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At least 91 records · Page 5

Suppressed PHA Activation of T Lymphocytes in Simulated Microgravity Is Restored by Direct Activation of Protein Kinase C with Phorbol Ester

Various aspects of spaceflight, including microgravity, cosmic radiation, and physiological stress, may perturb immune function. We sought to understand the impact of microgravity alone on the cellular mechanisms critical to immunity. We utilized clinostatic RWV bioreactors that simulate aspects of microgravity to analyze the response of human PBMC to polyclonal activation. PHA responsiveness in the RWV was almost completely diminished. IL-2 and IFN-gamma secretion was reduced whereas IL- 1 beta and IL-6 secretion was increased, suggesting that monocytes may not be as adversely affected by simulated microgravity as T cells. Activation marker expression (CD25, CD69, CD71) was significantly reduced in RWV cultures. Furthermore, addition of exogenous IL-2 to these cultures did not restore proliferation. Reduced cell-cell and cell-substratum interactions may play a role in the loss of PHA responsiveness. However, PHA activation in Teflon culture bags that limit cell-substratum interactions did not suppress PHA activation. Furthermore, increasing cell density and, therefore, cell-cell interactions in the RWV cultures did not help restore PHA activation. However, placing PBMC within small collagen beads did partially restore PHA responsiveness. Activation of both PBMC and purified T cells with PMA and ionomycin was unaffected by RWV culture, indicating that signaling mechanisms downstream of PKC activation and calcium flux are not sensitive to simulated microgravity. Furthermore, submitogenic doses of PMA alone but not ionomycin alone restored PHA responsiveness of PBMC in RWV culture. Thus, our data indicate that during polyclonal activation the signaling pathways upstream of PKC activation are sensitive to simulated microgravity.

Cooper, David↗

Deciphering the Long-Term Trend of Atlantic Basin Intense Hurricanes: More Active Versus Less Active During the Present Epoch

During the interval of 1944-1997, 120 intense hurricanes (i.e., those of category 3 or higher on the Saffir-Simpson hurricane damage potential scale) were observed in the Atlantic basin, having an annual frequency of 0-7 events per year, being more active prior to the mid 1960's than thereafter (hence a possible two-state division: more active versus less active), and being preferentially lower during El Nino years as compared to non-El Nino years. Because decadal averages of the frequency of intense hurricanes closely resemble those of average temperature anomalies for northern hemispheric and global standards and of the average temperature at the Armagh Observatory (Northern Ireland), a proxy for climatic change, it is inferred that the long-term trends of the annual frequency of intense hurricanes and temperature may be statistically related. Indeed, on the basis of 4- and 10-yr moving averages, one finds that there exists strong linear associations between the annual frequency of intense hurricanes in the Atlantic basin and temperature (specially, when temperature slightly leads). Because the long-term leading trends of temperature are now decidedly upward, beginning about the mid 1980's, it is inferred that the long-term consequential trends of the annual frequency of intense hurricanes should now also be upward, having begun near 1990, suggesting that a return to the more active state probably has already occurred. However, because of the anomalous El Nino activity of the early to mid 1990's, the switch from the less active to the more active state essentially went unnoticed (a marked increase in the number of intense hurricanes was not observed until the 1995 and 1996 hurricane seasons, following the end of the anomalous El Nino activity). Presuming that a return to the more active state has, indeed, occurred, one expects the number of seasonal intense hurricanes during the present epoch (continuing through about 2012) to usually be higher than average (i.e., greater than or equal to 2), except during El Nino-related seasons when the number usually will be less than average.

Wilson, Robert M.↗

The Main Sequence of Explosive Solar Active Regions: Comparison of Emerging and Mature Active Regions

For mature active regions, an active region s magnetic flux content determines the maximum free energy the active region can have. Most Large flares and CMEs occur in active regions that are near their free-energy limit. Active-region flare power radiated in the GOES 1-8 band increases steeply as the free-energy limit is approached. We infer that the free-energy limit is set by the rate of release of an active region s free magnetic energy by flares, CMEs and coronal heating balancing the maximum rate the Sun can put free energy into the active region s magnetic field. This balance of maximum power results in explosive active regions residing in a "mainsequence" in active-region (flux content, free energy content) phase space, which sequence is analogous to the main sequence of hydrogen-burning stars in (mass, luminosity) phase space.

Falconer, David↗

Patterns of Activity in A Global Model of A Solar Active Region

In this work we investigate the global activity patterns predicted from a model active region heated by distributions of nanoflares that have a range of frequencies. What differs is the average frequency of the distributions. The activity patterns are manifested in time lag maps of narrow-band instrument channel pairs. We combine hydrodynamic and forward modeling codes with a magnetic field extrapolation to create a model active region and apply the time lag method to synthetic observations. Our aim is not to reproduce a particular set of observations in detail, but to recover some typical properties and patterns observed in active regions. Our key findings are the following. (1) Cooling dominates the time lag signature and the time lags between the channel pairs are generally consistent with observed values. (2) Shorter coronal loops in the core cool more quickly than longer loops at the periphery. (3) All channel pairs show zero time lag when the line of sight passes through coronal loop footpoints. (4) There is strong evidence that plasma must be re-energized on a timescale comparable to the cooling timescale to reproduce the observed coronal activity, but it is likely that a relatively broad spectrum of heating frequencies are operating across active regions. (5) Due to their highly dynamic nature, we find nanoflare trains produce zero time lags along entire flux tubes in our model active region that are seen between the same channel pairs in observed active regions.

Bradshaw, S. J.↗

Behavioral Makers to Assess During Selection for Active and Non-Active Astronauts

INTRODUCTION: NASA and our international partners seek to stay ahead of the evolving nature of the astronaut role. Spaceflight comes with various risks to team and individual. NASA has worked with its international partners in developing selection guidelines for minimal behavioral competencies needed upon selection. Training should be provided on the remaining behavioral competencies required for spaceflight. We will provide an overview of the process of identifying competencies important to assess as part of a multi-method selection program for active and non-active astronauts. TOPIC: NASA, ESA, CSA, and JAXA agency representatives used their vast combined knowledge and experience to develop competency requirement standards that future selection programs should assess when selecting astronauts. The astronaut role is expanding to include astronauts whose purposes are quite varied. NASA and its international partners identified the need to identify what competencies are required for anyone who will be experiencing the incredible demands, risks, and unique circumstances associated with spaceflight. Competencies include those required for individual and team functioning within the isolated, confined, and extreme environment. This need grew out of greater commercialization of spaceflight and other budding spaceflight prospects. 1. Each agency rated previously defined spaceflight required competencies (not important 0, somewhat important .5, or extremely important 1) to assess during selection. We did this for short duration (<14 days) and for long duration (<14 days) missions as some competencies appear to become of greater importance with longer duration missions. 2. We rated competencies for non-active crew and revisited previous ratings for active crew. 3. We compared agency ratings for non-active/active and short-duration/long-duration requirements and discussed in ratings until consensus was reached. We will use ratings to compile selection standards for active and non-active astronauts. APPLICATION: Our working group has vast operational experience and knowledge of the risk factors present during spaceflight that can disrupt individual and team functioning. Selection is one of the most important countermeasures for mitigating risk to individual and team health and performance. Our work should inform future programs for selecting crewmembers for short- and long-duration spaceflight among active and non-active crews.

Alexa Baxley↗

Estimating Radionuclide Activity in Surface Contamination for GTCC Activated Metal Waste Streams - 18236

The U.S. Nuclear Regulatory Commission's licensing requirements for land disposal of low-level radioactive waste (LLRW) in 10 CFR Part 61 classify LLRW wastes as Class A, B, C, or Greater-Than- Class C (GTCC). GTCC waste includes activated metals that are generated primarily by nuclear power reactors. Activated metals represent a significant volume (880 cubic meters) of GTCC wastes that may be generated as current commercial power reactors are decommissioned. Additionally, these wastes are expected to contain radionuclides that are very long-lived and are mobile in the environment (e.g., Tc-99 and I-129) as well as transuranic radionuclides that, while not as mobile as other radionuclides, have greater potential for health consequences should such radionuclides reach receptor locations in sufficient concentrations. Quantities of surface contamination on activated metals have typically been reported using a combination of assumptions, calculations, and measurements. For example, projections of future activity associated with surface contamination, or the surface activity, for the activated metals is dependent on assumptions made regarding fuel behavior (e.g., modern fuel performance is expected to be different from fuel performance in the 1970's). In this study, we examined published information to better understand how assumptions, calculations, and measurements used for estimating quantities of surface contamination on activated metals can influence the estimated quantities. The analysis in this report was performed to better understand how estimates for the activated metal inventory of GTCC metal could influence potential decisions regarding the siting and design of disposal facilities. It was found that the variability in surface contamination either measured or estimated was sufficiently large that characterization of the radionuclide inventory for GTCC activated metals, especially the transuranic radionuclides, is critically important for establishing the siting and design requirements for a disposal facility. Overly conservative assumptions for the inventory could significantly limit disposal options, whereas, overly optimistic assumptions with respect to the inventory could lead to a disposal facility that may not protect off-site receptors. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Connecting cation site location to alkane dehydrogenation activity in Ni/BEA catalysts

Ni-modified beta zeolite (Ni/BEA) catalysts activate carbon-hydrogen bonds in light alkanes, as demonstrated through isobutane reaction testing. Controlled synthesis of Ni/BEA allows for efficient introduction of ion-exchanged Ni sites at varying Ni loadings (0.43% - 1.8%). These catalysts exhibit site time yields (STY) for H2 production that increase with increasing Ni loading. A detailed analysis of secondary reactions and carbon deposition based on the relative molar flowrates of product C and H indicates that the observed increase in H2 STY with increasing Ni loading is likely attributed to both increasing alkane activation activity and increasing formation of hydrogen-deficient aromatic products retained within the catalyst pores. In situ diffuse-reflectance UV-visible-NIR absorbance and X-ray absorption spectroscopies indicate isolated, 4-coordinate Ni(2+) species for all loadings. Quantum mechanics/molecular mechanics modeling identifies two distinct Ni(2+) sites consistent with the structural characterization, but with differing relative stabilities due to their coordination environment. Computed reaction energetics for isobutane dehydrogenation demonstrate that the more stable Ni(2+) species at a six-membered 4Si-2Al ring, Ni-6MR, is less active for isobutane dehydrogenation than the less stable Ni(2+) at the five-membered 3Si-2Al ring, Ni-5MR. The differing local structure of the isolated cationic Ni sites in Ni/BEA offers a possible rationalization for the increased H2 STY observed at greater Ni loadings.

catalysts↗

Best Practices and Testing Protocols for Benchmarking ORR Activities of Fuel Cell Electrocatalysts Using Rotating Disk Electrode

Abstract Thin-film-rotating disk electrodes (TF-RDEs) are the half-cell electrochemical system of choice for rapid screening of oxygen reduction reaction (ORR) activity of novel Pt supported on carbon black supports (Pt/C) electrocatalysts. It has been shown that the magnitude of the measured ORR activity and reproducibility are highly dependent on the system cleanliness, evaluation protocols, and operating conditions as well as ink formulation, composition, film drying, and the resultant film thickness and uniformity. Accurate benchmarks of baseline Pt/C catalysts evaluated using standardized protocols and best practices are necessary to expedite ultra-low-platinum group metal (PGM) catalyst development that is crucial for the imminent commercialization of fuel cell vehicles. We report results of evaluation in three independent laboratories of Pt/C electrocatalysts provided by commercial fuel cell catalyst manufacturers (Johnson Matthey, Umicore, Tanaka Kikinzoku Kogyo—TKK). The studies were conducted using identical evaluation protocols/ink formulation/film fabrication albeit employing unique electrochemical cell designs specific to each laboratory. The ORR activities reported in this work provide a baseline and criteria for selection and scale-up of novel high activity ORR electrocatalysts for implementation in proton exchange membrane fuel cells (PEMFCs).

Kocha, Shyam S.↗

Production of new activated bio-carbons by chemical activation of residue left after supercritical extraction of hops

Highlights: • An alternative method for bio-waste utilization has been proposed. • Activated bio-carbons were prepared from hops by Na{sub 2}CO{sub 3} activation. • The activated bio-carbons has been used for NO{sub 2}, methylene blue and iodine adsorption. A technology of activated bio-carbons production from the residue left after supercritical extraction of hops is described. The effect of the variant of chemical activation and impregnation ratio on the physicochemical properties as well as sorption capacity towards toxic gas of acidic character (nitrogen dioxide), basic organic dye (aqueous solution of methylene blue - MB) and iodine was investigated. The materials obtained were activated bio-carbons of well-developed surface area ranging between 897 and 1095 m{sup 2}/g, showing clearly acidic character of the surface. The sorption tests results proved that chemical activation of the residue left after supercritical extraction of hops allows obtaining activated bio-carbons with very high sorption capacity towards nitrogen dioxide, reaching to 77.2 and 155.3 mg/g in dry and wet conditions, respectively. The maximum sorption capacity of the adsorbents towards methylene blue was 328.75 mg/g, while towards iodine 1815 mg/g. The equilibrium data for aqueous solution of MB were analyzed by the Langmuir and Freundlich models, whereas the kinetics of the adsorption process was studied using pseudo-first and second-order models. According to the obtained data, the adsorption of MB from aqueous solution is better described by Langmuir model and pseudo-second order kinetic model.

54 ENVIRONMENTAL SCIENCES↗

Surface Organometallic Chemistry of Supported Iridium(III) as a Probe for Organotransition Metal–Support Interactions in C–H Activation

Systematic study of the interactions between organometallic catalysts and metal oxide support materials is essential for the realization of rational design in heterogeneous catalysis. Herein we describe the stoichiometric and catalytic chemistry of a [Cp*(PMe 3 )Ir(III)] complex chemisorbed on a variety of acidic metal oxides as a multifaceted probe for stereoelectronic communication between the support and organometallic center. Electrophilic bond activation was explored in the context of stoichiometric hydrogenolysis as well as catalytic H/D exchange. Further information was obtained from the observation of processes related to dynamic exchange between grafted organometallic species and those in solution. The supported organometallic species were characterized by a variety of spectroscopic techniques including dynamic nuclear polarization-enhanced solid-state NMR spectroscopy, diffuse reflectance infrared Fourier transform spectroscopy, and X-ray absorption spectroscopy. Finally, strongly acidic modified metal oxides such as sulfated zirconia engender high levels of activity toward electrophilic bond activation of both sp 2 and sp 3 C–H bonds, including the rapid deuteration of methane at room temperature; however, the global trend for the supports studied here does not suggest a direct correlation between activity and surface Brønsted acidity.

36 MATERIALS SCIENCE↗

Efficient gene activation in plants by the MoonTag programmable transcriptional activator

Abstract CRISPR/Cas-based transcriptional activators have been developed to induce gene expression in eukaryotic and prokaryotic organisms. The main advantages of CRISPR/Cas-based systems is that they can achieve high levels of transcriptional activation and are very easy to program via pairing between the guide RNA and the DNA target strand. SunTag is a second-generation system that activates transcription by recruiting multiple copies of an activation domain (AD) to its target promoters. SunTag is a strong activator; however, in some species it is difficult to stably express. To overcome this problem, we designed MoonTag, a new activator that works on the same basic principle as SunTag, but whose components are better tolerated when stably expressed in transgenic plants. We demonstrate that MoonTag is capable of inducing high levels of transcription in all plants tested. In Setaria, MoonTag is capable of inducing high levels of transcription of reporter genes as well as of endogenous genes. More important, MoonTag components are expressed in transgenic plants to high levels without any deleterious effects. MoonTag is also able to efficiently activate genes in eudicotyledonous species such as Arabidopsis and tomato. Finally, we show that MoonTag activation is functional across a range of temperatures, which is promising for potential field applications.

42 ENGINEERING↗

Spatio-temporal patterning of extensile active stresses in microtubule-based active fluids

Abstract Microtubule-based active fluids exhibit turbulent-like autonomous flows, which are driven by the molecular motor powered motion of filamentous constituents. Controlling active stresses in space and time is an essential prerequisite for controlling the intrinsically chaotic dynamics of extensile active fluids. We design single-headed kinesin molecular motors that exhibit optically enhanced clustering and thus enable precise and repeatable spatial and temporal control of extensile active stresses. Such motors enable rapid, reversible switching between flowing and quiescent states. In turn, spatio-temporal patterning of the active stress controls the evolution of the ubiquitous bend instability of extensile active fluids and determines its critical length dependence. Combining optically controlled clusters with conventional kinesin motors enables one-time switching from contractile to extensile active stresses. These results open a path towards real-time control of the autonomous flows generated by active fluids.

36 MATERIALS SCIENCE↗

Evidence of topological charge polarization at active-passive interfaces in acoustically powered active liquid crystals

Theoretical and computational studies predict topological charge separation at active-passive interfaces in active nematics, but reliable experimental validation has been lacking. We utilize a synthetic acoustically energized liquid crystal to experimentally investigate the dynamics of topological defects across an active-passive interface. The interference pattern induced by the acoustic wave inside the experimental cell creates a spatial distribution of activity, resulting in the formation of active-passive interfaces with the liquid-crystalline director field aligned parallel to those interfaces. The activity gradient drives the reorientation of positively charged topological defects along its direction, causing them to migrate into the passive zone and form a layer with net topological charge. That layer “discharges” upon cessation of activity through annihilation of positive and negative topological charges, resembling the discharge of a capacitor.

Active defects↗

Attributing runoff changes to climate variability and human activities: Uncertainty analysis using four monthly water balance models

Hydrological simulations to delineate the impacts of climate variability and human activities are subjected to uncertainties related to both parameter and structure of the hydrological models. To analyze the impact of these uncertainties on the model performance and to yield more reliable simulation results, a global calibration and multimodel combination method that integrates the Shuffled Complex Evolution Metropolis (SCEM) and Bayesian Model Averaging (BMA) of four monthly water balance models was proposed. The method was applied to the Weihe River Basin (WRB), the largest tributary of the Yellow River, to determine the contribution of climate variability and human activities to runoff changes. The change point, which was used to determine the baseline period (1956-1990) and human-impacted period (1991-2009), was derived using both cumulative curve and Pettitt’s test. Results show that the combination method from SCEM provides more skillful deterministic predictions than the best calibrated individual model, resulting in the smallest uncertainty interval of runoff changes attributed to climate variability and human activities. This combination methodology provides a practical and flexible tool for attribution of runoff changes to climate variability and human activities by hydrological models.

runoff change, uncertainty assessment, monthly wat↗

Activation of AMP-activated protein kinase by compound 991 protects osteoblasts from dexamethasone

Highlights: • Compound 991 (C991) activates AMPK signaling in osteoblast cells. • C991 attenuates dexamethasone (Dex)-induced osteoblast cell death. • AMPK activation is required for C991-mediated osteoblast protection against Dex. • C991 inhibits Dex-induced oxidative stress in osteoblasts. • Genetic AMPK inhibition reverses C991's anti-oxidant actions in osteoblasts. Dexamethasone (Dex) induces direct cytotoxicity to cultured osteoblasts. The benzimidazole derivative compound 991 (“C991”) is a novel and highly-efficient AMP-activated protein kinase (AMPK) activator. Here, in both MC3T3-E1 osteoblastic cells and primary murine osteoblasts, treatment with C991 activated AMPK signaling, and significantly attenuated Dex-induced apoptotic and non-apoptotic cell death. AMPKα1 knockdown (by shRNA), complete knockout (by CRISPR/Cas9 method) or dominant negative mutation (T172A) not only blocked C991-mediated AMPK activation, but also abolished its pro-survival effect against Dex in osteoblasts. Further studies showed that C991 boosted nicotinamide adenine dinucleotide phosphate (NADPH) activity and induced mRNA expression of NF-E2-related factor 2 (Nrf2)-regulated genes (heme oxygenase-1 and NADPH quinone oxidoreductase 1). Additionally, C991 alleviated Dex-induced reactive oxygen species (ROS) production in osteoblasts. Notably, genetic AMPK inhibition reversed the anti-oxidant actions by C991 in Dex-treated osteoblasts. Together, we conclude that C991 activates AMPK signaling to protect osteoblasts from Dex.

60 APPLIED LIFE SCIENCES↗

Synthesis and characterization of redox-active ferric nontronite

Heterogeneous redox reactions on clay mineral surfaces control mobility and bioavailability of redox-sensitive nutrients and contaminants. Iron (Fe) residing in clay mineral structures can either catalyze or directly participate in redox reactions; however, chemical controls over its reactivity are not fully understood. In our previous work we demonstrated that converting a minor portion of Fe(III) to Fe(II) (partial reduction) in the octahedral sheet of natural Fe-rich clay mineral nontronite (NAu-1) activates its surface, making it redox-active. In this study we produced and characterized synthetic ferric nontronite (SIP), highlighting structural and chemical similarities and differences between this synthetic nontronite and its natural counterpart NAu-1, and probed whether mineral surface is redox-active by reacting it with arsenic As(III) under oxic and anoxic conditions. We demonstrate that synthetic nontronite SIP undergoes the same activation as natural nontronite NAu-1 following the partial reduction treatment. Similar to NAu-1, SIP oxidized As(III) to As(V) under both oxic (catalytic pathway) and anoxic (direct oxidation) conditions. The similar reactivity trends observed for synthetic nontronite and its natural counterpart make SIP an appropriate analog for laboratory studies. The development of chemically pure analogs for ubiquitous soil minerals will allow for systematic research of the fundamental properties of these minerals.

Environmental Molecular Sciences Laboratory↗

Rosmarinic acid counteracts activation of hepatic stellate cells via inhibiting the ROS-dependent MMP-2 activity: Involvement of Nrf2 antioxidant system

Recently, oxidative stress is involved in hepatofibrogenesis. Matrix metalloproteinase-2 (MMP-2) is required for activation of hepatic stellate cells (HSCs) in response to reactive oxygen species (ROS). This study was designed to explore the hypothesis that the inhibitory effect of rosmarinic acid (RA) on HSCs activation might mainly result from its antioxidant capability by increasing the synthesis of glutathione (GSH) involved in nuclear factor kappa B (NF-κB)-dependent inhibition of MMP-2 activity. Here, we demonstrate that RA reverses activated HSCs to quiescent cells. Concomitantly, RA inhibits MMP-2 activity. RNA interference-imposed knockdown of NF-κB abolished down-regulation of MMP-2 by RA. RA-mediated inactivation of NF-κB could be blocked by the diphenyleneiodonium chloride (DPI; a ROS inhibitor). Conversely, transfection of dominant-negative (DN) mutant of extracellular signal-regulated kinases 2 (ERK2), c-Jun N-terminal kinase 1 (JNK1), or p38α kinase had no such effect. Simultaneously, RA suppresses ROS generation and lipid peroxidation (LPO) whereas increases cellular GSH in HSC-T6 cells. Furthermore, RA significantly increased antioxidant response element (ARE)-mediated luciferase activity, nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and catalytic subunits from glutamate cysteine ligase (GCLc) expression, but not modulatory subunits from GCL (GCLm). RA-mediated up-regulation of GClc is inhibited by the shRNA-induced Nrf2 knockdown. The knocking down of Nrf2 or buthionine sulfoximine (a GCL inhibitor) abolished RA-mediated inhibition of ROS. Collectively, these results provide novel insights into the mechanisms of RA as an antifibrogenic candidate in the prevention and treatment of liver fibrosis. - Highlights: • RA reverses activated HSCs to quiescent cells. • RA suppresses MMP-2 activity through a NF-κB-dependent pathway. • Inhibition of oxidative stress by RA is dependent on nuclear translocation of Nrf2. • RA-mediated down-regulation of MMP-2 was ROS-dependent.

60 APPLIED LIFE SCIENCES↗