312 research outputs found

    Controlled Carbon Dioxide Terpolymerizations to Deliver Toughened yet Recyclable Thermoplastics

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    Using CO2 polycarbonates as engineering thermoplastics has been limited by their mechanical performances, particularly their brittleness. Poly­(cyclohexene carbonate) (PCHC) has a high tensile strength (40 MPa) but is very brittle (elongation at break 250 °C). All the polymers are amorphous with a single, high glass transition temperature (96 < T g < 108 °C). The polymer entanglement molar masses, determined using dynamic mechanical analyses, range from 4 < M e < 23 kg mol–1 depending on the polymer composition (PCHC:PCPC). These polymers show superior mechanical performance to PCHC; specifically the lead material (PCHC0.28-grad-PCPC0.72) shows 25% greater tensile strength and 160% higher tensile toughness. These new plastics are recycled, using cycles of reprocessing by compression molding (150 °C, 1.2 ton m–2, 60 min), four times without any loss in mechanical properties. They are also efficiently chemically recycled to selectively yield the two epoxide monomers, CHO and CPO, as well as carbon dioxide, with high activity (TOF = 270–1653 h–1, 140 °C, 120 min). The isolated recycled monomers are repolymerized to form thermoplastic showing the same material properties. The findings highlight the benefits of the terpolymer strategy to deliver thermoplastics combining the beneficial low entanglement molar mass, high glass transition temperatures, and tensile strengths; PCHC properties are significantly improved by incorporating small quantities (23 mol %) of cyclopentene carbonate linkages. The general strategy of designing terpolymers to include chain segments of low entanglement molar mass may help to toughen other brittle and renewably sourced plastics

    Buschke-Ollendorff Syndrome Associated with Elevated Elastin Production by Affected Skin Fibroblasts in Culture

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    Buschke-Ollendorff syndrome (BOS; McKusick 16670) is an autosomal dominant connective-tissue disorder characterized by uneven osseous formation in bone (osteopoikilosis) and fibrous skin papules (dermatofibrosis lenticularis disseminata). We describe two patients in whom BOS occurred in an autosomal dominant inheritance pattern. The connective tissue of the skin lesions showed both collagen and elastin abnormalities by electron microscopy. Cultured fibroblasts from both patients produced 2–8 times more tropoelastin than normal skin fibroblasts in the presence of 10% calf serum. Involved skin flbroblasts of one patient produced up to eight times normal levels, whereas apparently uninvolved skin was also elevated more than threefold. In a second patient, whose involvement was nearly complete, elastin production was high in involved areas and less so in completely involved skin. Transforming growth factor-β1 (TGFβ1), a powerful stimulus for elastin production, brought about similar relative increases in normal and BOS strains. Basic fibroblast growth factor, an antagonist of TGFβ1-stimulated elastin production, was able to reduce elastin production in basal and TGFβ1 stimulated BOS strains. Elastin mRNA levels were elevated in all patient strains, suggesting that Buschke-Ollendorff syndrome may result, at least in part, from abnormal regulation of extracellular matrix metabolism that leads to increased steady-state levels of elastin mRNA and elastin accumulation in the dermis

    Zika virus tropism and interactions in myelinating neural cell cultures: CNS cells and myelin are preferentially affected

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    The recent global outbreak of Zika virus (ZIKV) infection has been linked to severe neurological disorders affecting the peripheral and central nervous systems (PNS and CNS, respectively). The pathobiology underlying these diverse clinical phenotypes are the subject of intense research; however, even the principal neural cell types vulnerable to productive Zika infection remain poorly characterised. Here we used CNS and PNS myelinating cultures from wild type and Ifnar1 knockout mice to examine neuronal and glial tropism and short-term consequences of direct infection with a Brazilian variant of ZIKV. Cell cultures were infected pre- or post-myelination for various intervals, then stained with cell-type and ZIKV-specific antibodies. In bypassing systemic immunity using ex vivo culture, and the type I interferon response in Ifnar1 deficient cells, we were able to evaluate the intrinsic infectivity of neural cells. Through systematic quantification of ZIKV infected cells in myelinating cultures, we found that ZIKV infection is enhanced in the absence of the type I interferon responses and that CNS cells are considerably more susceptible to infection than PNS cells. In particular, we demonstrate that CNS axons and myelinating oligodendrocytes are especially vulnerable to injury. These results have implications for understanding the pathobiology of neurological symptoms associated with ZIKV infection. Furthermore, we provide a quantifiable ex vivo infection model that can be used for fundamental and therapeutic studies on viral neuroinvasion and its consequences

    3-dimensional patient-derived lung cancer assays reveal resistance to standards-of-care promoted by stromal cells but sensitivity to histone deacetylase inhibitors

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    There is a growing recognition that current preclinical models do not reflect the tumor microenvironment in cellular, biological, and biophysical content and this may have a profound effect on drug efficacy testing, especially in the era of molecular-targeted agents. Here, we describe a method to directly embed low-passage patient tumor–derived tissue into basement membrane extract, ensuring a low proportion of cell death to anoikis and growth complementation by coculture with patient-derived cancer-associated fibroblasts (CAF). A range of solid tumors proved amenable to growth and pharmacologic testing in this 3D assay. A study of 30 early-stage non–small cell lung cancer (NSCLC) specimens revealed high levels of de novo resistance to a large range of standard-of-care agents, while histone deacetylase (HDAC) inhibitors and their combination with antineoplastic drugs displayed high levels of efficacy. Increased resistance was seen in the presence of patient-derived CAFs for many agents, highlighting the utility of the assay for tumor microenvironment-educated drug testing. Standard-of-care agents showed similar responses in the 3D ex vivo and patient-matched in vivo models validating the 3D-Tumor Growth Assay (3D-TGA) as a high-throughput screen for close-to-patient tumors using significantly reduced animal numbers. Mol Cancer Ther; 15(4); 753–63. ©2016 AACR

    Review: A Publication of LMDA, the Literary Managers and Dramaturgs of the Americas, volume 17, issue 1

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    Contents include: Editor\u27s Page: A Note from New LMDA President, Brian Quirt; Think Dramaturgically, Act Locally! A Conference Overview; I Was Mugged at My First LMDA Conference; First-Timer Fragments; Conference Photos; Introducing the Lessing (and Joe and Michael); A Message Faxed from Romania; Acceptance Speech, Michael Lupu; Producing The Belle\u27s Stratagem; Dramaturging Justice: The Exonerated Project at the Alley Theatre; Past President Liz Engeleman: Some Appreciations; The Toronto Mini-Conference (reprinted from the LMDA Canada newsletter); Gateway to the Americas, The LMDA Delegation, A Report from Mexico; Imag[in]ing Poverty: Creative Critical Dramaturgy for Suzan-Lori Parks\u27s In the Blood; Hester, La Negrita in Iowa City, Staging Spells and Homelessness in Suzan-Lori Parks\u27s In the Blood; The Future of Theatre is...(a creative contest); Seventh Annual Call for LMDA Residency Proposals. Issue editors: D.J. Hopkins, Madeleine Oldham, Carlenne Lacostahttps://soundideas.pugetsound.edu/lmdareview/1034/thumbnail.jp
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