402 research outputs found

    Manipulating the Sign: A Semiotic View of Li Shangyin’s Allusiveness

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    Focusing on the formal and semantic allusiveprocess in some of Li Shangyin’s (ca. 812-858 ) allusivepoems, this paper demonstrates how the (inter-) textualspace functions “as a principle of organization formaking signs out of linguistic items.” (MichaelRiffaterre

    Keeping Balance Between Genetic Stability and Plasticity at the Telomere and Subtelomere of Trypanosoma brucei

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    Telomeres, the nucleoprotein complexes at chromosome ends, are well-known for their essential roles in genome integrity and chromosome stability. Yet, telomeres and subtelomeres are frequently less stable than chromosome internal regions. Many subtelomeric genes are important for responding to environmental cues, and subtelomeric instability can facilitate organismal adaptation to extracellular changes, which is a common theme in a number of microbial pathogens. In this review, I will focus on the delicate and important balance between stability and plasticity at telomeres and subtelomeres of a kinetoplastid parasite, Trypanosoma brucei, which causes human African trypanosomiasis and undergoes antigenic variation to evade the host immune response. I will summarize the current understanding about T. brucei telomere protein complex, the telomeric transcript, and telomeric R-loops, focusing on their roles in maintaining telomere and subtelomere stability and integrity. The similarities and differences in functions and underlying mechanisms of T. brucei telomere factors will be compared with those in human and yeast cells

    Telomere Maintenance in African Trypanosomes

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    Telomere maintenance is essential for genome integrity and chromosome stability in eukaryotic cells harboring linear chromosomes, as telomere forms a specialized structure to mask the natural chromosome ends from DNA damage repair machineries and to prevent nucleolytic degradation of the telomeric DNA. In Trypanosoma brucei and several other microbial pathogens, virulence genes involved in antigenic variation, a key pathogenesis mechanism essential for host immune evasion and long-term infections, are located at subtelomeres, and expression and switching of these major surface antigens are regulated by telomere proteins and the telomere structure. Therefore, understanding telomere maintenance mechanisms and how these pathogens achieve a balance between stability and plasticity at telomere/subtelomere will help develop better means to eradicate human diseases caused by these pathogens. Telomere replication faces several challenges, and the end replication problem is a key obstacle that can cause progressive telomere shortening in proliferating cells. To overcome this challenge, most eukaryotes use telomerase to extend the G-rich telomere strand. In addition, a number of telomere proteins use sophisticated mechanisms to coordinate the telomerase-mediated de novo telomere G-strand synthesis and the telomere C-strand fill-in, which has been extensively studied in mammalian cells. However, we recently discovered that trypanosomes lack many telomere proteins identified in its mammalian host that are critical for telomere end processing. Rather, T. brucei uses a unique DNA polymerase, PolIE that belongs to the DNA polymerase A family (E. coli DNA PolI family), to coordinate the telomere G- and C-strand syntheses. In this review, I will first briefly summarize current understanding of telomere end processing in mammals. Subsequently, I will describe PolIE-mediated coordination of telomere G- and C-strand synthesis in T. brucei and implication of this recent discovery

    Global Health, Bioterrorism, and International Security

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    The threat of bioterrorism, long ignored and denied, has heightened over the past few years. The terrorist attacks of September 11 and the subsequent assaults with anthrax through the postal system underscored both strengths and weakness in the U.S. public health system and sounded a warning to global health. Globally, two candidate agents are of special concern: smallpox and anthrax. The magnitude of the problems and the gravity of the scenarios associated with release of these organisms have been vividly portrayed by two epidemics of smallpox in Europe during the 1970s and by an accidental release f aerosolized anthrax from a Russian bioweapons facility in 1979. This course will address the protection of the global public health from biological agents that cause disease and/or death. Students will learn current issues in disaster mitigation, how biological agents can be transmitted in the environment, measurement techniques, decontamination methods, the proper use of personal protective equipment and response strategies for bioterrorism emergencies and related catastrophic event. Students will analyze and synthesize the information to effectively analyze risk and communicate that risk to the populations they serve and critique policies to protect specific populations

    Competition vs. collaboration in the generation and adoption of a sequence of new technology

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    Although there is quite a rich literature relating to competitive innovation there is relatively little relating to technological collaboration. However, ignoring collaborative possibilities may result in overestimation of the importance of selfinnovation. This thesis is therefore mainly concerned with the determinants of collaboration in innovation, taking both a theoretical and an empirical approach. The empirics relate to the manufacturing industry in a Chinese region. The thesis is particularly innovative in emphasising how collaboration costs will be shared when collaboration occurs. We provide a game theoretic exploration of the decisions of firms on whether to compete or collaborate in the generation and adoption of a sequence of new technologies. Different from the models proposed by Vickers, who concentrates upon process innovation and a two-strategy (innovation or do nothing) set, our game theory model emphasises product innovation and either a three-strategy set (innovation, collaboration, and do nothing), or a fourstrategy set (innovation, collaboration, imitation and do nothing). In particular, MATLAB programming is employed for generating the equilibrium solution for each strategy set. We found that the relationship between imitation and collaboration and collaboration cost is not univariate. It depends upon the market type and various market characteristics, such as technology gap, technology level, the product substitution index, transaction costs and the discount rate of price sensitiveness. The results also show that the elasticity of collaboration opportunity with respect to transaction costs in a persistent dominance market is much greater than in an action reaction market. By using data on manufacturing in a Chinese region from 2005 to 2007, derived from the China Innovation Survey and the Annual Corporate Financial Survey, we empirically explored innovation and collaboration patterns. Three factors, innovative ability, absorptive capacity, and catching up capacity were proposed to positively affect both innovation and collaboration. This led to six hypotheses, which were tested using a number of econometric models encompassing selection bias, timing, and dynamics issues. The major finding from the empirical models suggests that innovative ability, absorptive capacity and catching up capacity all impact significantly and positively on collaboration, whilst innovation is positively related only to absorptive capacity. Also, we found that collaboration cost may increase with R&D, employees‘ education, the technology gap and collaboration cost in previous periods, but decrease with transaction cost, patents held, the technology level and perceived price. The thesis makes three contributions. Theoretically, our game theory model not only extends the understanding of the impacts of collaboration possibilities and collaboration cost in dynamic game theory, but also clarifies the impacts of transaction costs and imitation (and thus intellectual property rights (IPR)) on the outcome. Empirically, by introducing new data our work is the first to investigate collaboration patterns and collaboration cost sharing strategies in a mid-income level developing country. Last but not least, using MATLAB animation programming to simplify the calculation process of the game theory equilibrium may be considered as a methodological contribution

    Regulation of Antigenic Variation by Trypanosoma brucei Telomere Proteins Depends on Their Unique DNA Binding Activities

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    Trypanosoma brucei causes human African trypanosomiasis and regularly switches its major surface antigen, Variant Surface Glycoprotein (VSG), to evade the host immune response. Such antigenic variation is a key pathogenesis mechanism that enables T. brucei to establish long-term infections. VSG is expressed exclusively from subtelomere loci in a strictly monoallelic manner, and DNA recombination is an important VSG switching pathway. The integrity of telomere and subtelomere structure, maintained by multiple telomere proteins, is essential for T. brucei viability and for regulating the monoallelic VSG expression and VSG switching. Here we will focus on T. brucei TRF and RAP1, two telomere proteins with unique nucleic acid binding activities, and summarize their functions in telomere integrity and stability, VSG switching, and monoallelic VSG expression. Targeting the unique features of TbTRF and TbRAP10 s nucleic acid binding activities to perturb the integrity of telomere structure and disrupt VSG monoallelic expression may serve as potential therapeutic strategy against T. brucei

    Real-Time Work Zone Traffic Management via Unmanned Air Vehicles

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    Highway work zones are prone to traffic accidents when congestion and queues develop. Vehicle queues expand at a rate of 1 mile every 2 minutes. Back-of-queue, rear-end crashes are the most common work zone crash, endangering the safety of motorists, passengers, and construction workers. The dynamic nature of queuing in the proximity of highway work zones necessitates traffic management solutions that can monitor and intervene in real time. Fortunately, recent progress in sensor technology, embedded systems, and wireless communication coupled to lower costs are now enabling the development of real-time, automated, “intelligent” traffic management systems that address this problem. The goal of this project was to perform preliminary research and proof of concept development work for the use of UAS in realtime traffic monitoring of highway construction zones in order to create real-time alerts for motorists, construction workers, and first responders. The main tasks of the proposed system was to collect traffic data via the UAV camera, analyze that a UAV based highway construction zone monitoring systems would be capable of detecting congestion and back-of-queue information, and alerting motorists of stopped traffic conditions, delay times, and alternate route options. Experiments were conducted using UAS to monitor traffic and collect traffic videos for processing. Prototype software was created to analyze this data. The software was successful in detecting vehicle speed from zero mph to highway speeds. Review of available mobile traffic apps were conducted for future integration with advanced iterations of the UAV and software system that has been created by this research. This project has proven that UAS monitoring of highway construction zones and real-time alerts to motorists, construction crews, and first responders is possible in the near term and future research is needed to further development and implement the innovative UAS traffic monitoring system developed by this research

    Three Dimensions of COVID-19 Risk Perceptions and Their Socioeconomic Correlates in the United States: A Social Media Analysis

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    Social media analysis provides an alternate approach to monitoring and understanding risk perceptions regarding COVID-19 over time. Our current understandings of risk perceptions regarding COVID-19 do not disentangle the three dimensions of risk perceptions (perceived susceptibility, perceived severity, and negative emotion) as the pandemic has evolved. Data are also limited regarding the impact of social determinants of health (SDOH) on COVID-19-related risk perceptions over time. To address these knowledge gaps, we extracted tweets regarding COVID-19-related risk perceptions and developed indicators for the three dimensions of risk perceptions based on over502 million geotagged tweets posted by over 4.9 million Twitter users from January2020 to December 2021 in the United States. We examined correlations between risk perception indicator scores and county-level SDOH. The three dimensions of risk perceptions demonstrate different trajectories. Perceived severity maintained a high level throughout the study period. Perceived susceptibility and negative emotion peaked on March 11, 2020 (COVID-19 declared global pandemic by WHO) and then declined and remained stable at lower levels until increasing once again with the Omicron period. Relative frequency of tweet posts on risk perceptions did not closely follow epidemic trends of COVID-19 (cases, deaths). Users from socioeconomically vulnerable counties showed lower attention to perceived severity and susceptibility of COVID-19 than those from wealthier counties. Examining trends in tweets regarding the multiple dimensions of risk perceptions throughout the COVID-19 pandemic can help policymakers frame in-time, tailored, and appropriate responses to prevent viral spread and encourage preventive behavior uptake in the United States

    Building Ethical Business Cultures: BRIC by BRIC

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    As the economies of Brazil, Russia, India, and China (BRICs) continue to grow both in size and clout, and their resident multinational corporations become major players in global markets, questions pertaining to trust and integrity, and of universally shared standards for ethical business behavior become important concerns for numerous stakeholders. Whether or not managers and employees behave ethically depends on how one defines ethical behavior and applies it to an organization’s culture. We start this article by discussing attributes of ethical business behavior and cultures in each of the four BRICs countries, and then present results of our recent large scale survey-based studies, comparing managers’ and employees’ perceptions of ethical cultures in BRICs and in economically developed Western economies

    Molecular Basis for Strain Variation in the S. Cerevisiae adhesion Flo11p

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    FLO11 encodes a yeast cell wall flocculin that mediates a variety of adhesive phenotypes in Saccharomyces cerevisiae. Flo11p is implicated in many developmental processes, including flocculation, formation of pseudohyphae, agar invasion, and formation of microbial mats and biofilms. However, Flo11p mediates different processes in different yeast strains. To investigate the mechanisms by which FLO11 determines these differences in colony morphology, flocculation, and invasion, we studied gene structure, function, and expression levels. Nonflocculent Saccharomyces cerevisiae Σ1278b cells exhibited significantly higher FLO11mRNA expression, especially in the stationary phase, than highly flocculent S. cerevisiae var. diastaticus. The two strains varied in cell surface hydrophobicity, and Flo11p contributed significantly to surface hydrophobicity in S. cerevisiae var. diastaticus but not in strain Σ1278b. Sequencing of the FLO11 gene in S. cerevisiae var. diastaticus revealed strain-specific differences, including a 15-amino-acid insertion in the adhesion domain. Flo11p adhesion domains from strain Σ1278b and S. cerevisiae var. diastaticus were expressed and used to coat magnetic beads. The adhesion domain from each strain bound preferentially to homologous cells, and the preferences were independent of the cells in which the adhesion domains were produced. These results are consistent with the idea that strain-specific variations in the amino acid sequences in the adhesion domains cause different Flo11p flocculation activities. The results also imply that strain-specific differences in expression levels, posttranslational modifications, and allelic differences outside the adhesion domains have little effect on flocculation
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