276 research outputs found

    Evidence for Neutrino Oscillations from Muon Decay at Rest

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    A search for nu_bar_mu to nu_bar_e oscillations has been conducted at the Los Alamos Meson Physics Facility using nu_bar_mu from mu+ decay at rest. The nu_bar_e are detected via the reaction (nu_bar_e,p) -> (e+,n), correlated with the 2.2 MeV gamma from (n,p) -> (d,gamma). The use of tight cuts to identify e+ events with correlated gamma rays yields 22 events with e+ energy between 36 and 60 MeV and only 4.6 (+/- 0.6) background events. The probability that this excess is due entirely to a statistical fluctuation is 4.1E-08. A chi^2 fit to the entire e+ sample results in a total excess of 51.8 (+18.7) (-16.9) (+/- 8.0) events with e+ energy between 20 and 60 MeV. If attributed to nu_bar_mu -> nu_bar_e oscillations, this corresponds to an oscillation probability (averaged over the experimental energy and spatial acceptance) of 0.0031 (+0.0011) (-0.0010) (+/- 0.0005).Comment: 57 pages, 34 figures, revtex, additional information available at http://nu1.lampf.lanl.gov/~lsnd

    CRISPR-Cas9 ribonucleoprotein-mediated co-editing and counterselection in the rice blast fungus

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    The rice blast fungus Magnaporthe oryzae is the most serious pathogen of cultivated rice and a significant threat to global food security. To accelerate targeted mutation and specific genome editing in this species, we have developed a rapid plasmid-free CRISPR-Cas9-based genome editing method. We show that stable expression of Cas9 is highly toxic to M. oryzae. However efficient gene editing can be achieved by transient introduction of purified Cas9 pre-complexed to RNA guides to form ribonucleoproteins (RNPs). When used in combination with oligonucleotide or PCR-generated donor DNAs, generation of strains with specific base pair edits, in-locus gene replacements, or multiple gene edits, is very rapid and straightforward. We demonstrate a co-editing strategy for the creation of single nucleotide changes at specific loci. Additionally, we report a novel counterselection strategy which allows creation of precisely edited fungal strains that contain no foreign DNA and are completely isogenic to the wild type. Together, these developments represent a scalable improvement in the precision and speed of genetic manipulation in M. oryzae and are likely to be broadly applicable to other fungal species

    Energetic ion transport by microturbulence is insignificant in tokamaks

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    Energetic ion transport due to microturbulence is investigated in magnetohydrodynamic-quiescent plasmas by way of neutral beam injection in the DIII-D tokamak [J. L. Luxon, Nucl. Fusion 42, 614 (2002)]. A range of on-axis and off-axis beam injection scenarios are employed to vary relevant parameters such as the character of the background microturbulence and the value of Eb/Te , where Eb is the energetic ion energy and Te the electron temperature. In all cases, it is found that any transport enhancement due to microturbulence is too small to observe experimentally. These transport effects are modeled using numerical and analytic expectations that calculate the energetic ion diffusivity due to microturbulence. It is determined that energetic ion transport due to coherent fluctuations (e.g., Alfvén eigenmodes) is a considerably larger effect and should therefore be considered more important for ITER.United States. Dept. of Energy (DE-FC02-04ER54698)United States. Dept. of Energy (DE-FC02-99ER54512)United States. Dept. of Energy (DE-FG03-97ER54415)United States. Dept. of Energy (DE-FG02-07ER54917)United States. Dept. of Energy (DE-AC02-09CH11466)United States. Dept. of Energy (SC-G903402)United States. Dept. of Energy (DE-FG02-08ER54984)United States. Dept. of Energy ( DE-AC52-07NA27344)United States. Dept. of Energy ( DE-FG02-89ER53296)United States. Dept. of Energy (DE-FG02-08ER54999)United States. Dept. of Energy (DE-AC05-00OR22725

    Feasibility study for a correlation electron cyclotron emission turbulence diagnostic based on nonlinear gyrokinetic simulations

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    This paper describes the use of nonlinear gyrokinetic simulations to assess the feasibility of a new correlation electron cyclotron emission (CECE) diagnostic that has been proposed for the Alcator C-Mod tokamak (Marmar et al 2009 Nucl. Fusion 49 104014). This work is based on a series of simulations performed with the GYRO code (Candy and Waltz 2003 J. Comput. Phys. 186 545). The simulations are used to predict ranges of fluctuation level, peak poloidal wavenumber and radial correlation length of electron temperature fluctuations in the core of the plasma. The impact of antenna pattern and poloidal viewing location on measurable turbulence characteristics is addressed using synthetic diagnostics. An upper limit on the CECE sample volume size is determined. The modeling results show that a CECE diagnostic capable of measuring transport-relevant, long-wavelength (k[subscript θ]ρ[subscript s] < 0.5) electron temperature fluctuations is feasible at Alcator C-Mod.United States. Dept. of Energy (DE-FC02-C99ER54512-CMOD

    Adenoviral gene transfer of angiostatic ATF-BPTI inhibits tumour growth

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    BACKGROUND: The outgrowth of new vessels – angiogenesis – in the tumour mass is considered to be a limiting factor of tumour growth. To inhibit the matrix lysis that is part of the tumour angiogenesis, we employed the chimeric protein mhATF-BPTI, composed of the receptor binding part of the urokinase (ATF) linked to an inhibitor of plasmin (BPTI). METHODS: For delivery, recombinant adenovirus encoding the transgene of interest was injected intravenously or locally into the tumour. The anti tumour effect of this compound was compared to that of human endostatin and of mhATF alone in two different rat bronchial carcinomas growing either as subcutaneous implants or as metastases. RESULTS: Significant inhibition of the tumour growth and decrease of the number of lung metastasis was achieved when the concentration of mhATF-BPTI at the tumour site was above 400 of ng / g tissue. This concentration could be achieved via production by the liver, only if permissive to the recombinant adenovirus. When the tumour cells could be transduced, local delivery of the vector was enough to obtain a response. In the case of metastasis, the capacity of the lung tissue to concentrate the encoded protein was essential to reach the required therapeutic levels. Further, endostatin or mhATF could not reproduce the effects of mhATF-BPTI, at similar concentrations (mhATF) and even at 10-fold higher concentration (endostatin). CONCLUSION: The ATF-BPTI was shown to inhibit tumour growth of different rat lung tumours when critical concentration was reached. In these tumour models, endostatin or ATF induce almost no tumour response

    Computational Approaches and Analysis for a Spatio-Structural-Temporal Invasive Carcinoma Model

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    Spatio-temporal models have long been used to describe biological systems of cancer, but it has not been until very recently that increased attention has been paid to structural dynamics of the interaction between cancer populations and the molecular mechanisms associated with local invasion. One system that is of particular interest is that of the urokinase plasminogen activator (uPA) wherein uPA binds uPA receptors on the cancer cell surface, allowing plasminogen to be cleaved into plasmin, which degrades the extracellular matrix and this way leads to enhanced cancer cell migration. In this paper, we develop a novel numerical approach and associated analysis for spatio-structuro-temporal modelling of the uPA system for up to two-spatial and two-structural dimensions. This is accompanied by analytical exploration of the numerical techniques used in simulating this system, with special consideration being given to the proof of stability within numerical regimes encapsulating a central differences approach to approximating numerical gradients. The stability analysis performed here reveals instabilities induced by the coupling of the structural binding and proliferative processes. The numerical results expound how the uPA system aids the tumour in invading the local stroma, whilst the inhibitor to this system may impede this behaviour and encourage a more sporadic pattern of invasion.PostprintPeer reviewe
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