| 1. |
- Lamperti, I., et al.
(author)
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SUPER: V. ALMA continuum observations of z ∼2 AGN and the elusive evidence of outflows influencing star formation
- 2021
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 654
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Journal article (peer-reviewed)abstract
- We study the impact of active galactic nuclei (AGN) ionised outflows on star formation in high-redshift AGN host galaxies, by combining near-infrared integral field spectroscopic (IFS) observations, mapping the H emission and [O iii]5007 outflows, with matched-resolution observations of the rest-frame far-infrared (FIR) emission.We present high-resolution ALMA Band 7 observations of eight X-ray selected AGN (L2-10 keV = 1043:81045:2 erg s1) at z 2 from the SUPER (SINFONI Survey for Unveiling the Physics and Eect of Radiative feedback) sample, targeting the observed-frame 870 m (rest-frame 260 m) continuum at 2 kpc (0.200) spatial resolution. The targets were selected among the SUPER AGN with an [O iii] detection in the IFS maps and with a detection in the FIR photometry. We detected six out of eight targets with signal-to-noise ratio S=N & 10 in the ALMA maps, from which we measured continuum flux densities in the range 0:272:58 mJy and FIR half-light radii (Re) in the range 0:8-2:1 kpc. The other two targets were detected with S/N of 3.6 and 5.9, which are insucient for spatially resolved analysis. The FIR Re of our sample are comparable to other AGN and star-forming galaxies at a similar redshift from the literature. However, combining our sample with the literature samples, we find that the mean FIR size in X-ray AGN (Re = 1:16 0:11 kpc) is slightly smaller than in non-AGN (Re = 1:69 0:13 kpc). From spectral energy distribution fitting, we find that the main contribution to the 260 m flux density is dust heated by star formation, with 4% contribution from AGN-heated dust and 1% from synchrotron emission. The majority of our sample show dierent morphologies for the FIR (mostly due to reprocessed stellar emission) and the ionised gas emission (H and [O iii], mostly due to AGN emission). This could be due to the dierent locations of dust and ionised gas, the dierent sources of the emission (stars and AGN), or the eect of dust obscuration.We are unable to identify any residual H emission, above that dominated by AGN, that could be attributed to star formation. Under the assumption that the FIR emission is a reliable tracer of obscured star formation, we find that the obscured star formation activity in these AGN host galaxies is not clearly aected by the ionised outflows. However, we cannot rule out that star formation suppression is happening on smaller spatial scales than the ones we probe with our observations (<2 kpc) or on dierent timescales.
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| 2. |
- Vietri, G., et al.
(author)
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SUPER - III. Broad line region properties of AGNs at z ∼ 2
- 2020
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 644
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Journal article (peer-reviewed)abstract
- Aims. The SINFONI survey for Unveiling the Physics and Effect of Radiative feedback (SUPER) was designed to conduct a blind search for AGN-driven outflows on X-ray-selected AGNs at redshift z similar to 2 with high (similar to 2 kpc) spatial resolution, and to correlate them with the properties of their host galaxy and central black hole. The main aims of this paper are: (a) to derive reliable estimates for the masses of the black holes and accretion rates for the Type-1 AGNs in this survey; and (b) to characterise the properties of the AGN-driven winds in the broad line region (BLR).Methods. We analysed rest-frame optical and UV spectra of 21 Type-1 AGNs. We used H alpha, H beta, and MgII line profiles to estimate the masses of the black holes. We used the blueshift of the CIV line profile to trace the presence of winds in the BLR.Results. We find that the H alpha and H beta line widths are strongly correlated, as is the line continuum luminosity at 5100 angstrom with H alpha line luminosity, resulting in a well-defined correlation between black hole masses estimated from H alpha and H beta. Using these lines, we estimate that the black hole masses for our objects are in the range Log (M-BH/M-circle dot) = 8.4-10.8 and are accreting at lambda (Edd) = 0.04-1.3. Furthermore, we confirm the well-known finding that the CIV line width does not correlate with the Balmer lines and the peak of the line profile is blueshifted with respect to the [OIII]-based systemic redshift. These findings support the idea that the CIV line is tracing outflowing gas in the BLR for which we estimated velocities up to similar to 4700 km s(-1). We confirm the strong dependence of the BLR wind velocity on the UV-to-X-ray continuum slope, the bolometric luminosity, and Eddington ratio. We infer BLR mass outflow rates in the range 0.005-3 M-circle dot yr(-1), revealing a correlation with the bolometric luminosity consistent with that observed for ionised winds in the narrow line region (NLR), and X-ray winds detected in local AGNs, and kinetic power similar to 10(-7)-10(-4)xL(Bol). The coupling efficiencies predicted by AGN-feedback models are much higher than the values reported for the BLR winds in the SUPER sample; although it should be noted that only a fraction of the energy injected by the AGN into the surrounding medium is expected to become kinetic power in the outflow. Finally, we find an anti-correlation between the equivalent width of the [OIII] line and the CIV velocity shift, and a positive correlation between this latter parameter and [OIII] outflow velocity. These findings, for the first time in an unbiased sample of AGNs at z similar to 2, support a scenario where BLR winds are connected to galaxy-scale detected outflows, and are therefore capable of affecting the gas in the NLR located at kiloparsec scale distances.
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| 3. |
- Cicone, C., et al.
(author)
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SUPER VI. A giant molecular halo around a z similar to 2 quasar
- 2021
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 654
-
Journal article (peer-reviewed)abstract
- We present the discovery of copious molecular gas in the halo of cid_346, a z=2.2 quasar studied as part of the SINFONI survey for Unveiling the Physics and Effect of Radiative feedback (SUPER). New Atacama Compact Array (ACA) CO(3-2) observations detect a much higher flux (by a factor of 14 +/- 5) than measured on kiloparsec scales (r less than or similar to 8 kpc) using previous snapshot Atacama Large Millimeter/submillimeter Array data. Such additional CO(3-2) emission traces a structure that extends out to r similar to 200 kpc in projected size, as inferred through direct imaging and confirmed by an analysis of the uv visibilities. This is the most extended molecular circumgalactic medium (CGM) reservoir that has ever been mapped. It shows complex kinematics, with an overall broad line profile (FWHM=1000 km s(-1)) that is skewed towards redshifted velocities up to at least v similar to 1000 km s(-1). Using the optically thin assumption, we estimate a strict lower limit for the total molecular CGM mass observed by ACA of M-mol(CGM) > 10(10) M-circle dot. There is however room for up to M-mol(CGM) similar to 1.7 x 10(12) M-circle dot, once optically thick CO emission with alpha(CO) = 3.6 M-circle dot (K km s(-1) pc(2))(-1) and LCO(3- 2)'/LCO(1-0)' = 0.5 are assumed. Since cid_346 hosts quasar-driven ionised outflows and since there is no evidence of merging companions or an overdensity, we suggest that outflows may have played a crucial rule in seeding metal-enriched, dense gas on halo scales. However, the origin of such an extended molecular CGM remains unclear.
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| 4. |
- Kakkad, D., et al.
(author)
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SUPER: II. Spatially resolved ionised gas kinematics and scaling relations in z 2 ∼ AGN host galaxies
- 2020
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 642
-
Journal article (peer-reviewed)abstract
- Aims. The SINFONI survey for Unveiling the Physics and Effect of Radiative feedback (SUPER) aims to trace and characterise ionised gas outflows and their impact on star formation in a statistical sample of X-ray selected active galactic nuclei (AGN) at z ∼ 2. We present the first SINFONI results for a sample of 21 Type 1 AGN spanning a wide range in bolometric luminosity (log Lbol = 45.4-47.9 erg s-1). The main aims of this paper are to determine the extension of the ionised gas, characterise the occurrence of AGN-driven outflows, and link the properties of such outflows with those of the AGN. Methods. We used adaptive optics-assisted SINFONI observations to trace ionised gas in the extended narrow line region using the [O» III] λ5007 line. We classified a target as hosting an outflow if its non-parametric velocity of the [O» III] line, w80, was larger than 600 km s-1. We studied the presence of extended emission using dedicated point-spread function (PSF) observations, after modelling the PSF from the Balmer lines originating from the broad line region. Results. We detect outflows in all the Type 1 AGN sample based on the w80 value from the integrated spectrum, which is in the range ∼650-2700 km s-1. There is a clear positive correlation between w80 and the AGN bolometric luminosity (> 99% correlation probability), and the black hole mass (98% correlation probability). A comparison of the PSF and the [O» III] radial profile shows that the [O» III] emission is spatially resolved for ∼35% of the Type 1 sample and the outflows show an extension up to ∼6 kpc. The relation between maximum velocity and the bolometric luminosity is consistent with model predictions for shocks from an AGN-driven outflow. The escape fraction of the outflowing gas increases with the AGN luminosity, although for most galaxies, this fraction is less than 10%.
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| 5. |
- Houshmand, M, et al.
(author)
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Targeting Chronic Myeloid Leukemia Stem/Progenitor Cells Using Venetoclax-Loaded Immunoliposome
- 2021
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In: Cancers. - : MDPI AG. - 2072-6694. ; 13:6
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Journal article (peer-reviewed)abstract
- CML is a hematopoietic stem-cell disorder emanating from breakpoint cluster region/Abelson murine leukemia 1 (BCR/ABL) translocation. Introduction of different TKIs revolutionized treatment outcome in CML patients, but CML LSCs seem insensitive to TKIs and are detectable in newly diagnosed and resistant CML patients and in patients who discontinued therapy. It has been reported that CML LSCs aberrantly express some CD markers such as CD26 that can be used for the diagnosis and for targeting. In this study, we confirmed the presence of CD26+ CML LSCs in newly diagnosed and resistant CML patients. To selectively target CML LSCs/progenitor cells that express CD26 and to spare normal HSCs/progenitor cells, we designed a venetoclax-loaded immunoliposome (IL-VX). Our results showed that by using this system we could selectively target CD26+ cells while sparing CD26− cells. The efficiency of venetoclax in targeting CML LSCs has been reported and our system demonstrated a higher potency in cell death induction in comparison to free venetoclax. Meanwhile, treatment of patient samples with IL-VX significantly reduced CD26+ cells in both stem cells and progenitor cells population. In conclusion, this approach showed that selective elimination of CD26+ CML LSCs/progenitor cells can be obtained in vitro, which might allow in vivo reduction of side effects and attainment of treatment-free, long-lasting remission in CML patients.
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| 6. |
- Sainas, Stefano, et al.
(author)
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Targeting Acute Myelogenous Leukemia Using Potent Human Dihydroorotate Dehydrogenase Inhibitors Based on the 2-Hydroxypyrazolo[1,5- a]pyridine Scaffold : SAR of the Aryloxyaryl Moiety
- 2022
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 65:19, s. 12701-12724
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Journal article (peer-reviewed)abstract
- In recent years, human dihydroorotate dehydrogenase inhibitors have been associated with acute myelogenous leukemia as well as studied as potent host targeting antivirals. Starting from MEDS433 (IC50 1.2 nM), we kept improving the structure-activity relationship of this class of compounds characterized by 2-hydroxypyrazolo[1,5-a]pyridine scaffold. Using an in silico/crystallography supported design, we identified compound 4 (IC50 7.2 nM), characterized by the presence of a decorated aryloxyaryl moiety that replaced the biphenyl scaffold, with potent inhibition and pro-differentiating abilities on AML THP1 cells (EC50 74 nM), superior to those of brequinar (EC50 249 nM) and boosted when in combination with dipyridamole. Finally, compound 4 has an extremely low cytotoxicity on non-AML cells as well as MEDS433; it has shown a significant antileukemic activity in vivo in a xenograft mouse model of AML.
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| 7. |
- Sainas, Stefano, et al.
(author)
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Targeting Acute Myelogenous Leukemia Using Potent Human Dihydroorotate Dehydrogenase Inhibitors Based on the 2-Hydroxypyrazolo[1,5- a]pyridine Scaffold : SAR of the Biphenyl Moiety
- 2021
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 64:9, s. 5404-5428
-
Journal article (peer-reviewed)abstract
- The connection with acute myelogenous leukemia (AML) of dihydroorotate dehydrogenase (hDHODH), a key enzyme in pyrimidine biosynthesis, has attracted significant interest from pharma as a possible AML therapeutic target. We recently discovered compound 1, a potent hDHODH inhibitor (IC50 = 1.2 nM), able to induce myeloid differentiation in AML cell lines (THP1) in the low nM range (EC50 = 32.8 nM) superior to brequinar's phase I/II clinical trial (EC50 = 265 nM). Herein, we investigate the 1 drug-like properties observing good metabolic stability and no toxic profile when administered at doses of 10 and 25 mg/kg every 3 days for 5 weeks (Balb/c mice). Moreover, in order to identify a backup compound, we investigate the SAR of this class of compounds. Inside the series, 17 is characterized by higher potency in inducing myeloid differentiation (EC50 = 17.3 nM), strong proapoptotic properties (EC50 = 20.2 nM), and low cytotoxicity toward non-AML cells (EC30(Jurkat) > 100 μM).
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| 8. |
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