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  • 1
    Publication Date: 2018-11-01
    Description: Thermally induced deterioration behaviour can cause severe weathering in marbles. Most previous studies focus on the deterioration behaviour of calcitic marbles. Relevant studies of dolomitic marbles are generally carried out under a ‘high temperature and low cycling times' condition. Little attention is focused on the deterioration behaviour in dolomitic marbles when they are subjected to a large quantity of heating–cooling cycles under a ‘low temperature and high cycling times’ condition. This paper presents experimental investigations on the thermally induced deterioration behaviour of two Beijing dolomitic marbles (Qingbaishi Marble (QM) and Hanbaiyu Marble (HM)) under heating–cooling cycles up to 1000 cycling times. The applied temperature range is from –20°C to 60°C which is to simulate the seasonal temperature variations in Beijing city, China. Related properties such as weight loss, three-dimensional microtopography, elastic wave velocity and uniaxial compressive strength were measured at certain cycles. The results indicate that thermally induced deterioration behaviour will result in a continuous weight loss in dolomitic marble samples. Mechanical properties of those two marbles are strongly affected by heating and cooling treatments, which were reflected by the reductions of dynamic Young's modulus and uniaxial compressive strength with an increase of thermal cycles. Compared with QM, HM displays a higher level of thermally induced deterioration which should be due to the abundance of quartz mineral.
    Keywords: engineering geology
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 2
    Publication Date: 2018-01-09
    Description: T follicular helper (Tfh) cells play an essential role in the formation of germinal centers (GC) and generation of high-affinity Abs. The homing of activated CD4 + T cells into B cell follicles and the involvement of key costimulatory and coinhibitory molecules are critical in controlling both the initiation and the magnitude of GC responses. Meanwhile, studies have shown that a high number of single clone B cells leads to intraclonal competition, which inhibits the generation of high-affinity Abs. Our previous work has shown that transcription factor Foxp1 is a critical negative regulator of Tfh cell differentiation. In this study, we report that the deletion of Foxp1 leads to a high proportion of activated CD4 + T cells homing into B cell follicles with faster kinetics, resulting in earlier GC formation. In addition, we show that Foxp1-deficient Tfh cells restore the generation of high-affinity Abs when cotransferred with high numbers of single clone B cells. We find that Foxp1 regulates the expression levels of cytotoxic T lymphocyte–associated Ag-4 (CTLA-4) in activated CD4 + T cells and that Ctla4 is a direct Foxp1 target. Finally, we demonstrate that CTLA-4 expression on conventional CD4 + T cells plays a cell-intrinsic role in Tfh cell differentiation in vivo, and CTLA-4 blockade helps abolish the intraclonal competition of B cells in generating high-affinity Abs.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 3
    Keywords: evaluation ; Germany ; human ; MODEL ; MODELS ; ALGORITHM ; ALGORITHMS ; CLASSIFICATION ; COMMON ; CT ; IMAGES ; imaging ; segmentation ; SYSTEM ; SYSTEMS ; liver ; ACCURACY ; validation ; image analysis ; PERFORMANCE ; score ; EFFICIENT ; DATABASE ; REGISTRATION ; VARIABILITY ; DEFORMATION ; radiology ; TECHNOLOGY ; USA ; ERROR ; CLASSIFIERS ; WELL ; Statistical shape model ; DIAGNOSTIC SYSTEM ; FREE-FORM DEFORMATIONS ; IMAGE SEGMENTATION ; SHAPE MODELS
    Abstract: This paper presents a comparison study between 10 automatic and six interactive methods for liver segmentation from contrast-enhanced CT images. It is based on results from the "MICCAI 2007 Grand Challenge" workshop, where 16 teams evaluated their algorithms on a common database. A collection of 20 clinical images with reference segmentations was provided to train and tune algorithms in advance. Participants were also allowed to use additional proprietary training data for that purpose. All teams then had to apply their methods to 10 test datasets and submit the obtained results. Employed algorithms include statistical shape models, atlas registration, level-sets, graph-cuts and rule-based systems. All results were compared to reference segmentations five error measures that highlight different aspects of segmentation accuracy. All measures were combined according to a specific scoring system relating the obtained values to human expert variability. In general, interactive methods reached higher average scores than automatic approaches and featured a better consistency of segmentation quality. However, the best automatic methods (mainly based on statistical shape models with some additional free deformation) could compete well on the majority of test images. The study provides an insight in performance of different segmentation approaches under real-world conditions and highlights achievements and limitations of current image analysis techniques
    Type of Publication: Journal article published
    PubMed ID: 19211338
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  • 4
    Publication Date: 2018-07-03
    Description: We employ the language of Bayesian networks to systematically construct gene-regulation topologies from deep-sequencing single-nucleus RNA-Seq data for human neurons. From the perspective of the cell-state potential landscape, we identify attractors that correspond closely to different neuron subtypes. Attractors are also recovered for cell states from an independent data set confirming our models accurate description of global genetic regulations across differing cell types of the neocortex (not included in the training data). Our model recovers experimentally confirmed genetic regulations and community analysis reveals genetic associations in common pathways. Via a comprehensive scan of all theoretical three-gene perturbations of gene knockout and overexpression, we discover novel neuronal trans -differrentiation recipes (including perturbations of SATB2, GAD1, POU6F2 and ADARB2) for excitatory projection neuron and inhibitory interneuron subtypes.
    Electronic ISSN: 2160-1836
    Topics: Biology
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  • 5
    Publication Date: 2018-08-17
    Description: Shuang Li, Yong Suk Cho, Bing Wang, Shuangxi Li, and Jin Jiang Hedgehog (Hh) transduces signals by promoting cell surface accumulation and activation of the G-protein-coupled receptor (GPCR)-family protein Smoothened (Smo) in Drosophila , but the molecular mechanism underlying the regulation of Smo trafficking remains poorly understood. Here, we identified the Cul4–DDB1 E3 ubiquitin ligase complex as being essential for Smo ubiquitylation and cell surface clearance. We found that the C-terminal intracellular domain of Smo recruits Cul4–DDB1 through the β subunit of trimeric G protein (Gβ), and that Cul4–DDB1–Gβ promotes the ubiquitylation of both Smo and its binding partner G-protein-coupled-receptor kinase 2 (Gprk2) and induces the internalization and degradation of Smo. Hh dissociates Cul4–DDB1 from Smo by recruiting the catalytic subunit of protein kinase A (PKA) to phosphorylate DDB1, which disrupts its interaction with Gβ. Inactivation of the Cul4–DDB1 complex resulted in elevated Smo cell surface expression, whereas an excessive amount of Cul4–DDB1 blocked Smo accumulation and attenuated Hh pathway activation. Taken together, our study identifies an E3 ubiquitin ligase complex targeting Smo for ubiquitylation and provides new insight into how Hh signaling regulates Smo trafficking and cell surface expression.
    Keywords: Ubiquitin
    Print ISSN: 0021-9533
    Electronic ISSN: 1477-9137
    Topics: Biology , Medicine
    Published by Company of Biologists
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  • 6
    Publication Date: 2018-06-30
    Description: Human innate immunity responds to viral infection by activating the production of interferons (IFNs) and proinflammatory cytokines. The mitochondrial adaptor molecule MAVS plays a critical role in innate immune response to viral infection. In this study, we show that TRIM21 (tripartite motif-containing protein 21) interacts with MAVS to positively regulate innate immunity. Under viral infection, TRIM21 is upregulated through the IFN/JAK/STAT signaling pathway. Knockdown of TRIM21 dramatically impairs innate immune response to viral infection. Moreover, TRIM21 interacts with MAVS and catalyzes its K27-linked polyubiquitination, thereby promoting the recruitment of TBK1 to MAVS. Specifically, the PRY-SPRY domain of TRIM21 is the key domain for its interaction with MAVS, while the RING domain of TRIM21 facilitates the polyubiquitination chains of MAVS. In addition, the MAVS-mediated innate immune response is enhanced by both the PRY-SPRY and RING domains of TRIM21. Mutation analyses of all the lysine residues of MAVS further revealed that Lys325 of MAVS is catalyzed by TRIM21 for the K27-linked polyubiquitination. Overall, this study reveals a novel mechanism by which TRIM21 promotes the K27-linked polyubiquitination of MAVS to positively regulate innate immune response, thereby inhibiting viral infection. IMPORTANCE Activation of innate immunity is essential for host cells to restrict the spread of invading viruses and other pathogens. MAVS plays a critical role in innate immune response to RNA viral infection. In this study, we demonstrated that TRIM21 targets MAVS to positively regulate innate immunity. Notably, TRIM21 targets and catalyzes K27-linked polyubiquitination of MAVS and then promotes the recruitment of TBK1 to MAVS, leading to upregulation of innate immunity. Our study outlines a novel mechanism by which the IFN signaling pathway blocks RNA virus to escape immune elimination.
    Print ISSN: 0022-538X
    Electronic ISSN: 1098-5514
    Topics: Medicine
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  • 7
    Publication Date: 2018-07-05
    Description: With the development of cavitation, the high-energy pressure wave from a cavitation bubble collapsing is detrimental to the stable operation of centrifugal pumps. The present paper concentrates on pressure pulsations under cavitation conditions, and pressure amplitudes at the blade-passing frequency ( f BPF ) and RMS values in the 0–500 Hz frequency band are combined to investigate cavitation-induced pressure pulsations. The results show that components at f BPF always dominate the pressure spectrum even at the full cavitation stage. For points P1–P7 on the volute side wall, with a decreasing cavitation number, the pressure energy first remains unchanged and then it rises rapidly after the critical point. For point In1 in a volute suction pipe located close to the cavitation region, the pressure energy changes slightly at high cavitation numbers; then for a particular cavitation number range, the pressure energy decreases, and finally increases again. For different flow rates, the pressure energy at the critical point is much lower than the initial amplitude at the non-cavitation condition for In1. This demonstrates that the cavitation cloud in the typical stage is partially compressible, and the emitted pressure wave from a collapsing cavitation bubble is absorbed and attenuated significantly. Finally, this leads to the pressure energy decreasing rapidly for the measuring point In1 near the cavitation region.
    Keywords: mechanical engineering, power and energy systems, fluid mechanics
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 8
    Publication Date: 2018-11-20
    Description: In vertebrates, intron-containing and intronless type I IFN genes have recently been reported in amphibian model species Xenopus tropicalis and X. laevi s. However, whether intronless type I IFNs in amphibians are the ancestral genes of type I IFNs in amniotes or just represent the independent divergence in amphibians is unknown or even uninvestigated. In this study, both intron-containing and intronless type I IFN genes, as well as their receptor genes, were identified in the Tibetan frog Nanorana parkeri . The evidence obtained from homology, synteny, phylogeny, and divergence time showed that intronless type I IFN genes in N. parkeri and in Xenopus might have arisen from two independent retroposition events occurred in these two lineages, and the retrotransposition causing the generation of intronless type I IFN genes in amniotes is another independent event beyond the two in amphibians. It can then be proposed that intronless type I IFNs in N. parkeri and Xenopus may not be the ancestral genes of intronless type I IFNs in amniotes but may just represent two independent bifurcations in the amphibian lineage. Furthermore, both intronless and intron-containing type I IFNs in N. parkeri showed strong ability in inducing the expression of IFN-stimulated genes and the strong antiviral activity against frog virus 3. The present study thus provides the evolutionary evidence to support the independent retroposition hypothesis for the occurrence of intronless type I IFN genes in amphibians and contributes to a functional understanding of type I IFNs in this group of vertebrates.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 9
    Publication Date: 2011-08-05
    Description: Natural killer (NK) cells have an important role in the control of viral infections, recognizing virally infected cells through a variety of activating and inhibitory receptors. Epidemiological and functional studies have recently suggested that NK cells can also contribute to the control of HIV-1 infection through recognition of virally infected cells by both activating and inhibitory killer immunoglobulin-like receptors (KIRs). However, it remains unknown whether NK cells can directly mediate antiviral immune pressure in vivo in humans. Here we describe KIR-associated amino-acid polymorphisms in the HIV-1 sequence of chronically infected individuals, on a population level. We show that these KIR-associated HIV-1 sequence polymorphisms can enhance the binding of inhibitory KIRs to HIV-1-infected CD4(+) T cells, and reduce the antiviral activity of KIR-positive NK cells. These data demonstrate that KIR-positive NK cells can place immunological pressure on HIV-1, and that the virus can evade such NK-cell-mediated immune pressure by selecting for sequence polymorphisms, as was previously described for virus-specific T cells and neutralizing antibodies. NK cells might therefore have a previously underappreciated role in contributing to viral evolution.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3194000/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3194000/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alter, Galit -- Heckerman, David -- Schneidewind, Arne -- Fadda, Lena -- Kadie, Carl M -- Carlson, Jonathan M -- Oniangue-Ndza, Cesar -- Martin, Maureen -- Li, Bin -- Khakoo, Salim I -- Carrington, Mary -- Allen, Todd M -- Altfeld, Marcus -- HHSN261200800001E/PHS HHS/ -- P01 AI074415/AI/NIAID NIH HHS/ -- P01 AI074415-01A2/AI/NIAID NIH HHS/ -- P01 AI074415-02/AI/NIAID NIH HHS/ -- P01 AI074415-02S1/AI/NIAID NIH HHS/ -- P01 AI074415-03/AI/NIAID NIH HHS/ -- P01 AI074415-04/AI/NIAID NIH HHS/ -- P30 AI060354/AI/NIAID NIH HHS/ -- R01 AI067031/AI/NIAID NIH HHS/ -- R01 AI067031-05/AI/NIAID NIH HHS/ -- R01 AI067031-06/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- Wellcome Trust/United Kingdom -- England -- Nature. 2011 Aug 3;476(7358):96-100. doi: 10.1038/nature10237.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ragon Institute at MGH, MIT and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21814282" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological/genetics/*immunology ; Antibodies, Neutralizing/immunology ; CD4-Positive T-Lymphocytes/immunology/virology ; Decision Trees ; *Evolution, Molecular ; Genotype ; HIV Infections/*immunology/*virology ; HIV-1/genetics/*immunology/physiology ; Host-Pathogen Interactions/immunology ; Human Immunodeficiency Virus Proteins/genetics/immunology/metabolism ; Humans ; Immune Evasion/*immunology ; Killer Cells, Natural/*immunology ; Polymorphism, Genetic ; Receptors, KIR/deficiency/genetics/immunology/metabolism ; Receptors, KIR2DL2/chemistry/deficiency/genetics/immunology ; Viral Regulatory and Accessory Proteins/genetics/immunology/metabolism ; Virus Replication ; env Gene Products, Human Immunodeficiency Virus/genetics/immunology/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
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    Nature Publishing Group (NPG)
    Publication Date: 2011-01-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Bochong -- You, Lingchong -- England -- Nature. 2011 Jan 13;469(7329):171-2. doi: 10.1038/469171a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21228867" target="_blank"〉PubMed〈/a〉
    Keywords: Bioengineering ; Cell Compartmentation ; Escherichia coli/*cytology/genetics/*metabolism ; Gene Expression Regulation, Bacterial/genetics ; Gene Regulatory Networks ; *Logic ; *Models, Biological ; Peptides/*metabolism/pharmacology ; Pheromones/metabolism/pharmacology ; Quorum Sensing/*genetics/*physiology ; Saccharomyces cerevisiae/*cytology/drug effects/*metabolism ; Systems Biology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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