50 research outputs found

    An integrated proteomic and metabolomic study on the gender-specific responses of mussels Mytilus galloprovincialis to tetrabromobisphenol A (TBBPA)

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    Tetrabromobisphenol A (TBBPA), accounting for the largest production of brominated flame-retardants (BFRs) along the Laizhou Bay in China, is of great concern due to its diverse toxicities. In this study, we focused on the gender-specific responses of TBBPA in mussel Mytilus galloprovincialis using an integrated proteomic and metabolomic approach. After exposure of TBBPA (10 mu g L-1) for one month, a total of 9 metabolites and 67 proteins were altered in mussel gills from exposed group. The significant changes of metabolites in female mussel gills from exposed group exhibited the disturbances in energy metabolism and osmotic regulation, while in male samples only be found the variation of metabolites related to osmotic regulation. iTRAQ-based proteomic analysis showed biological differences between male and female mussel gills from solvent control group. The higher levels of proteins related to primary and energy metabolism and defense mechanisms in male mussel gills meant a greater anti-stress capability of male mussels. Further analysis revealed that TBBPA exposure affected multiple biological processes consisting of production and development, material and energy metabolism, signal transduction, gene expression, defense mechanisms and apoptosis in both male and female mussels with different mechanisms. Specially, the responsive proteins of TBBPA in male mussels signified higher tolerance limits than those in female individuals, which was consistent with the biological differences between male and female mussel gills from solvent control group. This work suggested that the gender differences should be considered in ecotoxicology. (C) 2015 Elsevier Ltd. All rights reserved

    Pan-cancer analysis of whole genomes

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    Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

    Solid-State Camera System for Fluorescence Lifetime Microscopy

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    Fluorescence microscopy is a well-established platform for biology and biomedical research (Chapter 2). Based on this platform, fluorescence lifetime imaging microscopy (FLIM) has been developed to measure fluorescence lifetimes, which are independent of fluorophore concentration and excitation intensity and offer more information about the physical and chemical environment of the fluorophore (Chapter 3). The frequency domain FLIM technique offers fast acquisition times required for dynamic processes at the sub-cellular level. A conventional frequency-domain FLIM system employs a CCD camera and an image intensifier, the gain of which is modulated at the same frequency as the light source with a controlled phase shift (time delay). At the moment these systems, based on modulated image intensifiers, have disadvantages such as high cost, low image quality (distortions, low resolution), low quantum efficiency, prone to damage by overexposure, and require high voltage sources and RF amplifiers. These disadvantages complicate the visualization of small sub-cellular organelles that could provide valuable fundamental information concerning several human diseases (Chapter 3 and 4). In order to characterize the constraints involved in current fluorescent microscope systems that are used for lifetime as well as intensity measurements and to design and fabricate new systems, we have constructed a mathematical model to analyze the photon efficiency of frequency-domain fluorescence lifetime imaging microscopy (FLIM) (Chapter 5). The power of the light source needed for illumination in a FLIM system and the signalto-noise ratio (SNR) of the detector have led us to a photon “budget”. A light source of only a few milliWatts is sufficient for a FLIM system using fluorescein as an example. For every 100 photons emitted, around one photon will be converted to a photoelectron, leading to an estimate for the ideal SNR for one fluorescein molecule in an image as 5 (14 dB). We have performed experiments to validate the parameters and assumptions used in the mathematical model. The transmission efficiencies of the lenses, filters, and mirrors in the optical chain can be treated as constant parameters. The Beer-Lambert law is applicable to obtain the absorption factor in the mathematical model. The Poisson distribution assumption used in deducing the SNR is also valid. We have built compact FLIM systems based on new designs of CCD image sensors that can be modulated at the pixel level. Two different designs: the horizontal toggled MEM-FLIM1 camera and vertical toggled MEM-FLIM2 camera are introduced (Chapter 6). By using the camera evaluation techniques described in Chapter 7, these two versions of the MEM-FLIM systems are extensively studied and compared to the conventional image intensifier based FLIM system (Chapter 8). The low vertical charge transport efficiency limited the MEM-FLIM1 camera to perform lifetime experiments, however, the MEM-FLIM2 camera is a success. The MEM-FLIM2 camera not only gives comparable lifetime results with the reference intensifier based camera, but also shows a much better image quality and reveals more detailed structures in the biological samples. The novel MEM-FLIM systems are able to shorten the acquisition time since they allows recording of two phase images at once. The MEM-FLIM2 camera is, however, not perfect. It can only be modulated at a single frequency (25 MHz) and requires that the light source be switched off during readout due to an aluminum mask that had a smaller area than intended. A redesign of the architecture based on the vertical toggling concept leads to the MEM-FLIM3 camera (Chapter 9). Several improvements have been made in the sensor design for the MEMFLIM3 camera, such as higher fill factor, greater number of pixels etc. The MEM-FLIM3 camera is able to operate at higher frequencies (40, 60 and 80 MHz) and has an option for electron multiplication. Evaluations of this updated MEM-FLIM system are presented (Chapter 10). The images obtained from the MEM-FLIM3 camera at 20 and 40 MHz can be used directly for the lifetime calculation and the obtained lifetimes are comparable with the ones from the reference camera. There are, however, differences in the even and odd columns (20 MHz) and four image sections (40 MHz) for the intensity and lifetime images. For higher frequencies (60 and 80 MHz) calibrations are needed before calculating lifetimes. The lifetimes derived from the modulation depth after the calibrations are in a reasonable range while the lifetime derived from the phase cannot be used. At 60 and 80 MHz we can use one phase register from the MEM-FLIM3 camera for the lifetime calculation, the same way the reference camera operates. The lifetimes obtained by this method from the MEM-FLIM3 at 60 and 80 MHz are comparable with the ones from the reference camera. The MEM-FLIM3 camera also has an electron multiplication feature for low-light experimental condition. We could get approximately 500 times multiplication. Lifetime measurement using the EM function, however, has not been tested due to the limitation of the project time.Imaging Science & TechnologyApplied Science

    New Development of China’s National Evaluation Standard for Green Building (ESGB-2014)

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    In 2006, China published the first National Evaluation Standard for Green Building (ESGB), which soon became the most widely spread evaluation system in the country. With the fast growth of urbanization, ESGB 2006 version no longer meets the current needs and requires an update. Based on the implementation outcomes of ESGB 2006 and expert opinions, the Ministry of Housing and Urban-rural Development published a new version of ESGB in 2014 (ESGB 2014). This research reviews the previous cases of buildings accredited with ESGB 2006 and collects the facts and data to explain the implementation results and identifies its weakness of the ESGB 2006. A comparative analysis of the ESGB 2014 with ESGB 2006 is based on an in-depth overview of both ESGB 2014 and ESGB 2006. The comparison results shows the improvement of the current ESGB 2014 in details, i.e., evaluated object, stage partition, weighted value, structure, indicators, etc. A case study is followed by choosing one building project to evaluate and calculate the green building accreditation according to both ESGB 2014 and ESGB 2006, and demonstrate the differences and development of ESGB 2014.OLD Housing Quality and Process Innovatio

    Repair and generalization of hand-made 3D building models

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    Many 3D GIS applications require 3D building models with different LoD (Level of Detail) that satisfy certain quality criteria. However, because of their complexity, most detailed 3D building models available are still produced manually, which results in inevitable geometric and topological errors. These errors hinder the downstream processing of such models. And existing researches on LoD production either focus on the simplification of smooth polygonal mesh or the generalization of regular prismatic building models. The generalization of detailed 3D building models is still immature. Aiming at producing cleaned models of different LoD for existing hand-made 3D building models, this paper starts by investigating two typical modeling errors of such models, incompleteness and separation. Repair methods with reasonable assumptions of buildings are then proposed for each type of errors. The generalization method based on morphological operations is then employed, coupled with model repair, to generate error-free simplified models.OTB ResearchOTB Research Institute for the Built Environmen

    Analytical approach for determining the mean water level profile in an estuary with substantial fresh water discharge

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    The mean water level in estuaries rises in the landward direction due to a combination of the density gradient, the tidal asymmetry, and the backwater effect. This phenomenon is more prominent under an increase of the fresh water discharge, which strongly intensifies both the tidal asymmetry and the backwater effect. However, the interactions between tide and river flow and their individual contributions to the rise of the mean water level along the estuary are not yet completely understood. In this study, we adopt an analytical approach to describe the tidal wave propagation under the influence of substantial fresh water discharge, where the analytical solutions are obtained by solving a set of four implicit equations for the tidal damping, the velocity amplitude, the wave celerity, and the phase lag. The analytical model is used to quantify the contributions made by tide, river, and tide–river interaction to the water level slope along the estuary, which sheds new light on the generation of backwater due to tide–river interaction. Subsequently, the method is applied to the Yangtze estuary under a wide range of river discharge conditions where the influence of both tidal amplitude and fresh water discharge on the longitudinal variation of the mean tidal water level is explored. Analytical model results show that in the tide-dominated region the mean water level is mainly controlled by the tide–river interaction, while it is primarily determined by the river flow in the river-dominated region, which is in agreement with previous studies. Interestingly, we demonstrate that the effect of the tide alone is most important in the transitional zone, where the ratio of velocity amplitude to river flow velocity approaches unity. This has to do with the fact that the contribution of tidal flow, river flow, and tide–river interaction to the residual water level slope are all proportional to the square of the velocity scale. Finally, we show that, in combination with extreme-value theory (e.g. generalized extremevalue theory), the method may be used to obtain a first-order estimation of the frequency of extreme water levels relevant for water management and flood control. By presenting these analytical relations, we provide direct insight into the interaction between tide and river flow, which will be useful for the study of other estuaries that experience substantial river discharge in a tidal region.Water ManagementCivil Engineering and Geoscience

    DisQ: Disentangling Quantitative MRI Mapping of the Heart

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    Quantitative MRI (qMRI) of the heart has become an important clinical tool for examining myocardial tissue properties. Because heart is a moving object, it is usually imaged with electrocardiogram and respiratory gating during acquisition, to “freeze” its motion. In reality, gating is more-often-than-not imperfect given the heart rate variability and nonideal breath-hold. qMRI of the heart, consequently, is characteristic of varying image contrast as well as residual motion, the latter compromising the quality of quantitative mapping. Motion correction is an important step prior to parametric mapping, however, a long-standing difficulty for registering the dynamic sequence is that the contrast across frames varies wildly: depending on the acquisition scheme some frames can have extremely poor contrast, which fails both traditional optimization-based and modern learning-based registration methods. In this work, we propose a novel framework named DisQ, which Disentangles Quantitative mapping sequences into the latent space of contrast and anatomy, fully unsupervised. The disentangled latent spaces serve for the purpose of generating a series of images with identical contrast, which enables easy and accurate registration of all frames. We applied our DisQ method to the modified Look-Locker inversion recovery (MOLLI) sequence, and demonstrated improved performance of T1 mapping. In addition, we showed the possibility of generating a dynamic series of baseline images with exactly the same shape, strictly registered and perfectly “frozen". Our proposed DisQ methodology readily extends to other types of cardiac qMRI such as T2 mapping and perfusion.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.ImPhys/Medical Imagin

    Clarifying the Relationship between the Lithium Deposition Coverage and Microstructure in Lithium Metal Batteries

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    Improving the reversibility of lithium metal batteries is one of the challenges in current battery research. This requires better fundamental understanding of the evolution of the lithium deposition morphology, which is very complex due to the various parameters involved in different systems. Here, we clarify the fundamental origins of lithium deposition coverage in achieving highly reversible and compact lithium deposits, providing a comprehensive picture in the relationship between the lithium microstructure and solid electrolyte interphase (SEI) for lithium metal batteries. Systematic variation of the salt concentration offers a framework that brings forward the different aspects that play a role in cycling reversibility. Higher nucleation densities are formed in lower concentration electrolytes, which have the advantage of higher lithium deposition coverage; however, it goes along with the formation of an organic-rich instable SEI which is unfavorable for the reversibility during (dis)charging. On the other hand, the growth of large deposits benefiting from the formation of an inorganic-rich stable SEI is observed in higher concentration electrolytes, but the initial small nucleation density prevents full coverage of the current collector, thus compromising the plated lithium metal density. Taking advantages of the paradox, a nanostructured substrate is rationally applied, which increases the nucleation density realizing a higher deposition coverage and thus more compact plating at intermediate concentration (∼1.0 M) electrolytes, leading to extended reversible cycling of batteries. RST/Storage of Electrochemical EnergyRID/TS/Instrumenten groe

    Designing lithium halide solid electrolytes

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    All-solid-state lithium batteries have attracted widespread attention for next-generation energy storage, potentially providing enhanced safety and cycling stability. The performance of such batteries relies on solid electrolyte materials; hence many structures/phases are being investigated with increasing compositional complexity. Among the various solid electrolytes, lithium halides show promising ionic conductivity and cathode compatibility, however, there are no effective guidelines when moving toward complex compositions that go beyond ab-initio modeling. Here, we show that ionic potential, the ratio of charge number and ion radius, can effectively capture the key interactions within halide materials, making it possible to guide the design of the representative crystal structures. This is demonstrated by the preparation of a family of complex layered halides that combine an enhanced conductivity with a favorable isometric morphology, induced by the high configurational entropy. This work provides insights into the characteristics of complex halide phases and presents a methodology for designing solid materials.RST/Storage of Electrochemical EnergyRID/TS/Instrumenten groe
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