Invloed van de verwerkingsomstandigheden op de producteigenschappen van polyvinylchloride

Bij de fabricage van kunststofartikelen blijkt, dat een wisselende productkwaliteit optreedt, die sterk afhankelijk is van de, bij de fabricage gekozen, verwerkingsomstandigheden. Dit is in het bijzonder het geval bij artikelen van hard PVC, zoals onder andere buizen. Het doel van het onderzoek was inzicht te verkrijgen in de chemische en fysische processen, die aan dit verschijnsel ten grondslag liggen. Hiertoe is nagegaan, hoe een aantal eigenschappen worden beïnvloed door een behandeling op de mengwals gedurende verschillende tijden. Onderzocht werden: (A.) Chemische structuureigenschappen: 1. gemiddeld moleculairgewicht, 2. Huggins’ constante, 3. moleculairgewichtsverdeling, 4. vertakkingsgraad, 5. tacticiteit, 6. concentratie van radicalen in het walsvel, (B.) Fysische structuureigenschappen 1. specifiek volume 2.specifieke enthalpie, (C.) Producteigenschappen, 1. elasticiteitsmodulus 2. afschuivingsmodulus 3. rek bij breuk.Applied SciencesChemische WerkwijzenLaboratorium voor Chemische Technologi

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Document(en) uit de collectie Chemische ProcestechnologieDelftChemTechApplied Science

Environmental Aesthetics. Crossing Divides and Breaking Ground

Clinical Pharmacy and Toxicolog

Epitope Selection for HLA-DQ2 Presentation: Implications for Celiac Disease and Viral Defense

We have reported that the major histocompatibility molecule HLA-DQ2 (DQA1*05:01/DQB1*02:01) (DQ2) is relatively resistant to HLA-DM (DM), a peptide exchange catalyst for MHC class IL In this study, we analyzed the role of DQ2/DM interaction in the generation of DQ2-restricted gliadin epitopes, relevant to celiac disease, or DQ2-restricted viral epitopes, relevant to host defense. We used paired human APC, differing in DM expression (DMnull versus DMhigh) or differing by expression of wild-type DQ2, versus a DM-susceptible, DQ2 point mutant DQ2 alpha+53G. The APC pairs were compared for their ability to stimulate human CD4(+) T cell clones. Despite higher DQ2 levels, DMhigh APC attenuated T cell responses compared with DMnull APC after intracellular generation of four tested gliadin epitopes. DMhigh APC expressing the DQ2 alpha+53G mutant further suppressed these gliadin-mediated responses. The gliadin epitopes were found to have moderate affinity for DQ2, and even lower affinity for the DQ2 mutant, consistent with DM suppression of their presentation. In contrast, DMhigh APC significantly promoted the presentation of DQ2-restricted epitopes derived intracellularly from inactivated HSV type 2, influenza hemagglutinin, and human papillomavirus E7 protein. When extracellular peptide epitopes were used as Ag, the DQ2 surface levels and peptide affinity were the major regulators of T cell responses. The differential effect of DM on stimulation of the two groups of T cell clones implies differences in DQ2 presentation pathways associated with nonpathogen- and pathogen-derived Ags in vivo.Experimental cancer immunology and therap

A Family of Water-Immiscible, Dipolar Aprotic, Diamide Solvents from Succinic Acid

Three dipolar aprotic solvents were designed to possess high dipolarity and low toxicity: N,N,N′,N′-tetrabutylsuccindiamide (TBSA), N,N′-diethyl-N,N′-dibutylsuccindiamide (EBSA), and N,N′-dimethyl-N,N′-dibutylsuccindiamide (MBSA). They were synthesized catalytically by using a K60 silica catalyst in a solventless system. Their water immiscibility stands out as an unusual and useful property for dipolar aprotic solvents. They were tested in a model Heck reaction, metal–organic framework syntheses, and a selection of polymer solubility experiments in which their performances were found to be comparable to traditional solvents. Furthermore, MBSA was found to be suitable for the production of an industrially relevant membrane from polyethersulfone. An integrated approach involving in silico analysis based on available experimental information, prediction model outcomes and read across data, as well as a panel of in vitro reporter gene assays covering a broad range of toxicological endpoints was used to assess toxicity. These in silico and in vitro tests suggested no alarming indications of toxicity in the new solvents

Integration of new approach methods in a structure based read-across for DART effects

Read-across is one of the most often applied alternative tools for hazard assessment, in particular for complex endpoints such as toxicity after repeated exposure or developmental and reproductive toxicity. We have applied this approach to a series of six aliphatic carboxylic acids that have developmental toxicity data, some being positive, some negative. For one of these compounds, 2-Methylhexanoic acid (MHA), we have specifically blinded this toxicity data, and we have applied new approach methodologies (NAM) to substantiate the read across of the other compounds (as source compounds) to MHA, and to explore whether these NAM correctly predict the in vivo developmental toxicity of MHA. Thus, we have tested MHA and the five analogues in a battery of in vitro tests with clear relevance to DART, i.e. the Zebrafish Embryo Test (ZET), mouse Embryonic Stem cell Test (mEST), iPSC-based neurodevelopmental model (UKN1), and a series of CALUX Reporter assays, and combined this with toxicokinetic models to calculate effective cellular concentrations and associated in vivo exposure doses. We also included two positive, and one negative control compound in this test. As the histone deacetylase enzyme is postulated to be the molecular initiating target leading to neural tube defects with these compounds, we have also investigated the potential of these six analogues to inhibit this enzyme in ZET, mEST, and UKN1 models. The NAM quite well predicted the in vivo developmental outcome of these six aliphatic carboxylic acids. This presentation will discuss the combining of results from multiple NAMs for predicting the teratogenic properties and potency of this series of structurally related chemicals and how this information can be used to establish a framework of testing for regulatory applications. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 681002

Evaluation of an alternative in vitro test battery for detecting reproductive toxicants

The application of alternative methods in developmental and reproductive toxicology is challenging in view of the complexity of mechanisms involved. A battery of complementary test systems may provide a better prediction of developmental and reproductive toxicity than single assays. We tested twelve compounds with varying mechanisms of toxic action in an assay battery including 24 CALUX transcriptional activation assays, mouse cardiac embryonic stem cell test, ReProGlo assay, zebrafish embryotoxicity assay, and two CYP17 and two CYP19 activity assays. The battery correctly detected 11/12 compounds tested, with one false negative occurring, which could be explained by the absence of the specific mechanism of action of this compound in the battery. Toxicokinetic modeling revealed that toxic concentrations were in the range expected from in vivo reproductive toxicity data. This study illustrates added value of combining assays that contain complementary biological processes and mechanisms, increasing predictive value of the battery over individual assays. © 2013

Selective inhibition of BRCA2-deficient mammary tumor cell growth by AZD2281 and cisplatin

Purpose: To assess efficacy of the novel, selective poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor AZD2281 against newly established BRCA2-deficient mouse mammary tumor cell lines and to determine potential synergy between AZD2281 and cisplatin. Experimental Design: We established and thoroughly characterized a panel of clonal cell lines from independent BRCA2-deficient mouse mammary tumors and BRCA2-proficient control tumors. Subsequently, we assessed sensitivity of these lines to conventional cytotoxic drugs and the novel PARP inhibitor AZD2281. Finally, in vitro combination studies were done to investigate interaction between AZD2281 and cisplatin. Results: Genetic, transcriptional, and functional analyses confirmed the successful isolation of BRCA2-deficient and BRCA2-proficient mouse mammary tumor cell lines. Treatment of these cell lines with 11 different anticancer drugs or with γ-irradiation showed that AZD2281, a novel and specific PARP inhibitor, caused the strongest differential growth inhibition of BRCA2-deficient versus BRCA2-proficient mammary tumor cells. Finally, drug combination studies showed synergistic cytotoxicity of AZD2281 and cisplatin against BRCA2-deficient cells but not against BRCA2-proficient control cells. Conclusion: We have successfully established the first set of BRCA2-deficient mammary tumor cell lines, which form an important addition to the existing preclinical models for BRCA-mutated breast cancer. The exquisite sensitivity of these cells to the PARP inhibitor AZD2281, alone or in combination with cisplatin, provides strong support for AZD2281 as a novel targeted therapeutic against BRCA-deficient cancers