Microbially induced calcite precipitation(MICP)and Enzyme induced calcite precipitation(EICP)techniques were implemented to reinforce the large-scale calcareous sand in this study.Then a coupled numerical model to pre...Microbially induced calcite precipitation(MICP)and Enzyme induced calcite precipitation(EICP)techniques were implemented to reinforce the large-scale calcareous sand in this study.Then a coupled numerical model to predict the biochemical reactions and hydraulic characteristics of MICP and EICP reactions was proposed and verified by physical experiments.Results showed that:This model could describe the variations of bacteria,calcium,calcite,permeability over time reasonably.It is necessary to consider the influence of the calculation domain scale when simulating the convection-diffusionreaction in the multi-process of MICP and EICP reactions.The numerical and experimental values of calcite content are 0.841 g/cm^(3) and 0.861 g/cm^(3) for MICP-reinforced sand,0.263 g/cm^(3) and 0.227 g/cm^(3) for EICP-reinforced sand after 192 h of reaction.The reaction rate k_(rea) is an important parameter to control the calcite content.Accordingly,the permeability coefficient of MICP and EICP reinforced calcareous sand decreases by 32%and 18%.Due to the influence of substance transportation and calcite precipitation,the calcite shows a trend of decreasing firstly and then increasing with the enhancing of the initial permeability coefficient in biochemical reactions.The optimal injecting ratio q11:q12 in this study is 100:300 mL/min.The process for the application of MICP and EICP coupled numerical model is also recommended,which provides reference for engineering projects in ground improvement.展开更多
Heterogeneous structure exhibits superiority in improving mechanical properties,whereas their effects on fatigue damage properties have rarely been studied.In this work,we employed a high-throughput gradient heat trea...Heterogeneous structure exhibits superiority in improving mechanical properties,whereas their effects on fatigue damage properties have rarely been studied.In this work,we employed a high-throughput gradient heat treatment method(757−857℃)to rapidly acquire the solution microstructure of the Ti-6554 alloy with different recrystallization degrees(0%,40%and 100%),followed by the same aging treatment.The results showed that theβ-hetero structure exhibited a yield strength(σ_(YS))of 1403 MPa,an increase of 6.7%,and a remarkable improvement in uniform elongation(UE)of 109.7%,reaching 6.5%,compared to the homogeneous structure.Interestingly,introducing a heterogeneous structure not only overcame the traditional trade-off between strength and ductility but also enhanced fatigue crack propagation(FCP)performance.During FCP process,β-hetero structure,through hetero-deformation induced(HDI)strengthening effects,promoted the accumulation of geometric necessary dislocations(GNDs)within coarseα_(S) phase,enabling faster attainment of the critical shear stress of twinning and increasing twinning density.This facilitated stress relief,improved plastic deformation in the crack tip zone,and increased the critical fast fracture threshold from 30.4 to 36.0 MPa·m^(1/2)showing an enlarged steady state propagation region.This study provides valuable insights on tailoring fatigue damage tolerance through heterogeneous structure for titanium alloys.展开更多
The prognosis of drug-induced acute liver failure(ALF)is poor,with a survival rate of 27.1%without liver transplantation.Liver transplantation significantly improved survival rates to 66.2%.[1]The shortage of availabl...The prognosis of drug-induced acute liver failure(ALF)is poor,with a survival rate of 27.1%without liver transplantation.Liver transplantation significantly improved survival rates to 66.2%.[1]The shortage of available grafts can be addressed by living donor liver transplantation(LDLT),an effective and safe method that expands the donor pool,enhances timely transplantation,and improves patient survival.展开更多
Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and repair.We previously reported that induced neural stem cells ...Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and repair.We previously reported that induced neural stem cells can modulate the behavior of activated microglia via CXCL12/CXCR4 signaling,influencing their activation such that they can promote neurological recovery.However,the mechanism of CXCR4 upregulation in induced neural stem cells remains unclear.In this study,we found that nuclear factor-κB activation induced by closed head injury mouse serum in microglia promoted CXCL12 and tumor necrosis factor-αexpression but suppressed insulin-like growth factor-1 expression.However,recombinant complement receptor 2-conjugated Crry(CR2-Crry)reduced the effects of closed head injury mouse serum-induced nuclear factor-κB activation in microglia and the levels of activated microglia,CXCL12,and tumor necrosis factor-α.Additionally,we observed that,in response to stimulation(including stimulation by CXCL12 secreted by activated microglia),CXCR4 and Crry levels can be upregulated in induced neural stem cells via the interplay among CXCL12/CXCR4,Crry,and Akt signaling to modulate microglial activation.In agreement with these in vitro experimental results,we found that Akt activation enhanced the immunoregulatory effects of induced neural stem cell grafts on microglial activation,leading to the promotion of neurological recovery via insulin-like growth factor-1 secretion and the neuroprotective effects of induced neural stem cell grafts through CXCR4 and Crry upregulation in the injured cortices of closed head injury mice.Notably,these beneficial effects of Akt activation in induced neural stem cells were positively correlated with the therapeutic effects of induced neural stem cells on neuronal injury,cerebral edema,and neurological disorders post–closed head injury.In conclusion,our findings reveal that Akt activation may enhance the immunoregulatory effects of induced neural stem cells on microglial activation via upregulation of CXCR4 and Crry,thereby promoting induced neural stem cell–mediated improvement of neuronal injury,cerebral edema,and neurological disorders following closed head injury.展开更多
0 INTRODUCTION.According to the China Earthquake Networks Center,an M6.8 earthquake struck Dingri County,Xizang Autonomous Region,China,on 7 January 2025 at 9:05 a.m.local time.The epicenter is located at 28.5°N,...0 INTRODUCTION.According to the China Earthquake Networks Center,an M6.8 earthquake struck Dingri County,Xizang Autonomous Region,China,on 7 January 2025 at 9:05 a.m.local time.The epicenter is located at 28.5°N,87.45°E,with a depth of~10 km.展开更多
To investigate the wind⁃induced vibration re⁃sponse characteristics of multispan double⁃layer cable photo⁃voltaic(PV)support structures,wind tunnel tests using an aeroelastic model were carried out to obtain the wind⁃...To investigate the wind⁃induced vibration re⁃sponse characteristics of multispan double⁃layer cable photo⁃voltaic(PV)support structures,wind tunnel tests using an aeroelastic model were carried out to obtain the wind⁃induced vibration response data of a three⁃span four⁃row double⁃layer cable PV support system.The wind⁃induced vibration characteristics with different PV module tilt angles,wind speeds,and wind direction angles were analyzed.The results showed that the double⁃layer cable large⁃span flexible PV support can effectively control the wind⁃induced vibration response and prevent the occur⁃rence of flutter under strong wind conditions.The maxi⁃mum value of the wind⁃induced vibration displacement of the flexible PV support system occurs in the windward first row.The upstream module has a significant shading effect on the downstream module,with a maximum effect of 23%.The most unfavorable wind direction angles of the structure are 0°and 180°.The change of the wind direction angle in the range of 0°to 30°has little effect on the wind vi⁃bration response.The change in the tilt angle of the PV modules has a greater impact on the wind vibration in the downwind direction and a smaller impact in the upwind di⁃rection.Special attention should be paid to the structural wind⁃resistant design of such systems in the upwind side span.展开更多
Discrete fracture network(DFN)commonly existing in natural rock masses plays an important role in geological complexity which can influence rock fracturing behaviour during fluid injection.This paper simulated the hyd...Discrete fracture network(DFN)commonly existing in natural rock masses plays an important role in geological complexity which can influence rock fracturing behaviour during fluid injection.This paper simulated the hydraulic fracturing process in lab-scale coal samples with DFNs and the induced seismic activities by the discrete element method(DEM).The effects of DFNs on hydraulic fracturing,induced seismicity and elastic property changes have been concluded.Denser DFNs can comprehensively decrease the peak injection pressure and injection duration.The proportion of strong seismic events increases first and then decreases with increasing DFN density.In addition,the relative modulus of the rock mass is derived innovatively from breakdown pressure,breakdown fracture length and the related initiation time.Increasing DFN densities among large(35–60 degrees)and small(0–30 degrees)fracture dip angles show opposite evolution trends in relative modulus.The transitional point(dip angle)for the opposite trends is also proportionally affected by the friction angle of the rock mass.The modelling results have much practical meaning to infer the density and geometry of pre-existing fractures and the elastic property of rock mass in the field,simply based on the hydraulic fracturing and induced seismicity monitoring data.展开更多
Rheumatoid arthritis(RA)is an autoimmune disease characterized by inflammation and abnormal osteoclast activation,leading to bone destruction.We previously demonstrated that the large extracellular loop(LEL)of Tm4sf19...Rheumatoid arthritis(RA)is an autoimmune disease characterized by inflammation and abnormal osteoclast activation,leading to bone destruction.We previously demonstrated that the large extracellular loop(LEL)of Tm4sf19 is important for its function in osteoclast differentiation,and LEL-Fc,a competitive inhibitor of Tm4sf19,effectively suppresses osteoclast multinucleation and prevent bone loss associated with osteoporosis.This study aimed to investigate the role of Tm4sf19 in RA,an inflammatory and abnormal osteoclast disease,using a mouse model of collagen-induced arthritis(CIA).Tm4sf19 expression was observed in macrophages and osteoclasts within the inflamed synovium,and Tm4sf19 expression was increased together with inflammatory genes in the joint bones of CIA-induced mice compared with the sham control group.Inhibition of Tm4sf19 by LEL-Fc demonstrated both preventive and therapeutic effects in a CIA mouse model,reducing the CIA score,swelling,inflammation,cartilage damage,and bone damage.Knockout of Tm4sf19 gene or inhibition of Tm4sf19 activity by LEL-Fc suppressed LPS/IFN-γ-induced TLR4-mediated inflammatory signaling in macrophages.LEL-Fc disrupted not only the interaction between Tm4sf19 and TLR4/MD2,but also the interaction between TLR4 and MD2.μCT analysis showed that LEL-Fc treatment significantly reduced joint bone destruction and bone loss caused by hyperactivated osteoclasts in CIA mice.Taken together,these findings suggest that LELFc may be a potential treatment for RA and RA-induced osteoporosis by simultaneously targeting joint inflammation and bone destruction caused by abnormal osteoclast activation.展开更多
The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease,the second most common human neurodegenerative disease.Although the detailed patho...The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease,the second most common human neurodegenerative disease.Although the detailed pathogenesis accounting for dopaminergic neuron degeneration in Parkinson's disease is still unclear,the advancement of stem cell approaches has shown promise for Parkinson's disease research and therapy.The induced pluripotent stem cells have been commonly used to generate dopaminergic neurons,which has provided valuable insights to improve our understanding of Parkinson's disease pathogenesis and contributed to anti-Parkinson's disease therapies.The current review discusses the practical approaches and potential applications of induced pluripotent stem cell techniques for generating and differentiating dopaminergic neurons from induced pluripotent stem cells.The benefits of induced pluripotent stem cell-based research are highlighted.Various dopaminergic neuron differentiation protocols from induced pluripotent stem cells are compared.The emerging three-dimension-based brain organoid models compared with conventional two-dimensional cell culture are evaluated.Finally,limitations,challenges,and future directions of induced pluripotent stem cell–based approaches are analyzed and proposed,which will be significant to the future application of induced pluripotent stem cell-related techniques for Parkinson's disease.展开更多
In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the c...In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained intriguing.Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as neurons.While embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns remained.These barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem cells.The advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal subpopulations.The precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed differentiation.While the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma formation.Cells of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of success.Although the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor cells.Furthermore,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration.Lastly,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression.Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes.This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration.展开更多
Crosstalk between the nervous system and cancer plays an important role in tumor metastasis yet is poorly understood.Recently,Padmanaban et al.demonstrated a novel mechanism for nerve-induced metastasis.Sensory nerve-...Crosstalk between the nervous system and cancer plays an important role in tumor metastasis yet is poorly understood.Recently,Padmanaban et al.demonstrated a novel mechanism for nerve-induced metastasis.Sensory nerve-derived substance P could induce apoptosis in breast cancer cells that overexpressed tachykinin receptors.Single-stranded RNAs(ssRNAs)leaking from dying cells subsequently interact with toll-like receptor 7(TLR7)on other cancer cells and finally promoted metastasis.This notable study displays a delicate loop between the nervous system and cancer and,more importantly,amplifies the conception of apoptosis-induced metastasis.Over the past years,a mass of breakthrough studies have proven the pivotal role of the nervous system in tumorigenesis and cancer progression thereby contributing to the creation of a new disciplinecancer neuroscience[1].Hanahan and Monje discussed in detail the interactions between the nervous system and tumors based on the theoretical framework of the cancer hallmarks,focused on nerve-mediated proliferation,angiogenesis,immune evasion,cell death resistance,and metastasis[2].展开更多
Minoxidil is a potent vasodilator primarily used for the treatment of severe hypertension,and androgenic alopecia.Although known adverse effects include fluid retention,tachycardia and hypertrichosis,its potential to ...Minoxidil is a potent vasodilator primarily used for the treatment of severe hypertension,and androgenic alopecia.Although known adverse effects include fluid retention,tachycardia and hypertrichosis,its potential to induce coronary vasospasm remains largely underreported.[1]Minoxidil is currently reserved for treating alopecia for various causes.展开更多
The oxygen reduction reaction(ORR)could be effectively regulated by adjusting electron configurations and optimizing chemical bonds.Herein,we have achieved the modulation of electron distribution in Fe single atomic(F...The oxygen reduction reaction(ORR)could be effectively regulated by adjusting electron configurations and optimizing chemical bonds.Herein,we have achieved the modulation of electron distribution in Fe single atomic(Fe_(SA))sites through Fe atomic clusters(Fe_(AC))via a confined pyrolysis approach,thereby enhancing their intrinsic ORR activity.X-ray absorption spectroscopy has confirmed that the presence of iron atomic dusters could influence the electron distribution at Fe-N_(4)sites.The Fe_(SA)/Fe_(AC)-NC catalyst exhibits a half-wave potential of 0.88 V,surpassing the individual Fe_(SA)-NC structure.Through electronic structure analysis,it could be seen that iron atom clusters can affect Fe-N_(4)sites through long-range effects,and then effectively lower reaction barriers and enhance the reaction kinetics at Fe-N_(4)sites.The synthetic approach might pave the way for constructing highly active catalysts with tunable atomic structures,representing an effective and universal technique for electron modulation in M-N-C systems.This work provides enlightenment for the exploration of more efficient single-atom electrocatalysts and the optimization of the performance of atomic electrocatalysts.Furthermore,a zinc-air battery assembled using it on their cathode deliver a high peak power density(205.7 mW cm^(-2))and a high-specific capacity of 807.5 mA h g^(-1).This study offers a fresh approach to effectively enhance the synergistic interaction of between Fe single atom and Fe atomic clusters for improving ORR activity and energy storage.展开更多
Background: Some studies have indicated a potential link between a history of induced abortion (IA) and the subsequent risk of gestational diabetes mellitus (GDM), but the relationship is not fully understood, and the...Background: Some studies have indicated a potential link between a history of induced abortion (IA) and the subsequent risk of gestational diabetes mellitus (GDM), but the relationship is not fully understood, and the aim of this study was to further elucidate the association. Methods: The case-control study was conducted at 2 hospitals in central China from April 2018 to October 2020. GDM was diagnosed by an oral glucose tolerance test (OGTT). Information on history of IA was obtained through a face-to-face interview. Results: Among 396 GDM cases and 904 controls, the proportion of participants with history of IA in the case group was 30.6%, which was higher than that in the control group (23.1%), and the difference was statistically significant (p = 0.005). After adjusting for potential confounders, women with a history of IA had an increased subsequent risk of GDM compared with women without (OR, 1.24, 95% CI, 1.10 - 1.40, p = 0.002). The subsequent risk of GDM in pregnant women increased as the number of previous IAs increased (p for trend was equal to 0.004). Stratified analysis showed that women with a history of medical abortion (OR, 1.28, 95% CI, 1.01 - 1.62, p = 0.048) or surgical abortion (OR, 1.20, 95% CI, 1.04 - 1.38, p = 0.024) both had an increased subsequent risk of GDM compared with women without. Conclusion: History of IA, either medical or surgical, was related to an increased risk of GDM in subsequent pregnancy. The greater the number of previous IAs, the greater the subsequent risk of GDM.展开更多
The defense mechanisms induced in wild Chinese pine(Pinus tabuliformis)in response to herbivores are not well characterized,especially in the field.To address this knowledge gap,we established a biological model syste...The defense mechanisms induced in wild Chinese pine(Pinus tabuliformis)in response to herbivores are not well characterized,especially in the field.To address this knowledge gap,we established a biological model system to evaluate proteome variations in pine needles after feeding by the Chinese pine caterpillar(Dendrolimus tabulaeformis),a major natural enemy and dominant herbivore.Quantitative tandem mass tag(TMT)proteomics and bioinformatics were utilized to systematically identify differentially abundant proteins implicated in the induced defense response of Chinese pine.We validated key protein changes using parallel reaction monitoring(PRM)technology.Pathway analysis revealed that the induced defenses involved phenylpropanoid,coumarin,and flavonoid biosynthesis,among other processes.To elucidate the regulatory patterns underlying pine resistance,we determined the activities of defense enzymes and levels of physiological and biochemical compounds.In addition,the expression of upstream genes for key proteins was validated by qRT-PCR.Our results provide new molecular insights into the induced defense mechanisms in Chinese pine against this caterpillar in the field.A better understanding of these defense strategies will inform efforts to breed more-resistant pine varieties.展开更多
Thermal shock damage in deep shale hydraulic fracturing can impact fracture propagation behaviors,potentially leading to the formation of complex fractures and enhancing gas recovery.This study introduces a thermalhyd...Thermal shock damage in deep shale hydraulic fracturing can impact fracture propagation behaviors,potentially leading to the formation of complex fractures and enhancing gas recovery.This study introduces a thermalhydraulic-mechnical(THM)coupled fracture propagation model relying on the phase field method to simulate thermal shock-induced fracturing in the deep shale considering dynamic temperature conditions.The validity of this model is confirmed through comparison of experimental and numerical results concerning the THM-coupled stress field and thermal cracking.Special attention is paid to the interaction of thermal shock-induced fractures in deep shale that contains weak planes.The results indicate that thermal shock-induced stress significantly amplifies the tensile stress range and deteriorates rock strength,resulting in a multi-point failure pattern within a fracture.The thermal shock damage degree is closely related to the fracture cooling efficiency,suggesting that considering downhole temperature conditions in THM-coupled fracture stress field calculations is advisable.Thermal shock can activate pre-existing natural fractures and enhance the penetration ability of hydraulic fractures,thereby leading to a fracture network.展开更多
Management of post-traumatic long-bone defects remains relevant and cha-llenging despite the rapid development of approaches to their treatment.Do-minant positions are occupied by the Ilizarov method,bone autogenous g...Management of post-traumatic long-bone defects remains relevant and cha-llenging despite the rapid development of approaches to their treatment.Do-minant positions are occupied by the Ilizarov method,bone autogenous grafting and the Masquelet induced membrane technique(IMT).The IMT is aimed at reducing extensive defect treatment duration and for this reason has gained great popularity.However,the assessment of its effectiveness is difficult due to a limited number of clinical series.The varying clinical manifestations of bone defect severity do not allow a comprehensive evaluation of IMT effectiveness.One of them is infection in the defect area.The purpose of our literature review is an analysis of studies on IMT application in infected vs non-infected long-bone defects of the lower extremities published over the last 10 years.It focuses on the investigation of similarities and fundamental differences in the need for antibiotics,timing of spacer fixation,methods of collecting donor bone and fixators used for consolidation.The studies show that the IMT has been globally used in aseptic and osteomyelitic defects due to its clinical effectiveness.Authors’variations and improvements in its practical implementation indicate the ongoing development and the interest of researchers in this technique.展开更多
The design and manufacturing of microchannels are crucial aspects of modern micro/nanomanufacturing processes,offering a versatile platform for manipulating and driving micro/nanoparticles or cells.In this study,we pr...The design and manufacturing of microchannels are crucial aspects of modern micro/nanomanufacturing processes,offering a versatile platform for manipulating and driving micro/nanoparticles or cells.In this study,we propose a method for manufacturing microchannels using optically induced dielectrophoresis technology to induce the polymerization of polyethylene glycol diacrylate solution.To overcome limitations related to the light intensity energy and the size of intact microchannels,we design and manufacture microstructures of various shapes with a height of 4µm.Additionally,we simulate and analyze the movement of and forces acting on polystyrene(PS)microspheres at different spatial positions within the microchannels.Finally,we successfully demonstrate applications involving the transport of PS microspheres in custom-fabricated microchannels.This novel biocompatible microchannel manufacturing method is simple and non-biotoxic.It provides a new approach for simulating physiological environments in vitro and cultivating and manipulating cells.展开更多
The Taklimakan Desert,located in the heart of central Asia,covers approximately 330000 km^(2),making it China's largest desert and the world's second-largest shifting desert(Dong et al.,2024).With an average a...The Taklimakan Desert,located in the heart of central Asia,covers approximately 330000 km^(2),making it China's largest desert and the world's second-largest shifting desert(Dong et al.,2024).With an average annual precipitation of less than 100 mm and evaporation rates ranging from 2000 to 3000 mm(Yang et al.,2020),it is recognized as one of the driest regions on Earth,often referred to as the“sea of death”.展开更多
In earthquake-prone areas,mountain tunnels often suffer from seismic damage when traversing active fault zones.To capture the seismic behavior of mountain tunnel under the action of active faults motion,the rate and s...In earthquake-prone areas,mountain tunnels often suffer from seismic damage when traversing active fault zones.To capture the seismic behavior of mountain tunnel under the action of active faults motion,the rate and state friction(RSF)relation is introduced to define the stickeslip dynamic behavior of a fault.The RSF relation is implemented in the finite element methods(FEMs).Numerical simulations of triaxial patch tests indicate that the RSF method can effectively capture the stickeslip dynamics.To reproduce the seismic damage to Daliang tunnel caused by slip of the Lenglongling fault,a three-dimensional(3D)numerical model including tunnel structure and plates of the fault is established.Seismic waves triggered by fault slip are then reproduced using the model.The simulation results show that the waves are dissipated while travelling and that their amplitudes decrease with depth.The failure of the tunnel lining is captured,and its seismic responses,including the displacement and strain of the structure,are extracted for various fault strike angles.The simulations are consistent with the observations,and it indicates that the movement of the simulated tunnel structure adjacent to the fault surface is significantly greater than those in the foot wall and in the middle of the fault.This study has the potential to provide a more direct means of understanding the seismic action of infrastructure induced by earthquakes.Seismic waves are no longer needed as input to the numerical simulation and instead,the earthquakes are generated by directly modeling the stickeslip motion of the fault.展开更多
基金supports from the National Key R&D Program of China(Grant No.2023YFB4203301)National Natural Science Foundation of China(Grant No.52238008)Postdoctoral Fellowship Program of CPSF(Grant No.GZC20241516).
文摘Microbially induced calcite precipitation(MICP)and Enzyme induced calcite precipitation(EICP)techniques were implemented to reinforce the large-scale calcareous sand in this study.Then a coupled numerical model to predict the biochemical reactions and hydraulic characteristics of MICP and EICP reactions was proposed and verified by physical experiments.Results showed that:This model could describe the variations of bacteria,calcium,calcite,permeability over time reasonably.It is necessary to consider the influence of the calculation domain scale when simulating the convection-diffusionreaction in the multi-process of MICP and EICP reactions.The numerical and experimental values of calcite content are 0.841 g/cm^(3) and 0.861 g/cm^(3) for MICP-reinforced sand,0.263 g/cm^(3) and 0.227 g/cm^(3) for EICP-reinforced sand after 192 h of reaction.The reaction rate k_(rea) is an important parameter to control the calcite content.Accordingly,the permeability coefficient of MICP and EICP reinforced calcareous sand decreases by 32%and 18%.Due to the influence of substance transportation and calcite precipitation,the calcite shows a trend of decreasing firstly and then increasing with the enhancing of the initial permeability coefficient in biochemical reactions.The optimal injecting ratio q11:q12 in this study is 100:300 mL/min.The process for the application of MICP and EICP coupled numerical model is also recommended,which provides reference for engineering projects in ground improvement.
基金Project(2021YFB3700801)supported by the National Key Research and Development Program of ChinaProject(2023JJ30683)supported by the Natural Science Foundation of Hunan Province,ChinaProject supported by the State Key Laboratory of Powder Metallurgy(Central South University),China。
文摘Heterogeneous structure exhibits superiority in improving mechanical properties,whereas their effects on fatigue damage properties have rarely been studied.In this work,we employed a high-throughput gradient heat treatment method(757−857℃)to rapidly acquire the solution microstructure of the Ti-6554 alloy with different recrystallization degrees(0%,40%and 100%),followed by the same aging treatment.The results showed that theβ-hetero structure exhibited a yield strength(σ_(YS))of 1403 MPa,an increase of 6.7%,and a remarkable improvement in uniform elongation(UE)of 109.7%,reaching 6.5%,compared to the homogeneous structure.Interestingly,introducing a heterogeneous structure not only overcame the traditional trade-off between strength and ductility but also enhanced fatigue crack propagation(FCP)performance.During FCP process,β-hetero structure,through hetero-deformation induced(HDI)strengthening effects,promoted the accumulation of geometric necessary dislocations(GNDs)within coarseα_(S) phase,enabling faster attainment of the critical shear stress of twinning and increasing twinning density.This facilitated stress relief,improved plastic deformation in the crack tip zone,and increased the critical fast fracture threshold from 30.4 to 36.0 MPa·m^(1/2)showing an enlarged steady state propagation region.This study provides valuable insights on tailoring fatigue damage tolerance through heterogeneous structure for titanium alloys.
基金approved by the Ethics Committee of the Second Affiliated Hospital,Zhejiang University School of Medicine(2024-0690).
文摘The prognosis of drug-induced acute liver failure(ALF)is poor,with a survival rate of 27.1%without liver transplantation.Liver transplantation significantly improved survival rates to 66.2%.[1]The shortage of available grafts can be addressed by living donor liver transplantation(LDLT),an effective and safe method that expands the donor pool,enhances timely transplantation,and improves patient survival.
基金supported by the National Natural Science Foundation of China,Nos.82271397(to MG),82001293(to MG),82171355(to RX),81971295(to RX),and 81671189(to RX)。
文摘Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and repair.We previously reported that induced neural stem cells can modulate the behavior of activated microglia via CXCL12/CXCR4 signaling,influencing their activation such that they can promote neurological recovery.However,the mechanism of CXCR4 upregulation in induced neural stem cells remains unclear.In this study,we found that nuclear factor-κB activation induced by closed head injury mouse serum in microglia promoted CXCL12 and tumor necrosis factor-αexpression but suppressed insulin-like growth factor-1 expression.However,recombinant complement receptor 2-conjugated Crry(CR2-Crry)reduced the effects of closed head injury mouse serum-induced nuclear factor-κB activation in microglia and the levels of activated microglia,CXCL12,and tumor necrosis factor-α.Additionally,we observed that,in response to stimulation(including stimulation by CXCL12 secreted by activated microglia),CXCR4 and Crry levels can be upregulated in induced neural stem cells via the interplay among CXCL12/CXCR4,Crry,and Akt signaling to modulate microglial activation.In agreement with these in vitro experimental results,we found that Akt activation enhanced the immunoregulatory effects of induced neural stem cell grafts on microglial activation,leading to the promotion of neurological recovery via insulin-like growth factor-1 secretion and the neuroprotective effects of induced neural stem cell grafts through CXCR4 and Crry upregulation in the injured cortices of closed head injury mice.Notably,these beneficial effects of Akt activation in induced neural stem cells were positively correlated with the therapeutic effects of induced neural stem cells on neuronal injury,cerebral edema,and neurological disorders post–closed head injury.In conclusion,our findings reveal that Akt activation may enhance the immunoregulatory effects of induced neural stem cells on microglial activation via upregulation of CXCR4 and Crry,thereby promoting induced neural stem cell–mediated improvement of neuronal injury,cerebral edema,and neurological disorders following closed head injury.
基金funded by the National Key R&D Program of China(No.2020YFC150071)partly supported by the Shaanxi Province Geoscience Big Data and Geohazard Prevention Innovation Team(2022)and the Research Funds for the Interdisciplinary Projects,CHU(No.300104240914)。
文摘0 INTRODUCTION.According to the China Earthquake Networks Center,an M6.8 earthquake struck Dingri County,Xizang Autonomous Region,China,on 7 January 2025 at 9:05 a.m.local time.The epicenter is located at 28.5°N,87.45°E,with a depth of~10 km.
基金The National Natural Science Foundation of China(No.52338011).
文摘To investigate the wind⁃induced vibration re⁃sponse characteristics of multispan double⁃layer cable photo⁃voltaic(PV)support structures,wind tunnel tests using an aeroelastic model were carried out to obtain the wind⁃induced vibration response data of a three⁃span four⁃row double⁃layer cable PV support system.The wind⁃induced vibration characteristics with different PV module tilt angles,wind speeds,and wind direction angles were analyzed.The results showed that the double⁃layer cable large⁃span flexible PV support can effectively control the wind⁃induced vibration response and prevent the occur⁃rence of flutter under strong wind conditions.The maxi⁃mum value of the wind⁃induced vibration displacement of the flexible PV support system occurs in the windward first row.The upstream module has a significant shading effect on the downstream module,with a maximum effect of 23%.The most unfavorable wind direction angles of the structure are 0°and 180°.The change of the wind direction angle in the range of 0°to 30°has little effect on the wind vi⁃bration response.The change in the tilt angle of the PV modules has a greater impact on the wind vibration in the downwind direction and a smaller impact in the upwind di⁃rection.Special attention should be paid to the structural wind⁃resistant design of such systems in the upwind side span.
基金Australian Research Council Linkage Program(LP200301404)for sponsoring this researchthe financial support provided by the State Key Laboratory of Geohazard Prevention and Geoenvironment Protection(Chengdu University of Technology,SKLGP2021K002)National Natural Science Foundation of China(52374101,32111530138).
文摘Discrete fracture network(DFN)commonly existing in natural rock masses plays an important role in geological complexity which can influence rock fracturing behaviour during fluid injection.This paper simulated the hydraulic fracturing process in lab-scale coal samples with DFNs and the induced seismic activities by the discrete element method(DEM).The effects of DFNs on hydraulic fracturing,induced seismicity and elastic property changes have been concluded.Denser DFNs can comprehensively decrease the peak injection pressure and injection duration.The proportion of strong seismic events increases first and then decreases with increasing DFN density.In addition,the relative modulus of the rock mass is derived innovatively from breakdown pressure,breakdown fracture length and the related initiation time.Increasing DFN densities among large(35–60 degrees)and small(0–30 degrees)fracture dip angles show opposite evolution trends in relative modulus.The transitional point(dip angle)for the opposite trends is also proportionally affected by the friction angle of the rock mass.The modelling results have much practical meaning to infer the density and geometry of pre-existing fractures and the elastic property of rock mass in the field,simply based on the hydraulic fracturing and induced seismicity monitoring data.
基金supported by GILO Foundation.This research is in part supported by Korea Drug Development Fund funded by Ministry of Science and ICT,Ministry of Trade,Industry,and Energy,and Ministry of Health and Welfare(RS-2023-00282595,Republic of Korea).
文摘Rheumatoid arthritis(RA)is an autoimmune disease characterized by inflammation and abnormal osteoclast activation,leading to bone destruction.We previously demonstrated that the large extracellular loop(LEL)of Tm4sf19 is important for its function in osteoclast differentiation,and LEL-Fc,a competitive inhibitor of Tm4sf19,effectively suppresses osteoclast multinucleation and prevent bone loss associated with osteoporosis.This study aimed to investigate the role of Tm4sf19 in RA,an inflammatory and abnormal osteoclast disease,using a mouse model of collagen-induced arthritis(CIA).Tm4sf19 expression was observed in macrophages and osteoclasts within the inflamed synovium,and Tm4sf19 expression was increased together with inflammatory genes in the joint bones of CIA-induced mice compared with the sham control group.Inhibition of Tm4sf19 by LEL-Fc demonstrated both preventive and therapeutic effects in a CIA mouse model,reducing the CIA score,swelling,inflammation,cartilage damage,and bone damage.Knockout of Tm4sf19 gene or inhibition of Tm4sf19 activity by LEL-Fc suppressed LPS/IFN-γ-induced TLR4-mediated inflammatory signaling in macrophages.LEL-Fc disrupted not only the interaction between Tm4sf19 and TLR4/MD2,but also the interaction between TLR4 and MD2.μCT analysis showed that LEL-Fc treatment significantly reduced joint bone destruction and bone loss caused by hyperactivated osteoclasts in CIA mice.Taken together,these findings suggest that LELFc may be a potential treatment for RA and RA-induced osteoporosis by simultaneously targeting joint inflammation and bone destruction caused by abnormal osteoclast activation.
基金supported by Singapore National Medical Research Council(NMRC)grants,including CS-IRG,HLCA2022(to ZDZ),STaR,OF LCG 000207(to EKT)a Clinical Translational Research Programme in Parkinson's DiseaseDuke-Duke-NUS collaboration pilot grant(to ZDZ)。
文摘The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease,the second most common human neurodegenerative disease.Although the detailed pathogenesis accounting for dopaminergic neuron degeneration in Parkinson's disease is still unclear,the advancement of stem cell approaches has shown promise for Parkinson's disease research and therapy.The induced pluripotent stem cells have been commonly used to generate dopaminergic neurons,which has provided valuable insights to improve our understanding of Parkinson's disease pathogenesis and contributed to anti-Parkinson's disease therapies.The current review discusses the practical approaches and potential applications of induced pluripotent stem cell techniques for generating and differentiating dopaminergic neurons from induced pluripotent stem cells.The benefits of induced pluripotent stem cell-based research are highlighted.Various dopaminergic neuron differentiation protocols from induced pluripotent stem cells are compared.The emerging three-dimension-based brain organoid models compared with conventional two-dimensional cell culture are evaluated.Finally,limitations,challenges,and future directions of induced pluripotent stem cell–based approaches are analyzed and proposed,which will be significant to the future application of induced pluripotent stem cell-related techniques for Parkinson's disease.
基金supported by Ohio State Start Up FundNational Institutes of Health(NIH)+12 种基金Department of Defense(DoD)Wings for Life Spinal Cord Research Foundation,Wings for Life Spinal Cord Research Foundation(Austria)California Institute of Regenerative Medicine(CIRM)International Spinal Research Trust(United Kingdom)Stanford University Bio-X Program Interdisciplinary Initiatives Seed Grant IIP-7Dennis Chan FoundationKlein Family FundLucile Packard Foundation for Children's HealthStanford Institute for Neuro-Innovation and Translational Neurosciences(SINTN)Saunders Family Neuroscience FundJames Doty Neurosurgery FundHearst Neuroscience FundEileen Bond Research Fund(to GP)。
文摘In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained intriguing.Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as neurons.While embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns remained.These barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem cells.The advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal subpopulations.The precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed differentiation.While the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma formation.Cells of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of success.Although the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor cells.Furthermore,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration.Lastly,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression.Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes.This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration.
文摘Crosstalk between the nervous system and cancer plays an important role in tumor metastasis yet is poorly understood.Recently,Padmanaban et al.demonstrated a novel mechanism for nerve-induced metastasis.Sensory nerve-derived substance P could induce apoptosis in breast cancer cells that overexpressed tachykinin receptors.Single-stranded RNAs(ssRNAs)leaking from dying cells subsequently interact with toll-like receptor 7(TLR7)on other cancer cells and finally promoted metastasis.This notable study displays a delicate loop between the nervous system and cancer and,more importantly,amplifies the conception of apoptosis-induced metastasis.Over the past years,a mass of breakthrough studies have proven the pivotal role of the nervous system in tumorigenesis and cancer progression thereby contributing to the creation of a new disciplinecancer neuroscience[1].Hanahan and Monje discussed in detail the interactions between the nervous system and tumors based on the theoretical framework of the cancer hallmarks,focused on nerve-mediated proliferation,angiogenesis,immune evasion,cell death resistance,and metastasis[2].
文摘Minoxidil is a potent vasodilator primarily used for the treatment of severe hypertension,and androgenic alopecia.Although known adverse effects include fluid retention,tachycardia and hypertrichosis,its potential to induce coronary vasospasm remains largely underreported.[1]Minoxidil is currently reserved for treating alopecia for various causes.
基金supported by the National Natural Science Foundations of China(Nos:22271018,22309012 and 22302013)the NSF of Guangdong Province(Nos:2023A1515010554 and 2024A1515010307)。
文摘The oxygen reduction reaction(ORR)could be effectively regulated by adjusting electron configurations and optimizing chemical bonds.Herein,we have achieved the modulation of electron distribution in Fe single atomic(Fe_(SA))sites through Fe atomic clusters(Fe_(AC))via a confined pyrolysis approach,thereby enhancing their intrinsic ORR activity.X-ray absorption spectroscopy has confirmed that the presence of iron atomic dusters could influence the electron distribution at Fe-N_(4)sites.The Fe_(SA)/Fe_(AC)-NC catalyst exhibits a half-wave potential of 0.88 V,surpassing the individual Fe_(SA)-NC structure.Through electronic structure analysis,it could be seen that iron atom clusters can affect Fe-N_(4)sites through long-range effects,and then effectively lower reaction barriers and enhance the reaction kinetics at Fe-N_(4)sites.The synthetic approach might pave the way for constructing highly active catalysts with tunable atomic structures,representing an effective and universal technique for electron modulation in M-N-C systems.This work provides enlightenment for the exploration of more efficient single-atom electrocatalysts and the optimization of the performance of atomic electrocatalysts.Furthermore,a zinc-air battery assembled using it on their cathode deliver a high peak power density(205.7 mW cm^(-2))and a high-specific capacity of 807.5 mA h g^(-1).This study offers a fresh approach to effectively enhance the synergistic interaction of between Fe single atom and Fe atomic clusters for improving ORR activity and energy storage.
文摘Background: Some studies have indicated a potential link between a history of induced abortion (IA) and the subsequent risk of gestational diabetes mellitus (GDM), but the relationship is not fully understood, and the aim of this study was to further elucidate the association. Methods: The case-control study was conducted at 2 hospitals in central China from April 2018 to October 2020. GDM was diagnosed by an oral glucose tolerance test (OGTT). Information on history of IA was obtained through a face-to-face interview. Results: Among 396 GDM cases and 904 controls, the proportion of participants with history of IA in the case group was 30.6%, which was higher than that in the control group (23.1%), and the difference was statistically significant (p = 0.005). After adjusting for potential confounders, women with a history of IA had an increased subsequent risk of GDM compared with women without (OR, 1.24, 95% CI, 1.10 - 1.40, p = 0.002). The subsequent risk of GDM in pregnant women increased as the number of previous IAs increased (p for trend was equal to 0.004). Stratified analysis showed that women with a history of medical abortion (OR, 1.28, 95% CI, 1.01 - 1.62, p = 0.048) or surgical abortion (OR, 1.20, 95% CI, 1.04 - 1.38, p = 0.024) both had an increased subsequent risk of GDM compared with women without. Conclusion: History of IA, either medical or surgical, was related to an increased risk of GDM in subsequent pregnancy. The greater the number of previous IAs, the greater the subsequent risk of GDM.
基金supported by the Science and Technology Development Program of Hebei Agricultural University,the Research on Molecular Mechanisms of Population Differentiation and Adaptation of Forest Pests and Insects under Environmental Stress(grant No.:30771739)Forest Pests and Diseases(grant No.:1528003)the National Natural Science Foundation of China for the study of community regulatory mechanisms of insect pest pandemics in larch plantation forests(Grant No.:32371882).
文摘The defense mechanisms induced in wild Chinese pine(Pinus tabuliformis)in response to herbivores are not well characterized,especially in the field.To address this knowledge gap,we established a biological model system to evaluate proteome variations in pine needles after feeding by the Chinese pine caterpillar(Dendrolimus tabulaeformis),a major natural enemy and dominant herbivore.Quantitative tandem mass tag(TMT)proteomics and bioinformatics were utilized to systematically identify differentially abundant proteins implicated in the induced defense response of Chinese pine.We validated key protein changes using parallel reaction monitoring(PRM)technology.Pathway analysis revealed that the induced defenses involved phenylpropanoid,coumarin,and flavonoid biosynthesis,among other processes.To elucidate the regulatory patterns underlying pine resistance,we determined the activities of defense enzymes and levels of physiological and biochemical compounds.In addition,the expression of upstream genes for key proteins was validated by qRT-PCR.Our results provide new molecular insights into the induced defense mechanisms in Chinese pine against this caterpillar in the field.A better understanding of these defense strategies will inform efforts to breed more-resistant pine varieties.
基金paper is funded by the CNOOC Science and Technology Project(KJGG2022-0701)the National Natural Science Foundation of China(51904258,51874250).
文摘Thermal shock damage in deep shale hydraulic fracturing can impact fracture propagation behaviors,potentially leading to the formation of complex fractures and enhancing gas recovery.This study introduces a thermalhydraulic-mechnical(THM)coupled fracture propagation model relying on the phase field method to simulate thermal shock-induced fracturing in the deep shale considering dynamic temperature conditions.The validity of this model is confirmed through comparison of experimental and numerical results concerning the THM-coupled stress field and thermal cracking.Special attention is paid to the interaction of thermal shock-induced fractures in deep shale that contains weak planes.The results indicate that thermal shock-induced stress significantly amplifies the tensile stress range and deteriorates rock strength,resulting in a multi-point failure pattern within a fracture.The thermal shock damage degree is closely related to the fracture cooling efficiency,suggesting that considering downhole temperature conditions in THM-coupled fracture stress field calculations is advisable.Thermal shock can activate pre-existing natural fractures and enhance the penetration ability of hydraulic fractures,thereby leading to a fracture network.
文摘Management of post-traumatic long-bone defects remains relevant and cha-llenging despite the rapid development of approaches to their treatment.Do-minant positions are occupied by the Ilizarov method,bone autogenous grafting and the Masquelet induced membrane technique(IMT).The IMT is aimed at reducing extensive defect treatment duration and for this reason has gained great popularity.However,the assessment of its effectiveness is difficult due to a limited number of clinical series.The varying clinical manifestations of bone defect severity do not allow a comprehensive evaluation of IMT effectiveness.One of them is infection in the defect area.The purpose of our literature review is an analysis of studies on IMT application in infected vs non-infected long-bone defects of the lower extremities published over the last 10 years.It focuses on the investigation of similarities and fundamental differences in the need for antibiotics,timing of spacer fixation,methods of collecting donor bone and fixators used for consolidation.The studies show that the IMT has been globally used in aseptic and osteomyelitic defects due to its clinical effectiveness.Authors’variations and improvements in its practical implementation indicate the ongoing development and the interest of researchers in this technique.
基金funded by the National Natural Science Foundation of China(Project No.62273289)The Youth Innovation Science and Technology Support Program of Shandong Province(Project No.2022KJ274)+1 种基金Natural Science Foundation of Shandong Province(Grant No.ZR2024MF007)Graduate Innovation Foundation of Yantai University,GIFYTU.
文摘The design and manufacturing of microchannels are crucial aspects of modern micro/nanomanufacturing processes,offering a versatile platform for manipulating and driving micro/nanoparticles or cells.In this study,we propose a method for manufacturing microchannels using optically induced dielectrophoresis technology to induce the polymerization of polyethylene glycol diacrylate solution.To overcome limitations related to the light intensity energy and the size of intact microchannels,we design and manufacture microstructures of various shapes with a height of 4µm.Additionally,we simulate and analyze the movement of and forces acting on polystyrene(PS)microspheres at different spatial positions within the microchannels.Finally,we successfully demonstrate applications involving the transport of PS microspheres in custom-fabricated microchannels.This novel biocompatible microchannel manufacturing method is simple and non-biotoxic.It provides a new approach for simulating physiological environments in vitro and cultivating and manipulating cells.
基金supported by the National Natural Science Foundation of China(No.42072211)the National Natural Science Foundation of China(No.42401048)the Third Xinjiang Scientific Expedition and Research Program(No.2021xjkk0302)。
文摘The Taklimakan Desert,located in the heart of central Asia,covers approximately 330000 km^(2),making it China's largest desert and the world's second-largest shifting desert(Dong et al.,2024).With an average annual precipitation of less than 100 mm and evaporation rates ranging from 2000 to 3000 mm(Yang et al.,2020),it is recognized as one of the driest regions on Earth,often referred to as the“sea of death”.
基金funded by the National Natural Science Foundation of China(Grant No.52178339,52090084,and 51938008)Shenzhen Natural Science Fund(Stable Support Plan Program Grant No.20220808150117002)。
文摘In earthquake-prone areas,mountain tunnels often suffer from seismic damage when traversing active fault zones.To capture the seismic behavior of mountain tunnel under the action of active faults motion,the rate and state friction(RSF)relation is introduced to define the stickeslip dynamic behavior of a fault.The RSF relation is implemented in the finite element methods(FEMs).Numerical simulations of triaxial patch tests indicate that the RSF method can effectively capture the stickeslip dynamics.To reproduce the seismic damage to Daliang tunnel caused by slip of the Lenglongling fault,a three-dimensional(3D)numerical model including tunnel structure and plates of the fault is established.Seismic waves triggered by fault slip are then reproduced using the model.The simulation results show that the waves are dissipated while travelling and that their amplitudes decrease with depth.The failure of the tunnel lining is captured,and its seismic responses,including the displacement and strain of the structure,are extracted for various fault strike angles.The simulations are consistent with the observations,and it indicates that the movement of the simulated tunnel structure adjacent to the fault surface is significantly greater than those in the foot wall and in the middle of the fault.This study has the potential to provide a more direct means of understanding the seismic action of infrastructure induced by earthquakes.Seismic waves are no longer needed as input to the numerical simulation and instead,the earthquakes are generated by directly modeling the stickeslip motion of the fault.
