Bidirectional causality between immunoglobulin G N-glycosylation and metabolic traits: A mendelian randomization study

Although the association between immunoglobulin G (IgG) N-glycosylation and metabolic traits has been previously identified, the causal association between them remains unclear. In this work, we used Mendelian randomization (MR) analysis to integrate genome-wide association studies (GWASs) and quantitative trait loci (QTLs) data in order to investigate the bidirectional causal association of IgG N-glycosylation with metabolic traits. In the forward MR analysis, 59 (including nine putatively causal glycan peaks (GPs) for body mass index (BMI) (GP1, GP6, etc.) and seven for fasting plasma glucose (FPG) (GP1, GP5, etc.)) and 15 (including five putatively causal GPs for BMI (GP2, GP11, etc.) and four for FPG (GP1, GP10, etc.)) genetically determined IgG N-glycans were identified as being associated with metabolic traits in one- and two-sample MR studies, respectively, by integrating IgG N-glycan-QTL variants with GWAS results for metabolic traits (all P \u3c 0.05). Accordingly, in the reverse MR analysis of the integrated metabolic-QTL variants with the GWAS results for IgG N-glycosylation traits, 72 (including one putatively causal metabolic trait for GP1 (high-density lipoprotein cholesterol (HDL-C)) and five for GP2 (FPG, systolic blood pressure (SBP), etc.)) and four (including one putatively causal metabolic trait for GP3 (HDL-C) and one for GP9 (HDL-C)) genetically determined metabolic traits were found to be related to the risk of IgG N-glycosylation in one- and two-sample MR studies, respectively (all P \u3c 0.05). Notably, genetically determined associations of GP11 BMI (fixed-effects model-Beta with standard error (SE): 0.106 (0.034) and 0.010 (0.005)) and HDL-C GP9 (fixed-effects model-Beta with SE: –0.071 (0.022) and –0.306 (0.151)) were identified in both the one- and two-sample MR settings, which were further confirmed by a meta-analysis combining the one- and two-sample MR results (fixed-effects model-Beta with 95% confidence interval (95% CI): 0.0109 (0.0012, 0.0207) and –0.0759 (–0.1186, –0.0332), respectively). In conclusion, the comprehensively bidirectional MR analyses provide suggestive evidence of bidirectional causality between IgG N-glycosylation and metabolic traits, possibly revealing a new richness in the biological mechanism between IgG N-glycosylation and metabolic traits. © 2022 THE AUTHOR

Quench of a Single-Layer ReBCO CORC Cable with Non-Uniform Terminal Contact Resistance

ReBCO conductor-on-round-core (CORC) cable has become a promising candidate for high temperature superconducting (HTS) power applications, due to its great mechanical strength, high current carrying capacity, high flexibility, and low ac losses. However, ReBCO coated conductors are at risk of quenching, which significantly affects the thermal stability and reliability of the CORC cable. Three-dimensional (3-D) numerical study on the quench behavior of the CORC cable remains a challenge, for its complex geometry is difficult to cope with. In this paper, a 3-D time-dependent multi-physics quench model based on the T-A formulation has been developed. Three modules are coupled in this model; the T-A formulation model, a heat transfer model, and an equivalent circuit model. The quench behavior of a single-layer ReBCO CORC cable with non-uniform terminal contact resistances has been studied, when a hotspot is imposed on one of the tapes to induce a local quench. Results show that, the CORC cable has the highest MQE; in other words, it is the most stable situation, when the hotspot-induced quench occurs on the tape with the middle value of terminal contact resistance

AC loss comparison between multifilament and nonstriated YBCO coils designed for HTS propulsion motors

In this paper, the properties of current capacity and ac transport loss of striated high temperature superconductor (HTS) coil is compared with ordinary HTS coil by using both experimental and simulation methods. The measurements were carried out by transporting a sinusoidal varying current at 77 K, with an amplitude range of 10-50 A in frequency from 70 up to 300 Hz. Measurement facilities and methods are explained in more detail in the paper. The critical current of the 4-mm width multifilament coil made with four filaments at a spacing 0.03 mm was found to be lower than that of the nonstriated coil. The frequency dependent characteristics agreed well in both experimental and simulated results. Reducing ac loss of HTS is one enabling factor for widespread adoption of the technology, and therefore, understanding its characteristics is important and discussed in this paper. Future plans based on this preliminary work are the testing of multifilament tapes in an axial flux motor field environment

Glycomics: Immunoglobulin GN-glycosylation associated with mammary gland hyperplasia in women

© Copyright 2020, Mary Ann Liebert, Inc., publishers 2020. Mammary gland hyperplasia (MGH) is very common, especially among young and middle-aged women. New diagnostics and biomarkers for MGH are needed for rational clinical management and precision medicine. We report, in this study, new findings using a glycomics approach, with a focus on immunoglobulin G (IgG) N-glycosylation. A cross-sectional study was conducted in a community-based population sample in Beijing, China. A total of 387 participants 40-65 years of age were enrolled in this study, including 194 women with MGH (cases) and 193 women who had no MGH (controls). IgG N-glycans were characterized in the serum by ultra-performance liquid chromatography. The levels of the glycan peaks (GPs) GP2, GP5, GP6, and GP7 were lower in the MGH group compared with the control group, whereas GP14 was significantly higher in the MGH group (p \u3c 0.05). A predictive model using GP5, GP21, and age was established and a receiver operating characteristic curve analysis was performed. The sensitivity and specificity of the model for MGH was 61.3% and 63.2%, respectively, likely owing to receptor mechanisms and/or inflammation regulation. To the best of our knowledge, this is the first study reporting on an association between IgG N-glycosylation and MGH. We suggest person-to-person variations in IgG N-glycans and their combination with multiomics biomarker strategies offer a promising avenue to identify novel diagnostics and individuals at increased risk of MGH

Lemur: Harmonizing Natural Language and Code for Language Agents

We introduce Lemur and Lemur-Chat, openly accessible language models optimized for both natural language and coding capabilities to serve as the backbone of versatile language agents. The evolution from language chat models to functional language agents demands that models not only master human interaction, reasoning, and planning but also ensure grounding in the relevant environments. This calls for a harmonious blend of language and coding capabilities in the models. Lemur and Lemur-Chat are proposed to address this necessity, demonstrating balanced proficiencies in both domains, unlike existing open-source models that tend to specialize in either. Through meticulous pre-training using a code-intensive corpus and instruction fine-tuning on text and code data, our models achieve state-of-the-art averaged performance across diverse text and coding benchmarks among open-source models. Comprehensive experiments demonstrate Lemur's superiority over existing open-source models and its proficiency across various agent tasks involving human communication, tool usage, and interaction under fully- and partially- observable environments. The harmonization between natural and programming languages enables Lemur-Chat to significantly narrow the gap with proprietary models on agent abilities, providing key insights into developing advanced open-source agents adept at reasoning, planning, and operating seamlessly across environments. https://github.com/OpenLemur/Lemu

The association between normal BMI with central adiposity and proinflammatory potential immunoglobulin G N-Glycosylation

Background: The mechanism by which normal body mass index (BMI) with central adiposity (NWCA) increases the risk of the diseases has not been completely elucidated. The inflammatory role of immunoglobulin G (IgG) N-glycosylation in obesity defined by BMI or central adiposity defined by waist-to-hip ratio (WHR) was reported, respectively. We undertook this three-center cross-sectional study to determine the association between the IgG N-glycans and NWCA. Methods: The participants were categorized into four different phenotypes: normal BMI with normal WHR (NW), normal BMI with central adiposity (NWCA), obesity with normal WHR (ONCA) and obesity with central adiposity (OCA). The IgG N-glycans were analyzed using ultra-performance liquid chromatography analysis of released glycans, and differences among groups were compared. Results: In total, 17 out of 24 initial IgG N-glycans were significantly different among the four groups (NW, ONCA, NWCA and OCA) (P\u3c0.05/6*78=0.0001). The changes of IgG glycans in central obesity (12 GPs) were more than those in obesity (3 GPs). In addition, lower galactosylation and bisecting GlcNAc and higher fucosylation were associated with increased risk of NWCA. Conclusion: Central obesity was involved in more changes of IgG N-glycosylation representing stronger inflammation than obesity, which might make a greater contribution to the risk of related disorders. NWCA was associated with an increased pro-inflammatory of IgG N-glycosylation, which was accompanied by the development of central obesity and other related disorders

Hand, Foot, and Mouth Disease in China: critical community size and spatial vaccination strategies

Hand Foot and Mouth Disease (HFMD) constitutes a considerable burden for health care systems across China. Yet this burden displays important geographic heterogeneity that directly affects the local persistence and the dynamics of the disease, and thus the ability to control it through vaccination campaigns. Here, we use detailed geographic surveillance data and epidemic models to estimate the critical community size (CCS) of HFMD associated enterovirus serotypes CV-A16 and EV-A71 and we explore what spatial vaccination strategies may best reduce the burden of HFMD. We found CCS ranging from 336,979 (±225,866) to 722,372 (±150,562) with the lowest estimates associated with EV-A71 in the southern region of China where multiple transmission seasons have previously been identified. Our results suggest the existence of a regional immigration-recolonization dynamic driven by urban centers. If EV-A71 vaccines doses are limited, these would be optimally deployed in highly populated urban centers and in high-prevalence areas. If HFMD vaccines are included in China's National Immunization Program in order to achieve high coverage rates (>85%), routine vaccination of newborns largely outperforms strategies in which the equivalent number of doses is equally divided between routine vaccination of newborns and pulse vaccination of the community at large