早稲田大学 常田聡 研究室の博士論文の疑惑まとめ

早稲田大学の常田聡氏は、小保方晴子氏の指導教員であり、かつ博士論文の主査でした。常田研究室では、既に、小保方晴子、松本慎也、古川和寛氏らの博士論文において、大規模コピペが発覚しています。同大学の武岡真司 研究室の博士論文においても、大規模コピペが発覚しており、早稲田では想像以上に盗用・剽窃の文化が普及している模様です。

---

調査１：早稲田大学の常田聡氏の研究室の松本慎也氏の博士論文における文章のコピペ（盗用、剽窃）についてのまとめ

著者：松本 慎也
論 文 題 目 ：（5051）Development of Methodology to Analyze Microbial Ecophysiology in Biofilms by Combining Molecular Biology Techniques and Mathematical Modeling
分子生物学的手法および数学モデルを併用した バイオフィルム微生物生理生態解析方法論の構築
（主査） 早稲田大学教授 博士（工学）東京大学 常田 聡
（副査）早稲田大学教授 工学博士（早稲田大学）酒井清孝
（副査）早稲田大学教授 工学博士（早稲田大学） 平沢 泉

博士論文概要 (写し http://www.webcitation.org/6O6JWbJlX）
博士論文審査報告書 (写し http://www.webcitation.org/6O6JXkO5c）
Chapter 1  (写し http://www.webcitation.org/6O6JaJZtP） (Introduction)
Chapter 2 (写し http://www.webcitation.org/6O6JbUb0u）
Chapter 3 (写し http://www.webcitation.org/6O6JdsQFi）
Chapter 4  (写し http://www.webcitation.org/6O6JeYkXi）
Chapter 5 （写し http://www.webcitation.org/6O6Jft7IY）
Chapter 6 (写し http://www.webcitation.org/6O6JhT98G） (Summary)
Acknowledgements (写し http://www.webcitation.org/6O6Jk3331）
http://hdl.handle.net/2065/34631（EN、複数分割）
2009 年 2 月 審査員

Anonymousさんのコメント（2014年3月15日 2:54、と2014年3月15日 8:36）の指摘で判明しました。

Chapter 1　（Introduction）の1.1.のBIOFILMSの20行文の文章（1.1の冒頭以外）が、オランダの研究者Picioreanu氏らの論文（Biofilms (2004) 1, 1–13）　のIntroductionの文章からの盗用です。

同一文章

During biofilm development, a large number of phenomena occur simultaneously and interact over a wide range of length and time scales. As a result of nutrient
conversions, the biofilm expands on the basis of bacterial growth and production of
extracellular polymeric substances (EPS). Chemical species need to be ontinuously
transported to and from the biofilm system by physical processes such as olecular
diffusion and convection. Fluid flow influences biofilm growth by determining the
concentrations of available substrates and products. On the other hand, the flow also shears the biofilm surface, and determines biofilm detachment processes. In the case of multi-species systems, microorganisms of different species interact in complex relationships of competition or cooperation. All these linked phenomena create a dynamic picture of the biofilm three-dimensional (3D) structure. The large number of localized interactions poses an important challenge for experimentalists. Mathematical models can prove useful because they allow testing of hypotheses and, in addition, can direct experimental efforts to complex regions of operation that can easily confound the general intuition. Although the word “modeling” is used for different purposes, the final result is invariably the same: models are no more than a simplified representation of reality based on hypotheses and equations used to rationalize observations. By providing a rational environment, models can lead to deeper and more general understanding. Ultimately, understanding the underlying principles becomes refined to such a state that it is possible to make accurate predictions.

1.1の冒頭は、下記（資料１）冒頭からの抽出の可能性がありますが、本資料が問題の博士論文の前に公開になったのかどうかが不明のため根拠は弱いです。
http://www.aquacircle.org/images/pdfdokumenter/kalender%2009/Biofilmseminar_apr09_full_program.pdf

1.2.1は、下記（資料２）の1および1.1からの大規模なコピペです。
http://biofilms.bt.tudelft.nl/pdf/2000_ChapterBook_2_SGM-Exeter.pdf
資料２は、著者が同じなためか下記（論文２）と同一な部分があります。
http://biofilms.bt.tudelft.nl/pdf/1999_WatSciTechnol_3_Noguera-et-al.pdf


1.2.2は、上記のPicioreanu氏らの論文（Biofilms (2004) 1, 1–13）のMICROBIAL GROWTH IN BIOFILMSからの完全なコピペです。

1.3.1および1.3.2は、上記資料２および論文２からの大規模なコピペです。

1.3.3は、下記（論文３）からの大規模なコピペです。
http://ronney.usc.edu/BiofilmReferences/049110137.pdf

1.3.4は、詳細には検討していませんが、下記（資料３）からコピペした可能性が高いです。
http://biofilms.bt.tudelft.nl/pdf/2003_ChapterBook_3_IrelandIWA_Picioreanu&VanLoosdrecht.pdf

1.3.4章ですが、別の論文名をそのまま章のタイトルにして、
『Particle-Based Multidimensional Multispecies Biofilm Model』
Cristian Picioreanu1,*, Jan-Ulrich Kreft2 andMark C. M. van Loosdrecht1
Appl. Environ. Microbiol. May 2004 vol. 70 no. 5 3024-3040
http://aem.asm.org/content/70/5/3024.full

内容は

In general, a quantitative representation…widely used in physics

部分を「ほぼ」そのまま流用しているようです（約3,700文字位？）。「ほぼ」は、文献の参照方法を変更したり、単語についての

studied→studies
methods→method
…

等の細かい変更から

mass(m)→biomass(m)

の大胆な変更迄あるようです。また参照も

Appl. Environ. Microbiol. May 2004vol. 70 >>no. 5<< 3024-3040
↓
2004. Particle-based multidimensional multispecies biofilm model. Appl Environ Microbiol.
70:3024-3040

と号数を落としたりして独特に不正確のようです。

尚、特別研究員のようです。
http://www.waseda.jp/sem-tsuneda/japanese/member.html 
（写し：　http://www.webcitation.org/6O6llv3Le）


1.4以降は検討していません。

---

調査２：早稲田大学の常田聡氏の研究室の古川和寛氏の博士論文における文章のコピペ（盗用、剽窃）についてのまとめ


古川和寛（5049）「生細胞内RNAイメージングを志向した機能性核酸プローブを用いる核酸分子蛍光検出法の開発」（EN、http://dspace.wul.waseda.ac.jp/dspace/bitstream/2065/34629/3/Honbun-5049.pdf）
（写し：　http://www.webcitation.org/6O8s5RjKp）
（主査） 早稲田大学教授 博士（工学）東京大学 常田 聡

（副査）早稲田大学教授 工学博士（早稲田大学）酒井清孝
（副査）早稲田大学教授 工学博士（早稲田大学） 平沢 泉

（副査）Humboldt-Universität zu Berlinの教授 Dr. Oliver Seitz

第一章のイントロがSilverman A氏らの論文（Adv Clin Chem. 2007;43:79-115.）や、
Takuya Terai氏らの論文（Curr Opin Chem Biol. 2008 Oct;12(5):515-21.）の文章とほとんど一致します。　

同一文章１　Silverman A氏らの論文からのコピペ文章


同一文章２　1.3. ”Fluorogenic molecule for bioimaging” の項が、 Takuya Terai氏らの論文の 丸ごとコピペです。Fig.1-4, 1-5, 1-6のレジェンドもコピペです。（12,000文字（2000単語）以上）。 

Compared to other technologies, such as radioisotope labeling, MRI, ESR, and electrochemical detection, fluorescence imaging has many advantages, as it enables highly sensitive, non-invasive, and safe detection using readily available instruments. Another advantage of fluorescence imaging we should emphasize here is that the fluorescence signal of a molecule can be drastically modulated, so that sensors relying on ‘activation’, not just accumulation, can be utilized. Until the 1980s, however, fluorescence imaging was mainly applied to fixed samples owing to the lack of fluorescent chemosensors, or probes, suitable for imaging in living cells. In this review, ‘fluorescent probes’ are defined as molecules that react specifically with biological molecules to induce a concomitant change of their photochemical properties (fluorescence intensity, excitation/emission wavelength, and so forth). In the past two decades, following pioneering work by Tsien and co-workers on Ca2+ probes [90], there has been an explosive increase in the number of fluorescent probes developed [91, 92]. Today, several design strategies for fluorescent probes, including photoinduced electron transfer (PeT) [91, 93], fluorescence resonance energy transfer (FRET) [94], intramolecular charge transfer (ICT) [91 and 93], and spirocyclization [95], are well established and have been applied to many probes. Recent examples, developed in Nagano laboratory (University of Tokyo), are shown in Figure 1.4 [95-98]. In the 1990s, probes based on fluorescent proteins utilizing the FRET mechanism [94, 99] emerged with great success. More recently, probes based on nanoparticles [100, 101] and conjugated polymers [102] have been introduced, and some of them have already been applied to in vivo imaging [100]. Although we appreciate the significance of these relatively new scaffolds for fluorescent probes, the scope of this review is limited to recent advances of small-molecular probes in two selected categories owing to limitations of space. For more comprehensive information, readers should consult earlier reviews [91, 92, 103] or monographs [104, 105]. In addition, probes for other analytes, including reactive oxygen species (ROS) [106], reactive nitrogen species (RNS) [107], anions [108], and saccharides [109], have recently been reviewed elsewhere, as have probes with near-infrared emission [110].

1.3.1. Fluorescent probes for metal ions Ever since the advent of fluorescent probes, metal ions have been one of the most fruitful targets. The chemical structures of probes for metal ions can generally be divided into two moieties: chelator and fluorophore. The chelator moiety binds to the metals with a certain dissociation constant (Kd) and induces a change of the spectroscopic properties of the fluorophore. To obtain a large spectroscopic response, the structure of this moiety must be carefully selected, because the Kd value should lie between the concentrations of the monitored ion before and after the stimulus. It should be also noted that intracellular Kd is often different from the value in vitro [104]. Up to now, selective chelators for various metal ions, such as BAPTA for Ca2+, TPEN for Zn2+, and APTRA for Mg2+ (Fig. 1.5.A), have been developed and incorporated into fluorescent probes. The fluorophore is the moiety that determines the wavelengths of excitation and emission, as well as the mode of spectral change (turn on/off or ratiometric). For cell imaging, fluorophores excited by visible light (fluorescein, rhodamine, BODIPY, etc.) are desirable owing to their brightness and low phototoxicity, but those requiring UV excitation (benzofuran, etc.) are still used because they are suitable for ratiometric measurements. Ratiometric sensors, which exhibit spectral shift upon reaction or binding to the target, have advantages over turn-on/off sensors, because the results of ratiometric measurements are independent of dye concentration, bleaching, and illumination intensity [90]. Although dozens of probes have already been developed for the detection of Ca2+ [104, 111], Zn2+ [112], and others, improvements are still ongoing. For example, Bradley and co-workers immobilized a Ca2+ probe, Indo-1, on polystyrene beads to develop a cell-permeable microsphere-based sensor (Fig. 1.5.B), and succeeded in real-time calcium sensing in living cells [113]. At present, most of the probes for cations must be loaded into cells in the form of their acetoxymethyl (AM) ester [103], which is subsequently hydrolyzed by intracellular esterases, because the probes themselves often contain free acid moieties that impede cell-permeability. This AM strategy has proved to be powerful and versatile, but it has some disadvantages, such as incomplete hydrolysis, compartmentalization, and leakage over time [113]. The microsphere-based probe developed by Bradley et al. is cell-permeable in the form of acid salts, and reports calcium concentration at the surface of the beads. While further studies are necessary concerning the mechanism of cellular uptake and the control of intracellular localization of the microspheres, the combination of nano/micro-materials and organic fluorescent sensors is a promising approach. These days, growing attention is focused on two-photon microscopy (TPM) [114], which allows non-invasive imaging deep (up to 1 mm) within tissues, with high resolution. Although existing one-photon probes can be used for TPM, high laser power is often required to obtain clear images owing to the small two-photon action cross section (Φδ). To address this problem, Cho and co-workers developed two fluorescent probes, AMg1 [115] and ACa1 [116] (Fig. 1.5.C), which are specific to Mg2+ and Ca2+, respectively. Both probes contain 2-acetyl-6-(dimethylamino)naphthalene, which was shown previously by the authors to be an efficient polarity-sensitive two-photon fluorophore [117]. One-photon fluorescence of AMg1 and ACa1 exhibited a dramatic (>10 fold) increase upon addition of Mg2+ and Ca2+, respectively, presumably as a result of the blocking of PeT upon metal complexation. Two-photon excitation at 780 nm gave similar results, and notably, the probes had Φδ values over 100 GM, more than five fold greater than those of commercial probes (Mag-fura-2 and Oregon Green 488 BAPTA-1) [104]. Interestingly, when the probes were applied to cultured cells via the AM strategy, bright spots with blue-shifted emission were detected in the cells. On the basis of the solvent-dependency of the fluorophore, the authors attributed the spots to membrane-associated organelles, in which uncleaved AM esters accumulated. Hence, the blue-shifted emission was cut off to acquire the ‘true’ signal from the free and metal-bound probes localized in the cytosol. This simple manipulation allowed the precise distributions of the analytes inside the cells to be imaged. To demonstrate the utility of AMg-1, acute hippocampal slices from mice were incubated with the probe. The TPM images clearly revealed the Mg2+ distribution in the pyramidal neuron layer of the CA1 region. ACa-1 was similarly applied to rat hypothalamic slices and spontaneous Ca2+ waves were clearly visualized by TPM. The results, taken together, validate the applicability of these probes for two-photon imaging of the analytes in living tissue. Other recently developed metal ion probes include visible [97] or near-infrared [118] ratiometric fluorescent probes for Zn2+ reported by our group, and selective turn-on probes for Cu+ [119] and Hg2+ [120] developed in Chang’s laboratory.
1.3.2. Fluorescent probes for proteolytic enzymeProteolytic enzymes, or proteases, are enzymes that catalyze hydrolysis of peptide bonds. They are said to occupy approximately 2% of the whole human genome, and are involved not only in many physiological events, but also in major diseases such as cancer, neurodegeneration, inflammation, and others [121]. Although several analytical methods have been established to investigate the biology of proteases [122], assays using fluorogenic substrates [123] are advantageous as they report not the mere expression, but rather the activity of the target enzymes. Another benefit of these substrate-based probes is that the signal is amplified by the catalytic enzyme reaction. Conventional fluorophores, however, are not optimal for applications using biological samples that have high levels of background signal (serum, urine, etc.). Lanthanide complexes with extraordinarily long-lived luminescence [124, 125] are expected to be advantageous for these applications, because the short-lived background fluorescence can be eliminated by time-resolved luminescence measurements. Recently, we have developed a novel long-lived protease probe by designing a method to modulate the PeT process within a lanthanide complex, and applied it to the diagnosis of cancer [126]. Another approach to elucidate the activities of specific enzymes in complex systems, termed activity-based protein profiling (ABPP), is currently attracting attention [127, 128]. In ABPP, samples are treated with small molecules known as activity-based probes (ABPs), which bind covalently to the active site of the target enzymes, and this is followed by analysis (imaging, SDS-PAGE, etc.) or purification of the target using tags (fluorescent molecules, biotin, etc.) attached to the ABPs. Compared with substrate-based Chapter 1 19 fluorescent probes, fluorescent ABPs have the advantage that they can provide direct biochemical evidence concerning the enzyme(s) responsible for the signal. Furthermore, the spatial distribution of the target can be precisely visualized with fluorescent ABPs. These features should be particularly advantageous in complicated systems containing various enzymes, such as living tissues. Hydrolytic enzymes, including proteases, are the most common targets of ABPP, which have been used in proteomic profiling of metalloproteases [129] and for the investigation of cysteine protease activity during tumor formation [130]. Although conventional ABPs are powerful tools with diverse applications, they are not suitable for live-cell or in vivo imaging owing to the lack of a fluorescence on/off switch. In other words, they are not ‘fluorescence probes’ in terms of the definition in this review, and extensive washout is necessary before images can be acquired. To overcome this limitation, Bogyo and co-workers developed ‘quenched’ probes (qABPs), which become fluorescent only after binding to the target [131]. The first qABP they developed (GB117) incorporated an acyloxymethyl ketone (AOMK) reactive moiety that targets cysteine proteases, together with BODIPY-TMR-X as a fluorophore, and QSY 7 as a quencher (Fig. 1.6.A). Before binding covalently to the enzyme, fluorescence of BODIPY-TMR-X was efficiently quenched (>70 fold) presumably via energy transfer to the quencher. When the probe binds to the active site of the enzyme, the quencher moiety is released from the probe, resulting in recovery of fluorescence. After confirming that qABP could successfully label cathepsins in vitro, the authors applied it to living cells. While non-specific staining of entire cells was observed with the unquenched ABP, a discrete labeling pattern that matched the distribution of lysosomes was obtained using GB117, without the need for a washing procedure. This result indicates that qABPs can provide a good signal-to-noise ratio, allowing direct imaging of protease activity in living cells. Interestingly, in an experiment using cell culture models, the probe and anti-cathepsin antibody gave different labeling patterns, illustrating the activity-directed nature of ABPs.
 Recently, an improved version of GB117, termed GB137, was reported by the same group [132]. GB137, with Cy 5 as a fluorophore, has excitation/emission in the NIR region, which is favorable for in vivo imaging (Fig. 1.6.B). GB137 was found to specifically label active cathepsins in a number of cancer cell lines, while it is insensitive to serum. After confirming in vivo that the probe with the AOMK ‘warhead’ was retained in cancer cells by covalently binding to cathepsins, the authors compared GB137 with the non-quenched counterpart (GB123). The non-quenched probe stained the whole body until unlabeled probe was completely eliminated from the animal. GB137, however, produced a specific and stable signal in tumors from the earliest time point, demonstrating the clear advantage of qABPs. The signal was reduced in mice treated with a cysteine protease inhibitor, K11777, suggesting the potential utility of the probe for the assessment of therapeutic agents that inhibit proteases.
 One possible disadvantage of ABPs over substrate-based approaches is the lack of signal amplification by the target enzymes. Although clear images with sufficient signal-to-noise ratios were acquired in the above cases, it remains yet to be seen whether this strategy is applicable to targets with lower expression levels. Another concern for activity-based imaging is that the inhibition of the target by ABPs might lead to undesirable and non-physiological biological responses. Furthermore, it is no less difficult to find specific activity-based inhibitors for the target enzyme, which are necessary to design ABPs, than to find substrates, which are required to develop substrate-based probes. Considering these points, it seems likely that ABPs and traditional probes will play complementary roles in the field of biological imaging.

さらに、
古川論文のFig.1-4は、Terai論文のFig.1
古川論文のFig.1-5は、Terai論文のFig.2
古川論文のFig.1-6は、Terai論文のFig.3
から盗用しています。Terai論文に関する引用情報も、どこにも見当たりません。

---

その他調査対象論文（常田聡氏関連）：

★2006年
・寺田昭彦（4149）「バイオフィルムの迅速形成を可能にする材料表面の設計と硝化脱窒逐次反応用の膜曝気型バイオフィルムリアクターへの応用」http://dspace.wul.waseda.ac.jp/dspace/handle/2065/5302（EN、複数分割）


★2007年
・岸田直裕（4484）「実時間制御法およびグラニュール法を用いた生物学的栄養塩除去プロセスの開発」http://dspace.wul.waseda.ac.jp/dspace/handle/2065/28454（EN、複数分割）


★2008年
・近藤貴志（4485）「汚泥減容化工程およびリン回収工程を付加した生物学的栄養塩除去プロセスの開発と微生物生態解析」http://dspace.wul.waseda.ac.jp/dspace/handle/2065/28440（EN、複数分割）

「The stirred ball-mill consists of a cylindrical or conical tank, vertically or horizontally arranged. It has a disc mixer and 0.2–0.3 mm ball-shaped millstones inside. 」検索すると、韓国の修論（こっちが数ヶ月後にでた）がヒットした。 でもマテメソの一部だから良いのかな。ちなみに一致した文章はØdegaard, H.という原著があるようだ。でも、本文(2003)と文献リスト(2004)で年号が違っている 一方、韓国の修論には引用は無い。 http://dspace.inha.ac.kr/pdfupload/9313.pdf


・井坂和一（4721）「嫌気性アンモニア酸化反応を活用した高効率窒素除去プロセスの開発」http://dspace.wul.waseda.ac.jp/dspace/handle/2065/28722（JP、複数分割）

・大坂利文（4755）「排水処理プロセスにおける脱窒細菌群集の分子生態解析と生態制御」http://dspace.wul.waseda.ac.jp/dspace/handle/2065/28753（EN、複数分割）

・副島孝一（4762）「新規生物学的栄養塩除去プロセスの開発および制御手法に関する研究」http://dspace.wul.waseda.ac.jp/dspace/handle/2065/28768（JP、複数分割）

・谷英典（4766）「蛍光消光現象を用いた新規核酸定量手法の開発」http://dspace.wul.waseda.ac.jp/dspace/handle/2065/28669（EN、http://dspace.wul.waseda.ac.jp/dspace/bitstream/2065/28669/3/Honbun-4766.pdf）（写し）

・寺原猛（4767）「T-RFLP法の環境バイオテクノロジーへの応用」http://dspace.wul.waseda.ac.jp/dspace/handle/2065/28664（EN、http://dspace.wul.waseda.ac.jp/dspace/bitstream/2065/28664/3/Honbun-4767.pdf）（写し）



★2009年
・足立賢(5040)「アフィニティーキャピラリー電気泳動法を用いた新規核酸解析手法の開発」http://dspace.wul.waseda.ac.jp/dspace/handle/2065/34620（EN、http://dspace.wul.waseda.ac.jp/dspace/bitstream/2065/34620/3/Honbun-5040.pdf）