days. Using our calibrated computational model, we subsequently explore the effect of small molecule charge and binding constant on the rate of cartilage degradation. The results from this analysis indicate that the small molecules are most effective in inhibiting cartilage degradation if they are either positively charged and/or bind strongly to IL-1α, or both. Furthermore, our results showed that the cartilage structural homeostasis can be restored by the small molecule if administered within six days following initial tissue exposure to IL-1α. We finally extended the scope of the computational model by simulating the competitive inhibition of cartilage degradation by the small molecule. Results from this model show that small molecules are more efficient in inhibiting cartilage degradation by binding directly to IL-1α rather than binding to IL-1α receptors. The results from this study can be used as a template for the design and

  9. Transfection of the IHH gene into rabbit BMSCs in a simulated microgravity environment promotes chondrogenic differentiation and inhibits cartilage aging.

    Science.gov (United States)

    Liu, Peng-Cheng; Liu, Kuan; Liu, Jun-Feng; Xia, Kuo; Chen, Li-Yang; Wu, Xing

    2016-09-27

    The effect of overexpressing the Indian hedgehog (IHH) gene on the chondrogenic differentiation of rabbit bone marrow-derived mesenchymal stem cells (BMSCs) was investigated in a simulated microgravity environment. An adenovirus plasmid encoding the rabbit IHH gene was constructed in vitro and transfected into rabbit BMSCs. Two large groups were used: conventional cell culture and induction model group and simulated microgravity environment group. Each large group was further divided into blank control group, GFP transfection group, and IHH transfection group. During differentiation induction, the expression levels of cartilage-related and cartilage hypertrophy-related genes and proteins in each group were determined. In the conventional model, the IHH transfection group expressed high levels of cartilage-related factors (Coll2 and ANCN) at the early stage of differentiation induction and expressed high levels of cartilage hypertrophy-related factors (Coll10, annexin 5, and ALP) at the late stage. Under the simulated microgravity environment, the IHH transfection group expressed high levels of cartilage-related factors and low levels of cartilage hypertrophy-related factors at all stages of differentiation induction. Under the simulated microgravity environment, transfection of the IHH gene into BMSCs effectively promoted the generation of cartilage and inhibited cartilage aging and osteogenesis. Therefore, this technique is suitable for cartilage tissue engineering.

  10. Neutron model for the formation of AGN jets with Cetral Radio Gap ...

    African Journals Online (AJOL)

    In this work, there has been an attempt to explain the formation of jets in some radio sources with gaps at their centers using the neutron “production-to-decay” process. The jet-light-up point is taken to coincide with the end of the lifetime of the neutrons. Calculated intrinsic opening angles for the jets of the selected Active ...

  11. Utility of T2 mapping and dGEMRIC for evaluation of cartilage repair after allograft chondrocyte implantation in a rabbit model.

    Science.gov (United States)

    Endo, J; Watanabe, A; Sasho, T; Yamaguchi, S; Saito, M; Akagi, R; Muramatsu, Y; Mukoyama, S; Katsuragi, J; Akatsu, Y; Fukawa, T; Okubo, T; Osone, F; Takahashi, K

    2015-02-01

    To investigate the effectiveness of quantitative Magnetic resonance imaging (MRI) for evaluating the quality of cartilage repair over time following allograft chondrocyte implantation using a three-dimensional scaffold for osteochondral lesions. Thirty knees from 15 rabbits were analyzed. An osteochondral defect (diameter, 4 mm; depth, 1 mm) was created on the patellar groove of the femur in both legs. The defects were filled with a chondrocyte-seeded scaffold in the right knee and an empty scaffold in the left knee. Five rabbits each were euthanized at 4, 8, and 12 weeks and their knees were examined via macroscopic inspection, histological and biochemical analysis, and quantitative MRI (T2 mapping and dGEMRIC) to assess the state of tissue repair following allograft chondrocyte implantation with a three-dimensional scaffold for osteochondral lesions. Comparatively good regenerative cartilage was observed both macroscopically and histologically. In both chondrocyte-seeded and control knees, the T2 values of repair tissues were highest at 4 weeks and showed a tendency to decrease with time. ΔR1 values of dGEMRIC also tended to decrease with time in both groups, and the mean ΔR1 was significantly lower in the CS-scaffold group than in the control group at all time points. ΔR1 = 1/r (R1post - R1pre), where r is the relaxivity of Gd-DTPA(2-), R1 = 1/T1 (longitudinal relaxation time). T2 mapping and dGEMRIC were both effective for evaluating tissue repair after allograft chondrocyte implantation. ΔR1 values of dGEMRIC represented good correlation with histologically and biochemically even at early stages after the implantation. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  12. Pandemic influenza and health system resource gaps in Bali: an analysis through a resource transmission dynamics model.

    Science.gov (United States)

    Adisasmito, Wiku; Hunter, Benjamin M; Krumkamp, Ralf; Latief, Kamal; Rudge, James W; Hanvoravongchai, Piya; Coker, Richard J

    2015-03-01

    The failure to contain pandemic influenza A(H1N1) 2009 in Mexico has shifted global attention from containment to mitigation. Limited surveillance and reporting have, however, prevented detailed assessment of mitigation during the pandemic, particularly in low- and middle-income countries. To assess pandemic influenza case management capabilities in a resource-limited setting, the authors used a health system questionnaire and density-dependent, deterministic transmission model for Bali, Indonesia, determining resource gaps. The majority of health resources were focused in and around the provincial capital, Denpasar; however, gaps are found in every district for nursing staff, surgical masks, and N95 masks. A relatively low pathogenicity pandemic influenza virus would see an overall surplus for physicians, antivirals, and antimicrobials; however, a more pathogenic virus would lead to gaps in every resource except antimicrobials. Resources could be allocated more evenly across Bali. These, however, are in short supply universally and therefore redistribution would not fill resource gaps. © 2011 APJPH.

  13. Gamma-ray pulsar physics: gap-model populations and light-curve analyses in the Fermi era

    International Nuclear Information System (INIS)

    Pierbattista, M.

    2010-01-01

    This thesis research focusses on the study of the young and energetic isolated ordinary pulsar population detected by the Fermi gamma-ray space telescope. We compared the model expectations of four emission models and the LAT data. We found that all the models fail to reproduce the LAT detections, in particular the large number of high E objects observed. This inconsistency is not model dependent. A discrepancy between the radio-loud/radio-quiet objects ratio was also found between the observed and predicted samples. The L γ α E 0.5 relation is robustly confirmed by all the assumed models with particular agreement in the slot gap (SG) case. On luminosity bases, the intermediate altitude emission of the two pole caustic SG model is favoured. The beaming factor f Ω shows an E dependency that is slightly visible in the SG case. Estimates of the pulsar orientations have been obtained to explain the simultaneous gamma and radio light-curves. By analysing the solutions we found a relation between the observed energy cutoff and the width of the emission slot gap. This relation has been theoretically predicted. A possible magnetic obliquity α alignment with time is rejected -for all the models- on timescale of the order of 10 6 years. The light-curve morphology study shows that the outer magnetosphere gap emission (OGs) are favoured to explain the observed radio-gamma lag. The light curve moment studies (symmetry and sharpness) on the contrary favour a two pole caustic SG emission. All the model predictions suggest a different magnetic field layout with an hybrid two pole caustic and intermediate altitude emission to explain both the pulsar luminosity and light curve morphology. The low magnetosphere emission mechanism of the polar cap model, is systematically rejected by all the tests done. (author) [fr

  14. The prototype GAPS (pGAPS) experiment

    Energy Technology Data Exchange (ETDEWEB)

    Mognet, S.A.I., E-mail: mognet@astro.ucla.edu [University of California, Los Angeles, CA 90095 (United States); Aramaki, T. [Columbia University, New York, NY 10027 (United States); Bando, N. [Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency (ISAS/JAXA), Sagamihara, Kanagawa 252-5210 (Japan); Boggs, S.E.; Doetinchem, P. von [Space Sciences Laboratory, University of California, Berkeley, CA 94720 (United States); Fuke, H. [Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency (ISAS/JAXA), Sagamihara, Kanagawa 252-5210 (Japan); Gahbauer, F.H.; Hailey, C.J.; Koglin, J.E.; Madden, N. [Columbia University, New York, NY 10027 (United States); Mori, K.; Okazaki, S. [Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency (ISAS/JAXA), Sagamihara, Kanagawa 252-5210 (Japan); Ong, R.A. [University of California, Los Angeles, CA 90095 (United States); Perez, K.M.; Tajiri, G. [Columbia University, New York, NY 10027 (United States); Yoshida, T. [Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency (ISAS/JAXA), Sagamihara, Kanagawa 252-5210 (Japan); Zweerink, J. [University of California, Los Angeles, CA 90095 (United States)

    2014-01-21

    The General Antiparticle Spectrometer (GAPS) experiment is a novel approach for the detection of cosmic ray antiparticles. A prototype GAPS (pGAPS) experiment was successfully flown on a high-altitude balloon in June of 2012. The goals of the pGAPS experiment were: to test the operation of lithium drifted silicon (Si(Li)) detectors at balloon altitudes, to validate the thermal model and cooling concept needed for engineering of a full-size GAPS instrument, and to characterize cosmic ray and X-ray backgrounds. The instrument was launched from the Japan Aerospace Exploration Agency's (JAXA) Taiki Aerospace Research Field in Hokkaido, Japan. The flight lasted a total of 6 h, with over 3 h at float altitude (∼33km). Over one million cosmic ray triggers were recorded and all flight goals were met or exceeded.

  15. The prototype GAPS (pGAPS) experiment

    International Nuclear Information System (INIS)

    Mognet, S.A.I.; Aramaki, T.; Bando, N.; Boggs, S.E.; Doetinchem, P. von; Fuke, H.; Gahbauer, F.H.; Hailey, C.J.; Koglin, J.E.; Madden, N.; Mori, K.; Okazaki, S.; Ong, R.A.; Perez, K.M.; Tajiri, G.; Yoshida, T.; Zweerink, J.

    2014-01-01

    The General Antiparticle Spectrometer (GAPS) experiment is a novel approach for the detection of cosmic ray antiparticles. A prototype GAPS (pGAPS) experiment was successfully flown on a high-altitude balloon in June of 2012. The goals of the pGAPS experiment were: to test the operation of lithium drifted silicon (Si(Li)) detectors at balloon altitudes, to validate the thermal model and cooling concept needed for engineering of a full-size GAPS instrument, and to characterize cosmic ray and X-ray backgrounds. The instrument was launched from the Japan Aerospace Exploration Agency's (JAXA) Taiki Aerospace Research Field in Hokkaido, Japan. The flight lasted a total of 6 h, with over 3 h at float altitude (∼33km). Over one million cosmic ray triggers were recorded and all flight goals were met or exceeded

  16. NONINVASIVE DETERMINATION OF KNEE CARTILAGE DEFORMATION DURING JUMPING

    Directory of Open Access Journals (Sweden)

    Djordje Kosanic

    2009-12-01

    Full Text Available The purpose of this investigation was to use a combination of image processing, force measurements and finite element modeling to calculate deformation of the knee cartilage during jumping. Professional athletes performed jumps analyzed using a force plate and high-speed video camera system. Image processing was performed on each frame of video using a color recognition algorithm. A simplified mass-spring-damper model was utilized for determination of global force and moment on the knee. Custom software for fitting the coupling characteristics was created. Simulated results were used as input data for the finite element calculation of cartilage deformation in the athlete's knee. Computer simulation data was compared with the average experimental ground reaction forces. The results show the three-dimensional mechanical deformation distribution inside the cartilage volume. A combination of the image recognition technology, force plate measurements and the finite element cartilage deformation in the knee may be used in the future as an effective noninvasive tool for prediction of injury during jumping

  17. The influence of electric charge transferred during electro-mechanical reshaping on mechanical behavior of cartilage

    Science.gov (United States)

    Protsenko, Dimitry E.; Lim, Amanda; Wu, Edward C.; Manuel, Cyrus; Wong, Brian J. F.

    2011-03-01

    Electromechanical reshaping (EMR) of cartilage has been suggested as an alternative to the classical surgical techniques of modifying the shape of facial cartilages. The method is based on exposure of mechanically deformed cartilaginous tissue to a low level electric field. Electro-chemical reactions within the tissue lead to reduction of internal stress, and establishment of a new equilibrium shape. The same reactions offset the electric charge balance between collagen and proteoglycan matrix and interstitial fluid responsible for maintenance of cartilage mechanical properties. The objective of this study was to investigate correlation between the electric charge transferred during EMR and equilibrium elastic modulus. We used a finite element model based on the triphasic theory of cartilage mechanical properties to study how electric charges transferred in the electro-chemical reactions in cartilage can change its mechanical responses to step displacements in unconfined compression. The concentrations of the ions, the strain field and the fluid and ion velocities within the specimen subject to an applied mechanical deformation were estimated and apparent elastic modulus (the ratio of the equilibrium axial stress to the axial strain) was calculated as a function of transferred charge. The results from numerical calculations showed that the apparent elastic modulus decreases with increase in electric charge transfer. To compare numerical model with experimental observation we measured elastic modulus of cartilage as a function of electric charge transferred in electric circuit during EMR. Good correlation between experimental and theoretical data suggests that electric charge disbalance is responsible for alteration of cartilage mechanical properties.

  18. Wage Growth and Job Mobility in the Early Career : Testing a Statistical Discrimination Model of the Gender Wage Gap

    OpenAIRE

    Belley , Philippe; Havet , Nathalie; Lacroix , Guy

    2012-01-01

    The paper focuses on the early career patterns of young male and female workers. It investigates potential dynamic links between statistical discrimination, mobility, tenure and wage profiles. The model assumes that it is more costly for an employer to assess female workers' productivity and that the noise/signal ratio tapers off more rapidly for male workers. These two assumptions yield numerous theoretical predictions pertaining to gender wage gaps. These predictions are tested using data f...

  19. Bridging the Gap

    DEFF Research Database (Denmark)

    Kramer Overgaard, Majken; Broeng, Jes; Jensen, Monika Luniewska

    Bridging the Gap (BtG) is a 2-year project funded by The Danish Industry Foundation. The goal of Bridging the Gap has been to create a new innovation model which will increase the rate at which Danish universities can spinout new technology ventures.......Bridging the Gap (BtG) is a 2-year project funded by The Danish Industry Foundation. The goal of Bridging the Gap has been to create a new innovation model which will increase the rate at which Danish universities can spinout new technology ventures....

  20. Coupled Flow and Geomechanics Modeling of Slow Earthquakes: Application to Slow Slip Events (SSE) in the Guerrero Gap, Mexico

    Science.gov (United States)

    Alves da Silva Junior, J.; Frank, W.; Castineira, D.; Jha, B.; Juanes, R.

    2016-12-01

    Three major cycles of slow slip events (SSE) have been reported since the early 2000s in the Guerrero gap, Mexico, on the boundary between the Cocos and North American plates. Analysis of teleseismic waveforms recorded on a dense temporary seismic network in the Guerrero gap have found low S-wave velocity and high Vp/Vs ratios at the depths corresponding to the sources of SSE, implying the possible presence of fluids and thus an active dewatering process that may result in near-lithostatic pore pressure at the plate interface. Here we use coupled flow and geomechanics analysis of the Guerrero gap to model transient changes in the stress field in the subduction zone as a result of pore pressure fluctuations and potential fluid flow along the subduction interface. Our computational modeling approach couples a multiphase flow simulator with a mechanical simulator using the unconditionally stable fixed stress scheme for the sequential solution of the two-way coupling between flow and geomechanics (Jha and Juanes, 2014). We assume quasi-static mechanical deformation and neglect the inertial term in the solid momentum balance equation—an approximation that is valid to model SSE assuming aseismic slip. We represent the subducting Cocos fault as a surface embedded in a three-dimensional medium, and use zero thickness interface elements to accurately model stick-slip behavior under dynamically evolving fluid pressure and fault strength. We employ the rate- and state-dependent friction model in the evolution of the coefficient of friction. We calibrate our model using two distinct datasets—GPS data and tremor catalogs in the area of Guerrero gap—and by separately constraining the rate of water production from a model of mineral hydration with depth. Our quantitative modeling approach furnishes a mechanistic understanding of the relationship between pore pressure evolution, stress transfer and tremor migration, and helps elucidate the origin of SSE in this area.

  1. Articular Cartilage of the Human Knee Joint: In Vivo Multicomponent T2 Analysis at 3.0 T

    Science.gov (United States)

    Choi, Kwang Won; Samsonov, Alexey; Spencer, Richard G.; Wilson, John J.; Block, Walter F.; Kijowski, Richard

    2015-01-01

    Purpose To compare multicomponent T2 parameters of the articular cartilage of the knee joint measured by using multicomponent driven equilibrium single-shot observation of T1 and T2 (mcDESPOT) in asymptomatic volunteers and patients with osteoarthritis. Materials and Methods This prospective study was performed with institutional review board approval and with written informed consent from all subjects. The mcDESPOT sequence was performed in the knee joint of 13 asymptomatic volunteers and 14 patients with osteoarthritis of the knee. Single-component T2 (T2Single), T2 of the fast-relaxing water component (T2F) and of the slow-relaxing water component (T2S), and the fraction of the fast-relaxing water component (FF) of cartilage were measured. Wilcoxon rank-sum tests and multivariate linear regression models were used to compare mcDESPOT parameters between volunteers and patients with osteoarthritis. Receiver operating characteristic analysis was used to assess diagnostic performance with mcDESPOT parameters for distinguishing morphologically normal cartilage from morphologically degenerative cartilage identified at magnetic resonance imaging in eight cartilage subsections of the knee joint. Results Higher cartilage T2Single (P cartilage FF (P cartilage T2F (P = .079) and T2S (P = .124) values were seen in patients with osteoarthritis compared with those in asymptomatic volunteers. Differences in T2Single and FF remained significant (P cartilage (P cartilage T2Single and significantly lower cartilage FF than did asymptomatic volunteers, and receiver operating characteristic analysis results suggested that FF may allow greater diagnostic performance than that with T2Single for distinguishing between normal and degenerative cartilage. © RSNA, 2015 Online supplemental material is available for this article. PMID:26024307

  2. Diode laser (980nm) cartilage reshaping

    Science.gov (United States)

    El Kharbotly, A.; El Tayeb, T.; Mostafa, Y.; Hesham, I.

    2011-03-01

    Loss of facial or ear cartilage due to trauma or surgery is a major challenge to the otolaryngologists and plastic surgeons as the complicated geometric contours are difficult to be animated. Diode laser (980 nm) has been proven effective in reshaping and maintaining the new geometric shape achieved by laser. This study focused on determining the optimum laser parameters needed for cartilage reshaping with a controlled water cooling system. Harvested animal cartilages were angulated with different degrees and irradiated with different diode laser powers (980nm, 4x8mm spot size). The cartilage specimens were maintained in a deformation angle for two hours after irradiation then released for another two hours. They were serially measured and photographed. High-power Diode laser irradiation with water cooling is a cheep and effective method for reshaping the cartilage needed for reconstruction of difficult situations in otorhinolaryngologic surgery. Key words: cartilage,diode laser (980nm), reshaping.

  3. Supporting Biomaterials for Articular Cartilage Repair

    Science.gov (United States)

    Duarte Campos, Daniela Filipa; Drescher, Wolf; Rath, Björn; Tingart, Markus

    2012-01-01

    Orthopedic surgeons and researchers worldwide are continuously faced with the challenge of regenerating articular cartilage defects. However, until now, it has not been possible to completely mimic the biological and biochemical properties of articular cartilage using current research and development approaches. In this review, biomaterials previously used for articular cartilage repair research are addressed. Furthermore, a brief discussion of the state of the art of current cell printing procedures mimicking native cartilage is offered in light of their use as future alternatives for cartilage tissue engineering. Inkjet cell printing, controlled deposition cell printing tools, and laser cell printing are cutting-edge techniques in this context. The development of mimetic hydrogels with specific biological properties relevant to articular cartilage native tissue will support the development of improved, functional, and novel engineered tissue for clinical application. PMID:26069634

  4. Feasibility of autologous bone marrow mesenchymal stem cell-derived extracellular matrix scaffold for cartilage tissue engineering.

    Science.gov (United States)

    Tang, Cheng; Xu, Yan; Jin, Chengzhe; Min, Byoung-Hyun; Li, Zhiyong; Pei, Xuan; Wang, Liming

    2013-12-01

    Extracellular matrix (ECM) materials are widely used in cartilage tissue engineering. However, the current ECM materials are unsatisfactory for clinical practice as most of them are derived from allogenous or xenogenous tissue. This study was designed to develop a novel autologous ECM scaffold for cartilage tissue engineering. The autologous bone marrow mesenchymal stem cell-derived ECM (aBMSC-dECM) membrane was collected and fabricated into a three-dimensional porous scaffold via cross-linking and freeze-drying techniques. Articular chondrocytes were seeded into the aBMSC-dECM scaffold and atelocollagen scaffold, respectively. An in vitro culture and an in vivo implantation in nude mice model were performed to evaluate the influence on engineered cartilage. The current results showed that the aBMSC-dECM scaffold had a good microstructure and biocompatibility. After 4 weeks in vitro culture, the engineered cartilage in the aBMSC-dECM scaffold group formed thicker cartilage tissue with more homogeneous structure and higher expressions of cartilaginous gene and protein compared with the atelocollagen scaffold group. Furthermore, the engineered cartilage based on the aBMSC-dECM scaffold showed better cartilage formation in terms of volume and homogeneity, cartilage matrix content, and compressive modulus after 3 weeks in vivo implantation. These results indicated that the aBMSC-dECM scaffold could be a successful novel candidate scaffold for cartilage tissue engineering. © 2013 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation.

  5. Indian Hedgehog in Synovial Fluid Is a Novel Marker for Early Cartilage Lesions in Human Knee Joint

    Science.gov (United States)

    Zhang, Congming; Wei, Xiaochun; Chen, Chongwei; Cao, Kun; Li, Yongping; Jiao, Qiang; Ding, Juan; Zhou, Jingming; Fleming, Braden C.; Chen, Qian; Shang, Xianwen; Wei, Lei

    2014-01-01

    To determine whether there is a correlation between the concentration of Indian hedgehog (Ihh) in synovial fluid (SF) and the severity of cartilage damage in the human knee joints, the knee cartilages from patients were classified using the Outer-bridge scoring system and graded using the Modified Mankin score. Expression of Ihh in cartilage and SF samples were analyzed with immunohistochemistry (IHC), western blot, and enzyme-linked immunosorbent assay (ELISA). Furthermore, we detected and compared Ihh protein levels in rat and mice cartilages between normal control and surgery-induced osteoarthritis (OA) group by IHC and fluorescence molecular tomography in vivo respectively. Ihh expression was increased 5.2-fold in OA cartilage, 3.1-fold in relative normal OA cartilage, and 1.71-fold in OA SF compared to normal control samples. The concentrations of Ihh in cartilage and SF samples was significantly increased in early-stage OA samples when compared to normal samples (r = 0.556; p Ihh protein was also an early event in the surgery-induced OA models. Increased Ihh is associated with the severity of OA cartilage damage. Elevated Ihh content in human knee joint synovial fluid correlates with early cartilage lesions. PMID:24786088

  6. Indian Hedgehog in Synovial Fluid Is a Novel Marker for Early Cartilage Lesions in Human Knee Joint

    Directory of Open Access Journals (Sweden)

    Congming Zhang

    2014-04-01

    Full Text Available To determine whether there is a correlation between the concentration of Indian hedgehog (Ihh in synovial fluid (SF and the severity of cartilage damage in the human knee joints, the knee cartilages from patients were classified using the Outer-bridge scoring system and graded using the Modified Mankin score. Expression of Ihh in cartilage and SF samples were analyzed with immunohistochemistry (IHC, western blot, and enzyme-linked immunosorbent assay (ELISA. Furthermore, we detected and compared Ihh protein levels in rat and mice cartilages between normal control and surgery-induced osteoarthritis (OA group by IHC and fluorescence molecular tomography in vivo respectively. Ihh expression was increased 5.2-fold in OA cartilage, 3.1-fold in relative normal OA cartilage, and 1.71-fold in OA SF compared to normal control samples. The concentrations of Ihh in cartilage and SF samples was significantly increased in early-stage OA samples when compared to normal samples (r = 0.556; p < 0.001; however, there were no significant differences between normal samples and late-stage OA samples. Up-regulation of Ihh protein was also an early event in the surgery-induced OA models. Increased Ihh is associated with the severity of OA cartilage damage. Elevated Ihh content in human knee joint synovial fluid correlates with early cartilage lesions.

  7. Identification of the parameters of an elastic material model using the constitutive equation gap method

    KAUST Repository

    Florentin, Éric

    2010-04-23

    Today, the identification ofmaterialmodel parameters is based more and more on full-field measurements. This article explains how an appropriate use of the constitutive equation gap method (CEGM) can help in this context. The CEGM is a well-known concept which, until now, has been used mainly for the verification of finite element simulations. This has led to many developments, especially concerning the techniques for constructing statically admissible stress fields. The originality of the present study resides in the application of these recent developments to the identification problem. The proposed CEGM is described in detail, then evaluated through the identification of heterogeneous isotropic elastic properties. The results obtained are systematically compared with those of the equilibrium gap method, which is a well-known technique for the resolution of such identification problems. We prove that the use of the enhanced CEGM significantly improves the quality of the results. © Springer-Verlag 2010.

  8. Cartilage Derived from Bone Marrow Mesenchymal Stem Cells Expresses Lubricin In Vitro and In Vivo

    Science.gov (United States)

    Nakagawa, Yusuke; Muneta, Takeshi; Otabe, Koji; Ozeki, Nobutake; Mizuno, Mitsuru; Udo, Mio; Saito, Ryusuke; Yanagisawa, Katsuaki; Ichinose, Shizuko; Koga, Hideyuki; Tsuji, Kunikazu; Sekiya, Ichiro

    2016-01-01

    expressed lubricin in the superficial cartilage. Conclusion Cartilage derived from MSCs expressed lubricin protein both in vitro and in vivo. Aggregation promoted lubricin expression of MSCs in vitro and transplantation of aggregates of MSCs regenerated cartilage including the superficial zone in a rat osteochondral defect model. Our results indicate that aggregated MSCs could be clinically relevant for therapeutic approaches to articular cartilage regeneration with an appropriate superficial zone in the future. PMID:26867127

  9. Human osteoarthritic cartilage is synthetically more active but in culture less vital than normal cartilage

    NARCIS (Netherlands)

    Lafeber, F. P.; van Roy, H.; Wilbrink, B.; Huber-Bruning, O.; Bijlsma, J. W.

    1992-01-01

    The proteoglycan turnover of human osteoarthritic (OA) cartilage was compared to that of normal (N) cartilage. The cartilage was obtained postmortem from human femoral knee condyles. Short term cultures were compared to longterm cultures, and proteoglycan synthesis rate, content and release

  10. Where do inmmigrants fare worse? Modeling workplace wage gap variation with longitudinal employer-employee data.

    Science.gov (United States)

    Tomaskovic-Devey, Donald; Hällsten, Martin; Avent-Holt, Dustin

    2015-01-01

    The authors propose a strategy for observing and explaining workplace variance in categorically linked inequalities. Using Swedish economy-wide linked employer-employee panel data, the authors examine variation in workplace wage inequalities between native Swedes and non-Western immigrants. Consistent with relational inequality theory, the authors' findings are that immigrant-native wage gaps vary dramatically across workplaces, even net of strong human capital controls. The authors also find that, net of observed and fixed-effect controls for individual traits, workplace immigrant-native wage gaps decline with increased workplace immigrant employment and managerial representation and increase when job segregation rises. These results are stronger in high-inequality workplaces and for white-collar employees: contexts in which one expects status-based claims on organizational resources, the central causal mechanism identified by relational inequality theory, to be stronger. The authors conclude that workplace variation in the non-Western immigrant-native wage gaps is contingent on organizational variationin the relative power of groups and the institutional context in which that power is exercised.

  11. Effects of counteracting external valgus moment on lateral tibial cartilage contact conditions and tibial rotation.

    Science.gov (United States)

    Shriram, Duraisamy; Parween, Rizuwana; Lee, Yee Han Dave; Subburaj, Karupppasamy

    2017-07-01

    Knee osteoarthritis that prevalently occurs at the medial compartment is a progressive chronic disorder affecting the articular cartilage of the knee joint, and lead to loss of joint functionality. Valgus braces have been used as a treatment procedure to unload the medial compartment for patients with medial osteoarthritis. Valgus braces through the application of counteracting external valgus moment shift the load from medial compartment towards the lateral compartment. Previous biomechanical studies focused only on the changes in varus moments before and after wearing the brace. The objective of this study was to investigate the influence of opposing external valgus moment applied by knee braces on the lateral tibial cartilage contact conditions using a 3D finite element model of the knee joint. Finite element simulations were performed on the knee joint model without and with the application of opposing valgus moment to mimic the unbraced and braced conditions. Lateral tibial cartilage contact pressures and contact area, and tibial rotation (varus-valgus and internal-external) were estimated for the complete walking gait cycle. The opposing valgus moment increased the maximum contact pressure and contact area on the lateral tibial cartilage compared to the normal gait moment. A peak contact pressure of 8.2 MPa and maximum cartilage loaded area of 28% (loaded cartilage nodes) on the lateral cartilage with the application of external valgus moment were induced at 50% of the gait cycle. The results show that the use of opposing valgus moment may significantly increase the maximum contact pressures and contact area on the lateral tibial cartilage and increases the risk of articular cartilage damage on the lateral compartment.

  12. Cellular and Acellular Approaches for Cartilage Repair

    Science.gov (United States)

    2015-01-01

    There are several choices of cells to use for cartilage repair. Cells are used as internal or external sources and sometimes in combination. In this article, an analysis of the different cell choices and their use and potential is provided. Embryonic cartilage formation is of importance when finding more about how to be able to perfect cartilage repair. Some suggestions for near future research based on up-to-date knowledge on chondrogenic cells are given to hopefully stimulate more studies on the final goal of cartilage regeneration. PMID:27340516

  13. Optical properties of nasal septum cartilage

    Science.gov (United States)

    Bagratashvili, Nodar V.; Sviridov, Alexander P.; Sobol, Emil N.; Kitai, Moishe S.

    1998-05-01

    Optical parameters (scattering coefficient s, absorption coefficient k and scattering anisotropy coefficient g) of hyaline cartilage were studied for the first time. Optical properties of human and pig nasal septum cartilage, and of bovine ear cartilage were examined using a spectrophotometer with an integrating sphere, and an Optical Multi-Channel Analyser. We measured total transmission Tt, total reflection Rt, and on-axis transmission Ta for light propagating through cartilage sample, over the visible spectral range (14000 - 28000 cm-1). It is shown that transmission and reflection spectra of human, pig and bovine cartilage are rather similar. It allows us to conclude that the pig cartilage can be used for in-vivo studies instead of human cartilage. The data obtained were treated by means of the one-dimensional diffusion approximation solution of the optical transport equation. We have found scattering coefficient s, absorption coefficient k and scattering anisotropy coefficient g by the iterative comparison of measured and calculated Tt, Rt and Ta values for human and pig cartilage. We found, in particular, that for 500 nm irradiation s equals 37,6 plus or minus 3.5 cm-1, g equals 0,56 plus or minus 0.05, k approximately equals 0,5 plus or minus 0.3 cm-1. The above data were used in Monte Carlo simulation for spatial intensity profile of light scattered by a cartilage sample. The computed profile was very similar to the profile measured using an Optical Multi-Channel Analyzer (OMA).

  14. Rabbit articular cartilage defects treated by allogenic chondrocyte transplantation

    OpenAIRE

    Boopalan, P. R. J. V. C.; Sathishkumar, Solomon; Kumar, Senthil; Chittaranjan, Samuel

    2006-01-01

    Articular cartilage defects have a poor capacity for repair. Most of the current treatment options result in the formation of fibro-cartilage, which is functionally inferior to normal hyaline articular cartilage. We studied the effectiveness of allogenic chondrocyte transplantation for focal articular cartilage defects in rabbits. Chondrocytes were cultured in vitro from cartilage harvested from the knee joints of a New Zealand White rabbit. A 3 mm defect was created in the articular cartilag...

  15. Near infrared spectroscopic evaluation of water in hyaline cartilage.

    Science.gov (United States)

    Padalkar, M V; Spencer, R G; Pleshko, N

    2013-11-01

    In diseased conditions of cartilage such as osteoarthritis, there is typically an increase in water content from the average normal of 60-85% to greater than 90%. As cartilage has very little capability for self-repair, methods of early detection of degeneration are required, and assessment of water could prove to be a useful diagnostic method. Current assessment methods are either destructive, time consuming, or have limited sensitivity. Here, we investigated the hypotheses that non-destructive near infrared spectroscopy (NIRS) of articular cartilage can be used to differentiate between free and bound water, and to quantitatively assess water content. The absorbances centered at 5200 and 6890 cm(-1) were attributed to a combination of free and bound water, and to free water only, respectively. The integrated areas of both absorbance bands were found to correlate linearly with the absolute water content (R = 0.87 and 0.86) and with percent water content (R = 0.97 and 0.96) of the tissue. Partial least square models were also successfully developed and were used to predict water content, and percent free water. These data demonstrate that NIRS can be utilized to quantitatively determine water content in articular cartilage, and may aid in early detection of degenerative tissue changes in a laboratory setting, and with additional validations, possibly in a clinical setting.

  16. Laser-assisted cartilage reshaping: in vitro and in vivo animal studies

    Science.gov (United States)

    Wang, Zhi; Pankratov, Michail M.; Perrault, Donald F., Jr.; Shapshay, Stanley M.

    1995-05-01

    Correction of cartilaginous defects in the head and neck area remains a challenge for the surgeon. This study investigated a new technique for laser-assisted cartilage reshaping. The pulsed 1.44 micrometers Nd:YAG laser was used in vitro and in vivo experiments to irradiate cartilage to change it's shape without carbonization or vaporization of tissue. Two watts of average power in non contact manner was used to irradiate and reshape the cartilage. The extracted reshaped cartilage specimens underwent testing of elastic force with a computer assisted measurement system that recorded the changes in elastic force in the specimens from 1 hr to 11 days post-irradiation. An animal model of defective tracheal cartilage (collapsed tracheal wall) was created, allowed to heal for 6 weeks and then corrected endoscopically with the laser-assisted technique. The results of the in vitro and in vivo investigations demonstrated that it was possible to alter the cartilage and that cartilage would retain its new shape. The clinical significance of the technique is evident and warrants further animal studies and clinical trials.

  17. A spectroscopic approach to imaging and quantification of cartilage lesions in human knee joints

    International Nuclear Information System (INIS)

    Johansson, A; Oeberg, P A; Sundqvist, T; Kuiper, J-H

    2011-01-01

    We have previously described a technology based on diffuse reflectance of broadband light for measuring joint articular cartilage thickness, utilizing that optical absorption is different in cartilage and subchondral bone. This study is the first evaluation of the technology in human material. We also investigated the prospects of cartilage lesion imaging, with the specific aim of arthroscopic integration. Cartilage thickness was studied ex vivo in a number of sites (n = 87) on human knee joint condyles, removed from nine patients during total knee replacement surgery. A reflectance spectrum was taken at each site and the cartilage thickness was estimated using the blue, green, red and near-infrared regions of the spectrum, respectively. Estimated values were compared with reference cartilage thickness values (taken after sample slicing) using an exponential model. Two-dimensional Monte Carlo simulations were performed in a theoretical analysis of the experimental results. The reference cartilage thickness of the investigated sites was 1.60 ± 1.30 mm (mean ± SD) in the range 0-4.2 mm. Highest correlation coefficients were seen for the calculations based on the near-infrared region after normalization to the red region (r = 0.86) and for the green region (r = 0.80).

  18. Serum Metabonomics of Articular Cartilage Destruction Induced by T-2 Toxin in Wistar Rats.

    Science.gov (United States)

    Zhu, Lei; Zhao, Zhi Jun; Ren, Xiao Bin; Li, Qiang; Ding, Hua; Sun, Zhou; Kao, Qing Jun; Wang, Li Hua

    2018-01-01

    The molecular pathogenesis of T-2 toxin-induced cartilage destruction has not been fully unraveled yet. The aim of this study was to detect changes in serum metabolites in a rat anomaly model with articular cartilage destruction. Thirty healthy male Wistar rats were fed a diet containing T-2 toxin (300 ng/kg chow) for 3 months. Histopathological changes in femorotibial cartilage were characterized in terms of chondrocyte degeneration/necrosis and superficial cartilage defect, and the endogenous metabolite profile of serum was determined by UPLC/Q-TOF MS. Treated rats showed extensive areas of chondrocyte necrosis and superficial cartilage defect in the articular cartilage. In addition, 8 metabolites were found to change significantly in these rats compared to the control group, including lysoPE (18:0/0:0), lysoPC(14:0), lysoPC[18:4 (6Z,9Z,12Z,15Z)], lysoPC[(16:1(9Z)], lysoPC(16:0), L-valine, hippuric acid, and asparaginyl-glycine. These 8 metabolites associated with cartilage injury are mainly involved in phospholipid and amino acid metabolic pathways. Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  19. Photoshop-based image analysis of canine articular cartilage after subchondral damage.

    Science.gov (United States)

    Lahm, A; Uhl, M; Lehr, H A; Ihling, C; Kreuz, P C; Haberstroh, J

    2004-09-01

    The validity of histopathological grading is a major problem in the assessment of articular cartilage. Calculating the cumulative strength of signal intensity of different stains gives information regarding the amount of proteoglycan, glycoproteins, etc. Using this system, we examined the medium-term effect of subchondral lesions on initially healthy articular cartilage. After cadaver studies, an animal model was created to produce pure subchondral damage without affecting the articular cartilage in 12 beagle dogs under MRI control. Quantification of the different stains was provided using a Photoshop-based image analysis (pixel analysis) with the histogram command 6 months after subchondral trauma. FLASH 3D sequences revealed intact cartilage after impact in all cases. The best detection of subchondral fractures was achieved with fat-suppressed TIRM sequences. Semiquantitative image analysis showed changes in proteoglycan and glycoprotein quantities in 9 of 12 samples that had not shown any evidence of damage during the initial examination. Correlation analysis showed a loss of the physiological distribution of proteoglycans and glycoproteins in the different zones of articular cartilage. Currently available software programs can be applied for comparative analysis of histologic stains of hyaline cartilage. After subchondral fractures, significant changes in the cartilage itself occur after 6 months.

  20. Noninvasive assessment of articular cartilage surface damage using reflected polarized light microscopy

    Science.gov (United States)

    Huynh, Ruby N.; Nehmetallah, George; Raub, Christopher B.

    2017-06-01

    Articular surface damage occurs to cartilage during normal aging, osteoarthritis, and in trauma. A noninvasive assessment of cartilage microstructural alterations is useful for studies involving cartilage explants. This study evaluates polarized reflectance microscopy as a tool to assess surface damage to cartilage explants caused by mechanical scraping and enzymatic degradation. Adult bovine articular cartilage explants were scraped, incubated in collagenase, or underwent scrape and collagenase treatments. In an additional experiment, cartilage explants were subject to scrapes at graduated levels of severity. Polarized reflectance parameters were compared with India ink surface staining, features of histological sections, changes in explant wet weight and thickness, and chondrocyte viability. The polarized reflectance signal was sensitive to surface scrape damage and revealed individual scrape features consistent with India ink marks. Following surface treatments, the reflectance contrast parameter was elevated and correlated with image area fraction of India ink. After extensive scraping, polarized reflectance contrast and chondrocyte viability were lower than that from untreated explants. As part of this work, a mathematical model was developed and confirmed the trend in the reflectance signal due to changes in surface scattering and subsurface birefringence. These results demonstrate the effectiveness of polarized reflectance microscopy to sensitively assess surface microstructural alterations in articular cartilage explants.

  1. Low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field (PEMF) treatments affect degeneration of cultured articular cartilage explants

    NARCIS (Netherlands)

    Tan, Lijun; Ren, Yijin; van Kooten, Theo G.; Grijpma, Dirk W.; Kuijer, Roelof

    PURPOSE: Articular cartilage has some capacity for self-repair. Clinically used low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field (PEMF) treatments were compared in their potency to prevent degeneration using an explant model of porcine cartilage. METHODS: Explants of porcine

  2. Low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field (PEMF) treatments affect degeneration of cultured articular cartilage explants

    NARCIS (Netherlands)

    Tan, Lijun; Tan, Lijun; Ren, Yijin; van Kooten, Theo G.; Grijpma, Dirk W.; Kuijer, Roel

    2015-01-01

    Purpose: Articular cartilage has some capacity for self-repair. Clinically used low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field (PEMF) treatments were compared in their potency to prevent degeneration using an explant model of porcine cartilage. Methods: Explants of porcine

  3. Large gap plasma display cell with auxiliary electrodes: macro-cell experiments and two-dimensional modelling

    International Nuclear Information System (INIS)

    Ouyang, J T; Callegari, Th; Caillier, B; Boeuf, J-P

    2003-01-01

    In this paper we use a two-dimensional fluid model and a 'macroscopic' PDP cell to investigate the possibility of using large gap configurations with auxiliary electrodes to improve the efficiency of PDP discharge cells. The large gap allows operation in a transient positive column regime where energy is more efficiently deposited into xenon excitation, while the auxiliary electrodes are used to keep reasonable values of the operating voltage. Two types of auxiliary electrode configurations (floating and powered) are considered. The discharge characteristics and the discharge efficiency in exciting xenon are studied with simulations and by measuring the intensity of infrared emission from xenon and visible emission from neon in a macroscopic PDP cell. The results show that an efficient positive column regime can be achieved at reasonably low operating voltages when the auxiliary electrode configuration is carefully designed

  4. Extended two-temperature model for ultrafast thermal response of band gap materials upon impulsive optical excitation

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Taeho [Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139-4307 (United States); Samsung Advanced Institute of Technology, Suwon 443-803 (Korea, Republic of); Teitelbaum, Samuel W.; Wolfson, Johanna; Nelson, Keith A., E-mail: kanelson@mit.edu [Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139-4307 (United States); Kandyla, Maria [Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139-4307 (United States); Theoretical and Physical Chemistry Institute, National Hellenic Research Foundation, Athens 116-35 (Greece)

    2015-11-21

    Thermal modeling and numerical simulations have been performed to describe the ultrafast thermal response of band gap materials upon optical excitation. A model was established by extending the conventional two-temperature model that is adequate for metals, but not for semiconductors. It considers the time- and space-dependent density of electrons photoexcited to the conduction band and accordingly allows a more accurate description of the transient thermal equilibration between the hot electrons and lattice. Ultrafast thermal behaviors of bismuth, as a model system, were demonstrated using the extended two-temperature model with a view to elucidating the thermal effects of excitation laser pulse fluence, electron diffusivity, electron-hole recombination kinetics, and electron-phonon interactions, focusing on high-density excitation.

  5. Predicting knee cartilage loss using adaptive partitioning of cartilage thickness maps

    DEFF Research Database (Denmark)

    Jørgensen, Dan Richter; Dam, Erik Bjørnager; Lillholm, Martin

    2013-01-01

    This study investigates whether measures of knee cartilage thickness can predict future loss of knee cartilage. A slow and a rapid progressor group was determined using longitudinal data, and anatomically aligned cartilage thickness maps were extracted from MRI at baseline. A novel machine learning...... framework was then trained using these maps. Compared to measures of mean cartilage plate thickness, group separation was increased by focusing on local cartilage differences. This result is central for clinical trials where inclusion of rapid progressors may help reduce the period needed to study effects...

  6. Model-based approach for maize yield gap analysis related to climate variability and nitrogen management

    OpenAIRE

    Maria Carolina da Silva Andréa

    2016-01-01

    To achieve food security and meet environmental requirements, the average rates of major crop yields in crops such as maize are expected to increase instead of expansion of cultivated areas. Maize crop has as main factors responsible for the low yields in Brazil the water and nitrogen (N) deficits. The concept of yield gaps is the difference between the maximum yield that can be achieved in a given place, limited by water (Yw) or not (Yp), and the average yields, observed under practical cond...

  7. Hyaline Articular Matrix Formed by Dynamic Self-Regenerating Cartilage and Hydrogels.

    Science.gov (United States)

    Meppelink, Amanda M; Zhao, Xing; Griffin, Darvin J; Erali, Richard; Gill, Thomas J; Bonassar, Lawrence J; Redmond, Robert W; Randolph, Mark A

    2016-07-01

    Injuries to the articular cartilage surface are challenging to repair because cartilage possesses a limited capacity for self-repair. The outcomes of current clinical procedures aimed to address these injuries are inconsistent and unsatisfactory. We have developed a novel method for generating hyaline articular cartilage to improve the outcome of joint surface repair. A suspension of 10(7) swine chondrocytes was cultured under reciprocating motion for 14 days. The resulting dynamic self-regenerating cartilage (dSRC) was placed in a cartilage ring and capped with fibrin and collagen gel. A control group consisted of chondrocytes encapsulated in fibrin gel. Constructs were implanted subcutaneously in nude mice and harvested after 6 weeks. Gross, histological, immunohistochemical, biochemical, and biomechanical analyses were performed. In swine patellar groove, dSRC was implanted into osteochondral defects capped with collagen gel and compared to defects filled with osteochondral plugs, collagen gel, or left empty after 6 weeks. In mice, the fibrin- and collagen-capped dSRC constructs showed enhanced contiguous cartilage matrix formation over the control of cells encapsulated in fibrin gel. Biochemically, the fibrin and collagen gel dSRC groups were statistically improved in glycosaminoglycan and hydroxyproline content compared to the control. There was no statistical difference in the biomechanical data between the dSRC groups and the control. The swine model also showed contiguous cartilage matrix in the dSRC group but not in the collagen gel and empty defects. These data demonstrate the survivability and successful matrix formation of dSRC under the mechanical forces experienced by normal hyaline cartilage in the knee joint. The results from this study demonstrate that dSRC capped with hydrogels successfully engineers contiguous articular cartilage matrix in both nonload-bearing and load-bearing environments.

  8. A novel therapeutic strategy for cartilage diseases based on lipid nanoparticle-RNAi delivery system

    Directory of Open Access Journals (Sweden)

    Wang S

    2018-01-01

    Full Text Available Shaowei Wang,1 Xiaochun Wei,1 Xiaojuan Sun,1 Chongwei Chen,1 Jingming Zhou,2 Ge Zhang,3 Heng Wu,3 Baosheng Guo,3 Lei Wei1,2 1Department of Orthopaedics, The 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi, China; 2Department of Orthopaedics, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, USA; 3Integrated Traditional Chinese and Western Medicine, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong Background: Cartilage degeneration affects millions of people but preventing its degeneration is a big challenge. Although RNA interference (RNAi has been used in human trials via silencing specific genes, the cartilage RNAi has not been possible to date because the cartilage is an avascular and very dense tissue with very low permeability. Purpose: The objective of this study was to develop and validate a novel lipid nanoparticle (LNP-siRNA delivery system that can prevent cartilage degeneration by knocking down specific genes. Methods: LNP transfection efficiency was evaluated in vitro and ex vivo. Indian Hedgehog (Ihh has been correlated with cartilage degeneration. The in vivo effects of LNP-Ihh siRNA complexes on cartilage degeneration were evaluated in a rat model of surgery-induced osteoarthritis (OA. Results: In vitro, 100% of chondrocytes were transfected with siRNA in the LNP-siRNA group. In accordance with the cell culture results, red positive signals could be detected even in the deep layer of cartilage tissue cultures treated by LNP-beacon. In vivo data showed that LNP is specific for cartilage, since positive signals were detected by fluorescence molecular tomography and confocal microscopy in joint cartilage injected with LNP-beacon, but not on the surface of the synovium. In the rat model of OA, intraarticular injection of LNP-Ihh siRNA attenuated OA progression, and PCR results showed LNP-Ihh siRNA exerted a positive impact on anabolic metabolism and negative

  9. Silk fibroin-chondroitin sulfate scaffold with immuno-inhibition property for articular cartilage repair.

    Science.gov (United States)

    Zhou, Feifei; Zhang, Xianzhu; Cai, Dandan; Li, Jun; Mu, Qin; Zhang, Wei; Zhu, Shouan; Jiang, Yangzi; Shen, Weiliang; Zhang, Shufang; Ouyang, Hong Wei

    2017-11-01

    The demand of favorable scaffolds has increased for the emerging cartilage tissue engineering. Chondroitin sulfate (CS) and silk fibroin have been investigated and reported with safety and excellent biocompatibility as tissue engineering scaffolds. However, the rapid degradation rate of pure CS scaffolds presents a challenge to effectively recreate neo-tissue similar to natural articular cartilage. Meanwhile the silk fibroin is well used as a structural constituent material because its remarkable mechanical properties, long-lasting in vivo stability and hypoimmunity. The application of composite silk fibroin and CS scaffolds for joint cartilage repair has not been well studied. Here we report that the combination of silk fibroin and CS could synergistically promote articular cartilage defect repair. The silk fibroin (silk) and silk fibroin/CS (silk-CS) scaffolds were fabricated with salt-leaching, freeze-drying and crosslinking methodologies. The biocompatibility of the scaffolds was investigated in vitro by cell adhesion, proliferation and migration with human articular chondrocytes. We found that silk-CS scaffold maintained better chondrocyte phenotype than silk scaffold; moreover, the silk-CS scaffolds reduced chondrocyte inflammatory response that was induced by interleukin (IL)-1β, which is in consistent with the well-documented anti-inflammatory activities of CS. The in vivo cartilage repair was evaluated with a rabbit osteochondral defect model. Silk-CS scaffold induced more neo-tissue formation and better structural restoration than silk scaffold after 6 and 12weeks of implantation in ICRS histological evaluations. In conclusion, we have developed a silk fibroin/ chondroitin sulfate scaffold for cartilage tissue engineering that exhibits immuno-inhibition property and can improve the self-repair capacity of cartilage. Severe cartilage defect such as osteoarthritis (OA) is difficult to self-repair because of its avascular, aneural and alymphatic nature

  10. Modeling of the water gap in BWR fuel elements using SCALE/TRITON; Modellierung des Wasserspalts bei SWR-BE mit SCALE/TRITON

    Energy Technology Data Exchange (ETDEWEB)

    Tittelbach, S.; Chernykh, M. [WTI Wissenschaftlich-Technische Ingenieurberatung GmbH, Juelich (Germany)

    2012-11-01

    The authors show that an adequate modeling of the water gap in BWR fuel element models using the code TRITON requires an explicit consideration of the Dancoff factors. The analysis of three modeling options reveals that considering the moderating effects of the water gap coolant for the peripheral fuel elements the resulting deviations of the U-235 and Pu-239 concentrations are significantly reduced. The increased temporal calculation efforts are justified with respect to the burnup credits for criticality safety analyses.

  11. Closing the gap between behavior and models in route choice: The role of spatiotemporal constraints and latent traits in choice set formation

    DEFF Research Database (Denmark)

    Kaplan, Sigal; Prato, Carlo Giacomo

    2012-01-01

    not account for individual-related spatiotemporal constraints. This paper reduces the gap by proposing a route choice model incorporating spatiotemporal constraints and latent traits. The proposed approach combines stochastic route generation with a latent variable semi-compensatory model representing......A considerable gap exists between the behavioral paradigm of choice set formation in route choice and its representation in route choice modeling. While travelers form their viable choice set by retaining routes that satisfy spatiotemporal constraints, existing route generation techniques do...

  12. FEAST 3.1: finite-element modeling of sheath deformation such as longitudinal ridging and collapse into axial gap

    Energy Technology Data Exchange (ETDEWEB)

    Wang, X.; Xu, Z.; Kim, Y-S.; Lai, L.; Cheng, G.; Xu, S. [Atomic Energy of Canada Limited, Mississauga, Ontario (Canada)

    2010-07-01

    During normal operation, the collapsible CANDU® fuel sheath deforms, especially, it may deform into longitudinal ridges or collapse instantaneously into the axial gaps between the end pellet and endcap or between two neighbouring pellets. These phenomena occur under certain conditions, such as the coolant pressure exceeding critical pressures for longitudinal ridging or axial collapse. Both longitudinal ridging and axial collapse phenomena result from plastic instability in the sheath under coolant pressure. Longitudinal ridging features one or multiple lobes or 'ridges' (outward from the sheath surface) formed along the sheath in the longitudinal direction. Axial collapse features a 'valley' around the sheath circumference. Both phenomena can lead to sheath overstrain, which in turn potentially leads to sheath failure. The LONGER code, which contains empirical correlations, has been used to predict the critical pressures for these two sheath deformation phenomena. To study fuel behaviour outside of the application ranges of the LONGER empirical correlations, a mechanistic model is needed. FEAST (Finite Element Analysis for Stresses) is an AECL computer code used to assess the structural integrity of the CANDU fuel element. The FEAST code has recently been developed (to Version 3.1) to model processes occurring during longitudinal ridge formation and instantaneous collapse into the axial gap. The new models include those for geometric non-linearity (large deformation, large material rotation), non-linear stress-strain curve for plastic deformation, Zr-4 sheath creep law, and variable Young’s Modulus etc. This paper describes the mechanistic model (FEAST 3.1) development for analyses of longitudinal ridging and instantaneous collapse into axial gap, and the comparison with the results from empirical correlations in LONGER. (author)

  13. FEAST 3.1: finite-element modeling of sheath deformation such as longitudinal ridging and collapse into axial gap

    International Nuclear Information System (INIS)

    Wang, X.; Xu, Z.; Kim, Y-S.; Lai, L.; Cheng, G.; Xu, S.

    2010-01-01

    During normal operation, the collapsible CANDU® fuel sheath deforms, especially, it may deform into longitudinal ridges or collapse instantaneously into the axial gaps between the end pellet and endcap or between two neighbouring pellets. These phenomena occur under certain conditions, such as the coolant pressure exceeding critical pressures for longitudinal ridging or axial collapse. Both longitudinal ridging and axial collapse phenomena result from plastic instability in the sheath under coolant pressure. Longitudinal ridging features one or multiple lobes or 'ridges' (outward from the sheath surface) formed along the sheath in the longitudinal direction. Axial collapse features a 'valley' around the sheath circumference. Both phenomena can lead to sheath overstrain, which in turn potentially leads to sheath failure. The LONGER code, which contains empirical correlations, has been used to predict the critical pressures for these two sheath deformation phenomena. To study fuel behaviour outside of the application ranges of the LONGER empirical correlations, a mechanistic model is needed. FEAST (Finite Element Analysis for Stresses) is an AECL computer code used to assess the structural integrity of the CANDU fuel element. The FEAST code has recently been developed (to Version 3.1) to model processes occurring during longitudinal ridge formation and instantaneous collapse into the axial gap. The new models include those for geometric non-linearity (large deformation, large material rotation), non-linear stress-strain curve for plastic deformation, Zr-4 sheath creep law, and variable Young’s Modulus etc. This paper describes the mechanistic model (FEAST 3.1) development for analyses of longitudinal ridging and instantaneous collapse into axial gap, and the comparison with the results from empirical correlations in LONGER. (author)

  14. [Predictive distribution and planting GAP of Cyathula officinalis in China based on 3S technology and MaxEnt modelling].

    Science.gov (United States)

    Wu, Ming-Yan; He, Lan; Chen, Jia-Li; Dong, Guang; Cheng, Wu-Xue

    2017-11-01

    Research on predictive distribution and planting GAP of Cyathula officinalis in China is helpful to provide scientific basis for its protection and planting popularization. According to the data in 63 distribution sites and 49 ecological variables, using MaxEnt ecological niche model and 3S technology, we performed a quantitative analysis of suitable distribution and planting GAP of C. officinalis in China. Our results show that: ① the area of suitable distribution of C. officinalis is about 634 385.80 km² in total, and mainly in Northeastern and Southeastern Sichuan, Northern and Southeastern Yunnan, Western and Southwestern Guizhou, Southwestern and Northeastern Chongqing, Southwestern Shaanxi, Southeastern Gansu, Western Guangxi, Southeastern Tibet. ② The main ecological factors determining the potential distribution are precipitation, altitude, minimum temperature of coldest month, soil type, monthly mean temperature. ③ The planting GAP region are mainly in Guangyuan, Mianyang, Ya'an, Leshan, Liangshan, Panzhihua of Sichuan province, Hanzhong of Shaanxi province, Dali, Nujiang, Chuxiong, Baoshan, Qujing, Wenshan of Yunnan province, southwestern autonomous prefecture in Guizhou province. The results are of great significance for realizing the growth environment, predicting the potential distribution and promoting planting popularization for C. officinalis. Copyright© by the Chinese Pharmaceutical Association.

  15. Comparison of modelling and experimental results of anode surface melting by femtosecond laser-stimulated electrical discharges in small gaps

    International Nuclear Information System (INIS)

    Chen Jian; He Lingna; Farson, Dave F; Rokhlin, Stanislav I

    2011-01-01

    Experiments and particle-in-cell simulations of femtosecond laser-stimulated electrical discharges in submicrometre gaps between scanning tunnelling microscope tip cathodes and gold film anodes are described. In experiments at applied potentials of 35 V and less, discharges were detected either as self-terminating low-current pulses with durations less than 10 ns and magnitudes less than 200 mA or as higher-current, longer-duration current waveforms. The probability of occurrence of low-current pulses increased as applied potential was decreased, being certain at low potentials of 20-25 V. Low-current pulse waveforms and surface melting of gold anodes predicted by the simulations were compared with experiments. Laser stimulation was modelled by introducing partially ionized electrode materials into the simulation domain at a controlled rate. Simulation results showed that the duration of low-current pulses was influenced by the time over which material was added to the gap region, establishing the importance of electrode vaporization on discharge duration. Subsequently, partially ionized electrode materials were preloaded into the gap in controlled amounts in subsequent simulations. Peak currents predicted by these simulations were nearly equal to the low-current pulse measurements but simulated pulse durations were shorter than experiments. Thus, the time axis of simulation current profiles was normalized for equality of charge transfer with experiments. Anode temperatures and melt diameters calculated from normalized simulated heat input profiles were well matched to experimental measurements.

  16. The O(N) model at nonzero temperature: renormalization of the gap equations in Hartree and large-N approximations

    International Nuclear Information System (INIS)

    Lenaghan, J.T.; Rischke, D.H.

    2000-01-01

    The temperature dependence of the sigma meson and pion masses is studied in the framework of the O(N ) model. The Cornwall-Jackiw-Tomboulis formalism is applied to derive gap equations for the masses in the Hartree and large-N approximations. Renormalization of the gap equations is carried out within the cut-off and counter-term renormalization schemes. A consistent renormalization of the gap equations within the cut-off scheme is found to be possible only in the large-N approximation and for a finite value of the cut-off. On the other hand, the counter-term scheme allows for a consistent renormalization of both the large-N and Hartree approximations. In these approximations, the meson masses at a given nonzero temperature depend in general on the choice of the cut-off or renormalization scale. As an application, we also discuss the in-medium on-shell decay widths for sigma mesons and pions at rest. (author)

  17. Boundary mode lubrication of articular cartilage by recombinant human lubricin.

    Science.gov (United States)

    Gleghorn, Jason P; Jones, Aled R C; Flannery, Carl R; Bonassar, Lawrence J

    2009-06-01

    Lubrication of cartilage involves a variety of physical and chemical factors, including lubricin, a synovial glycoprotein that has been shown to be a boundary lubricant. It is unclear how lubricin boundary lubricates a wide range of bearings from tissue to artificial surfaces, and if the mechanism is the same for both soluble and bound lubricin. In the current study, experiments were conducted to investigate the hypothesis that recombinant human lubricin (rh-lubricin) lubricates cartilage in a dose-dependent manner and that soluble and bound fractions of rh-lubricin both contribute to the lubrication process. An rh-lubricin dose response was observed with maximal lubrication achieved at concentrations of rh-lubricin greater than 50 microg/mL. A concentration-response variable-slope model was fit to the data, and indicated that rh-lubricin binding to cartilage was not first order. The pattern of decrease in equilibrium friction coefficient indicated that aggregation of rh-lubricin or steric arrangement may regulate boundary lubrication. rh-lubricin localized at the cartilage surface was found to lubricate a cartilage-glass interface in boundary mode, as did soluble rh-lubricin at high concentrations (150 microg/mL); however, the most effective lubrication occurred when both soluble and bound rh-lubricin were present at the interface. These findings point to two distinct mechanisms by which rh-lubricin lubricates, one mechanism involving lubricin bound to the tissue surface and the other involving lubricin in solution. Copyright 2008 Orthopaedic Research Society

  18. Subchondral drilling for articular cartilage repair: a systematic review of translational research.

    Science.gov (United States)

    Gao, Liang; Goebel, Lars K H; Orth, Patrick; Cucchiarini, Magali; Madry, Henning

    2018-05-03

    Articular cartilage defects may initiate osteoarthritis. Subchondral drilling, a widely applied clinical technique to treat small cartilage defects, does not yield cartilage regeneration. Various translational studies aiming to improve the outcome of drilling have been performed, however, a robust systematic analysis of its translational evidence has been still lacking. Here, we performed a systematic review of the outcome of subchondral drilling for knee cartilage repair in translational animal models. A total of 12 relevant publications studying 198 animals were identified, detailed study characteristics were extracted, and methodological quality and risk of bias were analyzed. Subchondral drilling was superior to defects untreated or treated with abrasion arthroplasty for cartilage repair in multiple translational models. Considerable subchondral bone changes were observed, including subchondral bone cysts and intralesional osteophytes. Furthermore, extensive alterations of the subchondral bone microarchitecture appeared in a temporal pattern in small and large animal models, together with specific topographic aspects of repair. Moreover, variable technical aspects directly affected the outcomes of osteochondral repair. The data from this systematic review indicate that subchondral drilling yields improved short-term structural articular cartilage repair compared with spontaneous repair in multiple small and large animal models. These results have important implications for future investigations aimed at an enhanced translation into clinical settings for the treatment of cartilage defects, highlighting the importance of considering specific aspects of modifiable variables such as improvements in the design and reporting of preclinical studies, together with the need to better understand the underlying mechanisms of cartilage repair following subchondral drilling. © 2018. Published by The Company of Biologists Ltd.

  19. [Progress in application of 3D bioprinting in cartilage regeneration and reconstruction for tissue engineering].

    Science.gov (United States)

    Liao, Junlin; Wang, Shaohua; Chen, Jia; Xie, Hongju; Zhou, Jianda

    2017-02-28

    Three-dimensional (3D) bioprinting provides an advanced technology for tissue engineering and regenerative medicine because of its ability to produce the models or organs with higher precision and more suitable for human body. It has been successfully used to produce a variety of cartilage scaffold materials. In addition, 3D bioprinter can directly to print tissue and organs with live chondrocytes. In conclusion, 3D bioprinting may have broad prospect for cartilage regeneration and reconstruction in tissue engineering.

  20. Coordinate and synergistic effects of extensive treadmill exercise and ovariectomy on articular cartilage degeneration

    OpenAIRE

    Miyatake, Kazumasa; Muneta, Takeshi; Ojima, Miyoko; Yamada, Jun; Matsukura, Yu; Abula, Kahaer; Sekiya, Ichiro; Tsuji, Kunikazu

    2016-01-01

    Background Although osteoarthritis (OA) is a multifactorial disease, little has been reported regarding the cooperative interaction among these factors on cartilage metabolism. Here we examined the synergistic effect of ovariectomy (OVX) and excessive mechanical stress (forced running) on articular cartilage homeostasis in a mouse model resembling a human postmenopausal condition. Methods Mice were randomly divided into four groups, I: Sham, II: OVX, III: Sham and forced running (60?km in 6?w...

  1. Gap Resolution

    Energy Technology Data Exchange (ETDEWEB)

    2017-04-25

    Gap Resolution is a software package that was developed to improve Newbler genome assemblies by automating the closure of sequence gaps caused by repetitive regions in the DNA. This is done by performing the follow steps:1) Identify and distribute the data for each gap in sub-projects. 2) Assemble the data associated with each sub-project using a secondary assembler, such as Newbler or PGA. 3) Determine if any gaps are closed after reassembly, and either design fakes (consensus of closed gap) for those that closed or lab experiments for those that require additional data. The software requires as input a genome assembly produce by the Newbler assembler provided by Roche and 454 data containing paired-end reads.

  2. Application of Stochastic Automata Networks for Creation of Continuous Time Markov Chain Models of Voltage Gating of Gap Junction Channels

    Directory of Open Access Journals (Sweden)

    Mindaugas Snipas

    2015-01-01

    Full Text Available The primary goal of this work was to study advantages of numerical methods used for the creation of continuous time Markov chain models (CTMC of voltage gating of gap junction (GJ channels composed of connexin protein. This task was accomplished by describing gating of GJs using the formalism of the stochastic automata networks (SANs, which allowed for very efficient building and storing of infinitesimal generator of the CTMC that allowed to produce matrices of the models containing a distinct block structure. All of that allowed us to develop efficient numerical methods for a steady-state solution of CTMC models. This allowed us to accelerate CPU time, which is necessary to solve CTMC models, ∼20 times.

  3. An improved model of induction motors for diagnosis purposes - Slot skewing effect and air-gap eccentricity faults

    Energy Technology Data Exchange (ETDEWEB)

    Ghoggal, A.; Zouzou, S.E.; Sahraoui, M. [Laboratoire de genie electrique de Biskra, Departement d' electrotechnique, Universite Mohamed Khider, BP 145, Biskra (Algeria); Razik, H. [Groupe de Recherche en Electrotechnique et Electronique de Nancy, Universite Henri Poincare, Faculte des Sciences et Techniques, BP 239, F-54506 Vandoeuvre-les-Nancy (France); Khezzar, A. [Laboratoire d' Electrotechnique de Constantine, Universite Mentouri, Constantine (Algeria)

    2009-05-15

    This paper describes an improved method for the modeling of axial and radial eccentricities in induction motors (IM). The model is based on an extension of the modified winding function approach (MWFA) which allows for all harmonics of the magnetomotive force (MMF) to be taken into account. It is shown that a plane view of IM gets easily the motor inductances and reduces considerably the calculation process. The described technique includes accurately the slot skewing effect and leads to pure analytical expressions of the inductances in case of radial eccentricity. In order to model the static, dynamic or mixed axial eccentricity, three suitable alternatives are explained. Unlike the previous proposals, the discussed alternatives take into account all the harmonics of the inverse of air-gap function without any development in Fourier series. Simulation results as well as experimental verifications prove the usefulness and the effectiveness of the proposed model. (author)

  4. An improved model of induction motors for diagnosis purposes - Slot skewing effect and air-gap eccentricity faults

    International Nuclear Information System (INIS)

    Ghoggal, A.; Zouzou, S.E.; Razik, H.; Sahraoui, M.; Khezzar, A.

    2009-01-01

    This paper describes an improved method for the modeling of axial and radial eccentricities in induction motors (IM). The model is based on an extension of the modified winding function approach (MWFA) which allows for all harmonics of the magnetomotive force (MMF) to be taken into account. It is shown that a plane view of IM gets easily the motor inductances and reduces considerably the calculation process. The described technique includes accurately the slot skewing effect and leads to pure analytical expressions of the inductances in case of radial eccentricity. In order to model the static, dynamic or mixed axial eccentricity, three suitable alternatives are explained. Unlike the previous proposals, the discussed alternatives take into account all the harmonics of the inverse of air-gap function without any development in Fourier series. Simulation results as well as experimental verifications prove the usefulness and the effectiveness of the proposed model.

  5. Application of Stochastic Automata Networks for Creation of Continuous Time Markov Chain Models of Voltage Gating of Gap Junction Channels

    Science.gov (United States)

    Pranevicius, Henrikas; Pranevicius, Mindaugas; Pranevicius, Osvaldas; Bukauskas, Feliksas F.

    2015-01-01

    The primary goal of this work was to study advantages of numerical methods used for the creation of continuous time Markov chain models (CTMC) of voltage gating of gap junction (GJ) channels composed of connexin protein. This task was accomplished by describing gating of GJs using the formalism of the stochastic automata networks (SANs), which allowed for very efficient building and storing of infinitesimal generator of the CTMC that allowed to produce matrices of the models containing a distinct block structure. All of that allowed us to develop efficient numerical methods for a steady-state solution of CTMC models. This allowed us to accelerate CPU time, which is necessary to solve CTMC models, ∼20 times. PMID:25705700

  6. Magnetic Resonance Imaging of Cartilage Repair

    Science.gov (United States)

    Trattnig, Siegfried; Winalski, Carl S.; Marlovits, Stephan; Jurvelin, Jukka S.; Welsch, Goetz H.; Potter, Hollis G.

    2011-01-01

    Articular cartilage lesions are a common pathology of the knee joint, and many patients may benefit from cartilage repair surgeries that offer the chance to avoid the development of osteoarthritis or delay its progression. Cartilage repair surgery, no matter the technique, requires a noninvasive, standardized, and high-quality longitudinal method to assess the structure of the repair tissue. This goal is best fulfilled by magnetic resonance imaging (MRI). The present article provides an overview of the current state of the art of MRI of cartilage repair. In the first 2 sections, preclinical and clinical MRI of cartilage repair tissue are described with a focus on morphological depiction of cartilage and the use of functional (biochemical) MR methodologies for the visualization of the ultrastructure of cartilage repair. In the third section, a short overview is provided on the regulatory issues of the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) regarding MR follow-up studies of patients after cartilage repair surgeries. PMID:26069565

  7. STOCHASTIC AND GEOMETRIC REASONING FOR INDOOR BUILDING MODELS WITH ELECTRIC INSTALLATIONS – BRIDGING THE GAP BETWEEN GIS AND BIM

    Directory of Open Access Journals (Sweden)

    Y. Dehbi

    2017-10-01

    Full Text Available 3D city and building models according to CityGML encode the geometry, represent the structure and model semantically relevant building parts such as doors, windows and balconies. Building information models support the building design, construction and the facility management. In contrast to CityGML, they include also objects which cannot be observed from the outside. The three dimensional indoor models characterize a missing link between both worlds. Their derivation, however, is expensive. The semantic automatic interpretation of 3D point clouds of indoor environments is a methodically demanding task. The data acquisition is costly and difficult. The laser scanners and image-based methods require the access to every room. Based on an approach which does not require an additional geometry acquisition of building indoors, we propose an attempt for filling the gaps between 3D building models and building information models. Based on sparse observations such as the building footprint and room areas, 3D indoor models are generated using combinatorial and stochastic reasoning. The derived models are expanded by a-priori not observable structures such as electric installation. Gaussian mixtures, linear and bi-linear constraints are used to represent the background knowledge and structural regularities. The derivation of hypothesised models is performed by stochastic reasoning using graphical models, Gauss-Markov models and MAP-estimators.

  8. Cartilage and bone malformations in the head of zebrafish (Danio rerio) embryos following exposure to disulfiram and acetic acid hydrazide

    Energy Technology Data Exchange (ETDEWEB)

    Strecker, Ruben, E-mail: Ruben.Strecker@cos.uni-heidelberg.de [Aquatic Ecology and Toxicology Section, Center for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, D-69120 Heidelberg (Germany); Weigt, Stefan, E-mail: stefan.weigt@merckgroup.com [Institute of Toxicology, Merck KGaA, 64293 Darmstadt (Germany); Braunbeck, Thomas, E-mail: braunbeck@uni-hd.de [Aquatic Ecology and Toxicology Section, Center for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, D-69120 Heidelberg (Germany)

    2013-04-15

    In order to investigate teratogenic effects, especially on cartilage and bone formation, zebrafish embryos were exposed for 144 h to the dithiocarbamate pesticide disulfiram (20–320 μg/L) and acetic acid hydrazide (0.375–12 g/L), a degradation product of isoniazid. After fixation and full-mount staining, disulfiram could be shown to induce strong cartilage malformations after exposure to ≥ 80 μg/L, whereas acetic acid hydrazide caused cartilage alterations only from 1.5 g/L. Undulating notochords occurred after exposure to disulfiram even at the lowest test concentration of 20 μg/L, whereas at the two lowest concentrations of acetic acid hydrazide (0.375 and 0.75 g/L) mainly fractures of the notochord were observed. Concentrations of acetic acid hydrazide ≥ 1.5 g/L resulted in undulated notochords similar to disulfiram. Cartilages and ossifications of the cranium, including the cleithrum, were individually analyzed assessing the severity of malformation and the degree of ossification in a semi-quantitative approach. Cartilages of the neurocranium such as the ethmoid plate proved to be more stable than cartilages of the pharyngeal skeleton such as Meckel's cartilage. Hence, ossification proved significantly more susceptible than cartilage. The alterations induced in the notochord as well as in the cranium might well be of ecological relevance, since notochord malformation is likely to result in impaired swimming and cranial malformation might compromise regular food uptake. - Highlights: ► Disulfiram and acetic acid hydrazide as notochord, cartilage and bone teratogens ► Zebrafish embryos to model effects on single cartilages and bones in the head ► LC50 calculation and head length measurements after six days post-fertilization ► Lethality, head length and teratogenic effects are dose-dependent. ► Cartilages of the neurocranium are the most stable elements in the head.

  9. Cartilage and bone malformations in the head of zebrafish (Danio rerio) embryos following exposure to disulfiram and acetic acid hydrazide

    International Nuclear Information System (INIS)

    Strecker, Ruben; Weigt, Stefan; Braunbeck, Thomas

    2013-01-01

    In order to investigate teratogenic effects, especially on cartilage and bone formation, zebrafish embryos were exposed for 144 h to the dithiocarbamate pesticide disulfiram (20–320 μg/L) and acetic acid hydrazide (0.375–12 g/L), a degradation product of isoniazid. After fixation and full-mount staining, disulfiram could be shown to induce strong cartilage malformations after exposure to ≥ 80 μg/L, whereas acetic acid hydrazide caused cartilage alterations only from 1.5 g/L. Undulating notochords occurred after exposure to disulfiram even at the lowest test concentration of 20 μg/L, whereas at the two lowest concentrations of acetic acid hydrazide (0.375 and 0.75 g/L) mainly fractures of the notochord were observed. Concentrations of acetic acid hydrazide ≥ 1.5 g/L resulted in undulated notochords similar to disulfiram. Cartilages and ossifications of the cranium, including the cleithrum, were individually analyzed assessing the severity of malformation and the degree of ossification in a semi-quantitative approach. Cartilages of the neurocranium such as the ethmoid plate proved to be more stable than cartilages of the pharyngeal skeleton such as Meckel's cartilage. Hence, ossification proved significantly more susceptible than cartilage. The alterations induced in the notochord as well as in the cranium might well be of ecological relevance, since notochord malformation is likely to result in impaired swimming and cranial malformation might compromise regular food uptake. - Highlights: ► Disulfiram and acetic acid hydrazide as notochord, cartilage and bone teratogens ► Zebrafish embryos to model effects on single cartilages and bones in the head ► LC50 calculation and head length measurements after six days post-fertilization ► Lethality, head length and teratogenic effects are dose-dependent. ► Cartilages of the neurocranium are the most stable elements in the head

  10. Biological aspects of tissue-engineered cartilage.

    Science.gov (United States)

    Hoshi, Kazuto; Fujihara, Yuko; Yamawaki, Takanori; Harai, Motohiro; Asawa, Yukiyo; Hikita, Atsuhiko

    2018-04-01

    Cartilage regenerative medicine has been progressed well, and it reaches the stage of clinical application. Among various techniques, tissue engineering, which incorporates elements of materials science, is investigated earnestly, driven by high clinical needs. The cartilage tissue engineering using a poly lactide scaffold has been exploratorily used in the treatment of cleft lip-nose patients, disclosing good clinical results during 3-year observation. However, to increase the reliability of this treatment, not only accumulation of clinical evidence on safety and usefulness of the tissue-engineered products, but also establishment of scientific background on biological mechanisms, are regarded essential. In this paper, we reviewed recent trends of cartilage tissue engineering in clinical practice, summarized experimental findings on cellular and matrix changes during the cartilage regeneration, and discussed the importance of further studies on biological aspects of tissue-engineered cartilage, especially by the histological and the morphological methods.

  11. TBA equations for the mass gap in the O(2r) non-linear σ-models

    International Nuclear Information System (INIS)

    Balog, Janos; Hegedues, Arpad

    2005-01-01

    We propose TBA integral equations for 1-particle states in the O(n) non-linear σ-model for even n. The equations are conjectured on the basis of the analytic properties of the large volume asymptotics of the problem, which is explicitly constructed starting from Luscher's asymptotic formula. For small volumes the mass gap values computed numerically from the TBA equations agree very well with results of three-loop perturbation theory calculations, providing support for the validity of the proposed TBA system

  12. Critical behavior of the Higgs- and Goldstone-mass gaps for the two-dimensional S=1 XY model

    Directory of Open Access Journals (Sweden)

    Yoshihiro Nishiyama

    2015-08-01

    Full Text Available Spectral properties for the two-dimensional quantum S=1 XY model were investigated with the exact diagonalization method. In the symmetry-broken phase, there appear the massive Higgs and massless Goldstone excitations, which correspond to the longitudinal and transverse modes of the spontaneous magnetic moment, respectively. The former excitation branch is embedded in the continuum of the latter, and little attention has been paid to the details, particularly, in proximity to the critical point. The finite-size-scaling behavior is improved by extending the interaction parameters. An analysis of the critical amplitude ratio for these mass gaps is made.

  13. An Evolutionary Robotics Approach to the Control of Plant Growth and Motion: Modeling Plants and Crossing the Reality Gap

    DEFF Research Database (Denmark)

    Wahby, Mostafa; Hofstadler, Daniel Nicolas; Heinrich, Mary Katherine

    2016-01-01

    approach where task performance is determined by monitoring the plant's reaction. First, we do initial plant experiments with simple, predetermined controllers. Then we use image sampling data as a model of the dynamics of the plant tip xy position. Second, we use this approach to evolve robot controllers...... in simulation. The task is to make the plant approach three predetermined, distinct points in an xy-plane. Finally, we test the evolved controllers in real plant experiments and find that we cross the reality gap successfully. We shortly describe how we have extended from plant tip to many points on the plant...

  14. Gap Junctions

    Science.gov (United States)

    Nielsen, Morten Schak; Axelsen, Lene Nygaard; Sorgen, Paul L.; Verma, Vandana; Delmar, Mario; Holstein-Rathlou, Niels-Henrik

    2013-01-01

    Gap junctions are essential to the function of multicellular animals, which require a high degree of coordination between cells. In vertebrates, gap junctions comprise connexins and currently 21 connexins are known in humans. The functions of gap junctions are highly diverse and include exchange of metabolites and electrical signals between cells, as well as functions, which are apparently unrelated to intercellular communication. Given the diversity of gap junction physiology, regulation of gap junction activity is complex. The structure of the various connexins is known to some extent; and structural rearrangements and intramolecular interactions are important for regulation of channel function. Intercellular coupling is further regulated by the number and activity of channels present in gap junctional plaques. The number of connexins in cell-cell channels is regulated by controlling transcription, translation, trafficking, and degradation; and all of these processes are under strict control. Once in the membrane, channel activity is determined by the conductive properties of the connexin involved, which can be regulated by voltage and chemical gating, as well as a large number of posttranslational modifications. The aim of the present article is to review our current knowledge on the structure, regulation, function, and pharmacology of gap junctions. This will be supported by examples of how different connexins and their regulation act in concert to achieve appropriate physiological control, and how disturbances of connexin function can lead to disease. © 2012 American Physiological Society. Compr Physiol 2:1981-2035, 2012. PMID:23723031

  15. Cartilage repair in the degenerative ageing knee

    Science.gov (United States)

    Brittberg, Mats; Gomoll, Andreas H; Canseco, José A; Far, Jack; Lind, Martin; Hui, James

    2016-01-01

    Background and purpose Cartilage damage can develop due to trauma, resulting in focal chondral or osteochondral defects, or as more diffuse loss of cartilage in a generalized organ disease such as osteoarthritis. A loss of cartilage function and quality is also seen with increasing age. There is a spectrum of diseases ranging from focal cartilage defects with healthy surrounding cartilage to focal lesions in degenerative cartilage, to multiple and diffuse lesions in osteoarthritic cartilage. At the recent Aarhus Regenerative Orthopaedics Symposium (AROS) 2015, regenerative challenges in an ageing population were discussed by clinicians and basic scientists. A group of clinicians was given the task of discussing the role of tissue engineering in the treatment of degenerative cartilage lesions in ageing patients. We present the outcomes of our discussions on current treatment options for such lesions, with particular emphasis on different biological repair techniques and their supporting level of evidence. Results and interpretation Based on the studies on treatment of degenerative lesions and early OA, there is low-level evidence to suggest that cartilage repair is a possible treatment for such lesions, but there are conflicting results regarding the effect of advanced age on the outcome. We concluded that further improvements are needed for direct repair of focal, purely traumatic defects before we can routinely use such repair techniques for the more challenging degenerative lesions. Furthermore, we need to identify trigger mechanisms that start generalized loss of cartilage matrix, and induce subchondral bone changes and concomitant synovial pathology, to maximize our treatment methods for biological repair in degenerative ageing joints. PMID:27910738

  16. Optical characterization of porcine articular cartilage using a polarimetry technique with differential Mueller matrix formulism.

    Science.gov (United States)

    Chang, Ching-Min; Lo, Yu-Lung; Tran, Nghia-Khanh; Chang, Yu-Jen

    2018-03-20

    A method is proposed for characterizing the optical properties of articular cartilage sliced from a pig's thighbone using a Stokes-Mueller polarimetry technique. The principal axis angle, phase retardance, optical rotation angle, circular diattenuation, diattenuation axis angle, linear diattenuation, and depolarization index properties of the cartilage sample are all decoupled in the proposed analytical model. Consequently, the accuracy and robustness of the extracted results are improved. The glucose concentration, collagen distribution, and scattering properties of samples from various depths of the articular cartilage are systematically explored via an inspection of the related parameters. The results show that the glucose concentration and scattering effect are both enhanced in the superficial region of the cartilage. By contrast, the collagen density increases with an increasing sample depth.

  17. 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...

  18. Exploiting endogenous fibrocartilage stem cells to regenerate cartilage and repair joint injury

    Science.gov (United States)

    Embree, Mildred C.; Chen, Mo; Pylawka, Serhiy; Kong, Danielle; Iwaoka, George M.; Kalajzic, Ivo; Yao, Hai; Shi, Chancheng; Sun, Dongming; Sheu, Tzong-Jen; Koslovsky, David A.; Koch, Alia; Mao, Jeremy J.

    2016-01-01

    Tissue regeneration using stem cell-based transplantation faces many hurdles. Alternatively, therapeutically exploiting endogenous stem cells to regenerate injured or diseased tissue may circumvent these challenges. Here we show resident fibrocartilage stem cells (FCSCs) can be used to regenerate and repair cartilage. We identify FCSCs residing within the superficial zone niche in the temporomandibular joint (TMJ) condyle. A single FCSC spontaneously generates a cartilage anlage, remodels into bone and organizes a haematopoietic microenvironment. Wnt signals deplete the reservoir of FCSCs and cause cartilage degeneration. We also show that intra-articular treatment with the Wnt inhibitor sclerostin sustains the FCSC pool and regenerates cartilage in a TMJ injury model. We demonstrate the promise of exploiting resident FCSCs as a regenerative therapeutic strategy to substitute cell transplantation that could be beneficial for patients suffering from fibrocartilage injury and disease. These data prompt the examination of utilizing this strategy for other musculoskeletal tissues. PMID:27721375

  19. Stem cells catalyze cartilage formation by neonatal articular chondrocytes in 3D biomimetic hydrogels.

    Science.gov (United States)

    Lai, Janice H; Kajiyama, Glen; Smith, Robert Lane; Maloney, William; Yang, Fan

    2013-12-19

    Cartilage loss is a leading cause of disability among adults and effective therapy remains elusive. Neonatal chondrocytes (NChons) are an attractive allogeneic cell source for cartilage repair, but their clinical translation has been hindered by scarce donor availability. Here we examine the potential for catalyzing cartilage tissue formation using a minimal number of NChons by co-culturing them with adipose-derived stem cells (ADSCs) in 3D hydrogels. Using three different co-culture models, we demonstrated that the effects of co-culture on cartilage tissue formation are dependent on the intercellular distance and cell distribution in 3D. Unexpectedly, increasing ADSC ratio in mixed co-culture led to increased synergy between NChons and ADSCs, and resulted in the formation of large neocartilage nodules. This work raises the potential of utilizing stem cells to catalyze tissue formation by neonatal chondrocytes via paracrine signaling, and highlights the importance of controlling cell distribution in 3D matrices to achieve optimal synergy.

  20. Elastic cartilage reconstruction by transplantation of cultured hyaline cartilage-derived chondrocytes.

    Science.gov (United States)

    Mizuno, M; Takebe, T; Kobayashi, S; Kimura, S; Masutani, M; Lee, S; Jo, Y H; Lee, J I; Taniguchi, H

    2014-05-01

    Current surgical intervention of craniofacial defects caused by injuries or abnormalities uses reconstructive materials, such as autologous cartilage grafts. Transplantation of autologous tissues, however, places a significant invasiveness on patients, and many efforts have been made for establishing an alternative graft. Recently, we and others have shown the potential use of reconstructed elastic cartilage from ear-derived chondrocytes or progenitors with the unique elastic properties. Here, we examined the differentiation potential of canine joint cartilage-derived chondrocytes into elastic cartilage for expanding the cell sources, such as hyaline cartilage. Articular chondrocytes are isolated from canine joint, cultivated, and compared regarding characteristic differences with auricular chondrocytes, including proliferation rates, gene expression, extracellular matrix production, and cartilage reconstruction capability after transplantation. Canine articular chondrocytes proliferated less robustly than auricular chondrocytes, but there was no significant difference in the amount of sulfated glycosaminoglycan produced from redifferentiated chondrocytes. Furthermore, in vitro expanded and redifferentiated articular chondrocytes have been shown to reconstruct elastic cartilage on transplantation that has histologic characteristics distinct from hyaline cartilage. Taken together, cultured hyaline cartilage-derived chondrocytes are a possible cell source for elastic cartilage reconstruction. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  1. Hyaline cartilage cells outperform mandibular condylar cartilage cells in a TMJ fibrocartilage tissue engineering application.

    Science.gov (United States)

    Wang, L; Lazebnik, M; Detamore, M S

    2009-03-01

    To compare temporomandibular joint (TMJ) condylar cartilage cells in vitro to hyaline cartilage cells cultured in a three-dimensional (3D) environment for tissue engineering of mandibular condylar cartilage. Mandibular condylar cartilage and hyaline cartilage cells were harvested from pigs and cultured for 6 weeks in polyglycolic acid (PGA) scaffolds. Both types of cells were treated with glucosamine sulfate (0.4 mM), insulin-like growth factor-I (IGF-I) (100 ng/ml) and their combination. At weeks 0 and 6, cell number, glycosaminoglycan (GAG) and collagen content were determined, types I and II collagen were visualized by immunohistochemistry and GAGs were visualized by histology. Hyaline cartilage cells produced from half an order to a full order of magnitude more GAGs and collagen than mandibular condylar cartilage cells in 3D culture. IGF-I was a highly effective signal for biosynthesis with hyaline cartilage cells, while glucosamine sulfate decreased cell proliferation and biosynthesis with both types of cells. In vitro culture of TMJ condylar cartilage cells produced a fibrous tissue with predominantly type I collagen, while hyaline cartilage cells formed a fibrocartilage-like tissue with types I and II collagen. The combination of IGF and glucosamine had a synergistic effect on maintaining the phenotype of TMJ condylar cells to generate both types I and II collagen. Given the superior biosynthetic activity by hyaline cartilage cells and the practical surgical limitations of harvesting cells from the TMJ of a patient requiring TMJ reconstruction, cartilage cells from elsewhere in the body may be a potentially better alternative to cells harvested from the TMJ for TMJ tissue engineering. This finding may also apply to other fibrocartilages such as the intervertebral disc and knee meniscus in applications where a mature cartilage cell source is desired.

  2. Cysts of the semilunar cartilage

    International Nuclear Information System (INIS)

    Bruessermann, M.

    1981-01-01

    On the basis of the studies listed in the bibliography, this dissertation reports on the pathology, clinical symptoms and radiology of cysts of the semilunar cartilage. The author analyses 118 cases of his own, with special regard to the results of pneumo-arthrographic investigations carried through according to a special technique by Schaefer. In the course of this work, measurements of the meniscal base are for the first time used as radiological criteria indicating the presence of a cyst of the semilunar cartilage. Furthermore the well-known radiological signs of cysts, such as bone defects according to Albert and Keller, light central spot in the meniscal body, as well as Rauber's sign and horizontal rupture, are investigated as to the frequency of their incidence. For that purpose all the X-ray pictures were subjected to a further dose scrutiny. A list of all the 118 cases with their clinical and radiological data is found in the annex, together with the results of the operations and patho-anatomical investigations. (orig.) [de

  3. Technical Report: Correlation Between the Repair of Cartilage and Subchondral Bone in an Osteochondral Defect Using Bilayered, Biodegradable Hydrogel Composites.

    Science.gov (United States)

    Lu, Steven; Lam, Johnny; Trachtenberg, Jordan E; Lee, Esther J; Seyednejad, Hajar; van den Beucken, Jeroen J J P; Tabata, Yasuhiko; Kasper, F Kurtis; Scott, David W; Wong, Mark E; Jansen, John A; Mikos, Antonios G

    2015-12-01

    The present work investigated correlations between cartilage and subchondral bone repair, facilitated by a growth factor-delivering scaffold, in a rabbit osteochondral defect model. Histological scoring indices and microcomputed tomography morphological parameters were used to evaluate cartilage and bone repair, respectively, at 6 and 12 weeks. Correlation analysis revealed significant associations between specific cartilage indices and subchondral bone parameters that varied with location in the defect (cortical vs. trabecular region), time point (6 vs. 12 weeks), and experimental group (insulin-like growth factor-1 only, bone morphogenetic protein-2 only, or both growth factors). In particular, significant correlations consistently existed between cartilage surface regularity and bone quantity parameters. Overall, correlation analysis between cartilage and bone repair provided a fuller understanding of osteochondral repair and can help drive informed studies for future osteochondral regeneration strategies.

  4. Imaging diagnosis of the articular cartilage disorders

    International Nuclear Information System (INIS)

    Liu Sirun; Zhu Tianyuan; Huang Li; Leng Xiaoming

    2003-01-01

    Objective: To evaluate the diagnosis and differential diagnosis among the chronic osteoarthritis, rheumatoid arthritis and other chronic cartilage lesions on the plain films and MR images. Methods: Eighty-nine cases, including 115 joints, underwent plain film and MRI examination, and enhanced MRI scan was performed on 32 of them, including 44 joints. MRI scan sequences consisted of T 1 WI, T 2 WI + PDWI, STIR, and 3D FS SPGR. There were 90 knee joints in this group and each of the articular cartilage was divided into four parts: patella, femoral medial condyle, femoral lateral condyle, and tibia facet on MR images. The cartilage disorders were classified according to the outerbridge method. In addition, 61 cases including 75 joints were observed as a control group on the plain films and MR images. Results: 115 cartilage lesions were found on MR images, in which thinness of the cartilage (58 cases, 50.4%), bone changes under the cartilage (22 cases, 19.7%), medullar edema (22 cases, 19.7%), and synovial hyperplasia (52 cases, 45.2%) were seen. The patella cartilage was the most likely affected part (81/90, 90%). So the patellar cartilage lesions were divided as group 1 (grade I-II) and group 2 (grade III-IV) on MR images, which were compared with the plain film signs. The narrowing of the joint space and saccules under the articular surface were statistically significant with each other, and χ 2 values were 9.349 and 9.885, respectively (P=0.002). Conclusion: No constant signs could be seen on the plain films with grade I-II cartilage disorders. While the narrowing joint space and saccules under the joint surface could be seen on them with grade III-IV cartilage disorders, which were mainly correlated with the cartilage disorders and bone changes under the articular cartilages. A combination of the plain films and MR images is the best imaging method for examining the joints and joint cartilages. Enhanced MRI scan is very helpful on the diagnosis and differential

  5. Centralization of extruded medial meniscus delays cartilage degeneration in rats.

    Science.gov (United States)

    Ozeki, Nobutake; Muneta, Takeshi; Kawabata, Kenichi; Koga, Hideyuki; Nakagawa, Yusuke; Saito, Ryusuke; Udo, Mio; Yanagisawa, Katsuaki; Ohara, Toshiyuki; Mochizuki, Tomoyuki; Tsuji, Kunikazu; Saito, Tomoyuki; Sekiya, Ichiro

    2017-05-01

    Meniscus extrusion often observed in knee osteoarthritis has a strong correlation with the progression of cartilage degeneration and symptom in the patients. We recently reported a novel procedure "arthroscopic centralization" in which the capsule was sutured to the edge of the tibial plateau to reduce meniscus extrusion in the human knee. However, there is no animal model to study the efficacy of this procedure. The purposes of this study were [1] to establish a model of centralization for the extruded medial meniscus in a rat model; and [2] to investigate the chondroprotective effect of this procedure. Medial meniscus extrusion was induced by the release of the anterior synovial capsule and the transection of the meniscotibial ligament. Centralization was performed by the pulled-out suture technique. Alternatively, control rats had only the medial meniscus extrusion surgery. Medial meniscus extrusion was evaluated by micro-CT and macroscopic findings. Cartilage degeneration of the medial tibial plateau was evaluated macroscopically and histologically. By micro-CT analysis, the medial meniscus extrusion was significantly improved in the centralization group in comparison to the extrusion group throughout the study. Both macroscopically and histologically, the cartilage lesion of the medial tibial plateau was prevented in the centralization group but was apparent in the control group. We developed medial meniscus extrusion in a rat model, and centralization of the extruded medial meniscus by the pull-out suture technique improved the medial meniscus extrusion and delayed cartilage degeneration, though the effect was limited. Centralization is a promising treatment to prevent the progression of osteoarthritis. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Seed Dispersal, Microsites or Competition—What Drives Gap Regeneration in an Old-Growth Forest? An Application of Spatial Point Process Modelling

    Directory of Open Access Journals (Sweden)

    Georg Gratzer

    2018-04-01