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Background: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies have emerged as promising therapeutic options for the treatment of chronic migraine. However, treatment response varies considerably among individuals, suggesting a potential role for genetic factors. This study aimed to identify genetic variants affecting the efficacy of anti-CGRP monoclonal antibody therapy in chronic migraine among the Han Chinese population in Taiwan to enhance treatment precision and to understand the genetic architecture of migraine. Methods: We conducted a quantitative trait locus (QTL) association study in patients with chronic migraines from a tertiary medical center in Taiwan using the Taiwan Precision Medicine Array Chip. The patients received fremanezumab or galcanezumab for at least 12 weeks. Treatment efficacy was assessed based on the improvement rate in monthly migraine days. Genetic variants were identified, and their associations with treatment efficacy were examined through quantitative trait loci analysis, linkage disequilibrium studies, and functional annotations using the Gene Ontology database. Results: Six single nucleotide polymorphisms (SNPs) relative variants were significantly associated with anti-CGRP therapy response (p < 1 × 10− 7): rs116870564, rs75244870, rs56216870, rs12938101, rs74655790, and rs149540851. These variants are located in or near genes, including LRRC4C, ATAD2B, and OXR1, which are involved in neuronal development, DNA-dependent ATPase activity, and oxidation-reduction processes, respectively. The rs116870564 variant in LRRC4C showed the strongest association (β = -0.551, p = 6.65 × 10− 9). The functional impact of these variants is attributed to their regulatory effects on gene expression, which are influenced by intron splicing regulation, transcription factors, and changes in chromatin structure. Conclusion: The identification of key genetic markers associated with response to anti-CGRP therapy emphasizes the importance of genetic variability in treatment efficacy. This could lead to more personalized chronic migraine management strategies and tailored therapeutic approaches based on individual genetic profiles. Further research in larger, diverse populations is warranted to validate these findings and refine our understanding of the role of CGRP in chronic migraine pathophysiology. Trial registration: Not applicable. [ABSTRACT FROM AUTHOR]

Cryogenic valves play a crucial role in the production and transportation of liquefied natural gas (LNG), and are primarily responsible for efficiently controlling the inflow and outflow of LNG and regulating pressure. However, due to their operation in low-temperature and high-humidity environments, crucial components such as drip trays are susceptible to frosting, which may lead to LNG leakage, thereby causing severe safety incidents. In this study, the user-defined function (UDF) is employed to redevelop Fluent, which integrates the frost growth model with the Eulerian multiphase flow model, to conduct a quantitative analysis of frosting on drip trays of cryogenic valves. The effects of environmental parameters, such as wind speed, ambient temperature, air humidity, and cold surface temperature on the growth of the frost layer were analyzed. This study reveals a limiting wind speed between 1 m/s and 2 m/s. Upon reaching this limit speed, the growth of the frost layer reaches its maximum, and further increases in the wind speed have no significant effect on the growth of the frost layer. Furthermore, the influence of the change in the flow field on droplet impingement and freezing during the growth of the frost layer is considered through the coupling method of the kinematic characteristics of water droplets and the collection coefficient of water droplets. This study identifies the influence of different parameters on the droplet impact efficiency, leading to the modification of the frost layer on the drip tray. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the value of CT-based whole lung radiomics nomogram for identifying the risk of cardiovascular disease (CVD) in patients with chronic obstructive pulmonary disease (COPD). Materials and methods: A total of 974 patients with COPD were divided into a training cohort (n = 402), an internal validation cohort (n = 172), and an external validation cohort (n = 400) from three hospitals. Clinical data and CT findings were analyzed. Radiomics features of whole lung were extracted from the non-contrast chest CT images. A radiomics signature was constructed with algorithms. Combined with the radiomics score and independent clinical factors, multivariate logistic regression analysis was used to establish a radiomics nomogram. ROC curve was used to analyze the prediction performance of the model. Results: Age, weight, and GOLD were the independent clinical factors. A total of 1218 features were extracted and reduced to 15 features to build the radiomics signature. In the training cohort, the combined model (area under the curve [AUC], 0.731) showed better discrimination capability (p < 0.001) than the clinical factors model (AUC, 0.605). In the internal validation cohort, the combined model (AUC, 0.727) performed better (p = 0.032) than the clinical factors model (AUC, 0.629). In the external validation cohort, the combined model (AUC, 0.725) performed better (p < 0.001) than the clinical factors model (AUC, 0.690). Decision curve analysis demonstrated the radiomics nomogram outperformed the clinical factors model. Conclusion: The CT-based whole lung radiomics nomogram has the potential to identify the risk of CVD in patients with COPD. Clinical relevance statement: This study helps to identify cardiovascular disease risk in patients with chronic obstructive pulmonary disease on chest CT scans. Key Points: • To investigate the value of CT-based whole lung radiomics features in identifying the risk of cardiovascular disease in chronic obstructive pulmonary disease patients. • The radiomics nomogram showed better performance than the clinical factors model to identify the risk of cardiovascular disease in patients with chronic obstructive pulmonary disease. • The radiomics nomogram demonstrated excellent performance in the training, internal validation, and external validation cohort (AUC, 0.731; AUC, 0.727; AUC, 0.725). [ABSTRACT FROM AUTHOR]

This article explores the topological entropy and topological sequence entropy of hom tree-shifts on unexpandable trees. Regarding topological entropy, we establish that the entropy, denoted as h (T X) on an unexpandable tree, equals the entropy h(X) of the base shift X when X is a subshift satisfying the almost specification property. Additionally, we derive some fundamental properties such as entropy approximation and the denseness of entropy for subsystems. Concerning topological sequence entropy, we show that the set of sequence entropies of hom tree-shifts with a base shift is generated by an irreducible matrix A, forming a subset of log N . Precisely, these entropies correspond to the logarithms of the largest cardinalities of the periodic classes of A. [ABSTRACT FROM AUTHOR]

Three types of steels were designed on the basis of GX40CrNiSi25-12 austenitic heat resistant steel by adding different Mn contents (2wt.%, 6wt.%, and 12wt.%). Thermodynamic calculation, microstructure characterization and mechanical property tests were conducted to investigate the effect of Mn addition on the microstructure and mechanical properties of the austenitic heat resistant steel. Results show that the matrix structure in all the three types of steels at room temperature is completely austenite. Carbides NbC and M23C6 precipitate at grain boundaries of austenite matrix. With the increase of Mn content, the number of carbides increases and their distribution becomes more uniform. With the Mn content increases from 1.99% to 12.06%, the ultimate tensile strength, yield strength and elongation increase by 14.6%, 8.0% and 46.3%, respectively. The improvement of the mechanical properties of austenitic steels can be explained by utilizing classic theories of alloy strengthening, including solid solution strengthening, precipitation strengthening, and grain refinement. The increase in alloy strength can be attributed to solid solution strengthening and precipitation strengthening caused by the addition of Mn. The improvement of the plasticity of austenitic steels can be explained from two aspects: grain refinement and homogenization of precipitated phases. [ABSTRACT FROM AUTHOR]

We investigate the low-order modeling of collective dynamics in a can-annular combustor consisting of four ring-coupled turbulent lean-premixed combustors. Each combustor is treated as an individual thermoacoustic oscillator, and the entire combustion system is modeled using four Van der Pol oscillators ring-coupled with dissipative, time-delay, and reactive coupling terms. We show that this model, despite its simplicity, can reproduce many collective dynamics observed in experiments under various combinations of equivalence ratios and combustor lengths, such as 2-can anti-phase synchronization, alternating anti-phase synchronization, pairwise anti-phase synchronization, spinning azimuthal mode, and 4 steady thermoacoustic oscillators. The phase relationship in the majority of cases can be quantitatively modeled. Moreover, by incorporating a reactive coupling term, the model is able to reproduce the frequency shift observed experimentally. This study demonstrates the feasibility of using a simple low-order model to reproduce collective dynamics in complex turbulent combustion systems. This suggests that this model could be used (i) to facilitate the interpretation of experimental data within the synchronization framework, (ii) to identify potential parameter regimes leading to amplitude death, and (iii) to serve as a basis for modeling the collective dynamics observed in more complicated multi-combustors. [ABSTRACT FROM AUTHOR]

Purpose: Ultrasound-guided percutaneous renal biopsy (PRB) has been considered as a golden standard for CKD diagnosis and is employed to identify potential therapeutic targets since 1950s. Post-biopsy hemorrhage is the most common complication, while severe bleeding complication might cause nephrectomy or death. Therefore, how to reduce the occurrence of complications while ensuring the success of PRB is always a clinical research topic. Methods: This study retrospectively collected and established a renal biopsy database of each patient who underwent ultrasound-guided PRB at a tertiary teaching hospital from September 2017 to December 2020 through the Health Information System. All the data were statistically processed by SPSS software. Results: A total of 1146 patients underwent PRB for various reasons. The overall rate of post-biopsy hemorrhage was 37.70% (432/1146). Of those bleedings, minor bleeding after PRB was found in 337 (29.41%), middle bleeding 84 (7.33%), major bleeding 11 (0.96%). Besides that, there were 96 patients (8.38%) reported their discomfort symptoms. There was no death. Females were at significantly increased risk of hemorrhagic complication than males (OR = 2.017, CI = 1.531–2.658). While the risk for hemorrhagic complication significantly decreased as BMI and platelet before renal biopsy increased (OR = 0.956, CI = 0.924–0.989; OR = 0.998, CI = 0.996–1.000). As the APTT time prolonged, the risk for hemorrhagic complication significantly increased (OR = 1.072, CI = 1.023–1.123). Those patients whose albumin were higher, also had higher risk for hemorrhagic complication than other patients (OR = 1.020, CI = 1.000–1.041). Specifically, postoperative urination within 4 h increased the risk for hemorrhagic complication (OR = 1.741, CI = 1.176–2.576). Conclusion: Our analysis finds that the incidence of post-biopsy bleeding complication is 37.70%, and its risk is associated with female, lower BMI, lower platelet before renal biopsy, prolonged APTT, higher albumin, and postoperative urination within 4 h. The findings highlighted the importance of perioperative management for renal biopsy, including adequate risk assessment, tailored careful observation after PRB. And medical staff should pay more attention to fluid management after ultrasound-guided PRB. [ABSTRACT FROM AUTHOR]

The use of AI-based social robots has been shown to be beneficial for learning English as a Second Language (ESL). Not much is known, however, about the drivers of parental intention to use those robots in support of their children's ESL learning. This study aims to explore the factors that drive parental intention to adopt AI-based social robots for children's ESL learning. The research model is proposed based on the theories and literature regarding motivations, product smartness, personality traits and physical risk perception. Data collected from 315 participants are analyzed using the partial least squares structural equation modeling (PLS-SEM) method. The results show that utilitarian and hedonic motivations positively affect parental intention to adopt AI-based social robots. In addition, utilitarian motivation is influenced by robots' autonomy and parental personal innovativeness, while hedonic motivation is influenced by robots' autonomy and humanlike interaction, and parental personal innovativeness. From the findings, important implications for promoting parental intention to adopt AI-based social robots in children's ELS learning are offered. [ABSTRACT FROM AUTHOR]

Soil erosion is a severe problem in Taiwan due to the steep terrain, fragile geology, and extreme climatic events resulting from global warming. Due to the rapidly changing hydrological conditions affecting the locations and the amount of transported sand and fine particles, timely impact evaluation and riverine dust control are difficult, particularly when resources are limited. To comprehend the impact of desertification in estuarine areas on the variation of air pollutant concentrations, this study utilized remote sensing technology coupled with an air pollutant dispersion model to determine the unit contribution of potential pollution sources and quantify the effect of riverine dust on air quality. The images of the downstream area of the Beinan River basin captured by Formosat-2 in May 2006 were used to analyze land use and land cover (LULC) composition. Subsequently, the diffusion model ISCST-3 based on Gaussian distribution was utilized to simulate the transport of PM across the study area. Finally, a mixed-integer programming model was developed to optimize resource allocation for dust control. Results reveal that sand deposition in specific river sections significantly influences regional air quality, owing to the unique local topography and wind field conditions. The present optimal plan model for regional air quality control further showed that after implementing engineering measures including water cover, revegetation, armouring cover, and revegetation, total PM concentrations would be reduced by 51%. The contribution equivalent calculation, using the air pollution diffusion model, was effectively integrated into the optimization model to formulate a plan for reducing riverine dust with limited resources based on air quality requirements. [ABSTRACT FROM AUTHOR]

Pretreatment patient-specific quality assurance (prePSQA) is conducted to confirm the accuracy of the radiotherapy dose delivered. However, the process of prePSQA measurement is time consuming and exacerbates the workload for medical physicists. The purpose of this work is to propose a novel deep learning (DL) network to improve the accuracy and efficiency of prePSQA. A modified invertible and variable augmented network was developed to predict the three-dimensional (3D) measurement-guided dose (MDose) distribution of 300 cancer patients who underwent volumetric modulated arc therapy (VMAT) between 2018 and 2021, in which 240 cases were randomly selected for training, and 60 for testing. For simplicity, the present approach was termed as "IVPSQA." The input data include CT images, radiotherapy dose exported from the treatment planning system, and MDose distribution extracted from the verification system. Adam algorithm was used for first-order gradient-based optimization of stochastic objective functions. The IVPSQA model obtained high-quality 3D prePSQA dose distribution maps in head and neck, chest, and abdomen cases, and outperformed the existing U-Net-based prediction approaches in terms of dose difference maps and horizontal profiles comparison. Moreover, quantitative evaluation metrics including SSIM, MSE, and MAE demonstrated that the proposed approach achieved a good agreement with ground truth and yield promising gains over other advanced methods. This study presented the first work on predicting 3D prePSQA dose distribution by using the IVPSQA model. The proposed method could be taken as a clinical guidance tool and help medical physicists to reduce the measurement work of prePSQA. [ABSTRACT FROM AUTHOR]

This study introduces an all-digital CMOS time-domain smart temperature sensor (STS) that offers a smaller circuit area and reduced complexity. In contrast to previous studies that utilized multiple delay lines or additional path selection circuits, the proposed new structure employs a single cyclic path and fewer delay lines. The functionality of high-resolution temperature sensing, pulse-shrinking time measurement, and built-in offset-error cancellation is achieved using only one cyclic delay line (CDL). The temperature-sensing delay line generates a thermal-dependent pulse width proportional to the absolute temperature (PTAT). Subsequently, a pulse-shrinking unit, implemented within the pulse-shrinking delay line, performs time-to-digital conversion by measuring the PTAT pulse width. Finally, a time-added delay line within the CDL incorporates a simple D-type Flip Flop to enable concise offset-error cancellation, thereby improving accuracy. This study further simplifies the cancellation circuitry to reduce the overall circuit area. The proposed sensor, fabricated using a TSMC 0.35 μ m CMOS process, occupies an area of 0.022 mm 2 , providing a cost-effective solution for pulse-shrinking STSs. The maximum inaccuracy after offset-error cancellation is 1. 3 ∘ C within a temperature range of 0 ∼ 80 ∘ C, with a high resolution of approximately 0. 035 ∘ C/LSB. This resolution enhancement significantly surpasses similar studies. By reducing circuit complexity, the proposed sensor successfully achieves improvements in both area and resolution. [ABSTRACT FROM AUTHOR]

This paper proposes wide-range and fast locking all-digital delay-locked loop (WRADDLL) circuit with one cycle dynamic synchronizing. The WRADDLL not only synchronizes the input and output clocks in 5 clock cycles but maintains one cycle dynamic locking. The WRADDLL reduces the clock skew between the input and output clocks with three innovative techniques. First, by improving the mirror control circuit, the WRADDLL operates correctly with a flexible duty cycle clock signal. Second, the WRADDLL works precisely and ignores the effect of output load changes by moving the measurement delay line beyond the output driver. Besides, it can achieve one-cycle dynamic locking. Finally, the WRADDLL utilizes the band selector to achieve wide-range operation. After fine tuning, the maximum static phase error is less than 3% of clock cycle. The chip is fabricated by 90 nm standard CMOS process. Its operating frequency range is from 200 MHz to 2 GHz. The power consumption and RMS jitter are 3.24 mW and 1.49 ps at 2 GHz, respectively. The active area of this chip is 0.011 mm2. [ABSTRACT FROM AUTHOR]

Background: Bladder cancer (BLCA) is a prevalent urinary system malignancy. Understanding the interplay of immunological and metabolic genes in BLCA is crucial for prognosis and treatment. Methods: Immune/metabolism genes were extracted, their expression profiles analyzed. NMF clustering found prognostic genes. Immunocyte infiltration and tumor microenvironment were examined. Risk prognostic signature using Cox/LASSO methods was developed. Immunological Microenvironment and functional enrichment analysis explored. Immunotherapy response and somatic mutations evaluated. RT-qPCR validated gene expression. Results: We investigated these genes in 614 BLCA samples, identifying relevant prognostic genes. We developed a predictive feature and signature comprising 7 genes (POLE2, AHNAK, SHMT2, NR2F1, TFRC, OAS1, CHKB). This immune and metabolism-related gene (IMRG) signature showed superior predictive performance across multiple datasets and was independent of clinical indicators. Immunotherapy response and immune cell infiltration correlated with the risk score. Functional enrichment analysis revealed distinct biological pathways between low- and high-risk groups. The signature demonstrated higher prediction accuracy than other signatures. qRT-PCR confirmed differential gene expression and immunotherapy response. Conclusions: The model in our work is a novel assessment tool to measure immunotherapy's effectiveness and anticipate BLCA patients' prognosis, offering new avenues for immunological biomarkers and targeted treatments. [ABSTRACT FROM AUTHOR]

Puerariae Thomsonii Radix (PTR) is not only widely used in disease prevention and treatment but is also an important raw material as a source of starch and other food. The growth years of PTR are closely related to its quality. The rapid and nondestructive identification of growth year is essential for the quality control of PTR and other traditional Chinese medicines. In this study, we proposed a convolutional neural network (CNN)-based classification framework in conjunction with hyperspectral imaging (HSI) technology for the rapid identification of the growth years of PTRs. Traditional treatment methods (i.e., multiplicative scatter correction, standard normal variate, and Savitzky-Golay smoothing) combined with machine learning algorithms (i.e., random forest, logistic regression, naive Bayes, and eXtreme gradient boost) were used as baseline models. Among them, the F1-score of CNN-based models based on PTRs' outer surfaces was over 90%, outperforming all the other baseline models. These results showed that it was feasible to use a deep learning algorithm in conjunction with HSI technology to identify the growth years of PTR. This method provides a fast, nondestructive, and simple method of identifying the growth years of PTR. It can be easily applied to other scenarios, such as for the identification of the locality or years of growth for other traditional Chinese herbs. [ABSTRACT FROM AUTHOR]

This study utilizes Q-learning to dynamically change the optimized parameters of independent low-rank matrix analysis (ILRMA). Notably, ILRMA, which combines independent vector analysis and non-negative matrix factorization, is a novel methodology adopted to realize multichannel blind source separation (BSS). In previous studies, ILRMA has used optimized parameters to improve separation efficiency. In this study, however, an optimized parameter is obtained from the parametric majorization–equalization algorithm, which adjusts the convergence speed to avoid poor local solutions. Two other optimized parameters are obtained using the isotropic complex Student's t-distribution, which adjusts the probability distribution to conform to the target mixed audio source distribution. To further improve the performance of BSS, this paper proposes a Q-learning off-policy temporal difference control algorithm (reinforcement learning) to dynamically change the three optimized parameters. To ensure the simplicity and efficiency of Q-learning, n-armed bandits are used to replace traditional high-dimensional Q-tables. Furthermore, experiments are conducted using instruments and vocal multichannel BSS tasks. The results confirm the validity of the proposed method. [ABSTRACT FROM AUTHOR]

This study presents a data augmentation technique that solves insufficient/imbalanced data problems during crowdsensing by the Internet of Medical Things (IoMT) or wireless sensor networks (WSNs), owing to diversified locations and heterogeneous conditions. This may cause problems because the samples in various categories may vary in quantities, which create skew distributions. Besides, pattern analysis of insufficient observed samples also generates biased models. In view of such, this work proposes synthetic minority oversampling generative adversarial networks (SMOGANs) for processing imbalanced data, where insufficient samples in quantities can be automatically expanded, so that different classes contain equal numbers of samples, subsequently avoiding biased modeling. The SMOGAN consists of two modules, where the first one is the synthetic minority oversampling technique (SMOTE), and the second involves a GAN. The former is used to initialize the proposed system, in which insufficient/imbalanced data samples are roughly augmented in quantities. Subsequently, the GAN enriches feature diversities of those pseudoreal samples formerly augmented by the SMOTE. Experiments on open datasets were carried out for evaluation. To assess the capability of data augmentation, only 4.00% of the real data were reserved as minority classes and then sent into different data augmentation methods for comparison. Analytical results showed that the proposed SMOGANs outperformed the baselines. Accuracy was increased compared with the baselines. Such results showed that the proposed SMOGAN could improve data collection problems of insufficient/imbalanced datasets by enhancing data quantities and qualities. [ABSTRACT FROM AUTHOR]

This study attempts to: (a) investigate whether positive and negative emotions mediate the pathways linking self-efficacy for learning programming with effort and persistence in undergraduates' learning Scratch programming combining with a programmable hardware platform (i.e., Arduino), and (b) assess the effect of academic major (i.e., information technology-related majors vs non-information technology-related majors) on self-efficacy for learning programming and emotions. With the use of responses collected from a sample of 156 undergraduate students, the research model is empirically validated using partial least squares structural equation modeling (PLS-SEM). The findings reveal that undergraduates' effort and persistence while learning programming were significantly predicted by positive emotions, but not by negative emotions. Self-efficacy for learning programming significantly and positively influenced positive emotions and negatively influenced negative emotions. Finally, variations in predicting positive emotions were found between different academic majors: students in information technology-related majors experienced less negative emotional experiences than those in non-information technology-related majors. [ABSTRACT FROM AUTHOR]

Data from QuikSCAT, ERA5, WAVERYS, drifters, and HYCOM + NCODA Reanalysis in the northern Pacific are analyzed under tropical cyclones (TCs) and extratropical cyclones (ECs). The EC (TC) has the stable (unstable) wind directions and wider (narrower) fetch resulting in a larger (smaller) significant wave height (Hs). For modest and weak wind speeds (W ≤ 26 m s−1), the current speed (U) is higher in low latitudes than in mid-latitudes since the oceanic mixed-layer thickness (ℎ) is not large enough. For strong wind speed (W > 26 m s−1), ℎ deepens more in low latitudes and causes lower U. [ABSTRACT FROM AUTHOR]

Background: Long noncoding RNAs (lncRNAs) are involved in tumor formation and development. KCNQ1OT1 regulates the malignant proliferation of retinoblastoma (RB), but the specific mechanism remains to be further investigated. Methods: The KCNQ1OT1, miR-339-3p and KIF23 expression levels in RB were detected by qRT-PCR and western blotting. The cell viability, proliferation, migration ability and caspase-3 activity of RB cells were evaluated by CCK-8, BrdU, transwell and caspase-3 activity analysis. Western blot was used to detect the Bax and Bcl-2 protein expression in RB cells. The binding relationship between KCNQ1OT1, miR-339-3p and KIF23 was detected by luciferase, RIP and RNA pull-down assay. Results: KCNQ1OT1 and KIF23 were up-regulated frequently in RB, and miR-339-3p was down-regulated. Functional studies showed that downregulation of KCNQ1OT1 or KIF23 inhibited the survival and migration of RB cells, and facilitated apoptosis. Interference with miR-339-3p showed the opposite effect. Mechanisms suggested that KCNQ1OT1 exited its oncogenic activity by positively regulating the expression of KIF23 and sponging miR-339-3p. Conclusion: KCNQ1OT1/miR-339-3p/KIF23 may be a new biomarker for the diagnosis and treatment of RB. [ABSTRACT FROM AUTHOR]

Background: The purpose of this scoping review was to organize and describe the literature on the application of clown care to the elderly population in nursing homes, including intervention time, intervention methods and intervention effects, so as to provide reference ideas for other scholars to explore clown care programs suitable for the elderly population in nursing homes. Methods: Employing Arksey and O'Malley's methodology, we searched for PubMed, Web of Science, Embase, Cochrane, CNKI, WanFang, VIP, and CBM systematically and thoroughly, and the search period was from the establishment of each database to December 12, 2022. Two researchers with evidence-based learning experience independently conducted literature retrieval, information extraction, and cross-checking in strict accordance with the inclusion and exclusion criteria. The review process is reported according to PRISMA. Results: 148 literature were initially obtained after searching, of which 18 were finally included. Among them, 17 were in English and 1 was in Chinese. There are 16 quantitative studies and 2 qualitative studies published from 2010 to 2022. It is found that the current clown care intervention program has not established a unified intervention standard and effective evaluation program. Conclusions: The results of this scoping review conclude that clown care played a significant role in the nursing home. At first, it can reduce negative emotions, cognitive impairments and physical pain among older adults. In addition, it can improve their quality of life, life satisfaction, etc. It is suggested to learn from the advanced experience of clown care in foreign countries and carry out more clown care among the elderly population in nursing homes in China. [ABSTRACT FROM AUTHOR]

Objective: To investigate the anti-coronavirus potential and the corresponding mechanisms of the two ingredients of Reduning Injection: quercetin and luteolin. Methods: A pseudovirus system was designed to test the efficacy of quercetin and luteolin to inhibit SARS-CoV-2 infection and the corresponding cellular toxicity. Luteolin was tested for its activities against the pseudoviruses of SARS-CoV-2 and its variants. Virtual screening was performed to predict the binding sites by Autodock Vina 1.1.230 and PyMol. To validate docking results, surface plasmon resonance (SPR) was used to measure the binding affinity of the compounds with various proteins of the coronaviruses. Quercetin and luteolin were further tested for their inhibitory effects on other coronaviruses by indirect immunofluorescence assay on rhabdomyosarcoma cells infected with HCoV-OC43. Results: The inhibition of SARS-CoV-2 pseudovirus by luteolin and quercetin were strongly dose-dependent, with concentration for 50% of maximal effect (EC50) of 8.817 and 52.98 µmol/L, respectively. Their cytotoxicity to BHK21-hACE2 were 177.6 and 405.1 µmol/L, respectively. In addition, luetolin significantly blocked the entry of 4 pseudoviruses of SARS-CoV-2 variants, with EC50 lower than 7 µmol/L. Virtual screening and SPR confirmed that luteolin binds to the S-proteins and quercetin binds to the active center of the 3CLpro, PLpro, and helicase proteins. Quercetin and luteolin showed over 99% inhibition against HCoV-OC43. Conclusions: The mechanisms were revealed of quercetin and luteolin inhibiting the infection of SARS-CoV-2 and its variants. Reduning Injection is a promising drug for COVID-19. [ABSTRACT FROM AUTHOR]

This paper establishes the large deviation principle (LDP) of certain types of nonconventional ergodic averages, namely, 1 N S N ∗ and 1 N S N # on N (defined later). The LDP for both averages are presented and such a result extends the preceding work of (Carinci et al. in Indag Math 23(3):589–602, 2012) to some specific cases of d-multiple averages for d ≥ 3 . [ABSTRACT FROM AUTHOR]

Background: Breast cancer is one of the solid tumors investigated for gene expression. Objective: Our research aimed to investigate the roles of transmembrane protein 106C (TMEM106C) on breast cancer and the underlying mechanisms. Results: The results from GEPIA website indicated that TMEM106C was up-regulated in breast cancer and the TMEM106C over-expression was concerned with poor outcomes in breast cancer patients. Moreover, western blotting and qRT-PCR assay also showed that TMEM106C level was up-regulated in breast cancer cells. Our results showed that over-expression of TMEM106C accelerated the malignant phenotypes of MCF7 cells, while TMEM106C silencing displayed the opposite outcomes in MDA-MB-231 cells. Furthermore, TMEM106C over-expression activated PI3K/AKT/mTOR signaling, which reversed by Wortmannin. Similarly, TMEM106C silencing inhibited PI3K/AKT/mTOR signaling, which abolished by 740Y-P. Moreover, we also confirmed that 740Y-P significantly reversed the function of TMEM106C silencing on the malignant phenotypes of MDA-MB-231 cells. Conclusion: This study indicated that TMEM106C could promote the malignant phenotypes of breast cancer cells by activating PI3K/AKT/mTOR signaling. [ABSTRACT FROM AUTHOR]

The wide spread of coronavirus disease 2019 (COVID-19) has significantly threatened public health. Human herd immunity induced by vaccination is essential to fight the epidemic. Therefore, highly immunogenic and safe vaccines are necessary to control SARS-CoV-2, whose S protein is the antigenic determinant responsible for eliciting antibodies that prevent viral entry and fusion. In this study, we developed a SARS-CoV-2 DNA vaccine expressing the S protein, named pVAX-S-OP, which was optimized according to the human-origin codon preference and using polyinosinic–polycytidylic acid as an adjuvant. pVAX-S-OP induced specific antibodies and neutralizing antibodies in BALB/c and hACE2 transgenic mice. Furthermore, we observed 1.43-fold higher antibody titers in mice receiving pVAX-S-OP plus adjuvant than in those receiving pVAX-S-OP alone. Interferon gamma production in the pVAX-S-OP-immunized group was 1.58 times (CD3+CD4+IFN-gamma+) and 2.29 times (CD3+CD8+IFN-gamma+) lower than that in the pVAX-S-OP plus adjuvant group but higher than that in the control group. The pVAX-S-OP vaccine was also observed to stimulate a Th1-type immune response. When, hACE2 transgenic mice were challenged with SARS-CoV-2, qPCR detection of N and E genes showed that the viral RNA loads in pVAX-S-OP-immunized mice lung tissues were 104 times and 106 times lower than those of the PBS control group, which shows that the vaccine could reduce the amount of live virus in the lungs of hACE2 mice. In addition, pathological sections showed less lung damage in the pVAX-S-OP-immunized group. Taken together, our results demonstrated that pVAX-S-OP has significant immunogenicity, which provides support for developing SARS-CoV-2 DNA candidate vaccines. [ABSTRACT FROM AUTHOR]

Purpose of Review: Chronic migraine (CM) is a highly disabling primary headache disorder with a substantial impact on patients' quality of life. Episodic migraine (EM) and CM are dynamic states; CM usually evolves from EM alongside increased headache frequency, comorbidities, and medication overuse, supporting the notion that migraine is a spectrum disorder. This narrative review aims to summarize neuroimaging studies to better understand the pathophysiology of CM. Recent Findings: Positron emission tomography studies have revealed abnormal energy metabolism and metabolic changes in the dorsal rostral pons in individuals with CM, suggesting that this structure has a key role in the pathophysiology of migraine generation and chronification. Magnetic resonance spectroscopy studies have suggested that thalamocortical pathway dysfunction may contribute to migraine chronification, while functional magnetic resonance imaging studies have highlighted that hypothalamic activity may be involved. Summary: Recent evidence highlights functional and structural alterations in cortical and subcortical pain-related brain regions in patients with CM. Whether these functional and structural abnormalities of the brain cause migraine chronification or are a consequence of repeated attacks is still debated. In the future, imaging patterns that predict the transformation from EM to CM should be identified. [ABSTRACT FROM AUTHOR]

Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is an autosomal dominant neurodegenerative disease. This disorder is caused by polyglutamine (polyQ)-containing mutant ataxin-3, which tends to misfold and aggregate in neuron cells. We previously demonstrated a protective function of carbonic anhydrase 8 (CA8) in MJD disease models and a decreased glycolytic activity associated with down-regulated CA8 in a human osteosarcoma (OS) cell model. Given that a reduction in body weight accompanied by gait and balance instability was observed in MJD patients and transgenic (Tg) mice, in this study, we aimed to examine whether metabolic defects are associated with MJD and whether CA8 expression is involved in metabolic dysfunction in MJD. Our data first showed that glucose uptake ability decreases in cells harboring mutant ataxin-3, but increases in cells overexpressing CA8. In addition, the expressions of glucose transporter 3 (GLUT3) and phosphofructokinase-1 (PFK1) were significantly decreased in the presence of mutant ataxin-3. Consistently, immunohistochemistry (IHC) showed that GLUT3 was less expressed in cerebella of aged MJD Tg mice, indicating that the dysfunction of GLUT3 may be associated with late-stage disease. On the other hand, transient down-regulation of CA8 revealed decreased expressions of GLUT3 and PFK1 in HEK293 cells harboring wild-type (WT) ataxin-3, but no further reduction of GLUT3 and PFK1 expressions were observed in HEK293 cells harboring mutant ataxin-3. Moreover, immunoprecipitation (IP) and immunofluorescence (IF) demonstrated that interactions exist between ataxin-3, CA8 and GLUT3 in MJD cellular and Tg models. These lines of evidence suggest that CA8 plays an important role in glucose metabolism and has different impacts on cells with or without mutant ataxin-3. Interestingly, the decreased relative abundance of Firmicutes/Bacteroidetes (F/B) ratio in the feces of aged MJD Tg mice coincided with weight loss and metabolic dysfunction in MJD. Taken together, our results are the first to demonstrate the effects of CA8 on glucose metabolism and its involvement in the metabolic defects in MJD disease. Further investigations will be required to clarify the underlying mechanisms for the metabolic defects associated with MJD. [ABSTRACT FROM AUTHOR]

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To further develop the active site mimics of azadithiolate-bridged [FeFe]-hydrogenases, a series of new diiron azadithiolate complexes [{(μ-SCH2)2N(C6H4CH2CH2OC(O)R)}Fe2(CO)6] (R = CH2C6H4Me-p, 2; C6H5, 3; CH3, 4) bearing bridgehead N-derivation were successfully prepared by facile esterification reaction of parent complex [{(μ-SCH2)2N(C6H4CH2CH2OH)}Fe2(CO)6] (1) and different carboxyl compounds RCO2H in the presence of 4-dimethylaminopyridine (DMAP) as catalyst and dicyclohexylcarbodiimide (DCC) as dehydrating reagent. Complexes 2–4 have been fully characterized by means of elemental analysis, FT-IR and NMR (1H, 13C) spectroscopies, and especially for 2 by X-ray crystallography. Further electrochemical and electrocatalytic properties of target complexes 2–4 and reference analogue 1 were studied and compared in the absence and presence of acetic acid (HOAc) as a proton source by cyclic voltammetry (CV), indicating that they may be considered as the active biomimetic electrocatalysts for proton reduction to hydrogen (H2). [ABSTRACT FROM AUTHOR]

To compare the trophic ecologies of mother–offspring pairs of the jumbo squid (Dosidicus gigas), we examined carbon and nitrogen stable isotopes in the eye lens core and lens cortex from 18 D. gigas specimens collected from the equatorial waters of the eastern-central Pacific. Both δ13C and δ15N values in lens cores were smaller than in lens cortexes. Significant difference in δ13C between lens cores and lens cortexes suggested that maternal squid used different habitats as compared with their offspring. Higher variation of δ15N in offspring than maternal squid indicated that maternal squid have a more general feeding strategy than their offspring. The degree of fitting of the probability density distribution curves of δ13C and δ15N and the isotopic niches of mothers and their offspring indicate that these squid have a flexible feeding strategy and that mothers and daughters are spawning in different locations. [ABSTRACT FROM AUTHOR]

Eco-geotechnical measures for debris flow mitigation and control have attracted wide attention, but the mitigation effect is lack of quantitative evaluation of coordinated measures. In order to evaluate the debris flow mitigation effect in the combinations of geotechnical engineering and ecological engineering, this study investigated the different trends of debris flows behaviour based on the sediment deposition on the gully bed and the loose material on the hillslope. Besides, this research proposed a new model involving vegetation coverage, source gravity energy and debris flow volume based on vegetation-erosion model. The new model validated that the debris flow volume was proportional to the gravity energy of gravel and rock fragments on the hillslope and inversely proportional to the vegetation coverage in a dry-hot valley setting. Furthermore, a typical area in the valley of the Xiaojiang River in Yunnan Province, China was quantified with the new model. The results showed that under different gravity energy conditions, the implementation order of check dam construction and afforestation was important for debris flow mitigation. [ABSTRACT FROM AUTHOR]

Schizophrenia stands out as one of the most devastating psychiatric disorders. Previous findings have shown that schizophrenia is a polygenic genetic disorder. Thus, abnormal neurodevelopment and neurogenesis may be associated with the etiology of schizophrenia, so genes which affect these processes may be potential candidate genes of schizophrenia. Mitogen-activated protein kinase kinase kinase 4 (MAP3K4) gene is a member of the mitogen-activated protein kinase family. Taking into account previous findings, MAP3K4 plays a crucial role in the fundamental pathology of various nervous system diseases. In the present study, we aim to explore the association of MAP3K4 and schizophrenia in an independent case-control sample including 627 schizophrenic patients and 1175 healthy controls from a Northeast Chinese Han population. Both the allelic and genotypic association analyses showed that 6 SNPs in MAP3K4 were significantly associated with schizophrenia (rs590988, rs625977, rs9295134, rs12110787, rs1001808 and rs9355870). After rigorous Bonferroni correction, 4 SNPs (rs9295134, rs12110787, rs1001808 and rs9355870) were still significantly associated with the disease. The haplotype composed of these four SNPs also showed significantly global and individual association with schizophrenia. These results suggest that MAP3K4 is a susceptibility gene for schizophrenia in the Northeast Chinese Han population. [ABSTRACT FROM AUTHOR]

Plasticizers are ubiquitous pollutants in the environment, whereas few efforts have been made to elucidate their emission sources in the atmosphere. In this research, the spatioseasonal variations and sources of particle-bound (PM2.5) phthalates (PAEs) and their substitutes (APs) at residential sites in seven districts and at four potential point-source sites across a megacity in South China were revealed. The total concentrations of PAEs ranging from 10.7 to 528 ng/m3 were substantially higher than those of APs (1.45.58.5 ng/m3). Significant spatial variations in the concentrations of the pollutants were observed, which were generally higher at the sites with intensive industrial activities and the point-source sites. Most atmospheric plasticizer levels peaked in summer, probably due to the temperature-promoted volatilization. Seven sources of plasticizers were identified by the positive matrix factorization (PMF) model. The sources in less industrialized districts are mainly associated with domestic and commercial emissions and with industry in the industrialized districts. Specifically, plastics and personal care products together contributed 60% of the plasticizers in the atmosphere of this city, followed by solvents and polyester industry sources. The incremental lifetime cancer risk of inhalation exposure to bis(2-ethylhexyl) phthalate in the study city is below the acceptable level. Relatively higher risks were found for residents living around sites with intensive industrial activities and around wastewater treatment plant. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review provides an update on sex differences in chronic migraine (CM), with a focus on clinical characteristics, pathophysiology, and treatments. Recent Findings: Approximately 6.8–7.8% of all migraineurs have CM, with an estimated prevalence of 1.4–2.2% in the general population. The economic burden caused by CM, including medical costs and lost working ability, is threefold higher than that caused by episodic migraine (EM). Notably, the prevalence of migraine is affected by age and sex. Female migraineurs with CM experience higher levels of headache-related disability, including longer headache duration, higher frequency of attacks, and more severely impacted efficiency at work. Sex hormones, including estrogen, testosterone, and progesterone, contribute to the sexually dimorphic characteristics and prevalence of migraine in men and women. Recent neuroimaging studies have indicated that migraine may have a greater impact and cause greater dysfunction in the organization of resting-state functional networks in women. Accumulating evidence suggests that topiramate, Onabotulinumtoxin A and calcitonin gene-related peptide (CGRP) monoclonal antibodies are effective as the preventative treatments for CM. Summary: Recent evidence highlights a divergence in the characteristics of CM between male and female populations. The data comparing the treatment response for CM regarding sex are lacking. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the most frequent malignancy in male urogenital system around worldwide. We performed molecular subtyping and prognostic assessment based on consensus genes in patients with PCa. Five cohorts containing 1,046 PCa patients with RNA expression profiles and recorded clinical follow-up information were included. Univariate, multivariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression were used to select prognostic genes and establish the signature. Immunohistochemistry staining, cell proliferation, migration and invasion assays were used to assess the biological functions of key genes. Thirty-nine intersecting consensus prognostic genes from five independent cohorts were identified. Subsequently, an eleven-consensus-gene classifier was established. In addition, multivariate Cox regression analyses showed that the classifier served as an independent indicator of recurrence-free survival in three of the five cohorts. Combined receiver operating characteristic (ROC) analysis achieved synthesized effects by combining the classifier with clinicopathological features in four of five cohorts. SRD5A2 inhibits cell proliferation, while ITGA11 promotes cell migration and invasion, possibly through the PI3K/AKT signaling pathway. To conclude, we established and validated an eleven-consensus-gene classifier, which may add prognostic value to the currently available staging system. By analysis of gene expression profiles of prostate cancer patients from multiple platforms, an eleven-consensus-gene classifier is constructed to provide a robust tool for the prediction of recurrence-free survival. [ABSTRACT FROM AUTHOR]

Faraday wave is a phenomenon of sloshing due to a heave motion of a partially filled tank, which is also called parametric instability or parametric resonance. In the present paper, the phenomenon of faraday wave in a pure heave excited square tank is numerically simulated through the moving particle semi-implicit (MPS) method. The surface tension effect and a new Dirichlet boundary condition for the pressure Poisson equation are considered to avert unphysical fragmentation and clustering of particles in splash simulation. In the numerical simulation, the evolution of wave motion, and the non-linearity together with breaking phenomenon of faraday wave can be observed. The agreement is good in general, both amplitude and phase. Besides, the parameter studies including the excitation frequency and the forcing amplitude are carried out to analyses the mechanism of resonances response. [ABSTRACT FROM AUTHOR]

Pulmonary sequelae following COVID-19 pneumonia have been emerging as a challenge; however, suitable cell sources for studying COVID-19 mechanisms and therapeutics are currently lacking. In this paper, we present a standardized primary alveolar cell culture method for establishing a human alveolar epithelium model that can recapitulate viral infection and cellular plasticity. The alveolar model is infected with a SARS-CoV-2 pseudovirus, and the clinically relevant features of the viral entry into the alveolar type-I/II cells, cytokine production activation, and pulmonary surfactant destruction are reproduced. For this damaged alveolar model, we find that the inhibition of Wnt signaling via XAV939 substantially improves alveolar repair function and prevents subsequent pulmonary fibrosis. Thus, the proposed alveolar cell culture strategy exhibits potential for the identification of pathogenesis and therapeutics in basic and translational research. Yang et al. present an alveolar cell culture method that utilizes primary human alveolar epithelial cells, culturing cells in a small-molecule cocktail supplemented media. The authors show that the longevity of the primary cells culture can be expanded, and study human alveolar development, infection, injury repair, while demonstrating its use for SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

The systematic design of functional peptides has technological and therapeutic applications. However, there is a need for pattern-based search engines that help locate desired functional motifs in primary sequences regardless of their evolutionary conservation. Existing databases such as The Protein Secondary Structure database (PSS) no longer serves the community, while the Dictionary of Protein Secondary Structure (DSSP) annotates the secondary structures when tertiary structures of proteins are provided. Here, we extract 1.7 million helices from the PDB and compile them into a database (Therapeutic Peptide Design database; TP-DB) that allows queries of compounded patterns to facilitate the identification of sequence motifs of helical structures. We show how TP-DB helps us identify a known purification-tag-specific antibody that can be repurposed into a diagnostic kit for Helicobacter pylori. We also show how the database can be used to design a new antimicrobial peptide that shows better Candida albicans clearance and lower hemolysis than its template homologs. Finally, we demonstrate how TP-DB can suggest point mutations in helical peptide blockers to prevent a targeted tumorigenic protein-protein interaction. TP-DB is made available at http://dyn.life.nthu.edu.tw/design/. Here, we present TP-DB; a pattern-based search engine based on 1.67 million helices from the Protein Database (PDB). We demonstrate the utility of TP-DB in identifying microbe-specific antigens, as well as the design of antimicrobial peptides and Protein-protein interaction blockers. [ABSTRACT FROM AUTHOR]

The Mizoroki-Heck reaction and its reductive analogue are staples of organic synthesis, but the ensuing products often lack a chemical handle for further transformation. Here we report an atom-economical cross-coupling of halopyridines and unactivated alkenes under photoredox catalysis to afford a series of alkene halopyridylation products. This protocol with mild and redox neutral conditions contributes broad substrate scope. As a complement to conventional Heck-type reaction, this radical process avoids the involvement of β-H elimination and thus useful pyridyl and halide groups could be simultaneously and regioselectively incorporated onto alkenes. The success depends on TFA-promoted domino photocatalytic oxidative quenching activation and radical-polar crossover pathway. Plausible mechanism is proposed based on mechanistic investigations. Moreover, the reserved C − X bonds of these products are beneficial for performing further synthetic elaborations. The Mizoroki–Heck reaction and its reductive analogue are staples of organic synthesis, but the ensuing products often lack a chemical handle for further transformation. Here the authors present a method to add a heterocycle and transformable halide across a double bond via iridium photocatalysis. [ABSTRACT FROM AUTHOR]

Epithelial-to-mesenchymal transition (EMT) is a transcriptionally governed process by which cancer cells establish a front-rear polarity axis that facilitates motility and invasion. Dynamic assembly of focal adhesions and other actin-based cytoskeletal structures on the leading edge of motile cells requires precise spatial and temporal control of protein trafficking. Yet, the way in which EMT-activating transcriptional programs interface with vesicular trafficking networks that effect cell polarity change remains unclear. Here, by utilizing multiple approaches to assess vesicular transport dynamics through endocytic recycling and retrograde trafficking pathways in lung adenocarcinoma cells at distinct positions on the EMT spectrum, we find that the EMT-activating transcription factor ZEB1 accelerates endocytosis and intracellular trafficking of plasma membrane-bound proteins. ZEB1 drives turnover of the MET receptor tyrosine kinase by hastening receptor endocytosis and transport to the lysosomal compartment for degradation. ZEB1 relieves a plus-end-directed microtubule-dependent kinesin motor protein (KIF13A) and a clathrin-associated adaptor protein complex subunit (AP1S2) from microRNA-dependent silencing, thereby accelerating cargo transport through the endocytic recycling and retrograde vesicular pathways, respectively. Depletion of KIF13A or AP1S2 mitigates ZEB1-dependent focal adhesion dynamics, front-rear axis polarization, and cancer cell motility. Thus, ZEB1-dependent transcriptional networks govern vesicular trafficking dynamics to effect cell polarity change. The way in which metastatic tumour cells control endocytic vesicular trafficking networks to establish a front-rear polarity axis that facilitates motility remains unclear. Here, the authors show that the EMT activator ZEB1 influences vesicular trafficking dynamics to execute cell polarity change. [ABSTRACT FROM AUTHOR]

The advent of pico-aerial vehicles (PAVs) for thermal surveillance has necessitated a better understanding of the flow field around airfoils at ultra-low Reynolds numbers (102 to 103). Previous studies have shown that two airfoils arranged in a tandem configuration can exhibit better aerodynamic performance than two identical airfoils in isolation, but this improvement has only been confirmed at relatively high Reynolds numbers (105 and above). In this parametric study, we numerically simulate the two-dimensional flow field around two tandem NACA 0012 airfoils in ground effect, at a Reynolds number low enough to be relevant to PAVs (Re = 500). With the angle of attack fixed at α = 5° on both airfoils, we investigate the effects of three control parameters, namely the stagger distance, the gap height and the ground clearance, for both isothermal airfoils and fore-heated airfoils. Results show that consistent with previous studies at higher Re, two tandem airfoils are more aerodynamically efficient than two identical airfoils in isolation, especially when the gap height is positive, i.e., when the fore airfoil is higher than the aft airfoil. The aerodynamics of the tandem-airfoil system are strongly influenced by the airfoil-to-airfoil interference arising from the downwash generated by the fore airfoil. The presence of a laminar separation bubble on the suction surface of both airfoils is found to alter the lift and drag coefficients as well as the overall lift-to-drag ratio. The wake of the fore airfoil is often seen impinging on the aft airfoil, which is a key mechanism by which the lift and drag forces are altered. The gains in aerodynamic efficiency achieved by the tandem airfoils become smaller as the stagger distance increases owing to weakened airfoil-to-airfoil interference. The effect of ground clearance on the tandem airfoils is found to be similar to that on two isolated airfoils, with both the lift and drag coefficients increasing with decreasing ground clearance. Heating the fore airfoil of a tandem-airfoil system in ground effect is found to decrease the lift coefficient without much affecting the drag coefficient, resulting in a drop in the lift-to-drag ratio. Overall these results lend new insight into the ultra-low-Re aerodynamics of tandem airfoils under both isothermal and heated conditions, advancing the development of the next generation of PAVs for thermal surveillance and other assorted applications. [ABSTRACT FROM AUTHOR]

In this numerical study, we use two-dimensional scale-adaptive simulations to investigate the lift characteristics of two tandem airfoils in the globally unstable wake of a cylinder at a Reynolds number of 104, with and without cylinder heating. Both airfoils have NACA 0012 profiles and are at the same angle of attack (α = 10°), implying zero decalage. We find that the lift characteristics of both airfoils depend strongly on the streamwise distance (X) between the trailing point of the cylinder and the leading edge of the fore airfoil. At the conditions of this study (1 ≤ X/D ≤ 5, where D is the cylinder diameter), both airfoils experience periodic limit-cycle oscillations in their lift coefficients (Cl) at the same frequency. However, when X/D < 3, abrupt decreases occur in both the Cl amplitude of the fore airfoil and the Cl oscillation frequency of both airfoils. We attribute these decreases to the fore airfoil entering the wavemaker region of the self-excited cylinder wake and altering its global instability properties. Heating the cylinder to a temperature above that of the free-stream leads to monotonic decreases in the oscillation frequency and amplitude of Cl for both airfoils. For the purpose of harvesting the maximum energy from two tandem airfoils behind a cylinder, our findings suggest that (i) the airfoils should be positioned as close as possible to the cylinder without disrupting the wavemaker of the globally unstable wake and (ii) the cylinder should be prevented from heating up. [ABSTRACT FROM AUTHOR]

Background: Considering the involvement of genetics in migraine pathogenesis in diverse ethnic populations, genome-wide association studies (GWAS) are being conducted to identify migraine-susceptibility genes. However, limited surveys have focused on the onset age of migraine (AoM) in Asians. Therefore, in this study, we aimed to identify the susceptibility loci of migraine considering the AoM in an Asian population. Methods: We conducted a GWAS in 715 patients with migraine of Han Chinese ethnicity, residing in Taiwan, to identify the susceptibility genes associated with AoM. Based on our standard demographic questionnaire, the population was grouped into different subsets. Single-nucleotide polymorphism (SNP) associations were examined using PLINK in different AoM onset groups. Results: We discovered eight novel susceptibility loci correlated with AoM that reached the GWAS significance level in the Han Chinese population. First, rs146094041 in ESRRG was associated with AoM ≤ 12 years. The other SNPs including rs77630941 in CUX1, rs146778855 in CDH18, rs117608715 in NOL3, rs150592309 in PRAP1, and rs181024055 in NRAP were associated with the later AoM. Conclusions: To our knowledge, this is the first GWAS to investigate the AoM in an Asian Han Chinese population. Our newly discovered susceptibility genes may have prospective associations with migraine pathogenesis. [ABSTRACT FROM AUTHOR]

A porous supramolecular framework has been for the first time revealed to undergo interpenetration in crystal and non-interpenetration in solution. A new supramolecular organic framework Bu-SOF has been constructed from the co-assembly of a tetracationic tetrahedral monomer and cucurbit[8]uril (CB[8]) in water through the encapsulation of two anti-parallel n-butyl chains by CB[8]. X-ray diffraction analysis reveals that Bu-SOF forms 3-fold interpenetrated networks in crystals grown by evaporation of its solution in water. 1H NMR, dynamic light scattering and isothermal titration calorimetric experiments confirm that Bu-SOF is also formed in water. Solid samples, prepared by lyophilizing the aqueous solution of Bu-SOF, can adsorb nanoscaled organic dyes, supporting the porosity of the framework and thus non-interpenetration in solution. The avoidance of interpenetration of Bu-SOF in solution has been attributed to the filling of water inside the porous framework as well as the electrostatic repulsion of the appended bipyridinium units of the tetrahedral building block. [ABSTRACT FROM AUTHOR]

The c-MET receptor is a receptor tyrosine kinase (RTK) that plays essential roles in normal cell development and motility. Aberrant activation of c-MET can lead to both tumors growth and metastatic progression of cancer cells. C-MET can be activated by either hepatocyte growth factor (HGF), or its natural isoform NK1. Here, we report the cryo-EM structures of c-MET/HGF and c-MET/NK1 complexes in the active state. The c-MET/HGF complex structure reveals that, by utilizing two distinct interfaces, one HGF molecule is sufficient to induce a specific dimerization mode of c-MET for receptor activation. The binding of heparin as well as a second HGF to the 2:1 c-MET:HGF complex further stabilize this active conformation. Distinct to HGF, NK1 forms a stable dimer, and bridges two c-METs in a symmetrical manner for activation. Collectively, our studies provide structural insights into the activation mechanisms of c-MET, and reveal how two isoforms of the same ligand use dramatically different mechanisms to activate the receptor. Activation of c-MET receptor tyrosine kinase involves hepatocyte growth factor (HGF) and glycosaminoglycans, but the molecular mechanism is still under debate. Here, the authors present cryoEM structures of c-MET bound to two HGF splice variants and heparin, revealing the structural basis for c-MET activation. [ABSTRACT FROM AUTHOR]

Context: Livestock grazing is one of the most widespread types of anthropogenic land use, even occurs in many protected areas and has become a threat to wildlife worldwide. Understanding livestock-wildlife interactions is crucial for rare large carnivores conservation. In China, free-ranging cattle within forests degrade the habitat of the tigers (Panthera tigris) and leopards (Panthera pardus), but quantitative assessments of how livestock affect the spatial and temporal use by the major ungulate prey of the two endangered felids are very limited. Objectives: This study aimed to examine the interactions of several sympatric wildlife species with livestock at a fine spatiotemporal scale in a human-dominated forest landscape. Methods: Based on a large-scale camera-trapping data across the China-Russia border, we used N-mixture models, two-species occupancy models and activity pattern overlap to understand the effects of cattle grazing on three ungulate species (sika deer Cervus nippon, wild boars Sus scrofa and roe deer Capreolus pygargus). Results: Spatially, with cattle activity increasing, wild boar and roe deer had different degrees of decline in the intensity of habitat use. Sika deer were displaced as more cattle encroached on forest habitat. Temporally, in the presence of cattle, wild boar and sika deer decreased their activities in the day. In addition, three wild ungulates trend to exhibit lower spatiotemporal overlap with cattle at shared camera sites. Conclusions: Our study shows that wildlife species may reduce the probability of habitat use by spatial avoidance and changing the daily activity patterns. We underscore that fine-scale (i.e. camera-site level) spatiotemporal avoidance is likely a key component of co-occurrence between livestock and the sympatry of competing ungulates inhabiting forest ecosystems. Given prey were depressed, efforts to minimize the livestock disturbance on these species need to be considered to ensure their sustained recoveries. [ABSTRACT FROM AUTHOR]