Investigation of Hepatoprotective Activity of Induced Pluripotent Stem Cells in the Mouse Model of Liver Injury

To date liver transplantation is the only effective treatment for end-stage liver diseases. Considering the potential of pluripotency and differentiation into tridermal lineages, induced pluripotent stem cells (iPSCs) may serve as an alternative of cell-based therapy. Herein, we investigated the effect of iPSC transplantation on thioacetamide- (TAA-) induced acute/fulminant hepatic failure (AHF) in mice. Firstly, we demonstrated that iPSCs had the capacity to differentiate into hepatocyte-like cells (iPSC-Heps) that expressed various hepatic markers, including albumin, α-fetoprotein, and hepatocyte nuclear factor-3β, and exhibited biological functions. Intravenous transplantation of iPSCs effectively reduced the hepatic necrotic area, improved liver functions and motor activity, and rescued TAA-treated mice from lethal AHF. 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate cell labeling revealed that iPSCs potentially mobilized to the damaged liver area. Taken together, iPSCs can effectively rescue experimental AHF and represent a potentially favorable cell source of cell-based therapy

Real-time and Customizable Inverse Kinematics for Extensible Multisection Continuum Robots: SLInKi and AMoRPH Algorithms

Extensible multisection continuum robots are characterized by their continuous and compliant structures, which provide them with superior adaptability and flexibility compared to traditional robots. Nonetheless, the complexity of their kinematics and inverse kinematics presents significant challenges. This study addresses these challenges by introducing two innovative algorithms for inverse kinematics: SLInKi and AMoRPH. SLInKi is a hybrid approach that combines state lattice searching algorithms, exFABRIKc, and analytical solvers. Its main focus is on real-time solution and optimization of shape and motion smoothness, allowing for customization. On the other hand, AMoRPH is a novel analytical solver that utilizes a virtual linkage model in order to efficiently solve the 5 degree-of-freedom inverse kinematics problem and find balanced and smooth solutions. When faced with non-uniform cases and obstacles, segment addition and geometry adjustments are employed. This algorithm effectively addresses the inverse kinematics problem with speed, accuracy, and versatility. The validity of both algorithms is demonstrated through simulations and experiments, which showcase their effectiveness in real-time control, precise tracking, and obstacle avoidance for continuum robots

Analyses of Honeybee Color Vision Using Spectral Images

研究使用影像處理技術，模擬並分析蜜蜂色彩視覺神經處理機制，以解釋在蜜蜂色彩視覺系統的色彩拮抗編碼（color opponent coding, COC）模型中，神經電生理實驗記錄與色彩分辨行為實驗結果之間的對應關係，前者已知有超過十九種的組合，後者卻僅有兩種。在影像擷取的方面，透過可接受紫外光與可見光的CCD攝影機搭配依照蜜蜂光感受器對波長敏感度特製的濾鏡，拍攝蜜蜂在大自然中所見的花朵或是蜘蛛，得到在紫外光、藍光以及綠光範圍的影像。在影像處理與分析部份，根據蜜蜂色彩視覺的神經處理機制合成影像。在二十七種可能的神經處理方式中，我們專注於多光譜影像的神經處理機制，因此剔除屬於窄域神經的七種組合方式，針對廣域神經與色彩拮抗神經的二十種組合，並且經由線性與非線性的計算方式進行數位影像合成。以影像相關係數與紋理特徵的差異作為比較影像相似程度的根據，再使用affinity propagation分群方法進行分析。分析結果顯示，二十種COC編碼合成影像的分群結果為兩大群，且行為實驗所得兩種組合分屬兩群，因此雖然有多種色彩拮抗編碼組合，經過神經處理機制之後，視覺訊號卻只有兩大類，符合行為實驗與神經電生理實驗所得到的結果。The objective of this research is to simulate and analyze the neural mechanisms of honeybee color vision using image processing technique, and to explain the relationship between the intercellular recording data and the color discrimination function. There are over 19 COC patterns in the former but only 2 patterns in the later. In order to acquire images matching to the spectral sensitivities of the honeybee''s photoreceptors, a CCD with ultraviolet sensitivity was employed with specific UV filter, blue light filter, and green light filter. The images of flowers and spiders which are usually seen by honeybees in the nature were acquired and analyzed. Image fusion with those spectral images according to the neural mechanisms of honeybee color vision was employed in this study. There are 27 patterns of color-coding neurons, including hypothesized patterns and real recorded neurons. Because the multi spectral neural mechanisms are more important, 7 patterns (narrow-band neurons) are ignored while the remained 20 patterns (board-band and color opponent neurons) were used for images fusion with linear or nonlinear COC patterns. After computing the correlation and the difference of texture features between two images in the image sets, these images were clustered by "affinity propagation" clustering algorithm. The experimental results reveal that there are essentially 2 clusters in the 20 COC patterns. This results is consistent with the finding from the behavior experiments in the existing literature.摘要 ibstract ii錄 iii目錄 v目錄 vi一章 緒論 1.1前言 1.2研究目的 4二章 文獻探討 6.1 視覺系統 6.1.1 眼睛 6.1.2 視覺神經 7.1.3 色彩與視覺 10.2昆蟲色覺 12.3 蜜蜂視覺 13.3.1 蜜蜂視覺系統 13.3.2 蜜蜂色覺神經機制 14.3.3 蜜蜂色彩視覺分辨行為實驗與神經電生理訊號記錄 15.4相關的影像特徵計算 16.4.1 灰階影像統計直方圖 16.4.2 相關係數 16.4.3 紋理 17.5 分群理論 18.5.1 K-均值法（k-means） 19.5.2 Affinity Propagation 20三章 材料與方法 22.1系統架構 22.2硬體基本架構 24.3 軟體基本架構 30.4 色彩拮抗編碼(color opponent coding, COC) 30.5 合成影像特徵擷取 32.5.1 基本介紹 32.5.2 流程說明 32.5.3 相關係數 33.5.4 紋理特徵 34.6 分群演算法 34.7 分群結果表示 35.8 實驗 36四章 模擬色彩視覺系統 37.1三種波段影像合成 37.1.1 程式介面 37.1.2 影像合成 37.2影像相關係數 38.3紋理特徵分析 46.4分群 46.5 結果分析 49五章 結果與討論 56.1 基礎實驗 56.1.1 圓形影像 56.1.2不同尺寸比較 57.2 真實影像 60.2.1 相關係數 60.2.2 紋理特徵 64六章 結論與建議 66.1 結論 66.2 建議 67考文獻 69錄 72. 人造不同尺寸圓形影像分群結果 72. 真實影像 7

Assessment of reasons for not intensifying antihypertensive treatment in the Taiwanese population

Despite availability of effective antihypertensives, blood pressure (BP) control is usually inadequate. The Reasons for not Intensifying Antihypertensive Treatment (RIAT) registry evaluated the reasons behind not modifying treatment in an international, cross-sectional study in 16 countries. Methods and results: The Taiwanese cohort of RIAT consisted of 8922 patients with untreated/uncontrolled essential hypertension recruited from 22 centers in the country. At the first visit, physicians selected target BP and antihypertensive treatment, and at the next three visits they measured BP and modified treatment/provided justification for not modifying treatment. Mean target BP selected by physicians was 134.6/84.6 ± 5.1/5.0 mmHg, respectively. Patients’ individual risk stratification determined the BP goals. More patients achieved targets according to the physicians’ opinion than based on actual BP measurements: visit 2–50.6% vs. 48.6%; visit 3–58.4% vs. 55.2%; and visit 4–61.2% vs. 57.0%. At each visit, treatment remained unchanged for >60% patients not reaching target; the most common reason for this at visit 2 was the assumption that the time was too short to assess new drug therapy and at visits 3 and 4 was the assumption that target was reached/had almost been reached. Conclusion: About 40% Taiwanese hypertensive patients in RIAT did not reach BP targets after an average of 4 months’ follow-up. The most common reason for not modifying treatment was the assumption that the target had been reached or had almost been reached

Selecting Tyrosine Kinase Inhibitors for Gastrointestinal Stromal Tumor with Secondary KIT Activation-Loop Domain Mutations

<div><p>Advanced gastrointestinal stromal tumors (GIST), a <i>KIT</i> oncogene-driven tumor, on imatinib mesylate (IM) treatment may develop secondary <i>KIT</i> mutations to confer IM-resistant phenotype. Second-line sunitinib malate (SU) therapy is largely ineffective for IM-resistant GISTs with secondary exon 17 (activation-loop domain) mutations. We established an <i>in vitro</i> cell-based platform consisting of a series of COS-1 cells expressing <i>KIT</i> cDNA constructs encoding common primary±secondary mutations observed in GISTs, to compare the activity of several commercially available tyrosine kinase inhibitors on inhibiting the phosphorylation of mutant KIT proteins at their clinically achievable plasma steady-state concentration (Css). The inhibitory efficacies on <i>KIT</i> exon 11/17 mutants were further validated by growth inhibition assay on GIST48 cells, and underlying molecular-structure mechanisms were investigated by molecular modeling. Our results showed that SU more effectively inhibited mutant KIT with secondary exon 13 or 14 mutations than those with secondary exon 17 mutations, as clinically indicated. On contrary, at individual Css, nilotinib and sorafenib more profoundly inhibited the phosphorylation of KIT with secondary exon 17 mutations and the growth of GIST48 cells than IM, SU, and dasatinib. Molecular modeling analysis showed fragment deletion of exon 11 and point mutation on exon 17 would lead to a shift of KIT conformational equilibrium toward active form, for which nilotinib and sorafenib bound more stably than IM and SU. In current preclinical study, nilotinib and sorafenib are more active in IM-resistant GISTs with secondary exon 17 mutation than SU that deserve further clinical investigation.</p></div