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Centrifuge model tests on slopes subject to shaking and rainfall have been performed to examine the response of slopes with shaking-induced cracks to subsequent rainfall and evaluate the corresponding landslide-triggering mechanisms. The failure pattern of the slope subject to shaking and then rainfall was found different from that of the slope subject to only rainfall. When shaking caused cracks on the slope shoulder and rupture line below, the mobilized soil slid along the slip surface that extended to the rupture line, the main crack became the crown of the undisturbed ground once the slope was subject to a subsequent rain event, and the progression of the landslide was related to the rainfall intensity. During the landslide caused by light rainfall, the main scarp kept exposing itself in the vertically downward direction while the ground behind the main crack in the crack-containing slope remained undisturbed. The detrimental effect of cracks on soil displacement was more evident when the slope was exposed to heavy post-shaking rainfall, resulting in a rapid and massive landslide. Additionally, the volume of displaced material of the landslide, the main scarp area on the upper edge, and the zone of accumulation were larger in the crack-containing slope subject to heavy rainfall, in comparison with those in the crack-free slope. The deformation pattern of slopes with shaking-induced cracks during rainfall was closely related to rainfall intensity and the factor of safety provided a preliminary estimation of slope stability during rainfall. Moreover, even when subjected to the same rainfall, the slopes with antecedent shaking-induced cracks displayed different levels of deformation. The slope that experienced larger shaking had greater deformation under the following rainfall, and the shaking-induced slope deformation also controlled the slip surface location. Finally, the velocity of rainfall-induced landslide could be greatly influenced by the prior shaking event alone. Despite being under light rainfall, the slope that has encountered intense previous shaking exhibited an instant landslide.

Aim In acute medicine, we occasionally treat life‐threatening conditions such as sepsis and trauma, which cause severe thrombocytopenia. Serum thrombopoietin levels have been reported to increase under the condition of thrombocytopenia related to severity. Collagen is a crucial activator of platelets, and Rho family members, such as Rho/Rho‐kinase and Rac, play roles as active molecules involved in the intracellular signaling pathways in platelet activation. The present study aimed to elucidate the effects of thrombopoietin (TPO) on subthreshold low‐dose collagen‐stimulated human platelets in terms of Rho/Rho‐kinase and Rac. Methods Platelet‐rich plasma donated from healthy volunteers was stimulated by the subthreshold low‐dose of collagen after pretreatment with TPO and/or NSC23766, an inhibitor of the Rac‐guanine nucleotide exchange factor interaction, or Y27632, an inhibitor of Rho‐kinase. Platelet aggregation was measured using an aggregometer based on laser‐scattering methods. Proteins involved in intracellular signaling were analyzed using western blotting, and the secretion of platelet‐derived growth factor‐AB from activated platelets was determined using an enzyme‐linked immunosorbent assay. Results Under the existence of TPO, the low dose of collagen remarkably elicited the aggregation and platelet‐derived growth factor‐AB secretion of platelets, which were suppressed by NSC23766 and Y27632. The combination of TPO and collagen considerably induced a transient increase of guanosine triphosphate (GTP)‐binding Rac and GTP‐binding Rho followed by an increase of phosphorylated cofilin, a Rho‐kinase substrate. Conclusion These results strongly suggest that TPO and collagen in low doses cooperatively potentiate human platelet activation through both Rac and Rho/Rho‐kinase mediated pathways. Thrombopoietin and collagen in low doses cooperatively potentiate human platelet activation via both Rac and Rho/Rho‐kinase mediated pathways. The effect of TPO on platelet activation under the stimulation of collagen, even though of which the levels are insufficient to trigger by itself, might indicate a compensatory mechanism to enhance platelet activation in thrombocytopenia.

This paper investigates the liquefaction hazard in the Port Area of Pulau Baai, Bengkulu City, during the large subduction earthquake of 2007. The study was conducted systematically, commencing with a site investigation that included shear wave velocity measurements. Spectral matching and ground motion predictions, based on a relevant attenuation model, were performed to derive representative ground motions for the study sites. Ground response analysis was carried out to examine soil behaviour under seismic loading. Non-linear finite element analysis was utilised to assess dynamic soil characteristics such as excess pore water pressure, shear stress-strain response and stress paths. Additionally, an empirical evaluation was conducted to assess the liquefaction potential. The results indicate that liquefaction at shallow depths could occur, particularly in the first two sand layers. They also suggest that potential seismic damage could range from VII to IX on the Modified Mercalli Intensity (MMI) scale. Both numerical and empirical analyses demonstrated consistent trends and alignment. The comparison of excess pore pressure ratios and safety factors aligns with findings from previous studies. These results underscore the importance of implementing seismic hazard mitigation measures for the study area.

Visual illusions are utilized to elucidate mechanism of visual information processing. For example, the Rotating Snakes illusion creates the illusory perception of motion when viewing a static image. This study investigated the difference in perception of illusory rotation between younger and older adults with normal visual acuity. The participants included 105 younger adults (mean age: 23.7 years) and 100 older adults (mean age: 74.2 years). Each participant was presented with the Rotating Snakes illusion, then asked to respond whether they perceived the snakes to be \"rotating\" or \"not rotating\". The rate of perception of illusory rotation was compared between the two groups. To evaluate the effects of cataracts, a major age-related optical change, comparisons were also made between older participants with bilateral cataracts versus those with bilateral intraocular lens (IOL) implantation. Rotation was perceived by 100% (105/105) of participants in the younger group, but only by 16% (16/100) of participants in the older group, showing a significant difference (p < 0.001). Among the older adults, the IOL and cataract groups had no significant difference in the rate of those who perceived the illusion (6/54 vs 10/45, p = 0.12). Significantly more younger adults perceived illusory motion in the Rotating Snakes illusion versus older adults. Lens opacity due to aging likely does not contribute to this phenomenon.

Soil strain is the key parameter to control the elasto-plastic deformation and even the failure processes. To overcome the defect that the strain of the model soil is always smaller than that of the prototype in Iai’s generalized scaling law (GSL), a modified scaling law was proposed based on Iai’s GSL to secure the same dynamic shear strain between the centrifuge model and the prototype by modulating the amplitude and frequency of the input motion at the base. A suite of dynamic centrifuge model tests of dry sand level ground was conducted with the same overall scaling factor ( λ =200) under different centrifugal accelerations by using the technique of “modeling of models” to validate the modified GSL. The test results show that the modified GSL could achieve the same dynamic strain in model as that of the prototype, leading to better modeling for geotechnical problems where dynamic strain dominates the response or failure of soils. Finally, the applicability of the proposed scaling law and possible constraints on geometry scaling due to the capability limits of existing centrifuge shaking tables are discussed.

Tramadol is a useful analgesic which acts as a serotonin and noradrenaline reuptake inhibitor in addition to μ-opioid receptor agonist. Cytoplasmic serotonin modulates the small GTPase activity through serotonylation, which is closely related to the human platelet activation. We recently reported that the combination of subthreshold collagen and CXCL12 synergistically activates human platelets. We herein investigated the effect and the mechanism of tramadol on the synergistic effect. Tramadol attenuated the synergistically stimulated platelet aggregation (300 μM of tramadol, 64.3% decrease, p<0.05). Not morphine or reboxetine, but duloxetine, fluvoxamine and sertraline attenuated the synergistic effect of the combination on the platelet aggregation (30 μM of fluvoxamine, 67.3% decrease, p<0.05; 30 μM of sertraline, 67.8% decrease, p<0.05). The geranylgeranyltransferase inhibitor GGTI-286 attenuated the aggregation of synergistically stimulated platelet (50 μM of GGTI-286, 80.8% decrease, p<0.05), in which GTP-binding Rac was increased. The Rac1-GEF interaction inhibitor NSC23766 suppressed the platelet activation and the phosphorylation of p38 MAPK and HSP27 induced by the combination of collagen and CXCL12. Tramadol and fluvoxamine almost completely attenuated the levels of GTP-binding Rac and the phosphorylation of both p38 MAPK and HSP27 stimulated by the combination. Suppression of the platelet aggregation after the duloxetine administration was observed in 2 of 5 patients in pain clinic. These results suggest that tramadol negatively regulates the combination of subthreshold collagen and CXCL12-induced platelet activation via Rac upstream of p38 MAPK.

CXCL12, belonging to the CXC chemokine family, is a weak agonist of platelet aggregation. We previously reported that the combination of CXCL12 and collagen at low doses synergistically activates platelets via not CXCR7 but CXCR4, a specific receptor for CXCL12 on the plasma membrane. Recently, we reported that not Rho/Rho kinase, but Rac is involved in the platelet aggregation induced by this combination. Ristocetin is an activator of the von Willebrand factor that interacts with glycoprotein (GP) Ib/IX/V, which generates thromboxane A2 via phospholipase A2 activation, resulting in the release of the soluble CD40 ligand (sCD40L) from human platelets. In the present study, we investigated the effects of a combination of ristocetin and CXCL12 at low doses on human platelet activation and its underlying mechanisms. Simultaneous stimulation with ristocetin and CXCL12 at subthreshold doses synergistically induce platelet aggregation. A monoclonal antibody against not CXCR7 but CXCR4 suppressed platelet aggregation induced by the combination of ristocetin and CXCL12 at low doses. This combination induces a transient increase in the levels of both GTP-binding Rho and Rac, followed by an increase in phosphorylated cofilin. The ristocetin and CXCL12-induced platelet aggregation as well as the sCD40L release were remarkably enhanced by Y27362, an inhibitor of Rho-kinase, but reduced by NSC23766, an inhibitor of the Rac-guanine nucleotide exchange factor interaction. These results strongly suggest that the combination of ristocetin and CXCL12 at low doses synergistically induces human platelet activation via Rac and that this activation is negatively regulated by the simultaneous activation of Rho/Rho-kinase.

Bone remodeling is tightly controlled by various factors, including hormones, autacoids and cytokines. Among them, oncostatin M (OSM) is a multifunctional cytokine produced by osteal macrophages, which serves as an essential modulator of bone remodeling. Macrophage colony-stimulating factor (M-CSF) and osteoprotegerin are secreted by osteoblasts, and also have pivotal roles in the regulation of the bone remodeling process. The binding of basic fibroblast growth factor (bFGF), a key regulator of bone remodeling, to the corresponding receptor [fibroblast growth factor receptor (FGFR)] triggers the dimerization and activation of FGFRs, which causes the phosphorylation of FGFR substrates and subsequent activation of downstream effectors, including mitogen-activated protein kinases (MAPKs), via Grb2. bFGF can activate MAPKs, resulting in the synthesis of osteoprotegerin and vascular endothelial growth factor in osteoblast-like MC3T3-E1 cells. In the present study, the effects of OSM on bFGF-induced osteoblast activation were investigated in the synthesis of osteoprotegerin and M-CSF in osteoblasts. The release of osteoprotegerin and M-CSF were analyzed using ELISA. The mRNA expression levels of osteoprotegerin and M-CSF were analyzed using reverse transcription-quantitative PCR. Phosphorylation of p38 MAPK, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p44/p42 MAPK was assessed using western blotting. OSM enhanced bFGF-induced osteoprotegerin release and bFGF-stimulated mRNA expression of osteoprotegerin. By contrast, OSM suppressed the bFGF-induced release of M-CSF and bFGF-stimulated mRNA expression of M-CSF. SB203580, a p38 MAPK inhibitor, and SP600125, a SAPK/JNK inhibitor, suppressed the bFGF-stimulated M-CSF release, whereas PD98059, an upstream kinase inhibitor of p44/p42 MAPK, failed to suppress the M-CSF release stimulated by bFGF. Furthermore, OSM enhanced the bFGF-induced phosphorylation of p38 MAPK, but attenuated the bFGF-stimulated phosphorylation of SAPK/JNK. By contrast, OSM had little effect on the bFGF-induced phosphorylation of p44/p42 MAPK. SB203580 markedly reduced the amplification of bFGF-stimulated osteoprotegerin release enhanced by OSM. These results strongly suggested that OSM may possess divergent effects on bFGF-induced osteoblast activation, upregulation of p38 MAPK and downregulation of SAPK/JNK, leading to the amplification of osteoprotegerin synthesis and the attenuation of M-CSF synthesis.

The stability of unsaturated soil slopes is comprehensively discussed with the rainfall characteristics. However, pre-existing groundwater table is also common in many tropical mountainous regions. Additionally, perched water table could be generated due to antecedent rainfall conditions on the soil-bedrock interface. The complex hydrological response process of slopes subjected to the integrated effect of groundwater and rainfall infiltration has not yet been entirely realized. Therefore, the current studyaimed at investigating the influence of initial groundwater table on initiation of landslides in slopes exposed to rainfall infiltration. The centrifuge modelling technique is utilized in this study. A centrifuge container was newly designed to reproduce the rainfall and groundwater table effects. Identical soil slopes made from silty sand were tested under 50g conditions. The unsaturated slopes behaviour was evaluated under two cases during the analysis: 01) rainfall only and 02) rainfall on a pre-existing groundwater table. The results demonstrated that the failure happened in case (02) was quicker, larger in volume and faster to respond to rainfall infiltration. The factor of safety calculated using the infinite slope equations portrayed a slight mismatch of failure timing compared to the experimental results. These results suggested i) a higher risk ofslope failure under pre-existing groundwater flow and ii) acceleration of the progression of landside due to a potential surcharge flow.

Subjective color (SC) refers to chromatic perception induced by achromatic stimuli, as classically demonstrated using Benham's top. Despite nearly two centuries of investigation, the underlying neural mechanisms remain unclear. We developed artificial neural network models trained on natural videos using predictive learning to investigate SC generation. These models successfully reproduced artificial subjective color (ASC) from achromatic testing stimuli that contained no explicit chromatic information. Critically, ASC characteristics were systematically influenced by the colors of moving objects in the training videos. Using progressively simplified stimuli, ranging from natural scenes to 3D computer graphics and 2D animations, we demonstrated that the colors of moving objects primarily determine ASC properties. We propose that predictive learning establishes color associations with motion patterns, causing the arcs on Benham's top to be perceived as moving objects with corresponding colors. These findings suggest that cortical predictive mechanisms may complement retinal processes in generating subjective color phenomena.