Temperature regulates NF-κB dynamics and function through timing of A20 transcription

NF-κB signaling plays a pivotal role in control of the inflammatory response. We investigated how the dynamics and function of NF-κB were affected by temperature within the mammalian physiological range (34 °C to 40 °C). An increase in temperature led to an increase in NF-κB nuclear/cytoplasmic oscillation frequency following Tumor Necrosis Factor alpha (TNFα) stimulation. Mathematical modeling suggested that this temperature sensitivity might be due to an A20-dependent mechanism, and A20 silencing removed the sensitivity to increased temperature. The timing of the early response of a key set of NF-κB target genes showed strong temperature dependence. The cytokine-induced expression of many (but not all) later genes was insensitive to temperature change (suggesting that they might be functionally temperature-compensated). Moreover, a set of temperature- and TNFα-regulated genes were implicated in NF-κB cross-talk with key cell-fate–controlling pathways. In conclusion, NF-κB dynamics and target gene expression are modulated by temperature and can accurately transmit multidimensional information to control inflammation

Chandra, HST/STIS, NICER, Swift, and TESS Detail the Flare Evolution of the Repeating Nuclear Transient ASASSN-14ko

ASASSN-14ko is a nuclear transient at the center of the AGN ESO 253-G003 that undergoes periodic flares. Optical flares were first observed in 2014 by the All-Sky Automated Survey for Supernovae (ASAS-SN) and their peak times are well-modeled with a period of $115.2^{+1.3}_{-1.2}$ days and period derivative of $-0.0026 \pm 0.0006$. Here we present ASAS-SN, Chandra, HST/STIS, NICER, Swift, and TESS data for the flares that occurred in December 2020, April 2021, July 2021, and November 2021. The HST/STIS UV spectra evolve from blue shifted broad absorption features to red shifted broad emission features over $\sim$10 days. The Swift UV/optical light curves peaked as predicted by the timing model, but the peak UV luminosities varied between flares and the UV flux in July 2021 was roughly half the brightness of all other peaks. The X-ray luminosities consistently decreased and the spectra became harder during the UV/optical rise but apparently without changes in absorption. Finally, two high-cadence TESS light curves from December 2020 and November 2018 showed that the slopes during the rising and declining phases changed over time, which indicates some stochasticity in the flare's driving mechanism. ASASSN-14ko remains observationally consistent with a repeating partial tidal disruption event, but, these rich multi-wavelength data are in need of a detailed theoretical model.Comment: 25 pages, 14 figures, 4 tables; Submitted to ApJ, comments welcom

Once is an Instance, Twice is a Hobby: Multiple Optical and Near-Infrared Changing-Look Events in NGC 5273

NGC 5273 is a known optical and X-ray variable AGN. We analyze new and archival IR, optical, UV, and X-ray data in order to characterize its long-term variability from 2000 to 2022. At least one changing-look event occurred between 2011 and 2014, when the AGN changed from a Type 1.8/1.9 Seyfert to a Type 1. It then faded considerably at all wavelengths, followed by a dramatic but slow increase in UV/optical brightness between 2021 and 2022. We propose that NGC 5273 underwent multiple changing-look events between 2000 and 2022 -- starting as a Type 1.8/1.9, NGC 5273 changes-look to a Type 1 only temporarily in 2002 and again in 2014, reverting back to a Type 1.8/1.9 by 2005 and 2017, respectively. In 2022, it is again a Type 1 Seyfert with optical and NIR broad emission lines. We characterize the changing-look events and their connection to the dynamic accretion and radiative processes in NGC 5273.Comment: 18 pages, 13 figures, 4 tables, submitting to MNRA

Strong Near-Infrared Carbon Absorption in the Transitional Type Ia SN 2015bp

Research by D.J.S. is supported by NSF grants AST-1821967, AST-1821987, AST-1813708, AST-1813466, and AST-1908972, as well as by the Heising-Simons Foundation under grant #20201864. The CSP-II has been supported by National Science Foundation (NSF) grants AST-1008343, AST-1613426, AST-1613455, and AST-1613472, as well as by the Danish Agency for Science and Technology and Innovation through a Sapere Aude Level 2 grant. E.Y.H. and J.L. also acknowledge the support of the Florida Space Grant Consortium. This work was partially performed at the Aspen Center for Physics, which is supported by NSF grant PHY-1607611. Research by S.V. is supported by NSF grants AST1813176 and AST-2008108. L.G. was funded by the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 839090. This work has been partially supported by the Spanish grant PGC2018-095317-B-C21 within the European Funds for Regional Development (FEDER). M.S. is supported by generous grants from Villum FONDEN (13261, 28021) and by a project grant (8021-00170B) from the Independent Research Fund Denmark. A.V.F. is grateful for financial assistance from the TABASGO Foundation, the Christopher R. Redlich Fund, and the Miller Institute for Basic Research in Science (U.C. Berkeley). Based on observations obtained at the international Gemini Observatory (GN-2015A-Q-8, GS-2015A-Q-5), a program of NSF's NOIRLab, which is managed by the Association of Universities for Research in Astronomy (AURA) under a cooperative agreement with the National Science Foundation. on behalf of the Gemini Observatory partnership: the National Science Foundation (United States), National Research Council (Canada), Agencia Nacional de Investigacion y Desarrollo (Chile), Ministerio de Ciencia, Tecnologia e Innovacion (Argentina), Ministerio da Ciencia, Tecnologia, Inovacoes e Comunicacoes (Brazil), and Korea Astronomy and Space Science Institute (Republic of Korea). This paper includes data gathered with the Nordic Optical Telescope (PI Stritzinger) at the Observatorio del Roque de los Muchachos, La Palma, Spain. This work is based in part on observations from the Deep Imaging Multi-Object Spectrograph at the Keck II telescope. We are grateful to the staff at the Keck Observatory for their assistance, and we extend special thanks to those of Hawaiian ancestry on whose sacred mountain we are privileged to be guests. The W. M. Keck Observatory is operated as a scientific partnership among the California Institute of Technology, the University of California, and NASA; it was made possible by the generous financial support of the W. M. Keck Foundation. We thank S. Bradley Cenko for assistance with the Keck spectral reductions, as well as Patrick Kelly, WeiKang Zheng, and John Mauerhan for their assistance with the observations. D.J.S. is a visiting Astronomer at the Infrared Telescope Facility, which is operated by the University of Hawaii under contract 80HQTR19D0030 with the National Aeronautics and Space Administration. Based on data products from observations made with ESO Telescopes at the La Silla Paranal Observatory under programmes 188.D-3003 and 191.D-0935: PESSTO (the Public ESO Spectroscopic Survey for Transient Objects).Unburned carbon is potentially a powerful probe of Type Ia supernova (SN) explosion mechanisms. We present comprehensive optical and near-infrared (NIR) data on the "transitional" Type Ia SN 2015bp. An early NIR spectrum (t=−9.9 days with respect to B-band maximum) displays a striking C I λ1.0693μm line at 11.9×103~km s−1, distinct from the prominent Mg II λ1.0927μm feature, which weakens toward maximum light. SN 2015bp also displays a clear C II λ6580A notch early (t=−10.9 days) at 13.2×103~km s−1, consistent with our NIR carbon detection. At MB=−18.46, SN 2015bp is less luminous than a normal SN Ia and, along with iPTF13ebh, is the second member of the transitional subclass to display prominent early-time NIR carbon absorption. We find it unlikely that the C I feature is misidentified He I λ1.0830μm because this feature grows weaker toward maximum light, while the helium line produced in some double-detonation models grows stronger at these times. Intrigued by these strong NIR carbon detections, but lacking NIR data for other SNe Ia, we investigated the incidence of optical carbon in the sample of nine transitional SNe Ia with early-time data (t≲−4 days). We find that four display C II λ6580A, while two others show tentative detections, in line with the SN Ia population as a whole. We conclude that at least ∼50% of transitional SNe Ia in our sample do not come from sub-Chandrasekhar mass explosions due to the clear presence of carbon in their NIR and optical spectra.National Science Foundation (NSF) AST-1821967 AST-1821987 AST-1813708 AST-1813466 AST-1908972 PHY-1607611 AST1813176 AST-2008108Heising-Simons Foundation 20201864National Science Foundation (NSF) AST-1008343 AST-1613426 AST-1613455 AST-1613472Danish Agency for Science and Technology and InnovationFlorida Space Grant ConsortiumEuropean Commission 839090Spanish grant within the European Funds for Regional Development (FEDER) PGC2018-095317-B-C21Villum Foundation 13261 28021Independent Research Fund Denmark 8021-00170BTABASGO FoundationChristopher R. Redlich FundMiller Institute for Basic Research in Science (U.C. Berkeley)International Gemini Observatory GN-2015A-Q-8 GS-2015A-Q-5W.M. Keck FoundationUniversity of Hawaii 80HQTR19D0030National Aeronautics & Space Administration (NASA)ESO Telescopes at the La Silla Paranal Observatory 188.D-3003 191.D-0935: PESST

Does high-dose metformin cause lactic acidosis in type 2 diabetic patients after CABG surgery? A double blind randomized clinical trial

Metformin is a dimethyl biguanide oral anti-hyperglycemic agent. Lactic acidosis due to metformin is a fatal metabolic condition that limits its use in patients in poor clinical condition, consequently reducing the number of patients who benefit from this medication. In a double blind randomized clinical trial, we investigated 200 type 2 diabetic patients after coronary artery bypass surgery in the open heart ICU of the Mazandaran Heart Center, and randomly assigned them to equal intervention and control groups. The intervention group received regular insulin infusion along with 2 metformin 500 mg tablets every twelve hours, while the control group received only intravenous insulin with 2 placebo tablets every twelve hours. Lactate level, pH, base excess, blood glucose and serum creatinine were measured over five 12 h periods, with data averaged for each period. The primary outcome in this study was high lactate levels. Comparison between the 2 groups was made by independent Student’s t-test. To compare changes in multiple measures in each group and analysis of group interaction, a repeated measurement ANOVA test was used

Two transitional type~Ia supernovae located in the Fornax cluster member NGC 1404: SN 2007on and SN 2011iv

We present an analysis of ultraviolet (UV) to near-infrared observations of the fast-declining Type Ia supernovae (SNe Ia) 2007on and 2011iv, hosted by the Fornax cluster member NGC 1404. The B-band light curves of SN 2007on and SN 2011iv are characterised by dm_15(B) decline-rate values of 1.96 mag and 1.77 mag, respectively. Although they have similar decline rates, their peak B- and H-band magnitudes differ by ~0.60 mag and ~0.35 mag, respectively. After correcting for the luminosity vs. decline rate and the luminosity vs. colour relations, the peak B-band and H-band light curves provide distances that differ by ~14% and ~9%, respectively. These findings serve as a cautionary tale for the use of transitional SNe Ia located in early-type hosts in the quest to measure cosmological parameters. Interestingly, even though SN 2011iv is brighter and bluer at early times, by three weeks past maximum and extending over several months, its B-V colour is 0.12 mag redder than that of SN 2007on. To reconcile this unusual behaviour, we turn to guidance from a suite of spherical one-dimensional Chandrasekhar-mass delayed-detonation explosion models. In this context, 56Ni production depends on both the so-called transition density and the central density of the progenitor white dwarf. To first order, the transition density drives the luminosity-width relation, while the central density is an important second-order parameter. Within this context, the differences in the B-V color evolution along the Lira regime suggests the progenitor of SN~2011iv had a higher central density than SN~2007on

Photometric and spectroscopic analysis of the Type II SN 2020jfo with a short plateau

We present high-cadence photometric and spectroscopic observations of SN~2020jfo in ultraviolet and optical/near-infrared bands starting from $\sim 3$ to $\sim 434$ days after the explosion, including the earliest data with the 10.4\,m GTC. SN~2020jfo is a hydrogen-rich Type II SN with a relatively short plateau duration ($67.0 \pm 0.6$ days). When compared to other Type II supernovae (SNe) of similar or shorter plateau lengths, SN~2020jfo exhibits a fainter peak absolute $V$-band magnitude ($M_V = -16.90 \pm 0.34$ mag). SN~2020jfo shows significant H$\alpha$ absorption in the plateau phase similar to that of typical SNe~II. The emission line of stable [Ni~II] $\lambda$7378, mostly seen in low-luminosity SNe~II, is very prominent in the nebular-phase spectra of SN~2020jfo. Using the relative strengths of [Ni~II] $\lambda$7378 and [Fe~II] $\lambda$7155, we derive the Ni/Fe production (abundance) ratio of 0.08--0.10, which is $\sim 1.5$ times the solar value. The progenitor mass of SN~2020jfo from nebular-phase spectral modelling and semi-analytical modelling falls in the range of 12--15\,$M_\odot$. Furthermore, semi-analytical modelling suggests a massive H envelope in the progenitor of SN~2020jfo, which is unlikely for SNe~II having short plateaus.Comment: 20 pages (plus 5 pages appendix), 19 figures, Accepted for publication in MNRA

Two transitional type Ia supernovae located in the Fornax cluster member NGC 1404: SN 2007 on and SN 2011iv

We present an analysis of ultraviolet (UV) to near-infrared observations of the fast-declining Type Ia supernovae (SNe Ia) 2007on and 2011iv, hosted by the Fornax cluster member NGC 1404. The B-band light curves of SN 2007on and SN 2011iv are characterised by Δm15 (B) decline-rate values of 1.96 mag and 1.77 mag, respectively. Although they have similar decline rates, their peak B- and H-band magnitudes differ by ~ 0.60 mag and ~0.35 mag, respectively. After correcting for the luminosity vs. decline rate and the luminosity vs. colour relations, the peak B-band and H-band light curves provide distances that differ by ~ 14% and ~ 9%, respectively. These findings serve as a cautionary tale for the use of transitional SNe Ia located in early-type hosts in the quest to measure cosmological parameters. Interestingly, even though SN 2011iv is brighter and bluer at early times, by three weeks past maximum and extending over several months, its B - V colour is 0.12 mag redder than that of SN 2007on. To reconcile this unusual behaviour, we turn to guidance from a suite of spherical one-dimensional Chandrasekhar-mass delayed-detonation explosion models. In this context, 56Ni production depends on both the so-called transition density and the central density of the progenitor white dwarf. To first order, the transition density drives the luminosity-width relation, while the central density is an important second-order parameter. Within this context, the differences in the B - V colour evolution along the Lira regime suggest that the progenitor of SN 2011iv had a higher central density than SN 2007on.Instituto de Astrofísica de La PlataFacultad de Ciencias Astronómicas y Geofísica

SN2017egm: A Helium-rich Superluminous Supernova with Multiple Bumps in the Light Curves

When discovered, SN~2017egm was the closest (redshift $z=0.03$) hydrogen-poor superluminous supernova (SLSN-I) and a rare case that exploded in a massive and metal-rich galaxy. Thus, it has since been extensively observed and studied. We report spectroscopic data showing strong emission at around He~I $\lambda$10,830 and four He~I absorption lines in the optical. Consequently, we classify SN~2017egm as a member of an emerging population of helium-rich SLSNe-I (i.e., SLSNe-Ib). We also present our late-time photometric observations. By combining them with archival data, we analyze high-cadence ultra-violet, optical, and near-infrared light curves spanning from early pre-peak ($\sim -20\,d$) to late phases ($\sim +300\,d$). We obtain its most complete bolometric light curve, in which multiple bumps are identified. None of the previously proposed models can satisfactorily explain all main light-curve features, while multiple interactions between the ejecta and circumstellar material (CSM) may explain the undulating features. The prominent infrared excess with a blackbody luminosity of $10^7$--$10^8\,L_{sun}$ detected in SN~2017egm could originate from the emission of either an echo of a pre-existing dust shell, or newly-formed dust, offering an additional piece of evidence supporting the ejecta-CSM interaction model. Moreover, our analysis of deep $Chandra$ observations yields the tightest-ever constraint on the X-ray emission of an SLSN-I, amounting to an X-ray-to-optical luminosity ratio $\lesssim 10^{-3}$ at late phases ($\sim100-200\,d$), which could help explore its close environment and central engine.Comment: 25 pages, 14 Figures, 4 Tables; accepted for publication in ApJ (Mar. 2023

Multiplexing information flow through dynamic signalling systems

We consider how a signalling system can act as an information hub by multiplexing information arising from multiple signals. We formally define multiplexing, mathematically characterise which systems can multiplex and how well they can do it. While the results of this paper are theoretical, to motivate the idea of multiplexing, we provide experimental evidence that tentatively suggests that the NF-κB transcription factor can multiplex information about changes in multiple signals. We believe that our theoretical results may resolve the apparent paradox of how a system like NF-κB that regulates cell fate and inflammatory signalling in response to diverse stimuli can appear to have the low information carrying capacity suggested by recent studies on scalar signals. In carrying out our study, we introduce new methods for the analysis of large, nonlinear stochastic dynamic models, and develop computational algorithms that facilitate the calculation of fundamental constructs of information theory such as Kullback–Leibler divergences and sensitivity matrices, and link these methods to a new theory about multiplexing information. We show that many current models such as those of the NF-κB system cannot multiplex effectively and provide models that overcome this limitation using post-transcriptional modifications