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Dark energy survey year 3 results: likelihood-free, simulation-based w CDM inference with neural compression of weak-lensing map statistics

We present simulation-based cosmological wcold dark matter (wCDM) inference using dark energy survey year 3 weak-lensing maps, via neural data compression of weak-lensing map summary statistics: power spectra, peak counts, and direct map-level compression/inference with convolutional neural networks (CNN). Using simulation-based inference, also known as likelihood-free or implicit inference, we use forward-modelled mock data to estimate posterior probability distributions of unknown parameters. This approach allows all statistical assumptions and uncertainties to be propagated through the forward-modelled mock data; these include sky masks, non-Gaussian shape noise, shape measurement bias, source galaxy clustering, photometric redshift uncertainty, intrinsic galaxy alignments, non-Gaussian density fields, neutrinos, and non-linear summary statistics. We include a series of tests to validate our inference results. This paper also describes the Gower Street simulation suite: 791 full-sky pkdgrav3 dark matter simulations, with cosmological model parameters sampled with a mixed active-learning strategy, from which we construct over 3000 mock dark energy survey lensing data sets. For wCDM inference, for which we allow –1 < w < –$\frac{1}{3}$⁠, our most constraining result uses power spectra combined with map-level (CNN) inference. Using gravitational lensing data only, this map-level combination gives Ω m = 0.283$^{+0.020}_{–0.027}$⁠, S 8 = 0.804$^{+0.025}_{–0.017⁠}$, and w < –0.80 (with a 68 per cent credible interval); compared to the power spectrum inference, this is more than a factor of two improvement in dark energy parameter (Ω⁠ DE , w⁠) precision.

79 ASTRONOMY AND ASTROPHYSICS

Identification of potent inhibitors of JUN N-terminal kinases for treatment of endometriosis and associated pain

Endometriosis, defined as the ectopic growth of endometrial tissue outside of the uterine cavity, is an inflammatory and hormone-dependent disease that causes excruciating pelvic pain, infertility, and significantly decreases quality of life in affected patients. The JUN N-terminal kinases (JNKs) are a leading class of nonhormonal therapeutic targets that have been validated in preclinical models of endometriosis and in a Phase 1/2 clinical trial. Despite their therapeutic potential, JNK inhibitors with increased potency and specificity are needed to address the inflammatory pathology of endometriosis and to prevent disease progression. Leveraging a DNA-encoded chemical library collection of ~4 billion compounds, we identified lead inhibitor CDD-2428 and optimized derivatives, CDD-2728 and CDD-3013, with excellent binding affinity to JNK1-3 (K d = 0.12 to 3.7 nM), enhanced selectivity, metabolic stability, and cellular permeability. Crystallographic and biochemical studies confirmed that CDD-3013 exhibited superior kinase selectivity with improved efficacy compared to existing JNK inhibitors. In primary endometriosis cell models, CDD-2728 and CDD-3013 suppressed JNK-dependent inflammatory signaling, dampening pathways linked to pain, invasion, angiogenesis, and macrophage recruitment. In an endometriosis mouse model, both CDD-2728 and CDD-3013 reduced endometriotic lesion size, macrophage infiltration, and cellular proliferation, showing in vivo efficacy. When tested in a lipopolysaccharide-induced hyperalgesia model, CDD-2728 and CDD-3013 decreased markers of induced pain, as measured by changes in a dynamic weight bearing test and Grimace scores. These findings nominate CDD-2728 and CDD-3013 as potent, nonhormonal therapeutic candidates for endometriosis with broad anti-inflammatory and analgesic activity, addressing a critical unmet clinical need.

Madasu, Chandrashekhar [Department of Pathology an

Application of Nuclear Technology to Art Identification Problems: First Annual Report

Throughout the centuries, as man has become increasingly affluent, his interest in antiquities and objects of art, and the price he has been willing to pay for them, has increased. Inevitably, one result has been to attract the unscrupulous to the production and sale of counterfeit paintings, sculptures, and other works of art. The skill of forgers varies but often is highly sophisticated. However, dealers, museum curators, and other experts have also become more skillful in the detection of forgeries. Scientific tools of increasing sensitivity and sophistication have gradually been applied to the examination of the materials of art and archaeology. Such tools frequently support and render more reliable the judgment of the experts. The quality of forgeries may improve further as their makers become acquainted with the new methods of detection and in turn learn to circumvent or confound the methods. Therefore, the development of still more advanced methods of examination has great utility in the art world. This is particularly true if the ultimate effect is to make circumvention of the methods of examination so costly that the economic incentives for producing forgeries may be substantially reduced, if not eliminated.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH

De Novo Design of High‐Affinity Miniprotein Binders Targeting Francisella Tularensis Virulence Factor

Abstract Francisella tularensis poses considerable public health risk due to its high infectivity and potential for bioterrorism. Francisella‐like lipoprotein (Flpp3), a key virulence factor unique to Francisella, plays critical roles in infection and immune evasion, making it a promising target for therapeutic development. However, the lack of well‐defined binding pockets and structural information on native interactions has hindered structure‐guided ligand discovery against Flpp3. Here, we used a combination of physics‐based and deep‐learning methods to design high‐affinity miniprotein binders targeting two distinct sites on Flpp3. We identified four binders for site I with binding affinities ranging between 24–110 nM. For the second site, an initial binder showed a dissociation constant ( K D ) of 81 nM, and subsequent site saturation mutagenesis yielded variants with sub‐nanomolar affinities. Circular dichroism confirmed the topology of designed miniproteins. The X‐ray crystal structure of Flpp3 in complex with a site I binder is nearly identical to the design model (Cα root‐mean‐square deviation (RMSD): 0.9 Å). These designed miniproteins provide research tools to explore the roles of Flpp3 in tularemia and should enable the development of new therapeutic candidates.

Gokce‐Alpkilic, Gizem [Molecular Engineering and S

Twist Engineering of Anisotropic Excitonic and Optical Properties of a Two-Dimensional Magnetic Semiconductor

Two-dimensional (2D) van der Waals (vdW) magnetic semiconductors are a new class of quantum materials for studying the emergent physics of excitons and spins in the 2D limit. Twist engineering provides a powerful tool to manipulate the fundamental properties of 2D vdW materials. Here, in this work, we show that twist engineering of the anisotropic ferromagnetic monolayer semiconductor CrSBr leads to bilayer magnetic semiconductors with continuously tunable magnetic moment, dielectric anisotropy, exciton energy, and linear dichroism. We furthermore provide a model for exciton energy in the media with tunable anisotropy. These results advance fundamental studies of 2D vdW materials and open doors to applications to nano-optics, twistronics, and spintronics.

36 MATERIALS SCIENCE

The SPT-deep Cluster Catalog: Sunyaev–Zel’dovich Selected Clusters from Combined SPT-3G and SPTpol Measurements over 100 Square Degrees

We present a catalog of 500 galaxy cluster candidates in the SPT-Deep field: a 100 deg$^{2}$ field that combines data from the SPT-3G and SPTpol surveys to reach noise levels of 3.0, 2.2, and 9.0 μK-arcmin at 95, 150, and 220 GHz, respectively. Candidates are selected via the thermal Sunyaev–Zel’dovich (SZ) effect with a minimum significance of ξ = 4.0, resulting in a catalog of purity ∼89%. Optical data from the Dark Energy Survey and infrared data from the Spitzer Space Telescope are used to confirm 442 cluster candidates. The clusters span 0.12 < z ≲ 1.8 and 1.0 × 10$^{14}$M$_{⊙}$/h$_{70}$ < M$_{500c}$ < 8.7 × 10$^{14}$M$_{⊙}$/h$_{70}$. The sample’s median redshift is 0.74, and the median mass is 1.7 × 10$^{14}$M$_{⊙}$/h$_{70}$; these are the lowest median mass and highest median redshift of any SZ-selected sample to date. We assess the effect of infrared emission from cluster member galaxies on cluster selection by performing a joint fit to the infrared dust and tSZ signals by combining measurements from SPT and overlapping submillimeter data from Herschel/SPIRE. We find that at high redshift (z > 1), the tSZ signal is reduced by $17.9_{−3.2}^{+3.8}$%$(3.8_{−0.7}^{+0.9}$%$)$ at 150 GHz (95 GHz) due to dust contamination. We repeat our cluster finding method on dust-nulled SPT maps and find the resulting catalog is consistent with the nominal SPT-Deep catalog, suggesting dust contamination does not significantly impact the SPT-Deep selection function; we attribute this lack of bias to the inclusion of the SPT 220 GHz band.

79 ASTRONOMY AND ASTROPHYSICS

SPT clusters with DES and HST weak lensing. II. Cosmological constraints from the abundance of massive halos

We present cosmological constraints from the abundance of galaxy clusters selected via the thermal Sunyaev-Zel’dovich (SZ) effect in South Pole Telescope (SPT) data with a simultaneous mass calibration using weak gravitational lensing data from the Dark Energy Survey (DES) and the Hubble Space Telescope (HST). The cluster sample is constructed from the combined SPT-SZ, SPTpol ECS, and SPTpol 500d surveys, and comprises 1,005 confirmed clusters in the redshift range 0.25–1.78 over a total sky area of 5200 deg 2 . We use DES Year 3 weak-lensing data for 688 clusters with redshifts 𝑧 < 0.95 and HST weak-lensing data for 39 clusters with 0.6 < 𝑧 < 1.7. The weak-lensing measurements enable robust mass measurements of sample clusters and allow us to empirically constrain the SZ observable-mass relation without having to make strong assumptions about, e.g., the hydrodynamical state of the clusters. For a flat Λ⁢ CDM cosmology, and marginalizing over the sum of massive neutrinos, we measure Ω m = 0.286 ± 0.032, 𝜎 8 = 0.817 ± 0.026, and the parameter combination 𝜎 8 ⁢(Ω m /0.3) 0.25 = 0.805 ± 0.016. Our measurement of 𝑆 8 ≡ 𝜎 8 ⁢$\sqrt{Ω_{m}/0.3}$ = 0.795 ± 0.029 and the constraint from Planck CMB anisotropies (2018 TT, TE, EE+lowE) differ by 1.1⁢𝜎. In combination with that Planck dataset, we place a 95% upper limit on the sum of neutrino masses ∑𝑚 𝜈 < 0.18 eV. When additionally allowing the dark energy equation of state parameter 𝑤 to vary, we obtain 𝑤 = −1.45 ± 0.31 from our cluster-based analysis. In combination with Planck data, we measure 𝑤 =−1.3⁢4$^{+0.22}_{−0.15}$, or a 2.2⁢𝜎 difference with a cosmological constant. We use the cluster abundance to measure 𝜎8 in five redshift bins between 0.25 and 1.8, and we find the results to be consistent with structure growth as predicted by the Λ⁢ CDM model fit to Planck primary CMB data.

79 ASTRONOMY AND ASTROPHYSICS

Search for New Physics via Low-Energy Electron Recoils with a 4.2 Tonne-Year Exposure from the LZ Experiment

We report results from searches for new physics models through electron recoils using data collected by the LUX-ZEPLIN experiment during its first two science runs, with a total exposure of 4.2 tonne−years. The observed data are consistent with a background-only hypothesis. Constraints are derived for electromagnetic interactions of solar neutrinos, solar axionlike particles (ALPs), mirror dark matter, and the absorption of bosonic dark matter candidates. The inverse Primakoff process for 57 Fe deexcitation solar ALPs is considered for the first time. These results represent the most stringent constraints to date on keV-scale Primakoff and 57 Fe solar ALPs, bosonic dark matter, mirror dark matter, and neutrino millicharge, while remaining competitive for the other signal models investigated.

Axion-like particles

Dark Energy Survey Year 6 results: Redshift calibration of the MagLim++ lens sample

In this work, we derive and calibrate the redshift distribution of the MagLim++ lens galaxy sample used in the Dark Energy Survey Year 6 (DES Y6) 3 x 2pt cosmology analysis. The 3 x 2pt analysis combines galaxy clustering from the lens galaxy sample and weak gravitational lensing. The redshift distributions are inferred using the SOMPZ method - a Self-Organizing Map framework that combines deep-field multi-band photometry, wide-field data, and a synthetic source injection ( B alrog) catalog. Key improvements over the DES Year 3 (Y3) calibration include a noise-weighted SOM metric, an expanded Balrog catalogue, and an improved scheme for propagating systematic uncertainties, which allows us to generate O(10 8 ) redshift realizations that collectively span the dominant sources of uncertainty. These realizations are then combined with independent clustering-redshift measurements via importance sampling. The resulting calibration achieves typical uncertainties on the mean redshift of 1-2%, corresponding to a 20-30% average reduction relative to DES Y3. We compress the n(z) uncertainties into a small number of orthogonal modes for use in cosmological inference. Marginalizing over these modes leads to only a minor degradation in cosmological constraints. Here, this analysis establishes the MagLim++ sample as a robust lens sample for precision cosmology with DES Y6 and provides a scalable framework for future surveys.

dark energy