Crowdsourcing as a service – from pilot projects to sustainable innovation routines

While crowdsourcing may strengthen a company's innovation performance, it is only rarely embedded in organizations as an innovation practice. Our action research shows that organizations often struggle with crowdsourcing projects as they represent a different form of innovation projects and require additional capabilities and skills e.g., to frame a crowd challenge, deal with IP rights, manage the crowd, or integrate the vast input into innovation projects. To overcome these problems, organizations have to invest in project-led learning to establish easy-to-use templates and routines e.g., to handle offered incentives or the applied winner selection processes. They further need to enable business-led learning as the established innovation structures, processes, and management practices do not cope with crowdsourcing projects and present some rigidities causing high coordination efforts. Organizations that are willing to run a number of consecutive crowdsourcing projects may rapidly improve their capabilities and even come up with scalable crowdsourcing services. Our findings further suggest that crowdsourcing, digital platforms, artificial intelligence, and as-a-service approaches may also add to general project capability building.     

Cell-Based Optimization of Covalent Reversible Ketoamide Inhibitors Bridging the Unprimed to the Primed Site of the Proteasome β5 Subunit

The ubiquitin-proteasome system (UPS) is an established therapeutic target for approved drugs to treat selected hematologic malignancies. While drug discovery targeting the UPS focuses on irreversibly binding epoxyketones and slowly-reversibly binding boronates, optimization of novel covalent-reversibly binding warheads remains largely unattended. We previously reported α-ketoamides to be a promising reversible lead motif, yet the cytotoxic activity required further optimization. This work focuses on the lead optimization of phenoxy-substituted α-ketoamides combining the structure-activity relationships from the primed and the non-primed site of the proteasome β5 subunit. Our optimization strategy is accompanied by molecular modeling, suggesting occupation of P1′ by a 3-phenoxy group to increase β5 inhibition and cytotoxic activity in leukemia cell lines. Key compounds were further profiled for time-dependent inhibition of cellular substrate conversion. Furthermore, the α-ketoamide lead structure 27 does not affect escape response behavior in Danio rerio embryos, in contrast to bortezomib, which suggests increased target specificity.     

Internal and external factors of competitiveness shaping the future of wooden multistory construction in Finland and Sweden

In transitioning to a renewable material-based bio economy, growing public and industry interest is apparent for using wooden multistory construction (WMC) as a sustainable urban housing solution in Europe, but its business implications are not well understood. In our study, we evaluate, which internal and external factors of competitiveness are shaping the future of WMC, especially in the context of Finland and Sweden. Based on a multi-level perspective of socio-technical transitions, we conducted a three-stage dissensus-based Delphi study. The identified internal and external factors affecting the future competitiveness of the WMC business emphasize the importance of skilled architects and builders and the role of standardized building systems. Based on our results, the key aspects influencing the future competitiveness of WMC in the region are related to the development of technical infrastructure and project-based business networks, while additional changes in regulatory framework are perceived as less important. We conclude that towards 2030, the strong cognitive rules founded in the concrete-based building culture in these countries is likely to inhibit the dynamics of the socio-technical regime level. A change is also needed in the WMC business culture towards more open cross-sectoral collaboration and new business networks between different-sized players.     

Modeling and optimal control of human platform diving with somersaults and twists

The model-based investigation of fast dynamic motions of anthropomorphic systems is an interesting interdisciplinary field combining research efforts from applied mathematics, robotics, biomechanics, computer graphics and sports. Somersaults and twists of professional platform divers represent a particularly fascinating and extremely difficult type of motion. The purpose of this paper is to show how optimal control methods based on whole-body dynamic models of the diver can be very useful in generating natural platform diving motions. We present 3D somersaults with twists as well as pure somersaults in the sagittal plane for a variety of different take-off configurations and positions to be attained in the aerial phase that all have been produced by optimization of criteria related to energy input. By formulating the dive as a problem with several dynamic phases, we are able to treat contact and flight phase simultaneously, and also to split the flight phase in several sub-phases to correctly model requested positions in the air. Divers are modeled as multibody systems with actuators and damper elements at each joint. For the solution of the optimal control problem we use efficient direct multiple shooting methods based on the boundary value problem approach. The optimization results can be used to generate motions in computer graphics or robotics, but also provide useful insights into biological motion, including joint kinematics and the required torques and forces.     

Influence of water on the generation of Strecker aldehydes from dry processed foods

Completeness of extraction, losses during isolation and, in particular, the formation of new constituents are challenges during the enrichment of volatiles for GC analysis. Especially the isolation of volatiles by simultaneous steam distillation/extraction has long been known to generate artifacts due to the hot water treatment. However, even a simple treatment of dry foods with cold water may already lead to the release of odour-active volatiles. After treatment of chocolate or cocoa beans with water, the concentrations of the four Strecker aldehydes 2- and 3-methylbutanal, 3-(methylthio)propanal and phenylacetaldehyde were increased by factors between 10 and 100. Also in other dry processed foods, such as malt or crackers, the concentrations of the Strecker aldehydes were substantially increased upon water addition. Although a physical release of the aldehydes weakly bound to, e.g. proteins or starch is possible, in a further experiment, it could be shown that a yet unknown precursor of 3-(methylthio)propanal and phenylacetaldehyde could be isolated by solvent extraction from caramalt and Munich malt. As a consequence, the presence or absence of water during the work-up procedure might either lead to an over- or underestimation of the relevance of the respective aroma compounds, which might also effect aroma formation and perception during the process of eating.     

Reversible collapse and Mg release of de- and rehydroxylated homoionic cis-vacant montmorillonites

Homoionic Na⁺, Ca²⁺, Sr²⁺, Li⁺, Cu²⁺ and Zn²⁺ samples of the <2 μm fraction of a cis-vacant montmorillonite from Linden (Bavaria) were steam treated at 200°C (≈1.5 MPa), 240°C (≈3.3 MPa) and 300°C (≈8.0 MPa) after dehydroxylation at temperatures up to 630°C. Cation exchange capacity (CEC) measurements, determination of exchangeable cations and X-ray diffraction (XRD), supplemented by thermoanalytical investigations of the evolved water in a thermobalance linked to a mass spectrometer, infrared (IR) and electron spin resonance (ESR) spectroscopy were employed to obtain information about the state of expandability and structural changes of swellable montmorillonite and the sites of interlayer and octahedral cations after heating and rehydroxylation.The XRD pattern of the initial samples showed a well-defined (001) reflection according to the interlayer cation and its hydration state under laboratory atmosphere. After dehydroxylation the pattern exhibited (001) reflections between 9.6 and 9.8 Å, corresponding to a collapsed structure for all samples. The Na⁺-, Ca²⁺- and Sr²⁺-rich montmorillonites regained partial expandability after rehydroxylation at 200°C and full expandability after rehydroxylation at 300°C if the dehydroxylation temperature was less than 630°C. Rehydroxylation at 300°C of the Cu²⁺- and Zn²⁺-rich montmorillonites did not cause reexpansion, whereas the Li⁺-rich samples recovered a partial swellability after rehydroxylation at 240°C and nearly the full swellability after rehydroxylation at 300°C.The Li⁺-, Cu²⁺- and Zn²⁺-rich samples underwent a strong CEC reduction due to migration of the interlayer cations into the 2:1 layer before dehydroxylation started. After rehydroxylation under water steam Cu²⁺- and Zn²⁺-rich samples released 16–30 meq/100 g of Mg²⁺ from the structure, increasing with the steam temperature. Mg²⁺ release was not observed for the Li⁺-rich montmorillonite.     

Development of a solid self-microemulsifying drug delivery system (SMEDDS) for solubility enhancement of naproxen

Context: Comparative evaluation of liquid and solid self-microemulsifying drug delivery systems (SMEDDS) as promising approaches for solubility enhancement.

Objective: The aim of this work was to develop, characterize, and evaluate a solid SMEDDS prepared via spray-drying of a liquid SMEDDS based on Gelucire® 44/14 to improve the solubility and dissolution rate of naproxen.

Material and methods: Various oils and co-surfactants in combination with Gelucire® 44/14 were evaluated during excipient selection study, solubility testing, and construction of (pseudo)ternary diagrams. The selected system was further evaluated for naproxen solubility, self-microemulsification ability, and in vitro dissolution of naproxen. In addition, its transformation into a solid SMEDDS by spray-drying using maltodextrin as a solid carrier was performed. Scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were used to evaluate the physical characteristics of the solid SMEDDS obtained.

Results: The selected formulation of SMEDDS was comprised of Miglyol 812®, Peceol?, Gelucire® 44/14, and Solutol® HS 15. The liquid and solid SMEDDS formed a microemulsion after dilution with comparable average droplet size and exhibited uniform droplet size distribution. In the solid SMEDDS, liquid SMEDDS was adsorbed onto the surface of maltodextrin and formed smooth granular particles with the encapsulated drug predominantly in a dissolved state and partially in an amorphous state. Overall, incorporation of naproxen in SMEDDS, either liquid or solid, resulted in improved solubility and dissolution rate compared to pure naproxen.

Conclusion: This study indicates that a liquid and solid SMEDDS is a strategy for solubility enhancement in the future development of orally delivered dosage forms.