Induced pluripotent stem cells in hematology: current and future applications

Reprogramming somatic cells into induced pluripotent stem (iPS) cells is nowadays approaching effectiveness and clinical grade. Potential uses of this technology include predictive toxicology, drug screening, pathogenetic studies and transplantation. Here, we review the basis of current iPS cell technology and potential applications in hematology, ranging from disease modeling of congenital and acquired hemopathies to hematopoietic stem and other blood cell transplantation

Improvements in BepiColombo and JUICE radio science experiments with a multi-station tracking configuration for the reduction of Doppler noise

Radio science experiments for planetary geodesy mostly rely on measurements of the Doppler shift of microwave signals sent to a spacecraft by an Earth station, and retransmitted back coherently in phase to the same antenna (two-way link). The retransmitted signal can also be received by a different station in a listen-only configuration (three-way link). In state-of-the-art tracking systems, such as the ones will be used on the future ESA's missions JUICE and BepiColombo, the Doppler error budget is dominated by local noise sources arising at the ground-station, in particular tropospheric scintillation and unmodeled motions of the antenna's structure. In this work, a novel technique aimed at reducing these disturbances is analyzed, with particular emphasis on its benefits to BepiColombo's and JUICE's radio science experiments. The method, referred to as Time-Delay Mechanical-noise Cancellation (TDMC), relies on simultaneous two-way and three-way spacecraft tracking, the latter employing a stiffer listen-only antenna with better mechanical stability and located in a favorable dry region more immune to tropospheric noise. In fact, a proper linear combination of time-shifted observables from the two-way and three-way links can replace local noises of the two-way ground-station with those coming from the listen-only antenna, translating into increased accuracy of the final measurements, while preserving the original Doppler content. We show the results of covariance analyses performed with a multi-arc weighted least square estimator for the entire BepiColombo's Hermean phase and JUICE's flybys of Callisto. We compare the two solutions obtained with and without the application of the TDMC technique. For BepiColombo and JUICE radio science experiments, the two-way links are baselined from the 35-m DSA-3 (Malargüe, Argentina) and the 34-m DSS 25 (Goldstone, California). For the three-way link, we select the 12-m Large Latin American Millimeter Array (LLAMA) antenna for three reasons: 1) its mechanical rigidity with respect to large beam-waveguide antennas, 2) its unique position in the extremely dry Puna de Atacama desert, that assures low tropospheric noise, and 3) its limited longitudinal separation from the two other ground-stations, granting sufficient common visibility time to perform the requested combination of the observables. Besides its noise-reduction effect, enabling unprecedented levels of accuracy on Doppler measurements, TDMC provides also a back-up for unique events: a crucial satellite flyby or a specific passage over a site of particular geophysical interest. Indeed, measurements become virtually independent of unfavorable meteorological conditions at the transmitting station

Supporting safe metamodel evolution with edelta

Metamodels play a crucial role in any model-based application. They underpin the definition of models and tools, and the development of model management operations, including model transformations and analysis. Like any software artifacts, metamodels are subject to evolution to improve their quality or implement unforeseen requirements. Metamodels can be defined in terms of existing ones to increase the separation of concerns and foster reuse. However, the induced coupling can give additional evolution complexity, and dedicated support is needed to avoid breaking metamodels defined in terms of those being changed. This paper presents a tool-supported approach that can automatically analyze the available metamodels and alert modelers in case of change operations that can give place to invalid situations like dangling references. The approach has been implemented in the Edelta development environment and successfully applied to metamodels retrieved from a publicly available Ecore models dataset

Detecting metamodel evolutions in repositories of model-driven projects

Model-Driven Engineering (MDE) is a discipline that leverages abstraction and automation in software development. Projects are typically composed of inherently different artifacts, including models, metamodels, model transformations, code generators, and concrete syntax definitions. Despite the increasing availability of reusable projects (e.g., through GitHub), their reuse possibilities depend on the availability of accurate, high-level metadata describing architectural information about the project at hand. In this paper, we enhance an existing approach for extracting relevant architectural information from model-driven projects to detect subsequent metamodel versions in evolution paths. In particular, we are interested in those refactorings that enhance the intrinsic quality of metamodels. The approach has been implemented by extending the existing MDEprofiler tool and has been validated on a dataset consisting of metamodels with different size and covering distinct application domains

Comparison of PBO solvers in a dependency solving domain

Linux package managers have to deal with dependencies and conflicts of packages required to be installed by the user. As an NP-complete problem, this is a hard task to solve. In this context, several approaches have been pursued. Apt-pbo is a package manager based on the apt project that encodes the dependency solving problem as a pseudo-Boolean optimization (PBO) problem. This paper compares different PBO solvers and their effectiveness on solving the dependency solving problem.Comment: In Proceedings LoCoCo 2010, arXiv:1007.083

DNMT1-interacting RNAs block gene specific DNA methylation

Summary DNA methylation was described almost a century ago. However, the rules governing its establishment and maintenance remain elusive. Here, we present data demonstrating that active transcription regulates levels of genomic methylation. We identified a novel RNA arising from the CEBPA gene locus critical in regulating the local DNA methylation profile. This RNA binds to DNMT1 and prevents CEBPA gene locus methylation. Deep sequencing of transcripts associated with DNMT1 combined with genome-scale methylation and expression profiling extended the generality of this finding to numerous gene loci. Collectively, these results delineate the nature of DNMT1-RNA interactions and suggest strategies for gene selective demethylation of therapeutic targets in disease

New constraints on the location of P9 obtained with the INPOP19a planetary ephemeris

Context. We used the new released INPOP19a planetary ephemerides benefiting from Jupiter-updated positions by the Juno mission and reanalyzed Cassini observations. Aims. We test possible locations of the unknown planet P9. To do this, we used the perturbations it produces on the orbits of the outer planets, more specifically, on the orbit of Saturn. Methods. Two statistical criteria were used to identify possible acceptable locations of P9 according to (i) the difference in planetary positions when P9 is included compared with the propagated covariance matrix, and (ii) the χ2 likelihood of postfit residuals for ephemerides when P9 is included. Results. No significant improvement of the residuals was found for any of the simulated locations, but we provide zones that induce a significant degradation of the ephemerides. Conclusions. Based on the INPOP19a planetary ephemerides, we demonstrate that if P9 exists, it cannot be closer than 500 AU with a 5 M⊕ and no closer than 650 AU with a 10 M⊕ . We also show that there is no clear zone that would indicate the positive existence of planet P9, but there are zones for which the existence of P9 is compatible with the 3σ accuracy of the INPOP planetary ephemerides

Low-code development and model-driven engineering: Two sides of the same coin?

The last few years have witnessed a significant growth of so-called low-code development platforms (LCDPs) both in gaining traction on the market and attracting interest from academia. LCDPs are advertised as visual development platforms, typically running on the cloud, reducing the need for manual coding and also targeting non-professional programmers. Since LCDPs share many of the goals and features of model-driven engineering approaches, it is a common point of debate whether low-code is just a new buzzword for model-driven technologies, or whether the two terms refer to genuinely distinct approaches. To contribute to this discussion, in this expert-voice paper, we compare and contrast low-code and model-driven approaches, identifying their differences and commonalities, analysing their strong and weak points, and proposing directions for cross-pollination

Search for the rare decays B0→J/ψγB^{0}\to J/\psi \gamma and Bs0→J/ψγB^{0}_{s} \to J/\psi \gamma

A search for the rare decay of a $B^{0}$ or $B^{0}_{s}$ meson into the final state $J/\psi\gamma$ is performed, using data collected by the LHCb experiment in $pp$ collisions at $\sqrt{s}=7$ and $8$ TeV, corresponding to an integrated luminosity of 3 fb$^{-1}$. The observed number of signal candidates is consistent with a background-only hypothesis. Branching fraction values larger than $1.7\times 10^{-6}$ for the $B^{0}\to J/\psi\gamma$ decay mode are excluded at 90% confidence level. For the $B^{0}_{s}\to J/\psi\gamma$ decay mode, branching fraction values larger than $7.4\times 10^{-6}$ are excluded at 90% confidence level, this is the first branching fraction limit for this decay.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-044.htm