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Abstract This study examined the effects of 24R,25‐dihydroxyvitamin D₃(24R,25(OH)₂D₃) in estrogen‐responsive laryngeal cancer tumorigenesis in vivo, the mechanisms involved, and whether the ability of the tumor cells to produce 24R,25(OH)₂D₃locally is estrogen‐dependent. Estrogen receptor alpha‐66 positive (ER+) UM‐SCC‐12 cells and ER− UM‐SCC‐11A cells responded differently to 24R,25(OH)₂D₃in vivo; 24R,25(OH)₂D₃enhanced tumorigenesis in ER+ tumors but inhibited tumorigenesis in ER− tumors. Treatment with 17β‐estradiol (E₂) for 24 h reduced levels of CYP24A1 protein but increased 24R,25(OH)₂D₃production in ER+ cells; treatment with E₂for 9 min reduced CYP24A1 at 24 h and reduced 24R,25(OH)₂D₃production in ER− cells. These findings suggest the involvement of E₂receptor(s) in addition to ERα66. To investigate if 24R,25(OH)₂D₃can act locally, ER+ and ER− cells were treated with 24R,25(OH)₂D₃after inhibiting putative 24R,25(OH)₂D₃receptors, and the cells were assessed for effects on DNA synthesis (proliferation) and p53 production (apoptosis). Specific inhibitors were used to assess downstream secondary messenger signaling pathways and requirements for palmitoylation and caveolae in both cell lines. The results show that 24R,25(OH)₂D₃binds to a complex of receptors, including TLCD3B2, VDR, and protein disulfide‐isomerase A3 (PDIA3) in ER+ UM‐SCC‐12 cells. The mechanism requires palmitoylation, and PLD, PI3K, and LPAR are involved. The anti‐tumorigenic effects of 24R,25(OH)₂D₃in ER− UM‐SCC‐11A cells involve a membrane‐receptor complex consisting of VDR, PDIA3, and ROR2 within caveolae to activate a yet‐to‐be‐elucidated downstream signaling cascade. This work demonstrates a driving mechanism for the therapeutic agent 24R,25(OH)₂D₃that may be used for laryngeal cancer patients. 

Abstract Gravitational lensing by massive objects along the line of sight to the source causes distortions to gravitational wave (GW) signals; such distortions may reveal information about fundamental physics, cosmology, and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO-Virgo network. We search for repeated signals from strong lensing by (1) performing targeted searches for subthreshold signals, (2) calculating the degree of overlap among the intrinsic parameters and sky location of pairs of signals, (3) comparing the similarities of the spectrograms among pairs of signals, and (4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by (1) frequency-independent phase shifts in strongly lensed images, and (2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the nondetection of GW lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects. 

Abstract We search for gravitational-wave (GW) transients associated with fast radio bursts (FRBs) detected by the Canadian Hydrogen Intensity Mapping Experiment Fast Radio Burst Project, during the first part of the third observing run of Advanced LIGO and Advanced Virgo (2019 April 1 15:00 UTC–2019 October 1 15:00 UTC). Triggers from 22 FRBs were analyzed with a search that targets both binary neutron star (BNS) and neutron star–black hole (NSBH) mergers. A targeted search for generic GW transients was conducted on 40 FRBs. We find no significant evidence for a GW association in either search. Given the large uncertainties in the distances of our FRB sample, we are unable to exclude the possibility of a GW association. Assessing the volumetric event rates of both FRB and binary mergers, an association is limited to 15% of the FRB population for BNS mergers or 1% for NSBH mergers. We report 90% confidence lower bounds on the distance to each FRB for a range of GW progenitor models and set upper limits on the energy emitted through GWs for a range of emission scenarios. We find values of order 10⁵¹–10⁵⁷erg for models with central GW frequencies in the range 70–3560 Hz. At the sensitivity of this search, we find these limits to be above the predicted GW emissions for the models considered. We also find no significant coincident detection of GWs with the repeater, FRB 20200120E, which is the closest known extragalactic FRB. 

Abstract We use 47 gravitational wave sources from the Third LIGO–Virgo–Kamioka Gravitational Wave Detector Gravitational Wave Transient Catalog (GWTC–3) to estimate the Hubble parameter H ( z ), including its current value, the Hubble constant H 0 . Each gravitational wave (GW) signal provides the luminosity distance to the source, and we estimate the corresponding redshift using two methods: the redshifted masses and a galaxy catalog. Using the binary black hole (BBH) redshifted masses, we simultaneously infer the source mass distribution and H ( z ). The source mass distribution displays a peak around 34 M ⊙ , followed by a drop-off. Assuming this mass scale does not evolve with the redshift results in a H ( z ) measurement, yielding H 0 = 68 − 8 + 12 km s − 1 Mpc − 1 (68% credible interval) when combined with the H 0 measurement from GW170817 and its electromagnetic counterpart. This represents an improvement of 17% with respect to the H 0 estimate from GWTC–1. The second method associates each GW event with its probable host galaxy in the catalog GLADE+ , statistically marginalizing over the redshifts of each event’s potential hosts. Assuming a fixed BBH population, we estimate a value of H 0 = 68 − 6 + 8 km s − 1 Mpc − 1 with the galaxy catalog method, an improvement of 42% with respect to our GWTC–1 result and 20% with respect to recent H 0 studies using GWTC–2 events. However, we show that this result is strongly impacted by assumptions about the BBH source mass distribution; the only event which is not strongly impacted by such assumptions (and is thus informative about H 0 ) is the well-localized event GW190814.