515 research outputs found
Cellular mechano-environment regulates the mammary circadian clock
Circadian clocks drive B24 h rhythms in tissue physiology. They rely on transcriptional/ translational feedback loops driven by interacting networks of clock complexes. However, little is known about how cell-intrinsic circadian clocks sense and respond to their microenvironment. Here, we reveal that the breast epithelial clock is regulated by the mechano-chemical stiffness of the cellular microenvironment in primary cell culture. Moreover, the mammary clock is controlled by the periductal extracellular matrix in vivo, which contributes to a dampened circadian rhythm during ageing. Mechanistically, the tension sensing cell-matrix adhesion molecule, vinculin, and the Rho/ROCK pathway, which transduces signals provided by extracellular stiffness into cells, regulate the activity of the core circadian clock complex. We also show that genetic perturbation, or age-associated disruption of self-sustained clocks, compromises the self-renewal capacity of mammary epithelia. Thus, circadian clocks are mechano-sensitive, providing a potential mechanism to explain how ageing influences their amplitude and function
Astrophysical science metrics for next-generation gravitational-wave detectors
The second generation of gravitational-wave (GW) detectors are being built and tuned all over the world. The detection of signals from binary black holes is beginning to fulfil the promise of GW astronomy. In this work, we examine several possible configurations for third-generation laser interferometers in existing km-scale facilities. We propose a set of astrophysically motivated metrics to evaluate detector performance. We measure the impact of detector design choices against these metrics, providing a quantitative cost-benefit analyses of the resulting scientific payoffs
The scientific potential of space-based gravitational wave detectors
The millihertz gravitational wave band can only be accessed with a
space-based interferometer, but it is one of the richest in potential sources.
Observations in this band have amazing scientific potential. The mergers
between massive black holes with mass in the range 10 thousand to 10 million
solar masses, which are expected to occur following the mergers of their host
galaxies, produce strong millihertz gravitational radiation. Observations of
these systems will trace the hierarchical assembly of structure in the Universe
in a mass range that is very difficult to probe electromagnetically. Stellar
mass compact objects falling into such black holes in the centres of galaxies
generate detectable gravitational radiation for several years prior to the
final plunge and merger with the central black hole. Measurements of these
systems offer an unprecedented opportunity to probe the predictions of general
relativity in the strong-field and dynamical regime. Millihertz gravitational
waves are also generated by millions of ultra-compact binaries in the Milky
Way, providing a new way to probe galactic stellar populations. ESA has
recognised this great scientific potential by selecting The Gravitational
Universe as its theme for the L3 large satellite mission, scheduled for launch
in ~2034. In this article we will review the likely sources for millihertz
gravitational wave detectors and describe the wide applications that
observations of these sources could have for astrophysics, cosmology and
fundamental physics.Comment: 18 pages, 2 figures, contribution to Gravitational Wave Astrophysics,
the proceedings of the 2014 Sant Cugat Forum on Astrophysics; v2 includes one
additional referenc
Comparison of in silico strategies to prioritize rare genomic variants impacting RNA splicing for the diagnosis of genomic disorders
The development of computational methods to assess pathogenicity of pre-messenger RNA splicing variants is critical for diagnosis of human disease. We assessed the capability of eight algorithms, and a consensus approach, to prioritize 249 variants of uncertain significance (VUSs) that underwent splicing functional analyses. The capability of algorithms to differentiate VUSs away from the immediate splice site as being 'pathogenic' or 'benign' is likely to have substantial impact on diagnostic testing. We show that SpliceAI is the best single strategy in this regard, but that combined usage of tools using a weighted approach can increase accuracy further. We incorporated prioritization strategies alongside diagnostic testing for rare disorders. We show that 15% of 2783 referred individuals carry rare variants expected to impact splicing that were not initially identified as 'pathogenic' or 'likely pathogenic'; one in five of these cases could lead to new or refined diagnoses
Scientific Objectives of Einstein Telescope
The advanced interferometer network will herald a new era in observational
astronomy. There is a very strong science case to go beyond the advanced
detector network and build detectors that operate in a frequency range from 1
Hz-10 kHz, with sensitivity a factor ten better in amplitude. Such detectors
will be able to probe a range of topics in nuclear physics, astronomy,
cosmology and fundamental physics, providing insights into many unsolved
problems in these areas.Comment: 18 pages, 4 figures, Plenary talk given at Amaldi Meeting, July 201
Gravitational Waves From Known Pulsars: Results From The Initial Detector Era
We present the results of searches for gravitational waves from a large selection of pulsars using data from the most recent science runs (S6, VSR2 and VSR4) of the initial generation of interferometric gravitational wave detectors LIGO (Laser Interferometric Gravitational-wave Observatory) and Virgo. We do not see evidence for gravitational wave emission from any of the targeted sources but produce upper limits on the emission amplitude. We highlight the results from seven young pulsars with large spin-down luminosities. We reach within a factor of five of the canonical spin-down limit for all seven of these, whilst for the Crab and Vela pulsars we further surpass their spin-down limits. We present new or updated limits for 172 other pulsars (including both young and millisecond pulsars). Now that the detectors are undergoing major upgrades, and, for completeness, we bring together all of the most up-to-date results from all pulsars searched for during the operations of the first-generation LIGO, Virgo and GEO600 detectors. This gives a total of 195 pulsars including the most recent results described in this paper.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyAustralian Research CouncilInternational Science Linkages program of the Commonwealth of AustraliaCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Economia y CompetitividadConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsNetherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFOCUS Programme of Foundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space AdministrationOTKA of HungaryLyon Institute of Origins (LIO)National Research Foundation of KoreaIndustry CanadaProvince of Ontario through the Ministry of Economic Development and InnovationNational Science and Engineering Research Council CanadaCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationAstronom
First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data
Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of
continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a
fully coherent search, based on matched filtering, which uses the position and rotational parameters
obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto-
noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch
between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have
been developed, allowing a fully coherent search for gravitational waves from known pulsars over a
fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of
11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial
outliers, further studies show no significant evidence for the presence of a gravitational wave signal.
Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of
the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for
the first time. For an additional 3 targets, the median upper limit across the search bands is below the
spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried
out so far
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