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Computational models are an essential tool for the design, characterization, and discovery of novel materials. Computationally hard tasks in materials science stretch the limits of existing high-performance supercomputing centers, consuming much of their resources for simulation, analysis, and data processing. Quantum computing, on the other hand, is an emerging technology with the potential to accelerate many of the computational tasks needed for materials science. In order to do that, the quantum technology must interact with conventional high-performance computing in several ways: approximate results validation, identification of hard problems, and synergies in quantum-centric supercomputing. In this paper, we provide a perspective on how quantum-centric supercomputing can help address critical computational problems in materials science, the challenges to face in order to solve representative use cases, and new suggested directions.

Existing haptic actuators are often rigid and limited in their ability to replicate real-world tactile sensations. We present a wearable haptic artificial muscle skin (HAMS) based on fully soft, millimeter-scale, multilayer dielectric elastomer actuators (DEAs) capable of significant out-of-plane deformation, a capability that typically requires rigid or liquid biasing. The DEAs use a thickness-varying multilayer structure to achieve large out-of-plane displacement and force, maintaining comfort and wearability. Experimental results demonstrate that HAMS can produce complex tactile feedback with high perception accuracy. Moreover, we show that HAMS can be integrated into extended reality (XR) systems, enhancing immersion and offering potential applications in entertainment, education, and assistive technologies.

Behavioral speech tasks have been widely used to understand the mechanisms of speech motor control in typical speakers as well as in various clinical populations. However, determining which neural functions differ between typical speakers and clinical populations based on behavioral data alone is difficult because multiple mechanisms may lead to the same behavioral differences. For example, individuals with cerebellar ataxia (CA) produce atypically large compensatory responses to pitch perturbations in their auditory feedback, compared to typical speakers, but this pattern could have many explanations. Here, computational modeling techniques were used to address this challenge. Bayesian inference was used to fit a state feedback control (SFC) model of voice fundamental frequency (fo) control to the behavioral pitch perturbation responses of speakers with CA and typical speakers. This fitting process resulted in estimates of posterior likelihood distributions for five model parameters (sensory feedback delays, absolute and relative levels of auditory and somatosensory feedback noise, and controller gain), which were compared between the two groups. Results suggest that the speakers with CA may proportionally weight auditory and somatosensory feedback differently from typical speakers. Specifically, the CA group showed a greater relative sensitivity to auditory feedback than the control group. There were also large group differences in the controller gain parameter, suggesting increased motor output responses to target errors in the CA group. These modeling results generate hypotheses about how CA may affect the speech motor system, which could help guide future empirical investigations in CA. This study also demonstrates the overall proof-of-principle of using this Bayesian inference approach to understand behavioral speech data in terms of interpretable parameters of speech motor control models.

ObjectiveDevelop a multi-functional imaging system that combines 1.7μm optical coherence tomography/angiography (OCT/OCTA) to accurately interrogate Hereditary Hemorrhagic Telangiectasia (HHT) skin lesions.MethodsThe study involved imaging HHT skin lesions on five subjects including lips, hands, and chest. We assessed the attributes of both HHT lesions and the healthy vasculature around them in these individuals, employing quantifiable measures such as vascular density and diameter. Additionally, we performed scans on an HHT patient who had undergone anti-angiogenic therapy, allowing us to observe changes in vasculature before and after treatment.ResultsThe results from this pilot study demonstrate the feasibility of evaluating the HHT lesion using this novel methodology and suggest the potential of OCTA to noninvasively track HHT lesions over time. The average percentage change in density between HHT patients' lesions and control was 37%. The percentage increase in vessel diameter between lesion and control vessels in HHT patients was 23.21%.ConclusionIn this study, we demonstrated that OCTA, as a functional extension of OCT, can non-invasively scan HHT lesions in vivo. We scanned five subjects with HHT lesions in various areas (lip, ear, finger, and palm) and quantified vascular density and diameter in both the lesions and adjacent healthy tissue. This non-invasive method will permit a more comprehensive examination of HHT lesions.SignificanceThis method of non-invasive imaging could offer new insights into the physiology, management, and therapeutics of HHT-associated lesion development and bleeding.

Alterations in the nuclear envelope are linked to a variety of rare diseases termed laminopathies. A single amino acid substitution at position 12 (A12T) of the human nuclear envelope protein BAF (Barrier to Autointegration Factor) causes Néstor-Guillermo Progeria Syndrome (NGPS). This premature ageing condition leads to growth retardation and severe skeletal defects, but the underlying mechanisms are unknown. Here, we have generated a novel in vivo model for NGPS by modifying the baf-1 locus in C. elegans to mimic the human NGPS mutation. These baf-1(G12T) mutant worms displayed multiple phenotypes related to fertility, lifespan, and stress resistance. Importantly, nuclear morphology deteriorated faster during aging in baf-1(G12T) compared to wild-type animals, recapitulating an important hallmark of cells from progeria patients. Although localization of BAF-1(G12T) was similar to wild-type BAF-1, lamin accumulation at the nuclear envelope was reduced in mutant worms. Tissue-specific chromatin binding and transcriptome analyses showed reduced BAF-1 association in most genes deregulated by the baf-1(G12T) mutation, suggesting that altered BAF chromatin association induces NGPS phenotypes via altered gene expression.

Observation of glacier surface characteristics through remotely sensed time-series data is essential for understanding glacier seasonality, mass balance, and long-term trends. Yet, the reliability of these observations depends significantly on the quality of the time-series data. This study presents a meticulous preprocessing scheme to improve the quality of Moderate Resolution Imaging Spectroradiometer (MODIS) Normalized Difference Snow Index (NDSI) time-series data for glacier monitoring. We propose a three-step algorithm specifically crafted to overcome the challenges associated with cloud contamination reduction, outlier removal and data gap handling. This innovative approach iteratively compares the median values of automatically adjusted asymmetrical moving windows to achieve convergence, removing outliers using minimal window size to keep the temporal resolution as high as possible. The methodology’s effectiveness is demonstrated through its application to two glaciers from the United States Geological Survey (USGS) Benchmark Project, showcasing significant improvements in the quality of smoothed MODIS NDSI time series. These results affirm the efficacy of the proposed scheme in rendering a more reliable evaluation of glacier surface condition and seasonal fluctuations. Consequently, this study contributes significant methodological advancements to the fields of remote sensing and glaciology, enhancing the accuracy of glacier monitoring techniques.

Memory for temporal structure enables both planning of future events and retrospection of past events. We investigated how the brain flexibly represents extended temporal sequences into the past and future during anticipation. Participants learned sequences of environments in immersive virtual reality. Pairs of sequences had the same environments in a different order, enabling context-specific learning. During fMRI, participants anticipated upcoming environments multiple steps into the future in a given sequence. Temporal structure was represented in the hippocampus and across higher-order visual regions (1) bidirectionally, with graded representations into the past and future and (2) hierarchically, with further events into the past and future represented in successively more anterior brain regions. In hippocampus, these bidirectional representations were context-specific, and suppression of far-away environments predicted response time costs in anticipation. Together, this work sheds light on how we flexibly represent sequential structure to enable planning over multiple timescales.

Self-control plays a pivotal role in pursuing long-term goals related to health and financial well-being. While ample evidence suggests that humans are prone to occasional self-control lapses, little is known about how changes in emotional and attentional states affect the ability to maintain self-control. In two studies (N1 = 109 and N2 = 90), we used emotion recognition software to decode participants' facial expressions while manipulating their attentional and emotional states during a Psychomotor Vigilance Task (PVT) before exerting self-control in a subsequent task. Our findings reveal dissociable roles of attention and valence in maintaining self-control, depending on the distinct demands of the task. Specifically, performance in a subsequent cognitive task was predominantly associated with changes in attentional states during the PVT rather than valence. Conversely, preferences in a subsequent social task were associated with changes in valence states during the PVT, while attention showed no effect. This dissociation between attention-invoked and emotion-invoked lapses in self-control holds significant implications for psychological and economic models of self-control, ultimately contributing to the development of policies to mitigate the detrimental consequences of individual self-control lapses.

Despite their role as innate sentinels, macrophages can serve as cellular reservoirs of chikungunya virus (CHIKV), a highly-pathogenic arthropod-borne alphavirus that has caused large outbreaks among human populations. Here, with the use of viral chimeras and evolutionary selection analysis, we define CHIKV glycoproteins E1 and E2 as critical for virion production in THP-1 derived human macrophages. Through proteomic analysis and functional validation, we further identify signal peptidase complex subunit 3 (SPCS3) and eukaryotic translation initiation factor 3 subunit K (eIF3k) as E1-binding host proteins with anti-CHIKV activities. We find that E1 residue V220, which has undergone positive selection, is indispensable for CHIKV production in macrophages, as its mutation attenuates E1 interaction with the host restriction factors SPCS3 and eIF3k. Finally, we show that the antiviral activity of eIF3k is translation-independent, and that CHIKV infection promotes eIF3k translocation from the nucleus to the cytoplasm, where it associates with SPCS3. These functions of CHIKV glycoproteins late in the viral life cycle provide a new example of an intracellular evolutionary arms race with host restriction factors, as well as potential targets for therapeutic intervention.

ObjectiveAlthough supervised machine learning is popular for information extraction from clinical notes, creating large annotated datasets requires extensive domain expertise and is time-consuming. Meanwhile, large language models (LLMs) have demonstrated promising transfer learning capability. In this study, we explored whether recent LLMs could reduce the need for large-scale data annotations.Materials and methodsWe curated a dataset of 769 breast cancer pathology reports, manually labeled with 12 categories, to compare zero-shot classification capability of the following LLMs: GPT-4, GPT-3.5, Starling, and ClinicalCamel, with task-specific supervised classification performance of 3 models: random forests, long short-term memory networks with attention (LSTM-Att), and the UCSF-BERT model.ResultsAcross all 12 tasks, the GPT-4 model performed either significantly better than or as well as the best supervised model, LSTM-Att (average macro F1-score of 0.86 vs 0.75), with advantage on tasks with high label imbalance. Other LLMs demonstrated poor performance. Frequent GPT-4 error categories included incorrect inferences from multiple samples and from history, and complex task design, and several LSTM-Att errors were related to poor generalization to the test set.DiscussionOn tasks where large annotated datasets cannot be easily collected, LLMs can reduce the burden of data labeling. However, if the use of LLMs is prohibitive, the use of simpler models with large annotated datasets can provide comparable results.ConclusionsGPT-4 demonstrated the potential to speed up the execution of clinical NLP studies by reducing the need for large annotated datasets. This may increase the utilization of NLP-based variables and outcomes in clinical studies.

The Proof-of-Work algorithm that underlies Bitcoin, Ethereum w , 1 and many other cryptocurrencies is well known for its energy-intensive requirements. The Proof-of-Stake algorithm that underlies Ethereum and various other cryptocurrencies is less impactful environmentally, but it has a second, looming issue: the problem of wealth inequality. We have developed an alternative to Proof-of-Work and Proof-of-Stake, called Proof-by-Location, that has the potential to address both of these issues. This article describes Proof-by-Location and a financial platform called Xylem that is based on it. This platform seeks to distribute transaction fees to billions of cryptocurrency “Notaries” around the world (essentially, anyone with a smartphone), who work together to establish a distributed consensus about financial transactions. In this article, we demonstrate that this platform can scale to more than 3.9 trillion transactions per year (more than triple the number of digital payments per year currently occurring). We show a reduction of electricity usage per transaction of 99.9999914% compared to Bitcoin, 99.999905% compared to Ethereum w , 99.83% compared to Ethereum, and 95.9% compared to the Visa financial services company. We demonstrate that this platform would have a redistributive rather than consolidatory effect on wealth compared to any of these platforms, leading to a source of income for more than 1 billion people around the world, including more than 110 million in the bottom 10th to 20th percentile by income, with income for that group equivalent to 8.8 million full-time jobs. Finally, this currency provides a positive, non-compulsory mechanism for shaping human habitation patterns in ways that can slow global biodiversity loss and enable ecological restoration. Using Xylem as a global financial infrastructure could lead to significantly better social and environmental outcomes than existing financial platforms. 2

Alon, Seymour, and Thomas [J. Amer. Math. Soc., 3 (1990), pp. 801-808] proved that every n-vertex graph excluding Kt as a minor has treewidth less than t3/2 \surdn. Illingworth, Scott, and Wood [Product Structure of Graphs with an Excluded Minor, preprint, arXiv:2104.06627, 2022] recently refined this result by showing that every such graph is a subgraph of some graph with treewidth t - 2, where each vertex is blown up by a complete graph of order \scrO(\surdtn). Solving an open problem of Illingworth, Scott, and Wood [2022], we prove that the treewidth bound can be reduced to 4 while keeping blowups of order \scrOt(\surdn). As an extension of the Lipton-Tarjan theorem, in the case of planar graphs, we show that the treewidth can be further reduced to 2, which is best possible. We generalize this result for K3,t-minor-free graphs, with blowups of order \scrO(t\surdn). This setting includes graphs embeddable on any fixed surface.

Advanced omics technologies and facilities generate a wealth of valuable data daily; however, the data often lack the essential metadata required for researchers to find, curate, and search them effectively. The lack of metadata poses a significant challenge in the utilization of these data sets. Machine learning (ML)-based metadata extraction techniques have emerged as a potentially viable approach to automatically annotating scientific data sets with the metadata necessary for enabling effective search. Text labeling, usually performed manually, plays a crucial role in validating machine-extracted metadata. However, manual labeling is time-consuming and not always feasible; thus, there is a need to develop automated text labeling techniques in order to accelerate the process of scientific innovation. This need is particularly urgent in fields such as environmental genomics and microbiome science, which have historically received less attention in terms of metadata curation and creation of gold-standard text mining data sets. In this paper, we present two novel automated text labeling approaches for the validation of ML-generated metadata for unlabeled texts, with specific applications in environmental genomics. Our techniques show the potential of two new ways to leverage existing information that is only available for select documents within a corpus to validate ML models, which can then be used to describe the remaining documents in the corpus. The first technique exploits relationships between different types of data sources related to the same research study, such as publications and proposals. The second technique takes advantage of domain-specific controlled vocabularies or ontologies. In this paper, we detail applying these approaches in the context of environmental genomics research for ML-generated metadata validation. Our results show that the proposed label assignment approaches can generate both generic and highly specific text labels for the unlabeled texts, with up to 44% of the labels matching with those suggested by a ML keyword extraction algorithm.

Phenotypic data are critical for understanding biological mechanisms and consequences of genomic variation, and are pivotal for clinical use cases such as disease diagnostics and treatment development. For over a century, vast quantities of phenotype data have been collected in many different contexts covering a variety of organisms. The emerging field of phenomics focuses on integrating and interpreting these data to inform biological hypotheses. A major impediment in phenomics is the wide range of distinct and disconnected approaches to recording the observable characteristics of an organism. Phenotype data are collected and curated using free text, single terms or combinations of terms, using multiple vocabularies, terminologies, or ontologies. Integrating these heterogeneous and often siloed data enables the application of biological knowledge both within and across species. Existing integration efforts are typically limited to mappings between pairs of terminologies; a generic knowledge representation that captures the full range of cross-species phenomics data is much needed. We have developed the Unified Phenotype Ontology (uPheno) framework, a community effort to provide an integration layer over domain-specific phenotype ontologies, as a single, unified, logical representation. uPheno comprises (1) a system for consistent computational definition of phenotype terms using ontology design patterns, maintained as a community library; (2) a hierarchical vocabulary of species-neutral phenotype terms under which their species-specific counterparts are grouped; and (3) mapping tables between species-specific ontologies. This harmonized representation supports use cases such as cross-species integration of genotype-phenotype associations from different organisms and cross-species informed variant prioritization.

Super-resolution fluorescence imaging has offered unprecedented insights and revolutionized our understanding of biology. In particular, localized plasmonic structured illumination microscopy (LPSIM) achieves video-rate super-resolution imaging with ∼50 nm spatial resolution by leveraging subdiffraction-limited nearfield patterns generated by plasmonic nanoantenna arrays. However, the conventional trial-and-error design process for LPSIM arrays is time-consuming and computationally intensive, limiting the exploration of optimal designs. Here, we propose a hybrid inverse design framework combining deep learning and genetic algorithms to refine LPSIM arrays. A population of designs is evaluated using a trained convolutional neural network, and a multiobjective optimization method optimizes them through iteration and evolution. Simulations demonstrate that the optimized LPSIM substrate surpasses traditional substrates, exhibiting higher reconstruction accuracy, robustness against noise, and increased tolerance for fewer measurements. This framework not only proves the efficacy of inverse design for tailoring LPSIM substrates but also opens avenues for exploring new plasmonic nanostructures in imaging applications.

Several models of visual search consider visual attention as part of a perceptual inference process, in which top-down priors disambiguate bottom-up sensory information. Many of these models have focused on gaze behavior, but there are relatively fewer models of covert spatial attention, in which attention is directed to a peripheral location in visual space without a shift in gaze direction. Here, we propose a biologically plausible model of covert attention during visual search that helps to bridge the gap between Bayesian modeling and neurophysiological modeling by using (1) top-down priors over target features that are acquired through Hebbian learning, and (2) spatial resampling of modeled cortical receptive fields to enhance local spatial resolution of image representations for downstream target classification. By training a simple generative model using a Hebbian update rule, top-down priors for target features naturally emerge without the need for hand-tuned or predetermined priors. Furthermore, the implementation of covert spatial attention in our model is based on a known neurobiological mechanism, providing a plausible process through which Bayesian priors could locally enhance the spatial resolution of image representations. We validate this model during simulated visual search for handwritten digits among nondigit distractors, demonstrating that top-down priors improve accuracy for estimation of target location and classification, relative to bottom-up signals alone. Our results support previous reports in the literature that demonstrated beneficial effects of top-down priors on visual search performance, while extending this literature to incorporate known neural mechanisms of covert spatial attention.

Contour trees describe the topology of level sets in scalar fields and are widely used in topological data analysis and visualization. A main challenge of utilizing contour trees for large-scale scientific data is their computation at scale using highperformance computing. To address this challenge, recent work has introduced distributed hierarchical contour trees for distributed computation and storage of contour trees. However, effective use of these distributed structures in analysis and visualization requires subsequent computation of geometric properties and branch decomposition to support contour extraction and exploration. In this work, we introduce distributed algorithms for augmentation, hypersweeps, and branch decomposition that enable parallel computation of geometric properties, and support the use of distributed contour trees as query structures for scientific exploration. We evaluate the parallel performance of these algorithms and apply them to identify and extract important contours for scientific visualization.

This work presents a detailed case study on using Generative AI (GenAI) to develop AI surrogates for simulation models in fusion energy research. The scope includes the methodology, implementation, and results of using GenAI to assist in model development and optimization, comparing these results with previous manually developed models.

Human papillomavirus (HPV) is the most common sexually transmitted infection on U.S. college campuses. Although HPV vaccination is recommended through age 26, current efforts to improve vaccination rates have predominantly focused on adolescents. Consequently, vaccine uptake remains suboptimal among young adults. This represents a significant missed opportunity, as young adults face the highest risk for new HPV infections. To contextualize the factors impacting decision-making process for this vulnerable population, this study reports key themes that emerged from in-depth interviews with participants (N = 30) who had completed an online intervention study for HPV vaccination among college students. Twelve (40%) of the interviewees vaccinated after exposure to the intervention. Findings centered around empowerment among young adults as the facilitator to get the HPV vaccine: key themes emerged were (1) convenience is critical and empowering; (2) adulthood identity, marked by a heightened sense of autonomy, accountability, and responsibility for self/future self and others, is empowering; (3) equal access to health care and preventive resources is empowering, especially for participants with low socioeconomic status; and (4) accurate knowledge provided in the intervention destigmatized HPV vaccination to empower young adults to make informed decisions. Digital interventions with messages highlighting a newly gained autonomy, future-oriented self and social responsibility, inclusive and accurate knowledge, and providing navigation to improve access may enhance HPV vaccination among young adults.

As one of the most complex systems known to science, modeling brain behavior and function is both fascinating and extremely difficult. Empirical data is increasingly available from ex vivo human brain organoids and surgical samples, as well as in vivo animal models, so the problem of modeling the behavior of large-scale neuronal systems is more relevant than ever. The statistical physics concept of a mean-field model offers a tractable way to bridge the gap between single-neuron and population-level descriptions of neuronal activity, by modeling the behavior of a single representative neuron and extending this to the population. However, existing neural mean-field methods typically either take the limit of small interaction sizes, or are applicable only to the specific neuron models for which they were derived. This paper derives a mean-field model by fitting a transfer function called Refractory SoftPlus, which is simple yet applicable to a broad variety of neuron types. The transfer function is fitted numerically to simulated spike time data, and is entirely agnostic to the underlying neuronal dynamics. The resulting mean-field model predicts the response of a network of randomly connected neurons to a time-varying external stimulus with a high degree of accuracy. Furthermore, it enables an accurate approximate bifurcation analysis as a function of the level of recurrent input. This model does not assume large presynaptic rates or small postsynaptic potential size, allowing mean-field models to be developed even for populations with large interaction terms.

Everyone agrees that feelings and actions are intertwined, but cannot agree how. According to dominant models, actions are directed by estimates of value and these values shape or are shaped by affect. I propose instead that affect is the only form of value that drives actions. Our mind constantly represents potential future states and how they would make us feel. These states collectively form a gradient reflecting feelings we could experience depending on actions we take. Motivated behavior reflects the process of traversing this affective gradient, towards desirable states and away from undesirable ones. This affective gradient hypothesis solves the puzzle of where values and goals come from, and offers a parsimonious account of apparent conflicts between emotion and cognition.

Prior work has suggested that visual working memory as measured in change detection tasks can be based on recollection, whereby participants consciously identify a specific feature of a stimulus that has changed, or on familiarity, whereby participants sense that a change has occurred but are unable to consciously access what has changed. Whether recollection and familiarity also contribute to auditory working memory is unclear. The present study aims to address that gap in knowledge by having participants make confidence judgments in change detection tests for speech sounds and pure tones. The results indicated that both recollection and familiarity contribute to auditory working memory across a variety of conditions, and showed that these two processes are functionally dissociable. With speech sounds, subjects were better able to detect syllable changes compared to tone or location changes, and this benefit reflected a selective increase in recollection rather than familiarity. Moreover, for pure tones, both recollection and familiarity also contributed to performance, but recollection was found to be selectively eliminated under stimulus-limited test conditions (i.e., noise-masked, brief dichotic presentations). The results indicate that recollection and familiarity contribute to auditory working memory in a manner that is functionally similar to that observed in visual working memory.

It is well known that people will exert effort on a task if sufficiently motivated, but how they distribute these efforts across different strategies (e.g., efficiency vs. caution) remains uncertain. Past work has shown that people invest effort differently for potential positive outcomes (rewards) versus potential negative outcomes (penalties). However, this research failed to account for differences in the context in which negative outcomes motivate someone - either as punishment or reinforcement. It is therefore unclear whether effort profiles differ as a function of outcome valence, motivational context, or both. Using computational modeling and our novel Multi-Incentive Control Task, we show that the influence of aversive outcomes on one's effort profile is entirely determined by their motivational context. Participants (N:91) favored increased caution in response to larger penalties for incorrect responses, and favored increased efficiency in response to larger reinforcement for correct responses, whether positively or negatively incentivized. STATEMENT OF RELEVANCE: People have to constantly decide how to allocate their mental effort, and in doing so can be motivated by both the positive outcomes that effort accrues and the negative outcomes that effort avoids. For example, someone might persist on a project for work in the hopes of being promoted or to avoid being reprimanded or even fired. Understanding how people weigh these different types of incentives is critical for understanding variability in human achievement as well as sources of motivational impairments (e.g., in major depression). We show that people not only consider both potential positive and negative outcomes when allocating mental effort, but that the profile of effort they engage under negative incentives differs depending on whether that outcome is contingent on sustaining good performance (negative reinforcement) or avoiding bad performance (punishment). Clarifying the motivational factors that determine effort exertion is an important step for understanding motivational impairments in psychopathology.

Inspired by recent human studies, this paper investigates the benefits of employing varying navigation strategies in robot teams. We explore how mixed navigation strategies impact task completion time, environment exploration, and overall system effectiveness in multi-robot systems. Experiments were conducted in a simulated rectangular environment using Clearpath PR2 robots and evaluated different navigation strategies observed in humans: 1) Route (RT) knowledge where agents follow a predefined path, 2) Survey (SW) knowledge where agents take the shortest path while avoiding obstacles, 3) Mixed strategies with varying proportions, such as 40% RT and 60% SW (0.4RT 0.6SW) and 60% RT and 40% SW (0.6RT 0.4SW), and 4) An additional strategy where agents switch from RT to SW 10% of the time (0.9RT 0.1SW). While SW strategy is the most time-efficient, RT strategy covers more of the environment. Mixed strategies offer a balanced trade-off. These findings highlight the advantages of variability in navigation strategies, suggesting benefits in both biological and robotic populations. Additionally, we have observed that human participants in a similar study would start on a route, and then 10% of the time switch to survey. Therefore, we investigate a 90% Route 10% Survey (0.9RT 0.1SW) strategy for individual team members. While a pure Survey strategy is the most efficient regarding time taken and a pure Route strategy covers more of the environment, a mixture of strategies appears to be a beneficial tradeoff between time taken to complete a mission and area coverage. These results highlight the advantages of population variability, suggesting potential benefits in both biological and robotic populations.

We present a new software module, QRCODE (Quantum Research for Calculating Optically Driven Excitations), for massively parallelized real-time time-dependent density functional theory (RT-TDDFT) calculations of periodic systems in the open-source Qbox software package. Our approach utilizes a custom implementation of a fast Fourier transformation scheme that significantly reduces inter-node message passing interface (MPI) communication of the major computational kernel and shows impressive scaling up to 16,344 CPU cores. In addition to improving computational performance, QRCODE contains a suite of various time propagators for accurate RT-TDDFT calculations. As benchmark applications of QRCODE, we calculate the current density and optical absorption spectra of hexagonal boron nitride (h-BN) and photo-driven reaction dynamics of the ozone-oxygen reaction. We also calculate the second and higher harmonic generation of monolayer and multi-layer boron nitride structures as examples of large material systems. Our optimized implementation of RT-TDDFT in QRCODE enables large-scale calculations of real-time electron dynamics of chemical and material systems with enhanced computational performance and impressive scaling across several thousand CPU cores.

During brain disease, astrocytes can reprogram into a reactive state that alters many of their functions. Here, we present a protocol for studying neuroinflammation and reactive astrogliosis in mice using lipopolysaccharide (LPS) from E. coli. We describe steps for employing the Lcn2CreERT2 mouse crossed into a fluorescent Cre reporter line to label a subset of reactive astrocytes during and after inflammation. We then detail procedures for the longitudinal study of reactive astrocytes during the induction, progression, and/or resolution of astrogliosis. For complete details on the use and execution of this protocol, please refer to Agnew-Svoboda et al.1.

Charged particle reconstruction in the presence of many simultaneous proton–proton (pp) collisions in the LHC is a challenging task for the ATLAS experiment’s reconstruction software due to the combinatorial complexity. This paper describes the major changes made to adapt the software to reconstruct high-activity collisions with an average of 50 or more simultaneous pp interactions per bunch crossing (pile-up) promptly using the available computing resources. The performance of the key components of the track reconstruction chain and its dependence on pile-up are evaluated, and the improvement achieved compared to the previous software version is quantified. For events with an average of 60pp collisions per bunch crossing, the updated track reconstruction is twice as fast as the previous version, without significant reduction in reconstruction efficiency and while reducing the rate of combinatorial fake tracks by more than a factor two.

The Electron-Ion Collider (EIC), a state-of-the-art facility for studying the strong force, is expected to begin commissioning its first experiments in 2028. This is an opportune time for artificial intelligence (AI) to be included from the start at this facility and in all phases that lead up to the experiments. The second annual workshop organized by the AI4EIC working group, which recently took place, centered on exploring all current and prospective application areas of AI for the EIC. This workshop is not only beneficial for the EIC, but also provides valuable insights for the newly established ePIC collaboration at EIC. This paper summarizes the different activities and R&D projects covered across the sessions of the workshop and provides an overview of the goals, approaches and strategies regarding AI/ML in the EIC community, as well as cutting-edge techniques currently studied in other experiments.

Synthetic biology enables the reprogramming of cellular functions for various applications. However, challenges in scalability and predictability persist due to context-dependent performance and complex circuit-host interactions. This study introduces an iModulon-based engineering approach, utilizing machine learning-defined co-regulated gene groups (iModulons) as design parts containing essential genes for specific functions. This approach identifies the necessary components for genetic circuits across different contexts, enhancing genome engineering by improving target selection and predicting module behavior. We demonstrate several distinct uses of iModulons: (i) discovery of unknown iModulons to increase protein productivity, heat tolerance and fructose utilization; (ii) an iModulon boosting approach, which amplifies the activity of specific iModulons, improved cell growth under osmotic stress with minimal host regulation disruption; (iii) an iModulon rebalancing strategy, which adjusts the activity levels of iModulons to balance cellular functions, significantly increased oxidative stress tolerance while minimizing trade-offs and (iv) iModulon-based gene annotation enabled natural competence activation by predictably rewiring iModulons. Comparative experiments with traditional methods showed our approach offers advantages in efficiency and predictability of strain engineering. This study demonstrates the potential of iModulon-based strategies to systematically and predictably reprogram cellular functions, offering refined and adaptable control over complex regulatory networks.

Structured representations of clinical data can support computational analysis of individuals and cohorts, and ontologies representing disease entities and phenotypic abnormalities are now commonly used for translational research. The Medical Action Ontology (MAxO) provides a computational representation of treatments and other actions taken for the clinical management of patients. Currently, manual biocuration is used to assign MAxO terms to rare diseases, enabling clinical management of rare diseases to be described computationally for use in clinical decision support and mechanism discovery. However, it is challenging to scale manual curation to comprehensively capture information about medical actions for the more than 10,000 rare diseases. We present AutoMAxO, a semi-automated workflow that leverages Large Language Models (LLMs) to streamline MAxO biocuration for rare diseases. AutoMAxO first uses LLMs to retrieve candidate curations from abstracts of relevant publications. Next, the candidate curations are matched to ontology terms from MAxO, Human Phenotype Ontology (HPO), and MONDO disease ontology via a combination of LLMs and post-processing techniques. Finally, the matched terms are presented in a structured form to a human curator for approval. We used this approach to process 4,918 unique medical abstracts and identified annotations for 21 rare genetic diseases, we extracted 18,631 candidate disease-treatment curations, 538 of which were confirmed and transferred to the MAxO annotation dataset. The results of this project underscore the potential of generative AI to accelerate precision medicine by enabling a robust and comprehensive curation of the primary literature to represent information about diseases and procedures in a structured fashion. Although we focused on MAxO in this project, similar approaches could be taken for other biomedical curation tasks.

SummaryHarmonizing variant indexing and allele assignments across datasets is crucial for data integrity in cross-dataset studies such as multi-cohort genome-wide association studies, meta-analyses, and the development, validation, and application of polygenic risk scores. Ensuring this indexing and allele consistency is a laborious, time-consuming, and error-prone process requiring a certain degree of computational proficiency. Here, we introduce GRIEVOUS, a command-line tool for cross-dataset variant homogenization. By means of an internal database and a custom indexing methodology, GRIEVOUS identifies, formats, and aligns all biallelic single nucleotide polymorphisms (SNPs) across all summary statistic and genotype files of interest. Upon completion of dataset harmonization, GRIEVOUS can also be used to extract the maximal set of biallelic SNPs common to all datasets.Availability and implementationGRIEVOUS and all supporting documentation and tutorials can be found at https://github.com/jvtalwar/GRIEVOUS. It is freely and publicly available under the MIT license and can be installed via pip.

Electrocardiogram (ECG) is a powerful tool to detect cardiovascular diseases (CVDs) and health conditions. We proposed a new method for evaluating ECG for efficient medical diagnosis in daily life. By splitting the signal according to the cardiac activity cycle, the periodic split attractor reconstruction (PSAR) method is proposed with time embedding, including three types of splitting methods to show its chaotic domain characteristics. We merged the CVDs dataset and the obstructive sleep apnea syndrome (OSAS) first-lead ECG signal dataset to validate the performance of PSAR for diagnosis and health monitoring using PSAR density maps as SE-ResNet input features. PSAR under 3 split methods showed different sensitivities for different CVDs. While in OSAS monitoring, PSAR showed good ability to recognize sleep abnormalities.

The Game of Life (GoL) is a paradigmatic computer simulation that exhibits the emergence of complex properties of the whole from relatively simple sets of heuristic rules operating at lower organizational levels. Therefore, it is widely understood as a valuable tool for investigating global properties of evolutionary processes. Cognizant of refined concepts that emerged in recent debates on the central role of historical contingency (historicity) in evolution, we modify the original GoL rules by introducing an updating feedback loop and a probability factor that reflect the degree of historicity in pattern evolution as both stochastic path dependence and sensitivity to initial conditions. We examine this trait in simulations of the emergence and breaking of bilateral and radial symmetries commonly observed in the evolution of life, most prominently as evolving body plans. We show that the implementation of historicity parameters leads to a more realistic sequential and gradual alternating emergence and the breaking of new symmetries than the original set of rules. Apart from its more realistic representations of evolutionary processes, the new approach allows for easier exploration of the parameter space, demonstrates the sequential and gradual emergence and breaking of symmetries, and provides a publicly available and modular simulation tool. We discuss the exploratory potential of the modified GoL platform we designed as an extended thought experiment to study the parameter space defining the historicity of biological processes.

We present a new method to measure sub-microcurie activities of photon-emitting radionuclides in organs and lesions of small animals in vivo. Our technique, named the collimator-less likelihood fit, combines a very high sensitivity collimatorless detector with a Monte Carlo-based likelihood fit in order to estimate the activities in previously segmented regions of interest along with their uncertainties. This is done directly from the photon projections in our collimatorless detector and from the region of interest segmentation provided by an x-ray computed tomography scan. We have extensively validated our approach with 225Ac experimentally in spherical phantoms and mouse phantoms, and also numerically with simulations of a realistic mouse anatomy. Our method yields statistically unbiased results with uncertainties smaller than 20% for activities as low as ~111Bq (3nCi) and for exposures under 30 minutes. We demonstrate that our method yields more robust recovery coefficients when compared to SPECT imaging with a commercial pre-clinical scanner, specially at very low activities. Thus, our technique is complementary to traditional SPECT/CT imaging since it provides a more accurate and precise organ and tumor dosimetry, with a more limited spatial information. Finally, our technique is specially significant in extremely low-activity scenarios when SPECT/CT imaging is simply not viable.

In this paper we present a novel method for solving the shallow-shelf equations in the presence of grounding lines. The shallow-self equations are a two-dimensional system of nonlinear elliptic PDEs with variable coefficients that are discontinuous across the grounding line, which we treat as a sharp interface between grounded and floating ice. The grounding line is “reconstructed” from ice thickness and basal topography data to provide necessary geometric information for our cut-cell, finite volume discretization. Our discretization enforces jump conditions across the grounding line and achieves high-order accuracy using stencils constructed with a weighted least-squares method. We demonstrate second and fourth order convergence of the velocity field, driving stress, and reconstructed geometric information.

Parallel I/O is a critical technique for moving data between compute and storage subsystems of supercomputers. With massive amounts of data produced or consumed by compute nodes, high-performant parallel I/O is essential. I/O benchmarks play an important role in this process; however, there is a scarcity of I/O benchmarks representative of current workloads on HPC systems. Toward creating representative I/O kernels from real-world applications, we have created h5bench, a set of I/O kernels that exercise hierarchical data format version 5 (HDF5) I/O on parallel file systems in numerous dimensions. Our focus on HDF5 is due to the parallel I/O library's heavy usage in various scientific applications running on supercomputing systems. The various tests benchmarked in the h5bench suite include I/O operations (read and write), data locality (arrays of basic data types and arrays of structures), array dimensionality (one-dimensional arrays, two-dimensional meshes, three-dimensional cubes), I/O modes (synchronous and asynchronous). In this paper, we present the observed performance of h5bench executed along several of these dimensions on existing supercomputers (Cori and Summit) and pre-exascale platforms (Perlmutter, Theta, and Polaris). h5bench measurements can be used to identify performance bottlenecks and their root causes and evaluate I/O optimizations. As the I/O patterns of h5bench are diverse and capture the I/O behaviors of various HPC applications, this study will be helpful to the broader supercomputing and I/O community.

Isthmic spondylolysis is characterized by a stress injury to the pars interarticularis bones of the lumbar spines and is often missed by conventional magnetic resonance imaging (MRI), necessitating a computed tomography (CT) for accurate diagnosis. We compare MRI techniques suitable for producing CT-like images. Lumbar spines of asymptomatic and low back pain (LBP) subjects were imaged at 3-Tesla with multi-echo ultrashort echo time (UTE) and field echo (FE) sequences followed by simple post-processing of averaging and inverting to depict spinal bones with a CT-like appearance. The contrast-to-noise ratio (CNR) for bone was determined to compare UTE vs. FE and single-echo vs. multi-echo data. Visually, both sequences depicted cortical bone with good contrast; UTE-processed sequences provided a flatter contrast for soft tissues that made them easy to distinguish from bone, while FE-processed images had better resolution and bone–muscle contrast, which are important for fracture detection. Additionally, multi-echo images provided significantly (p = 0.03) greater CNR compared with single-echo images. Using these techniques, progressive spondylolysis was detected in an LBP subject. This study demonstrates the feasibility of using spine bone MRI to yield CT-like contrast. Through the employment of multi-echo UTE and FE sequences combined with simple processing, we observe sufficient enhancements in image quality and contrast to detect pars fractures.

Covid-19 led to a dramatic change in the academic library work environment, with many workers shifting to a hybrid work schedule once they returned to in person work. The authors describe the impact of this schedule shift through the novel use of the socio-ecological model. The socio-ecological model looks at the impact of choices through varying circles or levels. The authors discuss the individual, interpersonal, community, and societal levels of impact that the switch to hybrid work had within their context and discuss their role as unit leaders and the decisions made to address these varying impacts.

IPv6 is the current version of IP, the protocol that is used to route traffic across internet connections. This standard was originally developed as a new approach to mitigate concerns about address exhaustion and allow for near infinite scalability. While this protocol has gained significant support in mobile and broadband networks, as well as being the default for networks in emerging economies, it has yet to be fully adopted as a standard deployment model. Complications include legacy devices unable to support the proposed changes, as well as potential challenges that exist between devices that may not be able to fully implement current standards or configuration norms. The SCinet volunteers who deliver advanced networking to support the SC Conference set an ambitious goal of deploying an IPv6-only network at SC23. While the necessary technology is widely available and understood, the implications of deployment to support more than 15,000 users, each with multiple devices of different operating environments and ages, presents a unique technology and policy challenge. This paper will highlight the effort put into designing, implementing, and operating this innovative IPv6-only environment.

Students in STEM and the health sciences have unique learning needs, including preparation for exams required for entering a STEM or health sciences profession. Students in these areas thus often seek, in addition to or instead of traditional course materials and library resources, digital study tools that utilize techniques such as spaced repetition. However, such tools are often sold as individual subscriptions that may be prohibitively expensive. The article outlines four approaches libraries may consider to help make digital study tools in STEM and the health sciences more equitable and affordable: assess, adopt, adapt, and create.

Garbage In Garbage Out is a universally agreed quote by computer scientists from various domains, including Artificial Intelligence (AI). As data is the fuel for AI, models trained on low-quality, biased data are often ineffective. Computer scientists who use AI invest a considerable amount of time and effort in preparing the data for AI. However, there are no standard methods or frameworks for assessing the “readiness” of data for AI. To provide a quantifiable assessment of the readiness of data for AI processes, we define parameters of AI data readiness and introduce AIDRIN (AI Data Readiness INspector). AIDRIN is a framework covering a broad range of readiness dimensions available in the literature that aid in evaluating the readiness of data quantitatively and qualitatively. AIDRIN uses metrics in traditional data quality assessment such as completeness, outliers, and duplicates for data evaluation. Furthermore, AIDRIN uses metrics specific to assess data for AI, such as feature importance, feature correlations, class imbalance, fairness, privacy, and FAIR (Findability, Accessibility, Interoperability, and Reusability) principle compliance. AIDRIN provides visualizations and reports to assist data scientists in further investigating the readiness of data. The AIDRIN framework enhances the efficiency of the machine learning pipeline to make informed decisions on data readiness for AI applications.

Students bring a multitude of ideas and experiences to the classroom while they are reasoning about scientific phenomena. They often need timely guidance to refine build upon their initial ideas. In this study we explore the development of guidance prompts to provide students with personalized, real-time feedback in the context of a pedagogically grounded chatbot. In the current version of the tool, guidance prompts are authored by learning scientists who are experts in the content of the items and in Knowledge Integration pedagogy. When students engage with the chatbot, an idea detection model is used to determine the ideas that are present in a student explanation and then the expert-authored guidance prompts are assigned based on rules about which ideas are or are not present in the student explanation. While this approach allows for close attention to and control of the pedagogical intent of each prompt, it is time consuming and not easily generalizable. Further this rule-based approach limits the ways in which students can interact with the chatbot. The work in progress study presented in this paper explores the potential of using generative AI to create similarly pedagogically grounded guidance prompts as a first step towards increasing the generalizability and scalability of this approach. Specifically, we ask: using criteria from the Knowledge Integration Pedagogical Framework, how do ChatGPT 3.5-authored guidance prompts compare to human expert-authored guidance prompts? We find that while prompt engineering can enhance the alignment of ChatGPT-authored guidance prompts with pedagogical criteria, the human expert-authored guidance prompts more consistently meet the pedagogical criteria.