Aberrant expression of long noncoding RNAs (lncRNAs) is associated with various human cancers. However, the role of lncRNAs in Bcr-Abl-mediated chronic myeloid leukemia (CML) is unknown. In this ...study, we performed a comprehensive analysis of lncRNAs in human CML cells using an lncRNA cDNA microarray and identified an lncRNA termed lncRNA-BGL3 that acted as a key regulator of Bcr-Abl-mediated cellular transformation. Notably, we observed that lncRNA-BGL3 was highly induced in response to disruption of Bcr-Abl expression or by inhibiting Bcr-Abl kinase activity in K562 cells and leukemic cells derived from CML patients. Ectopic expression of lncRNA-BGL3 sensitized leukemic cells to undergo apoptosis and inhibited Bcr-Abl-induced tumorigenesis. Furthermore, transgenic (TG) mice expressing lncRNA-BGL3 were generated. We found that TG expression of lncRNA-BGL3 alone in mice was sufficient to impair primary bone marrow transformation by Bcr-Abl. Interestingly, we identified that lncRNA-BGL3 was a target of miR-17, miR-93, miR-20a, miR-20b, miR-106a and miR-106b, microRNAs that repress mRNA of phosphatase and tensin homolog (PTEN). Further experiments demonstrated that lncRNA-BGL3 functioned as a competitive endogenous RNA for binding these microRNAs to cross-regulate PTEN expression. Additionally, our experiments have begun to address the mechanism of how lncRNA-BGL3 is regulated in the leukemic cells and showed that Bcr-Abl repressed lncRNA-BGL3 expression through c-Myc-dependent DNA methylation. Taken together, these results reveal that Bcr-Abl-mediated cellular transformation critically requires silence of tumor-suppressor lncRNA-BGL3 and suggest a potential strategy for the treatment of Bcr-Abl-positive leukemia.
We present empirical metallicity-dependent calibrations of effective temperature against colours for dwarfs of luminosity classes IV and V and for giants of luminosity classes II and III, based on a ...collection from the literature of about two hundred nearby stars with direct effective temperature measurements of better than 2.5 per cent. The calibrations are valid for an effective temperature range 3100–10 000 K for dwarfs of spectral types M5 to A0 and 3100–5700 K for giants of spectral types K5 to G5. A total of 21 colours for dwarfs and 18 colours for giants of bands of four photometric systems, i.e. the Johnson (UBVR
J
I
J
JHK), the Cousins (R
C
I
C), the Sloan Digital Sky Survey (gr) and the Two Micron All Sky Survey (JHK
s), have been calibrated. Restricted by the metallicity range of the current sample, the calibrations are mainly applicable for disc stars (Fe/H ≳ − 1.0). The normalized percentage residuals of the calibrations are typically 2.0 and 1.5 per cent for dwarfs and giants, respectively. Some systematic discrepancies at various levels are found between the current scales and those available in the literature (e.g. those based on the infrared flux method or spectroscopy). Based on the current calibrations, we have re-determined the colours of the Sun. We have also investigated the systematic errors in effective temperatures yielded by the current on-going large-scale low- to intermediate-resolution stellar spectroscopic surveys. We show that the calibration of colour (g − K
s) presented in this work provides an invaluable tool for the estimation of stellar effective temperature for those on-going or upcoming surveys.
The susceptible-infected-susceptible (SIS) model is a canonical model for emerging disease outbreaks. Such outbreaks are naturally modeled as taking place on networks. A theoretical challenge in ...network epidemiology is the dynamic correlations coming from that if one node is infected, then its neighbors are likely to be infected. By combining two theoretical approaches-the heterogeneous mean-field theory and the effective degree method-we are able to include these correlations in an analytical solution of the SIS model. We derive accurate expressions for the average prevalence (fraction of infected) and epidemic threshold. We also discuss how to generalize the approach to a larger class of stochastic population models.
Abstract
We present the second release of value-added catalogues of the LAMOST Spectroscopic Survey of the Galactic Anticentre (LSS-GAC DR2). The catalogues present values of radial velocity Vr, ...atmospheric parameters – effective temperature Teff, surface gravity log g, metallicity Fe/H, α-element to iron (metal) abundance ratio α/Fe (α/M), elemental abundances C/H and N/H and absolute magnitudes MV and $M_{K_{\rm s}}$ deduced from 1.8 million spectra of 1.4 million unique stars targeted by the LSS-GAC since 2011 September until 2014 June. The catalogues also give values of interstellar reddening, distance and orbital parameters determined with a variety of techniques, as well as proper motions and multiband photometry from the far-UV to the mid-IR collected from the literature and various surveys. Accuracies of radial velocities reach 5 km s−1 for the late-type stars, and those of distance estimates range between 10 and 30 per cent, depending on the spectral signal-to-noise ratios. Precisions of Fe/H, C/H and N/H estimates reach 0.1 dex, and those of α/Fe and α/M reach 0.05 dex. The large number of stars, the contiguous sky coverage, the simple yet non-trivial target selection function and the robust estimates of stellar radial velocities and atmospheric parameters, distances and elemental abundances make the catalogues a valuable data set to study the structure and evolution of the Galaxy, especially the solar-neighbourhood and the outer disc.
Loss of 1p36 heterozygosity commonly occurs with MYCN amplification in neuroblastoma tumors, and both are associated with an aggressive phenotype. Database searches identified five microRNAs that map ...to the commonly deleted region of 1p36 and we hypothesized that the loss of one or more of these microRNAs contributes to the malignant phenotype of MYCN-amplified tumors. By bioinformatic analysis, we identified that three out of the five microRNAs target MYCN and of these miR-34a caused the most significant suppression of cell growth through increased apoptosis and decreased DNA synthesis in neuroblastoma cell lines with MYCN amplification. Quantitative RT-PCR showed that neuroblastoma tumors with 1p36 loss expressed lower level of miR-34a than those with normal copies of 1p36. Furthermore, we demonstrated that MYCN is a direct target of miR-34a. Finally, using a series of mRNA expression profiling experiments, we identified other potential direct targets of miR-34a, and pathway analysis demonstrated that miR-34a suppresses cell-cycle genes and induces several neural-related genes. This study demonstrates one important regulatory role of miR-34a in cell growth and MYCN suppression in neuroblastoma.
The vast majority of slopes, both natural and constructed, exhibit a complex geometric configuration and three-dimensional (3D) state, whereas slopes satisfying the assumption of plane strain ...(infinite length) are seldom encountered. Existing research mainly emphasizes the 3D dimensions and boundary effect in slope stability analysis; however, the effect of complex geometric ground configuration on 3D slope stability is rarely reported. In this paper, an elastoplastic finite-element method using strength-reduction techniques is used to analyze the stability of special 3D geometric slopes. A typical 3D slope underlain by a weak layer with groundwater is described to validate the numerical modeling, safety factor values, and critical slip surface for the 3D slope. Furthermore, a series of special 3D slopes with various geometric configurations are analyzed numerically, and the effects of turning corners, slope gradient, turning arcs, and convex- and concave-shaped surface geometry on the stability and failure characteristics of slopes under various boundary conditions are discussed in detail.
Shear band is the key feature that controls the plastic deformation process of metallic glasses (MGs). However, the investigation directly on the shear band and its properties is rarely conducted as ...the band is perceived as extremely narrow. We have conducted a controlled experiment to form a single shear band in the specimen, which enabled us to probe shear-induced softening and dilatation directly on the shear band itself. Extreme dilatation and free volume increase as high as 1.14% and 1.40% respectively, have been observed, resulting from a drastic structure change due to severe plastic flow in the band. Nanoindentation on the individual shear band reveals significant softening of 36% and an unexpected wide width up to 160
μm, three magnitudes higher than what has been reported. These prove beyond doubt the dilatation as a mechanism for softening. The correlation between the free volume content and softening is discussed. Our findings provide a new insight for understanding the deformation behavior of metallic glass.
By combining LAMOST DR4 and Gaia DR2 common red clump stars with age and proper motion, we analyze the amplitude evolution of the stellar warp independently of any assumption with a simple model. The ...greatest height of the warp disk increases with galactocentric distance in different populations and is dependent on age: the younger stellar populations exhibit stronger warp features than the old ones, accompanied by the warp amplitude γ (age) decreasing with age, and its first derivative is different from zero. The azimuth of the line of nodes φw is stable at −5° without clear time evolution, which perfectly confirms some previous works. All of this self-consistent evidence supports that our Galactic warp should most likely be a long-lived but nonsteady structure and not a transient one, which is supporting that the warp originated from gas infall onto the disk or other hypotheses that suppose that the warp mainly affects the gas, and consequently, younger populations tracing the gas are stronger than older ones. In other words, the Galactic warp is induced by the nongravitational interaction over the disk models.
Mesenchymal stem cells (MSCs), a non-hematopoietic stem cell population first discovered in bone marrow, are multipotent cells capable of differentiating into mature cells of several mesenchymal ...tissues, such as fat and bone. As common progenitor cells of adipocytes and osteoblasts, MSCs are delicately balanced for their differentiation commitment. Numerous in vitro investigations have demonstrated that fat-induction factors inhibit osteogenesis, and, conversely, bone-induction factors hinder adipogenesis. In fact, a variety of external cues contribute to the delicate balance of adipo-osteogenic differentiation of MSCs, including chemical, physical, and biological factors. These factors trigger different signaling pathways and activate various transcription factors that guide MSCs to commit to either lineage. The dysregulation of the adipo-osteogenic balance has been linked to several pathophysiologic processes, such as aging, obesity, osteopenia, osteopetrosis, and osteoporosis. Thus, the regulation of MSC differentiation has increasingly attracted great attention in recent years. Here, we review external factors and their signaling processes dictating the reciprocal regulation between adipocytes and osteoblasts during MSC differentiation and the ultimate control of the adipo-osteogenic balance.
PDF
