Interconnecting bilayer networks

A typical complex system should be described by a supernetwork or a network of networks, in which the networks are coupled to some other networks. As the first step to understanding the complex systems on such more systematic level, scientists studied interdependent multilayer networks. In this letter, we introduce a new kind of interdependent multilayer networks, i.e., interconnecting networks, for which the component networks are coupled each other by sharing some common nodes. Based on the empirical investigations, we revealed a common feature of such interconnecting networks, namely, the networks with smaller averaged topological differences of the interconnecting nodes tend to share more nodes. A very simple node sharing mechanism is proposed to analytically explain the observed feature of the interconnecting networks.Comment: 9 page

Distribution of Spectral Lags in Gamma Ray Bursts

Using the data acquired in the Time To Spill (TTS) mode for long gamma-ray bursts (GRBs) collected by the Burst and Transient Source Experiment on board the Compton Gamma Ray Observatory (BATSE/CGRO), we have carefully measured spectral lags in time between the low (25-55 keV) and high (110-320 keV) energy bands of individual pulses contained in 64 multi-peak GRBs. We find that the temporal lead by higher-energy gamma-ray photons (i.e., positive lags) is the norm in this selected sample set of long GRBs. While relatively few in number, some pulses of several long GRBs do show negative lags. This distribution of spectral lags in long GRBs is in contrast to that in short GRBs. This apparent difference poses challenges and constraints on the physical mechanism(s) of producing long and short GRBs. The relation between the pulse peak count rates and the spectral lags is also examined. Observationally, there seems to be no clear evidence for systematic spectral lag-luminosity connection for pulses within a given long GRB.Comment: 20 pages, 4 figure

Hematopoietic-restricted Ptpn11E76K reveals indolent MPN progression in mice

Juvenile Myelomonocytic Leukemia (JMML) is a pediatric myeloproliferative neoplasm (MPN) that has a poor prognosis. Somatic mutations in Ptpn11 are the most frequent cause of JMML and they commonly occur in utero. Animal models of mutant Ptpn11 have probed the signaling pathways that contribute to JMML. However, existing models may inappropriately exacerbate MPN features by relying on non-hematopoietic-restricted Cre-loxP strains or transplantations into irradiated recipients. In this study we generate hematopoietic-restricted models of Ptpn11E76K-mediated disease using Csf1r-MCM and Flt3Cre. We show that these animals have indolent MPN progression despite robust GM-CSF hypersensitivity and Ras-Erk hyperactivation. Rather, the dominant pathology is pronounced thrombocytopenia with expanded extramedullary hematopoiesis. Furthermore, we demonstrate that the timing of tamoxifen administration in Csf1r-MCM mice can specifically induce recombinase activity in either fetal or adult hematopoietic progenitors. We take advantage of this technique to show more rapid monocytosis following Ptpn11E76K expression in fetal progenitors compared with adult progenitors. Finally, we demonstrate that Ptpn11E76K results in the progressive reduction of T cells, most notably of CD4+ and naïve T cells. This corresponds to an increased frequency of T cell progenitors in the thymus and may help explain the occasional emergence of T-cell leukemias in JMML patients. Overall, our study is the first to describe the consequences of hematopoietic-restricted Ptpn11E76K expression in the absence of irradiation. Our techniques can be readily adapted by other researchers studying somatically-acquired blood disorders

Ethyl 2-methyl-6-(propan-2-yl­amino)-4-sulfanyl­idene-3H,11H-pyrimido[1,6-c]quinazoline-1-carboxyl­ate

The title compound, C18H22N4O2S, contains a substituted pyrimidine ring fused to both a benzene ring and a substituted thioxopyrimidine ring. The pyrimidine and thioxopyrimidine rings adopt distorted chair conformations. In the crystal, adjacent mol­ecules are linked by pairs of N—H⋯S and N—H⋯O hydrogen bonds to generate centrosymmetric R 2 2(8) and R 2 2(16) loops, respectively. This combination leads to [100] chains of mol­ecules

Dimensionality Reduction and Generation of Human Motion

To reuse existing motion data and generate new motion, a method of human motion nonlinear dimensionality reduction and generation, based on fast adaptive scaled Gaussian process latent variable models, is proposed. Through statistical learning on motion data, the motion data are mapped from high-dimensional observation space to low-dimensional latent space to implement nonlinear dimensionality reduction, and probability distributing of posture space which measures the nature of posture is obtained. The posture which meets constraints and has maximal probability can be computed as the solution of inverse kinematics. This method can avoid cockamamie computation and posture distortion existing in traditional inverse kinematics.The experiments show that our method has higher convergence velocity and precision and extends editing range of motion by adapting motion editing direction

Inhibition of the Gab2/PI3K/mTOR signaling ameliorates myeloid malignancy caused by Ptpn11 (Shp2) gain-of-function mutations

Activating mutations, such as E76K and D61Y, in PTPN11 (SHP2), a protein tyrosine phosphatase implicated in multiple cell signaling processes, are associated with 35% of patients with juvenile myelomonocytic leukemia (JMML), an aggressive childhood myeloproliferative neoplasm (MPN). Here we show that the interaction between leukemia-associated mutant Shp2 and Gab2, a scaffolding protein important for cytokine-induced PI3K/Akt signaling, was enhanced, and that the mTOR pathway was elevated in Ptpn11E76K/+ leukemic cells. Importantly, MPN induced by the Ptpn11E76K/+ mutation was markedly attenuated in Ptpn11E76K/+/Gab2-/- double mutant mice-overproduction of myeloid cells was alleviated, splenomegaly was diminished and myeloid cell infiltration in nonhematopoietic organs was decreased in these double mutants. Excessive myeloid differentiation of stem cells was also normalized by depletion of Gab2. Acute leukemia progression of MPN was reduced in the double mutant mice and, as such, their survival was much prolonged. Furthermore, treatment of Ptpn11E76K/+ mice with Rapamycin, a specific and potent mTOR inhibitor, mitigated MPN phenotypes. Collectively, this study reveals an important role of the Gab2/PI3K/mTOR pathway in mediating the pathogenic signaling of the PTPN11 gain-of-function mutations and a therapeutic potential of Rapamycin for PTPN11 mutation-associated JMML

Critical role of ASCT2-mediated amino acid metabolism in promoting leukaemia development and progression

Amino acid (AA) metabolism is involved in diverse cellular functions, including cell survival and growth, however it remains unclear how it regulates normal hematopoiesis versus leukemogenesis. Here, we report that knockout of Slc1a5 (ASCT2), a transporter of neutral AAs, especially glutamine, results in mild to moderate defects in bone marrow and mature blood cell development under steady state conditions. In contrast, constitutive or induced deletion of Slc1a5 decreases leukemia initiation and maintenance driven by the oncogene MLL-AF9 or Pten deficiency. Survival of leukemic mice is prolonged following Slc1a5 deletion, and pharmacological inhibition of ASCT2 also decreases leukemia development and progression in xenograft models of human acute myeloid leukemia. Mechanistically, loss of ASCT2 generates a global effect on cellular metabolism, disrupts leucine influx and mTOR signaling, and induces apoptosis in leukemic cells. Given the substantial difference in reliance on ASCT2-mediated AA metabolism between normal and malignant blood cells, this in vivo study suggests ASCT2 as a promising therapeutic target for the treatment of leukemia