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  • 1
    Publication Date: 2014-06-10
    Description: Author(s): D. I. Bradley, M. J. Fear, S. N. Fisher, A. M. Guénault, R. P. Haley, C. R. Lawson, G. R. Pickett, R. Schanen, V. Tsepelin, and L. A. Wheatland We have studied the transition between pure potential flow and turbulent flow around a quartz tuning fork resonator in superfluid 4 He at millikelvin temperatures. Turbulent flow is identified by an additional drag force on the fork prongs due to the creation of quantized vortices. When driven at a c... [Phys. Rev. B 89, 214503] Published Mon Jun 09, 2014
    Keywords: Superfluidity and superconductivity
    Print ISSN: 1098-0121
    Electronic ISSN: 1095-3795
    Topics: Physics
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  • 2
    Publication Date: 2013-07-27
    Description: Author(s): K. Iwaya, D. R. Bowler, V. Brázdová, A. Ferreira da Silva, Ch. Renner, W. Wu, A. J. Fisher, A. M. Stoneham, and G. Aeppli The determining factor of the bulk properties of doped Si is the column rather than the row in the periodic table from which the dopants are drawn. It is unknown whether the basic properties of dopants at surfaces and interfaces, steadily growing in importance as microelectronic devices shrink, are ... [Phys. Rev. B 88, 035440] Published Fri Jul 26, 2013
    Keywords: Surface physics, nanoscale physics, low-dimensional systems
    Print ISSN: 1098-0121
    Electronic ISSN: 1095-3795
    Topics: Physics
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  • 3
    Publication Date: 2015-01-24
    Description: Adenosine deaminases acting on RNA (ADARs) hydrolytically deaminate adenosines (A) in a wide variety of duplex RNAs and misregulation of editing is correlated with human disease. However, our understanding of reaction selectivity is limited. ADARs are modular enzymes with multiple double-stranded RNA binding domains (dsRBDs) and a catalytic domain. While dsRBD binding is understood, little is known about ADAR catalytic domain/RNA interactions. Here we use a recently discovered RNA substrate that is rapidly deaminated by the isolated human ADAR2 deaminase domain (hADAR2-D) to probe these interactions. We introduced the nucleoside analog 8-azanebularine (8-azaN) into this RNA (and derived constructs) to mechanistically trap the protein–RNA complex without catalytic turnover for EMSA and ribonuclease footprinting analyses. EMSA showed that hADAR2-D requires duplex RNA and is sensitive to 2'-deoxy substitution at nucleotides opposite the editing site, the local sequence and 8-azaN nucleotide positioning on the duplex. Ribonuclease V1 footprinting shows that hADAR2-D protects ~23 nt on the edited strand around the editing site in an asymmetric fashion (~18 nt on the 5' side and ~5 nt on the 3' side). These studies provide a deeper understanding of the ADAR catalytic domain–RNA interaction and new tools for biophysical analysis of ADAR–RNA complexes.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 4
    Publication Date: 2014-01-31
    Description: Author(s): S. L. Ahlstrom, D. I. Bradley, M. Človečko, S. N. Fisher, A. M. Guénault, E. A. Guise, R. P. Haley, O. Kolosov, P. V. E. McClintock, G. R. Pickett, M. Poole, V. Tsepelin, and A. J. Woods We have measured the drag force from quantum turbulence on a series of quartz tuning forks in superfluid helium. The tuning forks were custom made from a 75-μm-thick wafer. They have identical prong widths and prong spacings, but different lengths to give different resonant frequencies. We have used... [Phys. Rev. B 89, 014515] Published Thu Jan 30, 2014
    Keywords: Superfluidity and superconductivity
    Print ISSN: 1098-0121
    Electronic ISSN: 1095-3795
    Topics: Physics
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  • 5
    Publication Date: 2014-07-23
    Description: Climate scientists, and natural scientists more generally, believe that climate change is a major, perhaps the most important, problem facing humankind this century, and that it is increasingly linked to extreme weather events. However, the impression one gets from much of the economic literature, particularly simulations from integrated assessment models used in policy analysis, is that the potential impacts of climate change are not large enough to warrant aggressive mitigation efforts in the near term. Although these models represent an important step in the needed interdisciplinary analysis of climate change by elucidating the links between climate and economy, we argue that they grossly underestimate potential impacts and associated damages because they (and the related policy analyses) fail to adequately capture extreme conditions, catastrophic events, and tipping points that trigger irreversible changes in the climate system, as well as impacts on the natural environment that cannot be monetized. Because the most severe impacts are expected in the later years of this century and beyond, discounting is crucial, and we argue that the appropriate rate is well below market rates. Moreover, we show that in the uniquely long period relevant to climate policy, the irreversibility of climate changes and impacts is more serious than the irreversibility of proposed mitigation measures. We conclude that an aggressive mitigation policy is warranted, one that holds further increases in global mean temperature to the scientific consensus on what is required to avoid the worst impacts, and that such a policy can be achieved at a cost that is well below potential damages. ( JEL : Q54)
    Keywords: Q54 - Climate ; Natural Disasters ; Global Warming
    Print ISSN: 1750-6816
    Electronic ISSN: 1750-6824
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Political Science , Economics
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  • 6
    Publication Date: 2015-04-04
    Description: Rett syndrome (RTT) is a severe neurodevelopmental disorder that is usually caused by mutations in Methyl-CpG-binding Protein 2 ( MECP2 ). Four of the eight common disease causing mutations in MECP2 are nonsense mutations and are responsible for over 35% of all cases of RTT. A strategy to overcome disease-causing nonsense mutations is treatment with nonsense mutation suppressing drugs that allow expression of full-length proteins from mutated genes with premature in-frame stop codons. To determine if this strategy is useful in RTT, we characterized a new mouse model containing a knock-in nonsense mutation (p.R255X) in the Mecp2 locus ( Mecp2 R255X ). To determine whether the truncated gene product acts as a dominant negative allele and if RTT-like phenotypes could be rescued by expression of wild-type protein, we genetically introduced an extra copy of MECP2 via an MECP2 transgene. The addition of MECP2 transgene to Mecp2 R255X mice abolished the phenotypic abnormalities and resulted in near complete rescue. Expression of MECP2 transgene Mecp2 R255X allele also rescued mTORC1 signaling abnormalities discovered in mice with loss of function and overexpression of Mecp2. Finally, we treated Mecp2 R255X embryonic fibroblasts with the nonsense mutation suppressing drug gentamicin and we were able to induce expression of full-length MeCP2 from the mutant p.R255X allele. These data provide proof of concept that the p.R255X mutation of MECP2 is amenable to the nonsense suppression therapeutic strategy and provide guidelines for the extent of rescue that can be expected by re-expressing MeCP2 protein.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 7
    Publication Date: 2015-07-10
    Description: Environmental exposures occurring early in life may have an important influence on cancer risk later in life. Here, we investigated carryover effects of dichloroacetic acid (DCA), a small molecule analog of pyruvate with metabolic programming properties, on age-related incidence of liver cancer. The study followed a stop-exposure/promotion design in which 4-week-old male and female B6C3F1 mice received the following treatments: deionized water alone (dH 2 O, control); dH 2 O with 0.06% phenobarbital (PB), a mouse liver tumor promoter; or DCA (1.0, 2.0 or 3.5g/l) for 10 weeks followed by dH 2 O or PB ( n = 20–30/group/sex). Pathology and molecular assessments were performed at 98 weeks of age. In the absence of PB, early-life exposure to DCA increased the incidence and number of hepatocellular tumors in male and female mice compared with controls. Significant dose trends were observed in both sexes. At the high dose level, 10 weeks of prior DCA treatment induced comparable effects (≥85% tumor incidence and number) to those seen after continuous lifetime exposure. Prior DCA treatment did not enhance or inhibit the carcinogenic effects of PB, induce persistent liver cytotoxicity or preneoplastic changes on histopathology or alter DNA sequence variant profiles within liver tumors compared with controls. Distinct changes in liver messenger RNA and micro RNA profiles associated with prior DCA treatment were not apparent at 98 weeks. Our findings demonstrate that early-life exposure to DCA may be as carcinogenic as life-long exposures, potentially via epigenetic-mediated effects related to cellular metabolism.
    Print ISSN: 0143-3334
    Electronic ISSN: 1460-2180
    Topics: Medicine
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  • 8
    Publication Date: 2016-03-01
    Description: Author(s): J. T. Moody, S. G. Anderson, G. Anderson, S. Betts, S. Fisher, A. Tremaine, and P. Musumeci In this paper we discuss the ultrashort pulse high gradient inverse free electron laser accelerator experiment carried out at the Lawrence Livermore National Laboratory which demonstrated gradients exceeding 200     MV / m using a 4 TW 100 fs long 800 nm Ti : Sa laser pulse. Due to the short laser and elec… [Phys. Rev. Accel. Beams 19, 021305] Published Mon Feb 29, 2016
    Keywords: New Acceleration Techniques
    Electronic ISSN: 1098-4402
    Topics: Physics
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  • 9
    Publication Date: 2016-06-16
    Print ISSN: 0002-9262
    Electronic ISSN: 1476-6256
    Topics: Medicine
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  • 10
    Publication Date: 2016-06-16
    Description: In the present study, we investigated how overall and specific domains of physical activity and sedentary behavior at the age of 7 years were associated with cognition at the age of 11 years in 8,462 children from the Millennium Cohort Study. Data were collected from 2001 to 2013. Participation in domains of physical activity and sedentary behavior at 7 years of age were reported. Activity levels were also measured objectively. Cognition was assessed using the British Ability Scales. General linear models were used to assess longitudinal associations of physical activity and sedentary behavior, measured both objectively and via self-report, with cognition. Analyses were adjusted for prespecified covariates. Sports/physical activity club attendance (B = 0.6, 95% confidence interval (CI): 0.2, 1.1), doing homework (B = 0.5, 95% CI: 0.0, 0.9), and objectively measured sedentary time (B = 0.8, 95% CI: 0.1, 1.4) at age 7 years were positively associated with cognition at age 11 years in final the models. Television viewing was negatively associated with cognition (B = –1.7, 95% CI: –2.4, –1.0), although the association was attenuated to the null after adjustments for baseline cognition. Objectively measured light physical activity was inversely associated with cognition (B = –0.7, 95% CI: –1.3, –0.1). Moderate-to-vigorous physical activity was also inversely associated with cognition in girls only (B = –1.1, 95% CI: –2.0, –0.3). Associations of physical activity and sedentary behavior with cognition appear to be context-specific in young people.
    Print ISSN: 0002-9262
    Electronic ISSN: 1476-6256
    Topics: Medicine
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