Implication of the Autologous Immune System in BCR-ABL Transcript Variations in Chronic Myelogenous Leukemia Patients Treated with Imatinib.

International audienceImatinib and other tyrosine kinase inhibitors (TKI) have improved treatment of chronic myelogenous leukemia (CML); however, most patients are not cured. Deeper mechanistic understanding may improve TKI combination therapies to better control the residual leukemic cell population. In analyzing our patients' data, we found that many patients who otherwise responded well to imatinib therapy still showed variations in their BCR-ABL transcripts. To investigate this phenomenon, we applied a mathematical model that integrates CML and an autologous immune response to the patients' data. We define an immune window or a range of leukemic loads for which the autologous immune system induces an improved response. Our modeling results suggest that, at diagnosis, a patient's leukemic load is able to partially or fully suppress the autologous immune response developed in a majority of patients, toward the CML clone(s). Imatinib therapy drives the leukemic population into the "immune window," allowing the patient's autologous immune cells to expand and eventually mount an efficient recognition of the residual leukemic burden. This response drives the leukemic load below this immune window, allowing the leukemic population to partially recover until another weaker immune response is initiated. Thus, the autologous immune response may explain the oscillations in BCR-ABL transcripts regularly observed in patients on imatinib

Characterization of the Subsurface of 67P/Churyumov-Gerasimenko's Abydos Site

We investigate the structure of the subsurface of the Abydos site using a cometary nucleus model with parameters adapted to comet 67P/Churyumov-Gerasimenko and the Abydos landing site. We aim to compare the production rates derived from our model with those of the main molecules measured by Ptolemy. This will allow us to retrieve the depths at which the different molecules still exist in solid form

Exploring out-of-equilibrium quantum magnetism and thermalization in a spin-3 many-body dipolar lattice system

Understanding quantum thermalization through entanglement build-up in isolated quantum systems addresses fundamental questions on how unitary dynamics connects to statistical physics. Here, we study the spin dynamics and approach towards local thermal equilibrium of a macroscopic ensemble of S = 3 spins prepared in a pure coherent spin state, tilted compared to the magnetic field, under the effect of magnetic dipole-dipole interactions. The experiment uses a unit filled array of 104 chromium atoms in a three dimensional optical lattice, realizing the spin-3 XXZ Heisenberg model. The buildup of quantum correlation during the dynamics, especially as the angle approaches pi/2, is supported by comparison with an improved numerical quantum phase-space method and further confirmed by the observation that our isolated system thermalizes under its own dynamics, reaching a steady state consistent with the one extracted from a thermal ensemble with a temperature dictated from the system's energy. This indicates a scenario of quantum thermalization which is tied to the growth of entanglement entropy. Although direct experimental measurements of the Renyi entropy in our macroscopic system are unfeasible, the excellent agreement with the theory, which can compute this entropy, does indicate entanglement build-up.Comment: 12 figure

Entrepreneurs’ age, institutions, and social value creation goals: a multi-country study

This study explores the relationship between an entrepreneur's age and his/her social value creation goals. Building on the lifespan developmental psychology literature and institutional theory, we hypothesize a U-shaped relationship between entrepreneurs’ age and their choice to create social value through their ventures, such that younger and older entrepreneurs create more social value with their businesses while middle age entrepreneurs are relatively more economically and less socially oriented with their ventures. We further hypothesize that the quality of a country’s formal institutions in terms of economic, social, and political freedom steepen the U-shaped relationship between entrepreneurs’ age and their choice to pursue social value creation as supportive institutional environments allow entrepreneurs to follow their age-based preferences. We confirm our predictions using multilevel mixed-effects linear regressions on a sample of over 15,000 entrepreneurs (aged between 18 and 64 years) in 45 countries from Global Entrepreneurship Monitor data. The findings are robust to several alternative specifications. Based on our findings, we discuss implications for theory and practice, and we propose future research directions

OSSOS. IV. DISCOVERY OF A DWARF PLANET CANDIDATE IN THE 9 : 2 RESONANCE WITH NEPTUNE

We report the discovery and orbit of a new dwarf planet candidate, 2015 RR245, by the Outer Solar System Origins Survey (OSSOS). The orbit of 2015 RR245 is eccentric (e = 0.586), with a semimajor axis near 82 au, yielding a perihelion distance of 34 au. 2015 RR245 has g - r = 0.59 +/- 0.11 and absolute magnitude H-r = 3.6 +/- 0.1; for an assumed albedo of p(V) = 12%, the object has a diameter of similar to 670. km. Based on astrometric measurements from OSSOS and Pan-STARRS1, we find that 2015 RR245 is securely trapped on ten-megayear timescales in the 9: 2 mean-motion resonance with Neptune. It is the first trans-Neptunian object (TNO) identified in this resonance. On hundred-megayear. timescales, particles in 2015 RR245-like orbits depart and sometimes return to the resonance, indicating that 2015 RR245 likely forms part of the long-lived metastable population of distant TNOs that drift between resonance sticking and actively scattering via gravitational encounters with Neptune. The discovery of a 9: 2 TNO stresses the role of resonances in the long-term evolution of objects in the scattering disk. and reinforces the view that distant resonances are heavily populated in the current solar system. This object further motivates detailed modeling of the transient sticking population.Peer reviewe

Combining Logics to Transform Organizational Agency: Blending Industry and Art at Alessi

To understand how organizations combine conflicting institutional logics strategically to create and pursue new market opportunities, we conducted an in-depth longitudinal study of the multiple efforts of the Italian manufacturer of household goods Alessi to combine the logics of industrial manufacturing and cultural production. Over three decades, Alessi developed three different strategies to combine normative elements of the two logics, using each strategy to envision and pursue different market opportunities. By combining the logics of industrial manufacturing and cultural production, Alessi was able to envision new possibilities for value creation and to enact them through innovation in product design. The three strategies triggered a common set of mechanisms through which the purposeful combining of logics enabled the pursuit of opportunity, while each strategy structured the process differently. We develop a theoretical model linking the development of recombinant strategies to the dynamic restructuring of organizational agency and the related capacity to create and pursue new market opportunities. Our findings and theoretical insights advance understanding of the processes through which organizations challenge taken-for-granted beliefs and practices to create new market opportunities, use logics as resources to enable embedded agency, and design hybrid organizational arrangements

The “Mirage” Sensor in a Industrial Environment: Optical and Thermal Losses Determinations

Since the first “Mirage” experiment run in the laboratory of ESPCI in 1979 [1], this method has been used by many other laboratories for the determination of optical and thermal properties and for non destructive evaluation [2] [3] [4]

The Outer Solar System Origins Survey : I. Design and First-Quarter Discoveries

We report the discovery, tracking, and detection circumstances for 85 trans-Neptunian objects (TNOs) from the first 42 deg(2) of the Outer Solar System Origins Survey. This ongoing r-band solar system survey uses the 0.9 deg(2) field of view MegaPrime camera on the 3.6m Canada-France-Hawaii Telescope. Our orbital elements for these TNOs are precise to a fractional semimajor axis uncertaintyPeer reviewe

Prosociality in business: a human empowerment framework

This study introduces a human empowerment framework to better understand why some businesses are more socially oriented than others in their policies and activities. Building on Welzel’s theory of emancipation, we argue that human empowerment—comprised of four components: action resources, emancipative values, social movement activity, and civic entitlements—enables, motivates, and entitles individuals to pursue social goals for their businesses. Using a sample of over 15,000 entrepreneurs from 43 countries, we report strong empirical evidence for two ecological effects of the framework components on prosociality. We find that human empowerment (1) lifts entrepreneurs’ willingness to choose a social orientation for their business, and (2) reinforces the gender effect on prosociality in business activity. We discuss the human empowerment framework’s added value in understanding how modernization processes fully leverage the potential of social business activities for societies

CSR and related terms in SME owner-managers' mental models in six European countries: national context matters

As a contribution to the emerging field of corporate social responsibility (CSR) cognition, this article reports on the findings of an exploratory study that compares SME owner–managers’ mental models with regard to CSR and related concepts across six European countries (Belgium, Italy, Norway, France, UK, Spain). Utilising Repertory Grid Technique, we found that the SME owner–managers’ mental models show a few commonalities as well as a number of differences across the different country samples. We interpret those differences by linking individual cognition to macro-environmental variables, such as language, national traditions and dissemination mechanisms. The results of our exploratory study show that nationality matters but that classifications of countries as found in the comparative capitalism literature do not exactly mirror national differences in CSR cognition and that these classifications need further differentiation. The findings from our study raise questions on the universality of cognition of academic management concepts and warn that promotion of responsible business practice should not rely on the use of unmediated US American management terminology