Contribution of components in Ce–Ti–Cr–Ox catalysts for selective propane-combustion in the presence of CO

Gas-phase combustion of hydrocarbons and CO in exhaust gases are normally performed competitively by supported noble metals. With the help of high-throughput technologies complex mixed oxides, such as the amorphous porous Ce₂₀Ti₅₀Cr₃₀O_x have been discovered, which selectively convert propane in the presence of excess of carbon monoxide. These findings are of fundamental importance for heterogeneous catalysis and may have implications on the future development of novel exhaust gas catalysts. In this study the effect of the various elements of the mixed oxide catalysts on activity and selectivity has been investigated and interpreted. The results of attempts to further improve the catalysts by additional doping are presented.     

Contribution of physico-chemical properties of interfaces on dispersibility, adhesion and flocculation of filler particles in rubber

Reinforcing fillers are added to elastomeric compounds to improve and adjust several mechanical, dynamical, tribological, etc. properties with respect to different applications, i.e. for automotive tires, or technical rubber goods. Carbon black and precipitated silica are widely used as rubber reinforcing fillers; however, some new classes of nanosized substances like organophilic modified clay or carbon nanotubes are presently intensive studied as possible future filler systems in combination with carbon black or silica.An important parameter for the dispersibility and compatibility of the filler in the polymer matrix of rubber compounds is the surface energy and surface polarity of the solid filler particles. Therefore, we systematically measured and compared the dynamic contact angles of a collection of different filler types (carbon blacks, silica, carbon nanotubes and organoclays) using the Wilhelmy method, whereby the particles were fixed as a thin layer at a double-sided adhesive tape. From the contact angle values the polar and disperse part of the surface energies of the filler particles were calculated by fitting Fowkes formula. For an estimation of the compatibility of the fillers with different types of rubber polymers we additionally analyzed the surface energy and polarity of the gum (unfilled) elastomers. From the evaluated surface energies and polarities, thermodynamic predictors for the dispersibility (enthalpy of immersion), the adhesion between filler particles and polymer matrix in the nanocomposite, and for the flocculation behaviour of the particles in a rubber matrix (difference in the works of adhesion) were derived. These thermodynamic predictors improve considerably the compounding process of novel rubber nanocomposites with respect to target-oriented adjustment of rubber properties.     

The Binary Bi-Rh Phase Diagram: Stable and Metastable Phases

The binary bismuth-rhodium (Bi-Rh) phase diagram was reinvestigated from 23 to 60 at.% Rh with focus on the BiRh phase, applying powder-x-ray diffraction (XRD), high temperature powder-XRD, differential thermal analyses and scanning electron microscopy. The phase boundaries of the BiRh phase at 750 °C and the temperature of its peritectic decomposition were refined. In addition, the existence of the two phases Bi₄Rh and Bi₂Rh (in two modifications depending on temperature) could be confirmed. Most of the reaction temperatures reported in the literature could be verified within a range of about ± 10 °C. Nevertheless, a few temperatures had to be revised, such as those of the peritectic reactions L + Rh \(\rightleftharpoons\) BiRh at 979 °C and L + BiRh \(\rightleftharpoons\) β-Bi₂Rh at 785 °C. No evidence could be found for the presence of a stable Bi₃Rh phase in well annealed samples; from the present results it must be concluded that Bi₃Rh is actually metastable. On the other hand, a new orthorhombic phase BiRh_0.81 was discovered which crystallizes in the MnP structure type (Pmna). It was found that the temperatures of the transition between the low-temperature modification α-Bi₂Rh and its high-temperature form β-Bi₂Rh depend considerably on the presence or absence of metastable Bi₃Rh and stable BiRh_0.81, respectively.     

Resource efficiency and environmental impact of fiber reinforced plastic processing technologies

The process energy demand and the environmental indicators of two carbon fiber reinforced plastic process chains have been investigated. More precisely, the impact of different production set-ups for a standard textile preforming process using bindered non-crimp fabric (NCF) and a material efficient 2D dry-fiber-placement (DFP) process are analyzed. Both 2D preforms are activated by an infrared heating system and formed in a press. The resin-transfer-molding (RTM) technology is selected for subsequent processing. Within a defined process window, the main parameters influencing the process energy demand are identified. Varying all parameters, a reduction of 77% or an increase of 700% of the electric energy consumption compared to a reference production set-up is possible, mainly depending on part size, thickness, and curing time. For a reference production set-up, carbon fiber production dominates the environmental indicators in the product manufacturing phase with a share of around 72–80% of the total global warming potential (GWP). Thus, the reduction of production waste, energy efficient carbon fiber production, and the use of renewable energy resources are the key environmental improvement levers. For the production of small and thin parts in combination with long curing cycles, the influence of the processing technologies is more pronounced. Whereas for a reference production set-up, only 10% (NCF–RTM) and 15% (DFP–RTM) of the total GWP are caused by the processing technologies, a production set-up leading to a high process energy demand results in a share of 40% (NCF–RTM) and 49% (DFP–RTM), respectively.     

Leucine Reconstitutes Phagocytosis-Induced Cell Death in E. coli-Infected Neonatal Monocytes—Effects on Energy Metabolism and mTOR Signaling

MΦ differentiate from circulating monocytes (Mo). The reduced ability of neonatal Mo to undergo apoptosis after E. coli infection (phagocytosis-induced cell death (PICD)) could contribute to sustained inflammatory processes. The objective of our study was to investigate whether immune metabolism in Mo can be modified to gain access to pro-apoptotic signaling. To this end, we supplemented Mo from neonates and from adults with the branched amino acid leucine. In neonatal Mo, we observed increased energy production via oxidative phosphorylation (Oxphos) after E. coli infection via Seahorse assay. Leucine did not change phagocytic properties. In neonatal Mo, we detected temporal activation of the AKT and mTOR pathways, accompanied with subsequent activation of downstream targets S6 Kinase (S6K) and S6. FACS analyses showed that once mTOR activation was terminated, the level of anti-apoptotic BCL-2 family proteins (BCL-2; BCL-X_L) decreased. Release of cytochrome C and cleavage of caspase-3 indicated involvement of the intrinsic apoptotic pathway. Concomitantly, the PICD of neonatal Mo was initiated, as detected by hypodiploid DNA. This process was sensitive to rapamycin and metformin, suggesting a functional link between AKT, mTOR and the control of intrinsic apoptotic signaling. These features were unique to neonatal Mo and could not be observed in adult Mo. Supplementation with leucine therefore could be beneficial to reduce sustained inflammation in septic neonates.     

Alzheimer’s Disease—Rationales for Potential Treatment with the Thrombin Inhibitor Dabigatran

Alzheimer’s disease (AD) is caused by neurodegenerative, but also vascular and hemostatic changes in the brain. The oral thrombin inhibitor dabigatran, which has been used for over a decade in preventing thromboembolism and has a well-known pharmacokinetic, safety and antidote profile, can be an option to treat vascular dysfunction in early AD, a condition known as cerebral amyloid angiopathy (CAA). Recent results have revealed that amyloid-β proteins (Aβ), thrombin and fibrin play a crucial role in triggering vascular and parenchymal brain abnormalities in CAA. Dabigatran blocks soluble thrombin, thrombin-mediated formation of fibrin and Aβ-containing fibrin clots. These clots are deposited in brain parenchyma and blood vessels in areas of CAA. Fibrin-Aβ deposition causes microvascular constriction, occlusion and hemorrhage, leading to vascular and blood–brain barrier dysfunction. As a result, blood flow, perfusion and oxygen and nutrient supply are chronically reduced, mainly in hippocampal and neocortical brain areas. Dabigatran has the potential to preserve perfusion and oxygen delivery to the brain, and to prevent parenchymal Aβ-, thrombin- and fibrin-triggered inflammatory and neurodegenerative processes, leading to synapse and neuron death, and cognitive decline. Beneficial effects of dabigatran on CAA and AD have recently been shown in preclinical studies and in retrospective observer studies on patients. Therefore, clinical studies are warranted, in order to possibly expand dabigatran approval for repositioning for AD treatment.     

Assessment of mechanical and microstructural properties of geopolymers produced from metakaolin,silica fume,and red mud

Geopolymers have been studied as viable alternative to traditional Portland cement-based products, given the use of industrial by-products as raw materials. This work evaluated the mechanical and microstructural properties of geopolymeric mortars produced with sodium hydroxide solution, metakaolin, silica fume, and red mud. The mixtures were produced by means of dosages with different molar ratios and curing conditions. The raw materials were characterized by granulometry, chemical, mineralogical, and thermal analysis. The characterization of mortars was performed by scanning electron microscopy (SEM) and axial compressive strength tests. The precalcination at 850°C of the red mud was sufficient to make it more reactive and suitable for use in geopolymers. Noteworthy, the best mechanical strengths of metakaolin mortars for curing at 50°C, and with the lowest SiO₂/Al₂O₃ ratios. In the mortars with incorporated red mud, there was a decrease of strength at thermal curing conditions and with the increase of residue content, whose microstructure indicates the formation of more pores in the geopolymer matrix. The thermal curing promoted the formation of sodalite crystals, and the significant presence of Na particles on the surface suggests that part of the added NaOH did not react with the precursors.     

Getting a Grip on the Undrugged: Targeting β-Catenin with Fragment-Based Methods

Aberrant WNT pathway activation, leading to nuclear accumulation of β-catenin, is a key oncogenic driver event. Mutations in the tumor suppressor gene APC lead to impaired proteasomal degradation of β-catenin and subsequent nuclear translocation. Restoring cellular degradation of β-catenin represents a potential therapeutic strategy. Here, we report the fragment-based discovery of a small molecule binder to β-catenin, including the structural elucidation of the binding mode by X-ray crystallography. The difficulty in drugging β-catenin was confirmed as the primary screening campaigns identified only few and very weak hits. Iterative virtual and NMR screening techniques were required to discover a compound with sufficient potency to be able to obtain an X-ray co-crystal structure. The binding site is located between armadillo repeats two and three, adjacent to the BCL9 and TCF4 binding sites. Genetic studies show that it is unlikely to be useful for the development of protein–protein interaction inhibitors but structural information and established assays provide a solid basis for a prospective optimization towards β-catenin proteolysis targeting chimeras (PROTACs) as alternative modality.     

Lipoprotein (a) metabolism estimated by nonsteady-state kinetics

Lipoprotein (a) [Lp(a)] is a low-density lipoprotein (LDL) particle with an additional apolipoprotein named apo(a). The concentration of Lp(a) in plasma is determined to a large extent by the size of the apo(a) isoform. Because elevated Lp(a) concentrations in plasma are associated with risk for premature coronary heart disease it is important to determine whether variations in production or catabolism mediate differences in Lp(a) concentration. We determined metabolic parameters of Lp(a) in 17 patients with heterozygous familial hypercholesterolemia or severe mixed hyperlipidemia by fitting a monoexponential function to the rebound of Lp(a) plasma concentration following LDL-apheresis. In 8 of those 17 patients this was done twice following two different aphereses. Although this approach allows one to estimate metabolic parameters without the use of a tracer, it requires several major assumptions such as that apheresis itself does not change production or catabolism of Lp(a) and that Lp(a) metabolism can be described by a single compartment. One apheresis decreased Lp(a) concentration by 59.1±8.3%. The fractional catabolic rate (FCR) was 0.16±0.12 d⁻¹ and production rate 6.27±5.26 mg·kg⁻¹·d⁻¹. However, observed (concentration before first apheresis) and predicted steady-state concentrations differed considerably (more than 20%) in 9 of 17 patients, indicating that not all assumptions were fulfille in all patients. Production rate but not FCR was correlated with Lp(a) plasma concentration (r ²=0.43. P=0.004) and molecular weight of apo(a) (r ²=0.48, P=0.011), which confirms radiotracer experiments showing that variations in Lp(a) plasma concentrations are due to differences in production not catabolism. When parameters were estimated tiwce in a subgroup of eight patients, satisfactory reproducibility was observed in six patients. Although parameters determined on two occasions correlated well, only FCR was concordant (intraclass correiation coefficient). Thus, despite the limitations arising from the assumptions implicit to this method, metabolic parameters of Lp(a) can be estimated from the rebound of plasma concentration following apheresis. Parts of this study were presented at the meeting of the International Atherosclerosis Society, Paris, October 5–9, 1997.