National-scale implementation of mandatory freshwater farm plans: a mechanism to deliver water quality improvement in productive catchments in New Zealand?

Nutrient Cycling in Agroecosystems - Reducing agriculturally derived diffuse contaminant losses (via non-point sources) from land to water has proven difficult for decades. Owing to the diversity...     

Discovery of GPR183 Agonists Based on an Antagonist Scaffold

The G protein-coupled receptor GPR183/EBI2, which is activated by oxysterols, is a therapeutic target for inflammatory and metabolic diseases where both antagonists and agonists are of potential interest. Using the piperazine diamide core of the known GPR183 antagonist (E)-3-(4-bromophenyl)-1-(4-(4-methoxybenzoyl)piperazin-1-yl)prop-2-en-1-one (NIBR189) as starting point, we identified and sourced 79 structurally related compounds that were commercially available. In vitro screening of this compound collection using a Ca²⁺ mobilization assay resulted in the identification of 10 compounds with agonist properties. To enable establishment of initial structure-activity relationship trends, these were supplemented with five in-house compounds, two of which were also shown to be GPR183 agonists. Taken together, our findings suggest that the agonist activity of this compound series is dictated by the substitution pattern of one of the two distal phenyl rings, which functions as a molecular efficacy-switch.     

Interfacial microstructure and mechanical properties of Ti3SiC2 ceramic and TC11 alloy joint diffusion bonded with a Cu interlayer

Reliable joints of Ti₃SiC₂ ceramic and TC11 alloy were diffusion bonded with a 50 μm thick Cu interlayer. The typical interfacial structure of the diffusion boned joint, which was dependent on the interdiffusion and chemical reactions between Al, Si and Ti atoms from the base materials and Cu interlayer, was TC11/α-Ti + β-Ti + Ti₂Cu + TiCu/Ti₅Si₄ + TiSiCu/Cu(s, s)/Ti₃SiC₂. The influence of bonding temperature and time on the interfacial structure and mechanical properties of Ti₃SiC₂/Cu/TC11 joint was analyzed. With the increase of bonding temperature and time, the joint shear strength was gradually increased due to enhanced atomic diffusion. However, the thickness of Ti₅Si₄ and TiSiCu layers with high microhardness increased for a long holding time, resulting in the reduction of bonding strength. The maximum shear strength of 251 ± 6 MPa was obtained for the joint diffusion bonded at 850 °C for 60 min, and fracture primarily occurred at the diffusion layer adjacent to the Ti₃SiC₂ substrate. This work provided an economical and convenient solution for broadening the engineering application of Ti₃SiC₂ ceramic.     

Multivariate process trajectories for molecular description of MF thermal curing and correlation with hydrolytic stability

During curing of thermosetting resins the technologically relevant properties of binders and coatings develop. However, curing is difficult to monitor due to the multitude of chemical and physical processes taking place. Precise prediction of specific technological properties based on molecular properties is very difficult. In this study, the potential of principal component analysis (PCA) and principal component regression (PCR) in the analysis of Fourier transform infrared (FTIR) spectra is demonstrated using the example of melamine-formaldehyde (MF) resin curing in solid state. FTIR/PCA-based reaction trajectories are used to visualize the influence of temperature on isothermal cure. An FTIR/PCR model for predicting the hydrolysis resistance of cured MF resin from their spectral fingerprints is presented which illustrates the advantages of FTIR/PCR compared to the combination differential scanning calorimetry/isoconversional kinetic analysis. The presented methodology is transferable to the curing reactions of any thermosetting resin and can be applied to model other technologically relevant final properties as well.     

Influence of pressure and dwell time on pressure-assisted sintering of calcium cobaltite

Calcium cobaltite Ca₃Co₄O₉, abbreviated Co349, is a promising thermoelectric material for high-temperature applications in air. Its anisotropic properties can be assigned to polycrystalline parts by texturing. Tape casting and pressure-assisted sintering (PAS) are a possible future way for a cost-effective mass-production of thermoelectric generators. This study examines the influence of pressure and dwell time during PAS at 900°C of tape-cast Co349 on texture and thermoelectric properties. Tape casting aligns lentoid Co349. PAS results in a textured Co349 microstructure with the thermoelectrically favorable ab-direction perpendicular to the pressing direction. By pressure variation during sintering, the microstructure of Co349 can be tailored either toward a maximum figure of merit as required for energy harvesting or toward a maximum power factor as required for energy harvesting. Moderate pressure of 2.5 MPa results in 25% porosity and a textured microstructure with a figure of merit of 0.13 at 700°C, two times higher than the dry-pressed, pressureless-sintered reference. A pressure of 7.5 MPa leads to 94% density and a high power factor of 326 µW/mK² at 800°C, which is 11 times higher than the dry-pressed reference (30 MPa) from the same powder.     

Influence of bearing ball recirculation on error motions of linear axes

For positioning systems utilizing linear guides and trucks with recirculating balls, a method is presented that uses the measured total error motions and the measured phase of ball loops within trucks to determine the influence of each ball loop on the error motions. The influence of ball recirculation on the error motions is estimated a priori via a least-squares solution based on data collected from a multitude of motion tests in which varying phases were measured by sensors integrated into the trucks. This method enables real-time estimation of performance degradations and identification of their sources.     

Rational Design of Potent Inhibitors of a Metallohydrolase Using a Fragment-Based Approach

Metallohydrolases form a large group of enzymes that have fundamental importance in a broad range of biological functions. Among them, the purple acid phosphatases (PAPs) have gained attention due to their crucial role in the acquisition and use of phosphate by plants and also as a promising target for novel treatments of bone-related disorders and cancer. To date, no crystal structure of a mammalian PAP with drug-like molecules bound near the active site is available. Herein, we used a fragment-based design approach using structures of a mammalian PAP in complex with the Maybridge^TM fragment CC063346, the amino acid L-glutamine and the buffer molecule HEPES, as well as various solvent molecules to guide the design of highly potent and efficient mammalian PAP inhibitors. These inhibitors have improved aqueous solubility when compared to the clinically most promising PAP inhibitors available to date. Furthermore, drug-like fragments bound in newly discovered binding sites mapped out additional scaffolds for further inhibitor discovery, as well as scaffolds for the design of inhibitors with novel modes of action.     

Interlaced layer thicknesses within single laser powder bed fusion geometries

The geometrical design freedoms associated with additive manufacturing techniques are currently well exploited and finding commercial application. The capability of layer-based processes to allow modification of composition and microstructure in process to achieve functional grading is currently a growing topic. In this work, a method is demonstrated for varying layer thickness within single components that allows part sections to be interlaced for the purpose of locally manipulating material and structural properties. Demonstrator geometries are explored here which exhibit the interfaces within specimens constituted of both 30 µm and 150 µm. Accordingly, a new design freedom for laser powder bed fusion is created.     

A novel solution of deep learning for endoscopic ultrasound image segmentation: enhanced computer aided diagnosis of gastrointestinal stromal tumor

Multimedia Tools and Applications - Gastrointestinal stromal tumor is one of the critical tumors that doctors do not suggest to get frequent endoscopy, so there is a need for a diagnosis system...     

Wall Rock Alteration,Uranium Mineralization,and Potentiality of Uranium and Iron Dissolution from Mineralized Abu Rusheid Gneiss Rock,South Eastern Desert,Egypt

Radiochemistry - Ferrugination, sericitization, desulfitization, chloritization, and kaolinitization of hydrothermal origin are the main wall rock alterations occurring within the NNW shear zones...