HI spectra and column densities toward HVC and IVC probes

We show 21-cm line profiles in the direction of stars and extragalactic objects, lying projected on high- and intermediate-velocity clouds (HVCs and IVCs). About half of these are from new data obtained with the Effelsberg 100-m telescope, about a quarter are extracted from the Leiden-Dwingeloo Survey (LDS) and the remaining quarter were observed with other single-dish telescopes. HI column densities were determined for each HVC/IVC. Wakker (2001) (Paper I) uses these in combination with optical and ultraviolet high-resolution measurements to derive abundances. Here, an analysis is given of the difference and ratio of N(HI) as observed with a 9 arcmin versus a 35 arcmin beam. For HVCs and IVCs the ratio N(HI-9 arcmin)/N(HI-35 arcmin) lies in the range 0.2-2.5. For low-velocity gas this ratio ranges from 0.75 to 1.3 (the observed ratio is 0.85-1.4, but it appears that the correction for stray radiation is slightly off). The smaller range for the low-velocity gas may be caused by confusion in the line of sight, so that a low ratio in one component can be compensated by a high ratio in another -- for 11 low-velocity clouds fit by one component the distribution of ratios has a larger dispersion. Comparison with higher angular resolution data is possible for sixteen sightlines. Eight sightlines with HI data at 1 arcmin-2 arcmin resolution show a range of 0.75-1.25 for N(HI-2 arcmin)/N(HI-9 arcmin), while in eight other sightlines N(HI-Ly-alpha)/N(HI-9 arcmin) ranges from 0.74 to 0.98.Comment: To appear in the "Astrophysical Journal Supplement"; 45 pages; degraded figures (astro-ph restriction) - ask for good version

Influence of short term storage conditions, concentration methods and excipients on extracellular vesicle recovery and function

Extracellular vesicles (EVs) are phospholipid bilayer enclosed vesicles which play an important role in intercellular communication. To date, many studies have focused on therapeutic application of EVs. However, to progress EV applications faster towards the clinic, more information about the physical stability and scalable production of EVs is needed. The goal of this study was to evaluate EV recovery and function after varying several conditions in the isolation process or during storage. Physical stability and recovery rates of EVs were evaluated by measuring EV size, particle and protein yields using nanoparticle tracking analysis, microBCA protein quantification assay and transmission electron microscopy. Western blot analyses of specific EV markers were performed to determine EV yields and purity. EV functionality was tested in an endothelial cell wound healing assay. Higher EV recovery rates were found when using HEPES buffered saline (HBS) as buffer compared to phosphate buffered saline (PBS) during EV isolation. When concentrating EVs, 15 ml spinfilters with a 10 kDa membrane cutoff gave the highest EV recovery. Next, EV storage in polypropylene tubes was shown to be superior compared to glass tubes. The use of protective excipients during EV storage, i.e. bovine serum albumin (BSA) and Tween 20, improved EV preservation without influencing their functionality. Finally, it was shown that both 4 °C and −80 °C are suitable for short term storage of EVs. Together, our results indicate that optimizing buffer compositions, concentrating steps, protective excipients and storage properties may collectively increase EV recovery rates significantly while preserving their functional properties, which accelerates translation of EV-based therapeutics towards clinical application

Functional siRNA Delivery by Extracellular Vesicle–Liposome Hybrid Nanoparticles

The therapeutic use of RNA interference is limited by the inability of siRNA molecules to reach their site of action, the cytosol of target cells. Lipid nanoparticles, including liposomes, are commonly employed as siRNA carrier systems to overcome this hurdle, although their widespread use remains limited due to a lack of delivery efficiency. More recently, nature's own carriers of RNA, extracellular vesicles (EVs), are increasingly being considered as alternative siRNA delivery vehicles due to their intrinsic properties. However, they are difficult to load with exogenous cargo. Here, EV–liposome hybrid nanoparticles (hybrids) are prepared and evaluated as an alternative delivery system combining properties of both liposomes and EVs. It is shown that hybrids are spherical particles encapsulating siRNA, contain EV-surface makers, and functionally deliver siRNA to different cell types. The functional behavior of hybrids, in terms of cellular uptake, toxicity, and gene-silencing efficacy, is altered as compared to liposomes and varies among recipient cell types. Moreover, hybrids produced with cardiac progenitor cell (CPC) derived-EVs retain functional properties attributed to CPC-EVs such as activation of endothelial signaling and migration. To conclude, hybrids combine benefits of both synthetic and biological drug delivery systems and might serve as future therapeutic carriers of siRNA

Cold gas accretion in galaxies

Evidence for the accretion of cold gas in galaxies has been rapidly accumulating in the past years. HI observations of galaxies and their environment have brought to light new facts and phenomena which are evidence of ongoing or recent accretion: 1) A large number of galaxies are accompanied by gas-rich dwarfs or are surrounded by HI cloud complexes, tails and filaments. It may be regarded as direct evidence of cold gas accretion in the local universe. It is probably the same kind of phenomenon of material infall as the stellar streams observed in the halos of our galaxy and M31. 2) Considerable amounts of extra-planar HI have been found in nearby spiral galaxies. While a large fraction of this gas is produced by galactic fountains, it is likely that a part of it is of extragalactic origin. 3) Spirals are known to have extended and warped outer layers of HI. It is not clear how these have formed, and how and for how long the warps can be sustained. Gas infall has been proposed as the origin. 4) The majority of galactic disks are lopsided in their morphology as well as in their kinematics. Also here recent accretion has been advocated as a possible cause. In our view, accretion takes place both through the arrival and merging of gas-rich satellites and through gas infall from the intergalactic medium (IGM). The infall may have observable effects on the disk such as bursts of star formation and lopsidedness. We infer a mean ``visible'' accretion rate of cold gas in galaxies of at least 0.2 Msol/yr. In order to reach the accretion rates needed to sustain the observed star formation (~1 Msol/yr), additional infall of large amounts of gas from the IGM seems to be required.Comment: To appear in Astronomy & Astrophysics Reviews. 34 pages. Full-resolution version available at http://www.astron.nl/~oosterlo/accretionRevie

Gas Accretion in Star-Forming Galaxies

Cold-mode gas accretion onto galaxies is a direct prediction of LCDM simulations and provides galaxies with fuel that allows them to continue to form stars over the lifetime of the Universe. Given its dramatic influence on a galaxy's gas reservoir, gas accretion has to be largely responsible for how galaxies form and evolve. Therefore, given the importance of gas accretion, it is necessary to observe and quantify how these gas flows affect galaxy evolution. However, observational data have yet to conclusively show that gas accretion ubiquitously occurs at any epoch. Directly detecting gas accretion is a challenging endeavor and we now have obtained a significant amount of observational evidence to support it. This chapter reviews the current observational evidence of gas accretion onto star-forming galaxies.Comment: Invited review to appear in Gas Accretion onto Galaxies, Astrophysics and Space Science Library, eds. A. J. Fox & R. Dav\'e, to be published by Springer. This chapter includes 22 pages with 7 Figure

The Interstellar Environment of our Galaxy

We review the current knowledge and understanding of the interstellar medium of our galaxy. We first present each of the three basic constituents - ordinary matter, cosmic rays, and magnetic fields - of the interstellar medium, laying emphasis on their physical and chemical properties inferred from a broad range of observations. We then position the different interstellar constituents, both with respect to each other and with respect to stars, within the general galactic ecosystem.Comment: 39 pages, 12 figures (including 3 figures in 2 parts

Planck 2013 results. XI. All-sky model of thermal dust emission

This paper presents an all-sky model of dust emission from the Planck 353, 545, and 857 GHz, and IRAS 100 \u3bcm data. Using a modified blackbody fit to the data we present all-sky maps of the dust optical depth, temperature, and spectral index over the 353-3000 GHz range. This model is a good representation of the IRAS and Planck data at 5\u2032 between 353 and 3000 GHz (850 and 100 \u3bcm). It shows variations of the order of 30% compared with the widely-used model of Finkbeiner, Davis, and Schlegel. The Planck data allow us to estimate the dust temperature uniformly over the whole sky, down to an angular resolution of 5\u2032, providing an improved estimate of the dust optical depth compared to previous all-sky dust model, especially in high-contrast molecular regions where the dust temperature varies strongly at small scales in response to dust evolution, extinction, and/or local production of heating photons. An increase of the dust opacity at 353 GHz, \u3c4353/NH, from the diffuse to the denser interstellar medium (ISM) is reported. It is associated with a decrease in the observed dust temperature, Tobs, that could be due at least in part to the increased dust opacity. We also report an excess of dust emission at H i column densities lower than 1020 cm-2 that could be the signature of dust in the warm ionized medium. In the diffuse ISM at high Galactic latitude, we report an anticorrelation between \u3c4353/NH and Tobs while the dust specific luminosity, i.e., the total dust emission integrated over frequency (the radiance) per hydrogen atom, stays about constant, confirming one of the Planck Early Results obtained on selected fields. This effect is compatible with the view that, in the diffuse ISM, Tobs responds to spatial variations of the dust opacity, due to variations of dust properties, in addition to (small) variations of the radiation field strength. The implication is that in the diffuse high-latitude ISM \u3c4353 is not as reliable a tracer of dust column density as we conclude it is in molecular clouds where the correlation of \u3c4353 with dust extinction estimated using colour excess measurements on stars is strong. To estimate Galactic E(B-V) in extragalactic fields at high latitude we develop a new method based on the thermal dust radiance, instead of the dust optical depth, calibrated to E(B-V) using reddening measurements of quasars deduced from Sloan Digital Sky Survey data. \ua9 2014 ESO

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

ASKAP and MeerKAT surveys of the magellanic clouds

The Magellanic Clouds are a stepping stone from the overwhelming detail of the Milky Way in which we are immersed, to the global characteristics of galaxies both in the nearby and distant universe. They are interacting, gas-rich dwarf galaxies of sub-solar metallicity, not unlike the building blocks that assembled the large galaxies that dominate groups and clusters, and representative of the conditions at the height of cosmic star formation. The Square Kilometre Array (SKA) can make huge strides in understanding galactic metabolism and the ecological processes that govern star formation, by observations of the Magellanic Clouds and other, nearby Magellanic-type irregular galaxies. Two programmes with SKA Pathfinders attempt to pave the way: the approved Galactic ASKAP Spectral Line Survey (GASKAP) includes a deep survey in H I and OH of the Magellanic Clouds, whilst MagiKAT is proposed to perform more detailed studies of selected regions within the Magellanic Clouds - also including Faraday rotation measurements and observations at higher frequencies. These surveys also close the gap with the revolutionizing surveys at far-IR wavelengths with the Spitzer Space Telescope and Herschel Space Observatory

New drug-strategies to tackle viral-host interactions for the treatment of influenza virus infections

The influenza virus (IV) is a highly contagious virus causing seasonal global outbreaks affecting annually up to 20% of the world's population and leading to 250,000-500,000 deaths worldwide. Current vaccines have variable effectiveness, and, in particular during a pandemic outbreak, they are probably not available in the amounts needed to protect the world population. Therefore we need effective small molecule drugs to combat an IV infection and that can be produced, in case of pandemic, rapidly and in large quantities. Unfortunately, natural occurring IV becomes more and more resistant to current anti-IV drugs. And thus, there is an urgent need for development of alternative agents with new mechanisms of action. This review provides an overview of the pharmacology and effectiveness of new anti-IV agents, focusing on inhibition mechanisms directed against virus-host interactions