Towards All-Solid-State Polymer Batteries: Going Beyond PEO with Hybrid Concepts

To go beyond polyethylene oxide in lithium metal batteries, a hybrid polymer/oligomer cell design is presented, where an ester oligomer provides high ionic conductivity of 0.2 mS cm⁻¹ at 40 °C within thicker composite cathodes with active mass loadings of up to 11 mg cm⁻² (LiNbO₃-coated) LiNi_0.6Mn_0.2Co_0.2 (NMC622), while a 30 µm thin scaffold-supported polymer electrolyte affords mechanical stability. Corresponding discharge capacities of the hybrid cells exceed 170 mAh g⁻¹ (11 mg cm⁻²) or 160 mAh g⁻¹ (6 mg cm⁻²) at rates of either 0.1 or 0.25 C. Multilayer pouch cells are projected to enable energy densities of 235 Wh L⁻¹ (6 mg cm⁻²) and even up to 356 Wh L⁻¹ (11 mg cm⁻²), clearly superior to other reported polymer-based cell designs. Polyester electrolytes are environmentally benign and safer compared to common liquid electrolytes, while the straightforward synthesis and affordability of precursors render hybrid polyester electrolytes suitable candidates for future application in solid-state lithium metal batteries.     

Gamified monetary reward designs: Offering certain versus chance-based rewards

To motivate visitors to engage with websites, e-tailers widely employ monetary rewards (e.g., vouchers, discounts) in their website designs. With advances in user interface technologies, many e-tailers have started to offer gamified monetary reward designs (MRDs), which require visitors to earn the monetary reward by playing a game, rather than simply claiming the reward. However, little is known about whether and why gamified MRDs engage visitors compared to their non-gamified counterpart. Even less is known about the effectiveness of gamified MRDs when providing certain or chance-based rewards, in that visitors do or do not know what reward they will gain for successfully performing in the game. Drawing on cognitive evaluation theory, we investigate gamified MRDs with certain or chance-based rewards and contrast them to non-gamified MRDs with certain rewards in user registration systems. Our results from a multi-method approach encompassing the complementary features of a randomised field experiment (N = 651) and a randomised online experiment (N = 330) demonstrate differential effects of the three investigated MRDs on user registration. Visitors encountering either type of gamified MRD are more likely to register than those encountering a non-gamified MRD. Moreover, gamified MRDs with chance-based rewards have the highest likelihood of user registrations. We also show that MRDs have distinct indirect effects on user registration via anticipated experiences of competence and sensation. Overall, the paper offers theoretical insights and practical guidance on how and why gamified MRDs are effective for e-tailers.     

Lignin from Annual Plants as Raw Material Source for Flavors and Basic Chemicals

The enzymatic conversion of lignins, possibly in combination with electrochemical oxidation, makes aromatics such as syringol, guaiacol, vanillin and catechol available in the qualities required by the fragrance industry. The lignins were obtained by soda digestion from wheat straw and Miscanthus, characterized and then converted with laccases. The overall yield amounted up to 9 wt % with a product spectrum confined to four substances. Catechol was the major product, with a fraction of ≈75 %. It can easily be isolated by extraction with acetone.     

Peptidyl Vinyl Ketone Irreversible Inhibitors of Rhodesain: Modifications of the P2 Fragment

In this paper, we report the design, synthesis and biological investigation of a series of peptidyl vinyl ketones obtained by modifying the P2 fragment of previously reported highly potent inhibitors of rhodesain, the main cysteine protease of Trypanosoma brucei rhodesiense. Investigation of the structure–activity relationship led us to identify new rhodesain inhibitors endowed with an improved selectivity profile (a selectivity index of up to 22 000 towards the target enzyme), and/or an improved antitrypanosomal activity in the sub-micromolar range.     

Towards patient‐centered packaging design: An industry perspective on processes,functions, and constraints

Medication packaging is essential to provide patients with guidance and correct use of their medicines for effective treatment. This research aims to increase knowledge about the medication packaging innovation process and its uptake towards patient‐centered packaging design. The study applied a qualitative research approach based on data from 25 in‐depth interviews with stakeholders involved in medication packaging design. The empirical data analysis revealed four themes that can improve and advance user‐centered packaging design: medication packaging innovation process, medication packaging functions and features, medication packaging design constraints, and patient‐centered medication packaging design. The findings suggest that medication packaging design is strongly affected by an emphasis on protective and safety packaging functions rather than on patients' needs. Packaging innovation usually is constrained by rigid incremental development processes, where compliance with regulations, extensive documentation, avoidance of manufacturing complexity, and considerations on cost prevail. These findings are discussed in relation to the three most evident trade‐offs for patient‐centered design: protection versus openability, utility versus cost, and complexity of manufacturability versus complexity of use. This research contributes with valuable input and additional evidence about the necessary shift to a user‐centered approach in a field that has not been design driven. This input complements previous research and provides an opportunity for industry decision makers and policy makers to lead patient‐centered packaging design that can benefit patients and relieve overloaded health care systems.     

Preclinical Evaluation of 99mTc-ZHER2:41071, a Second-Generation Affibody-Based HER2-Visualizing Imaging Probe with a Low Renal Uptake

Radionuclide imaging of HER2 expression in tumours may enable stratification of patients with breast, ovarian, and gastroesophageal cancers for HER2-targeting therapies. A first-generation HER2-binding affibody molecule [^99mTc]Tc-ZHER2:V2 demonstrated favorable imaging properties in preclinical studies. Thereafter, the affibody scaffold has been extensively modified, which increased its melting point, improved storage stability, and increased hydrophilicity of the surface. In this study, a second-generation affibody molecule (designated ZHER2:41071) with a new improved scaffold has been prepared and characterized. HER2-binding, biodistribution, and tumour-targeting properties of [^99mTc]Tc-labelled ZHER2:41071 were investigated. These properties were compared with properties of the first-generation affibody molecules, [^99mTc]Tc-ZHER2:V2 and [^99mTc]Tc-ZHER2:2395. [^99mTc]Tc-ZHER2:41071 bound specifically to HER2 expressing cells with an affinity of 58 ± 2 pM. The renal uptake for [^99mTc]Tc-ZHER2:41071 and [^99mTc]Tc-ZHER2:V2 was 25–30 fold lower when compared with [^99mTc]Tc-ZHER2:2395. The uptake in tumour and kidney for [^99mTc]Tc-ZHER2:41071 and [^99mTc]Tc-ZHER2:V2 in SKOV-3 xenografts was similar. In conclusion, an extensive re-engineering of the scaffold did not compromise imaging properties of the affibody molecule labelled with ^99mTc using a GGGC chelator. The new probe, [^99mTc]Tc-ZHER2:41071 provided the best tumour-to-blood ratio compared to HER2-imaging probes for single photon emission computed tomography (SPECT) described in the literature so far. [^99mTc]Tc-ZHER2:41071 is a promising candidate for further clinical translation studies.     

Functional Coupling of Slack Channels and P2X3 Receptors Contributes to Neuropathic Pain Processing

The sodium-activated potassium channel Slack (K_Na1.1, Slo2.2, or Kcnt1) is highly expressed in populations of sensory neurons, where it mediates the sodium-activated potassium current (I_KNa) and modulates neuronal activity. Previous studies suggest that Slack is involved in the processing of neuropathic pain. However, mechanisms underlying the regulation of Slack activity in this context are poorly understood. Using whole-cell patch-clamp recordings we found that Slack-mediated I_KNa in sensory neurons of mice is reduced after peripheral nerve injury, thereby contributing to neuropathic pain hypersensitivity. Interestingly, Slack is closely associated with ATP-sensitive P2X3 receptors in a population of sensory neurons. In vitro experiments revealed that Slack-mediated I_KNa may be bidirectionally modulated in response to P2X3 activation. Moreover, mice lacking Slack show altered nocifensive responses to P2X3 stimulation. Our study identifies P2X3/Slack signaling as a mechanism contributing to hypersensitivity after peripheral nerve injury and proposes a potential novel strategy for treatment of neuropathic pain.     

Production of the Carboxylate Reductase from Nocardia otitidiscaviarum in a Soluble,Active Form for in vitro Applications

Accessing aldehydes from carboxylate moieties is often a challenging task. In this regard, carboxylate reductases (CARs) are promising catalysts provided by nature that are able to accomplish this task in just one step, avoiding over-reduction to the alcohol product. However, the heterologous expression of CARs can be quite difficult due to the excessive formation of insoluble protein, thus hindering further characterization and application of the enzyme. Here, the heterologous production of the carboxylate reductase from Nocardia otitidiscaviarum (NoCAR) was optimized by a combination of i) optimized cultivation conditions, ii) post-translational modification with a phosphopantetheinyl transferase and iii) selection of an appropriate expression strain. Especially, the selection of Escherichia coli tuner cells as host had a strong effect on the final 110-fold increase in the specific activity of NoCAR. This highly active NoCAR was used to reduce sodium benzoate to benzaldehyde, and it was successfully assembled with an in vitro regeneration of ATP and NADPH, being capable of reducing about 30 mM sodium benzoate with high selectivity in only 2 h of reaction.     

Impact of Si on Microstructure and Mechanical Properties of 22MnB5 Hot Stamping Steel Treated by Quenching & Partitioning (Q&P)

Based on 22MnB5 hot stamping steel, three model alloys containing 0.5, 0.8, and 1.5 wt pct Si were produced, heat treated by quenching and partitioning (Q&P), and characterized. Aided by DICTRA calculations, the thermal Q&P cycles were designed to fit into industrial hot stamping by keeping partitioning times ≤ 30 seconds. As expected, Si increased the amount of retained austenite (RA) stabilized after final cooling. However, for the intermediate Si alloy the heat treatment exerted a particularly pronounced influence with an RA content three times as high for the one-step process compared to the two-step process. It appeared that 0.8 wt pct Si sufficed to suppress direct cementite formation from within martensite laths but did not sufficiently stabilize carbon-soaked RA at higher temperatures. Tensile and bending tests showed strongly diverging effects of austenite on ductility. Total elongation improved consistently with increasing RA content independently from its carbon content. In contrast, the bending angle was not impacted by high-carbon RA but deteriorated almost linearly with the amount of low-carbon RA.