213 research outputs found

    Identifying the Effects of Unprocessed let-7a-1 and let-7a-3 in Non-Small Cell Lung Cancer

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    MicroRNAs (miRNAs) are small, noncoding RNAs that regulate protein levels typically by interacting with the 3′ untranslated region (3′-UTR) of target messenger RNA (mRNAs) and are often aberrantly expressed in cancer. The let-7 miRNA family members are commonly regarded as cancer suppressors, by down-regulating the expression of oncoproteins such as RAS, HMGA2, and MYC. However, prior work indicates that unprocessed let-7 RNAs may be positively correlated with cancer phenotypes in lung cancer cell lines. Our study aims to identify the effects of unprocessed let-7a-1 and let-7a-3 in non-small cell lung cancer, by transfecting plasmids that express unprocessed let-7a-1 and let-7a-3 into 3 different lung cancer cell lines. We then proceeded to conduct functional assays to measure the differences in anchorage independent growth, cell proliferation, and cell migration in all cell lines transfected with unprocessed let-7, in contrast to cells transfected with a control vector and thus far determined that unprocessed let-7a-1 can enhance anchorage independent growth. Thus, we created truncations of the let-7a-1 miRNA to identify the cis regions of this miRNA that is responsible for the change in phenotype. Our results suggest that cells transfected with truncated, yet unprocessed let-7a-1 have increased anchorage independent growth, a major hallmark of cancer cell. There is still a need to replicate the functional assays that were conducted while continuing to create constructs of both let-7a-1 and let-7a-3 in order to further identify the sequence of the miRNAs responsible for the enhanced cancer phenotypes

    Fixtures for quality assurance of STS silicon sensors and STS-XYTER ASIC

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    The FPGA-based Continious FFT Tune Measurement System for the LHC and its test at the CERN SPS

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    A base band tune (BBQ) measurement system has been developed at CERN. This system is based on a high-sensitivity direct-diode detection technique followed by a high resolution FFT algorithm implemented in an FPGA. The system allows acquisition of continuous real-time spectra with 32-bit resolution, while a digital frequency synthesiser (DFS) can provide an acquisition synchronised chirp excitation. All the implemented algorithms support dynamic reconfiguration of processing and excitation parameters. Results from both laboratory measurements and tests performed with beam at the CERN SPS are presented

    Microscopic Analysis For Water Stressed By High Electric Fields In The Prebreakdown Regime

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    Analysis of the electrical double layer at the electrode-water interface for voltages close to the breakdown point has been carried out based on a static, Monte Carlo approach. It is shown that strong dipole realignment, ion-ion correlation, and finite-size effects can greatly modify the electric fields and local permittivity (hence, leading to optical structure) at the electrode interface. Dramatic enhancements of Schottky injection, providing a source for electronic controlled breakdown, are possible. It is also shown that large pressures associated with the Maxwell stress tensor would be created at the electrode boundaries. Our results depend on the ionic density, and are in keeping with recent observations. A simple, perturbative analysis shows that high field regions with a sharp variation in permittivity can potentially be critical spots for instability initiation. This suggests that the use of polished electrodes, or composite materials, or alternative nonpolar liquids might help enhance high-voltage operation

    Estimating Level of Engagement from Ocular Landmarks

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    E-learning offers many advantages like being economical, flexible and customizable, but also has challenging aspects such as lack of – social-interaction, which results in contemplation and sense of remoteness. To overcome these and sustain learners’ motivation, various stimuli can be incorporated. Nevertheless, such adjustments initially require an assessment of engagement level. In this respect, we propose estimating engagement level from facial landmarks exploiting the facts that (i) perceptual decoupling is promoted by blinking during mentally demanding tasks; (ii) eye strain increases blinking rate, which also scales with task disengagement; (iii) eye aspect ratio is in close connection with attentional state and (iv) users’ head position is correlated with their level of involvement. Building empirical models of these actions, we devise a probabilistic estimation framework. Our results indicate that high and low levels of engagement are identified with considerable accuracy, whereas medium levels are inherently more challenging, which is also confirmed by inter-rater agreement of expert coders

    MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer

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    MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether it represents a bystander event or actually drives tumor progression in vivo. We show that miR-135b overexpression is triggered in mice and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression and promotes tumor transformation and progression. We show that miR-135b upregulation is common in sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth by controlling genes involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment

    Opportunities to integrate new approaches in genetic toxicology: An ILSI-HESI workshop report

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    Genetic toxicity tests currently used to identify and characterize potential human mutagens and carcinogens rely on measurements of primary DNA damage, gene mutation, and chromosome damage in vitro and in rodents. The International Life Sciences Institute Health and Environmental Sciences Institute (ILSI-HESI) Committee on the Relevance and Follow-up of Positive Results in In Vitro Genetic Toxicity Testing held an April 2012 Workshop in Washington, DC, to consider the impact of new understanding of biology and new technologies on the identification and characterization of genotoxic substances, and to identify new approaches to inform more accurate human risk assessment for genetic and carcinogenic effects. Workshop organizers and speakers were from industry, academe, and government. The Workshop focused on biological effects and technologies that would potentially yield the most useful information for evaluating human risk of genetic damage. Also addressed was the impact that improved understanding of biology and availability of new techniques might have on genetic toxicology practices. Workshop topics included (1) alternative experimental models to improve genetic toxicity testing, (2) Biomarkers of epigenetic changes and their applicability to genetic toxicology, and (3) new technologies and approaches. The ability of these new tests and technologies to be developed into tests to identify and characterize genotoxic agents; to serve as a bridge between in vitro and in vivo rodent, or preferably human, data; or to be used to provide dose response information for quantitative risk assessment was also addressed. A summary of the workshop and links to the scientific presentations are provided.International Life Sciences Institute/Health and Environmental Sciences Institute Committe

    Diphenyl Difluoroketone: A Potent Chemotherapy Candidate for Human Hepatocellular Carcinoma

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    Diphenyl difluoroketone (EF24), a molecule having structural similarity to curcumin, was recently reported to inhibit proliferation of various cancer cells significantly. Here we try to determine the effect and mechanism of EF24 on hepatocellular carcinoma. 2 µM EF24 was found to inhibit the proliferation of PLC/PRF/5, Hep3B, HepG2, SK-HEP-1 and Huh 7 cell lines. However, even 8 µM EF24 treatment did not affect the proliferation of normal liver LO2 cells. Accordingly, 20 mg/kg/d EF24 inhibited the growth of the tumor xenografts conspicuously while causing no apparent change in liver, spleen or body weight. In addition, significant apoptosis and G2/M phase cell cycle arrest were found using flow cytometry. Besides, caspases and PARP activation and features typical of apoptosis including fragmented nuclei with condensed chromatin were also observed. Furthermore, the mechanism was targeted at the reduction of nuclear factor kappa b (NF-κB) pathway and the NF-κB–regulated gene products Bcl-2, COX-2, Cyclin B1. Our study has offered a strategy that EF24 being a therapeutic agent for hepatocellular carcinoma

    Computational modeling with spiking neural networks

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    This chapter reviews recent developments in the area of spiking neural networks (SNN) and summarizes the main contributions to this research field. We give background information about the functioning of biological neurons, discuss the most important mathematical neural models along with neural encoding techniques, learning algorithms, and applications of spiking neurons. As a specific application, the functioning of the evolving spiking neural network (eSNN) classification method is presented in detail and the principles of numerous eSNN based applications are highlighted and discussed
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