A General Light-Driven Organocatalytic Platform for the Activation of Inert Substrates.

Due to their strong covalent bonds and low reduction potentials, activating inert substrates is challenging. Recent advances in photoredox catalysis offered a number of solutions, each of which useful for activating specific inert bonds. Developing a general catalytic platform that can consistently target a broad range of inert substrates would be synthetically useful. Herein, we report a readily available indole thiolate organocatalyst that, upon excitation with 405 nm light, acquires a strongly reducing power. This excited-state reactivity served to activate, by single-electron reduction, strong C-F, C-Cl, and C-O bonds in both aromatic and aliphatic substrates. This catalytic platform was versatile enough to promote the reduction of generally recalcitrant electron-rich substrates (Ered <-3.0 V vs SCE), including arenes that afforded 1,4-cyclohexadienes. The protocol was also useful for the borylation and phosphorylation of inert substrates with a high functional group tolerance. Mechanistic studies identified an excited-state thiolate anion as responsible of the highly reducing reactivity.

[Experiencing leadership in the Corona pandemic in Hessian general hospitals: A descriptive qualitative study]. / Das Erleben der Führungsrolle in der Corona-Pandemie in hessischen Allgemeinkrankenhäusern.

Experiencing leadership in the Corona pandemic in Hessian general hospitals: A descriptive qualitative study Abstract. Background: The second corona pandemic wave is leading to high work demands on the part of nurses and managers of Hessian general hospitals. The associated organizational challenges result in burdens for the managers. Aim: Due to the importance of leaders in securing care structures, this study aims to explore their perception of their leadership role in dealing with the pandemic management. Methods: Telephone qualitative expert interviews with 13 ward and 13 nursing managers of Hessian general hospitals form the basis for the qualitative content analysis that structures the content. Results: To support the nursing staff, the managers choose a personal caring leadership style that also includes the psychosocial needs of the nursing staff. For their part, managers are exposed to high levels of burden, which they counter with professional experience, resilience and an optimistic attitude, among other things. Conclusions: Health-related leadership is essential for maintaining the health of employees. The self care of managers as well as the integration of workplace health promotion into the corporate goal of hospitals should receive more attention for the current and future safeguarding of crisis management.

Lewis Base-Catalysed Enantioselective Radical Conjugate Addition for the Synthesis of Enantioenriched Pyrrolidinones.

We report a catalytic asymmetric protocol for the preparation of chiral pyrrolidinones proceeding via a radical pathway. The chemistry exploits the combination of photoredox catalysis and Lewis base catalysis to realise the first example of asymmetric radical conjugate addition to α,ß-unsaturated anhydrides and esters. The reaction is initiated by photoredox activation of N-arylglycines to generate, upon decarboxylation, α-amino radicals. These radicals are then intercepted stereoselectively by α,ß-unsaturated acyl ammonium intermediates, whose formation is mastered by a chiral isothiourea organocatalyst. Cyclisation leads to catalyst turnover and formation of enantioenriched pyrrolidinones. The utility of the protocol was demonstrated with application to the synthesis of biologically-active γ-amino butyric acids.

Genome-wide linkage analysis of families with primary hyperhidrosis.

Primary focal hyperhidrosis (PFH, OMIM %144110) is a genetically influenced condition characterised by excessive sweating. Prevalence varies between 1.0-6.1% in the general population, dependent on ethnicity. The aetiology of PFH remains unclear but an autosomal dominant mode of inheritance, incomplete penetrance and variable phenotypes have been reported. In our study, nine pedigrees (50 affected, 53 non-affected individuals) were included. Clinical characterisation was performed at the German Hyperhidrosis Centre, Munich, by using physiological and psychological questionnaires. Genome-wide parametric linkage analysis with GeneHunter was performed based on the Illumina genome-wide SNP arrays. Haplotypes were constructed using easyLINKAGE and visualised via HaploPainter. Whole-exome sequencing (WES) with 100x coverage in 31 selected members (24 affected, 7 non-affected) from our pedigrees was achieved by next generation sequencing. We identified four genome-wide significant loci, 1q41-1q42.3, 2p14-2p13.3, 2q21.2-2q23.3 and 15q26.3-15q26.3 for PFH. Three pedigrees map to a shared locus at 2q21.2-2q23.3, with a genome-wide significant LOD score of 3.45. The chromosomal region identified here overlaps with a locus at chromosome 2q22.1-2q31.1 reported previously. Three families support 1q41-1q42.3 (LOD = 3.69), two families share a region identical by descent at 2p14-2p13.3 (LOD = 3.15) and another two families at 15q26.3 (LOD = 3.01). Thus, our results point to considerable genetic heterogeneity. WES did not reveal any causative variants, suggesting that variants or mutations located outside the coding regions might be involved in the molecular pathogenesis of PFH. We suggest a strategy based on whole-genome or targeted next generation sequencing to identify causative genes or variants for PFH.

Phonetic change in an Antarctic winter.

An acoustic analysis was made of the speech characteristics of individuals recorded before and during a prolonged stay in Antarctica. A computational model was used to predict the expected changes due to close contact and isolation, which were then compared with the actual recorded productions. The individuals were found to develop the first stages of a common accent in Antarctica whose phonetic characteristics were in some respects predicted by the computational model. These findings suggest that the phonetic attributes of a spoken accent in its initial stages emerge through interactions between individuals causing speech production to be incrementally updated.

Linking Cognitive and Social Aspects of Sound Change Using Agent-Based Modeling.

The paper defines the core components of an interactive-phonetic (IP) sound change model. The starting point for the IP-model is that a phonological category is often skewed phonetically in a certain direction by the production and perception of speech. A prediction of the model is that sound change is likely to come about as a result of perceiving phonetic variants in the direction of the skew and at the probabilistic edge of the listener's phonological category. The results of agent-based computational simulations applied to the sound change in progress, /u/-fronting in Standard Southern British, were consistent with this hypothesis. The model was extended to sound changes involving splits and mergers by using the interaction between the agents to drive the phonological reclassification of perceived speech signals. The simulations showed no evidence of any acoustic change when this extended model was applied to Australian English data in which /s/ has been shown to retract due to coarticulation in /str/ clusters. Some agents nevertheless varied in their phonological categorizations during interaction between /str/ and /ʃtr/: This vacillation may represent the potential for sound change to occur. The general conclusion is that many types of sound change are the outcome of how phonetic distributions are oriented with respect to each other, their association to phonological classes, and how these types of information vary between speakers that happen to interact with each other.

Direct synthesis of γ-pyrones by electrophilic condensation of ß-ketoesters.

Triflic anhydride is a versatile electrophile that is able to activate poor nucleophiles. Herein, we show that readily available ß-keto esters are activated by Tf2O furnishing γ-pyrones. Mechanistic studies suggest that this transformation proceeds via a double triflation, formation of an oxocarbenium intermediate and dealkylation promoted by a crucial nitrile additive.

The influence of alcoholic intoxication on the short-time energy function of speech.

This study investigates rhythmic features based on the short-time energy function of speech signals with the aim of finding robust, speaker-independent features that indicate speaker intoxication. Data from the German Alcohol Language Corpus, which comprises read, spontaneous, and command&control speech uttered by 162 speakers of both genders and various age groups when sober and intoxicated, were analyzed. Energy contours are compared directly (Root Mean Squared Error, statistical correlation, or the Euclidean distance in the spectral space of the contour) and by parameterization of the contour using the Discrete Cosine Transform (DCT) and the first and second moments of the lower DCT spectrum. Contours are also analyzed by Principal Components Analysis aiming at fundamental "eigen contour" changes that might encode intoxication. Energy contours differ significantly with intoxication in terms of distance measures, the second and fourth DCT coefficients, and the first and second moments of the lower DCT spectrum. Principal Components Analysis did not yield interpretable "eigen contours" that could be used in distinguishing intoxicated from sober contours.

The influence of alcoholic intoxication on the fundamental frequency of female and male speakers.

This study investigates long-term features and utterance contours of fundamental frequency (f0) derived from the German Alcohol Language Corpus. The corpus comprises read, spontaneous, and command&control speech uttered by 148 speakers of both genders and various age groups when sober and intoxicated. f0 median, f0 range, and f0 contours are analyzed for intoxication and interactions with gender and age. Contours are compared both directly (root mean squared error, statistical correlation, or the Euclidean distance in the spectral space of the contour) and by parameterization of the contour using discrete cosine transform and the first and second moment of the lower contour spectrum. Results partly confirm earlier findings, i.e., f0 average and range are mostly raised with intoxication, and also suggest that the majority of speakers do not follow a general trend, but show idiosyncratic alterations to f0. f0 contours differ significantly with intoxication, but a more detailed analysis could not assign these changes to specific general form changes like decline or curvature. The results suggest that it is not possible to predict intoxication from f0 in a single model across different speakers. Instead a speaker-dependent model to account for the individual speaker behavior is proposed.