60 research outputs found
Juxtaposition of Chemical and Mutation-Induced Developmental Defects in Zebrafish Reveal a Copper-Chelating Activity for Kalihinol F
SummaryA major hurdle in using complex systems for drug screening is the difficulty of defining the mechanistic targets of small molecules. The zebrafish provides an excellent model system for juxtaposing developmental phenotypes with mechanism discovery using organism genetics. We carried out a phenotype-based screen of uncharacterized small molecules in zebrafish that produced a variety of chemically induced phenotypes with potential genetic parallels. Specifically, kalihinol F caused an undulated notochord, defects in pigment formation, hematopoiesis, and neural development. These phenotypes were strikingly similar to the zebrafish mutant, calamity, an established model of copper deficiency. Further studies into the mechanism of action of kalihinol F revealed a copper-chelating activity. Our data support this mechanism of action for kalihinol F and the utility of zebrafish as an effective system for identifying therapeutic and target pathways
Bounding the mass of the graviton using gravitional-wave observations of inspiralling compact binaries
If gravitation is propagated by a massive field, then the velocity of
gravitational waves (gravitons) will depend upon their frequency and the
effective Newtonian potential will have a Yukawa form. In the case of
inspiralling compact binaries, gravitational waves emitted at low frequency
early in the inspiral will travel slightly slower than those emitted at high
frequency later, modifying the phase evolution of the observed inspiral
gravitational waveform, similar to that caused by post-Newtonian corrections to
quadrupole phasing. Matched filtering of the waveforms can bound such
frequency-dependent variations in propagation speed, and thereby bound the
graviton mass. The bound depends on the mass of the source and on noise
characteristics of the detector, but is independent of the distance to the
source, except for weak cosmological redshift effects. For observations of
stellar-mass compact inspiral using ground-based interferometers of the
LIGO/VIRGO type, the bound on the graviton Compton wavelength is of the order
of km, about double that from solar-system tests of Yukawa
modifications of Newtonian gravity. For observations of super-massive black
hole binary inspiral at cosmological distances using the proposed laser
interferometer space antenna (LISA), the bound can be as large as km. This is three orders of magnitude weaker than model-dependent
bounds from galactic cluster dynamics.Comment: 8 pages, RevTeX, submitted to Phys. Rev.
Evaluation of Pyridoacridine Alkaloids in a Zebrafish Phenotypic Assay
Three new minor components, the pyridoacridine alkaloids 1-hydroxy-deoxyamphimedine (1), 3-hydroxy-deoxyamphimedine (2), debromopetrosamine (3), and three known compounds, amphimedine (4), neoamphimedine (5) and deoxyamphimedine (6), have been isolated from the sponge Xestospongia cf. carbonaria, collected in Palau. Structures were assigned on the basis of extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Compounds 1–6 were evaluated in a zebrafish phenotype-based assay. Amphimedine (4) was the only compound that caused a phenotype in zebrafish embryos at 30 μM. No phenotype other than death was observed for compounds 1–3, 5, 6
Origin and evolution of the light nuclides
After a short historical (and highly subjective) introduction to the field, I
discuss our current understanding of the origin and evolution of the light
nuclides D, He-3, He-4, Li-6, Li-7, Be-9, B-10 and B-11. Despite considerable
observational and theoretical progress, important uncertainties still persist
for each and every one of those nuclides. The present-day abundance of D in the
local interstellar medium is currently uncertain, making it difficult to infer
the recent chemical evolution of the solar neighborhood. To account for the
observed quasi-constancy of He-3 abundance from the Big Bang to our days, the
stellar production of that nuclide must be negligible; however, the scarce
observations of its abundance in planetary nebulae seem to contradict this
idea. The observed Be and B evolution as primaries suggests that the source
composition of cosmic rays has remained quasi-constant since the early days of
the Galaxy, a suggestion with far reaching implications for the origin of
cosmic rays; however, the main idea proposed to account for that constancy,
namely that superbubbles are at the source of cosmic rays, encounters some
serious difficulties. The best explanation for the mismatch between primordial
Li and the observed "Spite-plateau" in halo stars appears to be depletion of Li
in stellar envelopes, by some yet poorly understood mechanism. But this
explanation impacts on the level of the recently discovered early ``Li-6
plateau'', which (if confirmed), seriously challenges current ideas of cosmic
ray nucleosynthesis.Comment: 18 pages, 9 figs. Invited Review in "Symposium on the Composition of
Matter", honoring Johannes Geiss on the occasion of his 80th birthday
(Grindelwald, Switzerland, Sept. 2006), to be published in Space Science
Series of ISS
Setting upper limits on the strength of periodic gravitational waves from PSR J1939+2134 using the first science data from the GEO 600 and LIGO detectors
Data collected by the GEO 600 and LIGO interferometric gravitational wave detectors during their first observational science run were searched for continuous gravitational waves from the pulsar J1939+2134 at twice its rotation frequency. Two independent analysis methods were used and are demonstrated in this paper: a frequency domain method and a time domain method. Both achieve consistent null results, placing new upper limits on the strength of the pulsar's gravitational wave emission. A model emission mechanism is used to interpret the limits as a constraint on the pulsar's equatorial ellipticity
Physics, Astrophysics and Cosmology with Gravitational Waves
Gravitational wave detectors are already operating at interesting sensitivity
levels, and they have an upgrade path that should result in secure detections
by 2014. We review the physics of gravitational waves, how they interact with
detectors (bars and interferometers), and how these detectors operate. We study
the most likely sources of gravitational waves and review the data analysis
methods that are used to extract their signals from detector noise. Then we
consider the consequences of gravitational wave detections and observations for
physics, astrophysics, and cosmology.Comment: 137 pages, 16 figures, Published version
<http://www.livingreviews.org/lrr-2009-2
A Pipeline Strategy for Grain Crop Domestication
In the interest of diversifying the global food system, improving human nutrition, and making agriculture more sustainable, there have been many proposals to domesticate wild plants or complete the domestication of semidomesticated orphan crops. However, very few new crops have recently been fully domesticated. Many wild plants have traits limiting their production or consumption that could be costly and slow to change. Others may have fortuitous preadaptations that make them easier to develop or feasible as high-value, albeit low-yielding, crops. To increase success in contemporary domestication of new crops, we propose a pipeline approach, with attrition expected as species advance through the pipeline. We list criteria for ranking domestication candidates to help enrich the starting pool with more preadapted, promising species. We also discuss strategies for prioritizing initial research efforts once the candidates have been selected: developing higher value products and services from the crop, increasing yield potential, and focusing on overcoming undesirable traits. Finally, we present new-crop case studies that demonstrate that wild species’ limitations and potential (in agronomic culture, shattering, seed size, harvest, cleaning, hybridization, etc.) are often only revealed during the early phases of domestication. When nearly insurmountable barriers were reached in some species, they have been (at least temporarily) eliminated from the pipeline. Conversely, a few species have moved quickly through the pipeline as hurdles, such as low seed weight or low seed number per head, were rapidly overcome, leading to increased confidence, farmer collaboration, and program expansion.Fil: DeHaan, Lee R.. The Land Institute; Estados UnidosFil: Van Tassel, David L.. The Land Institute; Estados UnidosFil: Anderson, James A.. University of Minnesota; Estados UnidosFil: Asselin, Sean R.. University of Manitoba; CanadáFil: Barnes, Richard. University of Minnesota; Estados UnidosFil: Baute, Gregory J.. University of British Columbia; CanadáFil: Cattani, Douglas J.. University of Manitoba; CanadáFil: Culman, Steve W.. Ohio State University; Estados UnidosFil: Dorn, Kevin M.. University of Minnesota; Estados UnidosFil: Hulke, Brent S.. United States Department of Agriculture. Agriculture Research Service; Estados UnidosFil: Kantar, Michael. University of British Columbia; CanadáFil: Larson, Steve. Forage and Range Research Laboratory; Estados UnidosFil: David Marks, M.. University of Minnesota; Estados UnidosFil: Miller, Allison J.. Saint Louis University; Estados UnidosFil: Poland, Jesse. Kansas State University; Estados UnidosFil: Ravetta, Damián AndrĂ©s. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina. Museo PaleontolĂłgico Egidio Feruglio; ArgentinaFil: Rude, Emily. University of Wisconsin; Estados UnidosFil: Ryan, Matthew R.. Cornell University; Estados UnidosFil: Wyse, Don. University of Minnesota; Estados UnidosFil: Zhang, Xiaofei. University of Minnesota; Estados Unido
The Confrontation between General Relativity and Experiment
The status of experimental tests of general relativity and of theoretical
frameworks for analysing them is reviewed. Einstein's equivalence principle
(EEP) is well supported by experiments such as the Eotvos experiment, tests of
special relativity, and the gravitational redshift experiment. Future tests of
EEP and of the inverse square law are searching for new interactions arising
from unification or quantum gravity. Tests of general relativity at the
post-Newtonian level have reached high precision, including the light
deflection, the Shapiro time delay, the perihelion advance of Mercury, and the
Nordtvedt effect in lunar motion. Gravitational-wave damping has been detected
in an amount that agrees with general relativity to better than half a percent
using the Hulse-Taylor binary pulsar, and other binary pulsar systems have
yielded other tests, especially of strong-field effects. When direct
observation of gravitational radiation from astrophysical sources begins, new
tests of general relativity will be possible.Comment: 89 pages, 8 figures; an update of the Living Review article
originally published in 2001; final published version incorporating referees'
suggestion
Primordial Nucleosynthesis for the New Cosmology: Determining Uncertainties and Examining Concordance
Big bang nucleosynthesis (BBN) and the cosmic microwave background (CMB) have
a long history together in the standard cosmology. The general concordance
between the predicted and observed light element abundances provides a direct
probe of the universal baryon density. Recent CMB anisotropy measurements,
particularly the observations performed by the WMAP satellite, examine this
concordance by independently measuring the cosmic baryon density. Key to this
test of concordance is a quantitative understanding of the uncertainties in the
BBN light element abundance predictions. These uncertainties are dominated by
systematic errors in nuclear cross sections. We critically analyze the cross
section data, producing representations that describe this data and its
uncertainties, taking into account the correlations among data, and explicitly
treating the systematic errors between data sets. Using these updated nuclear
inputs, we compute the new BBN abundance predictions, and quantitatively
examine their concordance with observations. Depending on what deuterium
observations are adopted, one gets the following constraints on the baryon
density: OmegaBh^2=0.0229\pm0.0013 or OmegaBh^2 = 0.0216^{+0.0020}_{-0.0021} at
68% confidence, fixing N_{\nu,eff}=3.0. Concerns over systematics in helium and
lithium observations limit the confidence constraints based on this data
provide. With new nuclear cross section data, light element abundance
observations and the ever increasing resolution of the CMB anisotropy, tighter
constraints can be placed on nuclear and particle astrophysics. ABRIDGEDComment: 54 pages, 20 figures, 5 tables v2: reflects PRD version minor changes
to text and reference
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