Johns Weiss (organchill17)

Increasing both the sensitivity and selectivity of thiol-functionalized gold nanoparticle chemiresistors remains a challenging issue in the quest to develop real-time gas sensors. The effects of thiol molecular structure on such sensor properties are not well understood. This study investigates the effects of steric as well as electronic effects in a panel of substituted thiol-urea compounds on the sensing properties of thiolate monolayer-protected gold nanoparticle chemiresistors. Three series of urea-substituted thiols with different peripheral end groups were synthesized for the study and used to prepare gold nanoparticle-based chemiresistors. The responses of the prepared sensors to trace volatile analytes were significantly affected by the urea functional motifs. The largest response for sensing acetone among the three series was observed for the thiol-urea sensor featuring a tert-butyl end group. Furthermore, the ligands fitted with N, N'-dialkyl urea moieties exhibit a much larger response to carbonyl analytes than the more acidic urea series containing N-alkoxy-N'-alkyl urea and N, N'-dialkoxy urea groups with the same peripheral end groups. The results show that the peripheral molecular structure of thiolate-coated gold nanoparticles plays a critical role in sensing target analytes.Physiologically-based pharmacokinetic (PBPK) modeling is a well-recognized method for quantitatively predicting the effect of intrinsic/extrinsic factors on drug exposure. However, there are only few verified, freely accessible, modifiable, and comprehensive drug-drug interaction (DDI) PBPK models. We developed a qualified whole-body PBPK DDI network for cytochrome P450 (CYP) CYP2C19 and CYP1A2 interactions. Template PBPK models were developed for interactions between fluvoxamine, S-mephenytoin, moclobemide, omeprazole, mexiletine, tizanidine, and ethinylestradiol as the perpetrators or victims. Predicted concentration-time profiles accurately described a validation dataset, including data from patients with genetic polymorphisms, demonstrating that the models characterized the CYP2C19 and CYP1A2 network over the whole range of DDI studies investigated. The models are provided on GitHub (GitHub Inc., San Francisco, CA, USA), expanding the library of publicly available qualified whole-body PBPK models for DDI predictions, and they are thereby available to support potential recommendations for dose adaptations, support labeling, inform the design of clinical DDI trials, and potentially waive those.The aromatic heterocyclic compound indole is widely spread in nature. Due to its floral odor indole finds application in dairy, flavor, and fragrance products. Indole is an inter- and intracellular signaling molecule influencing cell division, sporulation, or virulence in some bacteria that synthesize it from tryptophan by tryptophanase. Corynebacterium glutamicum that is used for the industrial production of amino acids including tryptophan lacks tryptophanase. To test if indole is metabolized by C. glutamicum or has a regulatory role, the physiological response to indole by this bacterium was studied. As shown by RNAseq analysis, indole, which inhibited growth at low concentrations, increased expression of genes involved in the metabolism of iron, copper, and aromatic compounds. In part, this may be due to iron reduction as indole was shown to reduce Fe3+ to Fe2+ in the culture medium. IDE397 cell line Mutants with improved tolerance to indole were selected by adaptive laboratory evolution. Among the mutations identified by genome sequencing, mutations in three transcriptional regulator genes were demonstrated to be causal for increased indole tolerance. These code for the regulator of iron homeostasis DtxR, the regulator of oxidative stress response RosR, and the hitherto uncharacterized Cg3388. Gel mobility shift analysis revealed that Cg3388 binds to the intergenic region between its own gene and the iolT2-rhcM2D2 operon encoding inositol u