inv(X)(p11.4p11.22) BCOR/CCNB3 in bone sarcoma

Review on inv(X)(p11.4p11.22) BCOR/CCNB3 in bone sarcoma, with data on clinics, and the genes involved

Deformation mechanisms of idealised cermets under multi-axial loading

The response of idealised cermets comprising approximately 60% by volume steel spheres in a Sn/Pb solder matrix is investigated under a range of axisymmetric compressive stress states. Digital volume correlation (DVC) analysis of X-ray micro-computed tomography scans (μ-CT), and the measured macroscopic stress-strain curves of the specimens revealed two deformation mechanisms. At low triaxialities the deformation is granular in nature, with dilation occurring within shear bands. Under higher imposed hydrostatic pressures, the deformation mechanism transitions to a more homogeneous incompressible mode. However, DVC analyses revealed that under all triaxialities there are regions with local dilatory and compaction responses, with the magnitude of dilation and the number of zones wherein dilation occurs decreasing with increasing triaxiality. Two numerical models are presented in order to clarify these mechanisms: (i) a periodic unit cell model comprising nearly rigid spherical particles in a porous metal matrix and (ii) a discrete element model comprising a large random aggregate of spheres connected by non-linear normal and tangential “springs”. The periodic unit cell model captured the measured stress-strain response with reasonable accuracy but under-predicted the observed dilation at the lower triaxialities, because the kinematic constraints imposed by the skeleton of rigid particles were not accurately accounted for in this model. By contrast, the discrete element model captured the kinematics and predicted both the overall levels of dilation and the simultaneous presence of both local compaction and dilatory regions with the specimens. However, the levels of dilation in this model are dependent on the assumed contact law between the spheres. Moreover, since the matrix is not explicitly included in the analysis, this model cannot be used to predict the stress-strain responses. These analyses have revealed that the complete constitutive response of cermets depends both on the kinematic constraints imposed by the particle aggregate skeleton, and the constraints imposed by the metal matrix filling the interstitial spaces in that skeleton.The authors are grateful to the Office of Naval Research (ONR) for their financial support through grant number N00014121063

Mechanisms of root reinforcement in soils:An experimental methodology using four-dimensional X-ray computed tomography and digital volume correlation

Vegetation on railway or highway slopes can improve slope stability through the generation of soil pore water suctions by plant transpiration and mechanical soil reinforcement by the roots. To incorporate the enhanced shearing resistance and stiffness of root-reinforced soils in stability calculations, it is necessary to understand and quantify its effectiveness. This requires integrated and sophisticated experimental and multiscale modelling approaches to develop an understanding of the processes at different length scales, from individual root-soil interaction through to full soil-profile or slope scale. One of the challenges with multiscale models is ensuring that they sufficiently closely represent real behaviour. This requires calibration against detailed high-quality and data-rich experiments. This study presents a novel experimental methodology, which combines in situ direct shear loading of a willow root reinforced soil with X-ray computed tomography to capture the 3D chronology of soil and root deformation within the shear zone. Digital volume correlation (DVC) analysis was applied to the computed tomography (CT) dataset to obtain full-field 3D displacement and strain information. This paper demonstrates the feasibility and discusses the challenges associated with DVC experiments on root-reinforced soils

Identification of plastic constitutive parameters at large deformations from three dimensional displacement fields

The aim of this paper is to provide a general procedure to extract the constitutive parameters of a plasticity model starting from displacement measurements and using the Virtual Fields Method. This is a classical inverse problem which has been already investigated in the literature, however several new features are developed here. First of all the procedure applies to a general three-dimensional displacement field which leads to large plastic deformations, no assumptions are made such as plane stress or plane strain although only pressure-independent plasticity is considered. Moreover the equilibrium equation is written in terms of the deviatoric stress tensor that can be directly computed from the strain field without iterations. Thanks to this, the identification routine is much faster compared to other inverse methods such as finite element updating. The proposed method can be a valid tool to study complex phenomena which involve severe plastic deformation and where the state of stress is completely triaxial, e.g. strain localization or necking occurrence. The procedure has been validated using a three dimensional displacement field obtained from a simulated experiment. The main potentialities as well as a first sensitivity study on the influence of measurement errors are illustrated

Magnetic properties of X-Pt (X=Fe,Co,Ni) alloy systems

We have studied the electronic and magnetic properties of Fe-Pt, Co-Pt and Ni-Pt alloy systems in ordered and disordered phases. The influence of various exchange-correlation functionals on values of equilibrium lattice parameters and magnetic moments in ordered Fe-Pt, Co-Pt and Ni-Pt alloys have been studied using linearized muffin-tin orbital method. The electronic structure calculations for the disordered alloys have been carried out using augmented space recursion technique in the framework of tight binding linearized muffin-tin orbital method. The effect of short range order has also been studied in the disordered phase of these systems. The results show good agreements with available experimental values.Comment: 21 pages, 4 eps figures, accepted for publication in Journal of Physics Condensed Matte

Methyl-CpG-binding domain sequencing reveals a prognostic methylation signature in neuroblastoma

Accurate assessment of neuroblastoma outcome prediction remains challenging. Therefore, this study aims at establishing novel prognostic tumor DNA methylation biomarkers. In total, 396 low- and high-risk primary tumors were analyzed, of which 87 were profiled using methyl-CpG-binding domain (MBD) sequencing for differential methylation analysis between prognostic patient groups. Subsequently, methylationspecific PCR (MSP) assays were developed for 78 top-ranking differentially methylated regions and tested on two independent cohorts of 132 and 177 samples, respectively. Further, a new statistical framework was used to identify a robust set of MSP assays of which the methylation score (i.e. the percentage of methylated assays) allows accurate outcome prediction. Survival analyses were performed on the individual target level, as well as on the combined multimarker signature. As a result of the differential DNA methylation assessment by MBD sequencing, 58 of the 78 MSP assays were designed in regions previously unexplored in neuroblastoma, and 36 are located in non-promoter or non-coding regions. In total, 5 individual MSP assays (located in CCDC177, NXPH1, lnc-MRPL3-2, lnc-TREX1-1 and one on a region from chromosome 8 with no further annotation) predict event-free survival and 4 additional assays (located in SPRED3, TNFAIP2, NPM2 and CYYR1) also predict overall survival. Furthermore, a robust 58-marker methylation signature predicting overall and eventfree survival was established. In conclusion, this study encompasses the largest DNA methylation biomarker study in neuroblastoma so far. We identified and independently validated several novel prognostic biomarkers, as well as a prognostic 58-marker methylation signature

MicroRNA and gene co-expression networks characterize biological and clinical behavior of rhabdomyosarcomas.

Rhabdomyosarcomas (RMS) in children and adolescents are heterogeneous sarcomas broadly defined by skeletal muscle features and the presence/absence of PAX3/7-FOXO1 fusion genes. MicroRNAs are small non-coding RNAs that regulate gene expression in a cell context specific manner. Sequencing analyses of microRNAs in 64 RMS revealed expression patterns separating skeletal muscle, fusion gene positive and negative RMS. Integration with parallel gene expression data assigned biological functions to 12 co-expression networks/modules that reassuringly included myogenic roles strongly correlated with microRNAs known in myogenesis and RMS development. Modules also correlated with clinical outcome and fusion status. Regulation of microRNAs by the fusion protein was demonstrated after PAX3-FOXO1 reduction, exemplified by miR-9-5p. MiR-9-5p levels correlated with poor outcome, even within fusion gene positive RMS, and were higher in metastatic versus non-metastatic disease. MiR-9-5p reduction inhibited RMS cell migration. Our findings reveal microRNAs in a regulatory framework of biological and clinical significance in RMS

Mutation Rate Switch inside Eurasian Mitochondrial Haplogroups: Impact of Selection and Consequences for Dating Settlement in Europe

R-lineage mitochondrial DNA represents over 90% of the European population and is significantly present all around the planet (North Africa, Asia, Oceania, and America). This lineage played a major role in migration “out of Africa” and colonization in Europe. In order to determine an accurate dating of the R lineage and its sublineages, we analyzed 1173 individuals and complete mtDNA sequences from Mitomap. This analysis revealed a new coalescence age for R at 54.500 years, as well as several limitations of standard dating methods, likely to lead to false interpretations. These findings highlight the association of a striking under-accumulation of synonymous mutations, an over-accumulation of non-synonymous mutations, and the phenotypic effect on haplogroup J. Consequently, haplogroup J is apparently not a Neolithic group but an older haplogroup (Paleolithic) that was subjected to an underestimated selective force. These findings also indicated an under-accumulation of synonymous and non-synonymous mutations localized on coding and non-coding (HVS1) sequences for haplogroup R0, which contains the major haplogroups H and V. These new dates are likely to impact the present colonization model for Europe and confirm the late glacial resettlement scenario

Current Trends in Satellite Laser Ranging

Satellite Laser Ranging (SLR) techniques are used to accurately measure the distance from ground stations to retroreflectors on satellites and the moon. SLR is one of the fundamental techniques that define the international Terrestrial Reference Frame (iTRF), which is the basis upon which we measure many aspects of global change over space, time, and evolving technology. It is one of the fundamental techniques that define at a level of precision of a few mm the origin and scale of the ITRF. Laser Ranging provides precision orbit determination and instrument calibration/validation for satellite-borne altimeters for the better understanding of sea level change, ocean dynamics, ice budget, and terrestrial topography. Laser ranging is also a tool to study the dynamics of the Moon and fundamental constants. Many of the GNSS satellites now carry retro-reflectors for improved orbit determination, harmonization of reference frames, and in-orbit co-location and system performance validation. The GNSS Constellations will be the means of making the reference frame available to worldwide users. Data and products from these measurements support key aspects of the GEOSS 10-Year implementation Plan adopted on February 16, 2005, The ITRF has been identified as a key contribution of the JAG to GEOSS and the ILRS makes a major contribution for its development since its foundation. The ILRS delivers weekly additional realizations that are accumulated sequentially to extend the ITRF and the Earth Orientation Parameter (EOP) series with a daily resolution. Additional products are currently under development such as precise orbits of satellites, EOP with daily availability, low-degree gravitational harmonics for studies of Earth dynamics and kinematics, etc. SLR technology continues to evolve toward the next generation laser ranging systems as programmatic requirements become more stringent. Ranging accuracy is improving as higher repetition rate, narrower pulse lasers and faster detectors are implemented. Automation and pass interleaving at some stations is already expanding temporal coverage. Web-based safety keys are allowing the SLR network stations to range to optically vulnerable satellites. Some stations are experimenting with two-wavelength operation as a means of better understanding the atmospheric refraction and with very low power laser to improve eye-safety conditions. New retroreflector designs are improving the signal link and enable daylight ranging. Dramatic improvements have also been made with lunar ranging with the new APOLLO Site in New ?Mexico, USA and the upgraded lunar station "MEO" in Grasse