Micellar Catalysis and Concept in Apolar Media

The active interest aroused by catalytically affected reactions in apolar surfactant solutions requires one to look for a relation to micelle formation and solubilization in an effort to attain a more unified description of phenomena peculiar to apolar surfactant systems. Since these catalytic phenomena are usually summarized by the notion »micellar catalysis« the present paper wants to contribute towards a sound abstraction of this concept. This was done by analyzing a particular catalyzed reaction (the catalyzed hydrolysis of p-nitrophenylacetate in the presence of dodecylammoniumpropionate in cyclohexane) in the frequently investigated apolar solutions of cationic surfactants. A quantitative description of the overall reaction was obtained which was found in satisfactory agreement with experimental details. It was concluded that micellar and multiple association patterns are reflected also in the relationships obtained by examining catalytically influenced reactions in these systems

Immediate and long-term consequences of COVID-19 infections for the development of neurological disease

Increasing evidence suggests that infection with Sars-CoV-2 causes neurological deficits in a substantial proportion of affected patients. While these symptoms arise acutely during the course of infection, less is known about the possible long-term consequences for the brain. Severely affected COVID-19 cases experience high levels of proinflammatory cytokines and acute respiratory dysfunction and often require assisted ventilation. All these factors have been suggested to cause cognitive decline. Pathogenetically, this may result from direct negative effects of the immune reaction, acceleration or aggravation of pre-existing cognitive deficits, or de novo induction of a neurodegenerative disease. This article summarizes the current understanding of neurological symptoms of COVID-19 and hypothesizes that affected patients may be at higher risk of developing cognitive decline after overcoming the primary COVID-19 infection. A structured prospective evaluation should analyze the likelihood, time course, and severity of cognitive impairment following the COVID-19 pandemic

Depth profile analyses of films grown at different temperatures

Cu(In,Ga)Se2films are used as absorber layers in chalcopyrite thin filmsolar cells. As the gallium concentration in the absorber can be used to control the band gap, there have been many efforts to vary the gallium concentration in depth to gain an optimum balance of light absorption, carrier collection, and recombination at different depths of the absorber film, leading to improved quantum efficiency. In this study, we investigate the effect of the maximum substrate temperature during film growth on the depth dependent gallium concentration. For the in-depth gallium concentration analyses, we use two techniques, covering complementary depth ranges. Angle dependent soft x-ray emission spectroscopy provides access to information depths between 20 and 470 nm, which covers the depth range of the space charge region, where most of the photoexcited carriers are generated. Therefore, this depth range is of particular interest. To complement this investigation we use secondary neutral mass spectrometry, which destructively probes the whole thickness of the absorber (≈2 μm). The two methods show increasingly pronounced gallium and indium gradients with decreasing maximum substrate temperature. The probing of the complementary depth ranges of the absorbers gives a consistent picture of the in-depth gallium distribution, which provides a solid basis for a comprehensive discussion about the effect of a reduced substrate temperature on the formation of gallium gradients in Cu(In,Ga)Se2 and the device performance of the corresponding reference solar cells

Chemical genetics reveals a kinase-independent role for protein kinase R in pyroptosis

Formation of the inflammasome, a scaffolding complex that activates caspase-1, is important in numerous diseases. Pyroptotic cell death induced by anthrax lethal toxin (LT) is a model for inflammasome-mediated caspase-1 activation. We discovered 7-desacetoxy-6,7-dehydrogedunin (7DG) in a phenotypic screen as a small molecule that protects macrophages from LT-induced death. Using chemical proteomics, we identified protein kinase R (PKR) as the target of 7DG and show that RNAi knockdown of PKR phenocopies treatment with 7DG. Further, we show that PKR's role in ASC assembly and caspase-1 activation induced by several different inflammasome stimuli is independent of PKR's kinase activity, demonstrating that PKR has a previously uncharacterized role in caspase-1 activation and pyroptosis that is distinct from its reported kinase-dependent roles in apoptosis and inflammasome formation in lipopolysaccharide-primed cells. Remarkably, PKR has different roles in two distinct cell death pathways and has a broad role in inflammasome function relevant in other diseases

Resolution of Racemic Guaifenesin Applying a Coupled Preferential Crystallization-Selective Dissolution Process: Rational Process Development

Preferential crystallization is a cost efficient method to provide pure enantiomers from a racemic mixture of a conglomerate forming system. Exploiting small amounts of pure crystals of both enantiomers, several batch or continuous processes were developed, capable of providing both species. However, an intermediate production step has to be used when pure enantiomers are not available. In such cases, partially selective synthesis, chromatography, or crystallization processes utilizing chiral auxiliaries have to be used to provide the initial seed material. Recently, it was shown that a coupled Preferential Crystallization-selective Dissolution process (CPCD) in two coupled crystallizers can be applied if at least one pure enantiomer is available to produce both antipodes within one batch. The corresponding process is carried out in one reactor (crystallization tank) by seeding a racemic supersaturated solution with the available enantiomer at a certain temperature. The second reactor (dissolution tank) contains a saturated racemic suspension at a higher temperature. Both reactors are coupled via the fluid phase, allowing for a selective dissolution of the preferentially crystallizing enantiomer from the solid racemic feed provided in the dissolution vessel. The dissolution and crystallization processes continue until the solid racemic material is completely resolved and becomes enantiopure. At this point, both enantiomers can be harvested in their pure crystalline form. For a specific pharmaceutically relevant case study, a rational process design and the applied empirical optimization procedure will be described. The achieved productivities after optimization show the great potential of this approach also for industrial applications. Also, a strategy to control this process based on inline turbidity measurement will be presented

Gallium gradients in chalcopyrite thin films: Depth profile analyses of films grown at different temperatures

The following article appeared in Journal of Applied Physics 110.9 (2011): 093509 and may be found at http://scitation.aip.org/content/aip/journal/jap/110/9/10.1063/1.3656986Cu(In,Ga)Se2 films are used as absorber layers in chalcopyrite thin film solar cells. As the gallium concentration in the absorber can be used to control the band gap, there have been many efforts to vary the gallium concentration in depth to gain an optimum balance of light absorption, carrier collection, and recombination at different depths of the absorber film, leading to improved quantum efficiency. In this study, we investigate the effect of the maximum substrate temperature during film growth on the depth dependent gallium concentration. For the in-depth gallium concentration analyses, we use two techniques, covering complementary depth ranges. Angle dependent soft x-ray emission spectroscopy provides access to information depths between 20 and 470 nm, which covers the depth range of the space charge region, where most of the photoexcited carriers are generated. Therefore, this depth range is of particular interest. To complement this investigation we use secondary neutral mass spectrometry, which destructively probes the whole thickness of the absorber (≈2 µm). The two methods show increasingly pronounced gallium and indium gradients with decreasing maximum substrate temperature. The probing of the complementary depth ranges of the absorbers gives a consistent picture of the in-depth gallium distribution, which provides a solid basis for a comprehensive discussion about the effect of a reduced substrate temperature on the formation of gallium gradients in Cu(In,Ga)Se2 and the device performance of the corresponding reference solar cells.The authors acknowledge the support of the European Commission in the framework of the ATHLET-project (Project No. 019670)

Sequence-dependent off-target inhibition of TLR7/8 sensing by synthetic microRNA inhibitors

Anti-microRNA (miRNA) oligonucleotides (AMOs) with 2\u27-O-Methyl (2\u27OMe) residues are commonly used to study miRNA function and can achieve high potency, with low cytotoxicity. Not withstanding this, we demonstrate the sequence-dependent capacity of 2\u27OMe AMOs to inhibit Toll-like receptor (TLR) 7 and 8 sensing of immunostimulatory RNA, independent of their miRNA-targeting function. Through a screen of 29 AMOs targeting common miRNAs, we found a subset of sequences highly inhibitory to TLR7 sensing in mouse macrophages. Interspecies conservation of this inhibitory activity was confirmed on TLR7/8 activity in human peripheral blood mononuclear cells. Significantly, we identified a core motif governing the inhibitory activity of these AMOs, which is present in more than 50 AMOs targeted to human miRNAs in miRBaseV20. DNA/locked nucleic acids (LNA) AMOs synthesized with a phosphorothioate backbone also inhibited TLR7 sensing in a sequence-dependent manner, demonstrating that the off-target effects of AMOs are not restricted to 2\u27OMe modification. Taken together, our work establishes the potential for off-target effects of AMOs on TLR7/8 function, which should be taken into account in their therapeutic development and in vivo application