Entity linking systems for literature reviews

Scientometrics - Computer-assisted methods and tools can help researchers automate the coding process of literature reviews and accelerate the literature review process. However, existing...     

Discovery of Affinity-Based Probes for Btk Occupancy Assays

Bruton's tyrosine kinase (Btk) is an attractive target for the treatment of a wide array of B-cell malignancies and autoimmune diseases. Small-molecule covalent irreversible Btk inhibitors targeting Cys481 have been developed for the treatment of such diseases. In clinical trials, probe molecules are required in occupancy studies to measure the level of engagement of the protein by these covalent irreversible inhibitors. The result of this pharmacodynamic (PD) activity provides guidance for appropriate dosage selection to optimize inhibition of the drug target and correlation of target inhibition with disease treatment efficacy. This information is crucial for successful evaluation of drug candidates in clinical trials. Based on the pyridine carboxamide scaffold of a novel solvent-accessible pocket (SAP) series of covalent irreversible Btk inhibitors, we successfully developed a potent and selective affinity-based biotinylated probe 12 (2-[(4-{4-[5-(1-{5-[(3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanamido}-3,6,9,12-tetraoxapentadecan-15-amido)pentanoyl]piperazine-1-carbonyl}phenyl)amino]-6-[1-(prop-2-enoyl)piperidin-4-yl]pyridine-3-carboxamide). Compound 12 has been used in Btk occupancy assays for preclinical studies to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon.     

Cultivation and downstream processing of microalgae and cyanobacteria to generate protein-based technofunctional food ingredients

Abstract

Microalgae are unicellular microorganisms that can be rich in proteins and are therefore a valuable ingredient in different foods. So far microalgae are mainly utilized in foods in low concentrations as a whole-cell ingredient even though it is known that proteins extracted from microalgae can possibly posess various technofunctional properties, such as high protein solubility, emulsification, foaming, and gelation properties. The widespread usage of protein-rich ingredients obtained from microalgae is for the most part prevented by the high price of the biomass, the lack of efficient downstream processes, and the adverse taste. The aim of this review is to give insights into the fundamental properties of the growth and processing of microalgae, highlight the advantages of microalgae ingredients and show potential applications based on the technofunctional, nutritional and sensory properties that were reported. Moreover, the existing challenges and knowledge gaps that hinder the application of microalgal proteins in foods are discussed.     

Driver detection and recognition of lineside signals and signs at different approach speeds

A study was carried out using simulation to investigate driver responses to lineside signals and signs at various approach speeds. The objectives of the study were: (1) to find out whether train speed would significantly affect signal/sign reading; (2) to examine at which point certain types of signs or signals could be detected or recognised, and (3) to determine a speed cut-off level above which certain types of signs or signals are no longer recognisable or detectable. Fifty-seven train drivers from 12 Train Operating Companies in the UK participated in the trials. Twenty different types of lineside signs and ten types of signals were tested under six different approach speeds ranging from 100 to 350 km/h (62–218 mph). Driver performance measures were ‘time remaining to the signal/sign’ at the point of detection or recognition, and reading error rate. The results showed a significant influence of train speed on driver responses to lineside signals/signs and demonstrated a non-linear relationship between driver responses to signals/signs and approach speed. This has been used to estimate a maximum approach speed limit within which a specific signal or sign can be correctly detected or recognised. The findings and implications of the study are discussed in the paper.     

Enabling simulation interoperability

Over the past years a series of architectures have addressed the need to link multiple simulations. These efforts have been driven primarily by the desire to reuse existing "best of breed" simulations in new combinations to avoid developing any single, monolithic architecture with the impossible goal of meeting all simulation needs. The US Department of Defense began developing the high level architecture (HLA) for distributed computer simulation systems. The high level architecture addresses the need to link multiple computer simulation systems. HLA separates the data model from the architecture's functions for exchanging information.     

Advanced adhesive restorations: the post-amalgam age

Due to patient demand for biocompatible, safe, and tooth-colored restorations, the use of amalgam as a restorative material has been declining. Currently, the profession of operative dentistry is in a state of transition from the amalgam age to the post-amalgam age. The learning objective of this article is to discuss the current state of the art of tooth-colored restoratives--amalgam substitutes and amalgam alternatives--used either as direct or laboratory fabricated restorations nationally and internationally. Adhesive dentistry is discussed in detail, with tooth preparation as the key element. The challenges facing the clinician during the transition period include clinician education, restorative concepts and teaching competence, costs, prevention, and maintenance.     

Symposium zur ?kologie des Schwarzwildes am 15. und 16. April 1996 in Mainz

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