Satellite Earth-observation (EO) time series in the optical and microwave ranges are often irregular due to orbital patterns and cloud obstruction, and while compositing addresses these issues, it loses critical phenological information. To overcome this, we present TESSERA, a pixel-wise foundation model for multi-modal (Sentinel-1/2) EO time series that learns robust, label-efficient embeddings. During training, TESSERA uses Barlow Twins and sparse random temporal sampling to enforce invariance to the selection of valid observations, aided by two key regularizers: global shuffling to decorrelate spatial neighborhoods and mix-based regulation for invariance under extreme sparsity. We find that for diverse classification, segmentation, and regression tasks, TESSERA embeddings deliver state-of-the-art accuracy with high label efficiency, often requiring only a small task head and minimal computation. To democratize access, adhere to FAIR principles, and simplify use, we release global, annual, 10m, pixel-wise int8 embeddings together with open weights/code and lightweight adaptation heads, providing practical tooling for large-scale retrieval and inference at planetary scale.

Crop type maps from satellite remote sensing are important tools for food security, local livelihood support and climate change mitigation in smallholder regions of the world, but most satellite-based methods are not well suited to smallholder conditions. To address this gap, we establish a four-part criteria for a useful embedding-based approach consisting of 1) performance, 2) plausibility, 3) transferability and 4) accessibility and evaluate geospatial foundation model (FM) embeddings -based approaches using TESSERA and AlphaEarth against current baseline methods for a region in the groundnut basin of Senegal. We find that the TESSERA -based approach to land cover and crop type mapping fulfills the selection criteria best, and in one temporal transfer example shows 28

Accurate tree segmentation is a key step in extracting individual tree metrics from forest laser scans, and is essential to understanding ecosystem functions in carbon cycling and beyond. Over the past decade, tree segmentation algorithms have advanced rapidly due to developments in AI. However, existing public 3D forest datasets are not large enough to build robust tree segmentation systems. Motivated by the success of synthetic data in other domains such as self-driving, we investigate whether similar approaches can help with tree segmentation. In place of expensive field data collection and annotation, we use synthetic data during pretraining, and then require only minimal, real forest plot annotation for fine-tuning. We have developed Cambridge Arboreal Modelling Panoptic 3D (CAMP3D), a new synthetic data generation pipeline to do this for forest vision tasks, integrating advances in game engines with physics-based LiDAR simulation. Using CAMP3D, we have produced a comprehensive, diverse, annotated 3D forest dataset on an unprecedented scale. Extensive experiments with a state-of-the-art tree segmentation algorithm and a popular real dataset show that our synthetic data can substantially reduce the need for labelled real data. After fine-tuning on just a single, real, forest plot of less than 0.1 hectare, the pretrained model achieves segmentations that are competitive with a model trained on the full scale real data. We have also identified critical factors for successful use of synthetic data: physics, diversity, and scale, paving the way for more robust 3D forest vision systems in the future. Our CAMP3D pipeline and the resulting dataset are available at https://github.com/yihshe/CAMP3D.git .

Tumour content plays a pivotal role in directing the bioinformatic analysis of molecular profiles such as copy number variation (CNV). In clinical application, tumour purity estimation (TPE) is achieved either through visual pathological review [conventional pathology (CP)] or the deconvolution of molecular data. While CP provides a direct measurement, it demonstrates modest reproducibility and lacks standardisation. Conversely, deconvolution methods offer an indirect assessment with uncertain accuracy, underscoring the necessity for innovative approaches. SoftCTM is an open-source, multiorgan deep-learning (DL) model for the detection of tumour and non-tumour cells in H&E-stained slides, developed within the Overlapped Cell on Tissue Dataset for Histopathology (OCELOT) Challenge 2023. Here, using three large multicentre colorectal cancer (CRC) cohorts (N = 1,097 patients) with digital pathology and multi-omic data, we compare the utility and accuracy of TPE with SoftCTM versus CP and bioinformatic deconvolution methods (RNA expression, DNA methylation) for downstream molecular analysis, including CNV profiling. SoftCTM showed technical repeatability when applied twice on the same slide (r = 1.0) and excellent correlations in paired H&E slides (r > 0.9). TPEs profiled by SoftCTM correlated highly with RNA expression (r = 0.59) and DNA methylation (r = 0.40), while TPEs by CP showed a lower correlation with RNA expression (r = 0.41) and DNA methylation (r = 0.29). We show that CP and deconvolution methods respectively underestimate and overestimate tumour content compared to SoftCTM, resulting in 6-13% differing CNV calls. In summary, TPE with SoftCTM enables reproducibility, automation, and standardisation at single-cell resolution. SoftCTM estimates (M = 58.9%, SD +/- 16.3%) reconcile the overestimation by molecular data extrapolation (RNA expression: M = 79.2%, SD +/- 10.5, DNA methylation: M = 62.7%, SD +/- 11.8%) and underestimation by CP (M = 35.9%, SD +/- 13.1%), providing a more reliable middle ground. A fully integrated computational pathology solution could therefore be used to improve downstream molecular analyses for research and clinics. (c) 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

The determination of the direction of a stellar core collapse via its neutrino emission is crucial for the identification of the progenitor for a multimessenger follow-up. A highly effective method of reconstructing supernova directions within the Deep Underground Neutrino Experiment (DUNE) is introduced. The supernova neutrino pointing resolution is studied by simulating and reconstructing electron-neutrino charged-current absorption on Ar-40 and elastic scattering of neutrinos on electrons. Procedures to reconstruct individual interactions, including a newly developed technique called "brems flipping," as well as the burst direction from an ensemble of interactions are described. Performance of the burst direction reconstruction is evaluated for supernovae happening at a distance of 10 kpc for a specific supernova burst flux model. The pointing resolution is found to be 3.4 degrees at 68% coverage for a perfect interaction-channel classification and a fiducial mass of 40 kton, and 6.6 degrees for a 10 kton fiducial mass respectively. Assuming a 4% rate of charged-current interactions being misidentified as elastic scattering, DUNE's burst pointing resolution is found to be 4.3 degrees (8.7 degrees) at 68% coverage.

Large neutrino liquid argon time projection chamber (LArTPC) experiments can broaden their physics reach by reconstructing and interpreting MeV-scale energy depositions, or blips, present in their data. We demonstrate new calorimetric and particle discrimination capabilities at the MeV energy scale using reconstructed blips in data from the MicroBooNE LArTPC at Fermilab. We observe a concentration of low-energy (<3 MeV) blips around fiberglass mechanical support struts along the time projection chamber edges with energy spectrum features consistent with the Compton edge of 2.614 MeV Tl208 decay γ rays. These features are used to verify proper calibration of electron energy scales in MicroBooNE’s data to few percent precision and to measure the specific activity of Tl208 in the fiberglass composing these struts, (11.7±0.2(stat)±3.1(syst)) Bq/kg. Cosmogenically produced blips above 3 MeV in reconstructed energy are used to showcase the ability of large LArTPCs to distinguish between low-energy proton and electron energy depositions. An enriched sample of low-energy protons selected using this new particle discrimination technique is found to be smaller in data than in dedicated cosmic-ray simulations, suggesting either incorrect modeling of incident cosmic fluxes or particle transport modeling issues in eant4. Published by the American Physical Society 2025

Background It is uncertain which biological features underpin the response of rectal cancer (RC) to radiotherapy. No biomarker is currently in clinical use to select patients for treatment modifications. Methods We identfied two cohorts of patients (total N = 249) with RC treated with neoadjuvant radiotherapy (45Gy/ 25) plus fl uoropyrimidine. This discovery set included 57 cases with pathological complete response (pCR) to chemoradiotherapy (23%). Pre-treatment cancer biopsies were assessed using transcriptome-wide mRNA expression and targeted DNA sequencing for copy number and driver mutations. Biological candidate and machine learning (ML) approaches were used to identify predictors of pCR to radiotherapy independent of tumour stage. Findings were assessed in 107 cases from an independent validation set (GSE87211). Findings Three gene expression sets showed signi fi cant independent associations with pCR: Fibroblast-TGF P Response Signature (F-TBRS) with radioresistance; and cytotoxic lymphocyte (CL) expression signature and consensus molecular subtype CMS1 with radiosensitivity. These associations were replicated in the validation cohort. In parallel, a gradient boosting machine model comprising the expression of 33 genes generated in the discovery cohort showed high performance in GSE87211 with 90% sensitivity, 86% speci fi city. Biological and ML signatures indicated similar mechanisms underlying radiation response, and showed better AUC and p-values than published transcriptomic signatures of radiation response in RC. Interpretation RCs responding completely to chemoradiotherapy (CRT) have biological characteristics of immune response and absence of immune inhibitory TGF P signalling. These tumours may be identi fi ed with a potential biomarker based on a 33 gene expression signature. This could help select patients likely to respond to treatment with a primary radiotherapy approach as for anal cancer. Conversely, those with predicted radio resistance may be candidates for clinical trials evaluating addition of immune-oncology agents and stromal TGF P signalling inhibition. Funding The Strati fi cation in Colorectal Cancer Consortium (S:CORT) was funded by the Medical Research Council and Cancer Research UK (MR/M016587/1).

Satellite-based monitoring is a key tool for supporting global food security and natural resource management but is challenged by cloud corruption and lack of labeled training data. To address these issues, self-supervised learning (SSL) techniques have been developed that first learn representations from almost limitless available unlabeled data, before using labeled samples for a specific downstream task. As the learned representations detect, integrate, and compress information in the dataset in a fully unsupervised manner, the downstream tasks require only small labeled datasets. In this study, we present spectral–temporal Barlow Twins (ST-BT), a new pixelwise SSL architecture that generates useful representations designed to be invariant to extensive cloudiness. We demonstrate that ST-BT representations enable stable and high F1 scores on the downstream task of crop classification even with cloud cover reaching 50% of available dates and using only a few labeled samples. The ST-BT representations achieve maximum F1 scores of 0.94 and 0.90 on the two benchmark classification datasets used. These results indicate that ST-BT can create useful representations of pixelwise multispectral Sentinel-2 timeseries despite cloud corruption.

Molecular stratification using gene-level transcriptional data has identified subtypes with distinctive genotypic and phenotypic traits, as exemplified by the consensus molecular subtypes (CMS) in colorectal cancer (CRC). Here, rather than gene-level data, we make use of gene ontology and biological activation state information for initial molecular class discovery. In doing so, we defined three pathway-derived subtypes (PDS) in CRC: PDS1 tumors, which are canonical/LGR5 + stem-rich, highly proliferative and display good prognosis; PDS2 tumors, which are regenerative/ANXA1 + stem-rich, with elevated stromal and immune tumor microenvironmental lineages; and PDS3 tumors, which represent a previously overlooked slow-cycling subset of tumors within CMS2 with reduced stem populations and increased differentiated lineages, particularly enterocytes and enteroendocrine cells, yet display the worst prognosis in locally advanced disease. These PDS3 phenotypic traits are evident across numerous bulk and single-cell datasets, and demark a series of subtle biological states that are currently under-represented in pre-clinical models and are not identified using existing subtyping classifiers.

Background It is uncertain which biological features underpin the response of rectal cancer (RC) to radiotherapy. No biomarker is currently in clinical use to select patients for treatment modifications. Methods We identified two cohorts of patients (total N = 249) with RC treated with neoadjuvant radiotherapy (45Gy/25) plus fluoropyrimidine. This discovery set included 57 cases with pathological complete response (pCR) to chemoradiotherapy (23%). Pre-treatment cancer biopsies were assessed using transcriptome-wide mRNA expression and targeted DNA sequencing for copy number and driver mutations. Biological candidate and machine learning (ML) approaches were used to identify predictors of pCR to radiotherapy independent of tumour stage. Findings were assessed in 107 cases from an independent validation set (GSE87211). Findings Three gene expression sets showed significant independent associations with pCR: Fibroblast-TGFβ Response Signature (F-TBRS) with radioresistance; and cytotoxic lymphocyte (CL) expression signature and consensus molecular subtype CMS1 with radiosensitivity. These associations were replicated in the validation cohort. In parallel, a gradient boosting machine model comprising the expression of 33 genes generated in the discovery cohort showed high performance in GSE87211 with 90% sensitivity, 86% specificity. Biological and ML signatures indicated similar mechanisms underlying radiation response, and showed better AUC and p-values than published transcriptomic signatures of radiation response in RC. Interpretation RCs responding completely to chemoradiotherapy (CRT) have biological characteristics of immune response and absence of immune inhibitory TGFβ signalling. These tumours may be identified with a potential biomarker based on a 33 gene expression signature. This could help select patients likely to respond to treatment with a primary radiotherapy approach as for anal cancer. Conversely, those with predicted radioresistance may be candidates for clinical trials evaluating addition of immune-oncology agents and stromal TGFβ signalling inhibition. Funding The Stratification in Colorectal Cancer Consortium (S:CORT) was funded by the Medical Research Council and Cancer Research UK (MR/M016587/1).

We introduce Hoop Diagrams, a new visualization technique for set data. Hoop Diagrams are a circular visualization with hoops representing sets and sectors representing set intersections. We present an interactive tool for drawing Hoop Diagrams and describe a user study comparing them with Linear Diagrams. The results show only small differences, with users answering questions more quickly with Linear Diagrams, but answering some questions more accurately with Hoop Diagrams. Interaction data indicates that those using set order and intersection highlighting were more successful at answering questions, but those who used other interactions had a slower response. The similarity in usability suggests that the diagram type should be chosen based on the presentation method. Linear Diagrams increase in the horizontal direction with the number of intersections, leading to difficulties fitting on a screen. Hoop Diagrams al-ways have a square aspect ratio.

Response to neoadjuvant radiotherapy (RT) in rectal cancer has been associated with immune and stromal features that are captured by transcriptional signatures. However, how such associations perform across different chemoradiotherapy regimens and within individual consensus molecular subtypes (CMS) and how they affect survival remain unclear. In this study, gene expression and clinical data of pretreatment biopsies from nine cohorts of primary rectal tumors were combined (N = 826). Exploratory analyses were done with transcriptomic signatures for the endpoint of pathologic complete response (pCR), considering treatment regimen or CMS subtype. Relevant findings were tested for overall survival and recurrence-free survival. Immune and stromal signatures were strongly associated with pCR and lack of pCR, respectively, in RT and capecitabine (Cap)/5-fluorouracil (5FU)-treated patients (N = 387), in which the radiosensitivity signature (RSS) showed the strongest association. Upon addition of oxaliplatin (Ox; N = 123), stromal signatures switched direction and showed higher chances to achieve pCR than without Ox (p for interaction 0.02). Among Cap/5FU patients, most signatures performed similarly across CMS subtypes, except cytotoxic lymphocytes that were associated with pCR in CMS1 and CMS4 cases compared with other CMS subtypes (p for interaction 0.04). The only variables associated with survival were pCR and RSS. Although the frequency of pCR across different chemoradiation regimens is relatively similar, our data suggest that response rates may differ depending on the biological landscape of rectal cancer. Response to neoadjuvant RT in stroma-rich tumors may potentially be improved by the addition of Ox. RSS in preoperative biopsies provides predictive information for response specifically to neoadjuvant RT with 5FU. SIGNIFICANCE:Rectal cancers with stromal features may respond better to RT and 5FU/Cap with the addition of Ox. Within patients not treated with Ox, high levels of cytotoxic lymphocytes associate with response only in immune and stromal tumors. Our analyses provide biological insights about the outcome by different radiotherapy regimens in rectal cancer.

The development of deep learning (DL) models to predict the consensus molecular subtypes (CMS) from histopathology images (imCMS) is a promising and cost-effective strategy to support patient stratification. Here, we investigate whether imCMS calls generated from whole slide histopathology images (WSIs) of rectal cancer (RC) pre-treatment biopsies are associated with pathological complete response (pCR) to neoadjuvant long course chemoradiotherapy (LCRT) with single agent fluoropyrimidine. DL models were trained to classify WSIs of colorectal cancers stained with hematoxylin and eosin into one of the four CMS classes using a multi-centric dataset of resection and biopsy specimens (n = 1057 WSIs) with paired transcriptional data. Classifiers were tested on a held out RC biopsy cohort (ARISTOTLE) and correlated with pCR to LCRT in an independent dataset merging two RC cohorts (ARISTOTLE, n = 114 and SALZBURG, n = 55 patients). DL models predicted CMS with high classification performance in multiple comparative analyses. In the independent cohorts (ARISTOTLE, SALZBURG), cases with WSIs classified as imCMS1 had a significantly higher likelihood of achieving pCR (OR = 2.69, 95% CI 1.01-7.17, p = 0.048). Conversely, imCMS4 was associated with lack of pCR (OR = 0.25, 95% CI 0.07-0.88, p = 0.031). Classification maps demonstrated pathologist-interpretable associations with high stromal content in imCMS4 cases, associated with poor outcome. No significant association was found in imCMS2 or imCMS3. imCMS classification of pre-treatment biopsies is a fast and inexpensive solution to identify patient groups that could benefit from neoadjuvant LCRT. The significant associations between imCMS1/imCMS4 with pCR suggest the existence of predictive morphological features that could enhance standard pathological assessment.

Doping of liquid argon TPCs (LArTPCs) with a small concentration of xenon is a technique for light-shifting and facilitates the detection of the liquid argon scintillation light. In this paper, we present the results of the first doping test ever performed in a kiloton-scale LArTPC. From February to May 2020, we carried out this special run in the single-phase DUNE Far Detector prototype (ProtoDUNE-SP) at CERN, featuring 720 t of total liquid argon mass with 410 t of fiducial mass. A 5.4 ppm nitrogen contamination was present during the xenon doping campaign. The goal of the run was to measure the light and charge response of the detector to the addition of xenon, up to a concentration of 18.8 ppm. The main purpose was to test the possibility for reduction of non-uniformities in light collection, caused by deployment of photon detectors only within the anode planes. Light collection was analysed as a function of the xenon concentration, by using the pre-existing photon detection system (PDS) of ProtoDUNE-SP and an additional smaller set-up installed specifically for this run. In this paper we first summarize our current understanding of the argon-xenon energy transfer process and the impact of the presence of nitrogen in argon with and without xenon dopant. We then describe the key elements of ProtoDUNE-SP and the injection method deployed. Two dedicated photon detectors were able to collect the light produced by xenon and the total light. The ratio of these components was measured to be about 0.65 as 18.8 ppm of xenon were injected. We performed studies of the collection efficiency as a function of the distance between tracks and light detectors, demonstrating enhanced uniformity of response for the anode-mounted PDS. We also show that xenon doping can substantially recover light losses due to contamination of the liquid argon by nitrogen.

We report the first measurement of $\pi^0$ production in neutral current (NC) interactions on argon with average neutrino energy of $\lesssim1$~GeV. We use data from the MicroBooNE detector's 85-tonne active volume liquid argon time projection chamber situated in Fermilab's Booster Neutrino Beam and exposed to $5.89\times10^{20}$ protons on target for this measurement. Measurements of NC $\pi^0$ events are reported for two exclusive event topologies without charged pions. Those include a topology with two photons from the decay of the $\pi^0$ and one proton and a topology with two photons and zero protons. Flux-averaged cross-sections for each exclusive topology and for their semi-inclusive combination are extracted (efficiency-correcting for two-plus proton final states), and the results are compared to predictions from the \textsc{genie}, \textsc{neut}, and \textsc{NuWro} neutrino event generators. We measure cross sections of $1.243\pm0.185$ (syst) $\pm0.076$ (stat), $0.444\pm0.098\pm0.047$, and $0.624\pm0.131\pm0.075$ $[10^{-38}\textrm{cm}^2/\textrm{Ar}]$ for the semi-inclusive NC$\pi^0$, exclusive NC$\pi^0$+1p, and exclusive NC$\pi^0$+0p processes, respectively.

A primary goal of the upcoming Deep Underground Neutrino Experiment (DUNE) is to measure the $\mathcal{O}(10)$ MeV neutrinos produced by a Galactic core-collapse supernova if one should occur during the lifetime of the experiment. The liquid-argon-based detectors planned for DUNE are expected to be uniquely sensitive to the $\nu_e$ component of the supernova flux, enabling a wide variety of physics and astrophysics measurements. A key requirement for a correct interpretation of these measurements is a good understanding of the energy-dependent total cross section $\sigma(E_\nu)$ for charged-current $\nu_e$ absorption on argon. In the context of a simulated extraction of supernova $\nu_e$ spectral parameters from a toy analysis, we investigate the impact of $\sigma(E_\nu)$ modeling uncertainties on DUNE's supernova neutrino physics sensitivity for the first time. We find that the currently large theoretical uncertainties on $\sigma(E_\nu)$ must be substantially reduced before the $\nu_e$ flux parameters can be extracted reliably: in the absence of external constraints, a measurement of the integrated neutrino luminosity with less than 10\% bias with DUNE requires $\sigma(E_\nu)$ to be known to about 5%. The neutrino spectral shape parameters can be known to better than 10% for a 20% uncertainty on the cross-section scale, although they will be sensitive to uncertainties on the shape of $\sigma(E_\nu)$. A direct measurement of low-energy $\nu_e$-argon scattering would be invaluable for improving the theoretical precision to the needed level.

Colorectal cancer (CRC) is usually treated with oxaliplatin-based regimens in stages II, III and IV as standard of care. However, no predictive oxaliplatin biomarker has ever been fully validated despite intensive research. Here we aimed to discover a biomarker of early progression on oxaliplatin based chemotherapy with potential use in the clinic to guide therapy selection. The COIN clinical trial was used as a discovery set selecting patients either on continuous or intermittent fluoropyrimidine chemotherapy combined with oxaliplatin. 3'RNAseq was successfully applied to primary CRCs from patients either progressing within the first 12 weeks (progressors, n=47) or progressing after 18 weeks (non-progressors, n=112). Validation was performed on two clinical trials profiled with Almac XCel microarray by the S:CORT consortium: FOCUS (N=359) and FOxTROT (N=93). The former is composed of stage IV CRCs randomised for 5FU/FA with or without oxaliplatin and the latter of high risk stage II and III CRCs treated with neoadjuvant FOLFOX. Analysis on COIN identified 29 differentially expressed genes comprising the new RNA signature. In the randomized FOCUS trial, this signature used as a continuous score in patients treated with single agent 5FU/FA (76 poor responders/211 good responders) did not show any signal (OR=1.09 (0.51-2.35), P=0.82). The FOLFOX arm was statistically underpowered (7 poor responders/67 good responders) but did show a trend in the expected direction (OR=3.25 (0.38-27.72), P=0.28) where the interaction with the 5FU/FA arm was not significant (OR=2.84 (0.14-57.07), P=0.49). In FOxTROT, using the endpoint pathological response post-treatment (69 progressors/24 non-progressors), the signature was significantly associated with poor response (OR=3.31 (1.03-10.60), P=0.04). A new RNA signature has been generated and validated in high quality clinical trial CRC data identifying patients with early progression on oxaliplatin + 5FU/FA. Despite heterogeneity in the clinical settings used, this signature has the potential to provide useful information for oxaliplatin stratification in future clinical trials.

The Deep Underground Neutrino Experiment (DUNE) is a next-generation long-baseline neutrino oscillation experiment with a primary physics goal of observing neutrino and antineutrino oscillation patterns to precisely measure the parameters governing long-baseline neutrino oscillation in a single experiment, and to test the three-flavor paradigm. DUNE's design has been developed by a large, international collaboration of scientists and engineers to have unique capability to measure neutrino oscillation as a function of energy in a broadband beam, to resolve degeneracy among oscillation parameters, and to control systematic uncertainty using the exquisite imaging capability of massive LArTPC far detector modules and an argon-based near detector. DUNE's neutrino oscillation measurements will unambiguously resolve the neutrino mass ordering and provide the sensitivity to discover CP violation in neutrinos for a wide range of possible values of $\delta_{CP}$. DUNE is also uniquely sensitive to electron neutrinos from a galactic supernova burst, and to a broad range of physics beyond the Standard Model (BSM), including nucleon decays. DUNE is anticipated to begin collecting physics data with Phase I, an initial experiment configuration consisting of two far detector modules and a minimal suite of near detector components, with a 1.2 MW proton beam. To realize its extensive, world-leading physics potential requires the full scope of DUNE be completed in Phase II. The three Phase II upgrades are all necessary to achieve DUNE's physics goals: (1) addition of far detector modules three and four for a total FD fiducial mass of at least 40 kt, (2) upgrade of the proton beam power from 1.2 MW to 2.4 MW, and (3) replacement of the near detector's temporary muon spectrometer with a magnetized, high-pressure gaseous argon TPC and calorimeter.

The ProtoDUNE-SP detector is a single-phase liquid argon time projection chamber (LArTPC) that was constructed and operated in the CERN North Area at the end of the H4 beamline. This detector is a prototype for the first far detector module of the Deep Underground Neutrino Experiment (DUNE), which will be constructed at the Sandford Underground Research Facility (SURF) in Lead, South Dakota, USA. The ProtoDUNE-SP detector incorporates full-size components as designed for DUNE and has an active volume of 7× 6× 7.2 m^3. The H4 beam delivers incident particles with well-measured momenta and high-purity particle identification. ProtoDUNE-SP's successful operation between 2018 and 2020 demonstrates the effectiveness of the single-phase far detector design. This paper describes the design, construction, assembly and operation of the detector components.

We report a search for an anomalous excess of inclusive charged-current (CC) $\nu_e$ interactions using the Wire-Cell event reconstruction package in the MicroBooNE experiment, which is motivated by the previous observation of a low-energy excess (LEE) of electromagnetic events from the MiniBooNE experiment. With a single liquid argon time projection chamber detector, the measurements of $\nu_{\mu}$ CC interactions as well as $\pi^0$ interactions are used to constrain signal and background predictions of $\nu_e$ CC interactions. A data set collected from February 2016 to July 2018 corresponding to an exposure of 6.369 $\times$ 10$^{20}$ protons on target from the Booster Neutrino Beam at FNAL is analyzed. With $x$ representing an overall normalization factor and referred to as the LEE strength parameter, we select 56 fully contained $\nu_e$ CC candidates while expecting 69.6 $\pm$ 8.0 (stat.) $\pm$ 5.0 (sys.) and 103.8 $\pm$ 9.0 (stat.) $\pm$ 7.4 (sys.) candidates after constraints for the absence (eLEE$_{x=0}$) of the median signal strength derived from the MiniBooNE observation and the presence (eLEE$_{x=1}$) of that signal strength, respectively. Under a nested hypothesis test using both rate and shape information in all available channels, the best-fit $x$ is determined to be 0 (eLEE$_{x=0}$) with a 95.5% confidence level upper limit of $x$ at 0.502. Under a simple-vs-simple hypotheses test, the eLEE$_{x=1}$ hypothesis is rejected at 3.75$\sigma$, while the eLEE$_{x=0}$ hypothesis is shown to be consistent with the observation at 0.45$\sigma$. In the context of the eLEE model, the estimated 68.3% confidence interval of the $\nu_e$ hypothesis to explain the LEE observed in the MiniBooNE experiment is disfavored at a significance level of more than 2.6$\sigma$ (3.0$\sigma$) considering MiniBooNE's full (statistical) uncertainties.