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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 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Transcriptome Analysis of Neisseria gonorrhoeae during Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants between Men and Women

Neisseria gonorrhoeae is a bacterial pathogen responsible for the sexually transmitted infection gonorrhea. Emergence of antimicrobial resistance (AMR) of N. gonorrhoeae worldwide has resulted in limited therapeutic choices for this infection. Men who seek treatment often have symptomatic urethritis; in contrast, gonococcal cervicitis in women is usually minimally symptomatic, but may progress to pelvic inflammatory disease. Previously, we reported the first analysis of gonococcal transcriptome expression determined in secretions from women with cervical infection. Here, we defined gonococcal global transcriptional responses in urethral specimens from men with symptomatic urethritis and compared these with transcriptional responses in specimens obtained from women with cervical infections and in vitro-grown N. gonorrhoeae isolates. This is the first comprehensive comparison of gonococcal gene expression in infected men and women. RNA sequencing analysis revealed that 9.4% of gonococcal genes showed increased expression exclusively in men and included genes involved in host immune cell interactions, while 4.3% showed increased expression exclusively in women and included phage-associated genes. Infected men and women displayed comparable antibiotic-resistant genotypes and in vitro phenotypes, but a 4-fold higher expression of the Mtr efflux pump-related genes was observed in men. These results suggest that expression of AMR genes is programed genotypically and also driven by sex-specific environments. Collectively, our results indicate that distinct N. gonorrhoeae gene expression signatures are detected during genital infection in men and women. We propose that therapeutic strategies could target sex-specific differences in expression of antibiotic resistance genes.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2026

Data for A Role for Differential Rubisco Activase Isoform Expression in C4 Bioenergy Grasses at High Temperature

Rubisco activase (Rca) facilitates the release of sugar-phosphate inhibitors at Rubisco catalytic sites during CO2 fixation. Most plant species express two Rca isoforms, the larger Rca-α and the shorter Rca-β, either by alternative splicing from a single gene or expression from separate genes. The mechanism of Rubisco activation by Rca isoforms has been intensively studied in C3 plants. However, the functional role of Rca in C4 plants where Rubisco and Rca are located in a much higher [CO2] compartment is less clear. In this study, we selected four C4 bioenergy grasses and the model C4 grass setaria ( Setaria viridis ) to investigate the role of Rca in C4 photosynthesis. All five C4 grass species contained two Rca genes, one encoding Rca-α and the other Rca-β, which were positioned closely together in the genomes. A variety of abiotic stress-related motifs were identified in the Rca-α promoter of each grass, and while the Rca-β gene was constantly highly expressed at ambient temperature, Rca-α isoforms were expressed only at high temperature but never surpassed 30% of Rca-β content. The pattern of Rca-α induction on transition to high temperature and reduction on return to ambient temperature was the same in all five C4 grasses. In sorghum ( Sorghum bicolor ), sugarcane ( Saccharum officinarum ), and setaria, the induction rate of Rca-α was similar to the recovery rate of photosynthesis and Rubisco activation at high temperature. This association between Rca-α isoform expression and maintenance of Rubisco activation at high temperature suggests that Rca-α has a functional thermo-protective role in carbon fixation in C4 grasses by sustaining Rubisco activation at high temperature.

Genomics↗
DOE OSTI2025

APOLLO: a facility-scale differentiable virtual accelerator at Fermilab FAST/IOTA

As the design complexity of modern accelerators grows, there is more interest in using advanced simulations that have fast execution time or yield additional insights like gradients. The FAST/IOTA facility has been working on implementing and experimentally validating an end-to-end digital twin that is both fast and gradient-aware, allowing for rapid prototyping of new software and experiments with minimal beam time costs. Our framework integrates physics and ML codes for linac and ring simulation through a set of generic interfaces between surrogate and physics-based sections. To reproduce device inputs and outputs, system state is exposed as a deterministic event loop in a specialized discrete event simulator architecture. Because Fermilab is undergoing control system transition, several APIs were implemented as final user interfaces - a fully asynchronous EPICS soft IOC, a gRPC-based Data Pool Manager (DPM), and legacy ACNET protocols. We discuss implementation details as well as challenges handling live data assimilation and future plans to extend modelling to main complex proton accelerators like PIPII and Booster.

Kuklev, Nikita [Fermilab]↗
DOE OSTI2018

Energy metabolic capacities of human adipose-derived mesenchymal stromal cells in vitro and their adaptations in osteogenic and adipogenic differentiation

Highlights: • Mesenchymal differentiation of adMSC causes adaptations of the energy metabolism. • Mesenchymal differentiation of adMSC comes along with changes in cell proliferation. • Osteogenic differentiation entails an increase of all metabolic pathways tested. • Adipogenic differentiation entails a decreasing capacity of carbohydrate metabolism. • Adipogenic differentiation indicates a shift towards lipid metabolism. Mesenchymal stromal/stem cells (MSC) are important in tissue homeostasis and regeneration due to their ability for self-renewal and multipotent differentiation. Differentiation, as well as proliferation, requires adaptations in the cell metabolism. However, only few data exist concerning the energy metabolism of non-differentiating and differentiating MSC. In this study we compared capacities of major energy metabolic pathways of MSC from human adipose tissue (adMSC) in vitro in the non-differentiated state with those of osteogenically or adipogenically differentiating adMSC. To this end we quantified the proliferation and differentiation status of adMSC and analyzed maximum enzyme capacities and several enzyme isoforms of major energy metabolic pathways regarding their activity and gene expression. We could show that non-differentiating and osteogenic cultivation conditions induced proliferation and showed increasing capacities of the glycolytic marker enzyme phosphofructokinase as well as the marker enzyme of the pentose phosphate pathway glucose-6-phosphate dehydrogenase. Adipogenic stimulation, which was accompanied by the absence of proliferation, reduced the glycolytic capacity (e.g. decreased glyceraldehyde 3-phosphate dehydrogenase capacity) and induced an increase in mitochondrial enzyme capacities. These changes in energy metabolism might represent an adaptation of adMSC to the high energy demand during proliferation and to the specific cellular functions during osteogenic or adipogenic differentiation respectively.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Phospholipase D and phosphatidylinositol-4-phosphate 5-kinase 1 are involved in the regulation of oligodendrocyte morphological differentiation

Highlights: • PLD and PIP5K1 are involved in the regulation of oligodendroglial cell morphological differentiation. • Inhibition of PLD or PIP5K1 decreases differentiation or myelin marker expression. • PLD and PIP5K1 regulate differentiation of oligodendrocyte precursor cells. • Inhibition of PLD or PIP5K1 decreases differentiation marker expression of oligodendrocyte precursor cells. Oligodendroglial cells (oligodendrocytes) differentiate to form the myelin that wraps neuronal axons in the central nervous system (CNS). This myelin sheath supports the propagation of saltatory conduction and protects axons from physical stresses. When oligodendrocytes do not normally differentiate to myelinate axons, their key functions as oligodendrocytes in the CNS are severely impaired. The molecular mechanics that control differentiation still remain to be clarified. Arf6 belongs to the small GTPase family and is known to be a positive regulator of oligodendrocyte differentiation. Here, we show that the phospholipase D (PLD) and phosphatidylinositol-4-phosphate 5-kinase 1 (PIP5K1) molecules, the major effectors of Arf6, are involved in the regulation of oligodendrocyte differentiation. Knockdown of PLD1 or PIP5K type 1γ (PIP5K1C) by their respective specific siRNAs in mouse oligodendroglial FBD-102b cells inhibited morphological differentiation into structures bearing myelin-like processes; this finding is consistent with the concurrent changes in expression of differentiation and myelin marker proteins. Treatment with VU0155069 or UNC3230, specific inhibitors of PLD and PIP5K1, respectively, blunted morphological differentiation and decreased expression of myelin and differentiation marker proteins. Similar results have been obtained in studies using primary oligodendrocytes. These results suggest that the major Arf6 effector molecules PLD and PIP5K1 are among the molecules involved in the regulation of morphological differentiation in oligodendrocytes prior to myelination.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Down-regulation of miR-193a-3p promotes osteoblast differentiation through up-regulation of LGR4/ATF4 signaling

Highlights: • miR-193a-3p was decreased during osteoblast differentiation. • Inhibition of miR-193a-3p promoted osteoblast differentiation. • LRG4 was a target gene of miR-193a-3p. • miR-193a-3p regulates osteoblast differentiation by LGR4/ATF4. Emerging evidence indicates that microRNAs (miRNAs) are crucial regulators of osteoblast differentiation. A previous study has reported that miR-193a-3p expression is altered during the induction of osteoblast differentiation. However, the precise biological function and regulatory mechanism of miR-193a-3p during osteoblast differentiation remains unclear. In this study, we aimed to investigate the precise role and underlying mechanism of miR-193a-3p in regulating osteoblast differentiation. The results showed that miR-193a-3p expression was significantly down-regulated during the induction of osteoblast differentiation. Functional experiments demonstrated that the overexpression of miR-193a-3p impeded osteoblast differentiation while miR-193a-3p inhibition promoted osteoblast differentiation. Bioinformatics analysis and a luciferase assay revealed that leucine-rich repeat-containing G-protein coupled receptor 4 (LGR4), a critical regulator of osteoblast differentiation, was a target gene of miR-193a-3p. We showed that miR-193a-3p negatively regulated the expression of LGR4 and activating transcription factor 4 (ATF4). Moreover, the knockdown of LGR4 or ATF4 significantly reversed the promotion effect of miR-193a-3p inhibition on osteoblast differentiation. Overall, these findings demonstrate that miR-193a-3p regulates osteoblast differentiation by modulating LGR4/ATF4 signaling and suggests that the miR-193a-3p/LGR4/ATF4 regulation axis may play an important role in regulating bone remodeling.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Vibsanin A sensitizes human acute myeloid leukemia cells to tyrosine kinase inhibitor-induced myeloid differentiation via activation of PKC and upregulation of Lyn

Highlights: • Vibsanin A sensitizes AML cells to tyrosine kinase inhibitor (TKI)-induced differentiation. • Both PKC activation and Lyn induction contribute to combination-induced AML cell differentiation. • The combination treatment enhanced the activation of the Raf/MEK/ERK cascade. • Vibsanin A coupled with TKIs may lead to new applications of differentiation-based approaches for AML. Differentiation therapies have been proposed to overcome the impaired cell differentiation in acute myeloid leukemia (AML). However, thus far the all-trans retinoic acid-based differentiation therapy has been the only successful modality in treating acute promyelocytic leukemia. Here, we showed that vibsanin A, a novel protein kinase C (PKC) activator, sensitized AML cells to tyrosine kinase inhibitor (TKI)-induced differentiation. Vibsanin A augmented the ability of TKIs to induce growth inhibition and G1 cell cycle arrest of AML cells. Mechanistically, PKC activation was involved in the differentiation-inducing effects of combining vibsanin A with TKIs. Moreover, we found that vibsanin A enhanced TKI-induced Lyn expression and suppression of Lyn interfered with AML cell differentiation, indicating an essential role for Lyn expression in the combination-induced differentiation. Finally, combining vibsanin A and TKIs enhanced the activation of the Raf/MEK/ERK cascade. Together, this is the first study to evaluate the synergy of vibsanin A and TKIs in AML cell differentiation. Our study lays the foundation in assessing new opportunities for the combination of vibsanin A and TKIs as a promising approach for future differentiation therapy.

60 APPLIED LIFE SCIENCES↗
NASA NTRSDate not supplied

Decision Aid for Conjunction Risk Mitigation by Differential Drag

In the previous five years, the rate of conjunctions that the NASA Conjunction Assessment Risk Analysis (CARA) team processed and analyzed has more than tripled. (NASA CARA, 2024) New missions in the early development phases are now required to plan for dealing with conjunctions under the present space environment, and also projecting forward into a future likely with even further increased utilization of the space environment. Some missions are investigating the possibility of using differential drag to remediate conjunctions without expending limited fuel or for missions without propulsive capabilities. The NASA CARA team studied the historical record of conjunctions to evaluate the circumstances under which differential drag may be successfully applied and have developed a series of tables to use as a decision aid for missions considering differential drag. Currently, if a CARA-protected mission with maneuvering capabilities is predicted to have a conjunction with probability of collision (Pc) greater than 7E-5 (the default value of the ‘yellow threshold’, which may have some other value agreed by CARA and the mission during the Orbital Collison Avoidance Planning (OCAP) process), CARA will use its Maneuver Trade Space (MTS) tool to evaluate and recommend options for the timing and magnitude of a risk mitigation maneuver (RMM), based on the mission’s capabilities. If the conjunction’s Pc is greater than 1E-4, the ‘red threshold’, then an RMM must be executed per NASA Procedural Requirements (NPR) 8079.1 (NASA, 2023), although missions may execute an RMM even if the Pc is lower. The magnitude of the maneuver is typically a few cm/s, and CARA estimates how many will be required for the mission’s nominal lifetime – typically a few per year – during the OCAP process, to inform the mission’s delta-V requirement. For traditional satellites, this is usually smaller than other requirements for orbit insertion, maintenance, and disposal, but for CubeSats or other small satellite missions, a propulsion system may not provide much more than a few cm/s of delta-V or may not fit at all within the available budget of money, time, size, weight, and/or power (SWaP). Conversely, CubeSats often have deployable solar panels, which offer the capacity to have much higher areas facing some directions than others. Such a mission can instead use ‘differential drag’ to remediate a conjunction -- in other words, change its drag area (usually increasing) to deviate from the predicted collision course. This is how Planet’s Dove spacecraft maintain their formations and remediate conjunction risks without having on-board propulsion (Foster, et al., 2017) (Griffith, et al., 2021). CARA has been developing improvements to MTS to support differential-drag for NASA's missions -- where it is effective. CARA records all conjunctions of their protected payloads, with historical records starting in 2005 (with significant conjunction events starting to occur on or after 2013). From this record, approximately 7,300 had a Pc greater than 1E-4 at 3 days prior to the time of closest approach, the time analyzed for differential drag efficacy. Of those, approximately 4,300 had fully-defined covariance matrices stored for both the primary and secondary objects; this set of conjunctions is the basis for the analysis of this work. CARA’s MTS tool was used to propagate the primary satellite forward from that decision point with varying degrees of increase to ballistic coefficient (BC). Because these conjunctions came from multiple missions, the nondimensional ‘delta-BC’ factor was used to quantify and normalize the increase in ballistic coefficient, defined as follows: Delta-BC = BC_new / BC_old - 1 Positive delta-BC factors represent an increase in drag compared to the nominal attitude, while negative delta-BC factors (to a minimum of -1) represent a decrease in drag. At the conclusion of the differential-drag ‘maneuver’, the Pc was recalculated to evaluate whether or not the conjunction was mitigated (Pc < 3E-6). These results were then binned and sorted along several axes, including altitude, amount of delta-BC, and (pre-maneuver) rate of energy dissipation (EDR), to identify underlying patterns. The altitude plot is shown in Figure 1. To validate this analysis, we consulted the record of a NASA mission which uses differential drag to maintain its orbit and remediate conjunction risk. CARA’s empirical record of the mission’s orbit history suggests it achieves a delta-BC of 2.2. Of the twenty-one RMM plans that were submitted by this mission, eighteen were matched with conjunctions in the historical record; of those, twelve were successfully remediated (final measured Pc < 3E-6), and six were not. This is consistent with the expected efficacy for missions orbiting at that altitude. We are presently simulating this mission’s RMMs with MTS; this work is ongoing, but so far, the MTS results are qualitatively in agreement with the empirical results -- correctly predicting that a maneuver would or would not remediate a conjunction, if not exactly matching the final post-remediation Pc value. We found that differential drag was most successful for satellites with perigees below 560 km, and which could adopt an average delta-BC of 2 or greater (that is, increasing their ballistic coefficient by a factor of 3). However, this is a difficult threshold for a mission to clear; very few spacecraft are capable of adopting a high-drag configuration for 72 hours continuously. Planet’s Dove spacecraft use differential drag to remediate conjunctions (Griffith, et al., 2021), and they have a maximum delta-BC factor of 9, but in practice (with mission and charging constraints) they achieve a time-averaged delta-BC that is closer to 2 (Foster, et al., 2017). A mission’s differential drag utility strongly depends on the operational constraints that has the capacity to limit the time-averaged delta-BC. A mission with a high maximum delta-BC of 5 or more can have an effective delta-BC of less than 1 due to operational constraints such as instrument and solar panel pointing, especially if this constraint results in holding an intermediate drag value for most of its orbit. CARA has developed tables that can be used as decision aids to advise missions-in-development about the best way to utilize their differential drag capabilities. For missions below 560 km with the operational flexibility to devote multiple days to holding a high-drag configuration (or a sufficiently high drag ratio to compensate for limitations on that time), they are -- more likely than not -- able to successfully remediate high-risk conjunctions. Conversely, missions that do not meet these exacting criteria -- most missions -- can instead be advised to use on-board propulsion systems to perform RMMs, or to turn their minimum-area face towards the approach vector, thereby reducing Pc at the moment of conjunction due to the decreased Hard-Body Radius (HBR), that is a strongly correlated variable in the Pc calculations. (NASA, 2023)

conjunction assessment↗
DOE OSTI2018

MicroRNA-374b promotes the proliferation and differentiation of neural stem cells through targeting Hes1

Highlights: • miR-374b expression was upregulated during NSC differentiation. • miR-374b promoted NSC proliferation and differentiation to neurons. • Hes1 was identified as a target gene of miR-374b. • miR-374b regulated NSC proliferation and differentiation by Hes1 Accumulating evidence has documented that microRNAs (miRNAs) are critical regulators of neural stem cell (NSC) proliferation and differentiation. MiRNA-374b (miR-374b) has been reported to play an important role in regulating various cellular processes, such as proliferation and differentiation. However, whether miR-374b is involved in NSC proliferation and differentiation remains unclear. In this study, we investigated the potential role of miR-374b in regulating NSC proliferation and differentiation to elucidate the underlying molecular mechanism. Our results showed that miR-374b expression was significantly upregulated during NSC differentiation. Functional experiments showed that overexpression of miR-374b promoted NSC proliferation and differentiation to neurons. By contrast, miR-374b inhibition showed the opposite effect. Hairy and enhancer of split 1 (Hes1), a master regulator of neurogenesis, was predicted as a potential target gene of miR-374b by bioinformatics analysis. Dual-luciferase reporter assays showed that miR-374b could directly target the 3′-untranslated region of Hes1. Further experiments showed that miR-374b negatively regulated the mRNA and protein expression of Hes1 in NSCs. Moreover, overexpression of Hes1 significantly reversed the miR-374b overexpression-mediated effect on NSC proliferation and differentiation. In addition, knockdown of Hes1 abrogated the miR-374b inhibition-mediated effect on NSC proliferation and differentiation. Taken together, these results demonstrate that miR-374b regulates the proliferation and differentiation of NSCs through targeting Hes1 and suggest that miR-374b is a potential target for modulating NSC-mediated neurogenesis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

miR-3065-5p regulates mouse odontoblastic differentiation partially through bone morphogenetic protein receptor type II

Highlights: • miR-3065-5p is significantly up-regulated during odontoblastic differentiation. • miR-3065-5p directly targets Bmpr2 and indirectly targets Adamts2. • Bmpr2 exerts different roles in the different stages of odontoblastic differentiation. Illumination of the molecular mechanisms regulating odontoblastic differentiation of dental papilla cells is of great significance for proper dentinogenesis and dental pulp regeneration. In this study, we discovered that microRNA (miR)-3065-5p is up-regulated during odontoblastic differentiation. Overexpression of miR-3065-5p promoted odontoblastic differentiation in vitro. Dual luciferase report assay verified that miR-3065-5p could bind to the 3′UTR of bone morphogenetic protein receptor type II (BMPR2), which dramatically increased in the beginning of odontoblastic differentiation but decreased in the terminal differentiation stage. Inhibition of Bmpr2 in the early stage retarded odontoblastic differentiation while knockdown of Bmpr2 in the terminal stage enhanced odontoblastic differentiation, resembling the effect of miR-3065-5p. Taken together, our present study suggests that miR-3065-5p positively regulates odontoblastic differentiation by directly binding to Bmpr2 in the terminal differentiation stage.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2003

Linear Back-Drive Differentials

Linear back-drive differentials have been proposed as alternatives to conventional gear differentials for applications in which there is only limited rotational motion (e.g., oscillation). The finite nature of the rotation makes it possible to optimize a linear back-drive differential in ways that would not be possible for gear differentials or other differentials that are required to be capable of unlimited rotation. As a result, relative to gear differentials, linear back-drive differentials could be more compact and less massive, could contain fewer complex parts, and could be less sensitive to variations in the viscosities of lubricants. Linear back-drive differentials would operate according to established principles of power ball screws and linear-motion drives, but would utilize these principles in an innovative way. One major characteristic of such mechanisms that would be exploited in linear back-drive differentials is the possibility of designing them to drive or back-drive with similar efficiency and energy input: in other words, such a mechanism can be designed so that a rotating screw can drive a nut linearly or the linear motion of the nut can cause the screw to rotate. A linear back-drive differential (see figure) would include two collinear shafts connected to two parts that are intended to engage in limited opposing rotations. The linear back-drive differential would also include a nut that would be free to translate along its axis but not to rotate. The inner surface of the nut would be right-hand threaded at one end and left-hand threaded at the opposite end to engage corresponding right- and left-handed threads on the shafts. A rotation and torque introduced into the system via one shaft would drive the nut in linear motion. The nut, in turn, would back-drive the other shaft, creating a reaction torque. Balls would reduce friction, making it possible for the shaft/nut coupling on each side to operate with 90 percent efficiency.

Waydo, Peter↗