To investigate the rate dependence on the mechanical behaviours of rocks under intermediate strain rate, three types of rock were loaded by using a newly developed servo-controlled dynamic triaxial ...apparatus. In this study, the dynamic strength and crack damage thresholds of rocks under different confinements were investigated at the strain rate range of 10−3∼100s−1, which is of significance to understand the rock damage subjected to earthquakes or far-field blasts. The results indicate that the apparatus could ensure the rock samples being loaded under a stable strain rate without causing prominent disturbance on the confining stress. In addition, the strength and damage thresholds are dependent on the strain rate, i.e., the increasing strain rate would result in the increase of dynamic strength and crack damage thresholds. The increase of confinement leads to a higher failure strength, the crack initiation and damage stresses are also positively correlated to the confining pressure under dynamic loads. Based on the theory of fracture mechanics that considers the crack growth velocity, it is found that the dynamic stress intensity factor exhibits a negative correlation with both the strain rate and confining pressure, whilst the fracture toughness presents an inverse trend. Therefore, the larger axial stress is required to initiate the cracks, which might further induce the variation of crack initiation stress.
•A novel dynamic triaxial apparatus with servo-controlled feature was developed to obtain rock strength.•Rate-dependent strength and crack damage thresholds under intermediate strain rates were obtained.•Effect of confinement on dynamic strength and crack damage thresholds was discussed.
The mechanical characteristics and failure behavior of rocks containing flaws or discontinuities have received wide attention in the field of rock mechanics. When external loads are applied to rock ...materials, stress-induced cracks would initiate and propagate from the flaws, ultimately leading to the irreversible failure of rocks. To investigate the cracking behavior and the effect of flaw geometries on the mechanical properties of rock materials, a series of samples containing one, two and multiple flaws have been widely investigated in the laboratory. In this paper, the experimental results for pre-cracked rocks under quasi-static compression were systematically reviewed. The progressive failure process of intact rocks is briefly described to reveal the background for experiments on samples with flaws. Then, the nondestructive measurement techniques utilized in experiments, such as acoustic emission (AE), X-ray computed tomography (CT), and digital image correlation (DIC), are summarized. The mechanical characteristics of rocks with different flaw geometries and under different loading conditions, including the geometry of pre-existing flaws, flaw filling condition and confining pressure, are discussed. Furthermore, the cracking process is evaluated from the perspective of crack initiation, coalescence, and failure patterns.
Microglia rapidly respond to changes in neural activity and inflammation to regulate synaptic connectivity. The extracellular signals, particularly neuron-derived molecules, that drive these ...microglial functions at synapses remain a key open question. Here we show that whisker lesioning, known to dampen cortical activity, induces microglia-mediated synapse elimination. This synapse elimination is dependent on signaling by CX3CR1, the receptor for microglial fractalkine (also known as CXCL1), but not complement receptor 3. Furthermore, mice deficient in CX3CL1 have profound defects in synapse elimination. Single-cell RNA sequencing revealed that Cx3cl1 is derived from cortical neurons, and ADAM10, a metalloprotease that cleaves CX3CL1 into a secreted form, is upregulated specifically in layer IV neurons and in microglia following whisker lesioning. Finally, inhibition of ADAM10 phenocopies Cx3cr1
and Cx3cl1
synapse elimination defects. Together, these results identify neuron-to-microglia signaling necessary for cortical synaptic remodeling and reveal that context-dependent immune mechanisms are utilized to remodel synapses in the mammalian brain.
The existence of bedding planes in rock materials has an obvious impact on the material mechanical properties and the failure process of engineering projects. In this study, a series of pre-cracked ...models with different bedding plane properties (i.e., strength reduction factor, bedding plane angle and spacing) were established and simulated to fail under the uniaxial compression. The results indicate that the increases of the strength reduction factor and the bedding plane spacing lead to the increasing peak strength, the change of peak strength regarding the bedding plane angle presents a concave upward trend. In terms of crack evolution, the proportion of cracks formed in rock matrix increases concerning the increasing strength reduction factor and bedding plane spacing, the abovementioned crack proportion in models with increasing bedding plane angles firstly decreases and then increases. The rock matrix has higher mechanical characteristics than bedding planes, the change of crack proportion can account for the changing peak strength from the microscopic viewpoint. By summarizing the failure patterns, the failure of models with the 45° ~ 75° bedding plane angle is induced by cracks formed in bedding planes, which can be depicted and discussed by the plane of weakness model. The above results imply that the rock slope stability can be evaluated by analyzing bedding plane properties in the field.
•Effects of bedding planes are systematically investigated by simulations.•The increase of bedding plane strength and spacing leads to the increasing peak strength.•Peak strength presents a downward concave regarding bedding plane angles.•Microcrack growth can account for the peak strength change.•Engineering stability can be evaluated by analyzing bedding plane property.
Apolipoprotein E4 (APOE4) is the greatest known genetic risk factor for developing sporadic Alzheimer’s disease. How the interaction of APOE4 microglia with neurons differs from microglia expressing ...the disease-neutral APOE3 allele remains unknown. Here, we employ CRISPR-edited induced pluripotent stem cells (iPSCs) to dissect the impact of APOE4 in neuron-microglia communication. Our results reveal that APOE4 induces a lipid-accumulated state that renders microglia weakly responsive to neuronal activity. By examining the transcriptional signatures of APOE3 versus APOE4 microglia in response to neuronal conditioned media, we established that neuronal cues differentially induce a lipogenic program in APOE4 microglia that exacerbates pro-inflammatory signals. Through decreased uptake of extracellular fatty acids and lipoproteins, we identified that APOE4 microglia disrupts the coordinated activity of neuronal ensembles. These findings suggest that abnormal neuronal network-level disturbances observed in Alzheimer’s disease patients harboring APOE4 may in part be triggered by impairment in lipid homeostasis in non-neuronal cells.
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•Microglia-like cells (iMGLs) respond to soluble factors secreted by neurons•APOE4 renders iMGLs weakly responsive to neuronal activity•APOE4 iMGLs disrupts the coordinated activity of neuronal ensembles•Microglial lipid homeostasis is critical to sustain surveillance states
Tsai and colleagues explored the impact of the Alzheimer’s disease-associated risk gene APOE4 onto the cellular communication of neurons and microglia. Through combinatorial experiments with cells derived from CRISPR-edited APOE isogenic lines, this work defines the functional consequence of impaired microglial lipid metabolism induced by APOE4 onto neuronal network activity.
•The hybrid continuum-discontinuum method is firstly used to investigate the filled flaws.•The σci presents a downward concave regarding the increasing flaw inclination angle.•Crack initiation ...sequences in the rock and infillings are closely related with the σci change.•Sliding crack model interprets the variation of mechanical properties of the filled-flaws.
The process of crack nucleation, initiation and propagation are of great significance in rock engineering such as hydrofracturing, underground excavation and gas or petroleum industry. In this study, the fracturing process of rock models with filled-flaws are mimicked by the hybrid continuum-discontinuum method. The effects both on mechanical response and cracking behaviors induced by the frictional properties including cohesion and friction coefficients of infilling materials are investigated. The results indicated that the minimum crack initiation stress of infilled flawed specimens lie in the inclination angle of 45–75° with different cohesions. When the friction angle changes, the minimum crack initiation stress appears when the inclination angle is in the range of 15–60°. The inclination angles are in accordance with that value when the normalized stress intensity factor of K1 acquired by changing cohesion and friction angle reaches maximum in the sliding crack model. Besides, with the increasing of cohesion and friction angle, the transition from wing crack to secondary crack appeared. The crack initiation sequence and pattern are comparable with the laboratory test.
Lead (Pb), one of the most toxic heavy metals, can be absorbed and accumulated by plant roots and then enter the food chain resulting in potential health risks for human beings. The radish (Raphanus ...sativus L.) is an important root vegetable crop with fleshy taproots as the edible parts. Little is known about the mechanism by which radishes respond to Pb stress at the molecular level. In this study, Next Generation Sequencing (NGS)-based RNA-seq technology was employed to characterize the de novo transcriptome of radish roots and identify differentially expressed genes (DEGs) during Pb stress. A total of 68,940 assembled unique transcripts including 33,337 unigenes were obtained from radish root cDNA samples. Based on the assembled de novo transcriptome, 4,614 DEGs were detected between the two libraries of untreated (CK) and Pb-treated (Pb1000) roots. Gene Ontology (GO) and pathway enrichment analysis revealed that upregulated DEGs under Pb stress are predominately involved in defense responses in cell walls and glutathione metabolism-related processes, while downregulated DEGs were mainly involved in carbohydrate metabolism-related pathways. The expression patterns of 22 selected genes were validated by quantitative real-time PCR, and the results were highly accordant with the Solexa analysis. Furthermore, many candidate genes, which were involved in defense and detoxification mechanisms including signaling protein kinases, transcription factors, metal transporters and chelate compound biosynthesis related enzymes, were successfully identified in response to heavy metal Pb. Identification of potential DEGs involved in responses to Pb stress significantly reflected alterations in major biological processes and metabolic pathways. The molecular basis of the response to Pb stress in radishes was comprehensively characterized. Useful information and new insights were provided for investigating the molecular regulation mechanism of heavy metal Pb accumulation and tolerance in root vegetable crops.
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•Quantum dots were used to measure the surface temperature of thin fibers.•The method is based on modulated laser heating and complex temperature via FFT.•Experimental and numerical ...simulations were performed.•The thermal diffusivity of a synthetic silk was measured as 3.3±0.8×107m2s−1.
To improve predictions of composite behavior under thermal loads, there is a need to measure the axial thermophysical properties of thin fibers. Current methods to accomplish this have prohibitively long lead times due to extensive sample preparation. This work details the use of quantum dots thermomarkers to measure the surface temperature of thin fibers in a non-contact manner and determine the fibers’ thermal diffusivity. Neural networks are trained on extracting the temperature of a sample from fluorescence spectra in calibrated, steady-state conditions, based on different spectral features such as peak intensity and peak wavelength. The trained neural networks are then used to reconstruct the evolution of the surface temperature in transient heating experiments. In order to determine the thermal properties of a thin fiber, modulated laser heating is applied and an FFT-based method is used to extract the phase and amplitude response of the temperature field at the modulation frequency. The spatiotemporal dependence of the fluorescence signal, obtained by scanning the distance between the excitation and detection laser spots and varying the frequency response due to an axial scan and a frequency scan, is then curve-fit to the resulting decay curves by a photothermal model in order to determine the thermal diffusivity of the fiber. The measured thermal diffusivity (3.3±0.8×10−7m2s−1) of a synthetic spider silk fiber by the current method has similar properties to other synthetic silk fibers, and demonstrates the ability of the current method to more rapidly measure thermophysical properties of thin fibers.
Novelty preference (NP) is an evolutionarily conserved, essential survival mechanism often dysregulated in neuropsychiatric disorders. NP is mediated by a motivational dopamine signal that increases ...in response to novel stimuli, thereby driving exploration. However, the mechanism by which once-novel stimuli transition to familiar stimuli is unknown. Here we describe a neuroanatomical substrate for familiarity signaling, the interpeduncular nucleus (IPN) of the midbrain, which is activated as novel stimuli become familiar with multiple exposures. In mice, optogenetic silencing of IPN neurons increases salience of and interaction with familiar stimuli without affecting novelty responses, whereas photoactivation of the same neurons reduces exploration of novel stimuli mimicking familiarity. Bidirectional control of NP by the IPN depends on familiarity signals and novelty signals arising from excitatory habenula and dopaminergic ventral tegmentum inputs, which activate and reduce IPN activity, respectively. These results demonstrate that familiarity signals through unique IPN circuitry that opposes novelty seeking to control NP.
The analytical solution of blasting seismic waves induced by cylindrical charge in a viscoelastic half space was lacked. In this study, an approximate analytical solution of this problem is proposed, ...with the combination of the exact analytical solution of the blasting seismic wave in viscoelastic full space and the reflection coefficients of plane waves in viscoelastic half space. To verify the accuracy of the proposed analytical solution, the finite difference method is employed and the numerical results is found well matched the theoretical analysis. The results indicate that the blast load parameters and the mechanical parameters of medium have predominant impact on the propagation of blasting seismic wave, the vibration attenuation on free surface can be divided into near field and far field according to charge depth. In the near field, the vibration amplitude decreases in the vertical direction but increases in the horizontal direction. In the far field, the vibration amplitude decreases in both the vertical and horizontal directions.
•An analytical solution for wave propagation in viscoelastic half space is proposed.•The analytical solution agrees well with the numerical solution.•The effects of model parameters on the vibration waveform are discussed.•The amplitude attenuation law of blasting seismic waves is studied.
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