208 research outputs found

    Landscape of gene fusions in epithelial cancers: seq and ye shall find

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    Abstract Enabled by high-throughput sequencing approaches, epithelial cancers across a range of tissue types are seen to harbor gene fusions as integral to their landscape of somatic aberrations. Although many gene fusions are found at high frequency in several rare solid cancers, apart from fusions involving the ETS family of transcription factors which have been seen in approximately 50 % of prostate cancers, several other common solid cancers have been shown to harbor recurrent gene fusions at low frequencies. On the other hand, many gene fusions involving oncogenes, such as those encoding ALK, RAF or FGFR kinase families, have been detected across multiple different epithelial carcinomas. Tumor-specific gene fusions can serve as diagnostic biomarkers or help define molecular subtypes of tumors; for example, gene fusions involving oncogenes such as ERG, ETV1, TFE3, NUT, POU5F1, NFIB, PLAG1, and PAX8 are diagnostically useful. Tumors with fusions involving therapeutically targetable genes such as ALK, RET, BRAF, RAF1, FGFR1–4, and NOTCH1–3 have immediate implications for precision medicine across tissue types. Thus, ongoing cancer genomic and transcriptomic analyses for clinical sequencing need to delineate the landscape of gene fusions. Prioritization of potential oncogenic “drivers” from “passenger” fusions, and functional characterization of potentially actionable gene fusions across diverse tissue types, will help translate these findings into clinical applications. Here, we review recent advances in gene fusion discovery and the prospects for medicine.http://deepblue.lib.umich.edu/bitstream/2027.42/116210/1/13073_2015_Article_252.pd

    MPPT oscillations minimization in PV system by controlling non-linear dynamics in SEPIC DC-DC converter

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    Solar PV power generation has achieved rapid growth in developing countries which has many merits such as absence of noise, longer life, no pollution, less time for installation, and ease of grid interface. A maximum power point tracking circuit (MPPT) consists of DC-DC power electronics converters that are used to improve the energy attainment from solar PV array. This paper presents a detailed analysis to control of chaos, a non-linear dynamic in SEPIC DC-DC converter interfaced solar PV system, to minimize the oscillations near to MPP. In SEPIC DC-DC converter, the input inductor current is continuous and capable of sweeping the whole I-V curve of a PV module from open circuit voltage (Voc) to short circuit current (Isc) operating points. To trace the true maximum power point and to nullify the oscillations near to MPP, the yield output voltage needs to ensure period-1 operation

    Mining Privacy-Preserving Association Rules based on Parallel Processing in Cloud Computing

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    With the onset of the Information Era and the rapid growth of information technology, ample space for processing and extracting data has opened up. However, privacy concerns may stifle expansion throughout this area. The challenge of reliable mining techniques when transactions disperse across sources is addressed in this study. This work looks at the prospect of creating a new set of three algorithms that can obtain maximum privacy, data utility, and time savings while doing so. This paper proposes a unique double encryption and Transaction Splitter approach to alter the database to optimize the data utility and confidentiality tradeoff in the preparation phase. This paper presents a customized apriori approach for the mining process, which does not examine the entire database to estimate the support for each attribute. Existing distributed data solutions have a high encryption complexity and an insufficient specification of many participants' properties. Proposed solutions provide increased privacy protection against a variety of attack models. Furthermore, in terms of communication cycles and processing complexity, it is much simpler and quicker. Proposed work tests on top of a realworld transaction database demonstrate that the aim of the proposed method is realistic

    Mechanism-based modeling of thermal and irradiation creep behavior:An application to ferritic/martensitic HT9 steel

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    In this work, the creep behavior of HT9 steel in both thermal and irradiation environments is predicted using an integrated modeling framework. Multiple physical mechanisms such as diffusional creep and dislocation climb are incorporated into crystal plasticity calculations using the Visco-Plastic Self-Consistent (VPSC) approach. Climb velocities are informed by mean field rate theory laws in place of empirical power law formulations. More interestingly, the climb velocities explicitly consider the contribution of irradiation-induced point defects, i.e., stress induced preferential absorption (SIPA) effect. The developed expressions are shown to apply under conventional thermal creep and to the more complex irradiation conditions as well. This physically-informed, mechanism-based model is used to simulate the creep strain evolution of HT9 pressurized tubes under various loading conditions. It is demonstrated that the experimental behavior of this material reported in the literature is well described by this theoretical framework. The role of each relevant mechanism is discussed

    Inundation mapping – a study based on December 2004 Tsunami Hazard along Chennai coast, Southeast India

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    Tsunami impact study has been undertaken along Chennai coast starting from Pulicat to Kovalam. The study area Chennai coast is mainly devoted to prepare large scale action plan maps on tsunami inundation incorporating land use details derived from satellite data along with cadastral data using a GIS tool. Under tsunami inundation mapping along Chennai coast an integrated approach was adopted to prepare thematic maps on land use/land cover and coastal geomorphology using multispectral remote sensing data. The RTK dGPS instruments are used to collect elevation contour data at 0.5 m intervals for the Chennai coast. The GIS tool has been used to incorporate the elevation data, tsunami inundation markings obtained immediately after tsunami and thematic maps derived from remote sensing data. The outcome of this study provides an important clue on variations in tsunami inundation along Chennai coast, which is mainly controlled by local geomorphologic set-up, coastal zone elevation including coastal erosion protection measures and near shore bathymetry. This study highlights the information regarding most vulnerable areas of tsunami and also provides indication to demarcate suitable sites for rehabilitation

    RhoC Induces Differential Expression of Genes Involved in Invasion and Metastasis in MCF10A Breast Cells

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    Inflammatory breast cancer (IBC) is the most deadly form of breast cancer in humans presumably due to its ability to metastasize from its inception. In our laboratory, overexpression of RhoC GTPase was observed to be specific for IBC tumors, but not for stage-matched, non-IBC tumors. RhoC is known to contribute to an IBC-like phenotype in HPV-E6E7 immortalized breast cells. To further study the effect of RhoC overexpression on IBC metastasis, we generated stable transfectants of spontaneous immortalized mammary epithelial cells (MCF10A) overexpressing wild-type RhoC or a constitutively active RhoC mutant (G14V). Both the RhoC wild type and the G14V transfectants were highly invasive and proliferated more rapidly compared to vector-only control clones. Overexpression of RhoC led to an increase in actin stress fiber and focal adhesion contact formation. Comparative microarray analysis of these clones further revealed that RhoC overexpression upregulated 108 genes whereas seven genes were down-regulated. We have further verified by quantitative RT-PCR that genes involved in cell proliferation, invasion/adhesion, and angiogenesis were modulated by RhoC. This work suggests strong candidates for the downstream oncogenic functions of RhoC.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44221/1/10549_2004_Article_5264607.pd

    Data-Driven Constitutive Model for the Inelastic Response of Metals:Application to 316H Steel

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    Predictions of the mechanical response of structural elements are conditioned by the accuracy of constitutive models used at the engineering length-scale. In this regard, a prospect of mechanistic crystal-plasticity-based constitutive models is that they could be used for extrapolation beyond regimes in which they are calibrated. However, their use for assessing the performance of a component is computationally onerous. To address this limitation, a new approach is proposed whereby a surrogate constitutive model (SM) of the inelastic response of 316H steel is derived from a mechanistic crystal plasticity-based polycrystal model tracking the evolution of dislocation densities on all slip systems. The latter is used to generate a database of the expected plastic response and dislocation content evolution associated with several instances of creep loading. From the database, a SM is developed. It relies on the use of orthogonal polynomial regression to describe the evolution of the dislocation content. The SM is then validated against predictions of the dead load creep response given by the polycrystal model across a range of temperatures and stresses. When the SM is used to predict the response of 316H during complex non monotonic loading, extrapolating to new loading conditions, it is found that predictions compare particularly well against those from the physics-based polycrystal model
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