The Adoption of ERP Applications in China

The adoption of enterprise resource planning (ERP) applications started in the early 1990s in the US and Europe. Although many researchers have studied the critical success factors (CSFs) or developed implementation framework to guide the deployment of the complex IT projects, there have been many failed implementations. The implementation of ERP systems in China began in the late 1990s but has resulted in a disappointing success rate of about 10 percent. This paper will investigate which issues facilitate or hinder the adoption of ERP applications in China in the light of previous research reported on Western firms. The research methodology is secondary data collection and case narratives. Twenty small case studies about the implementation of ERP systems in Chinese organisations will be discussed. Since the data has been collected and presented by other practitioners for certain purposes, the limitations of this research are also considered

Existence and asymptotic analysis of positive solutions for a singular fractional differential equation with nonlocal boundary conditions

In this paper, we focus on the existence and asymptotic analysis of positive solutions for a class of singular fractional differential equations subject to nonlocal boundary conditions. By constructing suitable upper and lower solutions and employing Schauder’s fixed point theorem, the conditions for the existence of positive solutions are established and the asymptotic analysis for the obtained solution is carried out. In our work, the nonlinear function involved in the equation not only contains fractional derivatives of unknown functions but also has a stronger singularity at some points of the time and space variables

Clearing Persistent Extracellular Antigen of Hepatitis B Virus: An Immunomodulatory Strategy To Reverse Tolerance for an Effective Therapeutic Vaccination

Development of therapeutic vaccines/strategies to control chronic hepatitis B virus (HBV) infection (CHB) has been challenging due to HBV-induced tolerance. In this study, we explored strategies for breaking tolerance and restoring the immune response to the HBV surface antigen in tolerant mice. We demonstrated that immune tolerance status is attributed to the level and duration of circulating HBsAg in HBV carrier models. Removal of circulating HBsAg by a monoclonal anti-HBsAg antibody in tolerant mice could gradually reduce tolerance and reestablish B cell and CD4+ T cell responses to subsequent Engerix-B vaccination, producing protective IgG. Furthermore, HBsAg-specific CD8+ T cells induced by the addition of a TLR agonist, resulted in clearance of HBV in both serum and liver. Thus, generation of protective immunity can be achieved by clearing extracellular viral antigen with neutralizing antibodies followed by vaccination

METTL14 Is a Chromatin Regulator Independent of Its RNA N6-Methyladenosine Methyltransferase Activity

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs

An allelic atlas of immunoglobulin heavy chain variable regions reveals antibody binding epitope preference resilient to SARS-CoV-2 mutation escape

BackgroundAlthough immunoglobulin (Ig) alleles play a pivotal role in the antibody response to pathogens, research to understand their role in the humoral immune response is still limited.MethodsWe retrieved the germline sequences for the IGHV from the IMGT database to illustrate the amino acid polymorphism present within germline sequences of IGHV genes. We aassembled the sequences of IgM and IgD repertoire from 130 people to investigate the genetic variations in the population. A dataset comprising 10,643 SARS-CoV-2 spike-specific antibodies, obtained from COV-AbDab, was compiled to assess the impact of SARS-CoV-2 infection on allelic gene utilization. Binding affinity and neutralizing activity were determined using bio-layer interferometry and pseudovirus neutralization assays. Primary docking was performed using ZDOCK (3.0.2) to generate the initial conformation of the antigen-antibody complex, followed by simulations of the complete conformations using Rosetta SnugDock software. The original and simulated structural conformations were visualized and presented using ChimeraX (v1.5).ResultsWe present an allelic atlas of immunoglobulin heavy chain (IgH) variable regions, illustrating the diversity of allelic variants across 33 IGHV family germline sequences by sequencing the IgH repertoire of in the population. Our comprehensive analysis of SARS-CoV-2 spike-specific antibodies revealed the preferential use of specific Ig alleles among these antibodies. We observed an association between Ig alleles and antibody binding epitopes. Different allelic genotypes binding to the same RBD epitope on the spike show different neutralizing potency and breadth. We found that antibodies carrying the IGHV1-69*02 allele tended to bind to the RBD E2.2 epitope. The antibodies carrying G50 and L55 amino acid residues exhibit potential enhancements in binding affinity and neutralizing potency to SARS-CoV-2 variants containing the L452R mutation on RBD, whereas R50 and F55 amino acid residues tend to have reduced binding affinity and neutralizing potency. IGHV2-5*02 antibodies using the D56 allele bind to the RBD D2 epitope with greater binding and neutralizing potency due to the interaction between D56 on HCDR2 and K444 on RBD of most Omicron subvariants. In contrast, IGHV2-5*01 antibodies using the N56 allele show increased binding resistance to the K444T mutation on RBD.DiscussionThis study provides valuable insights into humoral immune responses from the perspective of Ig alleles and population genetics. These findings underscore the importance of Ig alleles in vaccine design and therapeutic antibody development

HLungDB: an integrated database of human lung cancer research

The human lung cancer database (HLungDB) is a database with the integration of the lung cancer-related genes, proteins and miRNAs together with the corresponding clinical information. The main purpose of this platform is to establish a network of lung cancer-related molecules and to facilitate the mechanistic study of lung carcinogenesis. The entries describing the relationships between molecules and human lung cancer in the current release were extracted manually from literatures. Currently, we have collected 2585 genes and 212 miRNA with the experimental evidences involved in the different stages of lung carcinogenesis through text mining. Furthermore, we have incorporated the results from analysis of transcription factor-binding motifs, the promoters and the SNP sites for each gene. Since epigenetic alterations also play an important role in lung carcinogenesis, genes with epigenetic regulation were also included. We hope HLungDB will enrich our knowledge about lung cancer biology and eventually lead to the development of novel therapeutic strategies. HLungDB can be freely accessed at http://www.megabionet.org/bio/hlung

Global existence and temporal decay for the 3D compressible Hall-magnetohydrodynamic system

In this paper, we are concerned with the 3D compressible Hall-magnetohydrodynamic system in the whole space. We prove the global existence and temporal decay rates of the solutions to the system when the initial data are close to a stable equilibrium state by using a pure energy method