100 research outputs found
Modelling data: Acquired resistance to IDH inhibition through trans or cis dimer-interface mutations
No full textModelling structures, settings, and scripts for figure generation accompanying the manuscript:Acquired resistance to IDH inhibition through trans or cis dimer-interface mutationsAndrew M. Intlekofer, Alan H. Shih, Bo Wang, Abbas Nazir, Ariën S. Rustenburg, Steven K. Albanese, Minal Patel, Christopher Famulare, Fabian M. Correa, Naofumi Takemoto, Vidushi Durani, Hui Liu, Justin Taylor, Noushin R. Farnoud, Elli Papaemmannuil, Justin R. Cross, Martin S. Tallman, Maria E. Arcila, Mikhail Roshal, Gregory A. Petsko, Bin Wu, Sung Choe, Zenon D. Konteatis, Scott A. Biller, John D. Chodera, Craig B. Thompson*, Ross L. Levine, Eytan M. Stein(Reference to published manuscript to be added)<br
Computational tools for CNV detection using probe-level analysis of Affymetrix SNP arrays : application to the study of CNVs in follicular lymphoma
No full textCopy number variants (CNVs) account for both variations among normal individuals and pathogenic variations. The introduction of DNA microarrays had a significant impact on the resolution of detectable CNVs and yielded a new perspective on the submicroscopic CNVs. Oligonucleotide microarrays, such as Affymetrix SNP arrays, have been commonly used for genome-wide CNV analysis. Despite the improvements in the technology, a major concern of using microarrays is how a putative CNV is defined. A disadvantage of oligonucleotide arrays is the poor signal-to-noise ratio of the data that leads to considerable variation in reported intensity readouts. Such variation will lead to false positive and false negative results, regardless of how the data are analysed. The most common approach to circumvent this problem is looking for abrupt ratio intensity shifts in several consecutive markers (e.g., SNP probes). However this approach reduces the overall resolution and mitigates the sensitivity of detecting CNVs with fewer probes. This limitation emphasizes the importance of designing methods that can identify noisy readouts at the probe-level.
The main goals of this work were to study the scale of the variability in Affymetrix SNP arrays and to develop computational tools that can improve the resolution of CNV detection. By using simulated data, it was shown that the proposed method improved the accuracy and precision of detecting CNVs with fewer probes compared to standard methods. This approach was also applied to tumor/normal pairs from 25 follicular lymphoma patients and 286 candidate CNVs were found, from which 261 (91.2%) were also seen by other array-based method(s). Importantly, from 32 novel deletions, undetected by other array-based methods, at least 15 (47%) were real based on sequence-based validation. An example of a novel discovery was a partial deletion of the extracellular domain of the KIT proto-oncogene that may lead to constitutive activation of this gene. Gain of function mutations of KIT has been previously reported in several other hematologic cancers through other mechanisms such as point mutations.
In conclusion, CNV discovery contributes to our understanding of complex diseases and the methods presented here should provide means for better detection of CNVs and their interpretation.Medicine, Faculty ofMedical Genetics, Department ofGraduat
Affordability of fruits and vegetables and dietary quality worldwide
No full textRefers to:\ud
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Victoria Miller, Salim Yusuf, Clara K Chow, Mahshid Dehghan, Daniel J Corsi, Karen Lock, Barry Popkin, Sumathy Rangarajan, Rasha Khatib, Scott A Lear, Prem Mony, Manmeet Kaur, Viswanathan Mohan, Krishnapillai Vijayakumar, Rajeev Gupta, Annamarie Kruger, Lungiswa Tsolekile, Noushin Mohammadifard, Omar Rahman, Annika Rosengren, Alvaro Avezum, et al.\ud
Availability, affordability, and consumption of fruits and vegetables in 18 countries across income levels: findings from the Prospective Urban Rural Epidemiology (PURE) study\ud
The Lancet Global Health, Volume 4, Issue 10, October 2016, Pages e695-e70
Ultrasound Backscatter Signal Characterization and Classification Using Autoregressive Modeling and Machine Learning Algorithms
No full textThis research explores the possibility of monitoring apoptosis and classifying clusters of apoptotic cells based on the changes in ultrasound backscatter signals from the tissues. The backscatter from normal and apoptotic cells, using a high frequency ultrasound instrument are modeled through an autoregressive (AR) modeling technique. The proper model order is calculated by tracking the error criteria in the reconstruction of the original signal. The AR model coefficients, which are assumed to contain the main statistical features of the signal, are passed as the input to linear and nonlinear machine classifiers (Fisher linear discriminant, conditional Gaussian classifier, Naive Bayes classifier and neural networks with nonlinear activation functions). In addition, an adaptive signal segmentation method (least squares lattice filter) is used to differentiate the data from layers of different cell types into stationary parts ready for modeling and classification
Self-Heating Measurements for a Dual-Phase Steel under Ultrasonic Fatigue Loading for stress amplitudes below the conventional fatigue limit
No full textAbstractThe aim of the present research was to study the self-heating behavior of a dual-phase steel under ultrasonic fatigue loading for stress amplitudes lower than the conventional fatigue limit. The steel studied in this research was DP600 commercial dual phase steel. Fatigue tests were conducted for different values of stress amplitudes up to 107 cycles using an ultrasonic fatigue machine at a testing frequency of 20 kHz with flat specimens. An infrared camera was used to measure the mean temperature evolution during the tests. A specific form of heat diffusion equation was adopted in this work to calculate the intrinsic dissipation from temperature measurements. The variation of the dissipated energy versus stress amplitude under cyclic loading was also studied
Analysis of “Lady’s Last Game” based on Bakhtin’s Theory of Polyphony
No full text"Lady’s Last Game" is a novel by Belqeis Soleimani, author and critic of contemporary Iranian literature. This novel was awards the literary prize of Mehregan, and the prize for the best novel in the special event item in Isfahan, 1385. The incidents of the novel take place during the socio-political events of 1360s in Iran, and its central theme is to investigate women's issues in sub-layers of the society. Polyphony is a term coined by Bakhtin to contrast monophony in novel. This study is to prove that "Lady’s Last Game" is polyphonic. In this regard, elements such as intertextuality, hidden polemic, diversity, heteroglossia, sudden change of point of view, etc. prove validation. The main approach is to review the polyphony of Mikhail Bakhtin's view, though, post-Bakhtinian theorists are referred to for clarification as well. The research method is descriptive-analytical. The results indicate that a polyphonic novel helps the reader to get a new and different vision of the text otherwise not understood from the surface level
PD2-2-7: Two wrongs make a right: the use of whole genome amplification for pair-wise genome-wide copy number analysis of limited patient material
No full textAtypical Presentation of Erythroid/Megakaryocytic Leukemic Transformation of a Myeloproliferative Neoplasm Associated with Mutation and Loss of TP53
No full textTaxol productivity and physiological relationships in suspension cultures of Taxus Cuspidata
No full text1995 Fall.Includes bibliographic references (pages 143-159).Taxol, an extractive of the Pacific yew, is a plant secondary metabolite that has demonstrated anticancer activity. In an effort to prevent depletion of Pacific yew population and to obtain adequate supplies of taxol, alternative methods of production are being sought. The goal of this research was to produce taxol in sufficient quantities for clinical use by manipulating engineering parameters that affect production of secondary metabolites in plant cell culture systems. Production of taxol in suspension cultures of Taxus cuspidata in shake flasks exposed to different concentrations and combinations of oxygen, carbon dioxide, and ethylene was investigated. The effect of each gas on cell growth and taxol production was studied using several sets of factorial design experiments. Low head space oxygen con-centration (10% v/v) promoted production of taxol prior to day 14. High carbon dioxide concentration (10% v/v) inhibited taxol production. Taxol concentration increased as ethylene concentration was increased to 5 ppm; it leveled at 10 ppm ethylene. The utilization patterns of sugars were dependent on headspace gas composition. Average calcium uptake rates into the cultured cells decreased and average phosphate uptake rates increased as the ethylene concentration was in-creased from 0 to 10 ppm. Ethylene concentration at 50 ppm had an inhibitory effect on taxol production but not on phosphate uptake rate, suggesting independent regulation of taxol biosynthesis and physiological functions of the cell. The most effective gas mixture composition tested in terms of taxol production—10% (v/v) oxygen, 0.5% (v/v) carbon dioxide, and 5 ppm ethylene—is thought to be related to regulation of gene transcription. To stimulate taxol production, suspension cultures of Taxus cuspidata were challenged with various concentrations and combinations of methyl jasmonate (an elicitor derived from jasmonic acid) and ethylene. Taxol productivity increased 19-fold compared to the basal level when Taxus cuspidata suspension cultures were exposed to 5 ppm ethylene and 10 μM methyl jasmonate. The induction of taxol biosynthesis occurred within 51 hours after elicitation. Simple induction models were proposed to explain the action and effects of both ethylene and methyl jasmonate with regard to receptor binding and transcription regulation in plants
Additional file 1: of Indoor concentrations of VOCs in beauty salons; association with cosmetic practices and health risk assessment
No full textMore details of the chemical analyses and the detailed results of the statistical analyses are presented in the Additional file; other information is also available from the corresponding author upon reasonable request. (DOCX 70Â kb
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