In response to the problem of missing traffic flow data on highways, to solve the problem of insufficient mining of traffic flow characteristics using existing spatiotemporal correlation repair ...methods, a missing data repair method based on spatiotemporal fusion adversarial network is proposed based on analyzing the spatiotemporal characteristics of traffic flow, this method utilizes the fusion of GRU and GCN to capture the fine-grained spatiotemporal relationships of traffic flow, optimizes the generator and discriminator of the adversarial network, and achieves accurate repair of missing data. Experiments based on real data have shown that under various missing modes and rates, the model can learn the topological relationships of the road network, capture the temporal regularity and spatiotemporal correlation in the data, and effectively impute missing data.
Background Patients with peanut allergy have highly stable pathologic antibody repertoires to the immunodominant B-cell epitopes of the major peanut allergens Ara h 1 to 3. Objective We used a ...peptide microarray technique to analyze the effect of treatment with peanut oral immunotherapy (OIT) on such repertoires. Methods Measurements of total peanut-specific IgE (psIgE) and peanut-specific IgG4 (psIgG4 ) were made with CAP-FEIA. We analyzed sera from 22 patients with OIT and 6 control subjects and measured serum specific IgE and IgG4 binding to epitopes of Ara h 1 to 3 using a high-throughput peptide microarray technique. Antibody affinity was measured by using a competitive peptide microarray, as previously described. Results At baseline, psIgE and psIgG4 diversity was similar between patients and control subjects, and there was broad variation in epitope recognition. After a median of 41 months of OIT, polyclonal psIgG4 levels increased from a median of 0.3 μg/mL (interquartile range 25% to 75%, 0.1-0.43 μg/mL) at baseline to 10.5 μg/mL (interquartile range 25% to 75%, 3.95-45.48 μg/mL; P < .0001) and included de novo specificities. psIgE levels were reduced from a median baseline of 85.45 kUA /L (23.05-101.0 kUA /L) to 7.75 kUA /L (2.58-30.55 kUA /L, P < .0001). Affinity was unaffected. Although the psIgE repertoire contracted in most OIT-treated patients, several subjects generated new IgE specificities, even as the total psIgE level decreased. Global epitope-specific shifts from IgE to IgG4 binding occurred, including at an informative epitope of Ara h 2. Conclusion OIT differentially alters Ara h 1 to 3 binding patterns. These changes are variable between patients, are not observed in control subjects, and include a progressive polyclonal increase in IgG4 levels, with concurrent reduction in IgE amount and diversity.
Effective treatment using antibiotic vancomycin requires close monitoring of serum drug levels due to its narrow therapeutic index. In the current practice, physicians use various dosing algorithms ...for dosage titration, but these algorithms reported low success in achieving therapeutic targets. We explored using artificial intelligent to assist vancomycin dosage titration.
We used a novel method to generate the label for each record and only included records with appropriate label data to generate a clean cohort with 2,282 patients and 7,912 injection records. Among them, 64% of patients were used to train two machine learning models, one for initial dose recommendation and another for subsequent dose recommendation. The model performance was evaluated using two metrics: PAR, a pharmacology meaningful metric defined by us, and Mean Absolute Error (MAE), a commonly used regression metric.
In our 3-year data, only a small portion (34.1%) of current injection doses could reach the desired vancomycin trough level (14-20
). Both PAR and MAE of our machine learning models were better than the classical pharmacokinetic models. Our model also showed better performance than the other previously developed machine learning models in our test data.
We developed machine learning models to recommend vancomycin dosage. Our results show that the new AI-assisted dosage titration approach has the potential to improve the traditional approaches. This is especially useful to guide decision making for inexperienced doctors in making consistent and safe dosing recommendations for high-risk medications like vancomycin.
Driverless buses are expected to play a vital role in the future, and better public acceptance will provide a social foundation for its development. In this study, two new variables, personal ...innovativeness (PI) and perceived risk (PR), were incorporated into the integrated technology acceptance model (UTAUT, unified theory of acceptance and use of technology) to construct an extended model, which was then applied to explore the influencing factors for the public acceptance of driverless buses. The quality of this extended model was verified through survey data collected in Chongqing, China. The structural equation modeling (SEM) method was adopted to quantitatively describe the impact of each factor on acceptance intention (AI) as well as the mutual influence relationships between the factors. The moderating effects of demographic attributes (gender, age, and education level) on each factor in the model were also analyzed. The results showed that PI and PR are the most critical factors that affect the public’s acceptance intention; effort expectancy (EE), performance expectancy (PE), social influence (SI), and facilitating condition (FC) can also determine the acceptance intention to a certain extent; gender, age, and education level have exhibited significantly different moderating effects on the influencing factors. The explanatory power of the current research model for acceptance intention has reached 48%. This study has confirmed the applicability of the extended UTAUT model to the research of driverless bus acceptance and the research outcomes can serve as a reference basis for improving the service quality of driverless buses in China.
Background Peanut allergy is relatively common, typically permanent, and often severe. Double-blind, placebo-controlled food challenge is considered the gold standard for the diagnosis of food ...allergy–related disorders. However, the complexity and potential of double-blind, placebo-controlled food challenge to cause life-threatening allergic reactions affects its clinical application. A laboratory test that could accurately diagnose symptomatic peanut allergy would greatly facilitate clinical practice. Objective We sought to develop an allergy diagnostic method that could correctly predict symptomatic peanut allergy by using peptide microarray immunoassays and bioinformatic methods. Methods Microarray immunoassays were performed by using the sera from 62 patients (31 with symptomatic peanut allergy and 31 who had outgrown their peanut allergy or were sensitized but were clinically tolerant to peanut). Specific IgE and IgG4 binding to 419 overlapping peptides (15 mers, 3 offset) covering the amino acid sequences of Ara h 1, Ara h 2, and Ara h 3 were measured by using a peptide microarray immunoassay. Bioinformatic methods were applied for data analysis. Results Individuals with peanut allergy showed significantly greater IgE binding and broader epitope diversity than did peanut-tolerant individuals. No significant difference in IgG4 binding was found between groups. By using machine learning methods, 4 peptide biomarkers were identified and prediction models that can predict the outcome of double-blind, placebo-controlled food challenges with high accuracy were developed by using a combination of the biomarkers. Conclusions In this study, we developed a novel diagnostic approach that can predict peanut allergy with high accuracy by combining the results of a peptide microarray immunoassay and bioinformatic methods. Further studies are needed to validate the efficacy of this assay in clinical practice.
We have comprehensively mapped long-range associations between chromosomal regions throughout the fission yeast genome using the latest genomics approach that combines next generation sequencing and ...chromosome conformation capture (3C). Our relatively simple approach, referred to as enrichment of ligation products (ELP), involves digestion of the 3C sample with a 4 bp cutter and self-ligation, achieving a resolution of 20 kb. It recaptures previously characterized genome organizations and also identifies new and important interactions. We have modeled the 3D structure of the entire fission yeast genome and have explored the functional relationships between the global genome organization and transcriptional regulation. We find significant associations among highly transcribed genes. Moreover, we demonstrate that genes co-regulated during the cell cycle tend to associate with one another when activated. Remarkably, functionally defined genes derived from particular gene ontology groups tend to associate in a statistically significant manner. Those significantly associating genes frequently contain the same DNA motifs at their promoter regions, suggesting that potential transcription factors binding to these motifs are involved in defining the associations among those genes. Our study suggests the presence of a global genome organization in fission yeast that is functionally similar to the recently proposed mammalian transcription factory.
Background Shellfish allergy is a long-lasting disorder typically affecting adults. Despite its high prevalence, there is limited information about allergenic shrimp proteins and the epitopes ...implicated in such allergic reactions. Objective We sought to identify the IgE-binding epitopes of the 4 shrimp allergens and to characterize epitope recognition profiles of children and adults with shrimp allergy. Methods Fifty-three subjects, 34 children and 19 adults, were selected with immediate allergic reactions to shrimp, increased shrimp-specific serum IgE levels, and positive immunoblot binding to shrimp. Study subjects and 7 nonatopic control subjects were tested by means of peptide microarray for IgE binding with synthetic overlapping peptides spanning the sequences of Litopenaeus vannamei shrimp tropomyosin, arginine kinase (AK), myosin light chain (MLC), and sarcoplasmic calcium-binding protein (SCP). The Wilcoxon test was used to determine significant differences in z scores between patients and control subjects. Results The median shrimp IgE level was 4-fold higher in children than in adults (47 vs 12.5 kUA /L). The frequency of allergen recognition was higher in children (tropomyosin, 81% 94% for children and 61% for adults; MLC, 57% 70% for children and 31% for adults; AK, 51% 67% for children and 21% for adults; and SCP, 45% 59% for children and 21% for adults), whereas control subjects showed negligible binding. Seven IgE-binding regions were identified in tropomyosin by means of peptide microarray, confirming previously identified shrimp epitopes. In addition, 3 new epitopes were identified in tropomyosin (epitopes 1, 3, and 5b-c), 5 epitopes were identified in MLC, 3 epitopes were identified in SCP, and 7 epitopes were identified in AK. Interestingly, frequency of individual epitope recognition, as well as intensity of IgE binding, was significantly greater in children than in adults for all 4 proteins. Conclusions Children with shrimp allergy have greater shrimp-specific IgE antibody levels and show more intense binding to shrimp peptides and greater epitope diversity than adults.
Mesenchymal stem cell (MSC), a widely used adult stem cell candidate for regenerative medicine, has been shown to exert some of its therapeutic effects through the secretion of extracellular vesicles ...(EVs). These homogenously sized EVs of 100-150 ηm exhibited many exosome-like biophysical and biochemical properties and carry both proteins and RNAs. Recently, exosome-associated proteins in this MSC EV preparation were found to segregate primarily to those EVs that bind cholera toxin B chain (CTB), a GM1 ganglioside-specific ligand, and pulse-chase experiments demonstrated that these EVs have endosomal origin and carried many of the exosome-associated markers. Here, we report that only a fraction of the MSC EV proteome was found in CTB-bound EVs. Using Annexin V (AV) and Shiga toxin B subunit (ST) with affinities for phosphatidylserine and globotriaosylceramide, respectively, AV- and a ST-binding EV were identified. CTB-, AV- and ST-binding EVs all carried actin. However, the AV-binding EVs carried low or undetectable levels of the exosome-associated proteins. Only the ST-binding EVs carried RNA and EDA-containing fibronectin. Proteins in AV-binding EVs were also different from those released by apoptotic MSCs. CTB- and AV-binding activities were localized to the plasma membrane and cytoplasm of MSCs, while ST-binding activity was localized to the nucleus. Together, this study demonstrates that cells secrete many types of EVs. Specifically, MSCs secrete at least 3 types. They can be differentially isolated based on their affinities for membrane lipid-binding ligands. As the subcellular sites of the binding activities of these ligands and cargo load are different for each EV type, they are likely to have a different biogenesis pathway and possibly different functions.
Background The peptide microarray is a novel assay that facilitates high-throughput screening of peptides with a small quantity of sample. Objective We sought to use overlapping peptides of milk ...allergenic proteins as a model system to establish a reliable and sensitive peptide microarray-based immunoassay for large-scale epitope mapping of food allergens. Methods A milk peptide microarray was developed by using commercially synthesized peptides (20-mers, 3 offset) covering the primary sequences of αs1 -casein, αs2 -casein, β-casein, κ-casein, and β-lactoglobulin. Conditions for printing and immunolabeling were optimized using a serum pool of 5 patients with milk allergy. Reproducibility of the milk peptide microarray was evaluated using replicate arrays immunolabeled with the serum pool, whereas specificity and sensitivity were assessed by using serial dilution of the serum pool and a peptide inhibition assay. Results Our results show that epitopes identified by the peptide microarray were mostly consistent with those identified previously by SPOT membrane technology, but with specific binding to a few newly identified epitopes of milk allergens. Data from replicate arrays were reproducible ( r ≥ 0.92) regardless of printing lots, immunolabeling, and serum pool batches. Using the serially diluted serum pool, we confirmed that IgE antibody binding detected in the array was specific. Peptide inhibition of IgE binding to the same peptide and overlapping peptides further confirmed the specificity of the array. Conclusion A reliable peptide microarray was established for large-scale IgE epitope mapping of milk allergens, and this robust technology could be applied for epitope mapping of other food allergens.
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•ETCB and NDTC were synthesized. And their polymers were obtained by electropolymerization.•Both the polymer films showed well-defined oxidation and reduction process.•The PETCB and ...PNDTC films showed reasonable optical contrast and two colors under different potentials.•The copolymer film based on ETCB and EDOT could display five colors and higher optical contrast.
Two novel donor–acceptor type monomers, ethyl 4-(3,6-di(thiophen-2-yl)-9H-carbazole-9-yl)-benzoate (ETCB) and 9-(4-nitrophenyl)-3,6-di(thiophen-2-yl)-9H-carbazole (NDTC), were synthesized and characterized. Both the monomers show good electrochemical activity. UV–vis absorption studies reveal that the spectra of them are obviously different due to the introduction of the acceptor groups with different polarity, and the compound with –NO2 group has lower band gap. Fluorescent spectral studies indicate that the solution of ETCB in DCM exhibits sky-blue emission, while the NDTC hardly displays the fluorescence because of stronger intramolecular charge transfer. Their polymers can be synthesized by electropolymerization, and both the films show well-defined oxidation and reduction process. Spectroelectrochemical analysis reveals that PETCB film displays the color change from yellow–green (neutral) to blue–purple (oxidized), while the color change of PNDTC film is from yellow (neutral) to gray (oxidized). Both the polymer films exhibit reasonable optical contrast and switching time. Moreover, the copolymer based on ETCB and 3,4-ethylenedioxythiophene (EDOT) is also investigated. The copolymer could show five colors change under different applied potentials and higher optical contrast (50% of 1100nm) and coloration efficiency (356.88cm2C−1).
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