The safety of CRISPR (clustered regularly interspaced short palindromic repeats)-based genome editing in the context of human gene therapy is largely unknown.
is a reasonable but not absolutely ...protective target for a cure of human immunodeficiency virus type 1 (HIV-1) infection, because
-null blood cells are largely resistant to HIV-1 entry. We transplanted CRISPR-edited
-ablated hematopoietic stem and progenitor cells (HSPCs) into a patient with HIV-1 infection and acute lymphoblastic leukemia. The acute lymphoblastic leukemia was in complete remission with full donor chimerism, and donor cells carrying the ablated
persisted for more than 19 months without gene editing-related adverse events. The percentage of CD4+ cells with
ablation increased by a small degree during a period of antiretroviral-therapy interruption. Although we achieved successful transplantation and long-term engraftment of CRISPR-edited HSPCs, the percentage of
disruption in lymphocytes was only approximately 5%, which indicates the need for further research into this approach. (Funded by the Beijing Municipal Science and Technology Commission and others; ClinicalTrials.gov number, NCT03164135.).
Abstract
In complex high in-situ stress conditions, how to achieve the ideal rock blasting effect through effective methods is often a difficult point of blasting operations. This paper analyzes the ...influence of guide holes on blasting effect by adding guide holes to the rock pre-treatment method. Based on the particle expansion method to carry out double-hole blasting experiments, the influence of the blasthole spacing and ground stress on the blasting effect is investigated from the levels of macroscopic cracking effect, microscopic particle contact and so on. The study shows that: (i) the setting of empty holes between the gun holes can enhance the crack penetration effect, and the penetration effect is more obvious when the distance between the gun holes and the empty holes is less than 2.5 times the radius of the crushed zone. (ii) At the level of contact force chain, when the distance between blastholes and empty holes is less than 2.5 times the radius of the crushing zone. The compressive stress in the direction perpendicular to the direction of the blasthole line inhibits crack development, and the tensile stress in the direction parallel to the blasthole line promotes crack development. The main stress direction is perpendicular to the direction of the blasthole line. (iii) As the distance between the blastholes increases, the effect of crack suppression by stresses in the vertical direction decreases, and the main force direction is parallel to the direction of the blasthole line.
Considering anti-rotation of sand particles, two-dimensional Discrete Element Method (DEM) has been employed to reproduce direct shear behaviors of sand with different particle distribution sizes, so ...as to explore effects of anti-rotation of particle on responses of stress-displacement and dilatancy, the evolution law of shear stress, coordination number and vertical displacement of sand samples, and analyze the contact force chain, contact fabric and porosity of the samples after shearing.The results show that the anti-rotation ability of sand is enhanced, the torque of overcoming the relative rotation between particles is increased, and the peak shear stress, dilatancy and porosity in the middle of the sample are increased; with the increase of the anti-rotation coefficient, the coordination number decreases more obviously. The proportion of the contact number in the direction of 100°-160° to the total contact number decreases with the increase of the anti-rotation coefficient. The elliptical shape of the contact configuration becomes more flat, and the anisotropy of the contact force chain is more obvious; compared with fine sand, the coarse sand has greater shear capacity, more obvious dilatancy and larger porosity in the middle of the sample.The maximum minimum particle size ratio of the sample becomes larger, so that the shear strength of the sample is reduced, and the dilatancy is also weak.
Abstract Currently, the treatment of miscellaneous fill foundations, composed of a mixture of domestic garbage, construction solid waste, and natural soil, presents a significant challenge in urban ...peripheral engineering construction. This paper discusses the application of vibrating rod compaction technology for foundation treatment in Xinjiang. It evaluates the effectiveness of cross-section vibrating rod compaction equipment in reinforcing fine-grained miscellaneous fill foundations. The study analyzes the impact of construction disturbances caused by the insertion of the vibrating rod, monitoring horizontal stresses at various depths. Both laboratory and field tests show significant improvements: soil dry density increased by 8% to 18%, porosity decreased by 10% to 23%, compression modulus increased by 22% to 246%, and compression coefficient decreased by 8% to 70%. Additionally, cohesion (C) and angle of friction (ɸ) saw increases ranging from 7 to 38% and 3% to 25%, respectively. Below a depth of 3 m, cone tip resistance exceeded 10 MPa, and sidewall friction resistance increased to over 100 kPa, surpassing pre-treatment values. The standard penetration test results doubled stroke length compared to pre-treatment, indicating a substantial improvement in foundation bearing capacity. Surface wave tests before and after treatment showed a 15% increase in wave velocity, reflecting a more compact soil structure. The vibrating rod compaction method is innovative, energy-efficient, environmentally friendly, and economically beneficial, holding great potential for future miscellaneous fill treatments.
The mechanical properties of deep rock masses are significantly influenced by temperature and other factors. The effect of temperature on the strength of deep rock masses will pose a serious ...challenge to deep resource exploitation and engineering construction. In this paper, the thermal-mechanical coupling calculation model is established by particle flow code (PFC2D) to study the uniaxial compression response of rock masses with microcracks after temperature load. The strength of failure, microcracks, and strain was analyzed. The results show that: (i) When the soft rock thickness ratio Hs/H < 0.5, the displacement caused by the applied temperature is concentrated at the structural plane, and the contact force is concentrated at the end of the initial microcrack. When Hs/H ≥ 0.5, the displacement caused by the applied temperature is concentrated on both sides of the initial microcrack, and the contact force is concentrated in the hard rock area. (ii) The number of microcracks decreases with the increase of soft rock thickness under different working conditions. When the soft rock thickness ratio Hs/H < 0.5, the relationship curve between the number of microcracks and the vertical strain shows two stages of change. When Hs/H ≥ 0.5, the relationship curve between the number of cracks and the vertical strain changes shows three stages of change. (iii) When the soft rock thickness ratio Hs/H < 0.5, the failure strength decreases with the increase of soft rock thickness ratio at T = 100°C and 200°C. When T = 300°C and 400°C, the failure strength decreased first and then increased. When Hs/H ≥ 0.5, the failure strength increases with the increase of soft rock thickness at T = 200°C, 300°C, and 400°C. At T = 100°C, the failure strength decreases with the increase of soft rock thickness.
The uneven settlement of the surrounding ground surface caused by subway construction is not only complicated but also liable to cause casualties and property damage, so a timely understanding of the ...ground settlement deformation in the subway excavation and its prediction in real time is of practical significance. Due to the complex nonlinear relationship between subway settlement deformation and numerous influencing factors, as well as the existence of a time lag effect and the influence of various factors in the process, the prediction performance and accuracy of traditional prediction methods can no longer meet industry demands. Therefore, this paper proposes a surface settlement deformation prediction model by combining noise reduction and attention mechanism (AM) with the long short-term memory (LSTM). The complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and independent component analysis (ICA) methods are used to denoise the input original data and then combined with AM and LSTM for prediction to obtain the CEEMDAN-ICA-AM-LSTM (CIAL) prediction model. Taking the settlement monitoring data of the construction site of Urumqi Rail Transit Line 1 as an example for analysis reveals that the model in this paper has better effectiveness and applicability in the prediction of surface settlement deformation than multiple prediction models. The RMSE, MAE, and MAPE values of the CIAL model are 0.041, 0.033 and 0.384%; R2 is the largest; the prediction effect is the best; the prediction accuracy is the highest; and its reliability is good. The new method is effective for monitoring the safety of surface settlement deformation.
To study the deformation characteristics of reverse slope, this paper took the slope of Xiaodongcao as the research object, applied the Louvain community detection algorithm, considered the influence ...of reservoir water level change, and partitioned the slope deformation characteristics. The deformation characteristic zoning result was superimposed with the slope displacement cloud map and three types of geological geometric characteristic factor zoning map obtained by ArcGIS. The results show that: community detection can quickly identify the closely connected part of slope network, and the specific location of this part is affected by reservoir water. After the community detection result is superimposed with the displacement cloud map, the areas with large deformation and close connection in the slope can be identified. It is found that the community with severe deformation has at least 5% more displacement and up to 21% more displacement than that with slow deformation. In addition, the location of leader nodes can be identified, and the number of leader nodes does not exceed 20% of the total nodes in the community, and its average displacement is at least 10% more than that of ordinary nodes, up to 36%. After the community detection result is superimposed with the zoning map of slope grade, it can be concluded that the slope grade within the community with severe deformation is greater than 60°, indicating that the larger slope grade is more sensitive to the bank slope deformation.
The existence of various types of damage, small cracks, some large voids and the size of the sample in the rock will make the experimental results show great discreteness. In this paper, based on the ...results of laboratory experiments, a numerical model of large flawed rock samples is established by using particle flow software PFC2D, and the mechanical response of rocks with different length-diameter ratios and different flaw positions in uniaxial compression experiments is discussed. The results show that the specimen size has a significant effect on the crack characteristics, mechanical characteristics and energy characteristics of rock mass. From the perspective of energy and crack characteristics, the total number of cracks after the failure of the defective rock sample is slightly lower than that of the intact rock sample, resulting in a slightly lower peak strain energy during the rock failure process. From the mechanical properties of rock samples, the Poisson's ratio of intact rock samples is slightly smaller than that of defective rock samples. The strength of the defective sample is weakened relative to the complete rock sample, and the relationship formula between the weakening range and the aspect ratio is obtained through analysis. Moreover, different defect locations lead to different crack processes and crack modes, resulting in different uniaxial compressive strength.
Based on the digital elevation data, snow depth and snow cover remote sensing data, this paper divides six snow evolution areas and geographical partitions, extracts the geographical partitions of ...each evolution area and obtains the geographical characteristics of the evolution area for analysis. The results show that: (1) From 2003 to 2017, the average snow area decreased at a rate of - 0.004, and the average snow depth increased at a rate of 0.03. (2) The snow in the middle altitude hill with shady gentle slope area is the most obvious in the seasonal evolution, and the percentage of this region in the seasonal snow evolution area is 5.46%, the snow depth in the middle altitude hill with sunny and gentle slopes area increased and decreased significantly in the past 15 years, and the percentage of this region in the SD significant changes evolution area was 6.32%. The snow in the low relief middle altitude mountain with shady and moderate slope area not only shows obvious seasonal evolution, but also increases and decreases significantly in snow depth. And the percentage of this region in the seasonal snow significant evolution area is 5.82%. (3) The geographical partitions with the largest area in all evolution areas is the middle altitude hill with sunny and gentle slopes area (4.75%). (4) The geographical partition with the largest variation of snow depth in Tianshan region is the low relief middle altitude mountain with shady and moderate slope area (12.02 cm). (5) The snow accumulation and melting are obvious in the range of 1000-3500 m above altitude, different geomorphology types lead to obvious differences in snow characteristics. The snow melting is most obvious in the gentle slope area of the low topographic relief geomorphology types, and the snow accumulation is most obvious in the steep slope area of the middle relief geomorphology types.
Abstract
In order to explore the influence of weak interlayer on blasting characteristics in natural rock mass, by using the particle flow code (PFC
2D
), a single hole blasting numerical model of ...hard rock with soft interlayer is established. The blasting experiments at different positions and thicknesses of weak interlayer are carried out. Then an in-depth analysis from the perspectives of crack effect, stress field and energy field is made. Results showed that: (i) When the explosion is initiated outside the weak interlayer, if the interlayer is located within about twice the radius of the crushing area, the closer the interlayer is to the blast hole, the higher the damage degree of the rock mass around the blast hole. And the number of cracks will increase by about 1–2% when the distance between the weak interlayer and the blast hole decreases by 0.5 m. (ii) When detonating outside the weak interlayer, if the interlayer is within about 4 times radius of the crushing area, the hard rock on both sides of the weak interlayer will in a high stress state. Under the same case, the peak kinetic energy and peak friction energy will increase by about 23 and 13%, respectively, and the peak strain energy will increase by about 218 kJ for every 0.1 m increase in the thickness of the weak interlayer.
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