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A simple two-transition model for loss of infectivity of phages on exposure to organic solvent 噬菌体暴露于有机溶剂后感染性丧失的简单双过渡模型
Pub Date : 2007-06-01 DOI: 10.1016/j.bioeng.2007.02.002
Teruhiko Matsubara , Wakako Emoto , Katsuhiro Kawashiro

The effect of water-miscible organic solvents on the stability of filamentous phages displaying a random peptide library was investigated. A kinetic analysis of the time course of viral infectivity indicated that the transition between the noninfectious and infectious form was directly related to the concentration of organic solvent.

研究了水溶性有机溶剂对丝状噬菌体展示随机肽库稳定性的影响。病毒感染性时间过程的动力学分析表明,非感染性和感染性形式之间的转变与有机溶剂的浓度直接相关。
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引用次数: 10
Improving cluster-based missing value estimation of DNA microarray data 改进基于聚类的DNA微阵列数据缺失值估计
Pub Date : 2007-06-01 DOI: 10.1016/j.bioeng.2007.04.003
Lígia P. Brás, José C. Menezes

We present a modification of the weighted K-nearest neighbours imputation method (KNNimpute) for missing values (MVs) estimation in microarray data based on the reuse of estimated data. The method was called iterative KNN imputation (IKNNimpute) as the estimation is performed iteratively using the recently estimated values.

The estimation efficiency of IKNNimpute was assessed under different conditions (data type, fraction and structure of missing data) by the normalized root mean squared error (NRMSE) and the correlation coefficients between estimated and true values, and compared with that of other cluster-based estimation methods (KNNimpute and sequential KNN). We further investigated the influence of imputation on the detection of differentially expressed genes using SAM by examining the differentially expressed genes that are lost after MV estimation.

The performance measures give consistent results, indicating that the iterative procedure of IKNNimpute can enhance the prediction ability of cluster-based methods in the presence of high missing rates, in non-time series experiments and in data sets comprising both time series and non-time series data, because the information of the genes having MVs is used more efficiently and the iterative procedure allows refining the MV estimates. More importantly, IKNN has a smaller detrimental effect on the detection of differentially expressed genes.

我们提出了一种基于估计数据重用的加权k近邻插值方法(KNNimpute),用于微阵列数据中的缺失值(mv)估计。这种方法被称为迭代KNN imputation (IKNNimpute),因为它是使用最近的估计值进行迭代估计的。通过归一化均方根误差(NRMSE)和估计值与真值之间的相关系数,评估IKNNimpute在不同条件下(缺失数据类型、缺失数据比例和缺失数据结构)的估计效率,并与其他基于聚类的估计方法(KNNimpute和顺序KNN)进行比较。通过检测MV估计后丢失的差异表达基因,我们进一步研究了imputation对使用SAM检测差异表达基因的影响。性能测量结果一致,表明IKNNimpute的迭代过程可以提高基于聚类的方法在高缺失率、非时间序列实验和包含时间序列和非时间序列数据集的预测能力,因为具有MV的基因信息被更有效地利用,迭代过程允许细化MV估计。更重要的是,IKNN对差异表达基因检测的不利影响较小。
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引用次数: 80
The university-promoted patent at the crossroads of the research results and immediate industrial use 大学推动专利的十字路口的研究成果和直接的工业应用
Pub Date : 2007-02-01 DOI: 10.1016/j.bioeng.2006.05.004
R. Doddoli

The departments, indeed the laboratories of the public research institutions, no longer are satisfied with displaying a certain number of annual scientific publications meant to highlight their expertise and know-how. In effect, for some years now, a new trend has been in vogue: stimulated by all the national and international public bodies, they are calling increasingly on the “patent pending” solution to make optimum use of the results of specific researches on the one hand and, on the other hand, to assert their excellence vis-à-vis the Ministry of Research of their country which is supposed to finance them.

However, caught up in the euphoria of the research results, and lost in their formulae and practices, these researchers lose sight of the basis for a patent and its real reason for being (patent charter). A patent necessarily must be of service to the community, that is to say that essentially it must contribute to the improvement of the quality of life of the population. To achieve this goal, going through certain stages is a must, namely that to start with a patent must be absolutely profitable to industry in order that, subsequently, it be consistent with its being of service to the community. In this context, its validity is set at 10 years renewable for another 10 years based on specific parameters as stipulated by the national and international patent institutions, indeed by the EPO (European Patent Office) the headquarters of which is in Munich. Its use by industry ensures proceeds for 10, even 20 years and must represent the material fruit of the applicant's effort. Beyond this period, the patent becomes public and therefore available to everyone. But the crucial problem is this: when can a patent really be used and how to do so as best as possible to guarantee profits for both parties involved and thus justify its reason for being?

The purpose of this work thus is to incite university researchers to think about the real usefulness of a patent on the one hand and, on the other hand, to ponder over the best way of using, in close cooperation with industry, the fruit of the research and the registering of the patent, both financed by public funds. For the latter, owing to their nature, demand that there be no wastage and cautious management thereof.

各部门,实际上是公共研究机构的实验室,不再满足于展示一定数量的年度科学出版物,以突出他们的专业知识和诀窍。事实上,几年来,一种新的趋势已经流行起来:在所有国家和国际公共机构的刺激下,他们越来越多地呼吁“专利未决”的解决方案,一方面最佳地利用具体研究的结果,另一方面,向他们国家的研究部(-à-vis)证明他们的卓越,因为他们应该为他们提供资金。然而,这些研究人员沉浸在研究成果的喜悦中,迷失在他们的公式和实践中,忽视了专利的基础和它存在的真正原因(专利宪章)。专利必须为社会服务,也就是说,本质上它必须有助于提高人民的生活质量。为了实现这一目标,必须经过某些阶段,即开始的专利必须对工业界绝对有利,以便随后与它对社会的服务相一致。在这种情况下,其有效期设定为10年,可根据国家和国际专利机构,实际上是总部位于慕尼黑的EPO(欧洲专利局)规定的具体参数再延长10年。工业使用该专利可确保10年甚至20年的收益,并且必须代表申请人努力的实质性成果。超过这段时间,专利就公开了,因此每个人都可以使用。但关键的问题是:何时才能真正使用专利,以及如何尽可能最好地使用专利,以保证相关双方的利润,从而证明其存在的理由?因此,这项工作的目的是一方面激发大学研究人员思考专利的真正用途,另一方面,在与工业界密切合作的情况下,思考使用研究成果和专利注册的最佳方式,这两项工作都由公共基金资助。对于后者,由于其性质,要求不浪费,谨慎管理。
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引用次数: 2
Competitive protein adsorption on micro patterned polymeric biomaterials, and viscoelastic properties of tailor made extracellular matrices 微图案高分子生物材料对蛋白质的竞争性吸附,以及定制的细胞外基质的粘弹性
Pub Date : 2007-02-01 DOI: 10.1016/j.bioeng.2006.05.027
Alexander Welle , Antonio Chiumiento , Rolando Barbucci

Cell adhesion on biomaterial surfaces and the vitality of anchorage dependent cells is affected by several parameters of an adsorbate layer which is intentionally or spontaneously formed. Surface pre-treatments and several conditioning steps prior and during to the cell/biomaterial contact affect the composition, orientation, quantity and viscoelasticity of the interfacing layer between cells and biomaterial. This work was performed to elucidate the response of cells on two modified biomaterial surfaces based on protein or carbohydrate adsorbates:

  • (a)

    Masked UV irradiations opened a simple route to obtain chemically patterned substrates controlling serum protein adsorption and cell adhesion. It is possible to achieve structures of subcellular size and to produce immobilized gradients. In order to examine the protein matrix deposited on these substrates we applied a quartz microbalance technique (QCM-D) capable to extract viscoelastic data in addition to the mass uptake during plasma protein deposition. It was found that the quantity and viscosity of surface bound albumin is lowered when the surface is modified (patterned) by UV exposure. Hence, the UV modification promotes the competitive adsorption of cell adhesion proteins from the media or upon secretion by the cells and yields to the observed cell patterns.

  • (b)

    Another tissue engineering technique, using immobilized, modified and/or cross linked hyaluronic acid (HA), an important extra cellular matrix component in vivo, is also examined by QCM-D. Our data demonstrate that HA can be modified by an activation with a carbodiimide, followed by the application of an α,ω-bisamino polyethyleneglycol. The QCM-D data can be interpreted as a stiffening of the HA layer combined with the release of hydration water. Further, the hydration state and the viscoelastic behaviour of surface bound ultrathin HA hydrogels was examined.

Quantification of viscoelastic parameters of thin films of ECM by QCM-D is valuable for the interpretation of durotaxis, describing effects of mechanical substrate parameters on the adhesion and motility of cells.

细胞在生物材料表面的粘附和依赖于锚定的细胞的活力受到有意或自发形成的吸附层的几个参数的影响。细胞/生物材料接触之前和过程中的表面预处理和几个调理步骤影响细胞和生物材料之间界面层的组成、取向、数量和粘弹性。这项工作是为了阐明细胞对两种基于蛋白质或碳水化合物吸附的改性生物材料表面的反应:(a)屏蔽紫外线照射为获得控制血清蛋白吸附和细胞粘附的化学图案底物开辟了一条简单的途径。实现亚细胞大小的结构和产生固定梯度是可能的。为了检测沉积在这些基质上的蛋白质基质,我们应用了石英微平衡技术(QCM-D),该技术除了能够提取血浆蛋白质沉积过程中的质量摄取外,还能够提取粘弹性数据。研究发现,紫外照射对表面进行修饰(图案化)后,表面结合白蛋白的数量和粘度降低。(b)另一种组织工程技术,使用固定的、修饰的和/或交联的透明质酸(HA),一种重要的细胞外基质成分,也通过QCM-D进行了检验。我们的数据表明,HA可以通过碳二亚胺活化,然后应用α,ω-双氨基聚乙二醇来修饰。QCM-D数据可以解释为HA层的硬化和水化水的释放。进一步研究了表面结合超薄透明质酸水凝胶的水化状态和粘弹性行为。通过QCM-D对ECM薄膜的粘弹性参数进行量化,对于解释硬致性,描述机械衬底参数对细胞粘附和运动的影响是有价值的。
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引用次数: 16
Bioactive coatings based on polyelectrolyte multilayer architectures functionalized by embedded proteins, peptides or drugs 基于多电解质多层结构的生物活性涂层,由嵌入的蛋白质、多肽或药物功能化
Pub Date : 2007-02-01 DOI: 10.1016/j.bioeng.2006.05.023
Erell Leguen , Armelle Chassepot , Gero Decher , Pierre Schaaf , Jean-Claude Voegel , Nadia Jessel

In recent years, considerable effort has been devoted to the design and controlled fabrication of structured materials with functional properties. The layer by layer buildup of polyelectrolyte multilayer films (PEM films) from oppositely charged polyelectrolytes offers new opportunities for the preparation of functionalized biomaterial coatings. This technique allows the preparation of supramolecular nano-architectures exhibiting specific properties in terms of control of cell activation and may also play a role in the development of local drug delivery systems. Peptides, proteins, chemically bound to polyelectrolytes, adsorbed or embedded in PEM films, have been shown to retain their biological activities.

近年来,人们对具有功能特性的结构材料的设计和控制制造进行了大量的研究。聚电解质多层膜(PEM膜)的逐层积累为制备功能化生物材料涂层提供了新的机会。该技术允许制备超分子纳米结构,在控制细胞活化方面表现出特定的特性,也可能在局部药物输送系统的开发中发挥作用。研究表明,与聚电解质化学结合、吸附或嵌入PEM薄膜的多肽、蛋白质可保持其生物活性。
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引用次数: 76
Early stages of human plasma proteins adsorption probed by Atomic Force Microscope 原子力显微镜观察人血浆蛋白吸附的早期阶段
Pub Date : 2007-02-01 DOI: 10.1016/j.bioeng.2006.05.013
K. Mitsakakis, S. Lousinian, S. Logothetidis

Atomic Force Microscope (AFM) as a surface characterization technique has offered a great impulse in the advance of biocompatible materials. In this study AFM was implemented for the investigation of the early stages of adsorption of two human plasma proteins on titanium and hydrogenated carbon biocompatible thin films. The plasma proteins that were used were Human Serum Albumin and Fibrinogen, two of the most important proteins in human plasma. The concentration of the protein solutions was the same as that in human plasma. As the examined samples were soft, non-contact AFM mode was used to avoid their destruction. In order for the early stages of protein adsorption to be assessed, small incubation times were applied. AFM measurements in liquid buffer were also carried out, allowing the observation of the protein behaviour in an environment much closer to their native one. In addition, there was an assessment of the adsorption mechanism of the proteins on the above-mentioned biomaterials.

原子力显微镜(AFM)作为一种表面表征技术,为生物相容性材料的发展提供了巨大的推动力。在这项研究中,采用原子力显微镜研究了两种人血浆蛋白在钛和氢化碳生物相容性薄膜上的早期吸附。所使用的血浆蛋白是人类血清白蛋白和纤维蛋白原,这是人类血浆中最重要的两种蛋白质。蛋白质溶液的浓度与人血浆中的浓度相同。由于检测的样品是软的,因此采用非接触AFM模式以避免其破坏。为了评估蛋白质吸附的早期阶段,应用了小的孵育时间。在液体缓冲液中也进行了AFM测量,允许观察蛋白质在更接近其原生环境中的行为。此外,还对蛋白质在上述生物材料上的吸附机理进行了评价。
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引用次数: 29
Haemocompatibility of amorphous hydrogenated carbon thin films, optical properties and adsorption mechanisms of blood plasma proteins 非晶氢化碳薄膜的血液相容性、光学性质及血浆蛋白的吸附机制
Pub Date : 2007-02-01 DOI: 10.1016/j.bioeng.2006.05.014
S. Lousinian, S. Logothetidis, A. Laskarakis, M. Gioti

Haemocompatibility is one of the most important properties, together with the tissue compatibility and corrosion and wear resistance that determine the biocompatibility of the artificial implants. Carbon-based thin films, such as amorphous carbon (a-C) and amorphous hydrogenated diamond-like carbon (a-C:H or DLC) are considered as excellent candidates for use as biocompatible coatings on biomedical implants. The aim of this work is the comparative study of the haemocompatibility of the a-C:H thin films developed by magnetron sputtering under various deposition conditions, the development of a methodology in order to study the haemocompatibility of thin films, the optical properties of the adsorbed proteins (human serum albumin and fibrinogen) and their adsorption mechanisms. Haemocompatibility and the optical properties of a-C:H thin films and the adsorbed proteins were studied by spectroscopic ellipsometry (SE). The films grown under floating conditions performed better haemocompatibility compared with those deposited under application of bias voltage. In the range of vis–UV, proteins are transparent, while they present an absorption peak at higher energies, but except these characteristics, their optical functions are rather featureless. Adsorption mechanisms were studied through AFM technique too. AFM results are in accordance with those derived by SE. Combination of the two techniques gives us a more accurate description of protein adsorption mechanisms.

血液相容性与组织相容性、耐蚀性和耐磨性共同决定了人工种植体的生物相容性。碳基薄膜,如非晶碳(a-C)和非晶氢化类金刚石(a-C:H或DLC)被认为是生物医学植入物生物相容性涂层的优秀候选者。本工作的目的是比较研究磁控溅射制备的a- c:H薄膜在不同沉积条件下的血液相容性,建立一种方法来研究薄膜的血液相容性,吸附蛋白(人血清白蛋白和纤维蛋白原)的光学性质及其吸附机制。利用椭圆偏振光谱(SE)研究了a-C:H薄膜及其吸附蛋白的血液相容性和光学性质。与在偏置电压下沉积的膜相比,在漂浮条件下生长的膜具有更好的血液相容性。在可见-紫外范围内,蛋白质是透明的,而在更高的能量下,它们呈现一个吸收峰,但除了这些特征外,它们的光学功能相当无特征。并通过原子力显微镜技术研究了吸附机理。AFM结果与SE计算结果一致。这两种技术的结合使我们对蛋白质的吸附机理有了更准确的描述。
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引用次数: 42
Nanocomposites based on poly-d,l-lactide and multiwall carbon nanotubes 聚d、l-丙交酯和多壁碳纳米管的纳米复合材料
Pub Date : 2007-02-01 DOI: 10.1016/j.bioeng.2006.05.021
L.P. Krul , A.I. Volozhyn , D.A. Belov , N.A. Poloiko , A.S. Artushkevich , S.A. Zhdanok , A.P. Solntsev , A.V. Krauklis , I.A. Zhukova

A possibility of poly-d,l-lactide modification by multiwall carbon nanotubes (MWCNT) has been shown. MWCNT were prepared from methane-air mixture upon atmospheric pressure without catalyst on high voltage atmospheric pressure discharge plasma set-up. According to scanning and transmission electronic microscope data carbon nanotubes diameters were within 12–60 nm. Quantities of MWCNT incorporated did not exceed 0.5%. Nanocomposites were obtained by sonification of mixture of a poly-d,l-lactide solution in chloroform and MWCNT followed by film casting on glass substrates. Tensile strength and thermomechanical properties of the dried composite films were investigated.

Introduction of MWCNT into poly-d,l-lactide has been shown to cause the enhanced polymer stability to thermal oxidative destruction. Taking into account the results obtained one could anticipate that implants from nanocomposites of poly-d,l-lactide with MWCNT would be dispersed in a living organism more slowly as compared to implants from pure poly-d,l-lactide without additives.

多壁碳纳米管(MWCNT)修饰聚d -l -丙交酯的可能性已经被证明。在高压常压放电等离子体装置上,以甲烷-空气混合物为原料,在无催化剂的常压条件下制备MWCNT。扫描电镜和透射电镜数据显示,碳纳米管的直径在12 ~ 60 nm之间。MWCNT掺入量不超过0.5%。将聚d -l -丙交酯溶液与MWCNT混合在氯仿中进行超声处理,然后在玻璃基板上浇铸薄膜,得到纳米复合材料。研究了干燥后复合薄膜的拉伸强度和热力学性能。在聚d -l -丙交酯中引入MWCNT已被证明可以增强聚合物的热氧化破坏稳定性。考虑到获得的结果,我们可以预测,与不添加添加剂的纯聚d -l -丙交酯相比,由聚d -l -丙交酯与MWCNT组成的纳米复合材料制成的植入物在生物体中的分散速度要慢得多。
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引用次数: 22
Biomimetic implant coatings 仿生植入涂层
Pub Date : 2007-02-01 DOI: 10.1016/j.bioeng.2006.05.016
E. Eisenbarth , D. Velten , J. Breme

Biomaterials and tissue engineering technologies are becoming increasingly important in biomedical practice, particularly as the population ages. Cellular responses depend on topographical properties of the biomaterial at the nanometer scale. Structures on biomaterial surfaces are used as powerful tools to influence or even control interactions between implants and the biological system [Kawahara, H., Soeda, Y., Niwa, K., Takahashi, M., Kawahara, D., Araki, N., 2004. J. Mater. Sci. Mater. Med. 15 (12), 1297–1307; Winkelmann, M., Gold, J., Hauert, R., Kasemo, B., Spencer, N.D., Brunette, D.M., Textor, M., 2003. Biomaterials 24 (7), 1133–1145]. The influence of nanometer sized surface structures on osteoblastlike cell interactions was tested with niobium oxide coatings on polished titanium slices (cp-Ti grade 2). The aim of the study was to investigate the influence of nanoscopic surface structures on osteoblast interactions in order to support collagen I production and cell adhesion. The coatings were done by means of the sol–gel process. The surface structure was adjusted by annealing of the metaloxide ceramic coatings due to temperature depended crystal growth. The applied annealing temperatures were 450, 550 and 700 °C for 1 h, corresponding to Ra-numbers of 7, 15 and 40 nm. The surfaces were characterized by means of AFM, DTA/TG, diffractometry and white light interferometry. The cell reactions were investigated concerning adhesion kinetics, migration, spreading, cell adhesion, and collagen I synthesis. The smooth surface (Ra = 7 nm) resulted in the fastest cell anchorage and cell migration. The closest cell adhesion was reached with the surface structure of Ra = 15 nm. The roughest surface (Ra = 40 nm) impedes the cell migration as well as a proper spreading of the cells. The best results concerning cell adhesion and spreading was reached with an intermediate surface roughness of Ra = 15 nm of the niobium oxide coating on cp-titanium slices.

生物材料和组织工程技术在生物医学实践中变得越来越重要,特别是随着人口老龄化。细胞反应取决于生物材料在纳米尺度上的地形特性。生物材料表面的结构被用作影响甚至控制植入物与生物系统之间相互作用的有力工具[Kawahara, H., Soeda, Y., Niwa, K., Takahashi, M., Kawahara, D., Araki, N., 2004]。j .板牙。科学。板牙。医学杂志15 (12),1297-1307;Winkelmann, M., Gold, J., Hauert, R., Kasemo, B., Spencer, N.D, Brunette, d.m., Textor, M., 2003。中国生物医学工程学报,2016,33(7):1133-1145。纳米级表面结构对成骨细胞相互作用的影响通过氧化铌涂层在抛光钛片(cp-Ti级2)上进行测试。该研究的目的是研究纳米级表面结构对成骨细胞相互作用的影响,以支持胶原I的产生和细胞粘附。采用溶胶-凝胶法制备涂层。由于金属氧化物陶瓷涂层的晶体生长依赖于温度,通过退火对涂层表面结构进行了调整。退火温度分别为450、550和700℃,分别为7、15和40 nm。通过AFM、DTA/TG、衍射和白光干涉等手段对表面进行了表征。研究了细胞的粘附动力学、迁移、扩散、细胞粘附和I型胶原合成。光滑的表面(Ra = 7 nm)使细胞锚定和迁移速度最快。当表面结构为Ra = 15 nm时,细胞粘附最紧密。最粗糙的表面(Ra = 40 nm)阻碍了细胞的迁移和细胞的适当扩散。当氧化铌涂层的表面粗糙度为Ra = 15 nm时,细胞的粘附和扩散效果最好。
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引用次数: 86
Fabrication of a three-dimensional nanostructured biomaterial for tissue engineering of bone 用于骨组织工程的三维纳米生物材料的制备
Pub Date : 2007-02-01 DOI: 10.1016/j.bioeng.2006.05.017
E. Garreta , D. Gasset , C. Semino , S. Borrós

A plasma process for the surface modification of HA powders has been developed. Acrylic acid and acrylic acid/octadiene plasma deposited films onto HA particles have demonstrated to interact with SBF allowing the calcium dissolution–precipitation mechanism. Therefore, a nanostructured composite between HA and a self-assembling peptide scaffold (RAD16-I) has been developed. The differentiation of mESC in this scaffold has been studied, in order to test the osteogenic capacity of the new composite material. We have observed that the mESC can be iduced to produce Ca salts (mineralization) in a 3D-microenvironment and moreover, this activity can be enhanced by the presence of HA particules into the nanofiber scaffold.

提出了一种等离子体表面改性透明质酸粉末的方法。丙烯酸和丙烯酸/辛二烯等离子体沉积膜已被证明与SBF相互作用,从而实现钙的溶解沉淀机制。因此,开发了一种HA与自组装肽支架(RAD16-I)之间的纳米结构复合材料。为了测试这种新型复合材料的成骨能力,我们研究了mESC在这种支架中的分化情况。我们已经观察到,mESC可以在3d微环境中诱导产生钙盐(矿化),而且,这种活性可以通过HA颗粒进入纳米纤维支架而增强。
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引用次数: 44
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