Exosomes, the smallest sized extracellular vesicles ( 30-150 nm) packaged with lipids, proteins, functional messenger RNAs and microRNAs, and double-stranded DNA from their cells of origin, have ...emerged as key players in intercellular communication. Their presence in bodily fluids, where they protect their cargo from degradation, makes them attractive candidates for clinical application as innovative diagnostic and therapeutic tools. But routine isolation and analysis of high purity exosomes in clinical settings is challenging, with conventional methods facing a number of drawbacks including low yield and/or purity, long processing times, high cost, and difficulties in standardization. Here we review a promising solution, microfluidic-based technologies that have incorporated a host of separation and sensing capabilities for exosome isolation, detection, and analysis, with emphasis on point-of-care and clinical applications. These new capabilities promise to advance fundamental research while paving the way toward routine exosome-based liquid biopsy for personalized medicine.
Breakthroughs in adapting microfluidic systems for exosome isolation, detection, and analysis are providing new tools to revolutionize personalized medicine.
In a companion work (Paper I), we detected a large population of highly variable Young Stellar Objects (YSOs) in the Vista Variables in the Via Lactea (VVV) survey, typically with class I or flat ...spectrum spectral energy distributions and diverse light-curve types. Here we present infrared spectra (0.9-2.5 ...m) of 37 of these variables, many of them observed in a bright state. The spectra confirm that 15/18 sources with eruptive light curves have signatures of a high accretion rate, either showing EXor-like emission features (... = 2 CO, Br...) and/or FUor-like features (... = 2 CO and H sub( 2)O strongly in absorption). Similar features were seen in some long-term periodic YSOs and faders but not in dippers or short-term variables. The sample includes some dusty Mira variables (typically distinguished by smooth Mira-like light curves), two cataclysmic variables and a carbon star. In total, we have added 19 new objects to the broad class of eruptive variable YSOs with episodic accretion. Eruptive variable YSOs in our sample that were observed at bright states show higher accretion luminosities than the rest of the sample. Most of the eruptive variables differ from the established FUor and EXor subclasses, showing intermediate outburst durations and a mixture of their spectroscopic characteristics. This is in line with a small number of other recent discoveries. Since these previously atypical objects are now the majority amongst embedded members of the class, we propose a new classification for them as MNors. This term (pronounced emnor) follows V1647 Ori, the illuminating star of McNeil's Nebula. (ProQuest: ... denotes formulae/symbols omitted.)
FU Orionis-type objects (FUors) are young low-mass stars undergoing powerful accretion outbursts. The increased accretion is often accompanied by collimated jets and energetic, large-scale molecular ...outflows. The extra heating during the outburst may also induce detectable geometrical, chemical, and mineralogical changes in the circumstellar material, affecting possible planet formation around these objects. V346 Nor is a southern FUor with peculiar spectral characteristics. Decades after the beginning of its outburst, it unexpectedly underwent a fading event around 2010 due to a decrease in the mass accretion rate onto the star by at least two orders of magnitude. Here we present optical and near-infrared photometry and spectroscopy obtained after the minimum. Our light curves show a gradual re-brightening of V346 Nor, with its Ks-band brightness only 1.5 mag below the outburst brightness level. Our Very Large Telescope (VLT)/XSHOOTER spectroscopic observations display several strong forbidden emission lines toward the source from various metals and molecular hydrogen, suggesting the launch of a new jet. Our N-band spectrum obtained with VLT/VISIR outlines a deeper silicate absorption feature than before, indicating that the geometry of the circumstellar medium has changed in the post-outburst period compared to peak brightness.
Tuberculosis is an ongoing threat to global health, especially with the emergence of multi drug-resistant (MDR) and extremely drug-resistant strains that are motivating the search for new treatment ...strategies. One potential strategy is immunotherapy using Innate Defence Regulator (IDR) peptides that selectively modulate innate immunity, enhancing chemokine induction and cell recruitment while suppressing potentially harmful inflammatory responses. IDR peptides possess only modest antimicrobial activity but have profound immunomodulatory functions that appear to be influential in resolving animal model infections. The IDR peptides HH2, 1018 and 1002 were tested for their activity against two M. tuberculosis strains, one drug-sensitive and the other MDR in both in vitro and in vivo models. All peptides showed no cytotoxic activity and only modest direct antimicrobial activity versus M. tuberculosis (MIC of 15-30 µg/ml). Nevertheless peptides HH2 and 1018 reduced bacillary loads in animal models with both the virulent drug susceptible H37Rv strain and an MDR isolate and, especially 1018 led to a considerable reduction in lung inflammation as revealed by decreased pneumonia. These results indicate that IDR peptides have potential as a novel immunotherapy against TB.
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We present the discovery of 816 high-amplitude infrared variable stars (...K sub( s) > 1 mag) in 119 deg super( 2) of the Galactic mid-plane covered by the VISTA Variables in the Via Lactea (VVV) ...survey. Almost all are new discoveries and about 50 per cent are young stellar objects (YSOs). This provides further evidence that YSOs are the commonest high-amplitude infrared variable stars in the Galactic plane. In the 2010-2014 time series of likely YSOs, we find that the amplitude of variability increases towards younger evolutionary classes (class I and flat-spectrum sources) except on short time-scales (<25 d) where this trend is reversed. Dividing the likely YSOs by light-curve morphology, we find 106 with eruptive light curves, 45 dippers, 39 faders, 24 eclipsing binaries, 65 long-term periodic variables (P > 100 d) and 162 short-term variables. Eruptive YSOs and faders tend to have the highest amplitudes and eruptive systems have the reddest spectral energy distribution (SEDs). Follow-up spectroscopy in a companion paper verifies high accretion rates in the eruptive systems. Variable extinction is disfavoured by the two epochs of colour data. These discoveries increase the number of eruptive variable YSOs by a factor of at least 5, most being at earlier stages of evolution than the known FUor and EXor types. We find that eruptive variability is at least an order of magnitude more common in class I YSOs than class II YSOs. Typical outburst durations are 1-4 yr, between those of EXors and FUors. They occur in 3-6 per cent of class I YSOs over a 4 yr time span. (ProQuest: ... denotes formulae/symbols omitted.)
Aims. We aim to study the rotating and expanding gas in the Red Rectangle, which is a well known bipolar nebula surrounding a double stellar system whose primary is a post-asymptotic giant branch ...(post-AGB) star. We analyze the properties of both components and the relation between them. Rotating disks have been very elusive in post-AGB nebulae, in which gas is almost always found to be in expansion. Methods. We present new high-quality ALMA observations of this source in C17O J = 6−5 and H13CN J = 4−3 line emission and results from a new reduction of already published 13CO J = 3−2 data. A detailed model fitting of all the molecular line data, also discussing previous maps and single-dish observations of lines of CO, CII, and CI, was performed using a sophisticated code that includes an accurate nonlocal treatment of radiative transfer in 2D (assuming axial symmetry). These observations (of low- and high-opacity lines requiring various degrees of excitation) and the corresponding modeling allowed us to deepen the analysis of the nebular properties. We also stress the uncertainties, particularly in the determination of the boundaries of the CO-rich gas and some properties of the outflow. Results. We confirm the presence of a rotating equatorial disk and an outflow, which is mainly formed of gas leaving the disk. The mass of the disk is ~0.01 M⊙, and that of the CO-rich outflow is around ten times smaller. High temperatures of ≳100 K are derived for most components. From comparison of the mass values, we roughly estimate the lifetime of the rotating disk, which is found to be of about 10 000 yr. Taking data of a few other post-AGB composite nebulae into account, we find that the lifetimes of disks around post-AGB stars typically range between about 5000 and more than 20 000 yr. The angular momentum of the disk is found to be high, ~9 M⊙ AU km s-1, which is comparable to that of the stellar system at present. Our observations of H13CN show a particularly wide velocity dispersion and indicate that this molecule is only abundant in the inner Keplerian disk, at ≲60 AU from the stellar system. We suggest that HCN is formed in a dense photodissociation region (PDR) due to the UV excess known to be produced by the stellar system, following chemical mechanisms that are well established for interstellar medium PDRs and disks orbiting young stars. We further suggest that this UV excess could lead to an efficient formation and excitation of PAHs and other C-bearing macromolecules, whose emission is very intense in the optical counterpart.
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Binarity is believed to dramatically affect the history and geometry of mass loss in AGB and post-AGB stars, but observational evidence of binarity is sorely lacking. As part of a project to search ...for hot binary companions to cool AGB stars using the GALEX archive, we discovered a late-M star, Y Gem, to be a source of strong and variable UV and X-ray emission. Here we report UV spectroscopic observations of Y Gem obtained with the Hubble Space Telescope that show strong flickering in the UV continuum on timescales of 20 s, characteristic of an active accretion disk. Several UV lines with P-Cygni-type profiles from species such as Si iv and C iv are also observed, with emission and absorption features that are red- and blueshifted by velocities of ∼500 from the systemic velocity. Our model for these (and previous) observations is that material from the primary star is gravitationally captured by a companion, producing a hot accretion disk. The latter powers a fast outflow that produces blueshifted features due to the absorption of UV continuum emitted by the disk, whereas the redshifted emission features arise in heated infalling material from the primary. The outflow velocities support a previous inference by Sahai et al. that Y Gem's companion is a low-mass main-sequence star. Blackbody fitting of the UV continuum implies an accretion luminosity of about 13 L , and thus a mass-accretion rate >5 × 10−7 M yr−1; we infer that Roche-lobe overflow is the most likely binary accretion mode for Y Gem.
We have mapped 12CO J = 3-2 and other molecular lines from the "water fountain" bipolar pre-planetary nebula (PPN) IRAS 16342-3814 with ∼0 35 resolution using Atacama Large Millimeter/submillimeter ...Array. We find (i) two very high-speed knotty, jet-like molecular outflows; (ii) a central high-density ( cm−3), expanding torus of diameter 1300 au; and (iii) the circumstellar envelope of the progenitor AGB, generated by a sudden, very large increase in the mass-loss rate to M yr−1 in the past ∼455 years. Strong continuum emission at 0.89 mm from a central source (690 mJy), if due to thermally emitting dust, implies a substantial mass (0.017 M ) of very large (∼millimeter-sized) grains. The measured expansion ages of the above structural components imply that the torus (age ∼160 years) and the younger high-velocity outflow (age ∼110 years) were formed soon after the sharp increase in the AGB mass-loss rate. Assuming a binary model for the jets in IRAS 16342, the high momentum rate for the dominant jet-outflow in IRAS 16342 implies a high minimum accretion rate, ruling out standard Bondi-Hoyle-Lyttleton wind accretion and wind Roche-lobe overflow (RLOF) models with white-dwarf or main-sequence companions. Most likely, enhanced RLOF from the primary or accretion modes operating within common-envelope evolution are needed.
Context. The mechanism behind the shaping of bipolar planetary nebulae is still poorly understood. It is becoming increasingly clear that the main agents must operate at their innermost regions, ...where a significant equatorial density enhancement should be present and related to the collimation of light and jet launching from the central star preferentially towards the polar directions. Most of the material in this equatorial condensation must be lost during the asymptotic giant branch as stellar wind and later released from the surface of dust grains to the gas phase in molecular form. Accurately tracing the molecule-rich regions of these objects can give valuable insight into the ejection mechanisms themselves. Aims. We investigate the physical conditions, structure and velocity field of the dense molecular region of the planetary nebula NGC 6302 by means of ALMA band 7 interferometric maps. Methods. The high spatial resolution of the 12CO and 13CO J = 3−2 ALMA data allows for an analysis of the geometry of the ejecta in unprecedented detail. We built a spatio-kinematical model of the molecular region with the software SHAPE and performed detailed non-LTE calculations of excitation and radiative transfer with the shapemol plug-in. Results. We find that the molecular region consists of a massive ring out of which a system of fragments of lobe walls emerge and enclose the base of the lobes visible in the optical. The general properties of this region are in agreement with previous works, although the much greater spatial resolution of the data allows for a very detailed description. We confirm that the mass of the molecular region is 0.1 M⊙. Additionally, we report a previously undetected component at the nebular equator, an inner, younger ring inclined ~60° with respect to the main ring, showing a characteristic radius of 7.5 × 1016 cm, a mass of 2.7 × 10-3M⊙, and a counterpart in optical images of the nebula. This inner ring has the same kinematical age as the northwest optical lobes, implying it was ejected approximately at the same time, hundreds of years after the ejection of the bulk of the molecular ring-like region. We discuss a sequence of events leading to the formation of the molecular and optical nebulae, and briefly speculate on the origin of this intriguing inner ring.
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