12 research outputs found

    Qualitaetssicherung in der Einzel- und Kleinserienfertigung: Sicherung der aktuellen Fertigungsqualitaet unter Beruecksichtigung der Wirtschaftlichkeit

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    Available from Bibliothek des Instituts fuer Weltwirtschaft, ZBW, Duesternbrook Weg 120, D-24105 Kiel A 199987 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

    Site-directed Nanotherapeutics to Abrogate RRMS and Promote Remyelination Repair (Rev)

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    Multiple sclerosis (MS) is an inflammatory-mediated demyelinating disease of the human CNS. The clinical disease course is variable and starts with reversible episodes of neurological disability (remitting relapsing (RR-MS) stage). This transforms into a disease of continuous and irreversible neurological decline. Phosphodiesterase (PDE) inhibitors can prevent injury-induced reductions of cyclic AMP as well as facilitate tissue protection, anatomical repair, and functional recovery. We hypothesized that PDE inhibitor containing nanoparticles (NP), surface modified with peptides that recognize proteins extravasated at sites of vascular disruption (clotting factors, ECM), would accumulate at regions of CNS demyelination, reducing tissue injury and promote remyelination repair at very low drug doses. Initial work for this award focused on the characterization of polymeric (poly(ethylene glycol-b- -caprolactone)) NP size, fluorescent dye or drug incorporation and their functionalization with surface peptides for site-directed targeting. It was demonstrated that peptides (i.e. NQEQVSP, DPEAAE and NIDPNAV) can be conjugated to the aminated PEG-b-PCL and that PEG-b-PCL NPs can readily encapsulate fluorescent dyes (DiI, DiO) and PDE inhibitors (Rolipram and BRL-50481). Whereas the loading efficiency of the fluorescent dyes was high (45% and 80% respectively), drug loading was low in comparison, but could be improved by using more polymer. The drugs were released slowly over three weeks at 370C, after which the NPs started to aggregate/disassemble. Functionalization of the NP with peptides improved adherence in fibrin gels (blood clots) or onto tissue sections of injured spinal cord. The original document contains color images

    Abkehr vom Washington Concensus? Die wirtschaftspolitische Strategie der Weltbank zur Armutsbekaempfung

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    'In autumn 1999 the World Bank announced a renewal of its approaches and practices in development countries as well as the end of its structural adjustment politics based on the Washington consensus. But is this announced reorientation of the development strategy actually realized? This report analyses the World Bank's Poverty Reduction Strategy which is presented in the World Development Report 2000/2001. It seeks to answer the question of whether or not the Poverty Reduction Strategy is just old wine in new bottles. It follows the question, in which way the new strategy of the World Bank takes into account the criticisms of the theoretical basis of the Washington Consensus - which led to the so called Post-Washington Consensus. Furthermore it focuses on the issue, whether the integration of economic policy and measures of poverty reduction is successful. The study shows that there are some new elements adopted by the Poverty Reduction Strategy, while there is no renunciation of the Washington Consensus.' (author's abstract)'Im Herbst 1999 hat die Weltbank eine Abkehr von ihrer neoliberalen Strukturanpassungspolitik und dem Washington Consensus verkuendet. Doch wurde diese angekuendigte Neuausrichtung der entwicklungspolitischen Strategie tatsaechlich realisiert? Dieser Report untersucht, ob es sich bei dem von der Weltbank im Weltentwicklungsbericht 2000/2001 vorgestellten neuen Ansatz zur Armutsbekaempfung tatsaechlich um eine Neuausrichtung in der Entwicklungsstrategie der Weltbank oder nur um eine Fortfuehrung der alten Strategie unter neuem Namen handelt. Dabei geht er zum einen der Frage nach, in welcher Weise die Kritik an der wirtschaftstheoretischen Grundlage der Weltbankpolitik - die zum Post-Washington Consensus gefuehrt hat - in der neuen entwicklungspolitischen Strategie der Weltbank Beachtung findet. Zum anderen, ob es in der neuen entwicklungspolitischen Konzeption gelungen ist, wirtschaftspolitische Reformen und Massnahmen zur Armutsreduzierung miteinander zu verbinden und damit das Nebeneinander von 'harter' Wirtschaftspolitik und 'weicher' Armutsbekaempfung zu ueberwinden. Dabei stellt sich heraus, dass durchaus schon Ansaetze einer Neuausrichtung in der Armutsbekaempfungsstrategie der Weltbank zu erkennen sind, jedoch noch nicht von einer Abkehr vom 'alten' Konzept des Washington Consensus gesprochen werden kann.' (Autorenreferat)SIGLEAvailable from Universitaet Duisburg-Essen Campus Duisburg, FB Gesellschaftswissenschaften, Institut fuer Entwicklung und Frieden -INEF-, Duisburg (DE) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

    A bioengineered 3D ovarian cancer model for the assessment of peptidase-mediated enhancement of spheroid growth and intraperitoneal spread

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    Cancer-associated proteases promote peritoneal dissemination and chemoresistance in malignant progression. In this study, kallikrein-related peptidases 4, 5, 6, and 7 (KLK4-7)-cotransfected OV-MZ-6 ovarian cancer cells were embedded in a bioengineered three-dimensional (3D) microenvironment that contains RGD motifs for integrin engagement to analyze their spheroid growth and survival after chemotreatment. KLK4-7-cotransfected cells formed larger spheroids and proliferated more than controls in 3D, particularly within RGD-functionalized matrices, which was reduced upon integrin inhibition. In contrast, KLK4-7-expressing cell monolayers proliferated less than controls, emphasizing the relevance of the 3D microenvironment and integrin engagement. In a spheroid-based animal model, KLK4-7-overexpression induced tumor growth after 4 weeks and intraperitoneal spread after 8 weeks. Upon paclitaxel administration, KLK4-7-expressing tumors declined in size by 91% (controls: 87%) and showed 90% less metastatic outgrowth (controls: 33%, P<0.001). KLK4-7-expressing spheroids showed 53% survival upon paclitaxel treatment (controls: 51%), accompanied by enhanced chemoresistance-related factors, and their survival was further reduced by combination treatment of paclitaxel with KLK4/5/7 (22%, P=0.007) or MAPK (6%, P=0.006) inhibition. The concomitant presence of KLK4-7 in ovarian cancer cells together with integrin activation drives spheroid formation and proliferation. Combinatorial approaches of paclitaxel and KLK/MAPK inhibition may be more efficient for late-stage disease than chemotherapeutics alone as these inhibitory regimens reduced cancer spheroid growth to a greater extent than paclitaxel alone

    A tissue-engineered humanized xenograft model of human breast cancer metastasis to bone

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    The skeleton is a preferred homing site for breast cancer metastasis. To date, treatment options for patients with bone metastases are mostly palliative and the disease is still incurable. Indeed, key mechanisms involved in breast cancer osteotropism are still only partially understood due to the lack of suitable animal models to mimic metastasis of human tumor cells to a human bone microenvironment. In the presented study, we investigate the use of a human tissue-engineered bone construct to develop a humanized xenograft model of breast cancer-induced bone metastasis in a murine host. Primary human osteoblastic cell-seeded melt electrospun scaffolds in combination with recombinant human bone morphogenetic protein 7 were implanted subcutaneously in non-obese diabetic/severe combined immunodeficient mice. The tissue-engineered constructs led to the formation of a morphologically intact 'organ' bone incorporating a high amount of mineralized tissue, live osteocytes and bone marrow spaces. The newly formed bone was largely humanized, as indicated by the incorporation of human bone cells and human-derived matrix proteins. After intracardiac injection, the dissemination of luciferase-expressing human breast cancer cell lines to the humanized bone ossicles was detected by bioluminescent imaging. Histological analysis revealed the presence of metastases with clear osteolysis in the newly formed bone. Thus, human tissue-engineered bone constructs can be applied efficiently as a target tissue for human breast cancer cells injected into the blood circulation and replicate the osteolytic phenotype associated with breast cancer-induced bone lesions. In conclusion, we have developed an appropriate model for investigation of species-specific mechanisms of human breast cancer-related bone metastasis in vivo

    A 3d culture model of innervated human skeletal muscle enables studies of the adult neuromuscular junction

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    Two-dimensional (2D) human skeletal muscle fiber cultures are ill-equipped to support the contractile properties of maturing muscle fibers. This limits their application to the study of adult human neuromuscular junction (NMJ) development, a process requiring maturation of muscle fibers in the presence of motor neuron endplates. Here we describe a three-dimensional (3D) co- culture method whereby human muscle progenitors mixed with human pluripotent stem cell- derived motor neurons self-organize to form functional NMJ connections. Functional connectivity between motor neuron endplates and muscle fibers is confirmed with calcium imaging and electrophysiological recordings. Notably, we only observed epsilon acetylcholine receptor subunit protein upregulation and activity in 3D co-cultures. Further, 3D co-culture treatments with myasthenia gravis patient sera shows the ease of studying human disease with the system. Hence, this work offers a simple method to model and evaluate adult human NMJ de novo development or disease in culture

    A 3D culture model of innervated human skeletal muscle enables studies of the adult neuromuscular junction

    No full text
    International audienceTwo-dimensional (2D) human skeletal muscle fiber cultures are ill-equipped to support the contractile properties of maturing muscle fibers. This limits their application to the study of adult human neuromuscular junction (NMJ) development, a process requiring maturation of muscle fibers in the presence of motor neuron endplates. Here we describe a three-dimensional (3D) co-culture method whereby human muscle progenitors mixed with human pluripotent stem cell-derived motor neurons self-organize to form functional NMJ connections. Functional connectivity between motor neuron endplates and muscle fibers is confirmed with calcium imaging and electrophysiological recordings. Notably, we only observed epsilon acetylcholine receptor subunit protein upregulation and activity in 3D co-cultures. Further, 3D co-culture treatments with myasthenia gravis patient sera shows the ease of studying human disease with the system. Hence, this work offers a simple method to model and evaluate adult human NMJ de novo development or disease in culture
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