97 research outputs found

    Unraveling the ubiquitin-regulated signaling networks by mass spectrometry-based proteomics

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    Ubiquitin (Ub) is a small protein modifier that is covalently attached to the epsilon-amino group of lysine residues of protein substrates, generally targeting them for degradation. Due to the emergence of specific anti-diglycine (-GG) antibodies and the improvement in MS, it is now possible to identify more than 10 000 ubiquitylated sites in a single proteomics study. Besides cataloging ubiquitylated sites, it is equally important to unravel the biological relationship between ubiquitylated substrates and the ubiquitin conjugation machinery. Relevant to this, we discuss the role of affinity purification-MS (AP-MS), in characterizing E3 ligase-substrate complexes. Recently, such strategies have also been adapted to screen for binding partners of both deubiquitylating enzymes (DUBs) and ubiquitin-binding domains (UBDs). The complexity of the "ubiquitome" is further expanded by the fact that Ub itself can be ubiquitylated at any of its seven lysine residues forming polyubiquitin (polyUb), thus diversifying its lengths and topologies to suit a variety of molecular recognition processes. Therefore, applying MS to study polyUb linkages is also becoming an emerging and important area. Finally, we discuss the future of MS-based proteomics in answering important questions with respect to ubiquitylation

    Chinese literary works translated into Baba Malay: a bibliographical study

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    Analyses 68 unique titles of Baba translated works published between 1889 and 1950. The titles are held in the libraries of the University of Malaya (UM), Science University Malaysia (USM), National University of Malaysia (UKM), the Dewan Bahasa dan Pustaka (DBP), National University of Singapore (NUS), National Library of Singapore (NLS) and the British Library (BL). The results reveal three periods of active publication of Baba translated works. A total of 18 works were translated before World War I, followed by 10 just after the war, 39 titles were published before the break of the World War II and 1 was identified in 1950. There were 103 persons involved in the 68 translated works, some of whom are responsible for more than one title. The most prominent translators were Chan Kim Boon, Wan Boon Seng, Seow Chin San and Lee Seng Poh. Some of the translators were also be editors, illustrators or editors. There were 31 publishers and 21 printing presses involved, all were located in Singapore. The most active publishers were Wan Boon Seng, Kim Seck Chy Press and Nanyang Romanised Malay Book Co. The translated works mainly cover historical classical Chinese stories, chivalrous stories, romances, folklore and legends. The titles were priced between 10 cents to 2 dollars in Straits currency. The University of Malaya Library held the largest number of unique title (62) out of which 15 were unique titles

    Report on business attachment with K K Tham & associates.

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    The purpose of this report is to review the business attachment at K K Tham & Associates, a public accounting firm, value the experience gained and make recommendations to improve the program

    Report on business attachment with K K Tham & associates.

    No full text
    The purpose of this report is to review the business attachment at K K Tham & Associates, a public accounting firm, value the experience gained and make recommendations to improve the program

    Datasets from an interaction proteomics screen for substrates of the SCFβTrCP ubiquitin ligase

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    An affinity purification-mass spectrometry (AP-MS) method was employed to identify novel substrates of the SCFβTrCP ubiquitin ligase. A FLAG-HA tagged version of the F-box protein βTrCP2, the substrate recognition subunit of SCFβTrCP, was used as bait. βTrCP2 wild type and the two mutants βTrCP2-R447A and βTrCP2-ΔF were expressed and purified from HEK293T cells to be able to discriminate between potential substrates of SCFβTrCP and unspecific binders. Affinity-purified samples were analyzed by mass spectrometry-based proteomics, applying ultra-high performance liquid chromatography (UHPLC) coupled to high-resolution tandem mass spectrometry. The raw mass spectrometry data have been deposited to the PRIDE partner repository with the identifiers PXD001088 and PXD001224. The present dataset is associated with a research resource published in T.Y. Low, M. Peng, R. Magliozzi, S. Mohammed, D. Guardavaccaro, A.J.R. Heck, A systems-wide screen identifies substrates of the SCFβTrCP ubiquitin ligase

    Degradation of Tiam1 by casein kinase 1 and the SCFβTrCP ubiquitin ligase controls the duration of mTOR-S6K signaling

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    Tiam1 (T-cell lymphoma invasion and metastasis 1) is a guanine nucleotide exchange factor that specifically controls the activity of the small GTPase Rac, a key regulator of cell adhesion, proliferation, and survival. Here, we report that in response to mitogens, Tiam1 is degraded by the ubiquitin-proteasome system via the SCF(βTrCP) ubiquitin ligase. Mitogenic stimulation triggers the binding of Tiam1 to the F-box protein βTrCP via its degron sequence and subsequent Tiam1 ubiquitylation and proteasomal degradation. The proteolysis of Tiam1 is prevented by βTrCP silencing, inhibition of CK1 and MEK, or mutation of the Tiam1 degron site. Expression of a stable Tiam1 mutant that is unable to interact with βTrCP results in sustained activation of the mTOR/S6K signaling and increased apoptotic cell death. We propose that the SCF(βTrCP)-mediated degradation of Tiam1 controls the duration of the mTOR-S6K signaling pathway in response to mitogenic stimuli

    Using the Proteomics Toolbox to Resolve Topology and Dynamics of Compartmentalized cAMP Signaling

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    cAMP is a second messenger that regulates a myriad of cellular functions in response to multiple extracellular stimuli. New developments in the field have provided exciting insights into how cAMP utilizes compartmentalization to ensure specificity when the message conveyed to the cell by an extracellular stimulus is translated into the appropriate functional outcome. cAMP compartmentalization relies on the formation of local signaling domains where the subset of cAMP signaling effectors, regulators and targets involved in a specific cellular response cluster together. These domains are dynamic in nature and underpin the exacting spatiotemporal regulation of cAMP signaling. In this review, we focus on how the proteomics toolbox can be utilized to identify the molecular components of these domains and to define the dynamic cellular cAMP signaling landscape. From a therapeutic perspective, compiling data on compartmentalized cAMP signaling in physiological and pathological conditions will help define the signaling events underlying disease and may reveal domain-specific targets for the development of precision medicine interventions

    Implied volatility asymmetries in currency options.

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    Previous studies find evidence of asymmetric risk-return relationship in the stock market. In this paper, we extend the studies by testing for the presence of asymmetry in the conditional relationship between the perception of risk, proxied by the implied volatility of over-the-counter currency options, and the contemporaneous conditions of the currency market.Master of Science (Financial Engineering

    Option pricing under stochastic volatility model.

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    In this paper, we examine the stochastic volatility model of Schobel and Zhu (1999) where volatility follows a mean-reverting Ornstein-Uhlenbeck process. This is basically an extension of the Stein and Stein model (1991) but which allows for correlation between instantaneous volatilities and spot returns.Master of Science (Financial Engineering

    Investigation of radiant panel cooling systems for sensible cooling in air conditioning

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    The report describes an investigation on the possible implementation of the radiant panel cooling systems in the hot and humid Singapore climate. The project is based on the simulation modeling of a conventional chilled water cooling system and the radiant panel cooling system, in the form of the active chilled beam systems, in cooling a single storey office space comprising a total area of 1225 m2. The wellknown TRNSYS program was used to simulate the radiant panels and cooling systems in the project. In creating the active chilled beam systems, two air handling units were considered, namely Dedicated Outdoor Air System (DOAS) and the active desiccant dehumidification system. Based on hour-by-hour simulation approach, the project presents the energy consumption as well as the thermal comfort levels achieved by the active chilled beam systems in comparison with conventional cooling system. For the office space examined in the simulation, employing the active chilled beam systems instead of the conventional system can save between 9.1% and 29.1% of the total energy consumption. These results are based on several assumptions and references made on the power ratings of the components used throughout the simulation. It is observed that majority of the energy savings occur at the chiller, due largely to the higher chilled water supplied to the radiant panels and air handling units of the active chilled beam systems. In addition, no risks of condensation on the panels were present since the supply temperature of the chilled water to these panels is set higher than the dew point temperatures of the zones. Using comfort criterion adopted by Singapore Standards and International Standards Organization, results from simulation show that thermal comfort levels are better with the application of the active chilled beam systems. With reference to the Predicted Mean Vote index recorded by TRNSYS, the occupants are comfortable in 80.5%, 89.3% and 90.1% of the simulated hours for the conventional and the active chilled beam systems (i.e. Desiccant and DOAS) respectively. Further improvements must be carried out on the existing simulation models in order to get better and more reliable data for actual implementation of the radiant panel cooling system in Singapore. It is suggested that collaboration with a local supplier of desiccant dehumidification systems be considered. One recommendation is Munters with which electronic correspondence has been made between the author and the company representative.Bachelor of Engineering (Mechanical Engineering
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