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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 361 records · Page 20
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Preclinical characterization of Pan-NKG2D ligand-binding NKG2D receptor decoys

NKG2D and its ligands are critical regulators of protective immune responses controlling infections and cancer, defining a crucial immune signaling axis. Current therapeutic efforts targeting this axis almost exclusively aim at enhancing NKG2D-mediated effector functions. However, this axis can drive disease processes when dysregulated, in particular, driving stem-like cancer cell reprogramming and tumorigenesis through receptor/ligand self-stimulation on tumor cells. Despite complexities with its structure and biology, we developed multiple novel engineered proteins that functionally serve as axis-blocking NKG2D “decoys” and report biochemical, structural, in vitro , and in vivo evaluation of their functionality.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Melanoma Cell Intrinsic GABAA Receptor Enhancement Potentiates Radiation and Immune Checkpoint Inhibitor Response by Promoting Direct and T Cell-Mediated Antitumor Activity

Most patients with metastatic melanoma show variable responses to radiation therapy and do not benefit from immune checkpoint inhibitors. Improved strategies for combination therapy that leverage potential benefits from radiation therapy and immune checkpoint inhibitors are critical.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2020

CysLT1R receptor complex with Zafirlukast (P21 space group) structure (SFX@LCLS)

This dataset has overall quality of 2.4 Å (CC*=0.5), P1 space group and cell parameters 41.58, 68.56, 87.37, 76.33, 76.69, 81.19. Structure obtained from this data have been deposited under PDB ID 6RZ5. Data processing scripts are described in detail [here](https://gist.github.com/marinegor/96102c9b7ce87509a0832649d11ba927)

CXI↗
NASA NTRS1999

Abnormal norepinephrine clearance and adrenergic receptor sensitivity in idiopathic orthostatic intolerance

BACKGROUND: Chronic orthostatic intolerance (OI) is characterized by symptoms of inadequate cerebral perfusion with standing, in the absence of significant orthostatic hypotension. A heart rate increase of >/=30 bpm is typical. Possible underlying pathophysiologies include hypovolemia, partial dysautonomia, or a primary hyperadrenergic state. We tested the hypothesis that patients with OI have functional abnormalities in autonomic neurons regulating cardiovascular responses. METHODS AND RESULTS: Thirteen patients with chronic OI and 10 control subjects underwent a battery of autonomic tests. Systemic norepinephrine (NE) kinetics were determined with the patients supine and standing before and after tyramine administration. In addition, baroreflex sensitivity, hemodynamic responses to bolus injections of adrenergic agonists, and intrinsic heart rate were determined. Resting supine NE spillover and clearance were similar in both groups. With standing, patients had a greater decrease in NE clearance than control subjects (55+/-5% versus 30+/-7%, P<0.02). After tyramine, NE spillover did not change significantly in patients but increased 50+/-10% in control subjects (P<0.001). The dose of isoproterenol required to increase heart rate 25 bpm was lower in patients than in control subjects (0.5+/-0.05 versus 1.0+/-0.1 microg, P<0.005), and the dose of phenylephrine required to increase systolic blood pressure 25 mm Hg was lower in patients than control subjects (105+/-11 versus 210+/-12 microg, P<0.001). Baroreflex sensitivity was lower in patients (12+/-1 versus 18+/-2 ms/mm Hg, P<0.02), but the intrinsic heart rate was similar in both groups. CONCLUSIONS: The decreased NE clearance with standing, resistance to the NE-releasing effect of tyramine, and increased sensitivity to adrenergic agonists demonstrate dramatically disordered sympathetic cardiovascular regulation in patients with chronic OI.

Clinical Trial↗
NASA NTRS1989

Blockade of 5-hydroxytryptamine3 receptors prevents cisplatin-induced but not motion- or xylazine-induced emesis in the cat

5-Hydroxytryptamine3 antagonists have been reported to prevent emesis elicited by cisplatin and radiation. This study investigated the possibility that drugs with this mechanism of action may be useful in preventing emesis elicited by other stimuli. The drugs ICS 205-930 (0.1 and 1.0 mg/kg) and MDL 72222 (0.1 and 1.0 mg/kg) were administered SC to cats before challenging them with either provocative motion or an emetic dose of xylazine. In no instance was a significant reduction in emesis evident. Zacopride was also administered before motion testing (0.01 to 10.0 mg/kg) and found to not have efficacy. To test the possibility that species or route of administration were factors in the negative results, 1.0 mg/kg of ICS 205-930 was administered SC before IV infusion of 7.5 mg/kg of cisplatin. There was a total suppression of emesis for the duration of the six-hour observation periods. This result verifies other work which found 5-hydroxytryptamine3 antagonists to be effective in preventing emesis elicited by cancer chemotherapeutic treatments. However, there is no evidence that they are effective in other syndromes, such as motion sickness and xylazine-induced emesis.

NASA Discipline Number 16-10↗
DOE OSTI2020

Hanford Tank Vapors in Worker Breathing Zones - Source, Dispersion, and Receptor Data - 20373

A wide range of organic and inorganic chemicals from historical Hanford Site processes are now stored in 177 underground storage tanks at the Hanford tank farms. Workers at the Hanford tank farms have expressed concerns about chemical vapor exposures for many years. During the spring of 2014, worker reports of chemical odors and/or symptoms prompted the development of the Savannah River National Laboratory Hanford Tank Vapor Assessment Team (TVAT) and their resulting independent assessment and recommendations concerning tank farm worker reports of vapors. The Tank Vapor Assessment report included a hypothesis that 'vapors coming out of tanks in high concentration (bolus) plumes sporadically intersected with the breathing zones of workers, resulting in brief but intense exposures to some workers.' The focus of this effort is to present current knowledge to describe the mechanisms by which workers may experience short duration vapor concentrations above background in the tank farms environment. The TVAT hypothesis that workers have experienced concentrations approaching 80% of the tank headspace up to 3 meters (10 feet) from tank sources is not supported by sampling data or modeling results. Modeling indicates that concentrations are quickly reduced from the source, and that the upper end of predicted concentrations at worker breathing zones are a factor of 10 or more lower than source concentrations. Area measurements corroborate the fact that worker breathing zone concentrations are 10 to 100 times lower than source concentrations, and events with elevated concentrations are rare. These reduced vapor concentration levels may result in detectable odors or irritation, depending on a worker's specific odor threshold and sensitivity to the chemical species. Short-duration vapor events may be mitigated by evaluating daily atmospheric conditions in conjunction with planned tank farm activities. Monitoring changing conditions related to tank vapors concentrations at the source and within worker breathing zone is also an important step to protect workers from short duration elevated concentration events. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗