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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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42 records · Page 3

Establishing reference ranges for circulating biomarkers of drug‐induced liver injury in healthy human volunteers 1

Aims The potential of mechanistic biomarkers to improve prediction of drug‐induced liver injury (DILI) and hepatic regeneration is widely acknowledged. We sought to determine reference intervals for new biomarkers of DILI and regeneration, as well as to characterize their natural variability and impact of diurnal variation. Methods Serum samples from 227 healthy volunteers were recruited as part of a cross‐sectional study; of these, 25 subjects had weekly serial sampling over 3 weeks, while 23 had intensive blood sampling over a 24h period. Alanine aminotransferase (ALT), MicroRNA‐122 (miR‐122), High Mobility Group Box‐1 (HMGB1), total Keratin‐18 (K18), caspase‐cleaved Keratin‐18 (ccK18), Glutamate Dehydrogenase (GLDH) and Macrophage Colony‐Stimulating Factor‐1 (CSF‐1) were assayed. Results Reference intervals were established for each biomarker based on the 97.5% quantile (90% CI) following the assessment of fixed effects in univariate and multivariable models. Intra‐individual variability was found to be non‐significant, and there was no significant impact of diurnal variation. Conclusion Reference intervals for novel DILI biomarkers have been described. An upper limit of a reference range might represent the most appropriate mechanism to utilize these data. These data can now be used to interpret data from exploratory clinical DILI studies and to assist their further qualification as required by regulatory authorities.

Jorgensen, Andrea L. [Department of Health Data Sc↗

A NICER View of the Massive Pulsar PSR J0740+6620 Informed by Radio Timing and XMM-Newton Spectroscopy

We report on Bayesian estimation of the radius, mass, and hot surface regions of the massive millisecond pulsar PSR J0740+6620, conditional on pulse-profile modeling of Neutron Star Interior Composition Explorer X-ray Timing Instrument event data. We condition on informative pulsar mass, distance, and orbital inclination priors derived from the joint North American Nanohertz Observatory for Gravitational Waves and Canadian Hydrogen Intensity Mapping Experiment/Pulsar wideband radio timing measurements of Fonseca et al. We use XMM-Newton European Photon Imaging Camera spectroscopic event data to inform our X-ray likelihood function. The prior support of the pulsar radius is truncated at 16 km to ensure coverage of current dense matter models. We assume conservative priors on instrument calibration uncertainty. We constrain the equatorial radius and mass of PSR J0740+6620 to be ${12.39}_{-0.98}^{+1.30}$ km and ${2.072}_{-0.066}^{+0.067}$ M ⊙ respectively, each reported as the posterior credible interval bounded by the 16% and 84% quantiles, conditional on surface hot regions that are non-overlapping spherical caps of fully ionized hydrogen atmosphere with uniform effective temperature; a posteriori, the temperature is ${\mathrm{log}}_{10}(T\,[{\rm{K}}])={5.99}_{-0.06}^{+0.05}$ for each hot region. All software for the X-ray modeling framework is open-source and all data, model, and sample information is publicly available, including analysis notebooks and model modules in the Python language. Furthermore, our marginal likelihood function of mass and equatorial radius is proportional to the marginal joint posterior density of those parameters (within the prior support) and can thus be computed from the posterior samples.

79 ASTRONOMY AND ASTROPHYSICS↗

Quantile Vocoder

Parameters of spectral envelope obtained statistically. Algorithm for digital compression of speech signals encodes power spectral density of each short interval of speech by use of quantiles or order statistics. Purpose to reduce bit rate and bandwidth required for transmission. When fully developed, quantile vocoder - speech-encoding system based on new algorithm - expected moderately complicated compared with other speech-encoding systems and reproduce high-quality speech from code transmitted at relatively low bit rates. Speech signal treated mathematically as though amplitude spectrum stationary during short coding intervals, called "windows". Window duration of 20 or 35 ms, chosen as compromise between frequency resolution and time resolution. During each window, short-time amplitude and power spectra found by sampling at high rate (typically 10 kHz) and taking fast Fourier transforms (FFT's).

Swaminathan, Kumar↗

Trend Detection of Atmospheric Time Series: Incorporating Appropriate Uncertainty Estimates and Handling Extreme Events

This paper is aimed at atmospheric scientists without formal training in statistical theory. Its goal is to, 1) provide a critical review of the rationale for trend analysis of the time series typically encountered in the field of atmospheric chemistry; 2) describe a range of trend-detection methods; and 3) demonstrate effective means of conveying the results to a general audience. Trend detections in atmospheric chemical composition data are often challenged by a variety of sources of uncertainty, which often behave differently to other environmental phenomena such as temperature, precipitation rate, or stream flow, and may require specific methods depending on the science questions to be addressed. Some sources of uncertainty can be explicitly included in the model specification, such as autocorrelation and seasonality, but some inherent uncertainties are difficult to quantify, such as data heterogeneity and measurement uncertainty due to the combined effect of short- and long-term natural variability, instrumental stability, and aggregation of data from sparse sampling frequency. Failure to account for these uncertainties might result in an inappropriate inference of the trends and their estimation errors. On the other hand, the variation in extreme events might be interesting for different scientific questions, for example, the frequency of extremely high surface ozone events and their relevance to human health. In this study we aim to, 1) review trend detection methods for addressing different levels of data complexity in different chemical species; 2) demonstrate that the incorporation of scientifically interpretable covariates can outperform pure numerical curve fitting techniques in terms of uncertainty reduction and improved predictability; 3) illustrate the study of trends based on extreme quantiles that can provide insight beyond standard mean or median based trend estimates; and 4) present an advanced method of quantifying regional trends based on the inter-site correlations of multi-site data. All demonstrations are based on time series of observed trace gases relevant to atmospheric chemistry, but the methods can be applied to other environmental data sets.

Trace gas↗

An Inverse Chance-constrained Approach to the Calibration of Robust Models

This paper proposes a strategy to calibrate computational models according to uncertain input-output data. To this end, uncertainty in the data is first quantified by creating adversarial data sets. Samples drawn from such sets are then mapped from the input-output space to the parameter space using an inverse mapping. This mapping minimizes the collective output spread of an ensemble of point predictions while satisfying a set of individual data-matching requirements. The distribution of the resulting parameter points, which often exhibits strong parameter dependencies, is then modeled using sliced-normals. The chance-constrained formulation used to learn this distribution enables the analyst to trade-off a greater likelihood for most of the data against a lower likelihood for some of the data thereby relaxing the conservatism of the calibrated model. This formulation not only neglects the worst-performing quantiles of each adversarial distribution but also eliminates the potentially serious effects that outliers might have on the resulting model. This calibration approach not only has a considerably lower computational cost than the standard forward approach but it also allows for the identification of suitable distribution classes, which in turn yield better calibrated models.

Calibration↗

Uncertainty Quantification using Deep Ensembles for Decision Making in Cyber-Physical-Human Systems

In this paper and its companion, Differential Equation Approximation Using Gradient-Boosted Quantile Regression, Robison et al., we examine an approach to quantifying model uncertainty with the aim of increasing the trustworthiness of computational models in human-machine interactions. In Differential Equation Approximation Using Gradient-Boosted Quantile Regression, we focus on gradient-boosted decision trees, while in this one, we give more details about deep ensembles. Uncertainty quantification is crucial for building trustworthy autonomous decision-making agents in human-machine teams. There are two types of uncertainties: aleatoric and epistemic. The former is related to the inherent stochasticity (noise) of the process, whereas the latter is associated with the lack of knowledge or representation capability of models, such as neural networks. By lack of knowledge, we mean the model’s inability to accurately predict outputs for all possible inputs. The aleatory uncertainty can be estimated fairly easily with, for example, filters, whereas epistemic uncertainty is challenging to compute. This paper uses deep ensembles to quantify both aleatory and epistemic uncertainty. It can act as an uncertainty-aware surrogate transition model for decision-making frameworks. "Uncertainty-aware" means that the surrogate transition model should make predictions along with confidence in those predictions. In the context of decision-making, the transition models are ordinary differential equations (ODEs). Since ODEs can be simulated to make one-step or multi-step predictions, a good surrogate model for them should perform reasonably well in both modes. In a multi-step approach, the trajectory sampling method TS∞ was used to propagate uncertainty over multiple steps. The cartpole dynamical system was selected to demonstrate the ability of deep ensembles as good surrogate transition models for decision-making frameworks. The deep ensembles modeled the dynamics of cartpole ODEs and made uncertainty-aware predictions in single-step and multi-step transition modes.

CPH systems↗