Retrieving 2-D laterally varying structures from multistation surface wave dispersion curves using multiscale window analysis

The analysis of multistation surface wave records is of increasing popularity in imaging the structure of the Earth due to its robustness on dispersion measurement. Since the representation of multistation surface wave dispersion curves (DCs) is uncertain in laterally varying media, average information beneath the receiver array is assumed to be obtained by inverting the dispersion curves with a horizontally layered model. To retrieve a more realistic 2-D laterally varying structure, we present a multiscale window analysis of surface waves (MWASW) method for analysing 2-D active-source surface wave data. The MWASW method is based on the use of a forward algorithm for calculating the theoretical DCs over 2-D models and multisize spatial windows for estimating the dispersion data. The forward algorithm calculates the theoretical dispersion considering the lateral variation beneath the receiver array; hence, the estimated DC is not treated as representative of the average properties but as data containing the lateral variation information. By inverting the dispersion data extracted from different spatial windows, the subsurface information at different depth ranges and lateral extensions are integrated to produce a shear wave velocity model. The dispersion curves analysed from smaller spatial windows retrieve the shallow structure with a higher lateral resolution, whereas the phase velocity data from larger spatial windows provide average information with a greater depth. We test the effectiveness of the MWASW method using three synthetic examples and two field data sets. Both results show the improved lateral resolution of the S-wave velocity structure retrieved with the MWASW method compared to the traditional multistation method in which the local horizontally layered model is adopted

The Role of Breast Cancer Resistance Protein (BCRP) in Disposition of Glucuronide Conjugates

[Purpose] The overall objective is to explore and predict the impact of BCRP on disposition of glucuronides and to change the disposition of glucuronides by manipulating transporters. To approach this goal, three specific aims are: 1) To determine clearance by UGTs and clearance by BCRP for a series of compounds and their glucuronide metabolites; 2) To investigate the role of BCRP in disposition of glucuronide conjugates in vivo; 3) To increase the systemic exposure of glucuronides (and therefore the aglycones) by manipulating efflux transporters. [Methods] Human UGT1A9-overexpressing HeLa cells and MRP2-overexpressing MDCKII-UGT1A1 cells were used as in vitro cellular models to study the excretion of glucuronides by BCRP and MRP2, respectively. Pooled intestinal and hepatic S9 fractions were used to determine the intrinsic glucuronidation clearance. For in vivo studies, pharmacokinetic experiments were performed in wild-type (WT) and Bcrp1 (-/-) mice. A physiologically-based pharmacokinetic (i.e., PBPK) model containing seven organ compartments connected by arterial and venous blood supplies was constructed to predict pharmacokinetic profiles of parent compounds and their glucuronide metabolites. [Results] 1) The clearance by UGTs and the efflux clearance by BCRP were determined for eight compounds (daidzein, chrysin, maackiain, 3,6-DHF, resveratrol, genistein, sorafenib, and MPA) or their glucuronides. More than 4 orders of magnitude difference in glucuronidation clearance existed among these eight compounds. The rank orders of clearance values were almost the same in liver and in intestinal microsomes. Chrysin and maackiain had the highest glucuronidation clearances in mouse S9 fractions. Daidzein glucuronide had the highest clearance by BCRP in human UGT1A9-overexpressing HeLa cells, which was more than 30-fold higher than that of sorafenib glucuronide and maackiain glucuronide. A novel transport-glucuronidation classification system was proposed based on in vitro data. 2a) By using a newly developed and validated LC-MS/MS method, it was found that there was no significant change in systemic exposure of chrysin and its glucuronide, although the Tmax for chrysin glucuronide was significantly shorter (p<0.01) in Bcrp1 deficient mice. 2b) A PBPK model was developed to predict the impact of BCRP on glucuronide disposition for different compounds. For compounds with greater clearance by UGTs and the resulting glucuronides effluxed rapidly and predominantly by BCRP, significant increase in glucuronide AUC in Bcrp deficient mice was predicted and observed (daidzein and genistein). 3) An elevated systemic (i.e., blood) exposure of resveratrol glucuronides was achieved in wild-type and Bcrp1 knockout mice when animals were treated with curcumin, which was an inhibitor of efflux transporters. Curcumin achieved above-stated effects by inhibiting efflux transporters including MRP2 and BCRP, thereby promoting the distribution of resveratrol glucuronides into the systemic circulation (i.e., increased AUC and Cmax). [Conclusion] BCRP plays important role in disposition of glucuronide conjugates. In previous and current study, we observed that the extent of impact from BCRP varied among different compounds. By applying the newly developed transport-glucuronidation classification system and PBPK model, we for the first time demonstrated that the impact of BCRP on disposition of glucuronide can be predicted by knowing if a compound is subjected to fast or slow glucuronidation, with the resulting glucuronides subjected to rapid or slow efflux by BCRP. In addition, we showed that using curcumin as an inhibitor of efflux transporters could result in increased systemic exposure of resveratrol and its glucuronides in vivo, which could be expanded to other co-administered drugs using the similar disposition mechanisms.Pharmacological and Pharmaceutical Sciences, Department o

Retrieving 2-D laterally varying structures from multistation surface wave dispersion curves using multiscale window analysis

SUMMARY The analysis of multistation surface wave records is of increasing popularity in imaging the structure of the Earth due to its robustness on dispersion measurement. Since the representation of multistation surface wave dispersion curves (DCs) is uncertain in laterally varying media, average information beneath the receiver array is assumed to be obtained by inverting the dispersion curves with a horizontally layered model. To retrieve a more realistic 2-D laterally varying structure, we present a multiscale window analysis of surface waves (MWASW) method for analysing 2-D active-source surface wave data. The MWASW method is based on the use of a forward algorithm for calculating the theoretical DCs over 2-D models and multisize spatial windows for estimating the dispersion data. The forward algorithm calculates the theoretical dispersion considering the lateral variation beneath the receiver array; hence, the estimated DC is not treated as representative of the average properties but as data containing the lateral variation information. By inverting the dispersion data extracted from different spatial windows, the subsurface information at different depth ranges and lateral extensions are integrated to produce a shear wave velocity model. The dispersion curves analysed from smaller spatial windows retrieve the shallow structure with a higher lateral resolution, whereas the phase velocity data from larger spatial windows provide average information with a greater depth. We test the effectiveness of the MWASW method using three synthetic examples and two field data sets. Both results show the improved lateral resolution of the S-wave velocity structure retrieved with the MWASW method compared to the traditional multistation method in which the local horizontally layered model is adopted.</jats:p

Factors influencing microtremor data collected using nested-triangular array configurations

AbstractThe availability of microtremor data is potentially affected by various external factors. By combining field data and artificial interference, this work aims to determine the correlation between these factors and the dispersion curve of fundamental-mode Rayleigh waves extracted from microtremors. The first step was to obtain real, high-quality microtremor records using a triangular ten-station array of 48-m radius. Secondly, a series of artificial or semi-artificial interferences of varying type, duration, amplitude, etc., were generated and combined with the real records to imitate actual interferences. Thirdly, all the dispersion curves of the fundamental-mode Rayleigh waves of these modified microtremor records were estimated using the extended spatial autocorrelation method (ESAC). Finally, by comparing the experimental dispersion curves with the original curve, in terms of overlap ratio, we obtained useful conclusions that can be directly applied to microtremor data collection and analysis.</jats:p

Simultaneous Inversion of Multiwindow Surface Wave Dispersion Data in 2D Layered Media

Abstract Seismic Surface Wave Methods (SWMs) have been one of the effective tools for retrieving near-surface shear-wave velocity (Vs). However, a critical problem associated with the SWMs is that using a horizontally layered model assumption in inversion may introduce blurred errors into 2D Vs imaging due to the presence of lateral variations. In addition, the increase of investigation depth necessary for the SWMs may cause an increase in errors since a wider acquisition array is essential to acquire longer wavelength data precisely. In this study, we analyzed the relationship between the output power, calculated by an amplitude normalized frequency-domain beamforming and the local phase velocity following the ray-theory approximation. Based on this relationship, we calculated the theoretical dispersion curves of multichannel surface wave data using a local maximum search algorithm. Then, we presented an algorithm for simultaneously inverting surface wave dispersion data extracted from multi-size spatial windows. We parametrized the inverted model in a 2D layered pattern. Finally, we used synthetic and field data sets to test the effectivity of the proposed method. Both results showed that the lateral resolution of the Vs model retrieved by the simultaneous inversion is improved compared to the horizontally layered model-based inversion.</jats:p