Understanding Degradation Mechanisms in SrIrO3 Oxygen Evolution Electrocatalysts: Chemical and Structural Microscopy at the Nanoscale

Designing acid-stable oxygen evolution reaction electrocatalysts is key to developing sustainable energy technologies such as polymer electrolyte membrane electrolyzers but has proven challenging due to the high applied anodic potentials and corrosive electrolyte. This work showcases advanced nanoscale microscopy techniques supported by complementary structural and chemical characterization to develop a fundamental understanding of stability in promising SrIrO₃ thin film electrocatalyst materials. Cross-sectional high-resolution transmission electron microscopy illustrates atomic-scale bulk and surface structure, while secondary ion mass spectrometry imaging using a helium ion microscope provides the nanoscale lateral elemental distribution at the surface. After accelerated degradation tests under anodic potential, the SrIrO₃ film thins and roughens, but the lateral distribution of Sr and Ir remains homogeneous. A layer-wise dissolution mechanism is hypothesized, wherein anodic potential causes the IrO_x-rich surface to dissolve and be regenerated by Sr leaching. The characterization approaches utilized herein and mechanistic insights into SrIrO₃ are translatable to a wide range of catalyst systems.     

Pyrazolopyrimidines: Potent Inhibitors Targeting the Capsid of Rhino‐ and Enteroviruses

There are currently no drugs available for the treatment of enterovirus (EV)‐induced acute and chronic diseases such as the common cold, meningitis, encephalitis, pneumonia, and myocarditis with or without consecutive dilated cardiomyopathy. Here, we report the discovery and characterization of pyrazolopyrimidines, a well‐tolerated and potent class of novel EV inhibitors. The compounds inhibit the replication of a broad spectrum of EV in vitro with IC₅₀ values between 0.04 and 0.64 μM for viruses resistant to pleconaril, a known capsid‐binding inhibitor, without affecting cytochrome P450 enzyme activity. Using virological and genetics methods, the viral capsid was identified as the target of the most promising, orally bioavailable compound 3‐(4‐trifluoromethylphenyl)amino‐6‐phenylpyrazolo[3,4‐d]pyrimidine‐4‐amine (OBR‐5‐340). Its prophylactic as well as therapeutic application was proved for coxsackievirus B3‐induced chronic myocarditis in mice. The favorable pharmacokinetic, toxicological, and pharmacodynamics profile in mice renders OBR‐5‐340 a highly promising drug candidate, and the regulatory nonclinical program is ongoing.     

The effect of previous exposure to technology on acceptance and its importance in usability and accessibility engineering

In Usability and Accessibility Engineering, metric standards are vital. However, the development of a set of reciprocal metrics—which can serve as an extension of, and supplement to, current standards—becomes indispensable when the specific needs of end-user groups, such as the elderly and people with disabilities, are concerned. While ISO 9126 remains critical to the usability of a product, the needs of the elderly population are forcing the integration of other factors. Familiarity and recognisability are not relevant to someone with no experience and therefore no referent; however, acceptance becomes a major factor in their willingness to learn something new and this acceptance requires trust based on association. Readability and legibility are of less relevance to a blind person than to someone with failing eyesight. This paper describes some usability metrics ascertained on the basis of experiments made with applications for elderly people throughout the summer term of 2007. The factors that influence the older users’ acceptance of software, including the extent of their previous exposure to technology, are evaluated in order to provide short guidelines for software developers on how to design and develop software for the elderly. The evaluation of the expectations, behavior, abilities, and limitations of prospective end-users is considered of primary importance for the development of technology. A total of N = 31 participants (22 women/9 men) took part in various tests. The participants’ ages ranged from 49 to 96 years with an average age of 79. Five of the tests were designed for a PDA or cellular phone, one test was designed for a laptop PC. Of the total of 55 tests, 52 tests provided sufficient data to evaluate the results. In 23 of the tests, all tasks were completed. As a main outcome, it can be experimentally proved that the acceptance is related to a factor, which is this paper is called PET (Previous Exposure to Technology). This is discussed in light of the aforementioned metrics.     

Mapping the Binding Interface of PET Tracer Molecules and Alzheimer Disease Aβ Fibrils by Using MAS Solid-State NMR Spectroscopy

Positron emission tomography (PET) tracer molecules like thioflavin T specifically recognize amyloid deposition in brain tissue by selective binding to hydrophobic or aromatic surface grooves on the β-sheet surface along the fibril axis. The molecular basis of this interaction is, however, not well understood. We have employed magic angle spinning (MAS) solid-state NMR spectroscopy to characterize Aβ-PET tracer complexes at atomic resolution. We established a titration protocol by using bovine serum albumin as a carrier to transfer hydrophobic small molecules to Aβ(1-40) fibrillar aggregates. The same Aβ(1-40) amyloid fibril sample was employed in subsequent titrations to minimize systematic errors that potentially arise from sample preparation. In the experiments, the small molecules ¹³C-methylated Pittsburgh compound B (PiB) as well as a novel Aβ tracer based on a diarylbithiazole (DABTA) scaffold were employed. Classical ¹³C-detected as well as proton-detected spectra of protonated and perdeuterated samples with back-substituted protons, respectively, were acquired and analyzed. After titration of the tracers, chemical-shift perturbations were observed in the loop region involving residues Gly25-Lys28 and Ile32-Gly33, thus suggesting that the PET tracer molecules interact with the loop region connecting β-sheets β1 and β2 in Aβ fibrils. We found that titration of the PiB derivatives suppressed fibril polymorphism and stabilized the amyloid fibril structure.     

Cheaper faster drug development validated by the repositioning of drugs against neglected tropical diseases

There is an urgent need to make drug discovery cheaper and faster. This will enable the development of treatments for diseases currently neglected for economic reasons, such as tropical and orphan diseases, and generally increase the supply of new drugs. Here, we report the Robot Scientist ‘Eve’ designed to make drug discovery more economical. A Robot Scientist is a laboratory automation system that uses artificial intelligence (AI) techniques to discover scientific knowledge through cycles of experimentation. Eve integrates and automates library-screening, hit-confirmation, and lead generation through cycles of quantitative structure activity relationship learning and testing. Using econometric modelling we demonstrate that the use of AI to select compounds economically outperforms standard drug screening. For further efficiency Eve uses a standardized form of assay to compute Boolean functions of compound properties. These assays can be quickly and cheaply engineered using synthetic biology, enabling more targets to be assayed for a given budget. Eve has repositioned several drugs against specific targets in parasites that cause tropical diseases. One validated discovery is that the anti-cancer compound TNP-470 is a potent inhibitor of dihydrofolate reductase from the malaria-causing parasite Plasmodium vivax.     

Effect of internal curing by using superabsorbent polymers (SAP) on autogenous shrinkage and other properties of a high-performance fine-grained concrete: results of a RILEM round-robin test

The article presents the results of a round-robin test performed by 13 international research groups (representing fifteen institutions) in the framework of the activities of the RILEM Technical Committee 225-SAP “Applications of Superabsorbent Polymers in Concrete Construction”. Two commercially available SAP materials were used for internal curing of a high-performance, fine-grained concrete in combination with the addition of extra water. The concrete had the same mix composition in all laboratories involved but was composed of local materials. All found a considerable decrease in autogenous shrinkage attributable to internal curing. Also, with regard to the shrinkage-mitigating effect of both particular SAP materials, the results were consistent. This demonstrates that internal curing using SAP is a robust approach, working independently of some variations in the concretes’ raw materials, production process, or measuring technique. Furthermore, the effects of internal curing on other properties of concrete in its fresh and hardened states were investigated. These are consistent as well and expand considerably the existing data basis on properties of concrete materials containing SAP.     

Synthesis and characterization of new oligomeric/polymeric antistatic additives for sheet molding composites

For various applications it is necessary to lower the specific surface resistivity of polymers in an electrostatically conductive area. To improve the antistatic properties of sheet molding composites (SMC) usually conductive inorganic additives, like carbon black, inorganic salts, metal powder, or CNTs, are mixed physically into the matrix. A newly developed concept for antistatic treatment is using oligomeric/polymeric additives, which are synthesized on the base of ingredients of the used polymeric matrix itself. The received additives are compatible with the matrix. Furthermore, the migration of the additives to the surface is prevented and in the case they exhibit double bonds they are able to be linked in the polymeric network permanently by covalent bonds. So unsaturated, polymer‐based antistatic additives with ionic units were developed for unsaturated polyester resin based SMC. The synthesis was realized by polymer analogous reactions and polycondensation reactions from monomer building blocks with ionic units. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44741.