Copper accumulation and the effect of chelation treatment on cerebral amyloid angiopathy compared to parenchymal amyloid plaques
Abstract not provided
Zhu, Xiayoue↗
SEARCH · Engineering Papers
Results for “brain modeling”
Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.
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Quantum AI Based Enhanced Detection of Dementia
Quantum computing has the potential to significantly improve the early detection of Alzheimer's Disease and Related Dementias (ADRD). Quantum-enhanced machine learning can be used to perform an early screening of Alzheimer's disease using brain imaging data based on dataset of MRI scans from both healthy individuals and those diagnosed with Alzheimer's. This study aims to demonstrate the potential of quantum transfer learning to enhance the performance of the classical deep learning model for dementia detection. Using the MRI sagittal images available in the OASIS-2 (64 demented and 72 non-demented subjects between 60 and 96 years), we show how quantum techniques can transform a suboptimal classical model into a more effective solution for dementia detection, highlighting their potential impact on advancing healthcare technology. We begin with a simple classical deep learning model with a significantly smaller number of parameters, which gives suboptimal performance on the problem. Then, we apply different configurations of quantum transfer learning based on the pre-trained weak classifier (Figure 1). We fix the weak classifier's initial convolutional layers at their fixed pre-trained parameters and replace the last set of dense layers with a dressed quantum circuit (DQN), which we train to enhance performance. We performed 4-fold cross-validation for both the classical and the hybrid quantum models and trained them using Pennylane's `default.qubit' simulator and IonQ's Aria-1 simulator (noisy simulation). We showed that with significantly fewer parameters, the quantum transfer learning-based hybrid models showed significant performance enhancement over the base weak classical deep learning model for dementia detection. To classify between a demented and non-demented subject, the accuracy of quantum-based AI methods improved by 6 to 14% compared to classical methods. The sensitivity of the models improved by 4 to 17%. This shows that there are fewer chances of misclassifying demented patients. Figure 2 compares the performance of the hybrid quantum models and their base classical model, and Table 1 summarizes the results. We illustrated that with assistance from quantum machine learning, it is possible to enhance detection for dementia based on brain images. This shows the potential for practical utility of quantum computing in ADRD research.
Bhowmik, Sounak [University of Tennessee, Knoxvill↗
Enhancers that direct gene expression to central nervous system vascular endothelial cells in vivo
CNS vascular endothelial cells (ECs) exhibit a distinctive gene expression program that is foundational for the blood-brain barrier (BBB). Previous research identified candidate cis-regulatory elements (CREs) that were hypothesized to control this program. In this work, transgenic mice and recombinant adeno-associated virus (rAAV) vectors have been used to interrogate these candidate CREs in vivo. These experiments show that an 850 bp genomic DNA segment ∼60 kb 5′ of Slc2a1 possesses enhancer activity that is (1) specific for BBB+ CNS ECs and (2) both necessary and sufficient for BBB+ EC gene expression. A screen of >8,000 genomic DNA segments from CNS EC-specific CRE candidates reveals several hundred with enhancer activity. Transcription factors ERG and LEF1 are shown to occupy sites in brain ECs that are highly enriched in candidate and experimentally validated CREs, lending strong support to a model in which canonical Wnt signaling activates the BBB program via LEF1.
CUT&RUN↗
Fractionated Low-Dose Radiation Induces Long-Lasting Inflammatory Responses in the Hippocampal Stem Cell Niche
Despite major technical advances in hippocampus-sparing radiation therapy, radiation-induced injury to the neural stem cell compartment may affect neurocognitive functions. In the brain, glial cells modulate neuronal functions and are major mediators of neuroinflammation. In a preclinical mouse model with fractionated low-dose radiation (LDR), the complex response to radiation-induced injury was analyzed in the hippocampal stem cell compartment over a period of 6 months.
62 RADIOLOGY AND NUCLEAR MEDICINE↗
Sensory, Decision and Control Systems: April to July 1966
The quarter reported here for the NASA contract, and the longer period reported for the Air Force contract, saw the development of two system concepts for the transmission of video data from a remote location to Earth. In the simpler system, a stereoscopic outline together with other data such as reflectance and possibly the texture of objects will be transmitted to Earth. The objects considered are those larger than a predetermined size and within a predetermined range. From the stereoscopic outlines presented to the operator on Earth he will decide what objects he would like pictured in full TV frames and order these transmitted. In the more elaborate system, TV cameras will be carried on a vehicle and the direction in which the vehicle moves will be chosen by an onboard decision computer. Perceptual decisions may also be made to identify objects whose characteristics have been reported to Earth and whose value to the Earth observer has been communicated back to the perceptual computer. The assembly of cameras, perceptual computer, decision computer and vehicle is called a robot. Photosensors for this robot are television cameras, the first models of which have been tested under computer control. A model of both the perceptual computer and the decision computer has been simulated. It consists of 12 modules, each of which makes an initial guess as to what the response to incoming data should be. Each takes the data from all other modules and combines it in a nonlinear fashion with the data coming directly into it to arrive at a mixed guess as to what act should be performed. When 60% of the modules vote 0. 5 probability for one act, that act is performed. Convergence to a satisfactory decision took from 5 to 25 time steps. The model of the frog's retina previously reported is here extended to that part of the brain, called the tectum, where the frog begins to respond to objects detected by the retina.
Control system↗
Proceedings of the 1972 Lyndon B. Johnson Space Center Endocrine Program Conference
Subjects covered during the Endocrine Program Conference include the following: (1) endocrine/metabolic studies on the Apollo 16 crewmen; (2) changes in glucose, insulin, and growth hormone levels associated with bed rest; (3) circadian rhythms of heart rate and body temperature during 56 days of bed rest; (4) stress-induced changes in corticosteroid metabolism in man; (5) present status of physiological studies on parathyroid hormone and vitamin D; (6) antagonistic effect of lithium on antidiuretic hormone action; (7) proposed Skylab body-fluid volumes study; (8) daily rhythmic changes in serotonin content in areas of the mouse brain and norepinephrine content in areas of the hamster brain; (9) studies of sodium homeostasis during simulated weightlessness; and (10) application of the water immersion model to man.
Source record↗
Proceedings of the 1973 Lyndon B. Johnson Space Center Endocrine Program Conference
Papers given at the conference are presented. Subjects covered include the following: biochemical changes during 28 days of space flight, modulating the pituitary-adrenal response to stress, the significance of biorhythms in space flight, the importance of the rein-angiotensin system in normal cardiovascular homeostasis, a progress report of stress-induced changes in corticosteroid metabolism, recent studies of physiological factors involved in the regulation of serotonin content and turnover in the brain, the role of brain biogenic amines in the control of pituitary-adrenocortical activity, application of the water immersion model to man by studies of acid-base homeostasis during simulated weightlessness, the present status of physiological studies and analysis of calcium homeostasis in the Apollo and Skylab programs, and endocrine considerations in the red-cell-mass and plasma-volume changes of Skylab 2 and 3 crews.
Source record↗
Raised Relief Mars Globe Brings the Red Planet Closer
The Mars Globe 20x is the first digitally produced raised relief globe to be sold at retail establishments. The rises and dips of the Martian landscape have been multiplied by 20 to make the shapes more noticeable to human touch and sight. They make this globe, with its over 1 million elevation points, a visually stunning introduction to the planet. Spectrum 3D used the NASA digital land elevation data to aim lasers that then shaped and defined the master globe s surface. Subsequent copies were then made by creating a master globe mold. The molded copies are hand finished by workers who remove errant edges or lines that may appear on the raw globes and then paint the surfaces. The result is a globe that measures in at 18 inches in diameter, roughly 1:15,729,473 scale of the actual planet. The exaggerated raised relief is like having a 3-D digital microscope for planetary shapes. This makes the landmarks easier to learn and understand, as it provides easy visuals for orientation. People have a natural propensity for understanding 3-D shapes more easily than numbers or words. The 3-D globes appeal to both the kinetic and visual learning aspects of the brain, making it easy for people to readily memorize the landmarks and to make a mental model that they will remember for a long time.
Source record↗
Combining Clinical and Dosimetric Features in a PBS Proton Therapy Cohort to Develop a NTCP Model for Radiation-Induced Optic Neuropathy
Radiation-induced optic neuropathy (RION) is a rare, yet severe complication following radiation therapy for brain, head and neck, or skull-base tumors. Although several risk factors, such as age, metabolic syndrome, and delivered dose, have been identified, we aimed at expanding the understanding of the mechanisms of interplay regarding dosimetry and patient variables leading to the onset of RION with a focus on proton therapy.
62 RADIOLOGY AND NUCLEAR MEDICINE↗
Herpes simplex virus and rates of cognitive decline or whole brain atrophy in the Dominantly Inherited Alzheimer Network
Abstract Objective To investigate whether herpes simplex virus type 1 (HSV‐1) infection was associated with rates of cognitive decline or whole brain atrophy among individuals from the Dominantly Inherited Alzheimer Network (DIAN). Methods Among two subsets of the DIAN cohort (age range 19.6–66.6 years; median follow‐up 3.0 years) we examined (i) rate of cognitive decline ( N = 164) using change in mini‐mental state examination (MMSE) score, (ii) rate of whole brain atrophy ( N = 149), derived from serial MR imaging, calculated using the boundary shift integral (BSI) method. HSV‐1 antibodies were assayed in baseline sera collected from 2009–2015. Linear mixed‐effects models were used to compare outcomes by HSV‐1 seropositivity and high HSV‐1 IgG titres/IgM status. Results There was no association between baseline HSV‐1 seropositivity and rates of cognitive decline or whole brain atrophy. Having high HSV‐1 IgG titres/IgM was associated with a slightly greater decline in MMSE points per year (difference in slope − 0.365, 95% CI: −0.958 to −0.072), but not with rate of whole brain atrophy. Symptomatic mutation carriers declined fastest on both MMSE and BSI measures, however, this was not influenced by HSV‐1. Among asymptomatic mutation carriers, rates of decline on MMSE and BSI were slightly greater among those who were HSV‐1 seronegative. Among mutation‐negative individuals, no differences were seen by HSV‐1. Stratifying by APOE4 status yielded inconsistent results. Interpretation We found no evidence for a major role of HSV‐1, measured by serum antibodies, in cognitive decline or whole brain atrophy among individuals at high risk of early‐onset AD.
Warren‐Gash, Charlotte↗
Neurons die with heightened but functional macro- and chaperone mediated autophagy upon increased amyloid-ß induced toxicity with region-specific protection in prolonged intermittent fasting
Highlights: • Macroautophagy (MA) is strongly engaged upon APP overexpression and remains high over time. • APP colocalization with macroautophagy components remains increased until late, promoting continuous recruitment to the autophagy machinery. • Robust chaperone-mediated autophagy (CMA) engagement is observed in late APP overexpression. • Macroautophagic flux during APP overexpression is preserved, even at late time points, suggesting functional autophagy in the face of apoptosis onset. • Macroautophagy impairment increases markers of amyloidogenesis and further exacerbates the onset of apoptotic cell death. Alzheimer's disease (AD) is a devastating neurodegenerative condition with significant socio-economic impact that is exacerbated by the rapid increase in population aging, particularly impacting already burdened health care systems of poorly resourced countries. Accumulation of the amyloid-β (Aβ) peptide, generated through amyloid precursor protein (APP) processing, manifesting in senile plaques, is a well-established neuropathological feature. Aβ plays a key role in driving synaptic dysfunction, neuronal cell loss, glial cell activation and oxidative stress associated with the pathogenesis of AD. Thus, the enhanced clearance of Aβ peptide though modulation of the mechanisms that regulate intracellular Aβ metabolism and clearance during AD progression have received major attention. Autophagy, a lysosome-based major proteolytic pathway, plays a crucial role in intracellular protein quality control and has been shown to contribute to the clearance of Aβ peptide. However, to what extent autophagy activity remains upregulated and functional in the process of increasing Aβ neurotoxicity is largely unclear. Here, we investigated the extent of neuronal toxicity in vitro by characterising autophagic flux, the expression profile of key amyloidogenic proteins, and proteins associated with prominent subtypes of the autophagy pathway to dissect the interplay between the engagement of proteolytic pathways and cell death onset in the context of APP overexpression. Moreover, we assessed the neuroprotective effects of a caloric restriction regime in vivo on the modulation of autophagy in specific brain regions. Our results reveal that autophagy is upregulated in the presence of high levels of APP and Aβ and remains heightened and functional despite concomitant apoptosis induction, suggestive of a mismatch between autophagy cargo generation and clearance capacity. These findings were confirmed when implementing a prolonged intermittent fasting (IF) intervention in a model of paraquat-induced neuronal toxicity, where markers of autophagic activity were increased, while apoptosis onset and lipid peroxidation were robustly decreased in brain regions associated with neurodegeneration. This work highlights that especially caloric restriction mimetics and controlled prolonged IF may indeed be a highly promising therapeutic strategy at all stages of AD-associated pathology progression, for a cell-inherent and cell specific augmentation of Aβ clearance through the powerful engagement of autophagy and thereby robustly contributing to neuronal protection.
60 APPLIED LIFE SCIENCES↗
A robot conditioned reflex system modeled after the cerebellum.
Reduction of a theory of cerebellar function to computer software for the control of a mechanical manipulator. This reduction is achieved by considering the cerebellum, along with the higher-level brain centers which control it, as a type of finite-state machine with input entering the cerebellum via mossy fibers from the periphery and output from the cerebellum occurring via Purkinje cells. It is hypothesized that the cerebellum learns by an error-correction system similar to Perceptron training algorithms. An electromechanical model of the cerebellum is then developed for the control of a mechanical arm. The problem of modeling the granular layer which selects the set of parallel fibers which are active at any instant of time is considered, and a relevance matrix is constructed to model the relative degree of influence which mossy fibers from the various joints have on the sets of granule cells unique to each joint.
Albus, J. S.↗
Tracking elemental changes in an ischemic stroke model with X-ray fluorescence imaging
Stroke is a leading cause of long-term disability in adults and a leading cause of death in developed nations. The cascade of cellular events and signalling that occur after cerebral ischemia are complex, however, analyzing global element markers of metabolic state affords the means to monitor stroke severity, status of injury, and recovery. These markers provide a multi-parameter method for assessing changes through the post-stroke time course. We employ synchrotron-based elemental mapping to follow elemental changes in the brain at 1 h, 1-, 2-, and 3-days, and at 1-, 2-, 3-, and 4-weeks post-stroke in a photothrombotic stroke model in mice. Our analysis reveals a highly consistent metabolic penumbra that can be readily identified based on the level of dysregulated potassium and other key elements. Maps of elemental distributions are also useful to demarcate events in the cellular response to the inflammatory cascade, including ion dysregulation, recruitment of cells to the lesion, and glial scar formation.
59 BASIC BIOLOGICAL SCIENCES↗
Design-Technology Co-Optimization for NVM-based Neuromorphic Processing Elements
An emerging use-case of machine learning (ML) is to train a model on a high-performance system and deploy the trained model on energy-constrained embedded systems. Neuromorphic hardware platforms, which operate on principles of the biological brain, can significantly lower the energy overhead of a machine learning inference task, making these platforms an attractive solution for embedded ML systems. In this paper, we present a design-technology tradeoff analysis to implement such inference tasks on the processing elements (PEs) of a Non-Volatile Memory (NVM)-based neuromorphic hardware. Through detailed circuit-level simulations at scaled process technology nodes, we show the negative impact of technology scaling on the information-processing latency, which impacts the quality-of-service (QoS) of an embedded ML system. At a finer granularity, the latency inside a PE depends on 1) the delay introduced by parasitic components on its current paths, and 2) the varying delay to sense different resistance states of its NVM cells. Based on these two observations, we make the following three contributions. First, on the technology front, we propose an optimization scheme where the NVM resistance state that takes the longest time to sense is set on current paths having the least delay, and vice versa, reducing the average PE latency, which improves the QoS. Second, on the architecture front, we introduce isolation transistors within each PE to partition it into regions that can be individually power-gated, reducing both latency and energy. Finally, on the system-software front, we propose a mechanism to leverage the proposed technological and architectural enhancements when implementing a machine-learning inference task on neuromorphic PEs of the hardware. Evaluations with a recent neuromorphic hardware architecture show that our proposed design-technology co-optimization approach improves both performance and energy efficiency of machine-learning inference tasks without incurring high cost-per-bit.
42 ENGINEERING↗
Comparison of Predictable Smooth Ocular and Combined Eye-Head Tracking Behaviour in Patients with Lesions Affecting the Brainstem and Cerebellum
We compared the ability of eight normal subjects and 15 patients with brainstem or cerebellar disease to follow a moving visual stimulus smoothly with either the eyes alone or with combined eye-head tracking. The visual stimulus was either a laser spot (horizontal and vertical planes) or a large rotating disc (torsional plane), which moved at one sinusoidal frequency for each subject. The visually enhanced Vestibulo-Ocular Reflex (VOR) was also measured in each plane. In the horizontal and vertical planes, we found that if tracking gain (gaze velocity/target velocity) for smooth pursuit was close to 1, the gain of combined eye-hand tracking was similar. If the tracking gain during smooth pursuit was less than about 0.7, combined eye-head tracking was usually superior. Most patients, irrespective of diagnosis, showed combined eye-head tracking that was superior to smooth pursuit; only two patients showed the converse. In the torsional plane, in which optokinetic responses were weak, combined eye-head tracking was much superior, and this was the case in both subjects and patients. We found that a linear model, in which an internal ocular tracking signal cancelled the VOR, could account for our findings in most normal subjects in the horizontal and vertical planes, but not in the torsional plane. The model failed to account for tracking behaviour in most patients in any plane, and suggested that the brain may use additional mechanisms to reduce the internal gain of the VOR during combined eye-head tracking. Our results confirm that certain patients who show impairment of smooth-pursuit eye movements preserve their ability to smoothly track a moving target with combined eye-head tracking.
Grant, Michael P.↗
Deployment of Gaussian Surrogate Model for Ad-Hoc Adjustments to Elastic Scattering Angular Distributions [Slides]
This presentation is on the deployment of gaussian surrogate model for ad-hoc adjustments to elastic scattering angular distributions. Discussed throughout the presentation is motivation for this lecture. Specifically, the gaussian surrogate models, validation of method with Pb-208, and the application on Be-9 are highlighted. The presentation concludes with a summary.
97 MATHEMATICS AND COMPUTING↗
Subventricular Accumulation of Cu in the Aging Mouse Brain Does Not Associate with Anticipated Increases in Markers of Oxidative Stress
Natural aging is associated with mild memory loss and cognitive decline, and age is the greatest risk factor for neurodegenerative diseases, such as Alzheimer’s disease. There is substantial evidence that oxidative stress is a major contributor to both natural aging and neurodegenerative disease, and coincidently, levels of redox active metals such as Fe and Cu are known to be elevated later in life. Recently, a pronounced age-related increase in Cu content has been reported to occur in mice and rats around a vital regulatory brain region, the subventricular zone of lateral ventricles. In our study herein, we have characterized lateral ventricle Cu content in a unique murine model of accelerated aging, senescence accelerated mouse-prone 8 (SAMP8) mice. Our results confirm an age-related increase in ventricle Cu content, consistent with the studies by others in wild-type mice and rats. Specifically, we observed Cu content to increase over the time frame 1 to 5 months and 5 to 9 months, but interestingly, no significant increase occurred between 9 and 12 months (although brain Cu content at 12 months was significantly elevated relative to 1 and 5 month-old animals). Despite the magnitude of Cu increase observed within the cells that comprise the subventricular zone of lateral ventricles (average 3 mM Cu, with isolated subcellular concentrations of 17 mM), we did not detect spectroscopic markers of thiol oxidation, protein aggregation, or lipid oxidation. The lack of evidence for oxidative stress in ex vivo animal tissue is in contrast to in vitro studies demonstrating that thiol, protein, and lipid oxidation is pronounced at these Cu concentrations. We suggest that our findings most likely indicate that the Cu ions in this brain region are sequestered in an unreactive form, possibly extended chains of Cu-thiolate complexes, which do not readily redox cycle in the aqueous cytosol. In conclusion, these results also appear to partially challenge the long-held view that age-related increases in brain metal content drive oxidative stress as we did not observe a concomitant association between age-related Cu increase and markers of oxidative stress, nor did we observe a net increase in Cu content between mice aged 9 and 12 months.
X-ray fluorescence↗
Update: Advancement of Contact Dynamics Modeling for Human Spaceflight Simulation Applications
Pong is a new software tool developed at the NASA Johnson Space Center that advances interference-based geometric contact dynamics based on 3D graphics models. The Pong software consists of three parts: a set of scripts to extract geometric data from 3D graphics models, a contact dynamics engine that provides collision detection and force calculations based on the extracted geometric data, and a set of scripts for visualizing the dynamics response with the 3D graphics models. The contact dynamics engine can be linked with an external multibody dynamics engine to provide an integrated multibody contact dynamics simulation. This paper provides a detailed overview of Pong including the overall approach and modeling capabilities, which encompasses force generation from contact primitives and friction to computational performance. Two specific Pong-based examples of International Space Station applications are discussed, and the related verification and validation using this new tool are also addressed.
Contact dynamics↗