Deskription und Bewertung strukturierter Produkte unter besonderer Berücksichtigung verschiedener Marktszenarien

Due to a fast market development in volume and innovation on the structured products (certificates) side, critics are finding fault regarding a lack in transparency and comparability. However, certificates can provide characteristics for every market scenario as its explicit strength. The aim of the following working paper is to provide transparency and an analysis in the most common certificates. The analysis consists of a description, valuation and scenario analysis which then leads to a substantial overview and should provide knowledge which certificate can be used in specific market scenarios. --Financial engineering,strukturierte Produkte,Zertifikate,evaluation by duplication,Discountzertifikate,Aktienanleihe,Doppel-Aktienanleihe,Cheapest-to-deliver-Zertifikat,Bonus-Zertifikat,Sprint-Zertifikat,Outperformance-Zertifikat,Reverse Sprint-Zertifikat,Reverse Outperformance-Zertifikat

Circulating lymphocytes reflect the local immune response in patients with colorectal carcinoma

Tumor-infiltrating lymphocytes (TILs) correlate with the number and size of the surrounding lymph nodes in patients with colorectal carcinoma (CRC) and reflect the quality of the antitumor immune response. In this prospective study, we analyzed whether this response correlated with the circulating lymphocytes in peripheral blood (PB). In 47 patients with newly diagnosed CRC, flow cytometry was performed to analyze the B cells, T cells, NK cells, and a variety of their subsets in PB. The results were correlated with TILs in the resected tumor and with the number and size of the surrounding lymph nodes in nodal negative (N- patients (LN5: number of lymph nodes measuring ≥5 mm) and the metastasis-to-lymph node size ratio (MSR) in nodal positive patients (N+). Differences between the number of TILs could be seen between N+ and N- patients, dependent on the LN5 and MSR categories, with higher values in N- cases and in patients with a higher LN5 category or a lower MSR. Additionally, higher values of various circulating lymphocyte subgroups were observed in these patients. For the total PB lymphocytes, CD8 cells, and some of their subgroups, a positive correlation with the TILs was found. This study shows that circulating lymphocytes—in particular, cytotoxic T cells—correlate with the local antitumor immune response displayed by TILs and lymph node activation. Our findings indicate that local and generalized antitumor immune responses are concordant with their different components

The UBA domain of conjugating enzyme Ubc1/Ube2K facilitates assembly of K48/K63‐branched ubiquitin chains

The assembly of a specific polymeric ubiquitin chain on a target protein is a key event in the regulation of numerous cellular processes. Yet, the mechanisms that govern the selective synthesis of particular polyubiquitin signals remain enigmatic. The homologous ubiquitin-conjugating (E2) enzymes Ubc1 (budding yeast) and Ube2K (mammals) exclusively generate polyubiquitin linked through lysine 48 (K48). Uniquely among E2 enzymes, Ubc1 and Ube2K harbor a ubiquitin-binding UBA domain with unknown function. We found that this UBA domain preferentially interacts with ubiquitin chains linked through lysine 63 (K63). Based on structural modeling, in vitro ubiquitination experiments, and NMR studies, we propose that the UBA domain aligns Ubc1 with K63-linked polyubiquitin and facilitates the selective assembly of K48/K63-branched ubiquitin conjugates. Genetic and proteomics experiments link the activity of the UBA domain, and hence the formation of this unusual ubiquitin chain topology, to the maintenance of cellular proteostasis.Deutsche Forschungsgemeinschaft (DFG) http://dx.doi.org/10.13039/501100001659Max‐Planck‐Gesellschaft (MPG) http://dx.doi.org/10.13039/501100004189Peer Reviewe

Preventing and Reducing Coercive Measures—An Evaluation of the Implementation of the Safewards Model in Two Locked Wards in Germany

IntroductionAggression and violence are highly complex problems in acute psychiatry that often lead to the coercive interventions. The Safewards Model is an evidence-informed conflict-reduction strategy to prevent and reduce such incidents. The aim of this study was to evaluate the implementation of this model with regard to coercive interventions in inpatient care.Materials and MethodsWe evaluated outcomes of the implementation of the Safewards Model in two locked psychiatric wards in Germany. Frequency and duration of coercive interventions applied during a period of 11 weeks before and 11 weeks after the implementation period were assessed through routine data. Fidelity to the Safewards Model was assessed by the Organization Fidelity Checklist.ResultsFidelity to the Safewards Model was high in both wards. The overall use of coercive measures differed significantly between wards [case-wise: χ2 (1, n = 250) = 35.34, p ≤ 0.001; patient-wise: χ2 (1, n = 103) = 21.45, p ≤ 0.001] and decreased post-implementation. In one ward, the number of patients exposed to coercive interventions in relation to the overall number of Patients decreased significantly [χ2 (1, 281) = 6.40, p = 0.01]. Furthermore, the mean duration of coercive interventions overall declined significantly [U(55,21) = −2.142, p = 0.032] with an effect size of Cohen’s d = −0.282 (95% CI: −0.787, 0.222) in that ward. Both aspects declined as well in the other ward, but not significantly.DiscussionResults indicate that the implementation of the Safewards interventions according to the model in acute psychiatric care can reduce coercive measures. They also show the role of enabling factors as well as of obstacles for the implementation process

Structural and Functional analysis of the GABARAP interaction motif (GIM)

© 2017 The Authors. Published under the terms of the CC BY 4.0 license. Through the canonical LC3 interaction motif (LIR), [W/F/Y]-X 1 -X 2 -[I/L/V], protein complexes are recruited to autophagosomes to perform their functions as either autophagy adaptors or receptors. How these adaptors/receptors selectively interact with either LC3 or GABARAP families remains unclear. Herein, we determine the range of selectivity of 30 known core LIR motifs towards individual LC3s and GABARAPs. From these, we define a GABARAP Interaction Motif (GIM) sequence ([W/F] -[V/I]-X 2 -V) that the adaptor protein PLEKHM1 tightly conforms to. Using biophysical and structural approaches, we show that the PLEKHM1-LIR is indeed 11-fold more specific for GABARAP than LC3B. Selective mutation of the X 1 and X 2 positions either completely abolished the interaction with all LC3 and GABARAPs or increased PLEKHM1-GIM selectivity 20-fold towards LC3B. Finally, we show that conversion of p62/SQSTM1, FUNDC1 and FIP200 LIRs into our newly defined GIM, by introducing two valine residues, enhances their interaction with endogenous GABARAP over LC3B. The identification of a GABARAP-specific interaction motif will aid the identification and characterization of the expanding array of autophagy receptor and adaptor proteins and their in vivo functions

Nationwide, population-based observational study of the molecular epidemiology and temporal trend of carbapenemase-producing Enterobacterales in Norway, 2015 to 2021

National and regional carbapenemaseproducing Enterobacterales (CPE) surveillance is essential to understand the burden of antimicrobial resistance, elucidate outbreaks, and develop infection-control or antimicrobial-treatment recommendations. Aim: This study aimed to describe CPE and their epidemiology in Norway from 2015 to 2021. Methods: A nationwide, population-based observational study of all verified clinical and carriage CPE isolates submitted to the national reference laboratory was conducted. Isolates were characterised by antimicrobial susceptibility testing, whole genome sequencing (WGS) and basic metadata. Annual CPE incidences were also estimated. Results: A total of 389 CPE isolates were identified from 332 patients of 63years median age (range:0–98). These corresponded to 341 cases, 184 (54%) being male. Between 2015 and 2021, the annual incidence of CPE cases increased from 0.6 to 1.1per 100,000person-years. For CPEisolates with available data on colonisation/infection, 58% (226/389)were associated with colonisation and 38% (149/389) with clinical infections. WGS revealed a predominance of OXA-48-like (51%; 198/389) and NDM (34%; 134/389) carbapenemases in a diversified population of Escherichia coli and Klebsiella pneumoniae, including high-risk clones also detected globally. Most CPE isolates were travel-related (63%;245/389). Although local outbreaks and healthcare-associated transmission occurred, no interregional spread was detected. Nevertheless, 18% (70/389) of isolates not directly related to import points towards potentially unidentified transmission routes. A decline in travelassociated cases was observed during the COVID-19 pandemic. Conclusions: The close-to-doubling of CPE case incidence between 2015 and 2021 was associated with foreign travel and genomic diversity. To limit further transmission and outbreaks, continued screening and monitoring is essential