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Classification of age groups and task conditions provides additional evidence for differences in electrophysiological correlates of inhibitory control across the lifespan
No full textThe aim of this study was to extend previous findings on selective attention over a lifetime using machine learning procedures. By decoding group membership and stimulus type, we aimed to study differences in the neural representation of inhibitory control across age groups at a single-trial level. We re-analyzed data from 211 subjects from six age groups between 8 and 83 years of age. Based on single-trial EEG recordings during a flanker task, we used support vector machines to predict the age group as well as to determine the presented stimulus type (i.e., congruent, or incongruent stimulus). The classification of group membership was highly above chance level (accuracy: 55%, chance level: 17%). Early EEG responses were found to play an important role, and a grouped pattern of classification performance emerged corresponding to age structure. There was a clear cluster of individuals after retirement, i.e., misclassifications mostly occurred within this cluster. The stimulus type could be classified above chance level in ~ 95% of subjects. We identified time windows relevant for classification performance that are discussed in the context of early visual attention and conflict processing. In children and older adults, a high variability and latency of these time windows were found. We were able to demonstrate differences in neuronal dynamics at the level of individual trials. Our analysis was sensitive to mapping gross changes, e.g., at retirement age, and to differentiating components of visual attention across age groups, adding value for the diagnosis of cognitive status across the lifespan. Overall, the results highlight the use of machine learning in the study of brain activity over a lifetime
Concerto à 4 D-Dur für Traversflöte, Oboe d’amore, Violine und Basso continuo (D-RH Ms 161)
No full textDas Musikleben in den Residenzen Hohenlimburg und Rheda unter Graf Moritz Casimir I. von Bentheim-Tecklenburg (1701-1768) wurde maßgeblich von Johann Martin Doemming (geb. 1703 in Milz/Thüringen, gest. um 1760) geprägt. Über die musikalische Ausbildung des Verwaltungsangestellten Doemming ist nichts bekannt, jedoch muss sie so fundiert gewesen sein, dass er 1731 zum "Directore musices" bestellt wurde. Doemming hat zahlreiche Kompositionen für den Gebrauch der Hofmusik hinterlassen, insbesondere konzertante Musik für Bläser, Streicher und Basso continuo. Unter seiner Leitung wurde 1750 ein thematischer "Catalogus musicus" angelegt, der das Repertoire der Hofkapelle während der Regierungszeit von Moritz Casimir I. widerspiegelt. Die erhaltenen Werke von Johann Martin Doemming sind - vielfach als Autograph - ausschließlich in der Fürstlich zu Bentheim-Tecklenburgischen Musikbibliothek Rheda überliefert
Corporate Social Responsibility and Sustainable Human Resources Management Practices Among the Millennial Workforce in the Chemical Industry in Ireland
No full textCompanies around the globe are struggling to find the right talent. Therefore, the concepts of talent attraction and talent retention are central. Millennials are the most significant generational group in the current labor market in Ireland and worldwide. This study connects the Millennial workforce with Corporate Social Responsibility (CSR) and Sustainable Human Resource Management (SHRM) practices through the lens of a green employer brand, using the framework of Social Identity Theory (SIT). Consequently, this study poses the question: What relevance does the Millennial workforce in Ireland place on CSR and SHRM when considering employment with a company? A survey was conducted using non-probability and snowball sampling techniques. Data were collected from 100 individuals who were part of the job market in Ireland. The data were analyzed using SPSS 26 for both descriptive and inferential statistical analysis. Two simple t-tests were conducted to analyze the relationship between the variables, which provided several practical implications
Evidence of Neutrophils and Neutrophil Extracellular Traps in Human NMSC with Regard to Clinical Risk Factors, Ulceration and CD8^+ T Cell Infiltrate
No full textNon-melanoma skin cancers (NMSC), including basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and Merkel cell carcinoma (MCC), are increasingly common and present significant healthcare challenges. Neutrophil extracellular traps (NETs), chromatin fibers expulsed by neutrophil granulocytes, can promote immunotherapy resistance via an impairment of CD8^+ T cell-mediated cytotoxicity. Here, to identify a potential therapeutic target, we investigate the expulsion of NETs and their relation to CD8^+ T cell infiltration in NMSC. Immunofluorescence staining for neutrophils (CD15) and NETs (H3cit), as well as immunohistochemistry for cytotoxic T cells (CD8^+) on human cSCCs (n = 24), BCCs (n = 17) and MCCs (n = 12), revealed a correlation between neutrophil infiltration and ulceration diameter in BCC and MCC, but not in cSCC. In BCC and cSCC, neutrophil infiltration also correlated with the cross-sectional area (CSA). NETs were not associated with established risk factors but with the presence of an ulceration, and, in cSCC, with abscess-like structures. CD8^+ T cell infiltration was not reduced in tumors that were NET-positive nor in those with a denser neutrophil infiltration. This study is the first to report and characterize NETs in NMSC. Thus, it gives an incentive for further research in this relevant yet understudied topic
High-Voltage Instability of Vinylene Carbonate (VC): Impact of Formed Poly-VC on Interphases and Toxicity
No full textFull exhaustion in specific energy/energy density of state-of-the-art LiNixCoyMnzO2 (NCM)-based Li-ion batteries (LIB) is currently limited for reasons of NCM stability by upper cut-off voltages (UCV) below 4.3 V. At higher UCV, structural decomposition triggers electrode crosstalk in the course of enhanced transition metal dissolution and leads to severe specific capacity/energy fade; in the worst case to a sudden death phenomenon (roll-over failure). The additive lithium difluorophosphate (LiDFP) is known to suppress this by scavenging dissolved metals, but at the cost of enhanced toxicity due to the formation of organofluorophosphates (OFPs). Addition of film-forming electrolyte additives like vinylene carbonate (VC) can intrinsically decrease OFP formation in thermally aged LiDFP-containing electrolytes, though the benefit of this dual-additive approach can be questioned at higher UCVs. In this work, VC is shown to decrease the formation of potentially toxic OFPs within the electrolyte during cycling at conventional UCVs but triggers OFP formation at higher UCVs. The electrolyte contains soluble VC-polymerization products. These products are formed at the cathode during VC oxidation (and are found within the cathode electrolyte interphase (CEI), suggesting an OFP electrode crosstalk of VC decomposition species, as the OFP-precursor molecules are shown to be formed at the anode
Individual Decisions on Tax Use
No full textEs wird vorgeschlagen, die individuellen Steuerzahler jeweils entscheiden zu lassen, wofür die von ihnen gezahlten Steuern verwendet werden sollen, z. B. durch Zuweisung an einzelne Haushaltstitel oder größere Positionen im Staatshaushalt. Außerdem sollen die Steuerzahler wählen dürfen, diese Haushaltsentscheidungen weiterhin den gewählten Politikern zu überlassen oder Steuergelder zurückzuerstatten, jedoch nicht in Form eines individuellen Steuerrabatts, der quasi die zur Finanzierung von Kollektivgütern sinnvolle Steuerpflicht aufheben würde, sondern anteilig über einen Sondertopf, der individuell befüllt und proportional an alle Steuerzahler ausgeschüttet wird.It is proposed that individual taxpayers be allowed to decide how the taxes they pay should be used, for example, by allocating them to specific or larger budget items in the state budget. Furthermore, taxpayers should be allowed to choose whether to continue to leave these budgetary decisions to elected politicians or to refund tax revenues. However, this refund should not be done in the form of an individual tax rebate, which would essentially eliminate the tax liability that is useful for financing public goods, but rather proportionally through a special fund that is individually funded and distributed proportionally to all taxpayers
Is long time to reimplantation a risk factor for reinfection in two-stage revision for periprosthetic infection? A systematic review of the literature
No full textThe two-stage revision arthroplasty is a common treatment option for chronic periprosthetic infection (PJI). The time to reimplantation (TTR) reported in the literature varies substantially from a few days to several hundred days. It is hypothesized that longer TTR could be associated with worse infection control after second stage. A systematic literature search was performed according to Preferred Reporting items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in Pubmed, Cochrane Library and Web of Science Core Collection in clinical studies published until January 2023. Eleven studies investigating TTR as a potential risk factor for reinfection met the inclusion criteria (ten retrospective and one prospective study, published 2012–2022). Study design and outcome measures differed notably. The cutoff points above which TTR was regarded as “long” ranged from 4 to 18 weeks. No study observed a benefit for long TTR. In all studies, similar or even better infection control was observed for short TTR. The optimal TTR, however, is not yet defined. Larger clinical studies with homogeneous patient populations and adjustment for confounding factors are needed
One Dianionic Luminophore with Three Coordination Modes Binding Four Different Metals: Toward Unexpectedly Phosphorescent Transition Metal Complexes
No full textThis work reports on a battery of coordination compounds featuring a versatile dianionic luminophore adopting three different coordination modes (mono, bi, and tridentate) while chelating Pd(II), Pt(II), Au(III), and Hg(II) centers. An in-depth structural characterization of the ligand precursor (H2L) and six transition metal complexes ([HLPdCNtBu], [LPtCl], [LPtCNtBu], [LPtCNPhen], [HLHgCl], and [LAuCl]) is presented. The influence of the cations and coordination modes of the luminophore and co-ligands on the photophysical properties (including photoluminescence quantum yields (ΦL), excited state lifetimes (τ), and average (non-)radiative rate constants) are evaluated at various temperatures in different phases. Five complexes show interesting photophysical properties at room temperature (RT) in solution. Embedment in frozen glassy matrices at 77 K significantly boosts their luminescence by suppressing radiationless deactivation paths. Thus, the Pt(II)-based compounds provide the highest efficiencies, with slight variations upon exchange of the ancillary ligand. In the case of [HLPdCNtBu], both ΦL and τ increase over 30-fold as compared to RT. Furthermore, the Hg(II) complex achieves, for the first time in its class, a ΦL exceeding 60% and millisecond-range lifetimes. This demonstrates that a judicious ligand design can pave the way toward versatile coordination compounds with tunable excited state properties
Phagocytic cell death leads to enhanced release of pro-inflammatory S100A12 in familial Mediterranean fever
No full textBackground: Familial Mediterranean fever (FMF) is a prototypical autoinflammatory syndrome associated with phagocytic cell activation. Pyrin mutations are the genetic basis of this disease, and its expression has been shown in monocytes, granulocytes, dendritic cells, and synovial fibroblasts. Pyrin functions as a cytosolic pattern recognition receptor and forms a distinct pyrin inflammasome. The phagocyte-specific protein S100A12 is predominantly expressed in granulocytes and belongs to the group of damage associated molecular patterns (DAMP). S100A12 can be detected at massively elevated levels in the serum of FMF patients, even in clinically inactive disease. Whether this is crucial for FMF pathogenesis is as yet unknown, and we therefore investigated the mechanisms of S100A12 release from granulocytes of FMF patients presenting clinically inactive. Results: We demonstrate that FMF neutrophils from patients in clinical inactive disease possess an intrinsic activity leading to cell death even in exogenously unstimulated neutrophils. Cell death resembles NETosis and is dependent on ROS and pore forming protein gasdermin D (GSDMD), as inhibitors for both are capable of completely block cell death and S100A12 release. When pyrin-activator TcdA ('Clostridium difficile' toxin A) is used to stimulate, neutrophilic cell death and S100A12 release are significantly enhanced in neutrophils from FMF patients compared to neutrophils from HC. Conclusions: We are able to demonstrate that activation threshold of neutrophils from inactive FMF patients is decreased, most likely by pre-activated pyrin. FMF neutrophils present with intrinsically higher ROS production, when cultured ex vivo. This higher baseline ROS activity leads to increased GSDMD cleavage and subsequent release of, e.g., S100A12, and to increased cell death with features of NETosis and pyroptosis. We show for the first time that cell death pathways in neutrophils of inactive FMF patients are easily triggered and lead to ROS- and GSDMD-dependent activation mechanisms and possibly pathology. This could be therapeutically addressed by blocking ROS or GSDMD cleavage to decrease inflammatory outbreaks when becoming highly active
Pseudomonadal itaconate degradation gene cluster encodes enzymes for methylsuccinate utilization
No full textVerzweigtkettige C5-Dicarbonsäuren (z. B. Citramalat, Mesaconat oder Methylsuccinat) und ihre CoA-Ester sind wichtige Zwischenprodukte im bakteriellen Stoffwechsel, während Itaconat ein antimikrobielles Wirkstoff, ein wirksamer Immunmodulator und ein Wachstumssubstrat für viele Bakterien ist. Der Itaconat-Abbauweg besteht aus drei Reaktionen, die durch Itaconat-CoA-Transferase, Itaconyl-CoA-Hydratase und (S)-Citramalyl-CoA-Lyase katalysiert werden, die in einem Cluster kodiert sind, der in saprophytischen Bakterien zwei zusätzliche Gene für eine putative Acyl-CoA-Dehydrogenase und ein Protein der MmgE/PrpD-Familie enthält. Hier haben wir diese Proteine aus Cupriavidus necator und Pseudomonas aeruginosa heterolog produziert und gezeigt, dass sie die (RS)-Methylsuccinyl-C4-CoA-Dehydrogenase- bzw. eine (S)-(R)-Methylsuccinat-Isomerase-Reaktion katalysieren. Zusammen mit der Itaconat-CoA-Transferase, die gegenüber (R)-Methylsuccinat hochaktiv ist, aber nur eine geringe Aktivität gegenüber (S)-Methylsuccinat aufweist, ermöglichen diese Enzyme die Verwertung beider Stereoisomere von Methylsuccinat. Unsere bioinformatische Analyse ergab, dass 1,6 % der sequenzierten Prokaryoten (hauptsächlich Betaproteobacteria) eine identifizierte Methylsuccinat-Isomerase besitzen. Die Analyse der konservierten Aminosäuren von Methylsuccinat-Isomerase und anderen MmgE/PrpD-Proteinen legt nahe, dass sie einen gemeinsamen katalytischen Mechanismus über die Bildung eines Enolat-Zwischenprodukts haben. Das Vorhandensein spezifischer Methylsuccinat-Verwertungsgene im Itaconat-Abbaucluster, der in saprophytischen Bakterien weit verbreitet ist, deutet auf die Bedeutung von Methylsuccinat in der Umwelt hin.Branched-chain C5-dicarboxylic acids (e.g., citramalate, mesaconate or methylsuccinate) and their CoA-esters are important intermediates in bacterial metabolism, while itaconate is an antimicrobial agent, a potent immunomodulator and a growth substrate for many bacteria. The itaconate degradation pathway consists of three reactions catalyzed by itaconate CoA transferase, itaconyl-CoA hydratase and (S)-citramalyl-CoA lyase encoded in a cluster, which in saprophytic bacteria contains two additional genes for a putative acyl-CoA dehydrogenase and a protein of the MmgE/PrpD family. Here, we heterologously produced the corresponding proteins from Cupriavidus necator and Pseudomonas aeruginosa and showed that they catalyze the (RS)-methylsuccinyl-C4-CoA dehydrogenase and an (S)-(R)-methylsuccinate isomerase reaction, respectively. Together with itaconate CoA transferase, which is highly active with (R)-methylsuccinate but has low activity with (S)-methylsuccinate, these enzymes allow the utilization of both stereoisomers of methylsuccinate. Our bioinformatic analysis revealed that 1.6% of the sequenced prokaryotes (mainly Betaproteobacteria) possess an identified methylsuccinate isomerase. Analysis of the conserved amino acids of methylsuccinate isomerase and other MmgE/PrpD proteins suggests that they share a common catalytic mechanism via the formation of an enolate intermediate. The presence of specific methylsuccinate utilization genes in the itaconate degradation cluster, which is widespread in saprophytic bacteria, suggests the importance of methylsuccinate in the environment