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DOE OSTI2025

Plasma GFAP for populational enrichment of clinical trials in preclinical Alzheimer's disease

Abstract INTRODUCTION Cognitively unimpaired (CU) amyloid beta (Aβ)+ individuals with elevated plasma glial fibrillary acidic protein (GFAP) have an increased risk of Alzheimer's disease (AD)‐related progression. We tested the utility of plasma GFAP for population enrichment CU populations in clinical trials. METHODS We estimated longitudinal progression, effect size, and costs of hypothetical clinical trials designed to test an estimated 25% drug effect on reducing tau positron emission tomography (PET) accumulation in the medial temporal lobe (MTL) and temporal neocortical region (NEO‐T). RESULTS CU GFAP+/Aβ+ individuals present an increased annual rate of change and effect size in tau PET MTL and tau PET NEO‐T compared to the other groups. An enrichment strategy selecting CU GFAP+/Aβ+ individuals would require a smaller sample size (≈ 57% reduction) and fewer Aβ PET scans (≈ 74% reduction) than trials enriched with Aβ PET alone, reducing total clinical trial costs by up to 64%. DISCUSSION Our results suggest that clinical trials focusing on preclinical AD recruiting Aβ+ individuals with elevated GFAP levels would improve cost effectiveness. Highlights Cognitively unimpaired (CU) glial fibrillary acidic protein (GFAP)+/amyloid beta (Aβ)+ shows increased changes in tau positron emission tomography (PET) . CU GFAP+/Aβ+ enriched clinical trials require a reduced sample size compared to Aβ+ only. CU GFAP+/Aβ+ enrichment reduces Aβ PET scans required and costs. CU GFAP+/Aβ+ enrichment allows the selection of individuals at early stages of the Alzheimer's disease continuum.

Neurosciences & Neurology↗

NASA NTRS2021

Thermoelectric System Economics - The Apex: New Paradigms in Manufacturing and Interface Performance Relationships Driving System Cost Optimizations

Thermoelectric energy recovery systems require cost-optimized designs with high thermal and thermoelectric (TE) performance to surmount common commercialization barriers controlling the acceptance of thermoelectric generator (TEG) systems. Recent work has addressed this requirement with new analytic tools and paradigms that allow integrated TEG cost-performance analysis and optimization. New work herein has identified the existence of optimized TE element design (i.e., TE element length) for minimizing TEG cost and provides design guidelines associated with critical thermal and electrical contact resistance effects and TE manufacturing sensitivities. Once optimum hot-side heat flux criteria are satisfied, this work highlights the tradeoffs between interface resistance effects and manufacturing cost effects in determining optimum-cost TE element lengths, and then quantifies the increase in optimum-cost TE lengths as manufacturing costs become more sensitive to TE element lengths. Optimized TE element design criteria and key non-dimensional design parameters (i.e., [𝐶′′′LTE/𝐶′′], [TE/con], [con/(TE,aveLTE)]) driving the design are presented and explained showing the interdependencies between manufacturing cost parameters and thermal and electrical interface impacts on integrated TE cost-performance analysis and design. Comprehensive TEG system cost-performance relationships clearly demonstrate the two parameters that most greatly impact the TEG system cost are heat exchanger costs ($/(W/K)) and TE hot side heat flux. Reducing heat exhanger cost from $1/(W/K) to $0.5/(W/K) can decrease TEG system cost by $2/W to $4/W depending on TE hot side heat fluxes from 4-10 W/cm2. The impact of TE hot side heat flux on TEG system cost is larger; reducing TE system cost by factors of 2-4 as TE hot side heat flux increases from 4 W/cm2 to high levels around 18 W/cm2. The levels of thermal contact resistance and electrical contact resistance required to even approach the critical TEG system cost level of $1/W are characterized by con = 1.0 x 10-10 -m2 and r = 0.1, respectively. This not only lowers TEG costs, but it also makes the TEG system costs less sensitive to TE manufacturing dependences on TE element length. New design paradigms and relationships create holistic, integrated TE performance-cost models that enhance understanding of crucial interrelationships between component costs, TE design parameters and material properties, heat exchanger design parameters, interfacial heat flux, and now thermal and electrical interface effects in minimizing TEG system costs.

Hendricks, Terry J.↗

NASA NTRS1978

LSSA large area silicon sheet task continuous Czochralski process development

A Czochralski crystal growing furnace was converted to a continuous growth facility by installation of a premelter to provide molten silicon flow into the primary crucible. The basic furnace is operational and several trial crystals were grown in the batch mode. Numerous premelter configurations were tested both in laboratory-scale equipment as well as in the actual furnace. The best arrangement tested to date is a vertical, cylindrical graphite heater containing small fused silicon test tube liner in which the incoming silicon is melted and flows into the primary crucible. Economic modeling of the continuous Czochralski process indicates that for 10 cm diameter crystal, 100 kg furnace runs of four or five crystals each are near-optimal. Costs tend to asymptote at the 100 kg level so little additional cost improvement occurs at larger runs. For these conditions, crystal cost in equivalent wafer area of around $20/sq m exclusive of polysilicon and slicing was obtained.

Rea, S. N.↗

NASA NTRS1977

The influence of various test plans on mission reliability

Methods have been developed for the evaluation of cost effective vibroacoustic test plans for Shuttle Spacelab payloads. The shock and vibration environments of components have been statistically represented, and statistical decision theory has been used to evaluate the cost effectiveness of five basic test plans with structural test options for two of the plans. Component, subassembly, and payload testing have been performed for each plan along with calculations of optimum test levels and expected costs. The tests have been ranked according to both minimizing expected project costs and vibroacoustic reliability. It was found that optimum costs may vary up to $6 million with the lowest plan eliminating component testing and maintaining flight vibration reliability via subassembly tests at high acoustic levels.

Stahle, C. V.↗

NASA NTRS2019

The Value Proposition of Multi-Megawatt Electric Power/Propulsion for the Human Exploration of Mars

NASA and other space agencies have been offering stakeholders an architecture for the human exploration of Mars that has remained essentially unchanged since the 1960's. The mission duration and launch mass are the two first order figures of merit that drive the total cost of such an architecture. The options studied to date center on the "conjunction class" or "Long Stay" mission, in which surface infrastructure elements are sent ahead on uncrewed, slow trajectories requiring a minimum amount of propellant, and the crewed elements are sent at the synotic cycle's shortest trajectory, stay on Mars until the next close alignment, and then return to Earth. Total crewed mission durations for these architectures range from 900 to 1100 days, with variations driven primarily by trades between the amount of propellant launched and the effective specific mass of the propulsion technology assumed (e.g., chemical, nuclear thermal, solar electric, nuclear electric). Mars transit propulsion systems assumed in mission architectures studied to date have all resulted in architectural figures of merit that drive the cost to a level of "too much." However, nuclear electric propulsion (NEP) technology offers a "knob" that might be turned to enable a radically different Mars architecture, whose launch mass and mission duration may enable a value proposition more palatable to mission stakeholders. Mars architectures studied to date have assumed an NEP system providing 2.5 MWe at a specific mass of no less than 20 kg/kWe. This has often been seen as obtainable with a moderately high temperature fission reactor. An NEP system providing 15 MWe at specific mass of ~1 kg/kWe, though, could enable a short stay (30 days on surface) Mars mission, requiring only two or three SLS-class launch vehicles and a total mission duration of under one calendar year. However, turning this NEP "knob" would require a high risk development program driving innovation on the order of that delivered by the Manhattan Project, but for a fraction of the cost. Any technology option that might offer such a capability at such a development cost now stands at a low Technology Readiness Level (TRL) 3, would be based on a nuclear energy source (likely fusion), and would require an extremely high risk (and rapid) development effort. The aggressive, parallel path project management paradigm exemplified by the original Manhattan Project might have the best chance of success. An energy source developed in this manner may also have a major impact on the terrestrial power industry.

power↗

NASA NTRS2012

Update on Multi-Variable Parametric Cost Models for Ground and Space Telescopes

Parametric cost models can be used by designers and project managers to perform relative cost comparisons between major architectural cost drivers and allow high-level design trades; enable cost-benefit analysis for technology development investment; and, provide a basis for estimating total project cost between related concepts. This paper reports on recent revisions and improvements to our ground telescope cost model and refinements of our understanding of space telescope cost models. One interesting observation is that while space telescopes are 50X to 100X more expensive than ground telescopes, their respective scaling relationships are similar. Another interesting speculation is that the role of technology development may be different between ground and space telescopes. For ground telescopes, the data indicates that technology development tends to reduce cost by approximately 50% every 20 years. But for space telescopes, there appears to be no such cost reduction because we do not tend to re-fly similar systems. Thus, instead of reducing cost, 20 years of technology development may be required to enable a doubling of space telescope capability. Other findings include: mass should not be used to estimate cost; spacecraft and science instrument costs account for approximately 50% of total mission cost; and, integration and testing accounts for only about 10% of total mission cost.

Stahl, H. Philip↗

NASA NTRS2016

Towards a Multi-Variable Parametric Cost Model for Ground and Space Telescopes

Parametric cost models can be used by designers and project managers to perform relative cost comparisons between major architectural cost drivers and allow high-level design trades; enable cost-benefit analysis for technology development investment; and, provide a basis for estimating total project cost between related concepts. This paper hypothesizes a single model, based on published models and engineering intuition, for both ground and space telescopes: OTA Cost approximately (X) D(exp (1.75 +/- 0.05)) lambda(exp(-0.5 +/- 0.25) T(exp -0.25) e (exp (-0.04)Y). Specific findings include: space telescopes cost 50X to 100X more ground telescopes; diameter is the most important CER; cost is reduced by approximately 50% every 20 years (presumably because of technology advance and process improvements); and, for space telescopes, cost associated with wavelength performance is balanced by cost associated with operating temperature. Finally, duplication only reduces cost for the manufacture of identical systems (i.e. multiple aperture sparse arrays or interferometers). And, while duplication does reduce the cost of manufacturing the mirrors of segmented primary mirror, this cost savings does not appear to manifest itself in the final primary mirror assembly (presumably because the structure for a segmented mirror is more complicated than for a monolithic mirror).

Space Mirror Technology↗

NASA NTRS2019

Optical Telescope Assembly Cost Estimating Model

Stahl, H Philip↗

NASA NTRS2020

Parametric Cost Model for Ground and Space Telescopes

Parametric cost models can be used by designers and project managers to compare cost between major architectural cost drivers and allow high-level design trades; enable cost-benefit analysis for technology development investment; and, provide a basis for estimating total project cost between related concepts. The NASA Marshall Space Flight Center has developed a 5-parameter first-article optical telescope assembly cost model OTA$ (FY17) = $20M x 30(S/G)x D(1.7)x λ(-0.5)x T(-0.25)x e(-0.028) (Y-1960)Where S/G = 1 for space and 0 for ground telescopes, D = diameter, λ= diffraction limited wavelength, T = operating temperature and Y = year of development. The model explains 92% (Adjusted R2) of the cost variation in a database of 47 total ground and space telescope assemblies (OTA). The MSFC model estimates the most likely cost for only the OTA. Where an OTA is defined as the subsystem which collects electromagnetic radiation and focuses it (focal) or concentrates it (afocal) into the science instruments. An OTA consists of the primary mirror, secondary mirror, auxiliary optics and support structure (such as optical bench or truss structure, primary support structure, secondary support structure or spiders, straylight baffles, mechanisms for adjusting the optical components, electronics or power systems for operating these mechanisms, etc.). Finally, duplication only reduces cost for the manufacture of identical systems(i.e. multiple aperture sparse arrays or interferometers). And, while duplication does reduce the cost of manufacturing the mirrors of segmented primary mirror, this cost savings does not appear to manifest itself in the final primary mirror assembly(presumably because the structure for a segmented mirror is more complicated than for a monolithic mirror).

Space Telescope Cost Model, Parametric Cost Model↗

NASA NTRS2002

Internet Data Delivery for Future Space Missions

Ongoing work at National Aeronautics and Space Administration Goddard Space Flight Center (NASA/GSFC), seeks to apply standard Internet applications and protocols to meet the technology challenge of future satellite missions. Internet protocols and technologies are under study as a future means to provide seamless dynamic communication among heterogeneous instruments, spacecraft, ground stations, constellations of spacecraft, and science investigators. The primary objective is to design and demonstrate in the laboratory the automated end-to-end transport of files in a simulated dynamic space environment using off-the-shelf, low-cost, commodity-level standard applications and protocols. The demonstrated functions and capabilities will become increasingly significant in the years to come as both earth and space science missions fly more sensors and as the need increases for more network-oriented mission operations. Another element of increasing significance will be the increased cost effectiveness of designing, building, integrating, and operating instruments and spacecraft that will come to the fore as more missions take up the approach of using commodity-level standard communications technologies. This paper describes how an IP (Internet Protocol)-based communication architecture can support all existing operations concepts and how it will enable some new and complex communication and science concepts. The authors identify specific end-to-end data flows from the instruments to the control centers and scientists, and then describe how each data flow can be supported using standard Internet protocols and applications. The scenarios include normal data downlink and command uplink as well as recovery scenarios for both onboard and ground failures. The scenarios are based on an Earth orbiting spacecraft with downlink data rates from 300 Kbps to 4 Mbps. Included examples are based on designs currently being investigated for potential use by the Global Precipitation Measurement (GPM) mission.

Rash, James↗

NASA NTRS2002

Software for Estimating Costs of Testing Rocket Engines

A high-level parametric mathematical model for estimating the costs of testing rocket engines and components at Stennis Space Center has been implemented as a Microsoft Excel program that generates multiple spreadsheets. The model and the program are both denoted, simply, the Cost Estimating Model (CEM). The inputs to the CEM are the parameters that describe particular tests, including test types (component or engine test), numbers and duration of tests, thrust levels, and other parameters. The CEM estimates anticipated total project costs for a specific test. Estimates are broken down into testing categories based on a work-breakdown structure and a cost-element structure. A notable historical assumption incorporated into the CEM is that total labor times depend mainly on thrust levels. As a result of a recent modification of the CEM to increase the accuracy of predicted labor times, the dependence of labor time on thrust level is now embodied in third- and fourth-order polynomials.

Hines, Merion M.↗

NASA NTRS2004

Software for Estimating Costs of Testing Rocket Engines

Hines, Merlon M.↗

NASA NTRS2003

Software for Estimating Costs of Testing Rocket Engines

Hines, Merlon M.↗

DOE OSTI2024

Modeling the Cost of CO2 Saline Storage on a Regional and National Level

This poster presents the results of using the FECM/NETL CO2 Saline Storage Cost Model (CO2_S_COM) to evaluate the cost of saline storage in potential storage formations in the lower 48 U.S. states. Costs were calculated for 314 saline storage formations in the CO2_S_COM geologic property database. These results were used to generate national and regional cost-supply curves. In addition, a sensitivity analysis was performed that quantified how modifying several input variables in CO2_S_COM affected the costs. Poster presented (virtual) at the 2024 AGU Conference, December 9-13, 2024, Washington, D.C.

Morgan, David [NETL]↗

NASA NTRS1975

System trades for the SEOS telescope

The Synchronous Earth Observation Satellite (SEOS) is a geostationary system which provides unique possibilities for earth surveillance. Questions of SEOS applications are considered, taking into account the employment of the Large Earth Survey Telescope. Aspects of performance and costs are examined. The generation of a value function in connection with a quantitative ranking of the applications is discussed along with an analysis performed to determine those parameter values which will maximize mission performance capability at given levels of system cost.

Ritter, M.↗

DOE OSTI2026

Base-Level Optimization of Library Design Facilitates Cost-Effective Scale Up of Antibody Affinity Assays

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Biological and medical sciences↗

NASA NTRS2004

Outbrief - Long Life Rocket Engine Panel

This white paper is an overview of the JANNAF Long Life Rocket Engine (LLRE) Panel results from the last several years of activity. The LLRE Panel has met over the last several years in order to develop an approach for the development of long life rocket engines. Membership for this panel was drawn from a diverse set of the groups currently working on rocket engines (Le. government labs, both large and small companies and university members). The LLRE Panel was formed in order to determine the best way to enable the design of rocket engine systems that have life capability greater than 500 cycles while meeting or exceeding current performance levels (Specific Impulse and Thrust/Weight) with a 1/1,OOO,OOO likelihood of vehicle loss due to rocket system failure. After several meetings and much independent work the panel reached a consensus opinion that the primary issues preventing LLRE are a lack of: physics based life prediction, combined loads prediction, understanding of material microphysics, cost effective system level testing. and the inclusion of fabrication process effects into physics based models. With the expected level of funding devoted to LLRE development, the panel recommended that fundamental research efforts focused on these five areas be emphasized.

Quinn, Jason Eugene↗

DOE OSTI2025

Zigzag flow reactor for weekly thermochemical energy storage

This paper describes theoretical models and experimental performance of a novel Zigzag Flow Reactor (ZFR) for weekly thermochemical energy storage. The ZFR reduces redox-active metal oxide (MO x ) particles at high temperature (up to ~1100 °C) under inert gas sweep. A physical model demonstrates the approach to process equilibrium by minimizing the associated exergy destruction in a finite number of reaction steps, establishing the thermodynamic requirements for a practical reactor. The model results show several cost-relevant parameter tradeoffs, and the tradeoff analysis implies a cost-optimized set of boundary conditions. Numerical models and prototypes show that the ZFR enables significant gas phase homogenization while simultaneously enabling a customizable MO x residence time in the reactor, both key requirements for approaching an equilibrium process. A scaling model demonstrates the simplicity and affordability of sizing the ZFR to grid-scale levels, with fabrication costs at least five times lower than previously proposed scalable reactor concepts. As a result, a laboratory ZFR prototype achieved an energy storage density of ~90 Wh/kg with CaAl 0.2 Mn 0.8 O 3-δ as the MO x , at temperatures of ~850 °C in >10 h of total runtime.

Thermochemical energy storage↗