Radially polarized passively mode-locked thin-disk laser oscillator emitting sub-picosecond pulses with an average output power exceeding the 100 W level

We report on a high-power passively mode-locked radially polarized Yb:YAG thin-disk oscillator providing 125 W of average output power. To the best of our knowledge, this is the highest average power ever reported from a mode-locked radially polarized oscillator without subsequent amplification stages. Mode-locking was achieved by implementing a SESAM as the cavity end mirror and the radial polarization of the LG*01 mode was obtained by means of a circular Grating Waveguide Output Coupler. The repetition rate was 78 MHz. A pulse duration of 0.97 ps and a spectral bandwidth of 1.4 nm (FWHM) were measured at the maximum output power. This corresponds to a pulse energy of 1.6 μJ and a pulse peak power of 1.45 MW. A high degree of radial polarization of 97.3 ± 1% and an M2-value of 2.16 which is close to the theoretical value for the LG*01 doughnut mode were measured

Phylogenetic Relationship of the Complete Rauscher Murine Leukemia Virus Genome with Other Murine Leukemia Virus Genomes

AbstractWe report the complete nucleotide sequence of the genome of Rauscher murine leukemia virus (R-MuLV), the replication-competent helper virus present in the Rauscher virus complex, and its phylogenetic relationship with other murine leukemia virus genomes. An overall sequence identity of 97.6% was found between R-MuLV and the Friend helper virus (F-MuLV), and the two viruses were closely related on the phylogenetic trees constructed from eithergag, pol,orenvsequences. Moloney murine leukemia virus (Mo-MuLV) was the next closest relative to R-MuLV and F-MuLV on all trees, followed by Akv and radiation leukemia virus (RadLV). The most distantly related helper virus was Hortulanus murine leukemia virus (Ho-MuLV). Interestingly, Cas-Br-E branched with Mo-MuLV on thegagandpoltrees, whereas on theenvtree, it revealed the highest degree of relatedness to Ho-MuLV, possibly due to an ancient recombination with an Ho-MuLV ancestor. In summary, a phylogenetic analysis involving various MuLVs has been performed, in which the postulated close relationship between R-MuLV and F-MuLV has been confirmed, consistent with the pathobiology of the two viruses

Literatur-Rundschau

Literatur-RundschauStephan Brünjes/Ulrich Wenger, Radio-Report. Programme - Profile - Perspektiven (Susanne Kampmann)Andreas Kunkel, Fernsehleben. Mediennutzung als Sozialisationsfaktor. Auswirkungen des Fernsehens auf Gesellschaft und Individuum (Susanne Kampmann) Deutsche Presse-Agentur (Hg.), Alles über die Nachricht- Das dpa-Handbuch (Christof Haverkamp)Ralf Clasen/Dirk U. W allbrecht/Thomas Rommerskirchen, Internet für Journalisten. Online-Recherchen im Netz der Netze (Thomas Graf) Helmut Scherer/Hans-Bernd Brosius (Hg.), Zielgruppen, Publikationssegmente, Nutzergruppen. Beiträge aus der Rezeptionsforschung (SuK)Herbert Lepper (Hg.). Volk, Kirche und Vaterland. Wahlaufrufe, Aufrufe, Satzungen und Statuten des Zentrums 1870-1933. Eine Quellensammlung zur Geschichte insbesondere der Rheinischen und Westfälischen Zentrumspartei (Michael Schmolke)

Novel insights into the unfolded protein response using Pichia pastoris specific DNA microarrays

Background DNA Microarrays are regarded as a valuable tool for basic and applied research in microbiology. However, for many industrially important microorganisms the lack of commercially available microarrays still hampers physiological research. Exemplarily, our understanding of protein folding and secretion in the yeast Pichia pastoris is presently widely dependent on conclusions drawn from analogies to Saccharomyces cerevisiae. To close this gap for a yeast species employed for its high capacity to produce heterologous proteins, we developed full genome DNA microarrays for P. pastoris and analyzed the unfolded protein response (UPR) in this yeast species, as compared to S. cerevisiae. Results By combining the partially annotated gene list of P. pastoris with de novo gene finding a list of putative open reading frames was generated for which an oligonucleotide probe set was designed using the probe design tool TherMODO (a thermodynamic model-based oligoset design optimizer). To evaluate the performance of the novel array design, microarrays carrying the oligo set were hybridized with samples from treatments with dithiothreitol (DTT) or a strain overexpressing the UPR transcription factor HAC1, both compared with a wild type strain in normal medium as untreated control. DTT treatment was compared with literature data for S. cerevisiae, and revealed similarities, but also important differences between the two yeast species. Overexpression of HAC1, the most direct control for UPR genes, resulted in significant new understanding of this important regulatory pathway in P. pastoris, and generally in yeasts. Conclusion The differences observed between P. pastoris and S. cerevisiae underline the importance of DNA microarrays for industrial production strains. P. pastoris reacts to DTT treatment mainly by the regulation of genes related to chemical stimulus, electron transport and respiration, while the overexpression of HAC1 induced many genes involved in translation, ribosome biogenesis, and organelle biosynthesis, indicating that the regulatory events triggered by DTT treatment only partially overlap with the reactions to overexpression of HAC1. The high reproducibility of the results achieved with two different oligo sets is a good indication for their robustness, and underlines the importance of less stringent selection of regulated features, in order to avoid a large number of false negative results

Novel insights into the unfolded protein response using Pichia pastoris specific DNA microarrays

Background DNA Microarrays are regarded as a valuable tool for basic and applied research in microbiology. However, for many industrially important microorganisms the lack of commercially available microarrays still hampers physiological research. Exemplarily, our understanding of protein folding and secretion in the yeast Pichia pastoris is presently widely dependent on conclusions drawn from analogies to Saccharomyces cerevisiae. To close this gap for a yeast species employed for its high capacity to produce heterologous proteins, we developed full genome DNA microarrays for P. pastoris and analyzed the unfolded protein response (UPR) in this yeast species, as compared to S. cerevisiae. Results By combining the partially annotated gene list of P. pastoris with de novo gene finding a list of putative open reading frames was generated for which an oligonucleotide probe set was designed using the probe design tool TherMODO (a thermodynamic model-based oligoset design optimizer). To evaluate the performance of the novel array design, microarrays carrying the oligo set were hybridized with samples from treatments with dithiothreitol (DTT) or a strain overexpressing the UPR transcription factor HAC1, both compared with a wild type strain in normal medium as untreated control. DTT treatment was compared with literature data for S. cerevisiae, and revealed similarities, but also important differences between the two yeast species. Overexpression of HAC1, the most direct control for UPR genes, resulted in significant new understanding of this important regulatory pathway in P. pastoris, and generally in yeasts. Conclusion The differences observed between P. pastoris and S. cerevisiae underline the importance of DNA microarrays for industrial production strains. P. pastoris reacts to DTT treatment mainly by the regulation of genes related to chemical stimulus, electron transport and respiration, while the overexpression of HAC1 induced many genes involved in translation, ribosome biogenesis, and organelle biosynthesis, indicating that the regulatory events triggered by DTT treatment only partially overlap with the reactions to overexpression of HAC1. The high reproducibility of the results achieved with two different oligo sets is a good indication for their robustness, and underlines the importance of less stringent selection of regulated features, in order to avoid a large number of false negative results

Self-supported amorphous TaNx(Oy)/nickel foam thin film as an advanced electrocatalyst for hydrogen evolution reaction

Chemical vapor deposited (CVD) amorphous tantalum-oxy nitride film on porous three-dimensional (3D) nickel foam (TaNx(Oy)/NF) utilizing tantalum precursor, tris(diethylamino)(ethylimino)tantalum(V), ([Ta(NEt)(NEt2)3]) with preformed Ta–N bonds is reported as a potential self-supported electrocatalyst for hydrogen evolution reaction (HER). The morphological analyses revealed the formation of thin film of core–shell structured TaNx(Oy) coating (ca. 236 nm) on NF. In 0.5 M H2SO4, TaNx(Oy)/NF exhibited enhanced HER activity with a low onset potential as compared to the bare NF (−50 mV vs. −166 mV). The TaNx(Oy)/NF samples also displayed higher current density (−11.08 mA cm−2vs. −3.36 mA cm−2 at 400 mV), lower Tafel slope (151 mV dec−1vs. 179 mV dec−1) and lower charge transfer resistance exemplifying the advantage of TaNx(Oy) coating towards enhanced HER performance. The enhanced HER catalytic activity is attributed to the synergistic effect between the amorphous TaNx(Oy) film and the nickel foam

Rheumatoid Arthritis Naive T Cells Share Hypermethylation Sites With Synoviocytes.

ObjectiveTo determine whether differentially methylated CpGs in synovium-derived fibroblast-like synoviocytes (FLS) of patients with rheumatoid arthritis (RA) were also differentially methylated in RA peripheral blood (PB) samples.MethodsFor this study, 371 genome-wide DNA methylation profiles were measured using Illumina HumanMethylation450 BeadChips in PB samples from 63 patients with RA and 31 unaffected control subjects, specifically in the cell subsets of CD14+ monocytes, CD19+ B cells, CD4+ memory T cells, and CD4+ naive T cells.ResultsOf 5,532 hypermethylated FLS candidate CpGs, 1,056 were hypermethylated in CD4+ naive T cells from RA PB compared to control PB. In analyses of a second set of CpG candidates based on single-nucleotide polymorphisms from a genome-wide association study of RA, 1 significantly hypermethylated CpG in CD4+ memory T cells and 18 significant CpGs (6 hypomethylated, 12 hypermethylated) in CD4+ naive T cells were found. A prediction score based on the hypermethylated FLS candidates had an area under the curve of 0.73 for association with RA case status, which compared favorably to the association of RA with the HLA-DRB1 shared epitope risk allele and with a validated RA genetic risk score.ConclusionFLS-representative DNA methylation signatures derived from the PB may prove to be valuable biomarkers for the risk of RA or for disease status

An Innovative Protocol for Metaproteomic Analyses of Microbial Pathogens in Cystic Fibrosis Sputum

Hallmarks of cystic fibrosis (CF) are increased viscosity of mucus and impaired mucociliary clearance within the airways due to mutations of the cystic fibrosis conductance regulator gene. This facilitates the colonization of the lung by microbial pathogens and the concomitant establishment of chronic infections leading to tissue damage, reduced lung function, and decreased life expectancy. Although the interplay between key CF pathogens plays a major role during disease progression, the pathophysiology of the microbial community in CF lungs remains poorly understood. Particular challenges in the analysis of the microbial population present in CF sputum is (I) the inhomogeneous, viscous, and slimy consistence of CF sputum, and (II) the high number of human proteins masking comparably low abundant microbial proteins. To address these challenges, we used 21 CF sputum samples to develop a reliable, reproducible and widely applicable protocol for sputum processing, microbial enrichment, cell disruption, protein extraction and subsequent metaproteomic analyses. As a proof of concept, we selected three sputum samples for detailed metaproteome analyses and complemented and validated metaproteome data by 16S sequencing, metabolomic as well as microscopic analyses. Applying our protocol, the number of bacterial proteins/protein groups increased from 199-425 to 392-868 in enriched samples compared to nonenriched controls. These early microbial metaproteome data suggest that the arginine deiminase pathway and multiple proteases and peptidases identified from various bacterial genera could so far be underappreciated in their contribution to the CF pathophysiology. By providing a standardized and effective protocol for sputum processing and microbial enrichment, our study represents an important basis for future studies investigating the physiology of microbial pathogens in CF in vivo – an important prerequisite for the development of novel antimicrobial therapies to combat chronic recurrent airway infection in CF

Prothrombinase-Induced Clotting Time to Measure Drug Concentrations of Rivaroxaban, Apixaban, and Edoxaban in Clinical Practice: A Cross-Sectional Study.

Prothrombinase-induced clotting time (PiCT) is proposed as a rapid and inexpensive laboratory test to measure direct oral anticoagulant (DOAC) drug levels. In a prospective, multicenter cross-sectional study, including 851 patients, we aimed to study the accuracy of PiCT in determining rivaroxaban, apixaban, and edoxaban drug concentrations and assessed whether clinically relevant drug levels could be predicted correctly. Citrated plasma samples were collected, and the Pefakit® PiCT was utilized. Ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to measure drug concentrations. Cut-off levels were established using receiver-operating characteristics curves. We calculated sensitivities and specificities with respect to clinically relevant drug concentrations. Spearman's correlation coefficient between PiCT and drug concentrations was 0.85 in the case of rivaroxaban (95% CI 0.82, 0.88), 0.66 for apixaban (95% CI 0.60, 0.71), and 0.78 for edoxaban (95% CI 0.65, 0.86). The sensitivity to detect clinically relevant drug concentrations was 85.1% in the case of 30 µg L-1 (95% CI 82.0, 87.7; specificity 77.9; 72.1, 82.7), 85.7% in the case of 50 µg L-1 (82.4, 88.4; specificity 77.3; 72.5, 81.5), and 85.1% in the case of 100 µg L-1 (80.9, 88.4; specificity 73.2%; 69.1, 76.9). In conclusion, the association of PiCT with DOAC concentrations was fair, and the majority of clinically relevant drug concentrations were correctly predicted

Обзор и назначение экономических информационных систем

ObjectivesThis study was designed to develop a technique to selectively increase the sympathetic tone to the heart by cardiac sympathetic nerve stimulation (SNS).BackgroundAccess to the cardiac sympathetic neurons may allow modulating the adrenergic tone of the heart while avoiding systemic side effects.MethodsCardiac sympathetic nerves course within neural sleeves along the subclavian artery. Because of this proximity, transvascular SNS was attempted with electrode catheters inside the subclavian artery in 16 pigs.ResultsRight/left (R-/L-) SNS (20 Hz) during ventricular pacing at 200/min evoked a >100% increase of left ventricular systolic pressure (baseline: 51 ± 1 mm Hg; L-SNS: 118 ± 26 mm Hg; R-SNS: 116 ± 33 mm Hg; p < 0.001) while systemic vascular resistance remained unchanged. There was a sigmoid dose-response curve with rapid on- and offset of the effect during SNS initiation/cessation. Positive inotropic effects persisted for 12 h of continued SNS (n = 4). Besides positive dromotropic effects, L-SNS/R-SNS yielded a 41% and 77% sinus rate increase, respectively.ConclusionsThe neural adrenergic tone to the heart can be selectively increased by catheter stimulation of cardiac efferent sympathetic nerves