An investigation of the circumgalactic medium around z~2.2 AGN with ACA and ALMA

While observations of molecular gas at cosmic noon and beyond have focused on the gas within galaxies (i.e., the interstellar medium; ISM), it is also crucial to study the molecular gas reservoirs surrounding each galaxy (i.e., in the circumgalactic medium; CGM). Recent observations of galaxies and quasars hosts at high redshift (z>2) have revealed evidence for cold gaseous halos of scale r_CGM~10kpc, with one discovery of a molecular halo with r_CGM~200kpc and a molecular gas mass one order of magnitude larger than the ISM of the central galaxy. As a follow-up, we present deep ACA and ALMA observations of CO(3-2) from this source and two other quasar host galaxies at z~2.2. While we find evidence for CO emission on scales of r~10kpc, we do not find evidence for molecular gas on scales larger than r>20 kpc. Therefore, our deep data do not confirm the existence of massive molecular halos on scales of ~100 kpc for these X-ray selected quasars. As an interesting by-product of our deep observations, we obtain the tentative detection of a negative continuum signal on scales larger than r>200kpc, which might be tracing the Sunyaev-Zeldovich effect associated with the halo heated by the active galactic nucleus (AGN). If confirmed with deeper data, this could be direct evidence of the preventive AGN feedback process expected by cosmological simulations.Comment: 17 pages, 12 figures. Accepted for publication in MNRA

Tailoring CD19xCD3-DART exposure enhances T-cells to eradication of B-cell neoplasms.

Many patients with B-cell malignancies can be successfully treated, although tumor eradication is rarely achieved. T-cell-directed killing of tumor cells using engineered T-cells or bispecific antibodies is a promising approach for the treatment of hematologic malignancies. We investigated the efficacy of CD19xCD3 DART bispecific antibody in a broad panel of human primary B-cell malignancies. The CD19xCD3 DART identified 2 distinct subsets of patients, in which the neoplastic lymphocytes were eliminated with rapid or slow kinetics. Delayed responses were always overcome by a prolonged or repeated DART exposure. Both CD4 and CD8 effector cytotoxic cells were generated, and DART-mediated killing of CD4+ cells into cytotoxic effectors required the presence of CD8+ cells. Serial exposures to DART led to the exponential expansion of CD4 + and CD8 + cells and to the sequential ablation of neoplastic cells in absence of a PD-L1-mediated exhaustion. Lastly, patient-derived neoplastic B-cells (B-Acute Lymphoblast Leukemia and Diffuse Large B Cell Lymphoma) could be proficiently eradicated in a xenograft mouse model by DART-armed cytokine induced killer (CIK) cells. Collectively, patient tailored DART exposures can result in the effective elimination of CD19 positive leukemia and B-cell lymphoma and the association of bispecific antibodies with unmatched CIK cells represents an effective modality for the treatment of CD19 positive leukemia/lymphoma

Submillimetre compactness as a critical dimension to understand the main sequence of star-forming galaxies

We study the interstellar medium (ISM) properties as a function of the molecular gas size for 77 infrared-selected galaxies at z ∼ 1.3, having stellar masses 109.4 ≲ M⋆ ≲ 1012.0 M⊙ and star formation rates 12 ≲ SFRFIR ≲ 1000 M⊙ yr−1. Molecular gas sizes are measured on ALMA images that combine CO(2-1), CO(5-4), and underlying continuum observations, and include CO(4-3), CO(7-6) + [CI](3P2 − 3P1), [CI](3P1 − 3P0) observations for a subset of the sample. The ≳46 per cent of our galaxies have a compact molecular gas reservoir, and lie below the optical discs mass–size relation. Compact galaxies on and above the main sequence have higher CO excitation and star formation efficiency than galaxies with extended molecular gas reservoirs, as traced by CO(5-4)/CO(2-1) and CO(2-1)/LIR, SF ratios. Average CO + [CI] spectral line energy distributions indicate higher excitation in compacts relative to extended sources. Using CO(2-1) and dust masses as molecular gas mass tracers, and conversion factors tailored to their ISM conditions, we measure lower gas fractions in compact main-sequence galaxies compared to extended sources. We suggest that the submillimetre compactness, defined as the ratio between the molecular gas and the stellar size, is an unavoidable information to be used with the main sequence offset to describe the ISM properties of galaxies, at least above M⋆ ≥ 1010.6 M⊙, where our observations fully probe the main sequence scatter. Our results are consistent with mergers driving the gas in the nuclear regions, enhancing the CO excitation and star formation efficiency. Compact main-sequence galaxies are consistent with being an early post-starburst population following a merger-driven starburst episode, stressing the important role of mergers in the evolution of massive galaxies

The synergism between DHODH inhibitors and dipyridamole leads to metabolic lethality in acute myeloid leukemia

Dihydroorotate Dehydrogenase (DHODH) is a key enzyme of the de novo pyrimidine biosynthesis, whose inhibition can induce differentiation and apoptosis in acute myeloid leukemia (AML). DHODH inhibitors had shown promising in vitro and in vivo activity on solid tumors, but their effectiveness was not confirmed in clinical trials, probably because cancer cells exploited the pyrimidine salvage pathway to survive. Here, we investigated the antileukemic activity of MEDS433, the DHODH inhibitor developed by our group, against AML. Learning from previous failures, we mimicked human conditions (performing experiments in the presence of physiological uridine plasma levels) and looked for synergic combinations to boost apoptosis, including classical antileukemic drugs and dipyridamole, a blocker of the pyrimidine salvage pathway. MEDS433 induced apoptosis in multiple AML cell lines, not only as a consequence of differentiation, but also directly. Its combination with antileukemic agents further increased the apoptotic rate, but when experiments were performed in the presence of physiological uridine concentrations, results were less impressive. Conversely, the combination of MEDS433 with dipyridamole induced metabolic lethality and differentiation in all AML cell lines; this extraordinary synergism was confirmed on AML primary cells with different genetic backgrounds and was unaffected by physiological uridine concentrations, predicting in human activity

A titanic interstellar medium ejection from a massive starburst galaxy at redshift 1.4

Feedback-driven winds from star formation or active galactic nuclei might be a relevant channel for the abrupt quenching of star formation in massive galaxies. However, both observations and simulations support the idea that these processes are non-conflictingly co-evolving and self-regulating. Furthermore, evidence of disruptive events that are capable of fast quenching is rare, and constraints on their statistical prevalence are lacking. Here we present a massive starburst galaxy at redshift z = 1.4, which is ejecting 46 ± 13% of its molecular gas mass at a startling rate of ≳10,000 M⊙ yr−1. A broad component that is red-shifted from the galaxy emission is detected in four (low and high J) CO and [C i] transitions and in the ionized phase, which ensures a robust estimate of the expelled gas mass. The implied statistics suggest that similar events are potentially a major star-formation quenching channel. However, our observations provide compelling evidence that this is not a feedback-driven wind, but rather material from a merger that has been probably tidally ejected. This finding challenges some literature studies in which the role of feedback-driven winds might be overstated

The Quasar Feedback Survey: characterising CO excitation in quasar host galaxies

We present a comprehensive study of the molecular gas properties of 17 Type 2 quasars at $z$10^{42.1}$$\rm ergs^{-1}$), selected by their high [OIII] luminosities and displaying a large diversity of radio jet properties, but dominated by LIRG-like galaxies. With these data, we are able to investigate the impact of AGN and AGN feedback mechanisms on the global molecular interstellar medium. Using APEX and ALMA ACA observations, we measure the total molecular gas content using the CO(1-0) emission and homogeneously sample the CO spectral line energy distributions (SLEDs), observing CO transitions (J$_{up}$= 1, 2, 3, 6, 7). We observe high$r_{21}$ratios (r$_{21}$= L'$_{CO(2-1)}$/L'$_{CO(1-0)}$) with a median$r_{21}$= 1.06, similar to local (U)LIRGs (with$r_{21}$$\sim$1) and higher than normal star-forming galaxies (with r$_{21}$$\sim$0.65). Despite the high$r_{21} values, for the 7 targets with the required data we find low excitation in CO(6-5) & CO(7-6) (r_{61}$and$r_{62}$ < 0.6 in all but one target), unlike high redshift quasars in the literature, which are far more luminous and show higher line ratios. The ionised gas traced by [OIII] exhibit systematically higher velocities than the molecular gas traced by CO. We conclude that any effects of quasar feedback (e.g. via outflows and radio jets) do not have a significant instantaneous impact on the global molecular gas content and excitation and we suggest that it only occurs on more localised scales.Comment: 32 pages (20 in the main body of the paper and 12 in the appendix), 28 figures (10 in main body of paper and 18 in appendix) Accepted for publication in MNRAS. Data available at https://doi.org/10.25405/data.ncl.2431250

The ultra-dense, interacting environment of a dual AGN at z ∼\sim 3.3 revealed by JWST/NIRSpec IFS

LBQS 0302-0019 is a blue quasar (QSO) at z ~ 3.3, hosting powerful outflows, and residing in a complex environment consisting of an obscured AGN candidate, and multiple companions, all within 30 kpc in projection. We use JWST NIRSpec IFS observations to characterise the ionized gas in this complex system. We develop a procedure to correct for the spurious oscillations (or 'wiggles') in NIRSpec single-spaxel spectra, due to the spatial under-sampling of the point spread function. We perform a quasar-host decomposition with the QDeblend3D tools, and use multi-component kinematic decomposition of the optical emission line profiles to infer the physical properties of the emitting gas. The quasar-host decomposition allows us to identify i) a low-velocity component possibly tracing a warm rotating disk, with a dynamical mass Mdyn $\sim 10^{11}$ Msun and a rotation-to-random motion ratio $v_{rot}$/$\sigma_0 \sim 2$; ii) a spatially unresolved ionised outflow, with a velocity of $\sim$ 1000 km/s and an outflow mass rate of $\sim 10^4$ Msun/yr. We also detect eight interacting companion objects close to LBQS 0302-0019. Optical line ratios confirm the presence of a second, obscured AGN at $\sim 20$ kpc of the primary QSO; the dual AGN dominates the ionization state of the gas in the entire NIRSpec field-of-view. This work has unveiled with unprecedented detail the complex environment of this dual AGN, which includes nine interacting companions (five of which were previously unknown), all within 30 kpc of the QSO. Our results support a scenario where mergers can trigger dual AGN, and can be important drivers for rapid early SMBH growth.Comment: 23 pages, 23 figures; accepted for publication by A&

The effect of active galactic nuclei on the cold interstellar medium in distant star-forming galaxies

In the framework of a systematic study with the ALMA interferometer of IR-selected main-sequence and starburst galaxies at z ∼ 1 − 1.7 at typical ∼1″ resolution, we report on the effects of mid-IR- and X-ray-detected active galactic nuclei (AGN) on the reservoirs and excitation of molecular gas in a sample of 55 objects. We find widespread detectable nuclear activity in ∼30% of the sample. The presence of dusty tori influences the IR spectral energy distribution of galaxies, as highlighted by the strong correlation among the AGN contribution to the total IR luminosity budget (fAGN = LIR,  AGN/LIR), its hard X-ray emission, and the Rayleigh-Jeans to mid-IR (S1.2 mm/S24 μm) observed color, with evident consequences on the ensuing empirical star formation rate estimates. Nevertheless, we find only marginal effects of the presence and strength of AGN on the carbon monoxide CO (J = 2, 4, 5, 7) or neutral carbon ([C I](3P1  −  3P0), [C I](3P2  −  3P1)) line luminosities and on the derived molecular gas excitation as gauged by line ratios and the full spectral line energy distributions. The [C I] and CO emission up to J = 5, 7 thus primarily traces the properties of the host in typical IR luminous galaxies. However, our analysis highlights the existence of a large variety of line luminosities and ratios despite the homogeneous selection. In particular, we find a sparse group of AGN-dominated sources with the highest LIR,  AGN/LIR,  SFR ratios, ≳3, that are more luminous in CO (5−4) than what is predicted by the L′CO(5-4)−LIR, SFR relation, which might be the result of the nuclear activity. For the general population, our findings translate into AGN having minimal effects on quantities such as gas and dust fractions and star formation efficiencies. If anything, we find hints of a marginal tendency of AGN hosts to be compact at far-IR wavelengths and to display 1.8 times larger dust optical depths. In general, this is consistent with a marginal impact of the nuclear activity on the gas reservoirs and star formation in average star-forming AGN hosts with LIR > 5 × 1011 L⊙, typically underrepresented in surveys of quasars and submillimeter galaxies