Rational Design and Synthesis of Selective PRMT4 Inhibitors: A New Chemotype for Development of Cancer Therapeutics**

Protein arginine N-methyl transferase 4 (PRMT4) asymmetrically dimethylates the arginine residues of histone H3 and nonhistone proteins. The overexpression of PRMT4 in several cancers has stimulated interest in the discovery of inhibitors as biological tools and, potentially, therapeutics. Although several PRMT4 inhibitors have been reported, most display poor selectivity against other members of the PRMT family of methyl transferases. Herein, we report the structure-based design of a new class of alanine-containing 3-arylindoles as potent and selective PRMT4 inhibitors, and describe key structure–activity relationships for this class of compounds.     

Inferring Bias and Uncertainty in Camera Calibration

International Journal of Computer Vision - Accurate camera calibration is a precondition for many computer vision applications. Calibration errors, such as wrong model assumptions or imprecise...     

A Simple and Non-Trivial Ramsey Test

Journal of Logic, Language and Information - This paper expounds a simple and non-trivial Ramsey Test. Drawing on the work of Peter Gärdenfors, it aims to help establish an epistemic...     

Fluorophore-Labeled Cyclic Nucleotides as Potent Agonists of Cyclic Nucleotide-Regulated Ion Channels

High-affinity fluorescent derivatives of cyclic adenosine and guanosine monophosphate are powerful tools for investigating their natural targets. Cyclic nucleotide-regulated ion channels belong to these targets and are vital for many signal transduction processes, such as vision and olfaction. The relation of ligand binding to activation gating is still challenging, and there is a need for fluorescent probes that enable the process to be broken down to the single-molecule level. This inspired us to prepare fluorophore-labeled cyclic nucleotides, which are composed of a bright dye and a nucleotide derivative with a thiophenol motif at position 8 that has already been shown to enable superior binding affinity. These bioconjugates were prepared by a novel cross-linking strategy that involves substitution of the nucleobase with a modified thiophenolate in good yield. Both fluorescent nucleotides are potent activators of different cyclic nucleotide-regulated ion channels with respect to the natural ligand and previously reported substances. Molecular docking of the probes excluding the fluorophore reveals that the high potency can be attributed to additional hydrophobic and cation-π interactions between the ligand and the protein. Moreover, the introduced substances have the potential to investigate related target proteins, such as cAMP- and cGMP-dependent protein kinases, exchange proteins directly activated by cAMP or phosphodiesterases.     

Influence of Mixing on the Precipitation of Organic Nanoparticles: A Lagrangian Perspective on Scale‐up Based on Self‐Similar Distributions

Precipitation of nanoparticles is applied in various fields with a rising interest in the formulation of poorly soluble drugs. The impact of fluid mixing on the precipitation of organic nanoparticles is analyzed. Direct numerical simulations are applied to determine the spatiotemporal evolution of the liquid phase composition and to estimate the particle evolution along Langragian trajectories. The simulation results are compared with laboratory experiments of mixing and particle size evolution, which use a recently developed approach to rapidly stabilize the precipitated nanoparticles. The impact of mixing on precipitation is revealed, thereby enabling a parameter‐free estimation of the mean particle sizes and the particle size distributions. The distributions of residence time, supersaturation time, and particle size are self‐similar for Reynolds numbers in the turbulent regime and allow the derivation of scale‐up rules.     

Oxygen Poisoning in Laboratory Testing of Iron-Based Ammonia Synthesis Catalysts and its Potential Sources

The influence of oxygen poisoning on a state-of-the-art multipromoted iron-based industrial catalyst for ammonia synthesis as well as the effectivity of different gas purification methods to prevent oxygen poisoning for experiments on laboratory scale were studied in detail. Additionally, the observed results were compared to a common oxygen poisoning test from literature, which on the one hand confirmed its usability in a wide range of conditions, but on the other hand also demonstrated the limitations of this test.     

Methane Pyrolysis for CO2-Free H2 Production: A Green Process to Overcome Renewable Energies Unsteadiness

The Carbon2Chem® project aims to convert exhaust gases from the steel industry into chemicals such as methanol to reduce CO₂ emissions. Here, H₂ is required for the conversion of CO₂ into methanol. Although much effort is put to produce H₂ from renewables, the use of fossil fuels, especially natural gas, seems to be fundamental in the short term. For this reason, the development of clean technologies for the processing of natural gas with a low environmental impact has become a topic of utmost importance. In this context, methane pyrolysis has received special attention to produce CO₂-free H₂.     

TiO2 and ZrO2 supported Ru catalysts for CO mitigation following the water-gas shift reaction

CO oxidation and methanation over Ru-TiO₂ and Ru-ZrO₂ catalysts were investigated for CO removal for applications in proton exchange membrane fuel cells. The catalysts were synthesised by the deposition precipitation method at a pH of 7–7.5 for better interactions between the support and the active Ru metal. Various characterization experiments such as TPR, XPS, FTIR-CO, CO chemisorption and HRTEM were conducted to better understand the physio-chemical properties of Ru on the supports. Both catalysts showed excellent activity for the total oxidation of CO, however, with the addition of H₂, the catalysts activity to CO oxidation decreased significantly. Higher temperatures for the preferential oxidation reaction indicated that the Ru catalysts not only oxidize CO, but hydrogenate it as well. Furthermore, H₂ oxidation was favoured over the catalysts. Hydrogenation of CO over these catalysts gave high CO conversion and selectivity towards CH₄. Both the catalysts showed similar activity across the temperature range screened and gave maximum CO conversions of 99.9% from 240 °C onwards, with 99.9% selectivity towards CH₄. The catalysts also showed good stability in the reaction and the similarities in the catalytic activity of these were attributed to the well-dispersed Ru metal over the supports. The Ru catalysts effectively reduced CO concentrations in the reformate gas to less than 10 ppm, as is required for practical applications.     

Energy for water utilization in China and policy implications for integrated planning

Abstract

Significant energy resources are needed for traditional and nontraditional water utilization in China. Yet the interlinkages between water and energy have not received adequate attention in the country. To address this gap, this article disaggregates and quantifies the magnitude and direction of energy and water flows in China at the national level through Sankey diagrams. Spatial distributions of energy use by different components of the water supply were further mapped at the provincial level to discern regional differences. The results of this study show that the total energy consumption by water abstraction, treatment and distribution, as well as waste treatment and reuse, amounts to 193.5 TWh of electricity, or about 4% of the total national electricity usage. The outcome of this study offers important policy implications for integrated water and energy planning and management and will contribute to achieving the goal of low-energy water utilization in the future.