Pedestrian dynamics in single-file movement of crowd with different age compositions

An aging population is bringing new challenges to the management of escape routes and facility design in many countries. This paper investigates pedestrian movement properties of crowd with different age compositions. Three pedestrian groups are considered: young student group, old people group and mixed group. It is found that traffic jams occur more frequently in mixed group due to the great differences of mobilities and self-adaptive abilities among pedestrians. The jams propagate backward with a velocity 0.4 m/s for global density around 1.75 m-1 and 0.3 m/s for higher than 2.3 m-1. The fundamental diagrams of the three groups are obviously different from each other and cannot be unified into one diagram by direct non-dimensionalization. Unlike previous studies, three linear regimes in mixed group but only two regimes in young student group are observed in the headway-velocity relation, which is also verified in the fundamental diagram. Different ages and mobilities of pedestrians in a crowd cause the heterogeneity of system and influence the properties of pedestrian dynamics significantly. It indicates that the density is not the only factor leading to jams in pedestrian traffic. The composition of crowd has to be considered in understanding pedestrian dynamics and facility design.Comment: 11 pages, 13 figures, 3 table

Prediction of pediatric dose of tirzepatide from the reference adult dose using physiologically based pharmacokinetic modelling

Tirzepatide is an emerging hypoglycemic agent that has been increasing used in adults, yet its pharmacokinetic (PK) behavior and dosing regimen in pediatric population remain unclear. This study aimed to employ the physiologically based pharmacokinetic (PBPK) model to predict changes of tirzepatide exposure in pediatric population and to provide recommendations for its dose adjustments. A PBPK model of tirzepatide in adults was developed and verified by comparing the simulated plasma exposure with the observed data using PK-Sim&MoBi software. This model was then extrapolated to three specific age subgroups, i.e., children (10–12 years), early adolescents (12–15 years), and adolescents (15–18 years). Each subgroup included healthy and obese population, respectively. All known age-related physiological changes were incorporated into the pediatric model. To identify an appropriate dosing regimen that yielded PK parameters which were comparable to those in adults, the PK parameters for each aforementioned subgroup were predicted at pediatric doses corresponding to 87.5%, 75%, 62.5%, and 50% of the adult reference dose. According to the results of simulation, dose adjustments of tirzepatide are necessary for the individuals aged 10–12 years, as well as those aged 12–15 years with healthy body weights. In conclusion, the adult PBPK model of tirzepatide was successfully developed and validated for the first time, and the extrapolated pediatric model could be used to predict pediatric dosing regimen of tirzepatide, which will provide invaluable references for the design of future clinical trials and its rational use in the pediatric population

An improvement of sufficient condition for kk-leaf-connected graphs

For integer $k\geq2,$ a graph $G$ is called $k$-leaf-connected if $|V(G)|\geq k+1$ and given any subset $S\subseteq V(G)$ with $|S|=k,$ $G$ always has a spanning tree $T$ such that $S$ is precisely the set of leaves of $T.$ Thus a graph is $2$-leaf-connected if and only if it is Hamilton-connected. In this paper, we present a best possible condition based upon the size to guarantee a graph to be $k$-leaf-connected, which not only improves the results of Gurgel and Wakabayashi [On $k$-leaf-connected graphs, J. Combin. Theory Ser. B 41 (1986) 1-16] and Ao, Liu, Yuan and Li [Improved sufficient conditions for $k$-leaf-connected graphs, Discrete Appl. Math. 314 (2022) 17-30], but also extends the result of Xu, Zhai and Wang [An improvement of spectral conditions for Hamilton-connected graphs, Linear Multilinear Algebra, 2021]. Our key approach is showing that an $(n+k-1)$-closed non-$k$-leaf-connected graph must contain a large clique if its size is large enough. As applications, sufficient conditions for a graph to be $k$-leaf-connected in terms of the (signless Laplacian) spectral radius of $G$ or its complement are also presented.Comment: 15 pages, 2 figure

Gene-to-metabolite network for biosynthesis of lignans in MeJA-elicited Isatis indigotica hairy root cultures.

Root and leaf tissue of Isatis indigotica shows notable anti-viral efficacy, and are widely used as "Banlangen" and "Daqingye" in traditional Chinese medicine. The plants' pharmacological activity is attributed to phenylpropanoids, especially a group of lignan metabolites. However, the biosynthesis of lignans in I. indigotica remains opaque. This study describes the discovery and analysis of biosynthetic genes and AP2/ERF-type transcription factors involved in lignan biosynthesis in I. indigotica. MeJA treatment revealed differential expression of three genes involved in phenylpropanoid backbone biosynthesis (IiPAL, IiC4H, Ii4CL), five genes involved in lignan biosynthesis (IiCAD, IiC3H, IiCCR, IiDIR, and IiPLR), and 112 putative AP2/ERF transcription factors. In addition, four intermediates of lariciresinol biosynthesis were found to be induced. Based on these results, a canonical correlation analysis using Pearson's correlation coefficient was performed to construct gene-to-metabolite networks and identify putative key genes and rate-limiting reactions in lignan biosynthesis. Over-expression of IiC3H, identified as a key pathway gene, was used for metabolic engineering of I. indigotica hairy roots, and resulted in an increase in lariciresinol production. These findings illustrate the utility of canonical correlation analysis for the discovery and metabolic engineering of key metabolic genes in plants

Efficacy and safety of teneligliptin in patients with type 2 diabetes mellitus: a Bayesian network meta-analysis

BackgroundAs a popular antidiabetic drug, teneligliptin has been used for over 10 years, but its efficacy and safety have rarely been systematically evaluated. Therefore, a Bayesian network meta-analysis was conducted to evaluate the efficacy and safety of teneligliptin in patients with type 2 diabetes mellitus (T2DM).MethodsWe systematically searched PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. Randomized controlled trials (RCTs) comparing teneligliptin with placebo or active comparators in T2DM patients for at least 12 weeks were included in the study. Data analysis was performed using R 4.2.3 and Stata 17.0 software. Each outcome was presented as a mean difference (MD) or an odds ratio (OR) along with 95% confidence interval (CI) and the surface under the cumulative ranking curve value (SUCRA).ResultsA total of 18 RCTs with 3,290 participants with T2DM were included in this study. Generally, compared to placebo, sitagliptin, vildagliptin, metformin, and bromocriptine, 20 mg of teneligliptin showed better efficacy in reducing HbA1c (MD [95% CI], −0.78 [−0.86 to −0.70], −0.08 [−0.36 to 0.19], −0.04 [−0.72 to 0.60], −0.12 [−0.65 to 0.42], and −0.50 [−0.74 to −0.26], respectively) and fasting plasma glucose (FPG) (MD [95% CI], −18.02 [−20.64 to −15.13], 1.17 [−9.39 to 11.70], −8.06 [−30.95 to 14.35], −2.75 [−18.89 to 13.01], and −34.23 [−45.93 to −22.96], respectively), and 40 mg of teneligliptin also showed better efficacy in reducing HbA1c (MD [95% CI], −0.84 [−1.03 to −0.65], −0.15 [−0.49 to 0.19], −0.10 [−0.81 to 0.57], −0.18 [−0.76 to 0.39], and −0.56 [−0.88 to −0.26], respectively) and FPG (MD [95% CI], −20.40 [−26.07 to −14.57], −1.20 [−13.21 to 10.38], −10.43 [−34.16 to 12.65], −5.13 [−22.21 to 11.66], and −36.61 [−49.33 to −24.01], respectively). Compared to placebo, 20 mg of teneligliptin showed no significant difference in incidences of hypoglycemia and gastrointestinal adverse events (OR [95% CI], 1.30 [0.70 to 2.19] and 1.48 [0.78 to 2.98], respectively), and 40 mg of teneligliptin showed no significant difference in incidence of hypoglycemia (OR [95% CI], 2.63 [0.46 to 8.10]). Generally, antidiabetic effect and hypoglycemia risk of teneligliptin gradually increased as its dose increased from 5 mg to 40 mg. Compared to 20 mg of teneligliptin, 40 mg of teneligliptin showed superior efficacy and no-inferior safety, which was considered as the best option in reducing HbA1c, FPG, and 2h PPG and increasing proportion of the patients achieving HbA1c < 7% (SUCRA, 85.51%, 84.24%, 79.06%, and 85.81%, respectively) among all the included interventions.ConclusionCompared to sitagliptin, vildagliptin, metformin, bromocriptine, and placebo, teneligliptin displayed favorable efficacy and acceptable safety in treating T2DM. Twenty milligrams or 40 mg per day was the optimal dosage regimen of teneligliptin. The results of this study will provide important evidence-based basis for rational use of teneligliptin and clinical decision-making of T2DM medication

Zero-Shot Rumor Detection with Propagation Structure via Prompt Learning

The spread of rumors along with breaking events seriously hinders the truth in the era of social media. Previous studies reveal that due to the lack of annotated resources, rumors presented in minority languages are hard to be detected. Furthermore, the unforeseen breaking events not involved in yesterday's news exacerbate the scarcity of data resources. In this work, we propose a novel zero-shot framework based on prompt learning to detect rumors falling in different domains or presented in different languages. More specifically, we firstly represent rumor circulated on social media as diverse propagation threads, then design a hierarchical prompt encoding mechanism to learn language-agnostic contextual representations for both prompts and rumor data. To further enhance domain adaptation, we model the domain-invariant structural features from the propagation threads, to incorporate structural position representations of influential community response. In addition, a new virtual response augmentation method is used to improve model training. Extensive experiments conducted on three real-world datasets demonstrate that our proposed model achieves much better performance than state-of-the-art methods and exhibits a superior capacity for detecting rumors at early stages.Comment: AAAI 202

Coating effect of micro-sized droplets impacting on low temperature spherical particles

[EN] In this paper, the effect of spray droplets on the coating of cold spherical particles was studied.The microcapsule granulator produces micron-sized droplets to coat the spherical particles in cold storage, and the high-definition camera and precision balance are used to photograph and weigh the particles before and after the spraying. The droplets are obtained by using the image and data processing technology coating area and coating quality, the droplet coating effect was evaluated by a number of dimensionless parameters such as coating ratio and mass ratio.By orthogonal design experiment and uncertainty analysis, the effects of droplet size and flow rate, spherical particle temperature and diameter on coating effect were studied, and the effect of droplet group coating on low temperature spherical particles was obtained.The authors acknowledge Projects supported by the National Natural Science Foundation of China (Grant No. 31571906 & No.21506163).Wu, X.; Ma, X.; Xu, Q.; Li, Z.; Wang, R. (2018). Coating effect of micro-sized droplets impacting on low temperature spherical particles. En IDS 2018. 21st International Drying Symposium Proceedings. Editorial Universitat Politècnica de València. 1759-1766. https://doi.org/10.4995/IDS2018.2018.7734OCS1759176

Development of Structure-Switching Aptamers for Kanamycin Detection Based on Fluorescence Resonance Energy Transfer

The structure-switching aptamers are designed for the simple and rapid detection of kanamycin based on the signal transduction principle of fluorescence resonance energy transfer (FRET). The structure switch is composed of kanamycin-binding aptamers and the complementary strands, respectively labeled with fluorophore and quencher, denoted as FDNA and QDNA. In the absence of kanamycin, FDNA and QDNA form the double helix structure through the complementary pairing of bases. The fluorophore and the quencher are brought into close proximity, which results in the fluorescence quenching because of the FRET mechanism. In the presence of kanamycin, the FDNA specifically bind to the target due to the high affinity of aptamers, and the QDNA are dissociated. The specific recognition between aptamers and kanamycin will obstruct the formation of structure switch and reduce the efficiency of FRET between FDNA and QDNA, thus leading to the fluorescence enhancement. Therefore, based on the structure-switching aptamers, a simple fluorescent assay for rapid detection of kanamycin was developed. Under optimal conditions, there was a good linear relationship between kanamycin concentration and the fluorescence signal recovery. The linear range of this method in milk samples was 100–600 nM with the detection limit of 13.52 nM (3σ), which is well below the maximum residue limit (MRL) of kanamycin in milk. This method shows excellent selectivity for kanamycin over the other common antibiotics. The structure-switching aptamers have been successfully applied to the detection of kanamycin spiked in milk samples with the satisfying recoveries between 101.3 and 109.1%, which is well-consistent with the results from LC-MS/MS. Due to the outstanding advantages of facile operation, rapid detection, high sensitivity, excellent specificity, and low cost, the application and extension of this strategy for rapid determination of antibiotics in food samples may greatly improve the efficiency in food safety and quality supervision

Action Real-Time Strategy Gaming Experience Related to Increased Attentional Resources: An Attentional Blink Study

Action real-time strategy gaming (ARSG) is a cognitively demanding task which requires attention, sensorimotor skills, team cooperation, and strategy-making abilities. A recent study found that ARSG experts had superior visual selective attention (VSA) for detecting the location of a moving object that could appear in one of 24 different peripheral locations (Qiu et al., 2018), suggesting that ARSG experience is related to improvements in the spatial component of VSA. However, the influence of ARSG experience on the temporal component of VSA—the detection of an item among a sequence of items presented consecutively and quickly at a single location—still remains understudied. Using behavioral and electrophysiological measures, this study examined whether ARSG experts had superior temporal VSA performance compared to non-experts in an attentional blink (AB) task, which is typically used to examine temporal VSA. The results showed that the experts outperformed the non-experts in their detection rates of targets. Furthermore, compared to the non-experts, the experts had faster information processing as indicated by earlier P3 peak latencies in an AB period, more attentional resources distributed to targets as indicated by stronger P3 amplitudes, and a more flexible deployment of attentional resources. These findings suggest that experts were less prone to the AB effect. Thus, long-term ARSG experience is related to improvements in temporal VSA. The current findings support the benefit of video gaming experience on the development of VSA