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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

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

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.

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

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

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

When a space suit is used during ground testing, adequate carbon dioxide (CO2) washout must be provided for the suited subject. Symptoms of acute CO2 exposure depend on partial pressure of CO2 (ppCO2), metabolic rate of the subject, and other factors. This test was done to characterize inspired oronasal ppCO2 in the Rear Entry I-Suit (REI) and the Enhanced Mobility Advanced Crew Escape Suit (EM-ACES) for 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. 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 about 500 to 3000 BTU/hr. Supply airflow was varied between 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 in real time by gas analyzers with sampling tubes connected to the mask. Metabolic rate was calculated from the total CO2 production measured by an additional gas analyzer at the suit air outlet. 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 affected mainly by the metabolic rate of the subject: increased metabolic rate significantly (P < 0.05) increased inspired ppCO2. Decreased air flow caused small increases in inspired ppCO2. The effect of flow was more evident at metabolic rates . 2000 BTU/hr. CO2 washout values of the EM-ACES were slightly but not significantly better than those of the REI suit. 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-suit and EM-ACES.

Mitchell, Kathryn C.

CryoDRGN-AI: neural ab initio reconstruction of challenging cryo-EM and cryo-ET datasets

Proteins and other biomolecules form dynamic macromolecular machines that are tightly orchestrated to move, bind, and perform chemistry. Cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET) can access the intrinsic heterogeneity of these complexes and are therefore key tools for understanding their function. However, 3D reconstruction of the collected imaging data presents a challenging computational problem, especially without any starting information, a setting termed ab initio reconstruction. Here, in this study, we introduce cryoDRGN-AI, a method leveraging an expressive neural representation and combining an exhaustive search strategy with gradient-based optimization to process challenging heterogeneous datasets. Using cryoDRGN-AI, we reveal new conformational states in large datasets, reconstruct previously unresolved motions from unfiltered datasets, and demonstrate ab initio reconstruction of biomolecular complexes from in situ data. With this expressive and scalable model for structure determination, we hope to unlock the full potential of cryo-EM and cryo-ET as a high-throughput tool for structural biology and discovery.

Levy, Axel [Stanford Univ., CA (United States); SL

Targeted seed EMS mutagenesis reveals a basic helix–loop–helix transcription factor underlying male sterility in sorghum

Abstract Forward genetic screens of mutant populations are fundamental for functional genomics studies. However, isolating independent mutant alleles to molecularly identify causal genes is challenging in species recalcitrant to genetic manipulation. Here, we demonstrate that classic seed ethyl methanesulfonate (EMS) mutagenesis coupled with genome sequencing can overcome this limitation in sorghum. We used this method to generate new mutant alleles of sorghum MALE STERILE 8 (MS8) and identified the causal locus for the ms8 phenotype as Sobic.004G270900, which encodes the sorghum ortholog of maize bhlh122, a basic helix–loop–helix (bHLH) transcription factor required for male fertility in maize. Bulked segregant analysis mapped ms8-1 to a region on chromosome 4 containing Sobic.004G270900. Seeds from heterozygous MS8/ms8-1 plants were mutagenized and screened for chimeric inflorescences containing sectors with white, sterile anthers resembling the ms8-1 homozygous phenotype. DNA sequencing of sterile and fertile sectors from a single chimeric inflorescence revealed two mutations in Sobic.004G270900 within the sterile sector, but not the fertile sector. Isolation of this loss-of-function allele (ms8-2) established Sobic.004G270900 as the causative locus for male sterility in the ms8 mutant. We generated additional alleles of MS8 in a different genetic background using CRISPR/Cas9-based gene editing, where deletions in Sobic.004G270900 also resulted in male sterility. Our work identified a gene underlying male sterility in sorghum and provides a novel and straightforward genetic tool for researchers who lack access to advanced transformation facilities to validate gene candidates. Unlike gene editing, no prior knowledge of candidate genes is required for targeted seed EMS mutagenesis to aid identification of causal loci.

Genetics & Heredity

A laboratory experiment on EM backscatter from Farley-Buneman and gradient drift waves

Results of laboratory experiment on Bragg backscatter of 3-cm microwaves by turbulent waves driven by the Farley-Buneman and gradient drift instabilities are reported. It is noted that the study is the third in a series of laboratory experiments performed to test, under controlled conditions, prevalent ideas on EM scattering by equatorial and high-latitude ionospheric waves and irregularities. It is shown through separate backscattering from fast and slow ion beam modes that a beam of EM radiation actually provides, in backscatter, information on the spectral content of the scattering medium.

Alport, M. J.

Mixture densities, maximum likelihood, and the EM algorithm

The problem of estimating the parameters which determine a mixture density is reviewed as well as maximum likelihood estimation for it. A particular iterative procedure for numerically approximating maximum likelihood estimates for mixture density problems is considered. This EM algorithm, is a specialization to the mixture density context of a general algorithm of the same name used to approximate maximum likelihood estimates for incomplete data problems. The formulation and theoretical and practical properties of the EM algorithm for mixture densities are discussed focussing in particular on mixtures of densities from exponential families.

Redner, R. A.

A selective modal scheme for the analysis of EM coupling into or radiation from large open-ended waveguides

A selective modal scheme is proposed to efficiently analyze the problem of high-frequency (HF) electromagnetic (EM) coupling/penetration into or radiation from open-ended waveguides. This scheme is based on the phenomenon that at sufficiently high frequencies, the modes which contribute most significantly to the fields coupled into the waveguide are those whose modal ray directions are most nearly parallel to the incident-wave direction. This concept is illustrated by calculating the EM radiation and backscattering from open-ended parallel-plate, rectangular, circular, and sectoral waveguide geometries. The calculations use the usual geometrical optics, aperture field, and Ufimtsev edge current techniques. Also included are some measured results which further verify the accuracy of the above computations.

Altintas, Ayhan