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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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At least 415 records · Page 23
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

A phase 2 study of sorafenib combined with conventional therapies in refractory central nervous system leukemia

Background Patients with refractory central nervous system leukemia (CNSL) have a dismal prognosis and lack effective therapy. Case reports have shown that sorafenib is effective against brain metastases, including leukemia. Methods To explore the efficacy of sorafenib combined with conventional therapies for refractory CNSL, a phase 2 study was conducted. The primary end point was the complete remission rate (CRR) within 8 weeks of treatment. Secondary end points included the overall response rate (ORR), event‐free survival (EFS), overall survival (OS), and adverse events (AEs). Results Twenty‐six patients with refractory CNSL were enrolled; they included 17 with isolated CNSL, 7 with hematological relapse, and 2 with another extramedullary relapse. After 8 weeks of treatment, 21 patients achieved complete remission, 2 achieved partial remission, and 3 achieved no remission for a CRR of 80.8% (95% CI, 62.1%‐91.5%) and an ORR of 88.5% (95% CI, 71.0%‐96.0%). Twenty patients survived, and 6 died. The 2‐year EFS and OS rates were 75.0% (95% CI, 54.5%‐88.3%) and 76.9% (95% CI, 54.2%‐90.4%), respectively. Six patients experienced grade 3 or 4 treatment‐related AEs, including moderate chronic graft‐vs‐host disease (n = 3), grade 3 or 4 acute graft‐vs‐host disease (n = 2), and grade 3 skin rash (n = 1). No treatment‐related deaths occurred during the therapy of refractory CNSL. Conclusions Sorafenib combined with conventional therapies is effective and safe for refractory CNSL. Lay Summary Sorafenib combined with conventional therapies is effective and safe for refractory central nervous system leukemia.

Chen, Xiaoxia↗
DOE OSTI2024

Distinct cellular expression and subcellular localization of Kv2 voltage‐gated K + channel subtypes in dorsal root ganglion neurons conserved between mice and humans

Abstract The distinct organization of Kv2 voltage‐gated potassium channels on and near the cell body of brain neurons enables their regulation of action potentials and specialized membrane contact sites. Somatosensory neurons have a pseudounipolar morphology and transmit action potentials from peripheral nerve endings through axons that bifurcate to the spinal cord and the cell body within ganglia including the dorsal root ganglia (DRG). Kv2 channels regulate action potentials in somatosensory neurons, yet little is known about where Kv2 channels are located. Here, we define the cellular and subcellular localization of the Kv2 paralogs, Kv2.1 and Kv2.2, in DRG somatosensory neurons with a panel of antibodies, cell markers, and genetically modified mice. We find that relative to spinal cord neurons, DRG neurons have similar levels of detectable Kv2.1 and higher levels of Kv2.2. In older mice, detectable Kv2.2 remains similar, while detectable Kv2.1 decreases. Both Kv2 subtypes adopt clustered subcellular patterns that are distinct from central neurons. Most DRG neurons co‐express Kv2.1 and Kv2.2, although neuron subpopulations show preferential expression of Kv2.1 or Kv2.2. We find that Kv2 protein expression and subcellular localization are similar between mouse and human DRG neurons. We conclude that the organization of both Kv2 channels is consistent with physiological roles in the somata and stem axons of DRG neurons. The general prevalence of Kv2.2 in DRG as compared to central neurons and the enrichment of Kv2.2 relative to detectable Kv2.1 in older mice, proprioceptors, and axons suggest more widespread roles for Kv2.2 in DRG neurons.

Neurosciences & Neurology↗
DOE OSTI2021

Connectivity‐based parcellation of normal and anatomically distorted human cerebral cortex

Abstract For over a century, neuroscientists have been working toward parcellating the human cortex into distinct neurobiological regions. Modern technologies offer many parcellation methods for healthy cortices acquired through magnetic resonance imaging. However, these methods are suboptimal for personalized neurosurgical application given that pathology and resection distort the cerebrum. We sought to overcome this problem by developing a novel connectivity‐based parcellation approach that can be applied at the single‐subject level. Utilizing normative diffusion data, we first developed a machine‐learning (ML) classifier to learn the typical structural connectivity patterns of healthy subjects. Specifically, the Glasser HCP atlas was utilized as a prior to calculate the streamline connectivity between each voxel and each parcel of the atlas. Using the resultant feature vector, we determined the parcel identity of each voxel in neurosurgical patients ( n = 40) and thereby iteratively adjusted the prior. This approach enabled us to create patient‐specific maps independent of brain shape and pathological distortion. The supervised ML classifier re‐parcellated an average of 2.65% of cortical voxels across a healthy dataset ( n = 178) and an average of 5.5% in neurosurgical patients. Our patient dataset consisted of subjects with supratentorial infiltrating gliomas operated on by the senior author who then assessed the validity and practical utility of the re‐parcellated diffusion data. We demonstrate a rapid and effective ML parcellation approach to parcellation of the human cortex during anatomical distortion. Our approach overcomes limitations of indiscriminately applying atlas‐based registration from healthy subjects by employing a voxel‐wise connectivity approach based on individual data.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Physical Models from Physical Templates Using Biocompatible Liquid Crystal Elastomers as Morphologically Programmable Inks For 3D Printing

Advanced manufacturing has received considerable attention as a tool for the fabrication of cell scaffolds however, finding ideal biocompatible and biodegradable materials that fit the correct parameters for 3D printing and guide cells to align remain a challenge. Herein, a photocrosslinkable smectic-A (Sm-A) liquid crystal elastomer (LCE) designed for 3D printing is presented, that promotes cell proliferation but most importantly induces cell anisotropy. The LCE-based bio-ink allows the 3D duplication of a highly complex brain structure generated from an animal model. Vascular tissue models are generated from fluorescently stained mouse tissue spatially imaged using confocal microscopy and subsequently processed to create a digital 3D model suitable for printing. The 3D structure is reproduced using a Digital Light Processing (DLP) stereolithography (SLA) desktop 3D printer. Synchrotron Small-Angle X-ray Diffraction (SAXD) data reveal a strong alignment of the LCE layering within the struts of the printed 3D scaffold. The resultant anisotropy of the LCE struts is then shown to direct cell growth. This study offers a simple approach to produce model tissues built within hours that promote cellular alignment.

3D cell culture↗
DOE OSTI2021

Three-repeat and four-repeat tau isoforms form different oligomers

Different tauopathies are characterized by the isoform-specific composition of the aggregates found in the brain and by structurally distinct tau strains. Although tau oligomers have been implicated as important neurotoxic species, little is known about how the primary structures of the six human tau isoforms affect tau oligomerization because the oligomers are metastable and difficult to analyze. To address this knowledge gap, here, we analyzed the initial oligomers formed by the six tau isoforms in the absence of posttranslational modifications or other manipulations using dot blots probed by an oligomer-specific antibody, native-PAGE/western blots, photo-induced cross-linking of unmodified proteins, mass-spectrometry, and ion-mobility spectroscopy. We found that under these conditions, three-repeat (3R) isoforms are more prone than four-repeat (4R) isoforms to form oligomers. In this study, we also tested whether known inhibitors of tau aggregation affect its oligomerization using three small molecules representing different classes of tau aggregation inhibitors, Methylene Blue (MB), the molecular tweezer CLR01, and the all-D peptide TLKIVW, for their ability to inhibit or modulate the oligomerization of the six tau isoforms. Unlike their reported inhibitory effect on tau fibrillation, the inhibitors had little or no effect on the initial oligomerization. Our study provides novel insight into the primary–quaternary structure relationship of human tau and suggests that 3R-tau oligomers may be an important target for future development of compounds targeting pathological tau assemblies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Structures of a synthetic antibody selected against and bound to the C‐terminal domain of Clostridium perfringens enterotoxin

Abstract Clostridium perfringensenterotoxin (CpE) causes cytotoxic gastrointestinal disease in mammalian epithelium by binding membrane protein receptors called claudins. Claudins direct the formation of cell/cell tight junctions through oligomerization and govern the transport of molecules between individual cells. CpE binds claudins through its C‐terminal domain (cCpE) and induces cytotoxicity through its N‐terminal domain. The non‐toxic cCpE is a useful tool to study claudins, tight junctions, and for translational applications, such as increasing the permeability of restrictive tissues like the blood–brain barrier or selective targeting of claudin overexpressing cancers. Conversely, there are no specialized molecular tools to study CpE or cCpE, or to modulate or inhibit their functions. We previously reported the development of synthetic antigen‐binding fragments (sFabs) that bind cCpE, and low‐resolution structures of them bound to claudin/cCpE complexes. Here, we determine high‐resolution structures of sFab COP‐2 bound to cCpE using X‐ray crystallography and cryogenic electron microscopy. The structures and biophysical findings provide the mechanism of COP‐2 binding to cCpE and the molecular determinants driving their interactions. These insights can advance the design of new antibody‐based tools from our COP‐2 scaffold to study or alter cCpE function and give rise to a “Trojan horse” strategy that exploits cCpE's tight junction barrier disrupting function to selectively deliver conjugated therapeutics through normally impermeable tissues.

Biochemistry & Molecular Biology↗
DOE OSTI2024

Atomic Structure and Dynamics of Unusual and Wide-Gap Phase-Change Chalcogenides: A GeTe 2 Case

Brain-inspired computing, reconfigurable optical metamaterials, photonic tensor cores, and many other advanced applications require next-generation phase-change materials (PCMs) with better energy efficiency and a wider thermal and spectral range for reliable operations. Germanium ditelluride (GeTe 2 ), with higher thermal stability and a larger bandgap compared to current benchmark PCMs, appears promising for THz metasurfaces and the controlled crystallization of atomically thin 2D materials. Using high-energy X-Ray diffraction supported by first-principles simulation, the atomic structure in semiconducting pulsed laser deposition films and metallic high-temperature liquids is investigated. The results suggest that the structural and chemical metastability of GeTe 2 , leading to disproportionation into GeTe and Te, is related to high internal pressure during a semiconductor–metal transition, presumably occurring in the supercooled melt. Similar phenomena are expected for canonical GeS 2 and GeSe 2 under high temperatures and pressures.

74 ATOMIC AND MOLECULAR PHYSICS↗
DOE OSTI2024

Identifying Heterogeneous Micromechanical Properties of Biological Tissues via Physics–Informed Neural Networks

The heterogeneous micromechanical properties of biological tissues have profound implications across diverse medical and engineering domains. However, identifying full-field heterogeneous elastic properties of soft materials using traditional engineering approaches is fundamentally challenging due to difficulties in estimating local stress fields. Recently, there has been a growing interest in data-driven models for learning full-field mechanical responses, such as displacement and strain, from experimental or synthetic data. However, research studies on inferring full-field elastic properties of materials, a more challenging problem, are scarce, particularly for large deformation, hyperelastic materials. Here, a physics-informed machine learning approach is proposed to identify the elasticity map in nonlinear, large deformation hyperelastic materials. This study reports the prediction accuracies and computational efficiency of physics-informed neural networks (PINNs) in inferring the heterogeneous elasticity maps across materials with structural complexity that closely resemble real tissue microstructure, such as brain, tricuspid valve, and breast cancer tissues. Further, the improved architecture is applied to three hyperelastic constitutive models: Neo-Hookean, Mooney Rivlin, and Gent. Furthermore, the improved network architecture consistently produces accurate estimations of heterogeneous elasticity maps, even when there is up to 10% noise present in the training data.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Visualisation and outlier detection for probability density function ensembles

Abstract Exploratory data analysis (EDA) for functional data—data objects where observations are entire functions—is a difficult problem that has seen significant attention in recent literature. This surge in interest is motivated by the ubiquitous nature of functional data, which are prevalent in applications across fields such as meteorology, biology, medicine and engineering. Empirical probability density functions (PDFs) can be viewed as constrained functional data objects that must integrate to one and be nonnegative. They show up in contexts such as yearly income distributions, zooplankton size structure in oceanography and in connectivity patterns in the brain, among others. While PDF data are certainly common in modern research, little attention has been given to EDA specifically for PDFs. In this paper, we extend several methods for EDA on functional data for PDFs and compare them on simulated data that exhibit different types of variation, designed to mimic that seen in real‐world applications. We then use our new methods to perform EDA on the breakthrough curves observed in gas transport simulations for underground fracture networks.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2021

Science Personality and STEM Ambassador

Dr. Amy Elliott has had unique opportunities to serve as a STEM role model through her various media production projects. Her debut on screen was as a competitor on an engineering reality show competition called “The Big Brain Theory,” aired by The Discovery Channel. Following this competition, Dr. Elliott served as an on-camera host for RoboNation’s water-based, annual collegiate competitions and for The Science Channel’s viral video show, “Outrageous Acts of Science.” Dr. Elliott also serves as volunteer pit-crew for Green Envy Racing, a woman-lead race team that seeks to set and speed records with electric motorcycles. Because of Dr. Elliott’s public exposure, she was selected as an IF/THEN Ambassador by the American Associate for the Advancement of Science (AAAS), a program that seeks to highlight women as STEM role models. Dr. Elliott’s work in 3D printing is frequently a source of inspiration for her.

Elliott, Amy↗
DOE OSTI2023

Carbon nanospikes have improved sensitivity and antifouling properties for adenosine, hydrogen peroxide, and histamine

Carbon nanospikes (CNSs) are a new nanomaterial that has enhanced surface roughness and surface oxide concentration, increasing the sensitivity for dopamine detection. However, CNS-modified electrodes (CNSMEs) have not been characterized for other neurochemicals, particularly those with higher oxidation potentials. The purpose of this study was to evaluate CNSMEs for the detection of adenosine, hydrogen peroxide (H 2 O 2 ), and histamine. The sensitivity increased with CNSs, and signals at CNSMEs were about 3.3 times higher than CFMEs. Normalizing for surface area differences using background currents, CNSMEs show an increased signal of 4.8 times for adenosine, 1.5 times for H 2 O 2 , and 2 times for histamine. CNSMEs promoted the formation of secondary products for adenosine and histamine, which enables differentiation from other analytes with similar oxidation potentials. Furthermore, CNSs also selectively enhance the sensitivity for adenosine and histamine compared to H 2 O 2 . A scan rate test reveals that adenosine is more adsorption-controlled at CNS electrodes than CFMEs. CNSMEs are antifouling for histamine, with less fouling because the polymers formed after histamine electrooxidation do not adsorb due to an elevated number of edge planes. CNSMEs were useful for detecting each analyte applied in brain slices. Because of the hydrophilic surface compared to CFMEs, CNSMEs also have reduced biofouling when used in tissue. Therefore, CNSMEs are useful for tissue measurements of adenosine, hydrogen peroxide, and histamine with high selectivity and low fouling.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

Tissue Distribution of Mercury in the Bodies of Wild American Alligators ( Alligator mississippiensis ) from a Coastal Marsh in Louisiana (USA)

Total mercury (THg) concentrations were measured in wild alligators inhabiting a coastal marsh in southern Louisiana, to determine the tissue distribution of THg among various body organs and tissue compartments. Concentrations of THg in claws and dermal tail scutes were compared to those in blood, brain, gonad, heart, kidney, liver, and skeletal muscle to determine if the former tissues, commonly available by non-lethal sampling, could be used as measures of body burdens in various internal organs. Mercury was found in all body organs and tissue compartments. However, overall, THg concentrations measured in alligators were below the FDA action level for fish consumption and were comparable to previous data reported from southwestern Louisiana. Here, our results suggest consumption of meat from alligators found in this region may be of little public health concern. However, the extended period of time between sampling (in this study) and the present-day highlight the need for continuous, additional, and more recent sampling to ensure consumer safety. Total mercury concentrations were highest in the kidney (3.18 ± 0.69 mg/kg dw) and liver (3.12 ± 0.76 mg/kg dw). THg levels in non-lethal samples (blood, claws, and dermal tail scutes) were positively correlated with all tissue THg concentrations (blood: R 2 = 0.513 – 0.988; claw: R 2 = 0.347 – 0.637, scutes: R 2 = 0.333 – 0.649). Because THg concentrations from blood, claws, and scutes were correlated with those of the internal organs, non-lethal sampling methods may be a viable method of estimating levels of THg in other body tissues.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
DOE OSTI2023

Efficient multi-scale representation of visual objects using a biologically plausible spike-latency code and winner-take-all inhibition

Deep neural networks have surpassed human performance in key visual challenges such as object recognition, but require a large amount of energy, computation, and memory. In contrast, spiking neural networks (SNNs) have the potential to improve both the efficiency and biological plausibility of object recognition systems. Here we present a SNN model that uses spike-latency coding and winner-take-all inhibition (WTA-I) to efficiently represent visual stimuli using multi-scale parallel processing. Mimicking neuronal response properties in early visual cortex, images were preprocessed with three different spatial frequency (SF) channels, before they were fed to a layer of spiking neurons whose synaptic weights were updated using spike-timing-dependent-plasticity. We investigate how the quality of the represented objects changes under different SF bands and WTA-I schemes. We demonstrate that a network of 200 spiking neurons tuned to three SFs can efficiently represent objects with as little as 15 spikes per neuron. Furthermore, studying how core object recognition may be implemented using biologically plausible learning rules in SNNs may not only further our understanding of the brain, but also lead to novel and efficient artificial vision systems.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Biomechanical and Cortical Control of Tongue Movements During Chewing and Swallowing

Tongue function is vital for chewing and swallowing and lingual dysfunction is often associated with dysphagia. Better treatment of dysphagia depends on a better understanding of hyolingual morphology, biomechanics, and neural control in humans and animal models. Recent research has revealed significant variation among animal models in morphology of the hyoid chain and suprahyoid muscles which may be associated with variation in swallowing mechanisms. The recent deployment of XROMM (X-ray Reconstruction of Moving Morphology) to quantify 3D hyolingual kinematics has revealed new details on flexion and roll of the tongue during chewing in animal models, movements similar to those used by humans. XROMM-based studies of swallowing in macaques have falsified traditional hypotheses of mechanisms of tongue base retraction during swallowing, and literature review suggests that other animal models may employ a diversity of mechanisms of tongue base retraction. There is variation among animal models in distribution of hyolingual proprioceptors but how that might be related to lingual mechanics is unknown. In macaque monkeys, tongue kinematics—shape and movement—are strongly encoded in neural activity in orofacial primary motor cortex, giving optimism for development of brain–machine interfaces for assisting recovery of lingual function after stroke. However, more research on hyolingual biomechanics and control is needed for technologies interfacing the nervous system with the hyolingual apparatus to become a reality.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Formation and retrieval of cell assemblies in a biologically realistic spiking neural network model of area CA3 in the mouse hippocampus

The hippocampal formation is critical for episodic memory, with area Cornu Ammonis 3 (CA3) a necessary substrate for auto-associative pattern completion. Recent theoretical and experimental evidence suggests that the formation and retrieval of cell assemblies enable these functions. Yet, how cell assemblies are formed and retrieved in a full-scale spiking neural network (SNN) of CA3 that incorporates the observed diversity of neurons and connections within this circuit is not well understood. Here, we demonstrate that a data-driven SNN model quantitatively reflecting the neuron type-specific population sizes, intrinsic electrophysiology, connectivity statistics, synaptic signaling, and long-term plasticity of the mouse CA3 is capable of robust auto-association and pattern completion via cell assemblies. Our results show that a broad range of assembly sizes could successfully and systematically retrieve patterns from heavily incomplete or corrupted cues after a limited number of presentations. Furthermore, performance was robust with respect to partial overlap of assemblies through shared cells, substantially enhancing memory capacity. These novel findings provide computational evidence that the specific biological properties of the CA3 circuit produce an effective neural substrate for associative learning in the mammalian brain.

hetero-association↗
DOE OSTI2022

Effect of inoculation with prion dilutions within the dynamic range of ELISA absorbance on prion incubation period

This study examines the effect of various infectious prion titers within the dynamic range as measured by ELISA on incubation period. We inoculated ovinized transgenic mice with seven decreasing dilutions of a fast-incubating scrapie strain. The highest inoculum group was a 20% w/v brain homogenate from a sheep with scrapie. The subsequent six inoculum dilutions ranged from the highest ELISA optical density reading of 4.000 to a dilution where scrapie prions were not detectable by ELISA. Multiple comparison analysis demonstrated variation in the incubation periods between some inoculum groups. Incubation periods were similar between inoculum groups unless their optical density differed by more than ≈2 units of absorbance. These data will inform the interpretation of future studies that compare incubation periods in experimentally inoculated animals for TSE research.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

A critical review of cyber-physical security for building automation systems

Modern Building Automation Systems (BASs), as the brain that enable the smartness of a smart building, often require increased connectivity both among system components as well as with outside entities, such as the cloud, to enable low-cost remote management, optimized automation via outsourced cloud analytics, and increased building-grid integrations. As smart buildings move towards open communication technologies, providing access to BASs through the building's intranet, or even remotely through the Internet, has become a common practice. However, increased connectivity and accessibility come with increased cyber security threats. BASs were historically developed as closed environments with limited cyber-security considerations. As a result, BASs in many buildings are vulnerable to cyber-attacks that may cause adverse consequences, such as occupant discomfort, excessive energy usage, and unexpected equipment downtime. Therefore, there is a strong need to advance the state-of-the-art in cyber-physical security for BASs and provide practical solutions for attack mitigation in buildings. However, an inclusive and systematic review of BAS vulnerabilities, potential cyber-attacks with impact assessment, detection & defense approaches, and cyber resilient control strategies is currently lacking in the literature. This review paper fills the gap by providing a comprehensive up-to-date review of cyber-physical security for BASs at three levels in commercial buildings: management level, automation level, and field level. The general BASs vulnerabilities and protocol-specific vulnerabilities for the four dominant BAS protocols (i.e., BACnet, KNX, LonWorks, and Modbus) are reviewed, followed by a discussion on four attack targets and seven potential attack scenarios. Furthermore, the impact of cyber-attacks on BASs is summarized as signal corruption, signal delaying, and signal blocking. The typical cyber-attack detection and defense approaches are identified at the three levels. Cyber resilient control strategies for BASs under attack are categorized into passive and active resilient control schemes. Open challenges and future opportunities are finally discussed.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2022

Microglia are implicated in the development of paclitaxel chemotherapy-associated cognitive impairment in female mice

Chemotherapy remains a mainstay in the treatment of many types of cancer even though it is associated with debilitating behavioral side effects referred to as “chemobrain,” including difficulty concentrating and memory impairment. The predominant hypothesis in the field is that systemic inflammation drives these cognitive impairments, although the brain mechanisms by which this occurs remain poorly understood. Here, we hypothesized that microglia are activated by chemotherapy and drive chemotherapy-associated cognitive impairments. To test this hypothesis, we treated female C57BL/6 mice with a clinically-relevant regimen of a common chemotherapeutic, paclitaxel (6 i.p. doses at 30 mg/kg), which impairs memory of an aversive stimulus as assessed via a contextual fear conditioning (CFC) paradigm. In this work, paclitaxel increased the percent area of IBA1 staining in the dentate gyrus of the hippocampus. Moreover, using a machine learning random forest classifier we identified immunohistochemical features of reactive microglia in multiple hippocampal subregions that were distinct between vehicle- and paclitaxel-treated mice. Paclitaxel treatment also increased gene expression of inflammatory cytokines in a microglia-enriched population of cells from mice. Lastly, a selective inhibitor of colony stimulating factor 1 receptor, PLX5622, was employed to deplete microglia and then assess CFC performance following paclitaxel treatment. PLX5622 significantly reduced hippocampal gene expression of paclitaxel-induced proinflammatory cytokines and restored memory, suggesting that microglia play a critical role in the development of chemotherapy-associated neuroinflammation and cognitive impairments. This work provides critical evidence that microglia drive paclitaxel-associated cognitive impairments, a key mechanistic detail for determining preventative and intervention strategies for these burdensome side effects.

60 APPLIED LIFE SCIENCES↗