Comparison of Brain Nicotine Uptake From Electronic Cigarettes and Combustible Cigarettes

Brain accumulation rate and magnitude are critical for the acute reinforcing effects of nicotine. Despite electronic cigarettes’ (E-cigs) appeal as substitutes for traditional combustible cigarettes (C-cigs), brain nicotine accumulation (BNA) from E-cigs has not been compared with that from C-cigs using a within-subjects design. BNA was directly assessed with 16 adult dual users (10 females) of E-cigs (e-liquid pH 9.4) and C-cigs, using 11C-nicotine and positron emission tomography (PET). Participants went through two 15-min head scanning sessions during which they inhaled a single puff of E-cig vapor or C-cig smoke containing 11C-nicotine in a randomized order. A full-body scan was also conducted at each session to measure total absorbed dose of 11C-nicotine. Mean maximum concentration (Cmax) and area under curve of BNA were 22.1% and 22.7% lower, respectively, following E-cig compared with C-cig inhalation. Meanwhile, T1/2 was 2.7 times longer following inhalation of E-cig vapor relative to C-cig smoke (all ps \u3c 0.005). Whole-body imaging indicated greater nicotine retention in the respiratory tract from vapor versus smoke inhalation (p \u3c 0.0001). Following vapor inhalation, nicotine retention in the respiratory tract was correlated with Cmax values of BNA (rs = −0.59, p \u3c 0.02). Our results confirm that E-cigs with alkaline pH e-liquid can deliver nicotine rapidly to the brain, albeit less efficiently than C-cigs partly due to greater airway retention of nicotine. Since brain nicotine uptake mediates reinforcement, these results help elucidate actions of E-cigs in terms of abuse liability and effectiveness in substituting for combustible cigarettes

KnowCoder: Coding Structured Knowledge into LLMs for Universal Information Extraction

In this paper, we propose KnowCoder, a Large Language Model (LLM) to conduct Universal Information Extraction (UIE) via code generation. KnowCoder aims to develop a kind of unified schema representation that LLMs can easily understand and an effective learning framework that encourages LLMs to follow schemas and extract structured knowledge accurately. To achieve these, KnowCoder introduces a code-style schema representation method to uniformly transform different schemas into Python classes, with which complex schema information, such as constraints among tasks in UIE, can be captured in an LLM-friendly manner. We further construct a code-style schema library covering over $\textbf{30,000}$ types of knowledge, which is the largest one for UIE, to the best of our knowledge. To ease the learning process of LLMs, KnowCoder contains a two-phase learning framework that enhances its schema understanding ability via code pretraining and its schema following ability via instruction tuning. After code pretraining on around $1.5$B automatically constructed data, KnowCoder already attains remarkable generalization ability and achieves relative improvements by \textbf{49.8%} F1, compared to LLaMA2, under the few-shot setting. After instruction tuning, KnowCoder further exhibits strong generalization ability on unseen schemas and achieves up to \textbf{12.5%} and \textbf{21.9%}, compared to sota baselines, under the zero-shot setting and the low resource setting, respectively. Additionally, based on our unified schema representations, various human-annotated datasets can simultaneously be utilized to refine KnowCoder, which achieves significant improvements up to \textbf{7.5%} under the supervised setting

Disturbance-Observer-Based Model Predictive Control for Battery Energy Storage System Modular Multilevel Converters

Although the traditional model predictive control (MPC) can theoretically provide AC current and circulating current control for modular multilevel converters (MMCs) in battery energy storage grid-connected systems, it suffers from stability problems due to the power quality of the power grid and model parameter mismatches. A two discrete-time disturbance observers (DOBs)-based MPC strategy is investigated in this paper to solve this problem. The first DOB is used to improve the AC current quality and the second enhances the stability of the circulating current control. The distortion and fluctuation of grid voltage and inductance parameter variation are considered as lump disturbances in the discrete modeling of a MMC. Based on the proposed method, the output prediction is compensated by disturbance estimation to correct the AC current and circulating current errors, which eventually achieve the expected tracking performance. Moreover, the DOBs have a quite low computational cost with minimum order and optimal performance properties. Since the designed DOBs work in parallel with the MPC, the control effect is improved greatly under harmonics, 3-phase unbalance, voltage sag, inductance parameter mismatches and power reversal conditions. Simulation results confirm the validity of the proposed scheme

Avian Reovirus σB Interacts with Caveolin-1 in Lipid Rafts during Dynamin-Dependent Caveolae-Mediated Endocytosis

Caveolin-1 (Cav-1) is the basic component of caveolae, a specialized form of lipid raft that plays an essential role in endocytic viral entry. However, the evidence of direct involvement of caveolae and Cav-1 in avian reovirus (ARV) entry remains insufficient. In this study, the membrane lipid rafts were isolated as detergent-resistant microdomains (DRMs) by sucrose gradient centrifugation, and the capsid protein σB of ARV was found to associate with Cav-1 in DRMs fractions. Additionally, the interaction between ARV σB protein and Cav-1 was demonstrated by immunofluorescence co-localization and co-immunoprecipitation assays. Furthermore, we found that the internalization of ARV is sensitive to caveolae and dynamin inhibitors, while it is insensitive to clathrin inhibitors. In conclusion, these results indicate that the ARV σB protein interacts with Cav-1 during dynamin-dependent caveolae-mediated endocytosis for the entry of ARV

Identification and Functional Analyses of Host Proteins Interacting with the p17 Protein of Avian Reovirus

Avian reovirus (ARV) causes viral arthritis, chronic respiratory diseases, retarded growth and malabsorption syndrome. However, the precise molecular mechanism remains unclear. Here, we report the host cellular proteins that interact with ARV p17 by yeast two-hybrid screening. In this study, the p17 gene was cloned into pGBKT7 to obtain the bait plasmid pGBKT7-p17. After several rounds of screening of a chicken cDNA library, 43 positive clones were identified as possible host factors that interacted with p17. A BLAST search of the sequences was performed on the NCBI website, which ultimately revealed 19 interacting proteins. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genome analyses indicated that the acquired proteins were involved in multicellular organismal processes, metabolic processes, and biological regulation. When the subcellular localization of the host protein and ARV p17 protein was investigated, we observed colocalization of p17-GFP with IGF2BP1-RED and PQBP1-RED in the transfected cells but not with FGF1-RED. The direct interaction of ARV p17 protein with IGF2BP1 and PQBP1 was confirmed by coimmunoprecipitation and GST pulldown assays. We used RT-qPCR to assess the expression variation during ARV infection. The results showed that IGF2BP1, PAPSS2, RPL5, NEDD4L, PRPS2 and IFI16 were significantly upregulated, whereas the expression of FGF1, CDH2 and PQBP1 was markedly decreased in DF-1 cells infected with ARV. Finally, we demonstrated that IGF2BP1 had a positive effect on ARV replication, while PQBP1 had the opposite effect. Our findings provide valuable information for better insights into ARV\u27s pathogenesis and the role of the p17 protein in this process

The Prevalence and Associations of Peripheral Retinopathy: Baseline Study of Guangzhou Office Computer Workers

Purpose. To determine the prevalence of peripheral retinopathy and its associated risk factors among a sample of Guangzhou office computer workers. Methods. A cross-sectional study of Guangzhou Chinese computer workstations and operators in different departments and units of the Guangzhou Power Supply Bureau, China, in 2016. Peripheral retinopathy was recorded and analyzed using a scanning laser ophthalmoscope (SLO; Optos, Daytona, United Kingdom) and slit-lamp microscopy combined with a three-mirror contact lens. Results. The 1934 eyes of 967 subjects (513 females and 454 males) were included in this study. In total, 79.1% of the eyes were myopic in workers aged 20–29 years, 72.9% in workers aged 30–39 years, 62.2% in workers aged 40–49 years, and 43.4% in workers aged 50–59 years (p<0.001). Most eyes had optic nerve crescents (81.3%). Various peripheral degenerations were found: 7 eyes (0.4%) had microcystoid degeneration, 40 (2.1%) had peripheral pigmentary degeneration, 87 (4.5%) had lattice degeneration, and 4 (0.2%) had snail-track degeneration. Nineteen (1.0%) eyes had paving-stone degeneration, 11 (0.6%) eyes had a retinal hole or tear, and 16 (0.8%) eyes had chorioretinal degeneration. Multivariate regression confirmed that greater axial length (OR: 1.18 (1.03, 1.35), p=0.012) and more serious spherical equivalent (OR: 0.82 (0.77, 0.88), p<0.001) were significant risk factors for peripheral retinal changes. Conclusion. Peripheral retinal degenerative changes were found in a larger proportion of younger computer workers than older ones. Myopia is occurring in younger and younger people, accompanied by peripheral retinal degeneration

Multi-centric clinical study of the effect of intervention time on efficacy of gastroparesis external application prescription treatment of gastrointestinal tumor postsurgical gastroparesis

Objective: This intervention has been shown to be clinically efficacious and safe. The aim of this study was to determine the effect of different intervention times on the efficacy of gastroparesis external application prescription versus placebo for the treatment of gastrointestinal tumor postoperative, postsurgical gastroparesis. Methods: A multicenter, randomized, double-blind, placebo controlled phase III clinical trial was designed to demonstrate superiority and conducted at four grade 3A hospitals in Beijing. Patients diagnosed with gastrointestinal tumor postsurgical gastroparesis and local cold syndrome in the abdomen were enrolled and received conventional treatment (nutritional support, gastrointestinal decompression, and prokinetic medication). Treatment and control groups respectively received gastroparesis external application prescription or placebo acupoint application over a treatment course of 14 days or until the primary efficacy endpoint (clinical efficiency) was achieved. Results: A total of 120 patients were enrolled in the treatment and control groups (n = 60 per group), and 15 patients dropped out of the study because of skin allergies (n = 7) or poor efficacy (n = 8). The efficacy among patients in Class B of Group A(treatment group) was marginally better than that of Group B (control group) (64.28% vs. 55.56%) although the difference between the two groups was not significant. However, the efficacy among patients in Class C of Group A was significantly better than that of Group B (79.49% vs. 43.33%). For Group A, the time for patients in the three classes to achieve the efficacy endpoint increased significantly with disease progression (3.00, 6.78, and 8.29 days for Class A, B, and C, respectively). Conclusions: Gastroparesis external application prescription can effectively treat gastrointestinal tumor postsurgical gastroparesis and may be more efficacious in progressive disease compared placebo. Patients with gastrointestinal tumor postsurgical gastroparesis should therefore undergo intervention at an earlier stage

A Highly Thermostable In2O3/ITO Thin Film Thermocouple Prepared via Screen Printing for High Temperature Measurements

An In2O3/ITO thin film thermocouple was prepared via screen printing. Glass additives were added to improve the sintering process and to increase the density of the In2O3/ITO films. The surface and cross-sectional images indicate that both the grain size and densification of the ITO and In2O3 films increased with the increase in annealing time. The thermoelectric voltage of the In2O3/ITO thermocouple was 53.5 mV at 1270 °C at the hot junction. The average Seebeck coefficient of the thermocouple was calculated as 44.5 μV/°C. The drift rate of the In2O3/ITO thermocouple was 5.44 °C/h at a measuring time of 10 h at 1270 °C