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Evaluation of Correction Methods for NASA GeneLab Transcriptomic Datasets

Conducting space biology experiments aboard the International Space Station, particularly those utilizing complex model organisms like mice, is expensive and difficult due to limited crew availability, hardware, and space. As a result, sample numbers from these studies are low, reducing the statistical power of any one experiment. Aggregating spaceflight datasets serves as a method to increase sample numbers, allowing for novel insights through bioinformatic analysis of ‘omics data from merged datasets. However, aggregating datasets can introduce unwanted variation including 1) differences in sample handling, processing, and sequencing platforms between datasets (technical variation) as well as 2) differences in experimental design between datasets such as sex or age of the model organism used. In the present study, NASA GeneLab-hosted RNAseq datasets from rodent liver tissues were used to evaluate several statistical methods to correct for this unwanted variation through two approaches, reference-based and standard. The following correction algorithms were applied with (reference-based) and/or without (standard) considering Universal Mouse RNA Reference samples: ComBat and ComBat_seq from the SVA package, median polish, empirical Bayes, and ANOVA-based algorithms from the MBatch package, and negative binomial regression normalization in the DESeq2 package. For each approach, after the correction algorithm was applied, differential gene expression (DGE) analysis of flight and ground control samples was performed with the combined data. The robustness of each tool was evaluated using BatchQC, to determine statistical differences between datasets before and after correction, Principal Component Analysis, to evaluate global gene expression in samples before and after correction, and by comparing DGE analysis of individual datasets and combined datasets before and after correction. The results showed that the reference-based approach introduced several additional (and likely artificial) DEGs when compared with the standard approach. Thus, the most robust standard correction will be implemented in the GeneLab Visualization 2.0 platform when datasets are combined.

GeneLab, RNA-seq, Batch Correction↗

Robust control with structured perturbations

This semi-annual report describes continued progress on the research. Among several approaches in this area of research, our approach to the parametric uncertainties are being matured everyday. This approach deals with real parameter uncertainties which other techniques such as H (sup infinity) optimal control, micron analysis and synthesis, and l(sub 1) optimal control cannot deal. The primary assumption of this approach is that the mathematical models are well obtained so that the most of system uncertainties can be translated into parameter uncertainties of their linear system representations. These uncertainties may be due to modeling, nonlinearity of the physical system, some time-varying parameters, etc. In this report period of research, we are concentrating on implementing a computer aided analysis and design tool based on new results on parametric robust stability. This implementation will help us to reveal further details in this approach.

Keel, Leehyun↗

Dragonfly Entry and Descent Flight Mechanics Modeling and Analysis for Mission PDR

Dragonfly is a New Frontiers Program mission led by Johns Hopkins Applied Physics Laboratory (APL) which will deliver a rotorcraft lander to Saturn’s moon, Titan [1]. Relative to previous studies presented, Dragonfly recently passed its mission Preliminary Design Review (PDR) [2]. This study presents the updated design and analysis performed for the Dragonfly mission PDR. The entry vehicle analysis includes the phases of entry and descent prior to cruise stage separation until lander separation. These results discuss the robustness of the overall entry sequence as assessed through a Monte Carlo uncertainty analysis as well as sensitivity analysis.

Modeling↗

Evaluation of Correction Methods for NASA GeneLab Transcriptomic Datasets

Conducting space biology experiments aboard the International Space Station, particularly those utilizing complex model organisms like mice, is expensive and difficult due to limited crew availability, hardware, and space. As a result, sample numbers from these studies are low, reducing the statistical power of any one experiment. Aggregating spaceflight datasets serves as a method to increase sample numbers, allowing for novel insights through bioinformatic analysis of ‘omics data from merged datasets. However, aggregating datasets can introduce unwanted variation including 1) differences in sample handling, processing, and sequencing platforms between datasets (technical variation) as well as 2) differences in experimental design between datasets. In the present study, NASA GeneLab-hosted RNAseq datasets from mouse liver tissues were used to evaluate several statistical methods to correct for this unwanted variation through two approaches, reference-based and standard. The following correction algorithms were applied with (reference-based) and/or without (standard) considering Universal Mouse RNA Reference samples: ComBat and ComBat_seq from the SVA package, median polish, empirical Bayes, and ANOVA-based algorithms from the MBatch package, and negative binomial regression normalization in the DESeq2 package. For each approach, after the correction algorithm was applied, differential gene expression (DGE) analysis of flight and ground control samples was performed with the combined data. The robustness of each tool was evaluated using BatchQC to determine statistical differences between datasets before and after correction, Principal Component Analysis to evaluate global gene expression in samples before and after correction, and by comparing DGE analysis of individual datasets and combined datasets before and after correction. The results showed that the reference-based approach introduced several additional (and likely artificial) DEGs when compared with the respective standard approach. Of the methods tested, standard ComBat and DESeq2 were identified as the most robust correction methods for combining spaceflight mouse liver RNAseq datasets hosted on GeneLab.

GeneLab↗

Cost-Effectiveness Analysis of Preoperative Versus Postoperative Radiation Therapy in Extremity Soft Tissue Sarcoma

Purpose: Surgery combined with radiation therapy (RT) is the cornerstone of multidisciplinary management of extremity soft tissue sarcoma (STS). Although RT can be given in either the preoperative or the postoperative setting with similar local recurrence and survival outcomes, the side effect profiles, costs, and long-term functional outcomes are different. The aim of this study was to use decision analysis to determine optimal sequencing of RT with surgery in patients with extremity STS. Methods and Materials: A cost-effectiveness analysis was conducted using a state transition Markov model, with quality-adjusted life years (QALYs) as the primary outcome. A time horizon of 5 years, a cycle length of 3 months, and a willingness-to-pay threshold of $50,000/QALY was used. One-way deterministic sensitivity analyses were performed to determine the thresholds at which each strategy would be preferred. The robustness of the model was assessed by probabilistic sensitivity analysis. Results: Preoperative RT is a more cost-effective strategy ($26,633/3.00 QALYs) than postoperative RT ($28,028/2.86 QALYs) in our base case scenario. Preoperative RT is the superior strategy with either 3-dimensional conformal RT or intensity-modulated RT. One-way sensitivity analyses identified the relative risk of chronic adverse events as having the greatest influence on the preferred timing of RT. The likelihood of preoperative RT being the preferred strategy was 82% on probabilistic sensitivity analysis. Conclusions: Preoperative RT is more cost effective than postoperative RT in the management of resectable extremity STS, primarily because of the higher incidence of chronic adverse events with RT in the postoperative setting.

61 RADIATION PROTECTION AND DOSIMETRY↗

Multilevel probabilistic approach to evaluate manufacturing defect in composite aircraft structures

In this work it is developed a reliable approach and its feasibility to the design and analysis of a composite structures. The metric is compared the robustness and reliability designs versus the traditional design, to demonstrate the gain that can be achieved with a probabilistic approach. The use of the stochastic approach of the uncertain parameteters in combination with the multi-scale levels analysis is the main objective of this paper. The work is dedicated to analyze the uncertainties in the design, tests, manufacturing process, and key gates such as materials characteristic.

36 MATERIALS SCIENCE↗

Combining RNA-SEQ Datasets from NASA GENELAB: An Evaluation of Correction Methods

Background: Conducting space biology experiments aboard the International Space Station, particularly those utilizing complex model organisms like mice, is expensive and difficult due to limited crew availability, hardware, and space. As a result, sample numbers from these studies are low, reducing the statistical power of any one experiment. Aggregating spaceflight datasets serves as a method to increase sample numbers, allowing for novel insights through bioinformatic analysis of ‘omics data from merged datasets. However, aggregating datasets can introduce unwanted variation including 1) differences in sample handling, processing, and sequencing platforms between datasets (technical variation) as well as 2) differences in experimental design between datasets. Methods: In the present study, NASA GeneLab-hosted RNAseq datasets from mouse liver tissues were used to evaluate several statistical methods to correct for this unwanted variation through two approaches, reference-based and standard. The following correction algorithms were applied with (reference-based) and/or without (standard) considering Universal Mouse RNA Reference samples: ComBat and ComBat_seq from the SVA package, the median polish, empirical Bayes, and ANOVA-based algorithms from the MBatch package, and negative binomial regression normalization in the DESeq2 package. For each approach, after the correction algorithm was applied, differential gene expression (DGE) analysis of flight and ground control samples was performed with the combined data. The robustness of each tool was evaluated using BatchQC to determine statistical differences between datasets before and after correction, Principal Component Analysis to evaluate global gene expression in samples before and after correction, and by comparing DGE analysis of individual datasets and combined datasets before and after correction. Results: The results showed that the reference-based approach introduced several additional (and likely artificial) differentially expressed genes when compared with the respective standard approach. Conclusions: Of the methods tested, standard ComBat_seq and DESeq2 were identified as the most robust correction methods for combining spaceflight mouse liver RNAseq datasets hosted on GeneLab.

Finsam Samson↗

Testing T2K’s Bayesian constraints with priors in alternate parameterisations

Bayesian analysis results require a choice of prior distribution. In long-baseline neutrino oscillation physics, the usual parameterisation of the mixing matrix induces a prior that privileges certain neutrino mass and flavour state symmetries. Here we study the effect of privileging alternate symmetries on the results of the T2K experiment. We find that constraints on the level of CP violation (as given by the Jarlskog invariant) are robust under the choices of prior considered in the analysis. On the other hand, the degree of octant preference for the atmospheric angle depends on which symmetry has been privileged.

Bayesian Inference↗

Comparison of chamber beam geometry robustness to mispointing, imbalance and target offset for direct-drive laser fusion facilities

This study focuses on the optimization of beam chamber geometry designs for future direct-drive laser facilities. It provides a review of leading target chamber geometries, with a particular emphasis on random errors. Through comprehensive solid-sphere illuminations and analysis, we identify an optimized beam geometry design, highlighting its robustness and performance under realistic experimental conditions. Three major sources of random errors are evaluated, closely linked to experimental evaluations at OMEGA. The findings underscore the importance of optimizing the irradiation system alongside beam pattern considerations to enhance the efficiency and reliability of inertial confinement fusion experiments. We conclude that for a desired illumination uniformity of 1% in the presence of system errors, the split icosahedron design is the most robust. However, for a 0.3% uniformity goal, the charged-particle, icosahedron, and t-sphere methods exhibit similar performance.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

NASA Tech Briefs, September 2007

Topics covered include; Rapid Fabrication of Carbide Matrix/Carbon Fiber Composites; Coating Thermoelectric Devices To Suppress Sublimation; Ultrahigh-Temperature Ceramics; Improved C/SiC Ceramic Composites Made Using PIP; Coating Carbon Fibers With Platinum; Two-Band, Low-Loss Microwave Window; MCM Polarimetric Radiometers for Planar Arrays; Aperture-Coupled Thin-Membrane L-Band Antenna; WGM-Based Photonic Local Oscillators and Modulators; Focal-Plane Arrays of Quantum-Dot Infrared Photodetectors; Laser Range and Bearing Finder With No Moving Parts; Microrectenna: A Terahertz Antenna and Rectifier on a Chip; Miniature L-Band Radar Transceiver; Robotic Vision-Based Localization in an Urban Environment; Programs for Testing an SSME-Monitoring System; Cathodoluminescent Source of Intense White Light; Displaying and Analyzing Antenna Radiation Patterns; Payload Operations Support Team Tools; Space-Shuttle Emulator Software; Soft Real-Time PID Control on a VME Computer; Analyzing Radio-Frequency Coverage for the ISS; Nanorod-Based Fast-Response Pressure-Sensitive Paints; Capacitors Would Help Protect Against Hypervelocity Impacts; Diaphragm Pump With Resonant Piezoelectric Drive; Improved Quick-Release Pin Mechanism; Designing Rolling-Element Bearings; Reverse-Tangent Injection in a Centrifugal Compressor; Inertial Measurements for Aero-assisted Navigation (IMAN); Analysis of Complex Valve and Feed Systems; Improved Path Planning Onboard the Mars Exploration Rovers; Robust, Flexible Motion Control for the Mars Explorer Rovers; Solar Sail Spaceflight Simulation; Fluorine-Based DRIE of Fused Silica; Mechanical Alloying for Making Thermoelectric Compounds; Process for High-Rate Fabrication of Alumina Nanotemplates; Electroform/Plasma-Spray Laminates for X-Ray Optics; An Automated Flying-Insect Detection System; Calligraphic Poling of Ferroelectric Material; Blackbody Cavity for Calibrations at 200 to 273 K; KML Super Overlay to WMS Translator; High-Performance Tiled WMS and KML Web Server; Modeling of Radiative Transfer in Protostellar Disks; Composite Pulse Tube; Photometric Calibration of Consumer Video Cameras; Criterion for Identifying Vortices in High- Pressure Flows; Amplified Thermionic Cooling Using Arrays of Nanowires; Delamination-Indicating Thermal Barrier Coatings; Preventing Raman Lasing in High-Q WGM Resonators; Procedures for Tuning a Multiresonator Photonic Filter; Robust Mapping of Incoherent Fiber-Optic Bundles; Extended-Range Ultrarefractive 1D Photonic Crystal Prisms; Rapid Analysis of Mass Distribution of Radiation Shielding; Modeling Magnetic Properties in EZTB; Deep Space Network Antenna Logic Controller; Modeling Carbon and Hydrocarbon Molecular Structures in EZTB; BigView Image Viewing on Tiled Displays; and Imaging Sensor Flight and Test Equipment Software.

Source record↗

F-15B QuietSpike(TradeMark) Aeroservoelastic Flight Test Data Analysis

System identification or mathematical modelling is utilised in the aerospace community for the development of simulation models for robust control law design. These models are often described as linear, time-invariant processes and assumed to be uniform throughout the flight envelope. Nevertheless, it is well known that the underlying process is inherently nonlinear. The reason for utilising a linear approach has been due to the lack of a proper set of tools for the identification of nonlinear systems. Over the past several decades the controls and biomedical communities have made great advances in developing tools for the identification of nonlinear systems. These approaches are robust and readily applicable to aerospace systems. In this paper, we show the application of one such nonlinear system identification technique, structure detection, for the analysis of F-15B QuietSpike(TradeMark) aeroservoelastic flight test data. Structure detection is concerned with the selection of a subset of candidate terms that best describe the observed output. This is a necessary procedure to compute an efficient system description which may afford greater insight into the functionality of the system or a simpler controller design. Structure computation as a tool for black-box modelling may be of critical importance for the development of robust, parsimonious models for the flight-test community. Moreover, this approach may lead to efficient strategies for rapid envelope expansion which may save significant development time and costs. The objectives of this study are to demonstrate via analysis of F-15B QuietSpike(TradeMark) aeroservoelastic flight test data for several flight conditions (Mach number) that (i) linear models are inefficient for modelling aeroservoelastic data, (ii) nonlinear identification provides a parsimonious model description whilst providing a high percent fit for cross-validated data and (iii) the model structure and parameters vary as the flight condition is altered.

Kukreja, Sunil L.↗

A Polymer-Oriented Self-Assembly Strategy toward Mesoporous Metal Oxides with Ultrahigh Surface Areas

Mesoporous metal oxides (MMOs) have attracted comprehensive attention in many fields, including energy storage, catalysis, and separation. Current synthesis of MMOs mainly involve use of surfactants as templates to generate mesopores and organic reagents as solvents to hinder hydrolysis and condensation of inorganic precursors, which is adverse to adjusting the interactions between surfactants and inorganic precursors. The resulting products have uncontrollable pore structure, crystallinity, and relatively lower surface areas. Here, a facile and general polymer-oriented self-assembly strategy to synthesize a series of MMOs (e.g., TiO 2 , ZrO 2 , NbO 5 , Al 2 O 3 , Ta 2 O 5 , HfO 2 , and SnO 2 ) by using cationic polymers as porogens and metal alkoxides as metal oxide precursors in a robust aqueous synthesis system are reported. Nitrogen adsorption analysis and transmission electron microscopy confirm that the obtained MMOs have ultrahigh specific surface areas and large pore volumes (i.e., 733 m 2 g –1 and 0.485 cm 3 g –1 for mesoporous TiO 2 ). Moreover, the structural parameters (surface area, pore size, and pore volume) and crystallinity can be readily controlled by tuning the interactions between cationic polymers and precursors. The as-synthesized crystalline mesoporous TiO 2 exhibits promising performance in photocatalytic water splitting of hydrogen production and a high hydrogen production rate of 3.68 mol h –1 g –1 .

36 MATERIALS SCIENCE↗

Changes in ENSO amplitude under climate warming and cooling

The response of ENSO amplitude to climate warming and cooling is investigated using the Community Earth System Model (CESM), in which the warming and cooling scenarios are designed by adding heat fluxes of equal amplitude but opposite sign onto the ocean surface, respectively. Results show that the warming induces an increase of the ENSO amplitude but the cooling gives rise to a decrease of the ENSO amplitude, and these changes are robust in statistics. A mixed layer heat budget analysis finds that the increasing (decreasing) SST tendency under climate warming (cooling) is mainly due to an enhancement (weakening) of dynamical feedback processes over the equatorial Pacific, including zonal advective (ZA) feedback, meridional advective (MA) feedback, thermocline (TH) feedback, and Ekman (EK) feedback. As the climate warms, a wind anomaly of the same magnitude across the equatorial Pacific can induce a stronger zonal current change in the east (i.e., a stronger ZA feedback), which in turn produces a greater weakening of upwelling (i.e., a stronger EK feedback) and thus a larger thermocline change (i.e., a stronger TH feedback). In response to the climate warming, in addition, a slowdown of the subtropical cells (STCs) will result in a narrower meridional width of SST anomaly around the equator and thus a stronger MA feedback. And vice versa for the cooling case. Bjerknes linear stability (BJ) index is also evaluated for the linear stability of ENSO, with significantly larger (smaller) BJ index found for the warming (cooling) case.

ENSO amplitude, Climate Warming, Climate cooling, ↗

Heterogeneity or illusion? Track the carbon Kuznets curve of global residential building operations

Residential buildings, the “last mile” sector in the global decarbonization, have become the most significant uncertain factor hindering carbon neutrality with increasing household energy demand. To track the operational carbon in buildings, this study investigates the carbon Kuznets curve (CKC) and the corresponding decoupling status of residential building operations at four emission scales by using the data of 30 countries from 2000 to 2019. The results show that (1) the CKC model can fit more than half of the samples. Most curves have an inverted U-shape, with 76% of emission per household and 82% of total emissions. (2) In the presence of the CKC, over four-fifths of global residential buildings peak regardless of any emission scale. The analysis denotes that the carbon emissions of developed countries reach their peaks earlier. In the total emissions, the samples’ peaking proportion is 20% and 25% with income per capita < 20,000 United States dollars (USD) and 20,000–40,000 USD, respectively. (3) The Tapio decoupling analysis and the threshold regression effectively verify the robustness and the heterogeneity of CKCs, respectively. Strong decoupling effects of CKCs in most countries are demonstrated at the scales of emission per floor space and the total emissions, and the heterogeneity proves the classic inverted U-shaped relationship between economy and emissions doesn’t exist in all emitters. Overall, this study tracks the historical carbon emission trajectories of residential building operations at a global scale, providing reference for different economies to simulate the dynamic of building carbon emissions along with the economic booming.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Scalable algorithms for three-field mixed finite element coupled poromechanics

We introduce a class of block preconditioners for accelerating the iterative solution of coupled poromechanics equations based on a three-field formulation. The use of a displacement/velocity/pressure mixed finite-element method combined with a first order backward difference formula for the approximation of time derivatives produces a sequence of linear systems with a 3 x 3 unsymmetric and indefinite block matrix. The preconditioners are obtained by approximating the two-level Schur complement with the aid of physically-based arguments that can be also generalized in a purely algebraic approach. A theoretical and experimental analysis is presented that provides evidence of the robustness, efficiency and scalability of the proposed algorithm. In conclusion, the performance is also assessed for a real-world challenging consolidation experiment of a shallow formation.

42 ENGINEERING↗

Proteomic Characterization of Damaged Single Hairs Recovered after an Explosion for Protein-Based Human Identification

Evidence recovery is challenging where an explosion has occurred. Though hair evidence may be sufficiently robust to be recovered at the site, forensic analysis underutilizes the matrix by relying on morphological analysis. Where DNA is compromised, particularly in hair, protein-based human identification presents a promising alternative. Detection of amino acid polymorphisms in hair proteins as genetically variant peptides (GVPs) permits the inference of individualizing single nucleotide polymorphisms for identification. However, an explosive blast may damage hair proteins and compromise GVP identification. This work evaluates effects of an explosive blast on the hair proteome and GVP identification, investigates microscopy as a predictor of proteome profiling success in recovered hairs to improve analysis throughput, and quantifies discriminative power in damaged hairs. The proteomics dataset has been deposited into the ProteomeXchange Consortium (PXD017427). With the exception of degradation in keratins K75, K80, K40, and keratin-associated protein KAP10-11 as markers of hair cuticular damage, corroborated by scanning electron microscopic analysis, minimal hair proteome degradation following explosion allowed successful proteome profiling of single hairs regardless of morphological damage. Finally, GVP identification remained independent of explosion conditions, permitting similar discriminative power between exploded and undamaged hairs. These findings lend greater confidence to GVP analysis in one-inch hairs for forensic identification and provide information about hair protein localization.

59 BASIC BIOLOGICAL SCIENCES↗

Applying Magnetic Curvature to MMS Data to Identify Thin Current Sheets Relative to Tail Reconnection

Thin current sheets (TCSs) have been postulated to be a necessary precondition for reconnection onset. Magnetic reconnection X-lines in the magnetotail have been observed to be more common duskward of midnight. We take advantage of the MMS tetrahedral formation during the 2017–2020 MMS tail seasons to calculate the thickness of the cross-tail neutral sheet relative to ion gyroradius. While a similar technique was applied to Cluster data, current sheet thickness over a broader range of radial distances has not been robustly explored before this study. We compare our analysis to recent theories regarding mechanisms of tail current sheet thinning and to recent simulations. We find MMS spent more than twice as long in ion-scale TCSs in the pre-midnight sector than post-midnight, despite nearly even plasma sheet dwell time. The dawn-dusk asymmetry in the distribution of Ion Diffusion Regions, as previously reported in relation to regions of TCSs, is also analyzed.

79 ASTRONOMY AND ASTROPHYSICS↗

Carbon source–driven metabolic and regulatory remodeling defines phenomic states in Lipomyces starkeyi

Lipomyces is a genus of oleaginous yeasts with potential for contributing to reliable biomanufacturing supply chains. However, progress in advanced strain designs and engineering efforts are still constrained by a lack of understanding of the underlying molecular drivers of Lipomyces phenotypes. To address this gap, we collected a suite of multi-omic data to dissect how carbon source availability reshapes the metabolic network, lipid allocation, and regulatory architecture of Lipomyces starkeyi. We observed that glucose promotes biosynthetic and proliferative processes supported by abundant energy and carbon intermediates, xylose enhances redox-balancing mechanisms centered on the pentose phosphate pathway, and glycerol activates respiratory metabolism, ß-oxidation, and the glyoxylate cycle. Lipid species distributions remained consistent in both nitrogen replete and depleted conditions across the carbon sources, indicating robust production mechanisms. Regulatory protein identification and network analysis revealed glycerol-driven respiratory growth favors regulatory programs integrating stress tolerance, redox balance, and lipid-associated metabolism, whereas xylose growth activates compensatory transcriptional responses aimed at maintaining mitochondrial function. Nitrogen limitation modulates the strength of these responses but does not fundamentally alter their direction, reinforcing carbon source as the dominant driver of regulatory architecture. Taken together, this data enhances the understanding of Lipomyces molecular rearrangements and provides a foundation for further development of predictive phenotypic tools in this genus.

Biotechnology↗