The complete catalogue of light curves in equal-mass binary microlensing

The light curves observed in microlensing events due to binary lenses span an extremely wide variety of forms, characterised by U-shaped caustic crossings and/or additional smoother peaks. However, all peaks of the binary-lens light curve can be traced back to features of caustics of the lens system. Moreover, all peaks can be categorised as one of only four types (cusp-grazing, cusp-crossing, fold-crossing or fold-grazing). This enables us to present the first complete map of the parameter space of the equal-mass case by identifying regions in which light curves feature the same number and nature of peaks. We find that the total number of morphologies that can be obtained is 73 out of 232 different regions. The partition of the parameter space so-obtained provides a new key to optimise modelling of observed events through a clever choice of initial conditions for fitting algorithms.Comment: 22 pages, 18 figures, accepted for publication in MNRA

The humoral pattern recognition receptor PTX3 is stored in neutrophil granules and localizes in extracellular traps

The long pentraxin (PTX) 3 is produced by macrophages and myeloid dendritic cells in response to Toll-like receptor agonists and represents a nonredundant component of humoral innate immunity against selected pathogens. We report that, unexpectedly, PTX3 is stored in specific granules and undergoes release in response to microbial recognition and inflammatory signals. Released PTX3 can partially localize in neutrophil extracellular traps formed by extruded DNA. Eosinophils and basophils do not contain preformed PTX3. PTX3-deficient neutrophils have defective microbial recognition and phagocytosis, and PTX3 is nonredundant for neutrophil-mediated resistance against Aspergillus fumigatus. Thus, neutrophils serve as a reservoir, ready for rapid release, of the long PTX3, a key component of humoral innate immunity with opsonic activity

Genetic deletion of mGlu2 metabotropic glutamate receptors improves the short-term outcome of cerebral transient focal ischemia

Abstract We have recently shown that pharmacological blockade of mGlu2 metabotropic glutamate receptors protects vulnerable neurons in the 4-vessel occlusion model of transient global ischemia, whereas receptor activation amplifies neuronal death. This raised the possibility that endogenous activation of mGlu2 receptors contributes to the pathophysiology of ischemic neuronal damage. Here, we examined this possibility using two models of transient focal ischemia: (i) the monofilament model of middle cerebral artery occlusion (MCAO) in mice, and (ii) the model based on intracerebral infusion of endothelin-1 (Et-1) in rats. Following transient MCAO, mGlu2 receptor knockout mice showed a significant reduction in infarct volume and an improved short-term behavioural outcome, as assessed by a neurological disability scale and the “grip test”. Following Et-1 infusion, Grm2 gene mutated Hannover Wistar rats lacking mGlu2 receptors did not show changes in the overall infarct volume as compared to their wild-type counterparts, although they showed a reduced infarct area in the agranular insular cortex. Interestingly, however, mGlu2 receptor-deficient rats performed better than wild-type rats in the adhesive tape test, in which these rats did not show the laterality preference typically observed after focal ischemia. These findings support the hypothesis that activation of mGlu2 receptors is detrimental in the post-ischemic phase, and support the use of mGlu2 receptor antagonists in the experimental treatment of brain ischemia

Expanding the Arsenal of FGFR Inhibitors: A Novel Chloroacetamide Derivative as a New Irreversible Agent With Anti-proliferative Activity Against FGFR1-Amplified Lung Cancer Cell Lines

Fibroblast Growth Factor Receptors (FGFR1–4) have a critical role in the progression of several human cancers, including Squamous Non-Small-Cell Lung Cancer (SQCLC). Both non-selective and selective reversible FGFR inhibitors are under clinical investigation for the treatment of patients with tumors harboring FGFR alterations. Despite their potential efficacy, the clinical development of these drugs has encountered several challenges, including toxicity, and the appearance of drug resistance. Recent efforts have been directed at development of irreversible FGFR inhibitors, which have the potential to exert superior anti-proliferative activity in tumors carrying FGFR alterations. With this in mind, we synthetized, and investigated a set of novel inhibitors possessing a warhead potentially able to covalently bind a cysteine in the P-loop of FGFR. Among them, the chloroacetamide UPR1376 resulted able to irreversible inhibit FGFR1 phosphorylation in FGFR1 over-expressing cells generated from SQCLC SKMES-1 cells. In addition, this compound inhibited cell proliferation in FGFR1-amplified H1581 cells with a potency higher than the reversible inhibitor BGJ398 (infigratinib), while sparing FGFR1 low-expressing cells. The anti-proliferative effects of UPR1376 were demonstrated in both 2D and 3D systems and were associated with the inhibition of MAPK and AKT/mTOR signaling pathways. UPR1376 inhibited cell proliferation also in two BGJ398-resistant cell clones generated from H1581 by chronic exposure to BGJ398, although at concentrations higher than those effective in the parental cells, likely due to the persistent activation of the MAPK pathway associated to NRAS amplification. Combined blockade of FGFR1 and MAPK signaling, by UPR1376 and trametinib respectively, significantly enhanced the efficacy of UPR1376, providing a means of circumventing resistance to FGFR1 inhibition. Our findings suggest that the insertion of a chloroacetamide warhead on a suitable scaffold, as exemplified by UPR1376, is a valuable strategy to develop a novel generation of FGFR inhibitors for the treatment of SQCLC patients with FGFR alterations

KELT-21b: A Hot Jupiter Transiting the Rapidly Rotating Metal-poor Late-A Primary of a Likely Hierarchical Triple System

We present the discovery of KELT-21b, a hot Jupiter transiting the V = 10.5 A8V star HD 332124. The planet has an orbital period of P = 3.6127647 ± 0.0000033 days and a radius of 1.586-0.040+0.039 RJ. We set an upper limit on the planetary mass of at confidence. We confirmed the planetary nature of the transiting companion using this mass limit and Doppler tomographic observations to verify that the companion transits HD 332124. These data also demonstrate that the planetary orbit is well-aligned with the stellar spin, with a sky-projected spin-orbit misalignment of λ = -5.6-1.91.7. The star has Teff = 7598-8481 K, Mz.ast; = 1.458-0.028+0.029 M⊙, Rz.ast; = 1.638 ± 0.034 R⊙ and v sin I∗ = 146 km s-1, the highest projected rotation velocity of any star known to host a transiting hot Jupiter. The star also appears to be somewhat metal poor and α-enhanced, with [Fe/H] = -405-0.033+0.032 and [α/Fe] = 0.145 ± 0.053; these abundances are unusual, but not extraordinary, for a young star with thin-disk kinematics like KELT-21. High-resolution imaging observations revealed the presence of a pair of stellar companions to KELT-21, located at a separation of 1.″2 and with a combined contrast of ΔKs = 6.39 ± 0.06 with respect to the primary. Although these companions are most likely physically associated with KELT-21, we cannot confirm this with our current data. If associated, the candidate companions KELT-21 B and C would each have masses of ∼0.12 M⊙, a projected mutual separation of ∼20 au, and a projected separation of ∼500 au from KELT-21. KELT-21b may be one of only a handful of known transiting planets in hierarchical triple stellar systems

A giant planet undergoing extreme-ultraviolet irradiation by its hot massive-star host

The amount of ultraviolet irradiation and ablation experienced by a planet depends strongly on the temperature of its host star. Of the thousands of extrasolar planets now known, only six have been found that transit hot, A-type stars (with temperatures of 7,300-10,000 kelvin), and no planets are known to transit the even hotter B-type stars. For example, WASP-33 is an A-type star with a temperature of about 7,430 kelvin, which hosts the hottest known transiting planet, WASP-33b (ref. 1); the planet is itself as hot as a red dwarf star of type M (ref. 2). WASP-33b displays a large heat differential between its dayside and nightside, and is highly inflated-traits that have been linked to high insolation. However, even at the temperature of its dayside, its atmosphere probably resembles the molecule-dominated atmospheres of other planets and, given the level of ultraviolet irradiation it experiences, its atmosphere is unlikely to be substantially ablated over the lifetime of its star. Here we report observations of the bright star HD 195689 (also known as KELT-9), which reveal a close-in (orbital period of about 1.48 days) transiting giant planet, KELT-9b. At approximately 10,170 kelvin, the host star is at the dividing line between stars of type A and B, and we measure the dayside temperature of KELT-9b to be about 4,600 kelvin. This is as hot as stars of stellar type K4 (ref. 5). The molecules in K stars are entirely dissociated, and so the primary sources of opacity in the dayside atmosphere of KELT-9b are probably atomic metals. Furthermore, KELT-9b receives 700 times more extreme-ultraviolet radiation (that is, with wavelengths shorter than 91.2 nanometres) than WASP-33b, leading to a predicted range of mass-loss rates that could leave the planet largely stripped of its envelope during the main-sequence lifetime of the host star

KELT-12b: A P ∼ 5 day, Highly Inflated Hot Jupiter Transiting a Mildly Evolved Hot Star

We announce the discovery of KELT-12b, a highly inflated Jupiter-mass planet transiting the mildly evolved, V = 10.64 host star TYC 2619-1057-1. We followed up the initial transit signal in the KELT-North survey data with precise ground-based photometry, high-resolution spectroscopy, precise radial velocity measurements, and high-resolution adaptive optics imaging. Our preferred best-fit model indicates that the host star has = 6279 ±51 K, = 3.89 ±0.05, [Fe/H] = 0.19+0.08-0.09, = M∗ = 1.59+0.070.09M, and R ∗= 2.37 ±0.17 . The planetary companion has Mp= 0.95 ±0.14 MJ, RP = 1.78+0.17-0.16 RJ, log gP = 2.87+0.9-0.09 and density pp 0.210.070.05= g cm-3, making it one of the most inflated giant planets known. Furthermore, for future follow-up, we report a high-precision time of inferior conjunction in BJDTDB of 2,457,083.660459 ±0.000894 and period of P = 5.0316216 ± 0.000032days. Despite the relatively large separation of ∼0.07 au implied by its ∼5.03-day orbital period, KELT-12b receives significant flux of 2.38+0.32-0.29 × 109 erg s-1 cm-2 from its host. We compare the radii and insolations of transiting gas giant planets around hot (Teff 6250 K) and cool stars, noting that the observed paucity of known transiting giants around hot stars with low insolation is likely due to selection effects. We underscore the significance of long-term ground-based monitoring of hot stars and space-based targeting of hot stars with the Transiting Exoplanet Survey Satellite to search for inflated gas giants in longer-period orbits

OGLE-2019-BLG-0825: Constraints on the Source System and Effect on Binary-lens Parameters arising from a Five Day Xallarap Effect in a Candidate Planetary Microlensing Event

We present an analysis of microlensing event OGLE-2019-BLG-0825. This event was identified as a planetary candidate by preliminary modeling. We find that significant residuals from the best-fit static binary-lens model exist and a xallarap effect can fit the residuals very well and significantly improves $\chi^2$ values. On the other hand, by including the xallarap effect in our models, we find that binary-lens parameters like mass-ratio, $q$, and separation, $s$, cannot be constrained well. However, we also find that the parameters for the source system like the orbital period and semi major axis are consistent between all the models we analyzed. We therefore constrain the properties of the source system better than the properties of the lens system. The source system comprises a G-type main-sequence star orbited by a brown dwarf with a period of $P\sim5$ days. This analysis is the first to demonstrate that the xallarap effect does affect binary-lens parameters in planetary events. It would not be common for the presence or absence of the xallarap effect to affect lens parameters in events with long orbital periods of the source system or events with transits to caustics, but in other cases, such as this event, the xallarap effect can affect binary-lens parameters.Comment: 19 pages, 7 figures, 6 tables. Accepted by A

Event reconstruction for KM3NeT/ORCA using convolutional neural networks

The KM3NeT research infrastructure is currently under construction at two locations in the Mediterranean Sea. The KM3NeT/ORCA water-Cherenkov neutrino detector off the French coast will instrument several megatons of seawater with photosensors. Its main objective is the determination of the neutrino mass ordering. This work aims at demonstrating the general applicability of deep convolutional neural networks to neutrino telescopes, using simulated datasets for the KM3NeT/ORCA detector as an example. To this end, the networks are employed to achieve reconstruction and classification tasks that constitute an alternative to the analysis pipeline presented for KM3NeT/ORCA in the KM3NeT Letter of Intent. They are used to infer event reconstruction estimates for the energy, the direction, and the interaction point of incident neutrinos. The spatial distribution of Cherenkov light generated by charged particles induced in neutrino interactions is classified as shower- or track-like, and the main background processes associated with the detection of atmospheric neutrinos are recognized. Performance comparisons to machine-learning classification and maximum-likelihood reconstruction algorithms previously developed for KM3NeT/ORCA are provided. It is shown that this application of deep convolutional neural networks to simulated datasets for a large-volume neutrino telescope yields competitive reconstruction results and performance improvements with respect to classical approaches

Event reconstruction for KM3NeT/ORCA using convolutional neural networks

The KM3NeT research infrastructure is currently under construction at two locations in the Mediterranean Sea. The KM3NeT/ORCA water-Cherenkov neutrino de tector off the French coast will instrument several megatons of seawater with photosensors. Its main objective is the determination of the neutrino mass ordering. This work aims at demonstrating the general applicability of deep convolutional neural networks to neutrino telescopes, using simulated datasets for the KM3NeT/ORCA detector as an example. To this end, the networks are employed to achieve reconstruction and classification tasks that constitute an alternative to the analysis pipeline presented for KM3NeT/ORCA in the KM3NeT Letter of Intent. They are used to infer event reconstruction estimates for the energy, the direction, and the interaction point of incident neutrinos. The spatial distribution of Cherenkov light generated by charged particles induced in neutrino interactions is classified as shower-or track-like, and the main background processes associated with the detection of atmospheric neutrinos are recognized. Performance comparisons to machine-learning classification and maximum-likelihood reconstruction algorithms previously developed for KM3NeT/ORCA are provided. It is shown that this application of deep convolutional neural networks to simulated datasets for a large-volume neutrino telescope yields competitive reconstruction results and performance improvements with respect to classical approaches