Search

bayesian_pyhf is a Python package that allows for the parallel Bayesian and frequentist evaluation of multi-channel binned statistical models. The Python library pyhf is used to build such models according to the HistFactory framework and already includes many frequentist inference methodologies. The pyhf-built models are then used as data-generating model for Bayesian inference and evaluated with the Python library PyMC. Based on Monte Carlo Chain Methods, PyMC allows for Bayesian modelling and together with the arviz library offers a wide range of Bayesian analysis tools.

The goal of the present study is to understand the effects of laser shock peening (LSP)-induced residual stresses on the fatigue crack propagation (FCP) behaviour of the commonly used aircraft aluminium alloy AA2024 in T3 heat treatment condition. LSP treatment was performed using a pulsed Nd:YAG laser on compact tensile C(T)50-specimens with a thickness of 2.0 mm. LSP-treated specimens reveal a significant retardation of the fatigue crack propagation. The fatigue crack retardation effect can be correlated with the compressive residual stresses introduced by LSP throughout the entire specimen thickness. A possible application of the LSP process on a component like panel with three welded stringers representing a part of a fuselage structure was performed as well. The skin-stringer AA2024-AA7050 Tjoints were realised through stationary shoulder friction stir welding (SSFSW), a variant of the conventional friction stir welding process. In this relatively new process, the shoulder does not rotate and therefore does not contribute to the heat generation. Consequently, a reduced and more homogeneous heat input leads to a less affected microstructure and better mechanical properties. The efficiency of the LSP process has been demonstrated resulting in an increase of 200 – 400% in fatigue lifetime.

Abstract The amplification of putative oncogenes is a common finding within the genome of various cancer types. Identification and further targeting of specific junction sites within the sequence of genomic amplicons (amplicon fusion sites, AFS) by PCR (AFS-PCR) is suitable for quantification of minimal residual disease (MRD). This approach has recently been developed and described for MYCN amplified neuroblastomas. To compare AFS-PCR directly to routinely used MRD diagnostic strategies, we mapped the amplified genomic regions (ampGR) of an iAMP21-amplicon in high resolution of a patient with acute lymphoblastic leukemia (ALL). Successfully, we established AFS-PCR covering junction sites between ampGR within the iAMP21-amplicon. Quantification of MRD by AFS-PCR was directly comparable to IgH/TCR based real time quantitative PCR and fluorescence activated cell sorting (FACS) analysis in consecutive bone marrow (BM) specimens. Our data give an additional proof of concept of AFS-PCR for quantification of MRD. The method could be taken into account for ALL patients with genomic amplifications as alternative MRD diagnostic, if no or qualitatively poor Ig/TCR-PCRs are available.

Microphthalmia (Mi) is a bHLHZip transcription factor that is essential for melanocyte development and postnatal function. It is thought to regulate both differentiated features of melanocytes such as pigmentation as well as proliferation/survival, based on phenotypes of mutant mouse alleles. Mi activity is controlled by at least two signaling pathways. Melanocyte-stimulating hormone (MSH) promotes transcription of the Mi gene through cAMP elevation, resulting in sustained Mi up-regulation over many hours. c-Kit signaling up-regulates Mi function through MAP kinase phosphorylation of Mi, thereby recruiting the p300 transcriptional coactivator. The current study reveals that c-Kit signaling triggers two phosphorylation events on Mi, which up-regulate transactivation potential yet simultaneously target Mi for ubiquitin-dependent proteolysis. The specific activation/degradation signals derive from MAPK/ERK targeting of serine 73, whereas serine 409 serves as a substrate for p90 Rsk-1. An unphosphorylatable double mutant at these two residues is at once profoundly stable and transcriptionally inert. These c-Kit-induced phosphorylations couple transactivation to proteasome-mediated degradation. c-Kit signaling thus triggers short-lived Mi activation and net Mi degradation, in contrast to the profoundly increased Mi expression after MSH signaling, potentially explaining the functional diversity of this transcription factor in regulating proliferation, survival, and differentiation in melanocytes.