Pharmacological Promiscuity: Dependence on Compound Properties and Target Specificity in a Set of Recent Roche Compounds

What parameters determine promiscuity? A compound's potential for promiscuity (pharmacological activity at multiple targets) may be influenced by molecular parameters such as ionization state, lipophilicity, and molecular weight. In an analysis of recent Roche compounds we found that a positive charge is an important determinant for potential promiscuity; aminergic activity was found to be the main reason for overt promiscuity.

     

Influence of Irradiation Temperature on Grafting of Styrene into Poly(tetrafluoroethylene‐co‐hexafluoropropylene) Films

This study concerns with the investigation of the effect of irradiation conditions on grafting of styrene into FEP films by the pre‐irradiation method. EPR spectroscopy was used to characterize the base polymer material regarding the trapped radical species and their concentration. Radiation‐induced changes in the chemical structure were studied by IR spectroscopy. Tensile strength and elongation at break as well as yield of grafting were found to be strongly influenced by irradiation temperature. Main‐chain scissions were identified to be the reason for the deterioration of the mechanical properties after radiation treatment at temperatures below glass transition temperature.

     

Analytical investigation of the composition of plasma-induced functional groups on carbon nanotube sheets

To increase the applicability of carbon nanotubes (CNTs) oxygen-containing functional groups were generated on their widely inert surface by using glow-discharge plasmas. CNT-sheets (bucky papers) produced from the powder-like raw material were used as substrates allowing for a more defined characterization of one and the same surface by different analytical techniques. The plasma composition was analyzed by optical emission spectroscopy. Since the actual composition of the plasma-induced functional groups has still not been completely resolved, we performed an in-depth characterization of the treated samples by X-ray photoelectron (XPS) and Raman spectroscopy as well as electron spin resonance measurements. To overcome limitations of the XPS-analysis in distinguishing between groups featuring nearby binding energies, alcohol-, keto-/aldehyde-, and carboxyl-groups were tagged by derivatization techniques using fluorine-containing reagents (trifluoroaceticanhydride, trifluoromethylphenylhydrazine, and trifluoroethanol). Differential spectra were calculated to enhance the accuracy of the deconvolution of the XPS-spectra. This enabled us to determine dependencies of the plasma parameters, i.e. treatment time, process pressure, and gas composition (mixtures of Ar, O₂, H₂O, and H₂), on the composition of the generated functional groups as well as an up to 6-fold enhancement in derivatizable groups for switching process gas from Ar/O₂ to Ar/H₂O.     

Effect of Long-Term Forest Fertilization on Scots Pine Xylem Quality and Wood Borer Performance

We tested whether changes in long-term nutrient availability would affect the xylem quality and characteristics of Scots pine trees as a food source for the larvae of the xylophagous wood borer Hylotrupes bajulus L. (Cerambycidae). We looked for an effect of host plant growth and xylem structural traits on H. bajulus larval performance, and looked for delayed effects of long-term forest fertilization on xylem chemical quality. In general, larval performance was dependent on larval developmental stage. However, the growth of larvae also varied with host plant quality (increases in the concentration of nitrogen and carbon-based secondary compounds of xylem were correlated with a decrease in the larval growth rate). The greater annual growth of trees reduced tracheid length and correlated positively with second-instar H. bajulus growth rate. This is consistent with the hypothesis that intrinsic growth patterns of host plants influence the development of the xylophagous wood borer H. bajulus.     

A New Research Infrastructure for Investigating Flow Hydraulics and Process Equipment at Critical Fluid Properties

An optimized equipment design for natural gas processing and liquefaction plants becomes increasingly difficult with changing process conditions: Particularly low values of surface tension create rising challenges on the design of phase separators and column internals. The TERESA test rig at HZDR was designed to allow the investigation of multiphase thermohydraulics and phase separator performance under critical fluid properties in industrial dimensions. A versatile pipe test section is available in DN200 and equipment internals may be tested in a sectional DN300/DN500 test separator. The applied test fluid shows a high vapor-liquid density difference between 1470 and 940 kg m⁻³, viscosity as low as 0.12 mm²s⁻¹, and surface tension down to 1.3 mN m⁻¹. Volumetric liquid and vapor flow rates may be varied up to 9 and 530 m³h⁻¹ in the test rig, respectively.     

Morphology of Flashing Feeds at Critical Fluid Properties in Larger Pipes

Tailored conditioning and control of flashing feeds in industrial applications requires knowledge of the evolving flow morphology and phase fractions along the feed pipe. Design methods obtained from reference systems (e.g. water-air) are hardly applicable for commercial scales and critical fluid properties (e.g. high vapor densities, low surface tension). In this study, the flow morphology of flashing feeds in a novel refrigerant test rig at critical fluid properties was analyzed using wire-mesh sensors at two locations along the feed pipe and experimental data from the water-air system.     

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.     

Hydraulic reactivity and cement formation of baghdadite

In this study, the hydraulic reactivity and cement formation of baghdadite (Ca₃ZrSi₂O₉) was investigated. The material was synthesized by sintering a mixture of CaCO₃, SiO₂, and ZrO₂ and then mechanically activated using a planetary mill. This leads to a decrease in particle and crystallite size and a partial amorphization of baghdadite as shown by X-ray powder diffraction (XRD) and laser diffraction measurements. Baghdadite cements were formed by the addition of water at a powder to liquid ratio of 2.0 g/ml. Maximum compressive strengths were found to be ~2 MPa after 3-day setting for a 24-h ground material. Inductively coupled plasma mass spectrometry (ICP-MS) measurements showed an incongruent dissolution profile of set cements with a preferred dissolution of calcium and only marginal release of zirconium ions. Cement formation occurs under alkaline conditions, whereas the unground raw powder leads to a pH of 11.9 during setting, while prolonged grinding increased pH values to approximately 12.3.     

Liquid flow texture analysis in trickle bed reactors using high-resolution gamma ray tomography

Trickle bed reactor performance and safety may suffer from radial and axial liquid maldistribution and thus from non-uniform utilization of the catalyst packing. Therefore, experimental analysis and fluid dynamic simulation of liquid–gas flow in trickle bed reactors is an important topic in chemical engineering. In the present study for the first time a truly high-resolution gamma ray tomography technique was applied to the quantitative analysis of the liquid flow texture in a laboratory cold flow trickle bed reactor of 90 mm diameter. The objective of this study was to present the comparative analysis of the liquid flow dynamics for two different initial liquid distributions and two different types of reactor configurations. Thus, the hydrodynamic behavior of a glass bead packing was compared to a porous Al₂O₃ catalyst particle packing using inlet flow from a commercial spray nozzle (uniform initial liquid distribution) and inlet flow from a central point source (strongly non-uniform initial liquid distribution), respectively. The column was operated in downflow mode at a gas flow rate of 180 L h⁻¹ and at liquid flow rates of 15 and 25 L h⁻¹.     

Modelling of orthogonal cutting processes with the method of smoothed particle hydrodynamics

In the last decades, mesh-free methods for simulating various cutting processes have been used very widely as they can eliminate numerical problems in the simulation of material failure and large plastic deformations. This paper deals with the results from modelling the orthogonal cutting of AISI 1045 steel using smoothed particle hydrodynamics (SPH) method. Moreover, it is determined how the parameters of the SPH solver such as initial smoothing length, initial particle density and coefficient for the timestep increase affect the prediction error for the values of cutting force and chip compression ratio as well as computing time. The optimum values of the SPH solver parameters are determined by minimising an objective function. The best balance between the prediction error of machining variables and computing time is achieved for an initial particle density of 40 μm and a coefficient for the timestep increase of 0.4.