Human-Centric Contingency Analysis Metrics for Evaluating Operator Performance and Trust
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24 POWER TRANSMISSION AND DISTRIBUTION↗
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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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Behavioral Health Benefits of the ISS Pick-and-Eat Crop Growth System
Summary: We summarize findings related to assessing the pick-and-eat salad-crop productivity and acceptability of the ISS food system as a countermeasure to maintain behavioral health in long-duration spaceflight. BACKGROUND Plants are a potential countermeasure for the stresses of living in space. Caring for plants and eating fresh food have been shown to serve as a psychological benefit for previous astronauts and for others in analogous environments such as Antarctica [1,2]. Gardening can be therapeutic in terrestrial settings [3]. These effects may carry over or be more pronounced in austere environments such as spaceflight. It can reduce stress and increase sensory stimulation and enjoyment [2]. Growing crops may offer astronauts meaningful and engaging work as they care for living things in an austere environment away from Earth’s nature and as they provide sustenance for their crew. We examined the extent to which interacting with plants (e.g., tending to, consuming) was related to behavioral health outcomes in long-duration space missions. METHOD Participants were 27 astronauts that interacted with the plant system VEG-04, VEG-05, and HRF-VEG (VEG-03 I-L, PH-04). In total, there were 106 in-flight observations. Participants completed monthly measures of mood and well-being, enjoyment and time spent performing specific crop growth and consuming the plants, meaningfulness, performance, connections with others and the Earth, desire to work with and eat plants, and experiences with struggling or dying plants. Higher ends of the 7-point Likert scale indicated more positive outcomes, lower ends of the scale were anchored with more negative outcomes, and the scale midpoints indicated neutral positions. Participants selected a specific survey version based on whether they interacted with the plant system(s) or not, and we included only the scores from the crewmembers that participated in any given activity. RESULTS & DISCUSSION Results indicated that participants generally rated tasks related to the plants and crop growth as enjoyable. Consuming the harvested plants and voluntary viewing were the most enjoyable activities. Tending to the plants was reported as moderately enjoyable, indicating BHP benefits from this work task. The BHP impacts of whether the task was engaging, meaningful, supported well-being, or was demanding for a crewmember were generally positive and increased over time. As shown in the Figure, working with plants was reported as more engaging, meaningful, and beneficial to well-being over time, while the demand from the task was moderate to low and consistent over time. Engaging, meaningful, and supporting well-being were strongly, positively correlated with each other, which is consistent with research that suggests engaging and meaningful work can support well-being. Plant activities such as voluntary viewing, watering, harvesting, and consuming, were positively related to task engagement and meaning, and enjoyment and well-being. Findings suggest that working with plants and consuming them can be a behavioral health countermeasure for long-duration spaceflight. REFERENCES [1] Schlacht I, et al. (2020) Impact of plants in isolation: The EDEN-ISS…in Antarctica. In Advances in Human Factors of Transportation, Washington DC. [2] Vessel E, Russo S (2015) Effects of reduced sensory stimulation and…countermeasures…. NASA/TM-2015-218576. [3] Odeh R, Guy C (2017) Gardening for therapeutic people-plant interactions during LDSM. Open Agriculture, 2(1), 1-13. ACKNOWLEDGEMENTS This research was supported by the Human Health and Performance Contract NNJ15HK11B, and NASA grant MTL #1075 (PI G.D. Massa).
behavioral health↗
Behavioral Health Benefits of the ISS Pick-and-Eat Crop Growth System
Summary: We summarize findings related to assessing the pick-and-eat salad-crop productivity and acceptability of the ISS food system as a countermeasure to maintain behavioral health in long-duration spaceflight. BACKGROUND Plants are a potential countermeasure for the stresses of living in space. Caring for plants and eating fresh food have been shown to serve as a psychological benefit for previous astronauts and for others in analogous environments such as Antarctica [1,2]. Gardening can be therapeutic in terrestrial settings [3]. These effects may carry over or be more pronounced in austere environments such as spaceflight. It can reduce stress and increase sensory stimulation and enjoyment [2]. Growing crops may offer astronauts meaningful and engaging work as they care for living things in an austere environment away from Earth’s nature and as they provide sustenance for their crew. We examined the extent to which interacting with plants (e.g., tending to, consuming) was related to behavioral health outcomes in long-duration space missions. METHOD Participants were 27 astronauts that interacted with the plant system VEG-04, VEG-05, and HRF-VEG (VEG-03 I-L, PH-04). In total, there were 106 in-flight observations. Participants completed monthly measures of mood and well-being, enjoyment and time spent performing specific crop growth and consuming the plants, meaningfulness, performance, connections with others and the Earth, desire to work with and eat plants, and experiences with struggling or dying plants. Higher ends of the 7-point Likert scale indicated more positive outcomes, lower ends of the scale were anchored with more negative outcomes, and the scale midpoints indicated neutral positions. Participants selected a specific survey version based on whether they interacted with the plant system(s) or not, and we included only the scores from the crewmembers that participated in any given activity. RESULTS & DISCUSSION Results indicated that participants generally rated tasks related to the plants and crop growth as enjoyable. Consuming the harvested plants and voluntary viewing were the most enjoyable activities. Tending to the plants was reported as moderately enjoyable, indicating BHP benefits from this work task. The BHP impacts of whether the task was engaging, meaningful, supported well-being, or was demanding for a crewmember were generally positive and increased over time. As shown in the Figure, working with plants was reported as more engaging, meaningful, and beneficial to well-being over time, while the demand from the task was moderate to low and consistent over time. Engaging, meaningful, and supporting well-being were strongly, positively correlated with each other, which is consistent with research that suggests engaging and meaningful work can support well-being. Plant activities such as voluntary viewing, watering, harvesting, and consuming, were positively related to task engagement and meaning, and enjoyment and well-being. Findings suggest that working with plants and consuming them can be a behavioral health countermeasure for long-duration spaceflight. REFERENCES [1] Schlacht I, et al. (2020) Impact of plants in isolation: The EDEN-ISS…in Antarctica. In Advances in Human Factors of Transportation, Washington DC. [2] Vessel E, Russo S (2015) Effects of reduced sensory stimulation and…countermeasures…. NASA/TM-2015-218576. [3] Odeh R, Guy C (2017) Gardening for therapeutic people-plant interactions during LDSM. Open Agriculture, 2(1), 1-13. ACKNOWLEDGEMENTS This research was supported by the Human Health and Performance Contract NNJ15HK11B, and NASA grant MTL #1075 (PI G.D. Massa).
countermeasure↗
Evaluating Automated Face Identity-Masking Methods with Human Perception and a Deep Convolutional Neural Network
Face de-identification (or “masking”) algorithms have been developed in response to the prevalent use of video recordings in public places. Here, we evaluated the success of face identity masking for human perceivers and a deep convolutional neural network (DCNN). Eight de-identification algorithms were applied to videos of drivers’ faces, while they actively operated a motor vehicle. These masks were pre-selected to be applicable to low-quality video and to maintain coarse information about facial actions. Humans studied high-resolution images to learn driver identities and were tested on their recognition of active drivers in low-resolution videos. Faces in the videos were either unmasked or were masked by one of the eight algorithms. When participants were tested immediately after learning (Experiment 1), all masks reduced identification, with six of eight masks reducing identification to extremely poor performance. In a second experiment, two of the most effective masks were tested after a delay of 7 or 28 days. The delay did not further reduce identification of the masked faces. In all masked conditions, participants maintained stringent decision criteria, with low confidence in recognition, further indicating the effectiveness of the masks. Next, the DCNN performed an identity-matching task between high-resolution images and masked videos—a task analogous to that done by humans. The pattern of accuracy for the DCNN mirrored some, but not all, aspects of human performance, highlighting the need to test the effectiveness of identity masking for both humans and machines. The DCNN was also tested on its ability to match identity between masked and unmasked versions of the same video, based only on the face. DCNN performance for the eight masks offers insight into the nature of the information in faces that is coded in these networks.
97 MATHEMATICS AND COMPUTING↗
Crowd Sourcing for Challenging Technical Problems and Business Model
Crowd sourcing may be defined as the act of outsourcing tasks that are traditionally performed by an employee or contractor to an undefined, generally large group of people or community (a crowd) in the form of an open call. The open call may be issued by an organization wishing to find a solution to a particular problem or complete a task, or by an open innovation service provider on behalf of that organization. In 2008, the Space Life Sciences Directorate (SLSD), with the support of Wyle Integrated Science and Engineering, established and implemented pilot projects in open innovation (crowd sourcing) to determine if these new internet-based platforms could indeed find solutions to difficult technical challenges. These unsolved technical problems were converted to problem statements, also called "Challenges" or "Technical Needs" by the various open innovation service providers, and were then posted externally to seek solutions. In addition, an open call was issued internally to NASA employees Agency wide (10 Field Centers and NASA HQ) using an open innovation service provider crowd sourcing platform to post NASA challenges from each Center for the others to propose solutions). From 2008 to 2010, the SLSD issued 34 challenges, 14 externally and 20 internally. The 14 external problems or challenges were posted through three different vendors: InnoCentive, Yet2.com and TopCoder. The 20 internal challenges were conducted using the InnoCentive crowd sourcing platform designed for internal use by an organization. This platform was customized for NASA use and promoted as NASA@Work. The results were significant. Of the seven InnoCentive external challenges, two full and five partial awards were made in complex technical areas such as predicting solar flares and long-duration food packaging. Similarly, the TopCoder challenge yielded an optimization algorithm for designing a lunar medical kit. The Yet2.com challenges yielded many new industry and academic contacts in bone imaging, microbial detection and even the use of pharmaceuticals for radiation protection. The internal challenges through NASA@Work drew over 6000 participants across all NASA centers. Challenges conducted by each NASA center elicited ideas and solutions from several other NASA centers and demonstrated rapid and efficient participation from employees at multiple centers to contribute to problem solving. Finally, on January 19, 2011, the SLSD conducted a workshop on open collaboration and innovation strategies and best practices through the newly established NASA Human Health and Performance Center (NHHPC). Initial projects will be described leading to a new business model for SLSD.
Davis, Jeffrey R.↗
Full-wave and half-wave rectification in second-order motion perception
Microbalanced stimuli are dynamic displays which do not stimulate motion mechanisms that apply standard (Fourier-energy or autocorrelational) motion analysis directly to the visual signal. In order to extract motion information from microbalanced stimuli, Chubb and Sperling [(1988) Journal of the Optical Society of America, 5, 1986-2006] proposed that the human visual system performs a rectifying transformation on the visual signal prior to standard motion analysis. The current research employs two novel types of microbalanced stimuli: half-wave stimuli preserve motion information following half-wave rectification (with a threshold) but lose motion information following full-wave rectification; full-wave stimuli preserve motion information following full-wave rectification but lose motion information following half-wave rectification. Additionally, Fourier stimuli, ordinary square-wave gratings, were used to stimulate standard motion mechanisms. Psychometric functions (direction discrimination vs stimulus contrast) were obtained for each type of stimulus when presented alone, and when masked by each of the other stimuli (presented as moving masks and also as nonmoving, counterphase-flickering masks). RESULTS: given sufficient contrast, all three types of stimulus convey motion. However, only one-third of the population can perceive the motion of the half-wave stimulus. Observers are able to process the motion information contained in the Fourier stimulus slightly more efficiently than the information in the full-wave stimulus but are much less efficient in processing half-wave motion information. Moving masks are more effective than counterphase masks at hampering direction discrimination, indicating that some of the masking effect is interference between motion mechanisms, and some occurs at earlier stages. When either full-wave and Fourier or half-wave and Fourier gratings are presented simultaneously, there is a wide range of relative contrasts within which the motion directions of both gratings are easily determinable. Conversely, when half-wave and full-wave gratings are combined, the direction of only one of these gratings can be determined with high accuracy. CONCLUSIONS: the results indicate that three motion computations are carried out, any two in parallel: one standard ("first order") and two non-Fourier ("second-order") computations that employ full-wave and half-wave rectification.
Motion Perception/physiology↗
Distinct Pattern of Oculomotor Impairment Associated with Acute Sleep Loss and Circadian Misalignment
Sleep loss and circadianmisalignment have long been known to impair human cognitive and motor performance with significant societal and health consequences. It is well known that human reaction time to a visual cue is impaired following sleep loss and circadian misalignment, but it has remained unclear how more complex visuomotor control behaviour is altered under these conditions. In this study, we measured 14 parameters of the voluntary ocular tracking response of 12 human participants (six females) to systematically examine the effects of sleep loss and circadianmisalignment using a constant routine 24 h acute sleep-deprivation paradigm. The combination of state-of-the-art oculometric and sleep-research methodologies allowed us to document, for the first time, large changes in many components of pursuit, saccades and visual motion processing as a function of time awake and circadian phase. Further, we observed a pattern of impairment across our set of oculometric measures that is qualitatively different from that observed previously with other mild neural impairments. We conclude that dynamic vision and visuomotor control exhibit a distinct pattern of impairment linked with time awake and circadian phase. Therefore, a sufficiently broad set of oculometric measures could provide a sensitive and specific behavioural biomarker of acute sleep loss and circadian misalignment. We foresee potential applications of such oculometric biomarkers assisting in the assessment of readiness-to-perform higher risk tasks and in the characterization of sub-clinical neural impairment in the face of a multiplicity of potential risk factors, including disrupted sleep and circadian rhythms.
Stone, Leland S.↗
A level-of-details framework for representing occupant behavior in agent-based models
We report agent-based modeling is an advanced computational technique capable of representing complex and dynamic processes of human behavior in building performance simulation. Though the agent-based approach supports diverse applications concerning human behavior modeling within the built environment, there is no consensus on the optimal amount of information or level of granularity needed for occupant information representation. This paper attempts to formalize the level of details (LoD) needed for occupant behavior representation in agent-based environments. A novel framework, grounded on the concept of LoD, is proposed to select the required details in representing occupants in agent-based models. Ten attributes related to occupants' presence, movement, behavioral processes, and repertoire are considered to define the LoD. The framework identifies use case parameters as the guiding principle and allows a hybrid approach for selecting varying degrees of occupant attributes to serve the purpose of simulation. A discussion on the pertinence of different occupant behavior LoDs in relation to the desired objective and simulation context is also presented. The study intends to support the occupant behavior research by advancing agent-based occupant modeling in building performance simulation.
42 ENGINEERING↗
Considerations for Health and Performance During Surface Extravehicular Activities
BACKGROUND: NASA’s objectives for expanding human presence beyond low Earth orbit will require Extravehicular Activities (EVAs) on lunar and planetary surfaces. Given the physiological and functional demands of conducting surface EVAs in a pressurized spacesuit in reduced gravity environments, there is a possibility that crew injury and compromised physiological and/or functional performance may present. OVERVIEW: Many human health and performance knowledge gaps exist in regards to exploration EVA that require characterization to ensure safety, reliability, and mission success. To address knowledge gaps, EVA simulations in Earth-based analog environments and/or spacesuit simulators can be utilized to provide valuable insights into task-based physiologic and metabolic costs, cognitive loads, and associated operational limitations to inform future mission concepts. Physical workloads approaching 60% of maximum metabolic rates and 85% age-predicted heart rate maxima; core body temperatures approaching 100o F; and subjective responses indicating limited spare cognitive capacity via Bedford scale have been observed during ground-based exploration EVA simulations in the NASA Active Response Gravity Offload Simulator (ARGOS) and Neutral Buoyancy Lab (NBL) during simulated planetary EVAs in pressurized suits. Further, ground-based EVA analogs vary in their ability to simulate planetary EVA and resulting physical workloads. DISCUSSION: Metabolic costs, thermal burdens, functional strength, and cognitive impacts have been and must continue to be assessed in ground-based analogs to fully characterize operational demands and crew readiness levels for exploration EVA. Considerations should be given to enabling a new concept of high-tempo surface EVA operations and associated work-rest intervals, understanding human health and performance impacts of evolving commercial suit designs and capabilities, and predictive modeling and decision support capabilities to enable safe and successful EVA operations.
EVA↗
Two Wire System and Modified Olive Tip to Facilitate Implantation of Fenestrated TEVAR in Patient with Proximal Descending Aortic Pathology: First Two Cases
Introduction: Although Fenestrated TEVAR (F-TEVAR) has been considered to be a more physiologic approach to treat proximal descending aortic pathology, its application is still limited due to availability, cost and technical difficulties. We introduce a new design of fenestrated stent graft with a new delivery system and successfully performed first in human implantation in two patients, one with an aortic aneurysm and one with an acute aortic dissection. Materials and Methods: The design of these two wires fenestrated stent graft include creation of an additional lumen at the side of the olive tip during manufacture, from which an additional wire can be introduced for a side branch passing into the fenestration, running inside the stent graft and exit the delivery sheath through additional hub. The two wires will facilitate delivery and deployment of the stent graft. One patient with descending aortic aneurysm and another with Stanford B aortic dissection is included in this first in human study. Results: The aneurysm and dissection were completely excluded immediately after the TEVAR. Six month follow up CT showed good position of the stent graft and patent LSA in both patients. In the patient with aortic dissection, expansion of the true lumen and partial thrombosis of the false lumen was seen. Conclusions: This is a report of a two wire system in 2 patients with distal aortic arch pathology demonstrating a good technical and clinical success using pre-cannulated fenestrations through a modified nose cone olive. Level of Evidence: Level 4, report of two cases.
62 RADIOLOGY AND NUCLEAR MEDICINE↗
Studies on the analysis of 25-hydroxyvitamin D{sub 3} by isotope-dilution liquid chromatography–tandem mass spectrometry using enzyme-assisted derivatisation
Highlights: • New method for the analysis of 25-hydroxyvitamin D{sub 3} exploiting Girard P derivatisation. • Method also applicable to vitamin D{sub 3}, 1α,25- and 24,25-dihydroxyvitamin D{sub 3}. • By modification of the method 3-epi-25-hydroxyvitamin D{sub 3} can also be analysed. - Abstract: The total serum concentration of 25-hydroxyvitamins D (25-hydroxyvitamin D{sub 3} and 25-hydroxyvitamin D{sub 2}) is currently used as an indicator of vitamins D status. Vitamins D insufficiency is claimed to be associated with multiple diseases, thus accurate and precise reference methods for the quantification of 25-hydroxyvitamins D are needed. Here we present a novel enzyme-assisted derivatisation method for the analysis of vitamins D metabolites in adult serum utilising 25-[26,26,26,27,27,27-{sup 2}H{sub 6}]hydroxyvitamin D{sub 3} as the internal standard. Extraction of 25-hydroxyvitamins D from serum is performed with acetonitrile, which is shown to be more efficient than ethanol. Cholesterol oxidase is used to oxidize the 3β-hydroxy group in the vitamins D metabolites followed by derivatisation of the newly formed 3-oxo group with Girard P reagent. 17β-Hydroxysteroid dehydrogenase type 10 is shown to oxidize selectively the 3α-hydroxy group in the 3α-hydroxy epimer of 25-hydroxyvitamin D{sub 3}. Quantification is achieved by isotope-dilution liquid chromatography–tandem mass spectrometry. Recovery experiments for 25-hydroxyvitamin D{sub 3} performed on adult human serum give recovery of 102–106%. Furthermore in addition to 25-hydroxyvitamin D{sub 3}, 24,25-dihydroxyvitamin D{sub 3} and other uncharacterised dihydroxy metabolites, were detected in adult human serum.
60 APPLIED LIFE SCIENCES↗
Respiratory Amplitude Guided 4-Dimensional Magnetic Resonance Imaging
Purpose: To evaluate the feasibility of prospectively guiding 4-dimensional (4D) magnetic resonance imaging (MRI) image acquisition using triggers at preselected respiratory amplitudes to achieve T{sub 2} weighting for abdominal motion tracking. Methods and Materials: A respiratory amplitude-based triggering system was developed and integrated into a commercial turbo spin echo MRI sequence. Initial feasibility tests were performed on healthy human study participants. Four respiratory states, the middle and the end of inhalation and exhalation, were used to trigger 4D MRI image acquisition of the liver. To achieve T{sub 2} weighting, the echo time and repetition time were set to 75 milliseconds and 4108 milliseconds, respectively. Single-shot acquisition, together with parallel imaging and partial k-space imaging techniques, was used to improve image acquisition efficiency. 4D MRI image sets composed of axial or sagittal slices were acquired. Results: Respiratory data measured and logged by the MRI scanner showed that the triggers occurred at the appropriate respiratory levels. Liver motion could be easily observed on both 4D MRI image datasets by sensing either the change of liver in size and shape (axial) or diaphragm motion (sagittal). Both 4D MRI image datasets were T{sub 2}-weighted as expected. Conclusions: This study demonstrated the feasibility of achieving T{sub 2}-weighted 4D MRI images using amplitude-based respiratory triggers. With the aid of the respiratory amplitude-based triggering system, the proposed method is compatible with most MRI sequences and therefore has the potential to improve tumor-tissue contrast in abdominal tumor motion imaging.
62 RADIOLOGY AND NUCLEAR MEDICINE↗
Biotransformations of antidiabetic vanadium prodrugs in mammalian cells and cell culture media: A XANES spectroscopic study
The antidiabetic activities of vanadium(V) and -(IV) prodrugs are determined by their ability to release active species upon interactions with components of biological media. The first X-ray absorption spectroscopic study of the reactivity of typical vanadium (V) antidiabetics, vanadate ([V V O 4 ] 3– , A) and a vanadium(IV) bis(maltolato) complex (B), with mammalian cell cultures has been performed using HepG2 (human hepatoma), A549 (human lung carcinoma), and 3T3-L1 (mouse adipocytes and preadipocytes) cell lines, as well as the corresponding cell culture media. X-ray absorption near-edge structure data were analyzed using empirical correlations with a library of model vanadium(V), -(IV), and -(III) complexes. Both A and B ([V] = 1.0 mM) gradually converged into similar mixtures of predominantly five- and six-coordinate VV species (~75% total V) in a cell culture medium within 24 h at 310 K. Speciation of V in intact HepG2 cells also changed with the incubation time (from ~20% to ~70% V IV of total V), but it was largely independent of the prodrug used (A or B) or of the predominant V oxidation state in the medium. Subcellular fractionation of A549 cells suggested that V V reduction to V IV occurred predominantly in the cytoplasm, while accumulation of V V in the nucleus was likely to have been facilitated by noncovalent bonding to histone proteins. The nuclear V V is likely to modulate the transcription process and to be ultimately related to cell death at high concentrations of V, which may be important in anticancer activities. Mature 3T3-L1 adipocytes (unlike for preadipocytes) showed a higher propensity to form V IV species, despite the prevalence of V V in the medium. Lastly, the distinct V biochemistry in these cells is consistent with their crucial role in insulin-dependent glucose and fat metabolism and may also point to an endogenous role of V in adipocytes.
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
Understanding the Structure, Multimerization, Subcellular Localization and mC Selectivity of a Genomic Mutator and Anti-HIV Factor APOBEC3H
APOBEC3H (A3H) is a member of the APOBEC3 subfamily of DNA cytosine deaminases that are important for innate immune defense and have been implicated in cancer biogenesis. To understand the structural basis for A3H biochemical function, we determined a high-resolution structure of human A3H and performed extensive biochemical analysis. The 2.49 Å crystal structure reveals a uniquely long C-terminal helix 6 (h6), a disrupted β5 strand of the canonical five-stranded β-sheet core, and a long loop 1 around the Zn-active center. Mutation of a loop 7 residue, W115, disrupted the RNA-mediated dimerization of A3H yielding an RNA-free monomeric form that still possessed nucleic acid binding and deaminase activity. A3H expressed in HEK293T cells showed RNA dependent HMW complex formation and RNase A-dependent deaminase activity. A3H has a highly positively charged surface surrounding the Zn-active center, and multiple positively charged residues within this charged surface play an important role in the RNA-mediated HMW formation and deaminase inhibition. Furthermore, these positively charged residues affect subcellular localization of A3H between the nucleus and cytosol. Finally, we have identified multiple residues of loop 1 and 7 that contribute to the overall deaminase activity and the methylcytosine selectivity.
59 BASIC BIOLOGICAL SCIENCES↗
Clostridioides difficile Toxin A Remodels Membranes and Mediates DNA Entry Into Cells to Activate Toll-Like Receptor 9 Signaling
Background & Aims: Clostridioides difficile toxin A (TcdA) activates the innate immune response. TcdA co-purifies with DNA. Toll-like receptor 9 (TLR9) recognizes bacterial DNA to initiate inflammation. We investigated whether DNA bound to TcdA activates an inflammatory response in murine models of C difficile infection via activation of TLR9. Methods: We performed studies with human colonocytes and monocytes and macrophages from wild-type and TLR9 knockout mice incubated with TcdA or its antagonist (ODN TTAGGG) or transduced with vectors encoding TLR9 or small-interfering RNAs. Cytokine production was measured with enzyme-linked immunosorbent assay. We studied a transduction domain of TcdA (TcdA 57-80 ), which was predicted by machine learning to have cell-penetrating activity and confirmed by synchrotron small-angle X-ray scattering. Intestines of CD1 mice, C57BL6J mice, and mice that express a form of TLR9 that is not activated by CpG DNA were injected with TcdA, TLR9 antagonist, or both. Enterotoxicity was estimated based on loop weight to length ratios. A TLR9 antagonist was tested in mice infected with C difficile. We incubated human colon explants with an antagonist of TLR9 and measured TcdA-induced production of cytokines. Results: The TcdA 57-80 protein transduction domain had membrane remodeling activity that allowed TcdA to enter endosomes. TcdA-bound DNA entered human colonocytes. TLR9 was required for production of cytokines by cultured cells and in human colon explants incubated with TcdA. TLR9 was required in TcdA-induced mice intestinal secretions and in the survival of mice infected by C difficile. Even in a protease-rich environment, in which only fragments of TcdA exist, the TcdA 57-80 domain organized DNA into a geometrically ordered structure that activated TLR9. Conclusions: TcdA from C difficile can bind and organize bacterial DNA to activate TLR9. TcdA and TcdA fragments remodel membranes, which allows them to access endosomes and present bacterial DNA to and activate TLR9. Rather than inactivating the ability of DNA to bind TLR9, TcdA appears to chaperone and organize DNA into an inflammatory, spatially periodic structure.
59 BASIC BIOLOGICAL SCIENCES↗
Nonequilibrium and generalized-ensemble molecular dynamics simulations for amyloid fibril
Amyloids are insoluble and misfolded fibrous protein aggregates and associated with more than 20 serious human diseases. We perform all-atom molecular dynamics simulations of amyloid fibril assembly and disassembly.
71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
Integrated Multi-Scale Data Analytics and Machine Learning for the Distribution Grid
We consider the field of machine learning and where it is both useful, and not useful, for the distribution grid and buildings interface. While analytics, in general, is a growing field of interest, and often seen as the golden goose in the burgeoning distribution grid industry, its application is often limited by communications infrastructure, or lack of a focused technical application. Overall, the linkage of analytics to purposeful application in the grid space has been limited. In this paper we consider the field of machine learning as a subset of analytical techniques, and discuss its ability and limitations to enable the future distribution grid. To that end, we also consider the potential for mixing distributed and centralized analytics and the pros and cons of these approaches. There is an exponentially expanding volume of measured data being generated on the distribution grid, which, with appropriate application of analytics, may be transformed into intelligible, actionable information that can be provided to the right actors - such as grid and building operators, at the appropriate time to enhance grid or building resilience, efficiency, and operations against various metrics or goals - such as total carbon reduction or other economic benefit to customers. While some basic analysis into these data streams can provide a wealth of information, computational and human boundaries on performing the analysis are becoming significant, with more data and multi-objective concerns. Efficient applications of analysis and the machine learning field are being considered in the loop. This paper describes benefits and limits of present machine-learning applications for use on the grid and presents a series of case studies that illustrate the potential benefits of developing advanced local multi-variate analytics machine-learning-based applications.
24 POWER TRANSMISSION AND DISTRIBUTION↗
SU-E-J-25: End-To-End (E2E) Testing On TomoHDA System Using a Real Pig Head for Intracranial Radiosurgery
Purpose: To determine the MVCT imaging uncertainty on the TomoHDA system for intracranial radiosurgery treatments. To determine the end-to-end (E2E) overall accuracy of the TomoHDA system for intracranial radiosurgery. Methods: A pig head was obtained from the butcher, cut coronally through the brain, and preserved in formaldehyde. The base of the head was fixed to a positioning plate allowing precise movement, i.e. translation and rotation, in all 6 axes. A repeatability test was performed on the pig head to determine uncertainty in the image bone registration algorithm. Furthermore, the test studied images with MVCT slice thicknesses of 1 and 3 mm in unison with differing scan lengths. A sensitivity test was performed to determine the registration algorithm’s ability to find the absolute position of known translations/rotations of the pig head. The algorithm’s ability to determine absolute position was compared against that of manual operators, i.e. a radiation therapist and radiation oncologist. Finally, E2E tests for intracranial radiosurgery were performed by measuring the delivered dose distributions within the pig head using Gafchromic films. Results: The repeatability test uncertainty was lowest for the MVCTs of 1-mm slice thickness, which measured less than 0.10 mm and 0.12 deg for all axes. For the sensitivity tests, the bone registration algorithm performed better than human eyes and a maximum difference of 0.3 mm and 0.4 deg was observed for the axes. E2E test results in absolute position difference measured 0.03 ± 0.21 mm in x-axis and 0.28 ± 0.18 mm in y-axis. A maximum difference of 0.32 and 0.66 mm was observed in x and y, respectively. The average peak dose difference between measured and calculated dose was 2.7 cGy or 0.4%. Conclusion: Our tests using a pig head phantom estimate the TomoHDA system to have a submillimeter overall accuracy for intracranial radiosurgery.
60 APPLIED LIFE SCIENCES↗