362 research outputs found

    Noise Can Reduce Disorder in Chaotic Dynamics

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    We evoke the idea of representation of the chaotic attractor by the set of unstable periodic orbits and disclose a novel noise-induced ordering phenomenon. For long unstable periodic orbits forming the strange attractor the weights (or natural measure) is generally highly inhomogeneous over the set, either diminishing or enhancing the contribution of these orbits into system dynamics. We show analytically and numerically a weak noise to reduce this inhomogeneity and, additionally to obvious perturbing impact, make a regularizing influence on the chaotic dynamics. This universal effect is rooted into the nature of deterministic chaos.Comment: 11 pages, 5 figure

    A linguistic analysis of lying in negative evaluations: The speech act performance of Chinese learners of Korean

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    이 논문은 중국인 한국어 학습자와 한국어 화자들 사이의 ‘거짓말’ 화행 양상을 언어학적으로 분석한 연구이다. 여기서 말하는 ‘거짓말’이란 요청, 사과, 거절 등과 같은 화행의 일종으로서 ‘부정적 평가’에 속하며 대화 참여자나 상황을 고려한 소위 ‘선의의 거짓말’을 가리키는 것으로 이해할 수 있을 것이다. 우리는 중국인 한국어 학습자 15명과 한국어 화자 15명을 대상으로 담화완성테스트(DCT)와 부연설명질문지(QFE)를 사용하여 피실험자들의 화행을 분석하였다. 피실험자 자신들의 설명과 한국어교육 전문가 다섯 명의 판정을 종합해 ‘거짓말’ 화행을 가려내고 통계 처리를 바탕으로 다음과 같은 결론에 도달했다. 한국어 화자들이 중국인 한국어 학습자들보다 (선의의) 거짓말을 더 많이 수행하는 것으로 나타났다. 그리고 두 집단 모두 부정적 평가가 사물에 관련된 경우보다 사람에 관련된 경우에 ‘거짓말’ 화행을 더 많이 사용한다. 그러나 화자와 청자 사이의 친소관계(distance)나 상하관계(power)는 거짓말 사용에 직접적 상관 관계를 보여주지 않았다. 이 연구는 지금까지 화행 연구 중에서 상대적으로 연구가 부진했던 부정평가와 ‘거짓말’ 화행에 대한 분석을 시도했다는 점에서 의미가 있다. 또한 한국어 화자와 중국인 한국어 학습자 사이에 보이는 화행 수행의 차이를 문화인식(cultural awareness)의 관점에서 해석해 볼 수 있는 가능성도 열어 주었다

    CREB is a critical regulator of normal hematopoiesis and leukemogenesis

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    The cAMP-responsive element binding protein (CREB) is a 43-kDa nuclear transcription factor that regulates cell growth, memory, and glucose homeostasis. We showed previously that CREB is amplified in myeloid leukemia blasts and expressed at higher levels in leukemia stem cells from patients with myeloid leukemia. CREB transgenic mice develop myeloproliferative disease after 1 year, but not leukemia, suggesting that CREB contributes to but is not sufficient for leukemogenesis. Here, we show that CREB is most highly expressed in lineage negative hematopoietic stem cells (HSCs). To understand the role of CREB in hematopoietic progenitors and leukemia cells, we examined the effects of RNA interference (RNAi) to knock down CREB expression in vitro and in vivo. Transduction of primary HSCs or myeloid leukemia cells with lentiviral CREB shRNAs resulted in decreased proliferation of stem cells, cell- cycle abnormalities, and inhibition of CREB transcription. Mice that received transplants of bone marrow transduced with CREB shRNA had decreased committed progenitors compared with control mice. Mice injected with Ba/F3 cells expressing either Bcr-Abl wild-type or T315I mutation with CREB shRNA had delayed leukemic infiltration by bioluminescence imaging and prolonged median survival. Our results suggest that CREB is critical for normal myelopoiesis and leukemia cell proliferation

    The Mars Hopper: Development, Simulation and Experimental Validation of a Radioisotope Exploration Probe for the Martian Surface

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    An advanced exploration probe has been proposed by the Center for Space Nuclear Research (CSNR) to acquire detailed data from the Martian surface and subsurface, ‘hop’ large distances to multiple sites in short periods of time and perform this task repeatedly. Although several similar flying vehicles have been proposed utilizing various power sources and complex designs, e.g. solar-electric and chemical-based, the CSNR’s Mars Hopper is based on a radioisotope thermal rocket (RTR) concept. The Mars Hopper’s design relies on the high specific energies [J/kg] of radioisotopes and enhances their low specific power [W/kg] through the use of a thermal capacitance material to store thermal energy over time. During operation, the RTR transfers the stored thermal energy to a flowing gas, which is then expanded through a converging-diverging nozzle, producing thrust. Between flights, the platform will have ample time to perform in-depth science at each location while the propellant tanks and thermal capacitor recharge. Recharging the propellant tanks is accomplished by sublimation freezing of the ambient CO2 atmosphere with a cryocooler, followed by heating and pressurization to yield a liquid storage state. The proposed Mars Hopper will undergo a ballistic flight, consuming the propellant in both ascent and descent, and by using multiple hopper platforms, information can be gathered on a global scale, enabling better resource resolution and providing valuable information for a possible Mars sample-return mission. The CSNR, collaborating with the Idaho National Laboratory (INL) and three universities (University of Idaho, Utah State University and Oregon State University), has identified key components and sub-systems necessary for the proposed hopper. Current project activities include the development of a lab-scale prototypic Mars Hopper and test facility, along with computational fluid dynamics (CFD)/thermal-hydraulic models to yield a better understanding of the heat transfer process and complex nature of turbulent CO2 flow. Laboratory experimentation will aid design iterations and the development of both tethered and free-flying terrestrial hoppers that utilize an electrically heated core. The knowledge base acquired from these activities will refine the Mars Hopper’s future performance and optimize the RTR core components prior to constructing the final design

    Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues

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    Hormones and nutrients often induce genetic programs via signaling pathways that interface with gene-specific activators. Activation of the cAMP pathway, for example, stimulates cellular gene expression by means of the PKA-mediated phosphorylation of cAMP-response element binding protein (CREB) at Ser-133. Here, we use genome-wide approaches to characterize target genes that are regulated by CREB in different cellular contexts. CREB was found to occupy approximate to 4,000 promoter sites in vivo, depending on the presence and methylation state of consensus cAMP response elements near the promoter. The profiles for CREB occupancy were very similar in different human tissues, and exposure to a cAMP agonist stimulated CREB phosphorylation over a majority of these sites. Only a small proportion of CREB target genes was induced by cAMP in any cell type, however, due in part to the preferential recruitment of the coactivator CREB-binding protein to those promoters. These results indicate that CREB phosphorylation alone is not a reliable predictor of target gene activation and that additional CREB regulatory partners are required for recruitment of the transcriptional apparatus to the promoter

    Direct Observation of Dimerization between Different CREB1 Isoforms in a Living Cell

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    Cyclic AMP-responsive element binding protein 1 (CREB1) plays multiple functions as a transcription factor in gene regulation. CREB1 proteins are also known to be expressed in several spliced isoforms that act as transcriptional activators or repressors. The activator isoforms, possessing the functional domains for kinase induction and for interaction with other transcriptional regulators, act as transcriptional activators. On the other hand, some isoforms, lacking those functional domains, are reported to be repressors that make heterodimers with activator isoforms. The complex and ingenious function for CREB1 arises in part from the variation in their spliced isoforms, which allows them to interact with each other. To date, however, the dimerization between the activator and repressor isoforms has not yet been proved directly in living cells. In this study, we applied fluorescence cross-correlation spectroscopy (FCCS) to demonstrate direct observation of dimerization between CREB1 activator and repressor. The FCCS is a well established spectroscopic method to determine the interaction between the different fluorescent molecules in the aqueous condition. Using differently labeled CREB1 isoforms, we successfully observed the interaction of CREB1 activator and repressor via dimerization in the nuclei of cultured cells. As a result, we confirmed the formation of heterodimer between CREB1 activator and repressor isoforms in living cells

    Downregulation of uPAR and Cathepsin B Induces Apoptosis via Regulation of Bcl-2 and Bax and Inhibition of the PI3K/Akt Pathway in Gliomas

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    Glioma is the most commonly diagnosed primary brain tumor and is characterized by invasive and infiltrative behavior. uPAR and cathepsin B are known to be overexpressed in high-grade gliomas and are strongly correlated with invasive cancer phenotypes.In the present study, we observed that simultaneous downregulation of uPAR and cathepsin B induces upregulation of some pro-apoptotic genes and suppression of anti-apoptotic genes in human glioma cells. uPAR and cathepsin B (pCU)-downregulated cells exhibited decreases in the Bcl-2/Bax ratio and initiated the collapse of mitochondrial membrane potential. We also observed that the broad caspase inhibitor, Z-Asp-2, 6-dichlorobenzoylmethylketone rescued pCU-induced apoptosis in U251 cells but not in 5310 cells. Immunoblot analysis of caspase-9 immunoprecipitates for Apaf-1 showed that uPAR and cathepsin B knockdown activated apoptosome complex formation in U251 cells. Downregulation of uPAR and cathepsin B also retarded nuclear translocation and interfered with DNA binding activity of CREB in both U251 and 5310 cells. Further western blotting analysis demonstrated that downregulation of uPAR and cathepsin B significantly decreased expression of the signaling molecules p-PDGFR-β, p-PI3K and p-Akt. An increase in the number of TUNEL-positive cells, increased Bax expression, and decreased Bcl-2 expression in nude mice brain tumor sections and brain tissue lysates confirm our in vitro results.In conclusion, RNAi-mediated downregulation of uPAR and cathepsin B initiates caspase-dependent mitochondrial apoptosis in U251 cells and caspase-independent mitochondrial apoptosis in 5310 cells. Thus, targeting uPAR and cathepsin B-mediated signaling using siRNA may serve as a novel therapeutic strategy for the treatment of gliomas
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