Early stages of high-mass star formation

This thesis is dedicated to the formation of high-mass stars. In particular, we are interested in the initial conditions that allow massive stars to form. Therefore, we first examine the very initial stage of massive star formation. Based on a statistical survey study over 20 deg2 from mid-infrared to sub-millimeter wavelengths, we show that dense and massive starless clumps exist. Assuming that they will form stellar clusters instead of single objects, we estimate their lifetime to be between 15 kyr and 60 kyr. In order to understand such short lifetimes, we investigate the large-scale dynamical structure of high-mass star-forming regions. Using N2H+ observations we find smooth largescale velocity gradients in a number of filaments, which are consistent with gas flowing along the filament. Analyzing HCO+ and H13CO+ spectra, we find global supersonic gas infall onto a few regions. To understand whether the dynamics of an expanding Hii region can trigger star formation, we select a starless clump located on the rim of a bubble which is infrared-dark up to 160 μm. In a multi-wavelengths approach we search for imprints of the bubble on the gas. While an expanding Hii region might favor the formation of high-mass stars, we find no evidence that it triggers the collapse. In summary, this thesis emphasizes that high-mass star formation is a fast and dynamic process

Kinematic structure of massive star-forming regions. I. accretion along filaments

Context. The mid- and far-infrared view on high-mass star formation, in particular with the results from the Herschel space observatory, has shed light on many aspects of massive star formation. However, these continuum studies lack kinematic information. Aims: We study the kinematics of the molecular gas in high-mass star-forming regions. Methods: We complemented the PACS and SPIRE far-infrared data of 16 high-mass star-forming regions from the Herschel key project EPoS with N2H+ molecular line data from the MOPRA and Nobeyama 45 m telescope. Using the full N2H+ hyperfine structure, we produced column density, velocity, and linewidth maps. These were correlated with PACS 70 μm images and PACS point sources. In addition, we searched for velocity gradients. Results: For several regions, the data suggest that the linewidth on the scale of clumps is dominated by outflows or unresolved velocity gradients. IRDC 18454 and G11.11 show two velocity components along several lines of sight. We find that all regions with a diameter larger than 1 pc show either velocity gradients or fragment into independent structures with distinct velocities. The velocity profiles of three regions with a smooth gradient are consistent with gas flows along the filament, suggesting accretion flows onto the densest regions. Conclusions: We show that the kinematics of several regions have a significant and complex velocity structure. For three filaments, we suggest that gas flows toward the more massive clumps are present

G048.66-0.29: physical state of an isolated site of massive star formation

We present continuum observations of the infrared dark cloud (IRDC) G48.66-0.22 (G48) obtained with Herschel, Spitzer, and APEX, in addition to several molecular line observations. The Herschel maps are used to derive temperature and column density maps of G48 using a model based on a modified blackbody. We find that G48 has a relatively simple structure and is relatively isolated; thus, this IRDC provides an excellent target to study the collapse and fragmentation of a filamentary structure in the absence of complicating factors such as strong external feedback. The derived temperature structure of G48 is clearly non-isothermal from cloud to core scale. The column density peaks are spatially coincident with the lowest temperatures (~17.5 K) in G48. A total cloud mass of ~390 M ⊙ is derived from the column density maps. By comparing the luminosity-to-mass ratio of 13 point sources detected in the Herschel/PACS bands to evolutionary models, we find that two cores are likely to evolve into high-mass stars (M sstarf >= 8 M ⊙). The derived mean projected separation of point sources is smaller than in other IRDCs but in good agreement with theoretical predications for cylindrical collapse. We detect several molecular species such as CO, HCO+, HCN, HNC, and N2H+. CO is depleted by a factor of ~3.5 compared to the expected interstellar abundance, from which we conclude that CO freezes out in the central region. Furthermore, the molecular clumps, associated with the submillimeter peaks in G48, appear to be gravitationally unbound or just pressure confined. The analysis of critical line masses in G48 shows that the entire filament is collapsing, overcoming any internal support

Kinematic and thermal structure at the onset of high-mass star formation

Context. Even though high-mass stars are crucial for understanding a diversity of processes within our galaxy and beyond, their formation and initial conditions are still poorly constrained. Aims: We want to understand the kinematic and thermal properties of young massive gas clumps prior to and at the earliest evolutionary stages of high-mass star formation. Do we find signatures of gravitational collapse? Do we find temperature gradients in the vicinity or absence of infrared emission sources? Do we find coherent velocity structures toward the center of the dense and cold gas clumps? Methods: To determine kinematics and gas temperatures, we used ammonia, because it is known to be a good tracer and thermometer of dense gas. We observed the NH3 (1, 1) and (2, 2) lines within six very young high-mass star-forming regions comprised of infrared dark clouds (IRDCs), along with ISO-selected far-infrared emission sources (ISOSS) with the Karl G. Jansky Very Large Array (VLA) and the Effelsberg 100 m Telescope. Results: The molecular line data allows us to study velocity structures, linewidths, and gas temperatures at high spatial resolution of 3-5'', corresponding to ~0.05 pc at a typical source distance of 2.5 kpc. We find on average cold gas clumps with temperatures in the range between 10 K and 30 K. The observations do not reveal a clear correlation between infrared emission peaks and ammonia temperature peaks. Several infrared emission sources show ammonia temperature peaks up to 30 K, whereas other infrared emission sources show no enhanced kinetic gas temperature in their surrounding. We report an upper limit for the linewidth of ~1.3 km s-1, at the spectral resolution limit of our VLA observation. This indicates a relatively low level of turbulence on the scale of the observations. Velocity gradients are present in almost all regions with typical velocity differences of 1 to 2 km s-1 and gradients of 5 to 10 km s-1 pc-1. These velocity gradients are smooth in most cases, but there is one exceptional source (ISOSS23053), for which we find several velocity components with a steep velocity gradient toward the clump centers that is larger than 30 km s-1 pc-1. This steep velocity gradient is consistent with recent models of cloud collapse. Furthermore, we report a spatial correlation of ammonia and cold dust, but we also find decreasing ammonia emission close to infrared emission sources

The Earliest Phases of Star Formation (EPoS): A Herschel Key Program - The precursors to high-mass stars and clusters

(Abridged) We present an overview of the sample of high-mass star and cluster forming regions observed as part of the Earliest Phases of Star Formation (EPoS) Herschel Guaranteed Time Key Program. A sample of 45 infrared-dark clouds (IRDCs) were mapped at PACS 70, 100, and 160 micron and SPIRE 250, 350, and 500 micron. In this paper, we characterize a population of cores which appear in the PACS bands and place them into context with their host cloud and investigate their evolutionary stage. We construct spectral energy distributions (SEDs) of 496 cores which appear in all PACS bands, 34% of which lack counterparts at 24 micron. From single-temperature modified blackbody fits of the SEDs, we derive the temperature, luminosity, and mass of each core. These properties predominantly reflect the conditions in the cold, outer regions. Taking into account optical depth effects and performing simple radiative transfer models, we explore the origin of emission at PACS wavelengths. The core population has a median temperature of 20K and has masses and luminosities that span four to five orders of magnitude. Cores with a counterpart at 24 micron are warmer and bluer on average than cores without a 24 micron counterpart. We conclude that cores bright at 24 micron are on average more advanced in their evolution, where a central protostar(s) have heated the outer bulk of the core, than 24 micron-dark cores. The 24 micron emission itself can arise in instances where our line of sight aligns with an exposed part of the warm inner core. About 10% of the total cloud mass is found in a given cloud's core population. We uncover over 300 further candidate cores which are dark until 100 micron. These are candidate starless objects, and further observations will help us determine the nature of these very cold cores.Comment: Accepted for publication in A&A, 81 pages, 68 figures. For full resolution image gallery (Appendix B), see http://www.mpia.de/~ragan/epos.htm

K(2P)18.1 translates T cell receptor signals into thymic regulatory T cell development

It remains largely unclear how thymocytes translate relative differences in T cell receptor (TCR) signal strength into distinct developmental programs that drive the cell fate decisions towards conventional (Tconv) or regulatory T cells (Treg). Following TCR activation, intracellular calcium (Ca2+) is the most important second messenger, for which the potassium channel K(2P)18.1 is a relevant regulator. Here, we identify K(2P)18.1 as a central translator of the TCR signal into the thymus-derived Treg (tTreg) selection process. TCR signal was coupled to NF-kappa B-mediated K(2P)18.1 upregulation in tTreg progenitors. K(2P)18.1 provided the driving force for sustained Ca2+ influx that facilitated NF-kappa B- and NFAT-dependent expression of FoxP3, the master transcription factor for Treg development and function. Loss of K(2P)18.1 ion-current function induced a mild lymphoproliferative phenotype in mice, with reduced Treg numbers that led to aggravated experimental autoimmune encephalomyelitis, while a gain-of-function mutation in K(2P)18.1 resulted in increased Treg numbers in mice. Our findings in human thymus, recent thymic emigrants and multiple sclerosis patients with a dominant-negative missense K(2P)18.1 variant that is associated with poor clinical outcomes indicate that K(2P)18.1 also plays a role in human Treg development. Pharmacological modulation of K(2P)18.1 specifically modulated Treg numbers in vitro and in vivo. Finally, we identified nitroxoline as a K(2P)18.1 activator that led to rapid and reversible Treg increase in patients with urinary tract infections. Conclusively, our findings reveal how K(2P)18.1 translates TCR signals into thymic T cell fate decisions and Treg development, and provide a basis for the therapeutic utilization of Treg in several human disorders.Peer reviewe

Cerebrospinal fluid microRNAs are potential biomarkers of temporal lobe epilepsy and status epilepticus

There is a need for diagnostic biomarkers of epilepsy and status epilepticus to support clinical examination, electroencephalography and neuroimaging. Extracellular microRNAs may be potentially ideal biomarkers since some are expressed uniquely within specific brain regions and cell types. Cerebrospinal fluid offers a source of microRNA biomarkers with the advantage of being in close contact with the target tissue and sites of pathology. Here we profiled microRNA levels in cerebrospinal fluid from patients with temporal lobe epilepsy or status epilepticus, and compared findings to matched controls. Differential expression of 20 microRNAs was detected between patient groups and controls. A validation phase included an expanded cohort and samples from patients with other neurological diseases. This identified lower levels of miR-19b in temporal lobe epilepsy compared to controls, status epilepticus and other neurological diseases. Levels of miR-451a were higher in status epilepticus compared to other groups whereas miR-21-5p differed in status epilepticus compared to temporal lobe epilepsy but not to other neurological diseases. Targets of these microRNAs include proteins regulating neuronal death, tissue remodelling, gliosis and inflammation. The present study indicates cerebrospinal fluid contains microRNAs that can support differential diagnosis of temporal lobe epilepsy and status epilepticus from other neurological and non-neurological diseases

K18.1 translates T cell receptor signals into thymic regulatory T cell development.

It remains largely unclear how thymocytes translate relative differences in T cell receptor (TCR) signal strength into distinct developmental programs that drive the cell fate decisions towards conventional (Tconv) or regulatory T cells (Treg). Following TCR activation, intracellular calcium (Ca2+) is the most important second messenger, for which the potassium channel K2P18.1 is a relevant regulator. Here, we identify K2P18.1 as a central translator of the TCR signal into the thymus-derived Treg (tTreg) selection process. TCR signal was coupled to NF-κB-mediated K2P18.1 upregulation in tTreg progenitors. K2P18.1 provided the driving force for sustained Ca2+ influx that facilitated NF-κB- and NFAT-dependent expression of FoxP3, the master transcription factor for Treg development and function. Loss of K2P18.1 ion-current function induced a mild lymphoproliferative phenotype in mice, with reduced Treg numbers that led to aggravated experimental autoimmune encephalomyelitis, while a gain-of-function mutation in K2P18.1 resulted in increased Treg numbers in mice. Our findings in human thymus, recent thymic emigrants and multiple sclerosis patients with a dominant-negative missense K2P18.1 variant that is associated with poor clinical outcomes indicate that K2P18.1 also plays a role in human Treg development. Pharmacological modulation of K2P18.1 specifically modulated Treg numbers in vitro and in vivo. Finally, we identified nitroxoline as a K2P18.1 activator that led to rapid and reversible Treg increase in patients with urinary tract infections. Conclusively, our findings reveal how K2P18.1 translates TCR signals into thymic T cell fate decisions and Treg development, and provide a basis for the therapeutic utilization of Treg in several human disorders