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At least 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
NASA NTRS2010

GBM Observations of Terrestrial Gamma-Ray Flashes

The TGF detection rate of Gamma-ray Burst Monitor (GBM) has been increased twice since launch. The most recent improvement is from a new operating mode in which data for individual photons are down-linked for selected portions of the orbit, enabling a more sensitive ground-based search for TGFs. The new search has increased the TGF detection rate and is finding TGFs more than five times fainter than the TGFs of the previous GBM sample. We summarize the properties of the original GBM TGF sample and compare to the less intense TGFs now being detected. In addition to gamma-ray TGFs, GBM is observing distant TGFs from the propagation of charged particles along geomagnetic field lines. Strong 511 keV annihilation lines have been observed, demonstrating that both electrons and positrons are present in the particle beams. Spectral fits to these electron/positron TGFs will be shown.

Briggs, M. S.↗
NASA NTRS2011

Modularized TGFbeta-Smad Signaling Pathway

The Transforming Growth Factor beta (TGFbeta) signaling pathway is a prominent regulatory signaling pathway controlling various important cellular processes. It can be induced by several factors, including ionizing radiation. It is regulated by Smads in a negative feedback loop through promoting increases in the regulatory Smads in the cell nucleus, and subsequent expression of inhibitory Smad, Smad7 to form a ubiquitin ligase with Smurf targeting active TGF receptors for degradation. In this work, we proposed a mathematical model to study the radiation-induced Smad-regulated TGF signaling pathway. By modularization, we are able to analyze each module (subsystem) and recover the nonlinear dynamics of the entire network system. Meanwhile the excitability, a common feature observed in the biological systems, along the TGF signaling pathway is discussed by mathematical analysis and numerical simulation.

Li, Yongfeng↗
NASA NTRS2011

High-Energy Radiation from Thunderstorms with ADELE: TGFs, Steps, and Glows

The biggest challenge in the study of high-energy processes in thunderstorms is getting a detector to the vicinity of the electrically active regions of a storm. The Airborne Detector for Energetic Lightning Emissions (ADELE) has been used to detect gamma rays from aircraft above storms and from a storm-chasing van on the ground. In August 2009, ADELE flew above Florida storms in a Gulfstream V jet, detecting the first terrestrial gamma-ray flash (TGF) seen from a plane and continuous glows of high-energy emission above thunderclouds. The presence of these glows suggests that a gradual process of relativistic runaway and feedback may help limit the total amount of charging in thunderstorms, in contrast to the traditional view that only lightning discharges compete with the charging process. The upper limits on TGF emission from intracloud and cloud-to-ground lightning from the ADELE flights demonstrated conclusively that a TGF of the sort seen from space is not associated with most lightning and not necessary to trigger it. In August 2010, observations from a van detected stepped-leader x-ray emission from at least four lightning strikes in ten days of operations. This mode of operation is therefore promising for future observations of the stepping process, although a more varied suite of instrumentation, in particular a flash-distance detector, would be useful. We will report on these results and on future possibilities for ADELE campaigns.

Smith, David M.↗
NASA NTRS2017

Terrestrial Gamma Ray Flashes due to Particle Acceleration in Tropical Storm Systems

Terrestrial gamma ray flashes (TGFs) are submillisecond flashes of energetic radiation that are believed to emanate from intracloud lightning inside thunderstorms. This emission can be detected hundreds of kilometers from the source by space-based observatories such as the Fermi Gamma-ray Space Telescope (Fermi). The location of the TGF-producing storms can be determined using very low frequency (VLF) radio measurements made simultaneously with the Fermi detection, allowing additional insight into the mechanisms which produce these phenomena. In this paper, we report 37 TGFs originating from tropical storm systems for the first time. Previous studies to gain insight into how tropical cyclones formed and how destructive they can be include the investigation of lightning flash rates and their dependence on storm evolution. We find TGFs to emanate from a broad range of distances from the storm centers. In hurricanes and severe tropical cyclones, the TGFs are observed to occur predominately from the outer rainbands. A majority of our sample also show TGFs occurring during the strengthening phase of the encompassing storm system. These results verify that TGF production closely follows when and where lightning predominately occurs in cyclones. The intrinsic characteristics of these TGFs were not found to differ from other TGFs reported in larger samples. We also find that some TGF-producing storm cells in tropical storm systems far removed from land have a low number of WWLLN sferics. Although not unique to tropical cyclones, this TGF/sferic ratio may imply a high efficiency for the lightning in these storms to generate TGFs.

Roberts, O. S.↗
NASA NTRS1999

The Effects of Orbital Spaceflight on Human Osteoblastic Cell Physiology and Gene Expression

The purpose of the proposed study is to establish whether changes in gravitational loading have a direct effect on osteoblasts to regulate TGF-6 expression. The effects of spaceflight and reloading on TGF-B MRNA and peptide levels will be studied in a newly developed line of immortalized human fetal osteoblasts (HFOB) transfected with an SV-40 temperature dependent mutant to generate proliferating, undifferentiated hFOB cells at 33-34 C and a non-proliferating, differentiated HFOB cells at 37-39'C. Unlike previous cell culture models, HFOB cells have unlimited proliferative capacity yet can be precisely regulated to differentiate into mature cells which express mature osteoblast function. If isolated osteoblasts respond to changes in mechanical loading in a manner similar to their response in animals, the cell system could provide a powerful model to investigate the signal transduction pathway for gravitational loading.

Turner, R. T.↗
NASA NTRS2001

Physical and biological studies with protons and HZE particles in a NASA supported research center in radiation health

NASA has established and supports a specialized center for research and training (NSCORT) to specifically address the potential deleterious effects of HZE particles on human health. The NSCORT in radiation health is a joint effort between Lawrence Berkeley National Laboratory (LBNL) and Colorado State University (CSU). The overall scope of research encompasses a broad range of subjects from microdosimetric studies to cellular and tissue responses to initial damage produced by highly energetic protons and heavy charged particles of the type found in galactic cosmic rays (GCR) spectrum. The objectives of the microdosimetry studies are to determine the response of Tissue Equivalent Proportional Counter (TEPC) to cosmic rays using ground based accelerators. This includes evaluation of energy loss due to the escape of high-energy delta rays and increased energy deposition due to the enhanced delta ray production in the wall of the detector. In this report major results are presented for 56Fe at 1000, 740, 600 and 400 MeV/nucleon. An assessment of DNA repair and early development of related chromosomal changes is extremely important to our overall understanding of enhanced biological effectiveness of high LET particle radiation. Results are presented with respect to the fidelity of the rejoining of double strand breaks and the implications of misrejoining. The relationship between molecular and cytogenetic measurements is presented by studying damage processing in highly heterochromatic supernumerary (correction of sypernumerary) X chromosomes and the active X-chromosome. One of the important consequences of cell's inability to handle DNA damage can be evaluated through mutation studies. Part of our goal is the assessment of potential radioprotectors to reduce the mutation yield following HZE exposures, and some promising results are presented on one compound. A second goal is the integration of DNA repair and mutation studies. Results are presented on a direct comparison of initial double strand breaks induction, the time course and fidelity of double strand break rejoining, cell killing and mutation induction in the same human model system. In order to understand the carcinogenic potential of protons and HZE particles, the role of damaged microenvironment in this process must be understood. In this project it has been postulated that radiation affects the microenvironment, which then modifies cell interactions in a manner conducive to neoplastic progression. Both TGF-beta and FGF-2 are important components of microenvironment. A recent result on the assessment of the role of FGF-2 and its cross-talk with TGF-beta as a function of radiation quality is presented. Theoretical modeling has so far played a central role in analyzing and integrating experimental data on repair and mutation studies and predicting new phenomena. The integrated NSCORT program also provides a broad training experience for students and postdoctoral fellows in space radiation health.

NASA Discipline Radiation Health↗
NASA NTRS2000

Effects of orbital spaceflight on human osteoblastic cell physiology and gene expression

During long-term spaceflight, astronauts lose bone, in part due to a reduction in bone formation. It is not clear, however, whether the force imparted by gravity has direct effects on bone cells. To examine the response of bone forming cells to weightlessness, human fetal osteoblastic (hFOB) cells were cultured during the 17 day STS-80 space shuttle mission. Fractions of conditioned media were collected during flight and shortly after landing for analyses of glucose utilization and accumulation of type I collagen and prostaglandin E(2) (PGE(2)). Total cellular RNA was isolated from flight and ground control cultures after landing. Measurement of glucose levels in conditioned media indicated that glucose utilization occurred at a similar rate in flight and ground control cultures. Furthermore, the levels of type I collagen and PGE(2) accumulation in the flight and control conditioned media were indistinguishable. The steady-state levels of osteonectin, alkaline phosphatase, and osteocalcin messenger RNA (mRNA) were not significantly changed following spaceflight. Gene-specific reductions in mRNA levels for cytokines and skeletal growth factors were detected in the flight cultures using RNase protection assays. Steady-state mRNA levels for interleukin (IL)-1alpha and IL-6 were decreased 8 h following the flight and returned to control levels at 24 h postflight. Also, transforming growth factor (TGF)-beta(2) and TGF-beta(1) message levels were modestly reduced at 8 h and 24 h postflight, although the change was not statistically significant at 8 h. These data suggest that spaceflight did not significantly affect hFOB cell proliferation, expression of type I collagen, or PGE(2) production, further suggesting that the removal of osteoblastic cells from the context of the bone tissue results in a reduced ability to respond to weightlessness. However, spaceflight followed by return to earth significantly impacted the expression of cytokines and skeletal growth factors, which have been implicated as mediators of the bone remodeling cycle. It is not yet clear whether these latter changes were due to weightlessness or to the transient increase in loading resulting from reentry.

Non-NASA Center↗
NASA NTRS2009

Terrestrial Gamma-ray Flash (TGFs) Above Thunderstorms

Terrestrial gamma-ray flashes (TGFs) are being observed with the Gamma-ray Burst Monitor (GBM) detectors on Fermi about once every four weeks. These intense millisecond flashes of MeV photons have been observed with four space-borne experiments since their initial discovery by the BATSE-CGRO experiment in the early 1990s. TGFs have extremely hard spectra (harder than GRBs) and photons are seen to extend to over 30 MeV. The GBM-Fermi observations have the highest temporal resolution of any previous TGF observations and time-resolved coarse spectra can be derived. These features will be crucial for testing the leading current model of TGF production: relativistic run-away electron cascades formed in the intense electric fields within thunderstorms.

Fishman, Gerald J.↗
NASA NTRS2010

Intense Gamma-Ray Flashes Above Thunderstorms on the Earth and Other Planets

Intense millisecond flashes of MeV photons have been observed with space-borne detectors in Earth orbit. They are expected to be present on other planets that exhibit lightning. The terrestrial gamma-ray flashes (TGFs) were discovered with the Burst and Transient Source Experiment (BATSE) aboard the Compton Gamma-Ray Observatory (CGRO) in the early 1990s. They are now being observed with several other instruments, including the Gamma-ray Burst Monitor (GBM) detectors on the Fermi Gamma-ray Space Telescope. Although Fermi- GBM was designed and optimized for the observation of cosmic gamma-ray bursts (GRBs), it has unprecedented capabilities for TGF observations. The TGFs usually have extremely hard continuous spectra, typical of highly- Comptonized bremsstrahlung radiation. These spectral are harder than those of GRBs, with photons extending to over 40 MeV. The most likely origin of these high-energy photons is bremsstrahlung radiation produced by a relativistic "runaway avalanche" electron beam. Such a beam is expected to be produced in an extended, intense electric field in or above thunderstorm regions. The altitude of origin and beaming characteristics of the radiation are quite uncertain. They have generated considerable observational and theoretical interest in recent years. This talk will give an overview of the all of the space-borne observations of TGFs that have been made thus far. Instruments are being designed specifically for TGF observations from new spacecraft as well as from airborne platforms

Fishman, Gerald J.↗
NASA NTRS2010

Space-Borne Observations of Intense Gamma-Ray Flashes (TGFs) Above Thunderstorms

Intense millisecond flashes of MeV photons are being observed with space-borne detectors. These terrestrial gamma-ray flashes (TGFs) were discovered with the Burst and Transient Source Experiment (BATSE) aboard the Compton Gamma-Ray Observatory (CGRO) in the early 1990s. They are now being observed with several other instruments, including the Gamma-ray Burst Monitor (GBM) detectors on the Fermi Gamma-ray Space Telescope. Although Fermi-GBM was designed and optimized for the observation of cosmic gamma-ray bursts (GRBs), it has unprecedented capabilities for TGF observations. The TGFs usually have extremely hard continuous spectra, typical of highly-Comptonized bremsstrahlung radiation. These spectral are harder than those of GRBs, with photons extending to over 40 MeV. The most likely origin of these high-energy photons is bremsstrahlung radiation produced by a relativistic runaway avalanche electron beam. Such a beam is expected to be produced in an extended, intense electric field in or above thunderstorm regions. The altitude of origin and beaming characteristics of the radiation are quite uncertain. These TGFs may produce an appreciable radiation dose to passengers and crew in nearby aircraft. They have generated considerable observational and theoretical interest in recent years. Instruments are being designed specifically for TGF observations from new spacecraft as well as from airborne platforms.

Fishman, Gerald J.↗
NASA NTRS2010

Fermi GBM Observations of Terrestrial Gamma-Ray Flashes

This slide presentation explores the relationship between Terrestrial Gamma-Ray Flashes (TGF) and lightning. Using data from the World-Wide Lightning Location Network (WWLLN), and the gamma ray observations from Fermi's Gamma-ray Burst Monitor (GBM), the study reviews any causal relationship between TGFs and lightning. The conclusion of the study is that the TGF and lightning are simultaneous with out a causal relationship.

Wilson-Hodge, Colleen A.↗
NASA NTRS2017

Systemic Response to Microgravity: Utilizing GeneLab Datasets to Identify Molecular Targets for Future Hypotheses-Driven Spaceflight Studies

Biological risks associated with microgravity are a major concern for long-term space travel. Although determination of risk has been a focus for NASA research, data examining systemic (i.e., multi- or pan-tissue) responses to space flight are sparse. To perform our analysis, we utilized the NASA GeneLab database which is a publicly available repository containing a wide array of omics results from experiments conducted with: i) with different flight conditions (space shuttle (STS) missions vs. International Space Station (ISS); ii) a variety of tissues; and 3) assays that measure epigenetic, transcriptional, and protein expression changes. Meta-analysis of the transcriptomic data from 7 different murine and rat data sets, examining tissues such as liver, kidney, adrenal gland, thymus, mammary gland, skin, and skeletal muscle (soleus, extensor digitorum longus, tibialis anterior, quadriceps, and gastrocnemius) revealed for the first time, the existence of potential master regulators coordinating systemic responses to microgravity in rodents. We identified p53, TGF(beta)1 and immune related pathways as the highly prevalent pan-tissue signaling pathways that are affected by microgravity. Some variability in the degree of change in their expression across species, strain and time of flight was also observed. Interestingly, while certain skeletal muscle (gastrocnemius and soleus) exhibited an overall down-regulation of these genes, some other muscle types such as the extensor digitorum longus, tibialis anterior and quadriceps, showed an up-regulated expression, indicative of potential compensatory mechanisms to prevent microgravity-induced atrophy. Key genes isolated by unbiased systems analyses displayed a major overlap between tissue types and flight conditions and established TGF(beta)1 to be the most connected gene across all data sets. Finally, a set of microgravity responsive miRNA signature was identified and based on their predicted functional state and subsequent impact on health, a theoretical health risk score was calculated. The genes and miRNAs identified from our analyses can be targeted for future research involving efficient countermeasure design. Our study thus exemplifies the utility of GeneLab data repository to aid in the process of performing novel hypothesis based spaceflight research aimed at elucidating the global impact of environmental stressors at multiple biological scales.

GeneLab↗
NASA NTRS2004

Purification and Crystallization of Murine Myostatin: A Negative Regulator of Muscle Mass

Myostatin (MSTN) has been crystallized and its preliminary X-ray diffraction data were collected. MSTN is a negative regulator of muscle growt/differentiation and suppressor of fat accumulation. It is a member of TGF-b family of proteins. Like other members of this family, the regulation of MSTN is critically tied to its process of maturation. This process involves the formation of a homodimer followed by two proteolytic steps. The first proteolytic cleavage produces a species where the n-terminal portion of the dimer is covalently separated from, but remains non-covalently bound to, the c-terminal, functional, portion of the protein. The protein is activated upon removal of the n-terminal "pro-segment" by a second n-terminal proteolytic cut by BMP-1 in vivo, or by acid treatment in vitro. Understanding the structural nature and physical interactions involved in these regulatory processes is the objective of our studies. Murine MSTN was purified from culture media of genetically engineered Chinese Hamster Ovary cells by multicolumn purification process and crystallized using the vapor diffusion method.

Hong, Young S.↗
NASA NTRS2003

The impact of skeletal unloading on bone formation

Skeletal unloading leads to decreased bone formation and decreased bone mass. Bone resorption is uncoupled from bone formation, contributing to the bone loss. During space flight bone is lost principally from the bones most loaded in the 1 g environment. Determining the mechanism(s) by which loading of bone is sensed and translated into a signal(s) controlling bone formation remains the holy grail in this field. It seems likely that matrix/cell interactions will underlie much of the mechanocoupling. Integrins are a prime mediator of such interactions. The role for systemic hormones such as PTH, GH and 1,25(OH)2D compared to locally produced factors such as IGF-I, PTHrP, BMPs and TGF beta in modulating the cellular response to load remains unclear. Our studies demonstrate that skeletal unloading leads to resistance to the anabolic actions of IGF-I on bone as a result of failure of IGF-I to activate its own signaling pathways. This is associated with a reduction in integrin expression, suggesting crosstalk between these two pathways. As the mechanism(s) by which bone responds to changes in mechanical load with changes in bone formation is further elucidated, applications of this knowledge to other etiologies of osteoporosis are likely to develop. Skeletal unloading provides a perturbation in bone mineral homeostasis that can be used to understand the mechanisms by which bone mineral homeostasis is maintained, and that such understanding will lead to effective treatment for disuse osteoporosis in addition to preventive measures for the bone loss that accompanies space travel.

NASA Discipline Musculoskeletal↗
NASA NTRS2001

Changes in gene expression and signal transduction in microgravity

Studies from space flights over the past three decades have demonstrated that basic physiological changes occur in humans during space flight. These changes include cephalic fluid shifts, loss of fluid and electrolytes, loss of muscle mass, space motion sickness, anemia, reduced immune response, and loss of calcium and mineralized bone. The cause of most of these manifestations is not known and until recently, the general approach was to investigate general systemic changes, not basic cellular responses to microgravity. This laboratory has recently studied gene growth and activation of normal osteoblasts (MC3T3-El) during spaceflight. Osteoblast cells were grown on glass coverslips and loaded in the Biorack plunger boxes. The osteoblasts were launched in a serum deprived state, activated in microgravity and collected in microgravity. The osteoblasts were examined for changes in gene expression and signal transduction. Approximately one day after growth activation significant changes were observed in gene expression in 0-G flight samples. Immediate early growth genes/growth factors cox-2, c-myc, bcl2, TGF beta1, bFGF and PCNA showed a significant diminished mRNA induction in microgravity FCS activated cells when compared to ground and 1-G flight controls. Cox-1 was not detected in any of the samples. There were no significant differences in the expression of reference gene mRNA between the ground, 0-G and 1-G samples. The data suggest that quiescent osteoblasts are slower to enter the cell cycle in microgravity and that the lack of gravity itself may be a significant factor in bone loss in spaceflight. Preliminary data from our STS 76 flight experiment support our hypothesis that a basic biological response occurs at the tissue, cellular, and molecular level in 0-G. Here we examine ground-based and space flown data to help us understand the mechanism of bone loss in microgravity.

manned↗
NASA NTRS2003

A short pulse of mechanical force induces gene expression and growth in MC3T3-E1 osteoblasts via an ERK 1/2 pathway

Physiological mechanical loading is crucial for maintenance of bone integrity and architecture. We have calculated the strain caused by gravity stress on osteoblasts and found that 4-30g corresponds to physiological levels of 40-300 microstrain. Short-term gravity loading (15 minutes) induced a 15-fold increase in expression of growth-related immediate early gene c-fos, a 5-fold increase in egr-1, and a 3-fold increase in autocrine bFGF. The non-growth-related genes EP-1, TGF-beta, and 18s were unaffected by gravity loading. Short-term physiological loading induced extracellular signal-regulated kinase (ERK 1/2) phosphorylation in a dose-dependent manner with maximum phosphorylation saturating at mechanical loading levels of 12g (p < 0.001) with no effect on total ERK. The phosphorylation of focal adhesion kinase (FAK) was unaffected by mechanical force. g-Loading did not activate P38 MAPK or c-jun N-terminal kinase (JNK). Additionally, a gravity pulse resulted in the localization of phosphorylated ERK 1/2 to the nucleus; this did not occur in unloaded cells. The induction of c-fos was inhibited 74% by the MEK1/2 inhibitor U0126 (p < 0.001) but was not affected by MEK1 or p38 MAPK-specific inhibitors. The long-term consequence of a single 15-minute gravity pulse was a 64% increase in cell growth (p < 0.001). U0126 significantly inhibited gravity-induced growth by 50% (p < 0.001). These studies suggest that short periods of physiological mechanical stress induce immediate early gene expression and growth in MC3T3-E1 osteoblasts primarily through an ERK 1/2-mediated pathway.

NASA Discipline Cell Biology↗
NASA NTRS2001

Dose and dose rate effects of whole-body gamma-irradiation: II. Hematological variables and cytokines

The goal of part II of this study was to evaluate the effects of gamma-radiation on circulating blood cells, functional characteristics of splenocytes, and cytokine expression after whole-body irradiation at varying total doses and at low- and high-dose-rates (LDR, HDR). Young adult C57BL/6 mice (n = 75) were irradiated with either 1 cGy/min or 80 cGy/min photons from a 60Co source to cumulative doses of 0.5, 1.5, and 3.0 Gy. The animals were euthanized at 4 days post-exposure for in vitro assays. Significant dose- (but not dose-rate-) dependent decreases were observed in erythrocyte and blood leukocyte counts, hemoglobin, hematocrit, lipopolysaccharide (LPS)-induced 3H-thymidine incorporation, and interleukin-2 (IL-2) secretion by activated spleen cells when compared to sham-irradiated controls (p < 0.05). Basal proliferation of leukocytes in the blood and spleen increased significantly with increasing dose (p < 0.05). Significant dose rate effects were observed only in thrombocyte counts. Plasma levels of transforming growth factor-beta 1 (TGF-beta 1) and splenocyte secretion of tumor necrosis factor-alpha (TNF-alpha) were not affected by either the dose or dose rate of radiation. The data demonstrate that the responses of blood and spleen were largely dependent upon the total dose of radiation employed and that an 80-fold difference in the dose rate was not a significant factor in the great majority of measurements.

NASA Discipline Radiation Health↗
NASA NTRS1999

The response of bone to unloading

Skeletal unloading leads to decreased bone formation and decreased bone mass. Bone resorption is uncoupled from bone formation, contributing to the bone loss. During spaceflight bone is lost principally from the bones most loaded in the 1-g environment, and some redistribution of bone from the lower extremities to the head appears to take place. Although changes in calcitropic hormones have been demonstrated during skeletal unloading (PTH and 1,25(OH)2D decrease), it remains unclear whether such changes account for or are in response to the changes in bone formation and resorption. Bed rest studies with human volunteers and hindlimb elevation studies with rats have provided useful data to help explain the changes in bone formation during spaceflight. These models of skeletal unloading reproduce a number of the conditions associated with microgravity, and the findings from such studies confirm many of the observations made during spaceflight. Determining the mechanism(s) by which loading of bone is sensed and translated into a signal(s) controlling bone formation remains the holy grail in this field. Such investigations couple biophysics to biochemistry to cell and molecular biology. Although studies with cell cultures have revealed biochemical responses to mechanical loads comparable to that seen in intact bone, it seems likely that matrix-cell interactions underlie much of the mechanocoupling. The role for systemic hormones such as PTH, GH, and 1,25(OH)2D compared to locally produced factors such as IGF-I, PTHrP, BMPs, and TGF-beta in modulating the cellular response to load remains unclear. As the mechanism(s) by which bone responds to mechanical load with increased bone formation are further elucidated, applications of this knowledge to other etiologies of osteoporosis are likely to develop. Skeletal unloading provides a perturbation in bone mineral homeostasis that can be used to understand the mechanisms by which bone mineral homeostasis is maintained, with the expectation that such understanding will lead to effective treatment for disuse osteoporosis.

NASA Program Fundamental Space Biology↗