Brigitte Wex

The generation and evaluation of chemical reactions remain challenging with limited comprehensive studies addressing these issues. We introduce the Chemical Reaction (Rxn) Systematic Assessment of Generation and Evaluation (ChemRxnSAGE) framework, an adaptable end-to-end approach for evaluating the quality, validity, and diversity of machine-generated chemical reactions. Combining automated validity filters with quality metrics and expert insights, ChemRxnSAGE systematically eliminates invalid reactions. We tested its robustness using generative models, including Recurrent Neural Networks and Variational Autoencoders, followed by validation using a chemical "Turing test" with domain experts. Additionally, we assess reaction feasibility through thermodynamic analysis and compare the generated reactions against existing literature to ensure relevance and novelty. By combination of computational tools with expert-driven metrics, ChemRxnSAGE offers a comprehensive and extendable solution that advances the state of chemical reaction generation and evaluation.

Five alkylated derivatives of pyrene laterally extended by heteroaromatic or phenyl groups were explored by DFT and TD-DFT for spectroscopic, electronic and charge transfer properties and contrasted to nascent pyrene, alkylated pyrene and tetracene.

2,7-Bis(3,3′′,6,6′′-tetra(tert-butyl)-9′H-9,3′:6′,9′′-tercarbazol-9-yl)-4,5,9,10-tetrahydropyrene (3) and 2,7-bis(3,3′′,6,6′′-tetra(tert-butyl)-9′H-9,3′:6′,9′′-tercarbazol-9-yl)pyrene (4), along with a model compound, 3,3′′,6,6′′-tetra(tert-butyl)-9′-(4-(tert-butyl)phenyl)-9′H-9,3′:6′,9′′-tercarbazole (6), have been synthesized using microwave-assisted palladium-catalyzed coupling and compared to analogous 3,6-di(tert-butyl)carbazol-9-yl species (1, 2, and 5). Time-dependent density functional theory (TDDFT) calculations reveal absorption with quadrupolar (ter)carbazole-to-bridge CT character for 1–4. Compound 4 is unusual in showing dual fluorescence in a number of solvents; the longer wavelength feature of which is markedly more solvatochromic than the bands of the other compounds. Following the observed three oxidations on the TCz model compound 6, compounds 3 and 4 can be electrochemically reversibly oxidized to hexacations with four oxidation and three oxidation steps in a 2 : 2 : 1 : 1 and a 2 : 2 : 2 current ratio, respectively. Tercarbazole derivatives 3 and 4 have been used as the emissive layers of simple solution-processed few-layer organic light-emitting diodes.

Background: Candida albicans is present as part of the normal gut flora and detected in the oral cavities and GI tracts of around fifty percent of adults. Benign colonization can turn pathogenic causing a variety of mild to severe infections. In a pathogen, the cell wall and cell surface proteins are major antigenic determinants and drug targets as they are the primary structures that contact the host. Cell surface proteins perform a variety of functions necessary for virulence such as adhesion, host degradation, resistance to oxidative stress, and drug resistance. We have previously characterized Hwp2, a Candida albicans cell wall adhesin shown to play a major role in the cell wall architecture and function as hwp2 mutants were deficient in chitin deposition, filamentation, adhesion and invasive growth, virulence, and resistance to oxidative stress. Objective/Method: Here, we utilized tandem mass spectrometry coupled with a bioinformatics approach to differentially profile the cell wall proteome of a wild type strain compared to an hwp2 null mutant to determine key differentially expressed proteins. Result: Many proteins identified exclusively in the wild type go a long way in explaining the above-mentioned phenotypes. These include virulence factors such as members of the SAP family including Sap4, Sap5, and Sap10, as well as several lipases involved in host degradation. We also identified members of the PGA family of proteins Pga28, Pga32, Pga41 and Pga50, which function in adhesion, Cht2 a chitinase involved in chitin remodeling, and several proteins that function in promoting filamentation such as Phr1, Mts1, and Rbr1.

SLC35B4, solute receptor for UDP-N-acetylglucosamine and UDP-xylose, is associated with diabetes and predisposing conditions. This study investigated the localization of SLC35B4 and compared the differential expression between a knockdown of SLC35B4 and controls in HepG2. Responsiveness to glucose, expression, and localization were assayed using Western blot and immunostaining. Localization was confirmed using a proximity ligation assay. Two-dimensional (2D) gel electrophoresis and MALDI-TOF were used to identify differentially expressed proteins and pathway analysis was performed. SLC35B4 was increased by 60% upon glucose stimulation and localized in Golgi apparatus and endoplasmic reticulum. Presence of SLC35B4 in the Golgi apparatus suggests its involvement in the biosynthesis of glycoconjugate proteins. Four proteins were markedly under-expressed (Hsp60, HspA8, TUBA1A, and ENO1) and linked to the pathogenesis of diabetes or post-translationally modified by O-GlcNAc. Glucose levels activate SLC35B4 expression. This triggers a downstream effect via Hsp60 and other proteins. We hypothesize that the downstream effect on the proteins is mediated via altering the glycosylation pattern inside liver cells. The downstream cascade ultimately alters the ability of cultured liver cells to inhibit endogenous glucose production, and this could play a role in the association of the above-listed genes with the pathogenesis of diabetes.

We have previously characterized Pir32, a Candia albicans cell wall protein that we found to be involved in filamentation, virulence, chitin deposition, and resistance to oxidative stress. Other than defining the cell shape, the cell wall is critical for the interaction with the surrounding environment and the point of contact and interaction with the host surface. In this study, we applied tandem mass spectrometry combined with bioinformatics to investigate cell wall proteome changes in a pir32 null strain. A total of 16 and 25 proteins were identified exclusively in the null mutant strains grown under non-filamentous and filamentous conditions. These proteins included members of the PGA family with various functions, lipase and the protease involved in virulence, superoxide dismutases required for resisting oxidative stress, alongside proteins required for cell wall remodeling and synthesis such as Ssr1, Xog1, Dfg5 and Dcw1. In addition proteins needed for filamentation like Cdc42, Ssu81 and Ucf1, and other virulence proteins such as Als3, Rbt5, and Csa2 were also detected. The detection of these proteins in the mutant and their lack of detection in the wild type can explain the differential phenotypes previously observed.