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At least 145 records · Page 8

Shuttle-Data-Tape XML Translator

JSDTImport is a computer program for translating native Shuttle Data Tape (SDT) files from American Standard Code for Information Interchange (ASCII) format into databases in other formats. JSDTImport solves the problem of organizing the SDT content, affording flexibility to enable users to choose how to store the information in a database to better support client and server applications. JSDTImport can be dynamically configured by use of a simple Extensible Markup Language (XML) file. JSDTImport uses this XML file to define how each record and field will be parsed, its layout and definition, and how the resulting database will be structured. JSDTImport also includes a client application programming interface (API) layer that provides abstraction for the data-querying process. The API enables a user to specify the search criteria to apply in gathering all the data relevant to a query. The API can be used to organize the SDT content and translate into a native XML database. The XML format is structured into efficient sections, enabling excellent query performance by use of the XPath query language. Optionally, the content can be translated into a Structured Query Language (SQL) database for fast, reliable SQL queries on standard database server computers.

Barry, Matthew R.↗

Development of a High Performance, Low Profile Translation Table with Wire Feedthrough for a Deep Space CubeSat

NEAScout, a 6U cubesat and secondary payload on NASA's EM-1, will use an 85 sq m solar sail to travel to a near-earth asteroid at about 1 Astronomical Unit (about 1.5 x 10(exp 8) km) for observation and reconnaissance1. A combination of reaction wheels, reaction control system, and a slow rotisserie roll about the solar sail's normal axis were expected to handle attitude control and adjust for imperfections in the deployed sail during the 2.5-year mission. As the design for NEAScout matured, one of the critical design parameters, the offset in the center of mass and center of pressure (CP/CM offset), proved to be sub-optimal. After significant mission and control analysis, the CP/CM offset was accommodated by the addition of a new subsystem to NEAScout. This system, called the Active Mass Translator (AMT), would reside near the geometric center of NEAScout and adjust the CM by moving one portion of the flight system relative to the other. The AMT was given limited design space - 17 mm of the vehicle's assembly height-and was required to generate +/-8 cm by +/-2 cm translation to sub-millimeter accuracy. Furthermore, the design must accommodate a large wire bundle of small gage, single strand wire and coax cables fed through the center of the mechanism. The bend radius, bend resistance, and the exposure to deep space environment complicates the AMT design and operation and necessitated a unique design to mitigate risks of wire bundle damage, binding, and cold-welding during operation. This paper will outline the design constraints for the AMT, discuss the methods and reasoning for design, and identify the lessons learned through the designing, breadboarding and testing for the low-profile translation stages with wire feedthrough capability.

Few, Alex↗

Development of a High Performance, Low-Profile Translation Table with Wire Feedthrough

NEAScout, a 6U cubesat, will use an 85 sq m solar sail to travel to a near-earth asteroid for observation. Over the course of the 3-year mission, a combination of reaction wheels, cold gas reaction control system, and a slow rotisserie roll about the solar sail's normal axis were expected to handle attitude control and adjust for imperfections in the deployed sail. As the design for NEAScout matured, one of the critical design parameters, the offset in the center of mass and center of pressure (CP/CM offset), proved to be sub-optimal. After significant mission and control analysis, the CP/CM offset was addressed and a new subsystem was introduced to NEAScout. This system, called the Active Mass Translator (AMT), would reside near the geometric center of NEAScout and adjust the CM by moving one portion of the flight system relative to the other. The AMT was given limited design space-about 17 mm of the vehicle's assembly height-and was required to generate +/-10 cm by +/-5 cm translation to sub-millimeter accuracy. Furthermore, the design must accommodate a large wire bundle of small gage, single strand wire and coax cables fed through the center of the mechanism. The bend radius, bend resistance, and the exposure to deep space environment complicates the AMT design and operation and necessitated a unique design to mitigate risks of wire bundle damage, binding, and cold-welding during operation. This paper will outline the design constraints for the AMT, discuss the methods and reasoning for design, and identify the lessons learned through the design downselect process and breadboarding for designing low-profile translation stages with feedthrough capabilities.

Few, Alex↗

Development of a High-Performance, Low-Profile Translation Table with Wire Feedthrough for a Deep Space CubeSat

NEAScout, a 6U cubesat and secondary payload on NASA's EM-1, will use an 85 sq m solar sail to travel to a near-earth asteroid at about 1 Astronomical Unit (about 1.5 x 10(exp 8) km) for observation and reconnaissance1. A combination of reaction wheels, reaction control system, and a slow rotisserie roll about the solar sail's normal axis were expected to handle attitude control and adjust for imperfections in the deployed sail during the 2.5-year mission. As the design for NEAScout matured, one of the critical design parameters, the offset in the center of mass and center of pressure (CP/CM offset), proved to be sub-optimal. After significant mission and control analysis, the CP/CM offset was accommodated by the addition of a new subsystem to NEAScout. This system, called the Active Mass Translator (AMT), would reside near the geometric center of NEAScout and adjust the CM by moving one portion of the flight system relative to the other. The AMT was given limited design space - 17 mm of the vehicle's assembly height-and was required to generate +/-8 cm by +/-2 cm translation to sub-millimeter accuracy. Furthermore, the design must accommodate a large wire bundle of small gage, single strand wire and coax cables fed through the center of the mechanism. The bend radius, bend resistance, and the exposure to deep space environment complicates the AMT design and operation and necessitated a unique design to mitigate risks of wire bundle damage, binding, and cold-welding during operation. This paper will outline the design constraints for the AMT, discuss the methods and reasoning for design, and identify the lessons learned through the designing, breadboarding and testing for the low-profile translation stages with wire feedthrough capability.

Few, Alex↗

Comparison of Selected Weather Translation Products

Weather is a primary contributor to the air traffic delays within the National Airspace System (NAS). At present, it is the individual decision makers who use weather information and assess its operational impact in creating effective air traffic management solutions. As a result, the estimation of the impact of forecast weather and the quality of ATM response relies on the skill and experience level of the decision maker. FAA Weather-ATM working groups have developed a Weather-ATM integration framework that consists of weather collection, weather translation, ATM impact conversion and ATM decision support. Some weather translation measures have been developed for hypothetical operations such as decentralized free flight, whereas others are meant to be relevant in current operations. This paper does comparative study of two different weather translation products relevant in current operations and finds that these products have strong correlation with each other. Given inaccuracies in prediction of weather, these differences would not be expected to be of significance in statistical study of a large number of decisions made with a look-ahead time of two hours or more.

Kulkarni, Deepak↗

Novel Crash Sled with a Translating Support Mass

Background: A novel crash sled has been developed with a translating support, incorporating transducers that allow multiple methods of measuring energy absorption to fully characterize the dynamic crush response of composite components. Objective: The main goal of the current investigation was to demonstrate functionality, repeatability, and accuracy of crush testing using a crash sled with a translating support mass. Methods: A semi-automated algorithm for data reduction was developed based on impact mechanics principles. A preliminary set of tests was initially conducted using aluminum honeycomb specimens with a specified stable crushing force to quantify the accuracy and repeatability of the crush data. Following the success of these tests, triaxially-braided fiber-reinforced polymer (FRP) specimens were evaluated. Results: Crush tests with the aluminum honeycomb specimens showed excellent outcomes for all three specimens. These data provided close agreement with cumulative energy absorption between individual instruments and stable crushing forces at expected values. For the FRP specimens, specific energy absorption (SEA) and force-displacement curves were successfully measured; however, data from the translating support mass accelerometer was excluded from the dataset due to clipping. The SEA of the corrugated specimens was greater than the SEA for the C-channel specimens at both test speeds. Conclusions: The crash sled functionality was verified, the specimen geometry was found to contribute more to SEA than the impact speed in the speed range tested, and the support mass accelerometer will be upgraded to prevent clipping in future tests.

Dynamic Crush↗

Post-translational modifications: emerging directors of cell-fate decisions during endoplasmic reticulum stress in Arabidopsis thaliana

Homeostasis of the endoplasmic reticulum (ER) is critical for growth, development, and stress responses. Perturbations causing an imbalance in ER proteostasis lead to a potentially lethal condition known as ER stress. In ER stress situations, cell-fate decisions either activate pro-life pathways that reestablish homeostasis or initiate pro-death pathways to prevent further damage to the organism. Understanding the mechanisms underpinning cell-fate decisions in ER stress is critical for crop development and has the potential to enable translation of conserved components to ER stress-related diseases in metazoans. Post-translational modifications (PTMs) of proteins are emerging as key players in cell-fate decisions in situations of imbalanced ER proteostasis. In this review, we address PTMs orchestrating cell-fate decisions in ER stress in plants and provide evidence-based perspectives for where future studies may focus to identify additional PTMs involved in ER stress management.

59 BASIC BIOLOGICAL SCIENCES↗

Solving a class of infinite-dimensional tensor eigenvalue problems by translational invariant tensor ring approximations

Here, we examine a method for solving an infinite-dimensional tensor eigenvalue problem Hx = λx, where the infinite-dimensional symmetric matrix H exhibits a translational invariant structure. We provide a formulation of this type of problem from a numerical linear algebra point of view and describe how a power method applied to e -Ht is used to obtain an approximation to the desired eigenvector. This infinite-dimensional eigenvector is represented in a compact way by a translational invariant infinite Tensor Ring (iTR). Low rank approximation is used to keep the cost of subsequent power iterations bounded while preserving the iTR structure of the approximate eigenvector. We show how the averaged Rayleigh quotient of an iTR eigenvector approximation can be efficiently computed and introduce a projected residual to monitor its convergence. In the numerical examples, we illustrate that the norm of this projected iTR residual can also be used to automatically modify the time step to ensure accurate and rapid convergence of the power method.

97 MATHEMATICS AND COMPUTING↗

Translational research in the MPICH project

The MPICH project is an example of translational research in computer science before that term was well known or even coined. The project began in 1992 as an effort to develop a portable, high-performance implementation of the emerging Message-Passing Interface (MPI) Standard. It has enabled the widespread adoption of MPI as a way to write scalable parallel applications on systems of all sizes including upcoming exascale supercomputers. In this paper, we describe how the translational research process was used in MPICH, how that led to its success, the challenges encountered and lessons learned, and how the process could be applied to other similar projects.

97 MATHEMATICS AND COMPUTING↗

Antibiotic that inhibits trans -translation blocks binding of EF-Tu to tmRNA but not to tRNA

trans-Translation is conserved throughout bacteria and is essential in many species. High-throughput screening identified a tetrazole-based trans-translation inhibitor, KKL-55, that has broad-spectrum antibiotic activity. A biotinylated version of KKL-55 pulled down elongation factor thermo-unstable (EF-Tu) from bacterial lysates. Purified EF-Tu bound KKL-55 in vitro with a K d = 2 µM, confirming a high-affinity interaction. An X-ray crystal structure showed that KKL-55 binds in domain 3 of EF-Tu, and mutation of residues in the binding pocket abolished KKL-55 binding. RNA-binding assays in vitro showed that KKL-55 inhibits binding between EF-Tu and transfer-messenger RNA (tmRNA) but not between EF-Tu and tRNA. These data demonstrate a new mechanism for the inhibition of EF-Tu function and suggest that this specific inhibition of EF-Tu•tmRNA binding is a viable target for antibiotic development.

59 BASIC BIOLOGICAL SCIENCES↗

Enhancing chemical bioproduction with rational control of bacterial post-translational modifications

Efficient conversion of inexpensive feedstocks to valuable chemicals by microbes is critical for a robust bioeconomy, but the ability to rationally design bacteria is hampered by insufficient knowledge of how post translational modifications (PTMs) control bacterial protein function and thus bioproduction phenotypes. Our study will focus on the lysine acetylation, a ubiquitous bacterial PTM that can affect the function of enzymes in central metabolism that are often critical for bioproduction processes, disrupt transcriptional regulation, and reduce translation. However, most lysine acetylation data is observational, which means that we do not know when, how, and what specific acetylated residues affect protein function and bacterial physiology. For our model host, we will use a Pseudomonas putida strain that we previously engineered to convert lignocellulosic feedstocks into chemicals such as itaconic acid (ITA). With this strain, we use a dynamic two-stage bioproduction process in which ITA is produced during a non-growth associated production phase. Production is highest during growth stages when lysine acetylation is low in other organisms (early stationary phase) and stalls in conditions where acetylation is highest (late stationary phase). The switch from high to stalled ITA production is also correlated with an unexpected increase in acetate levels – the precursor to non-enzymatic lysine acetylation. As such, we predict that lysine acetylation plays a substantial role in regulating the metabolic pathways required for ITA production. We will develop a generalizable approach that combines high-throughput genetic screens and cutting-edge genome engineering with state-of-the-art proteomics, metabolomics, and genetic code expansion methods to identify and modulate lysine acetylation patterns in bacteria. Ultimately, these strategies aim to manipulate protein expression and acetylation patterns to enhance bioproduction phenotypes (e.g., sustained ITA production in late stationary phase).

60 APPLIED LIFE SCIENCES↗

Reinspection of a Clinical Proteomics Tumor Analysis Consortium (CPTAC) Dataset with Cloud Computing Reveals Abundant Post-Translational Modifications and Protein Sequence Variants

The Clinical Proteomic Tumor Analysis Consortium (CPTAC) has provided some of the most in-depth analyses of the phenotypes of human tumors ever constructed. Today, the majority of proteomic data analysis is still performed using software housed on desktop computers which limits the number of sequence variants and post-translational modifications that can be considered. The original CPTAC studies limited the search for PTMs to only samples that were chemically enriched for those modified peptides. Similarly, the only sequence variants considered were those with strong evidence at the exon or transcript level. In this multi-institutional collaborative reanalysis, we utilized unbiased protein databases containing millions of human sequence variants in conjunction with hundreds of common post-translational modifications. Using these tools, we identified tens of thousands of high-confidence PTMs and sequence variants. We identified 4132 phosphorylated peptides in nonenriched samples, 93% of which were confirmed in the samples which were chemically enriched for phosphopeptides. In addition, our results also cover 90% of the high-confidence variants reported by the original proteogenomics study, without the need for sample specific next-generation sequencing. Finally, we report fivefold more somatic and germline variants that have an independent evidence at the peptide level, including mutations in ERRB2 and BCAS1. In this reanalysis of CPTAC proteomic data with cloud computing, we present an openly available and searchable web resource of the highest-coverage proteomic profiling of human tumors described to date.

60 APPLIED LIFE SCIENCES↗

Co- and/or post-translational modifications are critical for TCH4 XET activity

TCH4 encodes a xyloglucan endotransglycosylase (XET) of Arabidopsis thaliana. XETs endolytically cleave and religate xyloglucan polymers; xyloglucan is one of the primary structural components of the plant cell wall. Therefore, XET function may affect cell shape and plant morphogenesis. To gain insight into the biochemical function of TCH4, we defined structural requirements for optimal XET activity. Recombinant baculoviruses were designed to produce distinct forms of TCH4. TCH4 protein engineered to be synthesized in the cytosol and thus lack normal co- and post-translational modifications is virtually inactive. TCH4 proteins, with and without a polyhistidine tag, that harbor an intact N-terminus are directed to the secretory pathway. Thus, as predicted, the N-terminal region of TCH4 functions as a signal peptide. TCH4 is shown to have at least one disulfide bond as monitored by a mobility shift in SDS-PAGE in the presence of dithiothreitol (DTT). This disulfide bond(s) is essential for full XET activity. TCH4 is glycosylated in vivo; glycosidases that remove N-linked glycosylation eliminated 98% of the XET activity. Thus, co- and/or post-translational modifications are critical for optimal TCH4 XET activity. Furthermore, using site-specific mutagenesis, we demonstrated that the first glutamate residue of the conserved DEIDFEFL motif (E97) is essential for activity. A change to glutamine at this position resulted in an inactive protein; a change to aspartic acid caused protein mislocalization. These data support the hypothesis that, in analogy to Bacillus beta-glucanases, this region may be the active site of XET enzymes.

NASA Discipline Cell Biology↗

Calibration and Validation of a Mechanistic COVID-19 Model for Translational Quantitative Systems Pharmacology – A Proof-of-Concept Model Development for Remdesivir

With the ongoing global pandemic of coronavirus disease 2019 (COVID-19), there is an urgent need to accelerate the traditional drug development process. Many studies identified potential COVID-19 therapies based on promising nonclinical data. However, the poor translatability from nonclinical to clinical settings has led to failures of many of these drug candidates in the clinical phase. In this study, we propose a mechanism-based, quantitative framework to translate nonclinical findings to clinical outcome. Adopting a modularized approach, this framework includes an in silico disease model for COVID-19 (virus infection and human immune responses) and a pharmacological component for COVID-19 therapies. Here, the disease model was able to reproduce important longitudinal clinical data for patients with mild and severe COVID-19, including viral titer, key immunological cytokines, antibody responses, and time courses of lymphopenia. Using remdesivir as a proof-of-concept example of model development for the pharmacological component, we developed a pharmacological model that describes the conversion of intravenously administered remdesivir as a prodrug to its active metabolite nucleoside triphosphate through intracellular metabolism and connected it to the COVID-19 disease model. After being calibrated with the placebo arm data, our model was independently and quantitatively able to predict the primary endpoint (time to recovery) of the remdesivir clinical study, Adaptive Covid-19 Clinical Trial (ACTT). Our work demonstrates the possibility of quantitatively predicting clinical outcome based on nonclinical data and mechanistic understanding of the disease and provides a modularized framework to aid in candidate drug selection and clinical trial design for COVID-19 therapeutics.

60 APPLIED LIFE SCIENCES↗

Spatiotemporal 4D Whole-cell Modeling of a Minimal Autotroph Reveals Central Carbon Metabolism Regulated Locally by Protein Megacomplexes via Post-translational Modifications under Light Disturbance

Photosynthetic microorganisms rely on multiple pathways in central carbon metabolism to adapt to fluctuating light and energy availability across diel cycles. Mechanistic insight into the regulatory dynamics of this adaptation requires integrating processes spanning disparate timescales, from rapid redox-dependent post-translational modifications (PTMs) to slower changes in protein expression and metabolic pathway usage. To address this complexity beyond genome-based inference and traditional modeling, we develop a whole-cell four-dimensional (3D + time) model of the marine cyanobacterium Prochlorococcus marinus MED4 that explicitly represents the spatial organization of enzymatic and molecular processes in central carbon metabolism under light perturbation. We employ a perturbation-based research design to experimentally generate time-series, multi-omics measurements that provide molecular descriptors and cryo-ET derived 3D segmented volumes as constraints for this dynamic 4D framework. The integration of experiments and modeling across defined light regimes enables quantitative validation of system-level responses and forecasting under distinct light disturbances. We test the hypothesis that light-dependent redox PTMs regulating the structural assembly of a protein megacomplex, the “dark complex,” modulate metabolic flux at a conserved regulatory node of the Calvin–Benson cycle (CBC) in cyanobacteria. Our model shows that subcellular spatial organization buffers rapid light-induced changes in thylakoid reaction rates, which are followed by redox-PTM-mediated sequestration or release of CBC enzymes in the dark complex, ultimately impacting carbon fixation dynamics within carboxysomes. Comparison with an equivalently parameterized well-mixed stochastic model demonstrates that post-translational regulation not only buffers transcriptional noise and diffusion-driven fluctuations but also stabilizes phenotypic outcomes, underscoring the importance of spatial heterogeneity in phenotypic robustness. This ability to probe adaptive, spatiotemporally resolved mechanisms in photosynthetic machinery and central carbon metabolism addresses a critical gap in genotype-to-phenotype inference and expands modeling and design capabilities for understudied or genetically intractable autotrophs such as P. marinus MED4.

Johnson, Connah G.↗

TRANSLATE - a Monte Carlo simulation of electron transport in liquid argon

Here, the microphysics of electron and photon propagation in liquid argon is a key component of detector design and calibrations needed to construct and perform measurements within a wide range of particle physics experiments. As experiments grow in scale and complexity, and as the precision of their intended measurements increases, the development of tools to investigate important microphysics effects impacting such detectors becomes necessary. In this paper we present a new time-domain Monte Carlo simulation of electron transport in liquid argon. The simulation models the TRANSport in Liquid Argon of near-Thermal Electrons (TRANSLATE) with the aim of providing a multi-purpose software package for the study and optimization of detector environments, with a particular focus on ongoing and next generation liquid argon neutrino experiments utilizing the time projection chamber technology. TRANSLATE builds on previous work of Wojcik and Tachiya, amongst others, introducing additional processes, including ionization, thus modeling the full range of drift electron scattering interactions. The simulation is validated by benchmarking its performance with swarm parameters from data collected in experimental setups operating in gas and liquid.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Translating nanoparticle dosimetry from conventional in vitro systems to occupational inhalation exposures

As encouraged by Toxicity Testing in the 21st Century, researchers increasingly apply high-throughput in vitro approaches to identify and characterize nanoparticle hazards, including conventional aqueous cell culture systems to assess respiratory hazards. Translating nanoparticle dose from conventional toxicity testing systems to relevant human exposures remains a major challenge for assessing occupational risk of nanoparticle exposures. Here, we explored existing computational tools and data available to translate nanoparticle dose metrics from cellular test systems to inhalation exposures of silver nanoparticles in humans. We used the Multiple-Path Particle Dosimetry (MPPD) Model to predict deposition of humans exposed to 20 and 110 nm silver nanoparticles at 0.9 µg/m3 over an 8 hr period, the proposed a National Institute of Occupational Safety and Health (NIOSH) recommended exposure limit (REL). MPPD predicts 1.88 and 0.98 µg of silver deposited in an 8 hr period for 20 and 110 nm nanoparticles, respectively, with 20 nm particles displaying nearly 11-fold higher total surface area deposited. Peak nanoparticle concentrations occurred more proximal in the pulmonary tract compared to mass deposition patterns (generation 5 vs. generations 20-21, respectively) due to regional differences in lung lining fluid volumes. Assuming 0.4% nanoparticle dissolution by mass as previously measured, we predict peak concentrations of silver ions in cells of 0.24 and 0.17 µg/mL for 20 and 110 nm particles, respectively. Both predicted concentrations are below the measured toxic threshold of 1.7 µg/mL of silver ions in cells from in vitro assessments. Assuming 4% dissolution by mass, we predict 10-fold higher silver concentrations in tissues, peaking at 2.4 and 1.7 µg/mL, for 20 and 110 nm nanoparticles respectively, exceeding the observed in vitro toxic threshold and highlighting the importance and sensitivity of dissolution rates. Overall, this approach offers a framework for extrapolating nanotoxicity results from in vitro cell culture systems to human exposures. Aligning appropriate dose metrics from in vitro and in vivo hazard characterizations and human pulmonary doses from occupational exposures are critical components for successful nanoparticle risk assessment and worker protection and provide guidance for designing future in vitro studies aimed at relevant human exposures.

Smith, Jordan N.↗

Insights into Rotational and Translational Dynamics in Mixtures of Ethylene Glycol and Choline Chloride Using Nuclear Magnetic Resonance Techniques

This work examines molecular dynamics and interactions in ethylene glycol–choline chloride (EG–ChCl) mixtures across 0–33 mol % ChCl, spanning the true eutectic region near 17–20 mol % and the commonly used 1:2 formulation. We combine pulsed-field-gradient (PFG) diffusion, fast-field-cycling (FFC) relaxometry, temperature-dependent 13 C T 1 , and nuclear Overhauser effect spectroscopy (NOESY) to disentangle local from macroscopic dynamics. PFG and FFC show that both translational and average rotational motions largely track the strong increase in viscosity with ChCl content, with ethylene glycol consistently diffusing faster than the choline cation and no global dynamical anomaly at the eutectic composition. More subtle, site-specific composition effects nevertheless emerge. The ratio of the diffusion coefficient of the hydroxyl group of choline to the diffusion coefficient of the methyl group of choline displays a shallow minimum in the 17–25 mol % region, indicating a modest change in how the hydroxyl-bearing end of choline samples the underlying translational motion relative to the methyl groups. 13 C T 1 analysis shows that rotational correlation times at 25 °C generally increase with ChCl, reflecting viscosity-coupled slowing, while the CH 2 –N α site exhibits a small but reproducible deviation from this monotonic trend near the eutectic. NOESY spectra at similar compositions reveal enhanced cross-relaxation between EG and choline protons, consistent with increased headgroup–solvent contact density rather than a wholesale structural rearrangement. Overall, our multitechnique study demonstrates that EG–ChCl dynamics are predominantly viscosity-dominated, with the eutectic region acting as a subtle dynamical crossover where specific choline segments become maximally coupled to the hydrogen-bond network. These insights refine the structure–dynamics picture of choline-chloride DESs and provide practical guidance for tuning composition in electrochemical, separation, and catalytic applications.

diffusion↗