Chemoresistance of Lung Cancer Cells: 2D and 3D In Vitro Models for Anticancer Drug Screening

Chemoresistance of lung cancer cells is a key factor that limits the treatment of lung cancer patients. Patients may initially respond to standard chemotherapy, but this is often followed by rapid development of drug resistance and disease progression. Tumor heterogeneity and the presence of putative cancer stem-like cells (CS-LCs) provide a viable explanation for the chemoresistance of several types of tumors. In this book chapter, we will first describe the current knowledge of the role of both tumor heterogeneity and CS-LCs in lung cancer chemoresistance, tumor progression and metastasis. Next, we will discuss ongoing strategies at the in vitro level to screen for more effective anticancer drugs. We will specifically focus in three-dimensional (3D) culture systems (Spheroids and tumorspheres) and their application in anticancer drug discovery for lung cancer

Coexistence of para and ferromagnetic phases of Fe3+ in undoped CdZnTe (Zn r-v 4%) crystals

The signatures of the coexistence of para and ferromagnetic phases for the Fe3+ charge state of iron have been identified in the low temperature electron spin resonance (ESR) spectra in undoped CdZnTe (Zn ~ 4%) crystals and independently verified by superconducting quantum interference device (SQUID)and AC susceptibility measurements. In the paramagnetic phase the inverse of AC susceptibility follows the Curie-Weiss law. In the ferromagnetic phase the thermal evolution of magnetization follows the well-known Bloch T3/2 law. This is further supported by the appearance of hysteresis in the SQUID measurements at 2 Kbelow Tc which is expected to lie in between 2 and 2.5 K

A comparison of morphometric traits of sheep breeds of Karnataka in the farmers' flocks

The study revealed that the 4 sheep breeds of Karnataka differed significantly with respect to body weight and other physical traits. Kenguri and Bellary breeds of sheep were larger and heavier than Hassan and Mandya sheep breeds. Amongst them Kenguri rams were heaviest followed by Bellary, Mandya and Hassan but in ewes the above order was reversed in breeds of southern Karnataka. The overall difference in body weights of Kenguri and Bellary rams was 9.66 kg whereas in Hassan and Mandya rams it was 4.37 kg. The corresponding values in ewes were 4.06 kg and 1.5 kg. In ewes, the increase in magnitude of a morphometric trait from a lower age group to next higher age group was marginal. All the sheep breeds of Karnataka attained maximum weight at 8-tooth age

SARS-CoV-2 Infections Among Patients With Liver Disease and Liver Transplantation Who Received COVID-19 Vaccination.

Many safe and effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations dramatically reduce risks of coronavirus disease 2019 (COVID-19) complications and deaths. We aimed to describe cases of SARS-CoV-2 infection among patients with chronic liver disease (CLD) and liver transplant (LT) recipients with at least one prior COVID-19 vaccine dose. The SECURE-Liver and COVID-Hep international reporting registries were used to identify laboratory-confirmed COVID-19 in CLD and LT patients who received a COVID-19 vaccination. Of the 342 cases of lab-confirmed SARS-CoV-2 infections in the era after vaccine licensing, 40 patients (21 with CLD and 19 with LT) had at least one prior COVID-19 vaccination, including 12 who were fully vaccinated (≥2 weeks after second dose). Of the 21 patients with CLD (90% with cirrhosis), 7 (33%) were hospitalized, 1 (5%) was admitted to the intensive care unit (ICU), and 0 died. In the LT cohort (n = 19), there were 6 hospitalizations (32%), including 3 (16%) resulting in mechanical ventilation and 2 (11%) resulting in death. All three cases of severe COVID-19 occurred in patients who had a single vaccine dose within the last 1-2 weeks. In contemporary patients with CLD, rates of symptomatic infection, hospitalization, ICU admission, invasive ventilation, and death were numerically higher in unvaccinated individuals. Conclusion: This case series demonstrates the potential for COVID-19 infections among patients with CLD and LT recipients who had received the COVID-19 vaccination. Vaccination against SARS-CoV-2 appears to result in favorable outcomes as attested by the absence of mechanical ventilation, ICU, or death among fully vaccinated patients

Fast-transient Searches in Real Time with ZTFReST: Identification of Three Optically-discovered Gamma-ray Burst Afterglows and New Constraints on the Kilonova Rate

While optical surveys regularly discover slow transients like supernovae on their own, the most common way to discover extragalactic fast transients, fading away in a few nights, is via follow-up observations of gamma-ray burst and gravitational-wave triggers. However, wide-field surveys have the potential to also identify rapidly fading transients independently of such external triggers. The volumetric survey speed of the Zwicky Transient Facility (ZTF) makes it sensitive to faint and fast-fading objects as kilonovae, the optical counterparts to binary neutron stars and neutron star-black hole mergers, out to almost 200Mpc. We introduce an open-source software infrastructure, the ZTF REaltime Search and Triggering, ZTFReST, designed to identify kilonovae and fast optical transients in ZTF data. Using the ZTF alert stream combined with forced photometry, we have implemented automated candidate ranking based on their photometric evolution and fitting to kilonova models. Automated triggering of follow-up systems, such as Las Cumbres Observatory, has also been implemented. In 13 months of science validation, we found several extragalactic fast transients independent of any external trigger (though some counterparts were identified later), including at least one supernova with post-shock cooling emission, two known afterglows with an associated gamma-ray burst, two known afterglows without any known gamma-ray counterpart, and three new fast-declining sources (ZTF20abtxwfx, ZTF20acozryr, and ZTF21aagwbjr) that are likely associated with GRB200817A, GRB201103B, and GRB210204A. However, we have not found any objects which appear to be kilonovae; therefore, we constrain the rate of GW170817-like kilonovae to $R < 900$Gpc$^{-3}$yr$^{-1}$. A framework such as ZTFReST could become a prime tool for kilonova and fast transient discovery with the Vera C. Rubin Observatory

SN 2020jgb: A Peculiar Type Ia Supernova Triggered by a Massive Helium-Shell Detonation in a Star-Forming Galaxy

The detonation of a thin ($\lesssim$$0.03\,\mathrm{M_\odot}$) helium shell (He-shell) atop a $\sim$$1\,\mathrm{M_\odot}$ white dwarf (WD) is a promising mechanism to explain normal Type Ia supernovae (SNe Ia), while thicker He-shells and less massive WDs may explain some recently observed peculiar SNe Ia. We present observations of SN 2020jgb, a peculiar SN Ia discovered by the Zwicky Transient Facility (ZTF). Near maximum light, SN 2020jgb is slightly subluminous (ZTF $g$-band absolute magnitude $M_g$ between $-18.2$ and $-18.7$ mag depending on the amount of host galaxy extinction) and shows an unusually red color ($g_\mathrm{ZTF}-r_\mathrm{ZTF}$ between 0.4 and 0.2 mag) due to strong line-blanketing blueward of $\sim$5000 $\r{A}$. These properties resemble those of SN 2018byg, a peculiar SN Ia consistent with a thick He-shell double detonation (DDet) SN. Using detailed radiative transfer models, we show that the optical spectroscopic and photometric evolution of SN 2020jgb are broadly consistent with a $\sim$$0.95\,\mathrm{M_\odot}$ (C/O core + He-shell; up to $\sim$$1.00\,\mathrm{M_\odot}$ depending on the total host extinction) progenitor ignited by a thick ($\sim$$0.13\,\mathrm{M_\odot}$) He-shell. We detect a prominent absorption feature at $\sim$1 $\mu\mathrm{m}$ in the near-infrared (NIR) spectrum of SN 2020jgb, which could originate from unburnt helium in the outermost ejecta. While the sample size is limited, similar 1 $\mu\mathrm{m}$ features have been detected in all the thick He-shell DDet candidates with NIR spectra obtained to date. SN 2020jgb is also the first subluminous, thick He-shell DDet SN discovered in a star-forming galaxy, indisputably showing that He-shell DDet objects occur in both star-forming and passive galaxies, consistent with the normal SN Ia population.Comment: 23 pages, 10 figures. Updated to accepted version (ApJ

Discovery and confirmation of the shortest gamma ray burst from a collapsar [Author Correction to: Nature Astronomy https://doi.org/10.1038/s41550-021-01428-7,]

Gamma-ray bursts (GRBs) are among the brightest and most energetic events in the universe. The duration and hardness distribution of GRBs has two clusters, now understood to reflect (at least) two different progenitors. Short-hard GRBs (SGRBs; T90 2 s) have been attributed to the collapse of peculiar massive stars (collapsars). The discovery of SN 1998bw/GRB 980425 marked the first association of a LGRB with a collapsar and AT 2017gfo/GRB 170817A/GW170817 marked the first association of a SGRB with a binary neutron star merger, producing also gravitational wave (GW). Here, we present the discovery of ZTF20abwysqy (AT2020scz), a fast-fading optical transient in the Fermi Satellite and the InterPlanetary Network (IPN) localization regions of GRB 200826A; X-ray and radio emission further confirm that this is the afterglow. Follow-up imaging (at rest-frame 16.5 days) reveals excess emission above the afterglow that cannot be explained as an underlying kilonova (KN), but is consistent with being the supernova (SN). Despite the GRB duration being short (rest-frame T90 of 0.65 s), our panchromatic follow-up data confirms a collapsar origin. GRB 200826A is the shortest LGRB found with an associated collapsar; it appears to sit on the brink between a successful and a failed collapsar. Our discovery is consistent with the hypothesis that most collapsars fail to produce ultra-relativistic jets

Constraining the Kilonova Rate with Zwicky Transient Facility Searches Independent of Gravitational Wave and Short Gamma-ray Burst Triggers

The first binary neutron star merger, GW170817, was accompanied by a radioactivity-powered optical/infrared transient called a kilonova. To date, no compelling kilonova has been found during optical surveys of the sky, independent of gravitational-wave triggers. In this work, we searched the first 23 months of the Zwicky Transient Facility (ZTF) data stream for candidate kilonovae in the form of rapidly evolving transients. We combined ZTF alert queries with forced point-spread-function photometry and nightly flux stacking to increase our sensitivity to faint and fast transients. Automatic queries yielded $>11,200$ candidates, 24 of which passed quality checks and strict selection criteria based on a grid of kilonova models tailored for both binary neutron star and neutron star-black hole mergers. None of the candidates in our sample was deemed a possible kilonova after thorough vetting, catalog cross-matching, and study of their color evolution. The sources that passed our selection criteria are dominated by Galactic cataclysmic variables. In addition, we identified two fast transients at high Galactic latitude, one of which is the confirmed afterglow of long-duration GRB190106A, and the other is a possible cosmological afterglow. Using a survey simulation code, we constrained the kilonova rate for a range of models including top-hat and linearly decaying light curves and synthetic light curves obtained with radiative transfer simulations. For prototypical GW170817-like kilonovae, we constrain the rate to be $R < 1775$ Gpc$^{-3}$ yr$^{-1}$ at 95% confidence level by requiring at least 2 high-significance detections. By assuming a population of kilonovae with the same geometry and composition of GW170817 observed under a uniform viewing angle distribution, we obtained a constraint on the rate of $R < 4029$ Gpc$^{-3}$ yr$^{-1}$.Comment: Submitted for publication in Ap