Retinoic acid-induced differentiation sensitizes myeloid progenitors cells to ER stress

The clonal expansion of hematopoietic myeloid precursors blocked at different stages of differentiation characterizes the acute myeloid leukemia (AML) phenotype. A subtype of AML, acute promyelocytic leukemia (APL), characterized by the chimeric protein PML-RARα is considered a paradigm of differentiation therapy. In this leukemia subtype the all-trans-retinoic acid (RA)-based treatments are able to induce PML-RARα degradation and leukemic blast terminal differentiation [1-2]. Granulocytic differentiation of APL cells driven by RA triggers a physiological Unfolded Protein Response (UPR), a series of pathways emanating from the ER in case of ER stress, which ensues when higher protein folding activity is required as during differentiation. We show here that, although mild, the ER stress induced by RA is sufficient to render human APL cell lines and primary blasts very sensitive to low doses of Tunicamycin (Tm), an ER stress inducing drug, at doses that are not toxic in the absence of RA. Importantly only human progenitors cells derived from APL patients resulted sensitive to the combined treatment with RA and Tm whereas those obtained from healthy donors were not affected. We also show that the UPR pathway downstream of PERK plays a major protective role against ER stress in differentiating cells and, by using a specific PERK inhibitor, we potentiated the toxic effect of the combination of RA and Tm. In conclusion, our findings identify the ER stress-related pathways as potential targets in the search for novel therapeutic strategies in AML

Short-range correlations in low-lying nuclear excited states

The electromagnetic transitions to various low-lying excited states of 16O, 48Ca and 208Pb are calculated within a model which considers the short-range correlations. In general the effects of the correlations are small and do not explain the required quenching to describe the data.Comment: 6 pages, 2 postscript figures, 1 tabl

Dynamical changes of the polar cap potential structure: an information theory approach

Some features, such as vortex structures often observed through a wide spread of spatial scales, suggest that ionospheric convection is turbulent and complex in nature. Here, applying concepts from information theory and complex system physics, we firstly evaluate a pseudo Shannon entropy, <i>H</i>, associated with the polar cap potential obtained from the Super Dual Auroral Radar Network (SuperDARN) and, then, estimate the degree of disorder and the degree of complexity of ionospheric convection under different Interplanetary Magnetic Field (IMF) conditions. The aforementioned quantities are computed starting from time series of the coefficients of the 4th order spherical harmonics expansion of the polar cap potential for three periods, characterised by: (i) steady IMF <i>B<sub>z</sub></i> > 0, (ii) steady IMF <i>B<sub>z</sub></i> < 0 and (iii) a double rotation from negative to positive and then positive to negative <i>B<sub>z</sub></i>. A neat dynamical topological transition is observed when the IMF <i>B<sub>z</sub></i> turns from negative to positive and vice versa, pointing toward the possible occurrence of an order/disorder phase transition, which is the counterpart of the large scale convection rearrangement and of the increase of the global coherence. This result has been confirmed by applying the same analysis to a larger data base of about twenty days of SuperDARN data, allowing to investigate the role of IMF <i>B<sub>y</sub></i> too

Análisis del ciclo de vida de la ventana de madera

Se analiza el ciclo de vida de una ventana de madera y se calcula su huella ecológica. Se compara con la bibliografía existente la huella ecológica de la ventana de madera con la de PVC y la de alumni

SENSE: A comparison of photon detection efficiency and optical crosstalk of various SiPM devices

This paper describes a comparison of photon detection efficiency and optical crosstalk measurements performed by three partners: Geneva University, Catania Observatory and Nagoya University. The measurements were compared for three different SiPM devices with different active areas: from 9 $mm^2$ up to 93.6 $mm^2$ produced by Hamamatsu. The objective of this work is to establish the measurements and analysis procedures for calculating the main SiPM parameters and their precision. This work was done in the scope of SENSE project which aims to build roadmap for the last developments in field of sensors for low light level detection

Development of a strategy for calibrating the novel SiPM camera of the SST-1M telescope proposed for the Cherenkov Telescope Array

CTA will comprise a sub-array of up to 70 small size telescopes (SSTs) at the southern array. The SST-1M project, a 4 m-diameter Davies Cotton telescope with 9 degrees FoV and a 1296 pixels SiPM camera, is designed to meet the requirements of the next generation ground based gamma-ray observatory CTA in the energy range above 3 TeV. Silicon photomultipliers (SiPM) cameras of gamma-ray telescopes can achieve good performance even during high night sky background conditions. Defining a fully automated calibration strategy of SiPM cameras is of great importance for large scale production validation and online calibration. The SST-1M sub-consortium developed a software compatible with CTA pipeline software (CTApipe). The calibration of the SST-1M camera is based on the Camera Test Setup (CTS), a set of LED boards mounted in front of the camera. The CTS LEDs are operated in pulsed or continuous mode to emulate signal and night sky background respectively. Continuous and pulsed light data analysis allows us to extract single pixel calibration parameters to be used during CTA operation.Comment: All CTA contributions at arXiv:1709.0348

Molecular characterization of a t(1;3)(p36;q21) in a patient with MDS. MEL1 is widely expressed in normal tissues, including bone marrow, and it is not overexpressed in the t(1;3) cells

Patients with myeloid malignancies and either the 3q21q26 syndrome or t(1;3)(p36;q21) have been reported to share similar clinicopathological features and a common molecular mechanism for leukemogenesis. Overexpression of MDS1/EVI1 (3q26) or MEL1/PRDM16 (1p36), both members of the PR-domain family, has been directly implicated in the malignant transformation of this subset of neoplasias. The breakpoints in both entities are outside the genes, and the 3q21 region, where RPN1 is located, seems to act as an enhancer. MEL1 has been reported to be expressed in leukemia cells with t(1;3) and in the normal uterus and fetal kidney, but neither in bone marrow (BM) nor in other tissues, suggesting that this gene is specific to t(1;3)-positive MDS/AML. We report the molecular characterization of a t(1;3)(p36;q21) in a patient with MDS (RAEB-2). In contrast to previous studies, we demonstrate that MEL1, the PR-containing form, and MEL1S, the PR-lacking form, are widely expressed in normal tissues, including BM. The clinicopathological features and the breakpoint on 1p36 are different from cases previously described, and MEL1 is not overexpressed, suggesting a heterogeneity in myeloid neoplasias with t(1;3)

Performance of a small size telescope (SST-1M) camera for gamma-ray astronomy with the Cherenkov Telescope Array

The foreseen implementations of the Small Size Telescopes (SST) in CTA will provide unique insights into the highest energy gamma rays offering fundamental means to discover and under- stand the sources populating the Galaxy and our local neighborhood. Aiming at such a goal, the SST-1M is one of the three different implementations that are being prototyped and tested for CTA. SST-1M is a Davies-Cotton single mirror telescope equipped with a unique camera technology based on SiPMs with demonstrated advantages over classical photomultipliers in terms of duty-cycle. In this contribution, we describe the telescope components, the camera, and the trigger and readout system. The results of the commissioning of the camera using a dedicated test setup are then presented. The performances of the camera first prototype in terms of expected trigger rates and trigger efficiencies for different night-sky background conditions are presented, and the camera response is compared to end-to-end simulations.Comment: All CTA contributions at arXiv:1709.0348