102 research outputs found

    Role of WD domain-containing proteins in cell cycle progression

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    In the eukaryotic proteome, WD domain is one of the most abundant protein motifs. The structure of WD domain allows it to interact with diverse protein partners and proteins containing WD domain have been shown to function in various cellular processes. In this thesis, I describe how two WD domain-containing proteins, LRWD1/ORCA and RFWD3, regulate different aspects of cell cycle progression. In eukaryotic cells, the duplication of the genome starts from the loading of a six-subunit complex, Origin Recognition Complex (ORC), onto replication origins on the chromosome. The loading of ORC triggers the assembly of the pre-replicative complex (pre-RC) at origins, which licensed the origins prior to entering S phase. Unlike yeast, replication origins in higher eukaryotes do not have consensus sequence and metazoan ORC does not bind to DNA in a specific manner. Thus, a long-standing question in the field has been, how are origins specified and how are ORCs recruited to origins? Studies suggest that ORC loading may be facilitate by ORC-associated proteins. LRWD1/ORCA is an ORC-associated protein that stabilizes ORC on chromatin. We have previously characterized ORCA’s role in replication initiation and heterochromatin organization. In Chapter 2, I describe my work to map the binding sites of ORCA genome-wide by ChIP- seq method at specific time points of G1. ORCA associates with chromatin in a dynamic manner and ORCA binding regions are enriched for heterochromatic marks, including H3K9me3 and methylated-CpGs. ORCA co-localizes with a subset of origins that are enriched for repressive marks, consistent with the fact that these origins replicate late during S phase. Further, ORCA directly associates with the repressive marks and interacts with the enzymes that catalyze these marks. ORCA regulates the level of H3K9me3 and methylated-CpG at its binding sites, suggesting a role of ORCA in maintaining the repressive chromatin marks at its binding sites. Importantly, repressive marks are required for ORCA’s association on chromatin. I propose that ORCA localizes to a subset of origins by association with repressive marks and recruits the enzymes to maintain the repressive chromatin environment. In Chapter 3, I focus on another WD domain containing protein, RFWD3, and describe how RFWD3 regulates cell cycle progression. Unlike previous studies that described how RFWD3 regulates DNA damage response, I focus on how RFWD3 regulate unperturbed cell cycle progression. I show that RFWD3 is required for proper cell cycle progression. Depletion of RFWD3 causes S phase defects including slower replication fork progression and prolonged S phase. There is also increased loading of replication fork proteins on S phase chromatin in the absence of RFWD3, potentially due to stalled replication fork. RFWD3 associates with the replication fork component, PCNA, via a PIP box motif. I purpose that RFWD3 localizes to replication fork by interacting with PCNA and regulate proper replication fork progression. In Chapter 4, I summarize my findings on the regulation of DNA replication, chromatin organization and S phase progression. I also discussed interesting areas of research that my work has opened up.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2019-08-01The student, Yating Wang, accepted the attached license on 2017-07-07 at 10:35.The student, Yating Wang, submitted this Dissertation for approval on 2017-07-07 at 10:47.This Dissertation was approved for publication on 2017-07-09 at 16:22.DSpace SAF Submission Ingestion Package generated from Vireo submission #11332 on 2017-09-29 at 11:14:35Made available in DSpace on 2017-09-29T16:39:20Z (GMT). No. of bitstreams: 2 WANG-DISSERTATION-2017.pdf: 2379470 bytes, checksum: 8df5906ffa8dfc73ce9ad20d8705e304 (MD5) LICENSE.txt: 4208 bytes, checksum: 4fad10476925e557cb3330ddd2373bd7 (MD5) Previous issue date: 2017-07-09Embargo set by: Colleen Fallaw for item 103402 Lift date: 2019-09-29T16:39:52Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemEmbargo set by: Colleen Fallaw for item 103402 Lift date: 2019-09-29T17:52:45Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemLimited Restriction Lifted for Item 103402 on 2019-09-30T09:15:17Z

    Modeling functional material

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    This report is a conclusion of what have been learned from the final year project which title is modeling functional materials by the author as a student during the period of final year project research. The aim of this one year project is to do research and learn more knowledge based on what the author have learned after four year university life time. In this period, she read books, journals and papers to get the knowledge about the function of one type of functional materials (which is one aromatic oligoamide--circular aromatic pentamers) and how to synthesis this functional material which is one and the function of this functional material. After that, the author suggests some other possible methods to synthesis this functional material. These are all consolidated in this report. The project helps the author to get a general idea of what are functions of this functional material and how can this functional material can be synthesized. More details like the functions of this functional material, process of synthesizing circular aromatic pentamers and suggestions for process of synthesizing circular aromatic pentamers are given in this report.Bachelor of Engineering (Materials Engineering

    Test Circuit Design of DC/DC Converter for Helicopter Starter/Generator

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    A test circuit is designed for testing the DC/DC converter of Helicopter's Starter/ Generator, including topology selection, operation principle analysis, components selections, simulations and 3D model building.Electrical Power ProcessingElectrical Power EngineeringElectrical Engineering, Mathematics and Computer Scienc

    Pin ren zhi gai ge bei jing xia Zhongguo da lu da xue jiao shi de xue shu shen fen: Liang suo yan jiu xing da xue de ge an yan jiu

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    新管理主義作為一種全球性的教育改革潮流,其產生的影響無遠弗屆。20世紀70年代改革開放以來,隨著中國社會轉型和社會主義市場經濟體制的日趨完善,以市場和管理為取向的新管理主義改革也對中國高等教育產生了深遠影響。本研究立足中國各高校聘任制改革的實踐背景,嘗試以學術身份為概念工具分析不同大學教師群體如何感知與應對改革,以及如何在變革情境中建構起關於何為一名大學教師的“主觀現實”。本研究從共同體視域下的學術身份建構視角出發採用意義-闡釋取向的質性研究方法選取中國兩所研究型大學自然科學、工程科學、社會科學和人文學科領域67名不同職稱和編制狀態的大學教師為研究對象,重點回答改革情境之下中國大學教師的學術身份內涵以及組織情境和學科共同體這兩大關鍵性共同體因素如何影響大學教師的學術身份建構這兩個核心問題。本研究的主要發現如下:首先,中國各高校的聘任制改革在原有編制管理的基礎上逐步引入崗位管理,效率和績效取向的大量外顯規則使得大學教師群體的價值觀念和行為方式等普遍受制於“管理主義”的理性“牢籠”裡。面對聘任制改革各項要求,大學教師不但需要改變專業行為來適應新的政策環境,同時也需要重新審視他們在新環境裡的角色、關係和邊界的改變;並在此基礎上協商改革環境的要求進而維持或是轉變自身所持有的作為一名大學教師的意義系統。本研究發現了教師個體在改革環境之下所持有的適應者、旁觀者和流浪者這三種主要身份類型,並且在這三重主要身份之下又存在有多種與學術工作相關的亞身份類型。其中,大多數受訪教師都在改革過程中選擇以外界改革所宣導的權威標準來框定自身的學術工作實踐,從中可以明顯看到,中國大學教師群體在聘任制改革過程中逐步實現了從“單位人”到“契約人”的轉變,聘任契約所規定的個體的聘任要求、崗位要求以及考核方式等規則不可避免地內化成了教師個體解讀何為一名大學教師的意義內涵。其次,從組織情境來看,大學教師個體被內嵌於由單位制、管理主義和專業主義等多元價值所充斥的各層級組織情境當中。各層級組織情境的組織特性、管理方式和組織文化等是大學教師個體在協商學術身份時的重要意義來源。其中,聘任制改革所強調的管理主義邏輯使得改革的“適應者”都在不同程度上轉變成了重效率、重產出和經濟效益的“為數字而活的人”;單位體制慣性的“庇護”之下,一些仍持有“單位人身份”的教師個體依舊在目前已經不太安全的體制內部“混年頭”和“熬資歷”;個別接受過西方學術共同體薰染的“海龜”教師在協商學術身份內涵時其對學術工作的自我規範遠遠超越了外部改革對學術工作所提出的契約規定。組織身份作為教師個體學術身份的重要維度反映的是個體在多大程度上以怎樣的方式受到大學組織情境的影響,持有不同組織身份的教師個體在解讀其作為一名大學教師的學術身份以及如何踐行教學和科研等學術工作實踐時都會有所差異。從學科共同體來看,學科範式、學科差異和學科等級等因素是大學教師個體協商學術身份時的重要意義來源,但是並非所有教師個體都帶有強烈的學科身份感,特別是對學術工作的內在性認同感較低的那幾類教師群體往往對諸如學科知識、學科特性和學科擔當等學科本身的“內在召喚”缺乏興趣和感受力。當下的聘任制改革在很大程度上阻礙了一些大學教師學科身份感的塑造或是造成了一些教師學科身份感的分裂或是碎片化,從而造成一批只談績效、產出和效益的學術工人而非關心學術、學科和知識本身的學術人。最後,當下的改革無疑是加劇了大學教師個體組織身份和學科身份之間的衝突。在本研究中,單向度的適應者根據改革的現實要求來執行身份,並且以個體利益最大化為目的很快優先排序了組織身份,以敷衍的方式呈現或是壓抑學科身份。符號性的適應者就是根據主觀重要性和情境相關性來對多重身份進行有限排序,並且發展出了組織身份和學科身份共存的理想情況。但是對於價值分裂的適應者來說,其沒有能力處理好組織身份和學科身份之間的衝突,且在改革要求和專業訴求中喪失了作為一名大學教師的幸福感。本研究的主要貢獻在於立足中國高校聘任制改革的本土情境,豐富了關於新管理主義改革對學術工作以及學術身份所帶來影響的學術討論。與已有研究不同的是,本研究發現,絕大多數教師個體會選擇把改革所要求的內容優先化為日常的工作內容;但是強烈的學科身份感是決定大學教師特別是初任教師是否服膺於管理體制要求的關鍵因素。當教師個體的學科身份感較為脆弱或是學科意識尚未內化為其日常學術工作的反思性話語時,外在的管理主義規則往往會很大程度上轄制了教師個體學術身份發展的軌跡。另外,共同體視域下中國高校教師的學術身份建構也體現出了中國本土情境的特殊性,例如受限於中國大學組織單位體制慣性和事業單位的束縛,高校教師的組織依附性要明顯強烈於學科忠誠度,其學術工作缺乏以學術為天職的傳統,更多的是以學術為謀生工具的現實考慮。最後,基於本研究中受訪教師個體對各項改革措施的意義賦予和相應的行動選擇,本研究對中國高校推行聘任制改革過程中所面臨的諸如大學教師的考核評價、激勵方式、非升即走和學科共同體建設等各方面都提出了具體的政策建議。關鍵字:新管理主義;聘任制改革;大學教師;學術身份;組織情境;學科共同體New managerialism with its global status has far-reaching impact on the worldwide educational reforms. Since the Economic Reforms and Openness in 1978, the market-led and managerial reforms have also exerted pervasive influence on Chinese higher education. Informed by the communitarian theoretical framework of academic identity, this doctoral study examines how academic staff at Chinese research-intensive universities perceive and comply with the faculty employment reforms and how they construct their ‘subjective reality’ of becoming an academic under the new managerial circumstances. Specifically, the research questions focus on how do Chinese university faculty negotiate their ways of being an academic under the changing environment and how the two defining communities, namely, higher education institutions and disciplinary communities, shape and reshape their academic identities. In-depth interviews were conducted with 67 academic staff from two Chinese research-intensive universities, ranging from different disciplinary areas as well as different contract tracks.The systematic qualitative data analysis indicates the following findings. Firstly, Chinese universities have implemented market-led and managerial faculty employment reforms that gradually replaced the traditional ‘steel bowl’ model, and during which Chinese university faculty have been being continually subjected to the ‘managerial cage’. Specifically, Chinese university faculty have been forced to change their professional behaviors as well as construct or reconstruct their ways of being an academic in the changing environment. The study has identified eight identity-related characterisations of how Chinese university faculty at these two case universities have reacted to this shifting context. The majority of the respondents have been labelled as adapters, including one-dimensional adapters, symbolic adapters and schizophrenic adapters. For the adapters, they tend to frame their academic work centred on the managerial rules and authorities, thereby changing their academic identities from the traditional national ganbu to contractual agent. Importantly, the adapters as contractual agents have internalized various performative academic roles and responsibilities that are requested by the contract-based recruitments and evaluations.Secondly, the defining features of Chinese higher education institutions emphasize dynamic interaction of pervasive managerialism, deep bureaucratic roots and weak professionalism. The key factors of higher education institutions, including organizational mission, organizational culture and leadership style have offered a framework within which academic staff negotiate their academic identities. Accordingly, managerial faculty employment reforms have urged Chinese university faculty to be economic, effective and efficient, whereas the deep danwei bureaucratic roots have protected some senior faculty to be immuned from the reforms and still laze away to wait for academic promotion. For some university faculty who have received their academic training within western academic community, the self-regulating of their sense of being an academic has gone beyond their contractual obligations. Organizational identity is typically taken to be an essential component of one’s academic identity that reflects the degree to which the university faculty have been embedded by the higher education institutions. Moreover, one’s organizational identity has contributed to create a coherent social reality that frames an academic’s sense of who he or she is and what he or she should do. Besides, the key factors of disciplinary community, including disciplinary paradigms, disciplinary differences and disciplinary hierarchies, are the powerful sources of academic identity. The sense of disciplinary identity is highly relevant to one’s commitment to academic work and the study has elaborated that the university faculty with fragile disciplinary identity have also lack interest about the inward calling of the disciplinary community. Under the strong influence of managerial faculty employment, the university faculty’s disciplinary identities have become to be fragile, restricted and compromising, which bring about the emergent identity of the knowledge worker and the declining one of an academic man.Lastly, the study has also explored the growing tensions between one’s organizational identity and disciplinary identity. One-dimensional adapters have prioritized the managerial organizational identity based on their personal calculation of the explicit benefits and have fulfilled the disciplinary identity in a perfunctory manner. The symbolic adapters have developed dual identities to buffer the identity conflicts. However, the schizophrenic adapters have failed to resolve the identity tensions and have undergone a clash of managerial rules and professional values. The doctoral study has contributed to the global empirically grounded knowledge of changing academic profession and academic identities. In contrast to the extant research, the study has revealed that the sense of disciplinary identity has played a crucial role in determining the extent to which the university faculty will comply with the managerial reforms. The university faculty who failed to build solid disciplinary identities will have significantly restricted to the managerial rules. In addition, the academic identity construction of Chinese university faculty has its own distinctive dimensions compared with its western counterparts. For instance, the deep danwei bureaucratic roots at Chinese universities have been exercised as the normative power for Chinese university faculty, leading them becoming more loyal to the higher education institutions than the disciplinary community. Consequently, for Chinese university faculty, the academic identities that centered on disciplinary community have been under greater potential placement by the academic identities that have been shaped by external contingencies. Finally, the study has made some practical suggestions concerning the improvements of the faculty employment reforms at Chinese research-intensive universities.Keywords: New managerialism; Faculty employment reform; Chinese university faculty; Academic identity; Higher education institutions; Disciplinary community黃亞婷.Thesis Ph.D. Chinese University of Hong Kong 2016.Includes bibliographical references (leaves ).Abstracts in English and Chinese.Title from PDF title page (viewed on …).Huang ya ting.Detailed summary in vernacular field only.Detailed summary in vernacular field only.Detailed summary in vernacular field only.Detailed summary in vernacular field only.Detailed summary in vernacular field only.Detailed summary in vernacular field only

    An Opportunistic Cooperative Packet Transmission Scheme in Wireless Multi-Hop Networks

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    Cooperative routing, combining cooperative communication in the physical layer and routing technology in the network layer, is one of the most widely used technologies for improving end-to-end transmission reliability and delay in the wireless multi-hop networks. However, the existing cooperative routing schemes are designed based on an optimal fixed-path routing so that the end-to-end performance is greatly restricted by the low spatial efficiency. To address this problem, in this paper an opportunistic cooperative packet transmission (OCPT) scheme is explored by combining cooperative communication and opportunistic routing. The proposed scheme divides the multi-hop route into multiple virtual multiple-input-multiple-output (MIMO) transmissions. Before each transmission, based on the idea of opportunistic routing, a cluster head (CH) is introduced to determine the multiple transmitters and multiple receivers to form a cluster. Then, the single-hop transmission distance is defined as the metric of forward progress to the destination. Each intra-cluster cooperative packet transmission is formulated as a transmit beamforming optimization problem, and an iterative optimal beamforming policy is proposed to solve the problem and maximize the single-hop transmission distance. CH organizes multiple transmitters to cooperatively transmit packets to multiple receivers with the optimized transmit beamforming vector. Finally, according to the transmission results, the cluster is updated and the new cooperative transmission is started. Iteratively, the transmission lasts until the destination has successfully received the packet. We comprehensively evaluate the OCPT scheme by comparing it with conventional routing schemes. The simulation results demonstrate that the proposed OCPT scheme is effective on shortening the end-to-end transmission delay, increasing the number of successful packet transmissions and improving the packet arrival ratio and transmission efficiency

    Mutations in gyrB play an important role in ciprofloxacin-resistant Pseudomonas aeruginosa

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    Xinyuan Feng,1,* Zhiqi Zhang,2,* Xiaoxia Li,3 Yan Song,3 Jianbang Kang,3 Donghong Yin,3 Yating Gao,3 Nan Shi,1 Jinju Duan3 1Department of Pharmacy, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Pharmacy, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3Department of Pharmacy, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China *These authors contributed equally to this work Purpose: To investigate the main molecular resistance mechanisms to fluoroquinolones (FQs) in Pseudomonas aeruginosa and also to investigate the effect of time and concentration on mutations in resistance genes.Materials and methods: The clinical isolates of P. aeruginosa which are sensitive to ciprofloxacin (CIP) or levofloxacin (LEV) were collected. The isolates were incubated with different concentrations of CIP or LEV for 5 days and the minimal inhibitory concentrations (MICs) of CIP, LEV and ofloxacin (OFX) were measured. The MIC of FQs to P. aeruginosa was measured by the agar dilution method. FQ resistance determining regions of gyrA, gyrB, parC and parE were amplified by PCR, and mutations in four genes were explored using sequence analysis with the Snapgene software. The relative expression levels of two efflux pumps genes (mexA and mexE) were measured by quantitative reverse transcription PCR.Results: A total of eleven isolates were collected from the Second Hospital of Shanxi Medical University. Amino acid alterations in gyrA and gyrB were mainly detected in resistant mutants, and the percentage of strains with amino acid alterations in gyrB was significantly higher than that in gyrA (P<0.001). MICs of strains with mutations both in gyrA and gyrB were not significantly higher than those of strains with mutations only in gyrB (P>0.05). No amino acid alterations were detected in genes of parC and parE. In both gyrA and gyrB, the number of amino acid alterations increased with incubation time prolonged and increased with increasing incubation concentration.Conclusion: CIP was more competent than LEV in making P. aeruginosa resistant to in vitro selection. Mutations occurring in gyrB played an important role in FQ resistance of P. aeruginosa in vitro selection. Keywords: Pseudomonas aeruginosa, fluoroquinolones, molecular resistance mechanisms, in vitr

    Abundance and Diversity of Insects in Coastal Grasslands (Fiscalini Ranch Preserve and Rancho Marino Reserve)

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    Site descriptionThe study was carried out over three days between August 30th, 2016 and September 1st 2016, in two sites in Cambria, San Luis Obispo County, California. Site one: Kenneth Norris Rancho Marino Reserve, located on the southern edge of Cambria. The reserve contains remnant coastal grasslands, consisting of areas that were cultivated and planted with Harding Grass (Phalaris aquatica), as well as those that have never been cultivated. The entire reserve has been grazed by livestock. Transect one is located in a previously cultivated planted area, transect two is located in an uncultivated area. Site two: Fiscalini Ranch Preserve is a coastal grassland located within the edges of Cambria town. The preserve has been grazed in the past by livestock but not cultivated. The reserve is no longer grazed and now functions as a nature reserveMethodsTwo 100m transects were laid out at site one and two. A total of 18 locations from each transect were sampled, six per day. The sampling locations were chosen by generating 25 random numbers between 1 and 100. The daily sites were chosen by generating six random numbers between 1 and 25 to correspond with the position on the original random number list. These final numbers were used to indicate the distance from the start of the transect.  At Rancho Marino, transect 1 was located at 35.53966, -121.09032 to 35.53896, -121.08968. Transect 2 was located at 35.52933, -121.07793 to 35.52862 , -121.07728. At Fiscalini transect 1 35.54944, -121.10043 to 35.55009, -121.10102. Transect 2 is from 35.55046, -121.10166 to 35.55117, -121.10227.Polaroid Cube cameras were used to capture visits by both flying and crawling insects. The cameras were placed six steps away from the transect northwards at each of six sampling distances. The cameras faced north to minimize interference from solar glare. The first hour of video was reviewed and each instance of an insect entering the field of view was recorded.  Insects that left the field of view and returned were counted as two separate observations because it was not possible to confirm the identity of an individual. Pan traps were used to sample the insect communities. The pan traps were made from white Solo bowls painted red, blue, yellow or left unpainted. The bowls were filled with an unscented dish detergent solution. The pan traps were placed at each of the six camera locations on each transect in the following order: red, white, yellow, blue with respect to the camera’s field of view. Pan traps were left out for three hours (on average 12:30 - 15:30). After collection, the insects were stored in 95% ethanol. Bees were identified to family at a minimum and genus where possible. The remaining insects were identified to order. To assess vegetation cover, 0.25 m2 quadrat was used to visually estimate the proportion of Harding grass, other exotics, native plants and bare ground at each sampling location and the presence/absence of scat was recorded. Any insects observed during the vegetation survey were recorded.Group Names: Jenna Braun, Simmy Kang, Aisa Kuper-Psenicnik, Yating Li, Mariam Nnanna, Yue Yin</div
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