CO line emission from galaxies in the Epoch of Reionization

We study the CO line luminosity ($L_{\rm CO}$), the shape of the CO Spectral Line Energy Distribution (SLED), and the value of the CO-to-$\rm H_2$ conversion factor in galaxies in the Epoch of Reionization (EoR). To this aim, we construct a model that simultaneously takes into account the radiative transfer and the clumpy structure of giant molecular clouds (GMCs) where the CO lines are excited. We then use it to post-process state-of-the-art zoomed, high resolution ($30\, \rm{pc}$), cosmological simulation of a main-sequence ($M_{*}\approx10^{10}\, \rm{M_{\odot}}$, $SFR\approx 100\,\rm{M_{\odot}\, yr^{-1}}$) galaxy, "Alth{\ae}a", at $z\approx6$. We find that the CO emission traces the inner molecular disk ($r\approx 0.5 \,\rm{kpc}$) of Alth{\ae}a with the peak of the CO surface brightness co-located with that of the [CII] 158$\rm \mu m$ emission. Its $L_{\rm CO(1-0)}=10^{4.85}\, \rm{L_{\odot}}$ is comparable to that observed in local galaxies with similar stellar mass. The high ($\Sigma_{gas} \approx 220\, \rm M_{\odot}\, pc^{-2}$) gas surface density in Alth{\ae}a, its large Mach number (\mach$\approx 30$), and the warm kinetic temperature ($T_{k}\approx 45 \, \rm K$) of GMCs yield a CO SLED peaked at the CO(7-6) transition, i.e. at relatively high-$J$, and a CO-to-$\rm H_2$ conversion factor $\alpha_{\rm CO}\approx 1.5 \, \rm M_{\odot} \rm (K\, km\, s^{-1}\, pc^2)^{-1}$ lower than that of the Milky Way. The ALMA observing time required to detect (resolve) at 5$\sigma$ the CO(7-6) line from galaxies similar to Alth{\ae}a is $\approx13$ h ($\approx 38$ h).Comment: 16 pages, 14 figures, accepted for publication in MNRA

Very extended cold gas, star formation and outflows in the halo of a bright QSO at z>6

Past observations of QSO host galaxies at z >6 have found cold gas and star formation on compact scales of a few kiloparsecs. We present new high sensitivity IRAM PdBI follow-up observations of the [CII] 158micron emission line and FIR continuum in the host galaxy of SDSS J1148+5152, a luminous QSO at redshift 6.4189. We find that a large fraction of the gas traced by [CII] is at high velocities, up to ~1400 km/s relative to the systemic velocity, confirming the presence of a major quasar-driven outflow indicated by previous observations. The outflow has a complex morphology and reaches a maximum projected radius of ~30 kpc. The extreme spatial extent of the outflow allows us, for the first time in an external galaxy, to estimate mass-loss rate, kinetic power and momentum rate of the outflow as a function of the projected distance from the nucleus and the dynamical time-scale. These trends reveal multiple outflow events during the past 100 Myr, although the bulk of the mass, energy and momentum appear to have been released more recently, within the past ~20 Myr. Surprisingly, we discover that also the quiescent gas at systemic velocity is extremely extended. More specifically, we find that, while 30% of the [CII] within v\in(-200, 200) km/s traces a compact component that is not resolved by our observations, 70% of the [CII] emission in this velocity range is extended, with a projected FWHM size of 17.4+-1.4 kpc. We detect FIR continuum emission associated with both the compact and the extended [CII] components, although the extended FIR emission has a FWHM of 11+-3 kpc, thus smaller than the extended [CII] source. Overall, our results indicate that the cold gas traced by [CII] is distributed up to r~30 kpc. A large fraction of extended [CII] is likely associated with star formation on large scales, but the [CII] source extends well beyond the FIR continuum.Comment: Accepted for publication in A&A, 21 pages, 18 figures, 3 tables (v2: accepted version, discussion expanded in Sect. 3, 4 and in the Appendices, minor changes elsewhere

Adipocytes and micrornas crosstalk: A key tile in the mosaic of breast cancer microenvironment

Breast cancer (BC) is a disease characterized by a high grade of heterogeneity. Consequently, despite the great achievements obtained in the last decades, most of the current therapeutic regimens still fail. The identification of new molecular mechanisms that will increase the knowledge of all steps of tumor initiation and growth is mandatory in finding new clinical strategies. The BC microenvironment, consisting of endothelial cells, fibroblasts, immune cells and adipocytes, plays an essential role in regulating BC development, and recently it has gained great attention in the scientific community. In particular, adipose tissue is emerging as an important target to investigate among mammary gland components. The mechanisms underlying BC progression driven by adipocytes are predominantly unexplored, especially that involving the switch from normal adipocytes to the so-called cancer-associated adipocytes (CAAs). MicroRNAs (miRNAs), a class of gene expression modulators, have emerged as the regulators of key oncogenes and tumor suppressor genes that affect multiple pathways of the tumor microenvironment and adipose tissue. This review concerns a presentation of the role of adipocytes in breast tissue, and describes the most recent discoveries about the interplay between adipocytes and miRNAs, which collaborate in the arrangement of a pro-inflammatory and cancerous microenvironment, laying the foundations for new concepts in the prevention and treatment of BC

The rest-frame UV-to-optical spectroscopy of APM 08279+5255 - BAL classification and black hole mass estimates

We present the analysis of the rest-frame optical-to-UV spectrum of APM 08279+5255, a well-known lensed broad absorption line (BAL) quasar at $z = 3.911$. The spectroscopic data are taken with the optical DOLoRes and near-IR NICS instruments at TNG, and include the previously unexplored range between C III] $\lambda$1910 and [O III] $\lambda\lambda$4959,5007. We investigate the possible presence of multiple BALs by computing "balnicity" and absorption indexes (i.e. BI, BI$_0$ and AI) for the transitions Si IV $\lambda$1400, C IV $\lambda$1549, Al III $\lambda$1860 and Mg II $\lambda$2800. No clear evidence for the presence of absorption features is found in addition to the already known, prominent BAL associated to C IV, which supports a high-ionization BAL classification for APM 08279+5255. We also study the properties of the [O III], H$\beta$ and Mg II emission lines. We find that [O III] is intrinsically weak ($F_{\rm [OIII]}/F_{\rm H\beta} \lesssim 0.04$), as it is typically found in luminous quasars with a strongly blueshifted C IV emission line ($\sim$2500 km s$^{-1}$ for APM 08279+5255). We compute the single-epoch black hole mass based on Mg II and H$\beta$ broad emission lines, finding $M_{\rm BH} = (2 \div 3) \times 10^{10}\mu^{-1}$ M$_\odot$, with the magnification factor $\mu$ that can vary between 4 and 100 according to CO and rest-frame UV-to-mid-IR imaging respectively. Using a Mg II equivalent width (EW)-to-Eddington ratio relation, the EW$_{\rm MgII} \sim 27$ \AA\ measured for APM 08279+5255 translates into an Eddington ratio of $\sim$0.4, which is more consistent with $\mu=4$. This magnification factor also provides a value of $M_{\rm BH}$ that is consistent with recent reverberation-mapping measurements derived from C IV and Si IV.Comment: 10 pages, 4 figures, 4 tables, accepted for publication in A&

The assembly of "normal" galaxies at z=7 probed by ALMA

We report new deep ALMA observations aimed at investigating the [CII]158um line and continuum emission in three spectroscopically confirmed Lyman Break Galaxies at 6.8<z<7.1, i.e. well within the re-ionization epoch. With Star Formation Rates of SFR ~ 5-15 Msun/yr these systems are much more representative of the high-z galaxy population than other systems targeted in the past by millimeter observations. For the galaxy with the deepest observation we detect [CII] emission at redshift z=7.107, fully consistent with the Lyalpha redshift, but spatially offset by 0.7" (4 kpc) from the optical emission. At the location of the optical emission, tracing both the Lyalpha line and the far-UV continuum, no [CII] emission is detected in any of the three galaxies, with 3sigma upper limits significantly lower than the [CII] emission observed in lower reshift galaxies. These results suggest that molecular clouds in the central parts of primordial galaxies are rapidly disrupted by stellar feedback. As a result, [CII] emission mostly arises from more external accreting/satellite clumps of neutral gas. These findings are in agreement with recent models of galaxy formation. Thermal far-infrared continuum is not detected in any of the three galaxies. However, the upper limits on the infrared-to-UV emission ratio do not exceed those derived in metal- and dust-poor galaxies.Comment: 15 pages, 9 figures, MNRAS in press, replaced with accepted versio

The dense molecular gas in the z∼6\rm z\sim6 QSO SDSS J231038.88+185519.7 resolved by ALMA

We present ALMA observations of the CO(6-5) and [CII] emission lines and the sub-millimeter continuum of the $z\sim6$ quasi-stellar object (QSO) SDSS J231038.88+185519.7. Compared to previous studies, we have analyzed a synthetic beam that is ten times smaller in angular size, we have achieved ten times better sensitivity in the CO(6-5) line, and two and half times better sensitivity in the [CII] line, enabling us to resolve the molecular gas emission. We obtain a size of the dense molecular gas of $2.9\pm0.5$ kpc, and of $1.4\pm0.2$ kpc for the 91.5 GHz dust continuum. By assuming that CO(6-5) is thermalized, and by adopting a CO--to--$H_2$ conversion factor $\rm \alpha_{CO} = 0.8~ M_{\odot}~K^{-1}~ (km/s)^{-1} ~pc^{2}$, we infer a molecular gas mass of $\rm M(H_2)=(3.2 \pm0.2) \times 10^{10}\rm M_{\odot}$. Assuming that the observed CO velocity gradient is due to an inclined rotating disk, we derive a dynamical mass of $\rm M_{dyn}~sin^2(i) = (2.4\pm0.5) \times 10^{10}~ M_{\odot}$, which is a factor of approximately two smaller than the previously reported estimate based on [CII]. Regarding the central black hole, we provide a new estimate of the black hole mass based on the C~IV emission line detected in the X-SHOOTER/VLT spectrum: $\rm M_{BH}=(1.8\pm 0.5) \times 10^{9}~ M_{\odot}$. We find a molecular gas fraction of $\rm \mu=M(H_2)/M^*\sim4.4$, where $\rm M^*\approx M_{dyn} - M(H_2)-M(BH)$. We derive a ratio $v_{rot}/\sigma \approx 1-2$ suggesting high gas turbulence, outflows/inflows and/or complex kinematics due to a merger event. We estimate a global Toomre parameter $Q\sim 0.2-0.5$, indicating likely cloud fragmentation. We compare, at the same angular resolution, the CO(6-5) and [CII] distributions, finding that dense molecular gas is more centrally concentrated with respect to [CII]. We find that the current BH growth rate is similar to that of its host galaxy.Comment: A&A in pres

Impressive long-term response with chemo-endocrine therapy in a premenopausal patient with metastatic breast cancer: A case report

RATIONALE: Patients with, or who develop, metastatic breast cancer have a 5-year relative survival of about 25%. Endocrine therapy clearly improves outcomes in patients with estrogen receptor-positive breast cancer. In the metastatic setting, the primary goal of treatment is to maintain long-term disease control with good quality of life. Rarely, exceptional responders achieve durable disease control, and potential cures cannot be ruled out. PATIENT CONCERNS: We report the case of a 39-year-old woman with primary breast cancer and associated synchronous bone metastases, who experienced a disease response of 12 years with hormonal therapy as maintenance after first line chemotherapy, with a good toxicity profile. DIAGNOSIS: The patient was diagnosed with estrogen receptor + human epidermal growth factor receptor 2 (HER2)- metastatic breast cancer with synchronous bone metastases. INTERVENTIONS: This patient was treated with chemotherapy for 6 cycles as a first-line therapy following by endocrine treatment given as a maintenance therapy. OUTCOMES: Our patient experienced a progression-free survival &gt;12 years with an exceptionally good quality of life. LESSONS: Our anecdotal experience highlights the existence of exceptional responders among patients with hormone receptor-positive metastatic breast cancer, who achieve clinical remission and durable disease control with endocrine therapy. Being able to identify these patients could help in the selection of the best treatment option among the many available

Dust attenuation law in JWST galaxies at z = 7-8

Attenuation curves in galaxies depend on dust chemical composition, content, and grain size distribution. Such parameters are related to intrinsic galaxy properties such as metallicity, star formation rate, and stellar age. Due to the lack of observational constraints at high redshift, dust empirical curves measured in the local Universe (e.g. Calzetti and SMC curves) have been employed to describe the dust attenuation at early epochs. We exploit the high sensitivity and spectral resolution of the JWST to constrain the dust attenuation curves in high-z galaxies. Our goals are to check whether dust attenuation curves evolve with redshift and quantify the dependence of the inferred galaxy properties on the assumed dust attenuation law. We develop a modified version of the SED fitting code BAGPIPES by including a detailed dust attenuation curve parametrization. Dust parameters are derived, along with galaxy properties, from the fit to the data from FUV to mm bands. Once applied to three star-forming galaxies at z = 7-8, we find that their attenuation curves differ from local templates. One out of three galaxies shows a characteristic MW bump, typically associated to the presence of small carbonaceous dust grains such as PAHs. This is one of the first evidences suggesting the presence of PAHs in early galaxies. Galaxy properties such as stellar mass and SFR inferred from SED fitting are strongly affected by the assumed attenuation curve, though the adopted star formation history also plays a major role. Our results highlight the importance of accounting for the potential diversity of dust attenuation laws when analyzing the properties of galaxies at the EoR, whose dust properties are still poorly understood. The application of our method to a larger sample of galaxies observed with JWST can provide us important insights into the properties of dust and galaxies in the early universe.Comment: 19 pages, 10 figure

Witnessing Galaxy Assembly at the Edge of the Reionization Epoch

We report the discovery of Serenity-18, a galaxy at z=5.939 for which we could measure the content of molecular gas, M(H_2)~ 5 x10^9 M_sun, traced by the CO(6-5) emission, together with the metal-poor ([Fe/H]=-3.08 +- 0.12, [Si/H]=-2.86 +- 0.14) gas clump/filament which is possibly feeding its growth. The galaxy has an estimated star formation rate of ~100 M_sun yr^{-1}, implying that it is a typical main sequence galaxy at these redshifts. The metal-poor gas is detected through a damped Lyman-alpha absorber (DLA) observed at a spatial separation of 40 kpc and at the same redshift of Serenity-18, along the line of sight to the quasar SDSS J2310+1855 (z_em = 6.0025). The chemical abundances measured for the damped Lyman-alpha system are in very good agreement with those measured for other DLAs discovered at similar redshifts, indicating an enrichment due to massive PopII stars. The galaxy/Damped system we discovered is a direct observational evidence of the assembly of a galaxy at the edge of the reionization epoch.STFC ER

Single-cell NGS-based analysis of copy number alterations reveals new insights in circulating tumor cells persistence in early-stage breast cancer

Circulating tumor cells (CTCs) are a rare population of cells representing a key player in the metastatic cascade. They are recognized as a validated tool for the identification of patients with a higher risk of relapse, including those diagnosed with breast cancer (BC). However, CTCs are characterized by high levels of heterogeneity that also involve copy number alterations (CNAs), structural variations associated with gene dosage changes. In this study, single CTCs were isolated from the peripheral blood of 11 early-stage BC patients at different time points. A label-free enrichment of CTCs was performed using OncoQuick, and single CTCs were isolated using DEPArray. Libraries were prepared from single CTCs and DNA extracted from matched tumor tissues for a whole-genome low-coverage next-generation sequencing (NGS) analysis using the Ion Torrent S5 System. The analysis of the CNA burden highlighted that CTCs had different degrees of aberration based on the time point and subtype. CTCs were found even six months after surgery and shared CNAs with matched tumor tissue. Tumor-associated CNAs that were recurrent in CTCs were patient-specific, and some alterations involved regions associated with BC and survival (i.e., gains at 1q21-23 and 5p15.33). The enrichment analysis emphasized the involvement of aberrations of terms, associated in particular with interferon (IFN) signaling. Collectively, our findings reveal that these aberrations may contribute to understanding the molecular mechanisms involving CTC-related processes and their survival ability in occult niches, supporting the goal of exploiting their application in patients’ surveillance and follow-up