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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 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Distinct expression patterns of Flk1 and Flt1 in the coronary vascular system during development and after myocardial infarction

Highlights: • Flk1 is expressed in ECs with an epicardial-to-endocardial transmural gradient. • Flt1 is homogeneously expressed in ECs in neonatal and adult mouse hearts. • Flk1 is transiently induced but Flt1 is maintained in coronary vessels after MI. • The kinetics of Flk1 and Flt1 after MI recapitulates that in cardiac development. The coronary vascular system is critical for myocardial growth and cardiomyocyte survival. However, the molecular mechanism regulating coronary angiogenesis remains elusive. Vascular endothelial growth factor (VEGF) regulates angiogenesis by binding to the specific receptors Flk1 and Flt1, which results in different functions. Despite the importance of Flk1 and Flt1, their expression in the coronary vasculature remains largely unknown due to the lack of appropriate antibodies for immunostaining. Here, we analyzed multiple reporter mice including Flk1-GFP BAC transgenic (Tg), Flk1-LacZ knock-in, Flt1-DsRed BAC Tg, and Flk1-GFP/Flt1-DsRed double Tg animals to determine expression patterns in mouse hearts during cardiac growth and after myocardial infarction (MI). We found that Flk1 was expressed in endothelial cells (ECs) with a pattern of epicardial-to-endocardial transmural gradients in the neonatal mouse ventricle, which was downregulated in adult coronary vessels with development. In contrast, Flt1 was homogeneously expressed in the ECs of neonatal mouse hearts and expression was maintained until adulthood. After MI, expression of both Flk1 and Flt1 was induced in the regenerating coronary vessels at day 7. Intriguingly, Flk1 expression was downregulated thereafter, whereas Flt1 expression was maintained in the newly formed coronary vessels until 30 days post-MI, recapitulating their expression kinetics during development. This is the first report demonstrating the spatiotemporal expression patterns of Flk1 and Flt1 in the coronary vascular system during development and after MI; thus, this study suggests that these factors have distinct and important functions in coronary angiogenesis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

CoolPINNs: A physics-informed neural network modeling of active cooling in vascular systems

Emerging technologies like hypersonic aircraft, space exploration vehicles, and batteries avail fluid circulation in embedded microvasculatures for efficient thermal regulation. Modeling is vital during the design and operational phases of these engineered systems. However, many challenges exist in developing a modeling framework. What is lacking is an accurate framework that (i) captures sharp jumps in the thermal flux across complex vasculature layouts, (ii) deals with oblique derivatives (involving tangential and normal components), (iii) handles nonlinearity because of radiative heat transfer, (iv) provides a high-speed forecast for real-time monitoring, and (v) facilitates robust inverse modeling. Here, this paper addresses these challenges by availing the power of physics-informed neural networks (PINNs). We develop a fast, reliable, and accurate Scientific Machine Learning (SciML) framework for vascular-based thermal regulation—called CoolPINNs: a PINNs-based modeling framework for active cooling. The proposed mesh-less framework elegantly overcomes all the mentioned challenges. The significance of the reported research is multi-fold. First, the framework is valuable for real-time monitoring of thermal regulatory systems because of rapid forecasting. Second, researchers can address complex thermoregulation designs since the approach is meshless. Finally, the framework facilitates systematic parameter identification and inverse modeling studies, perhaps the most significant utility of the current framework.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2022

Single-nuclei transcriptome analysis of the shoot apex vascular system differentiation in Populus

ABSTRACT Differentiation of stem cells in the plant apex gives rise to aerial tissues and organs. Presently, we lack a lineage map of the shoot apex cells in woody perennials – a crucial gap considering their role in determining primary and secondary growth. Here, we used single-nuclei RNA-sequencing to determine cell type-specific transcriptomes of the Populus vegetative shoot apex. We identified highly heterogeneous cell populations clustered into seven broad groups represented by 18 transcriptionally distinct cell clusters. Next, we established the developmental trajectories of the epidermis, leaf mesophyll and vascular tissue. Motivated by the high similarities between Populus and Arabidopsis cell population in the vegetative apex, we applied a pipeline for interspecific single-cell gene expression data integration. We contrasted the developmental trajectories of primary phloem and xylem formation in both species, establishing the first comparison of vascular development between a model annual herbaceous and a woody perennial plant species. Our results offer a valuable resource for investigating the principles underlying cell division and differentiation conserved between herbaceous and perennial species while also allowing us to examine species-specific differences at single-cell resolution.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

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↗
DOE OSTI2017

Fibroblast growth factor 21 plays an inhibitory role in vascular calcification in vitro through OPG/RANKL system

Vascular calcification is prevalent and associated with adverse outcome without available therapy. The benefits of fibroblast growth factor (FGF)-21 on metabolism and atherosclerosis make it a promising therapeutic agent for vascular calcification. We investigated the effects of FGF21 on vascular smooth muscle cell (VSMC) calcification by culturing rat VSMCs in a calcifying medium for 9days. FGF21 markedly attenuated mineral deposition and apoptosis at the indicated time points. In the presence of FGF21, the expression levels of osteoblastic protein including bone morphogenic protein-2, alkaline phosphatase(ALP), runt-related transcription factor(RUNX)-2 and nuclear factor-kappa B ligand (RANKL) were down-regulated, whereas the expression of osteoprotegerin (OPG) increased. Knockdown of OPG significantly impaired inhibition of FGF21 on apoptosis and the expression of pro-apoptotic genes including caspase-3 and Bax and osteoblastic –promoting markers including ALP, RUNX-2 and RANKL. Furthermore, FGF21 facilitated the phosphoryl of AKT but suppressed P38, while OPG knockdown attenuated the effects. LY29400 (inhibitor of PI3K) abrogated the activation of PI3K/AKT and SB203580 (inhibitor of P38) abolished the inhibition of FGF21 on P38, while alteration was observed in the expression of RUNX-2. FGF21 inhibited VSMCs calcification via OPG/RANKL system, and through P38 andPI3K/AKT pathways. - Highlights: • The article concerns the effect of FGF21 in regulating vascular calcification and the mechanisms involved. • The dataset provides insights into effect of FGF21. • The data is useful for exploring the pathogenesis and treatment of vascular calcification.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

MVP™ Micro Vascular Plug Systems for the Treatment of Pulmonary Arteriovenous Malformations

Purpose: To describe our institutional experience with MVP™ micro vascular plug systems for the treatment of pulmonary arteriovenous malformations (PAVMs). Materials and Methods: We performed a retrospective medical record review of 52 patients with 119 PAVMs treated exclusively with MVP™ systems (69 procedures/153 MVP™ systems) between July 2014 and July 2018. All patients had PAVMs with feeding artery diameters ≥ 2 mm. MVP™ systems were deployed according to physician preference. We collected patient demographic information; procedural data (including size of feeding artery, size and number of embolics used per PAVM, fluoroscopy time, contrast administration), technical success rates, complications, and persistence. Persistence was assessed using computed tomography angiography (CTA) performed 1–3 months and 3–5 years after embolization per clinical protocol. Results: All procedures were technically successful without major complications. Mean feeding artery diameter was 3.3 ± 1.2 mm. Mean fluoroscopy time per procedure and contrast volume administered per procedure were 35 ± 16 min and 217 ± 101 mL, respectively. A mean of 1.3 ± 0.8 MVP™ systems was used per PAVM. There were no instances of persistence during a mean follow-up time of 328 ± 258 days (range 26 to 914 days). Conclusions: For PAVMs with feeding artery diameters of 2 to 7.9 mm (mean 3.3 ± 1.2 mm), MVP™ systems are safe and effective given their high technical success rates and lack of persistence. Further prospective work will be required to elucidate the advantages and disadvantages of these MVP™ systems for PAVM embolization. Level of Evidence: Level III.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Aluminum exposure for one hour decreases vascular reactivity in conductance and resistance arteries in rats

Aims: Aluminum (Al) is an important environmental contaminant; however, there are not enough evidences of Al-induced cardiovascular dysfunction. We investigated the effects of acute exposure to aluminum chloride (AlCl{sub 3}) on blood pressure, vascular reactivity and oxidative stress. Methods and results: Male Wistar rats were divided into two groups: Untreated: vehicle (ultrapure water, ip) and AlCl{sub 3}: single dose of AlCl{sub 3} (100 mg/kg,ip). Concentration-response curves to phenylephrine in the absence and presence of endothelium, the nitric oxide synthase inhibitor L-NAME, the potassium channel blocker tetraethylammonium, and the NADPH oxidase inhibitor apocynin were performed in segments from aortic and mesenteric resistance arteries. NO released was assessed in aorta and reactive oxygen species (ROS), malondialdehyde, non-protein thiol levels, antioxidant capacity and enzymatic antioxidant activities were investigated in plasma, aorta and/or mesenteric arteries. After one hour of AlCl{sub 3} exposure serum Al levels attained 147.7 ± 25.0 μg/L. Al treatment: 1) did not affect blood pressure, heart rate and vasodilator responses induced by acetylcholine or sodium nitroprusside; 2) decreased phenylephrine-induced vasoconstrictor responses; 3) increased endothelial modulation of contractile responses, NO release and vascular ROS production from NADPH oxidase; 4) increased plasmatic, aortic and mesenteric malondialdehyde and ROS production, and 5) decreased antioxidant capacity and affected the antioxidant biomarkers non-protein thiol levels, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase enzymatic activities. Conclusion: AlCl{sub 3}-acute exposure reduces vascular reactivity. This effect is associated with increased NO production, probably acting on K{sup +} channels, which seems to occur as a compensatory mechanism against Al-induced oxidative stress. Our results suggest that Al exerts toxic effects to the vascular system. - Highlights: • One hour of aluminum exposure decreases vascular reactivity. • Vascular imbalance after aluminum exposure is related to increased oxidative stress. • Enhanced NO release is the first step against the effects of Al at vascular system.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Pulmonary Arteriovenous Malformations Embolized Using a Micro Vascular Plug System: Technical Note on a Preliminary Experience

AIMTo report our preliminary experience using a Micro Vascular Plug (MVP) deployed through a 2.8Fr micro-catheter for the treatment of pulmonary arteriovenous malformations (PAVMs) in a cohort of patients affected by Hereditary Haemorrhagic Telangiectasia (HHT).Materials and MethodsFour consecutive female patients (mean age 38.0 years; range 25–55 years) with PAVMs diagnosed on echocardiogram/bubble test and contrast-enhanced CT (CECT) underwent MVP embolization. One patient was symptomatic with recent transient ischaemic attack. Follow-up was undertaken at 1-month post-procedure with CECT to assess PAVMs permeability and MVP positioning and at 1-, 6-, and 12-month post-procedure, with echocardiography/bubble test and standard neurological history, to confirm absence of right-to-left shunts and recurrent symptoms.ResultsEight PAVMs were treated in 4 patients over 5 interventional sessions (mean 1.6 PAVMs per session). All PAVMs were simple, with mean feeding artery diameter of 4.25 mm. Eight 6.5 mm MVPs were deployed in total (one per lesion). Technical success was 100%. Mean procedural time and patient dose per session were 70 min (range 40–70 min) and 53418 mGy.cm{sup 2} (range 6113–101628 mGy.cm{sup 2}), respectively. No signs of reperfusion neither of MPV migration were noted at 1-month CECT follow-up. At early follow-up (mean 3.75 months; range 1–12 months), clinical success was 100% with no evidence of recurrent right-to-left shunt, and no neurological symptoms. No immediate or late complications were observed.ConclusionsMVP embolization of PAVMs appears technically feasible, safe, and effective at early follow-up. Further prospective studies are required to confirm long-term safety and efficacy of this promising technique.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Hydraulics in the 21st century

The science of plant hydraulics has long sought to understand the fundamental mechanisms of how water moves through plant 4 vascular systems (Dixon & Joly, 1895). Over the last 50 yr, advances in our understanding of embolism formation (Tyree & 5 Sperry, 1989), hydraulic segmentation (Zimmermann, 1978), and refilling (Sperry et al., 1987) were generated both through novel measurements (Scholander et al., 1965; Sperry et al., 1988; Alder 7 6 et al. 1997) andmodel development (Tyree&Sperry, 1989; Sperry et al., 1998). This knowledge provided a foundation of mechanistic understanding that has impacted fields of study from crop physiology to the global hydrologic cycle (Fig. 1; Sperry et al., 2003; Tang et al., 2015; Peters-Lidard et al., 2019). Scientific advances in our understanding of plant hydraulics and its implications for plant function have arguably accelerated over the last two decades. New empirical (Holbrook et al., 2001; Choat et al., 2015) and modeling (Christoffersen et al., 2016; Sperry et al., 2016; Venturas et al., 2018; Kennedy et al., 2019; Mencuccini 8 et al., 2019) approaches have been applied to tackle some of our largest challenges, and different perspectives have been integrated to better understand the entire vascular system (e.g. carbon 9 metabolismand xylemhydraulics;H€oltt€a et al., 2009; Secchi et al., 2011).

McDowell, Nate G.↗
DOE OSTI2021

Desiccation and rehydration dynamics in the epiphytic resurrection fern Pleopeltis polypodioides

The epiphytic resurrection—or desiccation-tolerant (DT)—fern Pleopeltis polypodioides can survive extreme desiccation and recover physiological activity within hours of rehydration. Yet, how epiphytic DT ferns coordinate between deterioration and recovery of their hydraulic and photosynthetic systems remains poorly understood. We examined the functional status of the leaf vascular system, chlorophyll fluorescence, and photosynthetic rate during desiccation and rehydration of P. polypodioides. Xylem tracheids in the stipe embolized within 3–4 h during dehydration. When the leaf and rhizome received water, tracheids refilled after ~24 h, which occurred along with dramatic structural changes in the stele. Photosynthetic rate and chlorophyll fluorescence recovered to predesiccation values within 12 h of rehydration, regardless of whether fronds were connected to their rhizome. Our data show that the epiphytic DT fern P. polypodioides can utilize foliar water uptake to rehydrate the leaf mesophyll and recover photosynthesis despite a broken hydraulic connection to the rhizome.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

X-ray fluorescence mapping of brain tissue reveals the profound extent of trace element dysregulation in stroke pathophysiology

Abstract The brain is a privileged organ with regard to its trace element composition and maintains a robust barrier system to sequester this specialized environment from the rest of the body and the vascular system. Stroke is caused by loss of adequate blood flow to a region of the brain. Without adequate blood flow ischaemic changes begin almost immediately, triggering an ischaemic cascade, characterized by ion dysregulation, loss of function, oxidative damage, cellular degradation, and breakdown of the barrier that helps maintain this environment. Ion dysregulation is a hallmark of stroke pathophysiology and we observe that most elements in the brain are dysregulated after stroke. X-ray fluorescence-based detection of physiological changes in the neurometallome after stroke reveals profound ion dysregulation within the lesion and surrounding tissue. Not only are most elements significantly dysregulated after stroke, but the level of dysregulation cannot be predicted from a cell-level description of dysregulation. X-ray fluorescence imaging reveals that the stroke lesion retains <25% of essential K+ after stroke, but this element is not concomitantly elevated elsewhere in the organ. Moreover, elements like Na+, Ca2+, and Cl− are vastly elevated above levels available in normal brain tissue (>400%, >200%, and >150%, respectively). We hypothesize that weakening of the blood–brain barrier after stroke allows elements to freely diffuse down their concentration gradient so that the stroke lesion is in equilibrium with blood (and the compartments containing brain interstitial fluid and cerebrospinal fluid). The change observed for the neurometallome likely has consequences for the potential to rescue infarcted tissue, but also presents specific targets for treatment.

Biochemistry & Molecular Biology↗
DOE OSTI2021

BdERECTA controls vasculature patterning and phloem-xylem organization in Brachypodium distachyon

Background: The vascular system of plants consists of two main tissue types, xylem and phloem. These tissues are organized into vascular bundles that are arranged into a complex network running through the plant that is essential for the viability of land plants. Despite their obvious importance, the genes involved in the organization of vascular tissues remain poorly understood in grasses. Results: We studied in detail the vascular network in stems from the model grass Brachypodium distachyon (Brachypodium) and identified a large set of genes differentially expressed in vascular bundles versus parenchyma tissues. To decipher the underlying molecular mechanisms of vascularization in grasses, we conducted a forward genetic screen for abnormal vasculature. We identified a mutation that severely affected the organization of vascular tissues. This mutant displayed defects in anastomosis of the vascular network and uncommon amphivasal vascular bundles. The causal mutation is a premature stop codon in ERECTA, a LRR receptor-like serine/threonine-protein kinase. Mutations in this gene are pleiotropic indicating that it serves multiple roles during plant development. This mutant also displayed changes in cell wall composition, gene expression and hormone homeostasis. Conclusion: In summary, ERECTA has a pleiotropic role in Brachypodium. We propose a major role of ERECTA in vasculature anastomosis and vascular tissue organization in Brachypodium.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Determining the impacts of venoarterial extracorporeal membrane oxygenation on cerebral oxygenation using a one-dimensional blood flow simulator

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a mechanical system that provides rapid and short-term support for patients with cardiac failure. In many patients, pulmonary function is also impaired, resulting in poorly-oxygenated cardiac outflow competing against well-oxygenated VA-ECMO outflow, a condition known as North-South syndrome. North-South syndrome is a primary concern because of its potential to cause cerebral hypoxia, which has a critical influence on neurological complications often seen in this patient population. In order to reduce ischemic neurological complications, it is important to understand how clinical decisions regarding VA-ECMO parameters influence blood oxygenation. In our work, we studied the impacts of flow rate and cannulation site on oxygenation using a one-dimensional (1D) model to simulate blood flow. Our model was initially tested by comparing blood flow results to those observed from experimental work in VA-ECMO patients. The 1D model was combined with a two-phase flow model to simulate oxygenation. Additionally, the influence of various other clinician-tunable parameters on oxygenation in the common carotid arteries (CCAs) were tested, including, blood viscosity, cannula position within the insertion artery, heart rate, and systemic vascular resistance (SVR), as well as geometrical changes such as arterial radius and length. Our results indicated that blood oxygenation to the brain strongly depended on the cannula insertion site and the VA-ECMO flow rate with a weaker but potentially significant dependence on arterial radius. During femoral cannulation, VA-ECMO flow rates greater than ~4.9 L/min were needed to perfuse the CCAs. However, axillary and central cannulation began to perfuse the CCAs at significantly lower flow (~1 L/min). These results may help explain the incidence of cerebral hypoxia in this patient population and the common need to change cannulation strategies during treatment to address this clinical problem. While this work describes patient-averaged results, determining these relationships between VA-ECMO parameters and cerebral hypoxia is an important step towards future work to develop patient-specific models that clinicians can use to improve outcomes.

1D blood flow↗
DOE OSTI2017

Differential gene expression profiling of human adipose stem cells differentiating into smooth muscle-like cells by TGFβ1/BMP4

Regenerative repair of the vascular system is challenging from the perspectives of translational medicine and tissue engineering. There are fundamental hurdles in front of creating bioartificial arteries, which involve recaputilation of the three-layered structure under laboratory settings. Obtaining and maintaining smooth muscle characteristics is an important limitation, as the transdifferentiated cells fail to display mature phenotype. This study aims to shed light on the smooth muscle differentiation of human adipose stem cells (hASCs). To this end, we first acquired hASCs from lipoaspirate samples. Upon characterization, the cells were induced to differentiate into smooth muscle (SM)-like cells using a variety of inducer combinations. Among all, TGFβ1/BMP4 combination had the highest differentiation efficiency, based on immunohistochemical analyses. hSM-like cell samples were compared to hASCs and to the positive control, human coronary artery-smooth muscle cells (hCA-SMCs) through gene transcription profiling. Microarray findings revealed the activation of gene groups that function in smooth muscle differentiation, signaling pathways, extracellular modeling and cell proliferation. Our results underline the effectiveness of the growth factors and suggest some potential variables for detecting the SM-like cell characteristics. Evidence in transcriptome level was used to evaluate the TGFβ1/BMP4 combination as a previously unexplored effector for the smooth muscle differentiation of adipose stem cells. - Highlights: • Human adipose stem cells (hASCs) were isolated, characterized and cultured. • Growth factor combinations were evaluated for their effectiveness in differentiation using IHC. • hASCs were differentiated into smooth muscle (SM)-like cells using TGF-β1 and BMP4 combination. • Microarray analysis was performed for hASCs, SM-like cells and coronary artery-SMCs. • Microarray data was used to perform hierarchical clustering and interpretation of activated pathways.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Chorioallantoic membrane vascularization. A meta-analysis

The CAM is a widely used experimental assay to study angiogenesis, wound healing, tumor growth and metastatic process. In this study, we have analyzed and compared the existent literature data concerning the growth of the CAM. Moreover, we have analyzed the data concerning the development of the vascular system and the expression of the most important pro-angiogenic and anti-angiogenic factors. The availability of these data and their comparative evaluation allow to better analyze the experimental data concerning the testing of different pro-angiogenic and anti-angiogenic molecules, as well as biomaterials in the CAM assay. Moreover, the dynamic of the angiogenic response to different tumor cell lines and or tumor bioptic specimens, may be also better evaluated and estimated.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Cell walls have a new family

Cell walls made mainly of polysaccharides are a distinguishing feature of plants. They play key roles in adaptation today and during pivotal evolutionary events, such as colonization of dry land and development of a water-conducting vascular system. A critical enzyme involved in cell wall biosynthesis has now been identified.

59 BASIC BIOLOGICAL SCIENCES↗