1,720,959 research outputs found
Molecular Barcoded Plasmid Yeast ORF Library: Linking Bioactive Compounds to their Cellular Targets and Mapping Dosage Suppressor Networks
No full textIn this thesis I describe a functional genomics resource in which each yeast gene, with its native promoter and 3’UTR, is cloned on a uniquely barcoded low-copy vector. We refer to this resource as the Molecular Barcoded Yeast ORF (MoBY-ORF) library 1.0. Each gene carried by MoBY-ORF 1.0 should mimic its native expression and thus is best suited for complementation cloning. The vector backbone of MoBY-ORF 1.0 is compatible with the mating-assisted genetically integrated cloning (MAGIC) system for recombination cloning in bacterial cells, which allows the transfer of the ORF fragment and its barcoded cassette to other vector backbones. Taking advantage of the MAGIC system, we created a multi-copy version of the library, which we refer to as MoBY-ORF 2.0.
I used MoBY-ORF 1.0 to map drug resistant mutants by complementation cloning with a barcode microarray readout. I investigated several drugs with known targets in my proof-of-principle experiments and showed the feasibility of this method. I identified a single mutation that causes resistance to two different natural products, theopalauamide and stichloroside. By doing so, I was able to link these two chemicals to their cellular target, ergosterol. In fact, theopalauamide represents a new class of sterol binding chemical.
I also describe the use of MoBY-ORF 2.0 to clone dosage suppressors of conditional temperature-sensitive mutants. By doing so, and combing our own data with published literature, we showed that dosage suppression interactions often overlap with protein-protein interactions and negative genetic interactions but not positive interactions; however the majority of dosage suppression interactions are unique and thus they represent an unique edge on a global functional interaction map. We also describe the first genome-wide dosage suppressor interaction map of budding yeast.Ph
Modelling of crystallization in emulsion droplets with Monte Carlo simulations
No full textSolution crystallization is a common separation and purification method. Miniaturization refers to crystallization in a confined space, which is a promising approach for improved control over crystal quality attributes such as crystal size distribution (CSD). Recently, a novel membrane-assisted emulsion crystallization process has been developed, which better enables the application of miniaturization on industrial scale. Validated process models can be important for further development of the novel process, which are still absent. The objective of this research is to develop and validate a novel process model for emulsion crystallization. The model is based on master equations which describe stochastic occurrence of primary nucleation events in emulsion droplets. The master equations describe a single Markov chain within a discretized process time interval and are solved via Monte Carlo simulations by assuming constant levels of supersaturation within a time interval. Supersaturation is updated at each time interval with material balances to account for crystal growth so that primary nucleation rate can be accurately modelled to sample a primary nucleation event in the next time interval. Kinetic parameters for primary nucleation rate expression are obtained by fitting experimental data of measured induction times from 1-ml cooling solution crystallization. A new expression has been developed based on two-step nucleation theory, which is shown to have a satisfactory quality of fit to the data. However, the kinetic model obtained cannot accurately predict behaviour in emulsion droplets. Therefore, miniaturization experimental data of average crystal length is directly fitted to the proposed model, which shows an adequate description. Yet, CSDs predicted by the model do not match experimental observations well, which may have been caused by an inaccurate description of nucleation rate or constraints for fitting. In conclusion, a novel process model for emulsion solution crystallization is presented, which can capture certain process trends after parameter estimation.</p
段玉裁《說文解字注》「渾言析言」之同義名詞辨析
No full text王力先生在《中國語言學史》說：「段氏於同義詞的辨析，非常精到。這是段注的精彩部分之一。」而段玉裁在《說文解字注》提出「渾言析言」術語，能精準歸納大部分的古漢語同義詞，有助後人理解古漢語的詞義演變。因此，本文以「渾言析言」術語作為研究目標，力求辨析古漢語同義詞詞義的共性與特性。
本文主要劃分為五個部分：第一章緒論集中歸納《段注》「渾言析言」的研究現況，並說明本文的研究意義及方法。第二章主要指出同義詞的內涵在於強調詞義的「同中之異」，故本文將同義詞定義作近義詞，不包括等義詞及反義詞。第三章主要簡介「渾言析言」術語的定義及形式。第四章主要從「同物異名」及「同類異物」兩大角度，辨析「渾言析言」術語的體例，並歸納不同詞組在析言時的詞義類別；第五章主要分析「渾言析言」術語的價值及不足，指出此術語如何反映古漢語詞匯發展的多元性，包括古漢語單音節詞與現代漢語雙音節詞的詞義聯繫，以及詞組本義與引申義的交叉義聯。然而，本文亦會指出此術語涉及的非同義詞，包括「同名異義的詞組」、「聲訓異義的詞組」、「特指詞義相差甚遠的詞組」。第六章結尾則總結「渾言析言」術語可視作判斷同義詞的輔助工具，但並非絕對依據
Molecular Barcoded Plasmid Yeast ORF Library: Linking Bioactive Compounds to their Cellular Targets and Mapping Dosage Suppressor Networks
Full text linkIn this thesis I describe a functional genomics resource in which each yeast gene, with its native promoter and 3’UTR, is cloned on a uniquely barcoded low-copy vector. We refer to this resource as the Molecular Barcoded Yeast ORF (MoBY-ORF) library 1.0. Each gene carried by MoBY-ORF 1.0 should mimic its native expression and thus is best suited for complementation cloning. The vector backbone of MoBY-ORF 1.0 is compatible with the mating-assisted genetically integrated cloning (MAGIC) system for recombination cloning in bacterial cells, which allows the transfer of the ORF fragment and its barcoded cassette to other vector backbones. Taking advantage of the MAGIC system, we created a multi-copy version of the library, which we refer to as MoBY-ORF 2.0.
I used MoBY-ORF 1.0 to map drug resistant mutants by complementation cloning with a barcode microarray readout. I investigated several drugs with known targets in my proof-of-principle experiments and showed the feasibility of this method. I identified a single mutation that causes resistance to two different natural products, theopalauamide and stichloroside. By doing so, I was able to link these two chemicals to their cellular target, ergosterol. In fact, theopalauamide represents a new class of sterol binding chemical.
I also describe the use of MoBY-ORF 2.0 to clone dosage suppressors of conditional temperature-sensitive mutants. By doing so, and combing our own data with published literature, we showed that dosage suppression interactions often overlap with protein-protein interactions and negative genetic interactions but not positive interactions; however the majority of dosage suppression interactions are unique and thus they represent an unique edge on a global functional interaction map. We also describe the first genome-wide dosage suppressor interaction map of budding yeast.Ph
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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