Search for: All records

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 Rotating nonaxisymmetric neutron stars (NSs) are promising sources for continuous gravitational waves (CWs). CWs may, if detected, inform us about the internal structure and equation of state of NSs. Here, we present a narrowband search for CWs from known pulsars, for which a matched-filter search can be applied. Narrowband searches are robust to mismatches between electromagnetic (EM) and gravitational emissions, in contrast to fully targeted searches where they are assumed to be phase-locked. In this work, we search for the CW counterparts emitted by 34 pulsars using data from the first and second parts of the fourth LIGO–Virgo–KAGRA observing run. We use the 5n-vector narrowband pipeline, which applies frequency-domain matched filtering. In previous searches, it covered a narrow range in the frequency—frequency time derivative (f— $\dot{f}$ ) space. Here, we also explore a range in the second time derivative of the frequency $\ddot{f}$ around the EM observations. Additionally, for the first time, we target sources in a binary system with this kind of search. We find no evidence for CWs and therefore set upper limits on the strain amplitude emitted by each pulsar. For 20 analyses, we report an upper limit below the theoretical spin-down limit. The tightest constraint is for pulsar PSR J0534+2200 (the Crab pulsar), for which our strain upper limit on the CW amplitude corresponds to ≤0.04% of the spin-down power being radiated in the CW channel. 

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 present Fermi Gamma-ray Burst Monitor (Fermi-GBM) and Swift Burst Alert Telescope (Swift-BAT) searches for gamma-ray/X-ray counterparts to gravitational-wave (GW) candidate events identified during the third observing run of the Advanced LIGO and Advanced Virgo detectors. Using Fermi-GBM onboard triggers and subthreshold gamma-ray burst (GRB) candidates found in the Fermi-GBM ground analyses, the Targeted Search and the Untargeted Search, we investigate whether there are any coincident GRBs associated with the GWs. We also search the Swift-BAT rate data around the GW times to determine whether a GRB counterpart is present. No counterparts are found. Using both the Fermi-GBM Targeted Search and the Swift-BAT search, we calculate flux upper limits and present joint upper limits on the gamma-ray luminosity of each GW. Given these limits, we constrain theoretical models for the emission of gamma rays from binary black hole mergers.