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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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At least 541 records · Page 30
All sourcesNASA NTRSDOE OSTI
NASA NTRS2000

A statistical model of the human core-temperature circadian rhythm

We formulate a statistical model of the human core-temperature circadian rhythm in which the circadian signal is modeled as a van der Pol oscillator, the thermoregulatory response is represented as a first-order autoregressive process, and the evoked effect of activity is modeled with a function specific for each circadian protocol. The new model directly links differential equation-based simulation models and harmonic regression analysis methods and permits statistical analysis of both static and dynamical properties of the circadian pacemaker from experimental data. We estimate the model parameters by using numerically efficient maximum likelihood algorithms and analyze human core-temperature data from forced desynchrony, free-run, and constant-routine protocols. By representing explicitly the dynamical effects of ambient light input to the human circadian pacemaker, the new model can estimate with high precision the correct intrinsic period of this oscillator ( approximately 24 h) from both free-run and forced desynchrony studies. Although the van der Pol model approximates well the dynamical features of the circadian pacemaker, the optimal dynamical model of the human biological clock may have a harmonic structure different from that of the van der Pol oscillator.

NASA Discipline Regulatory Physiology↗
NASA NTRS1991

Observer properties for understanding dynamical displays: Capacities, limitations, and defaults

People's ability to extract relevant information while viewing ongoing events is discussed in terms of human capabilities, limitations, and defaults. A taxonomy of event complexity is developed which predicts which dynamical events people can and cannot construe. This taxonomy is related to the distinction drawn in classical mechanics between particle and extended body motions. People's commonsense understandings of simple mechanical systems are impacted little by formal training, but rather reflect heuristical simplifications that focus on a single dimension of perceived dynamical relevance.

Proffitt, Dennis R.↗
NASA NTRSDate not supplied

Problem Complexity and LLM: H-M Team Reliability in Challenging Environments

In traditional human-machine operations, the functional decomposition of actions and responsibilities among various agents is assigned a priori. For instance, in current air traffic operations, although assisted by software, human pilots have the ultimate control of aircraft. Multiagent human-machine and machine-machine systems will face problems of varying and potentially unpredicted complexity in future challenging scenarios of planetary, en route, and orbital activities. Hence, it is important to enable dynamic transfer of decision-making to appropriate team members, human or machine, depending on which agent is best equipped to solve that specific problem on a time budget. In this paper, we consider aspects of problem-solving and its modeling that affect the outcomes of decision-making as a function of solution quality and the likelihood of solving the problem on a required time budget. We focus on Large Language Models (LLM) as potential machine teammates and conclude that practical, predictive modeling of their performance, at the current stage of their development, is infeasible. Simple examples help us illustrate that current LLM will require fundamental advancements to provide reliable support in team decision-making, especially in safety-critical and time-critical domains. The study is not meant to diminish the value of the remarkable capabilities of LLM, but rather to gain a better understanding of the technology’s appropriate use and the needed additions.

function allocation↗
DOE OSTI2020

Topology control of human fibroblast cells monolayer by liquid crystal elastomer

Eukaryotic cells in living tissues form dynamic patterns with spatially varying orientational order that affects important physiological processes such as apoptosis and cell migration. The challenge is how to impart a predesigned map of orientational order onto a growing tissue. Here, we demonstrate an approach to produce cell monolayers of human dermal fibroblasts with predesigned orientational patterns and topological defects using a photoaligned liquid crystal elastomer (LCE) that swells anisotropically in an aqueous medium. The patterns inscribed into the LCE are replicated by the tissue monolayer and cause a strong spatial variation of cells phenotype, their surface density, and number density fluctuations. Unbinding dynamics of defect pairs intrinsic to active matter is suppressed by anisotropic surface anchoring allowing the estimation of the elastic characteristics of the tissues. The demonstrated patterned LCE approach has potential to control the collective behavior of cells in living tissues, cell differentiation, and tissue morphogenesis.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2021

Establishment of FXS-A9 panel with a single human X chromosome from fragile X syndrome-associated individual

Highlights: • We established mouse A9 cells with human X chromosome from FXS carrier and patient. • FXS-associated CGG repeats were stably maintained in established rodent cells. • Epigenetic status of CGG repeat region were maintained in established rodent cells. • Human FMR1 expression in these cells was according to each CGG repeat length. Fragile X syndrome (FXS) is the most common inheritable form of intellectual disability. FMR1, the gene responsible for FXS, is located on human chromosome Xq27.3 and contains a stretch of CGG trinucleotide repeats in its 5′ untranslated region. FXS is caused by CGG repeats that expand beyond 200, resulting in FMR1 silencing via promoter hypermethylation. The molecular mechanism underlying CGG repeat expansion, a fundamental cause of FXS, remains poorly understood, partly due to a lack of experimental systems. Accumulated evidence indicates that the large chromosomal region flanking a CGG repeat is critical for repeat dynamics. In the present study, we isolated and introduced whole human X chromosomes from healthy, FXS premutation carriers, or FXS patients who carried disease condition-associated CGG repeat lengths, into mouse A9 cells via microcell-mediated chromosome transfer. The CGG repeat length-associated methylation status and human FMR1 expression in these monochromosomal hybrid cells mimicked those in humans. Thus, this set of A9 cells containing CGG repeats from three different origins (FXS-A9 panel) may provide a valuable resource for investigating a series of genetic and epigenetic CGG repeat dynamics during FXS pathogenesis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Predicting the effects of climate change on the cross-scale epidemiological dynamics of a fungal plant pathogen

The potential for climate change to exacerbate the burden of human infectious diseases is increasingly recognized, but its effects on infectious diseases of plants have received less attention. Understanding the impacts of climate on the epidemiological dynamics of plant pathogens is imperative, as these organisms play central roles in natural ecosystems and also pose a serious threat to agricultural production and food security. We use the fungal ‘flax rust’ pathogen (Melampsora lini) and its subalpine wildflower host Lewis flax (Linum lewisii) to investigate how climate change might affect the dynamics of fungal plant pathogen epidemics using a combination of empirical and modeling approaches. Our results suggest that climate change will initially slow transmission at both the within- and between-host scales. However, moderate resurgences in disease spread are predicted as warming progresses, especially if the rate of greenhouse gas emissions continues to increase at its current pace. These findings represent an important step towards building a holistic understanding of climate effects on plant infectious disease that encompasses demographic, epidemiological, and evolutionary processes. A core result is that neglecting processes at any one scale of plant pathogen transmission may bias projections of climate effects, as climate drivers have variable and cascading impacts on processes underlying transmission that occur at different scales.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2011

NASA Occupant Protection Standards Development

Current National Aeronautics and Space Administration (NASA) occupant protection standards and requirements are based on extrapolations of biodynamic models, which were based on human tests performed under pre-Space Shuttle human flight programs where the occupants were in different suit and seat configurations than is expected for the Multi Purpose Crew Vehicle (MPCV) and Commercial Crew programs. As a result, there is limited statistical validity to the occupant protection standards. Furthermore, the current standards and requirements have not been validated in relevant spaceflight suit, seat configurations or loading conditions. The objectives of this study were to develop new standards and requirements for occupant protection and rigorously validate these new standards with sub-injurious human testing. To accomplish these objectives we began by determining which critical injuries NASA would like to protect for. We then defined the anthropomorphic test device (ATD) and the associated injury metrics of interest. Finally, we conducted a literature review of available data for the Test Device for Human Occupant Restraint New Technology (THOR-NT) ATD to determine injury assessment reference values (IARV) to serve as a baseline for further development. To better understand NASA s environment, we propose conducting sub-injurious human testing in spaceflight seat and suit configurations with spaceflight dynamic loads, with a sufficiently high number of subjects to validate no injury during nominal landing loads. In addition to validate nominal loads, the THOR-NT ATD will be tested in the same conditions as the human volunteers, allowing correlation between human and ATD responses covering the Orion nominal landing environment and commercial vehicle expected nominal environments. All testing will be conducted without the suit and with the suit to ascertain the contribution of the suit to human and ATD responses. In addition to the testing campaign proposed, additional data analysis is proposed to mine existing human injury and response data from other sources, including military volunteer testing, automotive Crash Injury Research Engineering Network (CIREN), and IndyCar impact and injury data. These data sources can allow a better extrapolation of the ATD responses to off-nominal conditions above the nominal range that can safely be tested. These elements will be used to develop injury risk functions for each of the injury metrics measured from the ATD. These risk functions would serve as the basis for the NASA standards. Finally, we propose defining standard test methodology for evaluating future spacecraft designs against the IARVs, including developing a star-rating system to allow crew safety comparisons between vehicles.

Somers, Jeffrey T.↗
NASA NTRS2001

The Future of Human Exploration

This slide presentation reviews the near term future of human space exploration in terms of possible mission scenarios, propulsion technologies, orbital dynamics that lead to Low-Energy Transfer from Earth-Moon LI to Solar Libration Points and Return Potential Staging Point for Human Mars Missions. It also examines the required evolution of mission architecture, solar electric propulsion concept, vehicle concepts for future Mars missions, and an overview of a Mars Mission, Also in this presentation are pictures of several historic personages and occasions, and a view of a Mars Meteorite (i.e., ALH84001.0)

Cooke, Doug↗
NASA NTRS2003

Rethinking Human-Centered Computing: Finding the Customer and Negotiated Interactions at the Airport

The breakdown in the air transportation system over the past several years raises an interesting question for researchers: How can we help improve the reliability of airline operations? In offering some answers to this question, we make a statement about Huuman-Centered Computing (HCC). First we offer the definition that HCC is a multi-disciplinary research and design methodology focused on supporting humans as they use technology by including cognitive and social systems, computational tools and the physical environment in the analysis of organizational systems. We suggest that a key element in understanding organizational systems is that there are external cognitive and social systems (customers) as well as internal cognitive and social systems (employees) and that they interact dynamically to impact the organization and its work. The design of human-centered intelligent systems must take this outside-inside dynamic into account. In the past, the design of intelligent systems has focused on supporting the work and improvisation requirements of employees but has often assumed that customer requirements are implicitly satisfied by employee requirements. Taking a customer-centric perspective provides a different lens for understanding this outside-inside dynamic, the work of the organization and the requirements of both customers and employees In this article we will: 1) Demonstrate how the use of ethnographic methods revealed the important outside-inside dynamic in an airline, specifically the consequential relationship between external customer requirements and perspectives and internal organizational processes and perspectives as they came together in a changing environment; 2) Describe how taking a customer centric perspective identifies places where the impact of the outside-inside dynamic is most critical and requires technology that can be adaptive; 3) Define and discuss the place of negotiated interactions in airline operations, identifying how these interactions between customers and airline employees provided new insights into design problems in the airline system; 4) Show how taking a customer-centric perspective influences the HCC design of an airline system and make recommendations for new architectures and intelligent devices that will enable airline systems to adapt flexibly to delay situations, supporting both customers and airline employees.

Wales, Roxana↗
NASA NTRSDate not supplied

Soyuz Landing Risk Characterization

INTRODUCTION United States On-orbit Segment (USOS) astronauts have been returning to Earth from the International Space Station (ISS) aboard the Russian Soyuz vehicle since 2003. The energetics associated with Soyuz landings are comparable to our next generation of US space vehicles (Orion, Crew Dragon, and Starliner). Soyuz also lands crew in a similar state of spaceflight deconditioning that is anticipated using the future vehicles. A number of injuries have now been observed during these Soyuz landings. Currently it is unknown how Soyuz landing accelerations and the numbers and types of associated injuries relate to the new occupant protection requirements levied upon future space vehicles. Understanding this relationship will allow better quantification of the risk of injury for future spacecraft designs. METHODS An estimate of the occurrences of injury during Soyuz landings has been determined using data contained in NASA flight medicine databases and supplemented with data collected from crewmembers and flight surgeons. At the time of this abstract, 96 USOS astronauts have returned to Earth in the Soyuz (59 US, 31 International Partner, and 6 spaceflight participants). Of that total, data from 80 individual crew landings has been collected through this study. Injuries are classified as either contusions/abrasions, Class I (minor, no medical follow-up), Class II (moderate, medical follow-up necessary), Class III (severe), and Class IV (life threatening). Current NASA occupant protection standards are primarily based on the Multi-axial Dynamic Response Index (MDRI), which is a simple lumped-parameter spring, mass, damper model tuned to human impact responses in three orthogonal axes. RESULTS Using what is known about Soyuz landing dynamics from airborne and drop test data, the MDRI predicts essentially no Class IV or III injuries, < 1% Class II injuries, and < 5% Class I injuries. Approximately one-third of all USOS crewmembers for whom data has been gathered have suffered some sort of injury related to landing in the Soyuz vehicle. Most of these injuries fall into the contusion/abrasion category (21.3 %). Class I injuries have been sustained by 5.0% of all crew, and Class II injuries have been observed in 3.8%. No Class III or IV injuries have been sustained to date. Forty-three injuries have been documented, with some crewmembers sustaining more than one injury in a single landing. The knee was the most likely area of injury (n=9), followed by the back (n=8), and then the arm (n=7). CONCLUSION Soyuz landing dynamics are the most comparable analog environment for the anticipated loads associated with Orion and commercial crew vehicle landings. The MDRI under predicts the percentage of Class II injuries experienced during Soyuz landings. The MDRI is better at predicting Class I injury occurrences. However, if contusions/abrasions are included in the minor injury Class I category, then the MDRI also vastly under predicts those injuries as well. Given this data, it will be important to re-evaluate the expected injury rates for future vehicles, and work toward improving the predictive tools for spaceflight use. Spaceflight deconditioning may account for some of the under prediction, and work is ongoing to assess the relationship between landing injuries and impact tolerance changes due to spaceflight deconditioning.

N Newby↗
NASA NTRSDate not supplied

Soyuz Landing Risk Characterization

INTRODUCTION United States On-orbit Segment (USOS) astronauts have been returning to Earth from the International Space Station (ISS) aboard the Russian Soyuz vehicle since 2003. The energetics associated with Soyuz landings are comparable to our next generation of US space vehicles (Orion, Crew Dragon, and Starliner). Soyuz also lands crew in a similar state of spaceflight deconditioning that is anticipated using the future vehicles. A number of injuries have now been observed during these Soyuz landings. Currently it is unknown how Soyuz landing accelerations and the numbers and types of associated injuries relate to the new occupant protection requirements levied upon future space vehicles. Understanding this relationship will allow better quantification of the risk of injury for future spacecraft designs. METHODS An estimate of injury occurrence during Soyuz landings has been determined using data contained in NASA flight medicine databases and supplemented with data collected from crewmembers and flight surgeons. At the time of this abstract, 96 USOS astronauts have returned to Earth in the Soyuz (59 US, 31 International Partner, and 6 spaceflight participants). Of that total, data from 80 individual crew landings has been collected through this study as of 2021. Injuries are classified either as contusions/abrasions, Class I (minor, no medical follow-up), Class II (moderate, medical follow-up necessary), Class III (severe), or Class IV (life threatening). Current NASA occupant protection standards are primarily based on the Multi-axial Dynamic Response Index (MDRI), which is a simple lumped-parameter spring, mass, damper model tuned to human impact responses in three orthogonal axes. RESULTS Using what is known about Soyuz landing dynamics from airborne and drop test data, the MDRI predicts essentially no Class IV or III injuries, < 1% Class II injuries, and < 5% Class I injuries. Approximately one-third of all USOS crewmembers for whom data has been gathered have suffered some sort of injury related to landing in the Soyuz vehicle. Most of these injuries fall into the contusion/abrasion category (21.3 %) (n.b. This is the percent for whom contusion/abrasion was the worst injury. Those with class I or II injuries typically also received contusions/abrasions). Class I injuries have been sustained by 5.0% of all crew, and Class II injuries have been observed in 3.8%. No Class III or IV injuries have been sustained to date. Forty-three injuries have been documented, with some crewmembers sustaining more than one injury in a single landing. The knee was the most likely area of injury (n=9), followed by the back (n=8), then the arm (n=7). CONCLUSION Soyuz landing dynamics are the most comparable analog environment for the anticipated loads associated with Orion and commercial crew vehicle landings. The MDRI under predicts the percentage of Class II injuries experienced during Soyuz landings, but it is better at predicting Class I injury occurrences. However, if contusions/abrasions are included in the minor injury Class I category, then the MDRI vastly under predicts those injuries as well. Given this data, it is important to re-evaluate the expected injury rates for future vehicles and work toward improving the predictive tools for spaceflight use. Spaceflight deconditioning may account for some of the under prediction, and work is ongoing to assess the relationship between landing injuries and impact tolerance changes due to spaceflight deconditioning. Future work includes expanding this study to involve private space missions on new vehicles to better characterize the effects of time in flight, suit and seat design, and vehicle dynamics.

N Newby↗
NASA NTRSDate not supplied

Soyuz Landing Risk Characterization

INTRODUCTION United States On-orbit Segment (USOS) astronauts have been returning to Earth from the International Space Station (ISS) aboard the Russian Soyuz vehicle since 2003. The energetics associated with Soyuz landings are comparable to our next generation of US space vehicles (Orion, Crew Dragon, and Starliner). Soyuz also lands crew in a similar state of spaceflight deconditioning that is anticipated using the future vehicles. A number of injuries have now been observed during these Soyuz landings. Currently it is unknown how Soyuz landing accelerations and the numbers and types of associated injuries relate to the new occupant protection requirements levied upon future space vehicles. Understanding this relationship will allow better quantification of the risk of injury for future spacecraft designs. METHODS An estimate of injury occurrence during Soyuz landings has been determined using data contained in NASA flight medicine databases and supplemented with data collected from crew members and flight surgeons. At the time of this abstract, 96 USOS astronauts have returned to Earth in the Soyuz (59 US, 31 International Partner, and 6 spaceflight participants). Of that total, data from 80individual crew landings has been collected through this study as of September 2023. Injuries are classified either as contusions/abrasions, Class I (minor, no medical follow-up), Class II (moderate, medical follow-up necessary), Class III (severe), or Class IV (life threatening). Current NASA occupant protection standards are primarily based on the Multi-axial Dynamic Response Index (MDRI), which is a simple lumped-parameter spring, mass, damper model tuned to human impact responses in three orthogonal axes. RESULTS Using what is known about Soyuz landing dynamics from airborne and drop test data, the MDRI predicts essentially no Class IV or III injuries, < 1% Class II injuries, and < 5% Class I injuries. Approximately one-third of all USOS crewmembers for whom data has been gathered have suffered some sort of injury related to landing in the Soyuz vehicle. Most of these injuries fall into the contusion/abrasion category (21.3%) (n.b. This is the percent for whom contusion/abrasion was the worst injury. Those with class I or II injuries typically also received contusions/abrasions). Class I injuries have been sustained by 5.0% of all crew, and Class II injuries have been observed in 3.8%. No Class III or IV injuries have been sustained to date. Forty-three injuries have been documented, with some crewmembers sustaining more than one injury in a single landing. The knee was the most likely area of injury (n=9), followed by the back (n=8), then the arm (n=7). CONCLUSION Soyuz landing dynamics are the most comparable analog environment for the anticipated loads associated with Orion and commercial crew vehicle landings. The MDRI under predicts the percentage of Class II injuries experienced during Soyuz landings, but it is better at predicting Class I injury occurrences. However, if contusions/abrasions are included in the minor injury Class I category, then the MDRI vastly under predicts those injuries as well. Given this data, it is important to re-evaluate the expected injury rates for future vehicles and work toward improving the predictive tools for spaceflight use. Spaceflight deconditioning may account for some of the under prediction, and work is ongoing to assess the relationship between landing injuries and impact tolerance changes due to spaceflight deconditioning. Future work includes expanding this study to involve private space missions on new vehicles to better characterize the effects of time in flight, suit and seat design, and vehicle dynamics.

N Newby↗
NASA NTRSDate not supplied

Soyuz Landing Risk Characterization

INTRODUCTION United States On-orbit Segment (USOS) astronauts have been returning to Earth from the International Space Station (ISS) aboard the Russian Soyuz vehicle since 2003. The energetics associated with Soyuz landings are comparable to our next generation of US space vehicles (Orion, Crew Dragon, and Starliner). Soyuz also lands crew in a similar state of spaceflight deconditioning that is anticipated using the future vehicles. A number of injuries have now been observed during these Soyuz landings. Currently it is unknown how Soyuz landing accelerations and the numbers and types of associated injuries relate to the new occupant protection requirements levied upon future space vehicles. Understanding this relationship will allow better quantification of the risk of injury for future spacecraft designs. METHODS An estimate of injury occurrence during Soyuz landings has been determined using data contained in NASA flight medicine databases and supplemented with data collected from crewmembers and flight surgeons. At the time of this abstract, 96 USOS astronauts have returned to Earth in the Soyuz (59 US, 31 International Partner, and 6 spaceflight participants). Of that total, data from 80 individual crew landings has been collected through this study as of September 2023. Injuries are classified either as contusions/abrasions, Class I (minor, no medical follow-up), Class II (moderate, medical follow-up necessary), Class III (severe), or Class IV (life threatening). Current NASA occupant protection standards are primarily based on the Multi-axial Dynamic Response Index (MDRI), which is a simple lumped-parameter spring, mass, damper model tuned to human impact responses in three orthogonal axes. RESULTS Using what is known about Soyuz landing dynamics from airborne and drop test data, the MDRI predicts essentially no Class IV or III injuries, < 1% Class II injuries, and < 5% Class I injuries. Approximately one-third of all USOS crewmembers for whom data has been gathered have suffered some sort of injury related to landing in the Soyuz vehicle. Most of these injuries fall into the contusion/abrasion category (21.3 %) (n.b. This is the percent for whom contusion/abrasion was the worst injury. Those with class I or II injuries typically also received contusions/abrasions). Class I injuries have been sustained by 5.0% of all crew, and Class II injuries have been observed in 3.8%. No Class III or IV injuries have been sustained to date. Forty-three injuries have been documented, with some crewmembers sustaining more than one injury in a single landing. The knee was the most likely area of injury (n=9), followed by the back (n=8), then the arm (n=7). CONCLUSION Soyuz landing dynamics are the most comparable analog environment for the anticipated loads associated with Orion and commercial crew vehicle landings. The MDRI under predicts the percentage of Class II injuries experienced during Soyuz landings, but it is better at predicting Class I injury occurrences. However, if contusions/abrasions are included in the minor injury Class I category, then the MDRI vastly under predicts those injuries as well. Given this data, it is important to re-evaluate the expected injury rates for future vehicles and work toward improving the predictive tools for spaceflight use. Spaceflight deconditioning may account for some of the under prediction, and work is ongoing to assess the relationship between landing injuries and impact tolerance changes due to spaceflight deconditioning. Future work includes expanding this study to involve private space missions on new vehicles to better characterize the effects of time in flight, suit and seat design, and vehicle dynamics.

P Greenhalgh↗
DOE OSTI2020

The direct and indirect effects of copper on vector-borne disease dynamics

Metal pollution is a growing concern that affects the health of humans and animals globally. Copper is an essential insect micronutrient required for respiration, pigmentation and oxidative stress protection but can also act as a potentially toxic trace element. While several studies have focused on the negative fitness effects of copper on the aquatic larvae of mosquitoes, the effects of larval copper exposure on adult mosquito fitness (i.e., survival and fecundity) and their ability to transmit parasites (i.e., vector competence) remains unclear. Here, using a well-studied model vector-parasite system, the mosquito Aedes aegypti and parasite Dirofilaria immitis, we show that sublethal copper exposure in larval mosquitoes alters adult female fecundity and vector competence. Specifically, mosquitoes exposed to copper had a hormetic fecundity response and mosquitoes exposed to 600 μg/L of copper had significantly fewer infective parasite larvae than control mosquitoes not exposed to copper. Therefore, exposure of mosquito larvae to copper levels far below EPA-mandated safe drinking water limits (1300 μg/L) can impact vector-borne disease dynamics not only by reducing mosquito abundance (through increased larval mortality), but also by reducing parasite transmission risk. Our results also demonstrated that larval copper is retained through metamorphosis to adulthood in mosquitoes, indicating that these insects could transfer copper from aquatic to terrestrial foodwebs, especially in urban areas where they are abundant. To our knowledge this is the first study to directly link metal exposure with vector competence (i.e., ability to transmit parasites) in any vector-parasite system. Additionally, it also demonstrates unequivocally that mosquitoes can transfer contaminants from aquatic to terrestrial ecosystems. These results have broad implications for public health because they directly linking contaminants and vector-borne disease dynamics, as well as linking mosquitoes and contaminant dynamics.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

Duration of tick attachment necessary for transmission of Anaplasma phagocytophilum by Ixodes scapularis (Acari: Ixodidae) nymphs

This study assessed the duration of tick attachment necessary for a successful transmission of Anaplasma phagocytophilum by an infected I. scapularis nymph. Individual nymphs were placed upon BALB/c mice and allowed to feed for predetermined time intervals of 4 to 72 h. Ticks removed from mice at predetermined intervals were tested by PCR for verification of infection and evaluation of the bacterial load. The success of pathogen transmission to mice was assessed by blood-PCR at 7, 14 and 21 days postinfestation, and IFA at 21 days postinfestation. Anaplasma phagocytophilum infection was documented in 10-30 % of mice, from which ticks were removed within the first 20 h of feeding. However, transmission success was ≥70% if ticks remained attached for 36 h or longer. Notably, none of the PCR-positive mice that were exposed to infected ticks for 4 to 8 h and only half of PCR-positive mice exposed for 24 h developed antibodies within 3 weeks postinfestation. On the other hand, all mice with detectable bacteremia after being infested for 36 h seroconverted. This suggests that although some of the ticks removed prior to 24 h of attachment succeed in injecting a small amount of A. phagocytophilum, this amount is insufficient for stimulating humoral immunity and perhaps for establishing disseminated infection in BALB/c mice. Although A. phagocytophilum may be present in salivary glands of unfed I. scapularis nymphs, the amount of A. phagocytophilum initially contained in saliva appears insufficient to cause sustainable infection in a host. Replication and, maybe, reactivation of the agent for 12-24 h in a feeding tick is required before a mouse can be consistently infected.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Regulation of sarcomere formation and function in the healthy heart requires a titin intronic enhancer

Heterozygous truncating variants in the sarcomere protein titin (TTN) are the most common genetic cause of heart failure. To understand mechanisms that regulate abundant cardiomyocyte (CM) TTN expression, we characterized highly conserved intron 1 sequences that exhibited dynamic changes in chromatin accessibility during differentiation of human CMs from induced pluripotent stem cells (hiPSC-CMs). Homozygous deletion of these sequences in mice caused embryonic lethality, whereas heterozygous mice showed an allele-specific reduction in Ttn expression. A 296 bp fragment of this element, denoted E1, was sufficient to drive expression of a reporter gene in hiPSC-CMs. Deletion of E1 downregulated TTN expression, impaired sarcomerogenesis, and decreased contractility in hiPSC-CMs. Site-directed mutagenesis of predicted binding sites of NK2 homeobox 5 (NKX2-5) and myocyte enhancer factor 2 (MEF2) within E1 abolished its transcriptional activity. In embryonic mice expressing E1 reporter gene constructs, we validated in vivo cardiac-specific activity of E1 and the requirement for NKX2-5- and MEF2-binding sequences. Moreover, isogenic hiPSC-CMs containing a rare E1 variant in the predicted MEF2-binding motif that was identified in a patient with unexplained dilated cardiomyopathy (DCM) showed reduced TTN expression. Together, these discoveries define an essential, functional enhancer that regulates TTN expression. Manipulation of this element may advance therapeutic strategies to treat DCM caused by TTN haploinsufficiency.

Kim, Yuri↗
DOE OSTI2021

LANL Meteorological Program Self-Assessment 2021 Update

This self-assessment, documented in Table 1, has shown that there has been continued significant progress achieved in meeting the intent of the 21 recommendations from the 2015 DMCC Assist Visit. Every year after the Assist Visit, the LANL Met Program has improved, mainly by addressing the recommendations in the Assist Visit report. The Met Program management should continue to strive to apply its limited resources and seek to acquire additional human capital and physical resources to meet the dynamic needs of its growing sitewide customer base. This includes additional upgrading of the hardware and software elements of the Met Program and implementation of its operational procedures and QAPP to ensure it will consistently meet important present program requirements, as well as anticipated future requirements. These improvements have been summarized in the “present improvements and future initiatives” column in Table 1.

47 OTHER INSTRUMENTATION↗