Streamlining Computational Fragment-Based Drug Discovery through Evolutionary Optimization Informed by Ligand-Based Virtual Prescreening.

Recent advances in computational methods provide the promise of dramatically accelerating drug discovery. While mathematical modeling and machine learning have become vital in predicting drug-target interactions and properties, there is untapped potential in computational drug discovery due to the vast and complex chemical space. This paper builds on our recently published computational fragment-based drug discovery (FBDD) method called fragment databases from screened ligand drug discovery (FDSL-DD). FDSL-DD uses in silico screening to identify ligands from a vast library, fragmenting them while attaching specific attributes based on predicted binding affinity and interaction with the target subdomain. In this paper, we further propose a two-stage optimization method that utilizes the information from prescreening to optimize computational ligand synthesis. We hypothesize that using prescreening information for optimization shrinks the search space and focuses on promising regions, thereby improving the optimization for candidate ligands. The first optimization stage assembles these fragments into larger compounds using genetic algorithms, followed by a second stage of iterative refinement to produce compounds with enhanced bioactivity. To demonstrate broad applicability, the methodology is demonstrated on three diverse protein targets found in human solid cancers, bacterial antimicrobial resistance, and the SARS-CoV-2 virus. Combined, the proposed FDSL-DD and a two-stage optimization approach yield high-affinity ligand candidates more efficiently than other state-of-the-art computational FBDD methods. We further show that a multiobjective optimization method accounting for drug-likeness can still produce potential candidate ligands with a high binding affinity. Overall, the results demonstrate that integrating detailed chemical information with a constrained search framework can markedly optimize the initial drug discovery process, offering a more precise and efficient route to developing new therapeutics.

Parity changed fecal microbiota of sows and its correlation with milk long-chain fatty acid profiles.

The goal of this study was to characterize the fecal microbiota profiles of gestating sows, along with the fecal microbiota and milk fatty acid contents of lactating sows and their correlations with reproductive performance at different parities. The results showed that the microbiota of third parity gestating sows contained a greater abundance of Prevotella compared to the other two parity groups, while lactating sows exhibiting higher reproductive performance at fifth parity exhibited a greater abundance of Lactobacillus species. The lactating sows with higher reproductive performance also exhibited higher total monounsaturated fatty acid (MUFA) and higher total polyunsaturated fatty acid (PUFA) levels relative to sows with lower reproductive performance at all three analyzed parities, especially sows at fifth parity produced the lowest total saturated fatty acid (SFA) levels, and showed the highest C18:1n9c and C18:2n6c concentrations. In correlational analyses, the abundance of Oligella, Lactobacillus, and Corynebacterium was highly positively correlated with C18:1n9c, C18:2n6c, and C20:4n6. Overall, these results provide a rational basis for efforts to improve sow reproductive performance through the provision of precisely regulated nutrition. KEY POINTS: • Clear differences in the fecal microbiota were evident between sows of different parities. • Lactating sows with high reproductive performance showed distinct milk fatty acid profiles.

Self-Assembly Behavior, Aggregation Structure, and the Charge Carrier Transport Properties of S-Heterocyclic Annulated Perylene Diimide Derivatives.

The construction of high-performance n-type semiconductors is crucial for the advancement of organic electronics. As an attractive n-type semiconductor, molecular systems based on perylene diimide derivatives (PDIs) have been extensively investigated over recent years. Owing to the fascinating aggregated structure and high performance, S-heterocyclic annulated PDIs (SPDIs) are receiving increasing attention. However, the relationship between the structure and the electrical properties of SPDIs has not been deeply revealed, restricting the progress of PDI-based organic electronics. Here, we developed two novel SPDIs with linear and dendronized substituents in the imide position, named linear SPDI and dendronized SPDI, respectively. A series of structural and property characterizations indicated that linear SPDI formed a long-range-ordered crystalline structure based on helical supramolecular columns, while dendronized SPDI, with longer alkyl side chains, formed a 3D-ordered crystalline structure at a low temperature, which transformed into a hexagonal columnar liquid crystal structure at a high temperature. Moreover, no significant charge carrier transport signal was examined for linear SPDI, while dendronized SPDI had a charge carrier mobility of 3.5 × 10-3 cm2 V-1 s-1 and 2.1 × 10-3 cm2 V-1 s-1 in the crystalline and liquid crystalline state, respectively. These findings highlight the importance of the structure-function relationship in PDIs, and also offer useful roadmaps for the design of high-performance organic electronics for down-to-earth applications.

Synthesis of Vinylene-Linked Thiopyrylium-, Pyrylium-, and Pyridinium-Based Covalent Organic Frameworks by Acid-Catalyzed Aldol Condensation.

The development of new vinylene-linked covalent organic frameworks (COFs) with special ionic structure and high stability is challenging. Herein, we report a facile, general method for constructing ionic vinylene-linked thiopyrylium-based COFs from 2,4,6-trimethylpyrylium tetrafluoroborate and other common reagents by means of acid-catalyzed Aldol condensation. Besides, pyrylium-, and pyridinium-based COFs also can be prepared from the same monomer under slightly different reaction conditions. The COFs exhibited uniform nanofibrous morphologies with excellent crystallinities, special ionic structures, well-defined nanochannels, and high specific surface areas.

A New Contactless Cross-Correlation Velocity Measurement System for Gas-Liquid Two-Phase Flow.

Based on the principle of Contactless Conductivity Detection (CCD), a new contactless cross-correlation velocity measurement system with a three-electrode construction is developed in this work and applied to the contactless velocity measurement of gas-liquid two-phase flow in small channels. To achieve a compact design and to reduce the influence of the slug/bubble deformation and the relative position change on the velocity measurement, an electrode of the upstream sensor is reused as an electrode of the downstream sensor. Meanwhile, a switching unit is introduced to ensure the independence and consistency of the upstream sensor and the downstream sensor. To further improve the synchronization of the upstream sensor and the downstream sensor, fast switching and time compensation are also introduced. Finally, with the obtained upstream and downstream conductance signals, the velocity measurement is achieved by the principle of cross-correlation velocity measurement. To test the measurement performance of the developed system, experiments are carried out on a prototype with a small channel of 2.5 mm. The experimental results show that the compact design (three-electrode construction) is successful, and its measurement performance is satisfactory. The velocity range for the bubble flow is 0.312-0.816 m/s, and the maximum relative error of the flow rate measurement is 4.54%. The velocity range for the slug flow is 0.161 m/s-1.250 m/s, and the maximum relative error of the flow rate measurement is 3.70%.

Distributed Optical Measurement System for Plate Fin Heat Exchanger.

The acquirement of the flow information in plate-fin heat exchanger (PFHE) is limited by its metal structure and complex flow condition. This work develops a new distributed optical measurement system to obtain flow information and boiling intensity. The system utilizes numerous optical fibers installed at the surface of the PFHE to detect optical signals. The attenuation and fluctuation of the signals reflect the variation of the gas-liquid interfaces and can be further used to estimate the boiling intensity. Practical experiments of flow boiling in PFHE with different heating fluxes have been carried out. The results verify that the measurement system can obtain the flow condition. Meanwhile, according to the results, the boiling development in PFHE can be divided into four stages with the increase in the heating flux, including the unboiling stage, initiation stage, boiling developing stage, and fully developed stage.

On the Image Reconstruction of Capacitively Coupled Electrical Resistance Tomography (CCERT) with Entropy Priors.

Regularization with priors is an effective approach to solve the ill-posed inverse problem of electrical tomography. Entropy priors have been proven to be promising in radiation tomography but have received less attention in the literature of electrical tomography. This work aims to investigate the image reconstruction of capacitively coupled electrical resistance tomography (CCERT) with entropy priors. Four types of entropy priors are introduced, including the image entropy, the projection entropy, the image-projection joint entropy, and the cross-entropy between the measurement projection and the forward projection. Correspondingly, objective functions with the four entropy priors are developed, where the first three are implemented under the maximum entropy strategy and the last one is implemented under the minimum cross-entropy strategy. Linear back-projection is adopted to obtain the initial image. The steepest descent method is utilized to optimize the objective function and obtain the final image. Experimental results show that the four entropy priors are effective in regularization of the ill-posed inverse problem of CCERT to obtain a reasonable solution. Compared with the initial image obtained by linear back projection, all the four entropy priors make sense in improving the image quality. Results also indicate that cross-entropy has the best performance among the four entropy priors in the image reconstruction of CCERT.

Structure-based virtual screening, in silico docking, ADME properties prediction and molecular dynamics studies for the identification of potential inhibitors against SARS-CoV-2 Mpro.

COVID-19 is a viral pandemic caused by SARS-CoV-2. Due to its highly contagious nature, millions of people are getting affected worldwide knocking down the delicate global socio-economic equilibrium. According to the World Health Organization, COVID-19 has affected over 186 million people with a mortality of around 4 million as of July 09, 2021. Currently, there are few therapeutic options available for COVID-19 control. The rapid mutations in SARS-CoV-2 genome and development of new virulent strains with increased infection and mortality among COVID-19 patients, there is a great need to discover more potential drugs for SARS-CoV-2 on a priority basis. One of the key viral enzymes responsible for the replication and maturation of SARS-CoV-2 is Mpro protein. In the current study, structure-based virtual screening was used to identify four potential ligands against SARS-CoV-2 Mpro from a set of 8,722 ASINEX library compounds. These four compounds were evaluated using ADME filter to check their ADME profile and druggability, and all the four compounds were found to be within the current pharmacological acceptable range. They were individually docked to SARS-CoV-2 Mpro protein to assess their molecular interactions. Further, molecular dynamics (MD) simulations was carried out on protein-ligand complex using Desmond at 100 ns to explore their binding conformational stability. Based on RMSD, RMSF and hydrogen bond interactions, it was found that the stability of protein-ligand complex was maintained throughout the entire 100 ns simulations for all the four compounds. Some of the key ligand amino acid residues participated in stabilizing the protein-ligand interactions includes GLN 189, SER 10, GLU 166, ASN 142 with PHE 66 and TRP 132 of SARS-CoV-2 Mpro. Further optimization of these compounds could lead to promising drug candidates for SARS-CoV-2 Mpro target.

Response Characteristics of Contactless Impedance Detection (CID) Sensor on Slug Flow in Small Channels: The Investigation on Slug Separation Distance.

In recent years, CID sensors have displayed great development potential in parameter measurement of gas-liquid two-phase flow in small channels. However, the fundamental/mechanism research on the response characteristics of CID sensors is relatively insufficient. This work focuses on the investigation of the influence of separation distance between slugs on the impedance (real part, imaginary part and amplitude) response characteristics of slug flow in small channels. Experiments were carried out with the CID sensors in four small channels with inner pipe diameters of 1.96 mm, 2.48 mm, 3.02 mm and 3.54 mm, respectively. The experimental results show that for a CID sensor, the slug separation distance has significant influence on the impedance response characteristics. There is a critical value of slug separation distance. When the slug separation distance is larger than the critical value, the impedance response characteristics of each slug can be considered independent of each other, i.e., there is no interaction between the slugs. When the slug separation distance is less than the critical value, the impedance response characteristics show obvious interaction between the slugs. It is indicated that the ratios of the critical values to the pipe inner diameters are approximate 100.

A New Adaptive GCC Method and Its Application to Slug Flow Velocity Measurement in Small Channels.

In this work, an adaptive generalized cross-correlation (AGCC) method is proposed that focuses on the problem of the conventional cross-correlation method not effectively realizing the time delay estimation of signals with strong periodicity. With the proposed method, the periodicity of signals is judged and the center frequencies of the strongly periodical components are determined through the spectral analysis of the input signals. Band-stop filters that are used to suppress the strongly periodical components are designed and the mutual power spectral density of the input signals that is processed by the band-stop filters is calculated. Then, the cross-correlation function that is processed is the inverse Fourier transform of the mutual power spectral density. Finally, the time delay is estimated by seeking the peak position of the processed cross-correlation function. Simulation experiments and practical velocity measurement experiments were carried out to verify the effectiveness of the proposed AGCC method. The experimental results showed that the new AGCC method could effectively realize the time delay estimation of signals with strong periodicity. In the simulation experiments, the new method could realize the effective time delay estimation of signals with strong periodicity when the energy ratio of the strongly periodical component to the aperiodic component was under 150. Meanwhile, the cross-correlation method and other generalized cross-correlation methods fail in time delay estimation when the energy ratio is higher than 30. In the practical experiments, the velocity measurement of slug flow with strong periodicity was implemented in small channels with inner diameters of 2.0 mm, 2.5 mm and 3.0 mm. With the proposed method, the relative errors of the velocity measurement were less than 4.50%.

Choroidal changes in lens-induced myopia in guinea pigs.

INTRODUCTION: This study aimed to determine the role of the choroid in lens-induced myopia (LIM) in guinea pigs. METHODS: Guinea pigs were randomly divided into two groups: a normal control (NC) group and a LIM group. Refraction and axial length (AL) were measured by streak retinoscopy and A-scan ultrasonography. The choroidal thickness (ChT), vessel density of the choriocapillaris (VDCC) and vessel density of the choroidal layer (VDCL) were assessed by Spectral-domain Optical Coherence Tomography Angiography (SD-OCT). In addition, the choroidal expression of nitric oxide synthase (NOS) enzymes at the mRNA and protein levels was analyzed by real-time fluorescence quantitative PCR, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. RESULTS: In the LIM group, refraction and AL were increased significantly compared with those in the NC group at 2 weeks (refraction: LIM vs. NC, -4.23 ± 0.43 D vs. 2.20 ± 0.48 D; AL: LIM vs. NC, 8.36 ± 0.05 mm vs. 8.22 ± 0.03 mm) and 4 weeks (refraction: LIM vs. NC, -5.88 ± 0.49 D vs. 1.63 ± 0.41 D; AL: 8.57 ± 0.06 mm vs. 8.40 ± 0.04 mm). The ChT and VDCC were decreased significantly compared with those in the NC group at 2 weeks (ChT: LIM vs. NC, 60.92 ± 8.15 µm vs. 79.11 ± 7.47 µm; VDCC: LIM vs. NC, 23.43 ± 3.85% vs. 28.74 ± 4.11%) and 4 weeks (ChT: LIM vs. NC, 48.43 ± 6.85 µm vs. 76.38 ± 7.84 µm; VDCC: LIM vs. NC, 21.29 ± 2.17% vs. 27.64 ± 2.91%). The VDCL was also decreased compared with that in the NC group at 2 weeks and 4 weeks (NC vs. LIM, 24.87 ± 5.16% vs. 22.45 ± 3.26%; 23.37 ± 5.85% vs. 21.39 ± 2.62%; all P > 0.05). Moreover, the ChT was positively correlated with the VDCC and VDCL. The mRNA and protein expression of NOS enzymes (eNOS and nNOS) was increased. CONCLUSIONS: During the development of myopia, the ChT, VDCC and VDCL were decreased, while NOS expression in the choroid was increased. The expression of NOS was negatively correlated with the ChT, VDCC and VDCL. NO may play an important role in regulating the choroid during myopia development.

Nanoscale melamine-based porous organic frameworks as host material for efficient polysulfides chemisorption in lithium-sulfur batteries.

In order to improve the electrochemical capacity of lithium-sulfur batteries (LiSBs), it is necessary to introduce the porous organic frameworks with well-defined hetero atom species in cathode. In this work, porous nanomaterials with ultra-high nitrogen containing and adjustable porosity named Schiff-based networks (SNWs) were selected as potential candidate for sulfur host in LiSBs. Two SNW samples have been constructed by reacting melamine with phenyl or biphenyl dialdehydes through microwave-assisted method, respectively. The high BET surface area provided sufficient room to impregnate sulfur and mitigated volume changes during the cycling performance. Besides, the high density and homogeneous distribution of pyridinic-N and aminic-N in SNW nanoparticles can cooperatively form lithium polysulfides (LiPSs) chemisorption via enhanced Li+-N interactions to effectively suppressed the 'shuttle effect'. Attributed to its structural superiorities, SNW/S cathode demonstrates excellent electrochemical performance in LiSBs. In particular, SNW-2/S cathode delivers an excellent cyclability with a specific capacity of 620 mAh · g-1 after 500 cycles at 0.5 C, counting with a low capacity fading of 0.0508% per cycle. This work highlights the importance of rational design for effective LiPSs chemisorption and pioneers a facile strategy for developing suitable sulfur host materials towards high-performance LiSBs.

Sex-dependent changes in the microbiota profile, serum metabolism, and hormone levels of growing pigs after dietary supplementation with Lactobacillus.

Dietary supplementation with Lactobacillus can improve the intestinal microbial balance and exerts beneficial effects on pig health. However, whether these effects in pigs show differences between the sexes remains poorly understood. Therefore, we analyzed the sex-dependent patterns in the fecal microbiota after dietary supplementation with Lactobacillus acidophilus ZLA012 through high-throughput sequencing, determined the metabolomic profile of serum in barrows (immature castrated males) and gilts (sexually immature females) through nontargeted liquid chromatography-mass spectrometry, and measured the levels of various hormones, such as insulin, growth hormone, serotonin, triiodothyronine, and thyroxine. Lactobacillus supplementation resulted in more obvious effects on the microbial diversity and composition in barrows than in gilts. Specifically, supplementation with L. acidophilus ZLA012 significantly increased the abundance of the phylum Bacteroidetes and decreased that of Firmicutes in barrows. In contrast, more notable effects on metabolites, particularly those involved in lipid metabolism and glycerophospholipid metabolism, were observed in gilts than in barrows after Lactobacillus supplementation. Megasphaera, Dialister, Gemmiger, Faecalibacterium, Bulleidia, and Prevotella were the core functional genera associated with the significantly affected metabolites, which are involved in the biosynthesis, degradation, and elongation of fatty acids. L. acidophilus ZLA012 treatment increased the serum insulin, total bile acid, lipoprotein lipase, and nicotinamide adenine dinucleotide (NAD)+ levels in gilts, whereas higher serotonin levels were found in barrows than in gilts. The results indicated that the separate housing of barrows and gilts might be beneficial for targeted dietary supplementation and application of Lactobacillus in pig production. KEY POINTS: • L. acidophilus exerted obvious effects on microbiota profiles for barrows than gilts. • Gilts treated by L. acidophilus had a greater variety of lipid metabolism compared with barrows. • Lactobacillus regulated the dynamic balance among the microbiota, metabolism, and hormone in pigs.

Cognitive control and emotional response in attention-deficit/ hyperactivity disorder comorbidity with disruptive, impulse-control, and conduct disorders.

BACKGROUND: This study investigated cognitive and emotional functioning in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and disruptive, impulse-control, and conduct disorders (DICCD). METHODS: Thirty patients with ADHD, 26 with DICCD, 22 with ADHD+DICCD were recruited from the outpatient department of Shanghai Changning Mental Health Center, plus 20 healthy controls (HC). Differences between the groups in cognitive and emotional functioning were examined using Golden's Stroop and Emotional Stroop tests. For Emotional Stroop Mean reaction time (RT) of positive word (POS) and negative word (NEG) with color congruence (C) or incongruence (I) were recorded as POS-C, POS-I, NEG-C and NEG-I, respectively. RESULTS: For Golden's interference scores (IGs), both errors and RTs in the ADHD group were higher than in the other groups. Longer mean RTs of POS-C, POS-I, NEG-C and neural word (NEU) of the ADHD group, and NEG-I of ADHD+DICCD and DICCD groups were observed compared to HC. After 12 weeks of methylphenidate treatment, differences between ADHD subgroups and HC on Golden's Stroop RT disappeared, but differences in Golden's Stroop errors and Emotional Stroop mean RTs remained. The ADHD+DICCD group showed longer mean RTs in NEG-C, NEG-I and NEU of the Emotional Stroop test than the ADHD group. CONCLUSIONS: Our study shows that regardless of emotional responding, deficit in cognitive control is the core symptom of ADHD. However, emotionally biased stimuli may cause response inhibitory dysfunction among DICCD with callous-unemotional traits, and the comorbidity of ADHD and DICCD tends to account for the negative emotional response characteristic of DICCD. These deficits may be eliminated by medication treatment in ADHD, but not the ADHD with comorbid DICCD. Our results support the notion that ADHD with comorbid DICCD is more closely related to DICCD than to ADHD.

Investigation of the Effects of Electrode Geometry on the Performance of C4D Sensor with Radial Configuration.

Electrodes are basic components of C4D (capacitively coupled contactless conductivity detection) sensors, and different electrode structures (the configuration pattern or the electrode geometry) can lead to different measurement results. In this work, the effects of electrode geometry of radial configuration on the measurement performance of C4D sensors are investigated. Two geometrical parameters, the electrode length and the electrode angle, are considered. A FEM (finite element method) model based on the C4D method is developed. With the FEM model, corresponding simulation results of conductivity measurement with different electrode geometry are obtained. Meanwhile, practical experiments of conductivity measurement are also conducted. According to the simulation results and experimental results, the optimal electrode geometry of the C4D sensor with radial configuration is discussed and proposed. The recommended electrode length is 5-10 times of the pipe inner diameter and the recommended electrode angle is 120-160°.

A Low Excitation Working Frequency Capacitively Coupled Contactless Conductivity Detection (C4D) Sensor for Microfluidic Devices.

In this work, a new capacitively coupled contactless conductivity detection (C4D) sensor for microfluidic devices is developed. By introducing an LC circuit, the working frequency of the new C4D sensor can be lowered by the adjustments of the inductor and the capacitance of the LC circuit. The limits of detection (LODs) of the new C4D sensor for conductivity/ion concentration measurement can be improved. Conductivity measurement experiments with KCl solutions were carried out in microfluidic devices (500 µm × 50 µm). The experimental results indicate that the developed C4D sensor can realize the conductivity measurement with low working frequency (less than 50 kHz). The LOD of the C4D sensor for conductivity measurement is estimated to be 2.2 µS/cm. Furthermore, to show the effectiveness of the new C4D sensor for the concentration measurement of other ions (solutions), SO42- and Li+ ion concentration measurement experiments were also carried out at a working frequency of 29.70 kHz. The experimental results show that at low concentrations, the input-output characteristics of the C4D sensor for SO42- and Li+ ion concentration measurement show good linearity with the LODs estimated to be 8.2 µM and 19.0 µM, respectively.

Injectable and moldable hydrogels for use in sensitive and wide range strain sensing applications.

Recently, the use of hybrid double network (DN) hydrogels has become prominent due to their enhanced mechanical properties, which has opened the door for new applications of these soft materials. Only a few of these gels have demonstrated both injectable and moldable capabilities. In this work, we report the mechanical properties, gauge factor (GF) values and demonstrate both the injectability and moldability of a gelatin/polyacrylamide DN hydrogel. We optimized several parameters, such as, gelatin to polyacrylamide ratio, reactant concentrations and metal ion concentration, to produce a gelatin/polyacrylamide hydrogel with superior mechanical properties. The highest water content gel was capable of withstanding strains of 5000% before failure. These gels were facilely injected into molds where they effectively changed shape and maintained similar properties prior to remolding. When 20 mM calcium was doped into a similar gel, a tensile strength of 1.71 MPa was achieved. Aside from improving the mechanical properties of the gels, both Ca2+ and Mg2+ also improved their conductivity, so they were tested for use as strain sensors. The sensitivity of the hydrogel strain sensors were measured using the GF. For the 20 mM Ca2+ hydrogel, these GF values ranged from 1.63 to 6.85 for strains of 100% to 2100% respectively. Additionally, the sensors showed good stability over continuous cyclic stretching, demonstrating their long term reliability for strain sensing.

Nosocomial infections in psychiatric hospitals during the COVID-19 outbreak.

Since mid-December 2019, a new coronavirus disease (COVID-19) has emerged in China. It was reported that Wuhan Mental Health Center in China was affected from the very beginning of the outbreak. Coincidentally, another large-scale nosocomial infection occurred at the psychiatric ward of the Daenam Hospital in South Korea. It is important for the policymakers to pay full attention on this aspect worldwide and corresponding prevention recommendations should be provided.

3D Reconstruction of Slug Flow in Mini-Channels with a Simple and Low-Cost Optical Sensor.

The present work provides a new approach for 3D image reconstruction of gas-liquid two-phase flow (GLF) in mini-channels based on a new optical sensor. The sensor consists of a vertical and a horizontal photodiode array. Firstly, with the optical signals obtained by the vertical array, a measurement model developed by Support Vector Regression (SVR) was used to determine the cross-sectional information. The determined information was further used to reconstruct cross-sectional 2D images. Then, the gas velocity was calculated according to the signals obtained by the horizontal array, and the spatial interval of the 2D images was determined. Finally, 3D images were reconstructed by piling up the 2D images. In this work, the cross-sectional gas-liquid interface was considered as circular, and high-speed visualization was utilized to provide the reference values. The image deformation caused by channel wall was also considered. Experiments of slug flow in a channel with an inner diameter of 4.0 mm were carried out. The results verify the feasibility of the proposed 3D reconstruction method. The proposed method has the advantages of simple construct, low cost, and easily multipliable. The reconstructed 3D images can provide detailed and undistorted information of flow structure, which could further improve the measurement accuracy of other important parameters of gas-liquid two-phase flow, such as void fraction, pressure drop, and flow pattern.

A New Positioning Method Based on Multiple Ultrasonic Sensors for Autonomous Mobile Robot.

This work proposes a new positioning method based on multiple ultrasonic sensors for the autonomous mobile robot. Unlike the conventional ultrasonic positioning methods, this new method can realize higher accuracy ultrasonic positioning without additional temperature information. Three ultrasonic sensors are used for positioning. A generalized measurement model is established for general sensor configuration. A simplified measurement model, which considers the computational complexity, is also established for linear/simplified sensor configuration. Three time-of-flight signals are obtained from the three ultrasonic sensors. The coordinates of the target are calculated by the ratios of time-of-flights. Positioning experiments were carried out to verify the feasibility and effectiveness of the proposed method. Experimental results show that the new ultrasonic positioning method is effective, both the two established models can implement positioning successfully, and the positioning accuracy is satisfactory. Compared with the conventional ultrasonic positioning method with the default ultrasonic velocity, the positioning accuracy is greatly improved by the proposed method. Compared with the ultrasonic positioning method with additional temperature compensation, the results obtained by the proposed method are comparable.