Überblick über das deutsche Attribut am Beispiel des Romans von Thomas Mann „Der Zauberberg”

This article describes an attributive on the basis of a novel entitled “Der Zauberberg” of the famous German writer – Thomas Mann. This is a detailed analysis of the attributive and all examples come from the novel “Der Zauberberg”. At the outset of the article are quoted different definitions. Various classifications of attributive are presented. The article answers the questions: which part of speech can be used as an attributive. Finally I wishes to highlight the case of the subordinate clause, which also fulfil the role of an attributive and refer to the special form of attributive, namely to the apposition

Combined point of care nucleic acid and antibody testing for SARS-CoV-2 following emergence of D614G Spike Variant

Rapid COVID-19 diagnosis in hospital is essential, though complicated by 30-50% of nose/throat swabs being negative by SARS-CoV-2 nucleic acid amplification testing (NAAT). Furthermore, the D614G spike mutant now dominates the pandemic and it is unclear how serological tests designed to detect anti-Spike antibodies perform against this variant. We assess the diagnostic accuracy of combined rapid antibody point of care (POC) and nucleic acid assays for suspected COVID-19 disease due to either wild type or the D614G spike mutant SARS-CoV-2. The overall detection rate for COVID-19 is 79.2% (95CI 57.8-92.9%) by rapid NAAT alone. Combined point of care antibody test and rapid NAAT is not impacted by D614G and results in very high sensitivity for COVID-19 diagnosis with very high specificity

Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2

Abstract: Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating

Complement lectin pathway activation is associated with COVID-19 disease severity, independent of MBL2 genotype subgroups

IntroductionWhile complement is a contributor to disease severity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, all three complement pathways might be activated by the virus. Lectin pathway activation occurs through different pattern recognition molecules, including mannan binding lectin (MBL), a protein shown to interact with SARS-CoV-2 proteins. However, the exact role of lectin pathway activation and its key pattern recognition molecule MBL in COVID-19 is still not fully understood.MethodsWe therefore investigated activation of the lectin pathway in two independent cohorts of SARS-CoV-2 infected patients, while also analysing MBL protein levels and potential effects of the six major single nucleotide polymorphisms (SNPs) found in the MBL2 gene on COVID-19 severity and outcome.ResultsWe show that the lectin pathway is activated in acute COVID-19, indicated by the correlation between complement activation product levels of the MASP-1/C1-INH complex (p=0.0011) and C4d (p<0.0001) and COVID-19 severity. Despite this, genetic variations in MBL2 are not associated with susceptibility to SARS-CoV-2 infection or disease outcomes such as mortality and the development of Long COVID.ConclusionIn conclusion, activation of the MBL-LP only plays a minor role in COVID-19 pathogenesis, since no clinically meaningful, consistent associations with disease outcomes were noted

Single-cell multi-omics analysis of the immune response in COVID-19

Funder: Lister Institute of Preventive Medicine; doi: https://doi.org/10.13039/501100001255Funder: University College London, Birkbeck MRC Doctoral Training ProgrammeFunder: The Jikei University School of MedicineFunder: Action Medical Research (GN2779)Funder: NIHR Clinical Lectureship (CL-2017-01-004)Funder: NIHR (ACF-2018-01-004) and the BMA FoundationFunder: Chan Zuckerberg Initiative (grant 2017-174169) and from Wellcome (WT211276/Z/18/Z and Sanger core grant WT206194)Funder: UKRI Innovation/Rutherford Fund Fellowship allocated by the MRC and the UK Regenerative Medicine Platform (MR/5005579/1 to M.Z.N.). M.Z.N. and K.B.M. have been funded by the Rosetrees Trust (M944)Funder: Barbour FoundationFunder: ERC Consolidator and EU MRG-Grammar awardsFunder: Versus Arthritis Cure Challenge Research Grant (21777), and an NIHR Research Professorship (RP-2017-08-ST2-002)Funder: European Molecular Biology Laboratory (EMBL)Abstract: Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

Monitoring apoptosis in intact cells by high-resolution magic angle spinning 1H NMR spectroscopy

Apoptosis is a cellular process that maintains an equilibrium between cell proliferation and cell death. Induction of apoptosis is a well-known strategy in developing cancer treatments, therefore non-invasive monitoring of apoptosis in intact cells could contribute towards the characterisation of drug efficacy and hence drug discovery. A known metabolic marker of apoptosis is a notable increase in proton NMR resonances associated with lipids stored in lipid droplets (LDs). MRI-based studies of lipid accumulation have been used to monitor apoptosis-based cancer treatments. However, the cellular processes which lead to the accumulation of lipid droplets remain poorly understood, causing a bottleneck for targeting lipid metabolism in cancer cells. This thesis investigates the application of High-Resolution Magic Angle Spinning (HRMAS) 1H NMR spectroscopy in monitoring metabolic changes in intact cells during apoptosis. The technique is used to analyse metabolic profiles of cells treated with cisplatin and etoposide after 3, 8, 24 and 48 h. The results are compared to the analysis of organic cell extracts by solution-state 1H NMR spectroscopy to demonstrate lipid compartmentalisation and highlight the advantages of HRMAS 1H NMR spectroscopy in monitoring lipid metabolism during apoptosis. The lipid compartmentalisation is also confirmed by differential centrifugation and mass spectrometry-based lipidomics further validating the importance of LDs. Previous work linked NMR-visible lipid resonances to increased LD size. In this thesis, an NMR-based diffusion method is described for differentiating between control, apoptotic and necrotic cells. I demonstrate that as apoptosis-induced LDs become larger, the diffusion coefficient of NMR-visible lipids decreases. Therefore, diffusion measurements in conjunction with HRMAS 1H NMR-derived lipid signals provide a novel means of following apoptosis in intact cells. Mass spectrometry and transcriptomic analysis was used to elucidate the origin of LD during cisplatin and etoposide treatments. This work identifies two treatment-dependent mechanisms of lipid particle organisation, contributing to our understanding of LD formation during apoptosis. It may help validate magnetic resonance spectroscopy as a non-invasive tool for following the efficacy of apoptosis-inducing drugs.AstraZeneca, EPSR

The German attributive on the example of the novel of Thomas Mann “Der Zauberberg”

This article describes an attributive on the basis of a novel entitled “Der Zauberberg” of the famous German writer – Thomas Mann. This is a detailed analysis of the attributive and all examples come from the novel “Der Zauberberg”. At the outset of the article are quoted different definitions. Various classifications of attributive are presented. The article answers the questions: which part of speech can be used as an attributive. Finally I wishes to highlight the case of the subordinate clause, which also fulfil the role of an attributive and refer to the special form of attributive, namely to the apposition

The text type ‘column’ in the diachronical depiction

The aim of the paper is to describe the column as a type of text. This text type has its roots back in the 19th century France. But at the beginning this text type had a totally different character, different form, aim and features. It was a part of newspaper, where novels, critiques and poems were posted. Nowadays there may occur a problem to define the term ‘column’. Generally it is the text type with a polemical and derisive character, which serves as the entertainment, but sometimes the term ‘column’ still refers to a part of the newspaper. This article defines the term and how this text type has developed through the time

Gatunek tekstu felieton w niemieckiej i polskiej prasie - analiza kontrastywna

The aim of the dissertation titled “Die Textsorte Glosse in der deutschen und polnischen Presse - eine kontrastive Studie“ is to investigate, how the text type ‚column‘ is realized in Polish and German press. To prove or disprove if there are any similarities or differences between these realizations, the following newspapers and magazines were compared: „Frankfurter Allgemeine Zeitung“, „Die Welt“, „Focus“, „Bild“, „Gazeta Wyborcza“, „Rzeczpospolita“, „Focus“ and „Fakt“. All of the above were published in April 2015. Seventy-seven columns in total were made public in the mentioned newspapers and magazines but the detailed analysis in the dissertation is based on twelve most representative columns: - „Hillary und die Ganoven“ - „Frankfurter Allgemeinen Zeitung”, „Alles Wurst oder was?“ - „Frankfurter Allgemeinen Zeitung”, „Scheiben Bremse“ - „Frankfurter Allgemeinen Zeitung”, „Stressiger Stress ist besonders stressig“ - „Welt“, the column in „Welt“ from the 9th of April 2015, „Die Wahrheit über Neandertaler“ - „Focus“, „Helene Fischer und der Fluch von Vilshofen“ - „Bild“, „Gillmann über „Bauer sucht Frau“ - „Bild“, „Annasz przenoszony“ - „Gazeta Wyborcza”, „Zwątpienie w przedszkolach“ - „Gazeta Wyborcza”, „Minister Szczurek do prezydenta Malinowskiego“ - „Rzeczpospolita” and „Dzieci odchudzanie przez zniechęcanie“ - „Rzeczpospolita”. All columns were analyzed on the basis of the formal, structural and content related criteria