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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: 2018-08-17
    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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  • 5
    Publication Date: 2018-08-29
    Description: BACKGROUND: Gut microbial dysbiosis contributes to the development of colorectal cancer (CRC). We evaluated the utility of fecal bacterial biomarker candidates identified by our 16S rDNA sequencing analysis for CRC diagnosis. METHODS: We measured the relative abundance of Fusobacterium nucleatum ( Fn ), Faecalibacterium prausnitzii ( Fp ), Bifidobacterium ( Bb ), and Lactobacillus ( Lb ) by quantitative PCR in fecal samples from 2 cohorts of 903 individuals. We evaluated and validated the diagnostic performance of these microbial ratios and investigated the antagonistic effect of Fn against 3 different indicator stains. RESULTS: The microbial ratio of Fn to Bb ( Fn/Bb ) had a superior sensitivity of 84.6% and specificity of 92.3% in detecting CRC (area under the curve, AUC = 0.911). The combination of Fn/Bb and Fn/Fp improved the diagnostic value (AUC = 0.943). Moreover, the combination of Fn/Bb and Fn/Fp offered 60.0% specificity and 90.0% sensitivity in detecting stage I of CRC (AUC = 0.804). In particular, Fn was negatively correlated with Fp in the CRC group. The performance for CRC diagnosis was confirmed in the validation cohort II. The culture supernatant from Fn exhibited strong bactericidal activity against probiotics Fp and Bb strains. CONCLUSIONS: This study found that Fn could play a role in microbiota dysbiosis via the secreted antagonistic substances against probiotics. Moreover, the ratio of Fn to the important probiotics Fp and Bb was identified as a valuable biomarker for screening early CRC.
    Keywords: Cancer Diagnostics (since 2002)
    Print ISSN: 0009-9147
    Electronic ISSN: 1530-8561
    Topics: Medicine
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  • 6
    Publication Date: 2018-10-04
    Description: The PI3K-Akt-mTOR signaling pathway is a master regulator of RNA translation. Pharmacological inhibition of this pathway preferentially and coordinately suppresses, in a 4EBP1/2-dependent manner, translation of mRNAs encoding ribosomal proteins. However, it is unclear whether mechanistic target of rapamycin (mTOR)-4EBP1/2 is the exclusive translation regulator of this group of genes,...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 7
    Publication Date: 2018-10-13
    Description: Mechanically flexible, easy-to-process, and environmentally benign materials capable of current rectification are interesting alternatives to "hard" silicon-based devices. Among these materials are metallic/charged-organic nanoparticles in which electronic currents though metal cores are modulated by the gradients of counterions surrounding the organic ligands. Although layers of oppositely charged particles can respond to both electronic and chemical signals and can function even under significant mechanical deformation, the rectification ratios of these "chemoelectronic" elements have been, so far, low. This work shows that significantly steeper counterion gradients and significantly higher rectification ratios can be achieved with nanoparticles of only one polarity but in contact with a porous electrode serving as a counterion "sink." These composite structures act as rectifiers even at radio frequencies, providing a new means of interfacing counterions’ dynamics with high-frequency electronic currents.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 8
    Publication Date: 2018-04-26
    Description: UFD1 contributes to MYC-mediated leukemia aggressiveness through suppression of the proapoptotic unfolded protein response UFD1 contributes to MYC-mediated leukemia aggressiveness through suppression of the proapoptotic unfolded protein response, Published online: 25 April 2018; doi:10.1038/s41375-018-0141-x UFD1 contributes to MYC-mediated leukemia aggressiveness through suppression of the proapoptotic unfolded protein response
    Print ISSN: 0887-6924
    Electronic ISSN: 1476-5551
    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
    Publication Date: 2011-10-28
    Description: Parasitic diseases have a devastating, long-term impact on human health, welfare and food production worldwide. More than two billion people are infected with geohelminths, including the roundworms Ascaris (common roundworm), Necator and Ancylostoma (hookworms), and Trichuris (whipworm), mainly in developing or impoverished nations of Asia, Africa and Latin America. In humans, the diseases caused by these parasites result in about 135,000 deaths annually, with a global burden comparable with that of malaria or tuberculosis in disability-adjusted life years. Ascaris alone infects around 1.2 billion people and, in children, causes nutritional deficiency, impaired physical and cognitive development and, in severe cases, death. Ascaris also causes major production losses in pigs owing to reduced growth, failure to thrive and mortality. The Ascaris-swine model makes it possible to study the parasite, its relationship with the host, and ascariasis at the molecular level. To enable such molecular studies, we report the 273 megabase draft genome of Ascaris suum and compare it with other nematode genomes. This genome has low repeat content (4.4%) and encodes about 18,500 protein-coding genes. Notably, the A. suum secretome (about 750 molecules) is rich in peptidases linked to the penetration and degradation of host tissues, and an assemblage of molecules likely to modulate or evade host immune responses. This genome provides a comprehensive resource to the scientific community and underpins the development of new and urgently needed interventions (drugs, vaccines and diagnostic tests) against ascariasis and other nematodiases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jex, Aaron R -- Liu, Shiping -- Li, Bo -- Young, Neil D -- Hall, Ross S -- Li, Yingrui -- Yang, Linfeng -- Zeng, Na -- Xu, Xun -- Xiong, Zijun -- Chen, Fangyuan -- Wu, Xuan -- Zhang, Guojie -- Fang, Xiaodong -- Kang, Yi -- Anderson, Garry A -- Harris, Todd W -- Campbell, Bronwyn E -- Vlaminck, Johnny -- Wang, Tao -- Cantacessi, Cinzia -- Schwarz, Erich M -- Ranganathan, Shoba -- Geldhof, Peter -- Nejsum, Peter -- Sternberg, Paul W -- Yang, Huanming -- Wang, Jun -- Wang, Jian -- Gasser, Robin B -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Oct 26;479(7374):529-33. doi: 10.1038/nature10553.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Faculty of Veterinary Science, The University of Melbourne, Parkville, Victoria 3010, Australia. ajex@unimelb.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22031327" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antinematodal Agents ; Ascariasis/drug therapy/parasitology ; Ascaris suum/drug effects/*genetics ; Drug Design ; Genes, Helminth/genetics ; Genome, Helminth/*genetics ; Genomics ; Molecular Sequence Annotation ; Molecular Targeted Therapy
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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