Dust from AGBs: relevant factors and modelling uncertainties

The dust formation process in the winds of Asymptotic Giant Branch stars is discussed, based on full evolutionary models of stars with mass in the range $1$M$_{\odot} \leq$M$\leq 8$M$_{\odot}$, and metallicities $0.001 < Z <0.008$. Dust grains are assumed to form in an isotropically expanding wind, by growth of pre--existing seed nuclei. Convection, for what concerns the treatment of convective borders and the efficiency of the schematization adopted, turns out to be the physical ingredient used to calculate the evolutionary sequences with the highest impact on the results obtained. Low--mass stars with M$\leq 3$M$_{\odot}$ produce carbon type dust with also traces of silicon carbide. The mass of solid carbon formed, fairly independently of metallicity, ranges from a few $10^{-4}$M$_{\odot}$, for stars of initial mass $1-1.5$M$_{\odot}$, to $\sim 10^{-2}$M$_{\odot}$ for M$\sim 2-2.5$M$_{\odot}$; the size of dust particles is in the range $0.1 \mu$m$\leq a_C \leq 0.2\mu$m. On the contrary, the production of silicon carbide (SiC) depends on metallicity. For $10^{-3} \leq Z \leq 8\times 10^{-3}$ the size of SiC grains varies in the range $0.05 \mu {\rm m} < {\rm a_{SiC}} < 0.1 \mu$m, while the mass of SiC formed is $10^{-5}{\rm M}_{\odot} < {\rm M_{SiC}} < 10^{-3}{\rm M}_{\odot}$. Models of higher mass experience Hot Bottom Burning, which prevents the formation of carbon stars, and favours the formation of silicates and corundum. In this case the results scale with metallicity, owing to the larger silicon and aluminium contained in higher--Z models. At Z=$8\times 10^{-3}$ we find that the most massive stars produce dust masses $m_d \sim 0.01$M$_{\odot}$, whereas models of smaller mass produce a dust mass ten times smaller. The main component of dust are silicates, although corundum is also formed, in not negligible quantities ($\sim 10-20\%$).Comment: Paper accepted for publication in Monthly Notices of the Royal Astronomical Society Main Journal (2014 January 4

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

ALMA constraints on the faint millimetre source number counts and their contribution to the cosmic infrared background

We have analysed 18 ALMA continuum maps in Bands 6 and 7, with rms down to 7.8$\mu$Jy, to derive differential number counts down to 60$\mu$Jy and 100$\mu$Jy at $\lambda=$1.3 mm and $\lambda=$1.1 mm, respectively. The area covered by the combined fields is $\rm 9.5\times10^{-4}deg^2$ at 1.1mm and $\rm 6.6\times10^{-4}deg^{2}$ at 1.3mm. We improved the source extraction method by requiring that the dimension of the detected sources be consistent with the beam size. This method enabled us to remove spurious detections that have plagued the purity of the catalogues in previous studies. We detected 50 faint sources with S/N$>$3.5 down to 60$\mu$Jy, hence improving the statistics by a factor of four relative to previous studies. The inferred differential number counts are $\rm dN/d(Log_{10}S)=1\times10^5~deg^2$ at a 1.1 mm flux $S_{\lambda = 1.1~mm} = 130~\mu$Jy, and $\rm dN/d(Log_{10}S)=1.1\times10^5~deg^2$ at a 1.3 mm flux $\rm S_{\lambda = 1.3~mm} = 60~\mu$Jy. At the faintest flux limits, i.e. 30$\mu$Jy and 40$\mu$Jy, we obtain upper limits on the differential number counts of $\rm dN/d(Log_{10}S) < 7\times10^5~deg^2$ and $\rm dN/d(Log_{10}S)<3\times10^5~deg^2$, respectively. Our results provide a new lower limit to CIB intensity of 17.2${\rm Jy\ deg^{-2}}$ at 1.1mm and of 12.9${\rm Jy\ deg^{-2}}$ at 1.3mm. Moreover, the flattening of the integrated number counts at faint fluxes strongly suggests that we are probably close to the CIB intensity. Our data imply that galaxies with SFR$<40~M_{\odot}/yr$ certainly contribute less than 50% to the CIB while more than 50% of the CIB must be produced by galaxies with $\rm SFR>40~M_{\odot}/yr$. The differential number counts are in nice agreement with recent semi-analytical models of galaxy formation even as low as our faint fluxes. Consequently, this supports the galaxy evolutionary scenarios and assumptions made in these models.Comment: 11 pages, 9 figures, A&A accepte

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

Dissecting Molecular Heterogeneity of Circulating Tumor Cells (CTCs) from Metastatic Breast Cancer Patients through Copy Number Aberration (CNA) and Single Nucleotide Variant (SNV) Single Cell Analysis

Simple Summary Circulating tumor cells (CTCs) are rare cells found in the bloodstream of oncologic patients with a central role in the metastatic spread. In this study, we aim at exploring their heterogeneity levels in metastatic breast cancer patients focusing on single cell single nucleotide variant (SNV) and copy number aberration (CNA) analyses. Our results show high levels of heterogeneity, especially concerning SNVs. Further analysis revealed the presence of CNAs associated with breast tumorigenesis, while longitudinal CNA profiling was demonstrated to track clonal selection of CTCs during treatment. Despite this heterogeneity, we found a group of CTCs from different patients sharing common genomic aberrations, such as losses on 15q. Collectively, our findings demonstrate that single-cell molecular analyses could be exploited in future to better address therapeutic strategies. Further investigations to better characterize this mixed population are needed to understand its role in MBC. Circulating tumor cells' (CTCs) heterogeneity contributes to counteract their introduction in clinical practice. Through single-cell sequencing we aim at exploring CTC heterogeneity in metastatic breast cancer (MBC) patients. Single CTCs were isolated using DEPArray NxT. After whole genome amplification, libraries were prepared for copy number aberration (CNA) and single nucleotide variant (SNV) analysis and sequenced using Ion GeneStudio S5 and Illumina MiSeq, respectively. CTCs demonstrate distinctive mutational signatures but retain molecular traces of their common origin. CNA profiling identifies frequent aberrations involving critical genes in pathogenesis: gains of 1q (CCND1) and 11q (WNT3A), loss of 22q (CHEK2). The longitudinal single-CTC analysis allows tracking of clonal selection and the emergence of resistance-associated aberrations, such as gain of a region in 12q (CDK4). A group composed of CTCs from different patients sharing common traits emerges. Further analyses identify losses of 15q and enrichment of terms associated with pseudopodium formation as frequent and exclusive events. CTCs from MBC patients are heterogeneous, especially concerning their mutational status. The single-cell analysis allows the identification of aberrations associated with resistance, and is a candidate tool to better address treatment strategy. The translational significance of the group populated by similar CTCs should be elucidated

Dust formation around AGB and SAGB stars: a trend with metallicity?

We calculate the dust formed around AGB and SAGB stars of metallicity Z=0.008 by following the evolution of models with masses in the range 1M<M<8M throughthe thermal pulses phase, and assuming that dust forms via condensation of molecules within a wind expanding isotropically from the stellar surface. We find that, because of the strong Hot Bottom Burning (HBB) experienced, high mass models produce silicates, whereas lower mass objects are predicted to be surrounded by carbonaceous grains; the transition between the two regimes occurs at a threshold mass of 3.5M. These fndings are consistent with the results presented in a previous investigation, for Z=0.001. However, in the present higher metallicity case, the production of silicates in the more massive stars continues for the whole AGB phase, because the HBB experienced is softer at Z=0.008 than at Z=0.001, thus the oxygen in the envelope, essential for the formation of water molecules, is never consumed completely. The total amount of dust formed for a given mass experiencing HBB increases with metallicity, because of the higher abundance of silicon, and the softer HBB, both factors favouring a higher rate of silicates production. This behaviour is not found in low mass stars,because the carbon enrichment of the stellar surface layers, due to repeated Third Drege Up episodes, is almost independent of the metallicity. Regarding cosmic dust enrichment by intermediate mass stars, we find that the cosmic yield at Z=0.008 is a factor 5 larger than at Z=0.001. In the lower metallicity case carbon dust dominates after about 300 Myr, but at Z=0.008 the dust mass is dominated by silicates at all times,with a prompt enrichment occurring after about 40 Myr, associated with the evolution of stars with masses M =7.5 -8M.Comment: 14 pages, 10 figures, 2 Tables, accepted for publication in MNRA

Cna profiling of single ctcs in locally advanced esophageal cancer patients during therapy highlights unexplored molecular pathways

Background: Here, we monitored the evolution of CTCs spread in 11 patients affected by locally advanced EC who were undergoing therapy. Methods: In this perspective study, we designed multiple blood biopsies from individual patients: before and after neoadjuvant chemoradio therapy and after surgery. We developed a multi-target array, named Grab-all assay, to estimate CTCs for their epithelial (EpCAM/E-Cadherin/Cytokeratins) and mesenchymal/stem (N-Cadherin/CD44v6/ABCG2) phenotypes. Identified CTCs were isolated as single cells by DE-PArray, subjected to whole genome amplification, and copy number aberration (CNA) profiles were determined. Through bioinformatic analysis, we assessed the genomic imbalance of single CTCs, investigated specific focal copy number changes previously reported in EC and aberrant pathways using enrichment analysis. Results: Longitudinal monitoring allowed the identification of CTCs in at least one time-point per patient. Through single cell CNA analysis, we revealed that CTCs showed significantly dynamic genomic imbalance during treatment. Individual CTCs from relapsed patients displayed a higher degree of genomic imbalance relative to disease-free patients’ groups. Genomic aberrations previously reported in EC occurred mostly in post-neoadjuvant therapy CTCs. In-depth analysis showed that networks enrichment in all time-point CTCs were inherent to innate immune system. Transcription/gene regulation, post-transcriptional and epigenetic modifications were uniquely affected in CTCs of relapsed patients. Conclusions: Our data add clues to the comprehension of the role of CTCs in EC aggressiveness: chromosomal aberrations on genes related to innate immune system behave as relevant to the onset of CTC-status, whilst pathways of transcription/gene regulation, post-transcriptional and epigenetic modifications seem linked to patients’ outcome

Hpv-specific systemic antibody responses and memory b cells are independently maintained up to 6 years and in a vaccine-specific manner following immunization with cervarix and gardasil in adolescent and young adult women in vaccination programs in Italy

Human papillomavirus (HPV) persistent infections are associated with cervical cancer and other HPV-related diseases and tumors. Thus, the characterization of long lasting immunity to currently available HPV vaccines is important. A total of 149 female subjects vaccinated with Cervarix or Gardasil participated to the study and they were stratified according to age (10–12-year-old and 16–20-year-old). Humoral immune responses (IgG and neutralizing antibody titers, antibody avidity) and circulating memory B cells were analyzed after an average of 4–6 years from the third immunization. The humoral responses against HPV-16 and HPV-18 (and HPV-6 and HPV- 11 for Gardasil) were high in both age groups and vaccines up to six years from the third dose. However, Cervarix induced significantly higher and more persistent antibody responses, while the two vaccines were rather equivalent in inducing memory B cells against HPV-16 and HPV-18. Moreover, the percentage of subjects with vaccine-specific memory B cells was even superior among Gardasil vaccinees and, conversely, Cervarix vaccinated individuals with circulating antibodies, but undetectable memory B cells were found. Finally, a higher proportion of Cervarix-vaccinated subjects displayed cross-neutralizing responses against non-vaccine types HPV-31 and HPV-45. Gardasil and Cervarix may, thus, differently affect long-lasting humoral immunity from both the quantitative and qualitative point of view