Evi1 Counteracts Anti-Leukemic and Stem Cell Inhibitory Effects of All-Trans Retinoic Acid on Flt3-ITD/Npm1c-Driven Acute Myeloid Leukemia Cells.

All-trans retinoic acid (atRA) has a dramatic impact on the survival of patients with acute promyelocytic leukemia, but its therapeutic value in other types of acute myeloid leukemia (AML) has so far remained unclear. Given that AML is a stem cell-driven disease, recent studies have addressed the effects of atRA on leukemic stem cells (LSCs). atRA promoted stemness of MLL-AF9-driven AML in an Evi1-dependent manner but had the opposite effect in Flt3-ITD/Nup98-Hoxd13-driven AML. Overexpression of the stem cell-associated transcription factor EVI1 predicts a poor prognosis in AML, and is observed in different genetic subtypes, including cytogenetically normal AML. Here, we therefore investigated the effects of Evi1 in a mouse model for cytogenetically normal AML, which rests on the combined activity of Flt3-ITD and Npm1c mutations. Experimental expression of Evi1 on this background strongly promoted disease aggressiveness. atRA inhibited leukemia cell viability and stem cell-related properties, and these effects were counteracted by overexpression of Evi1. These data further underscore the complexity of the responsiveness of AML LSCs to atRA and point out the need for additional investigations which may lay a foundation for a precision medicine-based use of retinoids in AML

A novel method for measuring bowel motility and velocity with dynamic magnetic resonance imaging in two and three dimensions

Increasingly, dynamic magnetic resonance imaging (MRI) has potential as a noninvasive and accessible tool for diagnosing and monitoring gastrointestinal motility in healthy and diseased bowel. However, current MRI methods of measuring bowel motility have limitations: requiring bowel preparation or long acquisition times; providing mainly surrogate measures of motion; and estimating bowel-wall movement in just two dimensions. In this proof-of-concept study we apply a method that provides a quantitative measure of motion within the bowel, in both two and three dimensions, using existing, vendor-implemented MRI pulse sequences with minimal bowel preparation. This method uses a minimised cost function to fit linear vectors in the spatial and temporal domains. It is sensitised to the spatial scale of the bowel and aims to address issues relating to the low signal-to-noise in high-temporal resolution dynamic MRI scans, previously compensated for by performing thick-slice (10-mm) two-dimensional (2D) coronal scans. We applied both 2D and three-dimensional (3D) scanning protocols in two healthy volunteers. For 2D scanning, analysis yielded bi-modal velocity peaks, with a mean antegrade motion of 5.5 mm/s and an additional peak at similar to 9 mm/s corresponding to longitudinal peristalsis, as supported by intraoperative data from the literature. Furthermore, 3D scans indicated a mean forward motion of 4.7 mm/s, and degrees of antegrade and retrograde motion were also established. These measures show promise for the noninvasive assessment of bowel motility, and have the potential to be tuned to particular regions of interest and behaviours within the bowel.Radiolog

Shock wave apparatus for studying minerals at high pressure and impact phenomena on planetary surfaces

Shock wave and experimental impact phenomena research on geological and planetary materials is being carried out using two propellant (18 and 40 mm) guns (up to 2.5 km/sec) and a two‐stage light gas gun (up to 7 km/sec). Equation of state measurements on samples initially at room temperature and at low and high temperatures are being conducted using the 40 mm propellant apparatus in conjunction with Helmholtz coils, and radiative detectors and, in the case of the light gas gun, with streak cameras. The 18 mm propellant gun is used for recovery experiments on minerals, impact on cryogenic targets, and radiative post‐shock temperature measurements

Head and neck sarcomas: A single institute series

BACKGROUND: Sarcomas are tumours of mesenchymal origin, accounting for 1% of all malignancies. METHODS: This is a retrospective analysis of 107 head and neck sarcoma cases, treated over a period of thirteen years. RESULTS: Fifty-four patients had with craniofacial bone sarcomas (BSs) (male: 33; female: 21) with high grade osteosarcoma being the most predominant type. The soft tissue sarcomas (STS) (53 patients; male: 28, female: 25) were histologically diverse with rhabdomyosarcomas and myxofibrosarcomas being the predominant types. The majority of BSs were managed with neoadjuvant chemotherapy followed by surgery, whereas in STSs treatment included predominantly surgery followed by radiotherapy. Overall survival estimates were 79% at 2years and 64% at 5years (mean follow-up period was 48months). CONCLUSIONS: The mesenchymal origin of sarcomas, the pattern of disease spread and the different extent of cancellous bone infiltration in contrast to epithelial tumours, dictate distinct principles for surgical clearance

Transition Radiation Spectra of Electrons from 1 to 10 GeV/c in Regular and Irregular Radiators

We present measurements of the spectral distribution of transition radiation generated by electrons of momentum 1 to 10 GeV/c in different radiator types. We investigate periodic foil radiators and irregular foam and fiber materials. The transition radiation photons are detected by prototypes of the drift chambers to be used in the Transition Radiation Detector (TRD) of the ALICE experiment at CERN, which are filled with a Xe, CO2 (15 %) mixture. The measurements are compared to simulations in order to enhance the quantitative understanding of transition radiation production, in particular the momentum dependence of the transition radiation yield.Comment: 18 pages, 15 figures, submitted to Nucl. Instr. Meth. Phys. Res.

Search for the QCD critical point in nuclear collisions at the CERN SPS

Pion production in nuclear collisions at the SPS is investigated with the aim to search, in a restricted domain of the phase diagram, for power-laws in the behavior of correlations which are compatible with critical QCD. We have analyzed interactions of nuclei of different size (p+p, C+C, Si+Si, Pb+Pb) at 158$A$ GeV adopting, as appropriate observables, scaled factorial moments in a search for intermittent fluctuations in transverse dimensions. The analysis is performed for $\pi^+\pi^-$ pairs with invariant mass very close to the two-pion threshold. In this sector one may capture critical fluctuations of the sigma component in a hadronic medium, even if the $\sigma$-meson has no well defined vacuum state. It turns out that for the Pb+Pb system the proposed analysis technique cannot be applied without entering the invariant mass region with strong Coulomb correlations. As a result the treatment becomes inconclusive in this case. Our results for the other systems indicate the presence of power-law fluctuations in the freeze-out state of Si+Si approaching in size the prediction of critical QCD.Comment: 31 pages, 11 figure

Charged Particle Production in Proton-, Deuteron-, Oxygen- and Sulphur-Nucleus Collisions at 200 GeV per Nucleon

The transverse momentum and rapidity distributions of net protons and negatively charged hadrons have been measured for minimum bias proton-nucleus and deuteron-gold interactions, as well as central oxygen-gold and sulphur-nucleus collisions at 200 GeV per nucleon. The rapidity density of net protons at midrapidity in central nucleus-nucleus collisions increases both with target mass for sulphur projectiles and with the projectile mass for a gold target. The shape of the rapidity distributions of net protons forward of midrapidity for d+Au and central S+Au collisions is similar. The average rapidity loss is larger than 2 units of rapidity for reactions with the gold target. The transverse momentum spectra of net protons for all reactions can be described by a thermal distribution with `temperatures' between 145 +- 11 MeV (p+S interactions) and 244 +- 43 MeV (central S+Au collisions). The multiplicity of negatively charged hadrons increases with the mass of the colliding system. The shape of the transverse momentum spectra of negatively charged hadrons changes from minimum bias p+p and p+S interactions to p+Au and central nucleus-nucleus collisions. The mean transverse momentum is almost constant in the vicinity of midrapidity and shows little variation with the target and projectile masses. The average number of produced negatively charged hadrons per participant baryon increases slightly from p+p, p+A to central S+S,Ag collisions.Comment: 47 pages, submitted to Z. Phys.

Inclusive production of charged pions in p+C collisions at 158 GeV/c beam momentum

The production of charged pions in minimum bias p+C interactions is studied using a sample of 377000 inelastic events obtained with the NA49 detector at the CERN SPS at 158 GeV/c beam momentum. The data cover a phase space area ranging from 0 to 1.8 GeV/c in transverse momentum and from -0.1 to 0.5 in Feynman x. Inclusive invariant cross sections are given on a grid of 270 bins per charge thus offering for the first time a dense coverage of the projectile hemisphere and of the cross-over region into the target fragmentation zone.Comment: 31 pages, 30 figures, submitted to European Journal of Physic

System-size and centrality dependence of charged kaon and pion production in nucleus-nucleus collisions at 40A GeV and158A GeV beam energy

Measurements of charged pion and kaon production are presented in centrality selected Pb+Pb collisions at 40A GeV and 158A GeV beam energy as well as in semi-central C+C and Si+Si interactions at 40A GeV. Transverse mass spectra, rapidity spectra and total yields are determined as a function of centrality. The system-size and centrality dependence of relative strangeness production in nucleus-nucleus collisions at 40A GeV and 158A GeV beam energy are derived from the data presented here and published data for C+C and Si+Si collisions at 158A GeV beam energy. At both energies a steep increase with centrality is observed for small systems followed by a weak rise or even saturation for higher centralities. This behavior is compared to calculations using transport models (UrQMD and HSD), a percolation model and the core-corona approach.Comment: 32 pages, 14 figures, 4 tables, typo table II correcte