In industrial extrusion processes, increasing shear rates can lead to higher production rates. However, at high shear rates, extruded polymers and polymer compounds often exhibit melt instabilities ...ranging from stick‐slip to sharkskin to gross melt fracture. These instabilities result in challenges to meet the specifications on the extrudate shape. Starting with an existing published data set on melt instabilities in polymer extrusion, we assess the suitability of clustering, unsupervised machine learning algorithms combined with feature selection, to extract and identify hidden and important features from this data set, and their possible relationship with melt instabilities. The data set consists of both intrinsic features of the polymer as well as extrinsic features controlled and measured during an extrusion experiment. Using a range of commonly available clustering algorithms, it is demonstrated that the features related to only the intrinsic properties of the data set can be reliably divided into two clusters, and that in turn, these two clusters may be associated with either the stick‐slip or sharkskin instability. Furthermore, using a feature ranking on both the intrinsic and extrinsic features of the data set, it is shown that the intrinsic properties of molecular weight and polydispersity are the strongest indicators of clustering.
Unsupervised machine learning algorithms are used to predict two types of melt instabilities occurring during polymer extrusion. The influence of different physical and chemical properties on the clustering is analyzed by applying feature ranking procedures.
Nucleosomes were reconstituted from 170 bp long fragments of 5S rDNA and an optimal positioning sequence, the Selex 601, with recombinant histones. In free-solution single pair Förster resonance ...energy transfer (spFRET) measurements of the distance between fluorescently labeled bases in the nucleosomal DNA, the samples exhibited structural diversity. The structural heterogeneity correlated with the stability of the complexes and depended on the DNA sequence and histone acetylation. The stability of the nucleosomes was assessed via dilution-driven disruption: histone acetylation decreased nucleosome stability. The spFRET experiments used a new approach for data acquisition and analysis that we term "deliberately detuned detection" (D3). This permits the separation of subpopulations in the samples even for the low-FRET regime characteristic for the linker-DNA labeled nucleosomes. Thus, it became possible to study in more detail histone acetylation- and salt-dependent structural variations using either end- or internally labeled DNAs on the nucleosome. We found that the distance distribution of the fluorophore pairs on the linker DNA ends was much more sensitive to histone acetylation or sequence variation than that of labels on the internal part of the DNA, which was more tightly associated with the histone core. spFRET on freely diffusing nucleosomes allows us therefore to localize the influence of histone modifications and DNA sequence variations on the nucleosome structure and dynamics.
The flow curves of polymers often reveal the onset of melt instabilities such as sharkskin, stick–slip, or gross melt fracture, in order of increasing shear rates. The focus of this work lies in the ...application of the Göttfert sharkskin option to the investigation of flow curves of styrene-butadiene rubber (SBR) compounds. The sharkskin option consists of highly sensitive pressure transducers located inside a slit die of a capillary rheometer. This tool allows the detection of in-situ pressure fluctuation characteristics of different melt instabilities. It is shown that the change of slope of the transition region in the flow curves is only linked to slip. Dynamic Mechanical Analysis (DMA) measurements furthermore show that the shear rate at which the change of slope can be observed shows the same temperature dependency as the viscous and elastic properties of the compounds.
Uncured styrene-butadiene rubber (SBR) can be modelled as a viscoelastic material with at least two different relaxation mechanisms. In this paper we compare multi-mode constitutive models combining ...two viscoelastic modes (linear and/or nonlinear) in three possible ways. Our particular choice of the two modes was inspired by models originally developed to describe the response of asphalt binders. We select the model that best fits the experimental data obtained from a modified stress relaxation experiment in the torsional configuration of the plate–plate rheometer. The optimisation of the five model parameters for each model is achieved by minimising the weighted least-squares distance between experimental observations and the computer model output using a tree-structured Parzen estimator algorithm to find an initial guess, followed by further optimisation using the Nelder–Mead simplex algorithm. The results show that the model combining the linear mode and the nonlinear mode is the most suitable variant to describe the observed behaviour of SBR in the given regime. The predictive capabilities of the three models are further examined in changed experimental and numerical configurations. Full data and code to produce the figures in this article are included as supplementary material.
•We derive a viscoelastic constitutive model for uncured rubber compounds.•Model parameters are optimised using a two-stage global/local algorithm.•We demonstrate the predictive performance of the new model.
Nucleosomes were reconstituted from 170 bp long fragments of 5S rDNA and an optimal positioning sequence, the Selex 601, with recombinant histones. In free-solution single pair Förster resonance ...energy transfer (spFRET) measurements of the distance between fluorescently labeled bases in the nucleosomal DNA, the samples exhibited structural diversity. The structural heterogeneity correlated with the stability of the complexes and depended on the DNA sequence and histone acetylation. The stability of the nucleosomes was assessed via dilution-driven disruption: histone acetylation decreased nucleosome stability. The spFRET experiments used a new approach for data acquisition and analysis that we term “deliberately detuned detection” (D3). This permits the separation of subpopulations in the samples even for the low-FRET regime characteristic for the linker-DNA labeled nucleosomes. Thus, it became possible to study in more detail histone acetylation- and salt-dependent structural variations using either end- or internally labeled DNAs on the nucleosome. We found that the distance distribution of the fluorophore pairs on the linker DNA ends was much more sensitive to histone acetylation or sequence variation than that of labels on the internal part of the DNA, which was more tightly associated with the histone core. spFRET on freely diffusing nucleosomes allows us therefore to localize the influence of histone modifications and DNA sequence variations on the nucleosome structure and dynamics.
Purpose: The purpose of this research was to determine the safety, immunogenicity, pharmacokinetics, biodistribution, and tumor uptake
of repeat infusions of a complementarity-determining region ...grafted humanized antibody (sibrotuzumab) directed against human
fibroblast activation protein (FAP).
Experimental Design: A Phase I open-label dose escalation study was conducted in patients with cancers epidemiologically known to be FAP positive.
Patients were entered into one of four dosage tiers of 5, 10, 25, or 50 mg/m 2 sibrotuzumab, administered weekly for 12 weeks, with trace labeling with 8–10 mCi of 131 I in weeks 1, 5, and 9.
Results: A total of 26 patients were entered into the trial (15 males and 11 females; mean age, 59.9 years; age range, 41–81 years).
Twenty patients had colorectal carcinoma, and 6 patients had non-small cell lung cancer. A total of 218 infusions of sibrotuzumab
were administered during the first 12 weeks of the study, with 24 patients being evaluable. One patient received an additional
96 infusions on continued-use phase for a total of 108 infusions over a 2-year period, and 1 patient received an additional
6 infusions on continued use. There were no objective tumor responses. Only one episode of dose-limiting toxicity was observed.
Therefore, a maximum tolerated dose was not reached. Treatment-related adverse events were observed in 6 patients during the
infusional monitoring period. Four of the 6 patients, 3 of whom had associated positive serum human antihuman antibody, were
removed from the study because of clinical immune responses. Gamma camera images of 131 Isibrotuzumab demonstrated no normal organ uptake of sibrotuzumab, with tumor uptake evident within 24–48 h after infusion.
Analysis of pharmacokinetics demonstrated a similar mean terminal t 1/2 of 1.4–2.6 days at the 5, 10, and 25 mg/m 2 dose levels, and with a longer mean t 1/2 of 4.9 days at the 50 mg/m 2 dose level.
Conclusion: Repeat infusions of the humanized anti-FAP antibody sibrotuzumab can be administered safely to patients with advanced FAP-positive
cancer.
The chimeric monoclonal antibody cG250 recognises the G250/CAIX/MN antigen found on 95% of clear cell renal cell carcinomas (RCCs). We performed a phase I clinical trial to evaluate the safety, blood ...pharmacokinetics (PK), and biodistribution of repeated doses of cG250. The primary endpoint was toxicity. Secondary endpoints were cG250 biodistribution and PK; measurement of human anti-chimeric-antibodies (HACA); and tumour response rates. Eligible patients had unresectable or metastatic clear cell RCC. Doses of 5, 10, 25, or 50 mg/m(2) were given weekly by intravenous infusion for six weeks. Three patients were treated at each dose level. Trace (131)I-labelled cG250 was administered on weeks 1 and 5. Thirteen patients participated and were evaluable. One patient developed brain metastases and was replaced. No grade 3 or 4 toxicities and no dose-limiting toxicity occurred. One patient died due to progressive disease within 30 days of receiving the study drug. One patient developed HACA during the second six-week cycle. PK analysis showed mean whole body and blood alpha and beta half-lives of cG250 of 18.99 +/- 6.84 and 180.19 +/- 86.68 hours, respectively. All patients had cG250 tumour localization by gamma camera imaging in week 1 and 5. One patient had a complete response, nine patients had stable disease, and three had progressive disease. One patient received 11 six-week cycles of treatment with no toxicity or HACA. In conclusion, repeated intravenous doses of up to 50 mg/m(2) of cG250 are safe. Furthermore cG250 has a long half-life and targets clear cell RCC effectively.
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