Numerical models of collisions between core-collapse supernovae and circumstellar shells

Recent observations of luminous Type IIn supernovae (SNe) provide compelling evidence that massive circumstellar shells surround their progenitors. In this paper we investigate how the properties of such shells influence the SN lightcurve by conducting numerical simulations of the interaction between an expanding SN and a circumstellar shell ejected a few years prior to core collapse. Our parameter study explores how the emergent luminosity depends on a range of circumstellar shell masses, velocities, geometries, and wind mass-loss rates, as well as variations in the SN mass and energy. We find that the shell mass is the most important parameter, in the sense that higher shell masses (or higher ratios of M_shell/M_SN) lead to higher peak luminosities and higher efficiencies in converting shock energy into visual light. Lower mass shells can also cause high peak luminosities if the shell is slow or if the SN ejecta are very fast, but only for a short time. Sustaining a high luminosity for durations of more than 100 days requires massive circumstellar shells of order 10 M_sun or more. This reaffirms previous comparisons between pre-SN shells and shells produced by giant eruptions of luminous blue variables (LBVs), although the physical mechanism responsible for these outbursts remains uncertain. The lightcurve shape and observed shell velocity can help diagnose the approximate size and density of the circumstellar shell, and it may be possible to distinguish between spherical and bipolar shells with multi-wavelength lightcurves. These models are merely illustrative. One can, of course, achieve even higher luminosities and longer duration light curves from interaction by increasing the explosion energy and shell mass beyond values adopted here.Comment: Accepted for publication in MNRAS. Tables of numerical results (SN lightcurves and velocities) to be published online. (Updated to fix figures

MiR-17/20/93/106 promote hematopoietic cell expansion by targeting sequestosome 1-regulated pathways in mice

MicroRNAs (miRNAs) are pivotal for regulation of hematopoiesis but their critical targets remain largely unknown. Here, we show that ectopic expression of miR-17, -20,-93 and -106, all AAAGUGC seed-containing miRNAs, increases proliferation, colony outgrowth and replating capacity of myeloid progenitors and results in enhanced P-ERK levels. We found that these miRNAs are endogenously and abundantly expressed in myeloid progenitors and down-regulated in mature neutrophils. Quantitative proteomics identified sequestosome 1 (SQSTM1), an ubiquitin-binding protein and regulator of autophagy-mediated protein degradation, as a major target for these miRNAs in myeloid progenitors. In addition, we found increased expression of Sqstm1 transcripts during CSF3-induced neutrophil differentiation of 32D-CSF3R cells and an inverse correlation of SQSTM1 protein levels and miR-106 expression in AML samples. ShRNA-mediated silencing of Sqstm1 phenocopied the effects of ectopic miR-17/20/93/106 expression in hematopoietic progenitors in vitro and in mice. Further, SQSTM1 binds to the ligand-activated colony-stimulating factor 3 receptor (CSF3R) mainly in the late endosomal compartment, but not in LC3 positive autophagosomes. SQSTM1 regulates CSF3R stability and ligand-induced mitogen-activated protein kinase signaling. We demonstrate that AAAGUGC seed-containing miRNAs promote cell expansion, replating capacity and signaling in hematopoietic cells by interference with SQSTM1-regulated pathways

Beam characterisation of the 1.5 T MRI-linac

As a prerequisite for clinical treatments it was necessary to characterize the Elekta 1.5 T MRI-linac 7 MV FFF radiation beam. Following acceptance testing, beam characterization data were acquired with Semiflex 3D (PTW 31021), microDiamond (PTW 60019), and Farmer-type (PTW 30013 and IBA FC65-G) detectors in an Elekta 3D scanning water phantom and a PTW 1D water phantom. EBT3 Gafchromic film and ion chamber measurements in a buildup cap were also used. Special consideration was given to scan offsets, detector effective points of measurement and avoiding air gaps.
 
 Machine performance has been verified and the system satisfied the relevant beam requirements of IEC60976.
 
 Beam data were acquired for field sizes between 1 x 1 and 57 x 22 cm2. New techniques were developed to measure PDD curves including the electron return effect at beam exit, which exhibits an electron-type practical range of 1.2 +/- 0.1 cm. The Lorentz force acting on the secondary charged particles creates an asymmetry in the crossline profiles with an average shift of +0.24 cm. For a 10 x 10 cm2 beam, scatter from the cryostat contributes 1% of the dose at isocentre. This affects the relative output factors, scatter factors and beam profiles, both in-field and out-of-field. The average 20 -- 80% penumbral width measured for small fields with a microDiamond detector at 10 cm depth is 0.50 cm. MRI-linac penumbral widths are very similar to that of the Elekta Agility linac MLC, as is the near-surface dose PDD(0.2 cm) = 57%. The entrance surface dose is ~36% of D_max. Cryostat transmission is quantified for inclusion within the treatment planning system. 
 
 As a result, the 1.5 T MRI-linac 7 MV FFF beam has been characterised for the first time and is suitable for clinical use. This was a key step towards the first clinical treatments with the MRI-linac, which were delivered at University Medical Center Utrecht in May 2017

MiR-17/20/93/106 promote hematopoietic cell expansion by targeting sequestosome 1-regulated pathways in mice

MicroRNAs (miRNAs) are pivotal for regulation of hematopoiesis but their critical targets remain largely unknown. Here, we show that ectopic expression of miR-17, -20,-93 and -106, all AAAGUGC seed-containing miRNAs, increases proliferation, colony outgrowth and replating capacity of myeloid progenitors and results in enhanced P-ERK levels. We found that these miRNAs are endogenously and abundantly expressed in myeloid progenitors and down-regulated in mature neutrophils. Quantitative proteomics identified sequestosome 1 (SQSTM1), an ubiquitin-binding protein and regulator of autophagy-mediated protein degradation, as a major target for these miRNAs in myeloid progenitors. In addition, we found increased expression of Sqstm1 transcripts during CSF3-induced neutrophil differentiation of 32D-CSF3R cells and an inverse correlation of SQSTM1 protein levels and miR-106 expression in AML samples. ShRNA-mediated silencing of Sqstm1 phenocopied the effects of ectopic miR-17/20/93/106 expression in hematopoietic progenitors in vitro and in mice. Further, SQSTM1 binds to the ligand-activated colony-stimulating factor 3 receptor (CSF3R) mainly in the late endosomal compartment, but not in LC3 positive autophagosomes. SQSTM1 regulates CSF3R stability and ligand-induced mitogen-activated protein kinase signaling. We demonstrate that AAAGUGC seed-containing miRNAs promote cell expansion, replating capacity and signaling in hematopoietic cells by interference with SQSTM1-regulated pathways