Multimessenger Search for Sources of Gravitational Waves and High-Energy Neutrinos: Results for Initial LIGO-Virgo and IceCube

We report the results of a multimessenger search for coincident signals from the LIGO and Virgo gravitational-wave observatories and the partially completed IceCube high-energy neutrino detector, including periods of joint operation between 2007-2010. These include parts of the 2005-2007 run and the 2009-2010 run for LIGO-Virgo, and IceCube's observation periods with 22, 59 and 79 strings. We find no significant coincident events, and use the search results to derive upper limits on the rate of joint sources for a range of source emission parameters. For the optimistic assumption of gravitational-wave emission energy of $10^{-2}$\,M$_\odot$c$^2$ at $\sim 150$\,Hz with $\sim 60$\,ms duration, and high-energy neutrino emission of $10^{51}$\,erg comparable to the isotropic gamma-ray energy of gamma-ray bursts, we limit the source rate below $1.6 \times 10^{-2}$\,Mpc$^{-3}$yr$^{-1}$. We also examine how combining information from gravitational waves and neutrinos will aid discovery in the advanced gravitational-wave detector era

An automated system for rapid cellular extraction from live zebrafish embryos and larvae: Development and application to genotyping.

Zebrafish are a valuable model organism in biomedical research. Their rapid development, ability to model human diseases, utility for testing genetic variants identified from next-generation sequencing, amenity to CRISPR mutagenesis, and potential for therapeutic compound screening, has led to their wide-spread adoption in diverse fields of study. However, their power for large-scale screens is limited by the absence of automated genotyping tools for live animals. This constrains potential drug screen options, limits analysis of embryonic and larval phenotypes, and requires raising additional animals to adulthood to ensure obtaining an animal of the desired genotype. Our objective was to develop an automated system that would rapidly obtain cells and DNA from zebrafish embryos and larvae for genotyping, and that would keep the animals alive. We describe the development, testing, and validation of a zebrafish embryonic genotyping device, termed "ZEG" (Zebrafish Embryo Genotyper). Using microfluidic harmonic oscillation of the animal on a roughened glass surface, the ZEG is able to obtain genetic material (cells and DNA) for use in genotyping, from 24 embryos or larvae simultaneously in less than 10 minutes. Loading and unloading of the ZEG is performed manually with a standard pipette tip or transfer pipette. The obtained genetic material is amplified by PCR and can be used for subsequent analysis including sequencing, gel electrophoresis, or high-resolution melt-analysis. Sensitivity of genotyping and survival of animals are both greater than 90%. There are no apparent effects on body morphology, development, or motor behavior tests. In summary, the ZEG device enables rapid genotyping of live zebrafish embryos and larvae, and animals are available for downstream applications, testing, or raising

Flow diagram.

<p>Flow diagram for genetic material extraction using the ZEG.</p

Behavior results following ZEG genotyping.

<p>Behavior results for 7 dpf larvae, comparing embryos genotyped on the ZEG to controls; there were no statistically significant differences. Box-plot analyses.</p

Views of glass slides (chips) for genotoyping.

<p>A) Schematic of glass slide, hydrophobic tape, and well design. B) 24 channel chip, top view; C) 24 channel chip loaded with 72 hpf zebrafish embryos; D) Base unit; E) Base unit with loading of 24 channel chip.</p

Testing of ZEG parameters.

<p>A) Evaluation for cross-contamination. Neighboring wells on a 24 channel chip were loaded either with an embryo or with a control (water blank); extraction was performed, followed by PCR and then HRMA. No signal was obtained in the water blank controls. Note, well B8 was designated in the software as a negative control and was therefore marked as a “Water (Negative)” with a block box; the maroon boxes labeled “Negative” were scored by the software algorithm as being negative/not amplifying. B) Representative images of cellular material collected following ZEG extraction; trypan blue staining. Scale bar 5 μm.</p