Component procurement strategies in decentralized assembly systems under supply uncertainty

Copyright © 2015 “IIE” In this article we analyze the interactions among the assembler and two component suppliers in their procurement decisions under a Vendor-Managed Inventory (VMI) contract. Under the VMI contract, the assembler first offers a unit price for each component and will pay component suppliers only for the amounts used to meet the actual demand. The two independent component suppliers then decide on the production quantities of their individual components before the actual demand is realized. We assume that one of the component suppliers has uncertainty in the supply process, in which the actual number of components available for assembly is equal to a random fraction of the production quantity. Under the assembly structure, both component suppliers need to take into account the underlying supply uncertainty in deciding their individual production quantities, as both components are required for the assembly of the final product. We first analyze the special case under deterministic demand and then extend our analysis to the general case under stochastic demand. We derive the optimal component prices offered by the assembler and the corresponding equilibrium production quantities of the component suppliers

Transcriptional activity regulates alternative cleavage and polyadenylation

Transcriptomic and epigenomic data, as well as reporter and nuclear run-on assays collectively show that transcriptional activity regulates the relative abundance of alternative polyadenylation isoforms, indicating general coupling of 3′ end processing to transcription

SIRT2 regulates macrophage chemotaxis by de-modifying histone H4K8 lactylation

Objective·To explore the regulatory role of silent information regulator 2 (SIRT2) in modulating the immune phenotype of macrophages after infection by removing the lactylation at H4K8 site of histone and the corresponding mechanism.Methods·Human THP-1 leukemia cells were induced by phorbol 12-myristate 13-acetate (PMA) and stimulated by lipopolysaccharide (LPS) to establish a macrophage infection model. Macrophages without LPS treatment (pTHP-1) were set as the control (CTRL) group, and macrophages with LPS treatment were set as the infected (LPS) group. Western blotting was used to detect the level of histone modification and SIRT2 protein in macrophages. RT-qPCR was used to detect the expression level of glycolytic key enzymes [phosphofructokinase liver type (PFKL), lactate dehydrogenase A (LDHA)] and modulators genes hypoxia inducible factor 1α (HIF-1α), and the expression level of Sirtuin genes and HDAC genes between the two groups. Transwell was used to detect the ability of macrophage chemotaxis. Lentivirus packaging and cell infection were used to construct SIRT2 overexpression cell line. The interaction analysis method of RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) was used to analyze the difference and pathway enrichment of the genes specifically bound to H4K8 lactylation (H4K8la).Results·Compared to the CTRL group, macrophage glycolysis was upregulated and the level of H4K8la was significantly increased in the LPS group (P0.05). The interactive analysis of ChIP-seq and RNA-seq revealed that chemotaxis-related genes were regulated by H4K8la, and macrophage chemotaxis ability significantly decreased after the overexpression of SIRT2 and downregulation of H4K8la (P<0.05).Conclusion·SIRT2 can change the expression of target genes related to chemotaxis by removing H4K8la modification, thereby reducing the chemotaxis ability of macrophages. Targeting SIRT2 and H4K8la modification may help control inflammation mediated by macrophages

Association of Allergic Symptoms in the First 2 Years of Life With Sleep Outcomes Among Chinese Toddlers

Background: Previous studies have linked allergic symptoms to sleep in children, but the associations might be different when considering different types of allergic symptoms or sleep outcomes. Moreover, the combined effects of multiple allergic symptoms remain unclear in early life. This study aimed to investigate the associations between multiple allergic symptoms and sleep outcomes in early life. Methods: We included 673 toddlers aged 2 years from a birth cohort in Guangzhou, China. We identified allergic symptoms (skin, eyes and nose, gastrointestinal tract, mouth and lips, and wheeze) within 2 years via standard questionnaires. Sleep outcomes including sleep duration and quality over the past month were assessed based on the Chinese version of the Brief Infant Sleep Questionnaire. Associations between allergic symptoms and sleep outcomes were examined using multivariable linear regression and logistic regression. Results: Compared to children without allergic symptoms, children with allergic nasal and ocular symptoms had higher odds of frequent nighttime awakenings (OR = 1.41; 95% CI: 1.03, 1.93) and irregular sleep (OR = 1.45, 95% CI: 1.05, 2.00); children with allergic gastrointestinal symptoms slept 0.28 h less during nighttime (95% CI: -0.48, -0.07) and 0.25 h less per day (95% CI: -0.43, -0.08), and had 59% higher odds of irregular sleep (95% CI: 1.24, 2.04). We also found significant association of multiple allergic symptoms with shortened nighttime sleep duration and increased irregular sleep. Whereas, allergic skin, mouth and lips, and wheeze symptoms were not significantly associated with sleep outcomes. Conclusion: Allergic symptoms within 2 years of age were adversely associated with sleep outcomes, which highlight the importance of early screening of allergic symptoms in toddlers in order to improve their sleep outcomes

Prepared for PrEP:preferences for HIV pre-exposure prophylaxis among Chinese men who have sex with men in an online national survey

BACKGROUND: Pre-exposure prophylaxis (PrEP) is not widely available in China. Previous studies reported low awareness and inconclusive findings on the acceptability of PrEP among Chinese men who have sex with men (MSM). METHODS: We conducted a secondary analysis of an online national survey comparing preferences for oral and long-acting injectable PrEP among MSM and identifying correlates of preferences. The study did not collect detailed information about partner types that may influence negotiated safety and PrEP uptake. RESULTS: Nine-hundred and seventy-nine men from the larger sample of 1045 men responded to the PrEP survey questions. Most men (81.9%) had never heard of PrEP, but reported interest in using PrEP. More participants chose injectable PrEP (36.3%) as their preferred formulation than oral PrEP (24.6%). Men who had at least two HIV tests (adjusted OR = 1.36, 95%CI 1.04, 1.78) more commonly preferred injectable PrEP. CONCLUSION: Our findings may help inform PrEP messaging in areas where PrEP has yet to be scaled up

Effective TME-related signature to predict prognosis of patients with head and neck squamous cell carcinoma

Introduction: The tumor microenvironment (TME) is crucial for the development of head and neck squamous cell carcinoma (HNSCC). However, the correlation of the characteristics of the TME and the prognosis of patients with HNSCC remains less known.Methods: In this study, we calculated the immune and stromal cell scores using the “estimate” R package. Kaplan-Meier survival and CIBERSORT algorithm analyses were applied in this study.Results: We identified seven new markers: FCGR3B, IGHV3-64, AC023449.2, IGKV1D-8, FCGR2A, WDFY4, and HBQ1. Subsequently, a risk model was constructed and all HNSCC samples were grouped into low- and high-risk groups. The results of both the Kaplan-Meier survival and receiver operating characteristic curve (ROC) analyses showed that the prognosis indicated by the model was accurate (0.758, 0.756, and 0.666 for 1-, 3- and 5-year survival rates). In addition, we applied the CIBERSORT algorithm to reveal the significant differences in the infiltration levels of immune cells between the two risk groups.Discussion: Our study elucidated the roles of the TME and identified new prognostic biomarkers for patients with HNSCC

MEAformer: Multi-modal Entity Alignment Transformer for Meta Modality Hybrid

As an important variant of entity alignment (EA), multi-modal entity alignment (MMEA) aims to discover identical entities across different knowledge graphs (KGs) with relevant images attached. We noticed that current MMEA algorithms all globally adopt the KG-level modality fusion strategies for multi-modal entity representation but ignore the variation in modality preferences for individual entities, hurting the robustness to potential noise involved in modalities (e.g., blurry images and relations). In this paper, we present MEAformer, a multi-modal entity alignment transformer approach for meta modality hybrid, which dynamically predicts the mutual correlation coefficients among modalities for entity-level feature aggregation. A modal-aware hard entity replay strategy is further proposed for addressing vague entity details. Experimental results show that our model not only achieves SOTA performance on multiple training scenarios including supervised, unsupervised, iterative, and low resource, but also has a comparable number of parameters, optimistic speed, and good interpretability. Our code and data are available at https://github.com/zjukg/MEAformer.Comment: Repository: https://github.com/zjukg/MEAforme

Annealing novel nucleobase-lipids with oligonucleotides or plasmid DNA based on H-bonding or π-π interaction:Assemblies and transfections

Lipid derivatives of nucleoside analogs have been highlighted for their potential for effective gene delivery. A novel class of nucleobase-lipids are rationally designed and readily synthesized, comprising thymine/cytosine, an ester/amide linker and an oleyl lipid. The diversity of four nucleobase-lipids termed DXBAs (DOTA, DNTA, DOCA and DNCA) is investigated. Besides, DNCA is demonstrated to be an effective neutral transfection material for nucleic acid delivery, which enbles to bind to oligonucleotides via H-bonding and π-π stacking with reduced toxicity in vitro and in vivo. Several kinds of nucleic acid drugs including aptamer, ssRNA, antisense oligonucleotide, and plasmid DNAs can be delivered by DXBAs, especially DNCA. In particular, G4-aptamer AS1411 encapsulated by DNCA exhibits cellular uptake enhancement, lysosome degradation reduction, cell apoptosis promotion, cell cycle phase alteration in vitro and duration prolongation in vivo, resulting in significant anti-proliferative activity. Our results demonstrate that DNCA is a promising transfection agent for G4-aptamers and exhibites bright application prospects in the permeation improvement of single-stranded oligonucleotides or plasmid DNAs

High HIV Incidence Among Men Who Have Sex With Men in 8 Chinese Cities: Results From a Trial.

BACKGROUND: In China, while the overall HIV prevalence has been decreasing within key populations, the epidemic among men who have sex with men (MSM) is still on the rise. This study aims to assess the HIV incidence rate and identify driving forces of HIV seroconversion among MSM in a closed cohort. METHODS: This study is a secondary analysis of a large trial of HIV testing promotion among Chinese MSM in 2016-2017. Sexual behaviors, HIV testing activities, and HIV serostatus were measured at baseline and follow-up every 3 months. HIV seroconversion in this study was defined as a self-reported HIV-positive test result. Participants who reported testing for HIV at least twice during different follow-up periods were included. Subgroup analysis and Cox regression were used to examine the correlates with HIV seroconversion. RESULTS: Overall, 347 participants were included in this study, with a mean age of 25.3 ± 6.1, and 71.2% were migrants. The sociodemographic characteristics of the included participants were similar to the rest of the participants in the trial (n = 1034); 7.2% (25/347) of participants seroconverted during the study period, resulting in an incidence rate of 15.56/100 person-years. In subgroup analysis, the HIV incidence rate was higher among migrants than nonmigrants (incidence rate ratio, 1.26; 95% confidence interval [CI], 0.47-3.87). In the time-dependent Cox regression model, bisexual MSM had a higher risk of contracting HIV than gay men (adjusted hazard ratio, 2.19; 95% CI, 1.02-4.72). CONCLUSIONS: Our findings suggest a high HIV incidence rate among Chinese MSM. Further expansion of pre-exposure prophylaxis and other effective HIV prevention interventions are urgently needed