Cyclo­oxygenase-1-selective inhibitor SC-560

In the title compound, 5-(4-chloro­phen­yl)-1-(4-methoxy­phen­yl)-3-(trifluoro­meth­yl)-1H-pyrazole (SC-560), C17H12ClF3N2O, a COX-1-selective inhibitor, the dihedral angles between the heterocycle and the chlorobenzene and methoxybenzene rings are 41.66 (6) and 43.08 (7)°, respectively. The dihedral angle between the two phenyl rings is 59.94 (6)°. No classic hydrogen bonds are possible in the crystal, and intermolecular interactions must be mainly of the dispersion type. This information may aid the identification of dosage formulations with improved oral bioavailability

Tumor suppressive activity of prolyl isomerase Pin1 in renal cell carcinoma

Pin1 specifically recognizes and catalyzes the cis-trans isomerization of phosphorylated-Ser/Thr-Pro bonds, which modulate the stability, localization, and function of numerous Pin1 targets involved in tumor progression. However, the role of Pin1 in cancer remains enigmatic as the gene is located on chromosome 19p13.2, which is a region subject to loss of heterozygosity in several tumors. Since Pin1 protein is frequently under-expressed in kidney cancer, we have explored its role in human clear cell renal cell carcinoma (ccRCC). Here we show evidence for PIN1 gene deletion and mRNA under-expression as a mechanism of Pin1 reduction in ccRCC tumors. We demonstrate that restoration of Pin1 in cell lines found to be deficient in Pin1 protein expression can attenuate the growth of ccRCC cells in soft agar and a xenograft tumor model. Moreover, this ability of Pin1 to negatively influence tumor growth in ccRCC cells may be dependent on the presence of functional p53, which is infrequently mutated in ccRCC. These observations suggest Pin1 may have a mild tumor suppressive role in ccRCC

CI and CO in Nearby Spiral Galaxies -- I. Line Ratio and Abundance Variations at ~ 200 pc Scales

We present new neutral atomic carbon [CI](3P1-3P0) mapping observations within the inner ~7 kpc and ~4 kpc of the disks of NGC3627 and NGC4321 at a spatial resolution of 190 pc and 270 pc, respectively, using the ALMA Atacama Compact Array (ACA). We combine these with the CO(2-1) data from PHANGS-ALMA, and literature [CI] and CO data for two other starburst and/or active galactic nucleus (AGN) galaxies (NGC1808, NGC7469), to study: a) the spatial distributions of CI and CO emission; b) the observed line ratio RCICO = I_[CI](1-0)/I_CO(2-1) as a function of various galactic properties; and c) the abundance ratio of [CI/CO]. We find excellent spatial correspondence between CI and CO emission and nearly uniform RCICO ~0.1 across the majority of the star-forming disks of NGC3627 and NGC4321. However, RCICO strongly varies from ~0.05 at the centre of NGC4321 to >0.2-0.5 in NGC1808's starburst centre and NGC7469's centre with an X-ray AGN. Meanwhile, RCICO does not obviously vary with $U$, similar to the prediction of PDR models. We also find a mildly decreasing RCICO with an increasing metallicity over 0.7-0.85 solar metallicity, consistent with the literature. Assuming various typical ISM conditions representing GMCs, active star-forming regions and strong starbursting environments, we calculate the LTE radiative transfer and estimate the [CI/CO] abundance ratio to be ~0.1 across the disks of NGC3627 and NGC4321, similar to previous large-scale findings in Galactic studies. However, this abundance ratio likely has a substantial increase to ~1 and >1-5 in NGC1808's starburst and NGC7469's strong AGN environments, respectively, in line with the expectations for cosmic-ray dominated region (CRDR) and X-ray dominated region (XDR) chemistry. Finally, we do not find a robust evidence for a generally CO-dark, CI-bright gas in the disk areas we probed. (abbreviated)Comment: 23 pages, 13 figures and one table in total (17 pages and 9 figures in main text). Accepted for publication in A&A. For associated data cubes and moment maps, see https://www.canfar.net/storage/vault/list/phangs/RELEASES/DZLIU_etal_202

Star Formation Laws and Efficiencies across 80 Nearby Galaxies

We measure empirical relationships between the local star formation rate (SFR) and properties of the star-forming molecular gas on 1.5 kpc scales across 80 nearby galaxies. These relationships, commonly referred to as "star formation laws," aim at predicting the local SFR surface density from various combinations of molecular gas surface density, galactic orbital time, molecular cloud free-fall time, and the interstellar medium dynamical equilibrium pressure. Leveraging a multiwavelength database built for the PHANGS survey, we measure these quantities consistently across all galaxies and quantify systematic uncertainties stemming from choices of SFR calibrations and the CO-to-H$_2$ conversion factors. The star formation laws we examine show 0.3-0.4 dex of intrinsic scatter, among which the molecular Kennicutt-Schmidt relation shows a $\sim$10% larger scatter than the other three. The slope of this relation ranges $\beta\approx0.9{-}1.2$, implying that the molecular gas depletion time remains roughly constant across the environments probed in our sample. The other relations have shallower slopes ($\beta\approx0.6{-}1.0$), suggesting that the star formation efficiency (SFE) per orbital time, the SFE per free-fall time, and the pressure-to-SFR surface density ratio (i.e., the feedback yield) may vary systematically with local molecular gas and SFR surface densities. Last but not least, the shapes of the star formation laws depend sensitively on methodological choices. Different choices of SFR calibrations can introduce systematic uncertainties of at least 10-15% in the star formation law slopes and 0.15-0.25 dex in their normalization, while the CO-to-H$_2$ conversion factors can additionally produce uncertainties of 20-25% for the slope and 0.10-0.20 dex for the normalization.Comment: 10 pages main text + 2 appendices. ApJL in press. Data products available at https://www.canfar.net/storage/list/phangs/RELEASES/Sun_etal_2023 . Slides summarizing key results can be found at https://www.dropbox.com/s/5gsegexeo9n0t05/Sun_et_PHANGS_2023.pptx?dl=

The Physical Drivers and Observational Tracers of CO-to-H2 Conversion Factor Variations in Nearby Barred Galaxy Centers

The CO-to-H$_2$ conversion factor (\alpha_\rm{CO}) is central to measuring the amount and properties of molecular gas. It is known to vary with environmental conditions, and previous studies have revealed lower \alpha_\rm{CO} in the centers of some barred galaxies on kpc scales. To unveil the physical drivers of such variations, we obtained ALMA Band 3, 6, and 7 observations toward the inner 2 kpc of NGC 3627 and NGC 4321 tracing $^{12}$CO, $^{13}$CO, and C$^{18}$O lines on 100 pc scales. Our multi-line modeling and Bayesian likelihood analysis of these datasets reveal variations of molecular gas density, temperature, optical depth, and velocity dispersion, which are among the key drivers of \alpha_\rm{CO}. The central 300 pc nuclei in both galaxies show strong enhancement of temperature T_\rm{k}>100 K and density n_\rm{H_2}>10^3 cm$^{-3}$. Assuming a CO-to-H$_2$ abundance of $3\times10^{-4}$, we derive 4-15 times lower \alpha_\rm{CO} than the Galactic value across our maps, which agrees well with previous kpc-scale measurements. Combining the results with our previous work on NGC 3351, we find a strong correlation of \alpha_\rm{CO} with low-J $^{12}$CO optical depths (\tau_\rm{CO}), as well as an anti-correlation with T_\rm{k}. The \tau_\rm{CO} correlation explains most of the \alpha_\rm{CO} variation in the three galaxy centers, whereas changes in T_\rm{k} influence \alpha_\rm{CO} to second order. Overall, the observed line width and $^{12}$CO/$^{13}$CO 2-1 line ratio correlate with \tau_\rm{CO} variation in these centers, and thus they are useful observational indicators for \alpha_\rm{CO} variation. We also test current simulation-based \alpha_\rm{CO} prescriptions and find a systematic overprediction, which likely originates from the mismatch of gas conditions between our data and the simulations.Comment: Accepted for publication in ApJ; 30 pages of main text + 3 appendice

Fuelling the nuclear ring of NGC 1097

Galactic bars can drive cold gas inflows towards the centres of galaxies. The gas transport happens primarily through the so-called bar ``dust lanes'', which connect the galactic disc at kpc scales to the nuclear rings at hundreds of pc scales much like two gigantic galactic rivers. Once in the ring, the gas can fuel star formation activity, galactic outflows, and central supermassive black holes. Measuring the mass inflow rates is therefore important to understanding the mass/energy budget and evolution of galactic nuclei. In this work, we use CO datacubes from the PHANGS-ALMA survey and a simple geometrical method to measure the bar-driven mass inflow rate onto the nuclear ring of the barred galaxy NGC~1097. The method assumes that the gas velocity in the bar lanes is parallel to the lanes in the frame co-rotating with the bar, and allows one to derive the inflow rates from sufficiently sensitive and resolved position-position-velocity diagrams if the bar pattern speed and galaxy orientations are known. We find an inflow rate of $\dot{M}=(3.0 \pm 2.1)\, \rm M_\odot\, yr^{-1}$ averaged over a time span of 40 Myr, which varies by a factor of a few over timescales of $\sim$10 Myr. Most of the inflow appears to be consumed by star formation in the ring which is currently occurring at a rate of ${\rm SFR}\simeq~1.8$-$2 \rm M_\odot\, yr^{-1}$, suggesting that the inflow is causally controlling the star formation rate in the ring as a function of time.Comment: Accepted in MNRA

The ALMOND Survey: Molecular cloud properties and gas density tracers across 25 nearby spiral galaxies with ALMA

We use new HCN(1-0) data from the ALMOND (ACA Large-sample Mapping Of Nearby galaxies in Dense gas) survey to trace the kpc-scale molecular gas density structure and CO(2-1) data from PHANGS-ALMA to trace the bulk molecular gas across 25 nearby, star-forming galaxies. At 2.1 kpc scale, we measure the density-sensitive HCN/CO line ratio and the SFR/HCN ratio to trace the star formation efficiency in the denser molecular medium. At 150 pc scale, we measure structural and dynamical properties of the molecular gas via CO(2-1) line emission, which is linked to the lower resolution data using an intensity-weighted averaging method. We find positive correlations (negative) of HCN/CO (SFR/HCN) with the surface density, the velocity dispersion and the internal turbulent pressure of the molecular gas. These observed correlations agree with expected trends from turbulent models of star formation, which consider a single free-fall time gravitational collapse. Our results show that the kpc-scale HCN/CO line ratio is a powerful tool to trace the 150 pc scale average density distribution of the molecular clouds. Lastly, we find systematic variations of the SFR/HCN ratio with cloud-scale molecular gas properties, which are incompatible with a universal star formation efficiency. Overall, these findings show that mean molecular gas density, molecular cloud properties and star formation are closely linked in a coherent way, and observations of density-sensitive molecular gas tracers are a useful tool to analyse these variations, linking molecular gas physics to stellar output across galaxy discs.Comment: 48 pages, 40 figure

Missing OH reactivity in the global marine boundary layer

The hydroxyl radical (OH) reacts with thousands of chemical species in the atmosphere, initiating their removal and the chemical reaction sequences that produce ozone, secondary aerosols, and gas-phase acids. OH reactivity, which is the inverse of OH lifetime, influences the OH abundance and the ability of OH to cleanse the atmosphere. The NASA Atmospheric Tomography (ATom) campaign used instruments on the NASA DC-8 aircraft to measure OH reactivity and more than 100 trace chemical species. ATom presented a unique opportunity to test the completeness of the OH reactivity calculated from the chemical species measurements by comparing it to the measured OH reactivity over two oceans across four seasons. Although the calculated OH reactivity was below the limit of detection for the ATom instrument used to measure OH reactivity throughout much of the free troposphere, the instrument was able to measure the OH reactivity in and just above the marine boundary layer. The mean measured value of OH reactivity in the marine boundary layer across all latitudes and all ATom deployments was 1.9 s⁻¹, which is 0.5 s⁻¹ larger than the mean calculated OH reactivity. The missing OH reactivity, the difference between the measured and calculated OH reactivity, varied between 0 and 3.5 s⁻¹, with the highest values over the Northern Hemisphere Pacific Ocean. Correlations of missing OH reactivity with formaldehyde, dimethyl sulfide, butanal, and sea surface temperature suggest the presence of unmeasured or unknown volatile organic compounds or oxygenated volatile organic compounds associated with ocean emissions

The Related Transcriptional Enhancer Factor-1 Isoform, TEAD4216, Can Repress Vascular Endothelial Growth Factor Expression in Mammalian Cells

Increased cellular production of vascular endothelial growth factor (VEGF) is responsible for the development and progression of multiple cancers and other neovascular conditions, and therapies targeting post-translational VEGF products are used in the treatment of these diseases. Development of methods to control and modify the transcription of the VEGF gene is an alternative approach that may have therapeutic potential. We have previously shown that isoforms of the transcriptional enhancer factor 1-related (TEAD4) protein can enhance the production of VEGF. In this study we describe a new TEAD4 isoform, TEAD4216, which represses VEGF promoter activity. The TEAD4216 isoform inhibits human VEGF promoter activity and does not require the presence of the hypoxia responsive element (HRE), which is the sequence critical to hypoxia inducible factor (HIF)-mediated effects. The TEAD4216 protein is localized to the cytoplasm, whereas the enhancer isoforms are found within the nucleus. The TEAD4216 isoform can competitively repress the stimulatory activity of the TEAD4434 and TEAD4148 enhancers. Synthesis of the native VEGF165 protein and cellular proliferation is suppressed by the TEAD4216 isoform. Mutational analysis indicates that nuclear or cytoplasmic localization of any isoform determines whether it acts as an enhancer or repressor, respectively. The TEAD4216 isoform appears to inhibit VEGF production independently of the HRE required activity by HIF, suggesting that this alternatively spliced isoform of TEAD4 may provide a novel approach to treat VEGF-dependent diseases