APPleSOSS: A Producer of ProfiLEs for SOSS. Application to the NIRISS SOSS Mode

The SOSS mode of the NIRISS instrument is poised to be one of the workhorse modes for exoplanet atmosphere observations with the newly launched James Webb Space Telescope. One of the challenges of the SOSS mode, however, is the physical overlap of the first two diffraction orders of the G700XD grism on the detector. Recently, the ATOCA algorithm was developed and implemented as an option in the official JWST pipeline, as a method to extract SOSS spectra by decontaminating the detector -- that is, separating the first and second orders. Here, we present APPleSOSS (A Producer of ProfiLEs for SOSS), which generates the spatial profiles for each diffraction order upon which ATOCA relies. We validate APPleSOSS using simulated SOSS time series observations of WASP-52b, and compare it to ATOCA extractions using two other spatial profiles (a best and worst case scenario on-sky), as well as a simple box extraction performed without taking into account the order contamination. We demonstrate that APPleSOSS traces retain a high degree of fidelity to the true underlying spatial profiles, and therefore yield accurate extracted spectra. We further confirm that the effects of the order contamination for relative measurements (e.g., exoplanet transmission or emission observations) is small -- the transmission spectrum obtained from each of our four tests, including the contaminated box extraction, deviates by $\lesssim$0.1$\sigma$ from the atmosphere model input into our noiseless simulations. We further confirm via a retrieval analysis that the atmosphere parameters (metallicity and C/O) obtained from each transmission spectrum are consistent at the 1$\sigma$ level with the true underlying values.Comment: 12 pages, 9 figures. Submitted to PAS

Characterizing the Near-infrared Spectra of Flares from TRAPPIST-1 During JWST Transit Spectroscopy Observations

We present the first analysis of JWST near-infrared spectroscopy of stellar flares from TRAPPIST-1 during transits of rocky exoplanets. Four flares were observed from 0.6--2.8 $\mu$m with NIRISS and 0.6--3.5 $\mu$m with NIRSpec during transits of TRAPPIST-1b, f, and g. We discover P$\alpha$ and Br$\beta$ line emission and characterize flare continuum at wavelengths from 1--3.5 $\mu$m for the first time. Observed lines include H$\alpha$, P$\alpha$-P$\epsilon$, Br$\beta$, He I $\lambda$0.7062$\mu$m, two Ca II infrared triplet (IRT) lines, and the He I IRT. We observe a reversed Paschen decrement from P$\alpha$-P$\gamma$ alongside changes in the light curve shapes of these lines. The continuum of all four flares is well-described by blackbody emission with an effective temperature below 5300 K, lower than temperatures typically observed at optical wavelengths. The 0.6--1 $\mu$m spectra were convolved with the TESS response, enabling us to measure the flare rate of TRAPPIST-1 in the TESS bandpass. We find flares of 10$^{30}$ erg large enough to impact transit spectra occur at a rate of 3.6$\substack{+2.1 \\ -1.3}$ flare d$^{-1}$, $\sim$10$\times$ higher than previous predictions from K2. We measure the amount of flare contamination at 2 $\mu$m for the TRAPPIST-1b and f transits to be 500$\pm$450 and 2100$\pm$400 ppm, respectively. We find up to 80% of flare contamination can be removed, with mitigation most effective from 1.0--2.4 $\mu$m. These results suggest transits affected by flares may still be useful for atmospheric characterization efforts.Comment: 29 pages, 17 figures, 3 tables, accepted to The Astrophysical Journa

Distinct Effects of Two HIV-1 Capsid Assembly Inhibitor Families That Bind the Same Site within the N-Terminal Domain of the Viral CA Protein

The emergence of resistance to existing classes of antiretroviral drugs necessitates finding new HIV-1 targets for drug discovery. The viral capsid (CA) protein represents one such potential new target. CA is sufficient to form mature HIV-1 capsids in vitro, and extensive structure-function and mutational analyses of CA have shown that the proper assembly, morphology, and stability of the mature capsid core are essential for the infectivity of HIV-1 virions. Here we describe the development of an in vitro capsid assembly assay based on the association of CA-NC subunits on immobilized oligonucleotides. This assay was used to screen a compound library, yielding several different families of compounds that inhibited capsid assembly. Optimization of two chemical series, termed the benzodiazepines (BD) and the benzimidazoles (BM), resulted in compounds with potent antiviral activity against wild-type and drug-resistant HIV-1. Nuclear magnetic resonance (NMR) spectroscopic and X-ray crystallographic analyses showed that both series of inhibitors bound to the N-terminal domain of CA. These inhibitors induce the formation of a pocket that overlaps with the binding site for the previously reported CAP inhibitors but is expanded significantly by these new, more potent CA inhibitors. Virus release and electron microscopic (EM) studies showed that the BD compounds prevented virion release, whereas the BM compounds inhibited the formation of the mature capsid. Passage of virus in the presence of the inhibitors selected for resistance mutations that mapped to highly conserved residues surrounding the inhibitor binding pocket, but also to the C-terminal domain of CA. The resistance mutations selected by the two series differed, consistent with differences in their interactions within the pocket, and most also impaired virus replicative capacity. Resistance mutations had two modes of action, either directly impacting inhibitor binding affinity or apparently increasing the overall stability of the viral capsid without affecting inhibitor binding. These studies demonstrate that CA is a viable antiviral target and demonstrate that inhibitors that bind within the same site on CA can have distinct binding modes and mechanisms of action

Transmission Spectroscopy of the Habitable Zone Exoplanet LHS 1140 b with JWST/NIRISS

LHS 1140 b is the second-closest temperate transiting planet to Earth with an equilibrium temperature low enough to support surface liquid water. At 1.730 ± 0.025 R ⊕, LHS 1140 b falls within the radius valley separating H2-rich mini-Neptunes from rocky super-Earths. Recent mass and radius revisions indicate a bulk density significantly lower than expected for an Earth-like rocky interior, suggesting that LHS 1140 b could be either a mini-Neptune with a small envelope of hydrogen (∼0.1% by mass) or a water world (9%–19% water by mass). Atmospheric characterization through transmission spectroscopy can readily discern between these two scenarios. Here we present two JWST/NIRISS transit observations of LHS 1140 b, one of which captures a serendipitous transit of LHS 1140 c. The combined transmission spectrum of LHS 1140 b shows a telltale spectral signature of unocculted faculae (5.8σ), covering ∼20% of the visible stellar surface. Besides faculae, our spectral retrieval analysis reveals tentative evidence of residual spectral features, best fit by Rayleigh scattering from a N2-dominated atmosphere (2.3σ), irrespective of the consideration of atmospheric hazes. We also show through Global Climate Models (GCMs) that H2-rich atmospheres of various compositions (100×, 300×, 1000× solar metallicity) are ruled out to >10σ. The GCM calculations predict that water clouds form below the transit photosphere, limiting their impact on transmission data. Our observations suggest that LHS 1140 b is either airless or, more likely, surrounded by an atmosphere with a high mean molecular weight. Our tentative evidence of a N2-rich atmosphere provides strong motivation for future transmission spectroscopy observations of LHS 1140 b

Atmospheric Reconnaissance of TRAPPIST-1 b with JWST/NIRISS: Evidence for Strong Stellar Contamination in the Transmission Spectra

TRAPPIST-1 is a nearby system of seven Earth-sized, temperate, rocky exoplanets transiting a Jupiter-sized M8.5V star, ideally suited for in-depth atmospheric studies. Each TRAPPIST-1 planet has been observed in transmission both from space and from the ground, confidently rejecting cloud-free, hydrogen-rich atmospheres. Secondary eclipse observations of TRAPPIST-1 b with JWST/MIRI are consistent with little to no atmosphere given the lack of heat redistribution. Here we present the first transmission spectra of TRAPPIST-1 b obtained with JWST/NIRISS over two visits. The two transmission spectra show moderate to strong evidence of contamination from unocculted stellar heterogeneities, which dominates the signal in both visits. The transmission spectrum of the first visit is consistent with unocculted starspots and the second visit exhibits signatures of unocculted faculae. Fitting the stellar contamination and planetary atmosphere either sequentially or simultaneously, we confirm the absence of cloud-free hydrogen-rich atmospheres, but cannot assess the presence of secondary atmospheres. We find that the uncertainties associated with the lack of stellar model fidelity are one order of magnitude above the observation precision of 89 ppm (combining the two visits). Without affecting the conclusion regarding the atmosphere of TRAPPIST-1 b, this highlights an important caveat for future explorations, which calls for additional observations to characterize stellar heterogeneities empirically and/or theoretical works to improve model fidelity for such cool stars. This need is all the more justified as stellar contamination can affect the search for atmospheres around the outer, cooler TRAPPIST-1 planets for which transmission spectroscopy is currently the most efficient technique.Comment: 26 pages, 11 figures, accepted for publication in The Astrophysical Journal Letter

Near-Infrared Transmission Spectroscopy of HAT-P-18 \,b with NIRISS: Disentangling Planetary and Stellar Features in the Era of JWST

The JWST Early Release Observations (ERO) included a NIRISS/SOSS (0.6-2.8$\,\mu$m) transit of the $\sim\,$850$\,$K Saturn-mass exoplanet HAT-P-18$\,$b. Initial analysis of these data reported detections of water, escaping helium, and haze. However, active K dwarfs like HAT-P-18 possess surface heterogeneities $-$ starspots and faculae $-$ that can complicate the interpretation of transmission spectra, and indeed, a spot-crossing event is present in HAT-P-18$\,$b's NIRISS/SOSS light curves. Here, we present an extensive reanalysis and interpretation of the JWST ERO transmission spectrum of HAT-P-18$\,$b, as well as HST/WFC3 and $\textit{Spitzer}$/IRAC transit observations. We detect H$_2$O (12.5$\,\sigma$), CO$_2$ (7.3$\,\sigma$), a cloud deck (7.4$\,\sigma$), and unocculted starspots (5.8$\,\sigma$), alongside hints of Na (2.7$\,\sigma$). We do not detect the previously reported CH$_4$ ($\log$ CH$_4$ $<$ -6 to 2$\,\sigma$). We obtain excellent agreement between three independent retrieval codes, which find a sub-solar H$_2$O abundance ($\log$ H$_2$O $\approx -4.4 \pm 0.3$). However, the inferred CO$_2$ abundance ($\log$ CO$_2$ $\approx -4.8 \pm 0.4$) is significantly super-solar and requires further investigation into its origin. We also introduce new stellar heterogeneity considerations by fitting for the active regions' surface gravities $-$ a proxy for the effects of magnetic pressure. Finally, we compare our JWST inferences to those from HST/WFC3 and $\textit{Spitzer}$/IRAC. Our results highlight the exceptional promise of simultaneous planetary atmosphere and stellar heterogeneity constraints in the era of JWST and demonstrate that JWST transmission spectra may warrant more complex treatments of the transit light source effect

Awesome SOSS: Transmission Spectroscopy of WASP-96b with NIRISS/SOSS

The future is now - after its long-awaited launch in December 2021, JWST began science operations in July 2022 and is already revolutionizing exoplanet astronomy. The Early Release Observations (ERO) program was designed to provide the first images and spectra from JWST, covering a multitude of science cases and using multiple modes of each on-board instrument. Here, we present transmission spectroscopy observations of the hot-Saturn WASP-96b with the Single Object Slitless Spectroscopy (SOSS) mode of the Near Infrared Imager and Slitless Spectrograph, observed as part of the ERO program. As the SOSS mode presents some unique data reduction challenges, we provide an in-depth walk-through of the major steps necessary for the reduction of SOSS data: including background subtraction, correction of 1/f noise, and treatment of the trace order overlap. We furthermore offer potential routes to correct for field star contamination, which can occur due to the SOSS mode's slitless nature. By comparing our extracted transmission spectrum with grids of atmosphere models, we find an atmosphere metallicity between 1x and 5x solar, and a solar carbon-to-oxygen ratio. Moreover, our models indicate that no grey cloud deck is required to fit WASP-96b's transmission spectrum, but find evidence for a slope shortward of 0.9$\mu$m, which could either be caused by enhanced Rayleigh scattering or the red wing of a pressure-broadened Na feature. Our work demonstrates the unique capabilities of the SOSS mode for exoplanet transmission spectroscopy and presents a step-by-step reduction guide for this new and exciting instrument.Comment: MNRAS, in press. Updated to reflect published versio

Oxygen access to the active site of cholesterol oxidase through a narrow channel is gated by an Arg-Glu pair

Cholesterol oxidase is a monomeric flavoenzyme that catalyzes the oxidation and isomerization of cholesterol to cholest-4-en-3-one. Two forms of the enzyme are known, one containing the cofactor non-covalently bound to the protein and one in which the cofactor is covalently linked to a histidine residue. The x-ray structure of the enzyme from Brevibacterium sterolicum containing covalently bound FAD has been determined and refined to 1.7-Å resolution. The active site consists of a cavity sealed off from the exterior of the protein. A model for the steroid substrate, cholesterol, can be positioned in the pocket revealing the structural factors that result in different substrate binding affinities between the two known forms of the enzyme. The structure suggests that Glu475, located at the active site cavity, may act as the base for both the oxidation and the isomerization steps of the catalytic reaction. A water-filled channel extending toward the flavin moiety, inside the substrate-binding cavity, may act as the entry point for molecular oxygen for the oxidative half-reaction. An arginine and a glutamate residue at the active site, found in two conformations are proposed to control oxygen access to the cavity from the channel. These concerted side chain movements provide an explanation for the biphasic mode of reaction with dioxygen and the ping-pong kinetic mechanism exhibited by the enzyme

Synthesis, biological evaluation and structure-activity relationships of novel substituted N-phenyl ureidobenzenesulfonate derivatives blocking cell cycle progression in S-phase and inducing DNA double-strand breaks

Twenty-eight new substituted N-phenylureidobenzenesulfonate (PUB-SO) and 18 Nphenylureidobenzenesulfonamide (PUB-SA) derivatives were prepared. Several PUB-SOs exhibited antiproliferative activity at the micromolar level against the HT-29, M21 and MCF-7 cell lines and blocked cell cycle progression in S-phase similarly to cisplatin. In addition, PUBSOs induced histone H2AX (γH2AX) phosphorylation, evidencing that these molecules induce DNA double-strand breaks. In contrast, PUB-SAs were less active than PUB-SOs and did not block cell cycle progression in S-phase. Finally, PUB-SOs 4 and 46 exhibited potent antitumor activity in HT-1080 fibrosarcoma cells grafted onto chick chorioallantoic membranes, which was similar to cisplatin and combretastatin A-4 and without significant toxicity towards chick embryos. These new compounds are members of a promising new class of anticancer agents