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  • 1
    Publication Date: 2015-12-12
    Description: We describe recent upgrades to a 3D tracking microscope to include simultaneous Nipkow spinning disk imaging and time-gated single-particle tracking (SPT). Simultaneous 3D molecular tracking and spinning disk imaging enable the visualization of cellular structures and proteins around a given fluorescently labeled target molecule. The addition of photon time-gating to the SPT hardware improves signal to noise by discriminating against Raman scattering and short-lived fluorescence. In contrast to camera-based SPT, single-photon arrival times are recorded, enabling time-resolved spectroscopy (e.g., measurement of fluorescence lifetimes and photon correlations) to be performed during single molecule/particle tracking experiments.
    Print ISSN: 0034-6748
    Electronic ISSN: 1089-7623
    Topics: Electrical Engineering, Measurement and Control Technology , Physics
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  • 2
    Publication Date: 2009-02-17
    Description: Injury or impaired clearance of apoptotic cells leads to the pathological accumulation of necrotic corpses, which induce an inflammatory response that initiates tissue repair. In addition, antigens present in necrotic cells can sometimes provoke a specific immune response and it has been argued that necrosis could explain adaptive immunity in seemingly infection-free situations, such as after allograft transplantation or in spontaneous and therapy-induced tumour rejection. In the mouse, the CD8alpha+ subset of dendritic cells phagocytoses dead cell remnants and cross-primes CD8+ T cells against cell-associated antigens. Here we show that CD8alpha+ dendritic cells use CLEC9A (also known as DNGR-1), a recently-characterized C-type lectin, to recognize a preformed signal that is exposed on necrotic cells. Loss or blockade of CLEC9A does not impair the uptake of necrotic cell material by CD8+ dendritic cells, but specifically reduces cross-presentation of dead-cell-associated antigens in vitro and decreases the immunogenicity of necrotic cells in vivo. The function of CLEC9A requires a key tyrosine residue in its intracellular tail that allows the recruitment and activation of the tyrosine kinase SYK, which is also essential for cross-presentation of dead-cell-associated antigens. Thus, CLEC9A functions as a SYK-coupled C-type lectin receptor to mediate sensing of necrosis by the principal dendritic-cell subset involved in regulating cross-priming to cell-associated antigens.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671489/" 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/PMC2671489/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sancho, David -- Joffre, Olivier P -- Keller, Anna M -- Rogers, Neil C -- Martinez, Dolores -- Hernanz-Falcon, Patricia -- Rosewell, Ian -- Reis e Sousa, Caetano -- A3598/Cancer Research UK/United Kingdom -- Cancer Research UK/United Kingdom -- England -- Nature. 2009 Apr 16;458(7240):899-903. doi: 10.1038/nature07750.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunobiology Laboratory, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19219027" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD8/metabolism ; CD8-Positive T-Lymphocytes/immunology ; Cells, Cultured ; Cross-Priming/immunology ; Dendritic Cells/*immunology/*metabolism ; Humans ; Lectins, C-Type/deficiency/genetics/*metabolism ; Ligands ; Mice ; Necrosis/*immunology/*metabolism ; Phagocytosis ; Receptors, Immunologic/deficiency/genetics/*metabolism ; Receptors, Mitogen/genetics/*metabolism ; Signal Transduction
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Experimental Cell Research 161 (1985), S. 495-508 
    ISSN: 0014-4827
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0014-4827
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Distributed and parallel databases 3 (1995), S. 225-246 
    ISSN: 1573-7578
    Keywords: Replicated databases ; update propagation ; transaction reconciliation ; failures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science
    Notes: Abstract Update propagation and transaction atomicity are major obstacles to the development of replicated databases. Many practical applications, such as automated teller machine networks, flight reservation, and part inventory control, do not require these properties. In this paper we present an approach for incrementally updating a distributed, replicated database without requiring multi-site atomic commit protocols. We prove that the mechanism is correct, as it asymptotically performs all the updates on all the copies. Our approach has two important characteristics: it is progressive, and non-blocking.Progressive means that the transaction's coordinator always commits, possibly together with a group of other sites. The update is later propagated asynchronously to the remaining sites.Non-blocking means that each site can take unilateral decisions at each step of the algorithm. Sites which cannot commit updates are brought to the same final state by means of areconciliation mechanism. This mechanism uses the history logs, which are stored locally at each site, to bring sites to agreement. It requires a small auxiliary data structure, called reception vector, to keep track of the time unto which the other sites are guaranteed to be up-to-date. Several optimizations to the basic mechanism are also discussed.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Chichester [u.a.] : Wiley-Blackwell
    Developmental Genetics 2 (1981), S. 23-34 
    ISSN: 0192-253X
    Keywords: Paramecium tetraurelia ; trichocysts, nuclear differentiation ; cytoplasmic inheritance ; determination ; Life and Medical Sciences ; Genetics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: The mtFE mutation isolated in Paramecium tetraurelia affects mating type differentiation, trichocyst excretion, and viability. Its effect on mating type has already been shown to correspond to a restriction to the E mating type interpreted by an inefficiency of nuclear O-determining factors. In this paper we study the other two phenotypic characteristics whose hereditary transmission displays two unusual features. (1) In crosses between a wild-type strain and the mutant strain, the mutant characteristics do not reappear in F2 in the wild-type cytoplasmic lineage but only in F3 after the homozygous clones have undergone an additional nuclear reorganization. (2) Some F2 wild-type clones, in the mutant cytoplasmic lineage, retain some of the phenotypic characteristics of the mutant. We propose that the mtF gene product plays a role in the control of several macronuclearly differentiated functions.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0192-253X
    Keywords: nuclear differentiation ; cytoplasmic inheritance ; Paramecium tetraurelia ; mating type ; Life and Medical Sciences ; Genetics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: In P. tetraurelia each cell is determined to express only one of the two complementary mating types, O and E. This determination is under cytoplasmic control and seems to be achieved only by the commitment or noncommitment to the expression of mating type E. All the previously known mutations affecting the differentiation of mating type prevent the expression of the E mating type (O-restricted mutations) without affecting the determination process. An E-restricted mutation was obtained: mtFE. Its phenotypic properties indicate that the mutation affects the determination process itself. When an O cell becomes mtFE/mtFE it acquires the E mating type and an E-determining cytoplasm. We propose that this constitutive determination for the E mating type is due to the inefficiency of a factor which is normally active in an O cell. This factor would act like a repressor and stabilize the E functions under an inactive state.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Organic Magnetic Resonance 24 (1986), S. 831-832 
    ISSN: 0749-1581
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The 1H NMR spectra of 1,3-benzodithiole and eight derivatives have been analysed. Signals of the protons in positions 4 and 7 are shifted downfield compared with those for the protons in positions 5 and 6. The inter-ring proton-proton couplings have been determined.
    Additional Material: 2 Tab.
    Type of Medium: Electronic Resource
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  • 9
    Publication Date: 2012-03-29
    Description: Deregulation of cell signaling pathways plays a crucial role in the development of tumors. The identification of such pathways requires effective analysis tools that facilitate the interpretation of expression differences. Here, we present a novel and highly efficient method for identifying deregulated subnetworks in a regulatory network. Given a score for each node that measures the degree of deregulation of the corresponding gene or protein, the algorithm computes the heaviest connected subnetwork of a specified size reachable from a designated root node. This root node can be interpreted as a molecular key player responsible for the observed deregulation. To demonstrate the potential of our approach, we analyzed three gene expression data sets. In one scenario, we compared expression profiles of non-malignant primary mammary epithelial cells derived from BRCA1 mutation carriers and of epithelial cells without BRCA1 mutation. Our results suggest that oxidative stress plays an important role in epithelial cells of BRCA1 mutation carriers and that the activation of stress proteins may result in avoidance of apoptosis leading to an increased overall survival of cells with genetic alterations. In summary, our approach opens new avenues for the elucidation of pathogenic mechanisms and for the detection of molecular key players.
    Keywords: Computational Methods, Miscellaneous/other
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 10
    Publication Date: 2016-05-17
    Description: ABSTRACT Climate information provided by global or regional climate models (RCMs) are often too coarse and prone to substantial biases for local assessments or use in impact models. Hence, statistical downscaling becomes necessary. For the Swiss National Climate Change Initiative (CH2011), a delta-change approach was used to provide daily climate scenarios at the local scale. Here, we analyse a Richardson-type weather generator (WG) as an alternative method to downscale daily precipitation, minimum and maximum temperature. The WG is calibrated for 26 Swiss stations and the reference period is 1980–2009. It is perturbed with change factors derived from RCMs (ENSEMBLES) to represent the climate of 2070–2099 assuming the SRES A1B emission scenario. The WG can be run in multi-site mode, making it especially attractive for impact-modellers that rely on a realistic spatial structure in downscaled time-series. The results from the WG are benchmarked against the original delta-change approach that applies mean additive or multiplicative adjustments to the observations. According to both downscaling methods, the results reveal mean temperature increases and a precipitation decrease in summer, consistent with earlier studies. For the summer drying, the WG indicates primarily a decrease in wet-day frequency and correspondingly an increase in mean dry spell length of between 18 and 40% at low-elevation stations. By definition, these potential changes cannot be represented by a delta-change approach. In winter, both methods project a shortening of the frost period (−30 to −60 days) and a decrease of snow days (−20 to −100%). The WG demonstrates though, that almost present-day conditions in snow-days could still occur in the future. As expected, both methods have difficulties in representing extremes. If users focus on changes in temporal sequences and need a large number of future realizations, it is recommended to use data from a WG instead of a delta-change approach.
    Print ISSN: 0899-8418
    Electronic ISSN: 1097-0088
    Topics: Geosciences , Physics
    Published by Wiley
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