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R2: Incremental reprogramming Using Relocatable Code in Networked Embedded Systems

IEEE TRANSACTIONS ON COMPUTERS 2013年第9期62卷 1837-1849页

作者： Dong, Wei Liu, Yunhao Chen, Chun Bu, Jiajun Huang, Chao Zhao, Zhiwei Zhejiang Univ Coll Comp Sci Zhejiang Key Lab Serv Robot Hangzhou 310027 Zhejiang Peoples R China Tsinghua Univ Sch Software Beijing 100084 Peoples R China Tsinghua Univ TNLIST Beijing 100084 Peoples R China

We present R2, an incremental reprogramming approach using relocatable code, to improve program similarity for efficient incremental reprogramming in networked embedded systems. R2 achieves a higher degree of similarity than existing approaches by mitigating effects of both function shifts and data shifts. R2 adopts a content-aware differencing algorithm to generate small delta files for efficient dissemination. Besides, it makes efficient use of memory and does not degrade program quality. We implement R2 based on TinyOS 2.1 and demonstrate its advantages through detailed analysis of TinyOS examples. We also present case studies on the software programs of a large-scale sensor system-GreenOrbs. Results show that R2 reduces the dissemination cost by approximately 65 percent compared to state-of-the-art network reprogramming approach-Deluge, and reduces the dissemination cost by approximately 20 percent compared to Zephyr and Hermes-the latest works on incremental reprogramming.

关键词： Wireless sensor networks reprogramming relocatable code

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Evolutionary transition between invertebrates and vertebrates via methylation reprogramming in embryogenesis

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National Science Review 2019年第5期6卷 993-1003页

作者： Xiaocui Xu Guoqiang Li Congru Li Jing Zhang Qiang Wang David K.Simmons Xuepeng Chen Naveen Wijesena Wei Zhu Zhanyang Wang Zhenhua Wang Bao Ju Weimin Ci Xuemei Lu Daqi Yu Qian-fei Wang Neelakanteswar Aluru Paola Oliveri Yong E.Zhang Mark Q.Martindale Jiang Liu CAS Key Laboratory of Genome Sciences and Information Beijing Institute of Genomics Chinese Academy of Sciences University of Chinese Academy of Sciences Institute of Apiculture Research Chinese Academy of Agriculture Sciences Whitney Laboratory for Marine Bioscience University of Florida College of Life Sciences Yantai University CAS Key Laboratory of Genomics and Precision Medicine Beijing Institute of Genomics Chinese Academy of Sciences Institute of Zoology Chinese Academy of Sciences Biology Department Woods Hole Oceanographic Institution Departments of Genetics Evolution and Environment and Cell and Developmental Biology University College London CAS Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences

Major evolutionary transitions are enigmas, and the most notable enigma is between invertebrates and vertebrates, with numerous spectacular *** search for the molecular connections involved, we asked whether global epigenetic changes may offer a clue by surveying the inheritance and reprogramming of parental DNA methylation across *** focused on gametes and early embryos, where the methylomes are known to evolve divergently between fish and ***, we find that methylome reprogramming during embryogenesis occurs neither in pre-bilaterians such as cnidarians nor in protostomes such as insects, but clearly presents in deuterostomes such as echinoderms and invertebrate chordates, and then becomes more evident in *** association analysis suggests that DNA methylation reprogramming is associated with development, reproduction and adaptive immunity for vertebrates, but not for ***, the single HOX cluster of invertebrates maintains unmethylated status in all stages *** contrast, the multiple HOX clusters show dramatic dynamics of DNA methylation during vertebrate ***, the methylation dynamics of HOX clusters are associated with their spatiotemporal expression in *** study reveals that DNA methylation reprogramming has evolved dramatically during animal evolution, especially after the evolutionary transitions from invertebrates to vertebrates, and then to mammals.

关键词： DNA methylation evolution development reprogramming

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BMPs functionally replace Klf4 and support efficient reprogramming of mouse fibroblasts by Oct4 alone

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细胞研究（英文版） 2011年第1期21卷 205-212页

作者： Jiekai Chen Jing Liu Jiaqi Yang You Chen Jing Chen Su Ni Hong Song Lingwen Zeng Ke Ding Duanqing Pei Key Laboratory of Regenerative Biology South China Institute for Stem Cell Biology and Regenerative Medicine at Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China

Generation of induced pluripotent stem cells by defined factors has become a useful model to investigate the mechanism of reprogramming and cell fate determination. However, the precise mechanism of factor-based reprogramming remains unclear. Here, we show that Klf4 mainly acts at the initial phase of reprogramming to initiate mesenchymal-to-epithelial transition and can be functionally replaced by bone morphogenetic proteins (BMPs). BMPs boosted the efficiency of Oct4/Sox2-mediated reprogramming of mouse embryonic fibroblasts (MEFs) to ∼1%. BMPs also promoted single-factor Oct4-based reprogramming of MEFs and tail tibial fibroblasts. Our studies clarify the contribution of Klf4 in reprogramming and establish Oct4 as a singular setter of pluripotency in differentiated cells.

关键词： Oct4 iPSCs reprogramming stem cell BMPs MET

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SDRP: A Secure and Distributed reprogramming Protocol for Wireless Sensor Networks

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IEEE TRANSACTIONS ON INDUSTRIAL ELECTRONICS 2012年第11期59卷 4155-4163页

作者： He, Daojing Chen, Chun Chan, Sammy Bu, Jiajun Zhejiang Univ Natl Engn Res Ctr Intelligent Train Coll Comp Sci Hangzhou 310027 Zhejiang Peoples R China City Univ Hong Kong Dept Elect Engn Kowloon Hong Kong Peoples R China

Wireless reprogramming for a wireless sensor network is the process of uploading new code or changing the functionality of existing code. For security reasons, every code update must be authenticated to prevent an adversary from installing malicious code in the network. All existing reprogramming protocols are based on the centralized approach in which only the base station has the authority to initiate reprogramming. However, it is desirable and sometimes necessary for multiple authorized network users to simultaneously and directly reprogram sensor nodes without involving the base station, which is referred to as distributed reprogramming. In this case, the network owner can also assign different reprogramming privileges to different users. Motivated by this consideration, we develop a secure and distributed reprogramming protocol named SDRP, which is the first work of its kind. The protocol uses identity-based cryptography to secure the reprogramming and to reduce the communication and storage requirements of each node. Moreover, our theoretical analysis demonstrates the security properties of our protocol. We also implement SDRP in a network of resource-limited sensor nodes to show its high efficiency in practice.

关键词： Authentication reprogramming security wireless sensor networks (WSNs)

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Dynamics of 5-methylcytosine and 5-hydroxymethylcytosine during germ cell reprogramming

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细胞研究（英文版） 2013年第3期23卷 329-339页

作者： Shinpei Yamaguchi Kwonho Hong Rui Liu Azusa Inoue Li Shen Kun Zhang Yi Zhang Howard Hughes Medical Institute WAB-149G 200 Longwood Av. Boston MA 02115 USA Program in Cellular and Molecular Medicine WAB-149G 200 Longwood Av. Boston MA 02115 USA Division of Hematology/Oncology Department of Pediatrics Boston Children's HospitalWAB-149G 200 Longwood Av. Boston MA 02115 USA Departments of Bioengineering University of California at San DiegoLa Jolla CA 92093-0412 USA Howard Hughes Medical Institute WAB-149G 200 Longwood Av. Boston MA 02115 USA Program in Cellular and Molecular Medicine WAB-149G 200 Longwood Av. Boston MA 02115 USA Division of Hematology/Oncology Department of Pediatrics Boston Children's HospitalWAB-149G 200 Longwood Av. Boston MA 02115 USA Department of Genetics Harvard Medical SchoolWAB-149G 200 Longwood Av. Boston MA 02115 USA Harvard Stem Cell Institute WAB-149G 200 Longwood Av. Boston MA 02115 USA

Previous studies have revealed that mouse primordial germ cells (PGCs) undergo genome-wide DNA methylation reprogramming to reset the epigenome for totipotency. However, the precise 5-methylcytosine (5mC) dynamics and its relationship with the generation of 5-hydroxymethylcytosine (5hmC) are not clear. Here we analyzed the dynamics of 5mC and 5hmC during PGC reprograming and germ cell development. Unexpectedly, we found a specific period (E8.5-9.5) during which both 5mC and 5hmC levels are low. Subsequently, 5hmC levels increase reaching its peak at E11.5 and gradually decrease until E13.5 likely by replication-dependent dilution. Interestingly, 5hmC is enriched in chromocenters during this period. While this germ cell-specific 5hmC subnuclear localization pattern is maintained in female germ cells even in mature oocytes, such pattern is gradually lost in male germ cells as mitotic proliferation resumes during the neonatal stage. Pericentric 5hmC plays an important role in silencing major satellite repeat, especially in female PGCs. Global transcriptome analysis by RNA-seq revealed that the great majority of differentially expressed genes from E9.5 to 13.5 are upregulated in both male and female PGCs. Although only female PGCs enter meiosis during the prenatal stage, meiosis-related and a subset of imprinted genes are significantly upregulated in both male and female PGCs at E13.5. Thus, our study not only reveals the dynamics of 5mC and 5hmC during PGC reprogramming and germ cell development, but also their potential role in epigenetic reprogramming and transcriptional regulation of meiotic and imprinted genes.

关键词： DNA demethylation 5-hydroxymethylcytosine primordial germ cells reprogramming pericentric heterochromatin

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The Epigenetic reprogramming Roadmap in Generation of iPSCs from Somatic Cells

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Journal of Genetics and Genomics 2015年第12期42卷 661-670页

作者： Jacob Brix Yan Zhou Yonglun Luo Department of Biomedicine Aarhus University

reprogramming of somatic cells to induced pluripotent stem cells （iPSCs） is a comprehensive epigenetic process involving genome-wide modifications of histones and DNA methylation. This process is often incomplete, which subsequently affects iPSC reprograming, pluripotency, and differentiation capacity. Here, we review the epigenetic changes with a focus on histone modification （methylation and acetylation） and DNA modification （methylation） during iPSC induction. We look at changes in specific epigenetic signatures, aberrations and epigenetic memory during reprogramming and small molecules influencing the epigenetic reprogramming of somatic cells. Finally, we discuss how to improve iPSC generation and pluripotency through epigenetic manipulations.

关键词： Induced pluripotent stem cells (iPSCs) reprogramming Epigenetics Histone modification DNA methylation Epigenetic memory

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Yeast-derived nanocarriers enable binary reprogramming macrophages for cancer immunotherapy

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NANO TODAY 2024年 55卷

作者： Che, Junyi Zhang, Xiaoxuan Gao, Guangtao Yang, Yu Gan, Jingjing Chen, Kai Xu, Wei Zhao, Yuanjin Nanjing Univ Nanjing Drum Tower Hosp Affiliated Hosp Med SchDept Rheumatol & Immunol Nanjing 210008 Peoples R China Southeast Univ Sch Biol Sci & Med Engn State Key Lab Bioelect Nanjing 210096 Peoples R China Naval Med Univ Shanghai Changhai Hosp Dept Orthoped Shanghai 200433 Peoples R China Shanghai Jiao Tong Univ Sch Med Tongren Hosp Dept Orthoped Shanghai 200336 Peoples R China

Tumor-associated macrophages (TAMs) play an important role in promoting tumor growth and metastasis, thus reprogramming TAMs to modulate the tumor immune microenvironment is a promising tumor treatment stratagem. Here, we present novel yeast-derived nanocarriers (YNCs) as IPI-549 delivery system for binary reprogramming of TAMs to induce anticancer immunity. The nanocarriers were fabricated from yeast cell walls with immune-oncology agent IPI-549 loading and coated with a shielding polymer for prolonged blood circulation. After intravenous injection, these YNCs could accumulate at the tumor site and be phagocytosed by TAMs via the Dectin-1 pathway to induce macrophage polarization towards M1 phenotype. In combination with IPI549, the YNC system has efficiently inhibited tumor growth and modulated the tumor immune microenvironment through macrophage phenotypic alteration and increase of T cell-mediated antitumor immunity, which was demonstrated in a 4T1 orthotopic breast cancer mouse model. All these features indicate the promising values of our YNC delivery system in clinical antitumor applications.

关键词： Macrophage Immunotherapy reprogramming Yeast Drug delivery

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RE1-silencing Transcription Factor (REST) Is Required for Nuclear reprogramming by Inhibiting Transforming Growth Factor β Signaling Pathway

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JOURNAL OF BIOLOGICAL CHEMISTRY 2016年第53期291卷 27334-27342页

作者： Kong, Qing-Ran Xie, Bing-Teng Zhang, Heng Li, Jing-Yu Huang, Tian-Qing Wei, Ren-Yue Liu, Zhong-Hua Northeast Agr Univ Coll Life Sci Key Lab Anim Cell & Genet Engn Heilongjiang Prov Harbin 150030 Peoples R China

Differentiated cells can be reprogrammed by transcription factors, and these factors that are responsible for successful reprogramming need to be further identified. Here, we show that the neuronal repressor RE1-silencing transcription factor (REST) is rich in porcine oocytes and requires for nuclear transfer (NT)-mediated reprogramming through inhibiting TGF beta signaling pathway. REST was dramatically degraded after oocyte activation, but the residual REST was incorporated into the transferred donor nuclei during reprogramming in NT embryos. Inhibition of REST function in oocytes compromised the development of NT embryos but not that of IVF and PA embryos. Bioinformation analysis of putative targets of REST indicated that REST might function on reprogramming in NT embryos by inhibiting TGF beta pathway. Further results showed that the developmental failure of REST-inhibited NT embryos could be rescued by treatment of SB431542, an inhibitor of TGF beta pathway. Thus, REST is a newly discovered transcription factor that is required for NT-mediated nuclear reprogramming.

关键词： bioinformatics cloning oocyte repressor protein reprogramming

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Polyaminoglycoside-mediated cell reprogramming system for the treatment of diabetes mellitus

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JOURNAL OF CONTROLLED RELEASE 2022年 343卷 420-433页

作者： Pan, Yunqi Shao, Meiyu Li, Pan Xu, Chen Nie, Jingjun Zhang, Kai Wu, Sen Sui, Dandan Xu, Fu-Jian Beijing Univ Chem Technol Key Lab Biomed Mat Nat Macromolecules Coll Mat Sci & EngnBeijing Lab Biomed Mat State Key Lab Chem Resource EngnMinist Educ Beijing Peoples R China China Agr Univ Coll Biol Sci Beijing Adv Innovat Ctr Food Nutr & Human Hlth State Key Lab Agrobiotechnol Beijing Peoples R China

Diabetes mellitus is a disease of metabolism, featuring persistent hyperglycaemia due to insufficient insulin secretion or insulin resistance. At present, the generation of new beta cells from autologous cells by ectopic expression of specific transcription factors is a promising treatment for diabetes. The application of this strategy urgently needs safe and effective gene delivery vectors. In this work, a therapeutic plasmid (pNPMN-PBase), combined multiple specific transcription factors Ngn3, Pdx1, Mafa and Neruod1 (NPMN), was firstly constructed. Then, phenylboronic acid (PBA)-functionalized branched polymers (SS-HPT-P) have been proposed to deliver pNPMN-PBasefor the promising treatment of diabetes. SS-HPT-P had good biocompatibility and low cytotoxicity, and could achieve liver-targeted delivery. SS-HPT-P/pNPMN-PBase system can effectively realize the liver delivery of exogenous therapeutic genes, induce the reprogramming of hepatocytes into beta-like cells, reestablish the endogenous insulin-expression system, and alleviate diabetes and its complications. The present study thus provides an effective strategy for the cell replacement therapy of diabetes.

关键词： Diabetes reprogramming Phenylboronic acid Vector Liver-targeted Gene therapy

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Reliable and Efficient reprogramming in Sensor Networks

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ACM TRANSACTIONS ON SENSOR NETWORKS 2010年第1期7卷 1–32页

作者： Miller, Chris Poellabauer, Christian Univ Notre Dame Dept Comp Sci & Engn Notre Dame IN 46556 USA

Retasking and remote programming of sensor networks is an essential functionality to make these networks practical and effective. As the availability of more capable sensor nodes increases and new functional implementations continue to be proposed, these large collections of wireless nodes will need the ability to update and upgrade the software packages they are running. In order to do this, the new binary file must be distributed to all nodes in the network. Making a physical connection with each individual node is impractical in large wireless networks. Standard flooding mechanisms are too energy-costly and computationally expensive and they may interfere with the network's current tasks. A reliable method for distributing new code or binary files to every node in a wireless sensor network is needed. We propose a reprogramming/retasking framework for sensor networks that is energy efficient, responsive, and reliable, while maintaining a stable network.

关键词： Algorithms Design Performance Reliability Broadcast energy efficiency minimum energy broadcast reliable distribution reprogramming retasking sensor networks

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