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At least 271 records · Page 15
All sourcesNASA NTRSDOE OSTI
NASA NTRS1991

High Level Design Proof of a Reliable Computing Platform

An architecture for fault-tolerant computing is formalized and shown to satisfy a key correctness property. The reliable computing platform uses replicated processors and majority voting to achieve fault tolerance. Under the assumption of a majority of processors working in each frame, we show that the replicated system computes the same results as a single processor system not subject to failures. Sufficient conditions are obtained to establish that the replicated system recovers from transient faults within a bounded amount of time. Three different voting schemes are examined and proved to satisfy the bounded recovery time conditions.

DiVito, Ben L.↗
NASA NTRS1999

Cell and molecular biology of simian virus 40: implications for human infections and disease

Simian virus 40 (SV40), a polyomavirus of rhesus macaque origin, was discovered in 1960 as a contaminant of polio vaccines that were distributed to millions of people from 1955 through early 1963. SV40 is a potent DNA tumor virus that induces tumors in rodents and transforms many types of cells in culture, including those of human origin. This virus has been a favored laboratory model for mechanistic studies of molecular processes in eukaryotic cells and of cellular transformation. The viral replication protein, named large T antigen (T-ag), is also the viral oncoprotein. There is a single serotype of SV40, but multiple strains of virus exist that are distinguishable by nucleotide differences in the regulatory region of the viral genome and in the part of the T-ag gene that encodes the protein's carboxyl terminus. Natural infections in monkeys by SV40 are usually benign but may become pathogenic in immunocompromised animals, and multiple tissues can be infected. SV40 can replicate in certain types of simian and human cells. SV40-neutralizing antibodies have been detected in individuals not exposed to contaminated polio vaccines. SV40 DNA has been identified in some normal human tissues, and there are accumulating reports of detection of SV40 DNA and/or T-ag in a variety of human tumors. This review presents aspects of replication and cell transformation by SV40 and considers their implications for human infections and disease pathogenesis by the virus. Critical assessment of virologic and epidemiologic data suggests a probable causative role for SV40 in certain human cancers, but additional studies are necessary to prove etiology.

Review↗
NASA NTRS2003

[Technology Development for X-Ray Reflection for the Constellation-X Reflection Grating Spectrometer (RGS)]

This Grant covers MIT support for the technology development of x-ray reflection gratings for the Constellation-X Reflection Grating Spectrometer (RGS). Since the start of the Grant MIT has extended its previously-developed patterning and super-smooth, blazed grating fabrication technology to ten-times smaller grating periods and ten-times larger blaze angles to demonstrate feasibility and performance in the off-plane grating geometry. In the past year we successfully developed several nanoimprint grating replication methods that achieved very high fidelity replication of master silicon gratings. Grating geometry on the nano and macro scales were faithfully replicated, demonstrating the viability of the process for manufacturing the thousands of gratings required for the RGS. We also successfully developed an improved metrology truss for holding test grating substrates during metrology. The flatness goal of grating substrates is under 500 nm. In the past, grating holders would cause non-repeatable distortion of >> 500 nm to the substrates due to friction and gravity sag. The new holder has a repeatability of under 50 nm which is adequate for the proposed RGS grating substrates.

Schattenburg, Mark L.↗
NASA NTRS1993

B-DNA to Z-DNA structural transitions in the SV40 enhancer: stabilization of Z-DNA in negatively supercoiled DNA minicircles

During replication and transcription, the SV40 control region is subjected to significant levels of DNA unwinding. There are three, alternating purine-pyrimidine tracts within this region that can adopt the Z-DNA conformation in response to negative superhelix density: a single copy of ACACACAT and two copies of ATGCATGC. Since the control region is essential for both efficient transcription and replication, B-DNA to Z-DNA transitions in these vital sequence tracts may have significant biological consequences. We have synthesized DNA minicircles to detect B-DNA to Z-DNA transitions in the SV40 enhancer, and to determine the negative superhelix density required to stabilize the Z-DNA. A variety of DNA sequences, including the entire SV40 enhancer and the two segments of the enhancer with alternating purine-pyrimidine tracts, were incorporated into topologically relaxed minicircles. Negative supercoils were generated, and the resulting topoisomers were resolved by electrophoresis. Using an anti-Z-DNA Fab and an electrophoretic mobility shift assay, Z-DNA was detected in the enhancer-containing minicircles at a superhelix density of -0.05. Fab saturation binding experiments demonstrated that three, independent Z-DNA tracts were stabilized in the supercoiled minicircles. Two other minicircles, each with one of the two alternating purine-pyrimidine tracts, also contained single Z-DNA sites. These results confirm the identities of the Z-DNA-forming sequences within the control region. Moreover, the B-DNA to Z-DNA transitions were detected at superhelix densities observed during normal replication and transcription processes in the SV40 life cycle.

Non-NASA Center↗
NASA NTRS1987

High-resolution CCD imagers using area-array CCD's for sensing spectral components of an optical line image

CCD imagers with a novel replicated-line-imager architecture are abutted to form an extended line sensor. The sensor is preceded by optics having a slit aperture and having an optical beam splitter or astigmatic lens for projecting multiple line images through an optical color-discriminating stripe filter to the CCD imagers. A very high resolution camera suitable for use in a satellite, for example, is thus provided. The replicated-line architecture of the imager comprises an area-array CCD, successive rows of which are illuminated by replications of the same line segment, as transmitted by respective color filter stripes. The charge packets formed by accumulation of photoresponsive charge in the area-array CCD are read out row by row. Each successive row of charge packets is then converted from parallel to serial format in a CCD line register and its amplitude sensed to generate a line of output signal.

Elabd, Hammam↗
NASA NTRS1977

Bubble domain circuit organization

An on-chip bubble domain circuit organization. One or more storage registers are connected to a propagation path whereby data in the form of magnetic bubble domains (bubbles) may be transferred into and out of the storage registers. The propagation path includes a generator for producing the initial bubbles which are expanded into any desired number of new bubbles by a unique multiple output replicator. A unique input decoder is utilized to determine to which storage register the bubbles from the replicator will be directed along the propagation path. Those bubbles not selected may be annihilated. An output decoder utilizing essentially the same decoding scheme as the input decoder, selectively receives bubbles from the storage register. A transfer and replicate switch is utilized between the storage register and output decoder to selectively transfer bubbles to the output decoder. The output decoder may collapse all of the bubbles from certain storage registers so that only the information from the selected storage register reaches the detector. The detectors in turn produce the chip output signal. External control electronics are utilized to control the selective operation of the various devices utilized in the propagation path.

Chen, Thomas T.↗
NASA NTRS2011

Differential Processing of Low and High LET Radiation Induced DNA Damage: Investigation of Switch from ATM to ATR Signaling

The members of the phosphatidylinositol kinase-like kinase family of proteins namely ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) are directly responsible for the maintenance of genomic integrity by mounting DDR through signaling and facilitating the recruitment of repair factors at the sites of DNA damage along with coordinating the deployment of cell cycle checkpoints to permit repair by phosphorylating Checkpoint kinase Chk1, Chk2 and p53. High LET radiation from GCR (Galactic Cosmic Rays) consisting mainly of protons and high energy and charged (HZE) particles from SPE (Solar Particle Event) pose a major health risk for astronauts on their space flight missions. The determination of these risks and the design of potential safeguards require sound knowledge of the biological consequences of lesion induction and the capability of the cells to counter them. We here strive to determine the coordination of ATM and ATR kinases at the break sites directly affecting checkpoint signaling and DNA repair and whether differential processing of breaks induced by low and high LET radiation leads to possible augmentation of swap of these damage sensors at the sites of DNA damage. Exposure of cells to IR triggers rapid autophosphorylation of serine-1981 that causes dimer dissociation and initiates monomer formation of ATM. ATM kinase activity depends on the disruption of the dimer, which allows access and phosphorylation of downstream ATM substrates like Chk2. Evidence suggests that ATM is activated by the alterations in higher-order chromatin structure although direct binding of ATM to DSB ends may be a crucial step in its activation. On the other hand, in case of ATR, RPA (replication protein A)-coated ssDNA (single-stranded DNA) generated as a result of stalled DNA replication or during processing of chromosomal lesions is crucial for the localization of ATR to sites of DNA damage in association with ATR-interacting protein (ATRIP). Although the majority of RPA-coated ssDNA is generally present only during DNA replication, ATR activation in G1 and G2-phase might still require formation of RPA-coated ssDNA, probably initiated by the MRN-CtIP complex and then extended by the Exo1- or BLM-dependent mechanisms at the sites of DSBs. Evidence accumulates that activation of ATM and ATR are oppositely regulated by the length of single stranded overhangs generated at the break sites by processes mentioned above and these stretches of single stranded overhangs hold the clue for ATM to ATR switch at broken DNA ends. We irradiated 82-6hTERT human fibroblast cells with low LET gamma-rays and high LET Fe and Si particles. Preliminary results with cells exposed to 1Gy gamma-rays show that the kinetics of pChk2-pT68 foci formation is comparable to that of gamma-H2AX although they appear to recede quicker. The number and intensity of observed foci reaches a maximum at 30 min and 60 min post IR for Chk2-pT68 and gamma-H2AX foci respectively and all Chk2-pT68 foci colocalize with gamma-H2AX foci. The kinetics of Chk1-pS345 and ATRIP are being determined. Results of Chk2-pT68 foci kinetics was also corroborated by western blot experiments, although phosphorylation was detected as early as 10 min and started receding 30 min post IR with 2Gy of gamma-rays. On the other hand, level of ATR-pS428 reached its maximum between 60 and 120 min and was maintained until the last measured time point of 4 hours post IR as determined by western blotting. Experiments performed with high LET Fe and Si particles will be reported.

Saha, Janapriya↗
NASA NTRS2012

Grazing incidence neutron optics

Neutron optics based on the two-reflection geometries are capable of controlling beams of long wavelength neutrons with low angular divergence. The preferred mirror fabrication technique is a replication process with electroform nickel replication process being preferable. In the preliminary demonstration test an electroform nickel optics gave the neutron current density gain at the focal spot of the mirror at least 8 for neutron wavelengths in the range from 6 to 20 .ANG.. The replication techniques can be also be used to fabricate neutron beam controlling guides.

Gubarev, Mikhail V.↗
NASA NTRS2014

A Magnetron Sputter Deposition System for the Development of Multilayer X-Ray Optics

The proposal objective is to establish the capability to deposit multilayer structures for x-ray, neutron, and EUV optic applications through the development of a magnetron sputtering deposition system. A specific goal of this endeavor is to combine multilayer deposition technology with the replication process in order to enhance the MSFC's position as a world leader in the design of innovative X-ray instrumentation through the development of full shell replicated multilayer optics. The development of multilayer structures is absolutely necessary in order to advance the field of X-ray astronomy by pushing the limit for observing the universe to ever increasing photon energies (i. e. up to 200 keV or higher); well beyond Chandra (approx. 10 keV) and NuStar's (approx. 75 keV) capability. The addition of multilayer technology would significantly enhance the X-ray optics capability at MSFC and allow NASA to maintain its world leadership position in the development, fabrication and design of innovative X-ray instrumentation which would be the first of its kind by combining multilayer technology with the mirror replication process. This marriage of these technologies would allow astronomers to see the universe in a new light by pushing to higher energies that are out of reach with today's instruments.To this aim, a magnetron vacum sputter deposition system for the deposition of novel multilayer thin film X-ray optics is proposed. A significant secondary use of the vacuum deposition system includes the capability to fabricate multilayers for applications in the field of EUV optics for solar physics, neutron optics, and X-ray optics for a broad range of applications including medical imaging.

Broadway, David↗
NASA NTRS2013

Grazing Incidence Neutron Optics

Neutron optics based on the two-reflection geometries are capable of controlling beams of long wavelength neutrons with low angular divergence. The preferred mirror fabrication technique is a replication process with electroform nickel replication process being preferable. In the preliminary demonstration test an electroform nickel optics gave the neutron current density gain at the focal spot of the mirror at least 8 for neutron wavelengths in the range from 6 to 20.ANG.. The replication techniques can be also be used to fabricate neutron beam controlling guides.

Gubarev, Mikhail V.↗
NASA NTRS2015

A Magnetron Sputter Deposition System for the Development of X-Ray Multilayer Optics

The project objective is to establish the capability to deposit multilayer structures for x-ray, neutron, and extreme ultraviolet (EUV) optic applications through the development of a magnetron sputtering deposition system. A specific goal of this endeavor is to combine multilayer deposition technology with the replication process in order to enhance NASA Marshall Space Flight Center's (MSFC's) position as a world leader in the design of innovative x-ray instrumentation through the development of full shell replicated multilayer optics. The development of multilayer structures are absolutely necessary in order to advance the field of x-ray astronomy by pushing the limit for observing the universe to ever-increasing photon energies (i.e., up to 200 keV or higher), well beyond Chandra's (approx.10 keV) and NuStar's (approx.75 keV) capability. The addition of multilayer technology would significantly enhance the x-ray optics capability at MSFC and allow NASA to maintain its world leadership position in the development, fabrication, and design of innovative x-ray instrumentation, which would be the first of its kind by combining multilayer technology with the mirror replication process. This marriage of these technologies would allow astronomers to see the universe in a new light by pushing to higher energies that are out of reach with today's instruments. To this aim, a magnetron vacuum sputter deposition system for the deposition of novel multilayer thin film x-ray optics is proposed. A significant secondary use of the vacuum deposition system includes the capability to fabricate multilayers for applications in the field of EUV optics for solar physics, neutron optics, and x-ray optics for a broad range of applications including medical imaging.

Broadway, David↗
NASA NTRS2015

Grazing Incidence Optics Technology

This project is to demonstrate the capability to directly fabricate lightweight, high-resolution, grazing-incidence x-ray optics using a commercially available robotic polishing machine. Typical x-ray optics production at NASA Marshall Space Flight Center (MSFC) uses a replication process in which metal mirrors are electroformed on to figured and polished mandrels from which they are later removed. The attraction of this process is that multiple copies can be made from a single master. The drawback is that the replication process limits the angular resolution that can be attained. By directly fabricating each shell, errors inherent in the replication process are removed. The principal challenge now becomes how to support the mirror shell during all aspects of fabrication, including the necessary metrology to converge on the required mirror performance specifications. This program makes use of a Zeeko seven-axis computer-controlled polishing machine (see fig. 1) and supporting fabrication, metrology, and test equipment at MSFC. The overall development plan calls for proof-of-concept demonstration with relatively thick mirror shells (5-6 mm, fig. 2) which are straightforward to support and then a transition to much thinner shells (2-3 mm), which are an order of magnitude thinner than those used for Chandra. Both glass and metal substrates are being investigated. Currently, a thick glass shell is being figured. This has enabled experience to be gained with programming and operating the polishing machine without worrying about shell distortions or breakage. It has also allowed time for more complex support mechanisms for figuring/ polishing and metrology to be designed for the more challenging thinner shells. These are now in fabrication. Figure 1: Zeeko polishing machine.

Ramsey, Brian↗
NASA NTRS2020

Precision Assessment of the HPLC Phytoplankton Pigment Dataset Analyzed by NASA to Quantify Global Variability in Support of Ocean Color Remote Sensing

The ability to generate chlorophyll a (Chl a) assessments from ocean color orbital sensors, such as VIIRS and MODIS, that satisfy the requirements to be climate-quality data record (CDR) quality is contingent in part on the quality of the in situ ground or sea truth observations that serve as datasets for vicarious calibration and algorithm validation activities. NASA has a mandate to collect, analyze, and distribute in situ data of the highest possible quality with documented uncertainties and in keeping with established performance metrics. Using a dataset of over 18,000 HPLC phytoplankton pigment samples representing water collected in all major ocean basins analyzed a central laboratory (Field Support Group (FSG) of the Ocean Ecology Laboratory (OEL) at NASA Goddard Space Flight Center (GSFC)), we performed an assessment of the global precision among sample replicates of Chl a as well as major accessory pigments. We investigated the impacts of filtration volume, water basin, collection technique, pigment concentration, and different filtration volumes for replicate filters on replicate filter precision, as well as investigating any pigment-specific differences. Our results quantify sample variability with the goal of understanding any systemic biases or biogeographic influences.

Thomas, Crystal S.↗
NASA NTRSDate not supplied

Development of a Sensorimotor Ground Analog from Astronaut Postflight Experience

Exploration class missions including Artemis, Gateway, and beyond will require a new level of autonomy around periods of gravitational transition, where sensorimotor disturbances are great. Because of this, there is a need to define sensorimotor assessment thresholds that indicate when performance in operational tasks might be impacted or unsafe. To define these thresholds, a Sensorimotor Adaptation Analog (SAA) was proposed that could induce varying levels of sensorimotor disorientation through combined vestibular, visual, and proprioceptive disruptions. The purpose of this study was to gather subjective feedback on the SAA from previously flown astronauts that would mimic their post-flight experience and functional performance immediately after landing (R+0-4hrs; high level) and post-landing (R+24-48hrs; low level). The SAA consisted of galvanic vestibular stimulation (GVS), visual disorientation goggles, and a weighted suit to alter proprioceptive feedback and replicate subjective heaviness. A random sum-of-sines profile between 0-1Hz was used for the GVS with peak amplitudes ranging from 1-4mA. The GVS was applied first at the low (2mA) and high (3mA) levels, followed by the weighted suit alone, then combined with the GVS at the low (20% body weight) and high levels (40% body weight). Last, the disorientation goggles were applied alongside both the GVS and weighted suit at the low (0.07-0.10+ blood alcohol content (BAC)) and high (0.12-0.15+ BAC) levels. Each element of the SAA could be increased or decreased depending on crew feedback to find the disorientation levels that best matched their experience. Five USOS astronauts (1 male, 4 female) who had previously flown (average time since flight: 377 days) participated. Crewmembers reported that GVS alone replicated ~80-90% of their post-flight performance with the weighted suit fine-tuning the experience to replicate an additional 5-10% of their experience. Crewmembers did not believe the disorientation goggles represented either the visual disruptions or illusory sensations that they experienced, nor did they impact performance in post-flight tasks similarly. The final SAA, resulting from crewmember feedback, includes the GVS at the levels described above and the weighted suit at 15% and 30% body weight. The disorientation goggles were removed from SAA. These results provided a more realistic SAA that can be used to define the sensorimotor assessment thresholds through ground subjects and potentially expanded for use in countermeasure testing and as a pre-flight training tool.

S. C. Moudy↗
NASA NTRSDate not supplied

The Need for Earth-Based Experiments to Inform Microbial Evolution on Planetary Surfaces

Introduction: Historically, the focus of planetary protection at NASA has been on unmanned, robotic missions. Such missions have paved the way for understanding how to implement planetary protection in a feasible and cost-sensitive way. However, with the introduction of crewed missions to Mars in the not-sodistant future, there is a need to better define and understand how to implement planetary protection under new circumstances, as well as understand the risk of contaminating Mars. One unavoidable fact is that microbes will go where humans go. Therefore, it is critical to understand how these microbes may (and will) impact our ability to conduct meaningful, reliable astrobiological science. Microorganisms have spent millions of years evolving to survive in extreme environments here on Earth. Already there are indications that microbes aboard the International Space Station evolve and adapt to life in low earth orbit. The microbes that are eventually taken to Mars with humans will also adapt, potentially causing harmful effects to crew and/or the planetary or astrobiological science conducted. Therefore, it is of critical interest that we evaluate and characterize the potential risks of microbial evolution on Mars. It is expected that microbes carried by humans will begin to evolve to new environments even before landing on Mars, during the several month cruise phase. Once landed, microbes will encounter different stressors within the crew habitats on Mars. During extravehicular activities, venting, or other release events, microbes will find their way out onto the Martian surface. The induced environments around crewed systems will create potentially-favorable conditions for microbes to continue evolving on Mars. Eventually, microbes may find their way beyond the close confines of the crewed area and continue evolving so as to fill new or distant niches on the Martian surface. It is challenging to replicate Martian environments here on Earth, making it nearly impossible to predict the evolutionary changes that microbes would undergo on Mars. But this work is critical. Serial passaging experiments performed by Richard Lenski on E. coli show the dramatic changes microbes can undergo even within a laboratory setting. Furthermore, experiments performed by Michael Baym also demonstrate the power of single mutations in microbial development of antibiotic resistance [3]. Long duration experiments should be performed on a suite of microbes exposed to environments likely to be experienced on the Martian surface. While simulating space environments can be challenging, facilities exist that can achieve individual and combinatorial environmental conditions to simulate space and planetary conditions. Such chambers should be employed for microbial studies. Currently, at the Marshall Space Flight Center, we have used various stressors like drying, vacuum, proton radiation, and ultraviolet light both separately and in combination, to evaluate the survival of cleanroom microbes. Shockingly, several non-spore forming isolates have demonstrated the ability to survive many extreme conditions (manuscript in preparation). These short duration exposures must be augmented with larger and more gradual studies to replicate what microbes might experience in the transition from cruise, to surface habitats, to induced surface environments, and finally true Martian environments. While no Earth-based experiment can perfectly replicate the Martian environment, nor could we test every possible microbe in simulation experimental regimes, efforts should be made to examine the evolutionary potential of the “usual suspects” seen on the ISS or in other crewed environments to begin to fill this important knowledge gap.

Chelsi D. Cassilly↗
DOE OSTI2024

Gradient Coding With Iterative Block Leverage Score Sampling

Gradient coding is a method for mitigating straggling servers in a centralized computing network that uses erasure-coding techniques to distributively carry out first-order optimization methods. Randomized numerical linear algebra uses randomization to develop improved algorithms for large-scale linear algebra computations. In this study, we propose a method for distributed optimization that combines gradient coding and randomized numerical linear algebra. The proposed method uses a randomized ℓ 2 -subspace embedding and a gradient coding technique to distribute blocks of data to the computational nodes of a centralized network, and at each iteration the central server only requires a small number of computations to obtain the steepest descent update. The novelty of our approach is that the data is replicated according to importance scores, called block leverage scores, in contrast to most gradient coding approaches that uniformly replicate the data blocks. Furthermore, we do not require a decoding step at each iteration, avoiding a bottleneck in previous gradient coding schemes. We show that our approach results in a valid ℓ 2 -subspace embedding, and that our resulting approximation converges to the optimal solution.

97 MATHEMATICS AND COMPUTING↗
NASA NTRS1994

Continuous in vitro evolution of bacteriophage RNA polymerase promoters

Rapid in vitro evolution of bacteriophage T7, T3, and SP6 RNA polymerase promoters was achieved by a method that allows continuous enrichment of DNAs that contain functional promoter elements. This method exploits the ability of a special class of nucleic acid molecules to replicate continuously in the presence of both a reverse transcriptase and a DNA-dependent RNA polymerase. Replication involves the synthesis of both RNA and cDNA intermediates. The cDNA strand contains an embedded promoter sequence, which becomes converted to a functional double-stranded promoter element, leading to the production of RNA transcripts. Synthetic cDNAs, including those that contain randomized promoter sequences, can be used to initiate the amplification cycle. However, only those cDNAs that contain functional promoter sequences are able to produce RNA transcripts. Furthermore, each RNA transcript encodes the RNA polymerase promoter sequence that was responsible for initiation of its own transcription. Thus, the population of amplifying molecules quickly becomes enriched for those templates that encode functional promoters. Optimal promoter sequences for phage T7, T3, and SP6 RNA polymerase were identified after a 2-h amplification reaction, initiated in each case with a pool of synthetic cDNAs encoding greater than 10(10) promoter sequence variants.

Non-NASA Center↗
DOE OSTI2024

Tau Positron Emission Tomography for Predicting Dementia in Individuals With Mild Cognitive Impairment

An accurate prognosis is especially pertinent in mild cognitive impairment (MCI), when individuals experience considerable uncertainty about future progression. To evaluate the prognostic value of tau positron emission tomography (PET) to predict clinical progression from MCI to dementia. This was a multicenter cohort study with external validation and a mean (SD) follow-up of 2.0 (1.1) years. Data were collected from centers in South Korea, Sweden, the US, and Switzerland from June 2014 to January 2024. Participant data were retrospectively collected and inclusion criteria were a baseline clinical diagnosis of MCI; longitudinal clinical follow-up; a Mini-Mental State Examination (MMSE) score greater than 22; and available tau PET, amyloid-β (Aβ) PET, and magnetic resonance imaging (MRI) scan less than 1 year from diagnosis. A total of 448 eligible individuals with MCI were included (331 in the discovery cohort and 117 in the validation cohort). None of these participants were excluded over the course of the study. Exposures included Tau PET, Aβ PET, and MRI. Positive results on tau PET (temporal meta–region of interest), Aβ PET (global; expressed in the standardized metric Centiloids), and MRI (Alzheimer disease [AD] signature region) was assessed using quantitative thresholds and visual reads. Clinical progression from MCI to all-cause dementia (regardless of suspected etiology) or to AD dementia (AD as suspected etiology) served as the primary outcomes. The primary analyses were receiver operating characteristics. In the discovery cohort, the mean (SD) age was 70.9 (8.5) years, 191 (58%) were male, the mean (SD) MMSE score was 27.1 (1.9), and 110 individuals with MCI (33%) converted to dementia (71 to AD dementia). Only the model with tau PET predicted all-cause dementia (area under the receiver operating characteristic curve [AUC], 0.75; 95% CI, 0.70-0.80) better than a base model including age, sex, education, and MMSE score (AUC, 0.71; 95% CI, 0.65-0.77; P = .02), while the models assessing the other neuroimaging markers did not improve prediction. In the validation cohort, tau PET replicated in predicting all-cause dementia. Compared to the base model (AUC, 0.75; 95% CI, 0.69-0.82), prediction of AD dementia in the discovery cohort was significantly improved by including tau PET (AUC, 0.84; 95% CI, 0.79-0.89; P < .001), tau PET visual read (AUC, 0.83; 95% CI, 0.78-0.88; P = .001), and Aβ PET Centiloids (AUC, 0.83; 95% CI, 0.78-0.88; P = .03). In the validation cohort, only the tau PET and the tau PET visual reads replicated in predicting AD dementia. In this study, tau-PET showed the best performance as a stand-alone marker to predict progression to dementia among individuals with MCI. This suggests that, for prognostic purposes in MCI, a tau PET scan may be the best currently available neuroimaging marker.

59 BASIC BIOLOGICAL SCIENCES↗