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High-mass protostars (M$_{\star} >$ 8 M$_{\odot}$) are thought to gain the majority of their mass via short, intense bursts of growth. This episodic accretion is thought to be facilitated by gravitationally unstable and subsequently inhomogeneous accretion disks. Limitations of observational capabilities, paired with a lack of observed accretion burst events has withheld affirmative confirmation of the association between disk accretion, instability and the accretion burst phenomenon in high-mass protostars. Following its 2019 accretion burst, a heat-wave driven by a burst of radiation propagated outward from the high-mass protostar G358.93-0.03-MM1. Six VLBI (very long baseline interferometry) observations of the raditively pumped 6.7 GHz methanol maser were conducted during this period, tracing ever increasing disk radii as the heat-wave propagated outward. Concatenating the VLBI maps provided a sparsely sampled, milliarcsecond view of the spatio-kinematics of the accretion disk covering a physical range of $\sim$ 50 - 900 AU. We term this observational approach `heat-wave mapping'. We report the discovery of a Keplerian accretion disk with a spatially resolved four-arm spiral pattern around G358.93-0.03-MM1. This result positively implicates disk accretion and spiral arm instabilities into the episodic accretion high-mass star formation paradigm., Published in Nature Astronomy in 2023

Lipid nanoparticles serve as drug delivery vehicles for biopharmaceutical products. The lipid membrane shields internal nucleic-acid drug cargo from enzymatic degradation and facilitates cellular uptake of the drug. However, existing methods to assess drug loading within liposomes are limited to averaged bulk measurements, which obscures heterogeneity of the biopharmaceutical formulation. This report describes the development of a single-liposome analysis method to measure copy numbers of DNA within liposomes and assess population heterogeneity. This novel measurement was achieved by integrating two orthogonal polymerase chain reaction (PCR) techniques─digital PCR (dPCR) and quantitative PCR (qPCR)─within a single microfluidic assay. The dPCR dimension quantified liposomes to validate their capture in the single-liposome analysis regime. The qPCR dimension quantified DNA copy numbers packaged within each liposome. The ability of digital quantitative PCR (dqPCR) to analyze large numbers of individual liposomes in parallel revealed significant population heterogeneity, which could not be obtained from standard bulk analysis methods. Our innovative measurement of internal DNA cargo from single liposomes has the potential to inform liposome synthesis procedures and create more uniform liposomal biopharmaceutical formulations to enhance drug safety and efficacy.

MicroRNAs (miRNAs) are a class of biomolecules that have high clinical and pharmaceutical significance because of their ability to regulate protein expression. Better methods are needed to quantify target miRNAs, but their similar sequence lengths and low concentrations in biomedical samples impede analysis. This report aimed to develop a simple, rapid method to directly quantify multiple miRNAs using microfluidic thermal gel electrophoresis (TGE). Fluorescent probes were designed complementarily in sequence to four target miRNAs that also contained variable DNA overhangs to alter their electrophoretic mobilities. Samples and probes were directly added into thermal gel and loaded throughout a microchannel. Applying voltage resulted in an inline preconcentration and separation of the miRNAs that did not require a sample injection nor user intervention to switch between modes. Baseline resolution was achieved between four double-stranded miRNA-probe hybrids and four excess single-stranded probes. Analytical performance was then improved by designing an innovative microfluidic device with a tapered channel geometry. This device exhibited superior detection limits and separation resolution compared to standard channel devices without increasing the complexity of microfabrication or device operation. A proof-of-concept demonstration was then performed, showing that target miRNAs could be detected from cell extracts. These results demonstrate that TGE provides a simple, inexpensive means of conducting multiplexed miRNA measurements, with the potential for automation to facilitate future clinical and pharmaceutical analyses.

High-mass stars are thought to accumulate much of their mass via short, infrequent bursts of disk-aided accretion. Such accretion events are rare and difficult to observe directly but are known to drive enhanced maser emission. In this Letter we report high-resolution, multi-epoch methanol maser observations toward G358.93-0.03 which reveal an interesting phenomenon; the sub-luminal propagation of a thermal radiation "heat-wave" emanating from an accreting high-mass proto-star. The extreme transformation of the maser emission implies a sudden intensification of thermal infrared radiation from within the inner (40 mas, 270 au) region. Subsequently, methanol masers trace the radial passage of thermal radiation through the environment at $\geq$ 4-8\% the speed of light. Such a high translocation rate contrasts with the $\leq$ 10 km s$^{-1}$ physical gas motions of methanol masers typically observed using very long baseline interferometry (VLBI). The observed scenario can readily be attributed to an accretion event in the high-mass proto-star G358.93-0.03-MM1. While being the third case in its class, G358.93-0.03-MM1 exhibits unique attributes hinting at a possible `zoo' of accretion burst types. These results promote the advantages of maser observations in understanding high-mass star formation, both through single-dish maser monitoring campaigns and via their international cooperation as VLBI arrays., Comment: Published in Nature Astronomy in 2020

Polyacrylamide gel electrophoresis (PAGE) is a ubiquitous technique used in biochemical research laboratories to characterize protein samples. Despite its popularity, PAGE is relatively slow and provides limited separation resolution, especially for native proteins. This report describes the development of a microfluidic thermal gel transient isotachophoresis (TG-tITP) method to rapidly separate native proteins with high resolution. Thermal gels were employed as a separations matrix because of their unique ability to change viscosity in response to temperature. Proteins were added into thermal gel and loaded into a microfluidic device. Electrolyte optimization was conducted to achieve robust tITP to isotachophoretically preconcentrate proteins and then electrophoretically separate them. Electropherograms were collected through both time and distance to enable both small and large proteins to be measured within a single analysis. The effects of temperature were evaluated and found to exhibit a pronounced effect on the separation. Temperature gradients were then employed to alter thermal gel viscosity over time to maximize separation resolution between proteins. The results herein demonstrate how gradient TG-tITP achieves rapid, high-performance separations of native proteins. This analysis provided a wide mass range (6-464 kDa) with two-fold higher resolution than native PAGE while requiring 15,000-fold less protein loading and providing five-fold faster analysis times.

Digital PCR (dPCR) is a highly sensitive analytical technique used to quantify DNA targets. Detection sensitivity can be further enhanced by capturing target sequences onto beads for preconcentration and sample cleanup prior to analysis in microfluidic microwell arrays. However, robust digital analysis requires individual beads to be interrogated within individual wells. Fabricating microwells with dimensions ≤ 3 μm is challenging, and the high surface area-to-volume ratio of the wells leaves PCR susceptible to inhibition stemming from materials used during device processing. This report describes the development of a microfabrication procedure to create ultralow-volume wells (100 fL) for bead-based dPCR and characterize the effects of microprocessing materials on assay performance. Standard microfabrication protocols used for creating microelectronics resulted in devices with nanoscopic debris originating from photoresists used during processing. A model dPCR assay was developed to characterize the effects of this debris, which revealed variable PCR inhibition. Debris within microwells attenuated digital and analog assay signals to a greater extent than debris on the device surface. Spatial heterogeneity of debris across devices was quantified to characterize regional PCR inhibition and intra- and inter-device variability. Ultimately, a fabrication procedure was developed to create pristine microfluidic arrays using dual processes to remove positive resist and forgoing use of negative resist entirely, which enabled robust amplification with digital signals matching theoretical predictions. Results from this work catalog the unique performance artifacts from device microfabrication and provide a guide for future studies seeking to conduct robust, high-sensitivity bead-based dPCR assays.

Thermally reversible Pluronic gels have been employed as separation matrices in microfluidic devices in the analysis of biological macromolecules. The phase of these gels can be tuned between liquid and solid states using temperature to vary fluidic resistance and alter peak resolution. Although separations in thermal gels have been characterized, their effect on isotachophoresis has not. This study used fluorescein as a model analyte to evaluate isotachophoretic preconcentration as a function of thermal polymer concentration and temperature. Results demonstrated that increasing polymer concentration in microfluidic channels increased the apparent analyte concentration. A critical minimum of 10% (w/v) Pluronic was required to achieve efficient preconcentration with maximum focusing occurring in 20 and 25% polymer gels. Temperature of the thermal gel also impacted analyte focusing. Most efficient focusing was achieved at 25°C with diminishing analyte accumulation at higher and lower temperatures. Under optimal conditions, isotachophoretic preconcentration increased an additional threefold simply by including thermal gels in the system. This approach can be readily implemented in other applications to increase detection sensitivity and measure low-concentration analytes within simple microfluidic devices.

We report the detection of new 12.178, 12.229, 20.347, and 23.121 GHz methanol masers in the massive star-forming region G358.93-0.03, which are flaring on similarly short timescales (days) as the 6.668 GHz methanol masers also associated with this source. The brightest 12.178 GHz channel increased by a factor of over 700 in just 50 d. The masers found in the 12.229 and 20.347 GHz methanol transitions are the first ever reported and this is only the fourth object to exhibit associated 23.121 GHz methanol masers. The 12.178 GHz methanol maser emission appears to have a higher flux density than that of the 6.668 GHz emission, which is unusual. No associated near-infrared flare counterpart was found, suggesting that the energy source of the flare is deeply embedded., 9 pages, 3 figures, 2 tables, Published in MNRAS

Transient isotachophoresis (tITP) is a robust analytical technique that integrates sample preconcentration with electrophoretic separation. Despite the benefits afforded by tITP, its implementation poses a significant technical challenge because discontinuous electrolytes must remain spatially segregated for analysis. Here, we present a unique strategy to simplify tITP execution by using thermally reversible gels. Gels with distinct electrolyte compositions were introduced into separate microchannels in a cross-channel PDMS device while in their liquid states. Temperature was then altered to solidify the gels, which limited electrolyte diffusion and enabled reliable tITP analyses of both small molecule dyes and DNA. System performance was characterized using model fluorescent dyes. Separation efficiencies of >106 plates m−1 were achieved with detection limits of 5 pM. This strategy was then expanded to the analysis of DNA where distinct stacking and sieving gels were incorporated into the device for analyte preconcentration and separation. This proof-of-concept experiment demonstrated that a DNA ladder could be focused and separated in

Gel electrophoresis is a ubiquitous bioanalytical technique used to characterize the components of cell lysates. However, analyses of bulk lysates sacrifice detection sensitivity because intracellular biomolecules become diluted, and the liberation of proteases and nucleases can degrade target analytes. This report describes a method to enrich cells directly within a microfluidic gel as a first step toward online measurement of trace intracellular biomolecules with minimal dilution and degradation. Thermal gels were employed as the gel matrix because they can be reversibly converted between liquid and solid phases as a function of temperature. Rather than fabricate costly heating elements into devices to control temperature-and thus the phase of the gel-Joule heating was used instead. Adjoining regions of liquid-phase and solid-phase gel were formed within microfluidic channels by selectively inducing localized Joule heat. Cells migrated through the liquid gel but could not enter the solid gel-accumulating at the liquid-solid gel boundary-whereas small molecule contaminants passed through to waste. Barriers were then liquified on-demand by removing Joule heat to collect the purified, non-lysed cells for downstream analyses. Using voltage-controlled Joule heating to regulate the phase of thermal gels is an innovative approach to facilitate in-gel cell enrichment in low-cost microfluidic devices.

Context: The formation of high-mass star-forming regions from their parental gas cloud and the subsequent fragmentation processes lie at the heart of star formation research. Aims: We aim to study the dynamical and fragmentation properties at very early evolutionary stages of high-mass star formation. Methods: Employing the NOrthern Extended Millimeter Array (NOEMA) and the IRAM 30m telescope, we observed two young high-mass star-forming regions, ISOSS22478 and ISOSS23053, in the 1.3mm continuum and spectral line emission at a high angular resolution (~0.8''). Results: We resolved 29 cores that are mostly located along filament-like structures. Depending on the temperature assumption, these cores follow a mass-size relation of approximately M~r^2.0, corresponding to constant mean column densities. However, with different temperature assumptions, a steeper mass-size relation up to M~r^3.0, which would be more likely to correspond to constant mean volume densities, cannot be ruled out. The correlation of the core masses with their nearest neighbor separations is consistent with thermal Jeans fragmentation. We found hardly any core separations at the spatial resolution limit, indicating that the data resolve the large-scale fragmentation well. Although the kinematics of the two regions appear very different at first sight - multiple velocity components along filaments in ISOSS22478 versus a steep velocity gradient of more than 50km/s/pc in ISOSS23053 - the findings can be explained within the framework of a dynamical cloud collapse scenario. Conclusions: While our data are consistent with a dynamical cloud collapse scenario and subsequent thermal Jeans fragmentation, the importance of additional environmental properties, such as the magnetization of the gas or external shocks triggering converging gas flows, is nonetheless not as well constrained and would require future investigation., Comment: 16 pages, 16 figures, accepted for Astronomy and Astrophysics, a higher-resolution version can also be found at https://www.mpia.de/homes/beuther/papers.html

Aims. Current star formation research centers the characterization of the physical and chemical properties of massive stars, which are in the process of formation, at the spatial resolution of individual high-mass cores. Methods. We use sub-arcsecond resolution (~0.′′4) observations with the NOrthern Extended Millimeter Array at 1.37 mm to study the dust emission and molecular gas of 18 high-mass star-forming regions. With distances in the range of 0.7−5.5 kpc, this corresponds to spatial scales down to 300−2300 au that are resolved by our observations. We combined the derived physical and chemical properties of individual cores in these regions to estimate their ages. The temperature structures of these regions are determined by fitting the H2CO and CH3CN line emission. The density profiles are inferred from the 1.37 mm continuum visibilities. The column densities of 11 different species are determined by fitting the emission lines with XCLASS. Results. Within the 18 observed regions, we identified 22 individual cores with associated 1.37 mm continuum emission and with a radially decreasing temperature profile. We find an average temperature power-law index of q = 0.4 ± 0.1 and an average density power-law index of p = 2.0 ± 0.2 on scales that are on the order of several 1000 au. Comparing these results with values of p derived from the literature presumes that the density profiles remain unchanged from clump to core scales. The column densities relative to N(C18O) between pairs of dense gas tracers show tight correlations. We applied the physical-chemical model MUlti Stage ChemicaL codE to the derived column densities of each core and find a mean chemical age of ~60 000 yr and an age spread of 20 000−100 000 yr. With this paper, we release all data products of the CORE project. Conclusions. The CORE sample reveals well-constrained density and temperature power-law distributions. Furthermore, we characterized a large variety in molecular richness that can be explained by an age spread that is then confirmed by our physical-chemical modeling. The hot molecular cores show the greatest number of emission lines, but we also find evolved cores at an evolutionary stage in which most molecules are destroyed and, thus, the spectra appear line-poor once again.

Digital PCR (dPCR) is a highly sensitive analytical technique used to quantify DNA targets. Detection sensitivity can be further enhanced by capturing target sequences onto beads for preconcentration and sample cleanup prior to analysis in microfluidic microwell arrays. However, robust digital analysis requires individual beads to be interrogated within individual wells. Fabricating microwells with dimensions ≤ 3 μm is challenging, and the high surface area-to-volume ratio of the wells leaves PCR susceptible to inhibition stemming from materials used during device processing. This report describes the development of a microfabrication procedure to create ultralow-volume wells (100 fL) for bead-based dPCR and characterize the effects of microprocessing materials on assay performance. Standard microfabrication protocols used for creating microelectronics resulted in devices with nanoscopic debris originating from photoresists used during processing. A model dPCR assay was developed to characterize the effects of this debris, which revealed variable PCR inhibition. Debris within microwells attenuated digital and analog assay signals to a greater extent than debris on the device surface. Spatial heterogeneity of debris across devices was quantified to characterize regional PCR inhibition and intra- and inter-device variability. Ultimately, a fabrication procedure was developed to create pristine microfluidic arrays using dual processes to remove positive resist and forgoing use of negative resist entirely, which enabled robust amplification with digital signals matching theoretical predictions. Results from this work catalog the unique performance artifacts from device microfabrication and provide a guide for future studies seeking to conduct robust, high-sensitivity bead-based dPCR assays. Graphical abstract.

Proteins must maintain proper folding conformations and express the correct post-translational modifications (PTMs) to exhibit appropriate biological activity. However, assessing protein folding and PTMs is difficult because routine polyacrylamide gel electrophoresis (PAGE) methods lack the separation resolution necessary to identify variants of a single protein. Additionally, standard PAGE denatures proteins prior to analysis precluding determinations of folding states or PTMs. To overcome these limitations, a microfluidic thermal gel electrophoresis platform was developed to provide high-sensitivity, high-resolution analyses of native protein variants. A thermally reversible gel was utilized as a separation matrix while in its solid state (30 °C). This thermal gel provided sufficient separation resolution to identify three variants of a fluorescently labeled model protein. To increase detection sensitivity, analyte preconcentration was conducted in parallel with the separation. Continuous analyte enrichment afforded detection limits of 500 fg of protein (250 pM) while simultaneous baseline separation resolution was achieved between variants. The effects of temperature on thermal gel electrophoresis were also characterized. The unique temperature-dependent outcomes illustrated how method performance can be tuned through a thermal dimension. Ultimately, the high detection sensitivity and separation resolution provided by thermal gel electrophoresis enabled rapid screening of native protein variants.

The inner regions of the discs of high-mass young stellar objects (HMYSOs) are still poorly known due to the small angular scales and the high visual extinction involved. We deploy near-infrared (NIR) spectro-interferometry to probe the inner gaseous disc in HMYSOs and investigate the origin and physical characteristics of the CO bandhead emission (2.3-2.4 $\mu$m). We present the first GRAVITY/VLTI observations at high spectral (R=4000) and spatial (mas) resolution of the CO overtone transitions in NGC 2024 IRS2. The continuum emission is resolved in all baselines and is slightly asymmetric, displaying small closure phases ($\leq$8$^{\circ}$). Our best ellipsoid model provides a disc inclination of 34$^{\circ}$$\pm$1$^{\circ}$, a disc major axis position angle of 166$^{\circ}$$\pm$1$^{\circ}$, and a disc diameter of 3.99$\pm$0.09 mas (or 1.69$\pm$0.04 au, at a distance of 423 pc). The small closure phase signals in the continuum are modelled with a skewed rim, originating from a pure inclination effect. For the first time, our observations spatially and spectrally resolve the first four CO bandheads. Changes in visibility, as well as differential and closure phases across the bandheads are detected. Both the size and geometry of the CO-emitting region are determined by fitting a bidimensional Gaussian to the continuum-compensated CO bandhead visibilities. The CO-emitting region has a diameter of 2.74$\pm^{0.08}_{0.07}$ mas (1.16$\pm$0.03 au), and is located in the inner gaseous disc, well within the dusty rim, with inclination and $PA$ matching the dusty disc geometry, which indicates that both dusty and gaseous discs are coplanar. Physical and dynamical gas conditions are inferred by modelling the CO spectrum. Finally, we derive a direct measurement of the stellar mass of $M_*\sim$14.7$^{+2}_{-3.6}$ M$_{\odot}$ by combining our interferometric and spectral modelling results., Comment: Accepted for publication in A&A letters

With the $Karl~G.~Jansky$ Very Large Array (VLA) in C-configuration, we observed a large portion of the first Galactic quadrant ($l=14.0-67.4^\circ $ and $\lvert b \rvert \leq 1.25^\circ $) achieving an angular resolution of $\leq 40^{\prime\prime}$. At $L$ Band, the WIDAR correlator at the VLA was set to cover the 21~cm HI line, four OH transitions, a series of H$n\alpha$ radio recombination lines (RRLs; $n=151$ to 186), and eight 128~MHz wide continuum spectral windows (SPWs) simultaneously. The HI emission shows clear filamentary substructures at negative velocities with low velocity crowding. The emission at positive velocities is more smeared-out likely due to higher spatial and velocity crowding of structures at the positive velocities. Comparing to the spiral arm model of the Milky Way, the atomic gas follows the Sagittarius and Perseus Arm well but with significant material in the inter-arm regions. With the C-configuration-only HI+continuum data, we produced a HI optical depth map of the THOR areal coverage from 228 absorption spectra with the nearest-neighbor method. With this $\tau$ map, we corrected the HI emission for optical depth and the derived column density is 38% higher than the column density with optically thin assumption. The total HI mass with optical depth correction in the survey region is 4.7$\times10^8~M_\odot$, 31% more than the mass derived assuming the emission is optically thin. If we apply this 31% correction to the whole Milky Way, the total atomic gas mass would be 9.4-10.5$\times 10^9~M_\odot$. Comparing the HI with existing CO data, we find a significant increase in the atomic-to-molecular gas ratio from the spiral arms to the inter-arm regions., Comment: 22 pages, 13 figures, accepted to be published in Astronomy and Astrophysics

We report on one of the highest sensitivity surveys for molecular lines in the frequency range 6.0 to 7.4 GHz conducted to date. The observations were done with the 305m Arecibo Telescope toward a sample of twelve intermediate/high-mass star forming regions. We searched for a large number of transitions of different molecules, including CH3OH and OH. The low RMS noise of our data (~5 mJy for most sources and transitions) allowed detection of spectral features that have not been seen in previous lower sensitivity observations of the sources, such as detection of excited OH and 6.7 GHz CH3OH absorption. A review of 6.7 GHz CH3OH detections indicates an association between absorption and radio continuum sources in high-mass star forming regions, although selection biases in targeted projects and low sensitivity of blind surveys imply incompleteness. Absorption of excited OH transitions was also detected toward three sources. In particular, we confirm a broad 6.035 GHz OH absorption feature in G34.26+0.15 characterized by an asymmetric blue-shifted wing indicative of expansion, perhaps a large scale outflow in this HII region., 19 pages, 8 figures. Accepted for publication in MNRAS

Primary Ciliary Dyskinesia (PCD, MIM 242650) is a rare, hereditary multiorgan disease characterized by malfunction of motile cilia. Hallmark symptom is a chronic airway infection due to mucostasis leading to irreversible lung damage that may progress to respiratory failure. There is no cure for this genetic disease and evidence-based treatment is limited. Until recently, there were no randomized controlled trials performed in PCD, but this year, data of the first placebo-controlled trial on pharmacotherapy in PCD were published. This cornerstone in the management of PCD was decisive for reviewing currently used treatment strategies. This article is a consensus of patient representatives and clinicians, which are highly experienced in care of PCD-patients and provides an overview of the management of PCD. Treatments are mainly based on expert opinions, personal experiences, or are deduced from other lung diseases, notably cystic fibrosis (CF), COPD or bronchiectasis. Most strategies focus on routine airway clearance and treatment of recurrent respiratory tract infections. Non-respiratory symptoms are treated organ specific. To generate further evidence-based knowledge, other projects are under way, e. g. the International PCD-Registry. Participating in patient registries facilitates access to clinical and research studies and strengthens networks between centers. In addition, knowledge of genotype-specific course of the disease will offer the opportunity to further improve and individualize patient care.Die Primäre Ciliäre Dyskinesie (PCD, MIM 242650) ist eine seltene hereditäre Multisystemerkrankung mit klinisch heterogenem Phänotyp. Leitsymptom ist eine chronische Sekretretention der oberen und unteren Atemwege, welche durch die Dysfunktion motiler respiratorischer Zilien entsteht. In der Folge kommt es zur Ausbildung von Bronchiektasen, häufig zu einer Infektion durch Pseudomonas aeruginosa sowie einer abnehmenden Lungenfunktion bis hin zum Lungenversagen.Bislang gibt es kaum evidenzbasierte Therapieempfehlungen, da randomisierte Langzeitstudien zur Behandlung der PCD fehlten. In diesem Jahr wurden die Daten einer ersten placebokontrollierten Medikamentenstudie bei PCD veröffentlicht. Anlässlich dieses Meilensteins im Management der PCD wurde der vorliegende Übersichtsartikel als Konsens von Patientenvertretern sowie Klinikern, die langjährige Erfahrung in der Behandlung der PCD haben, verfasst. Diese Arbeit bietet eine Zusammenfassung aktuell eingesetzter Behandlungsverfahren, die überwiegend auf persönlichen Erfahrungen und Expertenmeinungen beruhen oder von anderen Atemwegserkrankungen wie der Cystischen Fibrose (CF), COPD oder Bronchiektasen-Erkrankung abgeleitet werden. Da es derzeit keine kurative Therapie für PCD gibt, stehen symptomatische Maßnahmen wie die regelmäßige Reinigung der Atemwege und die Behandlung von rezidivierenden Atemwegsinfektionen im Fokus. Nicht respiratorische Manifestationen werden organspezifisch behandelt. Um neben der ersten Medikamentenstudie mehr evidenzbasiertes Wissen zu generieren, werden weitere Projekte etabliert, u. a. ein internationales PCD-Register. Hierüber wird Patienten der Zugang zu klinischen und wissenschaftlichen Studien erleichtert und die Vernetzung behandelnder Zentren gefördert. Des Weiteren können Erkenntnisse über eine Genotyp-spezifische Erkrankungsschwere erlangt werden, um folglich die therapeutische Versorgung der Patienten zu verbessern und somit zu individualisieren.

We present a study of the filamentary structure in the emission from the neutral atomic hydrogen (HI) at 21 cm across velocity channels in the 40'' and 1.5-km/s resolution position-position-velocity cube resulting from the combination of the single-dish and interferometric observations in The HI/OH/Recombination (THOR) line survey. Using the Hessian matrix method in combination with tools from circular statistics, we find that the majority of the filamentary structures in the HI emission are aligned with the Galactic plane. Part of this trend can be assigned to long filamentary structures that are coherent across several velocity channels. However, we also find ranges of Galactic longitude and radial velocity where the HI filamentary structures are preferentially oriented perpendicular to the Galactic plane. These are located (i) around the tangent point of the Scutum spiral arm, $l \approx 28^{\circ}$ and $v_{\rm LSR}\approx 100$ km/s, (ii) toward $l \approx 45^{\circ}$ and $v_{\rm LSR}\approx 50$ km/s, (iii) around the Riegel-Crutcher cloud, and (iv) toward the terminal velocities. Comparison with numerical simulations indicates that the prevalence of horizontal filamentary structures is most likely the result of the large-scale dynamics and that vertical structures identified in (i) and (ii) may arise from the combined effect of supernova (SN) feedback and strong magnetic fields. The vertical filamentary structures in (iv) can be related to the presence of clouds from extra-planar HI gas falling back into the Galactic plane after being expelled by SNe. Our results indicate that a systematic characterization of the emission morphology toward the Galactic plane provides an unexplored link between the observations and the dynamical behaviour of the interstellar medium, from the effect of large-scale Galactic dynamics to the Galactic fountains driven by SNe., Comment: 28 pages. 37 figures. Accepted for publication in Astronomy & Astrophysics (09SEP2020)

Aims.We aim to determine far-infrared fluxes at 70, 100, and 160μm for the five major Uranus satellites, Titania, Oberon, Umbriel, Ariel, and Miranda. Our study is based on the available calibration observations at wavelengths taken with the PACS photometer aboard theHerschelSpace Observatory.Methods.The bright image of Uranus was subtracted using a scaled Uranus point spread function (PSF) reference established from all maps of each wavelength in an iterative process removing the superimposed moons. The photometry of the satellites was performed using PSF photometry. Thermophysical models of the icy moons were fitted to the photometry of each measurement epoch and auxiliary data at shorter wavelengths.Results.The best-fit thermophysical models provide constraints for important properties of the moons, such as surface roughness and thermal inertia. We present the first thermal infrared radiometry longward of 50μm for the four largest Uranian moons, Titania, Oberon, Umbriel, and Ariel, at epochs with equator-on illumination. Due to this inclination geometry, heat transport took place to the night side so that thermal inertia played a role, allowing us to constrain that parameter. Also, we found some indication for differences in the thermal properties of leading and trailing hemispheres. The total combined flux contribution of the four major moons relative to Uranus is 5.7 × 10−3, 4.8 × 10−3, and 3.4 × 10−3at 70, 100, and 160μm, respectively. We therefore precisely specify the systematic error of the Uranus flux by its moons when Uranus is used as a far-infrared prime flux calibrator. Miranda is considerably fainter and always close to Uranus, impeding reliable photometry.Conclusions.We successfully demonstrate an image processing technique for PACS photometer data that allows us to remove a bright central source and reconstruct point source fluxes on the order of 10−3of the central source as close as ≈3 × the half width at half maximum of the PSF. We established improved thermophysical models of the five major Uranus satellites. Our derived thermal inertia values resemble those of trans-neptunian object (TNO) dwarf planets, Pluto and Haumea, more than those of smaller TNOs and Centaurs at heliocentric distances of about 30 AU.

Context: The identification and characterisation of populations of young massive stars in (giant) HII regions provides important constraints on i) the formation process of massive stars and their early feedback on the environment, and ii) the initial conditions for population synthesis models predicting the evolution of ensembles of stars. Aims: We identify and characterise the stellar populations of the following young giant HII regions: M8, G333.6-0.2, and NGC6357. Methods: We acquired H- and K-band spectra of around 200 stars using The K-band KMOS on the ESO Very Large Telescope. The targets for M8 and NGC6357 were selected from the MYStIX project, which combines X-ray observations with near-infrared and mid-infrared data. For G333.6-0.2, the sample selection is based on the near-infrared colours combined with X-ray data. We introduce an automatic spectral classification method in order to obtain temperatures and luminosities for the observed stars. We analyse the stellar populations using their photometric, astrometric, and spectroscopic properties and compared the position of the stars in the Hertzprung-Russell diagram with stellar evolution models to constrain their ages and mass ranges. Results: We confirm the presence of candidate ionising sources in the three regions and report new ones, including the first spectroscopically identified O stars in G333.6-0.2. In M8 and NGC6357, two populations are identified: i) OB main-sequence stars ($M > 5~\rm{M_{\odot}}$) and ii) pre-main sequence stars ($M\approx0.5-5~\rm{M_{\odot}}$). The ages of the clusters are $\sim$1-3~Myr, $< 3$~Myr, and $\sim$0.5-3~Myr for M8, G333.6-0.2, and NGC6357, respectively. We show that MYStIX selected targets have $>$ 90\% probability of being members of the HII region, whereas a selection based on near infrared (NIR) colours leads to a membership probability of only $\sim$70\%., Accepted for publication in A&A. The arXiv version includes appendix C, which is an online only figure in A&A

We present a detailed observational and modeling study of the hot core VLA 3 in the high-mass star-forming region AFGL 2591, which is a target region of the NOrthern Extended Millimeter Array (NOEMA) large program CORE. Using NOEMA observations at 1.37 mm with an angular resolution of ~0."42 (1 400 au at 3.33 kpc), we derived the physical and chemical structure of the source. We modeled the observed molecular abundances with the chemical evolution code MUSCLE (MUlti Stage ChemicaL codE). Results. With the kinetic temperature tracers CH3CN and H2CO we observe a temperature distribution with a power-law index of q = 0.41+-0.08. Using the visibilities of the continuum emission we derive a density structure with a power-law index of p = 1.7+-0.1. The hot core spectra reveal high molecular abundances and a rich diversity in complex molecules. The majority of the molecules have an asymmetric spatial distribution around the forming protostar(s), which indicates a complex physical structure on scales < 1 400 au. Using MUSCLE, we are able to explain the observed molecular abundance of 10 out of 14 modeled species at an estimated hot core chemical age of ~21 100 years. In contrast to the observational analysis, our chemical modeling predicts a lower density power-law index of p < 1.4. Reasons for this discrepancy are discussed. Conclusions. Combining high spatial resolution observations with detailed chemical modeling allows us to derive a concise picture of the physical and chemical structure of the famous AFGL 2591 hot core. The next steps are to conduct a similar analysis for the whole CORE sample, and then use this analysis to constrain the chemical diversity in high-mass star formation to a much greater depth., 22 pages, 13 figures, accepted for publication in A&A

We present SOFIA/FIFI-LS observations of the [CII] 158${\mu}$m cooling line across the nearby spiral galaxy NGC 6946. We combine these with UV, IR, CO, and H I data to compare [CII] emission to dust properties, star formation rate (SFR), H$_2$, and HI at 560pc scales via stacking by environment (spiral arms, interarm, and center), radial profiles, and individual, beam-sized measurements. We attribute $73\%$ of the [CII] luminosity to arms, and $19\%$ and $8\%$ to the center and interarm region, respectively. [CII]/TIR, [CII]/CO, and [CII]/PAH radial profiles are largely constant, but rise at large radii ($\gtrsim$8kpc) and drop in the center ("[CII] deficit"). This increase at large radii and the observed decline with the 70${\mu}$m/100${\mu}$m dust color are likely driven by radiation field hardness. We find a near proportional [CII]-SFR scaling relation for beam-sized regions, though the exact scaling depends on methodology. [CII] also becomes increasingly luminous relative to CO at low SFR (interarm or large radii), likely indicating more efficient photodissociation of CO and emphasizing the importance of [CII] as an H$_2$ and SFR tracer in such regimes. Finally, based on the observed [CII] and CO radial profiles and different models, we find ${\alpha}_{CO}$ to increase with radius, in line with the observed metallicity gradient. The low ${\alpha}_{CO}$ (galaxy average $\lesssim2\,M_{sun}\,pc^{-2}\,(K\,km\,s^{-1})^{-1}$) and low [CII]/CO ratios ($\sim$400 on average) imply little CO-dark gas across NGC 6946, in contrast to estimates in the Milky Way., Comment: 12 pages, 6 Figures, published in ApJ

Context: Atomic and molecular cloud formation is a dynamical process. However, kinematic signatures of these processes are still observationally poorly constrained. Methods: Targeting the cloud-scale environment of the prototypical infrared dark cloud G28.3, we employ spectral line imaging observations of the two atomic lines HI and [CI] as well as molecular lines observations in 13CO in the 1--0 and 3--2 transitions. The analysis comprises investigations of the kinematic properties of the different tracers, estimates of the mass flow rates, velocity structure functions, a Histogram of Oriented Gradients (HOG) study as well as comparisons to simulations. Results: The central IRDC is embedded in a more diffuse envelope of cold neutral medium (CNM) traced by HI self-absorption (HISA) and molecular gas. The spectral line data as well as the HOG and structure function analysis indicate a possible kinematic decoupling of the HI from the other gas compounds. Spectral analysis and position-velocity diagrams reveal two velocity components that converge at the position of the IRDC. Estimated mass flow rates appear rather constant from the cloud edge toward the center. The velocity structure function analysis is consistent with gas flows being dominated by the formation of hierarchical structures. Conclusions: The observations and analysis are consistent with a picture where the IRDC G28 is formed at the center of two converging gas flows. While the approximately constant mass flow rates are consistent with a self-similar, gravitationally driven collapse of the cloud, external compression by, e.g., spiral arm shocks or supernovae explosions cannot be excluded yet. Future investigations should aim at differentiating the origin of such converging gas flows., 13 pages, 15 figures, Astronomy & Astrophysics in press, a higher resolution version can be found at http://www.mpia.de/homes/beuther/papers.html

We present Atacama Large Millimeter/sub-millimeter Array (ALMA) Cycle 2 observations of the 1.3 mm dust continuum emission of the protoplanetary disc surrounding the T Tauri star Elias 24 with an angular resolution of $\sim 0.2"$ ($\sim 28$ au). The dust continuum emission map reveals a dark ring at a radial distance of $0.47"$ ($\sim 65$ au) from the central star, surrounded by a bright ring at $0.58"$ ($\sim 81$ au). In the outer disc, the radial intensity profile shows two inflection points at $0.71"$ and $0.87"$ ($\sim 99$ and $121$ au respectively). We perform global three-dimensional smoothed particle hydrodynamic gas/dust simulations of discs hosting a migrating and accreting planet. Combining the dust density maps of small and large grains with three dimensional radiative transfer calculations, we produce synthetic ALMA observations of a variety of disc models in order to reproduce the gap- and ring-like features observed in Elias 24. We find that the dust emission across the disc is consistent with the presence of an embedded planet with a mass of $\sim 0.7\, \mathrm{M_{\mathrm{J}}}$ at an orbital radius of $\sim$ 60 au. Our model suggests that the two inflection points in the radial intensity profile are due to the inward radial motion of large dust grains from the outer disc. The surface brightness map of our disc model provides a reasonable match to the gap- and ring-like structures observed in Elias 24, with an average discrepancy of $\sim$ 5% of the observed fluxes around the gap region., Comment: 17 pages, 11 figures. Accepted for publication in MNRAS

Methods: We observed the high-mass hot core region G351.77-0.54 with ALMA and more than 16km baselines. Results: At a spatial resolution of 18/40au (depending on the distance), we identify twelve sub-structures within the inner few thousand au of the region. The brightness temperatures are high, reaching values greater 1000K, signposting high optical depth toward the peak positions. Core separations vary between sub-100au to several 100 and 1000au. The core separations and approximate masses are largely consistent with thermal Jeans fragmentation of a dense gas core. Due to the high continuum optical depth, most spectral lines are seen in absorption. However, a few exceptional emission lines are found that most likely stem from transitions with excitation conditions above1000K. Toward the main continuum source, these emission lines exhibit a velocity gradient across scales of 100-200au aligned with the molecular outflow and perpendicular to the previously inferred disk orientation. While we cannot exclude that these observational features stem from an inner hot accretion disk, the alignment with the outflow rather suggests that it stems from the inner jet and outflow region. The highest-velocity features are found toward the peak position, and no Hubble-like velocity structure can be identified. Therefore, these data are consistent with steady-state turbulent entrainment of the hot molecular gas via Kelvin-Helmholtz instabilities at the interface between the jet and the outflow. Conclusions: Resolving this high-mass star-forming region at sub-50au scales indicates that the hierarchical fragmentation process in the framework of thermal Jeans fragmentation can continue down to the smallest accessible spatial scales. Velocity gradients on these small scales have to be treated cautiously and do not necessarily stem from disks, but may be better explained with outflow emission., Comment: Accepted by Astronomy & Astrophysics, high-resolution version available at http://www.mpia.de/homes/beuther/papers.html

The fragmentation mode of high-mass molecular clumps and the properties of the central rotating structures surrounding the most luminous objects have yet to be comprehensively characterised. Using the IRAM NOrthern Extended Millimeter Array (NOEMA) and the IRAM 30-m telescope, the CORE survey has obtained high-resolution observations of 20 well-known highly luminous star-forming regions in the 1.37 mm wavelength regime in both line and dust continuum emission. We present the spectral line setup of the CORE survey and a case study for W3(H2O). At ~0.35" (700 AU at 2 kpc) resolution, the W3(H2O) clump fragments into two cores (West and East), separated by ~2300 AU. Velocity shifts of a few km/s are observed in the dense-gas tracer, CH3CN, across both cores, consistent with rotation and perpendicular to the directions of two bipolar outflows, one emanating from each core. The kinematics of the rotating structure about W3(H2O) W shows signs of differential rotation of material, possibly in a disk-like object. The observed rotational signature around W3(H2O) E may be due to a disk-like object, an unresolved binary (or multiple) system, or a combination of both. We fit the emission of CH3CN (12-11) K = 4-6 and derive a gas temperature map with a median temperature of ~165 K across W3(H2O). We create a Toomre Q map to study the stability of the rotating structures against gravitational instability. The rotating structures appear to be Toomre unstable close to their outer boundaries, with a possibility of further fragmentation in the differentially-rotating core W3(H2O) W. Rapid cooling in the Toomre-unstable regions supports the fragmentation scenario. Combining millimeter dust continuum and spectral line data toward the famous high-mass star-forming region W3(H2O), we identify core fragmentation on large scales, and indications for possible disk fragmentation on smaller spatial scales., Comment: 23 pages, 26 figures, accepted for publication in Astronomy and Astrophysics

Aims: We aim to understand the fragmentation as well as the disk formation, outflow generation and chemical processes during high-mass star formation on spatial scales of individual cores. Methods: Using the IRAM Northern Extended Millimeter Array (NOEMA) in combination with the 30m telescope, we have observed in the IRAM large program CORE the 1.37mm continuum and spectral line emission at high angular resolution (~0.4'') for a sample of 20 well-known high-mass star-forming regions with distances below 5.5kpc and luminosities larger than 10^4Lsun. Results: We present the overall survey scope, the selected sample, the observational setup and the main goals of CORE. Scientifically, we concentrate on the mm continuum emission on scales on the order of 1000AU. We detect strong mm continuum emission from all regions, mostly due to the emission from cold dust. The fragmentation properties of the sample are diverse. We see extremes where some regions are dominated by a single high-mass core whereas others fragment into as many as 20 cores. A minimum-spanning-tree analysis finds fragmentation at scales on the order of the thermal Jeans length or smaller suggesting that turbulent fragmentation is less important than thermal gravitational fragmentation. The diversity of highly fragmented versus singular regions can be explained by varying initial density structures and/or different initial magnetic field strengths. Conclusions: The smallest observed separations between cores are found around the angular resolution limit which indicates that further fragmentation likely takes place on even smaller spatial scales. The CORE project with its numerous spectral line detections will address a diverse set of important physical and chemical questions in the field of high-mass star formation., Comment: 29 pages, 17 figures, Astronomy & Astrophysics in press, for a higher-resolution version of the paper see http://www.mpia.de/homes/beuther/papers.html

There is a considerable deficiency in the number of known supernova remnants (SNRs) in the Galaxy compared to that expected. Searches for extended low-surface brightness radio sources may find new Galactic SNRs, but confusion with the much larger population of HII regions makes identifying such features challenging. SNRs can, however, be separated from HII regions using their significantly lower mid-infrared (MIR) to radio continuum intensity ratios. We use the combination of high-resolution 1-2 GHz continuum data from The HI, OH, Recombination line survey of the Milky Way (THOR) and lower-resolution VLA 1.4 GHz Galactic Plane Survey (VGPS) continuum data, together with MIR data from the Spitzer GLIMPSE, Spitzer MIPSGAL, and WISE surveys to identify SNR candidates. To ensure that the candidates are not being confused with HII regions, we exclude radio continuum sources from the WISE Catalog of Galactic HII Regions, which contains all known and candidate H II regions in the Galaxy. We locate 76 new Galactic SNR candidates in the THOR and VGPS combined survey area of 67.4deg>l>17.5deg, |b, Accepted for publication in A&A

Currently, reliable valving on integrated microfluidic devices fabricated from rigid materials is confined to expensive and complex methods. Freeze-thaw valves (FTVs) can provide a low cost, low complexity valving mechanism, but reliable implementation of them has been greatly hindered by the lack of ice nucleation sites within the valve body's small volume. Work to date has required very low temperatures (on the order of -40 °C or colder) to induce freezing without nucleation sites, making FTVs impractical due to instrument engineering challenges. Here, we report the use of ice-nucleating proteins (INPs) to induce ice formation at relatively warm temperatures in microfluidic devices. Microfluidic channels were filled with buffers containing femtomolar INP concentrations from Pseudomonas syringae. The channels were cooled externally with simple, small-footprint Peltier thermoelectric coolers (TECs), and the times required for channel freezing (valve closure) and thawing (valve opening) were measured. Under optimized conditions in plastic chips, INPs made sub-10 s actuations possible at TEC temperatures as warm as -13 °C. Additionally, INPs were found to have no discernible inhibitory effects in model enzyme-linked immunosorbent assays or polymerase chain reactions, indicating their compatibility with microfluidic systems that incorporate these widely used bioassays. FTVs with INPs provide a much needed reliable valving scheme for rigid plastic devices with low complexity, low cost, and no moving parts on the device or instrument. The reduction in freeze time, accessible actuation temperatures, chemical compatibility, and low complexity make the implementation of compact INP-based FTV arrays practical and attractive for the control of integrated biochemical assays.

We present results of a multi-epoch monitoring program on variability of 6$\,$cm formaldehyde (H$_2$CO) masers in the massive star forming region NGC$\,$7538$\,$IRS$\,$1 from 2008 to 2015 conducted with the GBT, WSRT, and VLA. We found that the similar variability behaviors of the two formaldehyde maser velocity components in NGC$\,$7538$\,$IRS$\,$1 (which was pointed out by Araya and collaborators in 2007) have continued. The possibility that the variability is caused by changes in the maser amplification path in regions with similar morphology and kinematics is discussed. We also observed 12.2$\,$GHz methanol and 22.2$\,$GHz water masers toward NGC$\,$7538$\,$IRS$\,$1. The brightest maser components of CH$_3$OH and H$_2$O species show a decrease in flux density as a function of time. The brightest H$_2$CO maser component also shows a decrease in flux density and has a similar LSR velocity to the brightest H$_2$O and 12.2$\,$GHz CH$_3$OH masers. The line parameters of radio recombination lines and the 20.17 and 20.97$\,$GHz CH$_3$OH transitions in NGC$\,$7538$\,$IRS$\,$1 are also reported. In addition, we observed five other 6$\,$cm formaldehyde maser regions. We found no evidence of significant variability of the 6$\,$cm masers in these regions with respect to previous observations, the only possible exception being the maser in G29.96$-$0.02. All six sources were also observed in the H$_2^{13}$CO isotopologue transition of the 6$\,$cm H$_2$CO line; H$_2^{13}$CO absorption was detected in five of the sources. Estimated column density ratios [H$_2^{12}$CO]/[H$_2^{13}$CO] are reported., Comment: 29 pages, 9 figures

Context: High-mass stars have a high degree of multiplicity and most likely form via disk accretion processes. The detailed physics of the binary and disk formation are still poorly constrained. Methods: Using the VLA in its most extended configuration at ~24GHz toward the prototypical high-mass star-forming region NGC7538IRS1 has allowed us to study the NH3 and thermal CH3OH emission and absorption as well as the cm continuum emission at an unprecedented spatial resolution of 0.06"x0.05", corresponding to a linear resolution of ~150AU at a distance of 2.7kpc. Results: A comparison of these new cm continuum data with previous VLA observations from 23yrs ago reveals no recognizable proper motions. If the emission were caused by a protostellar jet, proper motion signatures should have been easily identified. In combination with the high spectral indices S~nu^{alpha} (alpha between 1 and 2), this allows us to conclude that the continuum emission is from two hypercompact HII regions separated in projection by about 430AU. The NH3 spectral line data reveal a common rotating envelope indicating a bound high-mass binary system. In addition to this, the thermal CH3OH data show two separate velocity gradients across the two hypercompact HII regions. This indicates two disk-like structures within the same rotating circumbinary envelope. Disk and envelope structures are inclined by ~33deg, which can be explained by initially varying angular momentum distributions within the natal, turbulent cloud. Conclusions: Studying high-mass star formation at sub-0.1" resolution allows us to isolate multiple sources as well as to separate circumbinary from disk-like rotating structures., Comment: 11 pages, 9 figures, Astronomy & Astrophysics in press, a higher-resolution version can be found at http://www.mpia.de/homes/beuther/papers.html

Methylarginines (MAs) are a class of nitric oxide synthase inhibitors that have been implicated in respiratory complications of critically ill infants. This paper describes the development of an analytical method to measure these compounds in the plasma of newborns using capillary electrophoresis (CE). The CE separation method was optimized to enable complete baseline resolution of the four MA analogues of interest. Sample preparation concerns for infant-derived samples were addressed by validating a heat-assisted extraction method for the analysis of low volume (≤100 µL) samples from a plasma matrix. It was determined that the sample matrix (plasma versus serum) did not affect the measured MA concentrations, while extracting smaller volumes of plasma that underwent heat-induced gelation afforded higher MA recoveries than larger volume samples. These methods were then applied to blood samples collected from infants housed in the neonatal intensive care unit. It was discovered that these newborns had significantly elevated concentrations of MAs at younger ages (< 6 months) while amounts were similar between infants 6 months old and adults. The data are preliminary, but demonstrate an interesting age dependence on the concentrations of these nitric oxide inhibitors, which has not been previously reported.

Context. This study is part of the CORE project, an IRAM/NOEMA large program consisting of observations of the millimeter continuum and molecular line emission towards 20 selected high-mass star-forming regions. The goal of the program is to search for circumstellar accretion disks, study the fragmentation process of molecular clumps, and investigate the chemical composition of the gas in these regions. Aims. We focus on IRAS 23385+6053, which is believed to be the least-evolved source of the CORE sample. This object is characterized by a compact molecular clump that is IR-dark shortward of 24 μm and is surrounded by a stellar cluster detected in the near-IR. Our aim is to study the structure and velocity field of the clump. Methods. Observations were performed at ~1.4 mm and employed three configurations of NOEMA and additional single-dish maps, merged with the interferometric data to recover the extended emission. Our correlator setup covered a number of lines from well-known hot core tracers and a few outflow tracers. The angular (~0′′.45–0′′.9) and spectral (0.5 km s−1) resolutions were sufficient to resolve the clump in IRAS 23385+6053 and investigate the existence of large-scale motions due to rotation, infall, or expansion. Results. We find that the clump splits into six distinct cores when observed at sub-arcsecond resolution. These are identified through their 1.4 mm continuum and molecular line emission. We produce maps of the velocity, line width, and rotational temperature from the methanol and methyl cyanide lines, which allow us to investigate the cores and reveal a velocity and temperature gradient in the most massive core. We also find evidence of a bipolar outflow, possibly powered by a low-mass star. Conclusions. We present the tentative detection of a circumstellar self-gravitating disk lying in the most massive core and powering a large-scale outflow previously known in the literature. In our scenario, the star powering the flow is responsible for most of the luminosity of IRAS 23385+6053 (~3000 L⊙). The other cores, albeit with masses below the corresponding virial masses, appear to be accreting material from their molecular surroundings and are possibly collapsing or on the verge of collapse. We conclude that we are observing a sample of star-forming cores that is bound to turn into a cluster of massive stars.

Methylarginines (MAs) are potent vasoconstrictors that have been reported to be present at elevated concentrations in the blood of patients suffering from cardiovascular disease (CVD). To determine the diagnostic potential of MAs for CVD, a method capable of rapidly quantifying their endogenous concentrations from serum samples is required. To that end, a heat-assisted extraction method was developed. Serum was first rapidly heated, causing it to congeal into a gel, and then subjected to solid-liquid extraction. The extraction solution was then derivatized with a fluorogenic dye and analyzed by CE-LIF to permit quantitation of the MAs. This heat-assisted extraction procedure allowed a no-net-dilution extraction of the analytes to be performed into a solvent compatible with the subsequent CE analysis. This enabled direct detection of low abundance analytes, such as MAs, without the need for a preconcentration step. This sample preparation method was compared with a commonly used solid-phase extraction method for MA analysis. Endogenous MA concentrations determined by both the heating and SPE methods were found to be in good agreement with each other and with values previously reported in the literature.

For over a decade, the structure of the inner “hole” in the transition disk around TW Hydrae has been a subject of debate. To probe the innermost regions of the protoplanetary disk, observations at the highest possible spatial resolution are required. We present new interferometric data of TW Hya from near-infrared to millimeter wavelengths. We confront existing models of the disk structure with the complete data set and develop a new, detailed radiative-transfer model. This model is characterized by: 1) a spatial separation of the largest grains from the small disk grains; and 2) a smooth inner rim structure, rather than a sharp disk edge.

Charakteristika Die primare ziliare Dyskinesie (PCD) ist eine seltene angeborene Erkrankung der Zilien, die sich zumeist im respiratorischen System manifestiert.

To characterize the mechanisms of planet formation it is crucial to investigate the properties and evolution of protoplanetary disks around young stars, where the initial conditions for the growth of planets are set. Our goal is to study grain growth in the disk of the young, intermediate mass star HD163296 where dust processing has already been observed, and to look for evidence of growth by ice condensation across the CO snowline, already identified in this disk with ALMA. Under the hypothesis of optically thin emission we compare images at different wavelengths from ALMA and VLA to measure the opacity spectral index across the disk and thus the maximum grain size. We also use a Bayesian tool based on a two-layer disk model to fit the observations and constrain the dust surface density. The measurements of the opacity spectral index indicate the presence of large grains and pebbles ($\geq$1 cm) in the inner regions of the disk (inside $\sim$50 AU) and smaller grains, consistent with ISM sizes, in the outer disk (beyond 150 AU). Re-analysing ALMA Band 7 Science Verification data we find (radially) unresolved excess continuum emission centered near the location of the CO snowline at $\sim$90 AU. Our analysis suggests a grain size distribution consistent with an enhanced production of large grains at the CO snowline and consequent transport to the inner regions. Our results combined with the excess in infrared scattered light found by Garufi et al. (2014) suggests the presence of a structure at 90~AU involving the whole vertical extent of the disk. This could be evidence for small scale processing of dust at the CO snowline., Comment: 12 pages, 17 figures. Accepted for publication in A\&A

Constraining the temperature and density structure of dense molecular cloud cores is fundamental for understanding the initial conditions of star formation. We use Herschel observations of the thermal FIR dust emission from nearby isolated molecular cloud cores and combine them with ground-based submillimeter continuum data to derive observational constraints on their temperature and density structure. The aim of this study is to verify the validity of a ray-tracing inversion technique developed to derive the dust temperature and density structure of isolated starless cores directly from the dust emission maps and to test if the resulting temperature and density profiles are consistent with physical models. Using this ray-tracing inversion technique, we derive the dust temperature and density structure of six isolated starless cloud cores. We employ self-consistent radiative transfer modeling to the derived density profiles, treating the ISRF as the only heating source. The best-fit values of local strength of the ISRF and the extinction by the outer envelope are derived by comparing the self-consistently calculated temperature profiles with those derived by the ray-tracing method. We find that all starless cores are significantly colder inside than outside, with the core temperatures showing a strong negative correlation with peak column density. This suggests that their thermal structure is dominated by external heating from the ISRF and shielding by dusty envelopes. The temperature profiles derived with the ray-tracing inversion method can be well-reproduced with self-consistent radiative transfer models., Comment: 16 pages, 12 figures, accepted for publication in A&A

The methylated arginines (MAs) monomethylarginine (MMA), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) have been shown to be independent predictors of cardiovascular disease. This article describes progress regarding the development of an analytical method capable of rapidly analyzing MAs using capillary electrophoresis (CE) and microchip electrophoresis (MCE) with laser-induced fluorescence (LIF) detection. Several parameters including buffer composition and separation voltage were optimized to achieve an ideal separation. The analytes of interest were derivatized with naphthalene-2,3-dicarboxaldehyde (NDA) to produce fluorescent 1-cyanobenz[f]isoindole (CBI) derivatives and then subjected to CE analysis. Baseline resolution of SDMA, ADMA, MMA, and arginine was achieved in less than 8 min. The limits of detection for SDMA, ADMA, MMA, and arginine were determined to be 15, 20, 25, and 5 nM, respectively, which are well below the expected plasma concentrations. The CE separation method was then transferred to a glass MCE device with LIF detection. MAs were baseline resolved in 3 min on-chip using a 14 cm separation channel with detection limits of approximately 10 nM for each species. To the best of the authors’ knowledge, this is the first report of the separation of MAs by MCE.

We report results of an extensive observational campaign of the 6 cm formaldehyde maser in the young massive stellar object IRAS18566+0408 (G37.55+0.20) conducted from 2002 to 2009. Using Arecibo, VLA, and GBT, we discovered quasi-periodic formaldehyde flares (P ~ 237 days). Based on Arecibo observations, we also discovered correlated variability between formaldehyde (H2CO) and methanol (CH3OH) masers. The H2CO and CH3OH masers are not spatially coincident, as demonstrated by different line velocities and high angular resolution MERLIN observations. The flares could be caused by variations in the infrared radiation field, possibly modulated by periodic accretion onto a young binary system., Comment: 16 pages, 3 figures, accepted for publication in the Astrophysical Journal Letters

Aims: Our aims are to determine flux densities and their photometric accuracy for a set of seventeen stars that range in flux from intermediately bright (≲2.5 Jy) to faint (≳5 mJy) in the far- infrared (FIR). We also aim to derive signal-to-noise dependence with flux and time, and compare the results with predictions from the Herschel exposure-time calculation tool. Methods: We obtain aperture photometry from Herschel-PACS high-pass-filtered scan maps and chop/nod observations of the faint stars. The issues of detection limits and sky confusion noise are addressed by comparison of the field-of-view at different wavelengths, by multi-aperture photometry, by special processing of the maps to preserve extended emission, and with the help of large-scale absolute sky brightness maps from AKARI. This photometry is compared with flux-density predictions based on photospheric models for these stars. We obtain a robust noise estimate by fitting the flux distribution per map pixel histogram for the area around the stars, scaling it for the applied aperture size and correcting for noise correlation. Results: For 15 stars we obtain reliable photometry in at least one PACS filter, and for 11 stars we achieve this in all three PACS filters (70, 100, 160 μm). Faintest fluxes, for which the photometry still has good quality, are about 10-20 mJy with scan map photometry. The photometry of seven stars is consistent with models or flux predictions for pure photospheric emission, making them good primary standard candidates. Two stars exhibit source-intrinsic far- infrared excess: β Gem (Pollux), being the host star of a confirmed Jupiter-size exoplanet, due to emission of an associated dust disk, and η Dra due to dust emission in a binary system with a K1 dwarf. The investigation of the 160 μm sky background and environment of four sources reveals significant sky confusion prohibiting the determination of an accurate stellar flux at this wavelength. As a good model approximation, for nine stars we obtain scaling factors of the continuum flux models of four PACS fiducial standards with the same or quite similar spectral type. We can verify a linear dependence of signal-to- noise ratio (S/N) with flux and with square root of time over significant ranges. At 160 μm the latter relation is, however, affected by confusion noise. Conclusions: The PACS faint star sample has allowed a comprehensive sensitivity assessment of the PACS photometer. Accurate photometry allows us to establish a set of five FIR primary standard candidates, namely α Ari, ∊ Lep, ω Cap, HD 41047 and 42 Dra, which are 2-20 times fainter than the faintest PACS fiducial standard (γ Dra) with absolute accuracy of http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz- bin/qcat?J/A+A/613/A40

[abridged] Our knowledge of the inner structure of embedded massive young stellar objects is still quite limited. We attempt here to overcome the spatial resolution limitations of conventional thermal infrared imaging. We employed mid-infrared interferometry using the MIDI instrument on the ESO/VLTI facility to investigate M8E-IR, a well-known massive young stellar object suspected of containing a circumstellar disk. Spectrally dispersed visibilities in the 8-13 micron range were obtained at seven interferometric baselines. We resolve the mid-infrared emission of M8E-IR and find typical sizes of the emission regions of the order of 30 milli-arcseconds (~45 AU). Radiative transfer simulations have been performed to interpret the data. The fitting of the spectral energy distribution, in combination with the measured visibilities, does not provide evidence for an extended circumstellar disk with sizes > 100 AU but requires the presence of an extended envelope. The data are not able to constrain the presence of a small-scale disk in addition to an envelope. In either case, the interferometry measurements indicate the existence of a strongly bloated, relatively cool central object, possibly tracing the recent accretion history of M8E-IR. In addition, we present 24.5 micron images that clearly distinguish between M8E-IR and the neighbouring ultracompact HII region and which show the cometary-shaped infrared morphology of the latter source. Our results show that IR interferometry, combined with radiative transfer modelling, can be a viable tool to reveal crucial structure information on embedded massive young stellar objects and to resolve ambiguities arising from fitting the SED., 7 pages, 5 figures, accepted for publication in A&A, new version after language editing, one important reference added, conclusions unchanged