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Analysis of the genomic landscape of primary central nervous system lymphoma using whole-genome sequencing

《医学前沿（英文）》   页码 889-906 doi: 10.1007/s11684-023-0994-x

摘要： Primary central nervous system lymphoma (PCNSL) is an uncommon non-Hodgkin’s lymphoma with poor prognosis. This study aimed to depict the genetic landscape of Chinese PCNSLs. Whole-genome sequencing was performed on 68 newly diagnosed Chinese PCNSL samples, whose genomic characteristics and clinicopathologic features were also analyzed. Structural variations were identified in all patients with a mean of 349, which did not significantly influence prognosis. Copy loss occurred in all samples, while gains were detected in 77.9% of the samples. The high level of copy number variations was significantly associated with poor progression-free survival (PFS) and overall survival (OS). A total of 263 genes mutated in coding regions were identified, including 6 newly discovered genes (ROBO2, KMT2C, CXCR4, MYOM2, BCLAF1, and NRXN3) detected in ≥ 10% of the cases. CD79B mutation was significantly associated with lower PFS, TMSB4X mutation and high expression of TMSB4X protein was associated with lower OS. A prognostic risk scoring system was also established for PCNSL, which included Karnofsky performance status and six mutated genes (BRD4, EBF1, BTG1, CCND3, STAG2, and TMSB4X). Collectively, this study comprehensively reveals the genomic landscape of newly diagnosed Chinese PCNSLs, thereby enriching the present understanding of the genetic mechanisms of PCNSL.

关键词： primary central nervous system lymphoma     whole-genome sequencing     TMSB4X     copy number variation     gene mutation    

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Various brain-eating amoebae: the protozoa, the pathogenesis, and the disease

《医学前沿（英文）》 2021年 第15卷 第6期   页码 842-866 doi: 10.1007/s11684-021-0865-2

摘要： Among various genera of free-living amoebae prevalent in nature, some members are identified as causative agents of human encephalitis, in which Naegleria fowleri followed by Acanthamoeba spp. and Balamuthia mandrillaris have been successively discovered. As the three dominant genera responsible for infections, Acanthamoeba and Balamuthia work as opportunistic pathogens of granulomatous amoebic encephalitis in immunocompetent and immunocompromised individuals, whereas Naegleria induces primary amoebic meningoencephalitis mostly in healthy children and young adults as a more violent and deadly disease. Due to the lack of typical symptoms and laboratory findings, all these amoebic encephalitic diseases are difficult to diagnose. Considering that subsequent therapies are also affected, all these brain infections cause significant mortality worldwide, with more than 90% of the cases being fatal. Along with global warming and population explosion, expanding areas of human and amoebae activity in some regions lead to increased contact, resulting in more serious infections and drawing increased public attention. In this review, we summarize the present information of these pathogenic free-living amoebae, including their phylogeny, classification, biology, and ecology. The mechanisms of pathogenesis, immunology, pathophysiology, clinical manifestations, epidemiology, diagnosis, and therapies are also discussed.

关键词： free-living amoebae     central nervous system infection     primary amoebic meningoencephalitis     granulomatous amoebic encephalitis    

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Primary spinal epidural non-Hodgkin’s lymphoma presented with spinal cord compression syndrome

Chunquan CAI MD, PhD, Qingjiang ZHANG BM, Changhong SHEN MD, PhD,

《医学前沿（英文）》 2009年 第3卷 第4期   页码 499-502 doi: 10.1007/s11684-009-0075-9

摘要： The spinal epidural space is an uncommon presenting site in primary non-Hodgkin’s lymphomas, especially for children. A boy suffered spinal cord compression syndrome caused by primary spinal epidural non-Hodgkin’s lymphoma. Thoracolumbar magnetic resonance imaging (MRI) demonstrated an intraspinal mass. An operation was performed with gross total tumor removal. Histological examination revealed a non-Hodgkin’s B-cell lymphoma. Bone marrow aspiration was negative for lymphoma involvement. No other therapies (chemotherapy and/or radiotherapy) were performed according to the parents’ opinion. The patient died approximately one year after the operation due to brain metastases. The clinical course and imaging features were discussed with a review of literatures.

关键词： non-Hodgkin’     s lymphoma     primary     spinal cord compression syndrome     epidural space    

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Long-term results of suppressing thyroid-stimulating hormone during radiotherapy to prevent primary hypothyroidismin medulloblastoma/PNET and Hodgkin lymphoma: a prospective cohort study

Maura Massimino, Marta Podda, Lorenza Gandola, Emanuele Pignoli, Ettore Seregni, Carlo Morosi, Filippo Spreafico, Andrea Ferrari, Emilia Pecori, Monica Terenziani

《医学前沿（英文）》 2021年 第15卷 第1期   页码 101-107 doi: 10.1007/s11684-020-0752-2

摘要： Primary hypothyroidism commonly occurs after radiotherapy (RT), and coincides with increased circulating thyroid-stimulating hormone (TSH) levels. We tested therefore the protective effect of suppressing TSH with L-thyroxine during RT for medulloblastoma/PNET and Hodgkin lymphoma (HL) in a prospective cohort study. From 1998 to 2001, a total of 37 euthyroid children with medulloblastoma/PNET plus 14 with HL, scheduled for craniospinal irradiation and mediastinum/neck radiotherapy, respectively, underwent thyroid ultrasound and free triiodothyronine (FT3), free thyroxine (FT4), and TSH evaluation at the beginning and end of craniospinal iiradiation. From 14 days before and up to the end of radiotherapy, patients were administered L-thyroxine checking every 3 days TSH to ensure a value<0.3 μIU/mL. During follow-up, blood tests and ultrasound were repeated; primary hypothyroidism was considered an increased TSH level greater than normal range. Twenty-two/37 patients with medulloblastoma/PNET and all the 14 patients with HL were alive after a median 231 months from radiotherapy with 7/22 and 8/14 having correctly reached TSH levels ˂ 0.3 μIU/mL and well matched for other variables. Twenty years on, hypothyroidism-free survival rates differed significantly, being 60%±15% and 15.6%±8.2% in TSH-suppressed vs. not-TSH suppressed patients, respectively ( =0.001). These findings suggest that hypothyroidism could be durably prevented in two populations at risk of late RT sequelae, but it should be confirmed in a larger cohort.

关键词： iatrogenic primary hypothyroidism     late effects of radiotherapy     long-term follow-up     medulloblastoma     Hodgkin lymphoma    

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study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large B-cell lymphoma

《医学前沿（英文）》 2022年 第16卷 第2期   页码 285-294 doi: 10.1007/s11684-021-0843-8

摘要： Anti-CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive efficacy in treating B-cell malignancies. A single-center phase I dose-escalation study was conducted to evaluate the safety and efficacy of T cells transduced with CBM.CD19 CAR, a second-generation anti-CD19 CAR bearing 4-1BB costimulatory molecule, for the treatment of patients with refractory diffuse large B-cell lymphoma (DLBCL). Ten heavily treated patients with refractory DLBCL were given CBM.CD19 CAR-T cell (C-CAR011) treatment. The overall response rate was 20% and 50% at 4 and 12 weeks after the infusion of C-CAR011, respectively, and the disease control rate was 60% at 12 weeks after infusion. Treatment-emergent adverse events occurred in all patients. The incidence of cytokine release syndrome in all grades and grade≥3 was 90% and 0, respectively, which is consistent with the safety profile of axicabtagene ciloleucel and tisagenlecleucel. Neurotoxicity or other dose-limiting toxicities was not observed in any dose cohort of C-CAR011 therapy. Antitumor efficacy was apparent across dose cohorts. Therefore, C-CAR011 is a safe and effective therapeutic option for Chinese patients with refractory DLBCL, and further large-scale clinical trials are warranted.

关键词： CAR-T cell therapy     refractory diffuse large B-cell lymphoma     cytokine release syndrome     dose-limiting toxicity    

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System construction of a four-side primary permanent-magnet linear motor drive mechanical press

Jintao LIANG, Zhengfeng MING, Peida LI

《机械工程前沿（英文）》 2020年 第15卷 第4期   页码 600-609 doi: 10.1007/s11465-020-0597-z

摘要： A primary permanent-magnet linear motor (PPMLM) has a robust secondary structure and high force density and is appropriate for direct-drive mechanical press. The structure of a four-side PPMLM drive press is presented based on our previous research. The entire press control system is constructed to realize various flexible forming processes. The control system scheme is determined in accordance with the mathematical model of PPMLM, and active disturbance rejection control is implemented in the servo controller. Field-circuit coupling simulation is applied to estimate the system’s performance. Then, a press prototype with 6 kN nominal force is fabricated, and the hardware platform of the control system is constructed for experimental study. Punch strokes with 0.06 m displacement are implemented at trapezoidal speeds of 0.1 and 0.2 m/s; the dynamic position tracking errors are less than 0.45 and 0.82 mm, respectively. Afterward, continuous reciprocating strokes are performed, and the positioning errors at the bottom dead center are less than 0.015 mm. Complex pulse trajectories are also achieved. The proposed PPMLM drive press exhibits a fast dynamic response and favorable tracking precision and is suitable for various forming processes.

关键词： mechanical press     direct drive     primary permanent-magnet linear motor (PPMLM)     servo system     active disturbance rejection control (ADRC)     prototype experiment    

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Primary health care for all by 2020: The systematic reform of the medical and health system in China

《医学前沿（英文）》 2010年 第4卷 第1期   页码 3-7 doi: 10.1007/s11684-010-0024-7

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Immunosuppressive tumor microenvironment contributes to tumor progression in diffuse large B-cell lymphoma

《医学前沿（英文）》 2023年 第17卷 第4期   页码 699-713 doi: 10.1007/s11684-022-0972-8

摘要： Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved 40%–50% long-term complete response in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients. However, the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation. A multi-center phase I/II trial of anti-CD19 CD28z CAR-T (FKC876, ChiCTR1800019661) was conducted. Among 22 evaluable DLBCL patients, seven achieved complete remission, 10 experienced partial remissions, while four had stable disease by day 29. Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients, and compared at different stages of treatment. M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells, leading to CAR-T cell therapy failure and disease progression in DLBCL. Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy, during both cell expansion and disease progression, which could not be altered by infiltrating CAR-T cells. Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments. Thus, our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.

关键词： anti-CD19 chimeric antigen receptor T     immunotherapy     diffuse large B cell lymphoma     tumor microenvironment     tumor-associated macrophage     metabolism    

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参数自寻优模糊控制器在中央空调温度控制系统中的应用

吴爱国,杜春燕,宋晓强

《中国工程科学》 2004年 第6卷 第11期   页码 84-87

摘要：

在中央空调温度控制系统中设计应用了一种参数自寻优模糊控制器。针对中央空调温度控制系统被控对象非线性、大滞后和时变等特点，该模糊控制器在规则可调整模糊控制器基础上引入了加权因子α和比例因子Ku的在线调整优化算法。运行结果表明，这种算法增强了系统的鲁棒性，在不同工作条件下，系统保持了良好的控制品质。

关键词： 中央空调系统     温度控制     模糊控制器     参数自寻优    

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Evaluation of power regeneration in primary suspension for a railway vehicle

Ruichen WANG, Zhiwei WANG

《机械工程前沿（英文）》 2020年 第15卷 第2期   页码 265-278 doi: 10.1007/s11465-019-0571-9

摘要： To improve the fuel economy of rail vehicles, this study presents the feasibility of using power regenerating dampers (PRDs) in the primary suspension systems of railway vehicles and evaluates the potential and recoverable power that can be obtained. PRDs are configured as hydraulic electromagnetic-based railway primary vertical dampers and evaluated in parallel and series modes (with and without a viscous damper). Hydraulic configuration converts the linear behavior of the track into a unidirectional rotation of the generator, and the electromagnetic configuration provides a controllable damping force to the primary suspension system. In several case studies, generic railway vehicle primary suspension systems that are configured to include a PRD in the two configuration modes are modeled using computer simulations. The simulations are performed on measured tracks with typical irregularities for a generic UK passenger route. The performance of the modified vehicle is evaluated with respect to key performance indicators, including regenerated power, ride comfort, and running safety. Results indicate that PRDs can simultaneously replace conventional primary vertical dampers, regenerate power, and exhibit desirable dynamic performance. A peak power efficiency of 79.87% is theoretically obtained in series mode on a top-quality German Intercity Express track (Track 270) at a vehicle speed of 160 mile/h (~257 km/h).

关键词： railway vehicle     primary damper     power regeneration     ride comfort     running safety    

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Multiscale RBF-based central high resolution schemes for simulation of generalized thermoelasticity problems

Hassan YOUSEFI, Alireza TAGHAVI KANI, Iradj MAHMOUDZADEH KANI

《结构与土木工程前沿（英文）》 2019年 第13卷 第2期   页码 429-455 doi: 10.1007/s11709-018-0483-5

摘要： In this study, average-interpolating radial basis functions (RBFs) are successfully integrated with central high-resolution schemes to achieve a higher-order central method. This proposed method is used for simulation of generalized coupled thermoelasticity problems including shock (singular) waves in their solutions. The thermoelasticity problems include the LS (systems with one relaxation parameter) and GN (systems without energy dissipation) theories with constant and variable coefficients. In the central high resolution formulation, RBFs lead to a reconstruction with the optimum recovery with minimized roughness on each cell: this is essential for oscillation-free reconstructions. To guarantee monotonic reconstructions at cell-edges, the nonlinear scaling limiters are used. Such reconstructions, finally, lead to the total variation bounded (TVB) feature. As RBFs work satisfactory on non-uniform cells/grids, the proposed central scheme can handle adapted cells/grids. To have cost effective and accurate simulations, the multiresolution–based grid adaptation approach is then integrated with the RBF-based central scheme. Effects of condition numbers of RBFs, computational complexity and cost of the proposed scheme are studied. Finally, different 1-D coupled thermoelasticity benchmarks are presented. There, performance of the adaptive RBF-based formulation is compared with that of the adaptive Kurganov-Tadmor (KT) second-order central high-resolution scheme with the total variation diminishing (TVD) property.

关键词： central high resolution schemes     RBFs     higher order accuracy     generalized thermoelasticity     multiresolution-based adaptation    

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生成锁P<G,X,X'>和它的中央加密系统

史开泉,陈泽雄

《中国工程科学》 2000年 第2卷 第2期   页码 41-46

摘要：

利用数据生成技术，提出生成锁P <G ,X, X´>的概念和由P <G ,X, X´>构成的中央加密系统。这些系统是：生成锁P <G ,X, X´>与单齿中央加密系统，生成锁P <G ,X, X´>与多齿中央加密系统。给出单齿加密-解密算法，多齿加密-解密算法，多齿静态加密-解密算法，多齿动态加密-解密算法，中央加密系统的结构特性。研究指出：任意两个秘密通讯的双方A和B，它们各自选择无规则分布的正整数集合XA={x1，x2，…，xn}，XB={x1，x2，…，xm}，m,n≥4，XA≠XB，利用P <G ,X, X´>完成双方之间的秘密通讯。研究结果表明，所提出的方法具有良好的应用性，安全性。

关键词： 生成锁     中央加密系统     多齿加密-解密算法     P    X     X'>存在定理     数位签章唯一性定理    

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Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice

《医学前沿（英文）》   页码 957-971 doi: 10.1007/s11684-023-0988-8

摘要： Primary ciliary dyskinesia (PCD) is a congenital, motile ciliopathy with pleiotropic symptoms. Although nearly 50 causative genes have been identified, they only account for approximately 70% of definitive PCD cases. Dynein axonemal heavy chain 10 (DNAH10) encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella. Based on the common axoneme structure of motile cilia and sperm flagella, DNAH10 variants are likely to cause PCD. Using exome sequencing, we identified a novel DNAH10 homozygous variant (c.589C > T, p.R197W) in a patient with PCD from a consanguineous family. The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia. Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia, and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella. Subsequently, animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus. To the best of our knowledge, this study is the first to report DNAH10 deficiency related to PCD in human and mouse models, which suggests that DNAH10 recessive mutation is causative of PCD.

关键词： DNAH10     mice     motile cilia     mutation     primary ciliary dyskinesia    

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Experimental study of primary and secondary side coupling natural convection heat transfer characteristicsof the passive residual heat removal system in AP1000

Zhimin QIU, Daogang LU, Jingpin FU, Li FENG, Yuhao ZHANG

《能源前沿（英文）》 2021年 第15卷 第4期   页码 860-871 doi: 10.1007/s11708-021-0744-1

摘要： Passive residual heat removal heat exchanger (PRHR HX), which is a newly designed equipment in the advanced reactors of AP1000 and CAP1400, plays an important role in critical accidental conditions. The primary and secondary side coupling heat transfer characteristics of the passive residual heat removal system (PRHRS) determine the capacity to remove core decay heat during the accidents. Therefore, it is necessary to investigate the heat transfer characteristics and develop applicable heat transfer formulas for optimized design. In the present paper, an overall scaled-down natural circulation loop of PRHRS in AP1000, which comprises a scaled-down in-containment refueling water storage tank (IRWST) and PRHR HX models and a simulator of the reactor core, is built to simulate the natural circulation process in residual heat removal accidents. A series of experiments are conducted to study thermal-hydraulic behaviors in both sides of the miniaturized PRHR HX which is simulated by 12 symmetric arranged C-shape tubes. For the local PRHR HX heat transfer performance, traditional natural convection correlations for both the horizontal and vertical bundles are compared with the experimental data to validate their applicability for the specific heat transfer condition. Moreover, the revised natural convection heat transfer correlations based on the present experimental data are developed for PRHR HX vertical and lower horizontal bundles. This paper provides essential references for the PRHRS operation and further optimized design.

关键词： passive residual heat removal heat exchanger (PRHR HX)     C-shape tube     revised heat transfer correlations     coupled natural convection    

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Degradation of refractory organics in concentrated leachate by the Fenton process: Central composite

Senem Yazici Guvenc, Gamze Varank

《环境科学与工程前沿（英文）》 2021年 第15卷 第1期 doi: 10.1007/s11783-020-1294-1

摘要： Abstract • 90% total COD, 95.3% inert COD and 97.2% UV254 were removed. • High R2 values (over 95%) for all responses were obtained with CCD. • Operational cost was calculated to be 0.238 €/g CODremoved for total COD removal. • Fenton oxidation was highly-efficient method for inert COD removal. • BOD5/COD ratio of leachate concentrate raised from 0.04 to 0.4. The primary aim of this study is inert COD removal from leachate nanofiltration concentrate because of its high concentration of resistant organic pollutants. Within this framework, this study focuses on the treatability of leachate nanofiltration concentrate through Fenton oxidation and optimization of process parameters to reach the maximum pollutant removal by using response surface methodology (RSM). Initial pH, Fe2+ concentration, H2O2/Fe2+ molar ratio and oxidation time are selected as the independent variables, whereas total COD, color, inert COD and UV254 removal are selected as the responses. According to the ANOVA results, the R2 values of all responses are found to be over 95%. Under the optimum conditions determined by the model (pH: 3.99, Fe2+: 150 mmol/L, H2O2/Fe2+: 3.27 and oxidation time: 84.8 min), the maximum COD removal efficiency is determined as 91.4% by the model. The color, inert COD and UV254 removal efficiencies are determined to be 99.9%, 97.2% and 99.5%, respectively, by the model, whereas the total COD, color, inert COD and UV254 removal efficiencies are found respectively to be 90%, 96.5%, 95.3% and 97.2%, experimentally under the optimum operating conditions. The Fenton process improves the biodegradability of the leachate NF concentrate, increasing the BOD5/COD ratio from the value of 0.04 to the value of 0.4. The operational cost of the process is calculated to be 0.238 €/g CODremoved. The results indicate that the Fenton oxidation process is an efficient and economical technology in improvement of the biological degradability of leachate nanofiltration concentrate and in removal of resistant organic pollutants.

关键词： Concentrated leachate     Fenton oxidation     Central composite design     Biodegradability     Inert COD    

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标题 作者 时间 类型 操作

Analysis of the genomic landscape of primary central nervous system lymphoma using whole-genome sequencing

期刊论文

Various brain-eating amoebae: the protozoa, the pathogenesis, and the disease

期刊论文

Primary spinal epidural non-Hodgkin’s lymphoma presented with spinal cord compression syndrome

Chunquan CAI MD, PhD, Qingjiang ZHANG BM, Changhong SHEN MD, PhD,

期刊论文

Long-term results of suppressing thyroid-stimulating hormone during radiotherapy to prevent primary hypothyroidismin medulloblastoma/PNET and Hodgkin lymphoma: a prospective cohort study

Maura Massimino, Marta Podda, Lorenza Gandola, Emanuele Pignoli, Ettore Seregni, Carlo Morosi, Filippo Spreafico, Andrea Ferrari, Emilia Pecori, Monica Terenziani

期刊论文

study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large B-cell lymphoma

期刊论文

System construction of a four-side primary permanent-magnet linear motor drive mechanical press

Jintao LIANG, Zhengfeng MING, Peida LI

期刊论文

Primary health care for all by 2020: The systematic reform of the medical and health system in China

期刊论文

Immunosuppressive tumor microenvironment contributes to tumor progression in diffuse large B-cell lymphoma

期刊论文

参数自寻优模糊控制器在中央空调温度控制系统中的应用

吴爱国,杜春燕,宋晓强

期刊论文

Evaluation of power regeneration in primary suspension for a railway vehicle

Ruichen WANG, Zhiwei WANG

期刊论文

Multiscale RBF-based central high resolution schemes for simulation of generalized thermoelasticity problems

Hassan YOUSEFI, Alireza TAGHAVI KANI, Iradj MAHMOUDZADEH KANI

期刊论文

生成锁P<G,X,X'>和它的中央加密系统

史开泉,陈泽雄

期刊论文

Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice

期刊论文

Experimental study of primary and secondary side coupling natural convection heat transfer characteristicsof the passive residual heat removal system in AP1000

Zhimin QIU, Daogang LU, Jingpin FU, Li FENG, Yuhao ZHANG

期刊论文

Degradation of refractory organics in concentrated leachate by the Fenton process: Central composite

Senem Yazici Guvenc, Gamze Varank

期刊论文