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TGF-β, essential for development and immunity, is expressed as a latent complex (L-TGF-β) non-covalently associated with its prodomain and presented on immune cell surfaces by covalent association with GARP. Binding to integrin αvβ8 activates L-TGF-β1/GARP. The dogma is that mature TGF-β must physically dissociate from L-TGF-β1 for signaling to occur. Our previous studies discovered that αvβ8-mediated TGF-β autocrine signaling can occur without TGF-β1 release from its latent form. Here, we show that mice engineered to express TGF-β1 that cannot release from L-TGF-β1 survive without early lethal tissue inflammation, unlike those with TGF-β1 deficiency. Combining cryogenic electron microscopy with cell-based assays, we reveal a dynamic allosteric mechanism of autocrine TGF-β1 signaling without release where αvβ8 binding redistributes the intrinsic flexibility of L-TGF-β1 to expose TGF-β1 to its receptors. Dynamic allostery explains the TGF-β3 latency/activation mechanism and why TGF-β3 functions distinctly from TGF-β1, suggesting that it broadly applies to other flexible cell surface receptor/ligand systems.

The combined effect of stress and seepage is an important reason of engineering geological problems such as landslides, dam failures, and tunnel collapse. However, due to the limitations of the test apparatus, the existing studies rarely consider the stress effect in the seepage process. In this study, a soil column apparatus based on the wetting front advancing method was developed to explore the permeability properties of intensely weathered sandstone in a wide range of suction (10~106 kPa). The results suggest that the wetting front advancing velocity decreased as the vertical stress increased during infiltration, which indicates that the stress changes the infiltration channel and affects the infiltration rate. On the other hand, due to the water sensitivity of intensely weathered sandstone, the soil column deformation before and after wetting is significantly different, indicating that water infiltration further exacerbates the deformation. When vertical stress is applied to the soil column, the permeability coefficient-suction curves at different sections are paralleled in general, which is affected by the variation in dry density and the non-uniform distribution of stresses inside the soil column. Moreover, as the initial dry density increases, the influence of the vertical stress on the permeability coefficient gradually decreases. Key words: unsaturated soils, stress, permeability, hydro-mechanical coupling, wetting front, Introduction In mountainous areas with complex geological conditions, tunnel construction inevitably passes through extremely soft rocks, which are composed of soil formed by the weathering and decomposition of clastic rocks, [...]

A constitutive model of unsaturated soils is developed by incorporating the concept of intergranular stress into the framework of the modified Cam–Clay model. Within this context, the degree of saturation is viewed as an internal state variable, so that the soil–water retention function appears naturally as an evolution equation for the volume fraction of water. The new model not only has a neat structure but also includes fewer material parameters compared to the other models. A new volumetric-hardening law is proposed by taking into account the effect of wetting-induced pore collapse. It is shown that the collapsing void ratio (the current void ratio minus the void ratio at full saturation under the same effective stress) is dominated by the degree of pore air saturation (one minus the degree of water saturation) and practically independent of intergranular pulling forces, highlighting the important effect of soil fabric on the wetting-induced pore collapse. The proposed model is applied to simulate different types of experiments on unsaturated soils subjected to various combined hydraulic and mechanical loadings, showing its capability and diversity in modeling the hydraulic and mechanical behavior of unsaturated soils. [ABSTRACT FROM AUTHOR]

Pore water chemistry can exert significant controls over the chemo-mechanical behavior of chemically active soils, which has not been characterized by using the traditional Terzaghi's effective stress to a satisfactory extent. In this paper, based on the concept of intergranular stress, a generalized effective stress for saturated active soils is reconceptualized and incorporated into the framework of the modified Cam–Clay (MCC) model to describe the mechanical response of soils upon complex chemical and mechanical loadings. The proposed model is capable of capturing very well the diverse features of the chemo-behavior of saturated active soils, while inheriting all the advantages of the MCC model, by introducing only one additional parameter. Within this context, a simple equation is derived to predict the development of swelling pressure with the variation of pore water chemistry. It is shown that the proposed swelling-pressure equation predicts very well the development of swelling pressure for expansive soils with a dilute pore solution, though discrepancy appears at high concentration. Because the double layer of clay particles is severely suppressed at high salt concentration, the microfabric of soil can be significantly changed, pointing to the importance of taking into account the effect of soil fabric in the constitutive modeling of active soils with high pore water concentration. [ABSTRACT FROM AUTHOR]

There are relatively few experimental studies on the hydromechanical and critical state behaviours of unsaturated silty sand. In this paper, suction-controlled, consolidated, drained triaxial shear tests were conducted on silty sand under saturated (net confining pressures of 100, 200, 300 and 400 kPa) and unsaturated (suctions of 30, 100 and 200 kPa and net confining pressures of 100, 200 and 300 kPa) conditions. For unsaturated silty sand, the effects of dry density, matric suction and net confining pressure on the hydromechanical and critical state behaviour were investigated, and the critical state parameters were obtained. The main findings for unsaturated silty sand included shear shrinkage at low dry density (1·6 g/cm3) and dilatancy at higher density (1·96 g/cm3). The peak shear strength was positively correlated with dry density, matric suction and net confining pressure. The critical state volumetric strain and critical state degree of saturation were negatively correlated with dry density and matric suction but positively correlated with net confining pressure. A new dilatancy equation that includes the state parameter for unsaturated silty sand was established. A unique critical state line passes through the origin in the effective stress p ∗ –deviator q plane, and its slope is the saturated critical state stress ratio M s . In the lnp*–v plane ( v is the specific volume), the critical state lines corresponding to different matric suctions are parallel. [ABSTRACT FROM AUTHOR]

The hydro-mechanical behaviour of unsaturated soils is often highly influenced by the microstructure; therefore, it can be beneficial to consider the effect of microstructure in a hydro-mechanical constitutive model. This paper considers the use of a microstructure-related model that adopts the effective degree of saturation as a microstructural index. The model can be used to reproduce the hydro-mechanical behaviour while the effect of the microstructure is considered. For comparison, a non-microstructuredependent model is also employed. The models are applied to simulate the behaviour of two different soilsand a comparison of the models’ performance in simulating triaxial test behaviour is made. Based on the comparison with experimental results and the non-microstructure-dependent model, it can be concluded thatthe adoption of the effective degree of saturation is beneficial to studying the hydro-mechanical behaviour of unsaturated soils affected by the microstructure.