Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “Adult”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 361 records · Page 20
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Metabolomic profiles are reflective of hypoxia-induced insulin resistance during exercise in healthy young adult males

Hypoxia-induced insulin resistance appears to suppress exogenous glucose oxidation during metabolically matched aerobic exercise during acute (<8 h) high-altitude (HA) exposure. However, a better understanding of this metabolic dysregulation is needed to identify interventions to mitigate these effects. The objective of this study was to determine if differences in metabolomic profiles during exercise at sea level (SL) and HA are reflective of hypoxia-induced insulin resistance. Native lowlanders ( n = 8 males) consumed 145 g (1.8 g/min) of glucose while performing 80-min of metabolically matched treadmill exercise at SL (757 mmHg) and HA (460 mmHg) after 5-h exposure. Exogenous glucose oxidation and glucose turnover were determined using indirect calorimetry and dual tracer technique ([ 13 C]glucose and [6,6- 2 H 2 ]glucose). Metabolite profiles were analyzed in serum as change (Δ), calculated by subtracting postprandial/exercised state SL (ΔSL) and HA (ΔHA) from fasted, rested conditions at SL. Compared with SL, exogenous glucose oxidation, glucose rate of disappearance, and glucose metabolic clearance rate (MCR) were lower ( P < 0.05) during exercise at HA. One hundred and eighteen metabolites differed between ΔSL and ΔHA ( P < 0.05, Q < 0.10). Differences in metabolites indicated increased glycolysis, tricarboxylic acid cycle, amino acid catabolism, oxidative stress, and fatty acid storage, and decreased fatty acid mobilization for ΔHA. Branched-chain amino acids and oxidative stress metabolites, Δ3-methyl-2-oxobutyrate ( r = -0.738) and Δγ-glutamylalanine ( r = -0.810), were inversely associated ( P < 0.05) with Δexogenous glucose oxidation. Δ3-Hydroxyisobutyrate ( r = -0.762) and Δ2-hydroxybutyrate/2-hydroxyisobutyrate ( r = -0.738) were inversely associated ( P < 0.05) with glucose MCR. Coupling global metabolomics and glucose kinetic data suggest that the underlying cause for diminished exogenous glucose oxidative capacity during aerobic exercise is acute hypoxia-mediated peripheral insulin resistance.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Age, vascular disease, and Alzheimer’s disease pathologies in amyloid negative elderly adults

Background: We recently reported that CSF phosphorylated tau (p-Tau 181 ) relative to Aβ 40 (CSF p-Tau/Aβ 40 ratio) was less noisy and increased associations with Alzheimer’s disease (AD) biomarkers compared to CSF p-Tau 181 alone. While elevations of CSF p-Tau/Aβ 40 can occur in amyloid-β (Aβ) negative (Aβ-) individuals, the factors associated with these elevations and their role in neurodegeneration and cognitive decline are unknown. We aim to explore factors associated with elevated tau in CSF, and how these elevated tau are related to neurodegeneration and cognitive decline in the absence of Aβ positivity. Methods: We examined relationships between CSF p-Tau/Aβ 40 , and CSF Aβ 42 /Aβ 40 , Aβ PET, and white matter hyperintensities (WMH) as well as vascular risk factors in 149 cognitively unimpaired and 52 impaired individuals who were presumably not on the Alzheimer’s disease (AD) pathway due to negative Aβ status on both CSF and PET. Subgroups had 18 F-fluorodeoxyglucose (FDG) PET and adjusted hippocampal volume (aHCV), and longitudinal measures of CSF, aHCV, FDG PET, and cognition data, so we examined CSF p-Tau/Aβ 40 associations with these measures as well. Results: Elevated CSF p-Tau/Aβ 40 was associated with older age, male sex, greater WMH, and hypertension as well as a pattern of hippocampal atrophy and temporoparietal hypometabolism characteristic of AD. Lower CSF Aβ 42 /Aβ 40 , higher WMH, and hypertension but not age, sex, Aβ PET, APOE-ε4 status, body mass index, smoking, and hyperlipidemia at baseline predicted CSF p-Tau/Aβ 40 increases over approximately 5 years of follow-up. The relationship between CSF p-Tau/Aβ 40 and subsequent cognitive decline was partially or fully explained by neurodegenerative measurements. Conclusions: These data provide surprising clues as to the etiology and significance of tau pathology in the absence of Aβ. It seems likely that, in addition to age, both cerebrovascular disease and subthreshold levels of Aβ are related to this tau accumulation. Crucially, this phenotype of CSF tau elevation in amyloid-negative individuals share features with AD such as a pattern of metabolic decline and regional brain atrophy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Metaproteomics reveals persistent and phylum-redundant metabolic functional stability in adult human gut microbiomes of Crohn’s remission patients despite temporal variations in microbial taxa, genomes, and proteomes

The gut microbiome plays a fundamental role in the human host’s overall health by contributing key biological functions such as expanded metabolism and pathogen defense/immune control. In a healthy individual, the gut microbiome co-exists within the human host in a symbiotic, non-inflammatory relationship that enables mutual benefits, such as microbial degradation of indigestible food products into small molecules that the host can utilize, and enhanced pathogen defense. In abnormal conditions, such as Crohn’s disease, this favorable metabolic relationship breaks down and a variety of undesirable activities result, including chronic inflammation and other health-related issues. It has been difficult, however, to elucidate the overall functional characteristics of this relationship because the microbiota can vary substantially in composition for healthy humans and possibly even more in individuals with gut disease conditions such as Crohn’s disease. Overall, this suggests that microbial membership composition may not be the best way to characterize a phenotype. Alternatively, it seems to be more informative to examine and characterize the functional composition of a gut microbiome. Towards that end, this study examines 25 metaproteomes measured in several Crohn’s disease patients’ post-resection surgery across the course of 1 year, in order to examine persistence of microbial taxa, genes, proteins, and metabolic functional distributions across time in individuals whose microbiome might be more variable due to the gut disease condition. As a result, the measured metaproteomes were highly personalized, with all the temporally-related metaproteomes clustering most closely by individual. In general, the metaproteomes were remarkably distinct between individuals and to a lesser extent within individuals. This prompted a need to characterize the metaproteome at a higher functional level, which was achieved by annotating identified protein groups with KEGG orthologous groups to infer metabolic modules. At this level, similar and redundant metabolic functions across multiple phyla were observed across time and between individuals. Tracking through these various metabolic modules revealed a clear path from carbohydrate, lipid, and amino acid degradation to central metabolism and finally the production of fermentation products. In conclusion, the human gut metaproteome can vary quite substantially across time and individuals. However, despite substantial intra-individual variation in the metaproteomes, there is a clear persistence of conserved metabolic functions across time and individuals. Additionally, the persistence of these core functions is redundant across multiple phyla but is not always observable in the same sample. Finally, the gut microbiome’s metabolism is not driven by a set of discrete linear pathways but a web of interconnected reactions facilitated by a network of enzymes that connect multiple molecules across multiple pathways.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Improved accuracy of S-value-based dosimetry: a guide to transition from Cristy–Eckerman to ICRP adult phantoms

Background: In 2016, the International Commission on Radiological Protection (ICRP) published the results of Monte Carlo simulations performed using updated and anatomically realistic voxelized phantoms. The resulting specific absorbed fractions are based on more realistic human anatomy than those computed in the stylized, geometrical Cristy–Eckerman (CE) phantom. Despite this development, the ICRP-absorbed fractions have not been widely adopted for radiopharmaceutical dosimetry. To help make the transition, we have established a correspondence between source and target tissues defined in the CE phantom and those defined in the ICRP phantoms. Results: The ICRP phantom has 79 source regions and 43 target regions in comparison with the 23 source and 18 target tissue regions defined in the CE phantom. The ICRP phantom provides tissue regions with greater anatomical detail. Some of this additional detail is focused on radiation protection and dosimetry of inhaled/ingested radioactivity. Some, but not all, of this detail is useful and appropriate for radiopharmaceutical therapy. We have established the correspondence between CE and ICRP phantom source and target regions and attempted to highlight the ICRP source tissues relevant to radiopharmaceutical therapy (RPT). This paper provides tables and figures highlighting the correspondences established. Conclusion: The results provide assistance in transitioning from CE-stylized phantoms to the anatomically accurate voxelized ICRP phantoms. It provides specific guidance for porting the total absorbed activity for regions as defined in the CE phantom to regions within the ICRP phantoms.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2016

Dynamic PET Measures of Tau Accumulation in Cognitively Normal Older Adults and Alzheimer’s Disease Patients Measured Using [18F] THK-5351

Background [ 18F]THK5351, a recently-developed positron emission tomography (PET) tracer for measuring tau neurofibrillary tangle accumulation, may help researchers examine aging, disease, and tau pathology in living human brains. We examined THK5351 tracer pharmacokinetics to define an optimal acquisition time for static late images. Methods Primary measurements were calculation of regional values of distribution volume ratios (DVR) and standardized uptake value ratios (SUVR) in 6 healthy older control and 10 Alzheimer’s disease (AD) participants. We examined associations between DVR and SUVR, searching for a 20 min SUVR time window that was stable and comparable to DVR. We additionally examined diagnostic group differences in this 20 min SUVR. Results In healthy controls, [18F]THK5351 uptake was low, with increased temporal relative to frontal binding. In AD, regional uptake was substantially higher than in healthy controls, with temporal exceeding frontal binding. Retention in cerebellar gray matter, which was used as the reference region, was low compared to other regions. Both DVR and SUVR values showed minimal change over time after 40 min. SUVR 20–40, 30–50, and 40–60 min were most consistently correlated with DVR; SUVR 40–60 min, the most stable time window, was used in further analyses. Significant (AD > healthy control) group differences existed in temporoparietal regions, with marginal medial temporal differences. We found high basal ganglia SUVR 40–60 min signal, with no group differences. Conclusions We examined THK5351, a new PET tracer for measuring tau accumulation, and compared multiple analysis methods for quantifying regional tracer uptake. SUVR 40–60 min performed optimally when examining 20 min SUVR windows, and appears to be a practical method for quantifying relative regional tracer retention. The results of this study offer clinical potential, given the usefulness of THK5351-PET as a biomarker of tau pathology in aging and disease.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

The ASSIST trial: Acute effects of manipulating strength exercise volume on insulin sensitivity in obese adults: A protocol for a randomized controlled, crossover, clinical trial

Type 2 diabetes mellitus is a disease in which insulin action is impaired, and an acute bout of strength exercise can improve insulin sensitivity. Current guidelines for strength exercise prescription suggest that 8 to 30 sets could be performed, although it is not known how variations in exercise volume impact insulin sensitivity. Additionally, this means an almost 4-fold difference in time commitment, which might directly impact an individual’s motivation and perceived capacity to exercise. This study will assess the acute effects of high- and low-volume strength exercise sessions on insulin sensitivity. After being thoroughly familiarized, 14 obese individuals of both sexes (>40 year old) will undergo 3 random experimental sessions, with a minimum 4-day washout period between them: a high-volume session (7 exercises, 3 sets per exercise, 21 total sets); a low-volume session (7 exercises, 1 set per exercise, 7 total sets); and a control session, where no exercise will be performed. Psychological assessments (feeling, enjoyment, and self-efficacy) will be performed after the sessions. All sessions will be held at night, and the next morning, an oral glucose tolerance test will be performed in a local laboratory, from which indexes of insulin sensitivity will be derived. We believe this study will aid in strength exercise prescription for individuals who claim not to have time to exercise or who perceive high-volume strength exercise intimidating to adhere to. This trial was prospectively registered.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Quantifying neural information content: a case study of the impact of hippocampal adult neurogenesis

Neural networks have an intrinsic information content encapsulated by neural firing behaviors and constituted by their neural encoding. Shannon entropy is a fundamental method to quantize the amount of information in a variety of sources such as communication channels. Many approaches have been devised to apply this sort of information measure to neurons with mixed success. However, doing so typically requires knowledge of the firing behavior probability distributions for the neurons of interest (whether modeled or recordings), and furthermore often is only applicable for single neurons and not ensembles. We have observed that conventional compression methods may help overcome some of the limiting factors of standard techniques and allows us to approximate information in neural data. To do so we have used compressibility as a measure of complexity in order to estimate entropy to quantitatively assess information content of neural ensembles.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2013

Mechanisms Underlying CD4+ Treg Immune Regulation in the Adult: From Experiments to Models

To maintain immunological balance the organism has to be tolerant to self while remaining competent to mount an effective immune response against third-party antigens. An important mechanism of this immune regulation involves the action of regulatory T-cell (Tregs). In this mini-review, we discuss some of the known and proposed mechanisms by which Tregs exert their influence in the context of immune regulation, and the contribution of mathematical modeling for these mechanistic studies. These models explore the mechanisms of action of regulatory T cells, and include hypotheses of multiple signals, delivered through simultaneous antigen-presenting cell (APC) conjugation; interaction of feedback loops between APC, Tregs, and effector cells; or production of specific cytokines that act on effector cells. As the field matures, and competing models are winnowed out, it is likely that we will be able to quantify how tolerance-inducing strategies, such as CD4-blockade, affect T-cell dynamics and what mechanisms explain the observed behavior of T-cell based tolerance.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Viral Envelope Evolution in Simian–HIV-Infected Neonate and Adult-Dam Pairs of Rhesus Macaques

We recently demonstrated that Simian–HIV (SHIV)-infected neonate rhesus macaques (RMs) generated heterologous HIV-1 neutralizing antibodies (NAbs) with broadly-NAb (bNAb) characteristics at a higher frequency compared with their corresponding dam. Here, we characterized genetic diversity in Env sequences from four neonate or adult/dam RM pairs: in two pairs, neonate and dam RMs made heterologous HIV-1 NAbs; in one pair, neither the neonate nor the dam made heterologous HIV-1 NAbs; and in another pair, only the neonate made heterologous HIV-1 NAbs. Phylogenetic and sequence diversity analyses of longitudinal Envs revealed that a higher genetic diversity, within the host and away from the infecting SHIV strain, was correlated with heterologous HIV-1 NAb development. We identified 22 Env variable sites, of which 9 were associated with heterologous HIV-1 NAb development; 3/9 sites had mutations previously linked to HIV-1 Env bNAb development. These data suggested that viral diversity drives heterologous HIV-1 NAb development, and the faster accumulation of viral diversity in neonate RMs may be a potential mechanism underlying bNAb induction in pediatric populations. Moreover, these data may inform candidate Env immunogens to guide precursor B cells to bNAb status via vaccination by the Env-based selection of bNAb lineage members with the appropriate mutations associated with neutralization breadth.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

The connectome of the adult Drosophila mushroom body provides insights into function

Making inferences about the computations performed by neuronal circuits from synapse-level connectivity maps is an emerging opportunity in neuroscience. The mushroom body (MB) is well positioned for developing and testing such an approach due to its conserved neuronal architecture, recently completed dense connectome, and extensive prior experimental studies of its roles in learning, memory, and activity regulation. Here, we identify new components of the MB circuit in Drosophila , including extensive visual input and MB output neurons (MBONs) with direct connections to descending neurons. We find unexpected structure in sensory inputs, in the transfer of information about different sensory modalities to MBONs, and in the modulation of that transfer by dopaminergic neurons (DANs). We provide insights into the circuitry used to integrate MB outputs, connectivity between the MB and the central complex and inputs to DANs, including feedback from MBONs. Our results provide a foundation for further theoretical and experimental work.

Li, Feng↗