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As the surge in demand for the motor travel continues, the lane capacity is becoming increasingly ineffective in matching the operation of the traffic flow. A method that can utilize the reserved lane capacity and thereby effectively increase the lane capacity is urgently needed for this problem. It is considered in this paper that the formation of a mixed traffic flow which includes both the human-driven vehicles (HDVs) and the connected autonomous vehicles (CAVs) is one such method. Relying on the exploration of the following rules between the HDVs and the CAVs, a heterogeneous vehicle following model (HVFM) can be established as a guide for the formation of the mixed traffic flow. Under the guidance of the HVFM, the effects of different following mode types on the formation characteristics of the mixed traffic flow can be defined, determined and evaluated. At the same time, with the applicability of the three-phase traffic theory in mind, a three-phase traffic flow model under the mixed traffic flow condition (M-TTFM) is established for providing guidance on the operating mechanism of the mixed traffic flow, the determining method of the lane capacity and the utilizing method of the reserved lane capacity at the micro-theoretical level. The maximum lane capacity under the mixed traffic flow conditions can be up to 205.94 % of the lane capacity under HDV traffic flow conditions with the formation of the mixed traffic flow, which indicates that the reserved lane capacity can be greatly utilized by forming the mixed traffic flow. In particular, by mixing the CAV fleets platooned by the CAVs into the HDV traffic flow, the utilizing effect for the reserved lane capacity can be improved with a maximum level of 194.25 %, which is called the in-depth utilization of the reserved lane capacity. What is more, the fundamental diagrams expressing the relationship between the traffic flow rate and the density under the mixed traffic flow condition can be obtained and the recommended value of the lane capacity under the mixed traffic flow can be measured. In summary, the utilizing method for the reserved lane capacity in this paper is expected to further enhance the lane capacity and contribute to solving the problems caused by the lack of the lane capacity. [ABSTRACT FROM AUTHOR]

In this paper, the concept of reserve capacity has been extended to zone level to measure the land-use development potentiality of each trip generation zone. Bi-level programing models are proposed to determine the signal setting of individual intersections for maximizing possible increase in total travel demand and the corresponding reserve capacity for each zone. The change of the origin–destination pattern with the variation of upper level decision variables is presented through the combined distribution/assignment model under user equilibrium conditions. Both singly constrained and doubly constrained combined models are considered for different trip purposes and data information. Furthermore, we have introduced the continuous network design problem by increasing road capacity and examined its effect on the land-use development potentiality of trip generation zone. A numerical example is presented to illustrate the application of the models and how a genetic algorithm is applied to solve the problem. [ABSTRACT FROM AUTHOR]

Cyclosporine A and sirolimus are immunosuppressants that are widely used in many organ transplantation procedures. They exhibit some complementary mechanisms of action and interact synergistically when used together. However， they are critical-dose drugs and have a narrow therapeutic index. They provide the desired therapeutic effect with acceptable tolerability only within a specific range of blood concentrations. Therefore， the rapid and simultaneous detection of the concentrations of cyclosporine A and sirolimus in whole blood could provide valuable information on planning medicine administration after organ transplantations. In this study， firstly， the chromatographic behaviors of cyclosporine A and sirolimus on a biological liquid chromatography （BioLC） column and traditional liquid chromatography （TraLC） columns were investigated systematically under the same chromatographic conditions. The results suggested that the peak height and peak width of cyclosporine A and sirolimus on the BioLC column， ZORBAX 300SB C8 （250 mm×4.6 mm， 5.0 μm）， were the highest and narrowest， respectively. The number of theoretical plates of cyclosporine A and sirolimus on the ZORBAX 300SB C8 column increased significantly when the volume ratio of acetonitrile in the mobile phases was greater than 70%. Their retention time on the BioLC and TraLC columns was negligibly affected by the use of formic acid and trifluoroacetic acid as the mobile phases. In the range of the experimental column temperature， the number of theoretical plates of cyclosporine A and sirolimus on the ZORBAX 300SB C8 column was significantly higher than that on the two TraLC columns. Furthermore， the relationship between the retention factor and column temperature of cyclosporine A on the ZORBAX 300SB C8 column was different from that on the two TraLC columns. Subsequently， a high performance liquid chromatography method based on the ZORBAX 300SB C8 column was established for the rapid separation and determination of cyclosporin A and sirolimus in whole blood. A sample of whole blood with a volume of 50 μL was prepared by protein precipitation with 1 mol/L sodium hydroxide and then extracted into 500 μL of ether-methanol （95∶5， v/v）. After centrifugation at 14000 r/min for 10 min， the organic layer was removed and evaporated under a stream of nitrogen at 50 ℃. The residue was then reconstituted in 200 μL of methanol for use. Cyclosporin A and sirolimus were separated through isocratic elution on the ZORBAX 300SB C8 column. The column temperature was set at 60 ℃. The mobile phase was acetonitrile-water （70∶30， v/v） and the flow rate was 1.0 mL/min. The detection wavelengths were 205 nm for cyclosporine A and 278 nm for sirolimus. The injection volume was 20 μL. The external standard method was used to quantify cyclosporine A and sirolimus. Under the optimized conditions， cyclosporine A and sirolimus were well-separated within 6 min with a resolution of 3.7 at 205 nm. In addition， the endogenous substances in whole blood negligibly interfered in the detection of sirolimus， while two endogenous substances slightly affected the detection of cyclosporine A. Cyclosporine A and sirolimus both showed good linear relationships in their respective concentration （ r >0.997）. The limits of detection （LODs） of cyclosporine A and sirolimus were respectively calculated to be 10 ng/mL and 1 ng/mL based on a signal-to-noise ratio of 3， and the limits of quantification （LOQs） were 30 ng/mL and 2 ng/mL based on a signal-to-noise ratio of 10. In the whole blood samples， the recoveries of cyclosporine A and sirolimus at three spiked levels were in the ranges of 83.5%-89.7% and 95.8%-97.8% with relative standard deviations （RSDs） of 3.2%-9.0% and 3.4%-6.7% （ n =5）， respectively. The established method is simple in operation， can be performed with a simple mobile phase， has a short analysis time， and provides a wide linear range and high sensitivity； hence， it can be applied to the determination of cyclosporine A and sirolimus in whole blood.

The drug budesonide exists as 22R and 22S enantiomers. However, the drug activity of 22R-budesonide is 2-3 times stronger than that of 22S-budesonide. The development of enantiomeric separation and quantitative analysis methods for budesonide can provide an important basis for its drug development and quality control. At present, the enantiomers of budesonide are separated on a reversed C 18 solid phase column. However, chiral stationary phases are rarely reported for the separation of the enantiomers of budesonide. In this study, a high performance liquid chromatography (HPLC) method with a chiral stationary phase was developed for the rapid separation and determination of budesonide enantiomers. The effects of the type of chiral stationary phase, mobile phase additives, and column temperature on the resolution of the budesonide enantiomers were also investigated. The results showed that the chiral stationary phase amylose-tris-[(S)-1-phenylethyl carbamate] was more suitable for the separation of budesonide enantiomers. The mobile phase additives used in the experiment had no significant effect on the chromatographic parameters (peak height, peak width, and resolution) of the budesonide enantiomers. However, with an increase in the column temperature, the peak width of the budesonide enantiomers decreased, while the peak height and resolution increased. The optimized HPLC conditions were as follows: column, Chiralpak AS-RH (150 mm×4.6 mm, 5.0 μm); mobile phase, acetonitrile-water (45∶55, v/v); column temperature, 40 ℃; flow rate, 1.0 mL/min; detector, diode array detector (DAD); detection wavelength, 246 nm; injection volume, 10 μL. The external standard method was used to quantify the budesonide enantiomers. Under the optimized conditions, the enantiomers were well separated, and the retention times of 22R-budesonide and 22S-budesonide were 6.40 min and 7.77 min, respectively. The resolution of the enantiomers was 4.64. The linear ranges of 22R-budesonide and 22S-budesonide were 0.16-1000 μg/mL and 0.20-1000 μg/mL, respectively. The peak area of the enantiomers showed a good linear relationship with the corresponding concentration, and the correlation coefficients (R 2 ) were 0.9999. The limits of detection (LODs) of 22R-budesonide and 22S-budesonide were 0.05 μg/mL and 0.07 μg/mL, respectively, based on a signal-to-noise ratio of 3. The limits of quantification (LOQs) were calculated to be 0.16 μg/mL and 0.20 μg/mL, respectively, based on a signal-to-noise ratio of 10. The recoveries at four spiked levels were in the range of 102.63% to 104.17%, with the relative standard deviations (RSDs) of 0.08% to 0.57% (n=6). The budesonide solution was stored in dark at 4 ℃ for 24 h, and no obvious degradation was observed. Finally, the method was applied to determine four actual samples of budesonide suspension for inhalation in a batch. The samples were dissolved in methanol, filtered through a 0.45 μm microporous membrane, and then analyzed. The amounts of 22R-budesonide and 22S-budesonide in the samples were in the ranges of 283.15-284.63 μg/mL and 259.86-261.51 μg/mL, respectively. This method is simple and rapid, in addition to having good repeatability and high accuracy. It can be used for the resolution of budesonide enantiomers and for quality control in budesonide preparations.