166 research outputs found

    Which missing value imputation method to use in expression profiles: a comparative study and two selection schemes

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    <p>Abstract</p> <p>Background</p> <p>Gene expression data frequently contain missing values, however, most down-stream analyses for microarray experiments require complete data. In the literature many methods have been proposed to estimate missing values via information of the correlation patterns within the gene expression matrix. Each method has its own advantages, but the specific conditions for which each method is preferred remains largely unclear. In this report we describe an extensive evaluation of eight current imputation methods on multiple types of microarray experiments, including time series, multiple exposures, and multiple exposures × time series data. We then introduce two complementary selection schemes for determining the most appropriate imputation method for any given data set.</p> <p>Results</p> <p>We found that the optimal imputation algorithms (LSA, LLS, and BPCA) are all highly competitive with each other, and that no method is uniformly superior in all the data sets we examined. The success of each method can also depend on the underlying "complexity" of the expression data, where we take complexity to indicate the difficulty in mapping the gene expression matrix to a lower-dimensional subspace. We developed an entropy measure to quantify the complexity of expression matrixes and found that, by incorporating this information, the entropy-based selection (EBS) scheme is useful for selecting an appropriate imputation algorithm. We further propose a simulation-based self-training selection (STS) scheme. This technique has been used previously for microarray data imputation, but for different purposes. The scheme selects the optimal or near-optimal method with high accuracy but at an increased computational cost.</p> <p>Conclusion</p> <p>Our findings provide insight into the problem of which imputation method is optimal for a given data set. Three top-performing methods (LSA, LLS and BPCA) are competitive with each other. Global-based imputation methods (PLS, SVD, BPCA) performed better on mcroarray data with lower complexity, while neighbour-based methods (KNN, OLS, LSA, LLS) performed better in data with higher complexity. We also found that the EBS and STS schemes serve as complementary and effective tools for selecting the optimal imputation algorithm.</p

    Advanced Diagnostics for the Study of Linearly Polarized Emission. II: Application to Diffuse Interstellar Radio Synchrotron Emission

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    Diagnostics of polarized emission provide us with valuable information on the Galactic magnetic field and the state of turbulence in the interstellar medium, which cannot be obtained from synchrotron intensity alone. In Paper I (Herron et al. 2017b), we derived polarization diagnostics that are rotationally and translationally invariant in the QQ-UU plane, similar to the polarization gradient. In this paper, we apply these diagnostics to simulations of ideal magnetohydrodynamic turbulence that have a range of sonic and Alfv\'enic Mach numbers. We generate synthetic images of Stokes QQ and UU for these simulations, for the cases where the turbulence is illuminated from behind by uniform polarized emission, and where the polarized emission originates from within the turbulent volume. From these simulated images we calculate the polarization diagnostics derived in Paper I, for different lines of sight relative to the mean magnetic field, and for a range of frequencies. For all of our simulations, we find that the polarization gradient is very similar to the generalized polarization gradient, and that both trace spatial variations in the magnetoionic medium for the case where emission originates within the turbulent volume, provided that the medium is not supersonic. We propose a method for distinguishing the cases of emission coming from behind or within a turbulent, Faraday rotating medium, and a method to partly map the rotation measure of the observed region. We also speculate on statistics of these diagnostics that may allow us to constrain the physical properties of an observed turbulent region.Comment: 34 pages, 25 figures, accepted for publication in Ap

    The completion of the Mammalian Gene Collection (MGC)

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    Since its start, the Mammalian Gene Collection (MGC) has sought to provide at least one full-protein-coding sequence cDNA clone for every human and mouse gene with a RefSeq transcript, and at least 6200 rat genes. The MGC cloning effort initially relied on random expressed sequence tag screening of cDNA libraries. Here, we summarize our recent progress using directed RT-PCR cloning and DNA synthesis. The MGC now contains clones with the entire protein-coding sequence for 92% of human and 89% of mouse genes with curated RefSeq (NM-accession) transcripts, and for 97% of human and 96% of mouse genes with curated RefSeq transcripts that have one or more PubMed publications, in addition to clones for more than 6300 rat genes. These high-quality MGC clones and their sequences are accessible without restriction to researchers worldwide

    Lineage-specific evolution of the vertebrate Otopetrin gene family revealed by comparative genomic analyses

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    Background: Mutations in the Otopetrin 1 gene (Otop1) in mice and fish produce an unusual bilateral vestibular pathology that involves the absence of otoconia without hearing impairment. The encoded protein, Otop1, is the only functionally characterized member of the Otopetrin Domain Protein (ODP) family; the extended sequence and structural preservation of ODP proteins in metazoans suggest a conserved functional role. Here, we use the tools of sequence-and cytogenetic-based comparative genomics to study the Otop1 and the Otop2-Otop3 genes and to establish their genomic context in 25 vertebrates. We extend our evolutionary study to include the gene mutated in Usher syndrome (USH) subtype 1G (Ush1g), both because of the head-to-tail clustering of Ush1g with Otop2 and because Otop1 and Ush1g mutations result in inner ear phenotypes. Results: We established that OTOP1 is the boundary gene of an inversion polymorphism on human chromosome 4p16 that originated in the common human-chimpanzee lineage more than 6 million years ago. Other lineage-specific evolutionary events included a three-fold expansion of the Otop genes in Xenopus tropicalis and of Ush1g in teleostei fish. The tight physical linkage between Otop2 and Ush1g is conserved in all vertebrates. To further understand the functional organization of the Ushg1-Otop2 locus, we deduced a putative map of binding sites for CCCTC-binding factor (CTCF), a mammalian insulator transcription factor, from genome-wide chromatin immunoprecipitation-sequencing (ChIP-seq) data in mouse and human embryonic stem (ES) cells combined with detection of CTCF-binding motifs. Conclusions: The results presented here clarify the evolutionary history of the vertebrate Otop and Ush1g families, and establish a framework for studying the possible interaction(s) of Ush1g and Otop in developmental pathways

    Living on the edge: utilising lidar data to assess the importance of vegetation structure for avian diversity in fragmented woodlands and their edges

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    Context: In agricultural landscapes, small woodland patches can be important wildlife refuges. Their value in maintaining biodiversity may, however, be compromised by isolation, and so knowledge about the role of habitat structure is vital to understand the drivers of diversity. This study examined how avian diversity and abundance were related to habitat structure in four small woods in an agricultural landscape in eastern England. Objectives: The aims were to examine the edge effect on bird diversity and abundance, and the contributory role of vegetation structure. Specifically: what is the role of vegetation structure on edge effects, and which edge structures support the greatest bird diversity? Methods: Annual breeding bird census data for 28 species were combined with airborne lidar data in linear mixed models fitted separately at (i) the whole wood level, and (ii) for the woodland edges only. Results: Despite relatively small woodland areas (4.9–9.4 ha), bird diversity increased significantly towards the edges, being driven in part by vegetation structure. At the whole woods level, diversity was positively associated with increased vegetation above 0.5 m and especially with increasing vegetation density in the understorey layer, which was more abundant at the woodland edges. Diversity along the edges was largely driven by the density of vegetation below 4 m. Conclusions: The results demonstrate that bird diversity was maximised by a diverse vegetation structure across the wood and especially a dense understorey along the edge. These findings can assist bird conservation by guiding habitat management of remaining woodland patches

    Draft Genome Sequencing of Giardia intestinalis Assemblage B Isolate GS: Is Human Giardiasis Caused by Two Different Species?

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    Giardia intestinalis is a major cause of diarrheal disease worldwide and two major Giardia genotypes, assemblages A and B, infect humans. The genome of assemblage A parasite WB was recently sequenced, and the structurally compact 11.7 Mbp genome contains simplified basic cellular machineries and metabolism. We here performed 454 sequencing to 16× coverage of the assemblage B isolate GS, the only Giardia isolate successfully used to experimentally infect animals and humans. The two genomes show 77% nucleotide and 78% amino-acid identity in protein coding regions. Comparative analysis identified 28 unique GS and 3 unique WB protein coding genes, and the variable surface protein (VSP) repertoires of the two isolates are completely different. The promoters of several enzymes involved in the synthesis of the cyst-wall lack binding sites for encystation-specific transcription factors in GS. Several synteny-breaks were detected and verified. The tetraploid GS genome shows higher levels of overall allelic sequence polymorphism (0.5 versus <0.01% in WB). The genomic differences between WB and GS may explain some of the observed biological and clinical differences between the two isolates, and it suggests that assemblage A and B Giardia can be two different species

    Roadmap on Photovoltaic Absorber Materials for Sustainable Energy Conversion

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    Photovoltaics (PVs) are a critical technology for curbing growing levels of anthropogenic greenhouse gas emissions, and meeting increases in future demand for low-carbon electricity. In order to fulfil ambitions for net-zero carbon dioxide equivalent (CO2eq) emissions worldwide, the global cumulative capacity of solar PVs must increase by an order of magnitude from 0.9 TWp in 2021 to 8.5 TWp by 2050 according to the International Renewable Energy Agency, which is considered to be a highly conservative estimate. In 2020, the Henry Royce Institute brought together the UK PV community to discuss the critical technological and infrastructure challenges that need to be overcome to address the vast challenges in accelerating PV deployment. Herein, we examine the key developments in the global community, especially the progress made in the field since this earlier roadmap, bringing together experts primarily from the UK across the breadth of the photovoltaics community. The focus is both on the challenges in improving the efficiency, stability and levelized cost of electricity of current technologies for utility-scale PVs, as well as the fundamental questions in novel technologies that can have a significant impact on emerging markets, such as indoor PVs, space PVs, and agrivoltaics. We discuss challenges in advanced metrology and computational tools, as well as the growing synergies between PVs and solar fuels, and offer a perspective on the environmental sustainability of the PV industry. Through this roadmap, we emphasize promising pathways forward in both the short- and long-term, and for communities working on technologies across a range of maturity levels to learn from each other.Comment: 160 pages, 21 figure

    Succession Planning in Academic Libraries: A Reconsideration

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    It has been widely projected in the library literature that a substantial number of librarians will retire in the near future leaving significant gaps in the workforce, especially in library leadership. Many of those concerned with organizational development in libraries have promoted succession planning as an essential tool for addressing this much-anticipated wave of retirements. The purpose of this chapter is to argue that succession planning is the wrong approach for academic libraries. This chapter provides a review of the library literature on succession planning, as well as studies analyzing position announcements in librarianship which provide evidence as to the extent to which academic librarianship has changed in recent years. In a review of the library literature, the author found no sound explanation of why succession planning is an appropriate method for filling anticipated vacancies and no substantive evidence that succession planning programs in libraries are successful. Rather than filling anticipated vacancies with librarians prepared to fill specific positions by means of a succession planning program, the author recommends that academic library leaders should focus on the continual evaluation of current library needs and future library goals, and treat each vacancy as an opportunity to create a new position that will best satisfy the strategic goals of the library. In contrast to the nearly universal support for succession planning found in the library literature, this chapter offers a different point of view

    GH Receptor Antagonist: Mechanism of Action and Clinical Utility

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    This review focuses on the development of GH receptor antagonist as a novel agent for treatment of acromegaly, its mechanism of action and potential areas of use. A brief overview of acromegaly, its diagnosis and existing medical, surgical and radiotherapy options of treatment is necessary to justify the addition of yet another therapeutic modality to the already vast therapeutic armamentarium.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47874/1/11154_2005_Article_5219.pd

    CMB-S4

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    We describe the stage 4 cosmic microwave background ground-based experiment CMB-S4
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