28 research outputs found

    From symplectic cohomology to Lagrangian enumerative geometry

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    We build a bridge between Floer theory on open symplectic manifolds and the enumerative geometry of holomorphic disks inside their Fano compactifications, by detecting elements in symplectic cohomology which are mirror to Landau-Ginzburg potentials. We also treat the higher Maslov index versions of LG potentials. We discover a relation between higher disk potentials and symplectic cohomology rings of anticanonical divisor complements (themselves related to closed-string Gromov-Witten invariants), and explore several other applications to the geometry of Liouville domains.Comment: 47 pages, 13 figures; v2: reference fixes, minor correction

    A study on ensuring the quality and safety of pharmaceuticals and medical devices derived from processing of autologous human induced pluripotent stem(-like) cells

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    As a series of endeavors to establish suitable measures for the sound development of regenerative medicine using human stem cell-based products, we studied scientific principles, concepts, and basic technical elements to ensure the quality and safety of therapeutic products derived from autologous human iPS cells or iPS cell-like cells, taking into consideration scientific and technological advances, ethics, regulatory rationale, and international trends in human stem cell-derived products. This led to the development of the Japanese official Notification No. 0907-4, “Guideline on Ensuring the Quality and Safety of Pharmaceuticals and Medical Devices Derived from the Processing of Autologous Human Induced Pluripotent Stem(-Like) Cells, ” issued by Pharmaceuticals and Food Safety Bureau, Ministry of Health, Labour and Welfare of Japan, on September 7, 2012. The present paper addresses various aspects of products derived from autologous human iPS cells (or iPS cell-like cells), in addition to similar points to consider that are described previously for autologous human stem cell-based products. Major additional points include (1) possible existence of autologous human iPS cell-like cells that are different from iPS cells in terms of specific biological features; (2) the use of autologous human iPS(-like) cells as appropriate starting materials for regenerative medicine, where necessary and significant; (3) establishment of autologous human iPS(-like) cell lines and their characterization; (4) cell banking and/or possible establishment of intermediate cell lines derived from autologous human iPS(-like) cells at appropriate stage(s) of a manufacturing process, if necessary; and (5) concerns about the presence of undifferentiated cells in the final product; such cells may cause ectopic tissue formation and/or tumorigenesis. The ultimate goal of this guidance is to provide suitable medical opportunities as soon as possible to the patients with severe diseases that are difficult to treat with conventional modalities

    A study on ensuring the quality and safety of pharmaceuticals and medical devices derived from processing of autologous human induced pluripotent stem(-like) cells

    Get PDF
    As a series of endeavors to establish suitable measures for the sound development of regenerative medicine using human stem cell-based products, we studied scientific principles, concepts, and basic technical elements to ensure the quality and safety of therapeutic products derived from autologous human iPS cells or iPS cell-like cells, taking into consideration scientific and technological advances, ethics, regulatory rationale, and international trends in human stem cell-derived products. This led to the development of the Japanese official Notification No. 0907-4, “Guideline on Ensuring the Quality and Safety of Pharmaceuticals and Medical Devices Derived from the Processing of Autologous Human Induced Pluripotent Stem(-Like) Cells, ” issued by Pharmaceuticals and Food Safety Bureau, Ministry of Health, Labour and Welfare of Japan, on September 7, 2012. The present paper addresses various aspects of products derived from autologous human iPS cells (or iPS cell-like cells), in addition to similar points to consider that are described previously for autologous human stem cell-based products. Major additional points include (1) possible existence of autologous human iPS cell-like cells that are different from iPS cells in terms of specific biological features; (2) the use of autologous human iPS(-like) cells as appropriate starting materials for regenerative medicine, where necessary and significant; (3) establishment of autologous human iPS(-like) cell lines and their characterization; (4) cell banking and/or possible establishment of intermediate cell lines derived from autologous human iPS(-like) cells at appropriate stage(s) of a manufacturing process, if necessary; and (5) concerns about the presence of undifferentiated cells in the final product; such cells may cause ectopic tissue formation and/or tumorigenesis. The ultimate goal of this guidance is to provide suitable medical opportunities as soon as possible to the patients with severe diseases that are difficult to treat with conventional modalities

    A study on ensuring the quality and safety of pharmaceuticals and medical devices derived from the processing of human embryonic stem cells

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    As a series of endeavors to establish suitable measures for the sound development of regenerative medicine using human stem cell-based products, we studied scientific principles, concepts, and basic technical elements to ensure the quality and safety of therapeutic products derived from the processing of human embryonic stem cells (hESCs), taking into consideration scientific and technological advances, ethics, regulatory rationale, and international trends in human stem cell-derived products. This led to the development of the Japanese official Notification No. 0907-6, “Guideline on Ensuring the Quality and Safety of Pharmaceuticals and Medical Devices Derived from the Processing of Human Embryonic Stem Cells, ” issued by Pharmaceuticals and Food Safety Bureau, Ministry of Health, Labour and Welfare of Japan, on September 7, 2012. The present paper addresses various aspects of products derived from hESCs, in addition to similar points to consider that are described previously for allogeneic human stem cell-based products. Major additional points include 1) establishment of hESCs; 2) establishment of stable and well-characterized cell banks of hESCs and relevant intermediate cell products; 3) concerns about the presence of undifferentiated cells in final products, which may result in ectopic tissue formation and/or tumorigenesis; and 4) concerns about undesirable immunological reactions caused by the final products. The ultimate goal of this series of guidelines on regenerative medicine is to provide suitable medical opportunities as soon as possible to the patients with severe diseases that are difficult to treat with conventional modalities. If these guidelines are interpreted and employed in a flexible and meaningful way in this context, they should serve as a useful means to achieve their goals

    Fast Optimal Replica Placement with Exhaustive Search Using Dynamically Reconfigurable Processor

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    This paper proposes a new replica placement algorithm that expands the exhaustive search limit with reasonable calculation time. It combines a new type of parallel data-flow processor with an architecture tuned for fast calculation. The replica placement problem is to find a replica-server set satisfying service constraints in a content delivery network (CDN). It is derived from the set cover problem which is known to be NP-hard. It is impractical to use exhaustive search to obtain optimal replica placement in large-scale networks, because calculation time increases with the number of combinations. To reduce calculation time, heuristic algorithms have been proposed, but it is known that no heuristic algorithm is assured of finding the optimal solution. The proposed algorithm suits parallel processing and pipeline execution and is implemented on DAPDNA-2, a dynamically reconfigurable processor. Experiments show that the proposed algorithm expands the exhaustive search limit by the factor of 18.8 compared to the conventional algorithm search limit running on a Neumann-type processor

    A study on ensuring the quality and safety of pharmaceuticals and medical devices derived from the processing of allogeneic human somatic stem cells

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    As a series of endeavors to establish suitable measures for the sound development of regenerative medicine using human stem cell-based products, we studied scientific principles, concepts, and basic technical elements to ensure the quality and safety of therapeutic products derived from allogeneic human somatic stem cells, taking into consideration scientific and technological advances, ethics, regulatory rationale, and international trends in human stem cell-derived products. This led to the development of the Japanese official Notification No. 0907-3, “Guideline on Ensuring the Quality and Safety of Pharmaceuticals and Medical Devices Derived from the Processing of Allogeneic Human Somatic Stem Cells, ” issued by Pharmaceuticals and Food Safety Bureau, Ministry of Health, Labour and Welfare of Japan, on September 7, 2012. The present paper describes the background information and development of our study and the resulting guidance. For products derived from allogeneic somatic stem cells, major points to consider include 1) history, the source, and derivation of starting cells; 2) donor screening/testing and donor eligibility, especially in relation to the presence of adventitious agents, potential occurrence of donor-derived diseases, and immunocompatibility; 3) clinical records of a donor; 4) multipotency and self-replication ability of allogeneic human somatic stem cells; 5) cell banking; 6) potential presence of viruses in the final product; 7) extensive characterization of the cells at critical stage(s) of manufacture; 8) robustness of the manufacturing process; 9) quality consistency of the products such as the final products and critical intermediate(s) if any; and 10) robust application and function of the final products in a cell environment different from where the original cells were localized and were performing their natural endogenous function. The ultimate goal of this guidance is to provide suitable medical opportunities as soon as possible to the patients with severe diseases that are difficult to treat with conventional modalities

    Identification of the Microbiota in Carious Dentin Lesions Using 16S rRNA Gene Sequencing

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    <div><p>While mutans streptococci have long been assumed to be the specific pathogen responsible for human dental caries, the concept of a complex dental caries-associated microbiota has received significant attention in recent years. Molecular analyses revealed the complexity of the microbiota with the predominance of <i>Lactobacillus</i> and <i>Prevotella</i> in carious dentine lesions. However, characterization of the dentin caries-associated microbiota has not been extensively explored in different ethnicities and races. In the present study, the bacterial communities in the carious dentin of Japanese subjects were analyzed comprehensively with molecular approaches using the16S rRNA gene. Carious dentin lesion samples were collected from 32 subjects aged 4–76 years, and the 16S rRNA genes, amplified from the extracted DNA with universal primers, were sequenced with a pyrosequencer. The bacterial composition was classified into clusters I, II, and III according to the relative abundance (high, middle, low) of <i>Lactobacillus</i>. The bacterial composition in cluster II was composed of relatively high proportions of <i>Olsenella</i> and <i>Propionibacterium</i> or subdominated by heterogeneous genera. The bacterial communities in cluster III were characterized by the predominance of <i>Atopobium</i>, <i>Prevotella</i>, or <i>Propionibacterium</i> with <i>Streptococcus</i> or <i>Actinomyces</i>. Some samples in clusters II and III, mainly related to <i>Atopobium</i> and <i>Propionibacterium</i>, were novel combinations of microbiota in carious dentin lesions and may be characteristic of the Japanese population. Clone library analysis revealed that <i>Atopobium</i> sp. HOT-416 and <i>P. acidifaciens</i> were specific species associated with dentinal caries among these genera in a Japanese population. We summarized the bacterial composition of dentinal carious lesions in a Japanese population using next-generation sequencing and found typical Japanese types with <i>Atopobium</i> or <i>Propionibacterium</i> predominating.</p></div
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