Context Modulation Enables Model Robustness to Weight Noise in Recurrent Spiking Neural Networks
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Because of a lack of operation data during abnormal and accident scenarios, along with the existence of uncertainty in the evaluation model for transient and accident analysis, the established abnormal and emergency operating procedures can be biased in characterizing the reactor states and ensuring operational resilience. To improve state awareness and ensure operational flexibility for minimizing effects on the system due to anomaly, digital twin (DT) technology is suggested to support operator's decision-making by effectively extracting and using knowledge of the current and future plant states from the knowledge base. To demonstrate DT's capability for recovering the complete states of reactors and for predicting the future reactor behaviors, this paper develops and assesses both the diagnosis and prognosis DTs in a nearly autonomous management and control system for an Experimental Breeder Reactor-II simulator during different loss-of-flow scenarios.
Abstract not provided.
A method of identifying molecular parameters in a complex mixture may include receiving a set of combined transition frequencies and analyzing the set of combined transition frequencies using a first trained artificial neural network to generate a plurality of separated transition frequency sets. Each of the plurality of separated frequency sets may be analyzed using a second trained artificial neural network to generate a respective set of estimated spectral parameters. The method may include identifying a set of molecular parameters corresponding to the set of separated transition frequencies.
The epidermis of Chondrichthyan fishes consists of dermal denticles with production of minimal but protein-rich mucus that collectively, influence the attachment and biofilm development of microbes, facilitating a unique epidermal microbiome. Here, we use metagenomics to provide the taxonomic and functional characterization of the epidermal microbiome of the Triakis semifasciata (leopard shark) at three time-points collected across 4 years to identify links between microbial groups and host metabolism. Our aims include (1) describing the variation of microbiome taxa over time and identifying recurrent microbiome members (present across all time-points); (2) investigating the relationship between the recurrent and flexible taxa (those which are not found consistently across time-points); (3) describing the functional compositions of the microbiome which may suggest links with the host metabolism; and (4) identifying whether metabolic processes are shared across microbial genera or are unique to specific taxa. Microbial members of the microbiome showed high similarity between all individuals (Bray–Curtis similarity index = 82.7, where 0 = no overlap, 100 = total overlap) with the relative abundance of those members varying across sampling time-points, suggesting flexibility of taxa in the microbiome. One hundred and eighty-eight genera were identified as recurrent, including Pseudomonas, Erythrobacter, Alcanivorax, Marinobacter, and Sphingopxis being consistently abundant across time-points, while Limnobacter and Xyella exhibited switching patterns with high relative abundance in 2013, Sphingobium and Sphingomona in 2015, and Altermonas, Leeuwenhoekiella, Gramella, and Maribacter in 2017. Of the 188 genera identified as recurrent, the top 19 relatively abundant genera formed three recurrent groups. The microbiome also displayed high functional similarity between individuals (Bray–Curtis similarity index = 97.6) with gene function composition remaining consistent across all time-points. These results show that while the presence of microbial genera exhibits consistency across time-points, their abundances do fluctuate. Microbial functions however remain stable across time-points; thus, we suggest the leopard shark microbiomes exhibit functional redundancy. We show coexistence of microbes hosted in elasmobranch microbiomes that encode genes involved in utilizing nitrogen, but not fixing nitrogen, degrading urea, and resistant to heavy metal.
Phosphorus (P) loading to lakes is degrading the quality and usability of water globally. Accurate predictions of lake P dynamics are needed to understand whole-ecosystem P budgets, as well as the consequences of changing lake P concentrations for water quality. However, complex biophysical processes within lakes, along with limited observational data, challenge our capacity to reproduce short-term lake dynamics needed for water quality predictions, as well as long-term dynamics needed to understand broad scale controls over lake P. Here we use an emerging paradigm in modeling, process-guided machine learning (PGML), to produce a phosphorus budget for Lake Mendota (Wisconsin, USA) and to accurately predict epilimnetic phosphorus over a time range of days to decades. In our implementation of PGML, which we term a Process-Guided Recurrent Neural Network (PGRNN), we combine a process-based model for lake P with a recurrent neural network, and then constrain the predictions with ecological principles. We test independently the process-based model, the recurrent neural network, and the PGRNN to evaluate the overall approach. The process-based model accounted for most of the observed pattern in lake P; however it missed the long-term trend in lake P and had the worst performance in predicting winter and summer P in surface waters. The root mean square error (RMSE) for the process-based model, the recurrent neural network, and the PGRNN was 33.0 μg P L -1 , 22.7 μg P L -1 , and 20.7 μg P L -1 , respectively. All models performed better during summer, with RMSE values for the three models (same order) equal to 14.3 μg P L -1 , 10.9 μg P L -1 , and 10.7 μg P L -1 . Although the PGRNN had only marginally better RMSE during summer, it had lower bias and reproduced long-term decreases in lake P missed by the other two models. For all seasons and all years, the recurrent neural network had better predictions than process alone, with root mean square error (RMSE) of 23.8 μg P L -1 and 28.0 μg P L -1 , respectively. The output of PGRNN indicated that new processes related to water temperature, thermal stratification, and long term changes in external loads are needed to improve the process model. By using ecological knowledge, as well as the information content of complex data, PGML shows promise as a technique for accurate prediction in messy, real-world ecological dynamics, while providing valuable information that can improve our understanding of process.
Abstract Recurrent neural networks are used to forecast time series in finance, climate, language, and from many other domains. Reservoir computers are a particularly easily trainable form of recurrent neural network. Recently, a “next-generation” reservoir computer was introduced in which the memory trace involves only a finite number of previous symbols. We explore the inherent limitations of finite-past memory traces in this intriguing proposal. A lower bound from Fano’s inequality shows that, on highly non-Markovian processes generated by large probabilistic state machines, next-generation reservoir computers with reasonably long memory traces have an error probability that is at least $$\sim 60\%$$ ∼ 60 % higher than the minimal attainable error probability in predicting the next observation. More generally, it appears that popular recurrent neural networks fall far short of optimally predicting such complex processes. These results highlight the need for a new generation of optimized recurrent neural network architectures. Alongside this finding, we present concentration-of-measure results for randomly-generated but complex processes. One conclusion is that large probabilistic state machines—specifically, large $$\epsilon$$ ϵ -machines—are key to generating challenging and structurally-unbiased stimuli for ground-truthing recurrent neural network architectures.
Purpose: Multigene assays provide useful prognostic information regarding hormone receptor (HR)-positive breast cancer. Next-generation sequencing (NGS)-based platforms have numerous advantages including reproducibility and adaptability in local laboratories. Here we aimed to develop and validate an NGS-based multigene assay to predict the distant recurrence risk. Experimental Design: In total, 179 genes including 30 reference genes highly correlated with the 21-gene recurrence score (RS) algorithm were selected from public databases. Targeted RNA-sequencing was performed using 250 and 93 archived breast cancer samples with a known RS in the training and verification sets, respectively, to develop the algorithm and NGS–Prognostic Score (NGS-PS). The assay was validated in 413 independent samples with long-term follow-up data on distant metastasis. Results: In the verification set, the NGS-PS and 21-gene RS displayed 91.4% concurrence (85/93 samples). In the validation cohort of 413 samples, area under the receiver operating characteristic curve plotted using NGS-PS values classified for distant recurrence was 0.76. The best NGS-PS cut-off value predicting distant metastasis was 20. Furthermore, 269 and 144 patients were classified as low- and high-risk patients in accordance with the cut-off. Five- and 10-year estimates of distant metastasis–free survival (DMFS) for low- versus high-risk groups were 97.0% versus 77.8% and 93.2% versus 64.4%, respectively. The age-related HR for distant recurrence without chemotherapy was 9.73 (95% CI, 3.59–26.40) and 3.19 (95% CI, 1.40–7.29) for patients aged ≤50 and >50 years, respectively. Conclusions: The newly developed and validated NGS-based multigene assay can predict the distant recurrence risk in ER-positive, HER2-negative breast cancer.
Several studies provide insight into the landscape of breast cancer genomics with the genomic characterization of tumors offering exceptional opportunities in defining therapies tailored to the patient’s specific need. However, translating genomic data into personalized treatment regimens has been hampered partly due to uncertainties in deviating from guideline based clinical protocols. Here we report a genomic approach to predict favorable outcome to treatment responses thus enabling personalized medicine in the selection of specific treatment regimens. The genomic data were divided into a training set of N = 835 cases and a validation set consisting of 1315 hormone sensitive, 634 triple negative breast cancer (TNBC) and 1365 breast cancer patients with information on neoadjuvant chemotherapy responses. Patients were selected by the following criteria: estrogen receptor (ER) status, lymph node invasion, recurrence free survival. The k-means classification algorithm delineated clusters with low- and high- expression of genes related to recurrence of disease; a multivariate Cox’s proportional hazard model defined recurrence risk for disease. Classifier genes were validated by Immunohistochemistry (IHC) using tissue microarray sections containing both normal and cancerous tissues and by evaluating findings deposited in the human protein atlas repository. Based on the leave-on-out cross validation procedure of 4 independent data sets we identified 51-genes associated with disease relapse and selected 10, i.e. TOP2A, AURKA, CKS2, CCNB2, CDK1 SLC19A1, E2F8, E2F1, PRC1, KIF11 for in depth validation. Expression of the mechanistically linked disease regulated genes significantly correlated with recurrence free survival among ER-positive and triple negative breast cancer patients and was independent of age, tumor size, histological grade and node status. Importantly, the classifier genes predicted pathological complete responses to neoadjuvant chemotherapy (P < 0.001) with high expression of these genes being associated with an improved therapeutic response toward two different anthracycline-taxane regimens; thus, highlighting the prospective for precision medicine. Our study demonstrates the potential of classifier genes to predict risk for disease relapse and treatment response to chemotherapies. The classifier genes enable rational selection of patients who benefit best from a given chemotherapy thus providing the best possible care. The findings encourage independent clinical validation.
Abstract Patellar tendinopathy (PT) is a common nontraumatic orthopaedic disorder of the knee suffered by many service members. Understanding the make-up of usual care for PT at the system level can better frame current clinical gaps and areas that need improvement. Exercise therapy is recommended as a core treatment for PT, but it is unclear how often it is used as a part of usual care for PT within the Military Health System (MHS). The purpose of the study was to identify interventions used in the management of PT and the timing of these interventions. A secondary purpose was to determine if exercise therapy use was associated with reduced recurrence of knee pain. In total, 4,719 individuals aged 17 to 50 years in the MHS diagnosed with PT between 2010 and 2011 were included. Pharmacological and nonpharmacological interventions, visits to specialty providers, and imaging services were captured. Descriptive statistics were used to report the findings. Interventions were further categorized as being part of initial care (within the first 7 days), the initial episode of care (within the first 60 days), or the 2-year time period after diagnosis. Linear regression assessed the relationship between the number of exercise therapy visits in the initial episode of care and recurrences of knee pain. In total, 50.6% of this cohort had no more than one medical visit total for PT. Exercise therapy (18.2%) and nonsteroidal anti-inflammatory drugs (4.3%) were the two most used interventions in the initial episode of care. Radiographs were ordered for 23.1% of the cohort in the initial episode of care. The number of exercise therapy visits a patient received during the initial episode of care was not associated with recurrences of knee pain. Half of the individuals received no further care beyond an initial visit for the diagnosis of PT. Exercise therapy was the most common intervention used during the initial episode of care, but exercise therapy did not influence the recurrence of knee pain.
Fully coupled randomly disordered recurrent superconducting networks with additional open-ended channels for inputs and outputs are considered the basis to introduce a new architecture to neuromorphic computing in this work. Various building blocks of such a network are designed around disordered array synaptic networks using superconducting devices and circuits as an example, while emphasizing that a similar architectural approach may be compatible with several other materials and devices. A multiply coupled (interconnected) disordered array of superconducting loops containing Josephson junctions [equivalent to superconducting quantum interference devices (SQUIDs)] forms the aforementioned collective synaptic network that forms a fully recurrent network together with compatible neuron-like elements and feedback loops, enabling unsupervised learning. This approach aims to take advantage of superior power efficiency, propagation speed, and synchronizability of a small world or a random network over an ordered/regular network. Additionally, it offers a significant factor of increase in scalability. Here, a compatible leaky integrate-and-fire neuron made of superconducting loops with Josephson junctions is presented, along with circuit components for feedback loops as needed to complete the recurrent network. Several of these individual disordered array neural networks can further be coupled together in a similarly disordered way to form a hierarchical architecture of recurrent neural networks that is often suggested as similar to a biological brain.
In 2005, Britto, Cachazo, Feng, and Witten gave a recurrence (now known as the BCFW recurrence) for computing scattering amplitudes in N = 4 super Yang–Mills theory. Arkani-Hamed and Trnka subsequently introduced the amplituhedron to give a geometric interpretation of the BCFW recurrence. Arkani-Hamed and Trnka conjectured that each way of iterating the BCFW recurrence gives a “triangulation” or “tiling” of the m=4 amplituhedron. In this article, we prove the BCFW tiling conjecture of Arkani-Hamed and Trnka. We also prove the cluster adjacency conjecture for BCFW tiles of the amplituhedron, which says that facets of tiles are cut out by collections of compatible cluster variables for the Grassmannian Gr4,n. Moreover we show that each BCFW tile is the subset of the Grassmannian where certain cluster variables have particular signs.
Although genomic anomalies in glioblastoma (GBM) have been well studied for over a decade, its 5-year survival rate remains lower than 5%. We seek to expand the molecular landscape of high-grade glioma, composed of IDH-wildtype GBM and IDH-mutant grade 4 astrocytoma, by integrating proteomic, metabolomic, lipidomic, and post-translational modifications (PTMs) with genomic and transcriptomic measurements to uncover multi-scale regulatory interactions governing tumor development and evolution. Applying 14 proteogenomic and metabolomic platforms to 228 tumors (212 GBM and 16 grade 4 IDH-mutant astrocytoma), including 28 at recurrence, plus 18 normal brain samples and 14 brain metastases as comparators, reveals heterogeneous upstream alterations converging on common downstream events at the proteomic and metabolomic levels and changes in protein-protein interactions and glycosylation site occupancy at recurrence. Recurrent genetic alterations and phosphorylation events on PTPN11 map to important regulatory domains in three dimensions, suggesting a central role for PTPN11 signaling across high-grade gliomas.
Highlights: • Clinicians and researchers need to be cognizant of competing risks (ie, the occurrence of an event that precludes future development of the outcome of interest). • Censoring is appropriate when a patient being censored at a particular time (eg, owing to loss to follow-up) is deemed to have approximately the same future risk of developing the outcome of interest as patients still being followed, and when the reason for censoring is not related to events of interest. • Censoring is not appropriate in many scenarios; for example, a dead patient can never develop a future cancer recurrence or late effect. • Kaplan-Meier (KM) analysis is commonly used for a time-to-event analysis when the primary outcome (eg, overall survival) has no meaningful competing risk and censoring is appropriate. Cox proportional hazards modeling can be used for multivariable analysis to examine the association between covariates and the primary outcome. • In the presence of competing events, incorrect use of the KM analysis will likely lead to an overestimation of the risk of the outcome of interest and biased estimates from both univariable and multivariable analyses. Therefore, KM usually should not be used to determine local recurrence risk because humanity is always at risk for dying, which is a competing risk. • A competing risk analysis is therefore most appropriate when there are competing events to the primary outcome of interest. The most commonly used multivariable model in these situations is the Fine-Gray model. • Many fundamental questions in radiation oncology—local and regional recurrence, treatment-related toxicity—are best addressed using competing risk methodologies.
Highlights: • BCSLCs play a critical role for the high risk of recurrence and we identified that lncRNA-AK023096 was required for controls stemness of BCSLCs. • LncRNA-AK023096 recruits hnRNP-K and epigenetically upregulated SOX2 expression by modulating H3K4 trimethylation of SOX2 promoter. • Overexpression of lncRNA-AK023096 expression in the tumor tissue was significantly associated with high risk of recurrence following TUR-Bt. LncRNA contribution to self-renewal of bladder cancer stem-like cells (CSLCs) remains largely unknown. We investigated the expression profile and biological function of lncRNAs in urothelial CSLCs by microarray analysis. Among these, lncRNA-AK023096 was identified as potentially playing a role in maintaining self-renewal of CSLCs. Knockdown of this transcript inhibited spheroid formation and tumor formation. We found that AK023096 mediates recruitment of hnRNP-K to SOX2 promoter and increases H3K4 trimethylation status on SOX2 promoter, leading to a robust change in SOX2 mRNA and protein levels. Moreover, AK023096 expression in primary tumors was found to be a powerful predictor of recurrence following transurethral resection in patients with nonmuscle-invasive bladder cancer, highlighting the critical role of lncRNA in the bladder cancer regulatory network.
Projected precipitation changes in a warming climate vary considerably, spatially, and between intensities. The changes can be greater or less than the ~7% K -1 Clausius-Clapeyron (CC) prediction, owing to dynamic effects. Using two global-climate-model large ensembles, we quantify the dynamically induced changes to precipitation extremes from the present (1996–2005) to late-21st-century (2071–2080) climates, as a function of recurrence interval, focusing on the subtropics. We separate non-CC changes into a term proportional to the present-day vertical-velocity spatial pattern (i.e., an amplification or damping thereof by a constant factor) and a residual. The amplitude term varies with recurrence interval, approximately canceling (doubling) CC for moderate (large) extremes, increasing precipitation variability. Contrastingly, the residual is quasi-uniform across recurrence intervals but spatially heterogeneous, weakening extremes over dry zones. This residual may be related to Hadley cell expansion, although this explanation is insufficient to explain many features, and other possible mechanisms are discussed.
Time series forecasting (TSF) is one of the most important tasks in data science. TSF models are usually pre-trained with historical data and then applied on future unseen datapoints. However, real-world time series data is usually non-stationary and models trained offline usually face problems from data drift. Models trained and designed in an offline fashion can not quickly adapt to changes quickly or be deployed in real-time. To address these issues, this work presents the Online NeuroEvolution-based Neural Architecture Search (ONE-NAS) algorithm, which is a novel neural architecture search method capable of automatically designing and dynamically training recurrent neural networks (RNNs) for online forecasting tasks. Without any pre-training, ONE-NAS utilizes populations of RNNs that are continuously updated with new network structures and weights in response to new multivariate input data. ONE-NAS is tested on real-world, large-scale multivariate wind turbine data as well as the univariate Dow Jones Industrial Average (DJIA) dataset. These results demonstrate that ONE-NAS outperforms traditional statistical time series forecasting methods, including online linear regression, fixed long short-term memory (LSTM) and gated recurrent unit (GRU) models trained online, as well as state-of-the-art, online ARIMA strategies. Additionally, results show that utilizing multiple populations of RNNs which are periodically repopulated provide significant performance improvements, allowing this online neural network architecture design and training to be successful.
Building thermal models, which characterize the properties of a building’s envelope and thermal mass, are essential for accurate indoor temperature and cooling/heating demand prediction. Because of their flexibility and ease of use, data-driven models are increasingly used. Here, this study compared and analyzed the performance of gray-box (resistance-capacitance) and black-box (recurrent neural network) models for predicting indoor air temperature in a real multi-zone commercial building. The developed resistance-capacitance model served as a benchmark model for which full sets of temporal data and building information were used as inputs. The recurrent neural network models were trained and tested assuming various available types and amounts of temporal data and known building physical information to investigate the effects of data and information availability. Feature importance analysis was conducted to select the key variables for different prediction targets under different scenarios. This research provides guidance in selecting an appropriate building thermal response modeling method based on the measured data availability, building physical information, and application.