Aimed at the technical problems of low drilling speed and difficult rock-breaking in deep-well and hard rock-stratum, particle waterjet coupled impact rock-breaking technology in rotary drilling is ...put forward in this paper. Firstly, the working principle of particle jet impact rock-breaking in rotary drilling was introduced, and the acceleration model of particle jet and the damage model of rock were established. The acceleration mechanism of particles and dynamic damage evolution process of rock under particle jet were studied, which showed that the broken pit and rock damage would increase with time gone on, and damage evolution of rock presented the radial expansion. Then, experimental device of particle jet coupled impact rock-breaking in rotary state was developed, and the effect of jet parameters on penetration depth and failure volume was analyzed with comparison of la experiment and numerical simulation. The results showed that drilling speed with particle jet impact is twice that of conventional drilling, and combination nozzles layout of impact angle with 8°and 20° can achieve rock-drilled rapidly, which also demonstrated the correctness of simulation method. The device development and the rock-breaking results analysis would be of great value for engineering application.
Bone marrow (BM) perivascular stromal cells and vascular endothelial cells (ECs) are essential for hematopoietic stem cell (HSC) maintenance, but the roles of distinct niche compartments during HSC ...regeneration are less understood. Here we show that Leptin receptor-expressing (LepR+) BM stromal cells and ECs dichotomously regulate HSC maintenance and regeneration via secretion of pleiotrophin (PTN). BM stromal cells are the key source of PTN during steady-state hematopoiesis because its deletion from stromal cells, but not hematopoietic cells, osteoblasts, or ECs, depletes the HSC pool. Following myelosuppressive irradiation, PTN expression is increased in bone marrow endothelial cells (BMECs), and PTN+ ECs are more frequent in the niche. Moreover, deleting Ptn from ECs impairs HSC regeneration whereas Ptn deletion from BM stromal cells does not. These findings reveal dichotomous and complementary regulation of HSC maintenance and regeneration by BM stromal cells and ECs.
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•PTN secretion by BM stromal cells is essential for HSC maintenance•Hematologic recovery following irradiation requires PTN from BM stromal cells and ECs•PTN secretion by BMECs is essential for HSC regeneration following irradiation•Irradiation enriches for PTN-expressing BMECs in the niche
Himburg et al. demonstrate dichotomous regulation of blood stem cell maintenance and regeneration by BM stromal cells and ECs. Utilizing conditional genetic models, the authors show that blood stem cell maintenance requires PTN secretion by BM stromal cells, whereas blood stem cell regeneration requires complementary PTN production by BMECs.
Phase transition is common during (de)-intercalating layered sodium oxides, which directly affects the structural stability and electrochemical performance. However, the artificial control of phase ...transition to achieve advanced sodium-ion batteries is lacking, since the remarkably little is known about the influencing factor relative to the sliding process of transition-metal slabs upon sodium release and uptake of layered oxides. Herein, we for the first time demonstrate the manipulation of oxygen vacancy concentrations in multinary metallic oxides has a significant impact on the reversibility of phase transition, thereby determining the sodium storage performance of cathode materials. Results show that abundant oxygen vacancies intrigue the return of the already slide transition-metal slabs between O3 and P3 phase transition, in contrast to the few oxygen vacancies and resulted irreversibility. Additionally, the abundant oxygen vacancies enhance the electronic and ionic conductivity of the Na
0.9
Ni
0.3
Co
0.15
Mn
0.05
Ti
0.5
O
2
electrode, delivering the high initial Coulombic efficiency of 97.1%, large reversible capacity of 112.7 mAh·g
−1
, superior rate capability upon 100 C and splendid cycling performance over 1,000 cycles. Our findings open up new horizons for artificially manipulating the structural evolution and electrochemical process of layered cathodes, and pave a way in designing advanced sodium-ion batteries.
Ionizing radiation and chemotherapy deplete hematopoietic stem cells and damage the vascular niche wherein hematopoietic stem cells reside. Hematopoietic stem cell regeneration requires signaling ...from an intact bone marrow (BM) vascular niche, but the mechanisms that control BM vascular niche regeneration are poorly understood. We report that BM vascular endothelial cells secrete semaphorin 3 A (SEMA3A) in response to myeloablation and SEMA3A induces p53 - mediated apoptosis in BM endothelial cells via signaling through its receptor, Neuropilin 1 (NRP1), and activation of cyclin dependent kinase 5. Endothelial cell - specific deletion of Nrp1 or Sema3a or administration of anti-NRP1 antibody suppresses BM endothelial cell apoptosis, accelerates BM vascular regeneration and concordantly drives hematopoietic reconstitution in irradiated mice. In response to NRP1 inhibition, BM endothelial cells increase expression and secretion of the Wnt signal amplifying protein, R spondin 2. Systemic administration of anti - R spondin 2 blocks HSC regeneration and hematopoietic reconstitution which otherwise occurrs in response to NRP1 inhibition. SEMA3A - NRP1 signaling promotes BM vascular regression following myelosuppression and therapeutic blockade of SEMA3A - NRP1 signaling in BM endothelial cells accelerates vascular and hematopoietic regeneration in vivo.
•The rock failure volume model under particle jet impact is put forward and established.•Damage evolution and failure volume under particle jet impact are dynamically simulated and analyzed.•The ...correctness and applicability of mathematical model were verified by comparative analysis with experiment and simulation.
There are some difficult problems in deep and ultra-deep oil and natural gas drilling process due to the complex stress environment and hard formation, such as slow drilling speed, well deviation and high cost. As one of the important parameters to measure rock-breaking efficiency, mathematical model of failure volume is proposed in this paper, which is suitable for deep-well rock-breaking technology. First, the particle jet impact rock-breaking laboratory experiment was conducted based on the self-developed experimental platform, and the strength of rock specimen was tested. Then, the failure volume model of particle jet impact rock-breaking which varied with particle size, and water-jet velocity was established based on contact mechanics. Meanwhile, the simulation model and method of particle jet impact rock was carried out and introduced, and damage evolution was dynamical simulated. Comparative analysis of experiment results, model calculation and dynamic simulation was used to analyze the failure volume, and it showed, failure volume would increase linearly with increase of water-jet velocity, while particle size has little effect on failure volume under the condition of constant nozzle diameter. The comparison results of theoretical modeling and rock-breaking experiment are basically consistent, which proves the correctness and applicability of failure volume model.
Particle jet impact drilling technology is an efficient method which mainly uses high-velocity particles to break rock. As the important criterion for evaluating rock-breaking effect, rock-breaking ...depth and damage area were studied in this paper. Firstly, a particle jet impact rock-breaking test device was developed, and laboratory experiments have been carried out. Then, based on the spherical cavity expansion theory, the mathematical model of rock-breaking depth and damage area under particle jet impact was established. Afterward, the effect of water-jet impact velocity, impact angle, and particle diameter on rock-breaking depth and damage area was analyzed by comparing experimental results and mathematical calculation. The results show that rock-breaking depth and damage area would increase with increase of water-jet impact velocity and decrease slightly with increase of particle diameter. And the combination of 8° and 20° is recommended for nozzle layout. The experimental results and mathematical calculation are basically consistent, which could verify the correctness of the mathematical model. The study has significance for development and application of particle jet impact rock-breaking technology and perfection of theoretical research.
Receptor type protein tyrosine phosphatase-sigma (PTPσ) is primarily expressed by adult neurons and regulates neural regeneration. We recently discovered that PTPσ is also expressed by hematopoietic ...stem cells (HSCs). Here, we describe small molecule inhibitors of PTPσ that promote HSC regeneration in vivo. Systemic administration of the PTPσ inhibitor, DJ001, or its analog, to irradiated mice promotes HSC regeneration, accelerates hematologic recovery, and improves survival. Similarly, DJ001 administration accelerates hematologic recovery in mice treated with 5-fluorouracil chemotherapy. DJ001 displays high specificity for PTPσ and antagonizes PTPσ via unique non-competitive, allosteric binding. Mechanistically, DJ001 suppresses radiation-induced HSC apoptosis via activation of the RhoGTPase, RAC1, and induction of BCL-X
. Furthermore, treatment of irradiated human HSCs with DJ001 promotes the regeneration of human HSCs capable of multilineage in vivo repopulation. These studies demonstrate the therapeutic potential of selective, small-molecule PTPσ inhibitors for human hematopoietic regeneration.
Imprinted genes are differentially expressed by adult stem cells, but their functions in regulating adult stem cell fate are incompletely understood. Here we show that growth factor receptor-bound ...protein 10 (Grb10), an imprinted gene, regulates hematopoietic stem cell (HSC) self-renewal and regeneration. Deletion of the maternal allele of Grb10 in mice (Grb10m/+ mice) substantially increased HSC long-term repopulating capacity, as compared to that of Grb10+/+ mice. After total body irradiation (TBI), Grb10m/+ mice demonstrated accelerated HSC regeneration and hematopoietic reconstitution, as compared to Grb10+/+ mice. Grb10-deficient HSCs displayed increased proliferation after competitive transplantation or TBI, commensurate with upregulation of CDK4 and Cyclin E. Furthermore, the enhanced HSC regeneration observed in Grb10-deficient mice was dependent on activation of the Akt/mTORC1 pathway. This study reveals a function for the imprinted gene Grb10 in regulating HSC self-renewal and regeneration and suggests that the inhibition of Grb10 can promote hematopoietic regeneration in vivo.
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•Grb10, an imprinted gene, is upregulated in regenerating hematopoietic stem cells•Grb10 deletion promotes hematopoietic stem cell self-renewal following transplantation•Grb10 deletion increases hematopoietic stem cell regeneration following irradiation•Hematopoietic stem cell regeneration is mediated via mTORC1 in Grb10-deficient mice
Yan et al. find that an imprinted gene, growth factor receptor-bound protein 10 (Grb10), is differentially expressed during hematopoietic stem cell (HSC) regeneration and that deletion of Grb10 augments HSC self-renewal and regeneration in vivo.
•Analysis of dynamical damage process by establishing simulation model of particle water-jet coupling impact rock.•The effect factors of rock damage and failure depth were discussed with experiment ...and simulation.•The failure mechanism and damage expansion law were revealed by defining Gaussian points.
Aiming at the problems of difficult observation of rock damage mechanism and many influencing factors of rock-breaking process, the damage mechanism of particle water-jet coupling impact was studied. Based on SPH-FEM coupling algorithm, the numerical model of particle water-jet impact rock was established, and the mechanical properties of rock were characterized by JH-2 (Johnson Holmquist II) damage model. Then, damage evolution and failure effect under the impact of water-jet and particle water-jet were simulated. It shows that the failure of rock is a cyclic process of “damage–cumulative damage–failure–cumulative damage–failure”, which is mainly manifested as shear powder and tensile cracks. Meanwhile, particle water-jet coupling impact rock-breaking experiment system and methods were introduced and the comparison way of experiment and simulation was used to analyze the influence law of particle ratio, water-jet impact velocity, particle diameter, impact angle on rock damage and failure depth. The propagation law of transverse and longitudinal damage inside of rock was studied by defining Gaussian points and damage would often occur instantaneously which was basically microsecond level.
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