Superconducting Quantum Metamaterials from High Pressure Melt Infiltration of Metals into Block Copolymer Double Gyroid Derived Ceramic Templates

Mesoscale order can lead to emergent properties including phononic bandgaps or topologically protected states. Block copolymers offer a route to mesoscale periodic architectures, but their use as structure directing agents for metallic materials has not been fully realized. A versatile approach to mesostructured metals via bulk block copolymer self-assembly derived ceramic templates, is demonstrated. Molten indium is infiltrated into mesoporous, double gyroidal silicon nitride templates under high pressure to yield bulk, 3D periodic nanocomposites as free-standing monoliths which exhibit emergent quantum-scale phenomena. Vortices are artificially introduced when double gyroidal indium metal behaves as a type II superconductor, with evidence of strong pinning centers arrayed on the order of the double gyroid lattice size. Sample behavior is reproducible over months, showing high stability. High pressure infiltration of bulk block copolymer self-assembly based ceramic templates is an enabling tool for studying high-quality metals with previously inaccessible architectures, and paves the way for the emerging field of block-copolymer derived quantum metamaterials.     

Optimized Biocatalytic Synthesis of 2-Selenopyrimidine Nucleosides by Transglycosylation**

Selenium-modified nucleosides are powerful tools to study the structure and function of nucleic acids and their protein interactions. The widespread application of 2-selenopyrimidine nucleosides is currently limited by low yields in established synthetic routes. Herein, we describe the optimization of the synthesis of 2-Se-uridine and 2-Se-thymidine derivatives by thermostable nucleoside phosphorylases in transglycosylation reactions using natural uridine or thymidine as sugar donors. Reactions were performed at 60 or 80 °C and at pH 9 under hypoxic conditions to improve the solubility and stability of the 2-Se-nucleobases in aqueous media. To optimize the conversion, the reaction equilibria in analytical transglycosylation reactions were studied. The equilibrium constants of phosphorolysis of the 2-Se-pyrimidines were between 5 and 10, and therefore differ by an order of magnitude from the equilibrium constants of any other known case. Hence, the thermodynamic properties of the target nucleosides are inherently unfavorable, and this complicates their synthesis significantly. A tenfold excess of sugar donor was needed to achieve 40−48 % conversion to the target nucleoside. Scale-up of the optimized conditions provided four Se-containing nucleosides in 6–40 % isolated yield, which compares favorably to established chemical routes.     

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.     

ACHEMA 2022: Membranes and Membrane Processes

Numerous companies working in the field of membrane development, membrane production, and membrane separation engineering were present at ACHEMA 2022. Compared to the last ACHEMA in 2018, there were fewer attending companies and only few new topics since development has been blocked partially by the pandemic situation and the subsequent restrictions of this years. Nevertheless, some new developments have been identified concerning process design as well as ceramic and polymeric systems.     

Construction and evaluation of gRNA arrays for multiplex CRISPR-Cas9

Endonuclease system CRISPR-Cas9 represents a powerful toolbox for the budding yeast's Saccharomyces cerevisiae genome perturbation. The resulting double-strand breaks are preferentially repaired via highly efficient homologous recombination, which subsequently leads to marker-free genome editing. The goal of this study was to evaluate precise targeting of multiple loci simultaneously. To construct an array of independently expressing guide RNAs (gRNAs), the genes encoding them were assembled through a BioBrick construction procedure. We designed a multiplex CRISPR-Cas9 system for targeting 6 marker genes, whereby the gRNA array was expressed from a single plasmid. To evaluate the performance of the gRNA array, the activity of the designed system was assessed by the success rate of the introduction of perturbations within the target loci: successful gRNA expression, followed by target DNA double-strand breaks formation and their repair by homologous recombination led to premature termination of the coding sequence of the marker genes, resulting in the prevention of growth of the transformants on the corresponding selection media. In conclusion, we successfully introduced up to five simultaneous perturbations within single cells of yeast S. cerevisiae using the multiplex CRISPR-Cas9 system. While this has been done before, we here present an alternative sequential BioBrick assembly with the capability to accommodate many highly similar gRNA-expression cassettes, and an exhaustive evaluation of their performance.     

Click-Chemistry (CuAAC) Trimerization of an αvβ6 Integrin Targeting Ga-68-Peptide: Enhanced Contrast for in-Vivo PET Imaging of Human Lung Adenocarcinoma Xenografts

α_vβ₆ Integrin is an epithelial transmembrane protein that recognizes latency-associated peptide (LAP) and primarily activates transforming growth factor beta (TGF-β). It is overexpressed in carcinomas (most notably, pancreatic) and other conditions associated with α_vβ₆ integrin-dependent TGF-β dysregulation, such as fibrosis. We have designed a trimeric Ga-68-labeled TRAP conjugate of the α_vβ₆-specific cyclic pentapeptide SDM17 (cyclo[RGD-Chg-E]-CONH₂) to enhance α_vβ₆ integrin affinity as well as target-specific in-vivo uptake. Ga-68-TRAP(SDM17)₃ showed a 28-fold higher α_vβ₆ affinity than the corresponding monomer Ga-68-NOTA-SDM17 (IC₅₀ of 0.26 vs. 7.4 nM, respectively), a 13-fold higher IC₅₀-based selectivity over the related integrin α_vβ₈ (factors of 662 vs. 49), and a threefold higher tumor uptake (2.1 vs. 0.66 %ID/g) in biodistribution experiments with H2009 tumor-bearing SCID mice. The remarkably high tumor/organ ratios (tumor-to-blood 11.2; -to-liver 8.7; -to-pancreas 29.7) enabled high-contrast tumor delineation in PET images. We conclude that Ga-68-TRAP(SDM17)₃ holds promise for improved clinical PET diagnostics of carcinomas and fibrosis.     

Enzymatically Modified Shea Butter and Palm Kernel Oil as Potential Lipid Drug Delivery Matrices

Drug formulations based on lipids can enable a significantly better delivery of a pharmaceutically active substance and thus enhance their bioavailability. However, natural fats and oils usually have properties, which do not allow their direct use for drug delivery. Therefore, we have modified palm kernel oil (PKO) and shea butter (SB) via lipase‐catalyzed transesterification using either glycerol – to create a diglyceride‐enriched lipid – or using hexanoic acid via acidolysis – to alter their fatty acid composition – and hence to improve drug solubility of Celecoxib serving as model compound. The most suitable enzyme was immobilized Thermomyces lanuginosus lipase (Novozyme TL IM). The solubility of Celecoxib as determined in SB, pharmaceutical grade SB, glycerol‐modified SB, hexanoic acid‐modified SB, PKO, glycerol‐modified PKO, and hexanoic acid‐modified PKO. Incorporation of one or two equivalents of hexanoic acid enabled higher Celecoxib solubilization than the diglyceride rich oil. Although structured SB and PKO (15.8 ± 0.4 mg mL^?1) do not differ significantly (p < 0.05) as per the amount of Celecoxib dissolved, the use of the modified oils enhanced Celecoxib solubility in SB (15.5 ± 1.3 mg mL^?1) in comparison to shea butter (7.9 ± 0.5 mg mL^?1). The lipase‐catalyzed modification also improved the miscibility of the oils with surfactants such as Tween 20 and resulted in reduced droplet sizes (<70 nm at oil/surfactant ratios of 1:2 and 1:1) and reduced polydispersity index values of the resulting emulsions. Practical Application: The structured triglycerides synthesized in this work on the basis of natural shea butter oils could function as suppository bases and oil phase in oral and parenteral lipid‐based formulations for improving the solubility and absorption of poorly soluble drugs. As various lipases with distinct selectivity are available for the enzymatic synthesis of structured triglycerides and useful for this purpose, further tailor‐designed formations should be accessible. With the aim of developing novel lipid drug delivery matrices palm kernel oil (PKO) and shea butter (SB) were modified via lipase‐catalyzed transesterification to alter their fatty acid composition and hence to improve drug solubility of the model compound Celecoxib. Incorporation of one or two equivalents of hexanoic acid enabled better Celecoxib solubilization than the diglyceride‐rich oil. Overall, the successful modification process yielded structured lipids with promising miscibility with selected surfactants and potential enhancement of Celecoxib solubility and thus represents a promising approach for the development of novel safe and effective lipid‐based delivery systems.

     

Mass spectrometry-based metabolomics

This review presents an overview of the dynamically developing field of mass spectrometry-based metabolomics. Metabolomics aims at the comprehensive and quantitative analysis of wide arrays of metabolites in biological samples. These numerous analytes have very diverse physico-chemical properties and occur at different abundance levels. Consequently, comprehensive metabolomics investigations are primarily a challenge for analytical chemistry and specifically mass spectrometry has vast potential as a tool for this type of investigation. Metabolomics require special approaches for sample preparation, separation, and mass spectrometric analysis. Current examples of those approaches are described in this review. It primarily focuses on metabolic fingerprinting, a technique that analyzes all detectable analytes in a given sample with subsequent classification of samples and identification of differentially expressed metabolites, which define the sample classes. To perform this complex task, data analysis tools, metabolite libraries, and databases are required. Therefore, recent advances in metabolomics bioinformatics are also discussed.