Cesium lead halide perovskites are of interest for light‐emitting diodes and lasers. So far, thin‐films of CsPbX3 have typically afforded very low photoluminescence quantum yields (PL‐QY < 20%) and ...amplified spontaneous emission (ASE) only at cryogenic temperatures, as defect related nonradiative recombination dominated at room temperature (RT). There is a current belief that, for efficient light emission from lead halide perovskites at RT, the charge carriers/excitons need to be confined on the nanometer scale, like in CsPbX3 nanoparticles (NPs). Here, thin films of cesium lead bromide, which show a high PL‐QY of 68% and low‐threshold ASE at RT, are presented. As‐deposited layers are recrystallized by thermal imprint, which results in continuous films (100% coverage of the substrate), composed of large crystals with micrometer lateral extension. Using these layers, the first cesium lead bromide thin‐film distributed feedback and vertical cavity surface emitting lasers with ultralow threshold at RT that do not rely on the use of NPs are demonstrated. It is foreseen that these results will have a broader impact beyond perovskite lasers and will advise a revision of the paradigm that efficient light emission from CsPbX3 perovskites can only be achieved with NPs.
Highly efficient photoluminescence (PL‐QY = 68%), amplified spontaneous emission, and low‐threshold lasing in thin films of cesium lead bromide at room temperature are shown. Importantly, the films are not based on nanocrystals or quantum dots but consist of extended continuous layers that are formed upon recrystallization of as‐deposited layers by thermal imprint.
The serine/threonine kinase Par1 is a core component of the machinery that sets up polarity in the embryo and regulates cell fate decisions but its role in the homeostasis of adult tissues is poorly ...understood. Inhibition of Par1 by the bacterium Helicobacter pylori (H. pylori) represents the only established pathology that affects Par1 function in an adult epithelium. Thus, during chronic H. pylori infection of the gastric mucosa Par1 is one of the targets of the non-obligate H.pylori cytotoxic protein and oncogene CagA, which stimulates inflammation and triggers morphological changes, both believed to contribute to the gastric cancer risk imposed by H. pylori infection. Based on Par1's role in cell polarity, it has been speculated that Par1 inhibition affects epithelial polarity. Here we report the unexpected finding that CagA-mediated Par1-inhibition promotes the generation of DNA Double Strand Breaks in primary gastric epithelial cells, which likely contributes to the reported accumulation of mutations in chronically infected mucosal cells.
Abbreviations: AGS: human gastric adenocarcinoma cell line; CM: CagA Multimerization (and Par1 binding) domain; H. pylori: Helicobacter pylori; DSB: Double Strand Break; HGECs: human (primary) gastric epithelial cells; IB: immunoblot; IF: immunofluorescence; MOI: Multiplicity of Infection; ROS: reactive oxygen species; Par1: Partitioning Defective 1 kinase; WT: wild type
Helicobacter pylori strains associated with severe tissue damage and inflammation possess a unique genetic locus, cag, containing 31 genes originating from a distant event of horizontal transfer and ...retained as a pathogenicity island. The cag system is an Helicobacter-specific type IV secretion engine involved in cellular responses like induction of pedestals, secretion of IL-8, and phosphorylation of proteic targets. It has previously been reported that cocultivation of epithelial cells with Helicobacter pylori triggers signal transduction and tyrosine phosphorylation of a 145-kDa putative host cell protein. Herein, we demonstrate that this protein is not derived from the host but rather is the bacterial immunodominant antigen CagA, a virulence factor commonly expressed in peptic ulcer disease and thought to be an orphan of a specific biological function. Thus, CagA is delivered into the epithelial cells by the cag type IV secretion system where it is phosphorylated on tyrosine residues by an as yet unidentified host cell kinase and wired to eukaryotic signal transduction pathways and cytoskeletal plasticity.
Intense phase-locked terahertz (THz) pulses are the bedrock of THz lightwave electronics, where the carrier field creates a transient bias to control electrons on sub-cycle time scales. Key ...applications such as THz scanning tunnelling microscopy or electronic devices operating at optical clock rates call for ultimately short, almost unipolar waveforms, at megahertz (MHz) repetition rates. Here, we present a flexible and scalable scheme for the generation of strong phase-locked THz pulses based on shift currents in type-II-aligned epitaxial semiconductor heterostructures. The measured THz waveforms exhibit only 0.45 optical cycles at their centre frequency within the full width at half maximum of the intensity envelope, peak fields above 1.1 kV cm
and spectral components up to the mid-infrared, at a repetition rate of 4 MHz. The only positive half-cycle of this waveform exceeds all negative half-cycles by almost four times, which is unexpected from shift currents alone. Our detailed analysis reveals that local charging dynamics induces the pronounced positive THz-emission peak as electrons and holes approach charge neutrality after separation by the optical pump pulse, also enabling ultrabroadband operation. Our unipolar emitters mark a milestone for flexibly scalable, next-generation high-repetition-rate sources of intense and strongly asymmetric electric field transients.
The CagA protein of Helicobacter pylori interacts with numerous cellular factors and is associated with increased virulence and risk of gastric carcinoma. We present here the cocrystal structure of a ...subdomain of CagA with the human kinase PAR1b/MARK2, revealing that a CagA peptide mimics substrates of this kinase family, resembling eukaryotic protein kinase inhibitors. Mutagenesis of conserved residues central to this interaction renders CagA inactive as an inhibitor of MARK2.
Die Beiträge zur Altertumskunde enthalten Monographien, Sammelbände, Editionen, Übersetzungen und Kommentare zu Themen aus den Bereichen Klassische, Mittel- und Neulateinische Philologie, Alte ...Geschichte, Archäologie, Antike Philosophie sowie Nachwirken der Antike bis in die Neuzeit. Dadurch leistet die Reihe einen umfassenden Beitrag zur Erschließung klassischer Literatur und zur Forschung im gesamten Gebiet der Altertumswissenschaften.
Detergent-resistant membranes of eukaryotic cells are enriched in many important cellular signalling molecules and frequently targeted by bacterial pathogens. To learn more about pathogenic ...mechanisms of Helicobacter pylori and to elucidate novel effects on host epithelial cells, we investigated how bacterial co-cultivation changes the protein composition of detergent-resistant membranes of gastric adenocarcinoma (AGS) tissue culture cells. Using iTRAQ (isobaric tags for relative and absolute quantification) analysis we identified several cellular proteins, which are potentially related to H. pylori virulence. One of the proteins, which showed a significant infection-dependent increase in detergent resistance, was the polarity-associated serine/threonine kinase MARK2 (EMK1/Par-1b). We demonstrate that H. pylori causes the recruitment of MARK2 from the cytosol to the plasma membrane, where it colocalizes with the bacteria and interacts with CagA. Using Mardin Darby Canine Kidney (MDCK) monolayers and a three-dimensional MDCK tissue culture model we showed that association of CagA with MARK2 not only causes disruption of apical junctions, but also inhibition of tubulogenesis and cell differentiation.
Summary
The human pathogen Helicobacter pylori colonizes the mucous layer of the
stomach. During parasitic infection, freely swimming bacteria adhere to the gastric
epithelial cells and trigger ...intracellular signalling pathways. This process requires
the translocation of the effector protein CagA into the host cell through a specialized
type IV secretion system encoded in the cag pathogenicity island. Following transfer, CagA is phosphorylated on tyrosine re‐sidues by a host cell kinase. Here, we describe how the tyrosine phosphorylation of CagA is restricted to a previously identified repeated sequence called D1. This sequence is located in the C‐terminal half of the protein and contains the five‐amino‐acid motif EPIYA, which is amplified by duplications in a large fraction of clinical isolates. Tyrosine phosphorylation of CagA is essential for the activation process that leads to dramatic changes in the morphology of cells growing in culture. In addition, we observed that two members of the src kinases family, c‐Src and Lyn, account for most of the CagA‐specific kinase activity in host cell lysates. Thus, CagA translocation followed by tyrosine phosphorylation at the EPIYA motifs promotes a growth factor‐like response with intense cytoskeletal rearrangements, cell elongation effects and increased cellular motility.
The small-sample performance of alternatives to the usual likelihood ratio test in mixed linear models is investigated. Specifically, the following tests for fixed effects are considered: (i) a ...bootstrap-based test, (ii) the Bartlett-corrected usual test, and (iii) an adjusted profile likelihood ratio test. The last test is derived using an approximation to the modified profile likelihood proposed by Barndorff-Nielsen, based on the work of Severini. Bootstrap resampling is performed to numerically construct a Bartlett correction factor for the usual test statistic, and also to obtain a critical value that does not rely on first-order asymptotics. The numerical evidence presented in the paper slightly favors the Bartlett-corrected usual test. An application to real longitudinal data is presented.
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