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Microfluidics-assisted multiplexed biomarker detection for in situ mapping of immune cells in tumor sections

Microsystems & Nanoengineering 2019年第1期5卷 100-111页

作者： Daniel Migliozzi Benjamin Pelz Diego G.Dupouy anne-laure leblond Alex Soltermann Martin A.M.Gijs Laboratory of Microsystems Ecole Polytechnique Federale de Lausanne1015 LausanneCHSwitzerland Lunaphore Technologies SA EPFL Innovation ParkBuilding C1015 LausanneCHSwitzerland Universitatsspital Zürich Schmelzbergstrasse 128091 ZürichCHSwitzerland

Because of the close interaction between tumors and the immune system,immunotherapies are nowadays considered as the most promising treatment against *** order to define the diagnosis and the subsequent therapy,crucial information about the immune cells at the tumor site is ***,different types or activation status of cells may be indicative for specific and personalized ***,we present a quantitative method to identify ten different immuno-markers in the same tumor cut section,thereby saving precious samples and enabling correlative analysis on several cell families and their activation status in a tumor microenvironment *** designed and fabricated a microfluidic chip with optimal thermomechanical and optical properties for fast delivery of reagents on tissue slides and for fully automatic imaging by integration with an optical *** multiplexing capability of the system is enabled by an optimized cyclic immunofluorescence protocol,with which we demonstrated quantitative sequential immunostaining of up to ten biomarkers on the same tissue ***,we developed high-quality image-processing algorithms to map each cell in the entire *** proofof-concept analyses,we identified coexpression and colocalization patterns of biomarkers to classify the immune cells and their activation *** to the quantitativeness and the automation of both the experimental and analytical methods,we believe that this multiplexing approach will meet the increasing clinical need of personalized diagnostics and therapy in cancer pathology.

关键词： fluid thereby mapping

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世界能源展望2005：到2030年的能源需求

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国外石油动态 2006年第2期 1-3页

作者： Doris leblond 谢力（译）

位于巴黎的国际能源署（IEA）在最近发布的世界能源展望2005（WEO2005）中警告，如果政府坚持目前的政策，2030年的世界能源需求将比现在高50％。

关键词：世界能源能源需求展望国际能源署

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国际能源机构强调技术对未来石油供应的贡献

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国外石油动态 2006年第6期 1-5页

作者： Doris leblond 廉抗利（译）

总部设于巴黎的国际能源机构（IEA）宣称，随着油气工业将油气资源转变成世界需求量不断增长的燃料，它在“人力、财力和智力”方面都有着很大的需求。

关键词：国际能源机构石油供应技术油气资源油气工业需求量总部人力财力

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Characterization of CIAE developed double-sided silicon strip detector for charged particles

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Nuclear Science and Techniques 2018年第5期29卷 98-103页

作者： Xin-Xing Xu Fanurs C.E.Teh Cheng-Jian Lin Jenny Lee Feng Yang Zhao-Qiao Guo Tian-Shu Guo Li-Jie Sun Xin-Zhi Teng Jia-Jian Liu Peng-Jie Li Peng-Fei Liang Lei Yang Nan-Ru Ma Hui-Ming Jia Dong-Xi Wang Sylvain leblond Taras Lokotko Qing-Qing Zhao Huan-Qiao Zhang China Institute of Atomic Energy Beijing 102413China Department of Physics The University of Hong KongPokfulam RoadHong KongChina College of Physics and Technology Guangxi Normal UniversityGuilin 541004China Beijing Kelixing Photoelectric Technology Co. Ltd.Beijing 102413China

A double-sided silicon strip detector(DSSD)with active area of 48 mm x 48 mm and thickness of300μm has been developed. Each side of DSSD consists of48 strips, each with width of 0.9 mm and inter-strip separation of 0.1 mm. Electrical properties and detection performances including full depletion bias voltage, reverse leakage current, rise time, energy resolution and cross talk have been studied. At a bias of 80 V, leakage current in each strip is less than 15 nA, and rise time for alpha particle at 5157 keV is approximately 15 ns on both *** energy resolutions have been achieved with0.65-0.80% for the junction strips and 0.85-1.00% for the ohmic strips. The cross talk is found to be negligible on both sides. The overall good performance of DSSD indicates its readiness for various nuclear physics experiments.

关键词： Double-sided silicon strip detector P-stop Detection performance Cross talk

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降钙素原在儿童急性肾盂肾炎诊断中的应用

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世界核心医学期刊文摘（儿科学分册） 2005年第11期1卷 32-33页

作者： Bigot S. leblond P. Foucher C. 贺文龙 Clinique de Pédiatrie Hpital Jeanne-de-Flandre 2 avenue Oscar Lambret 59037 Lille Cedex France

Background. -Acute pyelonephritis can induce parenchymal scarring. The aim of this study was to evaluate the usefulness of procalcitonin (PCT) to predict renal involvement in febrile children with urinary tract infection (UTI). Methods. -In a prospective study serum PCT was measured and compared with others commonly used inflammatory markers in children admitted to the emergency unit with acute pyelonephritis. Renal parenchymal involvement was assessed by a 99mTc-labeled dimercaptosuccinic acid (DMSA) renal scar performed in the first 3 days after the admission. Results. -Among 42 enrolled patients, 19 (45%) had acute renal involvement (Group A) ; 23 (55%) (Group B) had normal DMSA scan (n = 16), or old scarring (n = 4) or various anomalies related to uropathy (n = 3). In group A, the mean PCT level was significantly higher than in the group B (5,4 ng/ml, vs 0,4 ng /ml, p < 10-5). In these 2 groups, mean C reactive protein (CRP) levels were 99,1 mg/l and 44,6 mg/l respectively (p < 0,001). For a level of serum PCT ≥0,5 ng/ml, the sensitivity and specificity to predict the renal involvement were 100%and 87%respectively; for a level ≥20 mg/l CRP had a sensitivity of 94%but a specificity of 30%. Conclusion. -Serum PCT levels were significantly increased in febrile children with UTI when acute renal parenchymal involvement was present. PCT seems a better marker than CRP for the prediction of patients at risk of renal lesions.

关键词：降钙素原急性肾盂肾炎二巯基丁二酸肾脏受累肾实质发热患儿瘢痕形成炎性标志物肾脏受损急诊科

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***-off the survivin stimulus:overcoming retinoblastoma drug resistance in vitro

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Annals of Eye Science 2019年第1期 220-220页

作者： Victor Passos Gibson Pierre Hardy Jeanne leblond Chain Gene Delivery Laboratory Faculty of PharmacyUniversitéde MontréalMontrealQCCanada Research Center of CHU SainteJustine MontrealQCCanada

Background:Cancer is the leading cause of death in *** of the major challenges in the cancer therapy is chemoresistance,which plays a critical role in cancer dissemination,relapse and patient clinical *** retinoblastoma,the most common cancer affecting children eyes,refractory cases are treated by enucleation in order to avoid brain *** of the oncogene survivin is recurrent in many cancer types,including in *** upregulation results in apoptosis inhibition,cell mitosis stimulation and DNA ***,survivin silencing through small-interfering RNA(siRNA)technology has emerged as a powerful approach in cancer therapy to overcome ***,the efficacy of siRNA mainly relies on its successful delivery,limited by its highly hydrophilic nature and rapid nucleases *** have recently developed lipid nanoparticle able to protect siRNA in the systemic circulation and release it within the cell in a pH-sensitive *** we propose to downregulate the survivin oncogene,in vitro,through a liposome-mediated siRNA delivery to improve drug’s effectiveness in a retinoblastoma cell line model(Y79).Methods:Firstly,we formulated a survivin-targeted nanocomplex(STN)composed of pH-sensitive liposomes and survivin-targeted *** was characterized regarding size,polydispersity index and zeta *** survivin silencing efficiency in retinoblastoma cells(Y79)was assessed through RT-qPCR and Western blotting ***,we evaluate the impact of survivin-silencing on Carboplatin,Topotecan,Teniposide and Melphalan’s effectiveness in Y79 cells through a cell viability ***:A novel STN was formulated within desired nanoscale *** was efficiently depleted at both mRNA(RT-qPCR)and protein levels(western Blot).Furthermore,survivin downregulation synergistically improved chemotherapeutics’effectiveness in vitro in Y79 ***,survivin downregulation did not modify

关键词： Retinoblastoma chemoresistance survivin siRNA pH-sensitive liposomes

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A Numerical Model for Multiple Phase Transformations in Steels during Thermal Processes

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Journal of Shanghai Jiaotong university(Science) 2000年第1期5卷 213-220页

作者： R. Fortunier, J.B. leblond, J.M Bergheau 1.ENSM-SE, centre SMS, 158 cours Fauriel, 42023 - St-Etienne cedex 02, France 2.LMM, UMR 7607/CNRS/Université Paris VI, Tour 66, case 162, 4 place Jussieu, 75252 Paris cedex 05, France 3.LTDS, UMIR 5513, CNRS/E

It is now well known that phase changes in steels can be reasonably well modelled by kinetics derived from the concept of extended volume. This has led to a large number of models based on the Koistinen-Marburger equation for martensitic type transformations, and on Johnson-Mehl-Avraxni-Kolmogorov type equations for transformations involving diffusion. These models are generally based on either isothermal transformation (IT) diagrams or on continuous cooling transformation (CCT) diagrams. Their efficiency is often linked to their ability to represent both CCT and IT diagrams of a given material. After describing classical models used to simulate phase changes in steels along isothermal as well as non-isothermal paths, this paper focuses on (i) the numerical implementation of these models, and (ii) their generalisation to the case where more than two phases are involved. We first show that, in the case of only one possible reaction between two phases, most of the kinetic models can be incorporated into a unique differential formulation. This formulation holds for both martensitic and diffusjonal transformations. For the case where several reactions between two or more phases can take place, an approach assuming that these reactions occur independently is proposed. This approach is illustrated on (i) calculations of CCT diagrams from data obtained on IT diagrams, and (ii) prediction of IT diagrams from parameters fitted on CCT diagrams.

关键词： Phase transformation modelling heat treatment heat transfer steels

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Numerical Study of the Plastic Behaviour of a Low Alloy Steel during Phase Transformation

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Journal of Shanghai Jiaotong university(Science) 2000年第1期5卷 206-212页

作者： J.Devaux, J.B. leblond , J.M. Bergheau 1.SYSTUS International, 84 Bvd Vivier Merle, 69485 Lyon Cedex 03, France 2.LMM, UMR 7607 CNRS/Universite Paris 6, 4 Place Jussieu, Tour 66, 75252 Paris Cedex 05, France 3.LTDS, UMR5513 CNRS/ECLIENISE, 58, rue 1.

Phase transformations in steels play a major role on the generation of residual stresses and distortions during thermal processes such as welding and heat treatments. In this paper, we focus on the influence of phase transformations on the plastic behaviour of a low-alloy steel. It is now well known that the plastic strain rate can then be decomposed as the sum of two terms. The first one corresponds to classical plasticity while the second one is due to the evolution of the transformation and is usually referred to as corresponding to transformation induced plasticity. A theoretical approach of the problem has been achieved ([1][2][3]] and a macroscopic model has been proposed in the case of ideal-plastic phases. The theoretical approach has been assessed and completed using micromechanical numerical simulations but these were based on rather coarse 3D meshes due to limited computer capabilities in the 80’s. This paper presents new finite element micromechanical calculations using refined meshes to analyse the classical plastic behaviour and transformation induced plasticity. The results of the computations are discussed and compared with the calculations initially performed. Finally improvements of the macroscopic model are proposed.

关键词： Phase transformation steel elastic-plastic behaviour modelling transformation plasticity Finite Element simulation.

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Computer simulation of thermochemical treatments: modelling diffusion and precipitation in metals

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Journal of Shanghai Jiaotong university(Science) 2000年第1期5卷 303-309页

作者： R. Fortunier, J.B. leblond, J.M Bergheau 1.ENSM-SE, centre SMS, 158 yours Fauriel, 42023 - St-Etienne cedex 02, France 2.LMM, UMR 7607/CNRS/Universite Paris VI, Tour 66, case 162, 4 place Jussieu, 75252 Paris cedex 05, France 3.LTDS, UMR 5513, CNRS/ECL

A model for simultaneous diffusion and precipitation in metals has been recently incorporated into a finite element computer code [1][2]. This model allows now for numerical simulations of various thermochemical treatments such as nitriding or carburizing. Subsequent quenching simulations are then made more accurate, by introducing the influence of the carbon content on the thermo-metallurgical and mechanical properties of the materials [3]. After recalling the mathematical equations used to model simultaneous diffusion and precipitation and their implementation into a finite element code, this paper deals with the method used to obtain the local fractions of precipitates as functions of the local content in each chemical element. The law of mass action is employed to calculate the fractions of precipitates obtained at thermodynamic equilibrium. This leads to a nonlinear complementarity problem. The method used to solve this problem is described in detail, and is validated by computing the phase diagram of a micro-alloyed steel. Finally, numerical simulations of combined diffusion and precipitation in steels point out the efficiency of the approach presented, as well as the important role played by precipitation during diffusion in metals.

关键词： Thermochemical treatment diffusion precipitation finite element method

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