141 research outputs found

    Lateral Stiffness and Damping Coefficient of Soils for Seismic Analysis of Buried Pipelines

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    The stiffness and damping coefficient of soil are critical parameters in the Winkler\u27s model for the seismic analysis of buried pipelines. This paper presents an analytical study in calculating the lateral dynamic stiffness (elastic and inelastic) and damping coefficient of soils for the seismic analysis of buried pipelines. The effects of the depth of the buried pipeline and the variation of Poisson\u27s ratio of soils are cons1dered. In the analysts, first, by using the elastic half-space theory, the elastic stiffness and geometrical damping coefficient of soils are obtained. From the numerical results, the elastic stiffness and geometrical damping coefficient by using best fitted formulas are presented. Secondly, empirical inelastic characteristics of soils are considered. The empirical data includes relationships among dynamic shear modulus, material damping ratio, and dynamic shear strain amplitude. The total damping coefficient of the system can be obtained by adding the material damping to the geometrical damping coefficient

    Band Structure, Phonon Scattering and the Ultimate Performance of Single-Walled Carbon Nanotube Transistors

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    Semiconducting single-walled carbon nanotubes are studied in the diffusive transport regime. The peak mobility is found to scale with the square of the nanotube diameter and inversely with temperature. The maximum conductance, corrected for the contacts, is linear in the diameter and inverse temperature. These results are in good agreement with theoretical predictions for acoustic phonon scattering in combination with the unusual band structure of nanotubes. These measurements set the upper bound for the performance of nanotube transistors operating in the diffusive regime

    Chinese ‘low-tar’ cigarettes do not deliver lower levels of nicotine and carcinogens

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    BackgroundLow-tar cigarette smoking is gaining popularity in China. The China National Tobacco Corporation (CNTC) promotes low-tar cigarettes as safer than regular cigarettes.MethodsA total of 543 male smokers smoking cigarettes with different tar yields (15 mg, regular cigarettes, 10-13 mg low-tar cigarettes and < 10 mg low-tar cigarettes) were recruited in Shanghai, China, who then completed a questionnaire on smoking behaviour and provided a urine sample for analysis of the nicotine metabolites cotinine and trans-3'-hydroxycotinine. A total of 177 urine samples were selected at random for the analysis of the carcinogens polycyclic aromatic hydrocarbon metabolites (PAHs) (1-hydroxypyrene, naphthols, hydroxyfluorenes and hydroxyphenanthrenes) and the tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-butanone (NNK) metabolites, 4-(methylnitrosamino)-1-(3-pyridyl)-butanol (NNAL) and NNAL-glucuronide. Values were normalised by creatinine to correct for possible distortions introduced by dilution or concentration of the urine.ResultsSmokers of low-tar cigarettes smoked fewer cigarettes per day (p=0.001) compared to smokers of regular cigarettes. Despite this lower reported consumption, levels of cotinine, trans-3'-hydroxycotinine and PAHs in urine of people smoking low-tar cigarettes were not correlated with nominal tar delivery of the cigarettes they smoked. Urine concentrations of NNAL were higher in smokers of lower tar than higher tar cigarettes.ConclusionsChinese low-tar cigarettes do not deliver lower doses of nicotine and carcinogens than regular cigarettes, therefore it is unlikely that there would be any reduction in harm. CNTC's promotion of low-tar cigarettes as 'less harmful' is a violation of the World Health Organization Framework Convention on Tobacco Control, which China ratified in 2005

    Epistasis between MicroRNAs 155 and 146a during T Cell-Mediated Antitumor Immunity

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    An increased understanding of antitumor immunity is necessary for improving cell-based immunotherapies against human cancers. Here, we investigated the roles of two immune system-expressed microRNAs (miRNAs), miR-155 and miR-146a, in the regulation of antitumor immune responses. Our results indicate that miR-155 promotes and miR-146a inhibits interferon γ (IFNγ) responses by T cells and reduces solid tumor growth in vivo. Using a double-knockout (DKO) mouse strain deficient in both miR-155 and miR-146a, we have also identified an epistatic relationship between these two miRNAs. DKO mice had defective T cell responses and tumor growth phenotypes similar to miR-155^(−/−) mice. Further analysis of the T cell compartment revealed that miR-155 modulates IFNγ expression through a mechanism involving repression of Ship1. Our work reveals critical roles for miRNAs in the reciprocal regulation of CD4^+ and CD8^+ T cell-mediated antitumor immunity and demonstrates the dominant nature of miR-155 during its promotion of immune responses

    Fingerprint Recognition with Identical Twin Fingerprints

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    Fingerprint recognition with identical twins is a challenging task due to the closest genetics-based relationship existing in the identical twins. Several pioneers have analyzed the similarity between twins' fingerprints. In this work we continue to investigate the topic of the similarity of identical twin fingerprints. Our study was tested based on a large identical twin fingerprint database that contains 83 twin pairs, 4 fingers per individual and six impressions per finger: 3984 (83*2*4*6) images. Compared to the previous work, our contributions are summarized as follows: (1) Two state-of-the-art fingerprint identification methods: P071 and VeriFinger 6.1 were used, rather than one fingerprint identification method in previous studies. (2) Six impressions per finger were captured, rather than just one impression, which makes the genuine distribution of matching scores more realistic. (3) A larger sample (83 pairs) was collected. (4) A novel statistical analysis, which aims at showing the probability distribution of the fingerprint types for the corresponding fingers of identical twins which have same fingerprint type, has been conducted. (5) A novel analysis, which aims at showing which finger from identical twins has higher probability of having same fingerprint type, has been conducted. Our results showed that: (a) A state-of-the-art automatic fingerprint verification system can distinguish identical twins without drastic degradation in performance. (b) The chance that the fingerprints have the same type from identical twins is 0.7440, comparing to 0.3215 from non-identical twins. (c) For the corresponding fingers of identical twins which have same fingerprint type, the probability distribution of five major fingerprint types is similar to the probability distribution for all the fingers' fingerprint type. (d) For each of four fingers of identical twins, the probability of having same fingerprint type is similar

    Differential Dynamic Properties of Scleroderma Fibroblasts in Response to Perturbation of Environmental Stimuli

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    Diseases are believed to arise from dysregulation of biological systems (pathways) perturbed by environmental triggers. Biological systems as a whole are not just the sum of their components, rather ever-changing, complex and dynamic systems over time in response to internal and external perturbation. In the past, biologists have mainly focused on studying either functions of isolated genes or steady-states of small biological pathways. However, it is systems dynamics that play an essential role in giving rise to cellular function/dysfunction which cause diseases, such as growth, differentiation, division and apoptosis. Biological phenomena of the entire organism are not only determined by steady-state characteristics of the biological systems, but also by intrinsic dynamic properties of biological systems, including stability, transient-response, and controllability, which determine how the systems maintain their functions and performance under a broad range of random internal and external perturbations. As a proof of principle, we examine signal transduction pathways and genetic regulatory pathways as biological systems. We employ widely used state-space equations in systems science to model biological systems, and use expectation-maximization (EM) algorithms and Kalman filter to estimate the parameters in the models. We apply the developed state-space models to human fibroblasts obtained from the autoimmune fibrosing disease, scleroderma, and then perform dynamic analysis of partial TGF-β pathway in both normal and scleroderma fibroblasts stimulated by silica. We find that TGF-β pathway under perturbation of silica shows significant differences in dynamic properties between normal and scleroderma fibroblasts. Our findings may open a new avenue in exploring the functions of cells and mechanism operative in disease development

    Exploiting antitumor immunity to overcome relapse and improve remission duration

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    Cancer survivors often relapse due to evolving drug-resistant clones and repopulating tumor stem cells. Our preclinical study demonstrated that terminal cancer patient’s lymphocytes can be converted from tolerant bystanders in vivo into effective cytotoxic T-lymphocytes in vitro killing patient’s own tumor cells containing drug-resistant clones and tumor stem cells. We designed a clinical trial combining peginterferon α-2b with imatinib for treatment of stage III/IV gastrointestinal stromal tumor (GIST) with the rational that peginterferon α-2b serves as danger signals to promote antitumor immunity while imatinib’s effective tumor killing undermines tumor-induced tolerance and supply tumor-specific antigens in vivo without leukopenia, thus allowing for proper dendritic cell and cytotoxic T-lymphocyte differentiation toward Th1 response. Interim analysis of eight patients demonstrated significant induction of IFN-γ-producing-CD8+, -CD4+, -NK cell, and IFN-γ-producing-tumor-infiltrating-lymphocytes, signifying significant Th1 response and NK cell activation. After a median follow-up of 3.6 years, complete response (CR) + partial response (PR) = 100%, overall survival = 100%, one patient died of unrelated illness while in remission, six of seven evaluable patients are either in continuing PR/CR (5 patients) or have progression-free survival (PFS, 1 patient) exceeding the upper limit of the 95% confidence level of the genotype-specific-PFS of the phase III imatinib-monotherapy (CALGB150105/SWOGS0033), demonstrating highly promising clinical outcomes. The current trial is closed in preparation for a larger future trial. We conclude that combination of targeted therapy and immunotherapy is safe and induced significant Th1 response and NK cell activation and demonstrated highly promising clinical efficacy in GIST, thus warranting development in other tumor types

    Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells

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    Transplantation of exogenous dopaminergic neuron (DA neurons) is a promising approach for treating Parkinson's disease (PD). However, a major stumbling block has been the lack of a reliable source of donor DA neurons. Here we show that a combination of five transcriptional factors Mash1, Ngn2, Sox2, Nurr1, and Pitx3 can directly and effectively reprogram human fibroblasts into DA neuron-like cells. The reprogrammed cells stained positive for various markers for DA neurons. They also showed characteristic DA uptake and production properties. Moreover, they exhibited DA neuron-specific electrophysiological profiles. Finally, they provided symptomatic relief in a rat PD model. Therefore, our directly reprogrammed DA neuron-like cells are a promising source of cell-replacement therapy for PD
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