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Genetic variants in the ADD1 and GNB3 genes and blood pressure response to potassium supplementation

Dai-Hai YU PhD, Jian-Feng HUANG MD, Ji-Chun CHEN MS, Jie CAO MS, Shu-Feng CHEN PhD, Dong-Feng GU MD, PhD, for the GenSalt Collaborative Research Group, De-Pei LIU PhD, Lai-Yuan WANG PhD, Jing CHEN MD, MSc, Jiang HE MD, PhD, Cashell E. JAQUISH PhD, Dabeeru C. RAO PhD, Charles GU PhD, James E. HIXSON PhD, Chung-Shiuan CHEN MS⁸, Paul K. WHELTON MD, MSc⁹,

《医学前沿（英文）》 2010年第4卷第1期页码 59-66 doi: 10.1007/s11684-010-0015-8

摘要： Dietary potassium-supplementation has been associated with a decreased risk of hypertension and other cardiovascular outcomes. However, blood pressure (BP) responses to potassium supplementation vary among individuals. This study was designed to examine the association between 12 single nucleotide polymorphisms (SNPs) in the adducin 1 alpha (ADD1) and guanine nucleotide binding protein (G protein) beta polypeptide 3 (GNB3) genes and systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) responses to potassium-supplementation. We conducted a 7-day high-sodium intervention (307.8 mmol sodium/day) followed by a 7-day high-sodium with potassium-supplementation (60 mmol potassium/day) among 1906 Han Chinese participants from rural north China. BP measurements were obtained at the end of each intervention period using a random-zero sphygmomanometer. We identified significant associations between ADD1 variant rs17833172 and SBP, DBP, and MAP responses to potassium-supplementation (all <0.0001) that remained significant after adjustment for multiple comparisons. In participants that were heterozygous or homozygous for the G allele of this marker, SBP, DBP, and MAP response to potassium-supplementation were −3.52 (−3.82, −3.21), −1.41 (−1.66, −1.15) and −2.12 (−2.37, −1.87), respectively, as compared to the corresponding responses of 1.99 (0.25, 3.73), −0.65 (−0.10, −0.21), and −0.23 (−0.37, 0.83), respectively, for those who were homozygous for A allele. In addition, participants with at least one copy of the G allele of rs12503220 of the ADD1 gene had significantly increased DBP and MAP response to potassium-supplementation ( = 0.0041 and 0.01, respectively), which was also significant after correction for multiple testing. DBP and MAP responses to potassium-supplementation were −1.36 (−1.63, −1.10) and −2.07 (−2.32, −1.82) for those with at least G allele compared to corresponding responses of 0.86 (−0.68, 2.40) and −0.45 (−1.74, 0.84) for those who were homozygous for A allele. In summary, our study identified novel associations between genetic variants of the ADD1 gene and BP response to potassium-supplementation, which could have important clinical and public health implications. Future studies aimed at replicating these novel findings are warranted.

关键词： blood pressure genetics polymorphism die-tary potassium potassium sensitivity adducin 1 alpha (ADD1) guanine nucleotide binding protein beta polypeptide 3 (GNB3)

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Effects of hypoxia inducible factor-1alpha siRNA on the invasion of human Hela cells and expression of

Bin YANG MS , Xianglin YUAN , Yanmei ZOU , Qingsong XI , Guoxian LONG , Qiang FU , Guangyuan HU MM ,

《医学前沿（英文）》 2009年第3卷第3期页码 303-308 doi: 10.1007/s11684-009-0060-3

摘要： The effects of hypoxia on the invasion and the related protein expression of Hela cells and the role of hypoxia inducible factor-1α (HIF-1α) were investigated. The Hela cells were divided into three groups, namely, H (non-transfected Hela cells), H (pGenesil-1 empty plasmid-transfected Hela cells), and H (HIF-1α-shRNA plasmid-transfected Hela cells), and were cultured under hypoxia (1% O) and normoxia for 48h. The expression of HIF-1α, E-cadherin, β-catenin, and actin was detected using Western blot. The scratch test and the invasion assay were applied to examine the invasion in each group. The expression of HIF-1α, E-cadherin, and β-catenin in tumor grafts was assayed immunohistochemically. Western blot results revealed that the bands of HIF-1α, E-cadherin, β-catenin, and actin proteins were detected in the H and H groups under hypoxia for 48h. The expression of E-cadherin, β-catenin, and actin was detected in the H group under hypoxia for 48h, and normoxia. In the H, H, and H groups under normoxia, and the H group under hypoxia for 48h, no expression of HIF-1α was detectable. The scratch test showed that the invasive ability in the H group was significantly alleviated. Immunohistochemically, it was found that there was a significant difference in the expression of HIF-1α, E-cadherin, and β-catenin between the H and H groups (<0.05), but the difference was not significant between the H and H groups. It was concluded that the effects of hypoxia on the invasion of human cervical cancer Hela cells and the expression of related proteins (E-cadherin, β-catenin, and actin) depend on HIF-1α.

关键词： hypoxia actin β -catenin E-cadherin invasion

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转录因子HNF1A、HNF4A和FOXA2调节肝细胞蛋白质N-糖基化 Article

Vedrana Vičić Bočkor,Nika Foglar,Goran Josipović,Marija Klasić,Ana Vujić,Branimir Plavša,Toma Keser,Samira Smajlović,Aleksandar Vojta,Vlatka Zoldoš

《工程（英文）》 2024年第32卷第1期页码 58-69 doi: 10.1016/j.eng.2023.09.019

摘要：

Hepatocyte nuclear factor 1 alpha (HNF1A), hepatocyte nuclear factor 4 alpha (HNF4A), and forkhead box protein A2 (FOXA2) are key transcription factors that regulate a complex gene network in the liver, creating a regulatory transcriptional loop. The Encode and ChIP-Atlas databases identify the recognition sites of these transcription factors in many glycosyltransferase genes. Our in silico analysis of HNF1A, HNF4A, and FOXA2 binding to the 10 candidate glyco-genes studied in this work confirms a significant enrichment of these transcription factors specifically in the liver. Our previous studies identified HNF1A as a master regulator of fucosylation, glycan branching, and galactosylation of plasma glycoproteins. Here, we aimed to functionally validate the role of the three transcription factors on downstream glyco-gene transcriptional expression and the possible effect on glycan phenotype. We used the state-of-the-art clustered regularly interspaced short palindromic repeats/dead Cas9 (CRISPR/dCas9) molecular tool for the downregulation of the HNF1A, HNF4A, and FOXA2 genes in HepG2 cells—a human liver cancer cell line. The results show that the downregulation of all three genes individually and in pairs affects the transcriptional activity of many glyco-genes, although downregulation of glyco-genes was not always followed by an unambiguous change in the corresponding glycan structures. The effect is better seen as an overall change in the total HepG2 N-glycome, primarily due to the extension of biantennary glycans. We propose an alternative way to evaluate the N-glycome composition via estimating the overall complexity of the glycome by quantifying the number of monomers in each glycan structure. We also propose a model showing feedback loops with the mutual activation of HNF1A–FOXA2 and HNF4A–FOXA2 affecting glyco-genes and protein glycosylation in HepG2 cells.

关键词： Clustered regularly interspaced short palindromic repeats/dead Cas9 (CRISPR/dCas9) Epigenetics Hepatocyte nuclear factor 1 alpha (HNF1A) Hepatocyte nuclear factor 4 alpha (HNF4A) Forkhead box protein A2 (FOXA2) N-glycosylation HepG2 cells

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灰色预测模型GM（１，１）的适用性分析及在火灾风险预测中的应用

陈子锦,王福亮,陆守香

《中国工程科学》 2007年第9卷第5期页码 91-94

摘要：

通过对灰色预测模型———GM（１，１）的理论分析，证明了该模型的预测值及其变化趋势均具有单调性，进而提出了GM（１，１）模型的适用性判据，并给出了该判据在火灾风险灰色预测中的应用实例。

关键词：火灾预测 GM(1 1)模型火灾伤人率

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用于设计量子点元胞自动机算术电路的可扩展 1 位全加器 Research Article

Hamideh KHAJEHNASIR-JAHROMI, Pooya TORKZADEH, Massoud DOUSTI

《信息与电子工程前沿（英文）》 2022年第23卷第8期页码 1264-1276 doi: 10.1631/FITEE.2100287

摘要：设计算术电路关键是基于1位全加器的结构。低复杂度的全加器模块有利于开发各种复杂结构。本文介绍了基于单元交互的可扩展1位QCA全加器结构。

关键词：量子点元胞自动机（QCA）；全加器；行波进位加法器（RCA）；加/减电路；乘数

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Metabolic interventions combined with CTLA-4 and PD-1/PD-L1 blockade for the treatment of tumors: mechanisms

《医学前沿（英文）》页码 805-822 doi: 10.1007/s11684-023-1025-7

摘要： Immunotherapies based on immune checkpoint blockade (ICB) have significantly improved patient outcomes and offered new approaches to cancer therapy over the past decade. To date, immune checkpoint inhibitors (ICIs) of CTLA-4 and PD-1/PD-L1 represent the main class of immunotherapy. Blockade of CTLA-4 and PD-1/PD-L1 has shown remarkable efficacy in several specific types of cancers, however, a large subset of refractory patients presents poor responsiveness to ICB therapy; and the underlying mechanism remains elusive. Recently, numerous studies have revealed that metabolic reprogramming of tumor cells restrains immune responses by remodeling the tumor microenvironment (TME) with various products of metabolism, and combination therapies involving metabolic inhibitors and ICIs provide new approaches to cancer therapy. Nevertheless, a systematic summary is lacking regarding the manner by which different targetable metabolic pathways regulate immune checkpoints to overcome ICI resistance. Here, we demonstrate the generalized mechanism of targeting cancer metabolism at three crucial immune checkpoints (CTLA-4, PD-1, and PD-L1) to influence ICB therapy and propose potential combined immunotherapeutic strategies co-targeting tumor metabolic pathways and immune checkpoints.

关键词： CTLA-4 PD-1 PD-L1 immune checkpoint blockade (ICB) metabolic reprogramming combined tumor therapeutic strategies

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渤海辽东带地质认识的突破与金县1-1大油田的发现

邓运华

《中国工程科学》 2011年第13卷第10期页码 13-18

摘要：在此认识指导下选择研究方向，评价有利目标，经钻探发现了金县1-1大油田，储量达1.5×10⁸ m³，充分显示了科研在油气勘探中的作用。

关键词：渤海辽东带金县1-1 地质认识大油田

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联邦无监督表示学习 Research Article

张凤达1,况琨1,陈隆1,游兆阳1,沈弢1,肖俊1,张寅1,吴超2,吴飞1,庄越挺1,李晓林3,4,5

《信息与电子工程前沿（英文）》 2023年第24卷第8期页码 1181-1193 doi: 10.1631/FITEE.2200268

摘要： FURL提出了两个新挑战：（1）客户端之间的数据分布转移（非独立同分布）会使本地模型专注于不同的类别，从而导致表示空间的不一致；（2）如果FURL中客户端之间没有统一的信息，客户端之间的表示就会错位。

关键词：联邦学习；无监督学习；表示学习；对比学习

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非等间距GM(1,1)幂模型及其工程应用

王正新,党耀国,刘思峰

《中国工程科学》 2012年第14卷第7期页码 98-102

摘要：

针对工程中大量存在的非等间距序列的建模问题，提出了非等间距GM(1, 1)幂模型。以平均相对误差绝对值最小化为目标，以模型参数之间的关系为约束，构建了一个非线性优化模型实现非等间距GM(1, 1)幂模型的参数估计。结果表明，非等间距GM(1, 1)幂模型的形式较为灵活，非等间距GM(1, 1)模型和灰色Verhulst模型均是非等间距GM(1, 1)幂模型的特殊情形，幂指数的优化有利于提高建模精度。最后通过一个工程实例验证了非等间距GM(1, 1)幂模型的有效性与实用性。

关键词：灰色系统非等间距序列 GM(1 1)幂模型参数优化

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磁控溅射法生长的带隙可调谐(GaxIn1−x)2O3 Research Articles

张法碧1,孙巾寓1,李海鸥1,周娟1,王荣1,孙堂友1,傅涛1,肖功利1,李琦1,刘兴鹏1,张秀云1,郭道友2,王相虎3,秦祖军1

《信息与电子工程前沿（英文）》 2021年第22卷第10期页码 1370-1378 doi: 10.1631/FITEE.2000330

摘要：采用磁控溅射技术和热退火技术在(0001)蓝宝石衬底上制备了多组分氧化物(GaxIn1−x)2O3薄膜，实现可调带隙。详细研究了三元化合物(GaxIn1−x)2O3在整个组成范围内的光学性质和能带结构演化。X射线衍射谱表明，Ga含量在0.11至0.55之间的(GaxIn1−x)2O3薄膜既有立方结构，也有单斜结构，而Ga含量高于0.74的(GaxIn1−x)2O3薄膜只有单斜结构。实验结果为透明导电化合物半导体(GaxIn1−x)2O3薄膜在光电和光伏行业的应用，特别是在显示器、发光二极管和太阳能电池的应用奠定了基础。

关键词： (GaxIn1−x)2O3薄膜；带隙可调谐；磁控溅射

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Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1): a potential biomarker for the diagnosis

Changlin Cao, Jingxian Gu, Jingyao Zhang

《医学前沿（英文）》 2017年第11卷第2期页码 169-177 doi: 10.1007/s11684-017-0505-z

摘要： Sensitive and useful biomarkers for the diagnosis and prognosis of infectious diseases have been widely developed. An example of these biomarkers is triggering receptor expressed on myeloid cell-1 (TREM-1), which is a cell surface receptor expressed on monocytes/macrophages and neutrophils. TREM-1 amplifies inflammation by activating the TREM-1/DAP12 pathway. This pathway is triggered by the interaction of TREM-1 with ligands or stimulation by bacterial lipopolysaccharide. Consequently, pro-inflammatory cytokines and chemokines are secreted. Soluble TREM-1 (sTREM-1) is a special form of TREM-1 that can be directly tested in human body fluids and well-known biomarker for infectious diseases. sTREM-1 level can be potentially used for the early diagnosis and prognosis prediction of some infectious diseases, including infectious pleural effusion, lung infections, sepsis, bacterial meningitis, viral infections (e.g., Crimean Congo hemorrhagic fever and dengue fever), fungal infections (e.g., infection), and burn-related infections. sTREM-1 is a more sensitive and specific biomarker than traditional indices, such as C-reactive protein and procalcitonin levels, for these infectious diseases. Therefore, sTREM-1 is a feasible biomarker for the targeted therapy and rapid and early diagnosis of infectious diseases.

关键词： soluble triggering receptor expressed on myeloid cells-1 infectious diseases diagnosis and prognosis biomarker

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Molecular characterization of two suppressor of cytokine signaling 1 genes (

Xue XU,Jiannan ZHANG,Juan LI,Yajun WANG

《农业科学与工程前沿（英文）》 2015年第2卷第1期页码 73-83 doi: 10.15302/J-FASE-2015044

摘要： Suppressor of cytokine signaling 1 (SOCS1) protein can inhibit the signal transduction triggered by some cytokines or hormones and thus are important in many physiological/pathological processes, including innate and adaptive immunity, inflammation, and development in mammals. However, there is sparse information about their structure, tissue expression, in birds, where their biological functions remain unknown. In this study, we cloned and characterized two genes (named and ) from chickens. is predicted to encode a 207-amino acid protein, which shares high amino acid sequence identity (64%–67%) with human and mouse SOCS1. Besides , a novel gene was also identified in chickens and other non-mammalian vertebrates including . Chicken is predicted to encode a 212-amino acid protein, which shares only 30%–32% amino acid sequence identity with human SOCS1 and cSOCS1a. RT-PCR assay revealed that both and are widely expressed in all chicken tissues. Using a luciferase reporter assay system, we further demonstrated that transient expression of and can significantly inhibit chicken growth hormone (GH)- or prolactin (PRL)-induced luciferase activities of Hep G2 cells expressing cGH receptor (or cPRL receptor), indicating that SOCS1a and SOCS1b proteins can negatively regulate GH/PRL signaling. Taken together, these data suggest that both cSOCS1a and cSOCS1b may function as negative regulators of cytokine/hormone actions, such as modulation of GH/PRL actions in chickens.

关键词： chicken SOCS1a SOCS1b growth hormone prolactin

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视觉知识引导的中国篆刻智能化生成 Research Article

张克俊1,2,张瑞1,殷叶航1,李一非3,伍文棋1,孙凌云1,2,吴飞1,邓晃煌1,潘云鹤1

《信息与电子工程前沿（英文）》 2022年第23卷第10期页码 1479-1493 doi: 10.1631/FITEE.2100094

摘要：

本文将传统篆刻艺术中的资源协同、设计创作、视觉呈现等过程以数字化方式再现，研制了篆刻艺术智能化创作的系统和平台（浙江大学智能篆刻系统：http://www. next.zju.edu.cn/seal/；篆刻搜索排版系统：http://www.next.zju.edu.cn/seal/search_app/），以视觉知识为引导突破计算机艺术学面临的难点问题。本文构建了包含字和印的求是篆刻数据库，并以此为视觉知识库，构建了篆字智能生成算法。此外，为创建印章布局，提出一种篆字变形算法调整印章字符，并结合视觉知识实现智能篆字布局，以实现智能结构。实验结果表明本文所提方法和系统可有效解决篆刻艺术生成中的难点问题，为篆刻艺术的守正与创新提供理论与应用借鉴。

关键词：篆刻；智能生成；深度学习；参数化模型；计算机艺术

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光致旋转技术综述 Review Article

朱琦1,李楠1,苏鹤鸣1,李文强1,胡慧珠1,2

《信息与电子工程前沿（英文）》 2022年第23卷第2期页码 171-185 doi: 10.1631/FITEE.2000338

摘要：光致旋转技术兴起于20世纪90年代。光镊为研究激光角动量提供了一个理想平台。近几十年来，光致旋转技术被广泛运用在光学微操控实验和生物与微流控领域。近年来，其在经典和量子物理领域的应用潜力引起人们广泛关注。本文回顾了光致旋转技术实验与应用进展。首先介绍了角动量的基本研究。其次，介绍了由轨道角动量引起的光致旋转技术的发展和应用，并给出自旋角动量的概念。最后，介绍了光致旋转技术在高真空光阱中的应用与前景。随着液体介质中精密光学操作技术的成熟，高真空光镊技术为高速微纳转子开辟了一条新道路。

关键词：光镊；光致旋转；角动量；微纳转子

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PD-1/PD-L1 blockade in cervical cancer: current studies and perspectives

Yumeng Wang, Guiling Li

《医学前沿（英文）》 2019年第13卷第4期页码 438-450 doi: 10.1007/s11684-018-0674-4

摘要： Cervical cancer (CC) is the fourth most commonly diagnosed female malignancy and a leading cause of cancer-related mortality worldwide, especially in developing countries. Despite the use of advanced screening and preventive vaccines, more than half of all CC cases are diagnosed at advanced stages, when therapeutic options are extremely limited and side effects are severe. Given these circumstances, new and effective treatments are needed. In recent years, exciting progress has been made in immunotherapies, including the rapid development of immune checkpoint inhibitors. Checkpoint blockades targeting the PD-1/PD-L1 axis have achieved effective clinical responses with acceptable toxicity by suppressing tumor progression and improving survival in several tumor types. In this review, we summarize recent advances in our understanding of the PD-1/PD-L1 signaling pathway, including the expression patterns of PD-1/PD-L1 and potential PD-1/PD-L1-related therapeutic strategies for CC.

关键词： PD-1 PD-L1 immune checkpoint blockade antibody immunotherapy cervical cancer