Long-term daily intake estimates of polychlorinated dibenzo-p-dioxins and furans, polychlorinated biphenyls and polybrominated diphenylethers from food in Finnish children: risk assessment implications

Food is contaminated by polychlorinated dibenzo-p-dioxins and furans (PCDD/F), polychlorinated biphenyls (PCB) and polybrominated diphenylethers (PBDE) worldwide. Previous data show elevated intakes in children. We determined intakes of POPs in Finnish children. Because no children-specific safe limit values exist, we used tolerable daily intakes (TDIs) set for adults by international expert bodies to examine the proportion of the study population that exceed those limits. We utilised dietary monitoring data with food consumption of Finnish boys and girls aged 1-6 years, measured the contaminant concentrations in all the main food items and calculated age-specific contaminant sum and congener-specific long-term daily intake levels. Our food intake and contaminant data correspond to years 2002-2005. The long-term upper-bound dioxin intakes ranged between 0.1 and 12.8?pg WHO(PCDD/F-PCB)-TEQ/kg bw/d (min and max). An immediate TDI for WHO(PCDD/F-PCB)-TEQs of 4.0?pg/kg?bw/d were exceeded by 2.5%-7.5% of the children. PBDE long-term upper-bound intake was between 0.1 and 5.8?ng/kg bw/d (min and max). Congener-specific analyses indicated a typical Finnish adult exposure pattern of the children to PCDD/Fs, PCBs and PBDEs. The highest POP intakes were observed in children aged 3 years. Long-term daily PCDD/F, PCB and PBDE intakes among Finnish children varied greatly between individuals and ages. In each age group of the study population, there was a proportion of children with their WHO(PCDD/F-PCB)-TEQ intake exceeding considered safe limits set for adults. Based on the exposure profile reported herein, children should be clearly considered as a specific sub-population in food-mediated contaminant risk assessment.     

Foam properties of algae soluble protein isolate: Effect of pH and ionic strength

In this study the foam properties of algae soluble protein isolate (ASPI), a mixture of mainly proteins and polysaccharides, were investigated as function of isolate concentration (0.1–1.0 mg/mL) and pH (3.0–7.0) at 10 mM and 200 mM NaCl. In addition, adsorption kinetics and dilatational elasticity at the air–water interface were studied. Whey protein isolate (WPI) and egg white albumin (EWA) were used as reference proteins. The consistent dilatational behaviour of ASPI at all pH values and ionic strengths tested indicated a similar interfacial composition at all these conditions. Adsorption kinetics, in contrast, were influenced by varying environmental conditions. At increased ionic strength and close to the theoretical isoelectric point calculated based purely on the amino acid composition of ASPI (pH 7) adsorption increased. Since similar adsorption behaviour was also observed for WPI and EWA, the interfacial properties of ASPI are most likely dominated by its protein fraction. This is further confirmed by the fact that ζ-potential measurements suggested an overall isoelectric point of ASPI below pH 3, while adsorption kinetics varied between pH 5 and pH 7 (the theoretical protein-based isoelectric point of ASPI). The overall foam stability of ASPI stabilized foams was superior to those of WPI and EWA in the pH range 5–7. In conclusion, the molecular and interfacial properties of ASPI, a mixture of proteins and polysaccharides, seem to favour the production of very stable foams in this pH range by the selective adsorption of its protein fraction to the air–water interface.     

Inhibition of Human Urokinase-Type Plasminogen Activator (uPA) Enzyme Activity and Receptor Binding by DNA Aptamers as Potential Therapeutics through Binding to the Different Forms of uPA

Urokinase-type plasminogen activator is widely discussed as a marker for cancer prognosis and diagnosis and as a target for cancer therapies. Together with its receptor, uPA plays an important role in tumorigenesis, tumor progression and metastasis. In the present study, systematic evolution of ligands by exponential enrichment (SELEX) was used to select single-stranded DNA aptamers targeting different forms of human uPA. Selected aptamers allowed the distinction between HMW-uPA and LMW-uPA, and therefore, presumably, have different binding regions. Here, uPAapt-02-FR showed highly affine binding with a K_D of 0.7 nM for HMW-uPA and 21 nM for LMW-uPA and was also able to bind to pro-uPA with a K_D of 14 nM. Furthermore, no cross-reactivity to mouse uPA or tissue-type plasminogen activator (tPA) was measured, demonstrating high specificity. Suppression of the catalytic activity of uPA and inhibition of uPAR-binding could be demonstrated through binding with different aptamers and several of their truncated variants. Since RNA aptamers are already known to inhibit uPA-uPAR binding and other pathological functions of the uPA system, these aptamers represent a novel, promising tool not only for detection of uPA but also for interfering with the pathological functions of the uPA system by additionally inhibiting uPA activity.     

Combining Radiation- with Immunotherapy in Prostate Cancer: Influence of Radiation on T Cells

Radiation of tumor cells can lead to the selection and outgrowth of tumor escape variants. As radioresistant tumor cells are still sensitive to retargeting of T cells, it appears promising to combine radio- with immunotherapy keeping in mind that the radiation of tumors favors the local conditions for immunotherapy. However, radiation of solid tumors will not only hit the tumor cells but also the infiltrated immune cells. Therefore, we wanted to learn how radiation influences the functionality of T cells with respect to retargeting to tumor cells via a conventional bispecific T cell engager (BiTE) and our previously described modular BiTE format UNImAb. T cells were irradiated between 2 and 50 Gy. Low dose radiation of T cells up to about 20 Gy caused an increased release of the cytokines IL-2, TNF and interferon-γ and an improved capability to kill target cells. Although radiation with 50 Gy strongly reduced the function of the T cells, it did not completely abrogate the functionality of the T cells.     

Prediction of Response to Cisplatin-Based Neoadjuvant Chemotherapy of Muscle-Invasive Bladder Cancer Patients by Molecular Subtyping including KRT and FGFR Target Gene Assessment

Patients with muscle-invasive urothelial carcinoma achieving pathological complete response (pCR) upon neoadjuvant chemotherapy (NAC) have improved prognosis. Molecular subtypes of bladder cancer differ markedly regarding sensitivity to cisplatin-based chemotherapy and harbor FGFR treatment targets to various content. The objective of the present study was to evaluate whether preoperative assessment of molecular subtype as well as FGFR target gene expression is predictive for therapeutic outcome—rate of ypT0 status—to justify subsequent prospective validation within the “BladderBRIDGister”. Formalin-fixed paraffin-embedded (FFPE) tissue specimens from transurethral bladder tumor resections (TUR) prior to neoadjuvant chemotherapy and corresponding radical cystectomy samples after chemotherapy of 36 patients were retrospectively collected. RNA from FFPE tissues were extracted by commercial kits, Relative gene expression of subtyping markers (e.g., KRT5, KRT20) and target genes (FGFR1, FGFR3) was analyzed by standardized RT-qPCR systems (STRATIFYER Molecular Pathology GmbH, Cologne). Spearman correlation, Kruskal–Wallis, Mann–Whitney and sensitivity/specificity tests were performed by JMP 9.0.0 (SAS software). The neoadjuvant cohort consisted of 36 patients (median age: 69, male 83% vs. female 17%) with 92% of patients being node-negative during radical cystectomy after 1 to 4 cycles of NAC. When comparing pretreatment with post-treatment samples, the median expression of KRT20 dropped most significantly from DCT 37.38 to 30.65, which compares with a 128-fold decrease. The reduction in gene expression was modest for other luminal marker genes (GATA3 6.8-fold, ERBB2 6.3-fold). In contrast, FGFR1 mRNA expression increased from 33.28 to 35.88 (~6.8-fold increase). Spearman correlation revealed positive association of pretreatment KRT20 mRNA levels with achieving pCR (r = 0.3072: p = 0.0684), whereas pretreatment FGFR1 mRNA was associated with resistance to chemotherapy (r = −0.6418: p < 0.0001). Hierarchical clustering identified luminal tumors of high KRT20 mRNA expression being associated with high pCR rate (10/16; 63%), while the double-negative subgroup with high FGFR1 expression did not respond with pCR (0/9; 0%). Molecular subtyping distinguishes patients with high probability of response from tumors as resistant to neoadjuvant chemotherapy. Targeting FGFR1 in less-differentiated bladder cancer subgroups may sensitize tumors for adopted treatments or subsequent chemotherapy.     

Interlaboratory study on lipid oxidation during accelerated storage trials with rapeseed and sunflower oil analyzed by conjugated dienes as primary oxidation products

Accelerated storage tests are frequently used to assess the oxidative stability of foods and related systems due to its reproducibility. Various methods and experimental conditions are used to measure lipid oxidation. Differences between laboratories make it necessary to determine the repeatability and reproducibility of oxidation tests performed under the same conditions. The objective of the present interlaboratory study was to evaluate the outcome of a storage test for two different bulk oils, sunflower oil (SFO) and rapeseed oil (RSO), during a period of 9 weeks at 20°C, 30°C, 40°C, and 60°C. Sixteen laboratories were provided with bottled oils and conducted the storage tests according to a detailed protocol. Lipid oxidation was monitored by the formation of conjugated dienes (CD) and the activation energy (E_a) was determined for comparative purposes and statistically evaluated. An increase in CD formation was observed for both oils when the storage temperature was increased in all laboratories. The E_a,1 ranged from 47.9 to 73.3 kJ mol⁻¹ in RSO and from 27.8 to 62.6 kJ mol⁻¹ in SFO, with average values of 58.2 and 46.8 kJ mol⁻¹, respectively. The reproducibility coefficients were 10.9% and 18.2% for RSO and SFO, respectively. Practical applications: In order to compare results on oxidative stability of foods derived from different studies, the reproducibility of storage tests and methods employed to evaluate the oxidation level should be considered. This study provides fundamental data on the reproducibility of lipid oxidation under accelerated storage conditions and defines important parameters to be considered for the conduction of experiments.     

Optical Properties of Metacrystals Based on Protein Nanocages

The optical properties of 3D metacrystals made of gold nanoparticles in protein nanocages are studied. These metacrystals have sizes of tens of micrometers and are of high structural and optical quality. Through microspectroscopy measurements and model calculations it is demonstrated that the metacrystals show plasmonic absorption in the green wavelength range and are largely transparent in the red and infrared ranges. By using empty nanocages as placeholders in the metacrystal lattice, it is possible to control how strongly the metamaterial absorbs. Measurements on a pyramidal metacrystal show that it deflects visible light. The deflection shows evidence for anomalous refraction at short wavelengths and normal refraction at long wavelengths. The refractive dispersion is ascribed to the optical dispersion relation of the plasmonic metamaterial.     

Die Scherkondetalbrücke,die erste semi‐integrale Talbrücke der DB AG auf der Neubaustrecke Erfurt – Leipzig/Halle VDE 8.2

Auf der Neubaustrecke Erfurt – Leipzig/Halle werden zurzeit einige Talbrücken realisiert, die einen neuen, ganzheitlich orientierten Entwurfsansatz verfolgen. Bei diesen integralen bzw. semi‐integralen Bauwerken sind die Überbauten monolithisch mit den Pfeilern und teilweise mit den Widerlagern verbunden. Sie können deshalb schlanker und mit stetigen Übergängen zwischen den Bauteilen ausgeführt werden. Durch den weitgehenden Verzicht auf Lager und Fugen und durch die robuste Bauweise besitzen integrale Bauwerke eine wesentlich längere Lebenserwartung als herkömmliche Talbrücken. Am Beispiel der Scherkondetalbrücke werden in diesem Beitrag die Unterschiede zwischen den konventionellen und den semi‐integralen Tragwerken erläutert sowie die Voraussetzungen und die Vorteile der Anwendung von integralen Bauwerken für die DB AG herausgearbeitet. Bridge over Scherkonde Valley – the First Large Semi‐Integral Bridge on High‐Speed Railway Route Erfurt – Leipzig/Halle Currently some large valley bridges are under construction on high‐speed railway route Erfurt‐Leipzig/Halle. These bridges follow a new holistic design philosophy. The superstructure of those integral or semi‐integral bridges is rigidly connected to the abutments and the columns. Therefore they are more slender than conventional bridges, and the bridges are very robust and durable because of the omitting of bearings and dilatation joints. The bridge over the Scherkonde valley is taken as an example for explaining the differences between conventional and semi‐integral bridges in this paper. This example shows the advantages and the requirements of integral buildings for high‐speed railway bridges.     

Wet Milling of Alginate Alco- and Hydrogel Composites: A Facile Top-Down Approach for Continuous Production of Aerogel Microparticles

Moving toward high-throughput production of biopolymer aerogel microparticles, in this work, the wet milling process is applied to hydrogels and alcogels. Alcogels are then converted into aerogels by well-established supercritical drying. Alginate and hybrid alginate/silica gels are used as a model system. As the Young's moduli of hydrogels significantly change when water is exchanged by ethanol, it is possible to study the effect of the gel stiffness on macroscopic and microstructural properties of the resulting aerogels. Influence of process parameters (milling speed and gap size) is also investigated. Smallest particles sizes and minimal changes in microstructure are obtained for completely solvent exchanged gels. The wet milling is shown to be a versatile method to obtain aerogel particles with diameters in the range 50–300 µm.     

Sulfation Pattern Dependent Iron(III) Mediated Interleukin-8 Glycan Binding

Cytokines such as interleukin-8 activate the immune system during infection and interact with sulfated glycosaminoglycans with specific sulfation patterns. In some cases, these interactions are mediated by metal ion binding which can be used to tune surface-based glycan-protein interactions. We evaluated the effect of both hyaluronan sulfation degree and Fe³⁺ on interleukin-8 binding by electrochemical impedance spectroscopy and surface characterizations. Our results show that sulfation degree and metal ion interactions have a synergistic effect in tuning the electrochemical response of the glycated surfaces to the cytokine.