Variants of human chorionic gonadotropin from pregnant women and tumor patients recognized by monoclonal antibodies

In biological fluids, hCG and its free alpha- (hCG alpha) and beta-subunits (hCG beta), occur in multiple forms. These various forms differ at the molecular level primarily in glycosylation, but also differ in protein backbone modifications corresponding to the urinary low molecular weight fragment of the hCG beta-subunit (beta-core fragment). This microheterogeneous nature can be demonstrated by isoelectric focusing in which variants are separated into bands with different isoelectric points (pI). To determine whether such isoelectric variants differ in antigenicity and consequently might escape immunoassay detection due to overspecificity of monoclonal antibodies (MCA), urinary pregnancy hCG (NIH, CR123) and tumor hCG preparations, such as a tumor-specific acidic variant of hCG (hCGav) and the hCG beta-core fragment, were separated by isoelectric focusing in the absence or presence of 8 M urea, or by sodium docedyl sulfate-polyacrylamide gel electrophoresis and enzymatically immunostained using an MCA panel directed against 17 different hCG epitopes. MCA against 14 different epitopes accessible on holo-hCG recognized all pI variants of pregnancy holo-hCG or tumor-derived hCGav, as was true for the three MCA recognizing epitopes hidden on holo-hCG but accessible on the free subunits after hCG dissociation by urea. We conclude that each individual pI-isoform of holo-hCG and its free subunits expresses the entire set of epitopes recognized by our MCA panel. The carbohydrate moieties that form a biochemical basis for hCG heterogeneity seem to be neither of major antigenic relevance, nor are they structurally related to any particular epitope. Thus, various glycosylation forms of hCG, hCG alpha, hCG beta, and hCG beta-core in normal as well as in pathological samples should safely be detectable and measureable by immunoassays employing MCA with appropriate subunit specificity

Multilevel Global-Local techniques for adaptive ductile phase-field fracture

This paper outlines a rigorous variational-based multilevel Global-Local formulation for ductile fracture. Here, a phase-field formulation is used to resolve failure mechanisms by regularizing the sharp crack topology on the local state. The coupling of plasticity to the crack phase-field is realized by a constitutive work density function, which is characterized through a degraded stored elastic energy and the accumulated dissipated energy due to plasticity and damage. Two different Global-Local approaches based on the idea of multiplicative Schwarz' alternating method are proposed: (i) A global constitutive model with an elastic-plastic behavior is first proposed, while it is enhanced with a single local domain, which, in turn, describes an elastic-plastic fracturing response. (ii) The main objective of the second model is to introduce an adoption of the Global-Local approach toward the multilevel local setting. To this end, an elastic-plastic global constitutive model is augmented with two distinct local domains; in which, the first local domain behaves as an elastic-plastic material and the next local domain is modeled due to the fracture state. To further reduce the computational cost, predictor-corrector adaptivity within Global-Local concept is introduced. An adaptive scheme is devised through the evolution of the effective global plastic flow (for only elastic-plastic adaptivity), and through the evolution of the local crack phase-field state (for only fracture adaptivity). Thus, two local domains are dynamically updated during the computation, resulting with two-way adaptivity procedure. The overall response of the Global-Local approach in terms of accuracy/robustness and efficiency is verified using single-scale problems. The resulting framework is algorithmically described in detail and substantiated with numerical examples.Comment: 50 pages, 24 Figures, 4 Table

Single walled carbon nanotubes (SWCNT) affect cell physiology and cell architecture

Single walled carbon nanotubes (SWCNT) find their way in various industrial applications. Due to the expected increased production of various carbon nanotubes and nanoparticle containing products, exposure to engineered nanoparticles will also increase dramatically in parallel. In this study the effects of SWCNT raw material and purified SWCNT (SWCNT bundles) on cell behaviour of mesothelioma cells (MSTO-211H) and on epithelial cells (A549) had been investigated. The effect on cell behaviour (cell proliferation, cell activity, cytoskeleton organization, apoptosis and cell adhesion) were dependent on cell type, SWCNT quality (purified or not) and SWCNT concentratio

PeC3 Spring School on Introduction to Numerical Modeling with Differential Equations

This spring school is part of the DAAD (German academic exchange service) program PeC3 : Peruvian Competence Center of Scientific Computing (https://www.pec3.org/)

Structure-activity relationship of graphene-related materials: A meta-analysis based on mammalian in vitro toxicity data

To support a safe application of graphene-related materials (GRMs) it is necessary to understand the potential negative impacts they could have on human health, in particular on the lung -one of the most sensitive exposure routes. Machine learning (ML) approaches can help analyse the results of multiple toxicity studies to understand the structure-activity relationship and the effect of experimental conditions, thus supporting predictive nano -toxicology. In this work we collected in vitro cytotoxicity data obtained from studies using lung cells; we then fitted multiple regression models to predict this endpoint based on the material properties and experimental conditions. Moreover, the data set was used to calculate the Benchmark Dose Lower Confidence Interval (BMDL), a dose descriptor widely used in risk assessment. Regression and classification models were applied for the prediction of the BMDL value and BMDL range. The analyses show that both cytotoxicity and the BMDL range can be predicted well (Q2 = 0.77 and accuracy = 0.71, respectively). Both physico-chemical characteristics such as the lateral size, number of layers, and functionalization, and experimental conditions such as the assay and media used were important predicting features, confirming the need for thorough characterization and reporting of these parameters

Penetration and effectiveness of micronized copper in refractory wood species

The North American wood decking market mostly relies on easily treatable Southern yellow pine (SYP), which is being impregnated with micronized copper (MC) wood preservatives since 2006. These formulations are composed of copper (Cu) carbonate particles (CuCO3 center dot Cu(OH)(2)), with sizes ranging from 1 nm to 250 mu m, according to manufacturers. MC-treated SYP wood is protected against decay by solubilized Cu2+ ions and unreacted CuCO3 center dot Cu(OH)(2) particles that successively release Cu2+ ions (reservoir effect). The wood species used for the European wood decking market differ from the North American SYP. One of the most common species is Norway spruce wood, which is poorly treatable i.e. refractory due to the anatomical properties, like pore size and structure, and chemical composition, like pit membrane components or presence of wood extractives. Therefore, MC formulations may not suitable for refractory wood species common in the European market, despite their good performance in SYP. We evaluated the penetration effectiveness of MC azole (MCA) in easily treatable Scots pine and in refractory Norway spruce wood. We assessed the effectiveness against the Cu-tolerant wood-destroying fungus Rhodonia placenta. Our findings show that MCA cannot easily penetrate refractory wood species and could not confirm the presence of a reservoir effect

The adsorption of biomolecules to multi-walled carbon nanotubes is influenced by both pulmonary surfactant lipids and surface chemistry

<p>Abstract</p> <p>Background</p> <p>During production and processing of multi-walled carbon nanotubes (MWCNTs), they may be inhaled and may enter the pulmonary circulation. It is essential that interactions with involved body fluids like the pulmonary surfactant, the blood and others are investigated, particularly as these interactions could lead to coating of the tubes and may affect their chemical and physical characteristics. The aim of this study was to characterize the possible coatings of different functionalized MWCNTs in a cell free environment.</p> <p>Results</p> <p>To simulate the first contact in the lung, the tubes were coated with pulmonary surfactant and subsequently bound lipids were characterized. The further coating in the blood circulation was simulated by incubating the tubes in blood plasma. MWCNTs were amino (NH₂)- and carboxyl (-COOH)-modified, in order to investigate the influence on the bound lipid and protein patterns. It was shown that surfactant lipids bind unspecifically to different functionalized MWCNTs, in contrast to the blood plasma proteins which showed characteristic binding patterns. Patterns of bound surfactant lipids were altered after a subsequent incubation in blood plasma. In addition, it was found that bound plasma protein patterns were altered when MWCNTs were previously coated with pulmonary surfactant.</p> <p>Conclusions</p> <p>A pulmonary surfactant coating and the functionalization of MWCNTs have both the potential to alter the MWCNTs blood plasma protein coating and to determine their properties and behaviour in biological systems.</p