Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “Complex system biology”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 577 records · Page 32
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

How data science methods can improve the quality and efficiency of ICF and HEDP research

Data Science methods (many that are Bayesian based) are widely used in the physical sciences to estimate model parameters from experimental data, synthesize heterogeneous data, calibrate models, design experiments, and determine statistical significance of data. These methods provide a wealth of advantages over traditional analysis techniques because: 1) uncertainties are rigorously defined and propagated naturally through complex systems including covariance, 2) prior information is captured within the analysis framework (including rad-MHD and rad-hydro simulations), 3) competing models can be selected and/or ruled out using quantitative criteria, and 4) complex, heterogeneous data can be incorporated simultaneously. While these methods have been widely adopted as the gold standard in fields such as particle physics, astronomy, and biology, they have been slow to catch on in Inertial Confinement Fusion (ICF) and High Energy Density Physics (HEDP) research. Recently, several teams at LLNL, SNL, LANL, and the LLE have been exploring the use of these tools in their research and have found success. Here we propose that a concerted effort to consolidate these independent research efforts by developing and deploying common tools for use across the complex can revolutionize the way we approach data analysis, assimilation of theory and experiment, and decision making. The Bayesian formalism provides a means to accomplish this, but we are lacking certain infrastructure to make it happen on a large scale. Furthermore, once adopted, these techniques can be used to develop standards by which discoveries can be judged, similar to the so-called 5σ rule in high energy particle physics. Such standards may be used in the future to address the issue of unknown reproducibility in ICF and HED experiments caused by low shot rate and high cost per experiment. Our goals as a group are to advance the state of the art in HED measurement science by enabling: 1) better inferences from data with well-defined uncertainties, 2) better use of the data we have and continue to collect, 3) intelligent synthesis of data, 4) evaluation of the statistical significance of our data, and 5) informed decision making regarding the design of new experiments and instruments.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
NASA NTRS1996

Transmembrane transport of peptide type compounds: prospects for oral delivery

Synthesis and delivery of potential therapeutic peptides and peptidomimetic compounds has been the focus of intense research over the last 10 years. While it is widely recognized that numerous limitations apply to oral delivery of peptides, some of the limiting factors have been addressed and their mechanisms elucidated, which has lead to promising strategies. This article will briefly summarize the challenges, results and current approaches of oral peptide delivery and give some insight on future strategies. The barriers determining peptide bioavailability after oral administration are intestinal membrane permability, size limitations, intestinal and hepatic metabolism and in some cases solubility limitations. Poor membrane permeabilities of hydrophilic peptides might be overcome by structurally modifying the compounds, thus increasing their membrane partition characteristics and/or their affinity to carrier proteins. Another approach is the site-specific delivery of the peptide to the most permeable parts of the intestine. The current view on size limitation for oral drug delivery has neglected partition considerations. Recent studies suggest that compounds with a molecular weight up to 4000 might be significantly absorbed, assuming appropriate partition behavior and stability. Metabolism, probably the most significant factor in the absorption fate of peptides, might be controlled by coadministration of competitive enzyme inhibitors, structural modifications and administration of the compound as a well absorbed prodrug that is converted into the therapeutically active agent after its absorption. For some peptides poor solubility might present a limitation to oral absorption, an issue that has been addressed by mechanistically defining and therefore improving formulation parameters. Effective oral peptide delivery requires further development in understanding these complex mechanisms in order to maximize the therapeutic potential of this class of compounds.

NASA Discipline Regulatory Physiology↗
NASA NTRS2007

Interactions of the C-terminal Domain of Human Ku70 with DNA Substrate: A Molecular Dynamics Study

NASA is developing a systems biology approach to improve the assessment of health risks associated with space radiation. The primary toxic and mutagenic lesion following radiation exposure is the DNA double strand break (DSB), thus a model incorporating proteins and pathways important in response and repair of this lesion is critical. One key protein heterodimer for systems models of radiation effects is the Ku(sub 70/80) complex. The Ku70/80 complex is important in the initial binding of DSB ends following DNA damage, and is a component of nonhomologous end joining repair, the primary pathway for DSB repair in mammalian cells. The C-terminal domain of Ku70 (Ku70c, residues 559-609), contains an helix-extended strand-helix motif and similar motifs have been found in other nucleic acid-binding proteins critical for DNA repair. However, the exact mechanism of damage recognition and substrate specificity for the Ku heterodimer remains unclear in part due to the absence of a high-resolution structure of the Ku70c/DNA complex. We performed a series of molecular dynamics (MD) simulations on a system with the subunit Ku70c and a 14 base pairs DNA duplex, whose starting structures are designed to be variable so as to mimic their different binding modes. By analyzing conformational changes and energetic properties of the complex during MD simulations, we found that interactions are preferred at DNA ends, and within the major groove, which is consistent with previous experimental investigations. In addition, the results indicate that cooperation of Ku70c with other subunits of Ku(sub 70/80) is necessary to explain the high affinity of binding as observed in experiments.

Hu, Shaowen↗
NASA NTRS2024

Experimentally Modeling the Emergence of Prebiotically Plausible Phospholipid Vesicles

The prebiotic emergence of protocells is an important part of any origins of life scenario. Although fatty-acid-based vesicles are well studied, how they transitioned to phospholipid vesicles is uncertain. Herein, we show that cyclic-phospholipids formed from fatty acids and glycerol could have played a role by generating a heterogeneous library of vesicles with diverse morphologies and tolerance to a range of metal ions, temperature, and pH. The cyclic phosphate moiety facilitates the natural emergence of vesicles composed of diacyl-phospholipids to become part of the chemical evolutionary process. Competing emergent properties of the various systems (facilitated by additives) could have led to an early preference of the sn-1,2-acyl-substitution on the glycerol backbone coincidental with extant biology. Thus, cyclic-phospholipids could have played a significant role not only in early prebiotic protocellular chemistry but also in facilitating the chemical evolution of protocells from the structurally simple to the functionally more complex.

Sunil Pulletikurti↗
DOE OSTI2020

Challenges and Solutions in Operation and Lay-Up of the Modular Caustic- Side Solvent Extraction Unit - 20078

The Modular Caustic-Side Solvent Extraction (CSSX) Unit (MCU) was designed and constructed to provide interim salt waste processing so that the Liquid Waste Disposition Program (LWDP) could continue waste removal and tank closure until start-up of the Salt Waste Processing Facility (SWPF). MCU processes Clarified Salt Solution (CSS), or salt solution (SS) that has undergone actinide removal/filtration, to produce two waste streams: the cesium laden Strip Effluent (SE), which is incorporated into glass at the Defense Waste Processing Facility (DWPF), and the cesium depleted Decontaminated SS (DSS), which is incorporated into grout at the Saltstone Production Facility (SPF). MCU completed start-up in 2008 with an initial operating life of 3 years and design life of 5 years. Prior to reaching the end of the design life, multiple critical components were upgraded and/or replaced to mitigate risks associated with any delays in SWPF start-up. During the remainder of operation (until June 2019), MCU was challenged to maximize processing with minimal additional modifications to repair/improve aging infrastructure, while maintaining low levels of risk to workers and the environment. Notable challenges during the extended operating life of the facility involved both mechanical and operational issues. Two of the most significant issues were the increased frequency of Process Vessel Ventilation (PVV) High Efficiency Particulate Air (HEPA) filter change-outs and the biofouling of the SE coalescer (SEC). The major impacts of both issues were that replacement of these components 1) resulted in high exposure to workers, and 2) required substantial downtime, thus hindering achievement of processing goals. PVV HEPA filter replacements are required based on dose rate and differential pressure (dP) limits. After introducing a higher-curie feed to MCU, the operating time between change outs was reduced by approximately half. SEC replacements are required based on dP limits. After restarting from an extended outage, the operating life of the SEC was significantly reduced by more than half due to biofouling. As a result of extensive troubleshooting and process improvements, the facility was able to recover performance and extend the operating life of the PVV HEPA filters and the SEC media. Through troubleshooting both of these issues, the facility was also able to learn from prior experience and adapt in order to minimize down time and maintain throughput. Although the facility took advantage of short periods of downtime to perform nonintrusive troubleshooting and minor corrective/preventative maintenance activities, longer outages were periodically required for corrective maintenance involving process cell entry. During these outages, remote tools and specialized shield plates were employed to minimize dose to workers. Mock-ups of non-routine maintenance activities were critical to early identification of potential issues and improvements, which shortened outage duration. Consistent with the facility's operational strategy, evolutions needed for MCU layup were identified and sequenced to ensure safe conditions within the facility, meet pre-defined criteria for lay-up configuration, and protect workers, while minimizing the impact to SWPF integration. De-inventory and flushing of process areas was prioritized so that the total residual inventory was reduced as efficiently as possible. This paper discusses lessons learned and best practices from troubleshooting unique issues, performing complex maintenance activities, and implementing a layup strategy that best supports the overall system mission. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
DOE OSTI2022

A wide-field micro-computed tomography detector: micron resolution at half-centimetre scale

Ideal three-dimensional imaging of complex samples made up of micron-scale structures extending over mm to cm, such as biological tissues, requires both wide field of view and high resolution. For existing optics and detectors used for micro-CT (computed tomography) imaging, sub-micron pixel resolution can only be achieved for fields of view of <2 mm. This article presents a unique detector system with a 6 mm field-of-view image circle and 0.5 µm pixel size that can be used in micro-CT units utilizing both synchrotron and commercial X-ray sources. A resolution-test pattern with linear microstructures and whole adult Daphnia magna were imaged at beamline 8.3.2 of the Berkeley Advanced Light Source. Volumes of 10000 × 10000 × 7096 isotropic 0.5 µm voxels were reconstructed over a 5.0 mm × 3.5 mm field of view. Measurements in the projection domain confirmed a 0.90 µm measured spatial resolution that is largely Nyquist-limited. This unprecedented combination of field of view and resolution dramatically reduces the need for sectional scans and computational stitching for large samples, ultimately offering the means to elucidate changes in tissue and cellular morphology in the context of larger, whole, intact model organisms and specimens. This system is also anticipated to benefit micro-CT imaging in materials science, microelectronics, agricultural science and biomedical engineering.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
NASA NTRSDate not supplied

Developing Open-Source Training Materials for AI/ML and Space Biological Sciences Using NASA Cloud-Based Data

Artificial Intelligence (AI) and Machine Learning (ML) has gained significant traction in the biological and biomedical research fields in the last two decades, in part thanks to an increasing culture of open data sharing and reuse. Due to its capability for identifying complex relationships and patterns, AI/ML methodology is particularly well suited to recognize and predict biological patterns from high-dimensional next-generation sequencing data (e.g. whole genome sequencing, transcriptomic sequencing), as well as from biological or medical imaging data (e.g. microscopy, computed tomography, ultrasound, magnetic resonance imaging, radiography). These methodologies hold particular promise for space biosciences research and automated space health monitoring systems. However, there are many key considerations for properly training, validating, and testing a machine learning model in biological research or clinical application. Even with the positive culture of Open Science and data sharing, inexperienced researchers working quickly without proper checks can produce models that perform poorly outside of the immediate training dataset. Lessons learned from biological AI/ML research indicate that Open Science principles such as data sharing and open-source code must go hand-in-hand with publicly available, high-quality training curricula in best practices, with modules centered on real-life scientific use cases and data so future AI/ML practitioners gain experience on real problems. Here we present the development of open-source training materials for AI/ML and space biosciences, as part of the NASA Transform to Open Science Training (TOPST) initiative. We develop 4 independent training programs, focused on the following topics: 1) Fundamentals of Machine Learning and Space Biosciences Domain, 2) Open Science, Artificial Intelligence, and Ethical Best Practices for Data Sharing and Analysis, 3) Using AI/ML Classification to Identify Gene Networks Affected By Space Exposure in Mouse Liver, and 4) Using Neural Networks to Find DNA Damage Patterns in Immune Cells after Radiation. All programs leverage cloud-based NASA biological datasets. The curriculum we present will enable worldwide access to training in AI/ML and scientific analysis.

James Andrew Casaletto↗
NASA NTRS1999

Co-Operative Mission Concepts Using Biomorphic Explorers

Inspired by the immense variety of naturally curious explorers (insects, animals, and birds), their well integrated biological sensor-processor suites that are efficiently packaged in compact but highly dexterous forms, and their complex, intriguing, cooperative behaviors, this study focuses on Biomorphic Explorers and presents cooperative biomorphic planetary exploration scenarios.

cooperative behaviors↗
DOE OSTI2023

Dissecting the Division of Labor in Microbial Consortia for the Production of Biofuels and Chemicals (Final Technical Report)

The overarching objective of this project is to elucidate the fundamental design rules for microbial division of labor (DOL), the core of ecosystem organization, in the context of artificial yeast—lactic acid bacteria consortia that produce advanced biofuel and chemical from cellulosic biomass. Over the course of four years, we have successfully achieved the objective through three lines of research that combines experiment with mathematical modeling. Specifically, we have shown that compositional and temporal DOL is effective in modulating mixed sugar fermentation by an engineered consortium and uncovered general quantitative criteria for conditions under which microbial DOL outperforms single superbugs for simultaneous utilization of mixed substrates. We also demonstrated, in synthetic consortia of yeast and lactic acid bacteria, that partitioning the labor for substrate breakdown and end-product synthesis can allow an efficient production of 2-butanol that is difficult otherwise for a single yeast strain. Additionally, by systematically probing the stability of an engineered cooperative consortium, we found that the stability of microbial symbiosis is governed by the topological structure of the underlying cellular interactions rather than specific microbial species and that rational modulation of the interactions may facilitate the restoration of collapsed consortia as well as the intervention of target communities. Together, this project has advanced the fundamental knowledge of microbial DOL in terms of its strength in mixed substrate fermentation, production of complex chemicals, and ecological system stability in the context of microbial consortia. It also provides valuable insights into the design, construction and optimization of artificial consortia for the utilization of cellulosic biomass and economic production of biofuel and chemicals.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1988

GAS-611 firefly in zero gravity

The Get Away Special 611 (GAS-611) project will carry a small, self-contained biological experiment into a microgravity environment for a period of 120 hours. The payload will be a colony of Lampyridae (fireflies). The ability of this beetle to produce light with an efficiency of 98 pct will be evaluated in the micro-G environment. The chemical process that occurs could be assisted by the earth's gravitational pull and the very complex tracheae system found within this species of beetle. The effects of microgravity on mating and beetle larvae will also be studied.

Williams, Tony↗
NASA NTRS2000

Cooperative Mission Concepts Using Biomorphic Explorers

Inspired by the immense variety of naturally curious explorers (insects, animals, and birds), their wellintegrated biological sensor-processor suites, efficiently packaged in compact but highly dexterous forms, and their complex, intriguing, cooperative behavior, this paper focuses on "Biomorphic Explorers", their defination/classification, their designs, and presents planetary exploration scenarios based on the designs. Judicious blend of bio-inspired concepts and recent advances in micro-air vehicles, microsensors, microinstruments, MEMS, and microprocessors clearly suggests that the time of small, dedicated, low cost explorers that capture some of the key features of biological systems has arrived. Just as even small insects like ants, termites, honey bees etc working cooperatively in colonies can achieve big tasks, the biomorphic explorers hold the potential for obtaining science in-accessible by current large singular exploration platforms.

Thakoor, S.↗
NASA NTRS1994

Identification of surface-exposed domains on the reducing side of photosystem I

Photosystem I (PSI) is a multisubunit enzyme that catalyzes the light-driven oxidation of plastocyanin or cytochrome c6 and the concomitant photoreduction of ferredoxin or flavodoxin. To identify the surface-exposed domains in PSI of the cyanobacterium Synechocystis sp. PCC 6803, we mapped the regions in PsaE, PsaD, and PsaF that are accessible to proteases and N-hydroxysuccinimidobiotin (NHS-biotin). Upon exposure of PSI complexes to a low concentration of endoproteinase glutamic acid (Glu)-C, PsaE was cleaved to 7.1- and 6.6-kD N-terminal fragments without significant cleavage of other subunits. Glu63 and Glu67, located near the C terminus of PsaE, were the most likely cleavage sites. At higher protease concentrations, the PsaE fragments were further cleaved and an N-terminal 9.8-kD PsaD fragment accumulated, demonstrating the accessibility of Glu residue(s) in the C-terminal domain of PsaD to the protease. Besides these major, primary cleavage products, several secondary cleavage sites on PsaD, PsaE, and PsaF were also identified. PsaF resisted proteolysis when PsaD and PsaE were intact. Glu88 and Glu124 of PsaF became susceptible to endoproteinase Glu-C upon extensive cleavage of PsaD and PsaE. Modification of PSI proteins with NHS-biotin and subsequent cleavage by endoproteinase Glu-C or thermolysin showed that the intact PsaE and PsaD, but not their major degradation products lacking C-terminal domains, were heavily biotinylated. Therefore, lysine-74 at the C terminus of PsaE was accessible for biotinylation. Similarly, lysine-107, or lysine-118, or both in PsaD could be modified by NHS-biotin.

Non-NASA Center↗
DOE OSTI2019

A high-capacity gene stacking toolkit for the oleaginous microalga, Nannochloropsis oceanica CCMP1779

Nannochloropsis oceanica CCMP1779 is an oleaginous heterokont microalga that is particularly amenable to synthetic biology approaches. The underlying complex genetic engineering often requires the expression of multiple transgenes (gene stacking). We integrated several techniques into a vector toolkit for multi-gene expression, including: multiple resistance marker genes, bidirectional promoters, and assembly of multiple expression cassettes into a single vector. We developed a series of gateway entry and destination vectors for assembly of two bidirectional promoter expression cassettes, which facilitates combinatorial high-capacity gene stacking. Several endogenous bidirectional promoters were demonstrated to be effective for driving transgene expression, with a dual-luciferase reporter system used to monitor transgene expression under different environmental conditions. The bidirectional promoter between the nitrate reductase and the nitrate transporter genes drives nitrogen source dependent transcription, enabling conditional transgene expression. Lethal concentrations of the antibiotics, Blasticidin, G418, and Nourseothricin, were determined and the corresponding marker genes used for genomic transformation selection.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Toward a Better Understanding of Species Interactions through Network Biology

Within the last decade, there has been an explosion of multi-omics data generated for several microbial systems. At the same time, new methods of analysis have emerged that are based on inferring networks that link features both within and between species based on correlation in abundance. These developments prompt two important questions. What can be done with network approaches to better understand microbial species interactions? What challenges remain in applying network approaches to query the more complex systems of natural settings? Here, I briefly describe what has been done and what questions still need to be answered. Over the next 5 to 10 years, we will be in a strong position to infer networks that contain multiple kinds of omic data and describe systems with multiple species. These applications will open the door for a better understanding and use of microbiomes across a variety of fields.

Microbiology↗
DOE OSTI2020

The biosynthesis of the anti–microbial diterpenoid leubethanol in Leucophyllum frutescens proceeds via an all– cis prenyl intermediate

Serrulatane diterpenoids are natural products found in plants from a subset of genera within the figwort family (Scrophulariaceae). Many of these compounds have been characterized as having anti–microbial properties and share a common diterpene backbone. One example, leubethanol from Texas sage (Leucophyllum frutescens) has demonstrated activity against multi–drug–resistant tuberculosis. Leubethanol is the only serrulatane diterpenoid identified from this genus; however, a range of such compounds have been found throughout the closely related Eremophila genus. Despite their potential therapeutic relevance, the biosynthesis of serrulatane diterpenoids has not been previously reported. Here we leverage the simple product profile and high accumulation of leubethanol in the roots of L. frutescens and compare tissue–specific transcriptomes with existing data from Eremophila serrulata to decipher the biosynthesis of leubethanol. A short–chain cis–prenyl transferase (LfCPT1) first produces the rare diterpene precursor nerylneryl diphosphate, which is cyclized by an unusual plastidial terpene synthase (LfTPS1) into the characteristic serrulatane diterpene backbone. Final conversion to leubethanol is catalyzed by a cytochrome P450 (CYP71D616) of the CYP71 clan. This pathway documents the presence of a short–chain cis–prenyl diphosphate synthase, previously only found in Solanaceae, which is likely involved in the biosynthesis of other known diterpene backbones in Eremophila. LfTPS1 represents neofunctionalization of a compartment–switching terpene synthase accepting a novel substrate in the plastid. Biosynthetic access to leubethanol will enable pathway discovery to more complex serrulatane diterpenoids which share this common starting structure and provide a platform for the production and diversification of this class of promising anti–microbial therapeutics in heterologous systems.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

The microbiome of a bacterivorous marine choanoflagellate contains a resource-demanding obligate bacterial associate

Abstract Microbial predators such as choanoflagellates are key players in ocean food webs. Choanoflagellates, which are the closest unicellular relatives of animals, consume bacteria and also exhibit marked biological transitions triggered by bacterial compounds, yet their native microbiomes remain uncharacterized. Here we report the discovery of a ubiquitous, uncultured bacterial lineage we name Candidatus Comchoanobacterales ord. nov., related to the human pathogen Coxiella and physically associated with the uncultured marine choanoflagellate Bicosta minor . We analyse complete ‘Comchoano’ genomes acquired after sorting single Bicosta cells, finding signatures of obligate host-dependence, including reduction of pathways encoding glycolysis, membrane components, amino acids and B-vitamins. Comchoano encode the necessary apparatus to import energy and other compounds from the host, proteins for host-cell associations and a type IV secretion system closest to Coxiella’s that is expressed in Pacific Ocean metatranscriptomes. Interactions between choanoflagellates and their microbiota could reshape the direction of energy and resource flow attributed to microbial predators, adding complexity and nuance to marine food webs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Nanoparticles caged with DNA nanostructures

Nanoparticles (NPs) offer many benefits in biotechnology because of their small size and unique properties. Furthermore, many applications require precise positioning of the NPs or biological targeting molecules on their surfaces. DNA cages constructed from DNA tile, origami, or wireframe nanostructures offer a promising path forward because of their simplicity and programmability that can be used to generate complex, dynamic 2D and 3D geometries. Such materials can be used to pattern DNA on NP surfaces and organize NPs into specific supramolecular structures. DNA-caged NPs can be implemented in biosensing and drug delivery applications with cavities precisely designed to encapsulate-specific biomolecules. Ultimately, such approaches provide a springboard for future DNA robot designs that will enable controlled interactions with biological systems.

59 BASIC BIOLOGICAL SCIENCES↗