Interpretable Performance Models for Energetic Materials using Parsimonious Neural Networks.

Predictive models for the performance of explosives and propellants are important for their design, optimization, and safety. Thermochemical codes can predict some of these properties from fundamental quantities such as density and formation energies that can be obtained from first principles. Models that are simpler to evaluate are desirable for efficient, rapid screening of material screening. In addition, interpretable models can provide insight into the physics and chemistry of these materials that could be useful to direct new synthesis. Current state-of-the-art performance models are based on either the parametrization of physics-based expressions or data-driven approaches with minimal interpretability. We use parsimonious neural networks (PNNs) to discover interpretable models for the specific impulse of propellants and detonation velocity and pressure for explosives using data collected from the open literature. A combination of evolutionary optimization with custom neural networks explores and trains models with objective functions that balance accuracy and complexity. For all three properties of interest, we find interpretable models that are Pareto optimal in the accuracy and simplicity space.

Scale dependence of coral reef oases and their environmental correlates.

Identifying relatively intact areas within ecosystems and determining the conditions favoring their existence is necessary for effective management in the context of widespread environmental degradation. In this study, we used 3766 surveys of randomly selected sites in the United States and U.S. Territories to identify the correlates of sites categorized as "oases" (defined as sites with relatively high total coral cover). We used occupancy models to evaluate the influence of 10 environmental predictors on the probability that an area (21.2-km2 cell) would harbor coral oases defined at four spatial extents: cross-basin, basin, region, and subregion. Across all four spatial extents, oases were more likely to occur in habitats with high light attenuation. The influence of the other environmental predictors on the probability of oasis occurrence were less consistent and varied with the scale of observation. Oases were most likely in areas of low human population density, but this effect was evident only at the cross-basin and subregional extents. At the regional and subregional extents oases were more likely where sea-surface temperature was more variable, whereas at the larger spatial extents the opposite was true. By identifying the correlates of oasis occurrence, the model can inform the prioritization of reef areas for management. Areas with biophysical conditions that confer corals with physiological resilience, as well as limited human impacts, likely support coral reef oases across spatial extents. Our approach is widely applicable to the development of conservation strategies to protect biodiversity and ecosystems in an era of magnified human disturbance.

Building Chemical Property Models for Energetic Materials from Small Datasets Using a Transfer Learning Approach.

For many experimentally measured chemical properties that cannot be directly computed from first-principles, the existing physics-based models do not extrapolate well to out-of-sample molecules, and experimental datasets themselves are too small for traditional machine learning (ML) approaches. To overcome these limitations, we apply a transfer learning approach, whereby we simultaneously train a multi-target regression model on a small number of molecules with experimentally measured values and a large number of molecules with related computed properties. We demonstrate this methodology on predicting the experimentally measured impact sensitivity of energetic crystals, finding that both characteristics of the computed dataset and model architecture are important to prediction accuracy of the small experimental dataset. Our directed-message passing neural network (D-MPNN) ML model using transfer learning outperforms direct-ML and physics-based models on a diverse test set, and the new methods described here are widely applicable to modeling many other structure-property relationships.

Bulbar urethrocavernous fistula in setting of inflatable penile prosthesis: a case report.

BACKGROUND: Urethral injury or erosion of an inflatable penile prosthetic (IPP) cylinder is a rare complication of IPP placement. It can present with varying symptoms and management can be difficult with risk for future complications. We present a patient with an eroded IPP who developed a secondary contralateral urethrocavernous fistula requiring repeat urethroplasty. We also describe the literature surrounding these complications and strategies to prevent them. CASE PRESENTATION: A 69-year-old man with poorly controlled diabetes presented to our clinic with 6 months of intermittent white urethral discharge first noted after IPP removal and replacement by an outside urologist for device malfunction. Office cystoscopy revealed an eroded right-sided prosthetic cylinder in the bulbar urethra. The patient was taken to the operating room for IPP explantation with closure of right corporal defect, left sided malleable prosthesis placement, and primary excision with anastomosis of his bulbar urethra. A catheter was left in place for two weeks postoperatively, at which time a peri-catheter retrograde urethrogram was performed which showed no evidence of contrast extravasation and his catheter was subsequently removed. Several months later, he presented with recurrent urethral discharge without evidence of recurrent erosion on cystoscopy with development of scrotal abscesses following office cystoscopy, concerning for an unidentified urethral defect. He returned to the operating room for scrotal exploration and was noted on cystoscopy to have a pinpoint fistula between his left corporal body and his bulbar urethra. He underwent left sided malleable prosthetic explant, and non-transecting bulbar urethroplasty. Peri-catheter retrograde urethrogram two weeks later showed no contrast extravasation and he has had no recurrence of urethral discharge or scrotal abscesses since. CONCLUSIONS: Urethral erosion and urethrocavernous fistula formation are rare complications of penile prosthesis placement. Risks are elevated in patients with corporal fibrosis, diabetes, those undergoing penile implant revision surgery, and those requiring prolonged urethral catheterization.

Prediction of Energetic Material Properties from Electronic Structure Using 3D Convolutional Neural Networks.

We develop a convolutional neural network capable of directly parsing the 3D electronic structure of a molecule described by spatial point data for charge density and electrostatic potential represented as a 4D tensor. This method effectively bypasses the need to construct complex representations, or descriptors, of a molecule. This is beneficial because the accuracy of a machine learned model depends on the input representation. Ideally, input descriptors encode the essential physics and chemistry that influence the target property. Thousands of molecular descriptors have been proposed, and proper selection of features requires considerable domain expertise or exhaustive and careful statistical downselection. In contrast, deep learning networks are capable of learning rich data representations. This provides a compelling motivation to use deep learning networks to learn molecular structure-property relations from "raw" data. The convolutional neural network model is jointly trained on over 20,000 molecules that are potentially energetic materials (explosives) to predict dipole moment, total electronic energy, Chapman-Jouguet (C-J) detonation velocity, C-J pressure, C-J temperature, crystal density, HOMO-LUMO gap, and solid phase heat of formation. This work demonstrates the first use of complete 3D electronic structure for machine learning of molecular properties.

Data Augmentation and Pretraining for Template-Based Retrosynthetic Prediction in Computer-Aided Synthesis Planning.

This work presents efforts to augment the performance of data-driven machine learning algorithms for reaction template recommendation used in computer-aided synthesis planning software. Often, machine learning models designed to perform the task of prioritizing reaction templates or molecular transformations are focused on reporting high-accuracy metrics for the one-to-one mapping of product molecules in reaction databases to the template extracted from the recorded reaction. The available templates that get selected for inclusion in these machine learning models have been previously limited to those that appear frequently in the reaction databases and exclude potentially useful transformations. By augmenting open-access data sets of organic reactions with explicitly calculated template applicability and pretraining a template-relevance neural network on this augmented applicability data set, we report an increase in the template applicability recall and an increase in the diversity of predicted precursors. The augmentation and pretraining effectively teaches the neural network an increased set of templates that could theoretically lead to successful reactions for a given target. Even on a small data set of well-curated reactions, the data augmentation and pretraining methods resulted in an increase in top-1 accuracy, especially for rare templates, indicating that these strategies can be very useful for small data sets.

Injections of concentrated bone marrow aspirate as treatment for Discogenic pain: a retrospective analysis.

BACKGROUND: There are an overwhelming number of patients suffering from low back pain (LBP) resulting from disc pathology. Although several strategies are being developed pre-clinically, simple strategies to treat the large number of patients currently affected is still needed. One option is to use concentrated bone marrow aspirate (cBMA), which may be effective due to its intrinsic stem cells and growth factors. METHODS: Thirty-three patients who received intradiscal injections of cBMA to relieve LBP were followed up based on Numeric Rating Scale (NRS), Oswestry Low Back Pain Disability Index (ODI), and Short Form-36 Health Survey (SF-36) scores. Patients were also subdivided into those with a pre-injection NRS > 5 and pre-injection NRS ≤ 5. The proportion of patients demonstrating at least 50% improvement (and 95% confidence intervals) from baseline at five follow-up visits for each outcome was evaluated. RESULTS: At least 50% improvement in NRS was observed for 13.8, 45.8, 41.1, 23.5, and 38.9% of patients across five follow-up visits, out to 1 year. When stratified by high (> 5) versus low (≤ 5) baseline NRS scores, the values were 14.3, 45.5, 71.4, 22.2, and 44.4% among those with high baseline pain, and 13.3, 46.2, 20.0, 25.0, and 33.3% among those with low baseline pain. The 50% improvement rates across visits were 4.3, 28.6, 30.0, 22.2, and 30.8% for SF-36, and 4.2, 26.7, 36.4, 55.6, and 30.8% for ODI. CONCLUSIONS: Intradiscal cBMA injections may be effective to reduce pain and improve function. Patients with relatively higher initial pain may have potential for greatest improvement.

Tissue-specific telomere dynamics in hibernating arctic ground squirrels (Urocitellus parryii).

Hibernation is used by a variety of mammals to survive seasonal periods of resource scarcity. Reactive oxygen species (ROS) released during periodic rewarming throughout hibernation, however, may induce oxidative damage in some tissues. Telomeres, which are the terminal sequences of linear chromosomes, may shorten in the presence of ROS, and thus the telomere length of an individual reflects the degree of accrued oxidative damage. This study quantified telomere length dynamics throughout hibernation in arctic ground squirrels (Urocitellus parryii). We hypothesized that telomere dynamics are tissue specific and predicted that telomere shortening would be most pronounced in brown adipose tissue (BAT), the organ that directly supports non-shivering thermogenesis during arousals. We used qPCR to determine relative telomere length (RTL) in DNA extracted from liver, heart, skeletal muscle (SM) and BAT of 45 juvenile and adult animals sampled either at mid- or late hibernation. Age did not have a significant effect on RTL in any tissue. At mid-hibernation, RTL of juvenile females was longer in BAT and SM than in liver and heart. In juvenile females, RTL in BAT and SM, but not in liver and heart, was shorter at late hibernation than at mid-hibernation. At late hibernation, juvenile males had longer RTL in BAT than did juvenile females, perhaps due to the naturally shorter hibernation duration of male arctic ground squirrels. Finally, BAT RTL at late hibernation negatively correlated with arousal frequency. Overall, our results suggest that, in a hibernating mammal, telomere shortening is tissue specific and that metabolically active tissues might incur higher levels of molecular damage.

Sex-Dependent Phenological Plasticity in an Arctic Hibernator.

Hibernation provides a means of escaping the metabolic challenges associated with seasonality, yet the ability of mammals to prolong or reenter seasonal dormancy in response to extreme weather events is unclear. Here, we show that Arctic ground squirrels in northern Alaska exhibited sex-dependent plasticity in the physiology and phenology of hibernation in response to a series of late spring snowstorms in 2013 that resulted in the latest snowmelt on record. Females and nonreproductive males responded to the >1-month delay in snowmelt by extending heterothermy or reentering hibernation after several days of euthermy, leading to a >2-week delay in reproduction compared to surrounding years. In contrast, reproductive males neither extended nor reentered hibernation, likely because seasonal gonadal growth and development and subsequent testosterone release prevents a return to torpor. Our findings reveal intriguing differences in responses of males and females to climatic stressors, which can generate a phenological mismatch between the sexes.

Entraining to the polar day: circadian rhythms in arctic ground squirrels.

Circadian systems are principally entrained to 24 h light-dark cycles, but this cue is seasonally absent in polar environments. Although some resident polar vertebrates have weak circadian clocks and are seasonally arrhythmic, the arctic ground squirrel (AGS) maintains daily rhythms of physiology and behavior throughout the summer, which includes 6 weeks of constant daylight. Here, we show that persistent daily rhythms in AGS are maintained through a circadian system that readily entrains to the polar day yet remains insensitive to entrainment by rapid light-dark transitions, which AGS generate naturally as a consequence of their semi-fossorial behavior. Additionally, AGS do not show 'jet lag', the slow realignment of circadian rhythms induced by the inertia of an intrinsically stable master circadian clock in the suprachiasmatic nucleus (SCN). We suggest this is due to the low expression of arginine vasopressin in the SCN of AGS, as vasopressin is associated with inter-neuronal coupling and robust rhythmicity.

Stable isotope analysis of CO2 in breath indicates metabolic fuel shifts in torpid arctic ground squirrels.

Stable carbon isotope ratios (δ13C) in breath show promise as an indicator of immediate metabolic fuel utilization in animals because tissue lipids have a lower δ13C value than carbohydrates and proteins. Metabolic fuel consumption is often estimated using the respiratory exchange ratio (RER), which has lipid and carbohydrate boundaries, but does not differentiate between protein and mixed fuel catabolism at intermediate values. Because lipids have relatively low δ13C values, measurements of stable carbon isotopes in breath may help distinguish between catabolism of protein and mixed fuel that includes lipid. We measured breath δ13C and RER concurrently in arctic ground squirrels (Urocitellus parryii) during steady-state torpor at ambient temperatures from -2 to -26°C. As predicted, we found a correlation between RER and breath δ13C values; however, the range of RER in this study did not reach intermediate levels to allow further resolution of metabolic substrate use with the addition of breath δ13C measurements. These data suggest that breath δ13C values are 1.1‰ lower than lipid tissue during pure lipid metabolism. From RER, we determined that arctic ground squirrels rely on nonlipid fuel sources for a significant portion of energy during torpor (up to 37%). The shift toward nonlipid fuel sources may be influenced by adiposity of the animals in addition to thermal challenge.

Persistence, entrainment, and function of circadian rhythms in polar vertebrates.

Polar organisms must cope with an environment that periodically lacks the strongest time-giver, or zeitgeber, of circadian organization-robust, cyclical oscillations between light and darkness. We review the factors influencing the persistence of circadian rhythms in polar vertebrates when the light-dark cycle is absent, the likely mechanisms of entrainment that allow some polar vertebrates to remain synchronized with geophysical time, and the adaptive function of maintaining circadian rhythms in such environments.

Proteomic Profiling Reveals Adaptive Responses to Surgical Myocardial Ischemia-Reperfusion in Hibernating Arctic Ground Squirrels Compared to Rats.

BACKGROUND: Hibernation is an adaptation to extreme environments known to provide organ protection against ischemia-reperfusion (I/R) injury. An unbiased systems approach was utilized to investigate hibernation-induced changes that are characteristic of the hibernator cardioprotective phenotype, by comparing the myocardial proteome of winter hibernating arctic ground squirrels (AGS), summer active AGS, and rats subjected to I/R, and further correlating with targeted metabolic changes. METHODS: In a well-defined rodent model of I/R by deep hypothermic circulatory arrest followed by 3 or 24 h of reperfusion or sham, myocardial protein abundance in AGS (hibernating summer active) and rats (n = 4 to 5/group) was quantified by label-free proteomics (n = 4 to 5/group) and correlated with metabolic changes. RESULTS: Compared to rats, hibernating AGS displayed markedly reduced plasma levels of troponin I, myocardial apoptosis, and left ventricular contractile dysfunction. Of the 1,320 rat and 1,478 AGS proteins identified, 545 were differentially expressed between hibernating AGS and rat hearts (47% up-regulated and 53% down-regulated). Gene ontology analysis revealed down-regulation in hibernating AGS hearts of most proteins involved in mitochondrial energy transduction, including electron transport chain complexes, acetyl CoA biosynthesis, Krebs cycle, glycolysis, and ketogenesis. Conversely, fatty acid oxidation enzymes and sirtuin-3 were up-regulated in hibernating AGS, with preserved peroxisome proliferator-activated receptor-α activity and reduced tissue levels of acylcarnitines and ceramides after I/R. CONCLUSIONS: Natural cardioprotective adaptations in hibernators involve extensive metabolic remodeling, featuring increased expression of fatty acid metabolic proteins and reduced levels of toxic lipid metabolites. Robust up-regulation of sirtuin-3 suggests that posttranslational modifications may underlie organ protection in hibernating mammals.

A coarse-grain force field for RDX: Density dependent and energy conserving.

We describe the development of a density-dependent transferable coarse-grain model of crystalline hexahydro-1,3,5-trinitro-s-triazine (RDX) that can be used with the energy conserving dissipative particle dynamics method. The model is an extension of a recently reported one-site model of RDX that was developed by using a force-matching method. The density-dependent forces in that original model are provided through an interpolation scheme that poorly conserves energy. The development of the new model presented in this work first involved a multi-objective procedure to improve the structural and thermodynamic properties of the previous model, followed by the inclusion of the density dependency via a conservative form of the force field that conserves energy. The new model accurately predicts the density, structure, pressure-volume isotherm, bulk modulus, and elastic constants of the RDX crystal at ambient pressure and exhibits transferability to a liquid phase at melt conditions.

Integrating physiology, behavior, and energetics: Biologging in a free-living arctic hibernator.

The use of animal-borne instruments (ABIs), including biologgers and biotransmitters, has played an integral role in advancing our understanding of adjustments made by animals in their physiology and behavior across their annual and daily cycles and in response to weather and environmental change. Here, we review our research employing body temperature (Tb), light, and acceleration biologgers to measure patterns of physiology and behavior of a free-living, semi-fossorial hibernator, the arctic ground squirrel (Urocitellus parryii). We have used these devices to address a variety of physiological, ecological, and evolutionary questions within the fields of hibernation physiology, phenology, behavioral ecology, and chronobiology. We have also combined biologging with other approaches, such as endocrinology and tracking the thermal environment, to provide insights into the physiological mechanisms that underlie fundamental questions in biology including physiological performance trade-offs, timing and functional energetics. Finally, we explore the practical and methodological considerations that need to be addressed in biologging studies of free-living vertebrates and discuss future technological advancements that will increase the power and potential of biologging as a tool for assessing physiological function in dynamic and changing environments.

Alternatives to autograft evaluated in a rabbit segmental bone defect.

PURPOSE: This study was designed to identify strategies for treating bone defects that can be completed on the day of surgery. METHODS: Forty New Zealand white rabbits with unilateral rabbit radius segmental defects (15 mm) were treated with commercially available scaffolds containing either demineralised bone matrix (DBM) or a collagen/beta-tricalcium phosphate composite (Col:ß-TCP); each scaffold was combined with either bone marrow aspirate (BMA) or concentrated BMA (cBMA). Bone regeneration was assessed through radiographic and histological analyses. RESULTS: The concentration of nucleated cells, colony-forming unit-fibroblasts and platelets were increased and haematocrit concentration decreased in cBMA as compared to BMA (p < 0.05). Radiographic analyses of bone formation and defect bridging demonstrated significantly greater bone regeneration in the defects treated with DBM grafts as compared to Col:ß-TCP grafts. The healing of bones treated with Col:ß-TCP was improved when augmented with cBMA. CONCLUSIONS: Scaffolds containing either DBM or Col:ß-TCP with BMA or cBMA are effective same-day strategies available to clinicians for the treatment of bone defects; the latter scaffold may be more effective if combined with cBMA.

Energy regulation in context: Free-living female arctic ground squirrels modulate the relationship between thyroid hormones and activity among life history stages.

Thyroid hormones (THs), key regulators of lipid and carbohydrate metabolism, are likely modulators of energy allocation within and among animal life history stages. Despite their role in modulating metabolism, few studies have investigated whether THs vary among life history stages in free-living animals or if they exhibit stage-specific relationships to total energy expenditure and activity levels. We measured plasma total triiodothyronine (tT3) and thyroxine (tT4) at four, discrete life history stages of female arctic ground squirrels from two different populations in northern Alaska to test whether plasma THs correlate with life history stage-specific changes in metabolic rate and energy demand. We also tested whether THs explained individual variation in aboveground activity levels within life history stages. T3 peaked during lactation and was lowest during pre-hibernation fattening, consistent with known changes in basal metabolism and core body temperature. In contrast, T4 was elevated shortly after terminating hibernation but remained low and stable across other life-history stages in the active season. THs were consistently higher in the population that spent more time above-ground but the relationship between THs and activity varied among life history stages. T3 was positively correlated with activity only during lactation (r(2)=0.50) whereas T4 was positively correlated with activity immediately following lactation (r(2)=0.48) and during fattening (r(2)=0.53). Our results support the hypothesis that THs are an important modulator of basal metabolism but also suggest that the relationship between THs and activity varies among life history stages.

Nucleation rate analysis of methane hydrate from molecular dynamics simulations.

Clathrate hydrates are solid crystalline structures most commonly formed from solutions that have nucleated to form a mixed solid composed of water and gas. Understanding the mechanism of clathrate hydrate nucleation is essential to grasp the fundamental chemistry of these complex structures and their applications. Molecular dynamics (MD) simulation is an ideal method to study nucleation at the molecular level because the size of the critical nucleus and formation rate occur on the nano scale. Various analysis methods for nucleation have been developed through MD to analyze nucleation. In particular, the mean first-passage time (MFPT) and survival probability (SP) methods have proven to be effective in procuring the nucleation rate and critical nucleus size for monatomic systems. This study assesses the MFPT and SP methods, previously used for monatomic systems, when applied to analyzing clathrate hydrate nucleation. Because clathrate hydrate nucleation is relatively difficult to observe in MD simulations (due to its high free energy barrier), these methods have yet to be applied to clathrate hydrate systems. In this study, we have analyzed the nucleation rate and critical nucleus size of methane hydrate using MFPT and SP methods from data generated by MD simulations at 255 K and 50 MPa. MFPT was modified for clathrate hydrate from the original version by adding the maximum likelihood estimate and growth effect term. The nucleation rates calculated by MFPT and SP methods are within 5%, and the critical nucleus size estimated by the MFPT method was 50% higher, than values obtained through other more rigorous but computationally expensive estimates. These methods can also be extended to the analysis of other clathrate hydrates.

A harmful algal bloom of Karenia brevis in the northeastern Gulf of Mexico as revealed by MODIS and VIIRS: a comparison.

The most recent Visible Infrared Imager Radiometer Suite (VIIRS) is not equipped with a spectral band to detect solar-stimulated phytoplankton fluorescence. The lack of such a band may affect the ability of VIIRS to detect and quantify harmful algal blooms (HABs) in coastal waters rich in colored dissolved organic matter (CDOM) because of the overlap of CDOM and chlorophyll absorption within the blue-green spectrum. A recent HAB dominated by the toxin-producing dinoflagellate Karenia brevis in the northeastern Gulf of Mexico, offshore of Florida's Big Bend region, allowed for comparison of the capacities of VIIRS and Moderate Resolution Imaging Spectroradiometer (MODIS) to detect blooms in CDOM-rich waters. Both VIIRS and MODIS showed general consistency in mapping the CDOM-rich dark water, which measured a maximum area of 8900 km2 by mid-July 2014. However, within the dark water, only MODIS allowed detection of bloom patches-as indicated by high normalized fluorescence line height (nFLH). Field surveys between late July and mid-September confirmed Karenia brevis at bloom abundances up to 20 million cells·L(-1) within these patches. The bloom patches were well captured by the MODIS nFLH images, but not by the default chlorophyll a concentration (Chla) images from either MODIS or VIIRS. Spectral analysis showed that VIIRS could not discriminate these high-phytoplankton water patches within the dark water due to its lack of fluorescence band. Such a deficiency may be overcome with new algorithms or future satellite missions such as the U.S. NASA's Pre-Aerosol-Clouds-Ecology mission and the European Space Agency's Sentinel-3 mission.