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Berlin Brandenburg

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  • 1
    In: Neuro-Oncology, 2018, Vol. 20(suppl2), pp.i131-i131
    Description: Many immunotherapies act by enhancing the ability of T cells to kill tumor cells. But T cell killing depends on recognition of antigens presented by Class I MHC (MHC-I) on the tumor cell surface; if a tumor lacks MHC-I, it cannot be recognized by T cells. To study the efficacy of immunotherapy for Group 3 medulloblastoma, we have used mouse models driven by overexpression of Myc and dominant negative p53 (“MP tumors”), or by overexpression of Myc and Gfi1 (“MG tumors”). While both tumors grow in immunodeficient mice, only MP tumors grow in immunocompetent mice. To understand this difference, we analyzed expression of immunoregulatory molecules, and found that MP tumors completely lack surface MHC-I. Mechanistically, this is because two key proteins required for MHC-I trafficking - TAP1 and ERAP1 - are targets of p53; since MP tumors lack functional p53, they also lack TAP1 and ERAP1, and surface MHC-I. These studies suggest that p53 plays a critical role in determining immunogenicity, and that p53-mutant tumors are resistant to immune attack. To overcome this resistance, we treated tumor cells with agents that regulate MHC-1. We found that low doses of tumor necrosis factor alpha (TNF alpha) can rescue expression of ERAP, TAP and MHC-I on MP tumor cells. In vivo, TNF alpha prolongs survival of tumor-bearing mice, and markedly augments the efficacy of immune checkpoint inhibitors. These results raise the possibility that TNF alpha could be used prior to immunotherapy to render tumors more sensitive to T cell attack.
    Keywords: Medicine;
    ISSN: 1522-8517
    E-ISSN: 1523-5866
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  • 2
    Language: English
    In: Polymer Degradation and Stability, Feb, 2014, Vol.100, p.21(8)
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.polymdegradstab.2013.12.037 Byline: J.-P. Garancher, A. Fernyhough Abstract: In this study, semi-crystalline PLA was foamed using CO.sub.2 as the blowing agent. The samples were foamed under various conditions of CO.sub.2 concentration, foaming temperature and foaming time. The samples were characterised by differential scanning calorimetry (DSC) and wide-angle X-ray scattering (WAXS). Their dimensional stability was also assessed at 70 [degrees]C. Results showed that dimensional stability was strongly related to the expansion ratio of the foam and the strain-induced crystallinity developed during foaming. Shrinkage at 70 [degrees]C virtually disappeared with crystallinity above 40% (expansion ratio of approximately 40), in accordance with published data. Author Affiliation: (a) Biopolymer Network Limited/Scion, Te Papa Tipu Innovation Park, 49 Sala Street, Rotorua 3010, New Zealand (b) Department of Mechanical Engineering, The University of Auckland, Auckland Mail Centre 1142, New Zealand Article History: Received 29 October 2013; Revised 16 December 2013; Accepted 26 December 2013
    Keywords: Biopolymers
    ISSN: 0141-3910
    Source: Cengage Learning, Inc.
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  • 3
    Language: English
    In: Polymer Degradation and Stability, February 2014, Vol.100, pp.21-28
    Description: In this study, semi-crystalline PLA was foamed using CO as the blowing agent. The samples were foamed under various conditions of CO concentration, foaming temperature and foaming time. The samples were characterised by differential scanning calorimetry (DSC) and wide-angle X-ray scattering (WAXS). Their dimensional stability was also assessed at 70 °C. Results showed that dimensional stability was strongly related to the expansion ratio of the foam and the strain-induced crystallinity developed during foaming. Shrinkage at 70 °C virtually disappeared with crystallinity above 40% (expansion ratio of approximately 40), in accordance with published data.
    Keywords: Polylactic Acid ; Foaming ; Crystallinity ; Dimensional Stability ; Engineering ; Chemistry
    ISSN: 0141-3910
    E-ISSN: 1873-2321
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  • 4
    Language: English
    In: Journal of Cellular Plastics, September 2012, Vol.48(5), pp.387-397
    Description: The use of carbon dioxide for the production of polylactic acid foams has been increasingly studied recently. Much of the reported work has used supercritical carbon dioxide as a processing or foaming medium. However, a new foaming process which uses sub-critical liquid carbon dioxide conditions has been developed by the Biopolymer Network Limited. It is generally recognised that processing crystalline thermoplastics, including crystalline polylactic acid polymers, into foam products using carbon dioxide is difficult due to lower solubility of liquid carbon dioxide in polymers and the increased polymer rigidity hindering the expansion of the polymer matrix. However, fundamental studies, and the associated knowledge of the foaming mechanisms at play, have allowed some new approaches to be developed within sub-critical carbon dioxide conditions which overcome many of these difficulties in polylactic acid foams. In this study, several commercially available grades of polylactic acid, ranging from crystalline to amorphous, were processed using carbon dioxide via the Biopolymer Network Limited process (sub-critical carbon dioxide). By adequately adjusting the process parameters, different crystalline grades were successfully foamed to low density. The resulting foams exhibited low to high levels of crystallinity, and consequently displayed varying thermal or physical properties. Cellular structures were observed by scanning electron microscopy. Crystallinity and thermal behaviour of the foamed samples were characterised using differential scanning calorimetry. Mechanical properties and dimensional stability were also investigated. It was shown that the selection of polylactic acid feedstock, and its associated processing conditions, had a significant impact on the final quality and properties of the foams.
    Keywords: Polylactic Acid ; Carbon Dioxide ; Crystallinity ; Foaming ; Dimensional Stability ; Engineering
    ISSN: 0021-955X
    E-ISSN: 1530-7999
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  • 5
    Language: French
    Description: MAF (MusculoAponeurotic Fibrosarcoma) transcription factors are involved in terminal differentiation during normal development, and also in oncogenesis. A functional uncoupling is observed between these two functional activities. Indeed, target genes involved in cancer or terminal differentiation...
    Keywords: Life Sciences ; Cancer ; Maf ; Nrl ; Apoptosis ; Medulloblastoma ; Transcription Factor ; Anti-Apoptotic Protein Bcl-XL ; Apoptose ; Médulloblastome ; Facteur de Transcription ; Protéine Anti-Apoptotique Bcl-XL
    Source: Hyper Article en Ligne (CCSd)
    Source: Hyper Article en Ligne Open Access (CCSd)
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  • 6
    In: Blood Cancer Journal, 2014, Vol.4(1), p.e175
    Description: Multiple myeloma (MM) is an incurable haematological malignancy characterised by the proliferation of mature antibody-secreting plasma B cells in the bone marrow. MM can arise from initiating translocations, of which the musculoaponeurotic fibrosarcoma (MAF) family is implicated in ∼5%. MMs bearing Maf translocations are of poor prognosis. These translocations are associated with elevated Maf expression, including c-MAF, MAFB and MAFA, and with t(14;16) and t(14;20) translocations, involving c-MAF and MAFB, respectively. c-MAF is also overexpressed in MM through MEK/ERK activation, bringing the number of MMs driven by the deregulation of a Maf gene close to 50%. Here we demonstrate that MAFB and c-MAF are phosphorylated by the Ser/Thr kinase GSK3 in human MM cell lines. We show that LiCl-induced GSK3 inhibition targets these phosphorylations and specifically decreases proliferation and colony formation of Maf-expressing MM cell lines. Interestingly, bortezomib induced stabilisation of Maf phosphorylation, an observation that could explain, at least partially, the low efficacy of bortezomib for patients carrying Maf translocations. Thus, GSK3 inhibition could represent a new therapeutic approach for these patients.
    Keywords: Medicine;
    ISSN: 20445385
    E-ISSN: 20445385
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  • 7
    Language: English
    In: Journal of Cellular Plastics, September 2017, Vol.53(5), pp.513-523
    Description: Polylactic acid films were foamed through a solid-state process using liquid carbon dioxide as a physical blowing agent. The foamed films were stretched to understand the effect of cell strut alignment on elastic modulus and yield stress normalised with density. Through stretching, cell strut alignment was achieved and verified with scanning electron microscopy. Aligning the cell struts improved the elastic modulus by a factor of 4 and the yield stress by a factor of 5 while decreasing the strain percentage at break. Aligned cell struts axially strain during tensile deformation which requires more force than unaligned cell struts which bend at initial deformations. The flexographic printability and surface topography of the foamed polylactic acid films was also analysed. The temperature used to impregnate carbon dioxide into the polylactic acid films was varied to understand its significance on printability and surface topography. Samples impregnated at ambient temperatures had smooth surface topography and a shiny lustre and good printability, whereas, samples impregnated at sub-ambient temperatures had a dull and rough texture and poor printability. Also, the carbon dioxide content had an effect on the surface topography and printability.
    Keywords: Polylactic Acid ; Pla ; Cell Structure ; Reinforcement ; Cell Alignment ; Expansion Ratio ; Foam Density ; Films ; Elastic Modulus ; Strength ; Engineering
    ISSN: 0021-955X
    E-ISSN: 1530-7999
    Source: Sage Journals (Sage Publications)
    Source: SAGE STM (Sage Publications)
    Source: SAGE Materials Science and Engineering (Sage Publications)
    Source: SAGE Communication and Media Studies (Sage Publications)
    Source: SAGE Journals (Sage Publications)
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  • 8
    Language: English
    In: Journal of Cellular Plastics, May 2011, Vol.47(3), pp.233-243
    Description: A commercially viable process to manufacture low-density expanded polylactic acid (E-PLA) products with environmental-friendly blowing agents such as carbon dioxide has been developed. The resulting material is a sustainable alternative to expanded polystyrene (EPS). The E-PLA has thermal conductivity and mechanical properties comparable to EPS and can be used in many similar applications. The process involves impregnation of PLA beads with carbon dioxide and fusing with heat, including steam heating. Gel permeation chromatography indicated that the PLA polymer molecular weight was not degraded by the foaming or steam heating process. Visual characterization showed that under some circumstances, PLA precursor beads exhibited voids, which disappeared during CO2 impregnation indicating some form of rearrangement or realignment of the polymer morphology or structure. Due to the effect of CO2 on the glass transition temperature of the PLA, a linear reduction of 5.5°C per wt% of absorbed CO2 was observed.
    Keywords: Polylactic Acid ; Co2 ; Foaming ; Expanded Polystyrene ; Mechanical Properties ; Engineering
    ISSN: 0021-955X
    E-ISSN: 1530-7999
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  • 9
    Language: English
    In: Annual review of neuroscience, 08 July 2018, Vol.41, pp.207-232
    Description: Brain tumors are the leading cause of cancer-related death in children, and medulloblastoma (MB) is the most common malignant pediatric brain tumor. Advances in surgery, radiation, and chemotherapy have improved the survival of MB patients. But despite these advances, 25-30% of patients still die from the disease, and survivors suffer severe long-term side effects from the aggressive therapies they receive. Although MB is often considered a single disease, molecular profiling has revealed a significant degree of heterogeneity, and there is a growing consensus that MB consists of multiple subgroups with distinct driver mutations, cells of origin, and prognosis. Here, we review recent progress in MB research, with a focus on the genes and pathways that drive tumorigenesis, the animal models that have been developed to study tumor biology, and the advances in conventional and targeted therapy.
    Keywords: Animal Models ; Medulloblastoma ; Molecular Subgroups ; Targeted Therapy
    ISSN: 0147006X
    E-ISSN: 1545-4126
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  • 10
    In: Macromolecular Symposia, February 2014, Vol.336(1), pp.53-60
    Description: Byline: Leonid Bulavin, Jean-Michel Guenet, Jean-Philippe Garancher, Alan Fernyhough, Nigel Kirby Summary In this work, the effect of low temperature (approximately -50[degrees]C to -20[degrees]C) liquid CO.sub.2 treatment on the morphology of semi-crystalline polylactic acid (PLA) was studied. This investigation was carried out by means of differential scanning calorimetry (DSC) and Synchrotron wide-angle X-ray scattering (WAXS). Under the experimental conditions used, DSC and WAXS revealed the existence of two main crystalline structures, namely the [alpha]" crystal structure and a mesomorphic structure. The [alpha]" crystals were found to be preferentially formed at higher temperature, whereas only the mesomorphic structure was detected at lower temperature. The transition between these two morphologies was observed at around -35[degrees]C.
    Keywords: Carbon Dioxide ; Crystallinity ; Plasticisation ; Polylactic Acid
    ISSN: 1022-1360
    E-ISSN: 1521-3900
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