Energy Metabolites as Biomarkers in Ischemic and Dilated Cardiomyopathy

With more than 25 million people affected, heart failure (HF) is a global threat. As energy production pathways are known to play a pivotal role in HF, we sought here to identify key metabolic changes in ischemic- and non-ischemic HF by using a multi-OMICS approach. Serum metabolites and mRNAseq and epigenetic DNA methylation profiles were analyzed from blood and left ventricular heart biopsy specimens of the same individuals. In total we collected serum from n = 82 patients with Dilated Cardiomyopathy (DCM) and n = 51 controls in the screening stage. We identified several metabolites involved in glycolysis and citric acid cycle to be elevated up to 5.7-fold in DCM (p = 1.7 × 10⁻⁶). Interestingly, cardiac mRNA and epigenetic changes of genes encoding rate-limiting enzymes of these pathways could also be found and validated in our second stage of metabolite assessment in n = 52 DCM, n = 39 ischemic HF and n = 57 controls. In conclusion, we identified a new set of metabolomic biomarkers for HF. We were able to identify underlying biological cascades that potentially represent suitable intervention targets.     

Is LRP2 Involved in Leptin Transport over the Blood-Brain Barrier and Development of Obesity?

The mechanisms underlying the transport of leptin into the brain are still largely unclear. While the leptin receptor has been implicated in the transport process, recent evidence has suggested an additional role of LRP2 (megalin). To evaluate the function of LRP2 for leptin transport across the blood-brain barrier (BBB), we developed a novel leptin-luciferase fusion protein (pLG), which stimulated leptin signaling and was transported in an in vitro BBB model based on porcine endothelial cells. The LRP inhibitor RAP did not affect leptin transport, arguing against a role of LRP2. In line with this, the selective deletion of LRP2 in brain endothelial cells and epithelial cells of the choroid plexus did not influence bodyweight, body composition, food intake, or energy expenditure of mice. These findings suggest that LRP2 at the BBB is not involved in the transport of leptin into the brain, nor in the development of obesity as has previously been described.     

A novel technique for the preparation of secondary fatty amides

A technique for the synthesis of monosubstituted fatty amides at low temperature and ambient pressure was developed. This method involved the condensation of an amine with a triacylglycerol. The primary amine (ethyl,n-butyl,n-hexyl andn-octyl were tested) acted as reagent and solvent for the fatty substrates. No additional organic solvent or catalyst was added. Tallow, vegetable oils and fish oil all served well as substrates, as did pure tripalmitin. The rate of amidation was dependent upon temperature and the ratio of fat to amine. In a series of experiments conducted with tallow andn-butylamine at a fat:amine molar ratio of 1:16, amidation could be carried out at 20°C, producingn-butyltallowamide in 83% yield in 24 hr. When the fat:amine molar ratio was reduced to 1:8, and the temperature raised to 45°C, the amide yield was 87.6% in 24 hr. When the reaction was carried out at the boiling point ofn-butylamine (78°C) and at a fat:amine ratio of 1:8, the amide yield was 93.2% in 4 hr. The reaction progressed more rapidly with higher molecular weight amines. The identity and purity of the amides was assessed by thin-layer chromatography and confirmed by elemental analyses and infrared and C¹³ nuclear magnetic resonance spectroscopy.     

Jet bundle formulation of infinite-dimensional port-Hamiltonian systems using differential operators

We consider infinite-dimensional port-Hamiltonian systems described on jet bundles. Based on a power balance relation we introduce the port-Hamiltonian system representation using differential operators regarding the structural mapping, the dissipation mapping and the input mapping. In contrast to the well-known representation on the basis of the underlying Stokes–Dirac structure our approach is not necessarily based on using energy-variables which leads to a different port-Hamiltonian representation of the analyzed partial differential equations. The presented constructions will be specialized to mechanical systems to which class also the presented examples belong.     

The impedance of the alkaline zinc-mercuric oxide cell. I. Cell behaviour and interpretation of impedance spectra

The impedances of small (2400 mA h) alkaline Zn-HgO cells have been measured in the range 10 kHz-0.001 Hz at various states of charge from fully charged to fully discharged. The behaviour of the cell conforms to that expected for rate control by charge transfer at the zinc electrode and diffusion in solution. At low frequencies there is a relaxation in the diffusive circuit elements which ultimately results in a complete suppression of the capacitative component of the impedance at zero frequency. The low-frequency behaviour is analogous to convective diffusion and is due to the effective distance between the electrodes being small compared with the characteristic length (D/)^1/2. The magnitude of the charge transfer resistance is the best measure of the state of charge.Nomenclature a effective electrode separation - C _DL double-layer capacitance of cell - C _R capacitative component of cell impedance - C concentration difference - D percentage discharge in Equation 12 - D _i diffusion coefficient of speciesi - R ohmic resistance of cell - R _R resistive component of cell Faradaic impedance - Ui constant defined by Equation 10 - Z total cell impedance - Z _F cell Faradaic impedance - Z _F cell impedance modified for porosity effect - Z _x cell impedance of Faradaic component plus double layer - cell Warburg coefficient (slope ofR _R and 1/C _Rversus su}-1/2) - _C Warburg coefficient calculated fromC _r values - _i cell Warburg coefficient for speciesi - Warburg coefficient calculated fromR _R values - dihedral angle of tail of Sluyters plot (after coming-off high-frequency semicircle) - angular frequency     

Aggregation behaviour of well defined amphiphilic diblock copolymers with poly(N-isopropylacrylamide) and hydrophobic blocks

Series of amphiphilic diblock copolymers with poly(N-isopropylacrylamide) as a hydrophilic block and a hydrophobic block consisting of either polystyrene or poly(tert-butyl methacrylate) were synthesised using RAFT polymerisations. Differential scanning calorimetry showed the chemically different blocks being phase separated in dry polymers. Light scattering and microcalorimetry studies were performed on aqueous solutions to investigate the phase behavior of the diblock copolymers. By carefully transferring the polymers from an organic solvent to water, either micellar particles or large aggregates were obtained depending on the relative lengths of the blocks. Large aggregates collapsed upon heating, whereas collapse occurred slowly within a broad temperature range in the case of micelle like structures. However, microcalorimetrically the collapse of the PNIPAM chains was observed to take place in all samples, suggesting that the shells of the micellar particles are crowded in a way which hinders the compression of the poly(N-isopropylacrylamide) chains.     

Organic Nanoparticles with Polypropyleneoxide Chains as Support for Metallocene Catalysts: Ethylene Homopolymerization and Ethylene/α-olefin Copolymerization

Summary Novel organic nanoparticles functionalized with nucleophilic polypropyleneoxide (PPO) chains on their surfaces for supporting metallocene catalysts in heterogeneous olefin polymerization are presented. The nanoparticles (60–100 nm) were obtained by miniemulsion polymerization of styrene, divinylbenzene and PPO functionalized styrene. It is demonstrated that Me₂Si(2MeBenzlnd)₂ZrCl₂/MAO supported on these nanoparticles is suitable for the homopolymerization of ethylene, resulting in excellent product morphologies and high activities. lt is shown that by varying the MAO/Zr ratios and Zr concentrations the activities and productivities of the catalysts as well as the qualities of the polyethylene products can be tuned. These new supported catalysts are also suitable for the copolymerization of ethylene with several comonomers (1-hexene, 1-octene, 1-decene or norbornene). As the obtained product properties like crystallinity, melting temperature or bulk density match the results of silica supported systems, these organic nanoparticles can be considered as alternative carriers in comparison to the established inorganic ones.     

Branching-time logics with path relativisation

We define extensions of the full branching-time temporal logic CTL^? in which the path quantifiers are relativised by formal languages of infinite words, and consider its natural fragments obtained by extending the logics CTL and CTL⁺ in the same way. This yields a small and two-dimensional hierarchy of temporal logics parametrised by the class of languages used for the path restriction on one hand, and the use of temporal operators on the other. We motivate the study of such logics through two application scenarios: in abstraction and refinement they offer more precise means for the exclusion of spurious traces; and they may be useful in software synthesis where decidable logics without the finite model property are required. We study the relative expressive power of these logics as well as the complexities of their satisfiability and model-checking problems.