The selection of random sampling points is crucial for the path quality generated by probabilistic roadmap (PRM) algorithm. Increasing the number of sampling points can enhance path quality. However, it may also lead to extended convergence time and reduced computational efficiency. Therefore, an improved probabilistic roadmap algorithm (TL-PRM) is proposed based on topological discrimination and lazy collision. TL-PRM algorithm first generates a circular grid area among start and goal points. Then, it constructs topological nodes. Subsequently, elliptical sampling areas are created between each pair of adjacent topological nodes. Random sampling points are generated within these areas. These sampling points are interconnected using a layer connection strategy. An initial path is generated using a delayed collision strategy. The path is then adjusted by modifying the nodes on the convex outer edges to avoid obstacles. Finally, a reconnection strategy is employed to optimize the path. This reduces the number of path waypoints. In dynamic environments, TL-PRM algorithm employs pose adjustment strategies for semi-static and dynamic obstacles. It can use either the same or opposite pose adjustments to avoid dynamic obstacles. Experimental results indicate that TL-PRM algorithm reduces the average number of generated sampling points by 70.9% and average computation time by 62.1% compared with PRM* and PRM-Astar algorithms. In winding and narrow passage maps, TL-PRM algorithm significantly decreases the number of sampling points and shortens convergence time. In dynamic environments, the algorithm can adjust its pose orientation in real time. This allows it to safely reach the goal point. TL-PRM algorithm provides an effective solution for reducing the generation of sampling points in PRM algorithm.

Accurate dynamic model is essential for the model-based control of robotic systems. However, on the one hand, the nonlinearity of the friction is seldom treated in robot dynamics. On the other hand, few of the previous studies reasonably balance the calculation time-consuming and the quality for the excitation trajectory optimization. To address these challenges, this article gives a Lie-theory-based dynamic modeling scheme of multi-degree-of-freedom (DoF) serial robots involving nonlinear friction and excitation trajectory optimization. First, we introduce two coefficients to describe the Stribeck characteristics of Coulomb and static friction and consider the dependency of friction on load torque, so as to propose an improved Stribeck friction model. Whereafter, the improved friction model is simplified in a no-load scenario, a novel nonlinear dynamic model is linearized to capture the features of viscous friction across the entire velocity range. Additionally, a new optimization algorithm of excitation trajectories is presented considering the benefits of three different optimization criteria to design the optimal excitation trajectory. On the basis of the above, we retrieve a feasible dynamic parameter set of serial robots through the hybrid least square algorithm. Finally, our research is supported by simulation and experimental analyses of different combinations on the seven-DoF Franka Emika robot. The results show that the proposed friction has better accuracy performance, and the modified optimization algorithm can reduce the overall time required for the optimization process while maintaining the quality of the identification results.

OBJECTIVES/GOALS: We aimed to conduct an updated genome-wide meta-analysis of keloids in expanded populations, including those most afflicted by keloids. Our overall objective was to improve understanding of keloid development though the identification and further characterization of keloid-associated genes with genetically predicted gene expression (GPGE). METHODS/STUDY POPULATION: We used publicly available summary statistics from several large-scale DNA biobanks, including the UK Biobank, FinnGen, and Biobank Japan. We also leveraged data from the Million Veterans Program and performed genome-wide association studies of keloids in BioVU and eMERGE. For each of these datasets, cases were determined from ICD-9/ICD-10 codes and phecodes. With these data we conducted fixed effects meta-analysis, both across ancestries and stratified by broad ancestry groups. This approach allowed us to consider cumulative evidence for genetic risk factors for keloids and explore potential ancestry-specific components of risk. We used FUMA for functional annotation of results and LDSC to estimate ancestry-specific heritability. We performed GPGE analysis using S-PrediXcan with GTEx v8 tissues. RESULTS/ANTICIPATED RESULTS: We detected 30 (23 novel) genomic risk loci in the cross-ancestry analysis. Major risk loci were broadly consistent between ancestries, with variable effects. Keloid heritability estimates from LDSC were 6%, 21%, and 34% for European, East Asian, and African ancestry, respectively. The top hit (P = 1.7e-77) in the cross-ancestry analysis was at a replicated variant (rs10863683) located downstream of LINC01705. GPGE analysis identified an association between decreased risk of keloids and increased expression of LINC01705 in fibroblasts (P = 3.6e10-20), which are important in wound healing. The top hit in the African-ancestry analysis (P = 5.5e-31) was a novel variant (rs34647667) in a conserved region downstream of ITGA11. ITGA11 encodes a collagen receptor and was previously associated with uterine fibroids. DISCUSSION/SIGNIFICANCE: This work significantly increases the yield of discoveries from keloid genetic association studies, describing both common and ancestry-specific effects. Stark differences in heritability support a potential adaptive origin for keloid disparities. Further work will continue to examine keloids in the broader context of other fibrotic diseases.

To investigate the effects of co-infection with Clonorchis sinensis (C. sinensis) on T cell exhaustion levels in patients with chronic hepatitis B, we enrolled clinical cases in this study, including the patients with concomitant C. sinensis and HBV infection. In this study, we detected inhibitory receptors and cytokine expression in circulating CD4+ and CD8+ T cells by flow cytometry. PD-1 and TIM-3 expression levels were significantly higher on CD4+ T and CD8+ T cells from co-infected patients than on those from the HBV patients. In addition, CD4+ T cells and CD8+ T cells function were significantly inhibited by C. sinensis and HBV co-infection compared with HBV single infection, secreting lower levels of Interferon gamma (IFN-γ), Interleukin-2 (IL-2), and TNF-α. Our current results suggested that C. sinensis co-infection could exacerbate T cell exhaustion in patients with chronic hepatitis B. PD-1 and TIM-3 could be novel biomarkers for T cell exhaustion in patients with Clonorchis sinensis and chronic hepatitis B co-infection. Furthermore, it may be one possible reason for the weaker response to antiviral therapies and the chronicity of HBV infection in co-infected patients. We must realize the importance of C. sinensis treatment for HBV-infected patients. It might provide useful information for clinical doctors to choose the right treatment plans.

High-intensity vortex beams with tunable topological charges and low coherence are highly demanded in applications such as inertial confinement fusion (ICF) and optical communication. However, traditional optical vortices featuring nonuniform intensity distributions are dramatically restricted in application scenarios that require a high-intensity vortex beam owing to their ineffective amplification resulting from the intensity-dependent nonlinear effect. Here, a low-coherence perfect vortex beam (PVB) with a topological charge as high as 140 is realized based on the super-pixel wavefront-shaping technique. More importantly, a globally adaptive feedback algorithm (GAFA) is proposed to efficiently suppress the original intensity fluctuation and achieve a flat-top PVB with dramatically reduced beam speckle contrast. The GAFA-based flat-top PVB generation method can pave the way for high-intensity vortex beam generation, which is crucial for potential applications in ICF, laser processing, optical communication and optical trapping.

Burn patients are at high risk of central line–associated bloodstream infection (CLABSI). However, the diagnosis of such infections is complex, resource-intensive, and often delayed. This study aimed to investigate the epidemiology of CLABSI and develop a prediction model for the infection in burn patients. The study analysed the infection profiles, clinical epidemiology, and central venous catheter (CVC) management of patients in a large burn centre in China from January 2018 to December 2021. In total, 222 burn patients with a cumulative 630 CVCs and 5,431 line-days were included. The CLABSI rate was 23.02 CVCs per 1000 line-days. The three most common bacterial species were Acinetobacter baumannii, Staphylococcus aureus, and Pseudomonas aeruginosa; 76.09% of isolates were multidrug resistant. Compared with a non-CLABSI cohort, CLABSI patients were significantly older, with more severe burns, more CVC insertion times, and longer total line-days, as well as higher mortality. Regression analysis found longer line-days, more catheterisation times, and higher burn wounds index to be independent risk factors for CLABSI. A novel nomogram based on three risk factors was constructed with an area under the receiver operating characteristic curve (AUROC) value of 0.84 (95% CI: 0.782–0.898) with a mean absolute error of calibration curve of 0.023. The nomogram showed excellent predictive ability and clinical applicability, and provided a simple, practical, and quantitative strategy to predict CLABSI in burn patients.

Coastal eutrophication and hypoxia remain a persistent environmental crisis despite the great efforts to reduce nutrient loading and mitigate associated environmental damages. Symptoms of this crisis have appeared to spread rapidly, reaching developing countries in Asia with emergences in Southern America and Africa. The pace of changes and the underlying drivers remain not so clear. To address the gap, we review the up-to-date status and mechanisms of eutrophication and hypoxia in global coastal oceans, upon which we examine the trajectories of changes over the 40 years or longer in six model coastal systems with varying socio-economic development statuses and different levels and histories of eutrophication. Although these coastal systems share common features of eutrophication, site-specific characteristics are also substantial, depending on the regional environmental setting and level of social-economic development along with policy implementation and management. Nevertheless, ecosystem recovery generally needs greater reduction in pressures compared to that initiated degradation and becomes less feasible to achieve past norms with a longer time anthropogenic pressures on the ecosystems. While the qualitative causality between drivers and consequences is well established, quantitative attribution of these drivers to eutrophication and hypoxia remains difficult especially when we consider the social economic drivers because the changes in coastal ecosystems are subject to multiple influences and the cause–effect relationship is often non-linear. Such relationships are further complicated by climate changes that have been accelerating over the past few decades. The knowledge gaps that limit our quantitative and mechanistic understanding of the human-coastal ocean nexus are identified, which is essential for science-based policy making. Recognizing lessons from past management practices, we advocate for a better, more efficient indexing system of coastal eutrophication and an advanced regional earth system modeling framework with optimal modules of human dimensions to facilitate the development and evaluation of effective policy and restoration actions.

Hormone-sensitive lipase (HSL) is one of the rate-determining enzymes in the hydrolysis of TAG, playing a crucial role in lipid metabolism. However, the role of HSL-mediated lipolysis in systemic nutrient homoeostasis has not been intensively understood. Therefore, we used CRISPR/Cas9 technique and Hsl inhibitor (HSL-IN-1) to establish hsla-deficient (hsla-/-) and Hsl-inhibited zebrafish models, respectively. As a result, the hsla-/- zebrafish showed retarded growth and reduced oxygen consumption rate, accompanied with higher mRNA expression of the genes related to inflammation and apoptosis in liver and muscle. Furthermore, hsla-/- and HSL-IN-1-treated zebrafish both exhibited severe fat deposition, whereas their expressions of the genes related to lipolysis and fatty acid oxidation were markedly reduced. The TLC results also showed that the dysfunction of Hsl changed the whole-body lipid profile, including increasing the content of TG and decreasing the proportion of phospholipids. In addition, the systemic metabolic pattern was remodelled in hsla-/- and HSL-IN-1-treated zebrafish. The dysfunction of Hsl lowered the glycogen content in liver and muscle and enhanced the utilisation of glucose plus the expressions of glucose transporter and glycolysis genes. Besides, the whole-body protein content had significantly decreased in the hsla-/- and HSL-IN-1-treated zebrafish, accompanied with the lower activation of the mTOR pathway and enhanced protein and amino acid catabolism. Taken together, Hsl plays an essential role in energy homoeostasis, and its dysfunction would cause the disturbance of lipid catabolism but enhanced breakdown of glycogen and protein for energy compensation.

The influence of second-order dispersion (SOD) on stimulated Raman scattering (SRS) in the interaction of an ultrashort intense laser with plasma was investigated. More significant backward SRS was observed with the increase of the absolute value of SOD ($\mid \kern-1pt\!{\psi}_2\!\kern-1pt\mid$). The integrated intensity of the scattered light is positively correlated to the driver laser pulse duration. Accompanied by the side SRS, filaments with different angles along the laser propagation direction were observed in the transverse shadowgraph. A model incorporating Landau damping and above-threshold ionization was developed to explain the SOD-dependent angular distribution of the filaments.