Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

The Study on Strategy of Patent Licensing and Technology Transferring of Taiwan Biotechnology Company

知識經濟時代的來臨，代表知識早已經取代勞力、土地、資本，成為最重要的生產要素，而知識創造的具體果實就是智慧財產，此項無形資產占企業財產的重要性已遠超過有形資產。個人、企業和國家唯有專注在智慧財產的創造、保護、管理和運用上，方可成為知識經濟下的大贏家。 近年來，隨著人類科學知識與生活智慧的增長與演進，與人類日常生活和生命安全息息相關的生物醫學技術日益突破且其重要性與日俱增，國際間生技產業發展迅速，並帶領生技產業走向多元化的發展；除此之外，生技產業也是台灣兩兆雙星計畫中所追求的新興產業之一。然而，台灣在這股趨勢洪流中，整體生技產業的發展上並不蓬勃。歸根究柢，生技產業乃為典型的高附加價值、知識導向型產業，智慧財產的重要性不言可喻並且更加突顯。智慧財產如同其他企業資產一樣，需要善加管理與運用才能發揮其價值，若企業擁有大量之智慧財產，但對該智慧財產欠缺有效之管理運用，亦無法為公司創造任何價值。因此，如何為智慧財產尋求正確的運用管道，應是智慧財產所有人最為關心的議題。由於生物技術產業十分重視技術的掌握與應用，故本論文研究將焦點放在與技術知識保護有關的「專利授權與技術移轉」上，並特別針對屬於智慧財產行銷管理層面的策略進行探討。 《時代》雜誌年度風雲人物華裔科學家何大一曾說過要用人才賭生技，其需要的是什麼樣的人才?又該如何賭?本論文研究希望能提出相對應之見解，藉由個案研究方法分析找出台灣生技企業在「專利授權與技術移轉」上的策略思考邏輯，並更加釐清智慧財產行銷管理對產業發展影響的角色與位置。 由於台灣生物技術公司目前本身先天條件不佳且資源不足，無法透過商品化與產業化之智慧財產實施方式來創造最大利益，因此透過智慧財產交換方式乃是其最佳模式，而考量相關環境條件後，其中又以「專利授權與技術移轉」為最具經濟效益且最可能成功之智慧財產商業模式與型態，因此本論文研究便針對此方面進行深入探討，以提供產業後續發展之參考借鏡。 本論文研究目的包括：1.探討推動台灣生物技術產業公司發展過程中，考量「專利授權與技術移轉」的重要因素。2.瞭解台灣生物技術產業公司目前在「專利授權與技術移轉」方面的運作機制。3.介紹台灣生物技術產業公司之指標性個案，分析其智慧財產行銷策略，歸納其關鍵成功因素，以茲其他業者參考。4.了解智慧財產行銷策略的核心結構，提出智慧財產行銷策略規劃上的建議。5.綜合研究結果，提出對台灣生物技術產業公司「專利授權與技術移轉」策略之建議，並分析該產業之潛在問題與可能限制。 本論文研究提出理論強調台灣生物技術產業公司必須考量智慧財產行銷的六大要素(6P)，以『主導產業鏈』、『控制價值鏈』、『分配供應鏈』等三鏈為目標，因而決定採取「專利授權與技術移轉」之正確的智慧財產商業模式後，站在目標被授權人的立場思考，透過「策略九說」來作檢驗，以找出最適合的智慧財產行銷之執行策略，並在執行時確實考量組織行銷之特性。 本論文研究方式採用個案研究法以及質化研究法，獲得以下結論： 1. 「專利授權與技術移轉」必須著重於專利品質，以更貼近產業與市場需求，進而強化技術移轉之成效。 2. 「專利授權與技術移轉」是屬於相當複雜且專業性高的領域，與市場互動至關密切。 3. 任何產業的任何公司當其智慧財產行銷策略之方向目標正確，且手段方法合理，則成功便是可以預期的。 4. 一旦擬定正確的智慧財產行銷策略，則後續的執行力，便成為是否成功之唯一重點。The coming of Knowledge-based Economy Era indicates the fact that knowledge had taken the place of labor, land and capital to become the most important production factor. The results of knowledge creation are Intellectual Property (IP). The Intangible Assets are much more important than Tangible Assets for industries in nowadays. It becomes crucial for individuals, industries, and countries to achieve success in the Knowledge-based Economy Era to concentrate on the creation, protection, management and application of intellectual property. In the recent years, because of the developments of scientific knowledge and life wisdom, the progress and importance of the biomedical technology which closely related to human life and safety advances rapidly. Besides, the biotechnology industry is also one of the booming industries of Taiwan “Two Millions, Two Stars” projects. However, the Taiwan Biotechnology Industry does not follow the trend well. The biotechnology industry is a typical high value added and knowledge oriented industry, and the importance of IP is much more distinct. Same as other corporation’s property, intellectual property needs to be managed and put to use well to manifest its value. If a corporation owns a lot of IP without effective management and application, none value or benefit will be produced for the corporation from the IP. Therefore, for the IP owner, how to find out the correct application ways of IP will be the most important concern. Since technology familiarity and application is a highly emphasized issue for biotechnology industry, this study will focus on the technology knowledge protection concerning “Patent Licensing and Technology Transferring,” especially on the IP Marketing Management Strategy. David Ho, a Chinese American scientist and the Man of the year 1996 of “Time” magazine, once said that “we have to bet on biotechnology with talents”. The question is what talents are needed, and how to bet? This study aims to provide some corresponding thoughts and find out the strategy of “Patent Licensing and Technology Transferring” for Taiwan biotechnology corporation through case study. Furthermore, the study will manifest how IP Marketing Management will influence industry development. Due to the immature company structure and small business size of Taiwan biotechnology corporations, these corporations are unable to create the best profit through IP commercialization or industrization. Thus, the best model for them will be through IP Exchange and the “Patent Licensing and Technology Transferring” will be the most effective and feasible IP Business Model given the conditions of Taiwan biotechnology industry. This thesis will concentrate on this aspect and provide advices for industrial developments. The purposes of this study include: a. the important factors and the significnace of “Patent Licensing and Technology Transferring” in the promotion of Taiwan biotechnology corporation development; b. the current mechanism of “Patent Licensing and Technology Transferring” of Taiwan biotechnology corporation; c. a case study of Taiwan biotechnology corporation, including the IP Marketing Strategy analysis and the key successful factors as reference for other corporations; d. the core structure of IP Marketing Strategy and IP Marketing Strategy planning; and e. strategy suggestions for “Patent Licensing and Technology Transferring” and the potential problem analysis of the industry to Taiwan biotechnology corporation. This study proposes that the Taiwan biotechnology corporation must put the 6P factors of IP Marketing into consideration and target to dominate Industry Chain, to control Value Chain, and to allocate Supply Chain. They should also take the correct IP Business Model of “Patent Licensing and Technology Transferring”, and then think in the position of the targeted licensee through the examination of “9 Theories of Strategy” to find out the most suitable IP Marketing strategy. They should also take the characteristics of “Organizational Marketing” into consideration in practice. This study comes to the conclusions below with case study and qualitative methods: a. The quality of patents is always important in “Patent Licensing and Technology Transferring” to meet the industry and market demand and thus to reinforce the technology transferring achievement. b. “Patent Licensing and Technology Transferring” is complicated, highly professional and closely related to the market. c. The success of any corporation of any industry lies on a correct IP Marketing Strategy and a legitimate method. d. Once the correct IP Marketing Strategy is settled, the only key factor to success will be how to enforce the strategy

A Model for Electrifying Fire Ambulance Service Stations Considering Practical Service Data and Charging Strategies

Due to concerns with air pollution and climate change, governments and transport operators around the world have engaged in transforming their fossil-fueled vehicles into electric vehicles (EVs). It is essential to build a model for the electrifying process to minimize the operation costs. This paper presents a systematic analytical approach for the electrification of a fire ambulance service station. This approach begins with the selection of suitable EVs to replace the current service vehicles. Subsequently, an in-depth analysis is conducted to determine the practical utilization of EVs at the station. The model proposes two charging strategies: immediate charging upon an EVs’ return and smart charging. Based on the chosen EVs and charging strategies, a comprehensive assessment of the load profiles for the planned EV charging station is performed. In accordance with the load profiles, a mathematical model to minimize the infrastructure and operation costs of the charging station is proposed. Various pricing schemes are compared to identify the most efficient pricing scheme for the charging station, and economic analyses of the EVs and traditional ambulance vehicles are proposed in this paper. The test results indicate that the progressive pricing scheme is well suited for immediate charging strategies, whereas smart charging should opt for the time-of-use pricing scheme. Selecting the appropriate pricing scheme has the potential to significantly reduce electric energy costs

Shape-shifting 3D protein microstructures with programmable directionality via quantitative nanoscale stiffness modulation

The ability to shape-shift in response to a stimulus increases an organism's survivability in nature. Similarly, man-made dynamic and responsive “smart” microtechnology is crucial for the advancement of human technology. Here, 10–30 μm shape-changing 3D BSA protein hydrogel microstructures are fabricated with dynamic, quantitative, directional, and angle-resolved bending via two-photon photolithography. The controlled directional responsiveness is achieved by spatially controlling the cross-linking density of BSA at a nanometer lengthscale. Atomic force microscopy measurements of Young's moduli of structures indicate that increasing the laser writing distance at the z-axis from 100–500 nm decreases the modulus of the structure. Hence, through nanoscale modulation of the laser writing z-layer distance at the nanoscale, control over the cross-linking density is possible, allowing for the swelling extent of the microstructures to be quantified and controlled with high precision. This method of segmented moduli is applied within a single microstructure for the design of shape-shifting microstructures that exhibit stimulus-induced chirality, as well as for the fabrication of a free-standing 3D microtrap which is able to open and close in response to a pH change

Multiplex plasmonic anti-counterfeiting security labels based on surface-enhanced Raman scattering

We demonstrate a multiplex plasmonic anti-counterfeiting platform by embedding multiple molecules on a single substrate with superior nanometer scale spectral and spatial resolution. The encoded specific molecular information can be read out only using Raman spectroscopy. Multiplexing increases the complexity of these plasmonic security labels without compromising the spectral resolution.Nanyang Technological UniversityNational Research Foundation (NRF)Accepted versionX.Y.L. is thankful for the support from National Research Foundation, Singapore (NRF-NRFF2012-04) and Nanyang Technological University’s start-up grant (M4080758

Synergistic effects of epoxy- and amine-silanes on microarray DNA immobilization and hybridization.

Most microarray slides are manufactured or coated with a layer of poly(L-lysine) or with silanes with different chemical functional groups, for the attachment of nucleic acids on to their surfaces. The efficiency with which nucleic acids bind to these surfaces is not high, because they can be washed away, especially in the case of spotting oligonucleotides. In view of this, we have developed a method to increase the binding capacity and efficiency of hybridization of DNA on to derivatized glass surfaces. This makes use of the synergistic effect of two binding interactions between the nucleic acids and the coating chemicals on the surface of the glass slides. The enhanced binding allows the nucleic acids to be bound tightly and to survive stringency washes. When immobilized, DNA exhibits a higher propensity for hybridization on the surface than on slides with only one binding chemical. By varying the silane concentrations, we have shown that maximal DNA oligonucleotide binding on glass surfaces occurs when the percentage composition of both of the surface-coating chemicals falls to 0.2%, which is different from that on binding PCR products. This new mixture-combination approach for nucleic-acid binding allows signals from immobilization and hybridization to have higher signal-to-noise ratios than for other silane-coated methods