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At least 1,765 records · Page 98

Using case-level context to classify cancer pathology reports

Individual electronic health records (EHRs) and clinical reports are often part of a larger sequence—for example, a single patient may generate multiple reports over the trajectory of a disease. In applications such as cancer pathology reports, it is necessary not only to extract information from individual reports, but also to capture aggregate information regarding the entire cancer case based off case-level context from all reports in the sequence. In this paper, we introduce a simple modular add-on for capturing case-level context that is designed to be compatible with most existing deep learning architectures for text classification on individual reports. We test our approach on a corpus of 431,433 cancer pathology reports, and we show that incorporating case-level context significantly boosts classification accuracy across six classification tasks—site, subsite, laterality, histology, behavior, and grade. We expect that with minimal modifications, our add-on can be applied towards a wide range of other clinical text-based tasks.

60 APPLIED LIFE SCIENCES↗

Dynamical Decoupling for Measuring and Suppressing Crosstalk

Dynamical decoupling (DD) is a noise-mitigating strategy in which sequences of pulses are applied to single qubits to average out their interaction with the environment. DD has been extensively studied and demonstrated for suppressing single-qubit decoherence and can be tailored for different noise spectrum. We report another important adaptation of DD where crosstalk between qubits are suppressed. We demonstrate the efficiency of this procedure on quantum circuits on superconducting transmon-based quantum devices. We designed a family of syncopated DD sequences that effectively suppress ZZ coupling between qubit pairs, which is the dominating crosstalk form on the device. We insert DD to a quantum circuit whenever single qubits are idle (often during two-qubits gates on other qubits). While standard periodic DD suppress crosstalk between these qubits and their neighbors, the syncopated DD further decouples crosstalk between these qubits. We further designed short sequences that maximize the application of DD without adding time to the quantum circuit execution. Such DD sequences yield significant improvement of the performance of the algorithm on the hardware. The performance is further boosted by combining DD with another mitigation strategy, randomized compilation. Our work demonstrated that syncopated DD is effective and practical way to suppress crosstalk in quantum circuits and serves as a great probe to characterize the crosstalk and inform hardware design.

Quantum Computing↗

Data from: Nucleotide polymorphism and copy number variant detection using exome capture and next generation sequencing in the polyploid grass Panicum virgatum

Switchgrass (Panicum virgatum) is a polyploid, outcrossing grass species native to North America and has recently been recognized as a potential biofuel feedstock crop. Significant phenotypic variation including ploidy is present across the two primary ecotypes of switchgrass, referred to as upland and lowland switchgrass. The tetraploid switchgrass genome is approximately 1400 Mbp, split between two subgenomes, with significant repetitive sequence content limiting the efficiency of re-sequencing approaches for determining genome diversity. To characterize genetic diversity in upland and lowland switchgrass as a first step in linking genotype to phenotype, we designed an exome capture probe set based on transcript assemblies that represent ~50 Mb of annotated switchgrass exome sequences. We then evaluated and optimized the probe set using solid phase comparative genome hybridization and liquid phase exome capture followed by next generation sequencing. Using the optimized probe set, we assessed variation in the exomes of eight switchgrass genotypes representing tetraploid lowland and octoploid upland cultivars to benchmark our exome capture probe set design. We identified ample variation in the switchgrass genome including 1,395,501 single nucleotide polymorphisms (SNPs), 8,173 putative copy number variants and 3,336 presence/absence variants. While the majority of the SNPs (84%) detected were biallelic, a substantial number were tri-allelic with limited occurrence of tetra-allelic polymorphisms consistent with the heterozygous and polyploid nature of the switchgrass genome. Collectively, these data demonstrate the efficacy of exome capture for discovery of genome variation in a polyploid species with a large, repetitive and heterozygous genome.

09 BIOMASS FUELS↗

In vivo gene correction with targeted sequence substitution through microhomology-mediated end joining

Highlights: • A novel microhomology mediated end joining (MMEJ) gene correction method was tested. • MMEJ resulted in precise targeted sequence substitution (TSS) in vitro and in vivo. • MMEJ-TSS showed superior efficiency than homology-directed repair (HDR) in vitro. • MMEJ-TSS resulted in the survival of mice model of hereditary tyrosinemia in vivo. • MMEJ-TSS could overcome the limitations of HDR for gene therapy. Genome editing technology using programmable nucleases has rapidly evolved in recent years. The primary mechanism to achieve precise integration of a transgene is mainly based on homology-directed repair (HDR). However, an HDR-based genome-editing approach is less efficient than non-homologous end-joining (NHEJ). Recently, a microhomology-mediated end-joining (MMEJ)-based transgene integration approach was developed, showing feasibility both in vitro and in vivo. We expanded this method to achieve targeted sequence substitution (TSS) of mutated sequences with normal sequences using double-guide RNAs (gRNAs), and a donor template flanking the microhomologies and target sequence of the gRNAs in vitro and in vivo. Our method could realize more efficient sequence substitution than the HDR-based method in vitro using a reporter cell line, and led to the survival of a hereditary tyrosinemia mouse model in vivo. The proposed MMEJ-based TSS approach could provide a novel therapeutic strategy, in addition to HDR, to achieve gene correction from a mutated sequence to a normal sequence.

60 APPLIED LIFE SCIENCES↗

The organization of an autonomous learning system

The organization of systems that learn from experience is examined, human beings and animals being prime examples of such systems. How is their information processing organized. They build an internal model of the world and base their actions on the model. The model is dynamic and predictive, and it includes the systems' own actions and their effects. In modeling such systems, a large pattern of features represents a moment of the system's experience. Some of the features are provided by the system's senses, some control the system's motors, and the rest have no immediate external significance. A sequence of such patterns then represents the system's experience over time. By storing such sequences appropriately in memory, the system builds a world model based on experience. In addition to the essential function of memory, fundamental roles are played by a sensory system that makes raw information about the world suitable for memory storage and by a motor system that affects the world. The relation of sensory and motor systems to the memory is discussed, together with how favorable actions can be learned and unfavorable actions can be avoided. Results in classical learning theory are explained in terms of the model, more advanced forms of learning are discussed, and the relevance of the model to the frame problem of robotics is examined.

Kanerva, Pentti↗

A user-friendly, menu-driven, language-free laser characteristics curves graphing program for desk-top IBM PC compatible computers

A facility was established that uses collected data and feeds it into mathematical models that generate improved data arrays by correcting for various losses, base line drift, and conversion to unity scaling. These developed data arrays have headers and other identifying information affixed and are subsequently stored in a Laser Materials and Characteristics data base which is accessible to various users. The two part data base: absorption - emission spectra and tabulated data, is developed around twelve laser models. The tabulated section of the data base is divided into several parts: crystalline, optical, mechanical, and thermal properties; aborption and emission spectra information; chemical name and formulas; and miscellaneous. A menu-driven, language-free graphing program will reduce and/or remove the requirement that users become competent FORTRAN programmers and the concomitant requirement that they also spend several days to a few weeks becoming conversant with the GEOGRAF library and sequence of calls and the continual refreshers of both. The work included becoming thoroughly conversant with or at least very familiar with GEOGRAF by GEOCOMP Corp. The development of the graphing program involved trial runs of the various callable library routines on dummy data in order to become familiar with actual implementation and sequencing. This was followed by trial runs with actual data base files and some additional data from current research that was not in the data base but currently needed graphs. After successful runs, with dummy and real data, using actual FORTRAN instructions steps were undertaken to develop the menu-driven language-free implementation of a program which would require the user only know how to use microcomputers. The user would simply be responding to items displayed on the video screen. To assist the user in arriving at the optimum values needed for a specific graph, a paper, and pencil check list was made available to use on the trial runs.

Klutz, Glenn↗

Capturing the genetic makeup of the active microbiome in situ

More than any other technology, nucleic acid sequencing has enabled microbial ecology studies to be complemented with the data volumes necessary to capture the extent of microbial diversity and dynamics in a wide range of environments. In order to truly understand and predict environmental processes, however, the distinction between active, inactive and dead microbial cells is critical. Also, experimental designs need to be sensitive toward varying population complexity and activity, and temporal as well as spatial scales of process rates. There are a number of approaches, including single-cell techniques, which were designed to study in situ microbial activity and that have been successively coupled to nucleic acid sequencing. The exciting new discoveries regarding in situ microbial activity provide evidence that future microbial ecology studies will indispensably rely on techniques that specifically capture members of the microbiome active in the environment. Herein, we review those currently used activity-based approaches that can be directly linked to shotgun nucleic acid sequencing, evaluate their relevance to ecology studies, and discuss future directions.

59 BASIC BIOLOGICAL SCIENCES↗

Pathosphere.org: pathogen detection and characterization through a web-based, open source informatics platform

The detection of pathogens in complex sample backgrounds has been revolutionized by wide access to next-generation sequencing (NGS) platforms. However, analytical methods to support NGS platforms are not as uniformly available. Pathosphere (found at Pathosphere.org) is a cloud - based open - sourced community tool that allows for communication, collaboration and sharing of NGS analytical tools and data amongst scientists working in academia, industry and government. The architecture allows for users to upload data and run available bioinformatics pipelines without the need for onsite processing hardware or technical support. The pathogen detection capabilities hosted on Pathosphere were tested by analyzing pathogen-containing samples sequenced by NGS with both spiked human samples as well as human and zoonotic host backgrounds. Pathosphere analytical pipelines developed by Edgewood Chemical Biological Center (ECBC) identified spiked pathogens within a common sample analyzed by 454, Ion Torrent, and Illumina sequencing platforms. ECBC pipelines also correctly identified pathogens in human samples containing arenavirus in addition to animal samples containing flavivirus and coronavirus. These analytical methods were limited in the detection of sequences with limited homology to previous annotations within NCBI databases, such as parvovirus. Utilizing the pipeline-hosting adaptability of Pathosphere, the analytical suite was supplemented by analytical pipelines designed by the United States Army Medical Research Institute of Infectious Diseases and Walter Reed Army Institute of Research (USAMRIID-WRAIR). These pipelines were implemented and detected parvovirus sequence in the sample that the ECBC iterative analysis previously failed to identify. By accurately detecting pathogens in a variety of samples, this work demonstrates the utility of Pathosphere and provides a platform for utilizing, modifying and creating pipelines for a variety of NGS technologies developed to detect pathogens in complex sample backgrounds. These results serve as an exhibition for the existing pipelines and web-based interface of Pathosphere as well as the plug-in adaptability that allows for integration of newer NGS analytical software as it becomes available.

59 BASIC BIOLOGICAL SCIENCES↗

Analysis of sequencing and scheduling methods for arrival traffic

The air traffic control subsystem that performs scheduling is discussed. The function of the scheduling algorithms is to plan automatically the most efficient landing order and to assign optimally spaced landing times to all arrivals. Several important scheduling algorithms are described and the statistical performance of the scheduling algorithms is examined. Scheduling brings order to an arrival sequence for aircraft. First-come-first-served scheduling (FCFS) establishes a fair order, based on estimated times of arrival, and determines proper separations. Because of the randomness of the traffic, gaps will remain in the scheduled sequence of aircraft. These gaps are filled, or partially filled, by time-advancing the leading aircraft after a gap while still preserving the FCFS order. Tightly scheduled groups of aircraft remain with a mix of heavy and large aircraft. Separation requirements differ for different types of aircraft trailing each other. Advantage is taken of this fact through mild reordering of the traffic, thus shortening the groups and reducing average delays. Actual delays for different samples with the same statistical parameters vary widely, especially for heavy traffic.

Neuman, Frank↗

PRIME: A bottom-up approach to probabilistic rule development

PRIME is a system to be used by an intelligent machine to allow it to operate in an abstract but uncertain (or stochastic) environment. It maintains a model of the effects of the machine's actions in the form of a rule base, which is induced from experience. This bottom-up approach to rule development allows the model to adapt to changes in the environment. Each rule consists of a condition under which the rule is active, an action, the effect of the action on the environment, and an estimate of the probability of this effect occurring. The effect probabilities are used to model the uncertainty in the environment, permitting multiple possible effects for a single action under a particular set of conditions. The objective of the intelligent machine is to satisfy user-specified goals with maximum probability of success. PRIME fulfills this requirement in two ways: it continuously updates the rule base with the most recent information, to ensure the validity of the model; and it generates plans which have the maximum probability of achieving the goals, based on the probability estimates in the rule base. PRIME is composed of three main processes: exploration, generalization, and planning. In exploration, the machine executes various randomly chosen actions, observes the effects on the environment, and updates the rule base accordingly. This process is used to develop the rule base in simulation, as well as to supplement the current knowledge during normal operation. Generalization is the procedure used to induce general rules from experience, which is encoded in the form of specific rules. These general rules extend the machine's knowledge to situations which have not been encountered yet, thereby increasing the capability of the machine to plan effectively. Planning is the process of constructing an optimal sequence of actions to satisfy a goal, using the rule base to predict the effects of these actions and to determine the probability of success of the plan. The rule representation and many other data structures were specifically chosen to maximize the efficiency of these processes. A simulated environment was designed to test the performance of PRIME. The results of experimentation were largely negative. The main problem was that the domain coverage of the rules was inadequate for the number of rules stored in the rule base, due to redundancies in general rules and numerous rules covering ineffective actions. It was determined that a more efficient generalization, and some form of goal-directed exploration, are necessary in order to solve most of the current deficiencies in PRIME.

Miller, Scott A.↗

Structural basis for angiopoietin-1–mediated signaling initiation

Angiogenesis is a complex cellular process involving multiple regulatory growth factors and growth factor receptors. Among them, the ligands for the endothelial-specific tunica intima endothelial receptor tyrosine kinase 2 (Tie2) receptor kinase, angiopoietin-1 (Ang1) and Ang2, play essential roles in balancing vessel stability and regression during both developmental and tumor-induced angiogenesis. Despite possessing a high degree of sequence identity, Ang1 and Ang2 have distinct functional roles and cell-signaling characteristics. Here, we present the crystal structures of Ang1 both unbound and in complex with the Tie2 ectodomain. Comparison of the Ang1-containing structures with their Ang2-containing counterparts provide insight into the mechanism of receptor activation and reveal molecular surfaces important for interactions with Tie2 coreceptors and associated signaling proteins. Using structure-based mutagenesis, we identify a loop within the angiopoietin P domain, adjacent to the receptor-binding interface, which confers the specific agonist/antagonist properties of the molecule. We demonstrate using cell-based assays that an Ang2 chimera containing the Ang1 loop sequence behaves functionally similarly to Ang1 as a constitutive Tie2 agonist, able to efficiently dissociate the inhibitory Tie1/Tie2 complex and elicit Tie2 clustering and downstream signaling.

cellular signaling↗

Hierarchic plate and shell models based on p-extension

Formulations of finite element models for beams, arches, plates and shells based on the principle of virtual work was studied. The focus is on computer implementation of hierarchic sequences of finite element models suitable for numerical solution of a large variety of practical problems which may concurrently contain thin and thick plates and shells, stiffeners, and regions where three dimensional representation is required. The approximate solutions corresponding to the hierarchic sequence of models converge to the exact solution of the fully three dimensional model. The stopping criterion is based on: (1) estimation of the relative error in energy norm; (2) equilibrium tests, and (3) observation of the convergence of quantities of interest.

Szabo, Barna A.↗

Sedimentology and Stratigraphy of the Lower Delta Sequence, Jezero Crater, Mars.

In April 2022, the Mars 2020 Perseverance rover arrived at the base of the ancient delta in Jezero crater after completing the first year of its mission exploring and sampling aqueously altered igneous rocks of the present-day crater floor. Perseverance then spent ~200 sols exploring the lower ~25 m of rock exposed within the eastern scarp of the Jezero delta, a sedimentary sequence informally named the ‘Shenandoah’ formation. This study describes the sedimentology and stratigraphy of the Shenandoah formation explored by Perseverance at two sections—'Cape Nukshak’ and ‘Hawksbill Gap’—including a description, interpretation, and depositional framework for the facies that comprise it.

K. M. Stack↗

Algorithm Optimally Orders Forward-Chaining Inference Rules

People typically develop knowledge bases in a somewhat ad hoc manner by incrementally adding rules with no specific organization. This often results in a very inefficient execution of those rules since they are so often order sensitive. This is relevant to tasks like Deep Space Network in that it allows the knowledge base to be incrementally developed and have it automatically ordered for efficiency. Although data flow analysis was first developed for use in compilers for producing optimal code sequences, its usefulness is now recognized in many software systems including knowledge-based systems. However, this approach for exhaustively computing data-flow information cannot directly be applied to inference systems because of the ubiquitous execution of the rules. An algorithm is presented that efficiently performs a complete producer/consumer analysis for each antecedent and consequence clause in a knowledge base to optimally order the rules to minimize inference cycles. An algorithm was developed that optimally orders a knowledge base composed of forwarding chaining inference rules such that independent inference cycle executions are minimized, thus, resulting in significantly faster execution. This algorithm was integrated into the JPL tool Spacecraft Health Inference Engine (SHINE) for verification and it resulted in a significant reduction in inference cycles for what was previously considered an ordered knowledge base. For a knowledge base that is completely unordered, then the improvement is much greater.

James, Mark↗

Formation and reconfiguration of tight multi-lane platoons

Advances in vehicular communication technologies are expected to facilitate cooperative driving in the future. Connected and Automated Vehicles (CAVs) are able to collaboratively plan and execute driving maneuvers by sharing their perceptual knowledge and future plans. In this paper, an architecture for autonomous navigation of tight multi-lane platoons traveling on public roads is presented. Using the proposed approach, CAVs are able to form single or multi-lane platoons of various geometrical configurations. They are able to reshape and adjust their configurations according to changes in the environment. The proposed architecture consists of two main components: an offline motion planner system and an online hierarchical control system. The motion planner uses an optimization-based approach for cooperative formation and reconfiguration in tight spaces. A constrained optimization scheme is used to plan smooth, dynamically feasible and collision-free trajectories for all the vehicles within the platoon. The paper addresses online computation limitations by employing a family of maneuvers precomputed offline and stored on a look-up table on the vehicles. The online hierarchical control system is composed of three levels: a traffic operation system (TOS), a decision-maker, and a path-follower. The TOS determines the desired platoon reconfiguration. The decision-maker checks the feasibility of the reconfiguration plan based on real-time information about the surrounding traffic. The reconfiguration maneuver is executed by a low-level path-following feedback controller in real-time. The effectiveness of the approach is demonstrated through simulations of three case studies: (1) formation reconfiguration (2) obstacle avoidance, and (3) benchmarking against behavior-based planning in which the desired formation is achieved using a sequence of motion primitives.

42 ENGINEERING↗

Predicting river turbidity in Pine Island Bayou using machine learning techniques coupled with variational mode decomposition

Elevated turbidity levels pose significant public health risks by facilitating the transport of harmful pollutants, including metals, organic compounds, and pathogenic microorganisms into the surface water. These conditions create serious challenges for public recreational water use and drinking water treatment, leading to economic losses and health risks. This study utilizes water monitoring data in Pine Island Bayou, Texas, and develops a Sequence-to-Sequence (S2S) model to predict turbidity using Attention-based Gated Recurrent Units with Encoder-Decoder (AT-GRU-ED) and Long Short-Term Memory (LSTM), coupled with Variational Mode Decomposition (VMD). Compared to the model without VMD, the model demonstrates satisfactory 72-hour turbidity prediction performance, achieving MAEs of 2.60 and 3.29 NTU (reductions of 53% and 58%), RMSEs of 21.08 and 31.49 NTU (reductions of 82% and 80%), and R² values of 0.96 and 0.84 on the validation and test sets, respectively. Feature importance analysis reveals that water temperature is the dominant factor influencing seasonal turbidity patterns, while real-time hourly rainfall significantly contributes to short-term variability. Turbidity typically peaks within 48 hours after rainfall events due to lagged effects from surface runoff and upstream flow. Findings suggest suspending recreational water use and water supply pumping for three days after heavy rainfall can benefit public health and improve water treatment processes. Discharges above 100 m3/s are found to accelerate sediment dilution and transport, reducing turbidity levels more quickly after the peak. In conclusion, the proposed model demonstrates reliable 72-hour turbidity prediction, supporting decision-making for water treatment plant operations and providing early warning for public recreational water use.

Deep learning↗

Detecting anomalous sequences in electronic health records using higher-order tensor networks

Detecting anomalous sequences is an integral part of building and protecting modern large-scale health information technology (HIT) systems. These HIT systems generate a large volume of records of patients’ state and significant events, which provide a valuable resource to help improve clinical decisions, patient care processes, and other issues. However, detecting anomalous sequences in electronic health records (EHR) remains a challenge in healthcare applications for several reasons, including imbalances in the data, complexity of relationships between events in the sequence, and the curse of dimensionality. Conventional anomaly detection methods use the finite sequence of events to discriminate sequences. They fail to incorporate salient event details under variable higher-order dependencies (e.g., duration between events) that can provide better discrimination of sequences in their models. To address this problem, we propose event sequence and subsequence anomaly detection algorithms that (1) use network-based representations of interactions in the data, (2) account for variable higher-order dependencies in the data, and (3) incorporate events duration for adequate discrimination of the data. The proposed approach identifies anomalies by monitoring the change in the graph after the test sequence is removed from the network. The change is quantified using graph distance metrics so that dramatic changes in the network can be attributed to the removed sequence. Furthermore, the proposed subsequence algorithm recommends plausible paths and salient information for the detected anomalous subsequences. Our results show that the proposed event sequence anomaly detection algorithm outperforms the baseline methods for both synthetic data and real-world EHR data.

96 KNOWLEDGE MANAGEMENT AND PRESERVATION↗

A CRITICAL LOOK AT THE MASS-METALLICITY-STAR FORMATION RATE RELATION IN THE LOCAL UNIVERSE. I. AN IMPROVED ANALYSIS FRAMEWORK AND CONFOUNDING SYSTEMATICS

It has been proposed that the (stellar) mass-(gas) metallicity relation of galaxies exhibits a secondary dependence on star formation rate (SFR), and that the resulting M {sub *}-Z-SFR relation may be redshift-invariant, i.e., ''fundamental''. However, conflicting results on the character of the SFR dependence, and whether it exists, have been reported. To gain insight into the origins of the conflicting results, we (1) devise a non-parametric, astrophysically motivated analysis framework based on the offset from the star-forming ({sup m}ain{sup )} sequence at a given M {sub *} (relative specific SFR); (2) apply this methodology and perform a comprehensive re-analysis of the local M {sub *}-Z-SFR relation, based on SDSS, GALEX, and WISE data; and (3) study the impact of sample selection and of using different metallicity and SFR indicators. We show that metallicity is anti-correlated with specific SFR regardless of the indicators used. We do not find that the relation is spurious due to correlations arising from biased metallicity measurements or fiber aperture effects. We emphasize that the dependence is weak/absent for massive galaxies (log M {sub *} > 10.5), and that the overall scatter in the M {sub *}-Z-SFR relation does not greatly decrease from the M {sub *}-Z relation. We find that the dependence is stronger for the highest SSFR galaxies above the star-forming sequence. This two-mode behavior can be described with a broken linear fit in 12+log(O/H) versus log (SFR/M {sub *}), at a given M {sub *}. Previous parameterizations used for comparative analysis with higher redshift samples that do not account for the more detailed behavior of the local M {sub *}-Z-SFR relation may incorrectly lead to the conclusion that those samples follow a different relationship.

79 ASTRONOMY AND ASTROPHYSICS↗