2,221 research outputs found

    REGULATION OF BREAST CANCER INITIATION AND PROGRESSION BY 14-3-3ZETA

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    14-3-3ζ is a ubiquitously expressed family member of proteins that have been implicated to have oncogenic potential through its interactions and involvement in cancer initiation and progression. 14-3-3ζ belongs to the highly conserved 14-3-3ζ protein family and modulates numerous pathways in cancer. Overexpression of 14-3-3ζ is an early event, occurs in more than 40% of human breast cancer cases, and is associated with disease recurrence and poor prognosis. Metabolic reprogramming is a hallmark of cancer. Cancer cells elevate aerobic glycolysis to produce metabolic intermediates and reducing equivalents, thereby facilitating cellular adaptation to the adverse environment and sustaining fast proliferation. Interestingly, new evidence has emerged that metabolic alteration may arise at early stages of breast cancer. However, little is known about what triggers metabolic reprogramming and how it mechanistically contributes to breast cancer initiation and progression. In this dissertation, I have characterized the functional role of 14-3-3ζ in metabolic alteration, cancer initiation and progression. The bioinformatic analyses of gene expression profiling from early-stages breast premalignant lesions showed that the expression of 14-3-3ζ is strongly correlated with the expressions of glycolytic genes, especially lactate dehydrogenase A (LDHA). Interestingly, this positive correlation was also preserved in the advanced stage of breast cancer. Experimentally, my work demonstrated that increasing 14-3-3ζ expression in human non-transformed mammary epithelial cells (hMECs), MCF10A and MCF12A, transcriptionally up-regulated LDHA expression and increased glycolytic activity, which increased colony formation and promoted early transformation of hMECs. Conversely, knockdown of LDHA in these 14-3-3ζ-overexpressing hMECs significantly decreased glycolytic activity and inhibited early transformation. Mechanistically, up-regulation of LDHA in 14-3-3ζ-overexpressing hMECs was directly mediated by the cAMP-response element-binding (CREB) transcription factor through 14-3-3ζ-mediated activation of the MEK-ERK signaling axis. Blocking MEK-ERK pathway in 14-3-3ζ-high expressing hMEC-derived MCF10DCIS.COM tumor lesions, significantly decreasing LDHA expression, reducing tumor cell proliferation, and effectively inhibiting tumor growth. Taken together, my studies demonstrate that 14-3-3ζ has pleiotropic functions on cancer metabolism dysregulation and tumorigenesis. While 14-3-3ζ has been identified as critical mediator in breast cancer initiation and early metabolic transformation, another key finding of this dissertation is that discovery of tumor cells selectively preserve high 14-3-3ζ expression during tumor progression process. 14-3-3ζ may involve in cell fitness mechanism that benefits cell survival and proliferation during cancer progression. Cancer is a sequential process of cell clone selection and competition. During cell competition; a “fit” clone population with better growth advantages outcompetes other subclones and eliminates “unfit” subclones. I found that 14-3-3ζ-low cells are eradicated by 14-3-3ζ-high cells when they grow together (HET tumors); however, 14-3-3ζ-low cells can still survive only when surrounded by cells with similar expression levels of 14-3-3ζ. Mechanistically, 14-3-3ζ-low tumor cells produce a high level of cytokine macrophage inhibitory factor (MIF). Juxtacrine signaling involving MIF, its receptor CXCR2 and downstream production of interleukin-8 (IL-8), augmented cell proliferation and reduced cell apoptosis in 14-3-3ζ-high cells. Disruption of IL-8 or its upstream signaling, MIF or CXCR2, led to diminish cell fitness in 14-3-3ζ-high tumor cells and reduced tumor growth. Moreover, unlike conventional cell fitness, this study has revealed that 14-3-3ζ-high cells out-compete to sequester MIF, thereby causing cell death of 14-3-3ζ-low cells. I show that cancer cells may utilize part of immunity to trigger winner-loser cell interaction that determines the cell fate in solid tumors. Targeting the MIF-CXCR2-IL-8 axis could be an effective strategy to intervene in breast cancer progression. In summary, my work demonstrates that 14-3-3ζ has two distinct roles involving in cancer metabolism and cell competition, which may be developed into novel therapeutic strategies to target human breast cancer

    Estimating the Impacts of Climate Change on Mortality in OECD Countries

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    The major contribution of this study is to combines both climatic and macroeconomic factors simultaneously in the estimation of mortality using the capital city of 22 OECD countries from the period 1990 to 2008. The empirical results provide strong evidences that higher income and a lower unemployment rate could reduce mortality rates, while the increases in precipitation and temperature variation have significantly positive impacts on the mortality rates. The effects of changing average temperature on mortality rates in summer and winter are asymmetrical and also depend on the location. Combining the future climate change scenarios with the estimation outcomes show that mortality rates in OECD countries in 2100 will be increased by 3.77% to 5.89%.Climate change; mortality; panel data model

    Modeling the Effect of Oil Price on Global Fertilizer Prices

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    The main purpose of this paper is to evaluate the effect of crude oil price on global fertilizer prices in both the mean and volatility. The endogenous structural breakpoint unit root test, the autoregressive distributed lag (ARDL) model, and alternative volatility models, including the generalized autoregressive conditional heteroskedasticity (GARCH) model, Exponential GARCH (EGARCH) model, and GJR model, are used to investigate the relationship between crude oil price and six global fertilizer prices. Weekly data for 2003-2008 for the seven price series are analyzed. The empirical results from ARDL show that most fertilizer prices are significantly affected by the crude oil price, which explains why global fertilizer prices reached a peak in 2008. We also find that that the volatility of global fertilizer prices and crude oil price from March to December 2008 are higher than in other periods, and that the peak crude oil price caused greater volatility in the crude oil price and global fertilizer prices. As volatility invokes financial risk, the relationship between oil price and global fertilizer prices and their associated volatility is important for public policy relating to the development of optimal energy use, global agricultural production, and financial integration.Volatility; Global fertilizer price; Crude oil price; Non-renewable fertilizers; Structural breakpoint unit root test

    ZigBee Wireless Sensor Nodes with Hybrid Energy Storage System Based on Li-Ion Battery and Solar Energy Supply

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    Most ZigBee sensor networks to date make use of nodes with limited processing, communication, and energy capabilities. Energy consumption is of great importance in wireless sensor applications as their nodes are commonly battery-driven. Once ZigBee nodes are deployed outdoors, limited power may make a sensor network useless before its purpose is complete. At present, there are two strategies for long node and network lifetime. The first strategy is saving energy as much as possible. The energy consumption will be minimized through switching the node from active mode to sleep mode and routing protocol with ultra-low energy consumption. The second strategy is to evaluate the energy consumption of sensor applications as accurately as possible. Erroneous energy model may render a ZigBee sensor network useless before changing batteries. In this paper, we present a ZigBee wireless sensor node with four key modules: a processing and radio unit, an energy harvesting unit, an energy storage unit, and a sensor unit. The processing unit uses CC2530 for controlling the sensor, carrying out routing protocol, and performing wireless communication with other nodes. The harvesting unit uses a 2W solar panel to provide lasting energy for the node. The storage unit consists of a rechargeable 1200 mAh Li-ion battery and a battery charger using a constant-current/constant-voltage algorithm. Our solution to extend node lifetime is implemented. Finally, a long-term sensor network test is used to exhibit the functionality of the solar powered system

    ZigBee Wireless Sensor Nodes with Hybrid Energy Storage System Based on Li-Ion Battery and Solar Energy Supply

    Get PDF
    Most ZigBee sensor networks to date make use of nodes with limited processing, communication, and energy capabilities. Energy consumption is of great importance in wireless sensor applications as their nodes are commonly battery-driven. Once ZigBee nodes are deployed outdoors, limited power may make a sensor network useless before its purpose is complete. At present, there are two strategies for long node and network lifetime. The first strategy is saving energy as much as possible. The energy consumption will be minimized through switching the node from active mode to sleep mode and routing protocol with ultra-low energy consumption. The second strategy is to evaluate the energy consumption of sensor applications as accurately as possible. Erroneous energy model may render a ZigBee sensor network useless before changing batteries. In this paper, we present a ZigBee wireless sensor node with four key modules: a processing and radio unit, an energy harvesting unit, an energy storage unit, and a sensor unit. The processing unit uses CC2530 for controlling the sensor, carrying out routing protocol, and performing wireless communication with other nodes. The harvesting unit uses a 2W solar panel to provide lasting energy for the node. The storage unit consists of a rechargeable 1200 mAh Li-ion battery and a battery charger using a constant-current/constant-voltage algorithm. Our solution to extend node lifetime is implemented. Finally, a long-term sensor network test is used to exhibit the functionality of the solar powered system

    ZigBee Wireless Sensor Nodes with Hybrid Energy Storage System Based on Li-Ion Battery and Solar Energy Supply

    Get PDF
    Most ZigBee sensor networks to date make use of nodes with limited processing, communication, and energy capabilities. Energy consumption is of great importance in wireless sensor applications as their nodes are commonly battery-driven. Once ZigBee nodes are deployed outdoors, limited power may make a sensor network useless before its purpose is complete. At present, there are two strategies for long node and network lifetime. The first strategy is saving energy as much as possible. The energy consumption will be minimized through switching the node from active mode to sleep mode and routing protocol with ultra-low energy consumption. The second strategy is to evaluate the energy consumption of sensor applications as accurately as possible. Erroneous energy model may render a ZigBee sensor network useless before changing batteries. In this paper, we present a ZigBee wireless sensor node with four key modules: a processing and radio unit, an energy harvesting unit, an energy storage unit, and a sensor unit. The processing unit uses CC2530 for controlling the sensor, carrying out routing protocol, and performing wireless communication with other nodes. The harvesting unit uses a 2W solar panel to provide lasting energy for the node. The storage unit consists of a rechargeable 1200 mAh Li-ion battery and a battery charger using a constant-current/constant-voltage algorithm. Our solution to extend node lifetime is implemented. Finally, a long-term sensor network test is used to exhibit the functionality of the solar powered system

    Pure spin current generation in a Rashba-Dresselhaus quantum channel

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    We demonstrate a spin pump to generate pure spin current of tunable intensity and polarization in the absence of charge current. The pumping functionality is achieved by means of an ac gate voltage that modulates the Rashba constant dynamically in a local region of a quantum channel with both static Rashba and Dresselhaus spin-orbit interactions. Spin-resolved Floquet scattering matrix is calculated to analyze the whole scattering process. Pumped spin current can be divided into spin-preserved transmission and spin-flip reflection parts. These two terms have opposite polarization of spin current and are competing with each other. Our proposed spin-based device can be utilized for non-magnetic control of spin flow by tuning the ac gate voltage and the driving frequency.Comment: 6 pages, 3 figure

    Profit Maximization by Forming Federations of Geo-Distributed MEC Platforms

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    This paper has been presented at: Seventh International Workshop on Cloud Technologies and Energy Efficiency in Mobile Communication Networks (CLEEN 2019). How cloudy and green will mobile network and services be? 15 April 2019 - Marrakech, MoroccoIn press / En prensaMulti-access edge computing (MEC) as an emerging technology which provides cloud service in the edge of multi-radio access networks aims to reduce the service latency experienced by end devices. When individual MEC systems do not have adequate resource capacity to fulfill service requests, forming MEC federations for resource sharing could provide economic incentive to MEC operators. To this end, we need to maximize social welfare in each federation, which involves efficient federation structure generations, federation profit maximization by resource provisioning configuration, and fair profit distribution among participants. We model the problem as a coalition game with difference from prior work in the assumption of latency and locality constraints and also in the consideration of various service policies/demand preferences. Simulation results show that the proposed approach always increases profits. If local requests are served with local resource with priority, federation improves profits without sacrificing request acceptance rates.This work was partially supported by the Ministry of Science and Technology, Taiwan, under grant numbers 106-2221-E-009-004 and by the H2020 collaborative Europe/Taiwan research project 5G-CORAL (grant number 761586)

    "An Econometric Analysis of SARS and Avian Flu on International Tourist Arrivals to Asia"

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    This paper compares the impacts of SARS and human deaths arising from Avian Flu on international tourist arrivals to Asia. The effects of SARS and human deaths from Avian Flu will be compared directly according to human deaths. The nature of the short run and long run relationship is examined empirically by estimating a static line fixed effect model and a difference transformation dynamic model, respectively. Empirical results from the static fixed effect and difference transformation dynamic models are consistent, and indicate that both the short run and long run SARS effect have a more significant impact on international tourist arrivals than does Avian Flu. In addition, the effects of deaths arising from both SARS and Avian Flu suggest that SARS is more important to international tourist arrivals than is Avian Flu. Thus, while Avian Flu is here to stay, its effect is currently not as significant as that of SARS.
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