Single-nucleotide polymorphism (SNPs) may cause the diverse functional impact on RNA or protein changing genotype and phenotype, which may lead to common or complex diseases like cancers. Accurate prediction of the functional impact of SNPs is crucial to discover the ‘influential’ (deleterious, pathogenic, disease-causing, and predisposing) variants from massive background polymorphisms in the human genome. Increasing computational methods have been developed to predict the functional impact of variants. However, predictive performances of these computational methods on massive genomic variants are still unclear. In this regard, we systematically evaluated 14 important computational methods including specific methods for one type of variant and general methods for multiple types of variants from several aspects; none of these methods achieved excellent (AUC ≥ 0.9) performance in both data sets. CADD and REVEL achieved excellent performance on multiple types of variants and missense variants, respectively. This comparison aims to assist researchers and clinicians to select appropriate methods or develop better predictive methods.
Background. Exosomes are extracellular vesicles that play important roles in various physiological and pathological functions. Previous studies have demonstrated that exosome-derived contents are promising biomarkers to inform the pathogenesis and diagnosis of major depressive disorder and schizophrenia. Methods. We used ultraperformance liquid chromatography-tandem mass spectrometry to analyze the differentially expressed metabolites in serum exosomes of patients with bipolar disorder (BD) and evaluated the potential of exosomal metabolites as biomarkers for BD. Results. Our results showed 26 differentially expressed serum exosomal metabolites in patients with BD (
) when compared with healthy control (HC) subjects (
), and these differentially expressed metabolites were enriched in pathways related to sugar metabolism. We then utilized random forest classifier and identified 15 exosomal metabolites that can be used to classify samples from patients with BD and HC subjects with 0.838 accuracy (95% CI, 0.604–1.00) in the training set of participants. These 15 metabolites showed excellent performance in differentiating between patients with BD and HC subjects in the testing set of participants, with 0.971 accuracy (95% CI, 0.865–1.00). Importantly, the 15 exosomal metabolites also showed good to excellent performance in differentiating between BD patients and other major psychiatric diseases (major depressive disorder and schizophrenia). Conclusion. Collectively, our findings for the first time revealed a potential role of exosomal metabolite dysregulations in the onset and/or development of BD and suggested that blood exosomal metabolites are strong candidates to inform the diagnosis of BD.
Landslide trails are important elements of landslide inventory maps, providing valuable information for landslide risk and hazard assessment. Compared with traditional manual mapping, skeletonization methods offer a more cost-efficient way to map landslide trails, by automatically generating centerlines from landslide polygons. However, a challenge to existing skeletonization methods is that expert knowledge and manual intervention are required to obtain a branchless skeleton, which limits the applicability of these methods. To address this problem, a new workflow for landslide trail extraction (LTE) is proposed in this study. To avoid generating redundant branches and to improve the degree of automation, two endpoints, i.e., the crown point and the toe point, of the trail were determined first, with reference to the digital elevation model. Thus, a fire extinguishing model (FEM) is proposed to generate skeletons without redundant branches. Finally, the effectiveness of the proposed method is verified, by extracting landslide trails from landslide polygons of various shapes and sizes, in two study areas. Experimental results show that, compared with the traditional grassfire model-based skeletonization method, the proposed FEM is capable of obtaining landslide trails without spurious branches. More importantly, compared with the baseline method in our previous work, the proposed LTE workflow can avoid problems including incompleteness, low centrality, and direction errors. This method requires no parameter tuning and yields excellent performance, and is thus highly valuable for practical landslide mapping.
Calcium (Ca2+) elevation is an essential secondary messenger in many cellular processes, including disease progression and adaptation to external stimuli, e.g., gravitational load. Therefore, mapping and quantifying Ca2+ signaling with a high spatiotemporal resolution is a key challenge. However, particularly on microgravity platforms, experiment time is limited, allowing only a small number of replicates. Furthermore, experiment hardware is exposed to changes in gravity levels, causing experimental artifacts unless appropriately controlled. We introduce a new experimental setup based on the fluorescent Ca2+ reporter CaMPARI2, onboard LED arrays, and subsequent microscopic analysis on the ground. This setup allows for higher throughput and accuracy due to its retrograde nature. The excellent performance of CaMPARI2 was demonstrated with human chondrocytes during the 75th ESA parabolic flight campaign. CaMPARI2 revealed a strong Ca2+ response triggered by histamine but was not affected by the alternating gravitational load of a parabolic flight.
The coefficient of thermal expansion (CTE) is an important property of ultra-low expansion (ULE) glass, and the ultrasonic velocity method has shown excellent performance for the nondestructive measurement of CTE in large ULE glass. In this method, the accurate acquisition of the ultrasonic velocity in ULE glass is necessary. Herein, we present a correlation method to determine the ultrasonic TOF in ULE glass and to further obtain the ultrasonic longitudinal wave velocity (cL) indirectly. The performance of this method was verified by simulations. Considering the dependence of cL on temperature (T), we carried out the derivation of the analytical model between cL and T. Based on reasonable constant assumptions in the physical sense, a cL–T exponential model was produced, and some experimental results support this model. Additional experiments were carried out to validate the accuracy of the cL–T exponential model. The studies we conducted indicate that the cL–T exponential model can reliably predict the ultrasonic velocity in ULE glass at different temperatures, providing a means for the nondestructive CTE measurement of large ULE glass at a specified temperature.
Sparse frequency agile orthogonal frequency division multiplexing (SFA-OFDM) signal brings excellent performance to electronic counter-countermeasures (ECCM) and reduces the complexity of the radar system. However, frequency agility makes coherent processing a much more challenging task for the radar, which leads to the discontinuity of the echo phase in a coherent processing interval (CPI), so the fast Fourier transform (FFT)-based method is no longer a valid way to complete the coherent integration. To overcome this problem, we proposed a novel scheme to estimate both super-resolution range and velocity. The subcarriers of each pulse are firstly synthesized in time domain. Then, the range and velocity estimations for the SFA-OFDM radar are regarded as the parameter estimations of a linear array. Finally, both the super-resolution range and velocity are obtained by exploiting the multiple signal classification (MUSIC) algorithm. Simulation results are provided to demonstrate the effectiveness of the proposed method.
BiFeO3 is a photocatalyst with excellent performance. However, its applications are limited due to its wide bandgap. In this paper, MIL-101(Fe)@BiOI composite material is synthesized by hydrothermal method and then calcined at high temperature to obtain BiFeO3@Bi5O7I composite material with high adsorption capacity. Among them, An n-n heterojunction is formed, which improves the efficiency of charge transfer, and the recombination of photo-generated electrons and holes prevents the improvement of photocatalytic efficiency and stability. The result of photocatalytic degradation of tetracycline under visible light irradiation showed, BiFeO3@Bi5O7I (1:2) has the best photodegradation effect, with a removal rate of 86.4%, which proves its potential as a photocatalytic degradation material.
This article disclosed the influence of acid-ether ratio, n(SH)/n(IPEG), and n(APS)/n(IPEG) on adsorption and fluidity performance. The optimum synthetic parameters of acid-ether ratio, n(SH)/n(IPEG) and n(APS)/n(IPEG) were 0.5, 0.35 and 0.05, respectively. The rheology fitting equation was τ= 719.55γ+ 1834.54. And the correlation coefficient was 0.9843. The cement paste conformed to the law of pseudoplastic fluid. The preferred PCE-11 had excellent performance in freshly mixed and hardened concrete.