| 1. |
- Schael, S., et al.
(författare)
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Electroweak measurements in electron positron collisions at W-boson-pair energies at LEP
- 2013
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 532:4, s. 119-244
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Forskningsöversikt (refereegranskat)abstract
- Electroweak measurements performed with data taken at the electron positron collider LEP at CERN from 1995 to 2000 are reported. The combined data set considered in this report corresponds to a total luminosity of about 3 fb(-1) collected by the four LEP experiments ALEPH, DELPHI, 13 and OPAL, at centre-of-mass energies ranging from 130 GeV to 209 GeV. Combining the published results of the four LEP experiments, the measurements include total and differential cross-sections in photon-pair, fermion-pair and four-fermion production, the latter resulting from both double-resonant WW and ZZ production as well as singly resonant production. Total and differential cross-sections are measured precisely, providing a stringent test of the Standard Model at centre-of-mass energies never explored before in electron positron collisions. Final-state interaction effects in four-fermion production, such as those arising from colour reconnection and Bose Einstein correlations between the two W decay systems arising in WW production, are searched for and upper limits on the strength of possible effects are obtained. The data are used to determine fundamental properties of the W boson and the electroweak theory. Among others, the mass and width of the W boson, m(w) and Gamma(w), the branching fraction of W decays to hadrons, B(W -> had), and the trilinear gauge-boson self-couplings g(1)(Z), K-gamma and lambda(gamma), are determined to be: m(w) = 80.376 +/- 0.033 GeV Gamma(w) = 2.195 +/- 0.083 GeV B(W -> had) = 67.41 +/- 0.27% g(1)(Z) = 0.984(-0.020)(+0.018) K-gamma - 0.982 +/- 0.042 lambda(gamma) = 0.022 +/- 0.019. (C) 2013 Elsevier B.V. All rights reserved.
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| 2. |
- Hernandez, Frank J, et al.
(författare)
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Degradation of nuclease-stabilized RNA oligonucleotides in Mycoplasma-contaminated cell culture media
- 2012
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Ingår i: Nucleic Acid Therapeutics. - : Mary Ann Liebert. - 2159-3337 .- 2159-3345. ; 22:1, s. 58-68
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Tidskriftsartikel (refereegranskat)abstract
- Artificial RNA reagents such as small interfering RNAs (siRNAs) and aptamers often must be chemically modified for optimal effectiveness in environments that include ribonucleases. Mycoplasmas are common bacterial contaminants of mammalian cell cultures that are known to produce ribonucleases. Here we describe the rapid degradation of nuclease-stabilized RNA oligonucleotides in a human embryonic kidney 293 (HEK) cell culture contaminated with Mycoplasma fermentans, a common species of mycoplasma. RNA with 2′-fluoro-or 2′-O-methyl-modified pyrimidines was readily degraded in conditioned media from this culture, but was stable in conditioned media from uncontaminated HEK cells. RNA completely modified with 2′-O-methyls was not degraded in the mycoplasma-contaminated media. RNA zymogram analysis of conditioned culture media and material centrifuged from the media revealed several distinct protein bands (ranging from 30 to 68kDa) capable of degrading RNA with 2′-fluoro-or 2′-O-methyl-modified pyrimidines. Finally, the mycoplasma-associated nuclease was detected in material centrifuged from the contaminated culture supernatants in as little as 15 minutes with an RNA oligo-containing 2′-O-methyl-modified pyrimidines and labeled with a 5′-fluorescein amidite (FAM) and 3′-quencher. These results suggest that mycoplasma contamination may be a critical confounding variable for cell culture experiments involving RNA-based reagents, with particular relevance for applications involving naked RNA (e.g., aptamer-siRNA chimeras). © 2012 Mary Ann Liebert, Inc.
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| 3. |
- Hernandez, Frank J, et al.
(författare)
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Noninvasive imaging of Staphylococcus aureus infections with a nuclease-activated probe
- 2014
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Ingår i: Nature Medicine. - : Nature Publishing Group. - 1078-8956 .- 1546-170X. ; 20:3, s. 301-306
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Tidskriftsartikel (refereegranskat)abstract
- Technologies that enable the rapid detection and localization of bacterial infections in living animals could address an unmet need for infectious disease diagnostics. We describe a molecular imaging approach for the specific, noninvasive detection of S. aureus based on the activity of the S. aureus secreted nuclease, micrococcal nuclease (MN). Several short synthetic oligonucleotides, rendered resistant to mammalian serum nucleases by various chemical modifications and flanked with a fluorophore and quencher, were activated upon degradation by purified MN and in S. aureus culture supernatants. A probe consisting of a pair of deoxythymidines flanked by several 2′-O-methyl-modified nucleotides was activated in culture supernatants of S. aureus but not in culture supernatants of several other pathogenic bacteria. Systemic administration of this probe to mice bearing S. aureus muscle infections resulted in probe activation at the infection sites in an MN-dependent manner. This new bacterial imaging approach has potential clinical applicability for infections with S. aureus and several other medically important pathogens. © 2014 Nature America, Inc.
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| 4. |
- Kiedrowski, Megan R., et al.
(författare)
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Staphylococcus aureus Nuc2 is a functional, surface-attached extracellular nuclease
- 2014
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Ingår i: PLOS ONE. - San Francisco, United States : Public Library of Science. - 1932-6203. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus is a prominent bacterial pathogen that causes a diverse range of acute and chronic infections. Recently, it has been demonstrated that the secreted nuclease (Nuc) enzyme is a virulence factor in multiple models of infection, and in vivo expression of nuc has facilitated the development of an infection imaging approach based on Nuc-activatable probes. Interestingly, S. aureus strains encode a second nuclease (Nuc2) that has received limited attention. With the growing interest in bacterial nucleases, we sought to characterize Nuc2 in more detail through localization, expression, and biochemical studies. Fluorescence microscopy and alkaline phosphatase localization approaches using Nuc2-GFP and Nuc2-PhoA fusions, respectively, demonstrated that Nuc2 is membrane bound with the C-terminus facing the extracellular environment, indicating it is a signal-anchored Type II membrane protein. Nuc2 enzyme activity was detectable on the S. aureus cell surface using a fluorescence resonance energy transfer (FRET) assay, and in time courses, both nuc2 transcription and enzyme activity peaked in early logarithmic growth and declined in stationary phase. Using a mouse model of S. aureus pyomyositis, Nuc2 activity was detected with activatable probes in vivo in nuc mutant strains, demonstrating that Nuc2 is produced during infections. To assess Nuc2 biochemical properties, the protein was purified and found to cleave both single- and double-stranded DNA, and it exhibited thermostability and calcium dependence, paralleling the properties of Nuc. Purified Nuc2 prevented biofilm formation in vitro and modestly decreased biomass in dispersal experiments. Altogether, our findings confirm that S. aureus encodes a second, surface-attached and functional DNase that is expressed during infections and displays similar biochemical properties to the secreted Nuc enzyme. © 2014 Kiedrowski et al.
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| 5. |
- Prowse, Terry, et al.
(författare)
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Effects of Changes in Arctic Lake and River Ice
- 2011
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 40:Suppl 1, s. 63-74
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Tidskriftsartikel (refereegranskat)abstract
- Climatic changes to freshwater ice in the Arctic are projected to produce a variety of effects on hydrologic, ecological, and socio-economic systems. Key hydrologic impacts include changes to low flows, lake evaporation regimes and water levels, and river-ice break-up severity and timing. The latter are of particular concern because of their effect on river geomorphology, vegetation, sediment and nutrient fluxes, and sustainment of riparian aquatic habitats. Changes in ice phenology will affect a wide range of related biological aspects of seasonality. Some changes are likely to be gradual, but others could be more abrupt as systems cross critical ecological thresholds. Transportation and hydroelectric production are two of the socio-economic sectors most vulnerable to change in freshwater-ice regimes. Ice roads will require expensive on-land replacements while hydroelectric operations will both benefit and be challenged. The ability to undertake some traditional harvesting methods will also be affected.
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| 6. |
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| 7. |
- Huang, Yang Zhong, et al.
(författare)
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RNA aptamer-based functional ligands of the neurotrophin receptor, TrkB
- 2012
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Ingår i: Molecular Pharmacology. - Bethesda, United States : American Society for Pharmacology and Experimental Therapeutics. - 0026-895X .- 1521-0111. ; 82:4, s. 623-635
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Tidskriftsartikel (refereegranskat)abstract
- Many cell surface signaling receptors, such as the neurotrophin receptor, TrkB, have emerged as potential therapeutic targets for diverse diseases. Reduced activation of TrkB in particular is thought to contribute to neurodegenerative diseases. Unfortunately, development of therapeutic reagents that selectively activate particular cell surface receptors such as TrkB has proven challenging. Like many cell surface signaling receptors, TrkB is internalized upon activation; in this proof-of-concept study, we exploited this fact to isolate a pool of nuclease-stabilized RNA aptamers enriched for TrkB agonists. One of the selected aptamers, C4-3, was characterized with recombinant protein-binding assays, cell-based signaling and functional assays, and, in vivo in a seizure model in mice. C4-3 binds the extracellular domain of TrkB with high affinity (KD ∼2 nM) and exhibits potent TrkB partial agonistic activity and neuroprotective effects in cultured cortical neurons. In mice, C4-3 activates TrkB upon infusion into the hippocampus; systemic administration of C4-3 potentiates kainic acid-induced seizure development. We conclude that C4-3 is a potentially useful therapeutic agent for neurodegenerative diseases in which reduced TrkB activation has been implicated. We anticipate that the cell-based aptamer selection approach used here will be broadly applicable to the identification of aptamer-based agonists for a variety of cell-surface signaling receptors. Copyright © 2012 The American Society for Pharmacology and Experimental Therapeutics.
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| 8. |
- McNamara, John M., et al.
(författare)
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Environmental variability can select for optimism or pessimism
- 2011
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 14:1, s. 58-62
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Tidskriftsartikel (refereegranskat)abstract
- We propose operational definitions of reproductive optimism and pessimism; optimism involves behaving in a way that gives too much weight (in terms of producing surviving offspring) to positive events, pessimism gives too much weight to negative events. Natural selection maximizes the long-term growth of a lineage rather than short-term measures such as numbers of offspring. Consequently, optimism or pessimism can be favoured by natural selection, even though such biases appear irrational from a short-term perspective. We investigate the evolution of optimism in a metapopulation. The circumstances of a patch change over time, independently of other patches. With sufficient dispersal between patches, stochasticity affects members of a lineage largely independently and optimism is favoured. With little dispersal, the temporal fluctuations of a patch affect many members similarly; pessimism is then favoured. Our results establish that the spatial and temporal structure of the environment is crucial in determining the direction of evolved biases. © 2010 Blackwell Publishing Ltd/CNRS.
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| 9. |
- McNamara, R. L., et al.
(författare)
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International comparisons of the management of patients with non-ST segment elevation acute myocardial infarction in the United Kingdom, Sweden, and the United States: The MINAP/NICOR, SWEDEHEART/RIKS-HIA, and ACTION Registry-GWTG/NCDR registries
- 2014
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 175:2, s. 240-247
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To compare management of patients with acute non-ST segment elevation myocardial infarction (NSTEMI) in three developed countries with national ongoing registries. Background: Results from clinical trials suggest significant variation in care across the world. However, international comparisons in "real world" registries are limited. Methods: We compared the use of in-hospital procedures and discharge medications for patients admitted with NSTEMI from 2007 to 2010 using the unselective MINAP/NICOR [England and Wales (UK); n = 137,009], the unselective SWEDEHEART/RIKS-HIA (Sweden; n = 45,069), and the selective ACTION Registry-GWTG/NCDR [United States (US); n = 147,438] clinical registries. Results: Patients enrolled among the three registries were generally similar except those in the US who were younger but had higher rates of smoking, diabetes, hypertension, prior heart failure, and prior MI than in Sweden or in UK. Angiography and percutaneous coronary intervention (PCI) were performed more often in the US (76% and 44%) and Sweden (65% and 42%) relative to the UK (32% and 22%). Discharge betablockers were also prescribed more often in the US (89%) and Sweden (89%) than in the UK (76%). In contrast, discharge statins, angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB), and dual antiplatelet agents (among those not receiving PCI) were higher in the UK (92%, 79%, and 71%) than in the US (85%, 65%, 41%) and Sweden (81%, 69%, and 49%). Conclusions: The care for patients with NSTEMI differed substantially among the three countries. These differences in care among countries provide an opportunity for future comparative effectiveness research as well as identify opportunities for global quality improvement. (C) 2014 The Authors. Published by Elsevier Ireland Ltd.
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| 10. |
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