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Methods for evaluation and treatment of data shift

This is a code repository for a set of tools for detecting and mitigating data shifts in machine learning. The goal of the tools is to provide capabilities for determining when new data sets differ from training data sets and for adapting existing models to new data or correcting data shifts (via domain adaptation). The components will be written in Python, a high-level programming language that takes advantage of the Python ecosystem of high-quality open-source packages for machine learning and signal processing.

Parikh, Nidhi↗

Case studies in bias reduction and inference for electronic health record data with selection bias and phenotype misclassification

Electronic health records (EHR) are not designed for population‐based research, but they provide easy and quick access to longitudinal health information for a large number of individuals. Many statistical methods have been proposed to account for selection bias, missing data, phenotyping errors, or other problems that arise in EHR data analysis. However, addressing multiple sources of bias simultaneously is challenging. We developed a methodological framework (R package, SAMBA ) for jointly handling both selection bias and phenotype misclassification in the EHR setting that leverages external data sources. These methods assume factors related to selection and misclassification are fully observed, but these factors may be poorly understood and partially observed in practice. As a follow‐up to the methodological work, we demonstrate how to apply these methods for two real‐world case studies, and we evaluate their performance. In both examples, we use individual patient‐level data collected through the University of Michigan Health System and various external population‐based data sources. In case study (a), we explore the impact of these methods on estimated associations between gender and cancer diagnosis. In case study (b), we compare corrected associations between previously identified genetic loci and age‐related macular degeneration with gold standard external summary estimates. These case studies illustrate how to utilize diverse auxiliary information to achieve less biased inference in EHR‐based research.

60 APPLIED LIFE SCIENCES↗

Carbon Ion Radiation Therapy With Concurrent Gemcitabine for Patients With Locally Advanced Pancreatic Cancer

Purpose: To determine, in the setting of locally advanced pancreatic cancer, the maximum tolerated dose of carbon ion radiation therapy (C-ion RT) and gemcitabine dose delivered concurrently and to estimate local effect and survival. Methods and Materials: Eligibility included pathologic confirmation of pancreatic invasive ductal carcinomas and radiographically unresectable disease without metastasis. Concurrent gemcitabine was administered on days 1, 8, and 15, and the dose levels were escalated from 400 to 1000 mg/m{sup 2} under the starting dose level (43.2 GyE) of C-ion RT. The dose levels of C-ion RT were escalated from 43.2 to 55.2 GyE at 12 fractions under the fixed recommended gemcitabine dose determined. Results: Seventy-six patients were enrolled. Among the 72 treated patients, dose-limiting toxicity was observed in 3 patients: grade 3 infection in 1 patient and grade 4 neutropenia in 2 patients. Only 1 patient experienced a late grade 3 gastric ulcer and bleeding 10 months after C-ion RT. The recommended dose of gemcitabine with C-ion RT was found to be 1000 mg/m{sup 2}. The dose of C-ion RT with the full dose of gemcitabine (1000 mg/m{sup 2}) was safely increased to 55.2 GyE. The freedom from local progression rate was 83% at 2 years using the Response Evaluation Criteria in Solid Tumors. The 2-year overall survival rates in all patients and in the high-dose group with stage III (≥45.6 GyE) were 35% and 48%, respectively. Conclusions: Carbon ion RT with concurrent full-dose gemcitabine was well tolerated and effective in patients with unresectable locally advanced pancreatic cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Examination of How Well Long-Range-Corrected Density Functionals Satisfy the Ionization Energy Theorem

For this work, we calculated the vertical ionization energies (VIE) of 99 species in two ways to examine the accuracy of several long-range-corrected (LC) hybrid meta functionals in comparison with a gradient approximation (GA), global hybrids, and doubly hybrids. In the category of LC functionals, we examined both those with meta ingredients (i.e., that depend on the kinetic energy density) and those without them. The LC-hybrid meta functionals examined are M11, revM11, M11plus, and ωB97M-V. The reference data used to assess accuracy consist of 95 molecules and 4 atoms in the GW100 set. The two methods studied are the ΔSCF method (involving the difference of neutral and cation self-consistent field (SCF) energies) and the ionization energy theorem (involving the orbital energy of the highest occupied molecular orbital, HOMO). We calculated linear correlation coefficients (r 2 ) and mean absolute deviations (MADs) between each approach and the reference VIE value from the CCSD(T)/def2-TZVPP level of theory. We compared the new LC-hybrid meta calculations to calculations with the 10 functionals in a previous VIE study by Brémond et al. and to the calculations with LC-BLYP (LC-Becke, Lee–Yang–Parr), CAM-B3LYP (Coulomb-attenuating-method Becke-3-parameter Lee–Yang–Parr), LC-ωHPBE, and ωB97X-D. The results show that Minnesota LC-hybrid meta functionals have the smallest mean absolute deviation of ionization energy theorem VIEs with the reference data; the LC-ωHPBE functional also does quite well in this test. This is very encouraging and indicates that LC-hybrid meta functionals would be the best starting points for the tuning strategy that has been shown to be a very good procedure for improving time-dependent density functional calculations, and it also helps explain the good success of LC-hybrid meta functionals for molecular excitation energies.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

An assessment of low-lying excitation energies and triplet instabilities of organic molecules with an ab initio Bethe-Salpeter equation approach and the Tamm-Dancoff approximation

The accurate prediction of singlet and triplet excitation energies is an area of intense research of significant fundamental interest and critical for many applications. Most calculations of singlet and triplet energies use time-dependent density functional theory (TDDFT) in conjunction with an approximate exchange-correlation functional. In this work, we examine and critically assess an alternative method for predicting low-lying neutral excitations with similar computational cost, the ab initio Bethe-Salpeter equation (BSE) approach, and compare results against high-accuracy wavefunction-based methods. We consider singlet and triplet excitations of 27 prototypical organic molecules, including members of Thiel’s set, the acene series, and several aromatic hydrocarbons exhibiting charge-transfer-like excitations. Analogous to its impact in TDDFT, we find that the Tamm-Dancoff approximation (TDA) overcomes triplet instabilities in the BSE approach, improving both triplet and singlet energetics relative to higher level theories. Lastly, we find that BSE-TDA calculations built on effective DFT starting points, such as those utilizing optimally tuned range-separated hybrid functionals, can yield accurate singlet and triplet excitation energies for gas-phase organic molecules.

74 ATOMIC AND MOLECULAR PHYSICS↗

Neighborhood sociome factors and pediatric asthma exacerbations: Protective role of tree crown density and importance of pharmacy access in Chicago's south side

Abstract Background Pediatric asthma exacerbations remain a critical public health concern, particularly in historically underserved urban settings. Objective This study investigates sociome factors—the social context of disease—associated with asthma exacerbations among children living in Chicago's South Side, leveraging clinical and publicly available generalizable census tract‐level datasets from agencies including ChiVes, the City of Chicago Data Portal, EPA, Census Bureau, HUD, NOAA, and more. The aim is to uncover novel hypotheses for potential new interventions. Methods A generalized linear model assessed associations with the outcome of asthma exacerbations while accounting for clustering at the patient level. Predictors included all variables from the Sociome Data Commons, including social, environmental, behavioral, economic, housing, and school variables. Results Predictors of decreased risk included patient age (+4.8 years, −22%), tree crown density (+6% coverage, −17%), parks per acre (+0.41, −8%), and labor market engagement (+0.8 points, −9%). Conversely, predictors of increased risk included increased distance to the nearest pharmacy (+0.28 miles, +12%), limited English skills (+2.3%, +10%), higher inequality (+0.08 points, +8%), and visits in the Spring (+11%) and Fall (+20%). Conclusion The results suggest that tree crown density, a novel finding in the context of asthma exacerbations, may play a protective role. Limited access to health care facilities such as pharmacies continues to complicate care. Clinical Implications These findings provide hypotheses for future interventions for long‐standing asthma disparities.

Allergy↗

Physical Uncertainty Bounds (PUB)

This paper introduces and motivates the need for a new methodology for determining upper bounds on the uncertainties in simulations of engineered systems due to limited fidelity in the composite continuum-level physics models needed to simulate the systems. We show that traditional uncertainty quantification methods provide, at best, a lower bound on this uncertainty. We propose to obtain bounds on the simulation uncertainties by first determining bounds on the physical quantities or processes relevant to system performance. By bounding these physics processes, as opposed to carrying out statistical analyses of the parameter sets of specific physics models or simply switching out the available physics models, one can obtain upper bounds on the uncertainties in simulated quantities of interest.

36 MATERIALS SCIENCE↗

Mass Spectrometric Determination of Uranium and Thorium in High Radiopurity Polymers Using Ultra Low Background Electroformed Copper Crucibles for Dry Ashing

A rapid new method for determining the U and Th mass concentrations in high radiopurity plastics is described, consisting of 1) dry ashing the plastic sample and tracers in low mass crucibles made of ultra low background electroformed copper (ULB EF-Cu) foil cut and folded into boats, 2) dissolving both the ash and the boat in acid, 3) performing a column separation to remove copper, and 4) determining the elements of interest by isotope dilution mass spectrometry. This method was demonstrated on both unfluorinated and fluorinated plastics, demonstrating high tracer recoveries and detection limits to pg/g (i.e., parts per trillion) levels or below, corresponding to μBq/kg of material. Samples of biomedical polyester (Max-Prene® 955) and a fluoropolymer (polyvinylidene fluoride, PVDF) were analyzed in powder raw material forms as well as solids in the form of pellets or injection molded parts. The polyester powder contained 6 pg/g and 2 pg/g for Th and U respectively. These levels correspond to 25 and 25 μBq/kg radioactivity, respectively. Determinations on samples of PVDF powder were typically below 1 pg/g for Th and 2 pg/g for U, corresponding to 4 and 25 μBq/kg radioactivity, respectively. The use of low mass ULB EF-Cu boats for dry ashing successfully overcame the problem of crucible-generated contaminants in the analysis; absolute detection limits, calculated as 3 × standard deviation of the process blanks, were typically 20-100 fg within a sample set. Complete dissolution of the ash and low mass boat provided high tracer recoveries, and provides a convincing method to recover both the tracer and sample isotopes when full equilibration of tracer isotopes with sample isotopes is not possible prior to beginning chemical sample processing on solids.

EFCu Electroformed copper↗

Disentangling Sources of Gene Tree Discordance in Phylogenomic Data Sets: Testing Ancient Hybridizations in Amaranthaceae s.l

Gene tree discordance in large genomic data sets can be caused by evolutionary processes such as incomplete lineage sorting and hybridization, as well as model violation, and errors in data processing, orthology inference, and gene tree estimation. Species tree methods that identify and accommodate all sources of conflict are not available, but a combination of multiple approaches can help tease apart alternative sources of conflict. Here, using a phylotranscriptomic analysis in combination with reference genomes, we test a hypothesis of ancient hybridization events within the plant family Amaranthaceae s.l. that was previously supported by morphological, ecological, and Sanger-based molecular data. The data set included seven genomes and 88 transcriptomes, 17 generated for this study. We examined gene-tree discordance using coalescent-based species trees and network inference, gene tree discordance analyses, site pattern tests of introgression, topology tests, synteny analyses, and simulations. We found that a combination of processes might have generated the high levels of gene tree discordance in the backbone of Amaranthaceae s.l. Furthermore, we found evidence that three consecutive short internal branches produce anomalous trees contributing to the discordance. Overall, our results suggest that Amaranthaceae s.l. might be a product of an ancient and rapid lineage diversification, and remains, and probably will remain, unresolved. This work highlights the potential problems of identifiability associated with the sources of gene tree discordance including, in particular, phylogenetic network methods. Our results also demonstrate the importance of thoroughly testing for multiple sources of conflict in phylogenomic analyses, especially in the context of ancient, rapid radiations. We provide several recommendations for exploring conflicting signals in such situations.

59 BASIC BIOLOGICAL SCIENCES↗

Estimating groundwater dynamics at a Colorado River floodplain site using historical hydrological data and climate information

Long-term prediction of groundwater dynamics is important for assessing water resources and their impacts on biogeochemical cycling. However, estimating future groundwater dynamics is challenging due to the wide range of spatiotemporal scales in hydrological processes and uncertainty in future climate conditions. In this study, we develop a Bayesian model to combine small-scale historical hydrological data with large-scale climate information to estimate groundwater dynamics at a floodplain site in Rifle, Colorado. Although we have only a few years of groundwater elevation measurements, we have 47 years of streamflow data from a gaging station approximately 43 km upstream and long-term climate prediction on the Upper Colorado River Basin. To estimate future daily groundwater dynamics, we first develop a time series model to downscale the monthly streamflow derived from climate information to daily streamflow, and then transform the daily streamflow to groundwater dynamics at the downstream floodplain site. We use Monte Carlo methods to estimate future groundwater dynamics at the site through sampling from the joint posterior probability distribution. The results suggest that although future groundwater levels are expected to be similar to the current levels, the timing of the high groundwater levels is predicted to occur about 1 month earlier. The developed framework is extendable to other sites to estimate future groundwater dynamics given disparate data sets and climate projections. Additionally, the obtained estimates are being used as input to a site-specific watershed reactive transport models to predict how climate-induced changes will influence future biogeochemical cycling relevant to a variety of ecosystem services.

58 GEOSCIENCES↗

Sizing ramping reserve using probabilistic solar forecasts: A data-driven method

Ramping products have been introduced or proposed in several U.S. power markets to mitigate the impact of load and renewable uncertainties on market efficiency and reliability. Current methods often rely on historical data to estimate the requirements of ramping products and fail to take into account the effects of the latest weather conditions and their uncertainties, which could lead to overly conservative or insufficient requirements. This study proposes a k-nearest-neighbor-based method to give weather-informed estimates of ramping needs based on short-term probabilistic solar irradiance forecasts. Forecasts from multiple sites are employed in conjunction with principal component analysis to derive numerical classifiers to characterize system-level weather conditions. In addition, we develop a data-driven method to optimize the model parameters in a rolling-forward manner. By using real-world data from the California Independent System Operator, we design two metrics to evaluate method performance: 1) frequency of shortage and 2) oversupply of ramping product. Our proposed method presents advantages in comparison with the baseline and a set of benchmark methods: without compromising system reliability, it reduces system ramping requirements by up to 25%, therefore improving both system reliability and economics.

14 SOLAR ENERGY↗

Consensus Recommendations for Radiation Therapy Contouring and Treatment of Vulvar Carcinoma

Purpose: The purpose of this study was to develop a radiation therapy (RT) contouring atlas and recommendations for women with postoperative and locally advanced vulvar carcinoma. Methods and Materials: An international committee of 35 expert gynecologic radiation oncologists completed a survey of the treatment of vulvar carcinoma. An initial set of recommendations for contouring was discussed and generated by consensus. Two cases, 1 locally advanced and 1 postoperative, were contoured by 14 physicians. Contours were compared and analyzed using an expectation-maximization algorithm for simultaneous truth and performance level estimation (STAPLE), and a 95% confidence interval contour was developed. The level of agreement among contours was assessed using a kappa statistic. STAPLE contours underwent full committee editing to generate the final atlas consensus contours. Results: Analysis of the 14 contours showed substantial agreement, with kappa statistics of 0.69 and 0.64 for cases 1 and 2, respectively. There was high specificity for both cases (≥99%) and only moderate sensitivity of 71.3% and 64.9% for cases 1 and 2, respectively. Expert review and discussion generated consensus recommendations for contouring target volumes and treatment for postoperative and locally advanced vulvar cancer. Conclusions: These consensus recommendations for contouring and treatment of vulvar cancer identified areas of complexity and controversy. Given the lack of clinical research evidence in vulvar cancer radiation therapy, the committee advocates a conservative and consistent approach using standardized recommendations.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

On the geometric dependence of the molecular dipole polarizability in water: A benchmark study of higher-order electron correlation, basis set incompleteness error, core electron effects, and zero-point vibrational contributions

In this work, we investigate how geometric changes influence the static dipole polarizability ($α$) of a water molecule by explicitly computing the corresponding dipole polarizability surface (DPS) across 3125 total (1625 symmetry-unique) geometries using linear response coupled cluster theory including single, double, and triple excitations (LR-CCSDT) and the doubly augmented triple-$ζ$ basis set (d-aug-cc-pVTZ). Analytical formulae based on power series expansions of this $ab initio$ surface are generated using linear least-squares analysis and provide highly accurate estimates of this quantity as a function of molecular geometry (i.e., bond and angle variations) in a computationally tractable manner. An additional database, which consists of 25 representative molecular geometries and incorporates a more thorough treatment of both basis sets and core electron effects, is provided as a current benchmark for this quantity and the corresponding leading-order $C_6$ dispersion coefficient. This database has been utilized to assess the importance of these effects as well as the relative accuracy that can be obtained using several quantum chemical methods and a library of density functional approximations. In addition to high-level electron correlation methods (like CCSD) and our analytical least-squares formulae, we find that the SCAN0, PBE0, MN15, and B97-2 hybrid functionals yield the most accurate descriptions of the molecular polarizability tensor in H 2 O. Using first-order perturbation theory, we compute the zero-point vibrational correction to $α$ at the CCSDT/d-aug-cc-pVTZ level and find that this correction contributes approximately 3% to the isotropic ($α$ iso ) and nearly 50% to the anisotropic ($α$ aniso ) polarizability values. In doing so, we find that $α$ iso = 9.8307 bohr 3 , which is in excellent agreement with the experimental value of 9.83 ± 0.02 bohr 3 provided by Russell and Spackman. The DPS reported herein provides a benchmark-quality quantum mechanical estimate of this fundamental quantity of interest and should find extensive use in the development (and assessment) of next-generation force fields and machine-learning based approaches for modeling water in complex condensed-phase environments.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Discriminative versus generative approaches to simulation-based inference

Most of the fundamental, emergent, and phenomenological parameters of particle and nuclear physics are determined through parametric template fits. Simulations are used to populate histograms which are then matched to data. This approach is inherently lossy, since histograms are binned and low-dimensional. Deep learning has enabled unbinned and high-dimensional parameter estimation through neural likelihood(-ratio) estimation. We compare two approaches for neural simulation-based inference (NSBI): one based on discriminative learning (classification) and one based on generative modeling. These two approaches are directly evaluated on the same datasets, with a similar level of hyperparameter optimization in both cases. In addition to a Gaussian dataset, we study NSBI using a Higgs boson dataset from the FAIR Universe Challenge. We find that both the direct likelihood and likelihood ratio estimation are able to effectively extract parameters with reasonable uncertainties. For the numerical examples and within the set of hyperparameters studied, we found that the likelihood ratio method is more accurate and/or precise. Both methods have a significant spread from the network training and would require ensembling or other mitigation strategies in practice.

high energy physics↗

CSGL: chemical synthesis graph learning for molecule representation

Abstract Motivation Molecule representation learning (MRL) translates molecules into a real vector space, serving as input to downstream tasks in biology, chemistry, and computer science. This article introduces a chemical synthesis graph learning (CSGL) framework, which enhances MRL by considering both the atomic structures of molecules and their roles in chemical reactions through a hierarchical graph representation. Specifically, molecules are first modeled based on their molecular graphs, which capture atomic-level structural information. They are then further refined using a chemical synthesis graph, where nodes represent reactant and product molecule sets, and edges encode chemical transformations between reactants and products (e.g. changes in molecular structures). CSGL optimizes molecular embeddings of reactant and product nodes in a fashion that ensures the embeddings conform to a chemical balance constraint. Results Experimental results show that our method CSGL achieves strong performance on a variety of tasks, including product prediction, reaction classification, and molecular property prediction. Availability and implementation https://github.com/li-2023/CSGL.

Biochemistry & Molecular Biology↗

The Architecture of Metabolism Maximizes Biosynthetic Diversity in the Largest Class of Fungi

Abstract Ecological diversity in fungi is largely defined by metabolic traits, including the ability to produce secondary or “specialized” metabolites (SMs) that mediate interactions with other organisms. Fungal SM pathways are frequently encoded in biosynthetic gene clusters (BGCs), which facilitate the identification and characterization of metabolic pathways. Variation in BGC composition reflects the diversity of their SM products. Recent studies have documented surprising diversity of BGC repertoires among isolates of the same fungal species, yet little is known about how this population-level variation is inherited across macroevolutionary timescales. Here, we applied a novel linkage-based algorithm to reveal previously unexplored dimensions of diversity in BGC composition, distribution, and repertoire across 101 species of Dothideomycetes, which are considered the most phylogenetically diverse class of fungi and known to produce many SMs. We predicted both complementary and overlapping sets of clustered genes compared with existing methods and identified novel gene pairs that associate with known secondary metabolite genes. We found that variation among sets of BGCs in individual genomes is due to nonoverlapping BGC combinations and that several BGCs have biased ecological distributions, consistent with niche-specific selection. We observed that total BGC diversity scales linearly with increasing repertoire size, suggesting that secondary metabolites have little structural redundancy in individual fungi. We project that there is substantial unsampled BGC diversity across specific families of Dothideomycetes, which will provide a roadmap for future sampling efforts. Our approach and findings lend new insight into how BGC diversity is generated and maintained across an entire fungal taxonomic class.

59 BASIC BIOLOGICAL SCIENCES↗

Limits on Stellar-Mass Compact Objects as Dark Matter from Gravitational Lensing of Type Ia Supernovae

We present that the nature of dark matter (DM) remains unknown despite very precise knowledge of its abundance in the Universe. An alternative to new elementary particles postulates DM as made of macroscopic compact halo objects (MACHO) such as black holes formed in the very early Universe. Stellar-mass primordial black holes (PBHs) are subject to less robust constraints than other mass ranges and might be connected to gravitational-wave signals detected by the Laser Interferometer Gravitational-Wave Observatory (LIGO). New methods are therefore necessary to constrain the viability of compact objects as a DM candidate. Here we report bounds on the abundance of compact objects from gravitational lensing of type Ia supernovae (SNe). Current SNe data sets constrain compact objects to represent less than 35.2% (Joint Lightcurve Analysis) and 37.2% (Union 2.1) of the total matter content in the Universe, at 95% confidence level. The results are valid for masses larger than ~ 0.01 M ⊙ (solar masses), limited by the size SNe relative to the lens Einstein radius. We demonstrate the mass range of the constraints by computing magnification probabilities for realistic SNe sizes and different values of the PBH mass. Our bounds are sensitive to the total abundance of compact objects with M ≳ 0.01 M ⊙ and complementary to other observational tests. These results are robust against cosmological parameters, outlier rejection, correlated noise, and selection bias. PBHs and other MACHOs are therefore ruled out as the dominant form of DM for objects associated to LIGO gravitational wave detections. Lastly, these bounds constrain early-Universe models that predict stellar-mass PBH production and strengthen the case for lighter forms of DM, including new elementary particles.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Model-ready benchmarks for NPP, ANPP, litter fluxes, and recruitment into the 1 cm dbh size class

The intended use of this dataset is to serve as an observational benchmark to evaluate model predictions of NPP, ANPP, litter fluxes, and recruitment at Barro Colorado Island, Panama. This dataset contains four CSV files and one text file. “Benchmarks-NPP-ANPP-R-L.csv” provides estimates of annual ecosystem-level reproductive litter flux (R), leaf litter flux (L), aboveground net primary productivity (ANPP), and net primary productivity (NPP) for 61 field plots throughout tropical, temperate, and boreal forest biomes. An additional 499 plots (n = 550) include estimates of just R, L, and R/L. Each row reports a distinct set of estimates for one sampling interval at one plot. “Metadata-Benchmarks-NPP-ANPP-R-L.csv” contains field descriptions for all data fields in “Benchmarks-NPP-ANPP-R-L.csv”. “References-Benchmarks-NPP-ANPP-R-L.txt” contains full references to the original studies used to produce the observations at each plot included in the data. “Benchmarks-Recruitment.csv” provides estimates of species-level recruitment rates into the 1 cm dbh size class at four CTFS-ForestGeo sites using methods that account for unobserved mortality of new recruits between census intervals (Kohyama et al., 2018). “Metadata-Benchmarks-Recruitment.csv” contains field descriptions for all data fields in “Benchmarks-Recruitment.csv”.

54 ENVIRONMENTAL SCIENCES↗