130 research outputs found

    Hot stamping of an Al-Li alloy: a feasibility study

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    The feasibility of forming a third generation aluminium-lithium alloy (AA2060) into a complex shaped panel component, was studied by using an advanced forming technology called solution heat treatment, cold die forming and in-die quenching (HFQa) process. The main challenges using HFQ technology to form complex shaped AA2060 component was to find out optimum forming parameters, such as forming temperature, forming speed, lubrication condition and blank holding force. In this paper, the optimum forming temperature was mainly concerned. The flow stresses of AA2060 were obtained at different temperatures ranging from 350 to 520 °C at the strain rate of 2 s−1. The suitable temperature to achieve the adequate ductility was found at 470 °C. By forming the AA2060 blanks at the optimum forming temperature, experimental results exhibited the feasibility for forming complex-shaped AA2060 components. The formed components were analysed through strain measurements. The post-form mechanical properties of AA2060 were assessed using hardness and tensile tests

    A Comparison of Global and Local Statistical and Machine Learning Techniques in Estimating Flash Flood Susceptibility (Short Paper)

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    Coenzyme Q deficiency may predispose to sudden unexplained death via an increased risk of cardiac arrhythmia

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    Cardiac arrhythmia is currently considered to be the direct cause of death in a majority of sudden unexplained death (SUD) cases, yet the genetic predisposition and corresponding endophenotypes contributing to SUD remain incompletely understood. In this study, we aimed to investigate the involvement of Coenzyme Q (CoQ) deficiency in SUD. First, we re-analyzed the exome sequencing data of 45 SUD and 151 sudden infant death syndrome (SIDS) cases from our previous studies, focusing on previously overlooked genetic variants in 44 human CoQ deficiency-related genes. A considerable proportion of the SUD (38%) and SIDS (37%) cases were found to harbor rare variants with likely functional effects. Subsequent burden testing, including all rare exonic and untranslated region variants identified in our case cohorts, further confirmed the existence of significant genetic burden. Based on the genetic findings, the influence of CoQ deficiency on electrophysiological and morphological properties was further examined in a mouse model. A significantly prolonged PR interval and an increased occurrence of atrioventricular block were observed in the 4-nitrobenzoate induced CoQ deficiency mouse group, suggesting that CoQ deficiency may predispose individuals to sudden death through an increased risk of cardiac arrhythmia. Overall, our findings suggest that CoQ deficiency-related genes should also be considered in the molecular autopsy of SUD

    3D Bioprinting of Multifunctional Dynamic Nanocomposite Bioinks Incorporating Cu‐Doped Mesoporous Bioactive Glass Nanoparticles for Bone Tissue Engineering

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    Abstract Bioprinting has seen significant progress in recent years for the fabrication of bionic tissues with high complexity. However, it remains challenging to develop cell‐laden bioinks exhibiting superior physiochemical properties and bio‐functionality. In this study, a multifunctional nanocomposite bioink is developed based on amine‐functionalized copper (Cu)‐doped mesoporous bioactive glass nanoparticles (ACuMBGNs) and a hydrogel formulation relying on dynamic covalent chemistry composed of alginate dialdehyde (oxidized alginate) and gelatin, with favorable rheological properties, improved shape fidelity, and structural stability for extrusion‐based bioprinting. The reversible dynamic microenvironment in combination with the impact of cell‐adhesive ligands introduced by aminated particles enables the rapid spreading (within 3 days) and high survival (>90%) of embedded human osteosarcoma cells and immortalized mouse bone marrow‐derived stroma cells. Osteogenic differentiation of primary mouse bone marrow stromal stem cells (BMSCs) and angiogenesis are promoted in the bioprinted alginate dialdehyde‐gelatin (ADA‐GEL or AG)‐ACuMBGN scaffolds without additional growth factors in vitro, which is likely due to ion stimulation from the incorporated nanoparticles and possibly due to cell mechanosensing in the dynamic matrix. In conclusion, it is envisioned that these nanocomposite bioinks can serve as promising platforms for bioprinting complex 3D matrix environments providing superior physiochemical and biological performance for bone tissue engineering

    Identification of COUP-TFII Orphan Nuclear Receptor as a Retinoic Acid–Activated Receptor

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    The chicken ovalbumin upstream promoter-transcription factors (COUP-TFI and II) make up the most conserved subfamily of nuclear receptors that play key roles in angiogenesis, neuronal development, organogenesis, cell fate determination, and metabolic homeostasis. Although the biological functions of COUP-TFs have been studied extensively, little is known of their structural features or aspects of ligand regulation. Here we report the ligand-free 1.48 Å crystal structure of the human COUP-TFII ligand-binding domain. The structure reveals an autorepressed conformation of the receptor, where helix α10 is bent into the ligand-binding pocket and the activation function-2 helix is folded into the cofactor binding site, thus preventing the recruitment of coactivators. In contrast, in multiple cell lines, COUP-TFII exhibits constitutive transcriptional activity, which can be further potentiated by nuclear receptor coactivators. Mutations designed to disrupt cofactor binding, dimerization, and ligand binding, substantially reduce the COUP-TFII transcriptional activity. Importantly, retinoid acids are able to promote COUP-TFII to recruit coactivators and activate a COUP-TF reporter construct. Although the concentration needed is higher than the physiological levels of retinoic acids, these findings demonstrate that COUP-TFII is a ligand-regulated nuclear receptor, in which ligands activate the receptor by releasing it from the autorepressed conformation

    A novel single nucleotide polymorphism within the NOD2 gene is associated with pulmonary tuberculosis in the Chinese Han, Uygur and Kazak populations

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    <p>Abstract</p> <p>Background</p> <p>The present study aimed to investigate the genetic polymorphisms in exon 4 of the <it>NOD2 </it>gene in tuberculosis patients and healthy controls, in order to clarify whether polymorphisms in the <it>NOD2 </it>gene is associated with tuberculosis.</p> <p>Methods</p> <p>A case-control study was performed on the Chinese Han, Uygur and Kazak populations. Exon 4 of the <it>NOD2 </it>gene was sequenced in 425 TB patients and 380 healthy controls to identify SNPs.</p> <p>Results</p> <p>The frequency of T/G genotypes for the Arg587Arg (CGT → CGG) single nucleotide polymorphism (SNP) in <it>NOD2 </it>was found to be significantly higher in the Uygur (34.9%) and Kazak (37.1%) populations than the Han population (18.6%). Also, the frequency of G/G genotypes for the Arg587Arg SNP was significantly higher in the Uyghur (8.3%) and Kazak (5.4%) populations than the Han population (0.9%). Meanwhile, no significant difference was found in the Arg587Arg polymorphism between the tuberculosis patients and healthy controls in the Uyghur and Kazak populations (<it>P </it>> 0.05) whereas, a significant difference was observed in the Arg587Arg polymorphism between the tuberculosis patients and healthy controls in the Han population (<it>P </it>< 0.01). The odd ratio of 2.16 (95% CI = 1.31-3.58; <it>P </it>< 0.01) indicated that the Arg587Arg SNP in <it>NOD2 </it>may be associated with susceptibility to tuberculosis in the Chinese Han population.</p> <p>Conclusions</p> <p>Our study is the first to demonstrate that the Arg587Arg SNP in <it>NOD2 </it>is a new possible risk factor for tuberculosis in the Chinese Han population, but not in the Uyghur and Kazak populations. Our results may reflect racial differences in genetic susceptibility to tuberculosis.</p

    3D bioactive composite scaffolds for bone tissue engineering

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    Bone is the second most commonly transplanted tissue worldwide, with over four million operations using bone grafts or bone substitute materials annually to treat bone defects. However, significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma, cancer, infection and arthritis. Developing bioactive three-dimensional (3D) scaffolds to support bone regeneration has therefore become a key area of focus within bone tissue engineering (BTE). A variety of materials and manufacturing methods including 3D printing have been used to create novel alternatives to traditional bone grafts. However, individual groups of materials including polymers, ceramics and hydrogels have been unable to fully replicate the properties of bone when used alone. Favourable material properties can be combined and bioactivity improved when groups of materials are used together in composite 3D scaffolds. This review will therefore consider the ideal properties of bioactive composite 3D scaffolds and examine recent use of polymers, hydrogels, metals, ceramics and bio-glasses in BTE. Scaffold fabrication methodology, mechanical performance, biocompatibility, bioactivity, and potential clinical translations will be discussed

    Comparative mitogenomes and phylogenetic analysisreveal taxonomicrelationship of genera Teredorus and Systolederus (Orthoptera, Tetrigoidea)

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    Li, Xuejuan, Liu, Yuxin, Lin, Liliang (2021): Comparative mitogenomes and phylogenetic analysisreveal taxonomicrelationship of genera Teredorus and Systolederus (Orthoptera, Tetrigoidea). Zootaxa 5027 (1): 127-135, DOI: https://doi.org/10.11646/zootaxa.5027.1.

    Evaluation of the red-crowned crane habitat in the Yellow River Delta Nature Reserve

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    AbstractAs a consequence of wildlife habitat is in constant evolution, periodic monitoring is essential to assess habitat quality. In this study the change to the red-crowned crane habitat in the Yellow River Delta Nature Reserve (YRDNR) was detected from multi-temporal remote sensing data from 1992 to 2008 in a geographic information system (GIS). The changing quality of the habitat was evaluated from both physical constraint and human disturbance. The results indicate that potential habitat shank 37.8% during 1992-2001, but recovered 96.8% by 2008. Human disturbance in the forms of roads, oil wells and residential areas caused a high degree of behavioral fragmentation. Suitable habitat shrank by 1,569ha to a level below that of 1992 despite an increase of 4,450ha in potential habitat due to an increase of 6,019ha in fragmented areas. Therefore, efforts should also be directed at improving habitat quality by minimizing human activities in the Reserv

    Cannabinoid Receptors in Myocardial Injury: A Brother Born to Rival

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    Cannabinoid receptors typically include type 1 (CB1) and type 2 (CB2), and they have attracted extensive attention in the central nervous system (CNS) and immune system. Due to more in-depth studies in recent years, it has been found that the typical CB1 and CB2 receptors confer functional importance far beyond the CNS and immune system. In particular, many works have reported the critical involvement of the CB1 and CB2 receptors in myocardial injuries. Both pharmacological and genetic approaches have been used for studying CB1 and CB2 functions in these studies, revealing that the brother receptors have many basic differences and sometimes antagonistic functions in a variety of myocardial injuries, despite some sequence or location identity they share. Herein, we introduce the general differences of CB1 and CB2 cannabinoid receptors, and summarize the functional rivalries between the two brother receptors in the setting of myocardial injuries. We point out the importance of individual receptor-based modulation, instead of dual receptor modulators, when treating myocardial injuries
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