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  • 1
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    Disease allele-dependent small-molecule sensitivities in blood cells from monogenic diabetes [Applied Biological Sciences] (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-01-12
    Description: Even as genetic studies identify alleles that influence human disease susceptibility, it remains challenging to understand their functional significance and how they contribute to disease phenotypes. Here, we describe an approach to translate discoveries from human genetics into functional and therapeutic hypotheses by relating human genetic variation to small-molecule sensitivities. We use small-molecule probes modulating a breadth of targets and processes to reveal disease allele-dependent sensitivities, using cells from multiple individuals with an extreme form of diabetes (maturity onset diabetes of the young type 1, caused by mutation in the orphan nuclear receptor HNF4α). This approach enabled the discovery of small molecules that show mechanistically revealing and therapeutically relevant interactions with HNF4α in both lymphoblasts and pancreatic β-cells, including compounds that physically interact with HNF4α. Compounds including US Food and Drug Administration–approved drugs were identified that favorably modulate a critical disease phenotype, insulin secretion from β-cells. This method may suggest therapeutic hypotheses for other nonblood disorders.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 2
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    Online monitoring of oil film using electrical capacitance tomography and level set method (2015)
    American Institute of Physics (AIP)
    Details
    Publication Date: 2015-08-11
    Description: In the application of oil-air lubrication system, electrical capacitance tomography (ECT) provides a promising way for monitoring oil film in the pipelines by reconstructing cross sectional oil distributions in real time. While in the case of small diameter pipe and thin oil film, the thickness of the oil film is hard to be observed visually since the interface of oil and air is not obvious in the reconstructed images. And the existence of artifacts in the reconstructions has seriously influenced the effectiveness of image segmentation techniques such as level set method. Besides, level set method is also unavailable for online monitoring due to its low computation speed. To address these problems, a modified level set method is developed: a distance regularized level set evolution formulation is extended to image two-phase flow online using an ECT system, a narrowband image filter is defined to eliminate the influence of artifacts, and considering the continuity of the oil distribution variation, the detected oil-air interface of a former image can be used as the initial contour for the detection of the subsequent frame; thus, the propagation from the initial contour to the boundary can be greatly accelerated, making it possible for real time tracking. To testify the feasibility of the proposed method, an oil-air lubrication facility with 4 mm inner diameter pipe is measured in normal operation using an 8-electrode ECT system. Both simulation and experiment results indicate that the modified level set method is capable of visualizing the oil-air interface accurately online.
    Print ISSN: 0034-6748
    Electronic ISSN: 1089-7623
    Topics: Electrical Engineering, Measurement and Control Technology , Physics
    Published by American Institute of Physics (AIP)
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  • 3
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    BLESS 2: accurate, memory-efficient and fast error correction method (2016)
    Oxford University Press
    Details
    Publication Date: 2016-07-30
    Description: : The most important features of error correction tools for sequencing data are accuracy, memory efficiency and fast runtime. The previous version of BLESS was highly memory-efficient and accurate, but it was too slow to handle reads from large genomes. We have developed a new version of BLESS to improve runtime and accuracy while maintaining a small memory usage. The new version, called BLESS 2, has an error correction algorithm that is more accurate than BLESS, and the algorithm has been parallelized using hybrid MPI and OpenMP programming. BLESS 2 was compared with five top-performing tools, and it was found to be the fastest when it was executed on two computing nodes using MPI, with each node containing twelve cores. Also, BLESS 2 showed at least 11% higher gain while retaining the memory efficiency of the previous version for large genomes. Availability and implementation: Freely available at https://sourceforge.net/projects/bless-ec Contact: dchen@illinois.edu Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 4
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    A new standardized Palmer drought index for hydro-meteorological use (2013)
    Wiley
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    Publication Date: 2013-09-13
    Description: Accepting the concept of standardization introduced by the standardized precipitation index (SPI), similar methodologies have been developed to construct some other standardized drought indices such as the standardized precipitation evapotranspiration index (SPEI). In this study, the authors provided deep insight into the SPEI and recognized potential deficiencies/limitations in relating to the climatic water balance it used. By coupling another well-known Palmer drought severity index (PDSI), we proposed a new standardized Palmer drought index (SPDI) through a moisture departure probabilistic approach, which allows multiscalar calculation for accurate temporal and spatial comparison of the hydro-meteorological conditions of different locations. Using datasets of monthly precipitation, temperature and soil available water capacity, the moisture deficit/surplus was calculated at multiple temporal scales and a couple of techniques were adopted to adjust corresponding time series to a generalized extreme value distribution out of several candidates. Results of the historical records (1900–2012) for diverse climates by multiple indices showed that the SPDI was highly consistent and correlated with the SPEI and self-calibrated PDSI (SC-PDSI) at most analyzed time scales. Furthermore, a simple experiment of hypothetical temperature and/or precipitation change scenarios also verified the effectiveness of this newly-derived SPDI index in response to climate change impacts. Being more robust and preferable in spatial consistency and comparability as well as combining the simplicity of calculation with sufficient accounting of the physical nature of water supply and demand relating to droughts, the SPDI is promising to serve as a competent reference and alternative for drought assessment and monitoring. This article is protected by copyright. All rights reserved.
    Print ISSN: 0885-6087
    Electronic ISSN: 1099-1085
    Topics: Architecture, Civil Engineering, Surveying , Geography
    Published by Wiley
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  • 5
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    Universal intracellular biomolecule delivery with precise dosage control (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018
    Description: 〈p〉Intracellular delivery of mRNA, DNA, and other large macromolecules into cells plays an essential role in an array of biological research and clinical therapies. However, current methods yield a wide variation in the amount of material delivered, as well as limitations on the cell types and cargoes possible. Here, we demonstrate quantitatively controlled delivery into a range of primary cells and cell lines with a tight dosage distribution using a nanostraw-electroporation system (NES). In NES, cells are cultured onto track-etched membranes with protruding nanostraws that connect to the fluidic environment beneath the membrane. The tight cell-nanostraw interface focuses applied electric fields to the cell membrane, enabling low-voltage and nondamaging local poration of the cell membrane. Concurrently, the field electrophoretically injects biomolecular cargoes through the nanostraws and into the cell at the same location. We show that the amount of material delivered is precisely controlled by the applied voltage, delivery duration, and reagent concentration. NES is highly effective even for primary cell types or different cell densities, is largely cargo agnostic, and can simultaneously deliver specific ratios of different molecules. Using a simple cell culture well format, the NES delivers into 〉100,000 cells within 20 s with 〉95% cell viability, enabling facile, dosage-controlled intracellular delivery for a wide variety of biological applications.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 6
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    Yap regulates glucose utilization and sustains nucleotide synthesis to enable organ growth (2018)
    Springer Nature
    Details
    Publication Date: 2018
    Description: 〈p〉The Hippo pathway and its nuclear effector Yap regulate organ size and cancer formation. While many modulators of Hippo activity have been identified, little is known about the Yap target genes that mediate these growth effects. Here, we show that 〈i〉yap〈/i〉〈sup〉–/–〈/sup〉 mutant zebrafish exhibit defects in hepatic progenitor potential and liver growth due to impaired glucose transport and nucleotide biosynthesis. Transcriptomic and metabolomic analyses reveal that Yap regulates expression of glucose transporter glut1, causing decreased glucose uptake and use for nucleotide biosynthesis in 〈i〉yap〈/i〉〈sup〉–/–〈/sup〉 mutants, and impaired glucose tolerance in adults. Nucleotide supplementation improves Yap deficiency phenotypes, indicating functional importance of glucose-fueled nucleotide biosynthesis. Yap-regulated 〈i〉glut1〈/i〉 expression and glucose uptake are conserved in mammals, suggesting that stimulation of anabolic glucose metabolism is an evolutionarily conserved mechanism by which the Hippo pathway controls organ growth. Together, our results reveal a central role for Hippo signaling in glucose metabolic homeostasis.〈/p〉
    Print ISSN: 0261-4189
    Electronic ISSN: 1460-2075
    Topics: Biology , Medicine
    Published by Springer Nature on behalf of The European Molecular Biology Organization (EMBO).
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  • 7
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    Genome-wide association analysis of self-reported events in 6135 individuals and 252 827 controls identifies 8 loci associated with thrombosis (2016)
    Oxford University Press
    Details
    Publication Date: 2016-07-06
    Description: Thrombotic diseases are among the leading causes of morbidity and mortality in the world. To add insights into the genetic regulation of thrombotic disease, we conducted a genome-wide association study (GWAS) of 6135 self-reported blood clots events and 252 827 controls of European ancestry belonging to the 23andMe cohort of research participants. Eight loci exceeded genome-wide significance. Among the genome-wide significant results, our study replicated previously known venous thromboembolism (VTE) loci near the F5, FGA-FGG, F11, F2, PROCR and ABO genes, and the more recently discovered locus near SLC44A2 . In addition, our study reports for the first time a genome-wide significant association between rs114209171, located upstream of the F8 structural gene, and thrombosis risk. Analyses of expression profiles and expression quantitative trait loci across different tissues suggested SLC44A2 , ILF3 and AP1M2 as the three most plausible candidate genes for the chromosome 19 locus, our only genome-wide significant thrombosis-related locus that does not harbor likely coagulation-related genes. In addition, we present data showing that this locus also acts as a novel risk factor for stroke and coronary artery disease (CAD). In conclusion, our study reveals novel common genetic risk factors for VTE, stroke and CAD and provides evidence that self-reported data on blood clots used in a GWAS yield results that are comparable with those obtained using clinically diagnosed VTE. This observation opens up the potential for larger meta-analyses, which will enable elucidation of the genetics of thrombotic diseases, and serves as an example for the genetic study of other diseases.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 8
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    Yttriaite-(Y): The natural occurrence of Y2O3 from the Bol'shaya Pol'ya River, Subpolar Urals, Russia (2011)
    Mineralogical Society of America
    Details
    Publication Date: 2011-07-01
    Description: Yttriaite-(Y), ideally Y2O3, is a new mineral (IMA2010-039) from the alluvial deposits of the Bol'shaya Pol'ya River, Subpolar Urals, Russia. The new mineral occurs as isolated crystals, typically cubo-octahedra
    Print ISSN: 0003-004X
    Electronic ISSN: 1945-3027
    Topics: Geosciences
    Published by Mineralogical Society of America
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  • 9
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    GNL1/GNOM-mediated basal polar targeting [Plant Biology] (2015)
    National Academy of Sciences
    Details
    Publication Date: 2015-02-18
    Description: Spatial regulation of the plant hormone indole-3-acetic acid (IAA, or auxin) is essential for plant development. Auxin gradient establishment is mediated by polarly localized auxin transporters, including PIN-FORMED (PIN) proteins. Their localization and abundance at the plasma membrane are tightly regulated by endomembrane machinery, especially the endocytic and recycling pathways...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 10
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    Pd/Ag coated fiber Bragg grating sensor for hydrogen monitoring in power transformers (2015)
    American Institute of Physics (AIP)
    Details
    Publication Date: 2015-04-24
    Description: Compared with conventional DGA (dissolved gas analysis) method for on-line monitoring of power transformers, FBG (fiber Bragg grating) hydrogen sensor represents marked advantages over immunity to electromagnetic field, time-saving, and convenience to defect location. Thus, a novel FBG hydrogen sensor based on Pd/Ag (Palladium/Silver) along with polyimide composite film to measure dissolved hydrogen concentration in large power transformers is proposed in this article. With the help of Pd/Ag composite coating, the enhanced performance on mechanical strength and sensitivity is demonstrated, moreover, the response time and sensitivity influenced by oil temperature are solved by correction lines. Sensitivity measurement and temperature calibration of the specific hydrogen sensor have been done respectively in the lab. And experiment results show a high sensitivity of 0.055 pm/( μ l/l) with instant response time about 0.4 h under the typical operating temperature of power transformers, which proves a potential utilization inside power transformers to monitor the health status by detecting the dissolved hydrogen concentration.
    Print ISSN: 0034-6748
    Electronic ISSN: 1089-7623
    Topics: Electrical Engineering, Measurement and Control Technology , Physics
    Published by American Institute of Physics (AIP)
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