A dual computational and experimental strategy to enhance TSLP antibody affinity for improved asthma treatment.

Thymic stromal lymphopoietin is a key cytokine involved in the pathogenesis of asthma and other allergic diseases. Targeting TSLP and its signaling pathways is increasingly recognized as an effective strategy for asthma treatment. This study focused on enhancing the affinity of the T6 antibody, which specifically targets TSLP, by integrating computational and experimental methods. The initial affinity of the T6 antibody for TSLP was lower than the benchmark antibody AMG157. To improve this, we utilized alanine scanning, molecular docking, and computational tools including mCSM-PPI2 and GEO-PPI to identify critical amino acid residues for site-directed mutagenesis. Subsequent mutations and experimental validations resulted in an antibody with significantly enhanced blocking capacity against TSLP. Our findings demonstrate the potential of computer-assisted techniques in expediting antibody affinity maturation, thereby reducing both the time and cost of experiments. The integration of computational methods with experimental approaches holds great promise for the development of targeted therapeutic antibodies for TSLP-related diseases.

[Dielectric properties of tidal volume changes in rabbit lung tissue in the 100 MHz~1 GHz band].

This paper investigates the variation of lung tissue dielectric properties with tidal volume under in vivo conditions to provide reliable and valid a priori information for techniques such as microwave imaging. In this study, the dielectric properties of the lung tissue of 30 rabbits were measured in vivo using the open-end coaxial probe method in the frequency band of 100 MHz to 1 GHz, and 6 different sets of tidal volumes (30, 40, 50, 60, 70, 80 mL) were set up to study the trends of the dielectric properties, and the data at 2 specific frequency points (433 and 915 MHz) were analyzed statistically. It was found that the dielectric coefficient and conductivity of lung tissue tended to decrease with increasing tidal volume in the frequency range of 100 MHz to 1 GHz, and the differences in the dielectric properties of lung tissue for the 6 groups of tidal volumes at 2 specific frequency points were statistically significant. This paper showed that the dielectric properties of lung tissue tend to vary non-linearly with increasing tidal volume. Based on this, more accurate biological tissue parameters can be provided for bioelectromagnetic imaging techniques such as microwave imaging, which could provide a scientific basis and experimental data support for the improvement of diagnostic methods and equipment for lung diseases.

Expression and clinical significance of interleukin-10, transforming growth factor-ß1, and CD4+CD25 cytokines in paediatric allergic rhinitis with allergic asthma.

Introduction: It was intended to research the level changes and clinical significance of interleukin (IL)-10, transforming growth factor ß1 (TGF-ß1), and CD4+CD25 cytokines in paediatric allergic rhinitis (AR) accompanied with allergic asthma (AA). Material and methods: Eighty children of AA with AR receiving immunotherapy indications were included as the experimental group (EG), while another 40 healthy children in the same period were selected as the control group (CG). IL-10, TGF-ß1, and CD4+CD25 levels in cells of the two groups before and after treatment were compared and analysed. Results: The serum TGF-ß1 level was determined as 1,045.7 ±44.7 pg/ml in the EG at admission, remarkably higher than that in the CG (p < 0.05). The IL-10 level was 21.4 ±2.8 pg/ml; CD4+CD25 cells accounted for 9.2 ±2.4%, CD4+CD25high cells accounted for 0.6 ±0.3%. These were all greatly lower than those in the CG (p < 0.05). At discharge, the serum TGF-ß1 level in the EG was 903.7 ±29.4 pg/ml, which was still memorably higher than that in the CG (p < 0.05). The IL-10 level changed to 32.8 ±3.7 pg/ml; the percentage of CD4+CD25 was 11.3 ±1.8, respectively, among CD4+T cells. These were also notably lower than those in the CG at discharge (p < 0.05). Conclusions: IL-10, TGF-ß1, and CD4+CD25 level changes in cells might be of reference value as therapeutic indicators for clinical treatment or evaluation of paediatric AR with AA.

Development and validation of nomograms for predicting overall survival and cancer-specific survival in elderly patients with locally advanced gastric cancer: a population-based study.

OBJECTIVE: To evaluate the multiple factors influencing the survival of elderly patients with locally advanced gastric cancer (LAGC) and develop and validate the novel nomograms for predicting the survival. METHODS: The clinical features of patients treated between 2000 and 2018 were collected and collated from the Surveillance, Epidemiology, and End Results (SEER) database and three medical centres in China, and the patients were randomly divided into a training cohort (3494), internal validation cohort (1497) and external validation cohort (841). Univariate and multivariate analyses of the prognostic values were performed to identify independent prognostic factors associated with overall survival (OS) and cancer-specific survival (CSS), and two nomogram models were developed. Harrell's concordance index (C-index) and calibration curves were employed to assess discrimination and calibration. Decision curve analysis (DCA) and receiver-operating characteristic (ROC) curves were utilized to investigate the clinical usefulness. RESULTS: In the SEER database, the 5-year OS of the patients was 31.08%, while the 5-year CSS of the patients was 44.09%. Furthermore, in the external validation set, the 5-year OS of the patients was 49.58%, and the 5-year CSS of these patients was 53.51%. After statistical analysis, nine independent prognostic factors of OS and CSS were identified, including age, race, tumour size, differentiation, TNM stage, gastrectomy type, lymph node metastasis (LNM), lymph node ratio (LNR) and chemotherapy. The C-index (approximately 0.7) and calibration curve (close to the optimal calibration line) indicated satisfactory discrimination and calibration of the nomogram. DCA and ROC curves showed that the developed nomogram was superior to TNM stage. CONCLUSION: The novel validated nomogram could accurately predict the prognosis of individual elderly patients with LAGC and guide the selection of clinical treatment measures.

Fast Iterative Shrinkage-Thresholding Algorithm with Continuation for Brain Injury Monitoring Imaging Based on Electrical Impedance Tomography.

Electrical impedance tomography (EIT) is low-cost and noninvasive and has the potential for real-time imaging and bedside monitoring of brain injury. However, brain injury monitoring by EIT imaging suffers from image noise (IN) and resolution problems, causing blurred reconstructions. To address these problems, a least absolute shrinkage and selection operator model is built, and a fast iterative shrinkage-thresholding algorithm with continuation (FISTA-C) is proposed. Results of numerical simulations and head phantom experiments indicate that FISTA-C reduces IN by 63.2%, 47.2%, and 29.9% and 54.4%, 44.7%, and 22.7%, respectively, when compared with the damped least-squares algorithm, the split Bergman, and the FISTA algorithms. When the signal-to-noise ratio of the measurements is 80-50 dB, FISTA-C can reduce IN by 83.3%, 72.3%, and 68.7% on average when compared with the three algorithms, respectively. Both simulation and phantom experiments suggest that FISTA-C produces the best image resolution and can identify the two closest targets. Moreover, FISTA-C is more practical for clinical application because it does not require excessive parameter adjustments. This technology can provide better reconstruction performance and significantly outperforms the traditional algorithms in terms of IN and resolution and is expected to offer a general algorithm for brain injury monitoring imaging via EIT.

Model of Heat Capacity in Volume Dimension.

Heat capacity is an important and fundamental thermodynamic parameter in materials. The temperature-dependent heat capacity (HC) was studied extensively. Here, the universal correlation between the experimental heat capacity Cp and the coefficient of thermal expansion ß in reference solids at high temperatures: Cp = Co + Eß (C0 and E: constants) and the volume-dependent heat capacity CTE in the temperature range from several Kelvins to melting temperatures is quantitatively determined: CTE = Eß, and a new phenomenological model of the experimental heat capacity below the melting temperature in the volume dimension is established: Cp = CT + CTE (the non-volume-dependent heat capacity CT = C0fD, fD: Debye function). Previous harmonic and anharmonic HC models explain the HC at low temperatures and high temperatures, respectively. The new model successfully explains the HC at the whole temperature range below the melting temperature and quantitatively determines the change behavior of the temperature and volume in solids after absorbing the heat.

A Nomogram for Prediction of Survival in Patients After Gastrectomy Within Enhanced Recovery After Surgery (ERAS): A Single-Center Retrospective Study.

BACKGROUND Enhanced Recovery After Surgery (ERAS) programs can optimize clinical outcomes and have been widely used across multiple specialties, but a personalized prediction model involving ERAS for the prognosis of gastric cancer is lacking. MATERIAL AND METHODS We retrospectively collected clinical data on 725 gastric cancer patients within ERAS who underwent curative gastric resection in the Affiliated Hospital of Qingdao University from 2007 to 2014. Kaplan-Meier method, log-rank test, and Cox proportional risk model were used to determine the independent prognostic factors of patients. The accuracy of model was evaluated by C-index, calibration curve, and Decision Curve Analysis (DCA), and the receiver operator characteristic (ROC) curve was used to compare the nomogram model with the predictive value of TNM staging system. RESULTS The 5-year overall survival (OS) of 725 patients within ERAS was 72.5%. Age at diagnosis, T stage, N stage, and postoperative complications were determined to be independent factors affecting the prognosis of patients within ERAS, and nomogram model was constructed. The C-index of the training group was 0.809 and that of the verification group was 0.804; the calibration curves and DCA of the 2 groups showed good accuracy. Through verification, we found that, compared with the TNM staging assessment method, the nomogram model was more accurate in predicting the prognosis of gastric cancer. CONCLUSIONS This study identified factors affecting the prognosis of patients with gastric cancer, and we constructed the first prognostic nomogram model in ERAS mode to facilitate postoperative personalized prognostic evaluation.

[A multifrequency time-difference electrical impedance tomography algorithm using spectral constraints].

This study aims to propose a multifrequency time-difference algorithm using spectral constraints. Based on the knowledge of tissue spectrum in the imaging domain, the fraction model was used in conjunction with the finite element method (FEM) to approximate a conductivity distribution. Then a frequency independent parameter (volume or area fraction change) was reconstructed which made it possible to simultaneously employ multifrequency time-difference boundary voltage data and then reduce the degrees of freedom of the reconstruction problem. Furthermore, this will alleviate the illness of the EIT inverse problem and lead to a better reconstruction result. The numerical validation results suggested that the proposed time-difference fraction reconstruction algorithm behaved better than traditional damped least squares algorithm (DLS) especially in the noise suppression capability. Moreover, under the condition of low signal-to-noise ratio, the proposed algorithm had a more obvious advantage in reconstructions of targets shape and position. This algorithm provides an efficient way to simultaneously utilize multifrequency measurement data for time-difference EIT, and leads to a more accurate reconstruction result. It may show us a new direction for the development of time-difference EIT algorithms in the case that the tissue spectrums are known.

An on-line processing strategy for head movement interferences removal of dynamic brain electrical impedance tomography based on wavelet decomposition.

BACKGROUND: Head movement interferences are a common problem during prolonged dynamic brain electrical impedance tomography (EIT) clinical monitoring. Head movement interferences mainly originate from body movements of patients and nursing procedures performed by medical staff, etc. These body movements will lead to variation in boundary voltage signals, which affects image reconstruction. METHODS: This study employed a data preprocessing method based on wavelet decomposition to inhibit head movement interferences in brain EIT data. Mixed Gaussian models were applied to describe the distribution characteristics of brain EIT data. We identified head movement signal through the differences in distribution characteristics of corresponding wavelet decomposition coefficients between head movement artifacts and normal signals, and then managed the contaminated data with improved on-line wavelet processing methods. RESULTS: To validate the efficacy of the method, simulated signal experiments and human data experiments were performed. In the simulation experiment, the simulated movement artifact was significantly reduced and data quality was improved with indicators' increase in PRD and correlation coefficient. Human data experiments demonstrated that this method effectively suppressed head movement in signals and reduce artifacts resulting from head movement artifacts in images. CONCLUSION: In this paper, we proposed an on-line strategy to manage the head movement interferences from the brain EIT data based on the distribution characteristics of wavelet coefficients. Our strategy is capable of reducing the movement interference in the data and improving the reconstructed images. This work would improve the clinical practicability of brain EIT and contribute to its further promotion.

Preoperative controlling nutritional status (CONUT) score as a predictor of long-term outcome after curative resection followed by adjuvant chemotherapy in stage II-III gastric Cancer.

BACKGROUND: The prognostic value of preoperative controlling nutritional status (CONUT) has been reported in many malignancies. In present study, we aimed to clarify the prognostic impact of CONUT in gastric cancer (GC) receiving curative resection and adjuvant chemotherapy. METHODS: We retrospectively reviewed 697 consecutive patients undergoing curative surgery followed by adjuvant chemotherapy for Stage II-III GC between November 2000 and September 2012. Patients were classified into high (≥3) and low (≤2) CONUT groups according to the receiver operating characteristic (ROC) analysis. RESULTS: Of the included patients, 217 (31.1%) belonged to the high CONUT group. The high CONUT group had a significantly lower 5-year cancer-specific survival (CSS) rate than the low CONUT group (39.3 vs. 55.5%, P < 0.001). High CONUT score was significantly associated with larger tumor size, more lymph node metastasis, and poorer nutritional status, including lower body mass index (BMI), higher prognostic nutritional index (PNI) and the presence of preoperative anemia (all P < 0.05). Multivariate analysis revealed that CONUT score was an independent prognostic factor (HR: 1.553; 95% CI: 1.080-2.232; P = 0.017). Of note, in the low PNI group, CONUT score still effectively stratified CSS (P = 0.016). Furthermore, the prognostic significance of CONUT score was also maintained when stratified by TNM stage (all P < 0.05). CONCLUSIONS: CONUT score is considered a useful nutritional marker for predicting prognosis in stage II-III GC patients undergoing curative resection and adjuvant chemotherapy, and may help to facilitate the planning of preoperative nutritional interventions.

Prognostic factors of primary gastrointestinal stromal tumors: a cohort study based on high-volume centers.

Objective: We aimed to evaluate the clinicopathologic characteristics, immunohistochemical expression and prognostic factors of patients with primary gastrointestinal stromal tumors (GISTs). Methods: Data from 2,570 consecutive GIST patients from four medical centers in China (January 2001-December 2015) were reviewed. Survival curves were constructed by the Kaplan-Meier method, and Cox regression models were used to identify independent prognostic factors. Results: Of the included patients, 1,375 (53.5%) were male, and the patient age range was 18 to 95 (median, 58) years. The tumors were mostly found in the stomach (64.5%), small intestine (25.1%) and colorectal region (5.1%). At the time of diagnosis, the median tumor size was 4.0 (range: 0.1-55.0) cm, and the median mitotic index per 50 high power fields (HPFs) was 3 (range: 0-254). Of the 2,168 resected patients, 2,009 (92.7%) received curative resection. According to the modified National Institutes of Health (NIH) classification, 21.9%, 28.9%, 14.1% and 35.1% were very low-, low-, intermediate- and high-risk tumors, respectively. The rate of positivity was 96.4% for c-Kit, 87.1% for CD34, 96.9% for delay of germination 1 (DOG-1), 8.0% for S-100, 31.0% for smooth muscle actin (SMA) and 5.1% for desmin. However, the prognostic value of each was limited. Multivariate analysis showed that age, tumor size, mitotic index, tumor site, occurrence of curative resection and postoperative imatinib were independent prognostic factors. Furthermore, we found that high-risk patients benefited significantly from postoperative imatinib (P<0.001), whereas intermediate-risk patients did not (P=0.954). Conclusions: Age, tumor size, mitotic index, tumor site, occurrence of curative resection and postoperative imatinib were independent prognostic factors in patients with GISTs. Moreover, determining whether intermediate-risk patients can benefit from adjuvant imatinib would be of considerable interest in future studies.

Prognostic significance of Epstein-Barr virus infection in gastric cancer: a meta-analysis.

BACKGROUND: The prognostic significance of Epstein-Barr virus (EBV) infection in gastric cancer (GC) remains unclear. Recently, a number of studies have investigated the association between EBV infection and the prognosis of GC with controversial results. We therefore conducted a meta-analysis to assess its prognostic significance. METHODS: PubMed and EMBASE were searched for studies up to October 1, 2014. We investigated the association between EBV infection with survival in patients with GC. The pooled hazard ratio (HR) and its 95% confidence interval (CI) were calculated to evaluate risk. RESULTS: A final analysis of 8,336 patients with GC from 24 studies was performed. Our analysis results indicated that the pooled HR was 0.67 (95% CI: 0.55-0.79; Z = 11.18, P < 0.001). Subgroup analyses stratified by region revealed that the protective role of EBV infection only remained in the Asian population (HR: 0.62, 95% CI: 0.48-0.75; P < 0.001). When stratified by study quality and statistical methodology, the protective role could also be identified in high quality studies (HR: 0.67, 95% CI: 0.55-0.79) and in univariate analysis studies (HR: 0.62, 95% CI: 0.50-0.74). There was no evidence of significant heterogeneity and publication bias. CONCLUSIONS: The presence of EBV has a favorable impact on GC patient's survival, especially in an Asian population. Future updated studies, especially large-scale randomized controlled studies stratified by region, are warranted as validation studies.

Multi-path Fusion in SFCF-Net for Enhanced Multi-frequency Electrical Impedance Tomography.

Multi-frequency electrical impedance tomography (mfEIT) offers a nondestructive imaging technology that reconstructs the distribution of electrical characteristics within a subject based on the impedance spectral differences among biological tissues. However, the technology faces challenges in imaging multi-class lesion targets when the conductivity of background tissues is frequency-dependent. To address these issues, we propose a spatial-frequency cross-fusion network (SFCF-Net) imaging algorithm, built on a multi-path fusion structure. This algorithm uses multi-path structures and hyper-dense connections to capture both spatial and frequency correlations between multi-frequency conductivity images, which achieves differential imaging for lesion targets of multiple categories through cross-fusion of information. According to both simulation and physical experiment results, the proposed SFCF-Net algorithm shows an excellent performance in terms of lesion imaging and category discrimination compared to the weighted frequency-difference, U-Net, and MMV-Net algorithms. The proposed algorithm enhances the ability of mfEIT to simultaneously obtain both structural and spectral information from the tissue being examined and improves the accuracy and reliability of mfEIT, opening new avenues for its application in clinical diagnostics and treatment monitoring.

Deciphering the tumor immune microenvironment of imatinib-resistance in advanced gastrointestinal stromal tumors at single-cell resolution.

The heterogeneous nature of tumors presents a considerable obstacle in addressing imatinib resistance in advanced cases of gastrointestinal stromal tumors (GIST). To address this issue, we conducted single-cell RNA-sequencing in primary tumors as well as peritoneal and liver metastases from patients diagnosed with locally advanced or advanced GIST. Single-cell transcriptomic signatures of tumor microenvironment (TME) were analyzed. Immunohistochemistry and multiplex immunofluorescence staining were used to further validate it. This analysis revealed unique tumor evolutionary patterns, transcriptome features, dynamic cell-state changes, and different metabolic reprogramming. The findings indicate that in imatinib-resistant TME, tumor cells with activated immune and cytokine-mediated immune responses interacted with a higher proportion of Treg cells via the TIGIT-NECTIN2 axis. Future immunotherapeutic strategies targeting Treg may provide new directions for the treatment of imatinib-resistant patients. In addition, IDO1+ dendritic cells (DC) were highly enriched in imatinib-resistant TME, interacting with various myeloid cells via the BTLA-TNFRSF14 axis, while the interaction was not significant in imatinib-sensitive TME. Our study highlights the transcriptional heterogeneity and distinct immunosuppressive microenvironment of advanced GIST, which provides novel therapeutic strategies and innovative immunotherapeutic agents for imatinib resistance.

Atomic-level polarization reversal in sliding ferroelectric semiconductors.

Intriguing "slidetronics" has been reported in van der Waals (vdW) layered non-centrosymmetric materials and newly-emerging artificially-tuned twisted moiré superlattices, but correlative experiments that spatially track the interlayer sliding dynamics at atomic-level remain elusive. Here, we address the decisive challenge to in-situ trace the atomic-level interlayer sliding and the induced polarization reversal in vdW-layered yttrium-doped γ-InSe, step by step and atom by atom. We directly observe the real-time interlayer sliding by a 1/3-unit cell along the armchair direction, corresponding to vertical polarization reversal. The sliding driven only by low energetic electron-beam illumination suggests rather low switching barriers. Additionally, we propose a new sliding mechanism that supports the observed reversal pathway, i.e., two bilayer units slide towards each other simultaneously. Our insights into the polarization reversal via the atomic-scale interlayer sliding provide a momentous initial progress for the ongoing and future research on sliding ferroelectrics towards non-volatile storages or ferroelectric field-effect transistors.

Inertial migration of spherical and oblate particles in a triangular microchannel.

The. inertial migration of both spherical and oblate particles within an equilateral triangular channel is studied numerically. Our study primarily focuses on the effects of fluid inertia, quantified by the Reynolds number (Re) and particle size (ß). Our observations reveal two distinct equilibrium positions: the corner equilibrium position (CEP) is situated along the angle bisector near the corner, while the face equilibrium position (FEP) is located on a segment of the line perpendicular from the triangle's center to one of its sides. Spherical particles with varying initial positions predominantly reach the FEP. For oblate particles initially positioned along the angle bisector with a specific orientation, meaning the particle's evolution axis is inside the plane bisecting the angle, they will migrate along the angle bisector to reach the CEP while rotating in the tumbling mode. Conversely, for particles with different initial orientations and positions, they will employ the log-rolling mode to reach the FEP. Notably, we identify a dual-stage particle migration process to the FEP, with trajectories converging to an equilibrium manifold, which bears a resemblance to the cross section of the channel. To further illustrate the transition between FEP and CEP under general initial conditions, except for those along the angle bisector, we construct a phase diagram in the (Re, ß) parameter space. This transition is often triggered by the size of larger particles (as the FEP cannot accommodate them) or the influence of inertia for smaller particles. For the FEP, especially for medium- or small-size particles, we notice an initial outward movement of the FEP from the center of the cross section as Re increases, followed by a return towards the center. This behavior results from the interplay of three forces acting on the particle. This research holds potential implications for the design of microfluidic devices, offering insights into the behavior of particles within equilateral triangular channels.

Early detection of acute ischemic stroke using Contrast-enhanced electrical impedance tomography perfusion.

A cerebral contrast-enhanced electrical impedance tomography perfusion method is developed for acute ischemic stroke during intravenous thrombolytic therapy. Several clinical contrast agents with stable impedance characteristics and high-conductivity contrast were screened experimentally as electrical impedance contrast agent candidates. The electrical impedance tomography perfusion method was tested on rabbits with focal cerebral infarction, and its capability for early detection was verified based on perfusion images. The experimental results showed that ioversol 350 performed significantly better as an electrical impedance contrast agent than other contrast agents (p < 0.01). Additionally, perfusion images of focal cerebral infarction in rabbits confirmed that the electrical impedance tomography perfusion method could accurately detect the location and area of different cerebral infarction lesions (p < 0.001). Therefore, the cerebral contrast-enhanced electrical impedance tomography perfusion method proposed herein combines traditional, dynamic continuous imaging with rapid detection and could be applied as an early, rapid-detection, auxiliary, bedside imaging method for patients after a suspected ischemic stroke in both prehospital and in-hospital settings.

Effective Electrical Impedance Tomography Based on Enhanced Encoder-Decoder Using Atrous Spatial Pyramid Pooling Module.

Electrical impedance tomography (EIT) is a noninvasive and radiation-free imaging method. As a "soft-field" imaging technique, in EIT, the target signal in the center of the measured field is frequently swamped by the target signal at the edge, which restricts its further application. To alleviate this problem, this study presents an enhanced encoder-decoder (EED) method with an atrous spatial pyramid pooling (ASPP) module. The proposed method enhances the ability to detect central weak targets by constructing an ASPP module that integrates multiscale information in the encoder. The multilevel semantic features are fused in the decoder to improve the boundary reconstruction accuracy of the center target. The average absolute error of the imaging results by the EED method reduced by 82.0%, 83.6%, and 36.5% in simulation experiments and 83.0%, 83.2%, and 36.1% in physical experiments compared with the errors of the damped least-squares algorithm, Kalman filtering method, and U-Net-based imaging method, respectively. The average structural similarity improved by 37.3%, 42.9%, and 3.6%, and 39.2%, 45.2%, and 3.8% in the simulation and physical experiments, respectively. The proposed method provides a practical and reliable means of extending the application of EIT by solving the problem of weak central target reconstruction under the effect of strong edge targets in EIT.

Synthesis, structure-activity analysis, and biological evaluation of sanguinamide B analogues.

We report the first synthesis of sanguinamide B analogues. Substituting N-methylated (N-Me) amino acids, glycine (Gly), and L- or D-phenylalanine (Phe) into the backbone of sanguinamide B showed that only l- and d-Phe residues controlled the macrocycle conformation. The N-methylated and glycine analogues all had multiple conformations, whereas the L- and D-Phe derivatives only had a single conformation. Testing of all conformer analogues showed that inclusion of an L- or D-Phe was a superior design element than incorporating the N-Me moiety that is often utilized to control macrocyclic conformation. Finally, we show that there is an ideal Phe residue (in this case L-Phe) for generating compounds that have the greatest inhibitory effect on bacterial motility. Our data support the hypothesis that the macrocyclic conformation is dictated by the benzyl moiety requiring a "pseudoequatorial" position, and all other energy considerations are secondary.

Collective behavior and hydrodynamic advantage of side-by-side self-propelled flapping foils.

Fish schools and their potential hydrodynamic advantages are intriguing problems and many underlying mechanisms are unclear due to the complexity of the system, especially for large schools. Here large schools containing four, six, and eight self-propelled foils in a side-by-side configuration are numerically studied. The effect of different combinations out of phase and in phase between two neighboring foils is studied. The results show that the multiple abreast self-propelled foils driven by synchronized harmonic flapping motions can spontaneously form stable side-by-side configurations. When compared with a single foil flapping alone, for cases in which any two neighboring foils are in an out-of-phase state, foils consume more energy with a specific cruising speed. For cases where any two neighboring foils are in an in-phase state, foils propel at a lower speed for a specific flapping frequency. Interestingly, the foils in hybrid states in which both out of phase and in phase coexist are preferred to enhance speed and save power. Further analysis indicates that the stability of the configuration and the lower cost of transport are attributed to the synchronized collaborative wake vortex structure and bow configuration formed by any three neighboring foils in a hybrid state. The collaborative vortices in the wake help the foils move forward alternatively during one flapping cycle. The bow configuration prevents the wake from spreading laterally and enhances the performance. Our paper sheds some light on understanding the self-organized collective behavior and hydrodynamic advantages of large schools.