123 research outputs found

    Multifragmentation near the threshold

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    We investigate the onset of multifragmentation employing an improved version of the N-body ‘‘quantum’’ molecular-dynamics approach. We study in detail the reaction 18O+197Au at 84 MeV/nucleon and find good agreement between the calculated results and the data for the double-differential proton cross section, the mass yield, the multiplicity, the kinetic energy of the fragments, and even for the kinematic correlations between intermediate mass fragments (IMF’s), which have been measured in this experiment for the first time. We observe a strong correlation between the impact parameter and both the size of the target remnant as well as the average proton multiplicity. Hence both observables can be used to determine the impact parameter experimentally. The IMF’s come from the most central collisions. The calculations confirm the experimental result that they are not emitted from an equilibrated system. Although the inclusive energy spectra look thermal, we cannot identify an impact parameter-independent isotropically emitting source. Even in central collisions global equilibrium is not observed. We find that multifragment emission at this bombarding energy is caused by a process very similar to that proposed in the macroscopic cold multifragmentation model. Thus it has a different origin than at beam energies around 1 GeV/nucleon, although the mass yield has an almost identical slope

    NKX3.1 immunohistochemistry and methylome profiling in mesenchymal chondrosarcoma: additional diagnostic value for a well-defined disease?

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    Mesenchymal chondrosarcoma (MCS) is a rare and highly aggressive tumour of soft tissue and bone that is defined by an underlying and highly specific fusion transcript involving HEY1 and NCOA2. Histologically, the tumours show a biphasic appearance consisting of an undifferentiated blue and round cell component as well as islands of highly differentiated cartilage. Particularly in core needle biopsies, the chondromatous component can be missed and the non-specific morphology and immunophenotype of the round cell component can cause diagnostic challenges. We applied NKX3.1 immunohistochemistry which was recently reported as a highly specific marker as well as methylome and copy number profiling to a set of 45 well characterised MCS cases to evaluate their potential diagnostic value. Methylome profiling revealed a highly distinct cluster for MCS. Notably, the findings were reproducible also when analysing the round cell and cartilaginous component separately. Furthermore, four outliers were identified by methylome profiling for which the diagnosis had to be revised. NKX3.1 immunohistochemistry showed positivity in 36% of tumours, the majority of which was rather focal and weak. Taken together, NKX3.1 expression showed a low sensitivity but a high specificity in our analysis. Methylome profiling on the other hand represents a sensitive, specific and reliable tool to support the diagnosis of MCS, particularly if only the round cell component is obtained in a biopsy and the diagnosis is not suspected. Furthermore, it can aid in confirming the diagnosis in case RNA sequencing for the HEY1::NCOA2 fusion transcript is not available

    Host–guest supramolecular chemistry in solid-state nanopores: potassium-driven modulation of ionic transport in nanofluidic diodes

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    We describe the use of asymmetric nanopores decorated with crown ethers for constructing robust signal-responsive chemical devices. The modification of single conical nanopores with 18-crown-6 units led to a nanodevice whose electronic readout, derived from the transmembrane ion current, can be finely tuned over a wide range of K⁺ concentrations. The electrostatic characteristics of the nanopore environment arising from host–guest ion-recognition processes taking place on the pore walls are responsible for tuning the transmembrane ionic transport and the rectification properties of the pore. This work illustrates the potential and versatility of host–guest chemistry, in combination with nanofluidic elements, as a key enabler to achieve addressable chemical nanodevices mimicking the ion transport properties and gating functions of specific biological channels.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

    Multiple roles of Pseudomonas aeruginosa TBCF10839 PilY1 in motility, transport and infection

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    Polymorphonuclear neutrophils are the most important mammalian host defence cells against infections with Pseudomonas aeruginosa. Screening of a signature tagged mutagenesis library of the non-piliated P. aeruginosa strain TBCF10839 uncovered that transposon inactivation of its pilY1 gene rendered the bacterium more resistant against killing by neutrophils than the wild type and any other of the more than 3000 tested mutants. Inactivation of pilY1 led to the loss of twitching motility in twitching-proficient wild-type PA14 and PAO1 strains, predisposed to autolysis and impaired the secretion of quinolones and pyocyanin, but on the other hand promoted growth in stationary phase and bacterial survival in murine airway infection models. The PilY1 population consisted of a major full-length and a minor shorter PilY1* isoform. PilY1* was detectable in small extracellular quinolone-positive aggregates, but not in the pilus. P. aeruginosa PilY1 is not an adhesin on the pilus tip, but assists in pilus biogenesis, twitching motility, secretion of secondary metabolites and in the control of cell density in the bacterial population

    Benchmarking whole exome sequencing in the German Network for Personalized Medicine

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    Introduction Whole Exome Sequencing (WES) has emerged as an efficient tool in clinical cancer diagnostics to broaden the scope from panel-based diagnostics to screening of all genes and enabling robust determination of complex biomarkers in a single analysis. Methods To assess concordance, six formalin-fixed paraffin-embedded (FFPE) tissue specimens and four commercial reference standards were analyzed by WES as matched tumor-normal DNA at 21 NGS centers in Germany, each employing local wet-lab and bioinformatics investigating somatic and germline variants, copy-number alteration (CNA), and different complex biomarkers. Somatic variant calling was performed in 494 diagnostically relevant cancer genes. In addition, all raw data were re-analyzed with a central bioinformatic pipeline to separate wet- and dry-lab variability. Results The mean positive percentage agreement (PPA) of somatic variant calling was 76% and positive predictive value (PPV) 89% compared a consensus list of variants found by at least five centers. Variant filtering was identified as the main cause for divergent variant calls. Adjusting filter criteria and re-analysis increased the PPA to 88% for all and 97% for clinically relevant variants. CNA calls were concordant for 82% of genomic regions. Calls of homologous recombination deficiency (HRD), tumor mutational burden (TMB), and microsatellite instability (MSI) status were concordant for 94%, 93%, and 93% respectively. Variability of CNAs and complex biomarkers did not increase considerably using the central pipeline and was hence attributed to wet-lab differences. Conclusion Continuous optimization of bioinformatic workflows and participating in round robin tests are recommend

    Am I My Peer's Keeper? Social Responsibility in Financial Decision Making

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    Decision makers often take risky decisions on the behalf of others rather than for themselves. Competing theoretical models predict both, higher as well as lower levels of risk aversion when taking risk for others, and the experimental evidence is mixed. In our within-subject design, money managers have substantial responsibility by taking investment decisions for themselves and for a group of six clients, when payments are either fixed or perfectly aligned. We find that money managers invest significantly less for others than for themselves (cautious shift) which is mainly driven by a less risk averse sub sample. Digging deeper we find money managers to rather act in line with what they believe the clients would invest for themselves. We derive a responsibility weighting function to show that with a perfectly aligned payment the money manager weights egoistic and social preferences. Finally we bring our results in perspective with the mixed experimental literature.Ein großer Teil risikoreicher, ökonomischer Entscheidungen wird von Dritten anstelle der Betroffenen getroffen. In solchen Fällen sagt die eine Klasse theoretischer Modelle geringere Risikoaversion voraus, eine andere Klasse aber höhere Risikoaversion im Vergleich zur Situation, bei der der Betroffene selbst die Entscheidung trifft. Die bisherigen empirischen Ergebnisse aus Laborexperimenten sind ebenso gemischt oder finden keine Unterschiede zwischen der Entscheidung für sich selbst oder für andere Personen. Wir verwenden ein 'within-subjects' für unser Experiment, bei dem Vermögensverwalter in unterschiedlichen Stufen für sich selbst, für eine Gruppe von Klienten, oder für sich selbst und eine Gruppe von Klienten Investitionsentscheidungen treffen. Wir erhöhen dabei die Soziale Verantwortung über die Größe der Gruppe von Investoren, um Verantwortungseffekte zu verstärken. Unsere Ergebnisse zeigen, dass das Risiko bei der Investition für andere signifikant geringer ist als bei der Investition für sich selbst. Dieses Aggregat-Ergebnis ist allerdings nur durch eine unterdurchschnittlich risikoaverse Subpopulation unserer Stichprobe getrieben. Eine genauere Analyse der Investitionsmotive zeigt, dass die Vermögensverwalter gemäß ihrer Erwartung der Klienten-Präferenzen handeln. Wir passen eine Nutzenfunktion mit Verantwortungs-Gewichten an und finden, dass die beobachtete Riskioaversion bei gemeinschaftlichen Investitionen durch egoistische und soziale Präferenzen erklärt werden kann. Abschließend stellen wir unsere Ergebnisse in den Kontext der bisherigen Literatur und versuchen die gemischten, bisherigen Ergebnisse aufgrund unserer Erkenntnisse zu erklären
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