System approach to modeling of liver glucose metabolism with physiologically interpreted model parameters outgoing from [18F]FDG concentrations measured by PET

New mathematical models from physiologically interpreted parameters capable of evaluating glucose metabolism within the liver and/or the whole body were developed. The group of pigs in a fasting state and the group of pigs with euglycemic supraphysiological hyperinsulinemia were scanned by positron emission tomography after a single dose of [(18)F]FDG tracer. Simultaneously frequent sampling of the dynamic data of [(18)F]FDG plasma concentration in artery, portal vein and hepatic vein was obtained. A system approach to the liver and/or the whole-body system by the tools of linear dynamic sysztem theory was used. Three kinds of structural models, single input and single output or multiple outputs and multiple inputs and single output, were identified. Differences between the group of fasting pigs and the group of pigs in euglycemic supraphysiological hyperinsulinemia were identified by estimated parameters of the structural models. The suitability of the structural mathematical models for the estimation of physiologically interpreted parameters from PET was validated.     

Physical solvent extraction of levulinic acid from dilute aqueous solution with 2-methyltetrahydrofuran

The results of the present investigation reveal that 2-methyltetrahydrofuran is a potential solvent for the extraction of levulinic acid from dilute aqueous solution. This conclusion is based on the relatively high values of distribution coefficient K_d (1.3-1.6) measured for the system of levulinic acid – water – 2-methyltetrahydrofuran at temperatures 298.2 K, 313.2 K, and 328.2 K, as well as encouraging performance of the continuous counter current Kühni column. The results give reason to believe, that 2-methyltetrahydrofuran can be considered for the extraction of other low molecular weight acids, such as formic or lactic acid, as well.     

Bivalent EGFR-Targeting DARPin-MMAE Conjugates

Epidermal growth factor receptor (EGFR) is a validated tumor marker overexpressed in various cancers such as squamous cell carcinoma (SSC) of the head and neck and gliomas. We constructed protein-drug conjugates based on the anti-EGFR Designed Ankyrin Repeat Protein (DARPin) E01, and compared the bivalent DARPin dimer (DD1) and a DARPin-Fc (DFc) to the monomeric DARPin (DM) and the antibody derived scFv425-Fc (scFvFc) in cell culture and a mouse model. The modular conjugation system, which was successfully applied for the preparation of protein-drug and -dye conjugates, uses bio-orthogonal protein-aldehyde generation by the formylglycine-generating enzyme (FGE). The generated carbonyl moiety is addressed by a bifunctional linker with a pyrazolone for a tandem Knoevenagel reaction and an azide for strain-promoted azide-alkyne cycloaddition (SPAAC). The latter reaction with a PEGylated linker containing a dibenzocyclooctyne (DBCO) for SPAAC and monomethyl auristatin E (MMAE) as the toxin provided the stable conjugates DD1-MMAE (drug-antibody ratio, DAR = 2.0) and DFc-MMAE (DAR = 4.0) with sub-nanomolar cytotoxicity against the human squamous carcinoma derived A431 cells. In vivo imaging of Alexa Fluor 647-dye conjugates in A431-xenografted mice bearing subcutaneous tumors as the SCC model revealed unspecific binding of bivalent DARPins to the ubiquitously expressed EGFR. Tumor-targeting was verified 6 h post-injection solely for DD1 and scFvFc. The total of four administrations of 6.5 mg/kg DD1-MMAE or DFc-MMAE twice weekly did not cause any sequela in mice. MMAE conjugates showed no significant anti-tumor efficacy in vivo, but a trend towards increased necrotic areas (p = 0.2213) was observed for the DD1-MMAE (n = 5).     

Levels of mycotoxins and sample cytotoxicity of selected organic and conventional grain-based products purchased from Finnish and Italian markets

The contamination levels of 16 different Fusarium- and Aspergillus-mycotoxins were chemically determined from randomly selected organic and conventional grain-based products purchased from Finnish and Italian markets. The cytotoxicity of the samples was analyzed with an in vitro test using feline fetal lung cells. Overall, the concentrations of the mycotoxins studied were low in all of the samples. Enniatins B and B1 as well as deoxynivalenol were the most predominant mycotoxins in the samples, being present in 97%, 97%, and 90% of the samples, respectively. The geographical origin or the agricultural practice had no influence on the mycotoxin concentrations of the samples. The babyfoods included in the samples had significantly lower concentrations of mycotoxins than the other products with a mean total mycotoxin content of 47 microg/kg compared with 99 microg/kg for the other kinds of food. All the samples evoked toxicity in the in vitro test, but no correlation between cytotoxicity and the mycotoxin concentrations was observed.     

Optimised selection of new protective coatings for biofuel boiler applications

Using biofuels in power and CHP boilers can pose a challenge for materials performance. Formation of deposits containing e.g. potassium, sulphur, calcium, sodium, and chlorine can result in severe corrosion of conventional steels and alloys at relatively modest temperatures. Given suitable component design and fabrication facilities, coatings may be considered to protect the fireside surfaces. This paper aims to present a systematic approach to the design and selection criteria for protective coatings of boilers. The approach includes modelling of the process and surface conditions, optimisation of the coating process and structure, and performance validation in the laboratory and plant scales. The applied examples have included iron and nickel based HVOF and arc sprayed coatings subjected to verification field testing in boiler testing under aggressive biofuel conditions. The coatings have shown good corrosion resistance in both laboratory tests and long‐term harsh field tests. The paper discusses the used approach for finding a suitable and cost effective coating for biofuel boiler applications. The paper gives test results from microstructural, corrosion resistance and field testing experience for the selected coatings.     

Characterization of polyesters prepared from three different phthalic acid isomers by CID-ESI-FT-ICR and PSD-MALDI-TOF mass spectrometry

Polyesters prepared from the same diol, 2-butyl-2-ethyl-1,3-propanediol, but different phthalic acid isomers, phthalic, isophthalic, and terephthalic acid, were characterized by collision-induced dissociation electrospray ionization Fourier transform ion cyclotron resonance (CID-ESI-FT-ICR) and postsource-decay matrix-assisted laser desorption/ionization time-of-flight (PSD-MALDI-TOF) mass spectrometry. Sodiated dihydroxyl-terminated polyester oligomers containing five repeating units at m/z 1634 were selected as precursor ions for dissociation studies. Two main mechanisms occurred in the fragmentation of all of the polyesters, since dissociation of the oligomers was initiated by hydrogen rearrangement or transesterification reactions. Polyesters prepared from different phthalic acid isomers could be distinguished by their fragmentation behavior. Polyester prepared from phthalic acid was easily identified by using both CID-ESI-FT-ICR and PSD-MALDI-TOF mass spectrometry. However, distinguishing between the polyesters prepared from isophthalic and terephthalic acid succeeded marginally only with CID-ESI-FT-ICR mass spectrometry. Molecular dynamics calculations were used to obtain an idea of the fragmentation behavior of the polyesters. The low-energy structures of the precursor ions were determined, and the coordination of the oxygen atoms of the polyester oligomers to the sodium cation was examined more closely. Both the experimental and the theoretical studies showed that the sodium ion affinity of polyester changed with the phthalic acid isomer.