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  • Chromatin and Epigenetics  (13)
  • Other low-carbon energy technologies  (13)
  • Oxford University Press  (26)
  • 2015-2019  (26)
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  • Oxford University Press  (26)
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  • 2015-2019  (26)
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  • 2017
  • 2016  (26)
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  • 1
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    De novo deciphering three-dimensional chromatin interaction and topological domains by wavelet transformation of epigenetic profiles (2016)
    Oxford University Press
    Details
    Publication Date: 2016-06-21
    Description: Defining chromatin interaction frequencies and topological domains is a great challenge for the annotations of genome structures. Although the chromosome conformation capture (3C) and its derivative methods have been developed for exploring the global interactome, they are limited by high experimental complexity and costs. Here we describe a novel computational method, called CITD, for de novo prediction of the chromatin interaction map by integrating histone modification data. We used the public epigenomic data from human fibroblast IMR90 cell and embryonic stem cell (H1) to develop and test CITD, which can not only successfully reconstruct the chromatin interaction frequencies discovered by the Hi-C technology, but also provide additional novel details of chromosomal organizations. We predicted the chromatin interaction frequencies, topological domains and their states (e.g. active or repressive) for 98 additional cell types from Roadmap Epigenomics and ENCODE projects. A total of 131 protein-coding genes located near 78 preserved boundaries among 100 cell types are found to be significantly enriched in functional categories of the nucleosome organization and chromatin assembly. CITD and its predicted results can be used for complementing the topological domains derived from limited Hi-C data and facilitating the understanding of spatial principles underlying the chromosomal organization.
    Keywords: Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 2
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    Inducible DamID systems for genomic mapping of chromatin proteins in Drosophila (2016)
    Oxford University Press
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    Publication Date: 2016-07-09
    Description: Dam identification (DamID) is a powerful technique to generate genome-wide maps of chromatin protein binding. Due to its high sensitivity, it is particularly suited to study the genome interactions of chromatin proteins in small tissue samples in model organisms such as Drosophila . Here, we report an intein-based approach to tune the expression level of Dam and Dam-fusion proteins in Drosophila by addition of a ligand to fly food. This helps to suppress possible toxic effects of Dam. In addition, we describe a strategy for genetically controlled expression of Dam in a specific cell type in complex tissues. We demonstrate the utility of the latter by generating a glia-specific map of Polycomb in small samples of brain tissue. These new DamID tools will be valuable for the mapping of binding patterns of chromatin proteins in Drosophila tissues and especially in cell lineages.
    Keywords: Chromatin and Epigenetics
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    Topics: Biology
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  • 3
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    Review of heat pipe heat exchangers for enhanced dehumidification and cooling in air conditioning systems (2016)
    Oxford University Press
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    Publication Date: 2016-08-26
    Description: Heat pipe heat exchangers could be employed as run-around coils in air conditioning systems for enhanced dehumidification and cooling. This article reviews some of the works conducted on the cooling and dehumidification aspects in various air conditioning systems. They have been proved to be effective in enhancing dehumidification and reducing air conditioning costs especially in hot and humid tropical countries.
    Keywords: Other low-carbon energy technologies
    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
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  • 4
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    Towards clean and sustainable distributed energy system: the potential of integrated PEMFC-CHP (2016)
    Oxford University Press
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    Publication Date: 2016-08-26
    Description: The mitigation options to meet the ambitious carbon reduction targets set by the UK government are discussed in this paper, including the use of carbon capture and storage (CCS) technology, clean renewable energy integration and a proposed system of integrated fuel cell combined heat and power (FC-CHP) technology. Analysis shows that the use of CCS technology within the current infrastructure can abate half the electricity-associated CO 2 emissions; however, this comes at a high cost penalty. The emissions associated with domestic heat cannot be prevented without changes in the energy infrastructure. Hydrogen-powered fuel cells can provide clean energy at a range of scales and high efficiencies, especially when employed with a CHP system. However, production of CO 2 -free hydrogen is essential for fuel cell technology to contribute substantially to a low carbon economy globally. In this work, three methods were investigated for small-scale distributed hydrogen production, namely steam methane reforming, water electrolysis (WE) and cold plasma jet (CPJ). The criteria used for comparisons include the associated CO 2 emissions and the cost of energy production. CPJ decomposition of methane shows a high potential when combined with integrated FC-CHP technology for economically viable and CO 2 -free generation of energy, especially in comparison to WE. Including the value of the solid carbon product makes the plasma system most attractive economically.
    Keywords: Other low-carbon energy technologies
    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
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  • 5
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    Endoreversible modeling and optimization of multistage isothermal chemical engines under linear mass transfer law via Hamilton-Jacobi-Bellman theory (2016)
    Oxford University Press
    Details
    Publication Date: 2016-08-26
    Description: A multistage continuous isothermal endoreversible chemical engine system with a finite driving fluid is investigated in this paper, and the mass transfer law obeys the linear mass transfer law [ $$g\propto \mathrm{\Delta }\mu $$ ]. Under the condition that both the initial time and the initial key component concentration in the driving fluid are fixed, the maximum power output of the multistage chemical engine system and the corresponding optimal concentration configuration of the key component in the driving fluid are derived by applying Hamilton–Jacobi–Bellman (HJB) theory, and numerical examples for three different boundary conditions are given. The results show that the difference between the chemical potential of the key component and the Carnot chemical potential for the maximum power output is a constant, and the key component concentration in the driving fluid decreases with the increase of time nonlinearly; when both the process period and the final concentration of the key component are fixed, there is an optimal control strategy for the maximum power output of the multistage chemical engine system, and the maximum power outputs of the system and the corresponding optimal control strategies are different for different final concentrations. The obtained results can provide some theoretical guidelines for the optimal designs and operations of practical energy conversion systems.
    Keywords: Other low-carbon energy technologies
    Print ISSN: 1748-1317
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    Topics: Energy, Environment Protection, Nuclear Power Engineering , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
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  • 6
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    Thermodynamic analysis and optimization of the Atkinson engine by using NSGA-II (2016)
    Oxford University Press
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    Publication Date: 2016-08-26
    Description: Recently, several studies have been conducted regarding the Atkinson cycle and Atkinson engine which have resulted in various thermal efficiency and output power analysis. In the present study, output power and engine thermal efficiency are maximized via employing the NSGA-II approach and thermodynamic analysis. The multi-objective evolutionary approach on the basis of the NSGA-II method is implemented throughout this work for optimizing the above-mentioned variables. To evaluate the aforementioned goal, two objective functions which comprises the power output ( W ) and cycle efficiency ( ) have been included in the optimization process simultaneously.
    Keywords: Other low-carbon energy technologies
    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
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  • 7
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    Establishment of a promoter-based chromatin architecture on recently replicated DNA can accommodate variable inter-nucleosome spacing (2016)
    Oxford University Press
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    Publication Date: 2016-09-03
    Description: Nucleosomes, the fundamental subunits of eukaryotic chromatin, are organized with respect to transcriptional start sites. A major challenge to the persistence of this organization is the disassembly of nucleosomes during DNA replication. Here, we use complimentary approaches to map the locations of nucleosomes on recently replicated DNA. We find that nucleosomes are substantially realigned with promoters during the minutes following DNA replication. As a result, the nucleosomal landscape is largely re-established before newly replicated chromosomes are partitioned into daughter cells and can serve as a platform for the re-establishment of gene expression programmes. When the supply of histones is disrupted through mutation of the chaperone Caf1, a promoter-based architecture is generated, but with increased inter-nucleosomal spacing. This indicates that the chromatin remodelling enzymes responsible for spacing nucleosomes are capable of organizing nucleosomes with a range of different linker DNA lengths.
    Keywords: Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 8
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    NEpiC: a network-assisted algorithm for epigenetic studies using mean and variance combined signals (2016)
    Oxford University Press
    Details
    Publication Date: 2016-09-20
    Description: DNA methylation plays an important role in many biological processes. Existing epigenome-wide association studies (EWAS) have successfully identified aberrantly methylated genes in many diseases and disorders with most studies focusing on analysing methylation sites one at a time. Incorporating prior biological information such as biological networks has been proven to be powerful in identifying disease-associated genes in both gene expression studies and genome-wide association studies (GWAS) but has been under studied in EWAS. Although recent studies have noticed that there are differences in methylation variation in different groups, only a few existing methods consider variance signals in DNA methylation studies. Here, we present a network-assisted algorithm, NEpiC, that combines both mean and variance signals in searching for differentially methylated sub-networks using the protein–protein interaction (PPI) network. In simulation studies, we demonstrate the power gain from using both the prior biological information and variance signals compared to using either of the two or neither information. Applications to several DNA methylation datasets from the Cancer Genome Atlas (TCGA) project and DNA methylation data on hepatocellular carcinoma (HCC) from the Columbia University Medical Center (CUMC) suggest that the proposed NEpiC algorithm identifies more cancer-related genes and generates better replication results.
    Keywords: Chromatin and Epigenetics
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    Topics: Biology
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  • 9
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    Single base resolution analysis of 5-hydroxymethylcytosine in 188 human genes: implications for hepatic gene expression (2016)
    Oxford University Press
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    Publication Date: 2016-08-20
    Description: To improve the epigenomic analysis of tissues rich in 5-hydroxymethylcytosine (hmC), we developed a novel protocol called TAB-Methyl-SEQ, which allows for single base resolution profiling of both hmC and 5-methylcytosine by targeted next-generation sequencing. TAB-Methyl-SEQ data were extensively validated by a set of five methodologically different protocols. Importantly, these extensive cross-comparisons revealed that protocols based on Tet1-assisted bisulfite conversion provided more precise hmC values than TrueMethyl-based methods. A total of 109 454 CpG sites were analyzed by TAB-Methyl-SEQ for mC and hmC in 188 genes from 20 different adult human livers. We describe three types of variability of hepatic hmC profiles: (i) sample-specific variability at 40.8% of CpG sites analyzed, where the local hmC values correlate to the global hmC content of livers (measured by LC-MS), (ii) gene-specific variability, where hmC levels in the coding regions positively correlate to expression of the respective gene and (iii) site-specific variability, where prominent hmC peaks span only 1 to 3 neighboring CpG sites. Our data suggest that both the gene- and site-specific components of hmC variability might contribute to the epigenetic control of hepatic genes. The protocol described here should be useful for targeted DNA analysis in a variety of applications.
    Keywords: Chromatin and Epigenetics
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    Topics: Biology
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  • 10
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    Control of micro-CHP and thermal energy storage for minimising electrical grid utilisation (2016)
    Oxford University Press
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    Publication Date: 2016-02-05
    Description: The efficient use of combined heat and power (CHP) systems in buildings presents a control challenge due to their simultaneous production of thermal and electrical energy. The use of thermal energy storage coupled with a CHP engine provides an interesting solution to the problem—the electrical demands of the building can be matched by the CHP engine, while the resulting thermal energy can be regulated by the thermal energy store. Based on the thermal energy demands of the building the thermal store can provide extra thermal energy or absorb surplus thermal energy production. This paper presents a multi-input multi-output inverse-dynamics-based control strategy that will minimise the electrical grid utilisation of a building, while simultaneously maintaining a defined operative temperature. Electrical demands from lighting and appliances within the building are considered. In order to assess the performance of the control strategy, a European Standard validated simplified dynamic building physics model is presented that provides verified heating demands. Internal heat gains from solar radiation and internal loads are included within the model. Results indicate the control strategy is effective in minimising the electrical grid use and maximising the utilisation of the available energy when compared with conventional heating systems.
    Keywords: Other low-carbon energy technologies
    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
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  • 11
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    Thermodynamic optimization of a triple-shaft open intercooled, recuperated gas turbine cycle. Part 2: power and efficiency optimization (2016)
    Oxford University Press
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    Publication Date: 2016-02-05
    Description: The power and the efficiency of a triple-shaft open intercooled, recuperated gas turbine cycle are analyzed and optimized based on the model established using thermodynamic optimization theory in Part 1 of this paper by adjusting the low-pressure compressor inlet relative pressure drop, the mass flow rate and the distribution of pressure losses along the flow path. First, the power output is optimized by adjusting the intercooling pressure ratio, the air mass flow rate or the distribution of pressure losses along the flow path. Second, the thermodynamic first-law efficiency is optimized subject to a fixed fuel flow rate and a fixed overall size by seeking the optimal intercooling pressure ratio, the compressor inlet pressure drop and optimal flow area allocation ratio between the low-pressure compressor inlet and the power turbine outlet. The numerical examples show that increase in effectiveness of intercooler increases power output and its corresponding efficiency and increase in effectiveness of recuperator decreases power output appreciably but increases its corresponding efficiency; there exist an optimal low-pressure compressor inlet relative pressure drop and an optimal intercooling pressure ratio, which lead to a maximum power. For a fixed fuel mass rate and a fixed overall area of low-pressure compressor inlet and power turbine outlet, maximum thermodynamic first-law efficiency is obtained by optimizing low-pressure compressor inlet relative pressure drop and intercooling pressure ratio. The double-maximum thermodynamic first-law efficiency is obtained by searching optimal flow area allocation between low-pressure compressor inlet and power turbine outlet.
    Keywords: Other low-carbon energy technologies
    Print ISSN: 1748-1317
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    Topics: Energy, Environment Protection, Nuclear Power Engineering , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
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  • 12
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    Transient simulation of a solar absorption cooling system (2016)
    Oxford University Press
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    Publication Date: 2016-02-05
    Description: With non-renewable energy sources depleting quickly, solar energy could prove a viable option owing to its abundance and eco-friendliness. Modeling and simulation of a solar energy-driven single-stage absorption chiller was carried out using the transient simulation software ‘TRNSYS’. An evacuated tube collector coupled with an insulated tank served as heat source for the absorption chiller. Experiments were conducted to evaluate the efficiency parameters of the collector as well as the loss coefficient for the storage tank. These parameters along with standard chiller performance data were used to model the system. The influence of climatic conditions, storage capacity and various control schemes with and without auxiliary heating on the output of the system is analyzed and presented in the paper.
    Keywords: Other low-carbon energy technologies
    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
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  • 13
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    Thermochemical cooling system based on adsorption pumping pipe (2016)
    Oxford University Press
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    Publication Date: 2016-02-05
    Description: Based upon the theoretical principle of the thermochemical energy storage pumping pipe system, a new cooling system has been presented. In order to analyse the performance and design of the system based on adsorption pumping pipe process, a simplified mathematical model is developed. Both simulation and experimental results are given and discussed. The comparison of various methods (ammonium dissolves, evaporation of CO 2 , etc.) showed that it is the simplest and most reliable to use adsorbents such as zeolite in this cooling system. A total of 250 g zeolite 13X could reduce the temperature of 330 ml by 15°C in 2–3 min (for beverage self-cooling applications). For future work, a large scale demonstration system is required to prove the viability and long term performance of thermochemical cooling/energy storage system.
    Keywords: Other low-carbon energy technologies
    Print ISSN: 1748-1317
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    Topics: Energy, Environment Protection, Nuclear Power Engineering , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
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  • 14
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    Thermodynamic optimization of a triple-shaft open intercooled-recuperated gas turbine cycle. Part 1: description and modeling (2016)
    Oxford University Press
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    Publication Date: 2016-02-05
    Description: Considering the flow processes of the working fluid with the pressure drops, a thermodynamic model for a triple-shaft open intercooled-recuperated gas turbine cycle is established using thermodynamic optimization theory in Part 1 of this paper. The relative pressure drops associated with the flow through various cross-sectional areas are derived as functions of the low-pressure compressor inlet relative pressure drop. The analytical formulae of the cycle's power and efficiency are derived. The performance of the model cycle is optimized by adjusting the compressor inlet pressure, the mass flow rate and the distribution of pressure losses along the flow path in Part 2 of this paper.
    Keywords: Other low-carbon energy technologies
    Print ISSN: 1748-1317
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    Topics: Energy, Environment Protection, Nuclear Power Engineering , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
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  • 15
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    Genome-wide profiling of nucleosome sensitivity and chromatin accessibility in Drosophila melanogaster (2016)
    Oxford University Press
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    Publication Date: 2016-02-20
    Description: Nucleosomal DNA is thought to be generally inaccessible to DNA-binding factors, such as micrococcal nuclease (MNase). Here, we digest Drosophila chromatin with high and low concentrations of MNase to reveal two distinct nucleosome types: MNase-sensitive and MNase-resistant. MNase-resistant nucleosomes assemble on sequences depleted of A/T and enriched in G/C-containing dinucleotides, whereas MNase-sensitive nucleosomes form on A/T-rich sequences found at transcription start and termination sites, enhancers and DNase I hypersensitive sites. Estimates of nucleosome formation energies indicate that MNase-sensitive nucleosomes tend to be less stable than MNase-resistant ones. Strikingly, a decrease in cell growth temperature of about 10°C makes MNase-sensitive nucleosomes less accessible, suggesting that observed variations in MNase sensitivity are related to either thermal fluctuations of chromatin fibers or the activity of enzymatic machinery. In the vicinity of active genes and DNase I hypersensitive sites nucleosomes are organized into periodic arrays, likely due to ‘phasing’ off potential barriers formed by DNA-bound factors or by nucleosomes anchored to their positions through external interactions. The latter idea is substantiated by our biophysical model of nucleosome positioning and energetics, which predicts that nucleosomes immediately downstream of transcription start sites are anchored and recapitulates nucleosome phasing at active genes significantly better than sequence-dependent models.
    Keywords: Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 16
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    ENmix: a novel background correction method for Illumina HumanMethylation450 BeadChip (2016)
    Oxford University Press
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    Publication Date: 2016-02-20
    Description: The Illumina HumanMethylation450 BeadChip is increasingly utilized in epigenome-wide association studies, however, this array-based measurement of DNA methylation is subject to measurement variation. Appropriate data preprocessing to remove background noise is important for detecting the small changes that may be associated with disease. We developed a novel background correction method, ENmix, that uses a mixture of exponential and truncated normal distributions to flexibly model signal intensity and uses a truncated normal distribution to model background noise. Depending on data availability, we employ three approaches to estimate background normal distribution parameters using (i) internal chip negative controls, (ii) out-of-band Infinium I probe intensities or (iii) combined methylated and unmethylated intensities. We evaluate ENmix against other available methods for both reproducibility among duplicate samples and accuracy of methylation measurement among laboratory control samples. ENmix out-performed other background correction methods for both these measures and substantially reduced the probe-design type bias between Infinium I and II probes. In reanalysis of existing EWAS data we show that ENmix can identify additional CpGs, and results in smaller P -value estimates for previously-validated CpGs. We incorporated the method into R package ENmix , which is freely available from Bioconductor website.
    Keywords: Chromatin and Epigenetics
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  • 17
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    Power and power density analyzes of an endoreversible modified variable-temperature reservoir Brayton cycle with isothermal heat addition (2016)
    Oxford University Press
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    Publication Date: 2016-02-05
    Description: The mistakes in recent literatures are analyzed, and a new model for an endoreversible closed modified Brayton cycle with isothermal heat addition coupled to variable-temperature reservoirs is established using finite-time thermodynamics in this paper. The range of isothermal heat addition modification is determined, and the analytical formulae of the dimensionless power output, thermal efficiency and dimensionless power density of the cycle are derived. The effects of the cycle parameters on the global performances of power output and power density and the performances at maximum power design and maximum power density are analyzed by numerical calculations. The results show that there exist optimal compressor pressure ratios, respectively, which lead to maximum dimensionless power output and maximum dimensionless power density, that the optimal compressor pressure ratio and the thermal efficiency at maximum power design are always smaller than the corresponding ones at maximum power density design, and that dimensionless power output and maximum specific volume at maximum power design are always bigger than the corresponding ones at maximum power density design. The results imply that the power density design possesses the advantages such as smaller equipment volume and higher thermal efficiency at the cost of disadvantages such as bigger compressor pressure ratio and power output loss. Maximizing the power density gives a compromise between power and the size of the engine. The calculations also show that an endoreversible closed modified Brayton cycle with isothermal heat addition cannot work at the maximum thermal efficiency design point.
    Keywords: Other low-carbon energy technologies
    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
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    Identification of a small-molecule ligand of the epigenetic reader protein Spindlin1 via a versatile screening platform (2016)
    Oxford University Press
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    Publication Date: 2016-05-20
    Description: Epigenetic modifications of histone tails play an essential role in the regulation of eukaryotic transcription. Writer and eraser enzymes establish and maintain the epigenetic code by creating or removing posttranslational marks. Specific binding proteins, called readers, recognize the modifications and mediate epigenetic signalling. Here, we present a versatile assay platform for the investigation of the interaction between methyl lysine readers and their ligands. This can be utilized for the screening of small-molecule inhibitors of such protein–protein interactions and the detailed characterization of the inhibition. Our platform is constructed in a modular way consisting of orthogonal in vitro binding assays for ligand screening and verification of initial hits and biophysical, label-free techniques for further kinetic characterization of confirmed ligands. A stability assay for the investigation of target engagement in a cellular context complements the platform. We applied the complete evaluation chain to the Tudor domain containing protein Spindlin1 and established the in vitro test systems for the double Tudor domain of the histone demethylase JMJD2C. We finally conducted an exploratory screen for inhibitors of the interaction between Spindlin1 and H3K4me3 and identified A366 as the first nanomolar small-molecule ligand of a Tudor domain containing methyl lysine reader.
    Keywords: Chromatin and Epigenetics
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    Topics: Biology
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    Substantial DNA methylation differences between two major neuronal subtypes in human brain (2016)
    Oxford University Press
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    Publication Date: 2016-04-08
    Description: The brain is built from a large number of cell types which have been historically classified using location, morphology and molecular markers. Recent research suggests an important role of epigenetics in shaping and maintaining cell identity in the brain. To elucidate the role of DNA methylation in neuronal differentiation, we developed a new protocol for separation of nuclei from the two major populations of human prefrontal cortex neurons—GABAergic interneurons and glutamatergic (GLU) projection neurons. Major differences between the neuronal subtypes were revealed in CpG, non-CpG and hydroxymethylation (hCpG). A dramatically greater number of undermethylated CpG sites in GLU versus GABA neurons were identified. These differences did not directly translate into differences in gene expression and did not stem from the differences in hCpG methylation, as more hCpG methylation was detected in GLU versus GABA neurons. Notably, a comparable number of undermethylated non-CpG sites were identified in GLU and GABA neurons, and non-CpG methylation was a better predictor of subtype-specific gene expression compared to CpG methylation. Regions that are differentially methylated in GABA and GLU neurons were significantly enriched for schizophrenia risk loci. Collectively, our findings suggest that functional differences between neuronal subtypes are linked to their epigenetic specification.
    Keywords: Chromatin and Epigenetics
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  • 20
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    Standardizing chromatin research: a simple and universal method for ChIP-seq (2016)
    Oxford University Press
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    Publication Date: 2016-04-21
    Description: Chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) is a key technique in chromatin research. Although heavily applied, existing ChIP-seq protocols are often highly fine-tuned workflows, optimized for specific experimental requirements. Especially the initial steps of ChIP-seq, particularly chromatin shearing, are deemed to be exceedingly cell-type-specific, thus impeding any protocol standardization efforts. Here we demonstrate that harmonization of ChIP-seq workflows across cell types and conditions is possible when obtaining chromatin from properly isolated nuclei. We established an ultrasound-based nuclei extraction method (NEXSON: Nuclei EXtraction by SONication) that is highly effective across various organisms, cell types and cell numbers. The described method has the potential to replace complex cell-type-specific, but largely ineffective, nuclei isolation protocols. By including NEXSON in ChIP-seq workflows, we completely eliminate the need for extensive optimization and sample-dependent adjustments. Apart from this significant simplification, our approach also provides the basis for a fully standardized ChIP-seq and yields highly reproducible transcription factor and histone modifications maps for a wide range of different cell types. Even small cell numbers (~10 000 cells per ChIP) can be easily processed without application of modified chromatin or library preparation protocols.
    Keywords: Chromatin and Epigenetics
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    Topics: Biology
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  • 21
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    Differential peak calling of ChIP-seq signals with replicates with THOR (2016)
    Oxford University Press
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    Publication Date: 2016-12-01
    Description: The study of changes in protein–DNA interactions measured by ChIP-seq on dynamic systems, such as cell differentiation, response to treatments or the comparison of healthy and diseased individuals, is still an open challenge. There are few computational methods comparing changes in ChIP-seq signals with replicates. Moreover, none of these previous approaches addresses ChIP-seq specific experimental artefacts arising from studies with biological replicates. We propose THOR, a Hidden Markov Model based approach, to detect differential peaks between pairs of biological conditions with replicates. THOR provides all pre- and post-processing steps required in ChIP-seq analyses. Moreover, we propose a novel normalization approach based on housekeeping genes to deal with cases where replicates have distinct signal-to-noise ratios. To evaluate differential peak calling methods, we delineate a methodology using both biological and simulated data. This includes an evaluation procedure that associates differential peaks with changes in gene expression as well as histone modifications close to these peaks. We evaluate THOR and seven competing methods on data sets with distinct characteristics from in vitro studies with technical replicates to clinical studies of cancer patients. Our evaluation analysis comprises of 13 comparisons between pairs of biological conditions. We show that THOR performs best in all scenarios.
    Keywords: Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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    Effects of thermocouples physical size on the performance of the TEG-TEH system (2016)
    Oxford University Press
    Details
    Publication Date: 2016-08-26
    Description: The effects of thermocouples physical size on the performance of a thermoelectric heat pump (TEH) driven by a thermoelectric generator (TEG) device are investigated in this article. The physical size refers to the length and the cross-sectional area of the thermocouples. The performance analysis is multiobjective, including stable electrical current, heating load, coefficient of performance, maximum heating load and maximum heating temperature difference. A characteristic parameter, i.e. area–length ratio, is defined to describe the thermocouples physical size. The influences of the parameter are analyzed by detailed numerical examples. A practical example is proposed to show how to select appropriate thermoelectric modules (TEMs) to construct a high-performance TEG–TEH system satisfying different requirements. The results show that an improvement in its performance is possible by optimizing internal physical size of thermocouples. The conclusion obtained could be used for the selection of TEMs and the design of the TEG–TEH system.
    Keywords: Other low-carbon energy technologies
    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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    Effect of the working liquid to the capillary pumped loop performance (2016)
    Oxford University Press
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    Publication Date: 2016-08-26
    Description: The purpose of this paper is to present a theoretical analysis of the capillary pumped loop (CPL) performance using different working liquids. CPL is a passive heat transfer device, using no mechanical pump to circulate the working liquid, usually composed of a liquid tank, an evaporator, a condenser, a liquid and a vapor line. Heat load is applied on the external surface of the evaporator, partially transferred to the wick inside. Because of this heat load capillary forces are developed inside the porous structure, due to meniscus formation between liquid and vapor surface of the liquid, causing a pressure oscillation capable to pump the flow out of the evaporator. In this paper CPL performance is evaluated using different working liquids, such as water, ammonia, acetone and freon-134. These have different thermophysical properties such as latent heat, viscosity and density, causing different behavior when used as working liquid. Water was found more stable for higher temperature differences, due to higher latent heat of vaporization, while ammonia could take advantage of its viscosity for small temperature differences.
    Keywords: Other low-carbon energy technologies
    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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  • 24
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    Design and optimization of a thermoacoustic heat engine using reinforcement learning (2016)
    Oxford University Press
    Details
    Publication Date: 2016-08-26
    Description: The thermoacoustic heat engine (TAHE) is a type of prime mover that converts thermal power to acoustic power. It is composed of two heat exchangers (the devices heat source and sink), some kind of porous medium where the conversion of power takes place and a tube that houses the acoustic wave produced. Its simple design and the fact that it is one of a few prime movers that do not require moving parts make such a device an attractive alternative for many practical applications. The acoustic power produced by the TAHE can be used to generate electricity, drive a heat pump or a refrigeration system. Although the geometry of the TAHE is simple, the behavior of the engine is complex with 30+ design parameters that affect the performance of the device; therefore, designing such a device remains a significant challenge. In this work, a radical design methodology using reinforcement learning (RL) is employed for the design and optimization of a TAHE for the first time. Reinforcement learning is a machine learning technique that allows optimization by specifying ‘good’ and ‘bad’ behavior using a simple reward scheme r . Although its framework is simple, it has proved to be a very powerful tool in solving a wide range of complex decision-making/optimization problems. The RL technique employed by the agent in this work is known as Q-learning. Preliminary results have shown the potential of the RL technique to solve this type of complex design problem, as the RL agent was able to figure out the correct configuration of components that would create positive acoustic power output. The learning agent was able to create a design that yielded an acoustic power output of 643.31 W with a thermal efficiency of 3.29%. It is eventually hoped that with increased understanding of the design problem, in terms of the RL framework, it will be possible to ultimately create an autonomous RL agent for the design and optimization of complex TAHEs with minimal predefined conditions/restrictions.
    Keywords: Other low-carbon energy technologies
    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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    PAtCh-Cap: input strategy for improving analysis of ChIP-exo data sets and beyond (2016)
    Oxford University Press
    Details
    Publication Date: 2016-12-04
    Description: Recently, a number of advances have been implemented into the core ChIP-seq (chromatin immunoprecipitation coupled with next-generation sequencing) methodology to streamline the process, reduce costs or improve data resolution. Several of these emerging ChIP-based methods perform additional chemical steps on bead-bound immunoprecipitated chromatin, posing a challenge for generating similarly treated input controls required for artifact removal during bioinformatics analyses. Here we present a versatile method for producing technique-specific input controls for ChIP-based methods that utilize additional bead-bound processing steps. This reported method, termed protein attached chromatin capture (PAtCh-Cap), relies on the non-specific capture of chromatin-bound proteins via their carboxylate groups, leaving the DNA accessible for subsequent chemical treatments in parallel with chromatin separately immunoprecipitated for the target protein. Application of this input strategy not only significantly enhanced artifact removal from ChIP-exo data, increasing confidence in peak identification and allowing for de novo motif searching, but also afforded discovery of a novel CTCF binding motif.
    Keywords: Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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    Quantification of DNA cleavage specificity in Hi-C experiments (2016)
    Oxford University Press
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    Publication Date: 2016-01-09
    Description: Hi-C experiments produce large numbers of DNA sequence read pairs that are typically analyzed to deduce genomewide interactions between arbitrary loci. A key step in these experiments is the cleavage of cross-linked chromatin with a restriction endonuclease. Although this cleavage should happen specifically at the enzyme's recognition sequence, an unknown proportion of cleavage events may involve other sequences, owing to the enzyme's star activity or to random DNA breakage. A quantitative estimation of these non-specific cleavages may enable simulating realistic Hi-C read pairs for validation of downstream analyses, monitoring the reproducibility of experimental conditions and investigating biophysical properties that correlate with DNA cleavage patterns. Here we describe a computational method for analyzing Hi-C read pairs to estimate the fractions of cleavages at different possible targets. The method relies on expressing an observed local target distribution downstream of aligned reads as a linear combination of known conditional local target distributions. We validated this method using Hi-C read pairs obtained by computer simulation. Application of the method to experimental Hi-C datasets from murine cells revealed interesting similarities and differences in patterns of cleavage across the various experiments considered.
    Keywords: Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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