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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

Homologous recombination as a potential target for caffeine radiosensitization in mammalian cells: reduced caffeine radiosensitization in XRCC2 and XRCC3 mutants

The radiosensitizing effect of caffeine has been associated with the disruption of multiple DNA damage-responsive cell cycle checkpoints, but several lines of evidence also implicate inhibition of DNA repair. The role of DNA repair inhibition in caffeine radiosensitization remains uncharacterized, and it is unknown which repair process, or lesion, is affected. We show that a radiosensitive cell line, mutant for the RAD51 homolog XRCC2 and defective in homologous recombination repair (HRR), displays significantly diminished caffeine radiosensitization that can be restored by expression of XRCC2. Despite the reduced radiosensitization, caffeine effectively abrogates checkpoints in S and G2 phases in XRCC2 mutant cells indicating that checkpoint abrogation is not sufficient for radiosensitization. Another radiosensitive line, mutant for XRCC3 and defective in HRR, similarly shows reduced caffeine radiosensitization. On the other hand, a radiosensitive mutant (irs-20) of DNA-PKcs with a defect in non-homologous end-joining (NHEJ) is radiosensitized by caffeine to an extent comparable to wild-type cells. In addition, rejoining of radiation-induced DNA DSBs, that mainly reflects NHEJ, remains unaffected by caffeine in XRCC2 and XRCC3 mutants, or their wild-type counterparts. These observations suggest that caffeine targets steps in HRR but not in NHEJ and that abrogation of checkpoint response is not sufficient to explain radiosensitization. Indeed, immortalized fibroblasts from AT patients show caffeine radiosensitization despite the checkpoint defects associated with ATM mutation. We propose that caffeine radiosensitization is mediated by inhibition of stages in DNA DSB repair requiring HRR and that checkpoint disruption contributes by allowing these DSBs to transit into irreparable states. Thus, checkpoints may contribute to genomic stability by promoting error-free HRR.

NASA Discipline Radiation Health↗

Caffeine Consumption Aboard the International Space Station

INTRODUCTION: Caffeine is the most widely used performance-enhancing drug on Earth and astronaut crews have access to liquid coffee. While caffeine is a potent countermeasure to improve alertness and performance, it can also interfere with sleep. This can lead to performance deficits on the following day, driving a cycle of caffeine use to counter the effects of caffeine-induced sleep disruption. Caffeine availability may be limited during future Artemis and/or Mars missions. Accordingly, it is important that we 1) determine the prevalence of caffeine use among astronauts, 2) characterize the impact of caffeine on performance, and 3) characterize the impact of caffeine on sleep. Our aim in this study is to describe the use of caffeine aboard the ISS and begin to examine the relationship between caffeine use and sleep and performance outcomes. METHODS: Daily caffeine consumption was determined from food and beverage intake tracking for 25 astronauts on 6 month International Space Station (ISS) missions. Data were recorded using the ISS Food Intake Tracker iPad App or other detailed recording technique. On average, crew recorded dietary intake on 179.7±68.6 (mean±SD) days inflight. RESULTS: Astronauts consumed 97±92 mg caffeine per day. All astronauts (25/25) in this study consumed caffeine at some point during flight, though the frequency, amounts, and regularity differed across crewmembers. Approximately a quarter of crewmembers were regular caffeine consumers (6/25), i.e., they ingested at least 90 mg caffeine (equivalent to one cup of coffee) on 90% of inflight days.

fatigue↗

Acute effects of bright light and caffeine on nighttime melatonin and temperature levels in women taking and not taking oral contraceptives

Caffeine and bright light effects on nighttime melatonin and temperature levels in women were tested during the luteal phase of the menstrual cycle (n=30) or the pseudo luteal phase for oral contraceptive users (n=32). Participants were randomly assigned to receive either bright (5000 lux) or dim room light (<88 lux) between 20:00 and 08:00 h under a modified constant routine protocol. Half the subjects in each lighting condition were administered either caffeine (100 mg) or placebo in a double-blind manner at 20:00, 23:00, 02:00 and 05:00 h. Results showed that the combination of bright light and caffeine enhanced nighttime temperature levels to a greater extent than did either caffeine or bright light alone. Both of the latter groups had higher temperature levels relative to the dim light placebo condition and the two groups did not differ. Temperature levels in the bright light caffeine condition were maintained at near peak circadian levels the entire night in the luteal and pseudo luteal phase. Melatonin levels were reduced throughout the duration of bright light exposure for all women. Caffeine reduced the onset of melatonin levels for women in the luteal phase, but it had little effect on melatonin levels for oral contraceptive users. The results for women in the luteal phase of the menstrual cycle are consistent with our previous findings in men. The results also suggest that oral contraceptives may alter the effects of caffeine on nighttime melatonin levels.

Clinical Trial↗

Caffeine potentiates the enhancement by choline of striatal acetylcholine release

We investigated the effect of peripherally administered caffeine (50 mg/kg), choline (30, 60, or 120 mg/kg) or combinations of both drugs on the spontaneous release of acetylcholine (ACh) from the corpus striatum of anesthetized rats using in vivo microdialysis. Caffeine alone or choline in the 30 or 60 mg/kg dose failed to increase ACh in microdialysis samples; the 120 mg/kg choline dose significantly enhanced ACh during the 80 min following drug administration. Coadministration of caffeine with choline significantly increased ACh release after each of the choline doses tested. Peak microdialysate levels with the 120 mg/kg dose were increased 112% when caffeine was additionally administered, as compared with 54% without caffeine. These results indicate that choline administration can enhance spontaneous ACh release from neurons, and that caffeine, a drug known to block adenosine receptors on these neurons, can amplify the choline effect.

Non-NASA Center↗

Mutant quantity and quality in mammalian cells (AL) exposed to cesium-137 gamma radiation: effect of caffeine

We examined the effect of caffeine (1,3,7-trimethylxanthine) on the quantity and quality of mutations in cultured mammalian AL human-hamster hybrid cells exposed to 137Cs gamma radiation. At a dose (1.5 mg/ml for 16 h) that reduced the plating efficiency (PE) by 20%, caffeine was not itself a significant mutagen, but it increased by approximately twofold the slope of the dose-response curve for induction of S1- mutants by 137Cs gamma radiation. Molecular analysis of 235 S1- mutants using a series of DNA probes mapped to the human chromosome 11 in the AL hybrid cells revealed that 73 to 85% of the mutations in unexposed cells and in cells treated with caffeine alone, 137Cs gamma rays alone or 137Cs gamma rays plus caffeine were large deletions involving millions of base pairs of DNA. Most of these deletions were contiguous with the region of the MIC1 gene at 11p13 that encodes the S1 cell surface antigen. In other mutants that had suffered multiple marker loss, the deletions were intermittent along chromosome 11. These "complex" mutations were rare for 137Cs gamma irradiation (1/63 = 1.5%) but relatively prevalent (23-50%) for other exposure conditions. Thus caffeine appears to alter both the quantity and quality of mutations induced by 137Cs gamma irradiation.

NASA Discipline Radiation Health↗

Caffeine: CoArray Fortran Framework of Efficient Interfaces to Network Environments

This paper provides an introduction to the CoArray Fortran Framework of Efficient Interfaces to Network Environments (Caffeine), a parallel runtime library built atop the GASNet-EX exascale networking library. Caffeine leverages several non-parallel Fortran features to write type- and rank-agnostic interfaces and corresponding procedure definitions that support parallel Fortran 2018 features, including communication, collective operations, and related services. One major goal is to develop a runtime library that can eventually be considered for adoption by LLVM Flang, enabling that compiler to support the parallel features of Fortran. The paper describes the motivations behind Caffeine's design and implementation decisions, details the current state of Caffeine's development, and previews future work. We explain how the design and implementation offer benefits related to software sustainability by lowering the barrier to user contributions, reducing complexity through the use of Fortran 2018 C-interoperability features, and high performance through the use of a lightweight communication substrate.

Rouson, Damian↗

Enhanced detection of volatile organic compounds (VOCs) by caffeine modified carbon nanotube junctions

Detection of vapor phase analytes and gas molecules is primarily essential for numerous applications including medical diagnostic, environmental monitoring, chemical threat detection, food quality control, and chemical warfare agents. Here, we developed Caffeine functionalized carbon nanotubes (CNTs) random network based vapor quantum resistive sensors (vQRSs) for volatile organic compounds (VOCs) detection. The localized transmission electron microscopy (TEM) image and energy dispersive X-ray spectroscopy (EDS) confirm migration of caffeine to CNT–CNT junction (CNTj). We have recorded more than one order of magnitude higher sensitivity and unique selectivity towards selective VOCs (e.g., acetone, toluene, ethanol, methanol, etc.) with short response time (few seconds) for caffeine modified CNT junction (Caf-CNTj) vQRSs. Molecular dynamics (MD) calculations suggest that the sensitivity of the sensor is diffusion limited, with an advective contribution for ethanol. Furthermore, the designed Caf-CNTj sensors can potentially be important candidate to be a part of electronic nose used for various application such as breath analysis and food quality monitoring.

36 MATERIALS SCIENCE↗

Low-Dose Caffeine Administration During Acute Sleep Deprivation Eliminates Visual Motion Processing Impairment, but Does Not Improve Saccadic Rate

Oculomotor tracking performance changes according to time awake. A constant routine (CR) study demonstrated that increasing time awake 1) reduces the precision of visual motion processing, 2) decreases steady-state closed-loop pursuit performance and 3) decreases peak saccadic velocity. We aimed to determine the contribution of homeostatic sleep pressure on these oculometric changes by administering low-dose caffeine over one night of sleep deprivation. Participants completed two weeks of at-home 8.5 hours sleep per day, followed by an approximately 24-hour laboratory CR in semi-recumbent posture under less than 4 lux of light. The visual tracking task was performed every two hours after waking and hourly overnight. Low-dose caffeine of 0.3 milligrams per kilogram was administered hourly during the biological night. Nine participants (5F) completed the study. Caffeine dosing: 1) prevented the impairment of visual motion processing, 2) reduced by approximately half the impairment of closed-loop pursuit performance (gain, minus 0.47 percent per hour, significance of slope change: p (probability) less than 0.006; proportion smooth, minus 0.35 percent per hour, p less than 0.005), and 3) had an insignificant (p less than 0.39) effect on the impairment of saccadic peak velocity (slope, minus 1.13 percent per hour; intercept, minus 0.62 percent per hour). These results suggest that visual motion processing and some proportion of closed-loop pursuit performance are impaired due to homeostatic mechanisms during sleep deprivation.

Sleep↗

Caffeine v0.1.0

Caffeine is the CoArray Fortran Framework of Efficient Interfaces to Network Environments. Caffeine aims to produce a parallel runtime library that will support Fortran compilers with a programming-model-agnostic application binary interface (ABI) to various lower-level communication libraries. The current version of Caffeine uses the GASNet-EX networking middleware, also developed at Berkeley Lab. On many combinations of applications and platforms, GASNet-EX outperforms the widely used Message Passing Interface (MPI). Through GASNet-EX's support for communicating between graphics processing units (GPU), GASNet-EX has features that specifically target the emerging, leading-edge exascale computing platforms.

Rouson, Damian↗

Thermoregulatory effects of caffeine ingestion during rest and exercise in men

Body temperatures and thermoregulatory responses were measured at rest and during submaximal exercise under normal ambient conditions in 11 aerobically-conditioned men (age = 29.2 +/- 6.2 yr, VO2(max) = 3.73 +/- 0.46 min(sup -1), relative body fat = 12.3 +/- 3.7 percent, mean +/- SD) with (CT) and without (NCT) the ingestion of 10 mg of caffeine per kg of body weight. Oxygen uptake (VO2), heart rate (HR), and rectal (T(sub re)) and mean skin (T-bar(sub sk)) temperatures were recorded for 100 minutes starting one minute after ingestion of caffeine or a placebo. Data were collected throughout 30 minutes of rest (sitting) and the following 70 minutes of sitting leg ergometer exercise using the same constant load (1,088 +/- 153 kgm/min) in both NCT and CT. The load resulted in a mean relative exercise intensity equal to approximately 68 percent of VO2(sub max). Skin heat conductance (H(sub sk)) and sweat rate were calculated. Two-way analysis of covariance revealed no significant (P greater than 0.05) differences between NCT and CT in VO2, HR, T(sub re), T-bar(sub sk), or H(sub sk). A dependent t-test indicated no significant difference between NCT and CT in sweat rate. Thus, a high level of caffeine ingestion has no detrimental effects on body temperatures and thermoregulatory responses during moderately heavy exercise in normal ambient conditions.

Dunagan, Nancy↗

Lowering and Runtime Support for Fortran’s Multi-Image Parallel Features using LLVM Flang, PRIF, and Caffeine

This paper provides an overview of the multi-image parallel features in Fortran 2023 and their implementation in the LLVM flang compiler and the Caffeine parallel runtime library. The features of interest support a Single-Program, Multiple-Data (SPMD) programming model based on executing multiple “images”, each of which is a program instance. The features also support a Partitioned Global Address Space (PGAS) in the form of “coarray” distributed data structures. The paper discusses the lowering of multi-image features to the Parallel Runtime Interface for Fortran (PRIF) and the implementation of PRIF in the Caffeine parallel runtime library. This paper also provides an early view into the design of a new multi-image dialect of the LLVM Multi-Level Intermediate Representation (MLIR). We describe validation and testing of the resulting software stack, and demonstrate that performance compares favorably to another open-source compiler and runtime library: GNU Compiler Collection (GCC) gfortran and OpenCoarrays, respectively.

Bonachea, Dan↗

Pathways and Mechanism of Caffeine Binding to Human Adenosine A 2A Receptor

Caffeine (CFF) is a common antagonist to the four subtypes of adenosine G-protein-coupled receptors (GPCRs), which are critical drug targets for treating heart failure, cancer, and neurological diseases. However, the pathways and mechanism of CFF binding to the target receptors remain unclear. In this study, we have performed all-atom-enhanced sampling simulations using a robust Gaussian-accelerated molecular dynamics (GaMD) method to elucidate the binding mechanism of CFF to human adenosine A 2A receptor (A 2A AR). Multiple 500–1,000 ns GaMD simulations captured both binding and dissociation of CFF in the A 2A AR. The GaMD-predicted binding poses of CFF were highly consistent with the x-ray crystal conformations with a characteristic hydrogen bond formed between CFF and residue N6.55 in the receptor. In addition, a low-energy intermediate binding conformation was revealed for CFF at the receptor extracellular mouth between ECL2 and TM1. While the ligand-binding pathways of the A 2A AR were found similar to those of other class A GPCRs identified from previous studies, the ECL2 with high sequence divergence serves as an attractive target site for designing allosteric modulators as selective drugs of the A 2A AR.

59 BASIC BIOLOGICAL SCIENCES↗