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At least 19 records

Cryo-EM Visualization of Intermolecular π-Electron Interactions within π-Conjugated Peptidic Supramolecular Polymers

The self-assembly of “π-peptides” – molecules with π-electron cores substituted with two or more oligopeptide chains – brings organic electronic function into biologically relevant nanomaterials. π-Peptides assemble into fibrillar nanomaterials as driven by enthalpic peptide-based hydrogen bonding networks and pi-core-based quadrupolar interactions. A large body of spectroscopic, morphological and computational studies informs on the nature of the self-assembly process and the resulting nanostructures, but detailed structural information has remained elusive. Here, inspired by the recent use of cryogenic electron microscopy (cryo-EM) to provide high-resolution structures for synthetic peptide nanomaterials, we present here the use of cryo-EM to offer ca. 3 Å resolution of π-peptide nanomaterial assemblies, visualizing for the first time the nature of the intermolecular π-core electronic interactions responsible for energy transport through these supramolecular materials.

Group theory

Pre-flight risk assessment in Emergency Medical Service (EMS) helicopters

The Emergency Medical Service (EMS) industry has been the subject of several television and newspaper articles (Harvey and Jensen, 1987) which emphasized the negative aspects, (e.g., fatalities and high accident rates), rather than the life saving services performed. Until recently, the accident rate of the EMS industry has been five times as high as that of other civil helicopters. This high accident rate has been coupled with the dramatic rise in the number of programs. The industry has built from a single service at its inception in 1972, to over 180 in 1987 (Spray, 1987), to the point that 93 percent of the contiguous U.S. is now covered by some type of EMS service. These factors prompted the National Transportation Safety Board (NTSB) to study the accidents that occurred between May 11, 1978 and December 3, 1986 (NTSB, 1988). The NTSB report concluded that 'Sound pilot judgment is central to safe flight operations.' They further stated that '... factors unique to EMS helicopter operations--such as the influence of the mission itself, program competition, and EMS program management perspectives--can drastically influence pilot judgment during the EMS mission.' One of the most difficult decisions that a pilot must make is whether to accept or decline a mission. A pre-flight risk assessment system (SAFE) was developed at NASA-Ames Research Center for civil EMS operations to aid pilots in making this decision objectively. The ability of the SAFE system to predict mission risk profiles was tested at an EMS facility. The results of this field study demonstrated that the usefulness of SAFE was highly dependent on the type of mission flown. SAFE is now being modified so that it can 'learn' with each mission flown. For example, after flying a mission to a particular site, an EMS pilot would input information about this mission into the system, such as new buildings, wires, or approach procedures. Then, the next time a pilot flew a similar mission or one to the same area, this additional information would be taken into account in computing a risk assessment.

Shively, R. J.

CryoTEN: efficiently enhancing cryo-EM density maps using transformers

Abstract Motivation Cryogenic electron microscopy (cryo-EM) is a core experimental technique used to determine the structure of macromolecules such as proteins. However, the effectiveness of cryo-EM is often hindered by the noise and missing density values in cryo-EM density maps caused by experimental conditions such as low contrast and conformational heterogeneity. Although various global and local map-sharpening techniques are widely employed to improve cryo-EM density maps, it is still challenging to efficiently improve their quality for building better protein structures from them. Results In this study, we introduce CryoTEN—a 3D UNETR++ style transformer to improve cryo-EM maps effectively. CryoTEN is trained using a diverse set of 1295 cryo-EM maps as inputs and their corresponding simulated maps generated from known protein structures as targets. An independent test set containing 150 maps is used to evaluate CryoTEN, and the results demonstrate that it can robustly enhance the quality of cryo-EM density maps. In addition, automatic de novo protein structure modeling shows that protein structures built from the density maps processed by CryoTEN have substantially better quality than those built from the original maps. Compared to the existing state-of-the-art deep learning methods for enhancing cryo-EM density maps, CryoTEN ranks second in improving the quality of density maps, while running >10 times faster and requiring much less GPU memory than them. Availability and implementation The source code and data are freely available at https://github.com/jianlin-cheng/cryoten.

Biochemistry & Molecular Biology

Emergency medical service (EMS): A unique flight environment

The EMS flight environment is unique in today's aviation. The pilots must respond quickly to emergency events and often fly to landing zones where they have never been before . The time from initially receiving a call to being airborne can be as little as two to three minutes. Often the EMS pilot is the only aviation professional on site, they have no operations people or other pilots to aid them in making decisons. Further, since they are often flying to accident scenes, not airports, there is often complete weather and condition information. Therefore, the initial decision that the pilot must make, accepting or declining a flight, can become very difficult. The accident rate of EMS helicopters has been relatively high over the past years. NASA-Ames research center has taken several steps in an attempt to aid EMS pilots in their decision making and situational awareness. A preflight risk assessment system (SAFE) was developed to aid pilots in their decision making, and was tested at an EMS service. The resutls of the study were promising and a second version incorporating the lessons learned is under development. A second line of research was the development of a low cost electronic chart display (ECD). This is a digital map display to help pilots maintain geographical orientation. Another thrust was undertaken in conjunction with the Aviation Safety Reporting System (ASRS). This involved publicizing the ASRS to EMS pilots and personnel, and calling each of the reporters back to gather additional information. This paper will discuss these efforts and how they may positively impact the safety of EMS operations.

Shively, R. Jay

An assessment of controlled source EM for monitoring subsurface CO 2 injection at the wyoming carbonSAFE geologic carbon storage site

Here we evaluate if electromagnetic (EM) geophysical methods for monitoring geologic carbon storage (GCS) efforts at the Wyoming CarbonSAFE project adjacent to the Dry Fork Station power plant near Gillette, Wyoming. This first involved acquiring both electric and magnetic fields at eleven different locations ranging in distance from immediately adjacent to 4 km from the plant. Passive EM measurements were made to provide spectral EM noise measurements generated by electricity production at the plant and to determine if useful magnetotelluric (MT) data can be successfully collected in the region. The processed data indicate that useful MT data can be collected as long as the site is located more than 2km away from the power plant as well as active roads and rail lines. Controlled source EM data were collected using three different source configurations, two of which connected to steel casings used to complete the injection wells. Comparing the EM noise measurements to the CSEM data show measurable electric and magnetic field signals at all sites. Next a series of three-dimensional (3D) numerical models were built that simulate resistivity changes caused by the proposed CO2 injection at depths ranging from 2.4 to 3.0km. These models were used to simulate various EM measurement configurations. The modeling shows that casing-source CSEM monitoring can provide sensitivity to the injected CO 2 if source electrodes are connected to the bottom of one or both of the injection wells.

58 GEOSCIENCES

Artificial intelligence in cryo-EM protein particle picking: recent advances and remaining challenges

Abstract Cryo-electron microscopy (cryo-EM) has revolutionized structural biology by enabling the determination of high-resolution 3-Dimensional (3D) structures of large biological macromolecules. Protein particle picking, the process of identifying individual protein particles in cryo-EM micrographs for building protein structures, has progressed from manual and template-based methods to sophisticated artificial intelligence (AI)-driven approaches in recent years. This review critically examines the evolution and current state of cryo-EM particle picking methods, with an emphasis on the impact of AI. We conducted a comparative evaluation of popular AI-based particle picking methods, using both general machine learning metrics and specific cryo-EM structure determination metrics. This analysis involved constructing the 3D density map from the picked protein particles and assessing the obtained resolution and particle orientation diversity, underscoring the significant impact of AI on cryo-EM particle picking. Despite the advancements, we also identified key obstacles, such as handling complex micrographs with small proteins. The analysis provides insights into the future development of more sophisticated and fully automated AI methods in cryo-EM particle recognition.

Biochemistry & Molecular Biology

Operations of the Optical Communications Demonstration for the Orion EM-2 Mission

The GSFC implementation of an Optical Communication System to demonstrate an operational optical communication link for Orion EM-2. It will serve as a base for providing an operational optical communications capability for future Orion missions. GSFC plans to maintain a development path for the optical communication flight terminal to allow commercialization and implementation on future Orion missions. The Orion optical module part of the optical communications flight terminal and its control electronics have a common architecture with the ILLUMA-T optical terminal provided by GSFC for use on the ISS. The plan is to flow data from Orion through the Optical Communication Fight Terminal to the Optical Communication Ground Terminal and reverse. NASA's Orion spacecraft is an exploratory vehicle designed for longer-duration flights beyond the Moon. Following Orion's Exploration Mission-1 (EM-1), during which the spacecraft will travel beyond the Moon, enter a distant retrograde orbit around the Moon and return to Earth unmanned, Exploration Mission-2 (EM-2) will see a crewed spacecraft complete a slightly different flight path. First crewed test flight of the Orion spacecraft, currently targeting a June 30, 2022 launch. The mission involves: One revolution in Low Earth Orbit (LEO) parking orbit to verify basic Orion systems functionality and deploy solar arrays. A single 42-hour Highly Elliptical Orbit (HEO) intermediate checkout orbit allows characterization of the Orion vehicle system performance prior to committing to a cis-lunar flight. Trans Lunar Injection (TLI) burn using Orion Service Module (SM) main engine, which sends Orion on a lunar flyby and free return. Skip reentry at lunar return velocities to splashdown off the coast of San Diego. Total mission duration is approximately 10 days. EM-2 is the first crewed mission of the Orion Spacecraft that crew brings more video up/downloads, file transfers, and real-time chats with family back home and high-rate communications enables live HD streaming for Crew conferences, Public Affairs Office (PAO) events, and significant mission events. Also still collecting vehicle data on numerous Orion subsystems via Development Flight Instrumentation (DFI) allows large data volume returns sooner for DFI and future science payloads, as opposed to waiting for end-of-mission. O2O is a demonstration of operational utility system tested as a Developmental Test Objective (DTO) and not required to meet mission requirements/success/ Flight Test Objectives (FTO). EM-2 architecture is as close to future mission operational architecture as possible.Orion subsystems (video, DFI, etc.) expected to generate ~250 GB of data in the first 24 hours of flight. Total data generated over the mission estimated to be more than 400 GBUsing S-Band alone, Orion limited to ~ 6GB of data downlink per day. Because of this limitation, Orion is planning to limit live video downlinks on EM-1 in order to downlink high priority fileswith 1 hour/day of Optical Communication, Orion could downlink ~6x more data per day (~ 36GB/day).The optical communication system is capable of multiple data rates up to at least 80 Mbps downlink for the transfer of Orion data to Earth while Orion is operating in the lunar vicinity.

Optical Communication

International Space Station (ISS) Emergency Mask (EM) Development

The Emergency Mask (EM) is considered a secondary response emergency Personal Protective Equipment (PPE) designed to provide respiratory protection to the International Space Station (ISS) crewmembers in response to a post-fire event or ammonia leak. The EM is planned to be delivered to ISS in 2012 to replace the current air purifying respirator (APR) onboard ISS called the Ammonia Respirator (AR). The EM is a one ]size ]fits ]all model designed to fit any size crewmember, unlike the APR on ISS, and uses either two Fire Cartridges (FCs) or two Commercial Off-the-Shelf (COTS) 3M(Trademark). Ammonia Cartridges (ACs) to provide the crew with a minimum of 8 hours of respiratory protection with appropriate cartridge swap ]out. The EM is designed for a single exposure event, for either post ]fire or ammonia, and is a passive device that cannot help crewmembers who cannot breathe on their own. The EM fs primary and only seal is around the wearer fs neck to prevent a crewmember from inhaling contaminants. During the development of the ISS Emergency Mask, several design challenges were faced that focused around manufacturing a leak free mask. The description of those challenges are broadly discussed but focuses on one key design challenge area: bonding EPDM gasket material to Gore(Registered Trademark) fabric hood.

Toon, Katherine P.

Towards interpretable Cryo-EM: disentangling latent spaces of molecular conformations

Molecules are essential building blocks of life and their different conformations (i.e., shapes) crucially determine the functional role that they play in living organisms. Cryogenic Electron Microscopy (cryo-EM) allows for acquisition of large image datasets of individual molecules. Recent advances in computational cryo-EM have made it possible to learn latent variable models of conformation landscapes. However, interpreting these latent spaces remains a challenge as their individual dimensions are often arbitrary. The key message of our work is that this interpretation challenge can be viewed as an Independent Component Analysis (ICA) problem where we seek models that have the property of identifiability. That means, they have an essentially unique solution, representing a conformational latent space that separates the different degrees of freedom a molecule is equipped with in nature. Thus, we aim to advance the computational field of cryo-EM beyond visualizations as we connect it with the theoretical framework of (nonlinear) ICA and discuss the need for identifiable models, improved metrics, and benchmarks. Moving forward, we propose future directions for enhancing the disentanglement of latent spaces in cryo-EM, refining evaluation metrics and exploring techniques that leverage physics-based decoders of biomolecular systems. Moreover, we discuss how future technological developments in time-resolved single particle imaging may enable the application of nonlinear ICA models that can discover the true conformation changes of molecules in nature. The pursuit of interpretable conformational latent spaces will empower researchers to unravel complex biological processes and facilitate targeted interventions. This has significant implications for drug discovery and structural biology more broadly. More generally, latent variable models are deployed widely across many scientific disciplines. Thus, the argument we present in this work has much broader applications in AI for science if we want to move from impressive nonlinear neural network models to mathematically grounded methods that can help us learn something new about nature.

59 BASIC BIOLOGICAL SCIENCES

CryoTRANS: predicting high-resolution maps of rare conformations from self-supervised trajectories in cryo-EM

Cryogenic electron microscopy (cryo-EM) has revolutionized structural biology, enabling efficient determination of structures at near-atomic resolutions. However, a common challenge arises from the severe imbalance among various conformations of vitrified particles, leading to low-resolution reconstructions in rare conformations due to a lack of particle images in these quasi-stable states. We introduce CryoTRANS, a method that predicts high-resolution maps of rare conformations by constructing a self-supervised pseudo-trajectory between density maps of varying resolutions. This trajectory is represented by an ordinary differential equation parameterized by a deep neural network, ensuring retention of detailed structures from high-resolution density maps. By leveraging a single high-resolution density map, CryoTRANS significantly improves the reconstruction of rare conformations and has been validated on four real-world datasets: alpha-2-macroglobulin, actin-binding protein complexes, SARS-CoV-2 spike glycoprotein, and the 70S ribosome. CryoTRANS can also predict high-resolution structures in cryogenic electron tomography maps using a high-resolution cryo-EM map.Cryogenic electron microscopy (cryo-EM) has revolutionized structural biology, enabling efficient determination of structures at near-atomic resolutions. However, a common challenge arises from the severe imbalance among various conformations of vitrified particles, leading to low-resolution reconstructions in rare conformations due to a lack of particle images in these quasi-stable states. We introduce CryoTRANS, a method that predicts high-resolution maps of rare conformations by constructing a self-supervised pseudo-trajectory between density maps of varying resolutions. This trajectory is represented by an ordinary differential equation parameterized by a deep neural network, ensuring retention of detailed structures from high-resolution density maps. By leveraging a single high-resolution density map, CryoTRANS significantly improves the reconstruction of rare conformations and has been validated on four real-world datasets: alpha-2-macroglobulin, actin-binding protein complexes, SARS-CoV-2 spike glycoprotein, and the 70S ribosome. CryoTRANS can also predict high-resolution structures in cryogenic electron tomography maps using a high-resolution cryo-EM map.

47 OTHER INSTRUMENTATION

System concept definition of the Grumman superconducting Electromagnetic Suspension (EMS) Maglev design

Grumman, under contract to the Army Corps of Engineers, completed a System Concept Definition (SCD) study to design a high-speed 134 m/s (300 m.p.h.) magnetically levitated (Maglev) transportation system. The primary development goals were to design a Maglev that is safe, reliable, environmentally acceptable, and low-cost. The cost issue was a predominant one, since previous studies have shown that an economically viable Maglev system (one that is attractive to investors for future models of passenger and/or freight transportation) requires a cost that is about $12.4 M/km ($20 Million per mile). The design is based on the electromagnetic suspension (EMS) system using superconducting iron-core magnets mounted along both sides of the vehicle. The EMS system has several advantages compared to the electrodynamic suspension (EDS) Maglev systems such as low stray magnetic fields in the passenger cabin and the surrounding areas, uniform load distribution along the full length of the vehicle, and small pole pitch for smoother propulsion and ride comfort. It is also levitated at all speeds and incorporates a wrap-around design of safer operation. The Grumman design has all the advantages of an EMS system identified above, while eliminating (or significantly improving) drawbacks associated with normal magnet powered EMS systems. Improvements include larger gap clearance, lighter weight, lower number of control servos, and higher off line switching speeds. The design also incorporates vehicle tilt (plus or minus 9 deg) for higher coordinated turn and turn out speed capability.

Proise, M.

Using System Mass (SM), Equivalent Mass (EM), Equivalent System Mass (ESM) or Life Cycle Mass (LCM) in Advanced Life Support (ALS) Reporting

The Advanced Life Support (ALS) has used a single number, Equivalent System Mass (ESM), for both reporting progress and technology selection. ESM is the launch mass required to provide a space system. ESM indicates launch cost. ESM alone is inadequate for technology selection, which should include other metrics such as Technology Readiness Level (TRL) and Life Cycle Cost (LCC) and also consider perfom.arxe 2nd risk. ESM has proven difficult to implement as a reporting metric, partly because it includes non-mass technology selection factors. Since it will not be used exclusively for technology selection, a new reporting metric can be made easier to compute and explain. Systems design trades-off performance, cost, and risk, but a risk weighted cost/benefit metric would be too complex to report. Since life support has fixed requirements, different systems usually have roughly equal performance. Risk is important since failure can harm the crew, but it is difficult to treat simply. Cost is not easy to estimate, but preliminary space system cost estimates are usually based on mass, which is better estimated than cost. Amass-based cost estimate, similar to ESM, would be a good single reporting metric. The paper defines and compares four mass-based cost estimates, Equivalent Mass (EM), Equivalent System Mass (ESM), Life Cycle Mass (LCM), and System Mass (SM). EM is traditional in life support and includes mass, volume, power, cooling and logistics. ESM is the specifically defined ALS metric, which adds crew time and possibly other cost factors to EM. LCM is a new metric, a mass-based estimate of LCC measured in mass units. SM includes only the factors of EM that are originally measured in mass, the hardware and logistics mass. All four mass-based metrics usually give similar comparisons. SM is by far the simplest to compute and easiest to explain.

Jones, Harry

Orion Heat Shield Manufacturing Producibility Improvements for the EM-1 Flight Test Program

This paper describes how the Orion program is incorporating improvements in the heat shield design and manufacturing processes reducing programmatic risk and ensuring crew safety in support of NASA’s Exploration Missions. The Orion program successfully completed the EFT-1 flight test in 2014 and is currently developing the EM-1 spacecraft to meet the test objectives of an orbital mission to the moon and return to earth in 2019. Lessons learned from the EFT-1 manufacturing and flight test experience are being incorporated into a wide variety of vehicle systems and manufacturing processes to reduce risk to the Orion missions and flight crew. A critical contributor to crew safety is the heat shield that protects the crew capsule during re-entry through the earth’s atmosphere for return from deep space. The first flight test vehicle, EFT-1, was manufactured and tested in the Neil Armstrong Operations and Checkout (O&C) facility at KSC to demonstrate early risk reduction including the functionality of the Thermal Protection Systems (TPS) for capsule safe return to earth. The approach for the EFT-1 heat shield utilized a low risk approach using Apollo heritage design and manufacturing processes using an Avcoat TPS ablator with a honeycomb substrate to provide a one piece heat shield to meet the mission re-entry heating environments. The manufacturing processes used honeycomb cell injection guns which were redeveloped from the Apollo Lunar Program processes to build the EFT-1 heat shield. The completed heat shield was transported across the country by aircraft to the O&C at KSC for installation onto the capsule. The EFT-1 heat shield successfully performed its mission and experienced ~80% of the re-entry velocity (50% heating rate) for a lunar return for an Exploration Mission. The second flight test vehicle is the EM-1 mission which will have additional flight systems installed to fly to the moon and return. Heat shield design and producibility improvements have been incorporated in the EM-1 vehicle to meet deep space mission and programmatic requirements. The design continues to use the Avcoat material, but in a “block” configuration to enable improvements in the application processes as well as additional improvements in the carrier structure design and manufacturing operations. Incorporating flight test results and producibility improvements from EFT-1 for the heat shield system design and processes have improved the thermal protection capability, improved the producibility, and cost for EM-1 flight test.

Producibility

EM Physics

Geant4 provides a comprehensive set of electromagnetic (EM) processes and models for electron/positron, gamma and long-lived charged particles, spanning energies from 100 eV to 100 TeV. Covering diverse energy regions often requires multiple models, which can be constructed using pre-packaged or user-defined EM physics constructors. Geant4 also supports detailed low-energy EM physics through models like Livermore, Penelope, and ICRU73, offering extensive data for elements across a wide energy range (250 eV–100 GeV). Application domains include space, medical, and radiobiology simulations. Additionally, Geant4 provides robust options for simulating complex optical photon production and transportation processes, enhancing its versatility in physics research and applications.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND

Propulsion From a Rotating EM Tether at Jupiter

The Jovian system with its rapid planetary rotation and strong magnetic field presents exciting opportunities for the use of electrodynamic (EM) tethers. Previous analysis for a radial, 10 km length tether demonstrated the possibility of propulsive forces as large as 50 Newtons near the planet. For orbital positions beyond about 2.5 Jovian radii, an EM tether can simultaneously be used for power and increases in the orbital altitude. Although the previous study demonstrated the physical feasibility of EM tether use at Jupiter, it did not address the issues of limited gravity gradient force for tether orientation and the practical use of this technology in an engineered system. This presentation will discuss these issues and current progress in an ongoing science/engineering transitional study.

Gallagher, D. L.

CO2 Washout Testing of the REI and EM-ACES Space Suits

Requirements for using a space suit during ground testing include providing adequate carbon dioxide (CO2) washout for the suited subject. Acute CO2 exposure can lead to symptoms including headache, dyspnea, lethargy and eventually unconsciousness or even death. Symptoms depend on several factors including partial pressure of CO2 (ppCO2), duration of exposure, metabolic rate of the subject and physiological differences between subjects. The objective of this test was to characterize inspired oronasal ppCO2 in the Rear Entry I-Suit (REI) and the Enhanced Mobility Advanced Crew Escape Suit (EM-ACES) across a range of workloads and flow rates for which ground testing is nominally performed. Three subjects were tested in each suit. In all but one case, each subject performed the test twice to allow for comparison between tests. Suit pressure was maintained at 4.3 psid. Subjects wore the suit while resting, performing arm ergometry, and walking on a treadmill to generate metabolic workloads of approximately 500 to 3000 BTU/hr. Supply airflow was varied at 6, 5 and 4 actual cubic feet per minute (ACFM) at each workload. Subjects wore an oronasal mask with an open port in front of the mouth and were allowed to breathe freely. Oronasal ppCO2 was monitored real-time via gas analyzers with sampling tubes connected to the oronasal mask. Metabolic rate was calculated from the total CO2 production measured by an additional gas analyzer at the air outlet from the suit. Real-time metabolic rate was used to adjust the arm ergometer or treadmill workload to meet target metabolic rates. In both suits, inspired CO2 was primarily affected by the metabolic rate of the subject, with increased metabolic rate resulting in increased inspired ppCO2. Suit flow rate also affected inspired ppCO2, with decreased flow causing small increases in inspired ppCO2. The effect of flow was more evident at metabolic rates greater than or equal to 2000 BTU/hr. Results were consistent between suits, with the EM-ACES demonstrating slightly better CO2 washout than the REI suit, but not statistically significant. Regression equations were developed for each suit to predict the mean inspired ppCO2 as a function of metabolic rate and suit flow rate. This paper provides detailed descriptions of the test hardware, methodology and results, as well as implications for future ground testing in the REI and EM-ACES.

Mitchell, Kate