Study on dynamic characteristic of closed-cell aluminum foam

Closed-cell aluminum foam has been widely used in aerospace, rail transit and mechanical for its outstanding performance. But for a long time, the research on its vibration damping performance is only limited to the material damping test, there are relatively few studies on its dynamic characteristics. In this paper, we studied the relationship between dynamic characteristic and feature parameters. Modal assurance criterion and Finite element method were used to verify the accuracy of experimental model. It turned out that the average pore diameter of closed-cell aluminum foam conforms to Gaussian distribution. The modal analysis method can be used in the research of dynamic characteristic of closed-cell aluminum foam. Its damping ratio showed increasing trend with the increase of porosity, natural frequency and the decrease of mean pore size. Each order natural frequency increases along with the increase of porosity

LRPPRC: A Multifunctional Protein Involved in Energy Metabolism and Human Disease

The pentatricopeptide repeat (PPR) family plays a major role in RNA stability, regulation, processing, splicing, translation, and editing. Leucine-rich PPR-motif-containing protein (LRPPRC), a member of the PPR family, is a known gene mutation that causes Leigh syndrome French–Canadian. Recently, growing evidence has pointed out that LRPPRC dysregulation is related to various diseases ranging from tumors to viral infections. This review presents available published data on the LRPPRC protein function and its role in tumors and other diseases. As a multi-functional protein, LRPPRC regulates a myriad of biological processes, including energy metabolism and maturation and the export of nuclear mRNA. Overexpression of LRPPRC has been observed in various human tumors and is associated with poor prognosis. Downregulation of LRPPRC inhibits growth and invasion, induces apoptosis, and overcomes drug resistance in tumor cells. In addition, LRPPRC plays a potential role in Parkinson's disease, neurofibromatosis 1, viral infections, and venous thromboembolism. Further investigating these new functions of LRPPRC should provide novel opportunities for a better understanding of its pathological role in diseases from tumors to viral infections and as a potential biomarker and molecular target for disease treatment

Clinical significance of a point mutation in DNA polymerase beta (POLB) gene in gastric cancer.

Gastric cancer (GC) is a major cause of global cancer mortality. Genetic variations in DNA repair genes can modulate DNA repair capability and, consequently, have been associated with risk of developing cancer. We have previously identified a T to C point mutation at nucleotide 889 (T889C) in DNA polymerase beta (POLB) gene, a key enzyme involved in base excision repair in primary GCs. The purpose of this study was to evaluate the mutation and expression of POLB in a larger cohort and to identify possible prognostic roles of the POLB alterations in GC. Primary GC specimens and their matched normal adjacent tissues were collected at the time of surgery. DNA, RNA and protein samples were isolated from GC specimens and cell lines. Mutations were detected by PCR-RFLP/DHPLC and sequencing analysis. POLB gene expression was examined by RT-PCR, tissue microarray, Western blotting and immunofluorescence assays. The function of the mutation was evaluated by chemosensitivity, MTT, Transwell matrigel invasion and host cell reactivation assays. The T889C mutation was detected in 18 (10.17%) of 177 GC patients. And the T889C mutation was associated with POLB overexpression, lymph nodes metastases and poor tumor differentiation. In addition, patients with- the mutation had significantly shorter survival time than those without-, following postoperative chemotherapy. Furthermore, cell lines with T889C mutation in POLB gene were more resistant to the treatment of 5-fluorouracil, cisplatin and epirubicin than those with wild type POLB. Forced expression of POLB gene with T889C mutation resulted in enhanced cell proliferation, invasion and resistance to anticancer drugs, along with increased DNA repair capability. These results suggest that POLB gene with T889C mutation in surgically resected primary gastric tissues may be clinically useful for predicting responsiveness to chemotherapy in patients with GC. The POLB gene alteration may serve as a prognostic biomarker for GC

Clinical Significance of a Point Mutation in DNA Polymerase Beta (POLB) Gene in Gastric Cancer.

Gastric cancer (GC) is a major cause of global cancer mortality. Genetic variations in DNA repair genes can modulate DNA repair capability and, consequently, have been associated with risk of developing cancer. We have previously identified a T to C point mutation at nucleotide 889 (T889C) in DNA polymerase beta (POLB) gene, a key enzyme involved in base excision repair in primary GCs. The purpose of this study was to evaluate the mutation and expression of POLB in a larger cohort and to identify possible prognostic roles of the POLB alterations in GC. Primary GC specimens and their matched normal adjacent tissues were collected at the time of surgery. DNA, RNA and protein samples were isolated from GC specimens and cell lines. Mutations were detected by PCR-RFLP/DHPLC and sequencing analysis. POLB gene expression was examined by RT-PCR, tissue microarray, Western blotting and immunofluorescence assays. The function of the mutation was evaluated by chemosensitivity, MTT, Transwell matrigel invasion and host cell reactivation assays. The T889C mutation was detected in 18 (10.17%) of 177 GC patients. And the T889C mutation was associated with POLB overexpression, lymph nodes metastases and poor tumor differentiation. In addition, patients with- the mutation had significantly shorter survival time than those without-, following postoperative chemotherapy. Furthermore, cell lines with T889C mutation in POLB gene were more resistant to the treatment of 5-fluorouracil, cisplatin and epirubicin than those with wild type POLB. Forced expression of POLB gene with T889C mutation resulted in enhanced cell proliferation, invasion and resistance to anticancer drugs, along with increased DNA repair capability. These results suggest that POLBgene with T889C mutation in surgically resected primary gastric tissues may be clinically useful for predicting responsiveness to chemotherapy in patients with GC. The POLB gene alteration may serve as a prognostic biomarker for GC

DNAJA1- and conformational mutant p53-dependent inhibition of cancer cell migration by a novel compound identified through a virtual screen

Cancers are frequently addicted to oncogenic missense mutant p53 (mutp53). DNAJA1, a member of heat shock protein 40 (HSP40), also known as J-domain proteins (JDPs), plays a crucial role in the stabilization and oncogenic activity of misfolded or conformational mutp53 by binding to and preventing mutp53 from proteasomal degradation. However, strategies to deplete mutp53 are not well-established, and no HSP40/JDPs inhibitors are clinically available. To identify compounds that bind to DNAJA1 and induce mutp53 degradation, we performed an in silico docking study of ~10 million of compounds from the ZINC database for the J-domain of DNAJA1. A compound 7-3 was identified, and its analogue A11 effectively reduced the levels of DNAJA1 and conformational mutp53 with minimal effects on the levels of wild-type p53 and DNA-contact mutp53. A11 suppressed migration and filopodia formation in a manner dependent on DNAJA1 and conformational mutp53. A mutant DNAJA1 with alanine mutations at predicted amino acids (tyrosine 7, lysine 44, and glutamine 47) failed to bind to A11. Cells expressing the mutant DNAJA1 became insensitive to A11-mediated depletion of DNAJA1 and mutp53 as well as A11-mediated inhibition of cell migration. Thus, A11 is the first HSP40/JDP inhibitor that has not been previously characterized for depleting DNAJA1 and subsequently conformational mutp53, leading to inhibition of cancer cell migration. A11 can be exploited for a novel treatment against cancers expressing conformational mutp53

A Point Mutation in DNA Polymerase β (POLB) Gene Is Associated with Increased Progesterone Receptor (PR) Expression and Intraperitoneal Metastasis in Gastric Cancer

Increased expression of progesterone receptor (PR) has been reported in gastric cancer (GC). We have previously identified a functional T889C point mutation in DNA polymerase beta (POLB), a DNA repair gene in GC. To provide a detailed analysis of molecular changes associated with the mutation, human cDNA microarrays focusing on 18 signal transduction pathways were used to analyze differential gene expression profiles between GC tissues with T889C mutant in POLB gene and those with wild type. Among the differentially expressed genes, notably, PR was one of the significantly up-regulated genes in T889C mutant POLB tissues, which were subsequently confirmed in POLB gene transfected AGS cell line. Interestingly, patients with T889C mutation and PR positivity were associated with higher incidence of intraperitoneal metastasis (IM). In vitro studies indicate that PR expression was upregulated in AGS cell line when transfected with T889C mutant expression vector. Cotransfection of T889C mutant allele and PR gene induced cell migration in the cell line. These data demonstrated that T889C mutation-associated PR overexpression results in increased IM. Therefore, T889C mutation-associated PR overexpression may serve as a biomarker for an adverse prognosis for human GC

Qwen Technical Report

Large language models (LLMs) have revolutionized the field of artificial intelligence, enabling natural language processing tasks that were previously thought to be exclusive to humans. In this work, we introduce Qwen, the first installment of our large language model series. Qwen is a comprehensive language model series that encompasses distinct models with varying parameter counts. It includes Qwen, the base pretrained language models, and Qwen-Chat, the chat models finetuned with human alignment techniques. The base language models consistently demonstrate superior performance across a multitude of downstream tasks, and the chat models, particularly those trained using Reinforcement Learning from Human Feedback (RLHF), are highly competitive. The chat models possess advanced tool-use and planning capabilities for creating agent applications, showcasing impressive performance even when compared to bigger models on complex tasks like utilizing a code interpreter. Furthermore, we have developed coding-specialized models, Code-Qwen and Code-Qwen-Chat, as well as mathematics-focused models, Math-Qwen-Chat, which are built upon base language models. These models demonstrate significantly improved performance in comparison with open-source models, and slightly fall behind the proprietary models.Comment: 59 pages, 5 figure