共查询到20条相似文献，搜索用时 15 毫秒
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Farah Perveen Mughal Ann Christina Bergmann Ha Uyen Buu Huynh Sarah Hyllekvist Jrgensen Inaam Mansha Meliha Kesmez Patrick Mark Schürch Alexandre Pierre Andr Theocharides Paul Robert Hansen Tina Friis Morten Orebo Holmstrm Evaldas Ciplys Rimantas Slibinskas Peter Hjrup Gunnar Houen Nicole Hartwig Trier 《International journal of molecular sciences》2022,23(12)
Myeloproliferative Neoplasms (MPNs) constitute a group of rare blood cancers that are characterized by mutations in bone marrow stem cells leading to the overproduction of erythrocytes, leukocytes, and thrombocytes. Mutations in calreticulin (CRT) genes may initiate MPNs, causing a novel variable polybasic stretch terminating in a common C-terminal sequence in the frameshifted CRT (CRTfs) proteins. Peptide antibodies to the mutated C-terminal are important reagents for research in the molecular mechanisms of MPNs and for the development of new diagnostic assays and therapies. In this study, eight peptide antibodies targeting the C-terminal of CRTfs were produced and characterised by modified enzyme-linked immunosorbent assays using resin-bound peptides. The antibodies reacted to two epitopes: CREACLQGWTE for SSI-HYB 385-01, 385-02, 385-03, 385-04, 385-07, 385-08, and 385-09 and CLQGWT for SSI-HYB 385-06. For the majority of antibodies, the residues Cys1, Trp9, and Glu11 were essential for reactivity. SSI-HYB 385-06, with the highest affinity, recognised recombinant CRTfs produced in yeast and the MARIMO cell line expressing CRTfs when examined in Western immunoblotting. Moreover, SSI-HYB 385-06 occasionally reacted to CRTfs from MPN patients when analysed by flow cytometry. The characterized antibodies may be used to understand the role of CRTfs in the pathogenesis of MPNs and to design and develop new diagnostic assays and therapeutic targets. 相似文献
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Arai MA Matsuo I Hagihara S Totani K Maruyama J Kitamoto K Ito Y 《Chembiochem : a European journal of chemical biology》2005,6(12):2281-2289
Calnexin (CNX) and its soluble homologue calreticulin (CRT) are lectin-like molecular chaperones that help newly synthesized glycoproteins to fold correctly in the rough endoplasmic reticulum (ER). To investigate the mechanism of glycoprotein-quality control, we have synthesized structurally defined high-mannose-type oligosaccharides related to this system. This paper describes the synthesis of the non-natural undecasaccharide 2 and heptasaccharide 16, designed as potential inhibitors of the ER quality-control system. Each possesses the key tetrasaccharide element (Glc1Man3) critical for the CNX/CRT binding, while lacking the pentamannosyl branch required for glucosidase II recognition. These oligosaccharides were evaluated for their ability to bind CRT by isothermal titration calorimetry (ITC). As expected, each of them had a significant affinity towards CRT. In addition, these compounds were shown to be resistant to glucosidase II digestion. Their activities in blocking the chaperone function of CRT were next measured by using malate dehydrogenase (MDH) as a substrate. Their inhibitory effects were shown to correlate well with their CRT-binding affinities, both being critically dependent upon the presence of the terminal glucose (Glc) residue. 相似文献
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Pei-Jun Tian Bao-Long Li Yu-Juan Shan Jin-Na Zhang Jing-Yu Chen Min Yu Lan-Wei Zhang 《International journal of molecular sciences》2015,16(8):20033-20049
L. paracasei subp. paracaseiX12 was previously isolated from a Chinese traditional fermented cheese with anticancer activities and probiotic potential. Herein, the integral peptidoglycan (X12-PG) was extracted by a modified trichloroacetic acid (TCA) method. X12-PG contained the four representative amino acids Asp, Glu, Ala and Lys, and displayed the similar lysozyme sensitivity, UV-visible scanning spectrum and molecular weight as the peptidoglycan standard. X12-PG could induce the production of apoptotic bodies observed by transmission electron microscopy (TEM). X12-PG could significantly induced the translocation of calreticulin (CRT) and the release of high mobility group box 1 protein (HMGB1), the two notable hallmarks of immunogenic cell death (ICD), with the endoplastic reticulum (ER) damaged and subsequently intracellular [Ca2+] elevated. Our findings implied that X12-PG could induce the ICD of HT-29 cells through targeting at the ER. The present results may enlighten the prospect of probiotics in the prevention of colon cancer. 相似文献
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Tijana Suboti
ki Olivera Mitrovi&#x; Ajti&#x; Emilija
ivkovi&#x; Milo&#x; Dikli&#x; Dragoslava &#x;iki&#x; Milica To&#x;i&#x; Bojana Beleslin-oki&#x; Teodora Dragojevi&#x; Mirjana Goti&#x; Juan F. Santibanez Vladan oki&#x; 《International journal of molecular sciences》2021,22(13)
Background: Chronic inflammation has been recognized in neoplastic disorders, including myeloproliferative neoplasm (MPN), as an important regulator of angiogenesis. Aims: We investigated the influence of vascular endothelial growth factor (VEGF) and pro-inflammatory interleukin-6 (IL-6) on the expression of angiogenic factors, as well as inflammation-related signaling in mononuclear cells (MNC) of patients with MPN and JAK2V617F positive human erythroleukemic (HEL) cells. Results: We found that IL-6 did not change the expression of angiogenic factors in the MNC of patients with MPN and HEL cells. However, IL-6 and the JAK1/2 inhibitor Ruxolitinib significantly increased angiogenic factors—endothelial nitric oxide synthase (eNOS), VEGF, and hypoxia-inducible factor-1 alpha (HIF-1α)—in patients with polycythemia vera (PV). Furthermore, VEGF significantly increased the expression of HIF-1α and eNOS genes, the latter inversely regulated by PI3K and mTOR signaling in the MNC of primary myelofibrosis (PMF). VEGF and inhibitors of inflammatory JAK1/2, PI3K, and mTOR signaling reduced the eNOS protein expression in HEL cells. VEGF also decreased the expression of eNOS and HIF-1α proteins in the MNC of PMF. In contrast, VEGF increased eNOS and HIF-1α protein expression in the MNC of patients with PV, which was mediated by the inflammatory signaling. VEGF increased the level of IL-6 immunopositive MNC of MPN. In summary, VEGF conversely regulated gene and protein expression of angiogenic factors in the MNC of PMF, while VEGF increased angiogenic factor expression in PV mediated by the inflammation-related signaling. Conclusion: The angiogenic VEGF induction of IL-6 supports chronic inflammation that, through positive feedback, further promotes angiogenesis with concomitant JAK1/2 inhibition. 相似文献
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苹果酸脱氢酶不仅是一种重要的糖代谢酶,而且具有较高的经济价值和理论研究价值。为了获得苹果酸脱氢酶包含体的有效体外复性方法,本文将渗透剂（蔗糖,甜菜碱,海藻糖）与人工伴侣体系（CTAB/β-CD）耦合,进行了大肠杆菌苹果酸脱氢酶（eMDH）包含体的体外复性研究。结果发现,人工伴侣与蔗糖或甜菜碱耦合,可明显提高eMDH包含体的复性效果,复性后产物的活性较稀释复性提高了2倍以上;但未发现海藻糖与人工伴侣存在这种耦合作用。同时发现,耦合作用还可降低人工伴侣体系中CTAB与β-CD的最佳配比（从1∶8下降到1∶6）,从而可提升人工伴侣体系的总用量,实现较高酶浓度条件下的有效复性。另外,利用渗透剂对蛋白质的热保护作用,实现了在较高温度（15℃）下eMDH包含体的复性。对复性产物结构的初步分析发现,耦合作用可使eMDH分子的α-螺旋及二聚体含量明显增多,因此复性产物的活性也显著提高。 相似文献
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人工伴侣促进溶菌酶复性动力学 总被引：3，自引：0，他引：3
利用复性和聚集竞争反应动力学模型描述自发复性和人工伴侣系统(十六烷基三甲基溴化铵与b -环糊精)促进溶菌酶复性动力学。在酶浓度为0.5~2.0 mgmL-1、盐酸胍浓度为0.5~2.2molL-1范围内,系统分析了盐酸胍浓度和人工伴侣浓度对复性动力学的影响。与自发复性相似,人工伴侣促进溶菌酶复性亦符合3级聚集反应动力学。人工伴侣系统的主要作用是抑制聚集体的生成速率,从而达到提高复性收率的效果。在盐酸胍浓度小于1.2mol稬-1时,人工伴侣系统和盐酸胍对促进变性溶菌酶复性具有协同作用,两者共同作用对促进蛋白质复性具有显著效果。 相似文献
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Machine learning (ML) models are valuable research tools for making accurate predictions. However, ML models often unreliably extrapolate outside their training data. The multiparameter delta method quantifies uncertainty for ML models (and generally for other nonlinear models) with parameters trained by least squares regression. The uncertainty measure requires the gradient of the model prediction and the Hessian of the loss function, both with respect to model parameters. Both the gradient and Hessian can be readily obtained from most ML software frameworks by automatic differentiation. We show examples of the uncertainty method in applications of molecular simulations and neural networks. We further show that the uncertainty measure is larger for input space regions that are not part of the training data. Therefore, this method can be used to identify extrapolation and to aid in selecting training data or assessing model reliability. 相似文献
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旋转机械是广泛应用于石化等行业的关键设备,随着计算机技术和人工智能技术的迅速发展,智能诊断技术为旋转机械的故障分析提供了先进手段。论文概述了旋转机械故障智能诊断最重要的九种方法及其工程运用,并对每种方法列举其优缺点。从大量的科研和实例中得出结论,指出了今后的发展方向。 相似文献
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Mehrad Ansari Heta A. Gandhi David G. Foster Andrew D. White 《American Institute of Chemical Engineers》2022,68(6):e17695
Computational fluid dynamics (CFD) analysis is widely used in chemical engineering. Although CFD calculations are accurate, the computational cost associated with complex systems makes it difficult to obtain empirical equations between system variables. Here, we combine active learning (AL) and symbolic regression (SR) to get a symbolic equation for system variables from CFD simulations. Gaussian process regression-based AL allows for automated selection of variables by selecting the most instructive points from the available range of possible parameters. The results from these experiments are then passed to SR to find empirical symbolic equations for CFD models. This approach is scalable and applicable for any desired number of CFD design parameters. To demonstrate the effectiveness, we use this method with two model systems. We recover an empirical equation for the pressure drop in a bent pipe and a new equation for predicting backflow in a heart valve under aortic insufficiency. 相似文献
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基于知识的调度技术及其应用 总被引：2，自引：0，他引：2
在分析间歇过程调度问题及其求解方法的基础上,综述了基于知识的调度技术及其工业应用,并对新一代智能调度系统致力解决的问题及相应的体系结构进行了探讨。最后就中国间歇化工企业推进计划、调度与控制系统集成和开发基于知识的调度系统提出了建议。 相似文献
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Ron Wallace 《International journal of molecular sciences》2010,11(6):2421-2442
Throughout much of the history of biology, the cell membrane was functionally defined as a semi-permeable barrier separating aqueous compartments, and an anchoring site for proteins. Little attention was devoted to its possible regulatory role in intracellular molecular processes and neuron electrical signaling. This article reviews the history of membrane studies and the current state of the art. Emphasis is placed on natural and artificial membrane studies of electric field effects on molecular organization, especially as these may relate to impulse propagation in neurons. Implications of these studies for new designs in artificial intelligence are briefly examined. 相似文献
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David Pratella Samira Ait-El-Mkadem Saadi Sylvie Bannwarth Vronique Paquis-Fluckinger Silvia Bottini 《International journal of molecular sciences》2021,22(19)
Rare diseases (RDs) concern a broad range of disorders and can result from various origins. For a long time, the scientific community was unaware of RDs. Impressive progress has already been made for certain RDs; however, due to the lack of sufficient knowledge, many patients are not diagnosed. Nowadays, the advances in high-throughput sequencing technologies such as whole genome sequencing, single-cell and others, have boosted the understanding of RDs. To extract biological meaning using the data generated by these methods, different analysis techniques have been proposed, including machine learning algorithms. These methods have recently proven to be valuable in the medical field. Among such approaches, unsupervised learning methods via neural networks including autoencoders (AEs) or variational autoencoders (VAEs) have shown promising performances with applications on various type of data and in different contexts, from cancer to healthy patient tissues. In this review, we discuss how AEs and VAEs have been used in biomedical settings. Specifically, we discuss their current applications and the improvements achieved in diagnostic and survival of patients. We focus on the applications in the field of RDs, and we discuss how the employment of AEs and VAEs would enhance RD understanding and diagnosis. 相似文献
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W. Zhu Y. Ma M. G. Benton J. A. Romagnoli Y. Zhan 《American Institute of Chemical Engineers》2019,65(2):582-591
Monitoring the operation of a pyrolysis reactor is always challenging due to the extremely high-operating temperature (over 800°C) in the fired furnace. To improve current monitoring capability, a monitoring framework is proposed that builds upon thermal photography to provide a detailed view inside the fired furnace. Based on the infrared images generated from the temperature data provided by cameras, a deep learning approach is introduced to automatically identify tube regions from the raw images. The pixel-wise tube segmentation network is named Res50-UNet, which combines the popular ResNet-50 and U-Net architectures. By this approach, the precise temperature and shape on pyrolysis tubes are monitored. The control limits are eventually drawn by the adaptive k-nearest neighbor method to raise alarms for faults. Through testing over real plant data, the framework assists process operators by providing in-depth operating information of the reactor and fault diagnosis. © 2018 American Institute of Chemical Engineers AIChE J, 65: 582–591, 2019 相似文献