We present analysis of 12,227 type-ab RR Lyraes (RRLs) found among the 200 million public light curves in Catalina Surveys Data Release 1. These stars span the largest volume of the Milky Way ever ...surveyed with RRLs, covering ~20,000 deg super(2) of the sky (0degrees < alpha < 360degrees, -22degrees < delta < 65degrees) to heliocentric distances of up to 60 kpc. Each of the RRLs is observed between 60 and 419 times over a six-year period. Using period finding and Fourier fitting techniques we determine periods and apparent magnitudes for each source. We find that the periods are generally accurate to sigma = 0.002% in comparison to 2842 previously known RRLs and 100 RRLs observed in overlapping survey fields. We photometrically calibrate the light curves using 445 Landolt standard stars and show that the resulting magnitudes are accurate to ~0.05 mag using Sloan Digital Sky Survey (SDSS) data for ~1000 blue horizontal branch stars and 7788 RRLs. By combining Catalina photometry with SDSS spectroscopy, we analyze the radial velocity and metallicity distributions for >1500 of the RRLs. Using the accurate distances derived for the RRLs, we show the paths of the Sagittarius tidal streams crossing the sky at heliocentric distances from 20 to 60 kpc. By selecting samples of Galactic halo RRLs, we compare their velocity, metallicity, and distance with predictions from a recent detailed N-body model of the Sagittarius system. We find that there are some significant differences between the distances and structures predicted and our observations.
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Tailored nanocarriers have gained huge research focus for brain drug delivery, aimed at combating several neuro-oncological conditions, such as the glioblastoma multiforme (GBM). The ...progress of knowledge on the pathogenesis of GBM has allowed identifying the major hurdles for efficient treatment, encompassing biological interfaces (blood-brain barrier and blood–brain tumour barrier), specificities of tumour microenvironment, as well as both bulk and glioma stem cell subpopulations. These findings provided new insights into the molecular basis of GBM, being a strong driving force behind development of targeted nanomedicines in this area. Diversified nanoparticles have been designed to target GBM surface markers, overexpressed receptors, aberrant genes and signalling pathways, in addition to contemplating barriers targeting strategies. Among the nanocarriers explored, lipid nanoparticles claim important and unique features, including the versatility in promoting both passive and active drug targeting, making them excellent candidates for brain drug delivery and one of the most appealing to overcome the obstacles of the current GBM treatment.
RNA-based therapies, and siRNAs in particular, have attractive therapeutic potential for cancer treatment due to their ability to silence genes that are imperative for tumor progression. To be ...effective and solve issues related to their poor half-life and poor pharmacokinetic properties, siRNAs require adequate drug delivery systems that protect them from degradation and allow intracellular delivery. Among the various delivery vehicles available, lipid nanoparticles have emerged as the leading choice. These nanoparticles consist of cholesterol, phospholipids, PEG-lipids and most importantly ionizable cationic lipids. These ionizable lipids enable the binding of negatively charged siRNA, resulting in the formation of stable and neutral lipid nanoparticles with exceptionally high encapsulation efficiency. Lipid nanoparticles have demonstrated their effectiveness and versatility in delivering not only siRNAs but also multiple RNA molecules, contributing to their remarkable success. Furthermore, the advancement of efficient manufacturing techniques such as microfluidics, enables the rapid mixing of two miscible solvents without the need for shear forces. This facilitates the reproducible production of lipid nanoparticles and holds enormous potential for scalability. This is shown by the increasing number of preclinical and clinical trials evaluating the potential use of siRNA-LNPs for the treatment of solid and hematological tumors as well as in cancer immunotherapy. In this review, we provide an overview of the progress made on siRNA-LNP development for cancer treatment and outline the current preclinical and clinical landscape in this area. Finally, the translational challenges required to bring siRNA-LNPs further into the clinic are also discussed.
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•RNA-based cancer therapy modifies the genetic signature of tumor cells, surrounding cells and the immune system causing tumor reduction.•siRNA represents a promising strategy within RNA-based therapy for cancer.•siRNAs face some obstacles including rapid elimination by nucleases and hindrances to internalization by cells due to their negative charge.•Lipid nanoparticles containing ionizable lipids can deliver siRNA to tumor cells by the endosomal escape pathway.•siRNA-lipid nanoparticles have still some challenges to overcome, mostly regarding long term storage stability.
ABSTRACT
The All-Sky Automated Survey for Supernovae (ASAS-SN) provides long baseline (∼4 yr) light curves for sources brighter than V ≲ 17 mag across the whole sky. As part of our effort to ...characterize the variability of all the stellar sources visible in ASAS-SN, we have produced ∼30.1 million V-band light curves for sources in the Southern hemisphere using the APASS DR9 (AAVSO Photometric All-Sky Survey Data Release) catalogue as our input source list. We have systematically searched these sources for variability using a pipeline based on random forest classifiers. We have identified ${\sim } 220\, 000$ variables, including ${\sim } 88\, 300$ new discoveries. In particular, we have discovered ${\sim }48\, 000$ red pulsating variables, ${\sim }23\, 000$ eclipsing binaries, ∼2200 δ-Scuti variables, and ${\sim }10\, 200$ rotational variables. The light curves and characteristics of the variables are all available through the ASAS-SN variable stars data base (https://asas-sn.osu.edu/variables). The pre-computed ASAS-SN V-band light curves for all the ∼30.1 million sources are available through the ASAS-SN photometry data base (https://asas-sn.osu.edu/photometry). This effort will be extended to provide ASAS-SN light curves for sources in the Northern hemisphere and for V ≲ 17 mag sources across the whole sky that are not included in APASS DR9.
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Since the discovery of the beneficial therapeutical effects of extracellular vesicles (EVs), these agents have been attracting great interest as next-generation therapies. EVs are ...nanosized membrane bodies secreted by all types of cells that mediate cell–cell communication. Although the classification of different subpopulations of EVs can be complex, they are broadly divided into microvesicles and exosomes based on their biogenesis and in large and small EVs based on their size. As this is an emerging field, current investigations are focused on basic aspects such as the more convenient method for EV isolation. In the present paper, we used cardiac progenitor cells (CPCs) to study and compare different cell culture conditions for EV isolation as well as two of the most commonly employed purification methods: ultracentrifugation (UC) and size-exclusion chromatography (SEC). Large and small EVs were separately analysed. We found that serum starvation of cells during the EV collecting period led to a dramatic decrease in EV secretion and major cell death. Regarding the isolation method, our findings suggest that UC and SEC gave similar EV recovery rates. Separation of large and small EV-enriched subpopulations was efficiently achieved with both purification protocols although certain difference in sample heterogeneity was observed. Noteworthy, while calnexin was abundant in large EVs, ALIX and CD63 were mainly found in small EVs. Finally, when the functionality of EVs was assessed on primary culture of adult murine cardiac fibroblasts, we found that EVs were taken up by these cells, which resulted in a pronounced reduction in the proliferative and migratory capacity of the cells. Specifically, a tendency towards a larger effect of SEC-related EVs was observed. No differences could be found between large and small EVs. Altogether, these results contribute to establish the basis for the use of EVs as therapeutic platforms, in particular in regenerative fields.
Astronomy. ASASSN-15lh: A highly super-luminous supernova Dong, Subo; Shappee, B J; Prieto, J L ...
Science (American Association for the Advancement of Science),
2016-Jan-15, 20160115, Letnik:
351, Številka:
6270
Journal Article
Recenzirano
We report the discovery of ASASSN-15lh (SN 2015L), which we interpret as the most luminous supernova yet found. At redshift z = 0.2326, ASASSN-15lh reached an absolute magnitude of Mu ,AB = -23.5 ± ...0.1 and bolometric luminosity Lbol = (2.2 ± 0.2) × 10(45) ergs s(-1), which is more than twice as luminous as any previously known supernova. It has several major features characteristic of the hydrogen-poor super-luminous supernovae (SLSNe-I), whose energy sources and progenitors are currently poorly understood. In contrast to most previously known SLSNe-I that reside in star-forming dwarf galaxies, ASASSN-15lh appears to be hosted by a luminous galaxy (MK ≈ -25.5) with little star formation. In the 4 months since first detection, ASASSN-15lh radiated (1.1 ± 0.2) × 10(52) ergs, challenging the magnetar model for its engine.
ABSTRACT On 2014 December 9.61, the All-sky Automated Survey for SuperNovae (ASAS-SN or "Assassin") discovered ASASSN-14lp just ∼2 days after first light using a global array of 14 cm diameter ...telescopes. ASASSN-14lp went on to become a bright supernova (V = 11.94 mag), second only to SN 2014J for the year. We present prediscovery photometry (with a detection less than a day after first light) and ultraviolet through near-infrared photometric and spectroscopic data covering the rise and fall of ASASSN-14lp for more than 100 days. We find that ASASSN-14lp had a broad light curve ( ), a B-band maximum at 2457015.82 0.03, a rise time of days, and moderate host-galaxy extinction ( ). Using ASASSN-14lp, we derive a distance modulus for NGC 4666 of , corresponding to a distance of 14.7 1.5 Mpc. However, adding ASASSN-14lp to the calibrating sample of Type Ia supernovae still requires an independent distance to the host galaxy. Finally, using our early-time photometric and spectroscopic observations, we rule out red giant secondaries and, assuming a favorable viewing angle and explosion time, any nondegenerate companion larger than 0.34 .
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The combination of polymeric surfactants into mixed micelles is expected to improve properties relevant to their use in drug delivery, such as micellar size, gelation, and toxicity. ...We investigated synergistic effects in mixtures of D-α-Tocopheryl polyethylene glycol succinate (TPGS), an FDA-approved PEGylated derivative of vitamin E, and Tetronic surfactants, pH-responsive and thermogelling polyethylene oxide (PEO)-polypropylene oxide (PPO) 4-arm block copolymers. We hypothesized that mixed micelles would form under specific conditions and provide a handle to tune formulation characteristics.
We examined the morphology of the self-assembled structures in mixtures of TPGS with two Tetronic: T1107 and T908, using a combination of dynamic light scattering (DLS), small-angle neutron scattering (SANS), NMR spectroscopy (NOESY and diffusion NMR) and oscillatory rheology, over a range of compositions, temperatures and pH. Cell viability was assessed in NIH/3T3 fibroblasts.
The combination of TPGS with either of the two Tetronic produces spherical core-shell micelles that comprise both surfactants in their structure (mixed micelles). T1107 unimers incorporate into TPGS aggregates below the critical micelle temperature of the poloxamine, while mixed micelles only form under limited conditions with T908. At high concentration/temperature, small proportions of TPGS extend the gel phase, more markedly with T1107, with similar elastic moduli (30–50 kPa) and a BCC crystalline structure. Cell viability of NIH/3T3 fibroblasts grown in the hydrogels increases significantly when the poloxamine gels are doped with TPGS, making the combination of poloxamines and TPGS a promising platform for drug delivery.
Abstract
Stars with unusual properties can provide a wealth of information about rare stages of stellar evolution and exotic physics. However, determining the true nature of peculiar stars is often ...difficult. In this work, we conduct a systematic search for cool and luminous stars in the Magellanic Clouds with extreme variability, motivated by the properties of the unusual Small Magellanic Cloud star and Thorne–Żytkow Object (TŻO) candidate HV 2112. Using light curves from ASAS-SN, we identify 38 stars with surface temperatures
T
< 4800 K, luminosities
(
L
/
L
⊙
) > 4.3, variability periods >400 days, and variability amplitudes Δ
V
> 2.5 mag. Eleven of these stars possess the distinctive double-peaked light-curve morphology of HV 2112. We use the pulsation properties and derived occurrence rates for these 12 objects to constrain their nature. From comparisons to stellar populations and models, we find that one star may be a red supergiant with large-amplitude pulsations. For the other 11 stars, we derive current masses of ∼5–10
M
⊙
, below the theoretical minimum mass of ∼15
M
⊙
for TŻOs to be stable, casting doubt on this interpretation. Instead, we find that the temperatures, luminosities, mass-loss rates (MLRs), and periods of these stars are consistent with predictions for super-asymptotic giant branch (s-AGB) stars that have begun carbon burning but have not reached the superwind phase. We infer lifetimes in this phase of ∼(1–7) × 10
4
yr, also consistent with an s-AGB interpretation. If confirmed, these objects would represent the first identified population of s-AGB stars, illuminating the transition between low- and high-mass stellar evolution.
ABSTRACT
We place statistical constraints on Type Ia supernova (SN Ia) progenitors using 227 nebular-phase spectra of 111 SNe Ia. We find no evidence of stripped companion emission in any of the ...nebular-phase spectra. Upper limits are placed on the amount of mass that could go undetected in each spectrum using recent hydrodynamic simulations. With these null detections, we place an observational 3σ upper limit on the fraction of SNe Ia that are produced through the classical H-rich non-degenerate companion scenario of $\lt 5.5 {{\ \rm per\ cent}}$. Additionally, we set a tentative 3σ upper limit otan He star progenitor scenarios of $\lt 6.4 {{\ \rm per\ cent}}$, although further theoretical modelling is required. These limits refer to our most representative sample including normal, 91bg-like, 91T-like, and ‘super-Chandrasekhar’ SNe Ia but excluding SNe Iax and SNe Ia-CSM. As part of our analysis, we also derive a Nebular Phase Phillips Relation, which approximates the brightness of an SN Ia from 150 to 500 d after maximum using the peak magnitude and decline rate parameter Δm15(B).
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