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Energy landscape decomposition for cell differentiation with proliferation effect

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National Science Review 2022年第8期9卷 144-152页

作者： Jifan Shi Kazuyuki aihara Tiejun Li Luonan Chen Research Institute of Intelligent Complex Systems Fudan University International Research Center for Neurointelligence The University of Tokyo Institutes for Advanced Study The University of Tokyo Key Laboratory of Mathematics and Its Applications (LMAM) and School of Mathematical Sciences Peking University Key Laboratory of Systems Biology Shanghai Institute of Biochemistry and Cell Biology Center for Excellence in Molecular Cell Science Chinese Academy of Sciences Key Laboratory of Systems Health Science of Zhejiang Province Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences Chinese Academy of Sciences School of Life Science and Technology Shanghai Tech University Guangdong Institute of Intelligence Science and Technology

Complex interactions between genes determine the development and differentiation of cells. We establish a landscape theory for cell differentiation with proliferation effect, in which the developmental process is modeled as a stochastic dynamical system with a birth-death term. We find that two different energy landscapes, denoted U and V, collectively contribute to the establishment of non-equilibrium steady differentiation. The potential U is known as the energy landscape leading to the steady distribution, whose metastable states stand for cell types, while V indicates the differentiation direction from pluripotent to differentiated cells. This interpretation of cell differentiation is different from the previous landscape theory without the proliferation effect. We propose feasible numerical methods and a mean-field approximation for constructing landscapes U and V. Successful applications to typical biological models demonstrate the energy landscape decomposition’s validity and reveal biological insights into the considered processes.

关键词： energy landscape cell differentiation stochastic systems

Theoretical analysis of nonlinear vibration characteristics of gear pair with shafts

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Theoretical & Applied Mechanics Letters 2022年第2期12卷 85-91页

作者： Tatsuhito aihara Kensho Sakamoto Department of Mechanical Engineering Faculty of Science and EngineeringHosei University3-7-2 KajinochoKoganei-shiTokyoJapan

The circumferential vibration of a gear pair is a parametric excitation caused by nonlinear tooth stiffness,which fluctuates with meshing.In addition,the vibration characteristics of the gear pair become complicated owing to the tooth profile error and backlash.It is considered that the circumferential vibration of the gear pair is affected by the torsional vibration of the shafts.It is important to understand quantitatively the vibration characteristics of the gear system considering the shafts.Therefore,the purpose of this research was to clarify the nonlinear vibration characteristics of a gear pair considering the influence of the shafts using theoretical methods.To achieve this objective,calculations were performed using equations of motion in which the circumferential vibration of the gear pair and the torsional vibration of the shafts were coupled.The nonlinear tooth stiffness was represented by a sine wave.The influence of tooth separation was considered by defining a nonlinear function using backlash and the tooth profile error.For the numerical calculations,both stable and unstable periodic solutions were obtained by using the shooting method.The effect of the shafts on the gear system vibration were clarified by comparing the results in the cases in which the shaft was not considered,one shaft was considered,and both shafts were considered.

关键词： Nonlinear Vibration Gear Chaos Shaft Tooth separation

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Dynamics-based data science in biology

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National Science Review 2021年第5期8卷 16-18页

作者： Jifan Shi Kazuyuki aihara Luonan Chen International Research Center for Neurointelligence The University of Tokyo Institutes for Advanced StudyThe University of Tokyo Shanghai Institute of Biochemistry and Cell Biology Center for Excellence in Molecular Cell ScienceChinese Academy of Sciences Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences School of Life Science and Technology Shanghai Tech University Key Laboratory of Systems Biology Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesChinese Academy of Sciences

Life science has long been a rich subject for research, and continues to develop at high speed. One of the major aims of life science is to study the mechanisms of various biological processes on the basis of biological big-data. Many statistics-based methods have been proposed to catch the essence by mining such data, including the popular category classification,variables regression, group clustering,statistical comparison, dimensionality reduction, and component analysis.

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Mathematically modelling and controlling prostate cancer under intermittent hormone therapy

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Asian Journal of Andrology 2012年第2期14卷 270-277页

作者： Yoshito Hirata Gouhei Tanaka Nicholas Bruchovsky Kazuyuki aihara Institute of Industrial Science University of Tokyo Tokyo 153-8505 Japan Vancouver Prostate Centre Vancouver General Hospital Vancouver BC V6H 3Z6 Canada

In this review, we summarize our recently developed mathematical models that predict the effects of intermittent androgen suppression therapy on prostate cancer （PCa）. Although hormone therapy for PCa shows remarkable results at the beginning of treatment, cancer cells frequently acquire the ability to grow without androgens during long-term therapy, resulting in an eventual relapse. To circumvent hormone resistance, intermittent androgen suppression was investigated as an alternative treatment option. However, at the present time, it is not possible to select an optimal schedule of on- and off-treatment cycles for any given patient. In addition, clinical trials have revealed that intermittent androgen suppression is effective for some patients but not for others. To resolve these two problems, we have developed mathematical models for PCa under intermittent androgen suppression. The mathematical models not only explain the mechanisms of intermittent androgen suppression but also provide an optimal treatment schedule for the on- and off-treatment periods.

关键词： diagnosis intermittent androgen suppression mathematical models personalized treatment schedule prognosis prostate cancer

Effectiveness of impedance monitoring during radiofrequency ablation for predicting popping

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World Journal of Gastroenterology 2012年第41期18卷 5870-5878页

作者： Hiroya Iida Tsukasa aihara Shinichi Ikuta Naoki Yamanaka Department of Surgery Meiwa Hospital4-31 Agenaruo-choNishinomiyaHyogo 663-8186Japan

AIM:To retrospectively evaluate the effectiveness of impedance monitoring for predicting popping during radiofrequency ablation(RFA) using internally cooled electrodes.METHODS:We reviewed 140 patients(94 males,46 females;age range 73.0 ± 11.1 year) who underwent RFA between February 2006 and November 2008 with a modified protocol using a limited power delivery rather than a conventional one to avoid popping.All the patients provided their written informed consent,and the study was approved by the institutional review board.Intraprocedural impedances were measured for the study subjects,and the tumors were classified into three types according to the characteristics of their impedance curves:increasing,flat,or decreasing.The tumors were further sorted into seven subtypes(A-G) depending on the curvature of the impedance curve' s increase or decrease.Relative popping rates were determined for the three types and seven subtypes.A chi-square test was performed to estimate statistical significance.RESULTS:A total of 148 nodules treated by RFA were analyzed.The study samples included 132 nodules of hepatocellular carcinoma,14 nodules of metastatic liver cancer,and two nodules of intrahepatic cholangiocarcinoma.The numbers of nodules with each impedance curve type were as follows:37 increasing-type nodules,43 flat-type nodules,and 68 decreasing-type nodules.Popping occurrence rates were 24.3%,46.5% and 64.7%,respectively.Flat-type nodules exhibited a significantly higher rate of popping compared to increasing-type nodules(P = 0.039).Decreasing-type nodules exhibited a significantly higher rate of popping compared to increasing-type nodules(P < 0.0001).Notably,nodules that showed a sharp decrease in impedance in the latter ablation period(subtype E) exhibited a significantly higher rate of popping compared to other subtypes.CONCLUSION:Intraprocedural impedance monitoring can be a useful tool to predict the occurrence of popping during liver tumor RFA performed with internally cooled electrodes.

关键词：阻抗曲线射频消融监测预测治疗内部冷却 RFA 增长型

Detection for disease tipping points by landscape dynamic network biomarkers

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National Science Review 2019年第4期6卷 775-785页

作者： Xiaoping Liu Xiao Chang Siyang Leng Hui Tang Kazuyuki aihara Luonan Chen Key Laboratory of Systems Biology Center for Excellence in Molecular Cell Science Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences School of Mathematics and Statistics Shandong University at Weihai Institute of Industrial Science the University of Tokyo Institute of Statistics and Applied Mathematics Anhui University of Finance & Economics School of Life Science and Technology Shanghai Tech University Center for Excellence in Animal Evolution and Genetics Research Center for Brain Science and Brain-Inspired Intelligence

A new model-free method has been developed and termed the landscape dynamic network biomarker(l-DNB) methodology. The method is based on bifurcation theory, which can identify tipping points prior to serious disease deterioration using only single-sample omics data. Here, we show that l-DNB provides early-warning signals of disease deterioration on a single-sample basis and also detects critical genes or network biomarkers(i.e. DNB members) that promote the transition from normal to disease states. As a case study, l-DNB was used to predict severe influenza symptoms prior to the actual symptomatic appearance in influenza virus infections. The l-DNB approach was then also applied to three tumor disease datasets from the TCGA and was used to detect critical stages prior to tumor deterioration using an individual DNB for each patient. The individual DNBs were further used as individual biomarkers in the analysis of physiological data, which led to the identification of two biomarker types that were surprisingly effective in predicting the prognosis of tumors. The biomarkers can be considered as common biomarkers for cancer, wherein one indicates a poor prognosis and the other indicates a good prognosis.

关键词： single-sample network dynamic network biomarkers tipping points of complex disease

Development and characterization of 43 microsatellite markers for the critically endangered primrose Primula reinii using MiSeq sequencing

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Plant Diversity 2018年第1期40卷 41-44页

作者： Masaya Yamamoto Yoshihiro Handa Hiroki aihara Hiroaki Setoguchi Graduate School of Human and Environmental Studies Kyoto University FASMAC Co. Ltd.

Primula reinii(Primulaceae), a perennial herb belonging to the Primula section Reinii, occurs on wet,shaded rocky cliffs in the mountains of Japan. This threatened species comprises four varieties; these plants are very localized and rare in the wild. In this study, 43 microsatellite markers were developed using MiSeq sequencing to facilitate conservation genetics of these critically endangered primroses. We developed novel microsatellite markers for three varieties of P. reinii, and tested its polymorphism and genetic diversity using natural populations. These novel markers displayed relatively high polymorphism; the number of alleles and expected heterozygosities ranged from 2 to 6(mean = 3.2) and 0.13 to 0.82(mean = 0.45), respectively. All loci were in Hardye Weinberg equilibrium. These microsatellite markers will be powerful tools to assess P. reinii genetic diversity and develop effective conservation and management strategies.

关键词： Microsatellites Polymorphism MiSeq Critically endangered plant Primula reinii

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Comparison of percutaneous transhepatic portal vein embolization and unilateral portal vein ligation

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World Journal of Gastroenterology 2012年第19期18卷 2371-2376页

作者： Hiroya Iida Tsukasa aihara Shinichi Ikuta Hidenori Yoshie Naoki Yamanaka Department of Surgery Meiwa Hospital 4-31 Agenaruo-choNisinomiyaHyogo 663-8186Japan

AIM:To compare the effect of percutaneous transhepatic portal vein embolization(PTPE) and unilateral portal vein ligation(PVL) on hepatic hemodynamics and right hepatic lobe(RHL) atrophy.METHODS:Between March 2005 and March 2009,13 cases were selected for PTPE(n = 9) and PVL(n = 4) in the RHL.The PTPE group included hilar bile duct carcinoma(n = 2),intrahepatic cholangiocarcinoma(n = 2),hepatocellular carcinoma(n = 2) and liver metastasis(n = 3).The PVL group included hepatocellular carcinoma(n = 2) and liver metastasis(n = 2).In addition,observation of postoperative hepatic hemodynamics obtained from computed tomography and Doppler ultrasonography was compared between the two groups.RESULTS:Mean ages in the two groups were 58.9 ± 2.9 years(PVL group) vs 69.7 ± 3.2 years(PTPE group),which was a significant difference(P = 0.0002).Among the indicators of liver function,including serum albumin,serum bilirubin,aspartate aminotransferase,alanine aminotransferase,platelets and indocyanine green retention rate at 15 min,no significant differences were observed between the two groups.Preoperative RHL volumes in the PTPE and PVL groups were estimated to be 804.9 ± 181.1 mL and 813.3 ± 129.7 mL,respectively,with volume rates of 68.9% ± 2.8% and 69.2% ± 4.2%,respectively.There were no significant differences in RHL volumes(P = 0.83) and RHL volume rates(P = 0.94),respectively.At 1 mo after PTPE or PVL,postoperative RHL volumes in the PTPE and PVL groups were estimated to be 638.4 ± 153.6 mL and 749.8 ± 121.9 mL,respectively,with no significant difference(P = 0.14).Postoperative RHL volume rates in the PTPE and PVL groups were estimated to be 54.6% ± 4.2% and 63.7% ± 3.9%,respectively,which was a significant difference(P = 0.0056).At 1 mo after the operation,the liver volume atrophy rate was 14.3% ± 2.3% in the PTPE group and 5.4% ± 1.6% in the PVL group,which was a significant difference(P = 0.0061).CONCLUSION:PTPE is a more effective procedure than PVL because PTPE is able to occlude completely the portal branch throughout

关键词：肝门静脉结扎单侧栓塞计算机断层扫描血流动力学血清白蛋白多普勒超声

Simultaneous bile duct and portal venous branch ligation in two-stage hepatectomy

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World Journal of Gastroenterology 2011年第30期17卷 3554-3559页

作者： Hiroya Iida Chiaki Yasui Tsukasa aihara Shinichi Ikuta Hidenori Yoshie Naoki Yamanaka Department of Surgery Meiwa Hospital 4-31 Agenaruo-choNisinomiya663-8186 HyogoJapan

Hepatectomy is an effective surgical treatment for multiple bilobar liver metastases from colon cancer;however,one of the primary obstacles to completing surgical resection for these cases is an insufficient volume of the future remnant liver,which may cause postoperative liver failure.To induce atrophy of the unilateral lobe and hypertrophy of the future remnant liver,procedures to occlude the portal vein have been conventionally used prior to major hepatectomy.We report a case of a 50-year-old woman in whom two-stage hepatectomy was performed in combination with intraoperative ligation of the portal vein and the bile duct of the right hepatic lobe.This procedure was designed to promote the atrophic effect on the right hepatic lobe more effectively than the conventional technique,and to the best of our knowledge,it was used for the first time in the present case.Despite successful induction of liver volume shift as well as the following procedure,the patient died of subsequent liver failure after developing recurrent tumors.We discuss the first case in which simultaneous ligation of the portal vein and the biliary system was successfully applied as part of the first step of two-stage hepatectomy.

关键词：肝功能衰竭门静脉切除术结扎胆管手术治疗手术切除结肠癌