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Although cone penetration test (CPT) is an in-situ test method to obtain conventional geotechnical properties accurately, CPT data cannot be directly linked to macro constitutive model parameters. The principal reason is that the comprehensive studies on the macro-micro penetration mechanism. Based on the cylindrical (cone) cavity expansion theory, a macro and micro coupling simulation method for the CPT process is established. Firstly, based on the cavity expansion theory, the relationships among the cone resistance, sleeve friction and the cavity limit pressure are derived. Secondly, the numerical triaxial compression tests with the same dimensions on the Shanghai ②1 silty clay in the shallow bearing layer are performed by both the maco and the micro simulation methods. The conversion formulas that relate the macro perfectly elastoplastic model (i.e., Mohr-Coulomb model) parameters to the micro linear parallel-bond model parameters have been proposed and implemented in the commonly used commercial software FLAC3D. The macro-micro conversion formulas are validated by the CPT data on Shanghai ②1 silty clay and = 5 \* GB3 ⑤1-1 gray clay. Finally, the discrepancies between the theoretical solution, numerical modelling results and the CPT measurements of cone resistance, sleeve friction and cavity limit pressure on the Shanghai ②1 silty clay are analyzed from a macro perspective. The distribution of soil displacement and the contact force chain are presented and discussed from the micro perspective. The discrepancies between the theoretical solutions and the CPT measurements of the cavity limit pressure, cone resistance and sleeve friction are 1.30%, 0.45% and 0.77%, respectively. The discrepancies between the macro and micro coupling simulation results and the CPT measurements of the cavity limit pressure, cone resistance, sleeve friction and pore pressure are 9.68%, 2.99%, 9.19% and 8.42%, respectively. It indicates that the macro and micro coupling numerical modelling results are not only in agreement with the cavity expansion theory-based theoretical solutions and the CPT measurements, but also the effect of pore pressure can be simulated. The proposed macro and micro coupling simulation provides insight into the CPT mechanism and the approach to estimating the macro-micro parameters of the specific constitutive models.

Background: The aerial parts of Peganum harmala L. (APP) is a well-known and effective herbal medicine in China, and has been commonly used for treating various ailments, including cough and asthma. Objectives: To evaluate the antitussive, expectorant, and bronchodilating effects of the quinazoline alkaloids ([+ or -])-vasicine(VAS), deoxyvasicine (DVAS) (both isolated from the alkaloid fraction of APP) and (±)- vasicinone (VAO) (synthesized from VAS). Methods: The three quinazoline alkaloids were tested as antitussive on cough models in mice and guinea pigs. VAO was synthesized from VAS via the oxidation of hydrogen peroxide. VAS, VAO, and DVAS were orally administered at dosages of 5,15, and 45 mg/kg. Cough in these models was induced by ammonia, capsaicin, and citric acid. Phenol red secretion experiments in mice were performed to evaluate the expectorant activity of the alkaloids. Bronchodilating effects were evaluated by using a bronchoconstrictive induced by acetylcholine chloride and histamine in guinea pigs. Results: In antitussive tests, VAS, VAO, and DVAS significantly inhibited coughing frequency and prolonged the cough latency period in animals. At the highest doses tested (45 mg/kg), they showed antitussive activities similar to codeine phosphate (30 mg/kg) in mice and guinea pigs. Expectorant evaluation showed that VAS, VAO, and DVAS could significantly increase phenol red secretion in mice by 0.54-, 0.79- and 0.97-fold, by 0.60-, 0.99-, and 1.06-fold, and by 0.46-, 0.73-, and 0.96-fold, respectively, at dosages of 5,15, and 45 mg/kg compared with the control (0.5% CMC-Na, 20 ml/kg). Ammonium chloride at 1500 mg/kg increased phenol red secretion in mice by 0.97-fold compared with the control. Bronchodilation tests showed that VAS, VAO, and DVAS prolonged the pre-convulsive time for 28.59%, 57.21%, and 29.66%, respectively, at a dose of 45 mg/kg in guinea pigs, whereas aminophylline prolonged the pre-convulsive time by 46.98% compared with pretreatment. Conclusions: Quinazoline alkaloids VAS, VAO, and DVAS have significant antitussive, expectorant, and bronchodilating activities. VAS, VAO, and DVAS are the active ingredients in APP, which can be used to treat respiratory disease. Keywords: Peganum harmala L Antitussive Expectorant Bronchodilating Quinazoline, Introduction Cough is among the common symptoms associated with many respiratory diseases, such as asthma, chronic bronchitis, and pneumonia (Ce et al., 2009; Irwing and Madison, 2000). These respiratory diseases [...]