REBOUND is a new multi-purpose N-body code which is freely available under an open-source license. It was designed for collisional dynamics such as planetary rings but can also solve the classical ...N-body problem. It is highly modular and can be customized easily to work on a wide variety of different problems in astrophysics and beyond. REBOUND comes with three symplectic integrators: leap-frog, the symplectic epicycle integrator (SEI) and a Wisdom-Holman mapping (WH). It supports open, periodic and shearing-sheet boundary conditions. REBOUND can use a Barnes-Hut tree to calculate both self-gravity and collisions. These modules are fully parallelized with MPI as well as OpenMP. The former makes use of a static domain decomposition and a distributed essential tree. Two new collision detection modules based on a plane-sweep algorithm are also implemented. The performance of the plane-sweep algorithm is superior to a tree code for simulations in which one dimension is much longer than the other two and in simulations which are quasi-two dimensional with less than one million particles. In this work, we discuss the different algorithms implemented in REBOUND, the philosophy behind the code’s structure as well as implementation specific details of the different modules. We present results of accuracy and scaling tests which show that the code can run efficiently on both desktop machines and large computing clusters.
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FMFMET, NUK, UL, UM, UPUK
The stacking fault energy (SFE) values of several typical face-centered-cubic (fcc) high-entropy alloys (HEAs) were experimentally measured by weak-beam dark-field transmission electron microscopy. ...It was found that the SFE of the Fe-Co-Ni-Cr-Mn HEA system strongly depends on the SFE of the individual constituents. Specifically, the SFE of this HEA system is closely associated with the Ni concentration in the alloys. Additionally, the lower SFE tends to promote formation of more deformation twins with a smaller thickness under loading, leading to better mechanical properties, especially at low temperatures.
•SFE of six Fe-Co-Ni-Cr-Mn HEAs was measured experimentally.•Constituents play an important role in the SFE, particularly the Ni content.•Lower SFE promotes formation of thinner twins during loading and better properties.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Mesenchymal stem cells (MSCs) are multi-potent progenitor cells that are isolated from the bone marrow and several adult organs and tissues. These cells possess remarkable immunosuppressive ...properties and can inhibit the proliferation and function of the major immune cell populations, including T cells, B cells and natural killer (NK) cells; modulate the activities of dendritic cells (DCs); and induce regulatory T cells both in vivo and in vitro. These unique properties make MSCs ideal candidates for clinical application as immunosuppressants. The immunomodulatory effect of MSCs is mediated by a non-specific anti-proliferative action of these cells, which is dependent on cell-cell contact or secreted soluble factors such as indoleamine 2,3-dioxygenase (IDO), prostaglandin E₂ (PGE₂), nitric oxide (NO), histocompatibility leucocyte antigen-G (HLA-G), transforming growth factor (TGF)-β, interferon (IFN)-γ and interleukin (IL)-1β. Considerable progress has been obtained in preclinical studies on MSCs, including those on their ability to activate allogeneic cells. This review examines the current understanding of the immunomodulatory properties of MSCs and its therapeutic implication for immune-mediated diseases and transplant rejection.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Face-centered cubic (fcc) HEAs, particularly the typical FeCoNiCrMn HEA, are promising for cryogenic applications but generally exhibit relatively low strength at ambient temperature, which limits ...their widespread uses. In this work, we present a systematic study of enhancing simultaneously the strength and ductility of FeCoNiCrMn HEAs via tailoring the phase stability and stacking fault energy (SFE). It was found that in Fe20CoxNi40-xCr20Mn20 (x = 20–30 at.%) HEAs, with the increase of Co, the SFE was gradually decreased and another hcp (hexagonal close-packed) phase was eventually formed in the alloy containing 28 at.% Co. As a result, the deformation mode changes from dislocation glide to mechanical twinning, then to γfcc → εhcp martensitic transformation. Our analysis indicates that the small critical shear stress for twinning resulted from the reduced SFE provides a steady strain hardening rate in a wide strain regime and postpones the plastic instability, eventually leading to the concurrent enhancement in the tensile strength and ductility. Our results not only shed lights on understanding of the effects of SFE on the mechanical properties, but also have important implications on the development of HEAs with a unique combination of high strength and large ductility.
•Increase of the Co content decreases the SFE and phase stability of FeCoNiCrMn alloy.•TRIP effects were achieved with the increase of Co content.•Increase of Co enhances the strength and ductility simultaneously.•Effects of the SFE on deformation mechanism were explored.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZRSKP
Soil acidification is a major problem in soils of intensive Chinese agricultural systems. We used two nationwide surveys, paired comparisons in numerous individual sites, and several long-term ...monitoring-field data sets to evaluate changes in soil acidity. Soil pH declined significantly (P < 0.001) from the 1980s to the 2000s in the major Chinese crop-production areas. Processes related to nitrogen cycling released 20 to 221 kilomoles of hydrogen ion (H⁺) per hectare per year, and base cations uptake contributed a further 15 to 20 kilomoles of H⁺ per hectare per year to soil acidification in four widespread cropping systems. In comparison, acid deposition (0.4 to 2.0 kilomoles of H⁺ per hectare per year) made a small contribution to the acidification of agricultural soils across China.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
A Nationwide Nitrogen Deposition Monitoring Network (NNDMN) containing 43 monitoring sites was established in China to measure gaseous NH3, NO2, and HNO3 and particulate NH4+ and NO3− in air and/or ...precipitation from 2010 to 2014. Wet/bulk deposition fluxes of Nr species were collected by precipitation gauge method and measured by continuous-flow analyzer; dry deposition fluxes were estimated using airborne concentration measurements and inferential models. Our observations reveal large spatial variations of atmospheric Nr concentrations and dry and wet/bulk Nr deposition. On a national basis, the annual average concentrations (1.3–47.0 μg N m−3) and dry plus wet/bulk deposition fluxes (2.9–83.3 kg N ha−1 yr−1) of inorganic Nr species are ranked by land use as urban > rural > background sites and by regions as north China > southeast China > southwest China > northeast China > northwest China > Tibetan Plateau, reflecting the impact of anthropogenic Nr emission. Average dry and wet/bulk N deposition fluxes were 20.6 ± 11.2 (mean ± standard deviation) and 19.3 ± 9.2 kg N ha−1 yr−1 across China, with reduced N deposition dominating both dry and wet/bulk deposition. Our results suggest atmospheric dry N deposition is equally important to wet/bulk N deposition at the national scale. Therefore, both deposition forms should be included when considering the impacts of N deposition on environment and ecosystem health.
Targeted immunotherapy in acute myeloid leukemia (AML) is challenged by the lack of AML-specific target antigens and clonal heterogeneity, leading to unwanted on-target off-leukemia toxicity and risk ...of relapse from minor clones. We hypothesize that combinatorial targeting of AML cells can enhance therapeutic efficacy without increasing toxicity. To identify target antigen combinations specific for AML and leukemic stem cells, we generated a detailed protein expression profile based on flow cytometry of primary AML (n = 356) and normal bone marrow samples (n = 34), and a recently reported integrated normal tissue proteomic data set. We analyzed antigen expression levels of CD33, CD123, CLL1, TIM3, CD244 and CD7 on AML bulk and leukemic stem cells at initial diagnosis (n = 302) and relapse (n = 54). CD33, CD123, CLL1, TIM3 and CD244 were ubiquitously expressed on AML bulk cells at initial diagnosis and relapse, irrespective of genetic characteristics. For each analyzed target, we found additional expression in different populations of normal hematopoiesis. Analyzing the coexpression of our six targets in all dual combinations (n = 15), we found CD33/TIM3 and CLL1/TIM3 to be highly positive in AML compared with normal hematopoiesis and non-hematopoietic tissues. Our findings indicate that combinatorial targeting of CD33/TIM3 or CLL1/TIM3 may enhance therapeutic efficacy without aggravating toxicity in immunotherapy of AML.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Antiangiogenic therapy resistance occurs frequently in patients with metastatic renal cell carcinoma (RCC). The purpose of this study was to understand the mechanism of resistance to sunitinib, an ...antiangiogenic small molecule, and to exploit this mechanism therapeutically. We hypothesized that sunitinib-induced upregulation of the prometastatic MET and AXL receptors is associated with resistance to sunitinib and with more aggressive tumor behavior. In the present study, tissue microarrays containing sunitinib-treated and untreated RCC tissues were stained with MET and AXL antibodies. The low malignant RCC cell line 786-O was chronically treated with sunitinib and assayed for AXL, MET, epithelial-mesenchymal transition (EMT) protein expression and activation. Co-culture experiments were used to examine the effect of sunitinib pretreatment on endothelial cell growth. The effects of AXL and MET were evaluated in various cell-based models by short hairpin RNA or inhibition by cabozantinib, the multi-tyrosine kinases inhibitor that targets vascular endothelial growth factor receptor, MET and AXL. Xenograft mouse models tested the ability of cabozantinib to rescue sunitinib resistance. We demonstrated that increased AXL and MET expression was associated with inferior clinical outcome in patients. Chronic sunitinib treatment of RCC cell lines activated both AXL and MET, induced EMT-associated gene expression changes, including upregulation of Snail and β-catenin, and increased cell migration and invasion. Pretreatment with sunitinib enhanced angiogenesis in 786-0/human umbilical vein endothelial cell co-culture models. The suppression of AXL or MET expression and the inhibition of AXL and MET activation using cabozantinib both impaired chronic sunitinib treatment-induced prometastatic behavior in cell culture and rescued acquired resistance to sunitinib in xenograft models. In summary, chronic sunitinib treatment induces the activation of AXL and MET signaling and promotes prometastatic behavior and angiogenesis. The inhibition of AXL and MET activity may overcome resistance induced by prolonged sunitinib therapy in metastatic RCC.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We describe here a comprehensive study on the effect of cellular structure and melt pool boundary (MPB) condition on the mechanical properties, deformation and failure behavior of AlSi10Mg alloy ...processed by selective laser melting (SLM). The morphology of melt pool (MP) on the load bearing face of tensile samples was significantly different with build directions. It resulted in different mechanical properties of the samples with different build directions. Furthermore, the microstructure analysis revealed that the MP in the SLM AlSi10Mg alloy mainly consisted of columnar α-Al grains which were made of ultra-fine elongated cellular structure. Electron back-scatter diffraction (EBSD) analysis revealed that the long axis of cellular structure and columnar grains were parallel to < 100 >, which resulted in < 100 > fiber texture in SLM AlSi10Mg alloy. However, Schmid factor calculation demonstrated that the anisotropy of mechanical properties of the SLM AlSi10Mg alloy built with different direction was mainly dependent on the distribution of MPB on the load bearing face, and not texture. The defects including pores, residual stress and heat affected zone (HAZ) located at MPB made it the weakest part in the SLM AlSi10Mg. The sample built along horizontal direction exhibited good combination of strength and plasticity and is attributed to the lowest fraction of MPBs that withstand load during tensile. MPB had strong influence on the mechanical properties and failure behavior of SLM AlSi10Mg built with different directions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cells apoptosis induced by intense heat stress is the prominent feature of heat-related illness. However, little is known about the biological effects of heat stress on cells apoptosis. Herein, we ...presented evidence that intense heat stress could induce early apoptosis of HUVEC cells through activating mitochondrial pathway with changes in mitochondrial membrane potential(ΔΨm), release of cytochrome c, and activation of caspase-9 and -3. We further revealed that p53 played a crucial role in heat stress-induced early apoptosis, with p53 protein rapidly translocated into mitochondria. Using pifithrin-α(PFT), a p53's mitochondrial translocation inhibitor, we found that pretreated with PFT, heat stress induced mitochondrial p53 translocation was significantly suppressed, accompanied by a significant alleviation in the loss of ΔΨm, cytochrome c release and caspase-9 activation. Furthermore, we also found that generation of reactive oxygen species (ROS) was a critical mediator in heat stress-induced apoptosis. In addition, the antioxidant MnTMPyP significantly decreased the heat stress-induced p53's mitochondrial translocation, followed by the loss of ΔΨm, cytochrome c release, caspase-9 activation and heat stress-mediated apoptosis. Conclusively, these findings indicate the contribution of the transcription-independent mitochondrial p53 pathway to early apoptosis in HUVEC cells induced by oxidative stress in response to intense heat stress.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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