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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 1,153 records · Page 64
All sourcesNASA NTRSDOE OSTI
DOE OSTI2016

Elevated plasma concentrations of bacterial ClpB protein in patients with eating disorders

ABSTRACT Objective Caseinolytic protease B (ClpB) produced by Enterobacteria , such as Escherichia coli , has been identified as a conformational mimetic of α‐melanocyte‐stimulating hormone (α‐MSH), an anorexigenic and anxiogenic neuropeptide. In mice, ClpB induces α‐MSH cross‐reactive antibodies and activates anorexigenic brain neurons. In patients with eating disorders (ED), anti‐ClpB and anti‐α‐MSH antibodies correlate with psychopathological traits. However, it is not known if ClpB is present in human plasma including ED patients. Methods Plasma concentrations of ClpB were measured using a recently developed ClpB immunoassay in female patients with anorexia nervosa, bulimia nervosa, and binge‐eating disorder and compared with healthy participants, all characterized by the Eating Disorder Inventory‐2 (EDI‐2) scale. Results We found that ClpB was readably detectable in plasma of healthy participants and ED patients and that its concentrations were elevated in ED patients, without significant differences in patient's subgroups. Plasma ClpB concentrations correlated with the EDI‐2 scores, with α‐MSH as well as with plasma levels of anti‐ClpB and anti‐α‐MSH antibodies. Discussion These data revealed that bacterial ClpB is naturally present in human plasma and that its concentrations can be elevated in ED patients and associated with ED‐related psychopathological traits. These results support a link between bacterial ClpB and the ED pathophysiology. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:805–808)

Breton, Jonathan↗
DOE OSTI2020

Lipids status and copper in a single astrocyte of the rat model for amyotrophic lateral sclerosis: Correlative synchrotron-based X-ray and infrared imaging

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, causing death of motor neurons controlling voluntary muscles. The pathological mechanisms of the disease are only partially understood. The hSOD1-G93A ALS rat model is characterized by an overexpression of human mutated SOD1, causing increased vulnerability by forming intracellular protein aggregates, inducing excitotoxicity, affecting oxidative balance and disturbing axonal transport. In this study we followed the bio-macromolecular organic composition and compartmentalization together with trace metal distribution in situ in single astrocytes from the ALS rat model and compared them to the control astrocytes from nontransgenic littermates by simultaneous use of two synchrotron radiation-based methods: Fourier transform infrared microspectroscopy (SRFTIR) and hard X-ray fluorescence microscopy (XRF). Here we show that ALS cells contained more Cu, which colocalized with total lipids, increased carbonyl groups and oxidized lipids, thus implying direct involvement of Cu in oxidative stress of lipidic components without direct connection to protein aggregation in situ.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Structural and functional analysis of the human cone‐rod homeobox transcription factor

Abstract The cone‐rod homeobox (CRX) protein is a critical K50 homeodomain transcription factor responsible for the differentiation and maintenance of photoreceptor neurons in the vertebrate retina. Mutant alleles in the human gene encoding CRX result in a variety of distinct blinding retinopathies, including retinitis pigmentosa, cone‐rod dystrophy, and Leber congenital amaurosis. Despite the success of using in vitro biochemistry, animal models, and genomics approaches to study this clinically relevant transcription factor over the past 25 years since its initial characterization, there are no high‐resolution structures in the published literature for the CRX protein. In this study, we use bioinformatic approaches and small‐angle X‐ray scattering (SAXS) structural analysis to further understand the biochemical complexity of the human CRX homeodomain (CRX‐HD). We find that the CRX‐HD is a compact, globular monomer in solution that can specifically bind functional cis‐regulatory elements encoded upstream of retina‐specific genes. This study presents the first structural analysis of CRX, paving the way for a new approach to studying the biochemistry of this protein and its disease‐causing mutant protein variants.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Nanoscale Imaging and Control of Volatile and Non-Volatile Resistive Switching in VO 2

Control of the metal-insulator phase transition is vital for emerging neuromorphic and memristive technologies. The ability to alter the electrically driven transition between volatile and non-volatile states is particularly important for quantum-materials-based emulation of neurons and synapses. The major challenge of this implementation is to understand and control the nanoscale mechanisms behind these two fundamental switching modalities. In this study, in situ X-ray nanoimaging is used to follow the evolution of the nanostructure and disorder in the archetypal Mott insulator VO 2 during an electrically driven transition. Our findings demonstrate selective and reversible stabilization of either the insulating or metallic phases achieved by manipulating the defect concentration. This mechanism enables us to alter the local switching response between volatile and persistent regimes and demonstrates a new possibility for nanoscale control of the resistive switching in Mott materials.

36 MATERIALS SCIENCE↗
DOE OSTI2016

Developmental regulation of RNA processing by Rbfox proteins

The Rbfox genes encode an ancient family of sequence-specific RNA binding proteins (RBPs) that are critical developmental regulators in multiple tissues including skeletal muscle, cardiac muscle, and brain. The hallmark of Rbfox proteins is a single high-affinity RRM domain, highly conserved from insects to humans, that binds preferentially to UGCAUG motifs at diverse regulatory sites in pre-mRNA introns, mRNA 3’UTRs, and pre-miRNAs hairpin structures. These versatile regulatory circuits operate on Rbfox pre-mRNA and mRNA to ensure proper expression of Rbfox1 protein isoforms, which then act on the broader transcriptome to regulate alternative splicing networks, mRNA stability and translation, and microRNA processing. Complex Rbfox expression is encoded in large genes encompassing multiple promoters and alternative splicing options that govern spatiotemporal expression of structurally distinct and tissue-specific protein isoforms with different classes of RNA targets. Nuclear Rbfox1 is a candidate master regulator that binds intronic UGCAUG elements to impact splicing efficiency of target alternative exons, many in transcripts for other splicing regulators. Tissue-specificity of Rbfox-mediated alternative splicing is executed by combinatorial regulation through the integrated activity of Rbfox proteins and synergistic or antagonistic splicing factors. Studies in animal models show that Rbfox1-related genes are critical for diverse developmental processes including germ cell differentiation and memory in Drosophila, neuronal migration and function in mouse brain, myoblast fusion and skeletal muscle function, and normal heart function. Finally, genetic and biochemical evidence suggest that aberrations in Rbfox-regulated circuitry are risk factors for multiple human disorders, especially neurodevelopmental disorders including epilepsy and autism, and cardiac hypertrophy.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Prolonged survival in secondary glioblastoma following local injection of targeted alpha therapy with 213 Bi-substance P analogue

Background Glioblastoma multiforme (GBM), the most common malignant brain tumor, mainly manifests as a primary de novo and less frequently as a secondary glial neoplasm. GBM has been demonstrated to overexpress the NK-1 receptor and substance P can be used as a ligand for targeted therapy. Alpha emitters, e.g. 213 Bi, that deposit their high energy within a short range allow the selective irradiation of tumor cells while sparing adjacent neuronal structures. Material and methods Among 50 glioma patients of different subtypes that have to date been treated with targeted alpha therapy at the Medical University Warsaw, we report here the data on nine patients with secondary GBM. Following surgery, chemo- and radiotherapy, recurrent GBM was treated by intracavitary injection of 1–6 doses of 0.9–2.3 GBq 213 Bi- DOTA-[Thi 8 ,Met(O 2 ) 11 ]-substance P ( 213 Bi-DOTA-SP) in 2-month intervals. 68 Ga-DOTA-[Thi 8 ,Met(O 2 ) 11 ]-substance P ( 68 Ga-DOTA-SP) was coinjected with the therapeutic doses to assess biodistribution using PET/CT. Therapeutic response was monitored with MRI. Results Treatment with activities ranging from 1.4 to 9.7 (median 5.8) GBq 213 Bi- DOTA-SP was well tolerated with only mild transient adverse reactions, mainly headaches due to a transient perfocal edema reaction. The median progression free survival and overall survival time following the initiation of alpha therapy was 5.8 and 16.4 months, respectively. The median overall survival time from the first diagnosis was 52.3 months. Two out of nine patients are still alive 39 and 51 months, respectively, after the initiation of the therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Histopathological Alterations after Single Epidural Injection of Ropivacaine, Methylprednizolone Acetate, or Contrast Material in Swine

Purpose: The consequences from the injection of different types of drugs in the epidural space remains unknown. Increasing evidence suggests that localized inflammation, fibrosis, and arachnoiditis can complicate sequential epidural blockades, or even epidural contrast injection. We investigate the in vivo effect of epidural injections in the epidural space in an animal model. Materials and Methods: A group of ten male adult pigs, five punctures to each at distinct vertebral interspaces under general anesthesia, were examined, testing different drugs, used regularly in the epidural space (iopamidol, methylprednisolone acetate, ropivacaine). Each site was marked with a percutaneous hook wire marker. Histological analysis of the epidural space, the meninges, and the underlying spinal cord of the punctured sites along with staining for caspase-3 followed 20 days later. Results: The epidural space did not manifest adhesions or any other pathology, and the outer surface of the dura was not impaired in any specimen. The group that had the contrast media injection showed a higher inflammation response compared to the other groups (P = 0.001). Positive staining for caspase-3 was limited to <5% of neurons with all substances used. Conclusion: No proof of arachnoiditis and/or fibrosis was noted in the epidural space with the use of the above-described drugs. A higher inflammation rate was noted with the use of contrast media.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2022

Variational and phase response analysis for limit cycles with hard boundaries, with applications to neuromechanical control problems

Motor systems show an overall robustness, but because they are highly nonlinear, understanding how they achieve robustness is difficult. In many rhythmic systems, robustness against perturbations involves response of both the shape and the timing of the trajectory. This makes the study of robustness even more challenging. To understand how a motor system produces robust behaviors in a variable environment, we consider a neuromechanical model of motor patterns in the feeding apparatus of the marine mollusk Aplysia californica (Shaw et al. in J Comput Neurosci 38(1):25–51, 2015; Lyttle et al. in Biol Cybern 111(1):25–47, 2017). We established in (Wang et al. in SIAM J Appl Dyn Syst 20(2):701–744, 2021. https://doi.org/10.1137/20M1344974) the tools for studying combined shape and timing responses of limit cycle systems under sustained perturbations and here apply them to study robustness of the neuromechanical model against increased mechanical load during swallowing. Interestingly, we discover that nonlinear biomechanical properties confer resilience by immediately increasing resistance to applied loads. In contrast, the effect of changed sensory feedback signal is significantly delayed by the firing rates’ hard boundary properties. Our analysis suggests that sensory feedback contributes to robustness in swallowing primarily by shifting the timing of neural activation involved in the power stroke of the motor cycle (retraction). This effect enables the system to generate stronger retractor muscle forces to compensate for the increased load, and hence achieve strong robustness. The approaches that we are applying to understanding a neuromechanical model in Aplysia, and the results that we have obtained, are likely to provide insights into the function of other motor systems that encounter changing mechanical loads and hard boundaries, both due to mechanical and neuronal firing properties.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Spatiotemporal pattern detection, generation, and computation with circuits

Abstract Implementations of neurons, delays, and synapse circuits are presented with simulations. These neural elements are used to create two small spiking neural networks, the Rate-Window and Order-Biased clusters, which are capable of detecting simple two-spike spatiotemporal patterns. A simple pattern detecting network (SPDN) is created by combining the Rate-Window and Order-Biased clusters, where clusters are small spiking neural networks, and its simple pattern detection ability is demonstrated in simulation. The SPDN is used to implement a complex pattern detecting network (CPDN) and its complex pattern detection ability is demonstrated in simulation. Methods for generating arbitrary spatiotemporal patterns are presented. The CPDN and spatiotemporal pattern generation methods are then used to implement a novel spatiotemporal computing paradigm based on detecting and responding to spatiotemporal symbols. A simulation of a spatiotemporal half adder is presented to demonstrate the computing paradigm.

97 - MATHEMATICS AND COMPUTING↗
DOE OSTI2021

Correlated conformational dynamics of the human GluN1-GluN2A type N-methyl-D-aspartate (NMDA) receptor

N-Methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels found in the nerve cell membranes. As a result of overexcitation of NMDARs, neuronal death occurs and may lead to diseases such as epilepsy, stroke, Alzheimer’s disease, and Parkinson’s disease. In this study, human GluN1- GluN2A type NMDAR structure is modeled based on the X-ray structure of the Xenopus laevis template and missing loops are added by ab-initio loop modeling. The final structure is chosen according to two different model assessment scores. To be able to observe the structural changes upon ligand binding, glycine and glutamate molecules are docked into the corresponding binding sites of the receptor. Subsequently, molecular dynamics simulations of 1.3 μs are performed for both apo and ligand-bound structures. Structural parameters, which have been considered to show functionally important changes in previous NMDAR studies, are monitored as conformational rulers to understand the dynamics of the conformational changes. Moreover, principal component analysis (PCA) is performed for the equilibrated part of the simulations. Additionally, from these analyses, the differences in between apo and ligand-bound simulations can be summarized as the following: The girdle right at the beginning of the pore loop, which connects M2 and M3 helices of the ion channel, partially opens. Ligands act like an adhesive for the ligand-binding domain (LBD) by keeping the bi-lobed structure together and consequently this is reflected to the overall dynamics of the protein as an increased correlation of the LBD with especially the amino-terminal domain (ATD) of the protein.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Morphological Changes in the Retina Under Conditions of Experimental In Vivo Regional Ischemia/Reperfusion

Two models of retinal ischemia/reperfusion were developed in an experiment on rats and structural changes in eye tissues in the early and late postischemic periods were studied. Ischemia/reperfusion was modeled by elevation of intraocular pressure to 110 mm Hg for 30 min with air injection into the anterior chamber of the eye with a special device or subconjunctival administration of 0.2 ml 4×10{sup –6} M endothelin-1. Morphological studies of the retina of enucleated eyes were performed in 3, 7, and 30 days after ischemia/reperfusion. In 3 days, signs of retinal ischemia were seen (retinal edema and ganglion cell damage). In the late post-ischemic period (30 days), atrophy of the outer nuclear and outer plexiform layer of the retina was observed in animals with retinal ischemia/reperfusion caused by intraocular pressure elevation and complete destruction of neuronal cells was found after administration of endothelin-1.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Possible Superconductivity in the Brain

The unprecedented power of the brain suggests that it may process information quantum-mechanically. Since quantum processing is already achieved in superconducting quantum computers, it may imply that superconductivity is the basis of quantum computation in the brain too. Superconductivity could also be responsible for long-term memory. Following these ideas, the paper reviews the progress in the search for superconductors with high critical temperature and tries to answer the question about the superconductivity in brain. It focuses on recent electrical measurements of brain slices, in which graphene was used as a room-temperature quantum mediator, and argues that these measurements could be interpreted as providing evidence of superconductivity in the neural network of mammalian brains. The estimated critical temperature of superconducting network in the brain is rather high, 2022 ± 157 K. A similar critical temperature was predicted in the Little’s model for one-dimensional organic chains linked to certain molecular complexes. A reasonable suggestion is that superconductivity develops in microtubules inside the neurons of the brain.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2018

Non-convex Multi-species Hopfield Models

In this work we introduce a multi-species generalization of the Hopfield model for associative memory, where neurons are divided into groups and both inter-groups and intra-groups pair-wise interactions are considered, with different intensities. Thus, this system contains two of the main ingredients of modern deep neural-network architectures: Hebbian interactions to store patterns of information and multiple layers coding different levels of correlations. The model is completely solvable in the low-load regime with a suitable generalization of the Hamilton–Jacobi technique, despite the Hamiltonian can be a non-definite quadratic form of the Mattis magnetizations. The family of multi-species Hopfield model includes, as special cases, the 3-layers Restricted Boltzmann Machine with Gaussian hidden layer and the Bidirectional Associative Memory model.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2018

Methyl esters of 2-aminotetrahydrobenzothiophene-3-carboxylic acids decorated with trifluoromethyl-containing heterocycles

Methyl 2-aminothiophene-3-carboxylates were modified with trifluoromethyl-containing five-membered heterocycles by cyclocondensation of methyl trifluoropyruvate N-thiophen-2-ylimines with 1,3-N,N-binucleophiles (2-aminothiazoline and benzamidines) to obtain the corresponding 5-oxo-6-trifluoromethyl-2,3,5,6-tetrahydroimidazoles and 5-oxo-2-phenyl-4-trifluoromethyl-4,5-dihydro-1H-imidazoles. Radioligand binding was used to study the in fluence of the synthesized compounds on the neuronal NMDA receptors.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2025

Evaluation of normalization strategies for mass spectrometry-based multi-omics datasets

Introduction Data normalization is crucial for multi-omics integration, reducing systematic errors and maximizing the likelihood of discovering true biological variation. Most studies assess normalization for a single omics type or use datasets from separate experiments. Few address time-course data, where normalization might bias temporal differentiation. In this study, we compared common normalization methods and a machine learning approach, Systematical Error Removal using Random Forest (SERRF), using multi-omics datasets generated from the same experiment—even from the same cell lysate. Objectives To develop a straightforward process to assess normalization effects and identify the most robust methods across multi-omics datasets. Methods We analyzed metabolomics, lipidomics, and proteomics datasets from primary human cardiomyocytes and motor neurons exposed to acetylcholine-active compounds over time. Normalization effectiveness was evaluated based on improvement in QC features consistency and observing the change in treatment and time-related variance. Results Probabilistic Quotient Normalization (PQN) and Locally Estimated Scatterplot Smoothing (LOESS) QC were identified as optimal for metabolomics and lipidomics, while PQN, Median, and LOESS normalization excelled for proteomics. These methods consistently enhanced QC feature consistency in metabolomics and lipidomics, and preserved time-related variance or treatment-related variance in proteomics, demonstrating their effectiveness and robustness. SERRF normalization, applied only to metabolomics in this study, outperformed other methods in some datasets but inadvertently masked treatment-related variance in others. Conclusion Our evaluation identified PQN and LoessQC as the top methods for metabolomics and lipidomics, and PQN, Median, and Loess normalization for proteomics, in multi-omics integration in a temporal study.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

On-Chip Spyhole Nanoelectrospray Ionization Mass Spectrometry for Sensitive Biomarker Detection in Small Volumes

A polyimide microfluidic chip with a microhole emitter (Ø 10–12 μm) created on top of a microchannel by scanning laser ablation has been designed for nanoelectrospray ionization (spyhole-nanoESI) to couple microfluidics with mass spectrometry. The spyhole-nanoESI showed higher sensitivity compared to standard ESI and microESI from the end of the microchannel. The limits of detection (LOD) for peptide with the spyhole-nanoESI MS reached 50 pM, which was 600 times lower than that with standard ESI. The present microchip emitter allows the analysis of small volumes of samples. As an example, a small cell lung cancer biomarker, neuron-specific enolase (NSE), was detected by monitoring the transition of its unique peptide with the spyhole-nanoESI MS/MS. NSE at 0.2 nM could be well identified with a signal to noise ratio (S/N) of 50, and thereby its LOD was estimated to be 12 pM. The potential application of the spyhole-nanoESI MS/MS in cancer diagnosis was further demonstrated with the successful detection of 2 nM NSE from 1 μL of human serum. Before the detection, the serum sample spiked with NSE was first depleted with immune spin column, then desalted by centrifugal filter device, and finally digested by trypsin, without any other complicated preparation steps. The concentration matched the real condition of clinical samples. In addition, the microchips can be disposable to avoid any cross contamination. The present technique provides a highly efficient way to couple microfluidics with MS, which brings additional values to various microfluidics and MS-based analysis. .

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2019

Metal Ion Binding to the Amyloid β Monomer Studied by Native Top-Down FTICR Mass Spectrometry

Native top-down mass spectrometry is a fast, robust biophysical technique that can provide molecular-scale information on the interaction between proteins or peptides and ligands, including metal cations. Here we have analyzed complexes of the full-length amyloid β (1-42) monomer with a range of (patho)physiologically relevant metal cations using native Fourier transform ion cyclotron resonance mass spectrometry and three different fragmentation methods—collision-induced dissociation, electron capture dissociation, and infrared multiphoton dissociation—all yielding consistent results. Amyloid β is of particular interest as its oligomerization and aggregation are major events in the etiology of Alzheimer’s disease, and it is known that interactions between the peptide and bioavailable metal cations have the potential to significantly damage neurons. Those metals which exhibited the strongest binding to the peptide (Cu{sup 2+}, Co{sup 2+}, Ni{sup 2+}) all shared a very similar binding region containing two of the histidine residues near the N-terminus (His6, His13). Notably, Fe{sup 3+} bound to the peptide only when stabilized toward hydrolysis, aggregation, and precipitation by a chelating ligand, binding in the region between Ser8 and Gly25. We also identified two additional binding regions near the flexible, hydrophobic C-terminus, where other metals (Mg{sup 2+}, Ca{sup 2+}, Mn{sup 2+}, Na{sup +}, and K{sup +}) bound more weakly—one centered on Leu34, and one on Gly38. Unexpectedly, collisional activation of the complex formed between the peptide and [Co{sup III}(NH{sub 3}){sub 6}]{sup 3+} induced gas-phase reduction of the metal to Co{sup II}, allowing the peptide to fragment via radical-based dissociation pathways. This work demonstrates how native mass spectrometry can provide new insights into the interactions between amyloid β and metal cations. .

74 ATOMIC AND MOLECULAR PHYSICS↗