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  • 1
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    General polytropic self-gravitating cylinder free-fall and accreting mass string with a chain of collapsed objects (2016)
    Oxford University Press
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    Publication Date: 2016-05-04
    Description: We present a theoretical model framework for general polytropic (GP) hydrodynamic cylinder under self-gravity of infinite length with axial uniformity and axisymmetry. For self-similar dynamic solutions, we derive valuable integrals, analytic asymptotic solutions, sonic critical curves, shock conditions, and global numerical solutions with or without expansion shocks. Among others, we investigate various dynamic solutions featured with central free-fall asymptotic behaviours, corresponding to a collapsed mass string with a sustained dynamic accretion from a surrounding mass reservoir. Depending on the allowed ranges of a scaling index a 〈 –1, such cylindrical dynamic mass accretion rate could be steady, increasing with time and decreasing with time. Physically, such a collapsed mass string or filament would break up into a sequence of sub-clumps and segments as induced by gravitational Jeans instabilities. Depending on the scales involved, such sub-clumps would evolve into collapsed objects or gravitationally bound systems. In diverse astrophysical and cosmological contexts, such a scenario can be adapted on various temporal, spatial and mass scales to form a chain of collapsed clumps and/or compact objects. Examples include the formation of chains of proto-stars, brown dwarfs and gaseous planets along molecular filaments; the formation of luminous massive stars along magnetized spiral arms and circum-nuclear starburst rings in barred spiral galaxies; the formation of chains of compact stellar objects such as white dwarfs, neutron stars, and black holes along a highly condensed mass string. On cosmological scales, one can perceive the formation of chains of galaxies, chains of galaxy clusters or even chains of supermassive and hypermassive black holes in the Universe including the early Universe. All these chains referred to above include possible binaries.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 2
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    A feasible energy-saving analysis of a new system for CO2 cryogenic capture (2016)
    Oxford University Press
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    Publication Date: 2016-05-27
    Description: A new CO 2 cryogenic capture and liquefaction system has been proposed previously in order to separate CO 2 from exhausted gases and make it as a resource for industry. This system combines CO 2 cryogenic capture with N 2 /O 2 separation together. Its energy consumption is lower than the traditional amine solution capture process as theoretical analysis. In this study, the simulation of the proposed system with several improvements was carried out aiming to reduce the energy consumption further. Many heat exchangers were introduced and the heat exchanger arrangements were optimized to recycle the refrigeration capacity from the returned N 2 after the N 2 /O 2 separation. The discharge pressure of mixture gas from the compressor was reduced from 10 to 3.493 MPa. The simulation results showed that the compression work could be greatly reduced and the energy consumption of CO 2 capture in this new system after these improvements reached 2.884 GJ/ton CO 2 . The new system is promising because not only liquid or solid CO 2 could be produced but also N 2 and O 2 could be separated.
    Print ISSN: 1748-1317
    Electronic ISSN: 1748-1325
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Published by Oxford University Press
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  • 3
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    Winter soil respiration during soil-freezing process in a boreal forest in Northeast China (2013)
    Oxford University Press
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    Publication Date: 2013-09-21
    Description: Aims Boreal forest is the largest and contains the most soil carbon among global terrestrial biomes. Soil respiration during the prolonged winter period may play an important role in the carbon cycles in boreal forests. This study aims to explore the characteristics of winter soil respiration in the boreal forest and to show how it is regulated by environmental factors, such as soil temperature, soil moisture and snowpack. Methods Soil respiration in an old-growth larch forest ( Larix gmelinii Ruppr.) in Northeast China was intensively measured during the winter soil-freezing process in 2011 using an automated soil CO 2 flux system. The effects of soil temperature, soil moisture and thin snowpack on soil respiration and its temperature sensitivity were investigated. Important Findings Total soil respiration and heterotrophic respiration both showed a declining trend during the observation period, and no significant difference was found between soil respiration and heterotrophic respiration until the snowpack exceeded 20cm. Soil respiration was exponentially correlated with soil temperature and its temperature sensitivity (Q 10 value) for the entire measurement duration was 10.5. Snow depth and soil moisture both showed positive effects on the temperature sensitivity of soil respiration. Based on the change in the Q 10 value, we proposed a ‘freeze–thaw critical point’ hypothesis, which states that the Q 10 value above freeze–thaw critical point is much higher than that below it (16.0 vs . 3.5), and this was probably regulated by the abrupt change in soil water availability during the soil-freezing process. Our findings suggest interactive effects of multiple environmental factors on winter soil respiration and recommend adopting the freeze–thaw critical point to model soil respiration in a changing winter climate.
    Print ISSN: 1752-993X
    Electronic ISSN: 1752-9921
    Topics: Biology
    Published by Oxford University Press
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  • 4
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    NEECF: a project of nutrient enrichment experiments in China's forests (2013)
    Oxford University Press
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    Publication Date: 2013-09-21
    Description: Anthropogenic nitrogen (N) emissions to atmosphere have increased dramatically in China since 1980s, and this increase has aroused great concerns on its ecological impacts on terrestrial ecosystems. Previous studies have showed that terrestrial ecosystems in China are acting as a large carbon (C) sink, but its potential in the future remains largely uncertain. So far little work on the impacts of the N deposition on C sequestration in China’s terrestrial ecosystems has been assessed at a national scale. Aiming to assess and predict how ecological processes especially the C cycling respond to the increasing N deposition in China’s forests, recently researchers from Peking University and their partners have established a manipulation experimental network on the ecological effects of the N deposition: Nutrient Enrichment Experiments in China’s Forests Project (NEECF). The NEECF comprises 10 experiments at 7 sites located from north to south China, covering major zonal forest vegetation in eastern China from boreal forest in Greater Khingan Mountains to tropical forests in Hainan Island. This paper introduces the framework of the NEECF project and its potential policy implications.
    Print ISSN: 1752-993X
    Electronic ISSN: 1752-9921
    Topics: Biology
    Published by Oxford University Press
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  • 5
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    TherMos: Estimating protein-DNA binding energies from in vivo binding profiles (2013)
    Oxford University Press
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    Publication Date: 2013-06-08
    Description: Accurately characterizing transcription factor (TF)-DNA affinity is a central goal of regulatory genomics. Although thermodynamics provides the most natural language for describing the continuous range of TF-DNA affinity, traditional motif discovery algorithms focus instead on classification paradigms that aim to discriminate ‘bound’ and ‘unbound’ sequences. Moreover, these algorithms do not directly model the distribution of tags in ChIP-seq data. Here, we present a new algorithm named T hermodynamic M odeling of ChIP- s eq (TherMos), which directly estimates a position-specific binding energy matrix (PSEM) from ChIP-seq/exo tag profiles. In cross-validation tests on seven genome-wide TF-DNA binding profiles, one of which we generated via ChIP-seq on a complex developing tissue, TherMos predicted quantitative TF-DNA binding with greater accuracy than five well-known algorithms. We experimentally validated TherMos binding energy models for Klf4 and Esrrb, using a novel protocol to measure PSEMs in vitro . Strikingly, our measurements revealed strong non-additivity at multiple positions within the two PSEMs. Among the algorithms tested, only TherMos was able to model the entire binding energy landscape of Klf4 and Esrrb. Our study reveals new insights into the energetics of TF-DNA binding in vivo and provides an accurate first-principles approach to binding energy inference from ChIP-seq and ChIP-exo data.
    Keywords: Protein-nucleic acid interaction, Computational Methods, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 6
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    Non-manifesting AHI1 truncations indicate localized loss-of-function tolerance in a severe Mendelian disease gene (2015)
    Oxford University Press
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    Publication Date: 2015-04-04
    Description: Determination of variant pathogenicity represents a major challenge in the era of high-throughput sequencing. Erroneous categorization may result if variants affect genes that are in fact dispensable. We demonstrate that this also applies to rare, apparently unambiguous truncating mutations of an established disease gene. By whole-exome sequencing (WES) in a consanguineous family with congenital non-syndromic deafness, we unexpectedly identified a homozygous nonsense variant, p.Arg1066*, in AHI1 , a gene associated with Joubert syndrome (JBTS), a severe recessive ciliopathy. None of four homozygotes expressed any signs of JBTS, and one of them had normal hearing, which also ruled out p.Arg1066* as the cause of deafness. Homozygosity mapping and WES in the only other reported JBTS family with a homozygous C-terminal truncation (p.Trp1088Leufs*16) confirmed AHI1 as disease gene, but based on a more N-terminal missense mutation impairing WD40-repeat formation. Morpholinos against N-terminal zebrafish Ahi1 , orthologous to where human mutations cluster, produced a ciliopathy, but targeting near human p.Arg1066 and p.Trp1088 did not. Most AHI1 mutations in JBTS patients result in truncated protein lacking WD40-repeats and the SH3 domain; disease was hitherto attributed to loss of these protein interaction modules. Our findings indicate that normal development does not require the C-terminal SH3 domain. This has far-reaching implications, considering that variants like p.Glu984* identified by preconception screening (‘Kingsmore panel’) do not necessarily indicate JBTS carriership. Genomes of individuals with consanguineous background are enriched for homozygous variants that may unmask dispensable regions of disease genes and unrecognized false positives in diagnostic large-scale sequencing and preconception carrier screening.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 7
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    Improved prediction of RNA secondary structure by integrating the free energy model with restraints derived from experimental probing data (2015)
    Oxford University Press
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    Publication Date: 2015-08-29
    Description: Recently, several experimental techniques have emerged for probing RNA structures based on high-throughput sequencing. However, most secondary structure prediction tools that incorporate probing data are designed and optimized for particular types of experiments. For example, RNAstructure-Fold is optimized for SHAPE data, while SeqFold is optimized for PARS data. Here, we report a new RNA secondary structure prediction method, restrained MaxExpect ( RME ), which can incorporate multiple types of experimental probing data and is based on a free energy model and an MEA (maximizing expected accuracy) algorithm. We first demonstrated that RME substantially improved secondary structure prediction with perfect restraints (base pair information of known structures). Next, we collected structure-probing data from diverse experiments (e.g. SHAPE, PARS and DMS-seq) and transformed them into a unified set of pairing probabilities with a posterior probabilistic model. By using the probability scores as restraints in RME , we compared its secondary structure prediction performance with two other well-known tools, RNAstructure-Fold (based on a free energy minimization algorithm) and SeqFold (based on a sampling algorithm). For SHAPE data, RME and RNAstructure - Fold performed better than SeqFold , because they markedly altered the energy model with the experimental restraints. For high-throughput data (e.g. PARS and DMS-seq) with lower probing efficiency, the secondary structure prediction performances of the tested tools were comparable, with performance improvements for only a portion of the tested RNAs. However, when the effects of tertiary structure and protein interactions were removed, RME showed the highest prediction accuracy in the DMS-accessible regions by incorporating in vivo DMS-seq data.
    Keywords: Nucleic acid structure, RNA characterisation and manipulation, Computational Methods
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 8
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    A novel method for discovering local spatial clusters of genomic regions with functional relationships from DNA contact maps (2016)
    Oxford University Press
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    Publication Date: 2016-06-16
    Description: Motivation: The three-dimensional structure of genomes makes it possible for genomic regions not adjacent in the primary sequence to be spatially proximal. These DNA contacts have been found to be related to various molecular activities. Previous methods for analyzing DNA contact maps obtained from Hi-C experiments have largely focused on studying individual interactions, forming spatial clusters composed of contiguous blocks of genomic locations, or classifying these clusters into general categories based on some global properties of the contact maps. Results: Here, we describe a novel computational method that can flexibly identify small clusters of spatially proximal genomic regions based on their local contact patterns. Using simulated data that highly resemble Hi-C data obtained from real genome structures, we demonstrate that our method identifies spatial clusters that are more compact than methods previously used for clustering genomic regions based on DNA contact maps. The clusters identified by our method enable us to confirm functionally related genomic regions previously reported to be spatially proximal in different species. We further show that each genomic region can be assigned a numeric affinity value that indicates its degree of participation in each local cluster, and these affinity values correlate quantitatively with DNase I hypersensitivity, gene expression, super enhancer activities and replication timing in a cell type specific manner. We also show that these cluster affinity values can precisely define boundaries of reported topologically associating domains, and further define local sub-domains within each domain. Availability and implementation: The source code of BNMF and tutorials on how to use the software to extract local clusters from contact maps are available at http://yiplab.cse.cuhk.edu.hk/bnmf/ . Contact: kevinyip@cse.cuhk.edu.hk 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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  • 9
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    Group-combined P-values with applications to genetic association studies (2016)
    Oxford University Press
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    Publication Date: 2016-09-12
    Description: Motivation: In large-scale genetic association studies with tens of hundreds of single nucleotide polymorphisms (SNPs) genotyped, the traditional statistical framework of logistic regression using maximum likelihood estimator (MLE) to infer the odds ratios of SNPs may not work appropriately. This is because a large number of odds ratios need to be estimated, and the MLEs may be not stable when some of the SNPs are in high linkage disequilibrium. Under this situation, the P -value combination procedures seem to provide good alternatives as they are constructed on the basis of single-marker analysis. Results: The commonly used P -value combination methods (such as the Fisher’s combined test, the truncated product method, the truncated tail strength and the adaptive rank truncated product) may lose power when the significance level varies across SNPs. To tackle this problem, a group combined P -value method (GCP) is proposed, where the P -values are divided into multiple groups and then are combined at the group level. With this strategy, the significance values are integrated at different levels, and the power is improved. Simulation shows that the GCP can effectively control the type I error rates and have additional power over the existing methods—the power increase can be as high as over 50% under some situations. The proposed GCP method is applied to data from the Genetic Analysis Workshop 16. Among all the methods, only the GCP and ARTP can give the significance to identify a genomic region covering gene DSC3 being associated with rheumatoid arthritis, but the GCP provides smaller P -value. Availability and implementation: http://www.statsci.amss.ac.cn/yjscy/yjy/lqz/201510/t20151027_313273.html Contact: liqz@amss.ac.cn 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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  • 10
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    Leucine-rich repeat kinase 2 deficiency is protective in rhabdomyolysis-induced kidney injury (2015)
    Oxford University Press
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    Publication Date: 2015-06-23
    Description: Mutations in the leucine-rich repeat kinase 2 ( LRRK2 ) gene are the most common known genetic cause of Parkinson's disease, and LRRK2 is also linked to Crohn's and Hansen's disease. LRRK2 is expressed in many organs in mammals but is particularly abundant in the kidney. We find that LRRK2 protein is predominantly localized to collecting duct cells in the rat kidney, with much lower expression in other kidney cells. While genetic knockout (KO) of LRRK2 expression is well-tolerated in mice and rats, a unique age-dependent pathology develops in the kidney. The cortex and medulla of LRRK2 KO rat kidneys become darkly pigmented in early adulthood, yet aged animals display no overt signs of kidney failure. Accompanying the dark pigment we find substantial macrophage infiltration in LRRK2 KO kidneys, suggesting the presence of chronic inflammation that may predispose to kidney disease. Unexpectedly, the dark kidneys of the LRRK2 KO rats are highly resistant to rhabdomyolysis-induced acute kidney injury compared with wild-type rats. Biochemical profiling of the LRRK2 KO kidneys using immunohistochemistry, proteomic and lipidomic analyses show a massive accumulation of hemoglobin and lipofuscin in renal tubules that account for the pigmentation. The proximal tubules demonstrate a corresponding up-regulation of the cytoprotective protein heme oxygenase-1 (HO-1) which is capable of mitigating acute kidney injury. The unusual kidney pathology of LRRK2 KO rats highlights several novel physiological roles for LRRK2 and provides indirect evidence for HO-1 expression as a protective mechanism in acute kidney injury in LRRK2 deficiency.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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