816 research outputs found
Immune System Dysregulation and Herpesvirus Reactivation Persist During Long-Duration Spaceflight
Background: Immunity, latent herpesvirus reactivation, physiological stress and circadian rhythms were assessed during six month spaceflight onboard ISS. Blood and saliva samples were collected early, mid and late in-flight and returned for immediate analysis. Mid-point study data (10 of 17 planned subjects) will be presented. Results: Some shifts in leukocyte distribution occurred during flight, including alterations in CD8+ T cell maturation. General T cell function was consistently reduced early in-flight. Levels CD8+/IFNg+ producing T cells were depressed early in-flight, and immediately upon landing. Persistent mitogen-dependant reductions were observed in IFNg, IL-17a, IL-10, TNFa and IL-6 production. Monocyte production of IL-10 was reduced, whereas IL-8 levels were increased. Levels of mRNA for the TNFa, IL-6 and IFNg were transiently elevated early in-flight, and the dynamics of TNF and IL-6 gene expression were somewhat antagonistic to their corresponding receptors during flight. The number of virus-specific CD8+ T-cells was measured using MHC tetramers, while their function was measured using intracellular cytokine analysis following peptide stimulation. Both the number and function of EBV-specific cells decreased during flight as compared to preflight levels. The number of CMV-specific T-cells generally increased as the mission progressed while their function was variable. Viral (EBV) load in blood was elevated postflight. Anti-EBV VCA antibodies were significantly elevated by R+0; anti-EA antibodies were not significantly elevated at landing; and anti-CMV antibodies were somewhat elevated during flight. Higher levels of salivary EBV DNA were found during flight. VZV DNA reactivation occurred in ~50 % of astronauts during flight, continuing for up to 30 days post-flight. CMV was shed in 35 % the in-flight and 30% of postflight urine samples of the crewmembers. There was generally a higher level of cortisol as measured in urine and saliva in the astronauts during flight, but plasma cortisol was relatively unchanged during flight. Circadian rhythm of salivary cortisol was altered during flight. Conclusion. Some alterations in immunity do not resolve during six month spaceflight, consequentially resulting in persistent herpesvirus reactivation. Ongoing immune dysregulation may represent specific clinical risks for exploration-class space missions
The ESA-NASA CHOICE Study: Winterover at Concordia Station, Interior Antarctica, A Potential Analog for Spaceflight-Associated Immune Dysregulation
For ground-based space physiological research, the choice of terrestrial analog must carefully match the system of interest. Antarctica winter-over at the European Concordia Station is potentially a superior ground-analog for spaceflight-associated immune dysregulation (SAID). Concordia missions consist of prolonged durations in an extreme/dangerous environment, station-based habitation, isolation, disrupted circadian rhythms and international crews. The ESA-NASA CHOICE study assesses innate and adaptive immunity, viral reactivation and stress factors during Concordia winterover deployment. Initial data obtained from the first study deployment (2009 mission; 'n' of 6) will be presented, and logistical challenges regarding analog usage for biological studies will also be discussed. The total WBC increased, and alterations in some peripheral leukocyte populations were observed during winterover at Concordia Station. Percentages of lymphocytes and monocytes increased, and levels of senescent CD8+ T cells were increased during deployment. Transient increases in constitutively activated T cell subsets were observed, at mission time points associated with endemic disease outbreaks. T cell function (early blastogenesis response) was increased near the entry/exit deployment phases, and production of most measured cytokines increased during deployment. Salivary cortisol demonstrated high variability during winterover, but was generally increased. A 2-point circadian rhythm of cortisol measurement (morning/evening) was unaltered during winterover. Perceived stress was mildly elevated during winterover. Other measures, including in-vitro DTH assessment, viral specific T cell number/function and latent herpesvirus reactivation have not yet been completed for the 2009 winterover subjects. Based on the preliminary data, alterations in immune cell distribution and function appear to persist during Antarctic winterover at Concordia Station. Some of these changes are similar to those observed in Astronauts, either during or immediately following spaceflight. Based on the initial immune data and environmental conditions, Concordia winterover may be an appropriate analog for some flight-associated immune changes
NASA 14 Day Undersea Missions: A Short-Duration Spaceflight Analog for Immune System Dysregulation
BACKGROUND Spaceflight-associated immune dysregulation (SAID) occurs during spaceflight and may represent specific clinical risks for exploration-class missions. An appropriate ground analog for spaceflight-associated immune dysregulation would offer a platform for ground-evaluation of various potential countermeasures. This study evaluated the NASA Undersea Mission Operations ( NEEMO ), consisting of 14 day undersea deployment at the Aquarius station, as an analog for SAID. Sixteen Aquanauts from missions NEEMO-12, 13 and 14 participated in the study. RESULTS Mid-mission alterations leukocyte distribution occurred, including granulocytosis and elevations in central-memory CD8+ T-cells. General T cell function was reduced during NEEMO missions in roughly 50% of subjects. Secreted cytokines profiles were evaluated following whole blood stimulation with CD3/CD28 (T cells) or LPS (monocytes). T cell production of IFNg, IL-5, IL-10, IL-2, TNFa and IL-6 were all reduced before and during the mission. Conversely, monocyte production of TNFa, IL-10, IL-6, IL-1b and IL-8 were elevated during mission, moreso at the MD-14 timepoint. Antibodies to Epstein-Barr virus (EBV) viral capsid antigen and early antigen were increased in approximately 40% of the subjects. Changes in EBV tetramer-positive CD8+ T-cells exhibited a variable pattern. Antibodies against Cytomegalovirus (CMV) were marginally increased during the mission. Herpesvirus reactivation was determined by PCR. EBV viral load was generally elevated at L-6. Higher levels of salivary EBV were found during the NEEMO mission than before and after as well as than the healthy controls. No VZV or CMV was found in any pre, during and after NEEMO mission or control samples. Plasma cortisol was elevated at L-6. CONCLUSION Unfortunately, L-6 may be too near to mission start to be an appropriate baseline measurement. The general immune changes in leukocyte distribution, T cell function, cytokine production, virus specific immunity and viral reactivation are similar to those observed during or following spaceflight. The NEEMO platform may thus have utility for short-duration, ground-based spaceflight-immune research, such as investigations of mechanism or countermeasures validation
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INVESTIGATION OF THE THERMODYNAMICS GOVERNING METAL HYDRIDE SYNTHESIS IN THE MOLTEN STATE PROCESS.
Complex metal hydrides have been synthesized for hydrogen storage through a new synthetic technique utilizing high hydrogen overpressure at elevated temperatures (molten state processing). This synthesis technique holds the potential of fusing different complex hydrides at elevated temperatures and pressures to form new species with enhanced hydrogen storage properties. Formation of these compounds is driven by thermodynamic and kinetic considerations. We report on investigations of the thermodynamics. Novel synthetic complexes were formed, structurally characterized, and their hydrogen desorption properties investigated. The effectiveness of the molten state process is compared with mechanicosynthetic ball milling
Environmental hazards and stress: evidence from the Texas City Stress and Health Study
Substantial research has suggested that exposure to environmental health hazards, such as polluting industrial activity, has deleterious effects on psychological and physiological well-being. However, one gap in the existing literature is comparative analysis of objective and subjective exposure's relative association with various measurable outcomes of exposure
Quantum Measurement of a Single Spin using Magnetic Resonance Force Microscopy
Single-spin detection is one of the important challenges facing the
development of several new technologies, e.g. single-spin transistors and
solid-state quantum computation. Magnetic resonance force microscopy with a
cyclic adiabatic inversion, which utilizes a cantilever oscillations driven by
a single spin, is a promising technique to solve this problem. We have studied
the quantum dynamics of a single spin interacting with a quasiclassical
cantilever. It was found that in a similar fashion to the Stern-Gerlach
interferometer the quantum dynamics generates a quantum superposition of two
quasiclassical trajectories of the cantilever which are related to the two spin
projections on the direction of the effective magnetic field in the rotating
reference frame. Our results show that quantum jumps will not prevent a
single-spin measurement if the coupling between the cantilever vibrations and
the spin is small in comparison with the amplitude of the radio-frequency
external field.Comment: 16 pages RevTeX including 4 figure
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Methylation by Set9 Modulates FoxO3 Stability and Transcriptional Activity
The FoxO family of transcription factors plays an important role in longevity and tumor suppression by regulating the expression of a wide range of target genes. FoxO3 has recently been found to be associated with extreme longevity in humans and to regulate the homeostasis of adult stem cell pools in mammals, which may contribute to longevity. The activity of FoxO3 is controlled by a variety of post-translational modifications that have been proposed to form a ‘code’ affecting FoxO3 subcellular localization, DNA binding ability, protein-protein interactions and protein stability. Lysine methylation is a crucial post-translational modification on histones that regulates chromatin accessibility and is a key part of the ‘histone code’. However, whether lysine methylation plays a role in modulating FoxO3 activity has never been examined. Here we show that the methyltransferase Set9 directly methylates FoxO3 in vitro and in cells. Using a combination of tandem mass spectrometry and methyl-specific antibodies, we find that Set9 methylates FoxO3 at a single residue, lysine 271, a site previously known to be deacetylated by Sirt1. Methylation of FoxO3 by Set9 decreases FoxO3 protein stability, while moderately increasing FoxO3 transcriptional activity. The modulation of FoxO3 stability and activity by methylation may be critical for fine-tuning cellular responses to stress stimuli, which may in turn affect FoxO3's ability to promote tumor suppression and longevity
Ultrasensitive force and displacement detection using trapped ions
The ability to detect extremely small forces is vital for a variety of
disciplines including precision spin-resonance imaging, microscopy, and tests
of fundamental physical phenomena. Current force-detection sensitivity limits
have surpassed 1 (atto ) through coupling of micro or
nanofabricated mechanical resonators to a variety of physical systems including
single-electron transistors, superconducting microwave cavities, and individual
spins. These experiments have allowed for probing studies of a variety of
phenomena, but sensitivity requirements are ever-increasing as new regimes of
physical interactions are considered. Here we show that trapped atomic ions are
exquisitely sensitive force detectors, with a measured sensitivity more than
three orders of magnitude better than existing reports. We demonstrate
detection of forces as small as 174 (yocto ), with a
sensitivity 390 using crystals of Be
ions in a Penning trap. Our technique is based on the excitation of normal
motional modes in an ion trap by externally applied electric fields, detection
via and phase-coherent Doppler velocimetry, which allows for the discrimination
of ion motion with amplitudes on the scale of nanometers. These experimental
results and extracted force-detection sensitivities in the single-ion limit
validate proposals suggesting that trapped atomic ions are capable of detecting
of forces with sensitivity approaching 1 . We anticipate that
this demonstration will be strongly motivational for the development of a new
class of deployable trapped-ion-based sensors, and will permit scientists to
access new regimes in materials science.Comment: Expanded introduction and analysis. Methods section added. Subject to
press embarg
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HIGH TEMPERATURE PRESSURE PROCESSING OF MIXED ALANATE COMPOUNDS
Mixtures of light-weight elements and hydrides were investigated to increase the understanding of the chemical reactions that take place between various materials. This report details investigations we have made into mixtures that include NaAlH{sub 4}, LiAlH{sub 4}, MgH{sub 2}, Mg{sub 2}NiH{sub 4}, alkali(ne) hydrides, and early third row transition metals (V, Cr, Mn). Experimental parameters such as stoichiometry, heat from ball milling versus hand milling, and varying the temperature of high pressure molten state processing were studied to examine the effects of these parameters on the reactions of the complex metal hydrides
Quantum noise in the position measurement of a cavity mirror undergoing Brownian motion
We perform a quantum theoretical calculation of the noise power spectrum for
a phase measurement of the light output from a coherently driven optical cavity
with a freely moving rear mirror. We examine how the noise resulting from the
quantum back action appears among the various contributions from other noise
sources. We do not assume an ideal (homodyne) phase measurement, but rather
consider phase modulation detection, which we show has a different shot noise
level. We also take into account the effects of thermal damping of the mirror,
losses within the cavity, and classical laser noise. We relate our theoretical
results to experimental parameters, so as to make direct comparisons with
current experiments simple. We also show that in this situation, the standard
Brownian motion master equation is inadequate for describing the thermal
damping of the mirror, as it produces a spurious term in the steady-state phase
fluctuation spectrum. The corrected Brownian motion master equation [L. Diosi,
Europhys. Lett. {\bf 22}, 1 (1993)] rectifies this inadequacy.Comment: 12 pages revtex, 2 figure
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