20 research outputs found

    Recommendation Framework Based on Subjective Logic in Decision Support Systems

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    In this thesis our goals are to investigate the suitability of subjective logic within the decision support context that requires connectivity to complex data, user specification of frames of discernment, representation of complex reasoning expressions, an architecture that supports distributed usage of a decision support tool based on a client-server approach that separates user interactions on the browser side from computational engines for calculations on the server side, and analysis of the suitability and limitations of the proposed architecture

    How important is the N-terminal acetylation of alpha-synuclein for its function and aggregation into amyloids?

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    N-α-acetylation is a frequently occurring post-translational modification in eukaryotic proteins. It has manifold physiological consequences on the regulation and function of several proteins, with emerging studies suggesting that it is a global regulator of stress responses. For decades, in vitro biochemical investigations into the precise role of the intrinsically disordered protein alpha-synuclein (αS) in the etiology of Parkinson’s disease (PD) were performed using non-acetylated αS. The N-terminus of α-synuclein is now unequivocally known to be acetylated in vivo, however, there are many aspects of this post-translational modifications that are not understood well. Is N-α-acetylation of αS a constitutive modification akin to most cellular proteins, or is it spatio-temporally regulated? Is N-α-acetylation of αS relevant to the as yet elusive function of αS? How does the N-α-acetylation of αS influence the aggregation of αS into amyloids? Here, we provide an overview of the current knowledge and discuss prevailing hypotheses on the impact of N-α-acetylation of αS on its conformational, oligomeric, and fibrillar states. The extent to which N-α-acetylation of αS is vital for its function, membrane binding, and aggregation into amyloids is also explored here. We further discuss the overall significance of N-α-acetylation of αS for its functional and pathogenic implications in Lewy body formation and synucleinopathies

    Efficacy of fecal microbiota therapy in steroid dependent ulcerative colitis: a real world intention-to-treat analysis

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    Background/Aims Four high-quality randomized controlled trials have proven the efficacy of fecal microbiota transplantation (FMT) in active ulcerative colitis (UC). We assessed the efficacy of FMT in a real-world setting involving steroid-dependent patients with UC. Methods This was a single-center prospective analysis of data from steroid-dependent patients with UC treated with FMT from September 2015 to September 2017 at the Dayanand Medical College, a tertiary care center in India. Fecal samples from random unrelated donors were administered through colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22. The primary outcome was achievement of steroid-free clinical remission, and the secondary outcomes were clinical response and endoscopic remission at 24 weeks. Modified intention-to-treat analysis was performed, which included subjects who underwent at least 1 FMT. Results Of 345 patients with UC treated during the study period, 49 (14.2%) had steroid-dependent UC. Of these 49 patients, 41 underwent FMT: 33 completed 7 sessions over 22 weeks according to the protocol, and 8 discontinued treatment (non-response, 5; lost to follow-up, 2; and fear of adverse effects, 1). At week 24, steroid-free clinical remission was achieved in 19 out of 41 (46.3%) patients, whereas clinical response and endoscopic remission were achieved in 31 out of 41 (75.6%) and 26 out of 41 (63.4%) patients, respectively. All patients with clinical response were able to withdraw steroids. There were no serious adverse events necessitating discontinuation. Conclusions A multisession FMT via the colonoscopic route is a promising therapeutic option for patients with steroid-dependent UC, as it can induce clinical remission and aid in steroid withdrawal

    Managing Intellectual Property for Agriculture Inventions in the University

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    194-199One essential function of a technology transfer office is the proactive management of intellectual property related to crops and germplasm. Most of the agriculture stations and universities over the world have established technology transfer offices to protect their own plant varieties all over the world. This paper focuses on the patent policies, technology transfer policies and special practices within the office of technology commercialization at the University of California, which, by some measures, is the largest public technology transfer program in the worl

    The Optimal Portfolios Under Different Ages-Portfolios Constructed By Country ETFS

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    摘要 據Bloomberg資料庫最新統計,至2007/12/31為止,全世界ETF高達1,171支,總資產規模高達7,961億美元。全球各類的指數型基金( ETF ) 商品正如火如荼的發行當中,相信投資人以ETF作為主要資產配置將會是未來的趨勢。 本文研究之主要目的,在探討不同年齡下的最適資產配置,因為每個人隨著年齡的增長與老去,面對相同的報酬所願意承擔的風險也不盡相同,在各個年齡層的投資人身上可以明顯發現,投資人依年齡的不同有著不同的風險偏好,學生希望可以建構出一套完善的模型,提供各個年齡層的投資人做投資時的參考,這樣有助於各個年齡層的投資人依照他們自己的風險偏好去做資產配置。 本研究將年齡變數放入風險趨避者的投資效用函數中,模擬檢視投資人在年齡增加的同時,其投資風險性資產的比重是否有顯著差異,並解釋之。首先,我們以三年為計算基期,去計算二十三個ETF之變異數,藉由三年內各ETF之波動性,將二十三個ETF區分為三組波動性組合,其中我們取波動最高之波動性組合視為高風險性資產,波動最低之風險性組合視為低風險性資產,再經由特定的比例配置,檢視以全球ETF為資產配置之投資組合,其各年齡下投資人之最適資產配置為何。 其次,介紹論文的模擬模型,風險趨避係數模型與投資人效用函數的出處和假設情況。最後,依照不同的年齡、不同的風險趨避程度與效用函數,模擬0~100歲最適合的投資組合,並有效的降低投資人的投資風險。最後,作出結論。Abstract According to the latest ETF statistics by Bloomberg, till the end of 2007, 1,171 ETFs are listed in the world market, and the asset totaling US$796.1 billion. All types of ETF are developed prosperously. We believe that it will be a big trend for investors using ETF as one of their asset allocation tools. The study aims to explore the best asset allocation of age-based methods. Investors' risk comfort level may change as they are getting older. In practice, investors at different age have different risk preference. We hereby establish a comprehensive model, which can provide investors with asset allocation advices according to their ages and risk tolerance. The study adopts age into the “Utility Function of Risk Aversive Investors” to find out whether the investment weight of risky asset will change accordingly when people are getting older. First of all, we calculate the variances of the selected 23 ETFs on the basis of 3 years and then divide the 23 ETFs into 3 groups based on their volatized levels. Among the 3 groups, the most volatized portfolio is considered as the high-risk asset, By contrast, the lowest volatized is considered as the low-risk asset. By allocating proper percentage of the portfolio, we can achieve the objective of diversity, to reduce risk and to enhance return. Moreover, the report also indicates the source and assumptions of the simulation model, “Coefficient of Risk Aversion” and “Utility Function of Risk Aversive Investors” used in the study. Finally, by different age, by different level of risk-averse and utility function, we find out the best asset allocation suitable for age from 20 to 80 years old. These findings can also reduce investing risk effectively.目錄 第一章 緒論 1 第一節 研究背景與動機 1 第二節 研究目的 1 第三節 研究架構 2 第二章 ETF簡介與概況 3 第一節 Exchange Traded Funds 3 第二節 ETF之特色 7 第三節 投資ETF可能遭遇之風險 10 第四節 ETF之現況及發展趨勢 11 第五節 台灣的首檔ETF商品-「臺灣50指數」之ETF 12 第三章 文獻回顧 14 第一節 投資組合理論 14 第二節 Life Cycle相關文獻 15 第三節 Exchange Traded Funds與Efficient Market相關文獻 15 第四節 Investment allocation與Diversification相關文獻 16 第四章 研究方法與資料 17 第一節 研究流程 17 第二節 研究方法 20 第四章 模擬分析 20 第一節 風險性資產之探討 21 第二節 最適投資組合之模擬分析 23 第六章 結論 30 第一節 研究討論 30 第二節 最適投資組合之模擬分析 30 第三節 建議未來研究方向 32 參考文獻 33 表目錄 表一、台灣市場中ETF與股票之比較 6 表二、ETF與共同基金之比較 7 表三、各年度全球ETF總數與資產總值 11 表四、全球23國家ETF每三年之波動 18 表五、各年度由高低風險波動所組成之高低風險性資產特性 23 表六、2004年模擬之最適投資高風險性資產比重 26 表七、2005年模擬之最適投資高風險性資產比重 27 表八、2006年模擬之最適投資高風險性資產比重 28 表九、2007年模擬之最適投資高風險性資產比重 29 圖目錄 圖一、ETF交易方式 4 圖二、申購與買回程序及ETF價格與淨值之關係 9 圖三、各年度全球ETF總市值 12 圖四、2004年模擬之最適投資高風險性資產比重 30 圖五、2005年模擬之最適投資高風險性資產比重 30 圖六、2006年模擬之最適投資高風險性資產比重 31 圖七、2007年模擬之最適投資高風險性資產比重 31 圖八、各年度各年齡投資人之最適資產配置之比較 3

    Conformational Compatibility Is Essential for Heterologous Aggregation of α-Synuclein

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    Under aggregation-prone conditions, soluble amyloidogenic protein monomers can self-assemble into fibrils or they can fibrillize on preformed fibrillar seeds (seeded aggregation). Seeded aggregations are known to propagate the morphology of the seeds in the event of cross-seeding. However, not all proteins are known to cross-seed aggregation. Cross-seeding has been proposed to be restricted either because of differences in the protein sequences or because of conformations between the seeds and the soluble monomers. Here, we examine cross-seeding efficiency between three α-synuclein sequences, wild-type, A30P, and A53T, each varying in only one or two amino acids but forming morphologically distinct fibrils. Results from bulk Thioflavin-T measurements, monomer incorporation quantification, single fibril fluorescence microscopy, and atomic force microscopy show that under the given solution conditions conformity between the conformation of seeds and monomers is essential for seed elongation. Moreover, elongation characteristics of the seeds are defined by the type of seed

    A hydrogen bond regulates slow motions in ubiquitin by modulating a β-turn flip

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    Proteins exist as conformational ensembles composed of multiple interchanging substates separated by kinetic barriers. Interconverting conformations are often difficult to probe, owing to their sparse population and transient nature. Here, we report the identification and characterization of a subset of conformations in ubiquitin that participate in microsecond-to-millisecond motions in the amides of Ile23, Asn25, and Thr55. A novel side chain to the backbone hydrogen bond that regulates these motions has also been identified. Combining our NMR studies with the available X-ray data, we have unearthed the physical process underlying slow motions-the interconversion of a type I into a type II β-turn flip at residues Glu51 through Arg54. Interestingly, the dominant conformer of wild-type ubiquitin observed in solution near neutral pH is only represented by about 22% of the crystal structures. The conformers generated as a result of the dynamics of the hydrogen bond appear to be correlated to ligand recognition by ubiquitin
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