38 results on '"Werner, Carsten"'
Search Results
2. Nerve growth factor receptor (Ngfr) induces neurogenic plasticity by suppressing reactive astroglial Lcn2/Slc22a17 signaling in Alzheimer's disease.
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Siddiqui, Tohid, Cosacak, Mehmet Ilyas, Popova, Stanislava, Bhattarai, Prabesh, Yilmaz, Elanur, Lee, Annie J., Min, Yuhao, Wang, Xue, Allen, Mariet, İş, Özkan, Atasavum, Zeynep Tansu, Rodriguez-Muela, Natalia, Vardarajan, Badri N., Flaherty, Delaney, Teich, Andrew F., Santa-Maria, Ismael, Freudenberg, Uwe, Werner, Carsten, Tosto, Giuseppe, and Mayeux, Richard
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NERVE growth factor ,ALZHEIMER'S disease ,GENE regulatory networks ,AMYLOID plaque ,GENE expression - Abstract
Neurogenesis, crucial for brain resilience, is reduced in Alzheimer's disease (AD) that induces astroglial reactivity at the expense of the pro-neurogenic potential, and restoring neurogenesis could counteract neurodegenerative pathology. However, the molecular mechanisms promoting pro-neurogenic astroglial fate despite AD pathology are unknown. In this study, we used APP/PS1dE9 mouse model and induced Nerve growth factor receptor (Ngfr) expression in the hippocampus. Ngfr, which promotes neurogenic fate of astroglia during the amyloid pathology-induced neuroregeneration in zebrafish brain, stimulated proliferative and neurogenic outcomes. Histological analyses of the changes in proliferation and neurogenesis, single-cell transcriptomics, spatial proteomics, and functional knockdown studies showed that the induced expression of Ngfr reduced the reactive astrocyte marker Lipocalin-2 (Lcn2), which we found was sufficient to reduce neurogenesis in astroglia. Anti-neurogenic effects of Lcn2 was mediated by Slc22a17, blockage of which recapitulated the pro-neurogenicity by Ngfr. Long-term Ngfr expression reduced amyloid plaques and Tau phosphorylation. Postmortem human AD hippocampi and 3D human astroglial cultures showed elevated LCN2 levels correlate with reactive gliosis and reduced neurogenesis. Comparing transcriptional changes in mouse, zebrafish, and human AD brains for cell intrinsic differential gene expression and weighted gene co-expression networks revealed common altered downstream effectors of NGFR signaling, such as PFKP, which can enhance proliferation and neurogenesis in vitro when blocked. Our study suggests that the reactive non-neurogenic astroglia in AD can be coaxed to a pro-neurogenic fate and AD pathology can be alleviated with Ngfr. We suggest that enhancing pro-neurogenic astroglial fate may have therapeutic ramifications in AD. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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3. Entropic repulsion of cholesterol-containing layers counteracts bioadhesion.
- Author
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Friedrichs, Jens, Helbig, Ralf, Hilsenbeck, Julia, Pandey, Prithvi Raj, Sommer, Jens-Uwe, Renner, Lars David, Pompe, Tilo, and Werner, Carsten
- Abstract
Control of adhesion is a striking feature of living matter that is of particular interest regarding technological translation1–3. We discovered that entropic repulsion caused by interfacial orientational fluctuations of cholesterol layers restricts protein adsorption and bacterial adhesion. Moreover, we found that intrinsically adhesive wax ester layers become similarly antibioadhesive when containing small quantities (under 10 wt%) of cholesterol. Wetting, adsorption and adhesion experiments, as well as atomistic simulations, showed that repulsive characteristics depend on the specific molecular structure of cholesterol that encodes a finely balanced fluctuating reorientation at the interface of unconstrained supramolecular assemblies: layers of cholesterol analogues differing only in minute molecular variations showed markedly different interfacial mobility and no antiadhesive effects. Also, orientationally fixed cholesterol layers did not resist bioadhesion. Our insights provide a conceptually new physicochemical perspective on biointerfaces and may guide future material design in regulation of adhesion.Entropic repulsion caused by interfacial orientational fluctuations of cholesterol layers restricts protein adsorption and bacterial adhesion, providing a conceptually new physicochemical perspective on biointerfaces that may guide future material design in regulation of adhesion. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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4. Selective vulnerability of inhibitory networks in multiple sclerosis.
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Zoupi, Lida, Booker, Sam A., Eigel, Dimitri, Werner, Carsten, Kind, Peter C., Spires-Jones, Tara L., Newland, Ben, and Williams, Anna C.
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MULTIPLE sclerosis ,CENTRAL nervous system diseases ,INTERNEURONS ,DEMYELINATION ,MYELIN proteins ,DISEASE progression - Abstract
In multiple sclerosis (MS), a chronic demyelinating disease of the central nervous system, neurodegeneration is detected early in the disease course and is associated with the long-term disability of patients. Neurodegeneration is linked to both inflammation and demyelination, but its exact cause remains unknown. This gap in knowledge contributes to the current lack of treatments for the neurodegenerative phase of MS. Here we ask if neurodegeneration in MS affects specific neuronal components and if it is the result of demyelination. Neuropathological examination of secondary progressive MS motor cortices revealed a selective vulnerability of inhibitory interneurons in MS. The generation of a rodent model of focal subpial cortical demyelination reproduces this selective neurodegeneration providing a new preclinical model for the study of neuroprotective treatments. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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5. Defined Geldrop Cultures Maintain Neural Precursor Cells.
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Vogler, Steffen, Prokoph, Silvana, Freudenberg, Uwe, Binner, Marcus, Tsurkan, Mikhail, Werner, Carsten, and Kempermann, Gerd
- Abstract
Distinct micro-environmental properties have been reported to be essential for maintenance of neural precursor cells (NPCs) within the adult brain. Due to high complexity and technical limitations, the natural niche can barely be studied systematically in vivo. By reconstituting selected environmental properties (adhesiveness, proteolytic degradability, and elasticity) in geldrop cultures, we show that NPCs can be maintained stably at high density over an extended period of time (up to 8 days). In both conventional systems, neurospheres and monolayer cultures, they would expand and (in the case of neurospheres) differentiate rapidly. Further, we report a critical dualism between matrix adhesiveness and degradability. Only if both features are functional NPCs stay proliferative. Lastly, Rho-associated protein kinase was identified as part of a pivotal intracellular signaling cascade controlling cell morphology in response to environmental cues inside geldrop cultures. Our findings demonstrate that simple manipulations of the microenvironment in vitro result in an important preservation of stemness features in the cultured precursor cells. [ABSTRACT FROM AUTHOR]
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- 2018
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6. Oxidation and structural changes in NMMO-regenerated cellulose films.
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Zimmermann, Ralf, Müller, Yvonne, Freudenberg, Uwe, Jehnichen, Dieter, Potthast, Antje, Rosenau, Thomas, and Werner, Carsten
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AMINE oxides ,MORPHOLINE ,CELLULOSE chemistry ,CARBONYL compounds ,CARBOXYL group ,IONIC conductivity ,MOLECULAR weights - Abstract
Carbonyl and carboxyl groups introduced by oxidative processes during production and purification of celluloses determine intra- and intermolecular interactions and thus application-related bulk and surface properties of cellulosic materials. We report a comprehensive approach to the quantification of carboxyl and carbonyl groups in cellulose films upon reconstitution from NMMO solutions. Measurements of the excess conductivity were combined with the determination of the molecular weight distribution, quantification of the carboxyl and carbonyl group content, crystallinity and film swelling in aqueous solutions. TEMPO-oxidized, NMMO-regenerated cellulose films were additionally analysed as a reference system for extensive cellulose oxidation. Our reported data demonstrate that dissolution of cellulose in NMMO results in the formation of onic acids, chain degradation, increased ionization and film swelling, whereas TEMPO-oxidation introduced carbonyl groups as well as onic and uronic acids causing a significantly increased charging, ion accumulation and swelling even at higher crystallinity. [ABSTRACT FROM AUTHOR]
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- 2016
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7. Quantifying Cellular Adhesion to Covalently Immobilized Extracellular Matrix Proteins by Single-Cell Force Spectroscopy.
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Friedrichs, Jens, Werner, Carsten, and Müller, Daniel J.
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- 2013
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8. Enzyme Immobilization on Reactive Polymer Films.
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Cordeiro, Ana L., Pompe, Tilo, Salchert, Katrin, and Werner, Carsten
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- 2011
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9. Interfacial Phenomena of Biomaterials.
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Stamm, Manfred and Werner, Carsten
- Abstract
Since biomaterials are generally used in diagnostic or therapeutic devices with direct contact to the human body, the bio-interfacial interactions are of great interest. Several aspects of surface interactions of biomaterials are discussed, in particular the interaction of polymeric biomaterials with proteins, cells and tissues. To ensure biocompatibility non-specific interactions should be minimized. This may be achieved by particular polymer coatings, but also by implementation of bioactive components or specific surface morphologies and supramolecular biopolymer assemblies. This chapter provides a simplistic survey of the current opinion about interfacial phenomena of polymeric biomaterials. Emphasis will be put rather on conceptual than on methodological aspects. After introducing the hierarchy of bio-interfacial phenomena, recent trends in the surface modification of polymeric materials will be briefly summarized. [ABSTRACT FROM AUTHOR]
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- 2008
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10. Fibronectin at Polymer Surfaces with Graduated Characteristics.
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Déjardin, Philippe, Pompe, Tilo, Renner, Lars, and Werner, Carsten
- Abstract
Globular proteins adsorbed onto artificialmaterials often exhibit different functional characteristics due to an altered availability formolecular interactions. This effect is caused by the patterns of substrate-protein interactions and is attributable to conformational changes as well as to the orientation and/or the anchorage of the surface-confined proteins. To highlight this interrelation we report a detailed experimental investigation of the adsorption and displacement of fibronectin, a key protein of the extracellular matrix that enables cell adhesion, at a set of polymer thin films with various hydrophilicity, charge density and swelling characteristics. The patterns of protein displacement were analysed quantitatively for several substrates and adsorbed protein amounts, referring to a model recently suggested by Huetz et al. (Langmuir 11:3145-3152, 1995). The patterns of protein displacement were related to the substrate characteristics and the conditions applied during the formation of the protein layer (i. e. the solution concentration). These findings were compared with the reorganisation of adsorbed fibronectin on the compared polymer substrates by endothelial cells in culture. The results demonstrate that a certain binding strength of fibronectin is required to support the cell-driven formation of fibronectin fibrils, which, in turn, is an important prerequisite for the differentiation of the cells. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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11. Glycosaminoglycan-based hydrogels to modulate heterocellular communication in in vitro angiogenesis models.
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Chwalek, Karolina, Tsurkan, Mikhail V., Freudenberg, Uwe, and Werner, Carsten
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NEOVASCULARIZATION ,ENDOTHELIAL cells ,MORPHOGENESIS ,CANCER cells ,CELL communication - Abstract
Angiogenesis, the outgrowth of blood vessels, is crucial in development, disease and regeneration. Studying angiogenesis in vitro remains challenging because the capillary morphogenesis of endothelial cells (ECs) is controlled by multiple exogenous signals. Therefore, a set of in situ-forming starPEG-heparin hydrogels was used to identify matrix parameters and cellular interactions that best support EC morphogenesis. We showed that a particular type of soft, matrix metalloproteinase-degradable hydrogel containing covalently bound integrin ligands and reversibly conjugated pro-angiogenic growth factors could boost the development of highly branched, interconnected, and lumenized endothelial capillary networks. Using these effective matrix conditions, 3D heterocellular interactions of ECs with different mural cells were demonstrated that enabled EC network modulation and maintenance of stable vascular capillaries over periods of about one month in vitro. The approach was also shown to permit in vitro tumor vascularization experiments with unprecedented levels of control over both ECs and tumor cells. In total, the introduced 3D hydrogel co-culture system could offer unique options for dissecting and adjusting biochemical, biophysical, and cell-cell triggers in tissue-related vascularization models. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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12. Tightly anchored tissue-mimetic matrices as instructive stem cell microenvironments.
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Prewitz, Marina C, Seib, F Philipp, von Bonin, Malte, Friedrichs, Jens, Stißel, Aline, Niehage, Christian, Müller, Katrin, Anastassiadis, Konstantinos, Waskow, Claudia, Hoflack, Bernard, Bornhäuser, Martin, and Werner, Carsten
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STEM cell culture ,EXTRACELLULAR matrix ,BONE marrow ,MESENCHYMAL stem cells ,HEMATOPOIETIC stem cells ,PROGENITOR cells ,CELL differentiation - Abstract
A major obstacle in defining the exact role of extracellular matrix (ECM) in stem cell niches is the lack of suitable in vitro methods that recapitulate complex ECM microenvironments. Here we describe a methodology that permits reliable anchorage of native cell-secreted ECM to culture carriers. We validated our approach by fabricating two types of human bone marrow-specific ECM substrates that were robust enough to support human mesenchymal stem cells (MSCs) and hematopoietic stem and progenitor cells in vitro. We characterized the molecular composition, structural features and nanomechanical properties of the MSC-derived ECM preparations and demonstrated their ability to support expansion and differentiation of bone marrow stem cells. Our methodology enables the deciphering and modulation of native-like multicomponent ECMs of tissue-resident stem cells and will therefore prepare the ground for a more rational design of engineered stem cell niches. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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13. Diversity and potential correlations to the function of Collembola cuticle structures.
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Nickerl, Julia, Helbig, Ralf, Schulz, Hans-Jürgen, Werner, Carsten, and Neinhuis, Christoph
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COLLEMBOLA ,INSECTS ,RESPIRATION ,HABITATS ,SCANNING electron microscopy - Abstract
Collembola (springtails) are soil arthropods, representing the most widespread hexapod group worldwide. Being skin-breathing animals, Collembola evolved special cuticular patterns, which are robust and antiadhesive allowing cuticular respiration under humid conditions in the soil environment. Details about function and formation of these unique cuticle characters are still unknown. Here we demonstrate that a high diversity of cuticular structures exists and that the different observed structural patterns of Collembola cuticles might go along with specific adaptations to life in soil. We examined the cuticle structures of 40 different species using scanning electron microscopy and compared the cuticle patterns of the different species with information about their preferred habitat. In addition, we compare the results with current systematic concepts, showing that certain cuticle structures are typical for different collembolan groups. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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14. Immobilized enzymes affect biofilm formation.
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Cordeiro, Ana L., Hippius, Catharina, and Werner, Carsten
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IMMOBILIZED enzymes ,PATHOGENIC bacteria ,NOSOCOMIAL infections ,PSEUDOMONAS aeruginosa ,PROTEOLYTIC enzymes ,SUBTILISINS ,CELLULASE ,STAPHYLOCOCCUS - Abstract
The effect of the activity of immobilized enzymes on the initial attachment of pathogenic bacteria commonly associated with nosocomial infections ( Pseudomonas aeruginosa and Staphylococcus epidermidis) was investigated. The proteolytic enzymes, subtilisin A and the glycoside hydrolase cellulose, were covalently attached onto poly(ethylene- alt-maleic) anhydride copolymer films. A comparison between active and heat-inactivated surfaces showed that while the activity of immobilized cellulase reduced the attachment of S. epidermidis by 67%, it had no effect on the attachment of P. aeruginosa. Immobilized subtilisin A had opposite effects: the active enzyme had no effect on the attachment of S. epidermidis but reduced the attachment of P. aeruginosa by 44%. The results suggest that different biomolecules are involved in the initial steps of attachment of different bacteria, and that the development of broad-spectrum antifouling enzymatic coatings will need to involve the co-immobilization of enzymes. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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15. Prolonged transendothelial migration of human haematopoietic stem and progenitor cells (HSPCs) towards hydrogel-released SDF1.
- Author
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Sobkow, Lidia, Seib, F., Prodanov, Ljupco, Kurth, Ina, Drichel, Juliane, Bornhäuser, Martin, and Werner, Carsten
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HEMATOPOIETIC stem cell transplantation ,MESENCHYMAL stem cells ,COLLOIDS in medicine ,COLLAGEN ,HEPARIN ,CELL migration - Abstract
The therapeutic success of haematopoetic stem and progenitor cell (HSPC) transplantation is critically dependent on HSPC engraftment in the bone marrow. Gradients of stromal cell-derived factor 1 (SDF1) direct HSPC homing, both in vitro and in vivo. Potentially, regulating the delivery levels of exogenous SDF1 applied to the bone marrow could augment HSPC engraftment. Thus, the aim of the present study was to revise the ability of biocompatible hydrogels to direct HSPC migration in vitro. The delivery system of choice is based on heparin cross-linked with collagen1. We confirm that hydrogel is capable of trapping and releasing SDF1 and using it to generate a protein gradient in transendothelial migration experiments. The use of SDF1-functionalised hydrogel to produce a chemokine gradient revealed, sustained and increased HSPC migration when compared to diffusible SDF1 controls. In conclusion, regulating SDF1 gradients with heparin-containing hydrogels may offer valuable options to direct site-specific migration of HSPC. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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16. Musculoskeletal response to whole-body vibration during fracture healing in intact and ovariectomized rats.
- Author
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Stuermer, Ewa K., Komrakova, Marina, Werner, Carsten, Wicke, Michael, Kolios, Leila, Sehmisch, Stephan, Tezval, Mohammad, Utesch, Clara, Mangal, Orzala, Zimmer, Sebastian, Dullin, Christian, and Stuermer, Klaus M.
- Subjects
TREATMENT of fractures ,MUSCULOSKELETAL system ,LABORATORY rats ,TIBIA ,BONE surgery ,VIBRATION therapy - Abstract
This study investigated the effect of vibration on bone healing and muscle in intact and ovariectomized rats. Thirty ovariectomized (at 3 months of age) and 30 intact 5-month old female Sprague-Dawley rats underwent bilateral metaphyseal osteotomy of tibia. Five days later, half of the ovariectomized and of the intact rats were exposed to whole-body vertical vibration (90 Hz, 0.5 mm, 4 x g acceleration) for 15 min twice a day during 30 days. The other animals did not undergo vibration. After decapitation of rats, one tibia was used for computed tomographic, biomechanical, and histological analyses; the other was used for gene expression analyses of alkaline phosphatase (Alp), osteocalcin (Oc), tartrate-resistant acid phosphatase 1, and insulinlike growth factor 1. Serum Alp and Oc were measured. Mitochondrial activity, fiber area and distribution, and capillary densities were analyzed in M. gastrocnemius and M. longissimus. We found that vibration had no effect on body weight and food intake, but it improved cortical and callus densities (97 vs. 99%, 72 vs. 81%), trabecular structure (9 vs. 14 trabecular nodes), blood supply (1.7 vs. 2.1 capillaries/fiber), and oxidative metabolism (17 vs. 23 pmol O(2)/s/mg) in ovariectomized rats. Vibration generally increased muscle fiber size. Tibia biomechanical properties were diminished after vibration. Oc gene expression was higher in vibrated rats. Serum Alp was increased in ovariectomized rats. In ovariectomized rats, vibration resulted in an earlier bridging; in intact rats, callus bridging occurred later after vibration. The chosen vibration regimen (90 Hz, 0.5 mm, 4 x g acceleration, 15 min twice a day) was effective in improving musculoskeletal tissues in ovariectomized rats but was not optimal for fracture healing. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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17. Designing and Engineering Stem Cell Niches.
- Author
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Teixeira, Ana I., Hermanson, Ola, and Werner, Carsten
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- 2010
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18. Synergistic effect of hydrophobic and anionic surface groups triggers blood coagulation in vitro.
- Author
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Fischer, Marion, Sperling, Claudia, and Werner, Carsten
- Subjects
BIOMEDICAL materials ,HYDROPHOBIC surfaces ,BLOOD coagulation ,BLOOD platelets ,MONOMOLECULAR films - Abstract
Biomaterial induced coagulation encompasses plasmatic and cellular processes. The functional loss of biomedical devices possibly resulting from these thrombotic reactions motivates the need for a better understanding of processes occurring at blood–biomaterial interfaces. Well defined model surfaces providing specific chemical–physical properties (self assembled monolayers (SAMs)) displaying hydrophobic or/and acidic terminal groups were used to uncover initial mechanisms of biomaterial induced coagulation. We investigated the influence of electrical charge and wettability on platelet- and contact activation, the two main actors of blood coagulation, which are often considered as separate mechanisms in biomaterials research. Our results show a dependence of contact activation on acidic surface groups and a correlation of platelet adhesion to surface hydrophobicity. Clot formation resulting from the interplay of blood platelets and contact activation was only found on surfaces combining both acidic and hydrophobic surface groups but not on monolayers displaying extreme hydrophobic/acidic properties. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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19. Functional immobilization of signaling proteins enables control of stem cell fate.
- Author
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Alberti, Kristin, Davey, Ryan E., Onishi, Kento, George, Sophia, Salchert, Katrin, Seib, F. Philipp, Bornhäuser, Martin, Pompe, Tilo, Nagy, Andras, Werner, Carsten, and Zandstra, Peter W.
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EMBRYONIC stem cells ,CELL determination ,LIGANDS (Biochemistry) ,LEUKEMIA inhibitory factor ,MITOGEN-activated protein kinases ,COPOLYMERS ,GENETICS - Abstract
The mode of ligand presentation has a fundamental role in organizing cell fate throughout development. We report a rapid and simple approach for immobilizing signaling ligands to maleic anhydride copolymer thin-film coatings, enabling stable signaling ligand presentation at interfaces at defined concentrations. We demonstrate the utility of this platform technology using leukemia inhibitory factor (LIF) and stem cell factor (SCF). Immobilized LIF supported mouse embryonic stem cell (mESC) pluripotency for at least 2 weeks in the absence of added diffusible LIF. Immobilized LIF activated signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase (MAPK) signaling in a dose-dependent manner. The introduced method allows for the robust investigation of cell fate responses from interface-immobilized ligands. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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20. Electroosmotic flow in microchannels with prismatic elements.
- Author
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Hu, Yandong, Xuan, Xiangchun, Werner, Carsten, and Li, Dongqing
- Abstract
Fundamental understanding of liquid flow through microchannels with 3D prismatic elements is important to the design and operation of lab-on-a-chip devices. In this paper, we studied experimentally and theoretically the electroosmotic flow (EOF) in slit microchannels with rectangular 3D prismatic elements fabricated on the bottom channel wall. The average electroosmotic velocity measured by the current-monitoring technique was found lower than that in a smooth microchannel. This velocity reduction becomes larger in microchannel with larger but less number of the prisms even though the space taken by the prisms are identical. The velocity distribution and streamlines on two typical horizontal planes in the microchannel are measured and visualized by a particle-based technique. These experimental observations are in good agreement with the numerical simulation. The comparison of streamlines near the prisms in the pressure-driven flow with that in the EOF showed that the EOF was more sensitive to the local geometry. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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21. Author Correction: Defined Geldrop Cultures Maintain Neural Precursor Cells.
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Vogler, Steffen, Prokoph, Silvana, Freudenberg, Uwe, Binner, Marcus, Tsurkan, Mikhail, Werner, Carsten, and Kempermann, Gerd
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ERROR correction (Information theory) ,CULTURE media (Biology) - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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22. Electrokinetic microslit experiments to analyse the charge formation at solid/liquid interfaces.
- Author
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Zimmermann, Ralf, Osaki, Toshihisa, Schweiß, Rüdiger, and Werner, Carsten
- Abstract
Electrokinetic effects play an important role in microfluidics and nanofluidics. Although the related phenomena are often utilized to control fluid flow and sample transport in lab-on-a-chip devices, their dependency on the surface charges on the channel walls often remain enigmatic. This is mainly due to the lack of adequate experimental methods to analyse the electrical charging of solid/liquid interfaces of interest. To address this need, an experimental set-up—designated as microslit electrokinetic set-up (MES)—has been recently developed and applied for the investigation of charge formation processes at planar solid/liquid interfaces. The device permits to perform streaming potential and streaming current measurements across a rectangular streaming channel formed by two parallel sample carriers (20×10×3 mm
3 ) at variable distance allowing for the determination of the surface conductivity. Utilizing the MES, charge characteristics can be determined for a wide variety of materials prepared as thin films on top of planar glass substrates. Streaming potential and streaming current data permit to investigate the mechanisms of charge formation while surface conductivity data provide information about mobile charge carriers located in different zones at the interface. The applicability of this advanced experimental approach is demonstrated with examples obtained for surfaces with different levels of complexity: [ABSTRACT FROM AUTHOR]- Published
- 2006
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23. Modulating Extracellular Matrix at Interfaces of Polymeric Materials.
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Werner, Carsten, Pompe, Tilo, and Salchert, Katrin
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BIOMOLECULES , *POLYMERS , *BONE marrow , *IMMUNE system , *EXTRACELLULAR matrix proteins - Abstract
As extracellular matrices (ECM) closely interact with cells in living tissues and, through this, influence essentially any aspect of life engineering of ECMcurrently receives a lot of attention in the advent of regenerative therapies. Artificial matrices based on biopolymers isolated from nature were successfully utilized to prepare various types of cell scaffolds to enhance the integration and performance of engineered tissues. Beyond that, translation of progress in matrix and cell biology into new concepts of materials science permits to further refine the functional characteristics of such reconstituted matrices to direct tissue regeneration processes. The review emphasizes research to modulate the functionality of ECM biopolymers through their combination with synthetic polymeric materials. Two examples referring to our own studies concern (1) the control of vasculogenesis by adjusting the availability of surface bound fibronectin for cell-driven reorganization and; (2) the imitation of the bone marrow niche with respect to the cultural amplification of hematopoietic progenitor cells using collagen I-based assemblies. As a perspective we briefly discuss the design of biohybrid ECM mimics where synthetic and natural polymers are combined on the molecular scale for future use as morphogenetic templates in in vivo tissue engineering applications. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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24. Interfaces to Control Cell-Biomaterial Adhesive Interactions.
- Author
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García, Andrés J. and Werner, Carsten
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CELL communication , *BIOLOGICAL interfaces , *CELL adhesion , *PROTEINS , *BIOMEDICAL materials - Abstract
Cell adhesion to adsorbed proteins and adhesive sequences engineered on surfaces is crucial to cellular and host responses to implanted devices, biological integration of biomaterials and tissue-engineered constructs, and the performance of biosensors, cell-based arrays, and biotechnological cell-culture supports. This review focuses on interfaces controlling cell-adhesive interactions, with particular emphasis on surfaces controlling protein adsorption, biomimetic substrates presenting bioadhesive motifs, and micropatterned surfaces to engineer adhesive areas. These approaches represent promising strategies to engineer cell-material biomolecular interactions in order to elicit specific cellular responses and enhance the biological performance of materials in biomedical and biotechnological applications. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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25. Biopolyesters in Tissue Engineering Applications.
- Author
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Freier, Thomas and Werner, Carsten
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CARDIOVASCULAR system , *CELLULAR mechanics , *BLOOD circulation , *LIGAMENTS , *POLYHYDROXYALKANOATES , *POLY-beta-hydroxybutyrate - Abstract
Tissue engineering is a rapidly growing interdisciplinary field of research focused on the development of vital autologous tissue through the use of a combination of biomaterials, cells, and bioactive molecules, for the purposes of repairing damaged or diseased tissue and organs. Due to their biocompatibility and biodegradability, as well as their broad range of mechanical properties, natural polyesters from the group of polyhydroxyalkanoates (PHAs) have emerged as promising materials for various tissue engineering applications, including cardiovascular system, nerve, bone, and cartilage repair applications. Thus far, the majority of research on medical applications of PHAs refers to poly(3-hydroxybutyrate) and its copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate). In recent years, other PHAs, such as poly(4-hydroxybutyrate) and poly(3-hydroxyoctanoate-co-3-hydroxyhexanoate), have drawn increasing attention as viable materials for biomedical applications. Copolymers of poly(3-hydroxybutyrate) and medium-chain-length hydroxyalkanoates offer the advantage of having elastomeric properties. This is of particular importance for engineering of elastomeric tissue, such as in the cardiovascular system, and for providing mechanical stimuli, such as in cartilage repair. This review will describe the characteristics of promising biopolyesters for tissue engineering, together with strategies that can be used to adjust the material properties to the clinical requirements; examples of potential applications will also be presented. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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26. Self-Assembling Nanopeptides Become a New Type of Biomaterial.
- Author
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Xiaojun Zhao, Shuguang Zhang, and Werner, Carsten
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PEPTIDES ,NANOSTRUCTURED materials ,MEMBRANE proteins ,BIOMEDICAL materials ,MOLECULAR biology - Abstract
Combining physics, engineering, chemistry and biology, we can now design, synthesize and fabricate biological nano-materials at the molecular scale using self-assembling peptide systems. These peptides have been used for fabrication of nanomaterials including nanofibers, nanotubes and vesicles, nanometer-thick surface coating and nanowires. Some of these peptides are used for stabilizing membrane proteins, and others provide a more permissive environment for cell growth, repair of tissues in regenerative medicine, and delivering genes and drugs. Self-assembling peptides are also useful for fabricating a wide spectrum of exquisitely fine architectures, new materials and nanodevices for nanobiotechnology and a variety of engineering. These systems lie at the interface between molecular biology, chemistry, materials science and engineering. Molecular self-assembly will harness nature's enormous power to benefit other disciplines and society. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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27. Hydrogels for Musculoskeletal Tissue Engineering.
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Varghese, Shyni, Elisseeff, Jennifer H., and Werner, Carsten
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EMBRYONIC stem cells ,HYDROGELS ,THERAPEUTICS ,EXTRACELLULAR matrix ,TISSUE engineering - Abstract
The advancements in scaffold-supported cell therapy for musculoskeletal tissue engineering have been truly dramatic in the last couple of decades. This article briefly reviews the role of natural and synthetic hydrogels in the above field. The most appealing feature of hydrogels as scaffolding materials is their structural similarity to extracellular matrix (ECM) and their easy processability under mild conditions. The primary developments in this field comprise formulation of biomimetic hydrogels incorporating specific biochemical and biophysical cues so as to mimic the natural ECM, design strategies for cell-mediated degradation of scaffolds, techniques for achieving in situ gelation which allow minimally invasive administration of cell-laden hydrogels into the defect site, scaffold-mediated differentiation of adult and embryonic stem cells, and finally, the integration of tissue-engineered “biological implants” with the native tissue. All these developments in regenerative medicine are reviewed in this article. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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28. Polymeric Systems for Bioinspired Delivery of Angiogenic Molecules.
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Fischbach, Claudia, Mooney, David J., and Werner, Carsten
- Subjects
CYTOKINES ,GROWTH factors ,PEPTIDES ,NERVOUS system regeneration ,NEOVASCULARIZATION - Abstract
Growth factors are increasingly utilized to promote regeneration of lost or compromised tissues and organs. However, current strategies applying growth factors by bolus injections typically fail to restore tissue functions. Delivery from polymeric systems may overcome this limitation by supplying growth factors in a well-controlled, localized, and sustained manner to the defect site. Traditional polymeric delivery vehicles have been developed based on physicochemical design variables; however, it has now become clear that the appropriate mimicry of certain biologic signaling events may be necessary to achieve full function from the delivered growth factors. Because of its central importance in the development and regeneration of various tissues (e.g., blood vessels, bone, and nerves) bioinspired VEGF supply may be particularly useful to successfully restore tissue functions. Following a brief overview of VEGF's biology, design attributes for polymeric systems for VEGF delivery will be discussed, and subsequently illustrated in the context of three specific applications: therapeutic angiogenesis, bone regeneration, and nerve regeneration. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
29. Electrokinetically controlled concentration gradients in micro-chambers in microfluidic systems.
- Author
-
Hu, Yandong, Lee, Jacky, Werner, Carsten, and Li, Dongqing
- Abstract
Concentration gradient in a chamber appended to a microchannel is important to cell-movement control and to the concentration-gradient based assays on Lab-on-a-Chip devises. In this paper, the effects on the concentration field of the asymmetrical injection, the Peclet number, the mobility ratio of electrophoresis to electroosmosis, the chamber’s downstream position, and the chamber’s geometry parameters are investigated. The most sensitive parameter is the asymmetrical injection, which can increase the concentration gradient twice as large as that in the symmetrical injection. Additionally, use of heterogeneous surface patches is a very effective way to enhance the concentration gradient generated in the chamber. Furthermore, the influence of a fixed cell-sized particle on the concentration gradient in the chamber and around the particle is examined as an example. The existence of the particle decreases the concentration difference between the front and the back of the particle. Finally, experimental visualization of the concentration fields was conducted, and good agreements were found between the numerical simulation results and the experimental results of the concentration fields generated in a micro-chamber with/without a particle and with/without a heterogeneous patch. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
30. Fibronectin fibril pattern displays the force balance of cell–matrix adhesion.
- Author
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Pompe, Tilo, Keller, Kristin, Mitdank, Claudia, and Werner, Carsten
- Subjects
FIBRONECTINS ,BLOOD proteins ,POLYMERS ,QUANTITATIVE research ,ADSORPTION (Chemistry) - Abstract
Formation of fibrillar patterns of fibronectin on polymer substrates with gradated physicochemical surface properties was analysed during early stages of endothelial cell adhesion. Fibronectin was pre-adsorbed onto three maleic anhydride copolymer thin films with distinct differences in the protein adsorption strength as verified by heteroexchange experiments. The evolved micrometer scale fibrillar patterns of fibronectin on the compared polymer surfaces were characterized after 50 min of cellular reorganization by an auto-correlation analysis using fluorescence microscopy data. Statistical analysis revealed a decrease of the typical spacings of the fibronectin fibrils from 2.6 to 1.8 μm with decreasing fibronectin adsorption strength to the substrate. Size and density of focal adhesions correlated with this dependence of the fibronectin fibril pattern. From these data a model was developed relating the fibronectin fibril pattern to the fibronectin-substrate adsorption strength through the cytoskeletal force regulation mechanism of the cell. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
31. Polymere Biomaterialien als zelluläre Mikromilieus.
- Author
-
Pompe, Tilo, Prewitz, Marina, and Werner, Carsten
- Abstract
Polymeric biomaterials can be instrumental for expanding and differentiating stem and progenitor cells in culture. Key to success of these approaches is the defined modulation of biomolecular and physical signals governing cellular microenvironments. Current concepts for effective stem cell culture carriers rely on cell-secreted decellularized matrices, reconstituted assemblies of biopolymers of extracellular matrices and on biohybrid or fully synthetic polymer hydrogels with bioactive units. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
32. Matrix-mediated modulation of neuron identity.
- Author
-
Werner, Carsten
- Published
- 2018
- Full Text
- View/download PDF
33. Fabrication of multifunctional titanium surfaces by producing hierarchical surface patterns using laser based ablation methods.
- Author
-
Zwahr, Christoph, Helbig, Ralf, Werner, Carsten, and Lasagni, Andrés Fabián
- Abstract
Textured implant surfaces with micrometer and sub-micrometer features can improve contact properties like cell adhesion and bacteria repellency. A critical point of these surfaces is their mechanical stability during implantation. Therefore, strategies capable to provide both biocompatibility for an improved implant healing and resistance to wear for protecting the functional surface are required. In this work, laser-based fabrication methods have been used to produce hierarchical patterns on titanium surfaces. Using Direct Laser Writing with a nanosecond pulsed laser, crater-like structures with a separation distance of 50 µm are produced on unpolished titanium surfaces. Directly on this texture, a hole-like pattern with 5 µm spatial period is generated using Direct Laser Interference Patterning with picosecond pulses. While the smaller features should reduce the bacterial adhesion, the larger geometry was designed to protect the smaller features from wear. On the multifunctional surface, the adherence of E. Coli bacteria is reduced by 30% compared to the untreated reference. In addition, wear test performed on the multiple-scale patterns demonstrated the possibility to protect the smaller features by the larger craters. Also, the influence of the laser treatment on the growth of a titanium oxide layer was evaluated using Energy Dispersive X-Ray Spectroscopy analysis. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
34. Cryogel-supported stem cell factory for customized sustained release of bispecific antibodies for cancer immunotherapy.
- Author
-
Aliperta, Roberta, Welzel, Petra B., Bergmann, Ralf, Freudenberg, Uwe, Berndt, Nicole, Feldmann, Anja, Arndt, Claudia, Koristka, Stefanie, Stanzione, Marcello, Cartellieri, Marc, Ehninger, Armin, Ehninger, Gerhard, Werner, Carsten, Pietzsch, Jens, Steinbach, Jörg, Bornhäuser, Martin, and Bachmann, Michael P.
- Abstract
Combining stem cells with biomaterial scaffolds provides a promising strategy for the development of drug delivery systems. Here we propose an innovative immunotherapeutic organoid by housing human mesenchymal stromal cells (MSCs), gene-modified for the secretion of an anti-CD33-anti-CD3 bispecific antibody (bsAb), in a small biocompatible star-shaped poly(ethylene glycol)-heparin cryogel scaffold as a transplantable and low invasive therapeutic machinery for the treatment of acute myeloid leukemia (AML). The macroporous biohybrid cryogel platform displays effectiveness in supporting proliferation and survival of bsAb-releasing-MSCs overtime in vitro and in vivo, avoiding cell loss and ensuring a constant release of sustained and detectable levels of bsAb capable of triggering T-cell-mediated anti-tumor responses and a rapid regression of CD33
+ AML blasts. This therapeutic device results as a promising and safe alternative to the continuous administration of short-lived immunoagents and paves the way for effective bsAb-based therapeutic strategies for future tumor treatments. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
35. Distinguishing autocrine and paracrine signals in hematopoietic stem cell culture using a biofunctional microcavity platform.
- Author
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Müller, Eike, Wang, Weijia, Qiao, Wenlian, Bornhäuser, Martin, Zandstra, Peter W., Werner, Carsten, and Pompe, Tilo
- Published
- 2016
- Full Text
- View/download PDF
36. Magnetically Controllable Polymer Nanotubes from a Cyclized Crosslinker for Site-Specific Delivery of Doxorubicin.
- Author
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Newland, Ben, Leupelt, Daniel, Zheng, Yu, Thomas, Laurent S. V., Werner, Carsten, Steinhart, Martin, and Wang, Wenxin
- Published
- 2015
- Full Text
- View/download PDF
37. Phenotypic, Morphological and Adhesive Differences of Human Hematopoietic Progenitor Cells Cultured on Murine versus Human Mesenchymal Stromal Cells.
- Author
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Reichert, Doreen, Friedrichs, Jens, Ritter, Steffi, Käubler, Theresa, Werner, Carsten, Bornhäuser, Martin, and Corbeil, Denis
- Subjects
HEMATOPOIESIS ,PROGENITOR cells ,BLOOD ,STROMAL cells ,ATOMIC force microscopy ,CADHERINS - Abstract
Xenogenic transplantation models have been developed to study human hematopoiesis in immunocompromised murine recipients. They still have limitations and therefore it is important to delineate all players within the bone marrow that could account for species-specific differences. Here, we evaluated the proliferative capacity, morphological and physical characteristics of human CD34
+ hematopoietic stem and progenitor cells (HSPCs) after co-culture on murine or human bone marrow-derived mesenchymal stromal cells (MSCs). After seven days, human CD34+ CD133- HSPCs expanded to similar extents on both feeder layers while cellular subsets comprising primitive CD34+ CD133+ and CD133+ CD34- phenotypes are reduced fivefold on murine MSCs. The number of migrating HSPCs was also reduced on murine cells suggesting that MSC adhesion influences cellular polarization of HSPC. We used atomic force microscopy-based single-cell force spectroscopy to quantify their adhesive interactions. We found threefold higher detachment forces of human HSPCs from murine MSCs compared to human ones. This difference is related to the N-cadherin expression level on murine MSCs since its knockdown abolished their differential adhesion properties with human HSPCs. Our observations highlight phenotypic, morphological and adhesive differences of human HSPCs when cultured on murine or human MSCs, which raise some caution in data interpretation when xenogenic transplantation models are used. [ABSTRACT FROM AUTHOR]- Published
- 2015
- Full Text
- View/download PDF
38. Bio-responsive polymer hydrogels homeostatically regulate blood coagulation.
- Author
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Maitz, Manfred F., Freudenberg, Uwe, Tsurkan, Mikhail V., Fischer, Marion, Beyrich, Theresa, and Werner, Carsten
- Published
- 2013
- Full Text
- View/download PDF
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