The Advanced LIGO gravitational-wave detectors are limited by optical quantum noise in most of their detection band. To overcome this limit, squeezed vacuum states have been injected into the ...Advanced LIGO detectors during the third observing run (O3), leading to an increase of their detection rate by about 40% to 50%. Here we present a key element of LIGO's squeezed vacuum source: the seismic isolation platform that houses core components placed in ultra-high vacuum. This paper describes the architecture of the isolation platform as well as the active control system, tuned to minimize backscattered light that otherwise deteriorates the sensitivity of the detectors. This architecture permits fewer optical Faraday isolators in the optical path of the squeezing system, minimizing optical losses to maximize the quantum noise improvement. The system reliably operated throughout LIGO's O3 with no evidence of noise from backscattered light. The innovative architecture of this platform makes it ideal for straightforward reshaping and adaptation to other gravitational-wave detector subsystems and low-noise optical instrumentation.
Histone deacetylases (HDACs) are a family of 18 epigenetic modifiers that fall into 4 classes. Histone deacetylase inhibitors (HDACi) are valid tools to assess HDAC functions. HDAC6 and HDAC10 belong ...to the class IIb subgroup of the HDAC family. The targets and biological functions of HDAC10 are ill-defined. This lack of knowledge is due to a lack of specific and potent HDAC10 inhibitors with cellular activity. Here, we have synthesized and characterized piperidine-4-acrylhydroxamates as potent and highly selective inhibitors of HDAC10. This was achieved by targeting the acidic gatekeeper residue Glu274 of HDAC10 with a basic piperidine moiety that mimics the interaction of the polyamine substrate of HDAC10. We have confirmed the binding modes of selected inhibitors using X-ray crystallography. Promising candidates were selected based on their specificity by in vitro profiling using recombinant HDACs. The most promising HDAC10 inhibitors 10c and 13b were tested for specificity in acute myeloid leukemia (AML) cells with the FLT3-ITD oncogene. By immunoblot experiments we assessed the hyperacetylation of histones and tubulin-α, which are class I and HDAC6 substrates, respectively. As validated test for HDAC10 inhibition we used flow cytometry assessing autolysosome formation in neuroblastoma and AML cells. We demonstrate that 10c and 13b inhibit HDAC10 with high specificity over HDAC6 and with no significant impact on class I HDACs. The accumulation of autolysosomes is not a consequence of apoptosis and 10c and 13b are not toxic for normal human kidney cells. These data show that 10c and 13b are nanomolar inhibitors of HDAC10 with high specificity. Thus, our new HDAC10 inhibitors are tools to identify the downstream targets and functions of HDAC10 in cells.
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•Structure-based optimization yielded a novel class of highly selective histone deacetylase 10 (HDAC10) inhibitors.•Four synthesized inhibitors were co-crystallized with HDAC10.•Cellular target engagement and selectivity were tested by western blots and hyperacetylation of histones and α-tubulin.•HDAC10 inhibitors modulate autophagy in aggressive FLT3-ITD positive acute myeloid leukemia cells.
The characterization of the Advanced LIGO detectors in the second and third observing runs has increased the sensitivity of the instruments, allowing for a higher number of detectable ...gravitational-wave signals, and provided confirmation of all observed gravitational-wave events. In this work, we present the methods used to characterize the LIGO detectors and curate the publicly available datasets, including the LIGO strain data and data quality products. We describe the essential role of these datasets in LIGO-Virgo Collaboration analyses of gravitational-waves from both transient and persistent sources and include details on the provenance of these datasets in order to support analyses of LIGO data by the broader community. Finally, we explain anticipated changes in the role of detector characterization and current efforts to prepare for the high rate of gravitational-wave alerts and events in future observing runs.
We present a tabletop six-axis vibration isolation system, compatible with Ultra-High Vacuum (UHV), which is actively damped and provides 25 dB of isolation at 10 Hz and 65 dB at 100 Hz. While this ...isolation platform has been primarily designed to support optics in the Laser Interferometer Gravitational-Wave Observatory (LIGO) detectors, it is suitable for a variety of applications. The system has been engineered to facilitate the construction and assembly process, while minimizing cost. The platform provides passive isolation for six degrees of freedom using a combination of vertical springs and horizontal pendula. It is instrumented with voice-coil actuators and optical shadow sensors to damp the resonances. All materials are compatible with stringent vacuum requirements. Thanks to its architecture, the system's footprint can be adapted to meet spatial requirements, while maximizing the dimensions of the optical table. Three units are currently operating for LIGO. We present the design of the system, controls principle, and experimental results.
Small, highly absorbing points are randomly present on the surfaces of the main interferometer optics in Advanced LIGO. The resulting nano-meter scale thermo-elastic deformations and substrate lenses ...from these micron-scale absorbers significantly reduces the sensitivity of the interferometer directly though a reduction in the power-recycling gain and indirect interactions with the feedback control system. We review the expected surface deformation from point absorbers and provide a pedagogical description of the impact on power build-up in second generation gravitational wave detectors (dual-recycled Fabry-Perot Michelson interferometers). This analysis predicts that the power-dependent reduction in interferometer performance will significantly degrade maximum stored power by up to 50% and hence, limit GW sensitivity, but suggests system wide corrections that can be implemented in current and future GW detectors. This is particularly pressing given that future GW detectors call for an order of magnitude more stored power than currently used in Advanced LIGO in Observing Run 3. We briefly review strategies to mitigate the effects of point absorbers in current and future GW wave detectors to maximize the success of these enterprises.
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