406 research outputs found

    A novel SNP analysis method to detect copy number alterations with an unbiased reference signal directly from tumor samples

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    <p>Abstract</p> <p>Background</p> <p>Genomic instability in cancer leads to abnormal genome copy number alterations (CNA) as a mechanism underlying tumorigenesis. Using microarrays and other technologies, tumor CNA are detected by comparing tumor sample CN to normal reference sample CN. While advances in microarray technology have improved detection of copy number alterations, the increase in the number of measured signals, noise from array probes, variations in signal-to-noise ratio across batches and disparity across laboratories leads to significant limitations for the accurate identification of CNA regions when comparing tumor and normal samples.</p> <p>Methods</p> <p>To address these limitations, we designed a novel "Virtual Normal" algorithm (VN), which allowed for construction of an unbiased reference signal directly from test samples within an experiment using any publicly available normal reference set as a baseline thus eliminating the need for an in-lab normal reference set.</p> <p>Results</p> <p>The algorithm was tested using an optimal, paired tumor/normal data set as well as previously uncharacterized pediatric malignant gliomas for which a normal reference set was not available. Using Affymetrix 250K Sty microarrays, we demonstrated improved signal-to-noise ratio and detected significant copy number alterations using the VN algorithm that were validated by independent PCR analysis of the target CNA regions.</p> <p>Conclusions</p> <p>We developed and validated an algorithm to provide a virtual normal reference signal directly from tumor samples and minimize noise in the derivation of the raw CN signal. The algorithm reduces the variability of assays performed across different reagent and array batches, methods of sample preservation, multiple personnel, and among different laboratories. This approach may be valuable when matched normal samples are unavailable or the paired normal specimens have been subjected to variations in methods of preservation.</p

    Aqueous dune-like bedforms in Athabasca Valles and neighbouring locations utilized in palaeoflood reconstruction

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    Putative fluvial dunes have been identified within the Athabasca Valles and associated network of channels on Mars. Previous published work identified and measured bedforms in Athabasca Valles using photoclinometry methods on 2–3 m/pixel resolution Mars Orbiter Camera Narrow Angle images, and argued that these were created by an aqueous megaflood that occurred between 2 and 8 million years ago. This event is likely to have occurred due to geological activity associated with the Cerberus Fossae fracture system at the source of Athabasca Vallis. The present study has used higher resolution, 25 cm/pixel images from the Mars Reconnaissance Orbiter HiRISE camera, as well as stereo-derived digital terrain models and GIS software, to re-measure and evaluate these bedforms together with data from newly discovered neighbouring fields of bedforms. The analysis indicates that the bedforms are aqueous dunes, in that they occur in channel locations where dunes would be expected to be preserved and moreover they have geometries very similar to megaflood dunes on Earth. Dune geometries are used to estimate megaflood discharge rates, including uncertainty, which results support previous flood estimates that indicate that a flood with a discharge of ∼2 × 106m3s−1 created these bedforms

    Integrated genomics of ovarian xenograft tumor progression and chemotherapy response

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    <p>Abstract</p> <p>Background</p> <p>Ovarian cancer is the most deadly gynecological cancer with a very poor prognosis. Xenograft mouse models have proven to be one very useful tool in testing candidate therapeutic agents and gene function <it>in vivo</it>. In this study we identify genes and gene networks important for the efficacy of a pre-clinical anti-tumor therapeutic, MT19c.</p> <p>Methods</p> <p>In order to understand how ovarian xenograft tumors may be growing and responding to anti-tumor therapeutics, we used genome-wide mRNA expression and DNA copy number measurements to identify key genes and pathways that may be critical for SKOV-3 xenograft tumor progression. We compared SKOV-3 xenografts treated with the ergocalciferol derived, MT19c, to untreated tumors collected at multiple time points. Cell viability assays were used to test the function of the PPARγ agonist, Rosiglitazone, on SKOV-3 cell growth.</p> <p>Results</p> <p>These data indicate that a number of known survival and growth pathways including Notch signaling and general apoptosis factors are differentially expressed in treated vs. untreated xenografts. As tumors grow, cell cycle and DNA replication genes show increased expression, consistent with faster growth. The steroid nuclear receptor, PPARγ, was significantly up-regulated in MT19c treated xenografts. Surprisingly, stimulation of PPARγ with Rosiglitazone reduced the efficacy of MT19c and cisplatin suggesting that PPARγ is regulating a survival pathway in SKOV-3 cells. To identify which genes may be important for tumor growth and treatment response, we observed that MT19c down-regulates some high copy number genes and stimulates expression of some low copy number genes suggesting that these genes are particularly important for SKOV-3 xenograft growth and survival.</p> <p>Conclusions</p> <p>We have characterized the time dependent responses of ovarian xenograft tumors to the vitamin D analog, MT19c. Our results suggest that PPARγ promotes survival for some ovarian tumor cells. We propose that a combination of regulated expression and copy number can identify genes that are likely important for chemotherapy response. Our findings suggest a new approach to identify candidate genes that are critical for anti-tumor therapy.</p

    Meteorites on Mars observed with the Mars Exploration Rovers

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    Reduced weathering rates due to the lack of liquid water and significantly greater typical surface ages should result in a higher density of meteorites on the surface of Mars compared to Earth. Several meteorites were identified among the rocks investigated during Opportunity&rsquo;s traverse across the sandy Meridiani plains. Heat Shield Rock is a IAB iron meteorite and has been officially recognized as &lsquo;&lsquo;Meridiani Planum.&rsquo;&rsquo; Barberton is olivine-rich and contains metallic Fe in the form of kamacite, suggesting a meteoritic origin. It is chemically most consistent with a mesosiderite silicate clast. Santa Catarina is a brecciated rock with a chemical and mineralogical composition similar to Barberton. Barberton, Santa Catarina, and cobbles adjacent to Santa Catarina may be part of a strewn field. Spirit observed two probable iron meteorites from its Winter Haven location in the Columbia Hills in Gusev Crater. Chondrites have not been identified to date, which may be a result of their lower strengths and probability to survive impact at current atmospheric pressures. Impact craters directly associated with Heat Shield Rock, Barberton, or Santa Catarina have not been observed, but such craters could have been erased by eolian-driven erosion.Additional co-authors: DW Ming, RV Morris, PA de Souza Jr, SW Squyres, C Weitz, AS Yen, J Zipfel, T Economo

    Alloplastische Implantate in der Kopf- und Halschirurgie.

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    Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

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    Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

    Measurement of the top quark mass using charged particles in pp collisions at root s=8 TeV

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