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Limiting cellular plasticity is of key importance for the therapeutic targeting of metastatic breast cancer (MBC). Fibroblast growth receptor (FGFR) is a critical molecule in cellular plasticity and potent inhibitors of FGFR enzymatic activity have been developed, but kinase independent functions for this receptor also contribute to MBC progression. Herein, we evaluated several FGFR inhibitors and find that while FGFR-targeted kinase inhibitors are effective at blocking ligand-induced cell growth, dormant cells persist eventually giving rise to MBC progression. To more broadly target FGFR and cellular plasticity, we examined the FGFR1 proximal promoter, and found several sequences with potential to form G-quadruplex secondary structures. Circular dichroism was used to verify formation of G-quadruplex in the FGFR1 proximal promoter. Importantly, use of the clinical G-quadruplex-stabilizing compound, CX-5461, stabilized the FGFR1 G-quadruplex structures, blocked the transcriptional activity of the FGFR1 proximal promoter, decreased FGFR1 expression, and resulted in potent inhibition of pulmonary tumor formation. Overall, our findings suggest G-quadruplex-targeted compounds could be a potential therapeutic strategy to limit the cellular plasticity of FGFR1 overexpressing MBC. This study demonstrates the regulation of FGFR1 expression in metastatic breast cancer through the stabilization of G-quadruplex in its proximal promoter. [ABSTRACT FROM AUTHOR]

Background: Serum lactate, as a single and an easily available biomarker, has been applied in various diseases. Aims: In this study, we aimed to explore the predictive value of serum lactate for short-term and long-term prognosis in acute pancreatitis (AP) admitted in intensive care unit (ICU) based on a large-scale database. Methods: AP patients admitted in ICU in the MIMIC-IV database were included. We constructed three different models to investigate the relationships between serum lactate and clinical outcomes, including 30-day, 180-day and 1-year mortality in AP. Smooth fitting curves were performed for intuitively demonstrating the relationship between serum lactate and different outcomes in AP by the generalized additive model. Results: A total of 895 AP patients admitted in ICU were included. The mortalities of 30 days, 180 days, and 1 year were 12.63% (n = 113), 16.87% (n = 151), and 17.54% (n = 157). In model B, with 1-mmol/L increment in serum lactate, the values of OR in 30-day, 180-day and 1-year mortality were 1.20 (95%CI 1.04–1.37, P = 0.0094), 1.21 (95%CI 1.06–1.37, P = 0.0039), and 1.21 (95%CI 1.07–1.38, P = 0.0035). The AUCs of serum lactate for predicting 30-day, 180-day, and 1-year mortality in AP were 0.688 (95%CI 0.633–0.743), 0.655 (95%CI 0.605–0.705), and 0.653 (95%CI 0.603–0.701), respectively. The cut-off value of serum lactate predicting 30-day, 180-day and 1-year mortality in AP was 2.4 mmol/L. Conclusion: Serum lactate could be an indicator for short-term and long-term mortality in patients with AP admitted in ICU. [ABSTRACT FROM AUTHOR]

Intermittent joints are widely found in slopes and the rock section (locking section) in intermittent joints is an important structure that prevents joints from interconnecting and maintains slope stability, but the exact shape of the locking section is not yet known. In this paper, based on the finite difference method (FDM), k-means algorithm, and alpha shape algorithm, a method is proposed to calculate the shape of locking sections and to quantitatively analyze the controlling effect of locking sections and non-locking sections areas on the stability of slopes. In addition, for slopes with high accuracy in the shape of the locking section, the original mesh in the FDM is reconstructed and a network of discrete points is arranged at the locking section at customised intervals and the maximum principal stresses at each discrete point are calculated by the inverse transformation method of the isoparametric elements. This method greatly reduces the influence of grid size on the shape of the locking section. Finally, eight working conditions were designed to investigate the effect of the position of the weak interlayer on the shape and area of the locking section. The results show that the shape of the locking section does not change much as the angle of the line connecting the end points of the weak interlayer increases, and the shape basically remains elliptical, while the area of the locking section changes by increasing and then decreasing. [ABSTRACT FROM AUTHOR]

Acquired drug resistance poses a challenge for single-target FGFR inhibitors, leading to the development of dual- or multi-target FGFR inhibitors. Sulfatinib is a multi-target kinase inhibitor for treating neuroendocrine tumors, selectively targeting FGFR1/CSF-1R. To elucidate the molecular mechanisms behind its binding and kinase selectivity, we determined the crystal structures of sulfatinib with FGFR1/CSF-1R. The results reveal common structural features and distinct conformational adaptability of sulfatinib in response to FGFR1/CSF-1R binding. Further biochemical and structural analyses disclose sensitivity of sulfatinib to FGFR/CSF-1R gatekeeper mutations. The insensitivity of sulfatinib to FGFR gatekeeper mutations highlights the indispensable interactions with the hydrophobic pocket for FGFR selectivity, whereas the rotatory flexibility may enable sulfatinib to overcome CSF-1RT663I. This study not only sheds light on the structural basis governing sulfatinib's FGFR/CSF-1R inhibition, but also provides valuable insights into the rational design of dual- or multi-target FGFR inhibitors with selectivity for CSF-1R and sensitivity to gatekeeper mutations. Sulfatinib is a multi-target angio-immuno kinase inhibitor for treating neuroendocrine tumors, selectively targeting FGFR1 and CSF-1R. Here, the authors elucidate the molecular mechanisms behind its binding and kinase selectivity, highlighting interactions with a hydrophobic pocket for FGFR selectivity, and rotatory flexibility to potentially overcome CSF-1RT663I gatekeeper mutation. [ABSTRACT FROM AUTHOR]

This paper examines the roles of digital finance development in household income, consumption, and financial asset holding from an extreme value theory perspective. Three types of extreme pairs (Min to Min, Max to Max, and Max to Min) are constructed, corresponding to the three aspects of the economic welfare of digital finance: fairness, efficiency, and their trade-off. Using panel data from the Peking University Digital Financial Inclusion Index of China (PKU-DFIIC) and China Family Panel Studies (CFPS) over time span 2014–2018, this paper models the block maxima and minima of variables by fitting them with generalized extreme value (GEV) distribution. The binary expansion testing (BET) is used to detect the nonlinear dependence between digital finance and household economic variables. The tail quotient correlation coefficient (TQCC) is used to quantify the tail dependencies. The results show that: (1) digital finance has significant fairness effects in reducing poverty, increasing consumption, and promoting financial asset holding; (2) digital finance shows effects of promoting incentives and efficiency in household income and financial asset holding, but this effect is relatively limited in household consumption; (3) digital finance generally increases efficiency without harming fairness in terms of all cases of household income and consumption, and most of the cases regarding household financial asset holding; (4) the positive spatial externality of digital finance exists for all household economic variables; and, for pairs regarding household income and consumption, the wider the scope, the greater the spatial spillover effect. The result of this paper implies many novel policy implications. [ABSTRACT FROM AUTHOR]

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The fatigue fracture behaviour and a constitutive model of the freeze-thaw (F-T) sandstone are studied to investigate the failure mechanism of engineering rock in cold regions. First, the fatigue properties of the samples are analysed in terms of stress-strain, deformation characteristics, and pore structure. Second, the types of hysteresis curves are analysed using the load-unload response ratio (LURR) method. Scanning electron microscopy (SEM) and acoustic emission (AE) techniques are then used to investigate the structural damage, crack evolution, and spectral characteristics of the samples. Based on the Lemaitre strain equivalence hypothesis, the improved Harris distribution is used to propose a new constitutive model of rock that underwent F-T cycles under multilevel fatigue loading. Finally, based on the strain difference model, the nonlinear stage of the model is corrected by defining new compaction coefficients using the Weibull distribution. Research shows that the deformation modulus of the F-T rock mass under fatigue loading has degradation behaviour and F-T cycles enhance the fatigue softening of samples. The dominant frequency range of samples under coupling is 70–330 kHz, showing multiband coexistence. As fatigue loading progresses, the hysteresis curve changes from stress hysteresis to strain hysteresis, and the frequency band gradually widens and develops towards low frequencies. The occurrence of a 0 kHz dominant frequency or LURR = 1 can be used as an early warning index of rock fatigue failure. As the number of F-T cycles progresses, the porosity composition curve shifts to the right, and the distribution of AE counts and the dominant frequency shift to the early loading stage. [ABSTRACT FROM AUTHOR]

This paper reports a typical case history of deep braced excavation for constructing the main bridge cushion cap of the Yangwan River Bridge to explore the excavation performance under embankment surcharge load. Three-dimensional finite difference analysis, simulating the whole construction process of this case history, was performed to capture the effects of the embankment–excavation distance, revel level, and excavation bottom sealing on the responses of the earth retaining structure and the ground. It was found that both the ground surface settlement and the retaining structure deformation are larger on the near-embankment side than the far-embankment side. The responses on the near-embankment side are more sensitive to the embankment–excavation distance and the river level. However, the effects of these parameters diminish greatly when the embankment–excavation distance exceeds 1.5 times the excavation depth. The excavation bottom sealing measures can reduce the retaining structure deformation, and effectively restrain basal heave. This restraint weakens as the excavation bottom sealing thickness exceeds 1 m. [ABSTRACT FROM AUTHOR]

Information encryption technique has broad applications in individual privacy, military confidentiality, and national security, but traditional electronic encryption approaches are increasingly unable to satisfy the demands of strong safety and large bandwidth of high-speed data transmission over network. Optical encryption technology could be more flexible and effective in parallel programming and multiple degree-of-freedom data transmitting application. Here, we show a dual-layer optical encryption fluorescent polymer waveguide chip based on optical pulse-code modulation technique. Fluorescent oligomers were doped into epoxy cross-linking SU-8 polymer as a gain medium. Through modifying both the external pumping wavelength and operating frequency of the pulse-code modulation, the sender could ensure the transmission of vital information is secure. If the plaintext transmission is eavesdropped, the external pumping light will be switched, and the receiver will get warning commands of ciphertext information in the standby network. This technique is suitable for high-integration and high-scalability optical information encryption communications. Data security of internet is increasingly more demanding in the current era, yet the traditional electronic approach is limited in speed and efficiency. Here, the authors proposed a dual-layer optical encryption fluorescent polymer waveguide chip based on optical pulse-code modulation to mitigate the limitations. [ABSTRACT FROM AUTHOR]

Rock sections in intermittent joints are important structures that prevent joints from interconnecting and maintain the stability of the rock mass, and they play a pivotal role in the strength and failure mode of the rock mass. In order to analyze the controlling effect of rock section in intermittent joints, the samples with different rock section angles were prepared and laboratory tests were carried out using Acoustic Emission and Digital Image Correlation (DIC) techniques. The results show that the uniaxial compressive strength of the samples reaches its minimum value when the orientation of the rock section in the intermittent joints coincides with the loading direction. Furthermore, as the angle of the rock section increases, the time share of the sample in the compaction stage increases and the time share in the plastic-yield stage decreases. The samples show the structural characteristics of being difficult to close at the early stage and easy to destroy at the late stage. In terms of the damage mode, the increase in the angle of the rock section reduces the difficulty of the rock section itself being penetrated, and the samples are more easily damaged. Finally, a damage constitutive model considering the compaction stage and initial damage was developed and the effect of rock section angle on the rate of rock damage was analyzed. Highlights: The influence of the angle of the rock section in the intermittent joints on the compressive strength and failure mode of the samples was investigated. Based on acoustic emission, DIC and damage constitutive models, the effect of the angle of the rock section in an intermittent joint on the deformation phase of the sample is quantified. A damage constitutive model considering the initial damage of the intermittent joints and the compaction stage of the rock is proposed. [ABSTRACT FROM AUTHOR]

The discrete element method (DEM) is widely used for its flexibility in handling a large number of geotechnical problems. To study the relationship between macro–micro parameters during the shear process, a series of rock direct shear tests were carried out by PFC2D in this paper. Firstly, the qualitative influence of main microparameters (particle contact elastic modulus, particle ratio of normal to shear stiffness, particle friction coefficient, parallel bond tensile strength, parallel bond cohesion, and parallel bond friction angle) and normal stress on macroscopic shear parameters were analyzed by simulation results. Subsequently, one-way analysis and multivariate nonlinear regression of the relationship between micro- and macro- parameters were performed, and the quantitative prediction models of the main shear macro-parameters (shear strength, shear stiffness, residual shear strength) were established. Finally, comparing the simulation results with the predicted values of the proposed model, it was found that the predicted values were very close to the simulation results, thus verifying the effectiveness of the model. [ABSTRACT FROM AUTHOR]

In this work, on-chip three-dimensional (3D) photonic integrated optical sources based on active fluorescent polymer waveguide microdisks are proposed for light display application. Fluorescent green and red oligomers with high-efficiency photoluminescence are doped into epoxy crosslinking SU-8 polymer as the waveguide gain medium. The microdisk-based on-chip optically pumping light sources are designed and fabricated using the organic functionalized materials by direct UV written process. The promising stacking dual-microdisk structures with double gain layers could provide white signal light source generated perpendicular to the chip, and green signal light source stimulated in the chip. The approach could realize the monolithically on-chip assembled vertical and horizontal bright emitters. The optical pumping threshold power is obtained as 50 mW with continuous-wave (CW) pumping. The average gain coefficient of a white light source is measured by vertical fiber coupling as 112 dB/W, and that of green light source by horizontal fiber coupling as 137 dB/W, respectively. The rising and falling response time of the on-chip optical sources are 60 and 80 µs under modulating pulsed pumping. This technique is very promising for achieving 3D integrated light display application, including photonic circuits and optical information encryption. [ABSTRACT FROM AUTHOR]

The mechanical behavior and constitutive relation of rock joints have caught more and more attention in the field of geotechnical engineering. The disturbed state concept (DSC) theory offers a powerful tool for building a constitutive model to interpret the mechanical response of geomaterials. In this paper, a new constitutive model for joint shear deformation was developed based on the DSC theory. The characteristics of quasi-elastic phase, pre-peak hardening phase, peak shear strength, post-peak softening phase and residual strength during the whole process of joint shear deformation are considered in this model. In the framework of this shear constitutive model, the rock material was assumed to consist of two kinds of micro-units with different mechanical responses, namely the relatively intact unit and the fully adjusted unit. Subsequently, the DSC theory was used to connect the mechanical behavior of micro-units with the macroscopic joint shear deformation characteristics, and a disturbance factor was introduced to reveal the disturbed state evolution process inside the rock. In addition, the proposed DSC model was simple in form, less in parameters and reasonable in physical meaning. The model was cross-validated by experimental data of different kinds of natural joints and artificial joint replicas. Finally, the model is compared with existing models, and the model effectiveness is quantitatively evaluated through statistical indicators. The values of R2 are greater than 0.9, and the AAREP and RMSE of the proposed DSC model are closer to 0 than those of other models. The research results can provide a valuable reference for further understanding of shear deformation mechanism. [ABSTRACT FROM AUTHOR]

In the synovial joint, mechanical force creates an important signal that influences chondrocyte behavior. The conversion of mechanical signals into biochemical cues relies on different elements in mechanotransduction pathways and culminates in changes in chondrocyte phenotype and extracellular matrix composition/structure. Recently, several mechanosensors, the first responders to mechanical force, have been discovered. However, we still have limited knowledge about the downstream molecules that enact alterations in the gene expression profile during mechanotransduction signaling. Recently, estrogen receptor α (ERα) has been shown to modulate the chondrocyte response to mechanical loading through a ligand-independent mechanism, in line with previous research showing that ERα exerts important mechanotransduction effects on other cell types, such as osteoblasts. In consideration of these recent discoveries, the goal of this review is to position ERα into the mechanotransduction pathways known to date. Specifically, we first summarize our most recent understanding of the mechanotransduction pathways in chondrocytes on the basis of three categories of actors, namely mechanosensors, mechanotransducers, and mechanoimpactors. Then, the specific roles played by ERα in mediating the chondrocyte response to mechanical loading are discussed, and the potential interactions of ERα with other molecules in mechanotransduction pathways are explored. Finally, we propose several future research directions that may advance our understanding of the roles played by ERα in mediating biomechanical cues under physiological and pathological conditions. [ABSTRACT FROM AUTHOR]

It is difficult to reflect the nonlinear characteristics of rock compaction by directly applying the damage statistical distribution of rock micro-elements during the establishment of freezing–thawing rock damage constitutive models, which show better agreements with those stress–strain curves with inapparent compaction stage. To remedy this, a new piecewise constitutive relation consisting of damage constitutive relation and compaction constitutive relation is proposed in this paper. First, the freezing–thawing damage was characterized by the change of rock deformation modulus, the improved Harris distribution was used to reflect the microscopic damage of rock under loading, and the damage statistical constitutive relation of freezing–thawing rock was founded based on the generalized equivalent strain theory. According to the geometric characteristics of the peak point on the stress–strain curve, the solution methods of relevant parameters were deduced. For the rock compaction relation, the rock material was divided into framework component and void component, and the corresponding compressive deformation was, respectively, calculated by Hooke's law and true strain analysis method. Then the stress–strain relation of rock compaction containing void equivalent deformation modulus and void factor was derived. Through combining the damage statistical constitutive relation and the compaction constitutive relation, the piecewise expression of the full stress–strain curve of rock subjected to freezing–thawing cycles and uniaxial compression can be achieved. Ultimately, the correctness and applicability of this expression were validated by repeatedly comparing the theoretical curves and the experimental curves of different experiment results. [ABSTRACT FROM AUTHOR]

In the process of exploiting mineral and geothermal energy resources, the influence of the cyclic heat effect on the mechanical properties of the surrounding rock becomes increasingly prominent. To further study the damage deterioration mechanism, deformation and failure characteristics of cyclic heating–cooling (H–C) of the rock, cyclic H–C treatment tests and uniaxial compression tests were conducted, acoustic emission (AE) events were monitored, and the mesoscale characteristics of the fracture surface were imaged and analysed. The results show that the number of H–C cycles played an important role in the evolutions of the strength, cumulative damage variables and deformation modulus of the red sandstone. The peak strength of the specimens decreased with the increase in the number of H–C cycles, and the damage variables increased with the number of H–C cycles. The cyclic H–C treatments promoted the development of microcracks and the growth of the stress–strain curve crack closure stage. Both the crack closure stress and crack closure strain increased with the number of H–C cycles. Furthermore, both the number of transgranular microcracks and the microcrack spacing increased during cyclic H–C treatment, which also led to the failure mode of the specimens gradually changing from shear failure to splitting failure. In addition, based on the principle of strain equivalence, a damage constitutive model under the coupling action of cyclic H–C treatment and loading was deduced. The crack closure deformation of specimens treated with different numbers of H–C cycles was well reflected by the proposed model, and the prediction of other mechanical parameters, such as the peak stress, peak strain and tangent modulus of the theoretical curves, was also verified by test data. [ABSTRACT FROM AUTHOR]

All inorganic CsPbX3 (X = Cl, Br, and I) perovskite nanocrystals have made unprecedented radical progresses for opto-electronic applications, but their instability and toxicity of lead impede their wide applications. Herein, we report the first precipitation of lead-free Mn:Cs2ZnX4 nanocrystals in glasses. Efficient green and red photoluminescence are realized from these Mn:Cs2ZnX4 nanocrystals in glasses. By adjusting the size and halide component in these nanocrystals, coordination environment of Mn2+ ions can be tuned, leading to tunable photoluminescence with improved quantum efficiency. It is illustrated that in-situ precipitation of these Mn:Cs2ZnX4 nanocrystals in glasses significantly improves their thermal-, chemical-, and photo-stabilities, making them promising for light-emitting diodes with stable chromaticity coordinates. [ABSTRACT FROM AUTHOR]

Rock joint surface roughness is usually characterized by heterogeneity, but the determination of a required number of samples for achieving a reasonable heterogeneity assessment remains a challenge. In this paper, a novel method, the global search method, was proposed to investigate the heterogeneity of rock joint roughness. In this method, the roughness heterogeneity was characterized based on a statistical analysis of the roughness of all samples extracted from different locations of a given rock joint. Analyses of the effective sample number were conducted, which showed that sampling bias was caused by an inadequate number of samples. To overcome this drawback, a large natural slate joint sample (1000 mm × 1000 mm in size) was digitized in a laboratory using a high-accuracy laser scanner. The roughness heterogeneities of both two-dimensional (2D) profiles and three-dimensional (3D) surface topographies were systematically investigated. The results show that the expected value obtained from conventional methods failed to accurately represent the overall roughness. The relative errors between the population parameter and the expected value varied not only from sample to sample but also with the scale. The roughness heterogeneity characteristics of joint samples of various sizes can be obtained using the global search method. This new method could facilitate the determination of the most representative samples and their positions. Highlights: We propose the global search method to investigate the heterogeneity of roughness. Analyses of the effective sample number are conducted to prove the sampling bias. We investigate roughness heterogeneity by 2D profiles and 3D surface topographies. The method is applied to determining the most representative samples. [ABSTRACT FROM AUTHOR]

Joint properties play a controlling role in the strength of rock mass. In response to the situation that existing researches on bolting mechanism of bolted rock joints principally concentrate on the macroelements, such as rock properties, bolting angle and joint morphology, the direct shear tests on unbolted and single-bolted rock joints under the conditions of different normal stress and different joint microproperties by numerical calculation method of particle flow (PFC) were carried out in this paper to reveal the microbolting mechanism and study the influences of joint properties. Subsequently, a comprehensive comparison of microfailure characteristics between unbolted and single-bolted rock joint demonstrated that during the shearing process, a triangle extrusion reinforcement area emerges around the bolt, where microcracks are extremely developed and rock blocks are considerably fractured, but it also improves the anti-shearing efficacy of rock joint. Meanwhile, both the macroshear behavior and microfailure characteristics of single-bolted rock joints with different joint microproperties was analyzed by comparing the shear stress–shear displacement curves and crack development. Specifically, the shear stiffness of single-bolted rock joints enhances with the increase of joint tangential stiffness, and the augmentation of joint tangential stiffness or friction coefficient intensifies the shearing resistance of single-bolted rock joints, whereas the joint normal stiffness was proven to share a negative correlation with the shear strength of single-bolted rock joints. Besides, the shear stiffness of single-bolted rock joints decreases approximately linearly with the increasing joint thickness. In addition, the thicker the joint, the lower the peak shear stress of single-bolted rock joints. With the increase of joint thickness, the crack number of single-bolted rock joint failure decreases, and the particle confinement of bolt is enhanced. [ABSTRACT FROM AUTHOR]

In order to study the hydraulic-mechanical coupling law of deep fractured rock aquifer, based on the existing principal of effective stress, this paper obtained the mechanical parameters such as axial stress, confining pressure, and pore water pressure through the conventional triaxial compression test, hydraulic-mechanical coupling test under triaxial compression condition, and numerical fitting of water-saturated sandstone, so as to obtain the effective stress coefficient and related mechanical conclusions. The results showed that the axial stress had a positive linear relationship with the confining pressure. Peak strength and deformation modulus of water-saturated sandstone were positively correlated with confining pressure and negatively correlated with pore water pressure, while Poisson's ratio was opposite. Under the same confining pressure, the effective stress coefficient of water-saturated sandstone was positively correlated with Poisson's ratio and negatively correlated with deformation modulus. The effective stress coefficient obtained by numerical fitting was a bilinear function of pore water pressure and volumetric stress, and the effective stress coefficient was positively correlated with pore water pressure and negatively correlated with volumetric stress. [ABSTRACT FROM AUTHOR]

The freeze–thaw cycles and joint will deteriorate the strength characteristics of jointed rock mass and may lead to geotechnical failures in cold regions. Former studies mainly focus on the effect of freeze–thaw conditions on the mechanical properties of rock. However, for rock engineering, rock joints are ubiquitous in rock mass engineering, and the water in rock joints will experience freeze–thaw process when temperature varies alternatively. The frost heaving pressure generated during this process causes the joints to propagate and hence will eventually leads to the failure of rock masses. However, few researches focus on the degradation of strength characteristics of rock joints under freeze–thaw cycles, especially for joint damage evolution mechanism of shear strength characteristics, which is actually crucial factor for rock masses stability. Therefore, in this paper, a large number of shear experiments were conducted to investigate the influence of freeze–thaw cycle-induced joint shearing degradation on cohesion as well as friction angle of joints with considering joint persistency values. Based on the damage mechanics, together with the experimental results, the damage variables of shear strength parameters under freezing–thawing cycles are analyzed. In addition, a damage evolution model for joint shearing under freeze–thaw cycles is established with considering freeze–thaw cycles as well as joint persistency, and the feasibility and capability of this proposed model are then further verified both experimentally and theoretically. [ABSTRACT FROM AUTHOR]

Hoek–Brown criterion is one of the most widely used strength criteria in the field of rock engineering, which can reflect the nonlinear empirical relationship between the ultimate principal stresses in rock failure, while the determination of Hoek–Brown parameters is still controversial. The evaluation of Hoek–Brown parameters according to geological strength index (GSI) classification of rock mass involves engineering experiences and subjectivity, and the fitting method of Hoek–Brown parameters based on laboratory triaxial experimental results of multiple fractured rocks is also not going to be easy. Besides, the majority of previous studies were still carried out through the triaxial tests of intact rocks. In this study, the shear expression of Hoek–Brown criterion was derived, and an approximate method for determining Hoek–Brown parameters based on shear tests was established. Primarily, Hoek–Brown criterion was briefly reviewed and the variations of Hoek–Brown parameters with the change of GSI was analyzed. When GSI decreases from 100 to 50, the reduction of a is only 0.006. While s shows almost no change and approximates to 0 when GSI decreases from 50 to 0. On this basis, the existing shear expression of Hoek–Brown criterion for intact rock (GSI = 100) was extended to the fractured rock mass with 50 < GSI < 100. In addition, the approximate shear expression of Hoek–Brown criterion for fractured rock mass in the range of 0 < GSI < 50 was deduced by assuming s = 0. Then, Hoek–Brown parameters can be calculated through shear tests and MATLAB programing. Finally, based on the structural plane occurrence information of Tangdan copper mine, a random fracture network was generated by Monte Carlo method to prepare random fractured rock mass samples for compression–shear experiments, which were employed to verify the proposed method. [ABSTRACT FROM AUTHOR]

The study of constitutive model is of great significance to engineering safety evaluation and geological disaster prevention. In this paper, rock materials were regarded as a composite geological material composed of voids and rock matrix, and then a piecewise constitutive model bounded by the yield point was proposed. It can reflect the complete stress–strain curves of rocks, including the compaction stage, the elastic stage, the plastic yield stage and the post-peak stage. Primarily, an objective method to determine the yield point based on the stress difference was proposed. For the rock deformation before yielding, the relationship between the strain of rock materials and the strains of voids and rock matrix was analyzed to establish the corresponding constitutive model. Subsequently, based on the modified Weibull distribution, a damage statistical constitutive model of rocks was established to describe the nonlinear deformation after the yield point. Meanwhile, the determining method of model parameters was given. Finally, the uniaxial and triaxial compression test data of different types of rocks were used to verify the proposed model. The results indicate that the model curves are in good agreement with the experimental results. Hence, it is feasible and reasonable to divide the macroscopic strain of rocks into the strains of voids and rock matrix. Additionally, there is a power function attenuation relationship between the deformation ratio of voids to rock matrix and the axial stress. [ABSTRACT FROM AUTHOR]

Researches on the energy evolution of the key blocks is helpful to reveal the failure process of locked-segment type slope, whose stability is governed by the locked segment along the potential slip surface. In order to study the failure mechanism of the locked segment in the process of slope progressive failure due to strength attenuation, a series of stability analysis on the numerical models of locked-segment type slope were implemented to record the relationship curve between energy and strength reduction coefficient. Then, according to the variation law and characteristic of energy evolution, the failure process of the locked segment was divided into four stages: elastic stage, initial damage stage, extensive damage stage and failure stage. And the reduction coefficient corresponding to the peak of the energy evolution curve was employed to achieve landslide warning. In addition, the method to determine the safety factor of locked-segment type slope was given, and its reliability was verified by comparing with other traditional methods. Finally, the formula for calculating the initial sliding velocity was presented based on the residual strain energy which is defined as the elastic strain energy of the locked segment when the slope is unstable. [ABSTRACT FROM AUTHOR]

We aimed to comprehensively investigate the associations of air pollutants with hospital admissions for critical illness in ED. Patients with critical illness including level 1 and level 2 of the Emergency Severity Index admitted in ED of Changsha Central Hospital from January 2016 to December 2020 were enrolled. Meteorological and air pollutants data source were collected from the National Meteorological Science Data Center. A Poisson generalized linear regression combined with a polynomial distributed lag model (PDLM) was utilized to explore the effect of air pollution on hospital admissions for critical illness in ED. Benchmarks as references (25th) were conducted for comparisons with high levels of pollutant concentrations (75th). At first, lagged effects of all different air pollutants were analyzed. Then, based on the most significant factor, analyses in subgroups were performed by gender (male and female), age (< 45, 45–65, and > 65), disorders (cardiovascular, neurological, respiratory), and seasons (spring, summer, autumn, and winter). A total of 47,290 patients with critical illness admitted in ED were included. The effects of air pollutants (PM2.5, PM10, SO2, NO2, O3 and CO) on critical illness ED visits were statistically significant. Strong collinearity between PM2.5 and PM10 (r = 0.862) was found. Both single-day lag and cumulative-day lag day models showed that PM2.5 had the strongest effects (lag 0, RR = 1.025, 95% CI 1.008–1.043, and lag 0–14, RR = 1.067, 95% CI 1.017–1.120, respectively). In both PM2.5 and PM10, the risks of critical illness in male, > 65 ages, respiratory diseases, and winter increased the most significant. Air pollutants, especially PM2.5 and PM10 exposure, could increase the risk of critical illness admission. [ABSTRACT FROM AUTHOR]

To better understand dynamic characteristic of rock in mud and water environment, quasi-static and dynamic uniaxial compressive tests were performed on cylindrical thick-walled granite specimen with various clay infillings. The results from quasi-static compressive tests show the existences of a central hole and clay infilling in cylindrical thick-walled specimen have no obvious effect on static mechanical behavior of specimens. Dynamic compressive tests indicate that the dynamic compressive strength (DCS) of cylindrical thick-walled granite specimen with clay infilling, which linearly increases with the strain rate, is the sum of DCS of hollow thick-walled granite specimen and the hydrodynamic pressure of clay fillings in the central hole space. The DCS of specimen increases with the increasing moisture content of clay infilling and the decreasing hole diameter at the same strain rate. [ABSTRACT FROM AUTHOR]

The slope stability has already become one of the most important factors directly related to the safety production and development of a mine, which is principally controlled by the properties of geological discontinuities of slope, such as bedding planes, faults, cleavage and joints. In this study, a new approach for the evaluation of slope stability in large open-pit mines was presented based on a comprehensive investigation of the geometry and shear strength of the geological discontinuities. This approach follows three steps: (1) graded kinematic analysis using stereographic projection techniques; (2) field estimation of shear strength of discontinuities with the consideration of the impact of uncertainty and scale dependency; and (3) slope stability assessment based on deterministic analysis by FoS and the probabilistic analysis by PoF. A case study, namely, the Yangtaowu Slope in the Dexing Copper Mine, was selected for the application of this approach. The stability assessment result shows good agreement with field observation, illustrating the ability of the proposed method in effectively predicting the stability of open-pit mine slopes. Furthermore, the comparison of the calculated results based on the precise and generalized calculation models demonstrated that the accuracy of the geometric model has a high influence on the stability assessment. [ABSTRACT FROM AUTHOR]

Significant cellular senescence has been observed in cartilage harvested from patients with osteoarthritis (OA). In this study, we aim to develop a senescence-relevant OA-like cartilage model for developing disease-modifying OA drugs (DMOADs). Specifically, human bone marrow-derived mesenchymal stromal cells (MSCs) were expanded in vitro up to passage 10 (P10-MSCs). Following their senescent phenotype formation, P10-MSCs were subjected to pellet culture in chondrogenic medium. Results from qRT-PCR, histology, and immunostaining indicated that cartilage generated from P10-MSCs displayed both senescent and OA-like phenotypes without using other OA-inducing agents, when compared to that from normal passage 4 (P4)-MSCs. Interestingly, the same gene expression differences observed between P4-MSCs and P10-MSC-derived cartilage tissues were also observed between the preserved and damaged OA cartilage regions taken from human samples, as demonstrated by RNA Sequencing data and other analysis methods. Lastly, the utility of this senescence-initiated OA-like cartilage model in drug development was assessed by testing several potential DMOADs and senolytics. The results suggest that pre-existing cellular senescence can induce the generation of OA-like changes in cartilage. The P4- and P10-MSCs derived cartilage models also represent a novel platform for predicting the efficacy and toxicity of potential DMOADs on both preserved and damaged cartilage in humans. [ABSTRACT FROM AUTHOR]

The wing cracks are usually the first crack that appears in the loading process in studies about fractured rocks, and a certain correlation exists between the wing crack propagation process and the peak strength of fractured specimens. To further explore the correlation between wing crack propagation and the peak strength of specimens, specimens containing the main flaw and prefabricated wing cracks were chosen as the test object, and compression tests and numerical simulations were carried in this study. To some extent, it can be regarded as a step-by-step simulation and reproduction of the propagation process of wing cracks. The loading and monitoring processes and the analysis of results reveal that specimens with the prefabricated wing cracks show more plasticity in the loading process than the other specimens without the prefabricated wing cracks. However, the length of prefabricated wing cracks does not affect the peak strength of the specimen. The wing crack has a critical length of the stable propagation for each specimen with a single flaw under uniaxial compression, which determines the peak strength of specimen. When the length of wing cracks extends to this critical value, the specimen reaches its peak strength. On this basis, the peak strength of the fractured specimen can be solved using this critical value. This paper provides a reference for the theoretical analysis of the peak strength of fractured specimens. [ABSTRACT FROM AUTHOR]

The mechanical behaviors and constitutive relationships of rocks in failure process have always been the hot issues in the field of geotechnical engineering. According to the characteristics of random distribution of rock micro-element strength, based on Weibull distribution function, the improved Harris distribution function, power function and composite power function, the evolution equations of rock damage under different distribution functions were derived, and the statistical constitutive models of rock damage in the form of axial deviatoric stress–strain curve were established by combining rock damage theory and statistical strength theory. The validity comparison and analysis of these models were then implemented underpinned by traditional triaxial experimental data of sandstone in reported literature. Primarily, the theoretical curves of four damage models are all in good agreement with the experimental finding in the pre-peak stage. The curve originated from the power function model failed to describe the strain softening characteristic in the post-peak stage, and a sharp drop could be observed, while the others presented a better consistency with the data to a certain extent. Wherein, similar matching effect of curves to data based on the Weibull distribution function and the composite power function was discovered. [ABSTRACT FROM AUTHOR]

The mechanics of rock masses in cold regions have attracted the attention of researchers from all over the world, and the concern here is that the mechanical properties of rock masses are inevitably weakened under freeze–thaw cycles. In this paper, first, granite samples were subjected to different freeze–thaw cycles, and then treated in four different states, such as saturated and frozen states, saturated and normal temperature states, dry and frozen states, as well as dry and normal temperature states. The impact compression test was carried out using the Split Hopkinson Pressure Bar (SHPB) device. Results show that the impact strength of granite samples deteriorates with the increase of freeze–thaw cycles in the same state; for samples in different states, although the number of freeze–thaw cycles is equal, the degree of deterioration of the impact strength is different. For freeze–thawed granite samples in the same state, the dynamic elastic modulus decreases with the increase of freeze–thaw cycles, and its degree of decrease is different for different states. Under the same freeze–thaw cycles, the deterioration of mechanical properties of granite samples is different in four different weather states; for example, the dynamic elastic modulus from large to small is generally as follows: saturated and frozen states, saturated and normal temperature states, dry and frozen states, as well as dry and normal temperature states. Finally, the freeze–thaw influence factor is proposed to describe the damage of granite samples. All in all, it can be concluded that water and low temperature strengthen the influence of freeze–thaw cycles on the dynamic mechanical properties of granite. [ABSTRACT FROM AUTHOR]

The locked section is a kind of geological structure that is commonly found in natural slopes. The instability criterion of the slope with a locked section structure is not yet studied. In accordance with the mechanical properties of this type of slope, the rock mass is divided into several rock blocks along its joint distribution, and the upper limit method of plastic limit analysis is introduced. By combining the principle of virtual work and the characteristics of the slope, a virtual speed is assigned to the slope and the locked section. In addition, the maximum elastic strain energy that can be accumulated in the locked section is calculated to derive its deformation rate and internal energy dissipation power. The virtual velocity, internal energy dissipation power, and gravity work power of the locked section and the rock slope are solved simultaneously in accordance with the Mohr–Coulomb correlation flow law. Finally, the formula for calculating the safety factor of this type of slope under shear failure mode is derived. A slope in Xikou, Sichuan, China, is taken as an example to verify the proposed model. [ABSTRACT FROM AUTHOR]

To better understand the effect of water content on shear behaviors of clay-infilled joint, a series of direct shear experiments were performed on clay-infilled joints prepared by reproducing the standard JRC profiles on a rock-like material and placing the clay infill with various water content inside the joint, and a shear strength model of infilled joints was established. For most of the clay-infilled joints, the shear stress versus shear displacement curve is characterized by gentle type; i.e., the residual shear stress value is close to the peak value, with the absence of a softening phase on the curve. There is a trend to negative correlation between the shear strength of clay-infilled joints and the t/a ratio when t/a is smaller than a critical value (t/a)cr. Shear strength of clay-infilled joints decreases with an increase in water content, if water content is below liquid limit of clay infill; however, the shear strength of infilled joint with liquid clay is higher than that of the infilled joint with plastic clay. Based on the JRC-JCS strength criterion, a revised shear strength model of infilled joint is proposed, by the proposed negative exponential equation between friction angle and t/a ratio. The good agreement between experimental results and predictions indicated that the revised shear strength model is capable of estimating the peak shear strength of infilled rock joints. [ABSTRACT FROM AUTHOR]

A series of uniaxial and triaxial compression tests were performed on slate samples with different diameters at different foliation orientations with respect to the direction of the major principal stress. The size effect and anisotropy in slate, as a transversely isotropic rock, were investigated, and the research focused on aspects of elastic properties, uniaxial compressive strength (UCS), triaxial compressive strength (TCS), and triaxial residual strength (TRS). In the five elastic constants for slate, only the Young's modulus parallel to the isotropic plane is size dependent. The UCS follows a descending size-effect model developed from coal. The size-effect behaviors of the UCS and TCS are similar. Two size-dependent failure criteria are proposed by incorporating the size-effect model for UCS into the modified Hoek–Brown and Saeidi failure criteria and are verified against experimental data. This is the first time that the relationship among the compressive strength, specimen size, foliation orientation and confining pressure has been comprehensively captured for transversely isotropic rock. Without an evident size effect, the anisotropic TRS has also been effectively captured by a modified cohesion loss model, and two bound equations for the brittleness index are finally proposed for transversely isotropic rock. This work promises to provide an upscaling method for determining the mechanical parameters of transversely isotropic rocks in practical engineering. [ABSTRACT FROM AUTHOR]

The rapid development of China's economy has largely relied on energy consumption, which has caused serious air pollution and affected public health, and economic development, energy consumption, air pollution, and public health have nowadays become the focus of academic attention. However, the previous literature failed to consider undesirable output when constructing the Dynamic Network DEA model to study the efficiencies of energy consumption, air pollution, and public health. As a result, past studies did not employ those three issues in a structure to effectively reflect and solve the problems. Therefore, this paper constructs the Two-Stage Dynamic Undesirable DEA model and puts energy consumption, air pollution, and public health into the same framework in order to fill the gap in the literature. Findings show that the production consumption efficiency stage is better than the health protection stage, and that the efficiency values of variables vary significantly in different regions. The efficiency of tumor and tuberculosis is the lowest, with oil consumption and birthrate efficiencies are the best, followed by coal, nitrogen oxide (NOx), and dust efficiencies. Coal efficiency exhibits a fluctuating downward trend, whereas the efficiencies of electricity, air pollutants, tuberculosis, and tumor tend to fluctuate upwards during the research period. In consideration of the varying performances of different regions in the two stages, we put forward suggestions based on these findings to improve the efficiencies of energy, environment, and public health in China. [ABSTRACT FROM AUTHOR]

The constitutive models of rock are essentially the general depictions of the mechanical responses of rock mass under complex geological environments. Statistical distribution-based constitutive models are of great efficacy in reflecting the rock failure process and the stress–strain relation from the perspective of damage, while most of which were achieved by adopting Drucker–Prager criterion or Mohr–Coulomb criterion to characterize microelement failure. In this study, underpinned by Hoek–Brown strength criterion and damage theory, a new statistical damage constitutive model, which is simple in terms of model expression and capable of reflecting the strain softening characteristics of rock in post-peak stage, was established. First, the rock in the failure process was divided into infinite microelements including elastic part satisfying Hooke’s law and damaged part retaining residual strength. Based on strain equivalence hypothesis, the relation between rock microelement strength and damage variable was derived. By assuming the statistical law of microelement strength obeying Weibull distribution and the microelement failure conforming to Hoek–Brown criterion, the new statistical damage constitutive model based on Hoek–Brown criterion was, therefore, gained. The mathematical expressions of the corresponding model parameters were subsequently deduced in accordance with the geometric characteristics of the deviatoric stress–strain curve. Last, the existing conventional triaxial compression test data of representative rock samples under different confining stresses were employed to compare with the theoretical curves by proposed model, the consistency between which was quantified by utilizing the correlation factor evaluation method. The result indicated that the proposed model could well describe the entire stress–strain relationship of rock failure process and manifest the characteristics of rock residual strength. It is of great significance to the researches on rock damage and softening issues and rock reinforcement treatments. [ABSTRACT FROM AUTHOR]

Food allergy has become one of the food safety issues in the world. As a common source of food allergy, soybean poses a dietary risk to allergic individuals due to the presence of β-conglycinin, a main allergenic protein in soybean. Therefore, an efficient and sensitive detection method using highly specific antibody materials is necessary for the detection of allergens. In this study, we have used soybean major allergen β-conglycinin as research object, using analysis software such as DNAStar subroutine Protean, SOPMA server, etc. Three main subunits (α, α′ and β subunits) of β-conglycinin were sequenced. After a series of predictions, screenings and validations, we have obtained the most active epitope peptide with the sequence SNLNFLAFGINAENNQ from the β subunit. This epitope peptide was used to prepare rabbit-derived polyclonal antibodies. Using this antibody, we developed a quantum-dot-based fluorescent lateral flow immunoassay (LFIA) to detect β-conglycinin in frozen surimi. In this detection method, relevant conditions were optimized, and the detection limit was found to be 1.6 mg/g. In conclusion, the epitope peptide SNLNFLAFGINAENNQ was synthesized and using this epitope peptide as the immunogen, rabbit-derived polyclonal antibodies were prepared. A QD-based fluorescent LFIA detection method was developed for a simple, sensitive and specific detection of soybean major allergen β-conglycinin in surimi. This method is beneficial to the healthy development of the frozen surimi industry. [ABSTRACT FROM AUTHOR]

The fatigue characteristics of rock materials are usually studied by cyclic load–unload tests, and the deformation and damage development reflect their weakening characteristics. In this paper, according to the mechanical characteristics of rock materials during load/unload cycles, the total strain can be separated into three types, that is, elastic strain, viscoelastic strain, and viscoplastic strain. The elastic strain is linear with stress, and viscoelastic strain exhibits a special behavior after unloading, the viscoplastic strain also displays its own unique features and reflects the damage in rocks. Based on their unique characteristics, we establish elastic, viscoelastic, and viscoplastic submodels, then an elastic-visco-plastic model can be obtained by connecting three submodels in series, which can reflect the development of the law of different strains. In order to verify the reliability of the model, red sandstone samples are selected for cyclic load/unload tests. The results show that the collected strain–time data are well fitted by the model. In addition, the characteristics of strain–time curves imply the deformation and damage development of rocks during load/unload cycles. [ABSTRACT FROM AUTHOR]

The damage of the interface between mortar and rock often occurs in engineering projects. The stability of the binary medium joint is the key factor in judging the stability of a hydraulic structure foundation. The shear characteristics of the flat mortar-rock joint were numerically simulated under the direct shear test by finite element using FLAC3D software. The results showed that the internal friction angle of mortar has little influence on the shear strength, its corresponding displacement, strain softening degree and residual shear strength for flat joint. Therefore, considering the roughness of the structural surface, the joint with regular serrated mortar-rock binary medium was established in this paper, and the direct shear test under the condition of constant normal stress was carried out for comparative study. The results showed that the shear strength, residual strength, peak strength displacement and strain softening degree of the serrated structure were strongly correlated with the internal friction angle of mortar. For the regular serrated binary joint, improving the mortar performance can improve the shear performance and stability of the whole structure more effectively than the flat joint. The relationship between the shear strength, residual strength and the friction angle were established respectively. [ABSTRACT FROM AUTHOR]

Most natural rock masses contain a large number of random joints and fissures, and most of the rock masses at the rock engineering are commonly in both compression and shear stress environment. However, the research on the failure characteristics of complex random jointed rock mass under compressive-shear loading is still limited. To address this gap, this paper uses the particle flow code 2D to establish a discrete fractured rock mass model and carry out a series of numerical tests with different compressive-shear angles (α) and different joint geometric parameters. The effects of compressive-shear angle and joint geometric parameters on the strength and failure characteristics of fractured rock masses are studied. The results indicate that with the increase of α, the peak strength of the specimen decreases gradually, and the failure mode changes from the composite shear failure mode (Mode-I) to a plane shear failure mode (Mode-II) and then to intact shear failure mode (Mode-III). Specifically, the three failure modes occur in the specimens with α = 15°, 30° or 45°, 60°, respectively. The existence of joints affects stress distribution on rock mass during the loading process. Furthermore, the stress at the joint tip is relatively concentrated, while on both sides of the joint is smaller. Three kinds of crack coalescence patterns are observed: tensile, shear, and tensile-shear mixed coalescence. The inclination angle of the rock bridge between adjacent joints affects the specific type of coalescence. [ABSTRACT FROM AUTHOR]

To study the damage characteristics of rock mass under multi-level creep load, damage variable D was defined based on the spatio-temporal evolution characteristics of deformation modulus E, and the Kachanov damage theory is used to describe the damage evolution, then the damage evolution equation of the rock mass under multi-level creep load is obtained. Combining the damage evolution equation with the Lemaitre strain equivalence principle, the creep damage constitutive model of rock mass under multi-level creep load considering initial damage is obtained. By comparing the results of uniaxial and triaxial tests with the calculated values of the model, the rationality, reliability, application range of the model proposed in this paper is verified. According to the results of parameter inversion, obtain the relationship between damage, stress and time. Results show that time and stress are the important factors influencing the damage of rock mass under multi-level creep loading, the damage increases with time and stress level. However, the influence of time and stress on damage has a significant stress response characteristics: under low stress, the instantaneous damage Dis caused by the instantaneous stress loading is the main reason for the damage. With the increase of the load level, the main cause of the damage gradually changes from the instantaneous loading of the stress to the creep accumulation of the damage, and the greater the initial damage, the higher the time-dependent damage DiT proportion in the global damage. [ABSTRACT FROM AUTHOR]

This paper investigated the relationship between the strength of fractured rock and the crack propagation process. A series of uniaxial compression tests were carried out on the rock-like material specimens with single pre-fabricated flaw. Moreover, DIC (digital image correlation) technology was utilized to monitor and analyze the failure process of specimens. The initiation of each crack was defined as a key event, and the relationship between several key events and the axial load of the specimen during the crack propagation was quantitatively analyzed. The time-sequence analysis of crack propagation was also conducted by selecting benchmark points on the both sides of major cracks. It can be found that only the wing crack propagation occurs and there is no obvious shear crack before the peak strength. When the first secondary crack initiated, the specimen reached its peak strength and the wing crack just reached its critical length. Beyond the peak strength, secondary cracks initiated and coalesced rapidly, which leads to the sudden failure of fractured rock. Therefore, the peak strength of the specimen can be assessed by taking the critical length of the steadily propagating wing crack as the condition which determines whether the specimen reaches the peak strength. Furthermore, the discrete element numerical simulation was also implemented to confirm the experimental results. [ABSTRACT FROM AUTHOR]

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From the perspective of macroscopic scale, the majority of natural rock mass should be categorized as non-penetrating jointed rock mass. The existing researches in the field of scale effect of joint properties were mainly implemented on penetrating joints, which contradicts engineering practice, and is of high possibility to make the strength estimation of large natural jointed rock mass inaccurate, leading to serious loss of life and property. In response to such case, a series of numerical calculations of direct shear test on non-penetrating horizontal rock-like joints with different scales were carried out by PFC in this paper, to investigate the scale effect of shear mechanical properties of non-penetrating horizontal rock-like joints. First, the model microparameters were calibrated by three physical experiments to guarantee the precise reproduction of the mechanical performances of target rock and joint. Next, the particle parameters (average particle size dave and radius ratio μ) of model were changed, the effect of particle size on joint strength was studied by direct shear calculation, and the determining method for the values of dave and μ was suggested. Then, based on two distribution forms of non-penetrating horizontal rock-like joint (type I and type II joints), the numerical shear tests were conducted on jointed rock models with different persistence rations and model scales, and the variations of shear stress displacement curve and strength characteristics were analyzed. The results indicate: The lower the persistence ration λ of the joint, the more obvious the negative scale effect of joint shear strength. Besides, the scale effect of shear strength gradually decreases when λ > 0.5 for type I joints while λ > 0.8 for type II joints and the scale effects of joint strength parameters only emerge in the case of λ < 0.2. [ABSTRACT FROM AUTHOR]