Swine are considered to be one of the major animal species used in translational research, surgical models, and procedural training and are increasingly being used as an alternative to the dog or ...monkey as the choice of nonrodent species in preclinical toxicologic testing of pharmaceuticals. There are unique advantages to the use of swine in this setting given that they share with humans similar anatomic and physiologic characteristics involving the cardiovascular, urinary, integumentary, and digestive systems. However, the investigator needs to be familiar with important anatomic, histopathologic, and clinicopathologic features of the laboratory pig and minipig in order to put background lesions or xenobiotically induced toxicologic changes in their proper perspective and also needs to consider specific anatomic differences when using the pig as a surgical model. Ethical considerations, as well as the existence of significant amounts of background data, from a regulatory perspective, provide further support for the use of this species in experimental or pharmaceutical research studies. It is likely that pigs and minipigs will become an increasingly important animal model for research and pharmaceutical development applications.
During the first few days after explosion, Type II supernovae (SNe) are dominated by relatively simple physics. Theoretical predictions regarding early-time SN light curves in the ultraviolet (UV) ...and optical bands are thus quite robust. We present, for the first time, a sample of 57 R-band SN II light curves that are well-monitored during their rise, with >5 detections during the first 10 days after discovery, and a well-constrained time of explosion to within 1–3 days. We show that the energy per unit mass (E/M) can be deduced to roughly a factor of five by comparing early-time optical data to the 2011 model of Rabinak and Waxman, while the progenitor radius cannot be determined based on R-band data alone. We find that SN II explosion energies span a range of E/M = (0.2–20) × 10{sup 51} erg/(10 M{sub ⊙}), and have a mean energy per unit mass of 〈E/M〉=0.85×10{sup 51} erg/(10 M{sub ⊙}), corrected for Malmquist bias. Assuming a small spread in progenitor masses, this indicates a large intrinsic diversity in explosion energy. Moreover, E/M is positively correlated with the amount of {sup 56}Ni produced in the explosion, as predicted by some recent models of core-collapse SNe. We further present several empirical correlations. The peak magnitude is correlated with the decline rate (Δm{sub 15}), the decline rate is weakly correlated with the rise time, and the rise time is not significantly correlated with the peak magnitude. Faster declining SNe are more luminous and have longer rise times. This limits the possible power sources for such events.
We present the results of a survey using the WASP archive to search for high-frequency pulsations in F-, A- and B-type stars. Over 1.5 million targets have been searched for pulsations with ...amplitudes greater than 0.5 millimagnitude. We identify over 350 stars which pulsate with periods less than 30 min. Spectroscopic follow-up of selected targets has enabled us to confirm 10 new rapidly oscillating Ap stars, 13 pulsating Am stars and the fastest known delta Scuti star. We also observe stars which show pulsations in both the high-frequency domain and the low-frequency delta Scuti range. This work shows the power of the WASP photometric survey to find variable stars with amplitudes well below the nominal photometric precision per observation.
Some reports of supernova (SN) discoveries turn out not to be true core-collapse explosions. One such case was SN 2009ip, which was recognized to be the eruption of a luminous blue variable (LBV) ...star. This source had a massive (50-80 M), hot progenitor star identified in pre-explosion data; it had documented evidence of pre-outburst variability and it was subsequently discovered to have a second outburst in 2010. In 2012, the source entered its third known outburst. Initial spectra showed the same narrow-line profiles as before, suggesting another LBV-like eruption. We present new photometry and spectroscopy of SN 2009ip, indicating that the 2012 outburst transitioned into a genuine SN explosion. The most striking aspect of these data is that unlike any previous episodes, the spectrum developed Balmer lines with very broad P-Cygni profiles characteristic of normal Type II supernovae (SNe II), in addition to overlying narrow emission components. The emission lines exhibit unprecedented (for any known non-terminal LBV-like eruption) full width at half-maximum intensity values of ∼8000 km s−1, while the absorption components seen just before the main brightening had blue wings extending out to −13 000 km s−1. These velocities are typical of core-collapse SN explosions, but have never been associated with emission lines from a non-terminal LBV-like eruption. SN 2009ip is the first object to have both a known massive blue progenitor star and LBV-like eruptions with accompanying spectra observed a few years prior to becoming a SN. Immediately after the broad lines first appeared, the peak absolute magnitude of M
V
−14.5 was fainter than that of normal SNe II. However, after a brief period of fading, the source quickly brightened again to M
R
= −17.5 mag in ∼2 d, suggesting a causal link to the prior emergence of the broad-line spectrum. Once the bright phase began, the broad lines mostly disappeared, and the spectrum resembled the early optically thick phases of luminous SNe IIn. The source reached a peak brightness of −18 mag about 2 weeks later, after which broad emission lines again developed in the spectrum as the source faded. We conclude that the most recent 2012 outburst of SN 2009ip was the result of a true core-collapse SN IIn that occurred when the progenitor star was in an LBV-like outburst phase, and where the SN was initially faint and then rapidly brightened due to interaction with circumstellar material. The pulsational pair instability, LBV-like eruptions or other instabilities due to late nuclear burning phases in massive stars may have caused the multiple pre-SN eruptions.
The Berkeley sample of stripped-envelope supernovae Shivvers, Isaac; Filippenko, Alexei V; Silverman, Jeffrey M ...
Monthly notices of the Royal Astronomical Society,
01/2019, Letnik:
482, Številka:
2
Journal Article
In this work, BV RI light curves of 55 Type II supernovae (SNe II) from the Lick Observatory Supernova Search program obtained with the Katzman Automatic Imaging Telescope and the 1 m Nickel ...telescope from 2006 to 2018 are presented. Additionally, more than 150 spectra gathered with the 3 m Shane telescope are published. We conduct an analyse of the peak absolute magnitudes, decline rates, and time durations of different phases of the light and colour curves. Typically, our light curves are sampled with a median cadence of 5.5 days for a total of 5093 photometric points. In average V-band plateau declines with a rate of 1.29 mag (100 days)-1, which is consistent with previously published samples. For each band, the plateau slope correlates with the plateau length and the absolute peak magnitude: SNe II with steeper decline have shorter plateau duration and are brighter. A time-evolution analysis of spectral lines in term of velocities and pseudoequivalent widths is also presented in this paper. Our spectroscopic sample ranges between 1 and 200 days post-explosion and has a median ejecta expansion velocity at 50 days post-explosion of 6500 km/s (Halpha line) and a standard dispersion of 2000 km/s. Nebular spectra are in good agreement with theoretical models using a progenitor star having a mass <16 Msol. All the data are available to the community and will help to understand SN II diversity better, and therefore to improve their utility as cosmological distance indicators.
Lung cancer remains among the most difficult-to-treat malignancies and is the leading cause of cancer-related deaths worldwide. The introduction of targeted therapies and checkpoint inhibitors has ...improved treatment outcomes; however, most patients with advanced-stage non-small cell lung cancer (NSCLC) eventually fail these therapies. Therefore, there is a major unmet clinical need for checkpoint refractory/resistant NSCLC. Here, we tested the combination of aPD-1 and adenovirus armed with TNFα and IL-2 (Ad5-CMV-mTNFα/mIL-2) in an immunocompetent murine NSCLC model. Moreover, although local delivery has been standard for virotherapy, treatment was administered intravenously to facilitate clinical translation and putative routine use. We showed that treatment of tumor-bearing animals with aPD-1 in combination with intravenously injected armed adenovirus significantly decreased cancer growth, even in the presence of neutralizing antibodies. We observed an increased frequency of cytotoxic tumor-infiltrating lymphocytes, including tumor-specific cells. Combination treatment led to a decreased percentage of immunosuppressive tumor-associated macrophages and an improvement in dendritic cell maturation. Moreover, we observed expansion of the tumor-specific memory T cell compartment in secondary lymphoid organs in the group that received aPD-1 with the virus. However, although the non-replicative Ad5-CMV-mTNFα/mIL-2 virus allows high transgene expression in the murine model, it does not fully reflect the clinical outcome in humans. Thus, we complemented our findings using NSCLC ex vivo models fully permissive for the TNFα and IL-2- armed oncolytic adenovirus TILT-123. Overall, our data demonstrate the ability of systemically administered adenovirus armed with TNFα and IL-2 to potentiate the anti-tumor efficacy of aPD-1 and warrant further investigation in clinical trials.
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