Uniform Partition in Population Protocol Model Under Weak Fairness

We focus on a uniform partition problem in a population protocol model. The uniform partition problem aims to divide a population into k groups of the same size, where k is a given positive integer. In the case of k=2 (called uniform bipartition), a previous work clarified space complexity under various assumptions: 1) an initialized base station (BS) or no BS, 2) weak or global fairness, 3) designated or arbitrary initial states of agents, and 4) symmetric or asymmetric protocols, except for the setting that agents execute a protocol from arbitrary initial states under weak fairness in the model with an initialized base station. In this paper, we clarify the space complexity for this remaining setting. In this setting, we prove that P states are necessary and sufficient to realize asymmetric protocols, and that P+1 states are necessary and sufficient to realize symmetric protocols, where P is the known upper bound of the number of agents. From these results and the previous work, we have clarified the solvability of the uniform bipartition for each combination of assumptions. Additionally, we newly consider an assumption on a model of a non-initialized BS and clarify solvability and space complexity in the assumption. Moreover, the results in this paper can be applied to the case that k is an arbitrary integer (called uniform k-partition)

Recent advances in coronary angioscopy

SummaryAngioscopy enables macroscopic pathological diagnosis of cardiovascular diseases from the inside. This imaging modality has been intensively directed to characterizing vulnerable coronary plaques. Scoring of plaque color was developed, and based on prospective studies; dark yellow or glistening yellow plaques were proposed as vulnerable ones. Colorimetry apparatus was developed to assess the yellow color of the plaques quantitatively. The effects of lipid-lowering therapies on coronary plaques were confirmed by angioscopy. However, since observation is limited to surface color and morphology, pitfalls of this imaging technology became evident. Dye-staining angioscopy and near-infrared fluorescence angioscopy were developed for molecular imaging, and the latter method was successfully applied to patients. Color fluorescence angioscopy was also established for molecular and chemical basis characterization of vulnerable coronary plaques in both in vitro and in vivo. Drug-eluting stents (DES) reduce coronary restenosis significantly, however, late stent thrombosis (LST) occurs, which requires long-term antiplatelet therapy. Angioscopic grading of neointimal coverage of coronary stent struts was established, and it was revealed that neointimal formation is incomplete and prevalence of LST is higher in DES when compared to bare-metal stent. Many new stents were devised and they are now under experimental or clinical investigations to overcome the shortcomings of the stents that have been employed clinically. Endothelial cells are highly anti-thrombotic. Neoendothelial cell damage is considered to be caused by friction between the cells and stent struts due to the thin neointima between them that might act as a cushion. Therefore, development of a DES that causes an appropriate thickness (around 100μm) of the neointima is a potential option with which to prevent neoendothelial cell damage and consequent LST while preventing restenosis

ニワトリ胚の前腸におけるGlypican-3の発現と機能解析

Anterior part of primitive digestive tract, the foregut provides various organs and also affects patterning of the anterior neural tissue and development of the heart. It is important to understand the mechanisms of the foregut formation which controls whole anterior embryogenesis. Foregut formation is initiated from HH Stage 6 by folding at the anterior tip of the embryo. The foregut is like a shallow sac in the beginning and subsequently, foregut elongates rapidly toward caudal. A few reports suggested that the midline cells in the anterior intestinal portal (AIP) are important for the foregut elongation in stage 7. In the present thesis, to understand the mechanisms of the foregut elongation, the fate of the midline cells in AIP was analyzed at the various stages. I found that the midline cells in AIP expanded widely into the ventral midline of the foregut until stage 9 and this expansion of AIP cells gradually restricted to posterior as the foregut formation progressed. In addition, proliferating cells in the ventral foregut during the foregut elongation were detected by BrdU treatment. Proliferating cells were found in whole ventral foregut between stage 6, before the foregut formation, and 8, but no proliferating area was found in the ventral midline between stage 7 and 9, during rapid foregut elongation. These results indicate that endodermal cells in the ventral midline of the foregut didn’t proliferate during the foregut elongation but presumptive ventral midline endoderm proliferates before foregut formation. The ventral midline cells were provided from AIP, so it is suggested that endodermal cells which contribute to the ventral midline proliferate and be stocked in AIP before the foregut elongation in order to supply sufficient number of cells for the ventral midline during the foregut elongation. Then non-proliferating area in the ventral midline was restricted posteriorly as the foregut developed. This area was consistent with the expansion area from AIP in almost the same developmental stage. Those observations suggested that the ventral midline of the foregut extends by only cell rearrangement from AIP. Next, Glypican-3 was cloned and its expression pattern was analyzed. Glypican-3 expressed in the ventral foregut, may control cell proliferation, rearrangement and specification in the ventral midline of the foregut via regulation of signaling such as Wnt, BMP, FGF and Shh. In this thesis full-length protein coding sequence of Glypican-3 was isolated. From expression pattern analysis, Glypican-3 was expressed in the presumptive foregut endoderm at stage 5 and 6, and strongly in the ventral midline endoderm of the foregut from stage 7 to 10. It is possible that Glypican-3 is involved in the cell rearrangement of the ventral midline from AIP in these stages. After stage 11 expression of Glypican-3 was restricted in thyroid, lung and liver primordia. Later stages, Glypican-3 may control differentiation of specific organs.胃や肝臓等前方の消化器官は、前腸と呼ばれる管から生じる。前腸の腹側正中は甲状腺や肺、肝臓の原基が形成される特別な領域であり、原基が形成される以前から腹側に突き出た特徴的な形状をしている。先行研究では各消化器官の領域化、分化に必要なシグナル伝達経路が複数同定されている。しかし、腹側正中領域の形成に関与する分子や、適切な領域でシグナルを伝達し、各消化器官の領域を決めるメカニズムは不明である。当研究室では前腸の腹側にGlypican-3が特異的に発現していることを明らかにした。Glypican-3は膜結合型プロテオグリカンの１つであり、糖鎖を介して他シグナルリガンドを集積することで、シグナル勾配の形成や局所的なシグナルの受容を可能とする。ショウジョウバエ胚では、プロテオグリカンがWntファミリー増殖因子リガンドの受容体への結合を促進していることが報告された(Tsuda et al.,1999)。またGlypican-3ノックアウトマウスでは組織が巨大化した表現型を示すことが報告されており(Gonzalez et al., 1998)、Glypican-3は細胞移動や分裂にも関与していると示唆されている。しかしニワトリ胚におけるGlypican-3の機能は未だ不明である。私はGlypican-3が腹側正中領域の形成やシグナル伝達に関与し、消化器官の領域決定に寄与しているのではないかと考え、Gypican-3の機能解析を行うことにした。前腸が形成される過程での細胞挙動の詳細な記載がなかったため、まず前腸内胚葉細胞をラベルした胚を培養し、前腸形成に伴う細胞配置の変化を観察した。Stage7~9の前腸門の細胞は、Stage10~11では前後軸に沿って前腸腹側の広範囲に寄与するが、Stage11以降の前腸門の細胞は広範囲に広がらなくなることが明らかになった。またStage7~8の前腸門の正中付近の細胞は、前腸の伸長と共に正中線上に配置されることが分かった。次に前腸が伸長する時期にBrdUを取り込ませ、分裂した細胞を検出した。前腸門付近の内胚葉でBrdU陽性細胞が多数観察された。前腸腹側側方内胚葉ではBrdU陽性細胞が観察されたが、腹側正中の内胚葉ではBrdU陽性細胞がほとんど検出されなかった。以上の結果から、Stage7~10における前腸の伸長は主に前腸門からの細胞の供給によって起こり、腹側正中では分裂が起こらず、細胞移動によって細胞が供給されることが分かった。ニワトリではGlypican-3の遺伝子配列が決定されていなかったため、CDS全長のクローニングを行った。また3’RACE法、5’RACE法を用いてUTRの塩基配列を解析した。クローニングで得られた塩基配列を基にRNAプローブを合成してWhole mount in situ hybridizationを行い、Glypican-3の発現パターンを詳細に解析した。Stage8では前腸の腹側全体で強いシグナルが観察されたが、Stage9以降は正中付近で発現が強くなることが明らかとなった。Glypican-3の機能を解析するため、強制発現コンストラクトとsiRNAを設計した。現在siRNAのターゲット特異性とノックダウン効率を検証している。今後は、Glypican-3強制発現胚・ノックダウン胚の細胞挙動を観察し、Glypican-3が正常な前腸形成・正中領域の形成に関与しているのか検証する予定である。また各消化器官のマーカー遺伝子発現や、シグナル伝達強度の変化を観察し、Glypican-3が前腸でシグナル伝達制御に関与しているのか明らかにしたい。首都大学東京, 2018-03-25, 修士（理学）首都大学東

Population Protocols for Graph Class Identification Problems

In this paper, we focus on graph class identification problems in the population protocol model. A graph class identification problem aims to decide whether a given communication graph is in the desired class (e.g. whether the given communication graph is a ring graph). Angluin et al. proposed graph class identification protocols with directed graphs and designated initial states under global fairness [Angluin et al., DCOSS2005]. We consider graph class identification problems for undirected graphs on various assumptions such as initial states of agents, fairness of the execution, and initial knowledge of agents. In particular, we focus on lines, rings, k-regular graphs, stars, trees, and bipartite graphs. With designated initial states, we propose graph class identification protocols for k-regular graphs and trees under global fairness, and propose a graph class identification protocol for stars under weak fairness. Moreover, we show that, even if agents know the number of agents n, there is no graph class identification protocol for lines, rings, k-regular graphs, trees, or bipartite graphs under weak fairness, and no graph class identification for lines, rings, k-regular graphs, stars, trees, or bipartite graphs with arbitrary initial states

Uniform Bipartition in the Population Protocol Model with Arbitrary Communication Graphs

In this paper, we focus on the uniform bipartition problem in the population protocol model. This problem aims to divide a population into two groups of equal size. In particular, we consider the problem in the context of arbitrary communication graphs. As a result, we investigate the solvability of the uniform bipartition problem with arbitrary communication graphs when agents in the population have designated initial states, under various assumptions such as the existence of a base station, symmetry of the protocol, and fairness of the execution. When the problem is solvable, we present protocols for uniform bipartition. When global fairness is assumed, the space complexity of our solutions is tight

Distinct roles of the Src family kinases, SRC-1 and KIN-22, that are negatively regulated by CSK-1 in C. elegans

AbstractTo elucidate the primitive roles of the Src family kinases (SFKs), here we characterized Caenorhabditis elegans orthologues of SFKs (src-1 and kin-22) and their regulator kinase Csk (csk-1). SRC-1 and KIN-22 possess the C-terminal regulatory tyrosines characteristic of SFKs, and their activities are negatively regulated by CSK-1 in a yeast expression system. The src-1 and csk-1 genes are co-expressed in some head neurons, the anchor cell and the tail region, while kin-22 and csk-1 genes are co-expressed in pharyngeal muscles and tail region. Expression of KIN-22 induced morphological defects in the pharynx, whereas expression of SRC-1 did not show any overt phenotype in adult. RNA interference of src-1, but not that of kin-22, caused a developmental arrest in early development. These results suggest that SRC-1 and KIN-22 play distinct roles under the control of CSK-1

New mechanisms modulating S100A8 gene expression

S100A8 is a highly-expressed calcium-binding protein in neutrophils and activated macrophages, and has proposed roles in myeloid cell differentiation and host defense. Functions of S100A8 are not fully understood, partly because of difficulties in generating S100A8 knockout mice. Attempts to silence S100A8 gene expression in activated macrophages and fibroblasts using RNA interference (RNAi) technology were unsuccessful. Despite establishing validated small interfering RNA (siRNA) systems, enzymaticallysynthesized siRNA targeted to S100A8 suppressed mRNA levels by only 40% in fibroblasts activated with FGF-2+heparin, whereas chemically-synthesized siRNAs suppressed S100A8 driven by an S100A8-expression vector by ~75% in fibroblasts. Suppression of the gene in activated macrophages/fibroblasts was low, and some enzymatically-synthesized siRNAs to S100A8, and unrelated siRNA to GAPDH, induced/enhanced S100A8 expression in macrophages. This indicated that S100A8 may be upregulated by type-1 interferon (IFN). IFN-β enhanced expression, but did not directly induce S100A8. Poly (I:C), a synthetic dsRNA, directly induced S100A8 through IL-10 and IFN-dependent pathways. Induction by dsRNA was dependent on RNA-dependent protein kinase (PKR), but not cyclooxygenase-2, suggesting divergent pathways in LPS- and dsRNA-induced responses. New mechanisms of S100A8 gene regulation are presented, that suggest functions in anti-viral defense. S100A8 expression was confirmed in lungs from influenza virus-infected mice and from a patient with severe acute respiratory syndrome (SARS). Multiple pathways via mitochondria mediated S100A8 induction in LPS-activated macrophages; Generation of reactive oxygen species via the mitochondrial electron transport chain and de novo synthesis of ATP may be involved. This pathway also regulated IL-10 production, possibly via PKR. Extracellular ATP and its metabolites enhanced S100A8 induction. Results support involvement of cell stress, such as transfection, in S100A8 expression. A breast tumor cell line (MCF-7) in which the S100A8 gene was silenced, was established using micro RNA technology; S100A8 induction by oncostatin M was reduced by >90% in stably-transfected cells. This did not alter MCF-7 growth. The new approach to investigate the role of S100A8 in a human tumor cell line may assist in exploring its functions and lead to new studies concerning its role in cancer