The Vera C. Rubin Observatory's Legacy Survey of Space and Time (LSST) will deliver an unprecedented Type Ia supernova (SN) sample, making photometric calibration systematics a dominant source of uncertainty in dark energy constraints. We perform a comprehensive analysis of calibration systematic effects in LSST, quantifying how uncertainties in the LSST passbands propagate into biases in SN distance moduli and, consequently, the dark energy equation of state parameters. Specifically, we examine how the inferred values and uncertainties of w_0 and w_a shift as a function of the amplitude of passband systematics. For linear passband tilts, we find that the best-fit (w_0,w_a) shifts by ∼0.025σ and the w_0-w_a contour area increases by ∼5

We present a synopsis of the project to establish 32 new faint (16.5 <= V <= 19.8) DA white dwarf (DAWD) spectrophotometric standards distributed over the whole sky. Our results validate the use of fully radiative pure hydrogen model fluxes for hot DA white dwarfs to predict the observed broadband fluxes from near-ultraviolet through the near-infrared to accuracies of a few parts per thousand. After fitting the line of sight reddenings simultaneously with the model spectral energy distributions of these stars against spectroscopic and multiband photometric observations, we have shown that residuals have an rms of typically 0.4%. This indicates that the complications from interstellar dust extinction have been adequately mitigated. Our stars supplement the three brighter DAWDs that define the flux scale of CALSPEC. The consequent photometric accuracy, their all-sky coverage, and their brightness range that matches the dynamic range of large telescopes, constitute an unprecedented ensemble of standard stars for both ground as well as space based use. This paper targets readers who may wish to use these as standard stars and provides them with the essential content to understand their strengths and limitations, without traversing the technical details of analysis that are already captured in a series of papers since 2016. The narrative here describes the motivation, justification, and evolution of the analysis methods; the input data that constrain the modeling; as well as the stability of our results in the face of future improvements in models.

As the frontier of precision astronomical photometry continues to advance, correcting for time-variable atmospheric transmission becomes increasingly important. We describe an observational approach to monitoring optical attenuation due to atmospheric aerosols, using a multiband filter and disperser on the Auxiliary Telescope at the Vera C. Rubin Observatory. This configuration allows us to perform simple aperture photometry on four notched-out spectral regions, covering 347-618 nm. We see clear evidence of temporal variations in extinction across these bands, which we attribute to variation in the aerosol content of the atmosphere above the observatory. The observed differences in extinction between the reddest and bluest band can exceed 5 mmag/airmass, highlighting the importance of including variable aerosols in the transmission of the atmosphere. We aspire to using precise determinations of the optical transmission of the atmosphere to enable a forward-modeling approach to achieving mmag photometric precision with Rubin data.

We report on the observation and measurement of astrometry, photometry, morphology, and activity of the interstellar object 3I/ATLAS, also designated C/2025 N1 (ATLAS) with the NSF-DOE Vera C. Rubin Observatory. Comet 3I/ATLAS, the third known interstellar object, was discovered on UT 2025 July 1. Rubin Observatory had coincidentally collected images of the object's region of the sky during routine commissioning. Facilitated by Rubin's high resolution and large aperture, we successfully recovered object detections from Rubin observations spanning UT 2025 June 21 (10 days before discovery, when 3I/ATLAS was 4.5 au from the Sun) through the date of discovery, and we acquired additional images through UT 2025 July 20 as part of commissioning. We measure on-sky locations of 3I/ATLAS in Rubin ugrizy bands, with a typical precision of similar to 70 mas, and briefly describe the reason this is coarser than our measured static source astrometric precision of similar to 3 mas in Rubin images. We measure grizy magnitudes of 3I/ATLAS photometry at similar to 0.01 mag precision, detecting no short-term photometric variability above 0.01 mag. We derive an estimated near-nucleus dust-to-nucleus scattering cross-sectional ratio of eta greater than or similar to 13 on UT 2025 July 2 based on Rubin photometry and an upper limit nucleus size computed from Hubble Space Telescope observations. We find Rubin colors of g - r = (0.657 +/- 0.013) mag, r - i = (0.235 +/- 0.018) mag, i - z = (0.147 +/- 0.042) mag, and z - y = (0.047 +/- 0.052) mag. These data represent the earliest observations of this object by a large (greater than or similar to 8 m class) telescope and illustrate the type of measurements (and discoveries) Rubin's Legacy Survey of Space and Time will provide after it begins in early 2026.

The measurement of type Ia supernovae magnitudes provides cosmological distances, which can be used to constrain dark energy parameters. Large photometric surveys require a substantial improvement in the calibration precision of their photometry to reduce systematic uncertainties in cosmological constraints. The StarDICE experiment is designed to establish accurate broadband flux references for these surveys, aiming for sub-percent precision in magnitude measurements. This requires a precise measurement of the filter bandpasses of both the StarDICE and survey instruments with sub-nanometer accuracy. To that end, we have developed the Collimated Beam Projector (CBP), an optical device capable of calibrating the throughput of an astronomical telescope and of its filters. The CBP is built from a tunable laser source and a reversed telescope to emit a parallel monochromatic light beam that is continuously monitored in flux and wavelength. The CBP output light flux is measured using a large area photodiode, previously calibrated relative to a NIST photodiode. We derive the StarDICE telescope throughput and filter transmissions from the CBP measurements, anchoring it to the absolute calibration provided by the NIST. After analyzing the systematic uncertainties, we achieved sub-nanometer accuracy in determining filter central wavelengths, measured each filter transmission with a precision of 0.5% per 1nm bin, and detected out-of-band leakages at 0.01%. Furthermore, we have synthesized the equivalent transmission for full pupil illumination from four sample positions in the StarDICE telescope mirror, with an accuracy of approximately 0.2nm for central wavelengths and 7mmag for broadband fluxes. We demonstrated our ability to characterize a telescope throughput down to the mmag, and paved the way for future developments, such as a portable CBP version for in-situ transmission monitoring.

Deflection of light along the optical path is a major source of image degradation for ground-based telescopes. Methods have been developed to measure upper atmospheric seeing based on models of the turbulence in the atmosphere, but due to boundary conditions, transmission within telescope enclosures is more complex. The Multi-beam Optical Seeing Sensor (MOSS) directly measures the component of the image quality degradation from inhomogeneity of the index of refraction within the telescope dome. MOSS outputs four near-parallel beams of light that travel along the optical path and are imaged by the telescope's detector, landing like starlight on the telescope's focal plane. By using a strobed light source, we can 'freeze' the instantaneous index variations transverse to the optical path. This system captures both 'dome' and 'mirror' seeing. Through plotting the standard deviation of differential motion between pairs of beams, MOSS enables characterization of the length scale of turbulence within the dome. The temporal coherence of temperature gradients can be probed with different pulse lengths, and the spatial coherence by comparing pairs at different separations across the aperture of the telescope. Optical path turbulence measurements, alongside other telemetry metrics, will guide thermal and airflow management to optimize image quality. A MOSS prototype was installed in the 1.2m Auxiliary Telescope (AuxTel) at the Vera C. Rubin Observatory in Chile, and preliminary data constrain the optical path turbulence with a lower bound of 1.4 arcsec. The optical path turbulence varied throughout the night of observing.

Precision photometric calibration is key to a number of astrophysical research areas such as supernova cosmology and dark energy studies. In the age of large surveys, pushing the limits of photometry is a worthy challenge, with traditional celestial calibrators limited to approximately percent precision. Here we present PANDORA, a novel calibration source that achieves sub-percent photometric precision across the optical spectrum with a selectable dynamic range and high optical efficiency. Building on proven collimated beam projector designs for relative throughput calibration of survey telescopes, PANDORA is capable of delivering photons anywhere in the 350-1100 nm spectral range. It uses selectable neutral density filters and sequential NIST-calibrated photodiode feedback to internally self-calibrate prior to operation, and is illuminated by an Energetiq EQ-99X-FC broadband laser-driven light source. We present here an overview of the system design, operation, and laboratory characterization results. PANDORA will begin science operations this year to support the upcoming LS4 survey on the ESO 1m Schmidt telescope.

We present the La Silla Schmidt Southern Survey (LS4), a new wide-field, time-domain survey to be conducted with the 1 m ESO Schmidt telescope. The 268 megapixel LS4 camera mosaics 32 2k x 4k fully depleted CCDs, providing a similar to 20 deg2 field of view with 1 '' pixel-1 resolution. The LS4 camera will have excellent performance at longer wavelengths: in a standard 45 s exposure the expected 5 sigma limiting magnitudes in g, i, z are similar to 21.5, similar to 20.9, and similar to 20.3 mag (AB), respectively. The telescope design requires a novel filter holder that fixes different bandpasses over each quadrant of the detector. Two quadrants will have i band, while the other two will be g and z band with color information obtained by dithering targets across the different quadrants. The majority (90%) of the observing time will be used to conduct a public survey that monitors the extragalactic sky at both moderate (3 days) and high (1 day) cadence, as well as focused observations within the Galactic plane and bulge. Alerts from the public survey will be broadcast to the community via established alert brokers. LS4 will run concurrently with the Vera C. Rubin Observatory's Legacy Survey of Space and Time (LSST). The combination of LS4+LSST will enable detailed holistic monitoring of many nearby transients: high-cadence LS4 observations will resolve the initial rise and peak of the light curve while less-frequent but deeper observations by LSST will characterize the years before and after explosion. Here, we summarize the primary science objectives of LS4 including microlensing events in the Galaxy, extragalactic transients powered by massive black holes or stellar explosions, the search for electromagnetic counterparts to multi-messenger events, and supernova cosmology.

MUS81 is a structure-selective endonuclease that cleaves various branched DNA structures arising from natural physiological processes such as homologous recombination and mitosis. Due to this, MUS81 is able to relieve replication stress, and its function has been reported to be critical to the survival of many cancers, particularly those with dysfunctional DNA-repair machinery. There is therefore interest in MUS81 as a cancer drug target, yet there are currently few small molecule inhibitors of this enzyme reported, and no liganded crystal structures are available to guide hit optimization. Here we report the fragment-based discovery of novel small molecule MUS81 inhibitors with sub-μM biochemical activity. These inhibitors were used to develop a novel crystal system, providing the first structural insight into the inhibition of MUS81 with small molecules.

The number of type Ia supernova observations will see a significant growth within the next decade, especially thanks to the Legacy Survey of Space and Time undertaken by the Vera Rubin Observatory in Chile. With this rise, the statistical uncertainties will decrease and the flux calibration will become the main uncertainty for the characterization of dark energy. The uncertainty over the telescope transmission is a major systematic when measuring SNe Ia colors. Here we introduce the Collimated Beam Projector (CBP), a device that can measure the transmission of a telescope and its filters. Composed of a tunable monochromatic light source and optics to provide a parallel output beam this device is able to measure with high precision the filter transmissions. In the following, we will show how measuring precisely a telescope transmission can also improve the precision of the dark energy parameters. As an example, we will present the first results of the CBP in the context of the StarDice experiment.

GW190425 is the second of only two binary neutron star (BNS) merger events to be significantly detected by the LIGO-Virgo- Kagra gravitational wave detectors. With a detection only in LIGO Livingston, the skymap containing the source was large and no plausible electromagnetic counterpart was found in real time searching in 2019. Here we summarise our ATLAS and Pan-STARRS wide-field optical coverage of the skymap beginning within 1 hour and 3 hours respectively of the GW190425 merger time. More recently, a potential coincidence between GW190425 and a fast radio burst FRB 190425 has been suggested, given their spatial and temporal coincidence. The smaller sky localisation area of FRB 190425 and its dispersion measure have led to the identification of a likely host galaxy, UGC 10667 at a distance of 141 +/- 10 Mpc. Our optical imaging covered the galaxy 6.0 hrs after GW190425 was detected and 3.5 hrs after the FRB 190425. No optical emission was detected and further imaging at +1.2 and +13.2 days also revealed no emission. If the FRB 190425 and GW190425 association were real, we highlight our limits on kilonova emission from a BNS merger in UGC 10667. The model for producing FRB 190425 from a BNS merger involves a supramassive magnetised neutron star spinning down by dipole emission on the timescale of hours. We show that magnetar enhanced kilonova emission is ruled out by optical upper limits. The lack of detected optical emission from a kilonova in UGC 10667 disfavours, but does not disprove, the FRB-GW link for this source.

PRMT5, a type 2 arginine methyltransferase, has a critical role in regulating cell growth and survival in cancer. With the aim of developing MTA-cooperative PRMT5 inhibitors suitable for MTAP-deficient cancers, herein we report our efforts to develop novel “MTA-cooperative” compounds identified through a high-throughput biochemical screening approach. Optimization of hits was achieved through structure-based design with a focus on improvement of oral drug-like properties. Bioisosteric replacement of the original thiazole guanidine headgroup, spirocyclization of the isoindolinone amide scaffold to both configurationally and conformationally lock the bioactive form, and fine-tuning of the potency, MTA cooperativity, and DMPK properties through specific substitutions of the azaindole headgroup were conducted. We have identified an orally available in vivo lead compound, 28 (“AZ-PRMT5i-1”), which shows sub-10 nM PRMT5 cell potency, >50-fold MTA cooperativity, suitable DMPK properties for oral dosing, and significant PRMT5-driven in vivo efficacy in several MTAP-deficient preclinical cancer models.

The Vera C. Rubin Observatory is nearing completion, and we are embarking on a campaign to optimize the image quality during its upcoming 10-year optical survey. Here, we present the tools and methods we are implementing to disentangle and quantify the different sources of image degradation, as well as our plans to correct and mitigate as many of these different contributions to seeing as possible. The tools include an on-site Differential Image Motion Monitor (DIMM) for measuring atmospheric seeing, multiple 2D and 3D sonic anemometers for measuring in-dome wind speed and turbulence, and direct dome seeing monitors. We also implement a guider mode that allows data to be taken at 9 Hz over small regions and a stuttered and streaked imaging mode that allows us to measure mount tracking and jitter and perform atmospheric tomography. Additionally, we use curvature wavefront sensing to estimate the residual wavefront error to support the telescope's alignment and focus. This is the same algorithm that we will use for the Simonyi Survey Telescope. Many of these tools, as well as additional techniques to quantify the contribution of astigmatism to seeing, have been tested at the Auxiliary Telescope (AuxTel). This 1.2 m telescope acts as a pathfinder for the Rubin Observatory. We present initial results and the creation of an image quality budget table for AuxTel to characterize and monitor significant sources of image quality degradation. We then discuss plans for implementing these techniques on the 8.4 m Simonyi Survey Telescope.

The paper outlines the Emission and Biofuel Directives relating to CO 2 emissions in cars and the fiscal penalties incurred by manufacturers failing to meet targets.The effect on emissions of the biofuel directives are quantified through a test programme which measures emissions from a turbo-charged diesel engine using a range of biodiesel fuels, using standard diesel fuel to obtain a comparison.The tests measure O 2 , NO x , THC and CO emissions data as well as CO 2 .The results are difficult to quantify but , with the exception of corn oil show an increase in CO 2 emissions .Corn oil also shows a reduction in other emissions.The discussion considers other mechanisms which can reduce overall global automotive emissions including range extenders for electric vehicles.

Various models of modified gravity invoke ‘screening’ mechanisms that are sensitive to the value of the local gravitational potential. This could have observable consequences for galaxies. These consequences might be seen by comparing two proxies for galaxy mass – their luminosity and their internal kinematics – as a function of local galaxy density. Motivated by this prospect, we have compared the observed properties of luminous red galaxies (LRGs) inside and outside of voids in the cosmic large scale structure. We used archival measurements of line widths, luminosities, redshifts, colors, and positions of galaxies in conjunction with recent void catalogs to construct comparison LRG samples inside and outside of voids. We fitted these two samples to the well-established fundamental plane of elliptical galaxies to constrain any differences between the inferred value of the Newtonian gravitational constant G for the two samples. We obtained a null result, with an upper limit on any fractional difference in G within and outside of cosmological voids to be α = δG/G ∼ 40%. This upper bound is dominated by the small-number statistics of our N ∼ 100 within-void LRG sample. With the caveat that environmental effects could influence various parameters such as star formation, we estimate that a 1% statistical limit on α could be attained with data from 105 elliptical galaxies within voids. This is within the reach of future photometric and spectroscopic surveys, both of which are required to pursue this method.

Abstract RAS proteins contribute to the activation of p110α by directly interacting with its RAS binding domain (RBD), resulting in the promotion of cellular functions such as cell growth, proliferation and survival. Previously, we have shown that blocking the interaction of p110α with oncogenic RAS, by introducing specific mutations in the RBD, had a significant impact on tumor initiation and growth in mouse models, whilst having little effect on the health of normal adult mice. These studies highlight the significance of the p110α/KRAS protein-protein interaction (PPI) in tumor progression and maintenance and strongly suggest its importance as a drug target. Thus, we initiated a drug discovery project aiming to identify molecules that bind to p110α and perturb its interaction with KRAS. However, the rather weak binding affinity of the p110α/KRAS interaction (Kd = 3 μM) and the poor solubility of p110α raised significant issues when considering the use of currently available biochemical assays. The NanoLuc® Binary Technology (NanoBiT®) assay was originally developed to detect PPIs in live mammalian cells. However, the assay in its current state was not ideal for high throughput screening (HTS) due to the requirement for large-scale cell based assays. Therefore, we developed the NanoBiT Biochemical Assay (NBBA) as a more suitable and cost-effective approach. The NBBA centres on expressing modified target proteins of interest in mammalian cells and then screening cell lysates rather than live cells. We have previously shown that the NBBA is suitable for detection of both strong and weak PPIs, as exemplified by KRAS/RAF and KRAS/PI3K. Here we present the first application of NBBA for HTS of the KRAS/p110α PPI, using tagged Sm-KRAS-G12D and Lg-p110α. The NBBA proved to be stable and produced good Z’ factor metrics. Our primary screen of more than 720,000 compounds on KRAS/p110α cell lysates produced around 8,000 initial hits. A concentration response screen comparing KRAS/p110α with two other p110 isoforms, p110δ and p110γ, identified selective p110α-specific compounds and enabled derivation of IC50s for these hits. We identified around 30 compounds showing greater than 20-fold selectivity towards p110α versus p110δ and p110γ with IC50 <2μM. Using 1D-NMR (1 – Dimension Nuclear Magnetic Resonance) we identified 9 compounds that binds directly to purified p110α. The positive and most potent hits will be followed up by co-crystallization with p110α to aid further elucidation of the nature of the interaction and extended optimisation of these compounds. Citation Format: Mohamed (Soly) Soliman Ismail, Julian Downward, Jonathan Tart, Gareth Davies, Tiziana Monteverde, David Hancock, Santosh Adhikari, Christopher Stubbs, Carolyn Blackett, Geoff Holdgate, Jason Kettle. High throughput application of the NanoBiT Biochemical Assay for the discovery of selective p110α isoform binders that block its interaction with KRAS [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C038.

Auxiliary data files for Axelrod et al. 2023 (in prep.). "HST_passbands" - Hubble Space Telescope photometric filter passthroughs. First column is vacuum wavelength in nm, second column is response. "SED" - calibrated spectral flux density distributions. First column is vacuum wavelength in Angstrom, second column is SED in erg/sec/cm**2/Angstrom. "Tables" - paper tables in LaTeX.

Image degradation impedes our ability to extract information from astronomical observations. One factor contributing to this degradation is ``dome seeing", the reduction in image quality due to variations in the index of refraction within the observatory dome. Addressing this challenge, we introduce a novel setup-DIMSUM (Differential Image Motion Sensor Using Multisources)-which offers a simple installation and provides direct characterization of local index of refraction variations. This is achieved by measuring differential image motion using strobed imaging that effectively``freezes" the atmosphere, aligning our captured images with the timescale of thermal fluctuations, thereby giving a more accurate representation of dome seeing effects. Our apparatus has been situated within the Auxiliary Telescope of the Vera C. Rubin Observatory. Early results from our setup are encouraging. Not only do we observe a correlation between the characteristic differential image motion (DIM) values and local temperature fluctuations (a leading cause of variations in index of refraction), but also hint at the potential of DIM measures to characterize dome seeing with greater precision in subsequent tests. Our preliminary findings underscore the potential of DIMSUM as a powerful tool for enhancing image quality in ground-based astronomical observations. Further refinement and data collection will likely solidify its place as a useful component for managing dome seeing in major observatories like the Vera C. Rubin Observatory.

With the increasingly large number of Type Ia supernova being detected by current-generation survey telescopes, and even more expected with the upcoming Rubin Observatory Legacy Survey of Space and Time, the precision of cosmological measurements will become limited by systematic uncertainties in flux calibration rather than statistical noise. One major source of systematic error in determining SNe Ia color evolution (needed for distance estimation) is uncertainty in telescope transmission, both within and between surveys. We introduce here the Collimated Beam Projector (CBP), which is meant to measure a telescope transmission with collimated light. The collimated beam more closely mimics a stellar wave front as compared to flat-field-based instruments, allowing for more precise handling of systematic errors such as those from ghosting and filter angle-of-incidence dependence. As a proof of concept, we present CBP measurements of the StarDICE prototype telescope, achieving a standard (1 σ ) uncertainty of 3% on average over the full wavelength range measured with a single beam illumination.

Hot DA white dwarfs have fully radiative pure hydrogen atmospheres that are the least complicated to model. Pulsationally stable, they are fully characterized by their effective temperature Teff, and surface gravity log g, which can be deduced from their optical spectra and used in model atmospheres to predict their spectral energy distribution (SED). Based on this, three bright DAWDs have defined the spectrophotometric flux scale of the CALSPEC system of HST. In this paper we add 32 new fainter (16.5 < V < 19.5) DAWDs spread over the whole sky and within the dynamic range of large telescopes. Using ground based spectra and panchromatic photometry with HST/WFC3, a new hierarchical analysis process demonstrates consistency between model and observed fluxes above the terrestrial atmosphere to < 0.004 mag rms from 2700 Å to 7750 Å and to 0.008 mag rms at 1.6μm for the total set of 35 DAWDs. These DAWDs are thus established as spectrophotometric standards with unprecedented accuracy from the near ultraviolet to the near-infrared, suitable for both ground and space based observatories. They are embedded in existing surveys like SDSS, PanSTARRS and GAIA, and will be naturally included in the LSST survey by Rubin Observatory. With additional data and analysis to extend the validity of their SEDs further into the IR, these spectrophotometric standard stars could be used for JWST, as well as for the Roman and Euclid observatories.