Studies of extra-solar Oort clouds and the Kuiper disk

NASA Technical Reports Server (NTRS)

Stern, S. Alan

1996-01-01

We are conducting research designed to enhance our understanding of the evolution and detectability of comet clouds and disks. According to 'standard' theory, both the Kuiper Belt and the Oort Cloud are (at least in part) natural products of the planetary accumulation stage of solar system formation. One expects such assemblages to be a common attribute of other solar systems. Therefore, searches for comet disks and clouds orbiting other stars offer a new method for inferring the presence of planetary systems. This project consists of two efforts: (1) observational work to predict and search for the signatures of Oort Clouds and comet disks around other stars; and (2) modelling studies of the formation and evolution of the Kuiper Belt (KB) and similar assemblages that may reside around other stars, including beta Pic.

Observational Studies of the Clearing Phase in Proto-Planetary Disks Surrounding Intermediate Mass Stars

NASA Technical Reports Server (NTRS)

Grady, Carol A.

1999-01-01

A detailed study of circumstellar gas associated with young, intermediate-mass stars has demonstrated that, far from being unique or an infrequently occurring phenomenon, beta Pic-like infall activity is routinely observed in stars younger than 10-50 Myr when the observer's line of sight lies within 15 degrees of the disk mid-plane. Detailed studies of 2 Herbig Ae/Be stars, AB Aur and HD 163296 demonstrate that enhanced infall episodes last 20-60 hours, comparable to the duration of similar episodes in beta Pictoris. The infall activity is consistent with detection of the comae of swarms of star-grazing bodies of asteroidal to cometary composition. Episodic fluctuations in the infall activity are clearly present by approximately 6 Myr, and may indicate the presence of massive planets within the disk. This study has therefore, directly contributed to NASA's Origins of Planetary Systems theme by identifying under what conditions extra-solar planetesimals can be remotely sensed, indicating that such bodies appear to be routinely detectable among young stars in the 1-10 Myr range, and suggesting that temporal studies of spectroscopic variability may provide a means of identifying those systems harboring massive planets. This study has resulted in 2 refereed review papers, 13 other refereed papers, and 17 conference papers.

Long-lived planetary vortices and their evolution: Conservative intermediate geostrophic model.

PubMed

Sutyrin, Georgi G.

1994-06-01

Large, long-lived vortices, surviving during many turnaround times and far longer than the dispersive linear Rossby wave packets, are abundant in planetary atmospheres and oceans. Nonlinear effects which prevent dispersive decay of intense cyclones and anticyclones and provide their self-propelling propagation are revised here using shallow water equations and their balanced approximations. The main physical mechanism allowing vortical structures to be long-lived in planetary fluid is the quick fluid rotation inside their cores which prevents growth in the amplitude of asymmetric circulation arising due to the beta-effect. Intense vortices of both signs survive essentially longer than the linear Rossby wave packet if their azimuthal velocity is much larger than the Rossby wave speed. However, in the long-time evolution, cyclonic and anticyclonic vortices behave essentially differently that is illustrated by the conservative intermediate geostrophic model. Asymmetric circulation governing vortex propagation is described by the azimuthal mode m=1 for the initial value problem as well as for steadily propagating solutions. Cyclonic vortices move west-poleward decaying gradually due to Rossby wave radiation while anticyclonic ones adjust to non-radiating solitary vortices. Slow weakening of an intense cyclone with decreasing of its size and shrinking of the core is described assuming zero azimuthal velocity outside the core while drifting poleward. The poleward tendency of the cyclone motion relative to the stirring flow corresponds to characteristic trajectories of tropical cyclones in the Earth's atmosphere. The asymmetry in dispersion-nonlinear properties of cyclones and anticyclones is thought to be one of the essential reasons for the observed predominance of anticyclones among long-lived vortices in the atmospheres of the giant planets and also among intrathermoclinic eddies in the ocean.

Observational studies of the clearing phase in proto-planetary disk systems

NASA Technical Reports Server (NTRS)

Grady, Carol A.

1994-01-01

A summary of the work completed during the first year of a 5 year program to observationally study the clearing phase of proto-planetary disks is presented. Analysis of archival and current IUE data, together with supporting optical observations has resulted in the identification of 6 new proto-planetary disk systems associated with Herbig Ae/Be stars, the evolutionary precursors of the beta Pictoris system. These systems exhibit large amplitude light and optical color variations which enable us to identify additional systems which are viewed through their circumstellar disks including a number of classical T Tauri stars. On-going IUE observations of Herbig Ae/Be and T Tauri stars with this orientation have enabled us to detect bipolar emission plausibly associated with disk winds. Preliminary circumstellar extinction studies were completed for one star, UX Ori. Intercomparison of the available sample of edge-on systems, with stars ranging from 1-6 solar masses, suggests that the signatures of accreting gas, disk winds, and bipolar flows and the prominence of a dust-scattered light contribution to the integrated light of the system decreases with decreasing IR excess.

Diamagnetic effect in the foremoon solar wind observed by Kaguya

NASA Astrophysics Data System (ADS)

Nishino, Masaki N.; Saito, Yoshifumi; Tsunakawa, Hideo; Miyake, Yohei; Harada, Yuki; Yokota, Shoichiro; Takahashi, Futoshi; Matsushima, Masaki; Shibuya, Hidetoshi; Shimizu, Hisayoshi

2017-04-01

Direct interaction between the lunar surface and incident solar wind is one of the crucial phenomena of the planetary plasma sciences. Recent observations by lunar orbiters revealed that strength of the interplanetary magnetic field (IMF) at spacecraft altitude often increases over crustal magnetic fields on the dayside. In addition, variations of the IMF on the lunar night side have been reported in the viewpoint of diamagnetic effect around the lunar wake. However, few studies have been performed for the IMF over non-magnetized regions on the dayside. Here we show an event where strength of the IMF decreases at 100 km altitude on the lunar dayside (i.e. in the foremoon solar wind) when the IMF is almost parallel to the incident solar wind flow, comparing the upstream solar wind data from ACE with Kaguya magnetometer data. The lunar surface below the Kaguya orbit is not magnetized (or very weakly magnetized), and the sunward-travelling protons show signatures of those back-scattered at the lunar surface. We find that the decrease in the magnetic pressure is compensated by the thermal pressure of the back-scattered protons. In other words, the IMF strength in the foremoon solar wind decreases by diamagnetic effect of sunward-travelling protons back-scattered at the lunar dayside surface. Such an effect would be prominent in the high-beta solar wind, and may be ubiquitous in the environment where planetary surface directly interacts with surrounding space plasma.

Parametric instabilities of the circularly polarized Alfven waves including dispersion. [for solar wind

NASA Technical Reports Server (NTRS)

Wong, H. K.; Goldstein, M. L.

1986-01-01

A class of parametric instabilities of large-amplitude, circularly polarized Alfven waves is considered in which finite frequency (dispersive) effects are included. The dispersion equation governing the instabilities is a sixth-order polynomial which is solved numerically. As a function of K identically equal to k/k-sub-0 (where k-sub-0 and k are the wave number of the 'pump' wave and unstable sound wave, respectively), there are three regionals of instability: a modulation instability at K less than 1, a decay instability at K greater than 1, and a relatively weak and narrow instability at K close to squared divided by v-sub-A squared (where c-sub-s and v-sub-A are the sound and Alfven speeds respectively), the modulational instability occurs when beta is less than 1 (more than 1) for left-hand (right-hand) pump waves, in agreement with the previous results of Sakai and Sonnerup (1983). The growth rate of the decay instability of left-hand waves is greater than the modulational instability at all values of beta. Applications to large-amplitude wave observed in the solar wind, in computer simulations, and in the vicinity of planetary and interplanetary collisionless shocks are discussed.

Direct observation of extrasolar planets and the development of the gemini planet imager integral field spectrograph

NASA Astrophysics Data System (ADS)

Chilcote, Jeffrey Kaplan

This thesis is focused on the development and testing of a new instrument capable of finding and characterizing recently-formed Jupiter-sized planets orbiting other stars. To observe these planets, I present the design, construction and testing of the Gemini Planet Imager (GPI) Integral Field Spectrograph (IFS). GPI is a facility class instrument for the Gemini Observatory with the primary goal of directly detecting young Jovian planets. The GPI IFS utilizes an infrared transmissive lenslet array to sample a rectangular 2.7 x 2.7 arcsecond field of view and provide low-resolution spectra across five bands between 1 and 2.5 mum. The dispersing element can be replaced with a Wollaston prism to provide broadband polarimetry across the same five filter bands. The IFS construction was based at the University of California, Los Angeles in collaboration with the Universite de Montreal, Immervision and Lawrence Livermore National Laboratory. I will present performance results, from in-lab testing, of the Integral Field Spectrograph (IFS) for the Gemini Planet Imager (GPI). The IFS is a large, complex, cryogenic, optical system requiring several years of development and testing. I will present the design and integration of the mechanical and optical performance of the spectrograph optics. The IFS passed its pre-ship review in 2011 and was shipped to University of California, Santa Cruz for integration with the remaining sub-systems of GPI. The UCLA built GPI IFS was integrated with the rest of GPI and is delivering high quality spectral datacubes of GPI's coronagraphic field. Using the NIRC2 instrument located at the Keck Observatory, my collaborators and I observed the planetary companion to beta Pictoris in L' (3.5--4.1mum). Observations taken in the fall of 2009 and 2012 are used to find the location and inclination of the planet relative to the massive debris disk orbiting beta Pictoris. We find that the planet's orbit has a position angle on the sky of 211.9+/-0.4 degrees, making the planet misaligned by 2.9+/-0.5 degrees from the main disk, consistent with other observations that beta Pic b is misaligned with the main disk, and part of the misaligned inner disk. In 2009 & 2012 we find a projected orbital separation of 312.8 +/- 18.3 and 466.35 +/- 8.4 milliarcseconds consistent with an orbital period of ˜ 20 years, and a semi-major axis of ˜ 9 AU as found by Macintosh et al. (2014). During the first commissioning observations with the Gemini Planet Imager (GPI), my collaborators and I took the first H-band spectrum of the planetary companion to the nearby young star beta Pictoris. The spectrum has a resolving power of ˜ 45 and demonstrates the distinctive triangular shape of a cool substellar object with low surface gravity. Using atmospheric models, we find an effective temperature of 1650 +/- 50K and a surface gravity of log(g) = 4.0 +/- 0.25 (cgs units). These values agree well with predictions from planetary evolution models for a gas giant with mass between 10 and 12 MJup and age between 10 and 20 Myrs. The spectrum is very similar to a known low mass field brown dwarf but has more flux at the long wavelength end of the filters compared to models. Given the very high signal-to-noise of our spectrum this likely indicates additional physics such as patchy clouds that need to be included in the model.

DISK AROUND STAR MAY BE WARPED BY UNSEEN PLANET

NASA Technical Reports Server (NTRS)

2002-01-01

NASA's Hubble Space Telescope has provided strong evidence for the existence of a roughly Jupiter-sized planet orbiting the star Beta Pictoris. Detailed Hubble images of the inner region of the 200-billion mile diameter dust disk encircling the star reveal an unexpected warp. Researchers say the warp can be best explained as caused by the gravitational pull of an unseen planet. The suspected planet would dwell within a five-billion mile wide clear zone in the center of the disk. This zone has long been suspected of harboring planets that swept it clear of debris, but the Hubble discovery provides more definitive evidence that a planet is there. (Alternative theories suggest the clear zone is empty because it is too warm for ice particles to exist.) 'We were surprised to find that the innermost region of the disk is orbiting in a different plane from the rest of the disk,' says Chris Burrows (Space Telescope Science Institute, Baltimore, Maryland, and the European Space Agency) who is presenting his results at the meeting of the American Astronomical Society in San Antonio, Texas. As he analyzed Hubble images, taken in January 1995 with the Wide Field Planetary Camera 2, Burrows discovered an unusual bulge in the nearly edge-on disk, which was mirrored on the other side of the star. 'Such a warp cannot last for very long,' says Burrows. 'This means that something is still twisting the disk and keeping out of a basic flat shape.' 'The presence of the warp is strong though indirect evidence for the existence of planets in this system. If Beta Pictoris had a solar system like ours, it would produce a warp like the one we see.' Burrows concludes, 'The Beta Pictoris system seems to contain at least one planet not too dissimilar from Jupiter in size and orbit. Rocky planets like Earth might circle Beta Pictoris as well. However, there is no evidence for these yet. Any planet will be at least a billion- times fainter than the star, and presently impossible to view directly, even with Hubble.' An alterative explanation of the warp is that the disk could have been perturbed by a passing star However this is very unlikely because only the inner region of the disk is affected. Burrows estimates that there is a one in 400,000 chance for Beta Pictoris to have such a close encounter with another star. 'Though Beta Pictoris is probably at least 100 million years old, other explanations for the warp do not allow it to last for very long.' The size of the warp allows Burrows to roughly measure the mass of the orbiting body. 'It must lie well within the warp, probably within the clear zone that exists around Beta Pictoris.' On the other hand, he points out, it cannot be too close to the star because its gravitational pull would cause the star to 'jiggle,' and such radial velocity variations have never been seen in Beta Pictoris. Burrows estimates the planet is from one-twentieth to twenty times the mass of Jupiter. The planet must lie within the range of distances typical of planetary distances within our solar system -- from about Earth's distance from the Sun to about Pluto's distance from the Sun (Pluto is roughly 30 times father from the Sun than Earth.) If the suspected planet were as far from Beta Pictoris as Jupiter is from our Sun, it also would have about the same mass as Jupiter. The planet's orbit must be inclined by about three degrees to the plane of the Beta Pictoris disk, and this is typical of the inclinations of the orbits of the planets in our solar system. The star is located 50 light-years away in the southern constellation Pictor (Painter's Easel). Though its precise age is not known, Beta Pictoris is generally considered a mature, main sequence star, slightly hotter than our Sun. Detections of substellar objects orbiting nearby stars have recently been reported for two other normal (i.e., main sequence) stars -- Gliese 229 and 51 Pegasus. However, Beta Pictoris is the only candidate that looks like it might possess a planetary system similar to our own. Beta Pictoris also is the only known star with a circumstellar disk of gas and dust that can be optically imaged. Despite the presence of dust around approximately one-third of the brightest nearby stars -- as deduced from NASA's Infrared Astronomy Satellite (IRAS) data -- ground-based telescope imaging has not detected other disks. Several Hubble programs are currently in progress to search for these disks. The NICMOS (Near Infrared Camera and Multi-Object Spectrometer), to be installed on Hubble during the February 1997 servicing mission, will provide a near-infrared capability needed for this type of search. * * * * * The Space Telescope Science Institute is operated by the Association of Universities for Research in Astronomy, Inc. (AURA), for NASA, under contract with the Goddard Space Flight Center, Greenbelt, MD. The Hubble Space Telescope is a project of international cooperation between NASA and the European Space Agency (ESA).

The search for extra-solar planetary systems.

PubMed

Paresce, F

1992-01-01

I review the observational evidence for planetary systems around nearby stars and, using our own solar system as a guide, assess the stringent requirements that new searches need to meet in order to unambiguously establish the presence of another planetary system. Basically, these requirements are: 1 milliarcsecond or better positional accuracy for astrometric techniques, 9 orders of magnitude or better star to planet luminosity ratio discrimination at 0.5 to 1" separation in the optical for direct imaging techniques, 10 meters sec-1 or better radial velocity accuracy for reflex motion techniques and +/-1% or better brightness fluctuation accuracy for planet/star occultation measurements. The astrometric accuracy is in reach of HST, direct imaging will require much larger telescopes and/or a 50 times smoother mirror than HST while the reflex motion and occultation techniques best performed on the ground are just becoming viable and promise exciting new discoveries. On the other band, new indirect evidence on the existence of other planetary systems also comes from the observation of large dusty disks around nearby main sequence stars not too dissimilar from our sun. In one particular case, that of Beta Pictoris, a flattened disk seen nearly edge-on has been imaged in the optical and near IR down to almost 70 AU of the star. It probably represents a young planetary system in its clearing out phase as planetesimals collide, erode and are swept out of the inner system by radiation pressure. The hypothesized Kuiper belt around our solar system may be the analogous structure in a later evolutionary stage. Features of this type have been detected in the far IR and sub-millimeter wavelength regions around 50-100 nearby main sequence and pre-main sequence stars. I discuss a battery of new accurate observations planned in the near future of these objects some of which may actually harbour planets or planetesimals that will certainly dramatically improve our knowledge of planetary system formation processes and our peculiar position in this scheme.

Cosmological Effects in Planetary Science

NASA Technical Reports Server (NTRS)

Blume, H. J.; Wilson, T. L.

2010-01-01

In an earlier discussion of the planetary flyby anomaly, a preliminary assessment of cosmological effects upon planetary orbits exhibiting the flyby anomaly was made. A more comprehensive investigation has since been published, although it was directed at the Pioneer anomaly and possible effects of universal rotation. The general subject of Solar System anomalies will be examined here from the point of view of planetary science.

10 micron Spectroscopy with OSCIR: Silicate Minerology and The Origins of Disks & Protoplanetesimals

NASA Astrophysics Data System (ADS)

Woodward, Chick; Wooden, Diane; Harker, David; Rodgers, Bernadette; Butner, Harold

1999-02-01

The analysis of the silicate mineralogy of pre-main sequence Herbig Ae/Be (HeAeBe) stars to main sequence (beta)-Pic systems, probes the chemical and physical conditions in these potentially planet-forming environments, the condensation of dust from the gas-disk, and the aggregation and accretion of these solids into planetesimals and comets. We propose to obtain 10 micron OSCIR spectra of a selected list of HeAeBe and (beta)-Pic like systems. Use of our ground-based data, combined with the ISO SWS database, and our extensive analytical modeling efforts will permit us to develop a fundamental understanding of connections between silicate mineralogy and the origins and evolution of disks and protoplanetesimals. This program will provide a framework to extend our understanding of planetary formation processes and the mineralogy of dust in differing circumstellar environs and comets to be studied with the NASA STARDUST and SIRTF missions.

Lunar and Planetary Surface Dynamics and Early History

NASA Technical Reports Server (NTRS)

2003-01-01

This document, submitted as part of this proposal renewal represents the Final Report required by NASA for Grant NAGS-9442. It should be emphasized that, while this work statement in the original proposal outlined anticipated directions of our research, the specific activities we carried out during this period differed slightly from those proposed, capitalizing on new unexpected results and new advances in analytical capability. The thrust of all the work we completed were completely within the stated research goals of the proposal and significantly advanced our knowledge of planetary processes and our understanding of the early solar system. The following summary outlines our achievements in the different areas of research. These include: A) Early solar system processes and time scales using I-Xe chronometry; B) The Active Capture of Volatiles: A new mechanism for the capture of heavy noble gases, possible implications for phase Q and planetary heavy noble gases; C) Separation of Xe-L from Xe-H: Physically selective experiments; D) Abundances of Presolar grains; E) Studies of Neon and Helium from single interstellar SiC and graphite grains; F) Pre-compaction exposure of meteoritic grains and chondrules; G) Geochemically Measured Half-Lives: Double beta-decay of Te and Ba isotopes; H) Noble gases in stratospheric interplanetary dust particles; I) New Analytical Instrument.

Studies of extra-solar Oort Clouds and the Kuiper disk

NASA Technical Reports Server (NTRS)

Stern, S. Alan

1992-01-01

In 1991 we detected extended 1.1 mm emission around Fomalhaut (alpha PsA) at distances in order of magnitude beyond previous detections. This emission is plausibly related to the presence of an extended comet cloud, like our Oort Cloud, and may therefore represent indirect evidence for the formation of a planetary system at Fomalhaut. We propose now to extend this work to create a map of the angular and spatial extent of this emission. Fomalhaut is the only known main-sequence, submm-resolved IR excess source besides beta Pic.

Biomarkers and Metabolic Patterns in the Sediments of Evolving Glacial Lakes as a Proxy for Planetary Lake Exploration.

PubMed

Parro, Víctor; Blanco, Yolanda; Puente-Sánchez, Fernando; Rivas, Luis A; Moreno-Paz, Mercedes; Echeverría, Alex; Chong-Díaz, Guillermo; Demergasso, Cecilia; Cabrol, Nathalie A

2018-05-01

Oligotrophic glacial lakes in the Andes Mountains serve as models to study the effects of climate change on natural biological systems. The persistent high UV regime and evolution of the lake biota due to deglaciation make Andean lake ecosystems potential analogues in the search for life on other planetary bodies. Our objective was to identify microbial biomarkers and metabolic patterns that represent time points in the evolutionary history of Andean glacial lakes, as these may be used in long-term studies as microscale indicators of climate change processes. We investigated a variety of microbial markers in shallow sediments from Laguna Negra and Lo Encañado lakes (Región Metropolitana, Chile). An on-site immunoassay-based Life Detector Chip (LDChip) revealed the presence of sulfate-reducing bacteria, methanogenic archaea, and exopolymeric substances from Gammaproteobacteria. Bacterial and archaeal 16S rRNA gene sequences obtained from field samples confirmed the results from the immunoassays and also revealed the presence of Alpha-, Beta-, Gamma-, and Deltaproteobacteria, as well as cyanobacteria and methanogenic archaea. The complementary immunoassay and phylogenetic results indicate a rich microbial diversity with active sulfate reduction and methanogenic activities along the shoreline and in shallow sediments. Sulfate inputs from the surrounding volcanic terrains during deglaciation may explain the observed microbial biomarker and metabolic patterns, which differ with depth and between the two lakes. A switch from aerobic and heterotrophic metabolisms to anaerobic ones such as sulfate reduction and methanogenesis in the shallow shores likely reflects the natural evolution of the lake sediments due to deglaciation. Hydrodynamic deposition of sediments creates compartmentalization (e.g., sediments with different structure and composition surrounded by oligotrophic water) that favors metabolic transitions. Similar phenomena would be expected to occur on other planetary lakes, such as those of Titan, where watery niches fed by depositional events would be surrounded by a "sea" of hydrocarbons. Key Words: Glacier lakes-Sedimentation-Prokaryotic metabolisms and biomarkers-Deglaciation-Life detection-Planetary exploration. Astrobiology 18, 586-606.

Inventoring Gas in Debris Disks: UV Spectroscopy of Eta Tel

NASA Astrophysics Data System (ADS)

Roberge, Aki

2015-10-01

Debris disks stand between gas-rich protoplanetary disks and mature planetary systems, shedding light on the late stages of planet formation. Their dust component has been extensively studied, yet has provided little information about disk chemical composition. More information can be provided by their gas content, but astonishingly little is known about it. Only two debris disks have measurements of their gas composition, which is shockingly carbon-rich (Beta Pictoris and 49 Ceti). Basic questions remain unanswered. What are the typical gas-to-dust ratios in debris disks? What is the chemical composition of debris gas and its parent material? The answers to these questions have profound implications for terrestrial planet assembly and the origins of planetary atmospheres.Most detections of debris gas to date were achieved with line of sight UV/optical absorption spectroscopy of edge-on disks, using the central star as the background source. This technique is far more sensitive to small amounts of gas than emission line studies. The UV bandpass is particularly important, since strong transitions of numerous atomic and molecular species lie there. We propose extending our intriguing studies of debris gas with STIS UV spectroscopy of a highly promising debris disk system, Eta Tel. This disk is edge-on and contains circumstellar atomic gas (CII). We will measure column densities of the most important gas species, find the relative elemental gas abundances, and determine the gas mass using a powerful gas disk modeling code. We will also divide our observations into two visits, to search for signs of star-grazing exocomets, which are seen in both Beta Pic and 49 Cet.

Similarities and Differences between the Termination Foreshock/ Bow Shock and Planetary Bow Shocks

NASA Astrophysics Data System (ADS)

Krimigis, S. M.; Decker, R. B.; Roelof, E. C.; Hill, M. E.

2006-05-01

It is now evident that Voyager 1 (V1) entered the termination foreshock (TFS) at ~~85 AU in mid-2002, exited this region in early 2003 and re-entered in the late 2003-early 2004 time frame, before finally crossing the termination shock (TS) at ~~94 AU on December 16, 2004. The TFS region is characterized by large intensities of tangentially outward-moving beams of energetic ions E > 40 keV, and generally isotropic electron intensity increases E > 350 keV (Krimigis et al, 2003; Decker et al, 2005). Elevated magnetic field intensities were observed throughout these periods (Burlaga et al, 2003, 2005) and comparison with particle pressures showed this region to be a high-beta plasma (Krimigis et al, 2004, 2005). Proximity of the TS was also evident from occasional electron plasma oscillations seen as early as 91 AU (Gurnett and Kurth, 2005). In this paper we examine the extent to which the TFS and TS exhibit properties seen in planetary bow shocks using data from Voyager?s flyby of the outer planets and Cassini data in the vicinity of Saturn. Magnetic field distributions in these high-beta regions appear to be Gaussian. A possible source for the TSF particles is the supertherma1 population residing in the heliosheath, similar to upstream ions observed leaking from planetary magnetospheres. Krimigis, S.M. et al, Nature, 426, pg 45-48, 2003. Decker, R. B. et al, Science, 309, 2020- 2024, 2005. Burlaga et al, Geophys. Res. Lett., 30, NO. 20, 2072, doi:10.1029/2003GL018291, 2003. Burlaga, L. F, et al, Science, 309, 2027-2029, 2005 Krimigis S. M., et al, V. Florinski, N. V. Pogorelov, and G. P. Zank (eds) CP719, American Institute of Physics, 0-7354-0199-3/04, 133-138, 2004. Krimigis, S. M., et al, Proceedings of the Solar Wind 11 / SOHO 16 Conference,12-17 June 2005, Whistler, Canada, , B. Fleck & T.H. Zurbuchen (eds), (ESA SP-592, September 2005) Gurnett, D. A., and W. S. Kurth, Science, 309, 2025- 2027, 2005

Planetary Quarantine Annual Review, Space Technology and Research, July 1971 - July 1972

NASA Technical Reports Server (NTRS)

1973-01-01

The effects of planetary quarantine constraints are assessed for advanced missions and unmanned planetary sample return missions. Considered are natural space environment factors, post launch recontamination effects, spacecraft microbial burden estimation and prediction, and spacecraft cleaning and decontamination techniques.

The Solar Dynamo

NASA Technical Reports Server (NTRS)

Hathaway, David H.

1998-01-01

The solar dynamo is the process by which the Sun's magnetic field is generated through the interaction of the field with convection and rotation. In this, it is kin to planetary dynamos and other stellar dynamos. Although the precise mechanism by which the Sun generates its field remains poorly understood despite decades of theoretical and observational work, recent advances suggest that solutions to this solar dynamo problem may be forthcoming. Two basic processes are involved in dynamo activity. When the fluid stresses dominate the magnetic stresses (high plasma beta = 8(pi)rho/B(sup 2)), shear flows can stretch magnetic field lines in the direction of the shear (the "alpha effect") and helical flows can lift and twist field lines into orthogonal planes (the "alpha effect"). These two processes can be active anywhere in the solar convection zone but with different results depending upon their relative strengths and signs. Little is known about how and where these processes occur. Other processes, such as magnetic diffusion and the effects of the fine scale structure of the solar magnetic field, pose additional problems.

A dynamical study on extrasolar comets

NASA Astrophysics Data System (ADS)

Loibnegger, B.; Dvorak, R.

2017-09-01

Since the detection of absorption features in spectra of beta Pictoris varying on short time scales it is known that comets exist in other stellar systems. We investigate the dynamics of comets in two differently build systems (HD 10180 and HIP 14810). The outcomes of the scattering process, as there are collisions with the planets, captures and ejections from the systems are analysed statistically. Collisions and close encounters with the planets are investigated in more detail in order to conclude about transport of water and organic material. We will also investigate the possibility of detection of comets in other planetary systems.

Temperature-dependent thermal diffusivity of the Earth's crust and implications for magmatism.

PubMed

Whittington, Alan G; Hofmeister, Anne M; Nabelek, Peter I

2009-03-19

The thermal evolution of planetary crust and lithosphere is largely governed by the rate of heat transfer by conduction. The governing physical properties are thermal diffusivity (kappa) and conductivity (k = kapparhoC(P)), where rho denotes density and C(P) denotes specific heat capacity at constant pressure. Although for crustal rocks both kappa and k decrease above ambient temperature, most thermal models of the Earth's lithosphere assume constant values for kappa ( approximately 1 mm(2) s(-1)) and/or k ( approximately 3 to 5 W m(-1) K(-1)) owing to the large experimental uncertainties associated with conventional contact methods at high temperatures. Recent advances in laser-flash analysis permit accurate (+/-2 per cent) measurements on minerals and rocks to geologically relevant temperatures. Here we provide data from laser-flash analysis for three different crustal rock types, showing that kappa strongly decreases from 1.5-2.5 mm(2) s(-1) at ambient conditions, approaching 0.5 mm(2) s(-1) at mid-crustal temperatures. The latter value is approximately half that commonly assumed, and hot middle to lower crust is therefore a much more effective thermal insulator than previously thought. Above the quartz alpha-beta phase transition, crustal kappa is nearly independent of temperature, and similar to that of mantle materials. Calculated values of k indicate that its negative dependence on temperature is smaller than that of kappa, owing to the increase of C(P) with increasing temperature, but k also diminishes by 50 per cent from the surface to the quartz alpha-beta transition. We present models of lithospheric thermal evolution during continental collision and demonstrate that the temperature dependence of kappa and C(P) leads to positive feedback between strain heating in shear zones and more efficient thermal insulation, removing the requirement for unusually high radiogenic heat production to achieve crustal melting temperatures. Positive feedback between heating, increased thermal insulation and partial melting is predicted to occur in many tectonic settings, and in both the crust and the mantle, facilitating crustal reworking and planetary differentiation.

Imaging of laboratory magnetospheric plasmas using coherence imaging technique

NASA Astrophysics Data System (ADS)

Nishiura, Masaki; Takahashi, Noriki; Yoshida, Zensho; Nakamura, Kaori; Kawazura, Yohei; Kenmochi, Naoki; Nakatsuka, Masataka; Sugata, Tetsuya; Katsura, Shotaro; Howard, John

2017-10-01

The ring trap 1 (RT-1) device creates a laboratory magnetosphere for the studies on plasma physics and advanced nuclear fusion. A levitated superconducting coil produces magnetic dipole fields that realize a high beta plasma confinement that is motivated by self-organized plasmas in planetary magnetospheres. The electron cyclotron resonance heating (ECRH) with 8.2 GHz and 50 kW produces the plasmas with hot electrons in a few ten keV range. The electrons contribute to the local electron beta that exceeded 1 in RT-1. For the ion heating, ion cyclotron range of frequencies (ICRF) heating with 2-4 MHz and 10 kW has been performed in RT-1. The radial profile of ion temperature by a spectroscopic measurement indicates the signature of ion heating. In the holistic point of view, a coherence imaging system has been implemented for imaging the entire ion dynamics in the laboratory magnetosphere. The diagnostic system and obtained results will be presented.

Mixing in heterogeneous internally-heated convection

NASA Astrophysics Data System (ADS)

Limare, A.; Kaminski, E. C.; Jaupart, C. P.; Farnetani, C. G.; Fourel, L.; Froment, M.

2017-12-01

Past laboratory experiments of thermo chemical convection have dealt with systems involving fluids with different intrinsic densities and viscosities in a Rayleigh-Bénard setup. Although these experiments have greatly improved our understanding of the Earth's mantle dynamics, they neglect a fundamental component of planetary convection: internal heat sources. We have developed a microwave-based method in order to study convection and mixing in systems involving two layers of fluid with different densities, viscosities, and internal heat production rates. Our innovative laboratory experiments are appropriate for the early Earth, when the lowermost mantle was likely enriched in incompatible and heat producing elements and when the heat flux from the core probably accounted for a small fraction of the mantle heat budget. They are also relevant to the present-day mantle if one considers that radioactive decay and secular cooling contribute both to internal heating. Our goal is to quantify how two fluid layers mix, which is still very difficult to resolve accurately in 3-D numerical calculations. Viscosities and microwave absorptions are tuned to achieve high values of the Rayleigh-Roberts and Prandtl numbers relevant for planetary convection. We start from a stably stratified system where the lower layer has higher internal heat production and density than the upper layer. Due to mixing, the amount of enriched material gradually decreases to zero over a finite time called the lifetime. Based on more than 30 experiments, we have derived a scaling law that relates the lifetime of an enriched reservoir to the layer thickness ratio, a, to the density and viscosity contrasts between the two layers, and to their two different internal heating rates in the form of an enrichment factor beta=1+2*a*H1/H, where H1 is the heating rate of the lower fluid and H is the average heating rate. We find that the lifetime of the lower enriched reservoir varies as beta**(-7/3) in the low viscosity contrast limit, and as beta**(-4/3) in the large viscosity contrast limit. Our state-of-the-art experimental technique thus provides insights on chemical differentiation processes and on the evolution of mantle heterogeneities on both short and long time-scales.

The properties of the gas around beta Pictoris

NASA Astrophysics Data System (ADS)

Roberge, A.

2014-09-01

Debris disks are often described as gas-free. Compared to protoplanetary disks, they do in general have low gas abundances, as evidenced by the very few detections of sub-mm CO emission from bona fide debris disks to date. However, some debris disks do contain low levels of detectable gas, typically seen in absorption against the stellar spectrum at UV and optical wavelengths. Of all debris disks, the gas in the Beta Pic disk is the best characterized and understood. Here, I describe those characteristics and explain our current understanding of the nature of the gas. Like the dust, the gas is secondary material coming from planetesimal destruction, and provides opportunities for sensitive probes of the bulk composition of young planetary bodies. The gas can also be a sensitive tracer of disk asymmetries and dynamical interactions, as shown by new ALMA observations of CO emission from Beta Pic (see attached infographic and YouTube video explaining the discovery). Very likely, every debris disk contains its due portion of gas, but how much that is, we do not yet know. We are poised to answer this question with the advent of ALMA. With its unprecedented sensitivity and spatial resolution, ALMA may usher in a golden age for general studies of debris gas.

The Effects of Core Composition on Iron Isotope Fractionation During Planetary Differentiation

NASA Astrophysics Data System (ADS)

Elardo, S. M.; Shahar, A.; Caracas, R.; Mock, T. D.; Sio, C. K. I.

2018-05-01

High pressure and temperature isotope exchange experiments and density functional theory calculations show how the composition of planetary cores affects the fractionation of iron isotopes during planetary differentiation.

Torsional vibration signal analysis as a diagnostic tool for planetary gear fault detection

NASA Astrophysics Data System (ADS)

Xue, Song; Howard, Ian

2018-02-01

This paper aims to investigate the effectiveness of using the torsional vibration signal as a diagnostic tool for planetary gearbox faults detection. The traditional approach for condition monitoring of the planetary gear uses a stationary transducer mounted on the ring gear casing to measure all the vibration data when the planet gears pass by with the rotation of the carrier arm. However, the time variant vibration transfer paths between the stationary transducer and the rotating planet gear modulate the resultant vibration spectra and make it complex. Torsional vibration signals are theoretically free from this modulation effect and therefore, it is expected to be much easier and more effective to diagnose planetary gear faults using the fault diagnostic information extracted from the torsional vibration. In this paper, a 20 degree of freedom planetary gear lumped-parameter model was developed to obtain the gear dynamic response. In the model, the gear mesh stiffness variations are the main internal vibration generation mechanism and the finite element models were developed for calculation of the sun-planet and ring-planet gear mesh stiffnesses. Gear faults on different components were created in the finite element models to calculate the resultant gear mesh stiffnesses, which were incorporated into the planetary gear model later on to obtain the faulted vibration signal. Some advanced signal processing techniques were utilized to analyses the fault diagnostic results from the torsional vibration. It was found that the planetary gear torsional vibration not only successfully detected the gear fault, but also had the potential to indicate the location of the gear fault. As a result, the planetary gear torsional vibration can be considered an effective alternative approach for planetary gear condition monitoring.

Gravitational effects on planetary neutron flux spectra

NASA Astrophysics Data System (ADS)

Feldman, W. C.; Drake, D. M.; O'dell, R. D.; Brinkley, F. W.; Anderson, R. C.

1989-01-01

The effects of gravity on the planetary neutron flux spectra for planet Mars, and the lifetime of the neutron, were investigated using a modified one-dimensional diffusion accelerated neutral-particle transport code, coupled with a multigroup cross-section library tailored specifically for Mars. The results showed the presence of a qualitatively new feature in planetary neutron leakage spectra in the form of a component of returning neutrons with kinetic energies less than the gravitational binding energy (0.132 eV for Mars). The net effect is an enhancement in flux at the lowest energies that is largest at and above the outermost layer of planetary matter.

Planetary quarantine. Space research and technology

NASA Technical Reports Server (NTRS)

1973-01-01

Planetary quarantine strategies for advanced spacecraft consider effects of satellite encounter, Jupiter atmosphere entry, space radiation, and cleaning and decontamination techniques on microbiological growth probability. Analytical restructuring is developed for microbial burden prediction and planetary contamination.

17 beta-estradiol modifies nitric oxide-sensitive guanylyl cyclase expression and down-regulates its activity in rat anterior pituitary gland.

PubMed

Cabilla, Jimena P; Díaz, María del Carmen; Machiavelli, Leticia I; Poliandri, Ariel H; Quinteros, Fernanda A; Lasaga, Mercedes; Duvilanski, Beatriz H

2006-09-01

Previous studies showed that 17 beta-estradiol (17 beta-E2) regulates the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cGMP pathway in many tissues. Evidence from our laboratory indicates that 17 beta-E2 disrupts the inhibitory effect of NO on prolactin release, decreasing sGC activity and affecting the cGMP pathway in anterior pituitary gland of adult ovariectomized and estrogenized rats. To ascertain the mechanisms by which 17 beta-E2 affects sGC activity, we investigated the in vivo and in vitro effects of 17 beta-E2 on sGC protein and mRNA expression in anterior pituitary gland from immature female rats. In the present work, we showed that 17 beta-E2 acute treatment exerted opposite effects on the two sGC subunits, increasing alpha1 and decreasing beta1 subunit protein and mRNA expression. This action on sGC protein expression was maximal 6-9 h after 17 beta-E2 administration. 17beta-E2 also caused the same effect on mRNA expression at earlier times. Concomitantly, 17 beta-E2 dramatically decreased sGC activity 6 and 9 h after injection. These effects were specific of 17 beta-E2, because they were not observed with the administration of other steroids such as progesterone and 17 alpha-estradiol. This inhibitory action of 17beta-E2 on sGC also required the activation of estrogen receptor (ER), because treatment with the pure ER antagonist ICI 182,780 completely blocked 17 beta-E2 action. 17 beta-E2 acute treatment caused the same effects on pituitary cells in culture. These results suggest that 17 beta-E2 exerts an acute inhibitory effect on sGC in anterior pituitary gland by down-regulating sGC beta 1 subunit and sGC activity in a specific, ER-dependent manner.

The Western Hemisphere of Venus: 3.5 CM Dual Circular-Polarization Radar Images

NASA Astrophysics Data System (ADS)

Haldemann, Albert F. C.; Muhleman, Duane O.; Butler, Bryan J.; Slade, Martin A.

1997-08-01

We present new dual circular-polarization radar maps of the western hemisphere of Venus. The results are from a 1993 experiment imaging Venus with 3.5 cm radar. Continuous-wave right circularly polarized flux was transmitted toward Venus from the 70 m Deep Space Network antenna in Goldstone, California. The echo was received in both the same sense (SS) and the opposite sense (OS) of circular polarization at the Very Large Array in New Mexico. By spatially reconstructing the echo with the interferometer, maps of Venusian radar albedo were made for each of two days of observation in both OS (echo principally due to specular reflection) and SS (diffuse echo) channels. On both days, the sub-earth longitude was near 300 E. The SS maps are dominated by a significant component of diffuse backscatter from the 285 E longitude highlands: Beta, Phoebe, and Themis Regiones. Beta Regio includes radar-anomalous regions with high reflectivity and low emissivity. The nature of these altitude-related electrical properties on Venus is one of the outstanding surface process questions that remain after Magellan. Our experiment adds the first full-disk polarization ratio (μc) maps to the discussion. The data show that different geology determines different radar scattering properties within Beta. Diffuse scattering is very important in Beta, and may be due to either surface or volume scattering. We find a strong correlation of the SS albedo σSSwith altitudeRp(km) in Beta, σSS∝ 0.3Rp. Also, σOS∝ 0.7Rp. The onset of this relationship is at theRp∼ 6054 km planetary radius contour. The nature and morphology of the highland radar anomalies in Beta is consistent with a diffuse scattering mechanism. In Beta Regio we find μc> 0.5 in general, with μcas high as 0.8 between Rhea and Theia Montes, to the west of Devana Chasma. These values are compatible with measurements of blocky terrestrial lava flows if surface scattering dominates. If volume scattering is important, the high RCP cross-sections may indicate an important decrease in embedded scatterer size with altitude, which could be related to enhanced weathering.

Life Support and Habitation and Planetary Protection Workshop

NASA Technical Reports Server (NTRS)

Hogan, John A. (Editor); Race, Margaret S. (Editor); Fisher, John W. (Editor); Joshi, Jitendra A. (Editor); Rummel, John D. (Editor)

2006-01-01

A workshop entitled "Life Support and Habitation and Planetary Protection Workshop" was held in Houston, Texas on April 27-29, 2005 to facilitate the development of planetary protection guidelines for future human Mars exploration missions and to identify the potential effects of these guidelines on the design and selection of related human life support, extravehicular activity and monitoring and control systems. This report provides a summary of the workshop organization, starting assumptions, working group results and recommendations. Specific result topics include the identification of research and technology development gaps, potential forward and back contaminants and pathways, mitigation alternatives, and planetary protection requirements definition needs. Participants concluded that planetary protection and science-based requirements potentially affect system design, technology trade options, development costs and mission architecture. Therefore early and regular coordination between the planetary protection, scientific, planning, engineering, operations and medical communities is needed to develop workable and effective designs for human exploration of Mars.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawahara, Hajime, E-mail: divrot@gmail.com

We consider the effect of planetary spin on the planetary radial velocity (PRV) in dayside spectra of exoplanets. To understand the spin effect qualitatively, we derive an analytic formula of the intensity-weighted radial velocity from the planetary surface on the following assumptions: (1) constant and solid rotation without precession, (2) stable and uniform distribution of molecules/atoms, (3) emission models from the dayside hemisphere, and (4) a circular orbit. On these assumptions, we find that the curve of the PRV is distorted by the planetary spin and this anomaly is characterized by the spin radial velocity at the equator and amore » projected angle on a celestial plane between the spin axis and the axis of orbital motion {lambda}{sub p} in a manner analogous to the Rossiter-McLaughlin effect. The latter can constrain the planetary obliquity. Creating mock PRV data with 3 km s{sup -1} accuracy, we demonstrate how {lambda}{sub p} and the spin radial velocity at the equator are estimated. We find that the stringent constraint of eccentricity is crucial to detect the spin effect. Though our formula is still qualitative, we conclude that the PRV in the dayside spectra will be a powerful means for constraining the planetary spin.« less

Solar-System Tests of Gravitational Theories

NASA Technical Reports Server (NTRS)

Shapiro, Irwin

1997-01-01

We are engaged in testing gravitational theory by means of observations of objects in the solar system. These tests include an examination of the Principle Of Equivalence (POE), the Shapiro delay, the advances of planetary perihelia, the possibility of a secular variation G in the "gravitational constant" G, and the rate of the de Sitter (geodetic) precession of the Earth-Moon system. These results are consistent with our preliminary results focusing on the contribution of Lunar Laser Ranging (LLR), which were presented at the seventh Marcel Grossmann meeting on general relativity. The largest improvement over previous results comes in the uncertainty for (eta): a factor of five better than our previous value. This improvement reflects the increasing strength of the LLR data. A similar analysis presented at the same meeting by a group at the Jet Propulsion Laboratory gave a similar result for (eta). Our value for (beta) represents our first such result determined simultaneously with the solar quadrupole moment from the dynamical data set. These results are being prepared for publication. We have shown how positions determined from different planetary ephemerides can be compared and how the combination of VLBI and pulse timing information can yield a direct tie between planetary and radio frames. We have continued to include new data in our analysis as they became available. Finally, we have made improvement in our analysis software (PEP) and ported it to a network of modern workstations from its former home on a "mainframe" computer.

HUBBLE CAPTURES UNVEILING OF PLANETARY NEBULA

NASA Technical Reports Server (NTRS)

2002-01-01

This Wide Field and Planetary Camera 2 image captures the infancy of the Stingray nebula (Hen-1357), the youngest known planetary nebula. In this image, the bright central star is in the middle of the green ring of gas. Its companion star is diagonally above it at 10 o'clock. A spur of gas (green) is forming a faint bridge to the companion star due to gravitational attraction. The image also shows a ring of gas (green) surrounding the central star, with bubbles of gas to the lower left and upper right of the ring. The wind of material propelled by radiation from the hot central star has created enough pressure to blow open holes in the ends of the bubbles, allowing gas to escape. The red curved lines represent bright gas that is heated by a 'shock' caused when the central star's wind hits the walls of the bubbles. The nebula is as large as 130 solar systems, but, at its distance of 18,000 light-years, it appears only as big as a dime viewed a mile away. The Stingray is located in the direction of the southern constellation Ara (the Altar). The colors shown are actual colors emitted by nitrogen (red), oxygen (green), and hydrogen (blue). The filters used were F658N ([N II]), F502N ([O III]), and F487N (H-beta). The observations were made in March 1996. Credit: Matt Bobrowsky, Orbital Sciences Corporation and NASA

The survival of large organic molecules during hypervelocity impacts with water ice: implications for sampling the icy surfaces of moons

NASA Astrophysics Data System (ADS)

Hurst, A.; Bowden, S. A.; Parnell, J.; Burchell, M. J.; Ball, A. J.

2007-12-01

There are a number of measurements relevant to planetary geology that can only be adequately performed by physically contacting a sample. This necessitates landing on the surface of a moon or planetary body or returning samples to earth. The need to physically contact a sample is particularly important in the case of measurements that could detect medium to low concentrations of large organic molecules present in surface materials. Large organic molecules, although a trace component of many meteoritic materials and rocks on the surface of earth, carry crucial information concerning the processing of meteoritic material in the surface and subsurface environments, and can be crucial indicators for the presence of life. Unfortunately landing on the surface of a small planetary body or moon is complicated, particularly if surface topography is only poorly characterised and the atmosphere thin thus requiring a propulsion system for a soft landing. One alternative to a surface landing may be to use an impactor launched from an orbiting spacecraft to launch material from the planets surface and shallow sub-surface into orbit. Ejected material could then be collected by a follow-up spacecraft and analyzed. The mission scenario considered in the Europa-Ice Clipper mission proposal included both sample return and the analysis of captured particles. Employing such a sampling procedure to analyse large organic molecules is only viable if large organic molecules present in ices survive hypervelocity impacts (HVIs). To investigate the survival of large organic molecules in HVIs with icy bodies a two stage light air gas gun was used to fire steel projectiles (1-1.5 mm diameter) at samples of water ice containing large organic molecules (amino acids, anthracene and beta-carotene a biological pigment) at velocities > 4.8 km/s.UV-VIS spectroscopy of ejected material detected beta-carotene indicating large organic molecules can survive hypervelocity impacts. These preliminary results are yet to be scaled up to a point where they can be accurately interpreted in the context of a likely mission scenario. However, they strongly indicate that in a low mass payload mission scenario where a lander has been considered unfeasible, such a sampling strategy merits further consideration.

Identifying chemicals that are planetary boundary threats.

PubMed

MacLeod, Matthew; Breitholtz, Magnus; Cousins, Ian T; de Wit, Cynthia A; Persson, Linn M; Rudén, Christina; McLachlan, Michael S

2014-10-07

Rockström et al. proposed a set of planetary boundaries that delimit a "safe operating space for humanity". Many of the planetary boundaries that have so far been identified are determined by chemical agents. Other chemical pollution-related planetary boundaries likely exist, but are currently unknown. A chemical poses an unknown planetary boundary threat if it simultaneously fulfills three conditions: (1) it has an unknown disruptive effect on a vital Earth system process; (2) the disruptive effect is not discovered until it is a problem at the global scale, and (3) the effect is not readily reversible. In this paper, we outline scenarios in which chemicals could fulfill each of the three conditions, then use the scenarios as the basis to define chemical profiles that fit each scenario. The chemical profiles are defined in terms of the nature of the effect of the chemical and the nature of exposure of the environment to the chemical. Prioritization of chemicals in commerce against some of the profiles appears feasible, but there are considerable uncertainties and scientific challenges that must be addressed. Most challenging is prioritizing chemicals for their potential to have a currently unknown effect on a vital Earth system process. We conclude that the most effective strategy currently available to identify chemicals that are planetary boundary threats is prioritization against profiles defined in terms of environmental exposure combined with monitoring and study of the biogeochemical processes that underlie vital Earth system processes to identify currently unknown disruptive effects.

Planetary sample rapid recovery and handling

NASA Technical Reports Server (NTRS)

1985-01-01

Methods for recovering and cost effectively handling planetary samples following return to the vicinity of Earth were designed for planetary mission planners. Three topics are addressed: (1) a rough cost estimate was produced for each of a series of options for the handling of planetary samples following their return to the vicinity of Earth; (2) the difficulty of quickly retrieving planetary samples from low circular and high elliptical Earth orbit is assessed; and (3) a conceptual design for a biological isolation and thermal control system for the returned sample and spacecraft is developed.

Probing the young circumplanetary environment of Beta Pic b during transit egress

NASA Astrophysics Data System (ADS)

Wang, Jason

2017-08-01

Among the thousands of known exoplanets, Beta Pic b is the only directly imaged exoplanet with a nearly edge-on orbit. We show that the latest astrometric measurements rule out a transit by the planet at 10-sigma significance, but we are certain that the Hill sphere of the planet will transit. With a period of 22 years and no other system like it, this Hill sphere transit provides a rare opportunity to study the evolving circumplanetary environment of a young and well-characterized exoplanet. To compliment GO-14621, our Cycle 25 proposal to monitor the ingress of the Hill sphere, we propose a modest HST program to photometrically search for signatures of the planet's large scale circumplanetary material during the egress of the Hill sphere transit. The existence of such material is plausible given that Beta Pic's young age is similar to that of the ring-bearing J1407b system. Combined with GO-14621 and less-precise but dedicated ground-based monitoring, these observations will give us a comprehensive set of observations about this young circumplanetary environment. Given the sparse observational data of circumplanetary environments, non-detections will also be valuable for constraining the timescales relevant to circumplanetary material and moon formation. If photometric variations are detected with HST, these results would yield empirical information concerning the dynamics of the system and the evolution of planetary systems as a whole.

Exoplanet Caught on the Move

NASA Astrophysics Data System (ADS)

2010-06-01

For the first time, astronomers have been able to directly follow the motion of an exoplanet as it moves from one side of its host star to the other. The planet has the smallest orbit so far of all directly imaged exoplanets, lying almost as close to its parent star as Saturn is to the Sun. Scientists believe that it may have formed in a similar way to the giant planets in the Solar System. Because the star is so young, this discovery proves that gas giant planets can form within discs in only a few million years, a short time in cosmic terms. Only 12 million years old, or less than three-thousandths of the age of the Sun, Beta Pictoris is 75% more massive than our parent star. It is located about 60 light-years away towards the constellation of Pictor (the Painter) and is one of the best-known examples of a star surrounded by a dusty debris disc [1]. Earlier observations showed a warp of the disc, a secondary inclined disc and comets falling onto the star. "Those were indirect, but tell-tale signs that strongly suggested the presence of a massive planet, and our new observations now definitively prove this," says team leader Anne-Marie Lagrange. "Because the star is so young, our results prove that giant planets can form in discs in time-spans as short as a few million years." Recent observations have shown that discs around young stars disperse within a few million years, and that giant planet formation must occur faster than previously thought. Beta Pictoris is now clear proof that this is indeed possible. The team used the NAOS-CONICA instrument (or NACO [2]), mounted on one of the 8.2-metre Unit Telescopes of ESO's Very Large Telescope (VLT), to study the immediate surroundings of Beta Pictoris in 2003, 2008 and 2009. In 2003 a faint source inside the disc was seen (eso0842), but it was not possible to exclude the remote possibility that it was a background star. In new images taken in 2008 and spring 2009 the source had disappeared! The most recent observations, taken during autumn 2009, revealed the object on the other side of the disc after a period of hiding either behind or in front of the star (in which case it is hidden in the glare of the star). This confirmed that the source indeed was an exoplanet and that it was orbiting its host star. It also provided insights into the size of its orbit around the star. Images are available for approximately ten exoplanets, and the planet around Beta Pictoris (designated "Beta Pictoris b") has the smallest orbit known so far. It is located at a distance between 8 and 15 times the Earth-Sun separation - or 8-15 Astronomical Units - which is about the distance of Saturn from the Sun. "The short period of the planet will allow us to record the full orbit within maybe 15-20 years, and further studies of Beta Pictoris b will provide invaluable insights into the physics and chemistry of a young giant planet's atmosphere," says student researcher Mickael Bonnefoy. The planet has a mass of about nine Jupiter masses and the right mass and location to explain the observed warp in the inner parts of the disc. This discovery therefore bears some similarity to the prediction of the existence of Neptune by astronomers Adams and Le Verrier in the 19th century, based on observations of the orbit of Uranus. "Together with the planets found around the young, massive stars Fomalhaut and HR8799, the existence of Beta Pictoris b suggests that super-Jupiters could be frequent byproducts of planet formation around more massive stars," explains Gael Chauvin, a member of the team. Such planets disturb the discs around their stars, creating structures that should be readily observable with the Atacama Large Millimeter/submillimeter Array (ALMA), the revolutionary telescope being built by ESO together with international partners. A few other planetary candidates have been imaged, but they are all located further from their host star than Beta Pictoris b. If located in the Solar System, they all would lie close to or beyond the orbit of the furthest planet, Neptune. The formation processes of these distant planets are likely to be quite different from those in our Solar System and in Beta Pictoris. "The recent direct images of exoplanets - many made by the VLT - illustrate the diversity of planetary systems," says Lagrange. "Among those, Beta Pictoris b is the most promising case of a planet that could have formed in the same way as the giant planets in our Solar System." Notes [1] Debris discs are composed of dust resulting from collisions among larger bodies such as planetary embryos or asteroids. They are larger versions of the zodiacal dust band in our Solar System. The disc around Beta Pictoris was the first to be imaged and is now known to extend up to about 1000 times the distance between the Earth and the Sun. [2] NACO is an adaptive optics instrument attached to ESO's Very Large Telescope, located in Chile. Thanks to adaptive optics, astronomers can remove most of the blurring effect of the atmosphere and obtain very sharp images. More information This research was presented in a paper to appear this week in Science Express ("A Giant Planet Imaged in the disk of the Young Star Beta Pictoris," by A.-M. Lagrange et al.). The team is composed of A.-M. Lagrange, M. Bonnefoy, G. Chauvin, D. Ehrenreich, and D. Mouillet (Laboratoire d'Astrophysique de l'Observatoire de Grenoble, Université Joseph Fourier, CNRS, France), D. Apai (Space Telescope Science Institute, Baltimore, USA), A. Boccaletti, D. Gratadour, D. Rouan, and S. Lacour (LESIA, Observatoire de Paris-Meudon, France), and M. Kasper (ESO). ESO, the European Southern Observatory, is the foremost intergovernmental astronomy organisation in Europe and the world's most productive astronomical observatory. It is supported by 14 countries: Austria, Belgium, the Czech Republic, Denmark, France, Finland, Germany, Italy, the Netherlands, Portugal, Spain, Sweden, Switzerland and the United Kingdom. ESO carries out an ambitious programme focused on the design, construction and operation of powerful ground-based observing facilities enabling astronomers to make important scientific discoveries. ESO also plays a leading role in promoting and organising cooperation in astronomical research. ESO operates three unique world-class observing sites in Chile: La Silla, Paranal and Chajnantor. At Paranal, ESO operates the Very Large Telescope, the world's most advanced visible-light astronomical observatory and VISTA, the world's largest survey telescope. ESO is the European partner of a revolutionary astronomical telescope ALMA, the largest astronomical project in existence. ESO is currently planning a 42-metre European Extremely Large optical/near-infrared Telescope, the E-ELT, which will become "the world's biggest eye on the sky".

The effects of mass and metallicity upon planetary nebula formation

NASA Astrophysics Data System (ADS)

Papp, K. A.; Purton, C. R.; Kwok, S.

1983-05-01

A parameterized function is constructed which describes the possible dependence of planetary nebula formation upon metal abundance and stellar mass. Data on galaxies in the Local Group compared with predictions made from the parameterized function indicate that heavy element abundance is the principal agent influencing the formation of planetary nebulae; stars which are rich in heavy elements are the progenitors of planetary nebulae. This analysis, when compared with the observations, argues for a modest degree of pre-enrichment in a few of the sample galaxies. The heavy element dependence of planetary nebula formation also accounts for the deficit of planetary nebulae in the nuclei of NGC 221 and NGC 224, and in the bulge of our Galaxy.

The signatures of the parental cluster on field planetary systems

NASA Astrophysics Data System (ADS)

Cai, Maxwell Xu; Portegies Zwart, Simon; van Elteren, Arjen

2018-03-01

Due to the high stellar densities in young clusters, planetary systems formed in these environments are likely to have experienced perturbations from encounters with other stars. We carry out direct N-body simulations of multiplanet systems in star clusters to study the combined effects of stellar encounters and internal planetary dynamics. These planetary systems eventually become part of the Galactic field population as the parental cluster dissolves, which is where most presently known exoplanets are observed. We show that perturbations induced by stellar encounters lead to distinct signatures in the field planetary systems, most prominently, the excited orbital inclinations and eccentricities. Planetary systems that form within the cluster's half-mass radius are more prone to such perturbations. The orbital elements are most strongly excited in the outermost orbit, but the effect propagates to the entire planetary system through secular evolution. Planet ejections may occur long after a stellar encounter. The surviving planets in these reduced systems tend to have, on average, higher inclinations and larger eccentricities compared to systems that were perturbed less strongly. As soon as the parental star cluster dissolves, external perturbations stop affecting the escaped planetary systems, and further evolution proceeds on a relaxation time-scale. The outer regions of these ejected planetary systems tend to relax so slowly that their state carries the memory of their last strong encounter in the star cluster. Regardless of the stellar density, we observe a robust anticorrelation between multiplicity and mean inclination/eccentricity. We speculate that the `Kepler dichotomy' observed in field planetary systems is a natural consequence of their early evolution in the parental cluster.

A phase angle based diagnostic scheme to planetary gear faults diagnostics under non-stationary operational conditions

NASA Astrophysics Data System (ADS)

Feng, Ke; Wang, Kesheng; Ni, Qing; Zuo, Ming J.; Wei, Dongdong

2017-11-01

Planetary gearbox is a critical component for rotating machinery. It is widely used in wind turbines, aerospace and transmission systems in heavy industry. Thus, it is important to monitor planetary gearboxes, especially for fault diagnostics, during its operational conditions. However, in practice, operational conditions of planetary gearbox are often characterized by variations of rotational speeds and loads, which may bring difficulties for fault diagnosis through the measured vibrations. In this paper, phase angle data extracted from measured planetary gearbox vibrations is used for fault detection under non-stationary operational conditions. Together with sample entropy, fault diagnosis on planetary gearbox is implemented. The proposed scheme is explained and demonstrated in both simulation and experimental studies. The scheme proves to be effective and features advantages on fault diagnosis of planetary gearboxes under non-stationary operational conditions.

Enviromnental Control and Life Support Systems for Mars Missions - Issues and Concerns for Planetary Protection

NASA Technical Reports Server (NTRS)

Barta, Daniel J.; Anderson, Molly S.; Lange, Kevin

2015-01-01

Planetary protection represents an additional set of requirements that generally have not been considered by developers of technologies for Environmental Control and Life Support Systems (ECLSS). Planetary protection guidelines will affect the kind of operations, processes, and functions that can take place during future human planetary exploration missions. Ultimately, there will be an effect on mission costs, including the mission trade space when planetary protection requirements begin to drive vehicle deisgn in a concrete way. Planetary protection requirements need to be considered early in technology development and mission programs in order to estimate these impacts and push back on requirements or find efficient ways to perform necessary functions. It is expected that planetary protection will be a significant factor during technology selection and system architecture design for future missions.

Planetary Science Research Discoveries (PSRD): Effective Education and Outreach Website at http://www.soest.hawaii.edu/PSRdiscoveries

NASA Technical Reports Server (NTRS)

Taylor, G. J.; Martel, L. M. V.

2000-01-01

Planetary Science Research Discoveries (PSRD) website reports the latest research about planets, meteorites, and other solar system bodies being made by NASA-sponsored scientists. In-depth articles explain research results and give insights to contemporary questions in planetary science.

Studies of extra-solar Oort Clouds and the Kuiper Disk

NASA Technical Reports Server (NTRS)

Stern, S. Alan

1994-01-01

The March 1994 Semi-Annual report for Studies of Extra-Solar Oort Clouds and the Kuiper Disk is presented. We are conducting research designed to enhance our understanding of the evolution and detectability of comet clouds and disks. This area holds promise for also improving our understanding of outer solar system formation, the bombardment history of the planets, the transport of volatiles and organics from the outer solar system to the inner planets, and to the ultimate fate of comet clouds around the Sun and other stars. According to 'standard' theory, both the Kuiper Disk and Oort Cloud are (at least in part) natural products of the planetary accumulation stage of solar system formation. One expects such assemblages to be a common attribute of other solar systems. Therefore, searches for comet disks and clouds orbiting other stars offer a new method for inferring the presence of planetary systems. Our three-year effort consists of two major efforts: observational work to predict and search for the signatures of Oort Clouds and comet disks around other stars; and modeling studies of the formation and evolution of the Kuiper Disk (KD) and similar assemblages that may reside around other stars, including beta Pic.

A search for ultraviolet circumstellar gas absorption features in alpha Piscis Austrinus (Fomalhaut), a possible Beta Pictoris-like system

NASA Technical Reports Server (NTRS)

Cheng, K.-P.; Bruhweiler, Fred C.; Kondo, Yoji

1994-01-01

Archival high-dispersion International Ultraviolet Explorer (IUE) spectra have been used to search for circumstellar gas absorption features in alpha PsA (A3 V), a nearby (6.7 pc) proto-planetary system candidate. Recent sub-millimeter mapping observations around the region of alpha PsA indicate a spatially resolved dust disk like the one seen around Beta Pic. To determine how closely this putative disk resembles that of Beta Pic, we have searched for signatures of circumstellar gaseous absorption in all the available IUE high-dispersion data of alpha PsA. Examination of co-added IUE spectra shows weak circumstellar absorptions from excited levels in the resonance multiplet of Fe II near 2600 A. We also conclude that the sharp C I feature near 1657 A, previously identified as interstellar absorption toward alpha PsA, likely has a circumstellar origin. However, because the weakness of these absorption features, we will consider the presence of circumstellar gas as tentative and should be verified by using the Goddard High-Resolution Spectrograph aboard the Hubble Space Telescope. No corresponding circumstellar absorption is detected in higher ionization Fe III and Al III. Since the collisionally ionized nonphotospheric Al III resonance absorption seen in Beta Pic is likely formed close to the stellar surface, its absence in the UV spectra of alpha PsA could imply that, in contrast with Beta Pic, there is no active gaseous disk infall onto the central star. In the alpha PsA gaseous disk, if we assume a solar abundance for iron and all the iron is in the form of Fe II, plus a disk temperature of 5000 K, the Fe II UV1 absorption at 2611.8743 A infers a total hydrogen column density along the line of sight through the circumstellar disk of N(H) approximately equals 3.8 x 10(exp 17)/cm.

Mantle plumes on Venus revisited

NASA Technical Reports Server (NTRS)

Kiefer, Walter S.

1992-01-01

The Equatorial Highlands of Venus consist of a series of quasicircular regions of high topography, rising up to about 5 km above the mean planetary radius. These highlands are strongly correlated with positive geoid anomalies, with a peak amplitude of 120 m at Atla Regio. Shield volcanism is observed at Beta, Eistla, Bell, and Atla Regiones and in the Hathor Mons-Innini Mons-Ushas Mons region of the southern hemisphere. Volcanos have also been mapped in Phoebe Regio and flood volcanism is observed in Ovda and Thetis Regiones. Extensional tectonism is also observed in Ovda and Thetis Regiones. Extensional tectonism is also observed in many of these regions. It is now widely accepted that at least Beta, Atla, Eistla, and Bell Regiones are the surface expressions of hot, rising mantel plumes. Upwelling plumes are consistent with both the volcanism and the extensional tectonism observed in these regions. The geoid anomalies and topography of these four regions show considerable variation. Peak geoid anomalies exceed 90 m at Beta and Atla, but are only 40 m at Eistla and 24 m at Bell. Similarly, the peak topography is greater at Beta and Atla than at Eistla and Bell. Such a range of values is not surprising because terrestrial hotspot swells also have a side range of geoid anomalies and topographic uplifts. Kiefer and Hager used cylindrical axisymmetric, steady-state convection calculations to show that mantle plumes can quantitatively account for both the amplitude and the shape of the long-wavelength geoid and topography at Beta and Atla. In these models, most of the topography of these highlands is due to uplift by the vertical normal stress associated with the rising plume. Additional topography may also be present due to crustal thickening by volcanism and crustal thinning by rifting. Smrekar and Phillips have also considered the geoid and topography of plumes on Venus, but they restricted themselves to considering only the geoid-topography ratio and did not examine either the geoid and topography amplitudes separately or the shapes of anomalies.

Lightning on Venus

NASA Technical Reports Server (NTRS)

Scarf, F. L.

1985-01-01

On the night side of Venus, the plasma wave instrument on the Pioneer-Venus Orbiter frequently detects strong and impulsive low-frequency noise bursts when the local magnetic field is strong and steady and when the field is oriented to point down to the ionosphere. The signals have characteristics of lightning whistlers, and an attempt was made to identify the sources by tracing rays along the B-field from the Orbiter down toward the surface. An extensive data set strongly indicates a clustering of lightning sources near the Beta and Phoebe Regios, with additional significant clustering near the Atla Regio at the eastern edge of Aphrodite Terra. These results suggest that there are localized lightning sources at or near the planetary surface.

Effects of eddy initial conditions on nonlinear forcing of planetary scale waves by amplifying baroclinic eddies

NASA Technical Reports Server (NTRS)

Young, Richard E.

1986-01-01

The previous study of Young and Villere concerning growth of planetary scale waves forced by wave-wave interactions of amplifying intermediate scale baroclinic eddies is extended to investigate effects of different eddy initial conditions. A global, spectral, primitive equation model is used for the calculations. For every set of eddy initial conditions considered, growth rates of planetary modes are considerably greater than growth rates computed from linear instability theory for a fixed zonally independent basic state. However, values of growth rates ranged over a factor of 3 depending on the particular set of eddy initial conditions used. Nonlinear forcing of planetary modes via wave-wave coupling becomes more important than baroclinic growth on the basic state at small values of the intermediate-scale modal amplitudes. The relative importance of direct transfer of kinetic energy from intermediate scales of motion to a planetary mode, compared to baroclinic conversion of available potential energy to kinetic energy within that planetary mode, depends on the individual case. In all cases, however, the transfer of either kinetic or available potential energy to the planetary modes was accomplished principally by wave-wave transfer from intermediate scale eddies, rather than from the zonally averaged state. The zonal wavenumber 2 planetary mode was prominent in all solutions, even in those for which eddy initial conditions were such that a different planetary mode was selectively forced at the start. General characteristics of the structural evolution of the planetary wave components of total heat and momentum flux, and modal structures themselves, were relatively insensitive to variations in eddy initial conditions, even though quantitative details varied from case to case.

Planetary Interiors: Parametric Modeling of Global Geophysical Properties

NASA Astrophysics Data System (ADS)

Montgomery, W.; Jeanloz, R.

2004-12-01

Taking into account a realistic form of equation of state, we parameterize the degree to which bulk geophysical properties of planets are sensitive to gravitational self-compression. For example, the normalized moment of mass of a uniform-composition planet is C/Ma2 = 0.40 only in the limit of zero planetary size or incompressible material, and decreases toward 0.32 for finite compressibility as the planetary radius increases toward a = 104 km (M is planetary mass). Central density correspondingly increases from ρ 0, the surface density, toward 10 * ρ 0. Our calculations, based on the Eulerian finite-strain equation of state, make it possible to distinguish the effects of self-compression from the effects of non-uniformity (due either to changes in bulk composition or in phase with depth) as these influence planetary mass and moment of inertia relative to size. As observations of extra-solar planets can provide estimates of their mass and diameter (hence mean density), our formulation can account for the effects of compression in modeling the internal constitution and evolution of these objects. The effects of compression are especially important for giant and super-giant planets, such as the majority that have been observed to date.

Path planning for planetary rover using extended elevation map

NASA Technical Reports Server (NTRS)

Nakatani, Ichiro; Kubota, Takashi; Yoshimitsu, Tetsuo

1994-01-01

This paper describes a path planning method for planetary rovers to search for paths on planetary surfaces. The planetary rover is required to travel safely over a long distance for many days over unfamiliar terrain. Hence it is very important how planetary rovers process sensory information in order to understand the planetary environment and to make decisions based on that information. As a new data structure for informational mapping, an extended elevation map (EEM) has been introduced, which includes the effect of the size of the rover. The proposed path planning can be conducted in such a way as if the rover were a point while the size of the rover is automatically taken into account. The validity of the proposed methods is verified by computer simulations.

Control of the immune response by DHEA and its metabolites.

PubMed

Loria, R M; Padgett, D A

1998-06-01

The 17 keto steroid, Dehydroepiandrosterone (5-androsten-3 beta-17-one, DHEA) has been shown to protect mice from a variety of lethal infections. This includes, but is not limited to, infection with viruses (herpesvirus type 2, coxsackievirus B4-CVB4),bacteria (Enterococcus faecalis, Pseudomonas aeruginosa), and a parasite (Cryptosporidium parvum). We have reported that androstenediol (5-androsten-3 beta-17 beta-diol, beta AED), which is derived from DHEA, is at least 100x more effective in up-regulating systemic resistance against CVB4-infection than its precursor. Furthermore, androstenetriol (5-androstene-3 beta-7 beta-17 beta-triol beta AET) which is formed by 7 beta hydroxylation of beta AED, was more effective against CVB4-infection than its precursor beta AED. Neither steroid however has shown any significant direct antiviral effects. The in-vitro influences of DHEA, beta AED, and beta AET on a mitogen-induced mixed splenocyte proliferation assay were determined. The results showed that DHEA suppressed the proliferation of concanavalin A (Con A) or lipopolysaccharide (LPS) activated cultures in a dose dependent manner. beta AED had little influence on the activation response. However, beta AET potentiated the response to both mitogens significantly above control. The regulation of interleukin-2 and interleukin-3 secretion from Con A-activated lymphocytes was analogous to these observations. These functions were suppressed by DHEA, unaffected by beta AED, and potently increased by beta AET. Moreover, the classic immuno-suppressive effects of hydro-cortisone on Con A-induced lymphocyte proliferation, as well as IL-2 and IL-3 production were unaffected by co-cultured with DHEA and only minimally counteracted by beta AED. In contrast, beta AET significantly counteracted the effect of hydrocortisone when co-cultured together. These results show that while in-vivo, DHEA, beta AED, and beta AET each function in a similar manner. In-vitro, their effects are dramatically different from one another with only beta AET potentiating the cellular response by increasing lymphocyte activation and counteracting the immuno-suppressive activity of hydrocortisone.

Fibronectin regulates the activation of THP-1 cells by TGF-beta1.

PubMed

Wang, A C; Fu, L

2001-03-01

To determine how fibronectin regulates the immunomodulatory effects of transforming growth factor (TGF)-beta on THP-1 cells. THP-1 monocytic cell line. THP-1 cells were primed for 48 h in the presence or absence of 250 pM TGF-beta1. Assays or assessments carried out, together with statistical test applied. We found that adherence to fibronectin dramatically modulates the effects of TGF-beta1 on the human monocytic cell line THP-1. TGF-beta did not significantly affect constitutive interleukin (IL)-8 secretion or IL-1beta-induced IL-8 secretion from suspended cells. In contrast, TGF-beta stimulated IL-8 secretion as well as augmented IL-1beta-induced IL-8 secretion from adherent cells. The differential effects of TGF-beta1 on IL-8 secretion from suspended and adherent cells could not be explained by differences in IL-1 receptor antagonist production. The effects of fibronectin on TGF-beta1 induced IL-8 secretion from THP-1 cells were mimicked by adhesion to immobilized anti-a4beta1 integrin antibody and to a fibronectin fragment containing the CS-1 domain. These results indicate that alpha4beta1-mediated adhesion to fibronectin may play a key role during inflammation by profoundly influencing the effects of TGF-beta1 on monocytes.

Bayesian assessment of moving group membership: importance of models and prior knowledge

NASA Astrophysics Data System (ADS)

Lee, Jinhee; Song, Inseok

2018-04-01

Young nearby moving groups are important and useful in many fields of astronomy such as studying exoplanets, low-mass stars, and the stellar evolution of the early planetary systems over tens of millions of years, which has led to intensive searches for their members. Identification of members depends on the used models sensitively; therefore, careful examination of the models is required. In this study, we investigate the effects of the models used in moving group membership calculations based on a Bayesian framework (e.g. BANYAN II) focusing on the beta-Pictoris moving group (BPMG). Three improvements for building models are suggested: (1) updating a list of accepted members by re-assessing memberships in terms of position, motion, and age, (2) investigating member distribution functions in XYZ, and (3) exploring field star distribution functions in XYZ and UVW. The effect of each change is investigated, and we suggest using all of these improvements simultaneously in future membership probability calculations. Using this improved MG membership calculation and the careful examination of the age, 57 bona fide members of BPMG are confirmed including 12 new members. We additionally suggest 17 highly probable members.

Impact erosion of terrestrial planetary atmospheres

NASA Technical Reports Server (NTRS)

Ahrens, Thomas J.

1992-01-01

I review current ideas about the nature of the planetesimals - composition, size distribution, and the planetary encounter velocity. Previous papers on accretion and erosion of planetary atmospheres as a result of multiple impacts are reviewed. Finally, the effects of blowing off a substantial fraction of the atmosphere from a terrestrial planet due to a single giant body impact are discussed.

Impact erosion of terrestrial planetary atmospheres

NASA Technical Reports Server (NTRS)

Ahrens, Thomas J.

1993-01-01

I review current ideas about the nature of the planetesimals - composition, size distribution, and the planetary encounter velocity. Previous papers on accretion and erosion of planetary atmospheres as a result of multiple impacts are reviewed. Finally, the effects of blowing off a substantial fraction of the atmosphere from a terrestrial planet due to a single giant body impact are discussed.

Identifying Young, Nearby Stars

NASA Technical Reports Server (NTRS)

Webb, Rich; Song, Inseok; Zuckerman, Ben; Bessell, Mike

2001-01-01

Young stars have certain characteristics, e.g., high atmospheric abundance of lithium and chromospheric activity, fast rotation, distinctive space motion and strong X-ray flux compared to that of older main sequence stars. We have selected a list of candidate young (<100Myr) and nearby (<60pc) stars based on their space motion and/or strong X-ray flux. To determine space motion of a star, one needs to know its coordinates (RA, DEC), proper motion, distance, and radial velocity. The Hipparcos and Tycho catalogues provide all this information except radial velocities. We anticipate eventually searching approx. 1000 nearby stars for signs of extreme youth. Future studies of the young stars so identified will help clarify the formation of planetary systems for times between 10 and 100 million years. Certainly, the final output of this study will be a very useful resource, especially for adaptive optics and space based searches for Jupiter-mass planets and dusty proto-planetary disks. We have begun spectroscopic observations in January, 2001 with the 2.3 m telescope at Siding Spring Observatory (SSO) in New South Wales, Australia. These spectra will be used to determine radial velocities and other youth indicators such as Li 6708A absorption strength and Hydrogen Balmer line intensity. Additional observations of southern hemisphere stars from SSO are scheduled in April and northern hemisphere observations will take place in May and July at the Lick Observatory of the University of California. AT SSO, to date, we have observed about 100 stars with a high resolution spectrometer (echelle) and about 50 stars with a medium spectral resolution spectrometer (the "DBS"). About 20% of these stars turn out to be young stars. Among these, two especially noteworthy stars appear to be the closest T-Tauri stars ever identified. Interestingly, these stars share the same space motions as that of a very famous star with a dusty circumstellar disk--beta Pictoris. This new finding better constrains the age of beta Pictoris to be approx. 10 Myr.

Selectivity of beta-adrenergic stimulating and blocking agents.

PubMed

Löfdahl, C G; Svedmyr, N

1984-01-01

Studies have been performed to answer two questions: whether there are subgroups of beta 2-receptors separating effects in bronchial and skeletal muscle and whether beta 1-receptors in asthmatic airways mediate bronchoconstriction. Asthmatic patients have been studied in randomised cross-over trials. Effects on FEV1, heart rate and skeletal muscle tremor have been monitored. In some experimental studies, two new compounds, D2343 and QH-25, have shown a selectivity for beta 2-receptors in bronchial muscle compared to skeletal muscle. Studies in asthmatics did not confirm this. Thus, the beta 2-receptors in the two organs appear to be identical. The clinical effect of beta 1-receptors in the the airways was studied by giving selective beta 1-receptor blocking agents. It was shown that pafenolol , a beta-blocker more beta 1-selective than metoprolol, had less effect on FEV1 than metoprolol given in equipotent beta 1-blocking doses. Beta 1-receptor stimulation with a new selective beta 1-stimulating agent, prenalterol, did not give bronchodilation in doses which gave a significant increase of heart rate. Thus, beta 1-receptors do not contribute to bronchodilation in asthmatic patients.

[Regulation of IL-1beta and IL-8 production by mu-, delta-opiate receptors agonists in vitro].

PubMed

Geĭn, S V; Gorshkova, K G; Tendriakova, S P

2008-07-01

The beta-endorphin 10(-7-)-10(-11) M in LPS (lypopolisaccharide) presence and in spontaneous cultures promoted the IL-1beta production in mixed leukocyte fraction. LPS-induced IL-8 production in leukocyte fraction was inhibited by beta-endorphin 10(-7), 10(-11) M. The enchasing effect of beta-endorphin on IL-1beta production was not blocked by naloxone and naltrindole. The inhibitory effect of beta-endorphin on IL-8 production was blocked by naloxone and naltrindole. In mononuclear and neutrophile fractions beta-endorphin and delta-agonist DADLE enchased IL-1beta production in spontaneous and LPS-stimulating cultures, when IL-8 production inhibited beta-endorphin and delta-agonist DADLE only in LPS presence. No effect of mu-agonist DAGO were observed on IL-1beta production, whereas LPS-induced IL-8 secretion in neutrophile fraction inhibited by DAGO.

The gaseous component of the disk around Beta Pictoris

NASA Technical Reports Server (NTRS)

Hobbs, L. M.; Vidal-Madjar, A.; Ferlet, R.; Albert, C. E.; Gry, C.

1985-01-01

Optical spectra of alpha Lyr, alpha PsA, and beta Pic have been obtained at a velocity resolution of 3 km/s. No circumstellar absorption lines of Ca II or Na I are detected toward alpha Lyr or alpha PsA at sensitive limits. In the favorable case of beta Pic, where the circumstellar disk imaged by Smith and Terrile (1984) is seen nearly edge-on, a strong, narrow, circumstellar Ca II K absorption line previously reported by Slettebak (1982) and weaker, still narrower circumstellar Na I D lines are detected. Negative results of high sensitivity also are obtained for the Ca I 4226 A and CH(+) 4232 A lines, along with upper limits on the Zn II 2026, 2062 A doublet from archival IUE spectra. Under assumptions which agree with other well-established observations of the gaseous abundances of calcium and zinc, the total gaseous column density of hydrogen along a radius of the circumstellar disk is between 10 to the 18th and 4 x 10 to the 20th/sq cm. Within the boundaries of the dust disk detected by Smith and Terrile (1984) the total gaseous mass then is less than about 2, or less than 1 percent of the mass of the planetary system. A simplified model of the density distribution in the gaseous disk yields a characteristic total density n(H) of about 100,000/cu cm, which exceeds that of all interplanetary gas at earth's position by a factor of about 10,000.

Planetary quarantine. Space research and technology

NASA Technical Reports Server (NTRS)

1973-01-01

The impact of satisfying satellite quarantine constraints on outer planet missions and spacecraft design are studied by considering the effects of planetary radiation belts, solar wind radiation, and space vacuum on microorganism survival. Post launch recontamination studies evaluate the effects of mission environments on particle distributions on spacecraft surfaces and effective cleaning and decontamination techniques.

Design Tools for Cost-Effective Implementation of Planetary Protection Requirements

NASA Technical Reports Server (NTRS)

Hamlin, Louise; Belz, Andrea; Evans, Michael; Kastner, Jason; Satter, Celeste; Spry, Andy

2006-01-01

Since the Viking missions to Mars in the 1970s, accounting for the costs associated with planetary protection implementation has not been done systematically during early project formulation phases, leading to unanticipated costs during subsequent implementation phases of flight projects. The simultaneous development of more stringent planetary protection requirements, resulting from new knowledge about the limits of life on Earth, together with current plans to conduct life-detection experiments on a number of different solar system target bodies motivates a systematic approach to integrating planetary protection requirements and mission design. A current development effort at NASA's Jet Propulsion Laboratory is aimed at integrating planetary protection requirements more fully into the early phases of mission architecture formulation and at developing tools to more rigorously predict associated cost and schedule impacts of architecture options chosen to meet planetary protection requirements.

Spatial Query for Planetary Data

NASA Technical Reports Server (NTRS)

Shams, Khawaja S.; Crockett, Thomas M.; Powell, Mark W.; Joswig, Joseph C.; Fox, Jason M.

2011-01-01

Science investigators need to quickly and effectively assess past observations of specific locations on a planetary surface. This innovation involves a location-based search technology that was adapted and applied to planetary science data to support a spatial query capability for mission operations software. High-performance location-based searching requires the use of spatial data structures for database organization. Spatial data structures are designed to organize datasets based on their coordinates in a way that is optimized for location-based retrieval. The particular spatial data structure that was adapted for planetary data search is the R+ tree.

Impurities block the alpha to omega martensitic transformation in titanium.

PubMed

Hennig, Richard G; Trinkle, Dallas R; Bouchet, Johann; Srinivasan, Srivilliputhur G; Albers, Robert C; Wilkins, John W

2005-02-01

Impurities control phase stability and phase transformations in natural and man-made materials, from shape-memory alloys to steel to planetary cores. Experiments and empirical databases are still central to tuning the impurity effects. What is missing is a broad theoretical underpinning. Consider, for example, the titanium martensitic transformations: diffusionless structural transformations proceeding near the speed of sound. Pure titanium transforms from ductile alpha to brittle omega at 9 GPa, creating serious technological problems for beta-stabilized titanium alloys. Impurities in the titanium alloys A-70 and Ti-6Al-4V (wt%) suppress the transformation up to at least 35 GPa, increasing their technological utility as lightweight materials in aerospace applications. These and other empirical discoveries in technological materials call for broad theoretical understanding. Impurities pose two theoretical challenges: the effect on the relative phase stability, and the energy barrier of the transformation. Ab initio methods calculate both changes due to impurities. We show that interstitial oxygen, nitrogen and carbon retard the transformation whereas substitutional aluminium and vanadium influence the transformation by changing the d-electron concentration. The resulting microscopic picture explains the suppression of the transformation in commercial A-70 and Ti-6Al-4V alloys. In general, the effect of impurities on relative energies and energy barriers is central to understanding structural phase transformations.

Activities in planetary geology for the physical and earth sciences

NASA Technical Reports Server (NTRS)

Dalli, R.; Greeley, R.

1982-01-01

A users guide for teaching activities in planetary geology, and for physical and earth sciences is presented. The following topics are discussed: cratering; aeolian processes; planetary atmospheres, in particular the Coriolis Effect and storm systems; photogeologic mapping of other planets, Moon provinces and stratigraphy, planets in stereo, land form mapping of Moon, Mercury and Mars, and geologic features of Mars.

Scientific and technical services directed toward the development of planetary quarantine measures for automated spacecraft

NASA Technical Reports Server (NTRS)

1973-01-01

Planetary quarantine requirements and parameters are evaluated for their effects upon automated spacecraft flights data describing the heat resistance of naturally occuring microorganisms and sterilization requirements are analyzed and a possible method for assessment of these data is developed. Pertinent data from planetary mission microbial contamination logs are compiled and maintained in the quarantine document system.

Structure-activity relationships of N-beta-phenylpropionyl-L-tyrosine and its derivatives on the inhibition of an identifiable giant neurone of an African giant snail (Achatina fulica Férussac).

PubMed Central

Ariyoshi, Y.; Takeuchi, H.

1982-01-01

1 Inhibitory effects of N-beta-phenylpropionyl-L-tyrosine, N-beta-phenylpropionyl-L-tryptophan and their derivatives on an identifiable giant neurone, TAN (tonically autoactive neurone) of an African giant snail (Achatina fulica Férussac) were examined in an attempt to elucidate which structural features are necessary to produce the effect. 2 Of the compounds examined, N-beta-cyclohexylpropionyl-L-tyrosine showed the strongest effect. Its critical concentration (c.c.) was 3 X 10(-8)-10(-7)M, about ten times lower than that of N-beta-phenylpropionyl-L-tyrosine (c.c., 3 X 10(-7)-10(-6)M). N-beta-cyclohexylpropionyl-L-tryptophan (c.c., 10(-6)M) had an effect almost similar to that of N-beta-phenylpropionyl-L-tryptophan (c.c., 10(-6)M). 3 N-beta-Phenylpropionyl-N-methyl-L-tyrosine had no effect at a high concentration. 4 Effects of N-beta-phenylpropionyl-L-tyrosine amide (c.c., 3 X 10(-7)-10(-6)M) and N-beta-phenylpropionyl-L-tryptophan amide (c.c., 10(-6)M) were very similar to those of N-beta-phenylpropionyl-L-tyrosine and N-beta-phenylpropionyl-L-tryptophan respectively. 5 N-beta-Phenylpropionyl-p-amino-L-phenylalanine (c.c., 3 X 10(-5)-10(-4)M) and N-beta-phenylpropionyl-p-chloro-L-phenylalanine (c.c., 10(-4)M) had only a weak effect. 6 It is proposed that the structural features producing the effect are as follows: the active compound has a phenyl or a cyclohexyl group (hydrophobic binding group), after a suitable distance a peptide bond (proton donor and proton acceptor), adjacently a carbonyl group (proton acceptor), and a phenolic hydroxyl or an indolyl imino group (proton donor) in the molecule. PMID:7150871

Contribution of beta 1- and beta 2-adrenoceptors of human atrium and ventricle to the effects of noradrenaline and adrenaline as assessed with (-)-atenolol.

PubMed Central

Lemoine, H.; Schönell, H.; Kaumann, A. J.

1988-01-01

1. (-)-Atenolol was used as a tool to assess the function of beta 1- and beta 2-adrenoceptors in human heart. Right atrial and left ventricular preparations from patients undergoing open heart surgery were set up to contract isometrically. Membrane particles were prepared for beta-adrenoceptor labelling with [3H]-(-)-bupranolol and adenylate cyclase assays. 2. The positive inotropic effects of (-)-noradrenaline were antagonized to a similar extent by (-)-atenolol in atrial and ventricular preparations. (-)-Atenolol consistently antagonized the effects of (-)-adrenaline to a lesser extent than those of (-)-noradrenaline in atrial preparations. In ventricular preparations (-)-atenolol antagonized the effects of low concentrations of (-)-adrenaline to a lesser extent than those of high concentrations. 3. pKB values (M) of (-)-atenolol, estimated with non-linear analysis from the blockade of the positive inotropic effects of the catecholamines, were 7.4 for beta 1-adrenoceptors and 6.0 for beta 2-adrenoceptors. 4. (-)-Atenolol inhibited the binding of [3H]-(-)-bupranolol to ventricular beta 1-adrenoceptors with a pKD (M) of 5.9 and to ventricular beta 2-adrenoceptors with a pKD of 4.6. 5. (-)-Atenolol inhibited the catecholamine-induced adenylate cyclase stimulation in the atrium and ventricle with pKB values of 5.8-6.4 for beta 1- and pKB values of 4.7-5.7 for beta 2-adrenoceptors. The binding and cyclase assays suggest a partial affinity loss for (-)-atenolol inherent to membrane preparations. 6. beta 1-Adrenoceptors mediate the maximum positive inotropic effects of (-)-noradrenaline in both the atrium and ventricle of man. beta 2-Adrenoceptors appear to be capable of mediating maximal positive inotropic effects of (-)-adrenaline in atrium. In contrast, ventricular beta 2-adrenoceptors mediated only submaximal effects of (-)-adrenaline. PMID:2851354

Beta-blocking agents in patients with insulin resistance: effects of vasodilating beta-blockers.

PubMed

Jacob, S; Balletshofer, B; Henriksen, E J; Volk, A; Mehnert, B; Löblein, K; Häring, H U; Rett, K

1999-01-01

Essential hypertension is--at least in many subjects--associated with a decrease in insulin sensitivity, while glycaemic control is (still) normal. It seems that in hypertensive patients, two major functions of insulin are impaired: there is insulin resistance of peripheral glucose uptake (primarily skeletal muscle) and insulin resistance of insulin-stimulated vasodilation. In view of some retrospective data and meta-analyses, which showed a less than expected reduction in coronary events (coronary paradox), the metabolic side effects of the antihypertensive treatment have received more attention. Many groups have shown that conventional antihypertensive treatment, both with beta-blockers and/or diuretics, decreases insulin sensitivity by various mechanisms. While low-dose diuretics seem to be free of these metabolic effects, there is no evidence for this in the beta-adrenergic blockers. However, recent metabolic studies evaluated the effects of vasodilating beta-blockers, such as dilevalol, carvedilol and celiprolol, on insulin sensitivity and the atherogenic risk factors. None of them decreased insulin sensitivity, as has been described for the beta-blockers with and without beta1 selectivity. This supports the idea that peripheral vascular resistance and peripheral blood flow play a central role in mediating the metabolic side effects of the beta-blocking agents, as the vasodilating action (either via beta2 stimulation or alpha1-blockade) seems to more than offset the detrimental effects of the blockade of beta (or beta1) receptors. Further studies are needed to elucidate the relevance of the radical scavenging properties of these agents and their connection to their metabolic effects. Therefore, the beneficial characteristics of these newer beta-adrenoreceptor blockers suggest that the vasodilating beta-blocking agents could be advantageous for hypertensive patients with insulin resistance or type 2 diabetes.

Modeling Resonant Structure in the Kuiper Belt

NASA Astrophysics Data System (ADS)

Holmes, E. K.; Dermott, S. F.; Grogan, K.

1999-12-01

There is a possible connection between structure in circumstellar disks and the presence of planets, our own zodiacal cloud being the prime example. Asymmetries in such a disk could be diagnostic of planets which would be otherwise undetectable. At least three different types of asymmetries can serve to indicate bodies orbiting a star in a disk: (1) a warp in the plane of symmetry of the disk, (2) an offset in the center of symmetry of the disk with respect to the central star, and (3) density anomalies in the plane of the disk due to resonant trapping of dust particles. In the asteroid belt, collisions between asteroids supply dust particles to the zodiacal cloud. By comparison, it has been postulated that collisions between KBOs could initiate a collisional cascade which would produce a Kuiper dust disk. In fact, the Kuiper Belt is the region of our solar system that is most analogous to the planetary debris disks we see around other stars such as Vega, β Pic, Fomalhaut, and ɛ Eridani (Backman and Paresce 1993). A Kuiper Disk would most likely have a resonant structure, with two concentrations in brightness along the ecliptic longitude. This large scale structure arises because many of the KBOs, the Plutinos, are in the 2:3 mean motion resonance with Neptune. By running numerical integrations of particles in Pluto-like orbits, the resonant structure of the Kuiper belt can be studied by determining the percentage of particles trapped in the resonance as a function of their initial velocity and beta, where β = Frad}/F{grav. The dynamical evolution of the particles is followed from source to sink with Poynting Robertson light drag, solar wind drag, radiation pressure, and the effects of planetary gravitational perturbations included. This research was funded in part by a NASA GSRP grant.

Influence of deep vortices on the ocean surface

NASA Astrophysics Data System (ADS)

Ciani, Daniele; Carton, Xavier; Bashmachnikov, Igor; Chapron, Bertrand

2015-04-01

The oceanic motion at mesoscale (20-200 km) and submesoscale (0.5-20 km) is highly populated by vortices. These recirculating structures are more energetic than the mean flow, they trap water masses from their origination areas and advect them across the ocean, with consequent impact on the 3D distribution of heat and tracers. Mesoscale and submesoscale structures characterize the ocean dynamics both at the sea-surface and at intrathermocline depths (0-1500 m), and are presently investigated by means of model outputs and satellite (surface) data, the latest being the only way to get high resolution and synoptic observations at planetary scale (e.g., thermal-band observations, future altimetric observations given by the SWOT mission). The scientific question arising from this context is related to the role of the ocean surface for inferring informations on mesoscale and submesoscale vortices at depth. This study has also been motivated by the recent detection of subsurface eddies east of the Arabian Peninsula (PHYSINDIEN experiment - 2011). Using analytical models in the frame of the quasi-geostrophic (QG) theory, we could describe the theoretical altimetric signature of non-drifting and of drifting subsurface eddies. Numerical experiments, using both QG and primitive equations models, allowed us to investigate the surface expression of intrathermocline eddies interacting with baroclinic currents or evolving under planetary beta-effect. The eddies' characteristics (radius, depth, thickness, velocity) were varied in order to represent various oceanic examples (Meddies, Swoddies, Reddies, Peddies, Leddies). Idealized simulations with the ROMS model, confirming theoretical estimates, showed that drifting subsurface-intensified vortices can induce dipolar sea level anomalies, up to 3 cm. This result, compatibly with future SWOT measurement accuracies (about 2 cm), represents a contribution for systematic and synoptic detection of subsurface vortices.

Polycyclic aromatic hydrocarbon analysis with the Mars organic analyzer microchip capillary electrophoresis system.

PubMed

Stockton, Amanda M; Chiesl, Thomas N; Scherer, James R; Mathies, Richard A

2009-01-15

The Mars Organic Analyzer (MOA), a portable microchip capillary electrophoresis (CE) instrument developed for sensitive amino acid analysis on Mars, is used to analyze laboratory standards and real-world samples for polycyclic aromatic hydrocarbons (PAHs). The microfabricated CE separation and analysis method for these hydrophobic analytes is optimized, resulting in a separation buffer consisting of 10 mM sulfobutylether-beta-cyclodextrin, 40 mM methyl-beta-cyclodextrin, 5 mM carbonate buffer at pH 10, 5 degrees C. A PAH standard consisting of seven PAHs found in extraterrestrial matter and two terrestrial PAHs is successfully baseline separated. Limits of detection for the components of the standard ranged from 2000 ppm to 6 ppb. Analysis of an environmental contamination standard from Lake Erie and of a hydrothermal vent chimney sample from the Guaymas Basin agreed with published composition. A Martian analogue sample from the Yungay Hills region of the Atacama Desert was analyzed and found to contain 9,10-diphenylanthracene, anthracene, anthanthrene, fluoranthene, perylene, and benzo[ghi]fluoranthene at ppm levels. This work establishes the viability of the MOA for detecting and analyzing PAHs in in situ planetary exploration.

Density and pressure variability in the mesosphere and thermosphere

NASA Technical Reports Server (NTRS)

Davis, T. M.

1986-01-01

In an effort to isolate the essential physics of the mesosphere and the thermosphere, a steady one-dimensional density and pressure model has been developed in support of related NASA activities, i.e., projects such as the AOTV and the Space Station. The model incorporates a zeroth order basic state including both the three-dimensional wind field and its associated shear structure, etc. A first order wave field is also incorporated in period bands ranging from about one second to one day. Both basic state and perturbation quantities satsify the combined constraints of mass, linear momentum and energy conservation on the midlatitude beta plane. A numerical (iterative) technique is used to solve for the vertical wind which is coupled to the density and pressure fields. The temperature structure from 1 to 1000 km and the lower boundary conditions are specified using the U.S. Standard Atmosphere 1976. Vertical winds are initialized at the top of the Planetary Boundary Layer using Ekman pumping values over flat terrain. The model also allows for the generation of waves during the geostrophic adjustment process and incorporates wave nonlinearity effects.

The Influence of Planetary Mass on the Dynamical Lifetime of Planetary Systems

NASA Technical Reports Server (NTRS)

Lissauer, J. J.; Duncan, M. J.; Young, Richard E. (Technical Monitor)

1997-01-01

Recent numerical and analytic studies of planetary orbits have demonstrated the importance of resonances and chaos in destabilizing planetary systems. Newton's "clockwork" description of regular, predictable planetary orbits has been replaced by a view in which many systems can have long but finite lifetimes. This new knowledge has altered our perceptions of the later stages of planetary growth and of the stability of planetary systems. Stability criteria are inexact and time dependent. Most previous studies have focused on the effects in initial planetary orbits on the stability of the system. We are conducting an investigation which focuses on the dependence of stability criteria on planetary mass. Synthetic systems are created by increasing the masses of the planets in our Solar System or of the moons of a particular planet; these systems are then integrated until orbit crossing occurs. We have found that over some ranges, the time until orbit crossing varies to a good approximation as a power clothe factor by which the masses of the secondaries arc increased; some scatter occurs as a consequence of vie chaotic nature of orbital evolution. The slope of this power law varies substantially from system to system, and for moons it is mildly dependent on the inclusion of the planet's quadrupole moment in the gravitational potential.

Re-evaluating the efficacy of beta-adrenergic agonists and antagonists in long QT-3 syndrome through computational modelling.

PubMed

Ahrens-Nicklas, Rebecca C; Clancy, Colleen E; Christini, David J

2009-06-01

Long QT syndrome (LQTS) is a heterogeneous collection of inherited cardiac ion channelopathies characterized by a prolonged electrocardiogram QT interval and increased risk of sudden cardiac death. Beta-adrenergic blockers are the mainstay of treatment for LQTS. While their efficacy has been demonstrated in LQTS patients harbouring potassium channel mutations, studies of beta-blockers in subtype 3 (LQT3), which is caused by sodium channel mutations, have produced ambiguous results. In this modelling study, we explore the effects of beta-adrenergic drugs on the LQT3 phenotype. In order to investigate the effects of beta-adrenergic activity and to identify sources of ambiguity in earlier studies, we developed a computational model incorporating the effects of beta-agonists and beta-blockers into an LQT3 mutant guinea pig ventricular myocyte model. Beta-activation suppressed two arrhythmogenic phenomena, transmural dispersion of repolarization and early after depolarizations, in a dose-dependent manner. However, the ability of beta-activation to prevent cardiac conduction block was pacing-rate-dependent. Low-dose beta-blockade by propranolol reversed the beneficial effects of beta-activation, while high dose (which has off-target sodium channel effects) decreased arrhythmia susceptibility. These results demonstrate that beta-activation may be protective in LQT3 and help to reconcile seemingly conflicting results from different experimental models. They also highlight the need for well-controlled clinical investigations re-evaluating the use of beta-blockers in LQT3 patients.

Experimental Studies of Phase Equilibria of Meteorites and Planetary Bodies

NASA Technical Reports Server (NTRS)

Stolper, Edward M.

2005-01-01

The primary theme of this project was the application of experimental petrology and geochemistry to a variety of problems in meteoritics and planetary geology. The studies were designed to help develop constraints on the histories of primitive meteorites and their components, the environments in which they formed and evolved, and to understand quantitatively the processes involved in the evolution of igneous rocks on the earth and other planetary bodies. We undertook several projects relating to the origin of CAIs and chondrules. Systematics in the thermodynamic properties of CAI-like liquids were investigated and used to elucidate speciation of multi-valent cations and sulfide capacity of silicate melts and to constrain redox conditions and the vapor pressures of volatile species over molten chondrules. We experimentally determined vanadium speciation in meteoritic pyroxenes and in pyroxenes crystallized from CAI-like melts under very reducing conditions. We also found that bulk oxygen isotope compositions of chondrules in the moderately unequilibrated LL chondrites are related to the relative timing of plagioclase crystallization. We completed an experimental study on the vaporization of beta-SiC and SiO2 (glass or cristobalite) in reducing gases and established the conditions under which these presolar grains could have survived in the solar nebula. We expanded our technique for determining the thermodynamic properties of minerals and liquids to iron-bearing systems. We determined activity-composition relationships in Pt-Fe, Pt-Cr and Pt-Fe-Cr alloys. Results were used to determine the thermodynamic properties of chromite-picrochromite spinels including the free energy of formation of end-member FeCr2O4. We also established a new approach for evaluating Pt-Fe saturation experiments. We calculated the T-fO2 relationships in equilibrated ordinary chondrites and thereby constrained the conditions of metamorphism in their parent bodies.

N-terminal tyrosine phosphorylation of caveolin-2 negates anti-proliferative effect of transforming growth factor beta in endothelial cells

PubMed Central

Abel, Britain; Willoughby, Cara; Jang, Sungchan; Cooper, Laura; Xie, Leike; Vo-Ransdell, Chi; Sowa, Grzegorz

2012-01-01

Here we show that tyrosine phosphorylation of caveolin-2 (Cav-2) negatively regulates the anti-proliferative function of transforming growth factor beta (TGF-beta) in endothelial cells. In contrast to wild-type-Cav-2, retroviral re-expression of Y19/27F-Cav-2 in Cav-2 knockout endothelial cells did not affect anti-proliferative effect of TGF-beta compared to empty vector. Conversely, although less effective than wild-type, re-expression of S23/36A-Cav-2 reduced the effect of TGF-beta compared to empty vector. This differential effect of tyrosine and serine phosphorylation mutants of Cav-2 correlated with TGF-beta-induced Smad3 phosphorylation and transcriptional activation of plasminogen activator inhibitor-1. Thus tyrosine-phosphorylated Cav-2 counteracts anti-proliferative effect of TGF-beta in endothelial cells. PMID:22819829

Osteoblast gene expression is differentially regulated by TGF-beta isoforms.

PubMed

Fagenholz, P J; Warren, S M; Greenwald, J A; Bouletreau, P J; Spector, J A; Crisera, F E; Longaker, M T

2001-03-01

The transforming growth factor beta (TGF-beta) superfamily encompasses a number of important growth factors including several TGF-beta isoforms, the bone morphogenetic proteins, activins, inhibins, and growth and differentiation factors. TGF-beta 1, -beta 2, and -beta 3 are three closely related isoforms that are widely expressed during skeletal morphogenesis and bone repair. Numerous studies suggest that each isoform has unique in vivo functions; however, the effects of these TGF-beta isoforms on osteoblast gene expression and maturation have never been directly compared. In the current study, we treated undifferentiated neonatal rat calvaria osteoblast-enriched cell cultures with 2.5 ng/ml of each TGF-beta isoform and analyzed gene expression at 0, 3, 6, and 24 hours. We demonstrated unique isoform-specific regulation of endogenous TGF-beta 1 and type I collagen mRNA transcription. To assess the effects of extended TGF-beta treatment on osteoblast maturation, we differentiated osteoblast cultures in the presence of 2.5 ng/ml of each TGF-beta isoform. Analysis of collagen I, alkaline phosphatase, and osteocalcin demonstrated that each TGF-beta isoform uniquely suppressed the transcription of these osteoblast differentiation markers. Interestingly, TGF-beta isoform treatment increased osteopontin expression in primary osteoblasts after 4 and 10 days of differentiation. To our knowledge, these data provide the first direct comparison of the effects of the TGF-beta isoforms on osteoblast gene expression in vitro. Furthermore, these data suggest that TGF-beta isoforms may exert their unique in vivo effects by differentially regulating osteoblast cytokine secretion, extracellular matrix production, and the rate of cellular maturation.

Immune-modulatory effects of dietary Yeast Beta-1,3/1,6-D-glucan

PubMed Central

2014-01-01

Beta-glucans are a heterogeneous group of natural polysaccharides mostly investigated for their immunological effects. Due to the low systemic availability of oral preparations, it has been thought that only parenterally applied beta-glucans can modulate the immune system. However, several in vivo and in vitro investigations have revealed that orally applied beta-glucans also exert such effects. Various receptor interactions, explaining possible mode of actions, have been detected. The effects mainly depend on the source and structure of the beta-glucans. In the meantime, several human clinical trials with dietary insoluble yeast beta-glucans have been performed. The results confirm the previous findings of in vivo studies. The results of all studies taken together clearly indicate that oral intake of insoluble yeast beta-glucans is safe and has an immune strengthening effect. PMID:24774968

Comparative studies of the influence of cyclodextrins on the stability of the sunscreen agent, 2-ethylhexyl-p-methoxycinnamate.

PubMed

Scalia, Santo; Casolari, Alberto; Iaconinoto, Antonietta; Simeoni, Silvia

2002-11-07

The effects of beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the base-catalyzed degradation and light-induced decomposition of the sunscreen agent, trans-2-ethylhexyl-p-methoxycinnamate (trans-EHMC) were investigated. Reversed-phase liquid chromatography was used to study the interaction between natural and modified cyclodextrins, added to the mobile phase, and the sunscreen. Among the available cyclodextrins (beta-CD, HP-beta-CD, hydroxypropyl-alpha-cyclodextrin and hydroxypropyl-gamma-cyclodextrin), only HP-beta-CD and beta-CD produced a significant decrease in the chromatographic retention of trans-EHMC. The complexation of the sunscreen agent with HP-beta-CD and beta-CD was confirmed by thermal analysis and nuclear magnetic resonance spectroscopy. beta-CD depressed the decomposition of trans-EHMC in alkaline solutions more effectively than HP-beta-CD. Moreover, the irradiation-induced degradation of the sunscreen agent in emulsion vehicles was reduced by complexation with beta-CD (the extent of degradation was 26.1% for the complex compared to 35.8% for free trans-EHMC) whereas HP-beta-CD had no significant effect. Therefore, the complex of beta-CD with trans-EHMC enhances the chemical- and photo-stability of the sunscreen agent. Moreover, it limits adverse interactions of the UV filter with other formulation ingredients.

Process engineering with planetary ball mills.

PubMed

Burmeister, Christine Friederike; Kwade, Arno

2013-09-21

Planetary ball mills are well known and used for particle size reduction on laboratory and pilot scales for decades while during the last few years the application of planetary ball mills has extended to mechanochemical approaches. Processes inside planetary ball mills are complex and strongly depend on the processed material and synthesis and, thus, the optimum milling conditions have to be assessed for each individual system. The present review focuses on the insight into several parameters like properties of grinding balls, the filling ratio or revolution speed. It gives examples of the aspects of grinding and illustrates some general guidelines to follow for modelling processes in planetary ball mills in terms of refinement, synthesis' yield and contamination from wear. The amount of energy transferred from the milling tools to the powder is significant and hardly measurable for processes in planetary ball mills. Thus numerical simulations based on a discrete-element-method are used to describe the energy transfer to give an adequate description of the process by correlation with experiments. The simulations illustrate the effect of the geometry of planetary ball mills on the energy entry. In addition the imaging of motion patterns inside a planetary ball mill from simulations and video recordings is shown.

A drilling tool design and in situ identification of planetary regolith mechanical parameters

NASA Astrophysics Data System (ADS)

Zhang, Weiwei; Jiang, Shengyuan; Ji, Jie; Tang, Dewei

2018-05-01

The physical and mechanical properties as well as the heat flux of regolith are critical evidence in the study of planetary origin and evolution. Moreover, the mechanical properties of planetary regolith have great value for guiding future human planetary activities. For planetary subsurface exploration, an inchworm boring robot (IBR) has been proposed to penetrate the regolith, and the mechanical properties of the regolith are expected to be simultaneously investigated during the penetration process using the drilling tool on the IBR. This paper provides a preliminary study of an in situ method for measuring planetary regolith mechanical parameters using a drilling tool on a test bed. A conical-screw drilling tool was designed, and its drilling load characteristics were experimentally analyzed. Based on the drilling tool-regolith interaction model, two identification methods for determining the planetary regolith bearing and shearing parameters are proposed. The bearing and shearing parameters of lunar regolith simulant were successfully determined according to the pressure-sinkage tests and shear tests conducted on the test bed. The effects of the operating parameters on the identification results were also analyzed. The results indicate a feasible scheme for future planetary subsurface exploration.

Beta-1-3-Glucan effect on sow antibody production and passive immunization of Progeny

USDA-ARS?s Scientific Manuscript database

Beta-glucans are glucose homopolymers known to modulate immunity. Here, the beta-glucan effect on sow antibody production and passive immunization of neonatal pigs was analyzed. Treatments included: 1) Corn-soy fed control group, 2) beta-glucan, 3) App vaccination, and 4) beta-glucan + App vaccinati...

Factors Affecting the Habitability of Earth-like Planets

NASA Astrophysics Data System (ADS)

Meadows, Victoria; NAI-Virtual Planetary Laboratory Team

2014-03-01

Habitability is a measure of an environment's potential to support life. For exoplanets, the concept of habitability can be used broadly - to inform our calculations of the possibility and distribution of life elsewhere - or as a practical tool to inform mission designs and to prioritize specific targets in the search for extrasolar life. Although a planet's habitability does depend critically on the effect of stellar type and planetary semi-major axis on climate balance, work in the interdisciplinary field of astrobiology has identified many additional factors that can affect a planet's environment and its potential ability to support life. Life requires material for metabolism and structures, a liquid medium for chemical transport, and an energy source to drive metabolism and other life processes. Whether a planet's surface or sub-surface can provide these requirements is the result of numerous planetary and astrophysical processes that affect the planet's formation and evolution. Many of these factors are interdependent, and fall into three main categories: stellar effects, planetary effects and planetary system effects. Key abiotic processes affecting the resultant planetary environment include photochemistry (e.g. Segura et al., 2003; 2005), stellar effects on climate balance (e.g. Joshii et al., 2012; Shields et al., 2013), atmospheric loss (e.g. Lopez and Fortney, 2013), and gravitational interactions with the star (e.g. Barnes et al., 2013). In many cases, the effect of these processes is strongly dependent on a specific planet's existing environmental properties. Examples include the resultant UV flux at a planetary surface as a product of stellar activity and the strength of a planet's atmospheric UV shield (Segura et al., 2010); and the amount of tidal energy available to a planet to drive plate tectonics and heat the surface (Barnes et al., 2009), which is in turn due to a combination of stellar mass, planetary mass and composition, planetary orbital parameters and the gravitational influence of other planets in the system. A thorough assessment of a planet's environment and its potential habitability is a necessary first step in the search for biosignatures. Targeted environmental characteristics include surface temperature and pressure (e.g. Misra et al., 2013), a census of bulk and trace atmospheric gases, and whether there are signs of liquid water on the planetary surface (e.g. Robinson et al., 2010). The robustness of a planetary biosignature is dependent on being able to characterize the environment sufficiently well, and to understand likely star-planet interactions, to preclude formation of a biosignature gas via abiotic processes such as photochemistry (e.g. Segura et al., 2007; Domagal-Goldman et al., 2011; Grenfell et al., 2012). Here we also discuss potential false positives for O2 and O3, which, in large quantities, are often considered robust biosignatures for oxygenic photosynthesis. There is clearly significant future work required to better identify and understand the key environmental processes and interactions that allow a planet to support life, and to distinguish life's global impact on an environment from the environment itself.

Robo-AO Kepler Survey. IV. The Effect of Nearby Stars on 3857 Planetary Candidate Systems

NASA Astrophysics Data System (ADS)

Ziegler, Carl; Law, Nicholas M.; Baranec, Christoph; Riddle, Reed; Duev, Dmitry A.; Howard, Ward; Jensen-Clem, Rebecca; Kulkarni, S. R.; Morton, Tim; Salama, Maïssa

2018-04-01

We present the overall statistical results from the Robo-AO Kepler planetary candidate survey, comprising of 3857 high-angular resolution observations of planetary candidate systems with Robo-AO, an automated laser adaptive optics system. These observations reveal previously unknown nearby stars blended with the planetary candidate host stars that alter the derived planetary radii or may be the source of an astrophysical false positive transit signal. In the first three papers in the survey, we detected 440 nearby stars around 3313 planetary candidate host stars. In this paper, we present observations of 532 planetary candidate host stars, detecting 94 companions around 88 stars; 84 of these companions have not previously been observed in high resolution. We also report 50 more-widely separated companions near 715 targets previously observed by Robo-AO. We derive corrected planetary radius estimates for the 814 planetary candidates in systems with a detected nearby star. If planetary candidates are equally likely to orbit the primary or secondary star, the radius estimates for planetary candidates in systems with likely bound nearby stars increase by a factor of 1.54, on average. We find that 35 previously believed rocky planet candidates are likely not rocky due to the presence of nearby stars. From the combined data sets from the complete Robo-AO KOI survey, we find that 14.5 ± 0.5% of planetary candidate hosts have a nearby star with 4″, while 1.2% have two nearby stars, and 0.08% have three. We find that 16% of Earth-sized, 13% of Neptune-sized, 14% of Saturn-sized, and 19% of Jupiter-sized planet candidates have detected nearby stars.

Use of a multimission system for cost effective support of planetary science data processing

NASA Technical Reports Server (NTRS)

Green, William B.

1994-01-01

JPL's Multimission Operations Systems Office (MOSO) provides a multimission facility at JPL for processing science instrument data from NASA's planetary missions. This facility, the Multimission Image Processing System (MIPS), is developed and maintained by MOSO to meet requirements that span the NASA family of planetary missions. Although the word 'image' appears in the title, MIPS is used to process instrument data from a variety of science instruments. This paper describes the design of a new system architecture now being implemented within the MIPS to support future planetary mission activities at significantly reduced operations and maintenance cost.

Studies of extra-solar OORT clouds and the Kuiper disk

NASA Technical Reports Server (NTRS)

Stern, S. Alan

1993-01-01

This is the second report for NAGW-3023, Studies of Extra-Solar Oort Clouds and the Kuiper Disk. We are conducting research designed to enhance our understanding of the evolution and detectability of comet clouds and disks. This area holds promise for also improving our understanding of outer solar system formation, the bombardment history of the planets, the transport of volatiles and organics from the outer solar system to the inner planets, and the ultimate fate of comet clouds around the Sun and other stars. According to 'standard' theory, both the Kuiper Disk and Oort Cloud are (at least in part) natural products of the planetary accumulation stage of solar system formation. One expects such assemblages to be a common attribute of other solar systems. Therefore, searches for comet disks and clouds orbiting other stars offer a new method for infering the presence of planetary systems. Our three-year effort consists of two major efforts: (1) observational work to predict and search for the signatures of Oort Clouds and comet disks around other stars; and (2) modelling studies of the formation and evolution of the Kuiper Disk (KD) and similar assemblages that may reside around other stars, including Beta Pic. These efforts are referred to as Task 1 and 2, respectively.

Studies of extra-solar Oort Clouds and the Kuiper Disk

NASA Technical Reports Server (NTRS)

Stern, Alan

1995-01-01

This is the September 1995 Semi-Annual report for Studies of Extra-Solar Oort Clouds and the Kuiper Disk. We are conducting research designed to enhance our understanding of the evolution and detectability of comet clouds and disks. This area holds promise for also improving our understanding of outer solar system formation the bombardment history of the planets, the transport of volatiles and organics from the outer solar system to the inner planets, and to the ultimate fate of comet clouds around the Sun and other stars. According to 'standard' theory, both the Kuiper Disk and the Oort Cloud are (at least in part) natural products of the planetary accumulation stage of solar system formation. One expects such assemblages to be a common attribute of other solar systems. Therefore, searches for comet disks and clouds orbiting other stars offer a new method for inferring the presence of planetary systems. This project consists of two major efforts: (1) observational work to predict and search for the signatures of Oort Clouds and comet disks around other stars; and (2) modelling studies of the formation and evolution of the Kuiper Disk (KD) and similar assemblages that may reside around other stars, including beta Pic. These efforts are referred to as Task 1 and 2.

Beta-blocker-induced psoriasis: a rare side effect--a case report.

PubMed

Yilmaz, Mehmet Birhan; Turhan, Hasan; Akin, Yesim; Kisacik, Halil L; Korkmaz, Sule

2002-01-01

Beta blockers are one of the oral agents shown to decrease cardiovascular morbidity and mortality rates in randomized, controlled trials, and hence, they are widely used for the management of many cardiovascular situations. In terms of side effects there are 3 major modes of action: (1) contraction of smooth muscles, particularly of bronchi with nonselective agents; (2) exaggerated cardiac effects; and (3) central nervous system effects. There are also some rare side effects of beta blockers, some of which are unpredictable, but the others are related to mode of action at the cellular level. Beta-blocking agents may cause psoriaform eruptions and worsen existing psoriasis. Psoriasis may be an inconvenient side effect of beta blockade. Herein, we report a case of beta-blocker-induced psoriasis.

Ten tandem repeats of {beta}-hCG 109-118 enhance immunogenicity and anti-tumor effects of {beta}-hCG C-terminal peptide carried by mycobacterial heat-shock protein HSP65

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Yankai; Yan Rong; He Yi

2006-07-14

The {beta}-subunit of human chorionic gonadotropin ({beta}-hCG) is secreted by many kinds of tumors and it has been used as an ideal target antigen to develop vaccines against tumors. In view of the low immunogenicity of this self-peptide,we designed a method based on isocaudamer technique to repeat tandemly the 10-residue sequence X of {beta}-hCG (109-118), then 10 tandemly repeated copies of the 10-residue sequence combined with {beta}-hCG C-terminal 37 peptides were fused to mycobacterial heat-shock protein 65 to construct a fusion protein HSP65-X10-{beta}hCGCTP37 as an immunogen. In this study, we examined the effect of the tandem repeats of this 10-residuemore » sequence in eliciting an immune by comparing the immunogenicity and anti-tumor effects of the two immunogens, HSP65-X10-{beta}hCGCTP37 and HSP65-{beta}hCGCTP37 (without the 10 tandem repeats). Immunization of mice with the fusion protein HSP65-X10-{beta}hCGCTP37 elicited much higher levels of specific anti-{beta}-hCG antibodies and more effectively inhibited the growth of Lewis lung carcinoma (LLC) in vivo than with HSP65-{beta}hCGCTP37, which should suggest that HSP65-X10-{beta}hCGCTP37 may be an effective protein vaccine for the treatment of {beta}-hCG-dependent tumors and multiple tandem repeats of a certain epitope are an efficient method to overcome the low immunogenicity of self-peptide antigens.« less

A method based on multi-sensor data fusion for fault detection of planetary gearboxes.

PubMed

Lei, Yaguo; Lin, Jing; He, Zhengjia; Kong, Detong

2012-01-01

Studies on fault detection and diagnosis of planetary gearboxes are quite limited compared with those of fixed-axis gearboxes. Different from fixed-axis gearboxes, planetary gearboxes exhibit unique behaviors, which invalidate fault diagnosis methods that work well for fixed-axis gearboxes. It is a fact that for systems as complex as planetary gearboxes, multiple sensors mounted on different locations provide complementary information on the health condition of the systems. On this basis, a fault detection method based on multi-sensor data fusion is introduced in this paper. In this method, two features developed for planetary gearboxes are used to characterize the gear health conditions, and an adaptive neuro-fuzzy inference system (ANFIS) is utilized to fuse all features from different sensors. In order to demonstrate the effectiveness of the proposed method, experiments are carried out on a planetary gearbox test rig, on which multiple accelerometers are mounted for data collection. The comparisons between the proposed method and the methods based on individual sensors show that the former achieves much higher accuracies in detecting planetary gearbox faults.

Corrections for Exchange and Screening Effects in Low-energy Beta Decays

NASA Astrophysics Data System (ADS)

Mougeot, X.; Bé, M.-M.; Bisch, C.; Loidl, M.

2014-06-01

The beta spectra of 241Pu and 63Ni have been recently measured using metallic magnetic calorimeters. This powerful experimental technique allows theoretical beta spectra calculations to be tested at low energy with an accuracy never before achievable. Their comparison with classical beta calculations exhibits a significant deviation below 4 keV for 241Pu and 8 keV for 63Ni. The atomic exchange effect explains the main part of this deviation in the 63Ni beta spectrum. This effect has a significant contribution, equivalent to the magnitude of the screening, in the 241Pu beta spectrum.

Specific beta1-adrenergic receptor silencing with small interfering RNA lowers high blood pressure and improves cardiac function in myocardial ischemia.

PubMed

Arnold, Anne-Sophie; Tang, Yao Liang; Qian, Keping; Shen, Leping; Valencia, Valery; Phillips, Michael Ian; Zhang, Yuan Clare

2007-01-01

Beta-blockers are widely used and effective for treating hypertension, acute myocardial infarction (MI) and heart failure, but they present side-effects mainly due to antagonism of beta2-adrenergic receptor (AR). Currently available beta-blockers are at best selective but not specific for beta1 or beta2-AR. To specifically inhibit the expression of the beta1-AR, we developed a small interfering RNA (siRNA) targeted to beta1-AR. Three different sequences of beta1 siRNA were delivered into C6-2B cells with 90% efficiency. One of the three sequences reduced the level of beta1-AR mRNA by 70%. The siRNA was highly specific for beta1-AR inhibition with no overlap with beta2-AR. To test this in vivo, systemic injection of beta1 siRNA complexed with liposomes resulted in efficient delivery into the heart, lung, kidney and liver, and effectively reduced beta1-AR expression in the heart without altering beta2-AR. beta1 siRNA significantly lowered blood pressure of spontaneously hypertensive rats (SHR) for at least 12 days and reduced cardiac hypertrophy following a single injection. Pretreatment with beta1 siRNA 3 days before induction of MI in Wistar rats significantly improved cardiac function, as demonstrated by dP/dt and electrocardiogram following the MI. The protective mechanism involved reduction of cardiomyocyte apoptosis in the beta1 siRNA-treated hearts. The present study demonstrates the possibility of using siRNA for treating cardiovascular diseases and may represent a novel beta-blocker specific for beta1-AR.

Improved Strength and Damage Modeling of Geologic Materials

NASA Astrophysics Data System (ADS)

Stewart, Sarah; Senft, Laurel

2007-06-01

Collisions and impact cratering events are important processes in the evolution of planetary bodies. The time and length scales of planetary collisions, however, are inaccessible in the laboratory and require the use of shock physics codes. We present the results from a new rheological model for geological materials implemented in the CTH code [1]. The `ROCK' model includes pressure, temperature, and damage effects on strength, as well as acoustic fluidization during impact crater collapse. We demonstrate that the model accurately reproduces final crater shapes, tensile cracking, and damaged zones from laboratory to planetary scales. The strength model requires basic material properties; hence, the input parameters may be benchmarked to laboratory results and extended to planetary collision events. We show the effects of varying material strength parameters, which are dependent on both scale and strain rate, and discuss choosing appropriate parameters for laboratory and planetary situations. The results are a significant improvement in models of continuum rock deformation during large scale impact events. [1] Senft, L. E., Stewart, S. T. Modeling Impact Cratering in Layered Surfaces, J. Geophys. Res., submitted.

Theory for planetary exospheres: III. Radiation pressure effect on the Circular Restricted Three Body Problem and its implication on planetary atmospheres

NASA Astrophysics Data System (ADS)

Beth, A.; Garnier, P.; Toublanc, D.; Dandouras, I.; Mazelle, C.

2016-12-01

The planetary exospheres are poorly known in their outer parts, since the neutral densities are low compared with the instruments detection capabilities. The exospheric models are thus often the main source of information at such high altitudes. We present a new way to take into account analytically the additional effect of the stellar radiation pressure on planetary exospheres. In a series of papers, we present with a Hamiltonian approach the effect of the radiation pressure on dynamical trajectories, density profiles and escaping thermal flux. Our work is a generalization of the study by Bishop and Chamberlain [1989] Icarus, 81, 145-163. In this third paper, we investigate the effect of the stellar radiation pressure on the Circular Restricted Three Body Problem (CR3BP), called also the photogravitational CR3BP, and its implication on the escape and the stability of planetary exospheres, especially for hot Jupiters. In particular, we describe the transformation of the equipotentials and the location of the Lagrange points, and we provide a modified equation for the Hill sphere radius that includes the influence of the radiation pressure. Finally, an application to the hot Jupiter HD 209458b and hot Neptune GJ 436b reveals the existence of a blow-off escape regime induced by the stellar radiation pressure.

Constraints on Wave Drag Parameterization Schemes for Simulating the Quasi-Biennial Oscillation. Part II: Combined Effects of Gravity Waves and Equatorial Planetary Waves.

NASA Astrophysics Data System (ADS)

Campbell, Lucy J.; Shepherd, Theodore G.

2005-12-01

This study examines the effect of combining equatorial planetary wave drag and gravity wave drag in a one-dimensional zonal mean model of the quasi-biennial oscillation (QBO). Several different combinations of planetary wave and gravity wave drag schemes are considered in the investigations, with the aim being to assess which aspects of the different schemes affect the nature of the modeled QBO. Results show that it is possible to generate a realistic-looking QBO with various combinations of drag from the two types of waves, but there are some constraints on the wave input spectra and amplitudes. For example, if the phase speeds of the gravity waves in the input spectrum are large relative to those of the equatorial planetary waves, critical level absorption of the equatorial planetary waves may occur. The resulting mean-wind oscillation, in that case, is driven almost exclusively by the gravity wave drag, with only a small contribution from the planetary waves at low levels. With an appropriate choice of wave input parameters, it is possible to obtain a QBO with a realistic period and to which both types of waves contribute. This is the regime in which the terrestrial QBO appears to reside. There may also be constraints on the initial strength of the wind shear, and these are similar to the constraints that apply when gravity wave drag is used without any planetary wave drag.In recent years, it has been observed that, in order to simulate the QBO accurately, general circulation models require parameterized gravity wave drag, in addition to the drag from resolved planetary-scale waves, and that even if the planetary wave amplitudes are incorrect, the gravity wave drag can be adjusted to compensate. This study provides a basis for knowing that such a compensation is possible.

In vitro effects of beta-lactams combined with beta-lactamase inhibitors against methicillin-resistant Staphylococcus aureus.

PubMed Central

Kobayashi, S; Arai, S; Hayashi, S; Sakaguchi, T

1989-01-01

The effects of combinations of beta-lactams with two beta-lactamase inhibitors, sulbactam and clavulanic acid, were determined in vitro against 22 clinical isolates of methicillin-resistant Staphylococcus aureus. Combinations of cefpirome, cefotaxime, and cefazolin with sulbactam (10 micrograms/ml) showed synergistic effects against more than 70% of the strains. Combinations of methicillin and penicillin G with sulbactam also showed synergistic effects against 50 and 68% of the strains, respectively, while cefotiam, moxalactam, flomoxef, and cefmetazole in combination with sulbactam showed such effects against only 40% or fewer. Clavulanic acid was synergistic only when combined with penicillin G, the effect probably being due to the beta-lactamase inhibition by the inhibitor. Sulbactam did not improve the antimicrobial activities of the beta-lactams against methicillin-susceptible S. aureus strains. At 42 degrees C the MICs of cefotaxime, methicillin, and flomoxef alone were markedly decreased from the values at 35 degrees C, and no synergy between these beta-lactams and sulbactam appeared. The resistance to penicillin G was not inhibited by incubation at 42 degrees C, and combinations of penicillin G with sulbactam and clavulanic acid showed synergy. The amounts of beta-lactamase produced were not related to the decreases in the MICs of the beta-lactams, except for penicillin G combined with sulbactam. Clavulanic acid showed slightly stronger beta-lactamase-inhibiting activity than sulbactam did. These results suggest that the synergy between sulbactam and the beta-lactams, except for penicillin G, may not be due to beta-lactamase inhibition but to suppression of the methicillin-resistant S. aureus-specific resistance based on other factors. PMID:2786369

Special Software for Planetary Image Processing and Research

NASA Astrophysics Data System (ADS)

Zubarev, A. E.; Nadezhdina, I. E.; Kozlova, N. A.; Brusnikin, E. S.; Karachevtseva, I. P.

2016-06-01

The special modules of photogrammetric processing of remote sensing data that provide the opportunity to effectively organize and optimize the planetary studies were developed. As basic application the commercial software package PHOTOMOD™ is used. Special modules were created to perform various types of data processing: calculation of preliminary navigation parameters, calculation of shape parameters of celestial body, global view image orthorectification, estimation of Sun illumination and Earth visibilities from planetary surface. For photogrammetric processing the different types of data have been used, including images of the Moon, Mars, Mercury, Phobos, Galilean satellites and Enceladus obtained by frame or push-broom cameras. We used modern planetary data and images that were taken over the years, shooting from orbit flight path with various illumination and resolution as well as obtained by planetary rovers from surface. Planetary data image processing is a complex task, and as usual it can take from few months to years. We present our efficient pipeline procedure that provides the possibilities to obtain different data products and supports a long way from planetary images to celestial body maps. The obtained data - new three-dimensional control point networks, elevation models, orthomosaics - provided accurate maps production: a new Phobos atlas (Karachevtseva et al., 2015) and various thematic maps that derived from studies of planetary surface (Karachevtseva et al., 2016a).

Spin of Planetary Probes in Atmospheric Flight

NASA Astrophysics Data System (ADS)

Lorenz, R. D.

Probes that enter planetary atmospheres are often spun during entry or descent for a variety of reasons. Their spin rate histories are influenced by often subtle effects. The spin requirements, control methods and flight experience from planetary and earth entry missions are reviewed. An interaction of the probe aerodynamic wake with a drogue parachute, observed in Gemini wind tunnel tests, is discussed in connection with the anomalous spin behaviour of the Huygens probe.

Effect of polymorphism of the beta(2)-adrenergic receptor on response to regular use of albuterol in asthma.

PubMed

Israel, E; Drazen, J M; Liggett, S B; Boushey, H A; Cherniack, R M; Chinchilli, V M; Cooper, D M; Fahy, J V; Fish, J E; Ford, J G; Kraft, M; Kunselman, S; Lazarus, S C; Lemanske, R F; Martin, R J; McLean, D E; Peters, S P; Silverman, E K; Sorkness, C A; Szefler, S J; Weiss, S T; Yandava, C N

2001-01-01

Regular use of inhaled beta-adrenergic agonists may have adverse effects in some asthma patients. Polymorphisms of the beta(2)-adrenergic receptor (beta(2)-AR) can affect its regulation; however, results of smaller studies of the effects of such polymorphisms on response to beta-agonist therapy have been inconsistent. We examined the possible effects of polymorphisms at codons 16 (beta(2)-AR-16) and 27 (beta(2)-AR-27) on response to albuterol by genotyping 190 asthmatics who had participated in a trial of regular versus as-needed albuterol use. During the 16-week treatment period, patients homozygous for arginine (Arg/Arg) at beta(2)-AR-16 who used albuterol regularly had a small decline in morning peak expiratory flow (AM PEF). This effect was magnified during a 4-week run-out period, when all patients returned to as-needed albuterol only. By the end of the study, Arg/Arg subjects who had used albuterol regularly had an AM PEF 30.5 +/- 12.1 liters/min lower (p = 0.012) than Arg/Arg patients who had used albuterol as needed only. Subjects homozygous for glycine at beta(2)-AR-16 showed no such decline. Evening PEF also declined in the Arg/Arg regular but not in as-need albuterol users. No significant differences between regular and as-needed treatment were associated with polymorphisms at beta(2)-AR-27. Polymorphisms of the beta(2)-AR may influence airway responses to regular inhaled beta-agonist treatment. Copyright 2001 S. Karger AG, Basel

Protective effects of melittin on transforming growth factor-{beta}1 injury to hepatocytes via anti-apoptotic mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Woo-Ram; Park, Ji-Hyun; Kim, Kyung-Hyun

Melittin is a cationic, hemolytic peptide that is the main toxic component in the venom of the honey bee (Apis mellifera). Melittin has multiple effects, including anti-bacterial, anti-viral and anti-inflammatory, in various cell types. However, the anti-apoptotic mechanisms of melittin have not been fully elucidated in hepatocytes. Apoptosis contributes to liver inflammation and fibrosis. Knowledge of the apoptotic mechanisms is important to develop new and effective therapies for treatment of cirrhosis, portal hypertension, liver cancer, and other liver diseases. In the present study, we investigated the anti-apoptotic effect of melittin on transforming growth factor (TGF)-{beta}1-induced apoptosis in hepatocytes. TGF-{beta}1-treated hepatocytesmore » were exposed to low doses (0.5 and 1 {mu}g/mL) and high dose (2 {mu}g/mL) of melittin. The low doses significantly protected these cells from DNA damage in TGF-{beta}1-induced apoptosis compared to the high dose. Also, melittin suppressed TGF-{beta}1-induced apoptotic activation of the Bcl-2 family and caspase family of proteins, which resulted in the inhibition of poly-ADP-ribose polymerase (PARP) cleavage. These results demonstrate that TGF-{beta}1 induces hepatocyte apoptosis and that an optimal dose of melittin exerts anti-apoptotic effects against TGF-{beta}1-induced injury to hepatocytes via the mitochondrial pathway. These results suggest that an optimal dose of melittin can serve to protect cells against TGF-{beta}1-mediated injury. - Highlights: > We investigated the anti-apoptotic effect of melittin on TGF-{beta}1-induced hepatocyte. > TGF-{beta}1 induces hepatocyte apoptosis. > TGF-{beta}1-treated hepatocytes were exposed to low doses and high dose of melittin. > Optimal dose of melittin exerts anti-apoptotic effects to hepatocytes.« less

Effects of Planetary Gear Ratio on Mean Service Life

NASA Technical Reports Server (NTRS)

Savage, M.; Rubadeux, K. L.; Coe, H. H.

1996-01-01

Planetary gear transmissions are compact, high-power speed reductions which use parallel load paths. The range of possible reduction ratios is bounded from below and above by limits on the relative size of the planet gears. For a single plane transmission, the planet gear has no size at a ratio of two. As the ratio increases, so does the size of the planets relative to the sizes of the sun and ring. Which ratio is best for a planetary reduction can be resolved by studying a series of optimal designs. In this series, each design is obtained by maximizing the service life for a planetary with a fixed size, gear ratio, input speed power and materials. The planetary gear reduction service life is modeled as a function of the two-parameter Weibull distributed service lives of the bearings and gears in the reduction. Planet bearing life strongly influences the optimal reduction lives which point to an optimal planetary reduction ratio in the neighborhood of four to five.

Planetary quarantine impacts on probe design

NASA Technical Reports Server (NTRS)

Defrees, R. E.

1974-01-01

The design of space probes for Saturn and Uranus and the effects of imposing planetary quarantine constraints on that design are discussed. Special attention was given to probability of contamination and procedures for eliminating contamination including dry heat.

Planetary Gearbox Fault Detection Using Vibration Separation Techniques

NASA Technical Reports Server (NTRS)

Lewicki, David G.; LaBerge, Kelsen E.; Ehinger, Ryan T.; Fetty, Jason

2011-01-01

Studies were performed to demonstrate the capability to detect planetary gear and bearing faults in helicopter main-rotor transmissions. The work supported the Operations Support and Sustainment (OSST) program with the U.S. Army Aviation Applied Technology Directorate (AATD) and Bell Helicopter Textron. Vibration data from the OH-58C planetary system were collected on a healthy transmission as well as with various seeded-fault components. Planetary fault detection algorithms were used with the collected data to evaluate fault detection effectiveness. Planet gear tooth cracks and spalls were detectable using the vibration separation techniques. Sun gear tooth cracks were not discernibly detectable from the vibration separation process. Sun gear tooth spall defects were detectable. Ring gear tooth cracks were only clearly detectable by accelerometers located near the crack location or directly across from the crack. Enveloping provided an effective method for planet bearing inner- and outer-race spalling fault detection.

Workshop on Oxygen in Asteroids and Meteorites

NASA Technical Reports Server (NTRS)

2005-01-01

Contents include the following: Constraints on the detection of solar nebula's oxidation state through asteroid observation. Oxidation/Reduction Processes in Primitive Achondrites. Low-Temperature Chemical Processing on Asteroids. On the Formation Location of Asteroids and Meteorites. The Spectral Properties of Angritic Basalts. Correlation Between Chemical and Oxygen Isotopic Compositions in Chondrites. Effect of In-Situ Aqueous Alteration on Thermal Model Heat Budgets. Oxidation-Reduction in Meteorites: The Case of High-Ni Irons. Ureilite Atmospherics: Coming up for Air on a Parent Body. High Temperature Effects Including Oxygen Fugacity, in Pre-Planetary and Planetary Meteorites and Asteroids. Oxygen Isotopic Variation of Asteroidal Materials. High-Temperature Chemical Processing on Asteroids: An Oxygen Isotope Perspective. Oxygen Isotopes and Origin of Opaque Assemblages from the Ningqiang Carbonaceous Chondrite. Water Distribution in the Asteroid Belt. Comparative Planetary Mineralogy: V Systematics in Planetary Pyroxenes and fo 2 Estimates for Basalts from Vesta.

Regulation of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase expression and activity in the hypophysectomized rat ovary: Interactions between the stimulatory effect of human chorionic gonadotropin and the luteolytic effect of prolactin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martel, C.; Labrie, C.; Dupont, E.

1990-12-01

The enzyme 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) catalyzes an obligatory step in the conversion of pregnenolone and other 5-ene-3 beta-hydroxysteroids into progesterone as well as precursors of all androgens and estrogens in the ovary. Since 3 beta-HSD is likely to be an important target for regulation by pituitary hormones, we have studied the effect of chronic treatment with LH (hCG), FSH, and PRL on ovarian 3 beta-HSD expression and activity in hypophysectomized adult female rats. Human CG (hCG) (10 IU, twice a day (bid)), ovine FSH (0.5 microgram, bid), and ovine PRL (1 mg, bid) were administered,more » singly or in combination, for a period of 10 days starting 15 days after hypophysectomy. In hypophysectomized rats, PRL exerted a potent inhibitory effect on all the parameters studied. In fact, PRL caused a 81% decrease in ovarian 3 beta-HSD mRNA content accompanied by a similar decrease in 3 beta-HSD activity and protein levels. In addition, ovarian weight decreased by 40% whereas serum progesterone fell dramatically from 1.92 nmol/liter to undetectable levels after treatment with PRL. Whereas hCG alone had only slight stimulatory effects on 3 beta-HSD mRNA, protein content and activity levels, treatment with the gonadotropin partially or completely reversed the potent inhibitory effects of oPRL on all the parameters measured. FSH, on the other hand, had no significant effect on 3 beta-HSD expression and activity. In situ hybridization experiments using the 35S-labeled rat ovary 3 beta-HSD cDNA probe show that the inhibitory effect of PRL is exerted primarily on luteal cell 3 beta-HSD expression and activity. On the other hand, it can be seen that hCG stimulates 3 beta-HSD mRNA accumulation in interstitial cells.« less

Side effects of beta-blocker treatments as related to the central nervous system.

PubMed

Dahlöf, C; Dimenäs, E

1990-04-01

During the last decade beta-adrenoceptor antagonists have become one of the first-line treatments for hypertension. Generally, they have been shown to be safe with a low frequency of serious side effects. However, minor subjective symptoms, usually considered to be CNS-related, have been reported for all beta-blockers used. Thus, all beta-blockers on the market seem to have a high benefit:risk ratio; independent of their physicochemical properties and pharmacodynamic profile, however, they seem to cause CNS-related side effects to about the same extent. These minor side effects, the mechanisms of which are unclear, consist of subtle effects on general well being, decreased initiative, a depressed frame of mind, and disturbed sleep. Generally, however, beta-blockers in therapeutic dosages do not affect the qualitative functions of the brain. The results so far available have been obtained primarily by using objective methods. Further comparison has now been initiated using documented subjective methods to investigate whether the objectively documented differences are of any clinical relevance to the patient's quality of life. Although it cannot be claimed with certainty, nonselective beta-blockers seem to cause CNS-related side effects to a greater extent than beta 1-selective blockers. Differences in the degree of hydrophilicity of the beta-blocker are apparently of no clinical relevance in this respect. Rather, the plasma concentration of the beta-blocking drug (degree of beta-blockade) seems to be the major determinant of whether or not CNS-related symptoms appear in susceptible patients.

Allosteric modulation of alpha4beta2 nicotinic acetylcholine receptors by HEPES✩

PubMed Central

Weltzin, Maegan M; Huang, Yanzhou; Schulte, Marvin K

2013-01-01

A number of new positive allosteric modulators (PAMs) have been reported that enhance responses of neuronal alpha7 and alpha4beta2 nicotinic acetylcholine receptor subtypes to orthosteric ligands. PAMs represent promising new leads for the development of therapeutic agents for disorders involving alterations in nicotinic neurotransmission including Autism, Alzheimer's and Parkinson's disease. During our recent studies of alpha4beta2 PAMs, we identified a novel effect of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES). The effects of HEPES were evaluated in a phosphate buffered recording solution using two-electrode voltage clamp techniques and alpha4beta2 and alpha7 nicotinic acetylcholine receptor subtypes expressed in Xenopus laevis oocytes. Acetylcholine induced responses of high-sensitivity alpha4beta2 receptors were potentiated 190% by co-exposure to HEPES. Responses were inhibited at higher concentrations (bell-shaped concentration/response curve). Coincidentally, at concentrations of HEPES typically used in oocyte recording (5–10 mM), the potentiating effects of HEPES are matched by its inhibitory effects, thus producing no net effect. Mutagenesis results suggest HEPES potentiates the high-sensitivity stoichiometry of the alpha4beta2 receptors through action at the beta2+/beta2− interface and is dependent on residue beta2D218. HEPES did not potentiate low-sensitivity alpha4beta2 receptors and did not produce any observable effect on acetylcholine induced responses on alpha7 nicotinic acetylcholine receptors. PMID:22732654

Allosteric modulation of alpha4beta2 nicotinic acetylcholine receptors by HEPES.

PubMed

Weltzin, Maegan M; Huang, Yanzhou; Schulte, Marvin K

2014-06-05

A number of new positive allosteric modulators (PAMs) have been reported that enhance responses of neuronal alpha7 and alpha4beta2 nicotinic acetylcholine receptor subtypes to orthosteric ligands. PAMs represent promising new leads for the development of therapeutic agents for disorders involving alterations in nicotinic neurotransmission including Autism, Alzheimer's and Parkinson's disease. During our recent studies of alpha4beta2 PAMs, we identified a novel effect of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES). The effects of HEPES were evaluated in a phosphate buffered recording solution using two-electrode voltage clamp techniques and alpha4beta2 and alpha7 nicotinic acetylcholine receptor subtypes expressed in Xenopus laevis oocytes. Acetylcholine induced responses of high-sensitivity alpha4beta2 receptors were potentiated 190% by co-exposure to HEPES. Responses were inhibited at higher concentrations (bell-shaped concentration/response curve). Coincidentally, at concentrations of HEPES typically used in oocyte recording (5-10mM), the potentiating effects of HEPES are matched by its inhibitory effects, thus producing no net effect. Mutagenesis results suggest HEPES potentiates the high-sensitivity stoichiometry of the alpha4beta2 receptors through action at the beta2+/beta2- interface and is dependent on residue beta2D218. HEPES did not potentiate low-sensitivity alpha4beta2 receptors and did not produce any observable effect on acetylcholine induced responses on alpha7 nicotinic acetylcholine receptors. Copyright © 2012 Elsevier B.V. All rights reserved.

Effect of beta-phenylethylamine on extracellular concentrations of dopamine in the nucleus accumbens and prefrontal cortex.

PubMed

Murata, Mikio; Katagiri, Nobuyuki; Ishida, Kota; Abe, Kenji; Ishikawa, Masago; Utsunomiya, Iku; Hoshi, Keiko; Miyamoto, Ken-ichi; Taguchi, Kyoji

2009-05-07

It is known that psychostimulants stimulate dopamine transmission in the nucleus accumbens. In the present study, we examined the effects of systemically administered beta-phenylethylamine (beta-PEA), a psychomotor-stimulating trace amine, on dopamine concentrations in the nucleus accumbens and prefrontal cortex in freely moving rats, using an in vivo microdialysis technique. Intraperitoneal administration of beta-PEA (12.5 and 25 mg/kg) significantly increased extracellular dopamine levels in the nucleus accumbens shell. The observed increase in the dopamine concentration in nucleus accumbens shell dialysate after intraperitoneal administration of 25 mg/kg beta-PEA was inhibited by pre-treatment with a dopamine uptake inhibitor, GBR12909 (10 mg/kg, i.p.). In contrast, beta-PEA (25 mg/kg, i.p.) did not affect dopamine release in the nucleus accumbens core. Although a high dose of beta-PEA (50 mg/kg) significantly increased dopamine levels in the nucleus accumbens core, the dopamine increasing effect of beta-PEA was more potent in the nucleus accumbens shell. Systemic administration of 12.5 and 25 mg/kg beta-PEA also increased extracellular dopamine levels in the prefrontal cortex of rats. However, systemic 25 mg/kg beta-PEA-induced increases in extracellular dopamine levels were not blocked by GBR12909 within the prefrontal cortex. These results suggest that beta-PEA has a greater effect in the shell than in the core and low-dose beta-PEA stimulates dopamine release in the nucleus accumbens shell through uptake by a dopamine transporter. Similarly, beta-PEA increased extracellular dopamine levels in the prefrontal cortex. Thus, beta-PEA may increase extracellular dopamine concentrations in the mesocorticolimbic pathway.

Strontium iodide gamma ray spectrometers for planetary science (Conference Presentation)

NASA Astrophysics Data System (ADS)

Prettyman, Thomas H.; Rowe, Emmanuel; Butler, Jarrhett; Groza, Michael; Burger, Arnold; Yamashita, Naoyuki; Lambert, James L.; Stassun, Keivan G.; Beck, Patrick R.; Cherepy, Nerine J.; Payne, Stephen A.; Castillo-Rogez, Julie C.; Feldman, Sabrina M.; Raymond, Carol A.

2016-09-01

Gamma rays produced passively by cosmic ray interactions and by the decay of radioelements convey information about the elemental makeup of planetary surfaces and atmospheres. Orbital missions mapped the composition of the Moon, Mars, Mercury, Vesta, and now Ceres. Active neutron interrogation will enable and/or enhance in situ measurements (rovers, landers, and sondes). Elemental measurements support planetary science objectives as well as resource utilization and planetary defense initiatives. Strontium iodide, an ultra-bright scintillator with low nonproportionality, offers significantly better energy resolution than most previously flown scintillators, enabling improved accuracy for identification and quantification of key elements. Lanthanum bromide achieves similar resolution; however, radiolanthanum emissions obscure planetary gamma rays from radioelements K, Th, and U. The response of silicon-based optical sensors optimally overlaps the emission spectrum of strontium iodide, enabling the development of compact, low-power sensors required for space applications, including burgeoning microsatellite programs. While crystals of the size needed for planetary measurements (>100 cm3) are on the way, pulse-shape corrections to account for variations in absorption/re-emission of light are needed to achieve maximum resolution. Additional challenges for implementation of large-volume detectors include optimization of light collection using silicon-based sensors and assessment of radiation damage effects and energetic-particle induced backgrounds. Using laboratory experiments, archived planetary data, and modeling, we evaluate the performance of strontium iodide for future missions to small bodies (asteroids and comets) and surfaces of the Moon and Venus. We report progress on instrument design and preliminary assessment of radiation damage effects in comparison to technology with flight heritage.

beta-Citryl-L-glutamate is an endogenous iron chelator that occurs naturally in the developing brain.

PubMed

Hamada-Kanazawa, Michiko; Kouda, Makiko; Odani, Akira; Matsuyama, Kaori; Kanazawa, Kiyoka; Hasegawa, Tatsuya; Narahara, Masanori; Miyake, Masaharu

2010-01-01

The compound beta-citryl-L-glutamate (beta-CG) was initially isolated from developing brains, while it has also been found in high concentrations in testes and eyes. However, its functional roles are unclear. To evaluate its coordination with metal ions, we performed pH titration experiments. The stability constant, logbeta(pqr) for M(p)(beta-CG)(q)H(r) was calculated from pH titration data, which showed that beta-CG forms relatively strong complexes with Fe(III), Cu(II), Fe(II) and Zn(II). beta-CG was also found able to solubilize Fe more effectively from Fe(OH)(2) than from Fe(OH)(3). Therefore, we examined the effects of beta-CG on Fe-dependent reactive oxygen species (ROS)-generating systems, as well as the potential ROS-scavenging activities of beta-CG and metal ion-(beta-CG) complexes. beta-CG inhibited the Fe-dependent degradation of deoxyribose and Fe-dependent damage to DNA or plasmid DNA in a dose-dependent manner, whereas it had no effect on Cu-mediated DNA damage. In addition, thermodynamic data showed that beta-CG in a physiological pH solution is an Fe(II) chelator rather than an Fe(III) chelator. Taken together, these findings suggest that beta-CG is an endogenous low molecular weight Fe chelator.

TU Berlin Rover Family for Terrestrial Testing of Complex Planetary Mission Scenarios

NASA Astrophysics Data System (ADS)

Kryza, L.; Brieß, K.

2018-04-01

The TU Berlin has developed a family of planetary rovers for educational use and research activities. The paper will introduce these cost-effective systems, which can be used for analogue mission demonstration on Earth.

Geoneutrinos

DOE Office of Scientific and Technical Information (OSTI.GOV)

Machulin, I. N., E-mail: machulin@lngs.infn.it; Collaboration: Borexino Collaboration

2015-12-15

Academician M.A. Markov in the 1960s first proposed detecting the electron antineutrino in the reaction of inverse beta decay on a proton to study the processes inside the Earth. The radioactive isotopes {sup 238}U, {sup 232}Th, and {sup 40}K present in our planet decay with radiation of neutrinos (antineutrinos). Neutrinos that are produced reach the Earth’s surface practically without absorption and carry information about the internal structure of the planet. However, because of the smallness of the antineutrino fluxes and interaction cross sections with matter, antineutrinos of geological origin were first registered in only two experiments (Borexino and Kamland) inmore » recent years. The experimental observation of antineutrinos from the isotope decays in the depths of the Earth is the only way to study the radiation in our planetary interior.« less

Psychomotor stimulant effects of beta-phenylethylamine in monkeys treated with MAO-B inhibitors.

PubMed

Bergman, J; Yasar, S; Winger, G

2001-12-01

Sufficiently high doses of beta-phenylethylamine (beta-PEA), a trace amine that is rapidly metabolized by monoamine oxidase-type B (MAO-B), can produce effects comparable to those of cocaine or methamphetamine (MA). The present experiments were conducted to study how the discriminative-stimulus (S(D)) and reinforcing-stimulus (S(R)) effects of beta-PEA in monkeys are modified by treatment with inhibitors of MAO-B [R-(-)-deprenyl and MDL 72974]. In studies of its S(D) effects, doses of beta-PEA up to 30 mg/kg engendered only sporadic responding on the drug-associated lever in squirrel monkeys that discriminated intramuscular injections of 0.3 mg/kg MA from vehicle whereas lower doses of 0.3-1.0 mg/kg beta-PEA produced full substitution when administered after either R-(-)-deprenyl or MDL 72974 (0.3 mg/kg). The MA-like S(D) effects of beta-PEA were attenuated by either dopamine D(1) or D(2) receptor blockers. In studies of its S(R) effects, high doses of beta-PEA maintained responding in two of three monkeys under a second-order fixed-interval schedule (3.0 or 10 mg/kg per injection) and two of three monkeys under a simple fixed ratio (FR) schedule (0.3-1.0 mg/kg per injection) of intravenous (i.v.) self-administration. MAO-B inhibition by R-(-)-deprenyl or MDL 72974 enhanced the S(R) effects of beta-PEA in all monkeys and, under the FR schedule, induced a 30-fold or greater leftward shift in the dose-response function for its i.v. self-administration. Based on time-course determinations, the enhanced S(R) effects of beta-PEA under the FR schedule were long-lasting and dissipated gradually over 3-7 days. These results show that inhibition of MAO-B enhances S(D) and S(R) effects of beta-PEA in monkeys, presumably by delaying its inactivation. MAO-B inhibition leading to increased levels of beta-PEA may be useful, alone or in combination with other therapeutic agents, in the pharmacological management of selected aspects of drug dependence.

Hypothermia blocks beta-catenin degradation after focal ischemia in rats.

PubMed

Zhang, Hanfeng; Ren, Chuancheng; Gao, Xuwen; Takahashi, Tetsuya; Sapolsky, Robert M; Steinberg, Gary K; Zhao, Heng

2008-03-10

Dephosphorylated and activated glycogen synthase kinase (GSK) 3beta hyperphosphorylates beta-catenin, leading to its ubiquitin-proteosome-mediated degradation. beta-catenin-knockdown increases while beta-catenin overexpression prevents neuronal death in vitro; in addition, protein levels of beta-catenin are reduced in the brain of Alzheimer's patients. However, whether beta-catenin degradation is involved in stroke-induced brain injury is unknown. Here we studied activities of GSK 3beta and beta-catenin, and the protective effect of moderate hypothermia (30 degrees C) on these activities after focal ischemia in rats. The results of Western blot showed that GSK 3beta was dephosphorylated at 5 and 24 h after stroke in the normothermic (37 degrees C) brain; hypothermia augmented GSK 3beta dephosphorylation. Because hypothermia reduces infarction, these results contradict with previous studies showing that GSK 3beta dephosphorylation worsens neuronal death. Nevertheless, hypothermia blocked degradation of total GSK 3beta protein. Corresponding to GSK 3beta activity in normothermic rats, beta-catenin phosphorylation transiently increased at 5 h in both the ischemic penumbra and core, and the total protein level of beta-catenin degraded after normothermic stroke. Hypothermia did not inhibit beta-catenin phosphorylation, but it blocked beta-catenin degradation in the ischemic penumbra. In conclusion, moderate hypothermia can stabilize beta-catenin, which may contribute to the protective effect of moderate hypothermia.

The effects of lower than conventional doses of oral nadolol on relative beta 1/beta 2-adrenoceptor blockade.

PubMed

Wheeldon, N M; McDevitt, D G; Lipworth, B J

1994-08-01

1. The aim of the present study was to evaluate the relative beta 1/beta 2 antagonist selectivity of the beta-adrenoceptor blocker nadolol, in lower than conventional clinical doses. 2. Eight normal volunteers received single oral doses of either placebo (PL), nadolol 5 mg (N5), 20 mg (N20) or 80 mg (N80) in a single-blind, randomised crossover design. beta 1-adrenoceptor antagonism was assessed by attenuation of exercise tachycardia, and beta 2-adrenoceptor blockade by effects on salbutamol-induced chronotropic, hypokalaemic and finger tremor responses. The relative percentage attenuation of beta 2 and beta 1-mediated responses was calculated and expressed as beta 2:beta 1 selectivity ratios. 3. Nadolol produced dose-related reductions in exercise tachycardia in keeping with increasing beta 1-adrenoceptor blockade; mean % reduction (95% CI) compared with placebo: N5 10.7 (6.6 to 14.8), N20 21.4 (17.3 to 25.4), N80 38.9 (34.8 to 42.9). However, even the lowest dose of nadolol (5 mg) produced almost complete blunting of beta 2-mediated effects and significantly increase exercise hyperkalaemia; peak exercise hyperkalaemia (mmol l-1) (means and 95% CI): PL 4.88 (4.68 to 5.07), N5 5.36 (5.17 to 5.55), N20 5.48 (5.28 to 5.67), N80 5.42 (5.22 to 5.61). beta 2:beta 1 selectivity ratios significantly increased as the dose of nadolol was reduced. 4. These data suggest that whereas in the clinical dose range nadolol behaves as a non-selective beta-adrenoceptor antagonist, as the dose is reduced this drug demonstrates an increasing degree of selectivity for the beta 2-adrenoceptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of IL-1 beta and 5-HT2 receptors in midbrain periaqueductal gray (PAG) in potentiating defensive rage behavior in cat.

PubMed

Bhatt, Suresh; Bhatt, Rekha; Zalcman, Steven S; Siegel, Allan

2008-02-01

Feline defensive rage, a form of aggressive behavior that occurs in response to a threat can be elicited by electrical stimulation of the medial hypothalamus or midbrain periaqueductal gray (PAG). Our laboratory has recently begun a systematic examination of the role of cytokines in the regulation of rage and aggressive behavior. It was shown that the cytokine, interleukin-2 (IL-2), differentially modulates defensive rage when microinjected into the medial hypothalamus and PAG by acting through separate neurotransmitter systems. The present study sought to determine whether a similar relationship exists with respect to interleukin 1-beta (IL-1 beta), whose receptor activation in the medial hypothalamus potentiates defensive rage. Thus, the present study identified the effects of administration of IL-1 beta into the PAG upon defensive rage elicited from the medial hypothalamus. Microinjections of IL-1 beta into the dorsal PAG significantly facilitated defensive rage behavior elicited from the medial hypothalamus in a dose and time dependent manner. In addition, the facilitative effects of IL-1 beta were blocked by pre-treatment with anti-IL-1 beta receptor antibody, while IL-1 beta administration into the PAG had no effect upon predatory attack elicited from the lateral hypothalamus. The findings further demonstrated that IL-1 beta's effects were mediated through 5-HT(2) receptors since pretreatment with a 5-HT(2C) receptors antagonist blocked the facilitating effects of IL-1 beta. An extensive pattern of labeling of IL-1 beta and 5-HT(2C) receptors in the dorsal PAG supported these findings. The present study demonstrates that IL-beta in the dorsal PAG, similar to the medial hypothalamus, potentiates defensive rage behavior and is mediated through a 5-HT(2C) receptor mechanism.

The Arg389Gly beta1-adrenoceptor polymorphism does not affect cardiac effects of exercise after parasympathetic inhibition by atropine.

PubMed

Leineweber, Kirsten; Bruck, Heike; Temme, Thomas; Heusch, Gerd; Philipp, Thomas; Brodde, Otto-Erich

2006-01-01

In vitro, Arg389Gly beta1-adrenoceptor (AR) polymorphism exhibits decreased beta-AR signalling. In vivo, beta1-AR-mediated cardiac effects of exercise showed no genotype-dependent differences in Arg389 vs. Gly389 beta1-AR subjects. We studied in 16 male subjects homozygous Arg389 or Gly389 beta1-AR, whether blockade of parasympathetic activity might unmask genotype-dependence of exercise effects. Subjects were infused with atropine (10 microg/kg i.v. loading dose followed by continuous i.v. infusion of 0.15 microg/kg/min throughout exercise-time); 20 min after start of atropine bicycle-exercise in supine position (25, 50, 75 and 100 W for 5 min each) was performed and heart rate, contractility, blood pressure, plasma noradrenaline and plasma-renin activity were assessed. Exercise-evoked increases in all but one parameters were not different between Arg389 and Gly389 beta1-AR subjects; only plasma noradrenaline increased slightly more in Gly389 vs. Arg389 beta1-AR subjects. It appears to be unlikely that lack of Arg389Gly beta1-AR genotype-dependence of exercise-effects can be explained by influences of parasympathetic activity.

IL-1beta suppresses the formation of osteoclasts by increasing OPG production via an autocrine mechanism involving celecoxib-related prostaglandins in chondrocytes.

PubMed

Watanabe, Yusuke; Namba, Aki; Aida, Yukiko; Honda, Kazuhiro; Tanaka, Hideki; Suzuki, Naoto; Matsumura, Hideo; Maeno, Masao

2009-01-01

Elevated interleukin (IL)-1 concentrations in synovial fluid have been implicated in joint bone and cartilage destruction. Previously, we showed that IL-1beta stimulated the expression of prostaglandin (PG) receptor EP4 via increased PGE(2) production. However, the effect of IL-1beta on osteoclast formation via chondrocytes is unclear. Therefore, we examined the effect of IL-1beta and/or celecoxib on the expression of macrophage colony-stimulating factor (M-CSF), receptor activator of NF-kappaB ligand (RANKL), and osteoprotegerin (OPG) in human chondrocytes, and the indirect effect of IL-1beta on osteoclast-like cell formation using RAW264.7 cells. OPG and RANKL expression increased with IL-1beta; whereas M-CSF expression decreased. Celecoxib blocked the stimulatory effect of IL-1beta. Conditioned medium from IL-1beta-treated chondrocytes decreased TRAP staining in RAW264.7 cells. These results suggest that IL-1beta suppresses the formation of osteoclast-like cells via increased OPG production and decreased M-CSF production in chondrocytes, and OPG production may increase through an autocrine mechanism involving celecoxib-related PGs.

Release of IL-1beta via IL-1beta-converting enzyme in a skin dendritic cell line exposed to 2,4-dinitrofluorobenzene.

PubMed

Matos, Teresa J; Jaleco, Sara P; Gonçalo, Margarida; Duarte, Carlos B; Lopes, M Celeste

2005-08-14

We used a mouse fetal skin dendritic cell line (FSDC) to study the effect of the strong allergen 2,4-dinitrofluorobenzene (DNFB) on interleukin (IL)-1beta release and IL-1beta receptor immunoreactivity. Stimulation with DNFB (30 minutes) increased IL-1 release without changing the mRNA levels of the protein. Furthermore, DNFB increased transiently the interleukin-1beta-converting enzyme (ICE) activity, as measured with its fluorogenic substrate Z-Tyr-Val-Ala-Asp-AFC. The ICE inhibitor Z-YVAD-FMK prevented the release of IL-1beta evoked by DNFB. Incubation of the cells with DNFB (30 minutes) strongly increased IL-1beta receptor immunoreactivity. The rapid effect of DNFB on the release of mature IL-1beta, without inducing an increase of IL-1beta mRNA in FSDC, suggests a posttranslational modification of pro-IL-1beta by ICE activity.

Publications of the exobiology program for 1984: A special bibliography

NASA Technical Reports Server (NTRS)

Wallace, J. S. (Compiler); Devincenzi, D. L. (Compiler)

1986-01-01

A bibliography of NASA exobiology programs is given. Planetary environments; chemical evolution; organic geochemistry; extraterrestrial intelligence; and the effect of planetary solar and astrophysical phenomena on the evolution of complex life in the universe are among the topics listed.

Spacecraft Radio Scintillation and Solar System Exploration

NASA Technical Reports Server (NTRS)

Woo, Richard

1993-01-01

When a wave propagates through a turbulent medium, scattering by the random refractive index inhomogeneities can lead to a wide variety of phenomena that have been the subject of extensive study. The observed scattering effects include amplitude or intensity scintillation, phase scintillation, angular broadening, and spectral broadening, among others. In this paper, I will refer to these scattering effects collectively as scintillation. Although the most familiar example is probably the twinkling of stars (light wave intensity scintillation by turbulence in the Earth's atmosphere), scintillation has been encountered and investigated in such diverse fields as ionospheric physics, oceanography, radio astronomy, and radio and optical communications. Ever since planetary spacecraft began exploring the solar system, scintillation has appeared during the propagation of spacecraft radio signals through planetary atmospheres, planetary ionospheres, and the solar wind. Early studies of these phenomena were motivated by the potential adverse effects on communications and navigation, and on experiments that use the radio link to conduct scientific investigations. Examples of the latter are radio occultation measurements (described below) of planetary atmospheres to deduce temperature profiles, and the search for gravitational waves. However,these concerns soon gave way to the emergence of spacecraft radio scintillation as a new scientific tool for exploring small-scale dynamics in planetary atmospheres and structure in the solar wind, complementing in situ and other remote sensing spacecraft measurements, as well as scintillation measurements using natural (celestial) radio sources. The purpose of this paper is to briefly describe and review the solar system spacecraft radio scintillation observations, to summarize the salient features of wave propagation analyses employed in interpreting them, to underscore the unique remote sensing capabilities and scientific relevance of the scintillation measurements, and to highlight some of the scientific results obtained to date. Special emphasis is placed on comparing the remote sensing features of planetary and terrestrial scintillation measurements, and on contrasting spacecraft and natural radio source scintillation measurements. I will first discuss planetary atmospheres and ionospheres, and then the solar wind.

Modeling, Modal Properties, and Mesh Stiffness Variation Instabilities of Planetary Gears

NASA Technical Reports Server (NTRS)

Parker, Robert G.; Lin, Jian; Krantz, Timothy L. (Technical Monitor)

2001-01-01

Planetary gear noise and vibration are primary concerns in their applications in helicopters, automobiles, aircraft engines, heavy machinery and marine vehicles. Dynamic analysis is essential to the noise and vibration reduction. This work analytically investigates some critical issues and advances the understanding of planetary gear dynamics. A lumped-parameter model is built for the dynamic analysis of general planetary gears. The unique properties of the natural frequency spectra and vibration modes are rigorously characterized. These special structures apply for general planetary gears with cyclic symmetry and, in practically important case, systems with diametrically opposed planets. The special vibration properties are useful for subsequent research. Taking advantage of the derived modal properties, the natural frequency and vibration mode sensitivities to design parameters are investigated. The key parameters include mesh stiffnesses, support/bearing stiffnesses, component masses, moments of inertia, and operating speed. The eigen-sensitivities are expressed in simple, closed-form formulae associated with modal strain and kinetic energies. As disorders (e.g., mesh stiffness variation. manufacturing and assembling errors) disturb the cyclic symmetry of planetary gears, their effects on the free vibration properties are quantitatively examined. Well-defined veering rules are derived to identify dramatic changes of natural frequencies and vibration modes under parameter variations. The knowledge of free vibration properties, eigen-sensitivities, and veering rules provide important information to effectively tune the natural frequencies and optimize structural design to minimize noise and vibration. Parametric instabilities excited by mesh stiffness variations are analytically studied for multi-mesh gear systems. The discrepancies of previous studies on parametric instability of two-stage gear chains are clarified using perturbation and numerical methods. The operating conditions causing parametric instabilities are expressed in closed-form suitable for design guidance. Using the well-defined modal properties of planetary gears, the effects of mesh parameters on parametric instability are analytically identified. Simple formulae are obtained to suppress particular instabilities by adjusting contact ratios and mesh phasing.

Physical studies of the planetary rings

NASA Technical Reports Server (NTRS)

Ip, W.-H.

1980-01-01

In this review paper, the physical properties of the Saturnian and Uranian rings as derived from ground-based observations are first discussed. Focus is then shifted to the study of the orbital dynamics of the ring particles. Numerical simulations of the evolutionary history of a system of colliding particles in differential rotation together with theoretical modeling of the inelastic collision processes are surveyed. In anticipation of the information returned from in situ measurements by space probes, interactions of the planetary rings with the interplanetary meteoroids and planetary magnetospheres are briefly considered. Finally, models of planetary ring origin are examined. In this connection, some recent work on the satellite resonant perturbation effects on the ring structure are also touched upon.

REVIEWS OF TOPICAL PROBLEMS: The physics of planetary rings

NASA Astrophysics Data System (ADS)

Gor'kavyĭ, N. N.; Fridman, Aleksei M.

1990-02-01

A review of the collisional, collective, and resonance phenomena in planetary rings is presented. The following questions are examined: the reasons for the existence of planetary rings and the properties of a typical particle, the collisional breaking of loose bodies, and the azimuthal asymmetry effect for the rings of Saturn. A transfer theory is being developed for differentially rotating disks of inelastic particles, and the collective instabilities of planetary rings and a protoplanetary disk are discussed. A model for the resonance origin for the rings of Uranus is described, which enabled one to predict unknown satellites of Uranus that were later discovered by "Voyager-2". The problem of the stability of the rings of Uranus is examined.

Partitioning diversity into independent alpha and beta components.

PubMed

Jost, Lou

2007-10-01

Existing general definitions of beta diversity often produce a beta with a hidden dependence on alpha. Such a beta cannot be used to compare regions that differ in alpha diversity. To avoid misinterpretation, existing definitions of alpha and beta must be replaced by a definition that partitions diversity into independent alpha and beta components. Such a unique definition is derived here. When these new alpha and beta components are transformed into their numbers equivalents (effective numbers of elements), Whittaker's multiplicative law (alpha x beta = gamma) is necessarily true for all indices. The new beta gives the effective number of distinct communities. The most popular similarity and overlap measures of ecology (Jaccard, Sorensen, Horn, and Morisita-Horn indices) are monotonic transformations of the new beta diversity. Shannon measures follow deductively from this formalism and do not need to be borrowed from information theory; they are shown to be the only standard diversity measures which can be decomposed into meaningful independent alpha and beta components when community weights are unequal.

Synthetic peptides corresponding to human follicle-stimulating hormone (hFSH)-beta-(1-15) and hFSH-beta-(51-65) induce uptake of 45Ca++ by liposomes: evidence for calcium-conducting transmembrane channel formation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grasso, P.; Santa-Coloma, T.A.; Reichert, L.E. Jr.

1991-06-01

We have previously described FSH receptor-mediated influx of 45Ca++ in cultured Sertoli cells from immature rats and receptor-enriched proteoliposomes via activation of voltage-sensitive and voltage-independent calcium channels. We have further shown that this effect of FSH does not require cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding protein or activation of adenylate cyclase. In the present study, we have identified regions of human FSH-beta-subunit which appear to be involved in mediating calcium influx. We screened 11 overlapping peptide amides representing the entire primary structure of hFSH-beta-subunit for their effects on 45Ca++ flux in FSH receptor-enriched proteoliposomes. hFSH-beta-(1-15) and hFSH-beta-(51-65) inducedmore » uptake of 45Ca++ in a concentration-related manner. This effect of hFSH-beta-(1-15) and hFSH-beta-(51-65) was also observed in liposomes lacking incorporated FSH receptor. Reducing membrane fluidity by incubating liposomes (containing no receptor) with hFSH-beta-(1-15) or hFSH-beta-(51-65) at temperatures lower than the transition temperatures of their constituent phospholipids resulted in no significant (P greater than 0.05) difference in 45Ca++ uptake. The effectiveness of the calcium ionophore A23187, however, was abolished. Ruthenium red, a voltage-independent calcium channel antagonist, was able to completely block uptake of 45Ca++ induced by hFSH-beta-(1-15) and hFSH-beta-(51-65) whereas nifedipine, a calcium channel blocker specific for L-type voltage-sensitive calcium channels, was without effect. These results suggest that in addition to its effect on voltage-sensitive calcium channel activity, interaction of FSH with its receptor may induce formation of transmembrane aqueous channels which also facilitate influx of extracellular calcium.« less

Measuring and interpreting X-ray fluorescence from planetary surfaces.

PubMed

Owens, Alan; Beckhoff, Burkhard; Fraser, George; Kolbe, Michael; Krumrey, Michael; Mantero, Alfonso; Mantler, Michael; Peacock, Anthony; Pia, Maria-Grazia; Pullan, Derek; Schneider, Uwe G; Ulm, Gerhard

2008-11-15

As part of a comprehensive study of X-ray emission from planetary surfaces and in particular the planet Mercury, we have measured fluorescent radiation from a number of planetary analog rock samples using monochromatized synchrotron radiation provided by the BESSY II electron storage ring. The experiments were carried out using a purpose built X-ray fluorescence (XRF) spectrometer chamber developed by the Physikalisch-Technische Bundesanstalt, Germany's national metrology institute. The XRF instrumentation is absolutely calibrated and allows for reference-free quantitation of rock sample composition, taking into account secondary photon- and electron-induced enhancement effects. The fluorescence data, in turn, have been used to validate a planetary fluorescence simulation tool based on the GEANT4 transport code. This simulation can be used as a mission analysis tool to predict the time-dependent orbital XRF spectral distributions from planetary surfaces throughout the mapping phase.

On the Interactions Between Planetary and Mesoscale Dynamics in the Oceans

NASA Astrophysics Data System (ADS)

Grooms, I.; Julien, K. A.; Fox-Kemper, B.

2011-12-01

Multiple-scales asymptotic methods are used to investigate the interaction of planetary and mesoscale dynamics in the oceans. We find three regimes. In the first, the slow, large-scale planetary flow sets up a baroclinically unstable background which leads to vigorous mesoscale eddy generation, but the eddy dynamics do not affect the planetary dynamics. In the second, the planetary flow feels the effects of the eddies, but appears to be unable to generate them. The first two regimes rely on horizontally isotropic large-scale dynamics. In the third regime, large-scale anisotropy, as exists for example in the Antarctic Circumpolar Current and in western boundary currents, allows the large-scale dynamics to both generate and respond to mesoscale eddies. We also discuss how the investigation may be brought to bear on the problem of parameterization of unresolved mesoscale dynamics in ocean general circulation models.

Precise Chemical Analyses of Planetary Surfaces

NASA Technical Reports Server (NTRS)

Kring, David; Schweitzer, Jeffrey; Meyer, Charles; Trombka, Jacob; Freund, Friedemann; Economou, Thanasis; Yen, Albert; Kim, Soon Sam; Treiman, Allan H.; Blake, David;

The changes in beta-adrenoceptor-mediated cardiac function in experimental hypothyroidism: the possible contribution of cardiac beta3-adrenoceptors.

PubMed

Arioglu, E; Guner, S; Ozakca, I; Altan, V M; Ozcelikay, A T

2010-02-01

Thyroid hormone deficiency has been reported to decrease expression and function of both beta(1)- and beta(2)-adrenoceptor in different tissues including heart. The purpose of this study was to examine the possible contribution of beta(3)-adrenoceptors to cardiac dysfunction in hypothyroidism. In addition, effect of this pathology on beta(1)- and beta(2)-adrenoceptor was investigated. Hypothyroidism was induced by adding methimazole (300 mg/l) to drinking water of rats for 8 weeks. Cardiac hemodynamic parameters were measured in anesthetised rats in vivo. Responses to beta-adrenoceptor agonists were examined in rat papillary muscle in vitro. We also studied the effect of hypotyroidism on mRNA expression of beta-adrenoceptors, Gialpha, GRK, and eNOS in rat heart. All of the hemodynamic parameters (systolic, diastolic and mean arterial pressure, left ventricular pressure, heart rate, +dp/dt, and -dp/dt) were significantly reduced by the methimazole treatment. The negative inotropic effect elicited by BRL 37344 (a beta(3)-adrenoceptor preferential agonist) and positive inotropic effects produced by isoprenaline and noradrenaline, respectively, were significantly decreased in papillary muscle of hypothyroid rats as compared to those of controls. On the other hand, hypothyroidism resulted in increased cardiac beta(2)- and beta(3)-adrenoceptor, Gialpha(2), Gialpha(3), GRK3, and eNOS mRNA expressions. However, beta(1)-adrenoceptor and GRK2 mRNA expressions were not changed significantly in this pathology. These results show that mRNA expression of beta(3)-adrenoceptors as well as the signalling pathway components mediated through beta(3)-adrenoceptors are significantly increased in hypothyroid rat heart. Since we could not correlate these alternates with the decreased negative inotropic response mediated by this receptor subtype, it is not clear whether these changes are important for hypothyroid induced reduction in cardiac function.

Study of the Effects of Photometric Geometry on Spectral Reflectance Measurements

NASA Technical Reports Server (NTRS)

Helfenstein, Paul

1998-01-01

The objective of this research is to investigate how the spectrophotometric properties of planetary surface materials depend on photometric geometry by refining and applying radiative transfer theory to data obtained from spacecraft and telescope observations of planetary surfaces, studies of laboratory analogs, and computer simulations. The goal is to perfect the physical interpretation of photometric parameters in the context of planetary surface geological properties and processes. The purpose of this report is to document the research achievements associated with this study.

Impact Processes in the Solar System

NASA Technical Reports Server (NTRS)

Ahrens, Thomas J.

2004-01-01

The three main topics of this program as described initially in our May 2003 proposal are: 1) Shock-induced damage and attenuation in planetary materials. 2 ) Shock-induced melting and phase changes. 3) Impact-induced volatilization and vapor speciation of planetary materials Topic 4 has been the subject of a continuing investigation since approximately 1990. On Topic 5, we have a paper in preparation and have submitted a proposal to Astrobiology. 4) Responses of planetary atmospheres to giant impact, 5) Effects of impact-induced shock waves on microbial life

Antagonistic effects of beta-phenylethylamine on quinpirole- and (-)-sulpiride-induced changes in evoked dopamine release from rat striatal slices.

PubMed

Yamada, S; Harano, M; Tanaka, M

1998-02-19

To assess the role of beta-phenylethylamine in aspects of dopamine release, we measured the level of beta-phenylethylamine in the rat striatum after killing the rats by microwave irradiation. We then investigated the effect of beta-phenylethylamine on electrically evoked dopamine release from rat striatal slices in vitro. The striatal beta-phenylethylamine level was 46.5 +/- 3.5 ng/g wet tissue, equivalent to 0.3 micromol/l. Superfusion with low concentrations of beta-phenylethylamine up to 1 micromol/l had no effect on spontaneous or electrically evoked dopamine release from striatal slices. Quinpirole reduced the evoked dopamine release from slices in a concentration-dependent manner. The quinpirole-induced reduction of evoked dopamine release was attenuated 30% by superfusion with 0.3 micromol/l beta-phenylethylamine. Moreover, the (-)-sulpiride (0.1 micromol/l)-induced increase in evoked dopamine release was also attenuated by superfusion with 0.3 micromol/l beta-phenylethylamine. These data indicate that submicromolar levels of beta-phenylethylamine could modify the dopamine autoreceptor mediated changes in evoked dopamine release from rat striatal slices.

Selective regulation of beta 1- and beta 2-adrenoceptors in the human heart by chronic beta-adrenoceptor antagonist treatment.

PubMed Central

Michel, M. C.; Pingsmann, A.; Beckeringh, J. J.; Zerkowski, H. R.; Doetsch, N.; Brodde, O. E.

1988-01-01

1. In 44 patients undergoing coronary artery bypass grafting, the effect of chronic administration of the beta-adrenoceptor antagonists sotalol, propranolol, pindolol, metoprolol and atenolol on beta-adrenoceptor density in right atria (containing 70% beta 1- and 30% beta 2-adrenoceptors) and in lymphocytes (having only beta 2-adrenoceptors) was studied. 2. beta-Adrenoceptor density in right atrial membranes and in intact lymphocytes was assessed by (-)-[125I]-iodocyanopindolol (ICYP) binding; the relative amount of right atrial beta 1- and beta 2-adrenoceptors was determined by inhibition of ICYP binding by the selective beta 2-adrenoceptor antagonist ICI 118,551 and analysis of the resulting competition curves by the iterative curve fitting programme LIGAND. 3. With the exception of pindolol, all beta-adrenoceptor antagonists increased right atrial beta-adrenoceptor density compared to that observed in atria from patients not treated with beta-adrenoceptor antagonists. 4. All beta-adrenoceptor antagonists increased right atrial beta 1-adrenoceptor density; on the other hand, only sotalol and propranolol also increased right atrial beta 2-adrenoceptor density, whereas metoprolol and atenolol did not affect it and pindolol decreased it. 5. Similarly, in corresponding lymphocytes, only sotalol or propranolol increased beta 2-adrenoceptor density, while metoprolol and atenolol did not affect it and pindolol decreased it. 6. It is concluded that beta-adrenoceptor antagonists subtype-selectively regulate cardiac and lymphocyte beta-adrenoceptor subtypes. The selective increase in cardiac beta 1-adrenoceptor density evoked by metoprolol and atenolol may be one of the reasons for the beneficial effects observed in patients with end-stage congestive cardiomyopathy following intermittent treatment with low doses of selective beta 1-adrenoceptor antagonists. PMID:2902891

[Effect of IL-1beta on growth properties of vaginal microsymbionts].

PubMed

Kremleva, E A; Bukharin, O V

2013-01-01

Study the effect of IL-1beta in concentrations that are characteristic for vaginal normo- and pathocenosis on growth properties of vaginal microsymbionts. Concentration of IL-1beta in vaginal contents of women during bacterial vaginosis and normocenosis was determined by using enzume immunoassay. Changes of growth characteristics and biofilm formation ability of Staphylococcus aureus, Escherichia coli, Lactobacilus spp., Corynebacterium spp. under the effect of various IL-1beta concentrations by method of O'Toole G.A. (1999) were studied. IL-1beta in concentrations characteristic for normocenosis was shown to be able to cause stimulating effect on growth properties of lactobacilli and corynebacteria and suppress growth of S. aureus and E. coli in both plankton and biofilm cultures. IL-1beta concentrations characteristic for vaginal dysbiosis on the contrary result in suppression of growth of lactobacilli biomass against the background of stimulation of growth properties and biofilm formation ability of S. aureus and E. coli. Differential dose-dependent effect of IL-1beta on biomass growth and biofilm formation ability of vaginal microsymbionts is a mechanism of regulation of vaginal microbiocenosis.

Effects of beta-phenylethylamine on dopaminergic neurons of the ventral tegmental area in the rat: a combined electrophysiological and microdialysis study.

PubMed

Ishida, Kota; Murata, Mikio; Katagiri, Nobuyuki; Ishikawa, Masago; Abe, Kenji; Kato, Masatoshi; Utsunomiya, Iku; Taguchi, Kyoji

2005-08-01

The effects of systemic administration of beta-phenylethylamine (beta-PEA) and microiontophoretically applied beta-PEA on the spontaneous discharge of dopamine (DA) neurons in the ventral tegmental area (VTA) of the anesthetized rat were examined. Intravenous administration of beta-PEA (1.0, 2.5, and 5.0 mg/kg) and microiontophoretic applications of beta-PEA caused inhibitory responses in DA neurons. Systemic administration and microiontophoretic applications of beta-PEA induced dose- or current-dependent responses. The systemic beta-PEA-induced inhibitory responses were reversed by pretreatment with the DA D(2) receptor antagonists haloperidol (0.5 mg/kg i.p.) and sulpiride (10 mg/kg i.p). Pretreatment with reserpine (5 mg/kg i.p. 24 h earlier) did not completely block the systemic administration of beta-PEA (2.5 mg/kg) inhibition. A microdialysis study of freely moving rats demonstrated that the extracellular DA level increased significantly in response to local application of beta-PEA (100 muM) in the VTA via a microdialysis probe, and local application of beta-PEA-stimulated somatodendritic DA release in the VTA. The beta-PEA-induced release of DA was calcium ion-independent and was enhanced by pretreatment with pertussis toxin. These findings indicate that beta-phenylethylamine inhibits DA neuron activity via DA D(2) autoreceptors in the rat VTA and that this inhibitory effect is mediated by the somatodendritic DA release.

Effect of electroacupuncture on the expression of interlukin-1beta mRNA after transient focal cerebral ischemia.

PubMed

Xu, Zhen-Feng; Wu, Gen-Cheng; Cao, Xiao-Ding

2002-01-01

It has been reported that interleukin-1beta (IL-1beta ) play a key role in the pathogenesis of cerebral ischemia. Acupuncture is an effective traditional medical therapy in China. The aim of present study was to evaluate the effect of electroacupuncture (EA) on IL-1beta mRNA expression after middle cerebral artery occlusion (MCAO) in rats. Using in situ hybridization technique, it was found that in the MCAO group the expression of IL-1beta mRNA was significantly increased at 2h, 6h, 12h after reperfusion in cerebral ischemic cortex compared with normal group. In EA+ MCAO group the expression of IL-1beta mRNA was significantly decreased at 2h, 6h and 12h in ischemic cortex compared with MCAO group. The results indicated that EA might decrease the IL-1beta protein expression by reducing the IL-beta mRNA expression in ischemic cortex.

Protein synthesis in skeletal muscle of neonatal pigs is enhanced by administration of Beta-hydroxy-Beta-methylbutyrate

USDA-ARS?s Scientific Manuscript database

Many low-birth-weight infants experience failure to thrive. The amino acid leucine stimulates protein synthesis in skeletal muscle of the neonate, but less is known about the effects of the leucine metabolite Beta-hydroxy-Beta-methylbutyrate (HMB). To determine the effects of HMB on protein synthesi...

Protein synthesis in skeletal muscle of neonatal pigs is enhanced by administration of beta-hydroxy-beta-methylbutyrate

USDA-ARS?s Scientific Manuscript database

Many low-birth-weight infants experience failure to thrive. The amino acid leucine stimulates protein synthesis in skeletal muscle of the neonate, but less is known about the effects of the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB). To determine the effects of HMB on protein synthesi...

Use of beta-methylphenylalanine (beta MeF) residues to probe the nature of the interaction of substance P with its receptor: effects of beta MeF-containing substance P analogs on rabbit iris smooth muscle contraction.

PubMed

Birney, D M; Cole, D C; Crosson, C E; Kahl, B F; Neff, B W; Reid, T W; Ren, K; Walkup, R D

1995-06-23

The effects of substituting (2S,3S)-beta-methylphenylalanine (S-beta MeF) or (2S,3R)-beta-methylphenylalanine (R-beta MeF) for the Phe7 and/or Phe8 residues of the tachykinin substance P (SP, RPKPQQFFGLM-NH2) upon the ability of SP to stimulate contraction of the rabbit iris smooth muscle were investigated. The eight beta MeF-containing SP analogs (four monosubstituted analogs, four disubstituted analogs) 1-8 were synthesized and found to be agonsts of SP in the smooth muscle contraction assay, having EC50 values ranging from 0.15 to 10.0 nM. Three analogs are significantly more active than SP [8R-(beta MeF)SP (4), 7S,8S-(beta MeF)2SP (5), and 7R,8S-(beta MeF)2SP (6)], three analogs are approximately equipotent with SP [7S-(beta MeF)SP (1), 7R-(beta MeF)SP (2), and 7S,8R-(beta MeF)2SP (8)], and two analogs are significantly less active than SP [8S-(beta MeF)SP (3) and 7R,8R-(beta MeF)2SP (7)]. The effects of the beta MeF substitutions upon the activity of SP are not additive and cannot be explained using simple conformational models which focus only on the side chain conformations of the beta MeF residues. It is postulated that the beta MeF residues induce minor distortions in the peptide backbone with resultant consequences upon peptide-receptor binding which are not dictated soley by the side chain conformations. This idea is consistent with 1H-NMR data for the monosubstituted analogs 1-4, which imply that the beta MeF substitutions cause slight distortions in the peptide backbone and that the beta MeF side chains are assuming trans or gauche(-) conformations.

Cosmic rays and other rpace phenomena influenced on the Earth's climate

NASA Astrophysics Data System (ADS)

Lev, Dorman

2016-07-01

We consider effects of cosmic rays (CR) and some other space phenomena on the Earth's climate change. It is well known that the system of internal and external factors formatting the Earth's climate is very unstable: decreasing of planetary average annual temperature leads to an increase of planetary snow surface, and decreasing of the total annual solar energy input into the system decreases the planetary temperature even more. And inverse: increasing planetary temperature leads to an decrease of snow surface, and increasing of the total solar energy input into the system increases the planetary temperature even more. From this follows that even energetically small factors acted long time in one direction may have a big influence on climate change. In our opinion, the most important of these factors are CR (mostly through its influence on planetary cloudiness) and space dust (SD) through their influence on the flux of solar irradiation and on formation of clouds (these actions are in one direction). It is important that CR and SD influenced on global climate change in the same direction. Increasing of CR planetary intensity leads to increasing of formation clouds (especially low clouds on altitudes smaller than 3 km), increasing annual average of raining and decreasing of annual average planetary temperature. Increasing of SD decreases of solar irradiation and increases cloudiness what leads also to decreasing of annual average planetary temperature. Moreover, interactions of CR particles with dust granules decreases their dimensions what increased effectiveness of their actions on clouds. We consider data great variations of planetary temperature much before the beginning of the Earth's technological civilization (mostly caused by moving of the solar system around our Galaxy centre and collisions with molecular-dust clouds). We consider in details not only situation during the last hundred years, but also situation in the last one thousand years (and especially situation during Maunder minimum of solar activity), during many thousand and many millions years. It is shown that very big changes in climate were caused also by some rarely phenomena as impacts of asteroids and nearby supernova explosions with great influence on biosphere. We discuss also the problem on forecasting of global climate change what is especially important for saving present civilization from great climate catastrophes.

Developmentally-regulated sodium channel subunits are differentially sensitive to {alpha}-cyano containing pyrethroids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meacham, Connie A.; Brodfuehrer, Peter D.; Watkins, Jennifer A.

2008-09-15

Juvenile rats have been reported to be more sensitive to the acute neurotoxic effects of the pyrethroid deltamethrin than adults. While toxicokinetic differences between juveniles and adults are documented, toxicodynamic differences have not been examined. Voltage-gated sodium channels, the primary targets of pyrethroids, are comprised of {alpha} and {beta} subunits, each of which have multiple isoforms that are expressed in a developmentally-regulated manner. To begin to test whether toxicodynamic differences could contribute to age-dependent deltamethrin toxicity, deltamethrin effects were examined on sodium currents in Xenopus laevis oocytes injected with different combinations of rat {alpha} (Na{sub v}1.2 or Na{sub v}1.3) andmore » {beta} ({beta}{sub 1} or {beta}{sub 3}) subunits. Deltamethrin induced tail currents in all isoform combinations and increased the percent of modified channels in a concentration-dependent manner. Effects of deltamethrin were dependent on subunit combination; Na{sub v}1.3-containing channels were modified to a greater extent than were Na{sub v}1.2-containing channels. In the presence of a {beta} subunit, deltamethrin effects were significantly greater, an effect most pronounced for Na{sub v}1.3 channels; Na{sub v}1.3/{beta}{sub 3} channels were more sensitive to deltamethrin than Na{sub v}1.2/{beta}{sub 1} channels. Na{sub v}1.3/{beta}{sub 3} channels are expressed embryonically, while the Na{sub v}1.2 and {beta}{sub 1} subunits predominate in adults, supporting the hypothesis for age-dependent toxicodynamic differences. Structure-activity relationships for sensitivity of these subunit combinations were examined for other pyrethroids. Permethrin and tetramethrin did not modify currents mediated by either subunit combination. Cypermethrin, {beta}-cyfluthrin, esfenvalerate and fenpropathrin all modified sodium channel function; effects were significantly greater on Na{sub v}1.3/{beta}{sub 3} than on Na{sub v}1.2/{beta}{sub 1} channels. These data demonstrate a greater sensitivity of Na{sub v}1.3 vs Na{sub v}1.2 channels to deltamethrin and other cyano-containing pyrethroids, particularly in the presence of a {beta} subunit.« less

TGF{beta} induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ebi, Masahide; Kataoka, Hiromi, E-mail: hkataoka@med.nagoya-cu.ac.jp; Shimura, Takaya

2010-11-19

Research highlights: {yields} TGF{beta} induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. {yields} TGF{beta} induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. {yields} TGF{beta} enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. {yields} Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGF{beta}. {yields} ADAM17 may play a crucial role in this TGF{beta}-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGF{beta}) is known to potently inhibit cell growth. Loss of responsiveness to TGF{beta} inhibition on cellmore » growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGF{beta} and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGF{beta}. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGF{beta} was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGF{beta} was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGF{beta}-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGF{beta} induced shedding of proHB-EGF allowing HB-EGF-CTF to translocate to the nucleus. ADAM inhibitors blocked this nuclear translocation. TGF{beta} enhanced gastric cancer cell growth and ADAM inhibitors suppressed this effect. EGFR phosphorylation, HB-EGF-CTF nuclear translocation, and cell growth were suppressed in ADAM17 knockdown cells. Conclusion: HB-EGF-CTF nuclear translocation and EGFR transactivation from proHB-EGF shedding mediated by ADAM17 activated by TGF{beta} might be an important pathway of gastric cancer cell proliferation by TGF{beta}.« less

Effects of orography on planetary scale flow

NASA Technical Reports Server (NTRS)

Smith, R. B.

1986-01-01

The earth's orography is composed of a wide variety of scales, each contributing to the spectrum of atmospheric motions. A well studied subject (originating with Charney and Eliassen) is the direct forcing of planetary scale waves by the planetary scale orography: primarily the Tibetan plateau and the Rockies. However, because of the non-linear terms in the equations of dynamic meteorology, even the smallest scales of mountain induced flow can contribute to the planetary scale if the amplitude of the small scale disturbance is sufficintly large. Two possible mechanisms for this are illustrated. First, preferentially located lee cyclones can force planetary waves by their meridional transport of heat and momentum (Hansen and Chen). Recent theories are helping to explain the phenomena of lee cyclogenesis (e.g., Smith, 1984, J.A.S.). Second, mesoscale mountain wave and severe downslope wind phenomena produce such a large local drag, that planetary scale waves can be produced. The mechanism of upscale transfer is easy to understand in this case as the standing planetary scale wave has a wavelength which depends on the mean structure of the atmosphere, and not on the width of the mountain (just as in small scale lee wave theory). An example of a theoretical description of a severe wind flow with very large drag is shown.

Safety margins in the implementation of planetary quarantine requirements

NASA Technical Reports Server (NTRS)

Schalkowsky, S.; Jacoby, I.

1972-01-01

The formulation of planetary quarantine requirements, and their implementation as determined by a risk allocation model, is discussed. The model defines control safety margins with particular emphasis on utility in achieving the desired minimization of excessive margins, and their effect on implementation procedures.

Current Scientific Issues in Large Scale Atmospheric Dynamics

NASA Technical Reports Server (NTRS)

Miller, T. L. (Compiler)

1986-01-01

Topics in large scale atmospheric dynamics are discussed. Aspects of atmospheric blocking, the influence of transient baroclinic eddies on planetary-scale waves, cyclogenesis, the effects of orography on planetary scale flow, small scale frontal structure, and simulations of gravity waves in frontal zones are discussed.

Nebivolol: the somewhat-different beta-adrenergic receptor blocker.

PubMed

Münzel, Thomas; Gori, Tommaso

2009-10-13

Although its clinical use in Europe dates almost 10 years, nebivolol is a beta-blocker that has been only recently introduced in the U.S. market. Like carvedilol, nebivolol belongs to the third generation of beta-blockers, which possess direct vasodilator properties in addition to their adrenergic blocking characteristics. Nebivolol has the highest beta(1)-receptor affinity among beta-blockers and, most interestingly, it substantially improves endothelial dysfunction via its strong stimulatory effects on the activity of the endothelial nitric oxide synthase and via its antioxidative properties. Because impaired endothelial activity is attributed a major causal role in the pathophysiology of hypertension, coronary artery disease, and congestive heart failure, the endothelium-agonistic properties of nebivolol suggest that this drug might provide additional benefit beyond beta-receptor blockade. Although lesser beta-blocker-related side effects have been reported in patients with chronic obstructive pulmonary disease or impotence taking nebivolol, side effects and contraindications overlap those of other beta-blockers. Clinically, this compound has been proven to have antihypertensive and anti-ischemic effects as well as beneficial effects on hemodynamics and prognosis in patients with chronic congestive heart failure. Further studies are now necessary to compare the benefit of nebivolol with that of other drugs in the same class and, most importantly, its prognostic impact in patients with hypertension.

[Effects of beta blockers on lipoprotein metabolism].

PubMed

Ritter, M M; Richter, W O; Schwandt, P

1992-10-10

With respect to prevention of its most common complication--mortality from coronary heart disease--treatment of hypertension had disappointed. It is possible that this is due to negative effects of antihypertensives on lipid metabolism. The effects of beta blockers on lipid metabolism can be differentiated principally, in accordance with the classification of beta blockers into those with and those without intrinsic sympathomimetic activity (ISA), as also selectivity and non-selectivity. Thus, non-selective beta blockers with no ISA usually lead to an increase in triglycerides of 25% to 30%, and a decrease in HDL cholesterol of about 15%. On average, beta-1 selective blockers result in a smaller increase in triglycerides. Beta blockers with ISA, in contrast, are largely neutral vis-à-vis lipid metabolism. In the individual case, in particular in the presence of hyperlipoproteinemia, the effects cannot be reliably predicted. Lipoprotein concentrations should be monitored during treatment with beta blockers. If necessary, a change in the agent employed is recommended. In the case of prevention of a second myocardial infarction, for which various studies have unequivocally shown a reduction in mortality associated with treatment with beta blockers with no ISA, these side effects will, however, be accepted--with the exception of extreme changes--for a limited period of time.

Space station impact experiments

NASA Technical Reports Server (NTRS)

Schultz, P.; Ahrens, T.; Alexander, W. M.; Cintala, M.; Gault, D.; Greeley, R.; Hawke, B. R.; Housen, K.; Schmidt, R.

1986-01-01

Four processes serve to illustrate potential areas of study and their implications for general problems in planetary science. First, accretional processes reflect the success of collisional aggregation over collisional destruction during the early history of the solar system. Second, both catastrophic and less severe effects of impacts on planetary bodies survivng from the time of the early solar system may be expressed by asteroid/planetary spin rates, spin orientations, asteroid size distributions, and perhaps the origin of the Moon. Third, the surfaces of planetary bodies directly record the effects of impacts in the form of craters; these records have wide-ranging implications. Fourth, regoliths evolution of asteroidal surfaces is a consequence of cumulative impacts, but the absence of a significant gravity term may profoundly affect the retention of shocked fractions and agglutinate build-up, thereby biasing the correct interpretations of spectral reflectance data. An impact facility on the Space Station would provide the controlled conditions necessary to explore such processes either through direct simulation of conditions or indirect simulation of certain parameters.

Beta-adrenergic blockade for the treatment of hyperthyroidism.

PubMed

Geffner, D L; Hershman, J M

1992-07-01

To review the clinical and biochemical effects of beta-adrenergic blocking drugs on hyperthyroidism. Studies published since 1972 were identified through a computerized search of MEDLINE and extensive searching of the bibliographies of the articles identified. Based on an understanding of the differences in beta-blocker metabolism in euthyroid and hyperthyroid patients, we reviewed the differences in pharmacokinetics and metabolic and clinical outcomes during their use in hyperthyroidism, as reported in the articles reviewed. beta Blockers have been used to modify the severity of the hyperadrenergic symptoms of hyperthyroidism for the past 20 years. The clinical efficacy of these agents is affected by hyperthyroid-induced alterations in their gastrointestinal absorption, hepatic metabolism, and renal excretion. The mechanisms whereby these clinical changes are effected is unknown. The agents differ in their beta 1 cardioselectivity, membrane-stabilizing activity, intrinsic sympathomimetic activity, and lipid solubility. They do not appear to alter synthesis or secretion of thyroid hormone by the thyroid gland. Their effects on thyroxine metabolism are contradictory. Decreased thyroxine to triiodothyronine conversion is caused by some, but not all, beta blockers, and this appears to correlate with membrane-stabilizing activity. There does not appear to be any alteration in catecholamine sensitivity during beta-adrenergic blockade. The principal mechanism of action of beta blockers in hyperthyroidism is to antagonize beta-receptor-mediated effects of catecholamines. beta Blockers are effective in treating hypermetabolic symptoms in a variety of hyperthyroid states. Used alone, they offer significant symptomatic relief. They are also useful adjuvants to antithyroid medications, surgery, and radioactive iodide treatment in patients with Graves' disease and toxic nodular goiters.

Systematic review of genuine versus spurious side-effects of beta-blockers in heart failure using placebo control: Recommendations for patient information☆☆☆

PubMed Central

Barron, Anthony J.; Zaman, Nabeela; Cole, Graham D.; Wensel, Roland; Okonko, Darlington O.; Francis, Darrel P.

2013-01-01

Background Patients trying life-preserving agents such as beta-blockers may be discouraged by listings of harmful effects provided in good faith by doctors, drug information sheets, and media. We systematically review the world experience of side-effect information in blinded, placebo-controlled beta-blockade in heart failure. We present information for a physician advising a patient experiencing an unwanted symptom and suspecting the drug. Methods We searched Medline for double-blinded randomized trials of beta-blocker versus placebo in heart failure reporting side-effects. We calculated, per 100 patients reporting the symptom on beta-blockade, how many would have experienced it on placebo: the “proportion of symptoms non-pharmacological”. Results 28 of the 33 classically-described side-effects are not significantly more common on beta-blockers than placebo. Of the 100 patients developing dizziness on beta-blockers, 81 (95% CI 73–89) would have developed it on placebo. For diarrhoea this proportion is 82/100 (70–95), and hyperglycaemia 83/100 (68–98). For only two side-effects is this under half (i.e. predominantly due to beta-blocker): bradycardia (33/100, CI 21–44) and intermittent claudication (41/100, 2–81). At least 6 so-called side-effects are less common on beta-blocker than placebo, including depression (reduced by 35%, p < 0.01) and insomnia (by 27%, p = 0.01). Conclusions Clinicians might reconsider whether it is scientifically and ethically correct to warn a patient that a drug might cause them a certain side-effect, when randomized controlled trials show no significant increase, or indeed a significant reduction. A better informed consultation could, in patients taking beta-blockers, alleviate suffering. In patients who might otherwise not take the drug, it might prevent deaths. PMID:23796325

Effect of Beta-Hydroxy Beta-Methylbutyrate on the Onset of Blood Lactate Accumulation and VO2peak in Endurance-Trained Cyclists.

ERIC Educational Resources Information Center

Vukovich, Matthew D.; Dreifort, Geri D.

2001-01-01

Examined the effect of beta-hydroxy beta-methylbutyrate (HMB) supplementation on maximal oxygen consumption (VO2peak) and onset of blood lactate accumulation (OBLA) in endurance-trained cyclists. Acute exercise did not affect plasma HMB concentrations. OBLA increased with HMB and leucine, with blood glucose significantly greater during the HMB…

Characterization of beta-phenylethylamine-induced monoamine release in rat nucleus accumbens: a microdialysis study.

PubMed

Nakamura, M; Ishii, A; Nakahara, D

1998-05-22

In vivo microdialysis was used to investigate the effect of beta-phenylethylamine on extracellular levels of monoamines and their metabolites in the nucleus accumbens of conscious rats. At all doses tested (1, 10 and 100 microM), infusion of beta-phenylethylamine through the microdialysis probe significantly increased extracellular levels of dopamine in the nucleus accumbens. These increases were dose-related. The increase in dopamine levels induced by 100 microM beta-phenylethylamine was not affected by co-perfusion of 4 microM tetrodotoxin. The ability of 100 microM beta-phenylethylamine to increase the extracellular level of dopamine was comparable to that of the same dose of methamphetamine. On the other hand, beta-phenylethylamine had a much less potent enhancing effect on 5-hydroxytryptamine (5-HT) than dopamine levels. Only the highest dose (100 microM) caused a statistically significant effect on 5-HT levels. Over the dose range tested (1, 10 and 100 microM), beta-phenylethylamine had no effect on extracellular metabolite levels of dopamine and 5-HT. The results suggest that beta-phenylethylamine increases the efflux of monoamines, preferentially dopamine, without affecting monoamine metabolism, in the nucleus accumbens.

Beta-glycerophosphate accelerates RANKL-induced osteoclast formation in the presence of ascorbic acid.

PubMed

Noh, A Long Sae Mi; Yim, Mijung

2011-03-01

Despite numerous reports of the synergistic effects of beta-glycerophosphate and ascorbic acid in inducing the differentiation of osteoblasts, little is known about their roles in osteoclastic differentiation. Therefore, we investigated the effect of beta-glycerophosphate on osteoclastogenesis in the presence of ascorbic acid using primary mouse bone marrow cultures treated with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor (NF)-kappaB ligand (RANKL). Beta-Glycerophosphate dose-dependently increased RANKL-induced osteoclast formation in the presence of ascorbic acid. This stimulatory effect was apparent when beta-glycerophosphate and ascorbic acid were only added during the late stages of the culture period, indicating that they influence later events in osteoclastic differentiation. While the combination of beta-glycerophosphate and ascorbic acid inhibited RANKL-stimulated activation of ERK and p38, and degradation of IkappaB, it increased the induction of c-Fos and NFATc1. In addition, beta-glycerophosphate and ascorbic acid together enhanced the induction of COX-2 following RANKL stimulation. Taken together, our data suggest that beta-glycerophosphate and ascorbic acid have synergistic effects on osteoclast formation, increasing RANKL-mediated induction of c-Fos, NFATc1 and COX-2 in osteoclast precursors.

Energy Balance Models and Planetary Dynamics

NASA Technical Reports Server (NTRS)

Domagal-Goldman, Shawn

2012-01-01

We know that planetary dynamics can have a significant affect on the climate of planets. Planetary dynamics dominate the glacial-interglacial periods on Earth, leaving a significant imprint on the geological record. They have also been demonstrated to have a driving influence on the climates of other planets in our solar system. We should therefore expect th.ere to be similar relationships on extrasolar planets. Here we describe a simple energy balance model that can predict the growth and thickness of glaciers, and their feedbacks on climate. We will also describe model changes that we have made to include planetary dynamics effects. This is the model we will use at the start of our collaboration to handle the influence of dynamics on climate.

Additive Construction with Mobile Emplacement (ACME)

NASA Technical Reports Server (NTRS)

Vickers, John

2015-01-01

The Additive Construction with Mobile Emplacement (ACME) project is developing technology to build structures on planetary surfaces using in-situ resources. The project focuses on the construction of both 2D (landing pads, roads, and structure foundations) and 3D (habitats, garages, radiation shelters, and other structures) infrastructure needs for planetary surface missions. The ACME project seeks to raise the Technology Readiness Level (TRL) of two components needed for planetary surface habitation and exploration: 3D additive construction (e.g., contour crafting), and excavation and handling technologies (to effectively and continuously produce in-situ feedstock). Additionally, the ACME project supports the research and development of new materials for planetary surface construction, with the goal of reducing the amount of material to be launched from Earth.

The Golgi localization of phosphatidylinositol transfer protein beta requires the protein kinase C-dependent phosphorylation of serine 262 and is essential for maintaining plasma membrane sphingomyelin levels.

PubMed

van Tiel, Claudia M; Westerman, Jan; Paasman, Marten A; Hoebens, Martha M; Wirtz, Karel W A; Snoek, Gerry T

2002-06-21

Recombinant mouse phosphatidylinositol transfer protein (PI-TP)beta is a substrate for protein kinase C (PKC)-dependent phosphorylation in vitro. Based on site-directed mutagenesis and two-dimensional tryptic peptide mapping, Ser(262) was identified as the major site of phosphorylation and Ser(165) as a minor phosphorylation site. The phospholipid transfer activities of wild-type PI-TP beta and PI-TP beta(S262A) were identical, whereas PI-TP beta(S165A) was completely inactive. PKC-dependent phosphorylation of Ser(262) also had no effect on the transfer activity of PI-TP beta. To investigate the role of Ser(262) in the functioning of PI-TP beta, wtPI-TP beta and PI-TP beta(S262A) were overexpressed in NIH3T3 fibroblast cells. Two-dimensional PAGE analysis of cell lysates was used to separate PI-TP beta from its phosphorylated form. After Western blotting, wtPI-TP beta was found to be 85% phosphorylated, whereas PI-TP beta(S262A) was not phosphorylated. In the presence of the PKC inhibitor GF 109203X, the phosphorylated form of wtPI-TP beta was strongly reduced. Immunolocalization showed that wtPI-TP beta was predominantly associated with the Golgi membranes. In the presence of the PKC inhibitor, wtPI-TP beta was distributed throughout the cell similar to what was observed for PI-TP beta(S262A). In contrast to wtPI-TP beta overexpressors, cells overexpressing PI-TP beta(S262A) were unable to rapidly replenish sphingomyelin in the plasma membrane upon degradation by sphingomyelinase. This implies that PKC-dependent association with the Golgi complex is a prerequisite for PI-TP beta to express its effect on sphingomyelin metabolism.

A ray tracing model of gravity wave propagation and breakdown in the middle atmosphere

NASA Technical Reports Server (NTRS)

Schoeberl, M. R.

1985-01-01

Gravity wave ray tracing and wave packet theory is used to parameterize wave breaking in the mesosphere. Rays are tracked by solving the group velocity equations, and the interaction with the basic state is determined by considering the evolution of the packet wave action density. The ray tracing approach has a number of advantages over the steady state parameterization as the effects of gravity wave focussing and refraction, local dissipation, and wave response to rapid changes in the mean flow are more realistically considered; however, if steady state conditions prevail, the method gives identical results. The ray tracing algorithm is tested using both interactive and noninteractive models of the basic state. In the interactive model, gravity wave interaction with the polar night jet on a beta-plane is considered. The algorithm produces realistic polar night jet closure for weak topographic forcing of gravity waves. Planetary scale waves forced by local transfer of wave action into the basic flow in turn transfer their wave action into the zonal mean flow. Highly refracted rays are also found not to contribute greatly to the climatology of the mesosphere, as their wave action is severely reduced by dissipation during their lateral travel.

The electrophysiologic properties of esmolol, a short acting beta-blocker.

PubMed

Greenspan, A M; Spielman, S R; Horowitz, L N; Laddu, A; Senior, S

1988-04-01

Although beta-blockers have established efficacy in treating ventricular ectopy and PSVT, their applicability for acute antiarrhythmic interventions in patients with organic heart disease or COPD, is frequently limited by negative inotropic or bronchospastic side effects. The development of an ultrashort acting beta-blocker with rapid reversibility of its side effects would widen their applicability. Therefore, we tested the electrophysiologic properties of such a new short acting beta-blocker, esmolol, in 14 patients (10 with organic heart disease) with a mean EF of 47.6 +/- 17%, undergoing standard clinical electrophysiologic studies for various indications. Like most other beta-blockers, esmolol's major direct effects were on sinus node function and AV nodal conduction characteristics; significantly prolonging sinus cycle length, cycle length to Wenckebach and AH interval in sinus rhythm and at a paced cycle length of 600 ms. In contrast to most other beta-blockers, following termination of its infusion, esmolol shortened parameters of sinus node function and AV nodal refractoriness, with respect to the control values, suggesting a possible rebound phenomena. These effects occurred within 5 min of terminating the intravenous drug infusion. Esmolol had no significant effect on systolic blood pressure, electrocardiographic intervals and had rare adverse reactions. We conclude that esmolol is an ultra-short acting beta-blocker, with typical direct electrophysiologic effects on sinus node and AV nodal function, and a possible rebound phenomena following its discontinuation that may make it particularly suited to acute antiarrhythmic interventions in patients susceptible to adverse beta-blocker side effects.

Beta-phenylethylamine inhibits K+ currents in neocortical neurons of the rat: a possible mechanism of beta-phenylethylamine-induced seizures.

PubMed

Kitamura, Taro; Munakata, Mitsutoshi; Haginoya, Kazuhiro; Tsuchiya, Shigeru; Iinuma, Kazuie

2008-08-01

beta-Phenylethylamine (beta-PEA), an endogenous amine synthesized in the brain, serves as a neuromodulator and is involved in the pathophysiology of various neurological disorders such as depression, schizophrenia, and attention-deficit hyperactivity disorder. beta-PEA fully exerts the physiological effects within the nanomolar concentration range via the trace amine receptors, but beta-PEA also causes convulsions at much higher concentrations via an as yet unknown mechanism. To investigate the electrophysiological mechanism by which beta-PEA induces convulsions, we examined the effect of beta-PEA on ionic currents passing through the cell membrane of dissociated rat cerebral cortical neurons, using a patch-clamp technique. The external application of beta-PEA suppressed ionic currents which continuously flowed when the membrane potential was held at -25 mV. The suppression was in a concentration-dependent manner and a half-maximal effective concentration was 540 muM. These currents suppressed by beta-PEA consisted of two K(+) currents: a time- and voltage-dependent K(+) current (M-current) and a leakage K(+) current. The suppression of the M-current reduces the efficacy of the current in limiting excessive neuronal firing, and the suppression of the leakage K(+) current can cause membrane depolarization and thus promote neuronal excitation. Reducing both of these currents in concert may produce neuronal seizing activity, which could conceivably underlie the convulsions induced by high-dose beta-PEA.

Mesalamine inhibits epithelial beta-catenin activation in chronic ulcerative colitis.

PubMed

Brown, Jeffrey B; Lee, Goo; Managlia, Elizabeth; Grimm, Gery R; Dirisina, Ramanarao; Goretsky, Tatiana; Cheresh, Paul; Blatner, Nichole R; Khazaie, Khashayarsha; Yang, Guang-Yu; Li, Linheng; Barrett, Terrence A

2010-02-01

Mesalamine is a mainstay therapeutic agent in chronic ulcerative colitis (CUC) in which condition it reverses crypt architectural changes and reduces colitis-associated cancer (CAC). The present study addressed the possibility that mesalamine reduces beta-catenin-associated progenitor cell activation, Akt-phosphorylated beta-catenin(Ser552) (P-beta-catenin), and colitis-induced dysplasia (CID). Effects of mesalamine on P-beta-catenin staining and function were assessed by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in biopsy specimens of CUC in mild or "refractory" severe mucosal inflammation. Effects of mesalamine on epithelial proliferation and activation of Akt and beta-catenin were assessed in interleukin (IL)-10(-/-) colitis and CID by immunohistochemistry and Western blotting. Dysplasia was assessed by counting the number and lengths of lesions per colon. Data from IL-10(-/-) and human colitis samples show that mesalamine reduced Akt activation and P-beta-catenin levels in the middle and upper crypt. Reductions in P-beta-catenin in CUC biopsy specimens with severe inflammation suggested that mesalamine reduced P-beta-catenin levels in tissue refractory to mesalamine's anti-inflammatory effects. In IL-10(-/-) mice, mesalamine reduced CID concordant with inhibition of crypt Akt and beta-catenin signaling. The results are consistent with the model that mesalamine contributes to chemoprevention in CAC by reducing beta-catenin signaling within intestinal progenitors.

The effect of altered 5-hydroxytryptamine levels on beta-endorphin

NASA Technical Reports Server (NTRS)

Soliman, Karam F. A.; Mash, Deborah C.; Walker, Charles A.

1986-01-01

The purpose of the present study was to examine the effect of altering the concentration of 5-hydroxytryptamine (5-HT) on beta-endorphin (beta-Ep) content in the hypothalamus, thalamus, and periaqueductal gray (PAG)-rostral pons regions of the rat brain. The selective 5-HT reuptake inhibitor, fluoxetine (10 mg/kg), significantly lowered beta-Ep content in the hypothalamus and the PAG. Parachlorophenylalanine, which inhibits 5-HT synthesis, significantly elevated beta-Ep in all brain parts studied. Intracisternal injections of the neurotoxin 5-prime, 7-prime-dihydroxytryptamine with desmethylimipramine pretreatment significantly increased beta-Ep content in the hypothalamus and the PAG. In adrenalectomized rats, fluoxetine significantly decreased beta-Ep levels in the hypothalamus and increased the levels in the PAG. The results indicate that 5-HT may modulate the levels of brain beta-Ep.

Transforming growth factor-beta inhibits human antigen-specific CD4+ T cell proliferation without modulating the cytokine response.

PubMed

Tiemessen, Machteld M; Kunzmann, Steffen; Schmidt-Weber, Carsten B; Garssen, Johan; Bruijnzeel-Koomen, Carla A F M; Knol, Edward F; van Hoffen, Els

2003-12-01

Transforming growth factor (TGF)-beta has been demonstrated to play a key role in the regulation of the immune response, mainly by its suppressive function towards cells of the immune system. In humans, the effect of TGF-beta on antigen-specific established memory T cells has not been investigated yet. In this study antigen-specific CD4(+) T cell clones (TCC) were used to determine the effect of TGF-beta on antigen-specific proliferation, the activation status of the T cells and their cytokine production. This study demonstrates that TGF-beta is an adequate suppressor of antigen-specific T cell proliferation, by reducing the cell-cycle rate rather than induction of apoptosis. Addition of TGF-beta resulted in increased CD69 expression and decreased CD25 expression on T cells, indicating that TGF-beta is able to modulate the activation status of in vivo differentiated T cells. On the contrary, the antigen-specific cytokine production was not affected by TGF-beta. Although TGF-beta was suppressive towards the majority of the T cells, insensitivity of a few TCC towards TGF-beta was also observed. This could not be correlated to differential expression of TGF-beta signaling molecules such as Smad3, Smad7, SARA (Smad anchor for receptor activation) and Hgs (hepatocyte growth factor-regulated tyrosine kinase substrate). In summary, TGF-beta has a pronounced inhibitory effect on antigen-specific T cell proliferation without modulating their cytokine production.

Effect of interlukin-1beta on proliferation of gastric epithelial cells in culture.

PubMed

Beales, Ian L P

2002-04-05

Helicobacter pylori is the main risk factor for the development of non-cardia gastric cancer. Increased proliferation of the gastric mucosa is a feature of H. pylori infection. Mucosal interkeukin-1beta production is increased in H. pylori infection and IL-1beta genotypes associated with increased pro-inflammatory activity are risk factors for the development of gastric cancer. The effect of IL-1beta on gastric epithelial cell proliferation has been examined in this study. AGS cells were cultured with IL-1beta. DNA synthesis was assed by [3H]thymidine incorporation and total viable cell numbers by MTT assay. IL-1beta dose dependently increased DNA synthesis and cell numbers. The enhanced proliferation was blocked by interleukin-1 receptor antagonist. Addition of neutralising antibody to GM-CSF reduced IL-1beta-stimulated proliferation by 31 +/- 4 %. GM-CSF alone significantly stimulated proliferation. Addition or neutralisation of IL-8 had no effect on basal or IL-1beta-stimulated proliferation. The tyrosine kinase inhibitor genistein completely blocked IL-1beta-stimulated proliferation and inhibition of the extracellular signal related kinase pathway with PD 98059 inhibited IL-1beta stimulated proliferation by 58 +/- 5 %. IL-1beta stimulates proliferation in gastric epithelial cells. Autocrine stimulation by GM-CSF contributes to this proliferative response. Signalling via tyrosine kinase activity is essential to the mitogenic response to IL-1beta. The extracellular signal related kinase pathway is involved in, but not essential to downstream signalling. IL-1beta may contribute to the hyperproliferation seen in H. pylori- infected gastric mucosa, and be involved in the carcinogenic process.

The costo-uterine muscle of the rat contains a homogeneous population of beta-adrenoceptors.

PubMed Central

Hartley, M. L.; Pennefather, J. N.

1985-01-01

The effects of two selective beta-adrenoceptor antagonists on the inhibitory responses to some sympathomimetic amines of electrically-stimulated preparations of costo-uterine muscle, taken from virgin rats, have been examined quantitatively. pA2 values for the antagonist, atenolol (beta 1-selective) and ICI 118,551 (beta 2-selective) were obtained using as agonists, fenoterol (beta 2-selective agonist) and noradrenaline (alpha- and beta-adrenoceptor agonist, beta 1-selective); and in addition, with ICI 118,551 only, isoprenaline (beta-agonist, non-selective) and adrenaline (alpha- and beta-adrenoceptor agonist, beta 2-selective). Catecholamine uptake mechanisms and alpha-adrenoceptors were not blocked in any of these experiments. Atenolol competitively antagonized the effects of fenoterol and noradrenaline to a similar extent, the pA2 values being 5.4 and 5.7, respectively. ICI 118,551 competitively antagonized the effects of fenoterol, isoprenaline, adrenaline and noradrenaline to a similar extent; pA2 values ranged from 8.7 with noradrenaline to 9.1 with isoprenaline. These results extend our previous observations which indicated that the adrenoceptors mediating inhibition of electrically-evoked contractions of costo-uterine muscle of the virgin rat are homogeneous and of the beta 2-subtype. The potency of the beta 1-selective agonist RO 363 in producing inhibition of electrically-evoked contractions of this tissue was also examined. RO 363 was 200 times less potent than isoprenaline but was a full agonist. This indicates that there is efficient coupling between beta 2-adrenoceptor activation and tissue response in this non-innervated preparation. PMID:2858239

Effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation depend on treatment dose, treatment duration and meal contents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arakawa, Masayuki; Ebato, Chie; Mita, Tomoya

2009-12-18

Beta-cell proliferation is regulated by various metabolic demands including peripheral insulin resistance, obesity, and hyperglycemia. In addition to enhancement of glucose-induced insulin secretion, agonists for glucagon-like peptide-1 receptor (GLP-1R) stimulate proliferation and inhibit apoptosis of beta-cells, thereby probably preserve beta-cell mass. To evaluate the beta-cell preserving actions of GLP-1R agonists, we assessed the acute and chronic effects of exendin-4 on beta-cell proliferation, mass and glucose tolerance in C57BL/6J mice under various conditions. Short-term administration of high-dose exendin-4 transiently stimulated beta-cell proliferation. Comparative transcriptomic analysis showed upregulation of IGF-1 receptor and its downstream effectors in islets. Treatment of mice with exendin-4more » daily for 4 weeks (long-term administration) and feeding high-fat diet resulted in significant inhibition of weight gain and improvement of glucose tolerance with reduced insulin secretion and beta-cell mass. These findings suggest that long-term GLP-1 treatment results in insulin sensitization of peripheral organs, rather than enhancement of beta-cell proliferation and function, particularly when animals are fed high-fat diet. Thus, the effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation largely depend on treatment dose, duration of treatment and meal contents. While GLP-1 enhances proliferation of beta-cells in some diabetic mice models, our results suggest that GLP-1 stimulates beta-cell growth only when expansion of beta-cell mass is required to meet metabolic demands.« less

Non-fibrillar amyloid-{beta} peptide reduces NMDA-induced neurotoxicity, but not AMPA-induced neurotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Niidome, Tetsuhiro, E-mail: tniidome@pharm.kyoto-u.ac.jp; Goto, Yasuaki; Kato, Masaru

2009-09-04

Amyloid-{beta} peptide (A{beta}) is thought to be linked to the pathogenesis of Alzheimer's disease. Recent studies suggest that A{beta} has important physiological roles in addition to its pathological roles. We recently demonstrated that A{beta}42 protects hippocampal neurons from glutamate-induced neurotoxicity, but the relationship between A{beta}42 assemblies and their neuroprotective effects remains largely unknown. In this study, we prepared non-fibrillar and fibrillar A{beta}42 based on the results of the thioflavin T assay, Western blot analysis, and atomic force microscopy, and examined the effects of non-fibrillar and fibrillar A{beta}42 on glutamate-induced neurotoxicity. Non-fibrillar A{beta}42, but not fibrillar A{beta}42, protected hippocampal neurons frommore » glutamate-induced neurotoxicity. Furthermore, non-fibrillar A{beta}42 decreased both neurotoxicity and increases in the intracellular Ca{sup 2+} concentration induced by N-methyl-D-aspartate (NMDA), but not by {alpha}-amino-3-hydrozy-5-methyl-4-isoxazole propionic acid (AMPA). Our results suggest that non-fibrillar A{beta}42 protects hippocampal neurons from glutamate-induced neurotoxicity through regulation of the NMDA receptor.« less

Preformed {beta}-amyloid fibrils are destabilized by coenzyme Q{sub 10} in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ono, Kenjiro; Hasegawa, Kazuhiro; Naiki, Hironobu

2005-04-29

Inhibition of the formation of {beta}-amyloid fibrils (fA{beta}), as well as the destabilization of preformed fA{beta} in the CNS, would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We reported previously that nordihydroguaiaretic acid (NDGA) and wine-related polyphenol, myricetin (Myr), inhibit fA{beta} formation from A{beta} and destabilize preformed fA{beta} in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of coenzyme Q{sub 10} (CoQ{sub 10}) on the formation, extension, and destabilization of fA{beta} at pH 7.5 at 37 deg C in vitro. We next compared the anti-amyloidogenic activities of CoQ{submore » 10} with NDGA and Myr. CoQ{sub 10} dose-dependently inhibited fA{beta} formation from amyloid {beta}-peptide (A{beta}), as well as their extension. Moreover, it destabilized preformed fA{beta}s. The anti-amyloidogenic effects of CoQ{sub 10} were slightly weaker than those of NDGA and Myr. CoQ{sub 10} could be a key molecule for the development of therapeutics for AD.« less

Effect of beta-blockers on exacerbation rate and lung function in chronic obstructive pulmonary disease (COPD).

PubMed

Duffy, Sean; Marron, Robert; Voelker, Helen; Albert, Richard; Connett, John; Bailey, William; Casaburi, Richard; Cooper, J Allen; Curtis, Jeffrey L; Dransfield, Mark; Han, MeiLan K; Make, Barry; Marchetti, Nathaniel; Martinez, Fernando; Lazarus, Stephen; Niewoehner, Dennis; Scanlon, Paul D; Sciurba, Frank; Scharf, Steven; Reed, Robert M; Washko, George; Woodruff, Prescott; McEvoy, Charlene; Aaron, Shawn; Sin, Don; Criner, Gerard J

2017-06-19

Beta-blockers are commonly prescribed for patients with cardiovascular disease. Providers have been wary of treating chronic obstructive pulmonary disease (COPD) patients with beta-blockers due to concern for bronchospasm, but retrospective studies have shown that cardio-selective beta-blockers are safe in COPD and possibly beneficial. However, these benefits may reflect symptom improvements due to the cardiac effects of the medication. The purpose of this study is to evaluate associations between beta-blocker use and both exacerbation rates and longitudinal measures of lung function in two well-characterized COPD cohorts. We retrospectively analyzed 1219 participants with over 180 days of follow up from the STATCOPE trial, which excluded most cardiac comorbidities, and from the placebo arm of the MACRO trial. Primary endpoints were exacerbation rates per person-year and change in spirometry over time in association with beta blocker use. Overall 13.9% (170/1219) of participants reported taking beta-blockers at enrollment. We found no statistically significant differences in exacerbation rates with respect to beta-blocker use regardless of the prevalence of cardiac comorbidities. In the MACRO cohort, patients taking beta-blockers had an exacerbation rate of 1.72/person-year versus a rate of 1.71/person-year in patients not taking beta-blockers. In the STATCOPE cohort, patients taking beta-blockers had an exacerbation rate of 1.14/person-year. Patients without beta-blockers had an exacerbation rate of 1.34/person-year. We found no detrimental effect of beta blockers with respect to change in lung function over time. We found no evidence that beta-blocker use was unsafe or associated with worse pulmonary outcomes in study participants with moderate to severe COPD.

A wide variety of putative extremophiles and large beta-diversity at the Mars Desert Research Station (Utah)

NASA Astrophysics Data System (ADS)

Direito, Susana O. L.; Ehrenfreund, Pascale; Marees, Andries; Staats, Martijn; Foing, Bernard; Röling, Wilfred F. M.

2011-07-01

Humankind's innate curiosity makes us wonder whether life is or was present on other planetary bodies such as Mars. The EuroGeoMars 2009 campaign was organized at the Mars Desert Research Station (MDRS) to perform multidisciplinary astrobiology research. MDRS in southeast Utah is situated in a cold arid desert with mineralogy and erosion processes comparable to those on Mars. Insight into the microbial community composition of this terrestrial Mars analogue provides essential information for the search for life on Mars: including sampling and life detection methodology optimization and what kind of organisms to expect. Soil samples were collected from different locations. Culture-independent molecular analyses directed at ribosomal RNA genes revealed the presence of all three domains of life (Archaea, Bacteria and Eukarya), but these were not detected in all samples. Spiking experiments revealed that this appears to relate to low DNA recovery, due to adsorption or degradation. Bacteria were most frequently detected and showed high alpha- and beta-diversity. Members of the Actinobacteria, Proteobacteria, Bacteroidetes and Gemmatimonadetes phyla were found in the majority of samples. Archaea alpha- and beta-diversity was very low. For Eukarya, a diverse range of organisms was identified, such as fungi, green algae and several phyla of Protozoa. Phylogenetic analysis revealed an extraordinary variety of putative extremophiles, mainly Bacteria but also Archaea and Eukarya. These comprised radioresistant, endolithic, chasmolithic, xerophilic, hypolithic, thermophilic, thermoacidophilic, psychrophilic, halophilic, haloalkaliphilic and alkaliphilic micro-organisms. Overall, our data revealed large difference in occurrence and diversity over short distances, indicating the need for high-sampling frequency at similar sites. DNA extraction methods need to be optimized to improve extraction efficiencies.

Diamagnetic effect in the foremoon solar wind observed by Kaguya

NASA Astrophysics Data System (ADS)

Nishino, M. N.; Saito, Y.; Tsunakawa, H.; Miyake, Y.; Harada, Y.; Yokota, S.; Takahashi, F.; Matsushima, M.; Shibuya, H.; Shimizu, H.

2016-12-01

Interaction between the lunar surface and incident solar wind is one of the crucial phenomena of the lunar plasma sciences. Recent observations by lunar orbiters revealed that strength of the interplanetary magnetic field (IMF) at spacecraft altitude increases over crustal magnetic fields on the dayside. In addition, variations of the IMF on the lunar night side have been reported in the viewpoint of diamagnetic effect around the lunar wake. However, few studies have been performed for the IMF over non-magnetized regions on the dayside. Here we show an event where strength of the IMF decreases at 100 km altitude on the lunar dayside (i.e. in the foremoon solar wind) when the IMF is almost parallel to the incident solar wind flow, comparing the upstream solar wind data from ACE and WIND with Kaguya magnetometer data. The lunar surface below the Kaguya orbit is not magnetized (or very weakly magnetized), and the sunward-travelling protons show signatures of those back-scattered at the lunar surface. We find that the decrease in the magnetic pressure is compensated by the thermal pressure of the back-scattered protons. In other words, the IMF strength in the foremoon solar wind decreases by diamagnetic effect of sunward-travelling protons back-scattered at the lunar dayside surface. Such diamagnetic effect would be prominent in the high-beta solar wind environment, and may be ubiquitous in the environment where planetary surface directly interacts with surrounding space plasma.

A comparative 2-year study of the effects of sequential regimens of 1 mg 17beta-estradiol and trimegestone with a regimen containing estradiol valerate and norethisterone on the bleeding profile and endometrial safety in postmenopausal women.

PubMed

Koninckx, P R; Spielmann, D

2005-08-01

To compare the bleeding profiles and endometrial protection of two sequential regimens of 17beta-estradiol (17beta-E2) and trimegestone (TMG) with a sequential estradiol valerate (E2V)/norethisterone (NET) regimen. This was a randomized, double-blind, multicenter study conducted in eight countries in healthy, postmenopausal women with an intact uterus. A total of 1218 women were enrolled into the initial 1-year study (13 cycles), and subsequently 531 of these received treatment for a further year (26 cycles). Treatment regimens were 1 mg 17beta-E2 on days 1-14 and 1 mg 17beta-E2/0.125 mg TMG or 1 mg 17beta-E2/0.25 mg TMG on days 15-28, and 1 mg E2V on days 1-16 and 1 mg E2V/1 mg NET on days 17-28. Mean percentage of women reporting onset of withdrawal bleeding episodes during the week following discontinuation of progestogen was higher in the 1 mg 17beta-E2/0.25 mg TMG group than in the other two treatments, showing a more efficient progestogen effect on the endometrium and good predictability of bleeding onset with this treatment. The mean numbers and average lengths of bleeding episodes were similar in the three treatment groups. Overall, the bleeding profile was more favorable with 1 mg 17beta-E2/0.25 mg TMG than with the lower-dose TMG preparation. Both of the TMG regimens demonstrated a good protective effect on endometrial proliferation, with the 0.25 mg TMG dose showing a lower incidence of proliferative endometrium. The 1 mg 17beta-E2/0.25 mg TMG regimen showed an adequate protection of the endometrium, with an overall favorable bleeding profile.

Sequence swapping does not result in conformation swapping for the beta4/beta5 and beta8/beta9 beta-hairpin turns in human acidic fibroblast growth factor.

PubMed

Kim, Jaewon; Lee, Jihun; Brych, Stephen R; Logan, Timothy M; Blaber, Michael

2005-02-01

The beta-turn is the most common type of nonrepetitive structure in globular proteins, comprising ~25% of all residues; however, a detailed understanding of effects of specific residues upon beta-turn stability and conformation is lacking. Human acidic fibroblast growth factor (FGF-1) is a member of the beta-trefoil superfold and contains a total of five beta-hairpin structures (antiparallel beta-sheets connected by a reverse turn). beta-Turns related by the characteristic threefold structural symmetry of this superfold exhibit different primary structures, and in some cases, different secondary structures. As such, they represent a useful system with which to study the role that turn sequences play in determining structure, stability, and folding of the protein. Two turns related by the threefold structural symmetry, the beta4/beta5 and beta8/beta9 turns, were subjected to both sequence-swapping and poly-glycine substitution mutations, and the effects upon stability, folding, and structure were investigated. In the wild-type protein these turns are of identical length, but exhibit different conformations. These conformations were observed to be retained during sequence-swapping and glycine substitution mutagenesis. The results indicate that the beta-turn structure at these positions is not determined by the turn sequence. Structural analysis suggests that residues flanking the turn are a primary structural determinant of the conformation within the turn.

Warfighter Sustainability: Maximizing Human Performance in Hostile Environments

DTIC Science & Technology

2008-10-01

Study 4: Effects of Beta Glucan on Symptoms of Upper Tract Infection in Wildland Firefighters. ix Approved for public release...Study 4: Effects of Beta Glucan on Symptoms of Upper Tract Infection in Wildland Firefighters. The use of a beta glucan supplement may decrease...reduce the required fluid intake during extended operations without compromising work output. In addition, the ingestion of a beta glucan supplement may

Joint High-Order Synchrosqueezing Transform and Multi-Taper Empirical Wavelet Transform for Fault Diagnosis of Wind Turbine Planetary Gearbox under Nonstationary Conditions.

PubMed

Hu, Yue; Tu, Xiaotong; Li, Fucai; Meng, Guang

2018-01-07

Wind turbines usually operate under nonstationary conditions, such as wide-range speed fluctuation and time-varying load. Its critical component, the planetary gearbox, is prone to malfunction or failure, which leads to downtime and repair costs. Therefore, fault diagnosis and condition monitoring for the planetary gearbox in wind turbines is a vital research topic. Meanwhile, the signals measured by the vibration sensors mounted in the gearbox exhibit time-varying and nonstationary features. In this study, a novel time-frequency method based on high-order synchrosqueezing transform (SST) and multi-taper empirical wavelet transform (MTEWT) is proposed for the wind turbine planetary gearbox under nonstationary conditions. The high-order SST uses accurate instantaneous frequency approximations to obtain a sharper time-frequency representation (TFR). As the acquired signal consists of many components, like the meshing and rotating components of the gear and bearing, the fault component may be masked by other unrelated components. The MTEWT is used to separate the fault feature from the masking components. A variety of experimental signals of the wind turbine planetary gearbox under nonstationary conditions have been analyzed to demonstrate the effectiveness and robustness of the proposed method. Results show that the proposed method is effective in diagnosing both gear and bearing faults.

Joint High-Order Synchrosqueezing Transform and Multi-Taper Empirical Wavelet Transform for Fault Diagnosis of Wind Turbine Planetary Gearbox under Nonstationary Conditions

PubMed Central

Li, Fucai; Meng, Guang

2018-01-01

Wind turbines usually operate under nonstationary conditions, such as wide-range speed fluctuation and time-varying load. Its critical component, the planetary gearbox, is prone to malfunction or failure, which leads to downtime and repair costs. Therefore, fault diagnosis and condition monitoring for the planetary gearbox in wind turbines is a vital research topic. Meanwhile, the signals measured by the vibration sensors mounted in the gearbox exhibit time-varying and nonstationary features. In this study, a novel time-frequency method based on high-order synchrosqueezing transform (SST) and multi-taper empirical wavelet transform (MTEWT) is proposed for the wind turbine planetary gearbox under nonstationary conditions. The high-order SST uses accurate instantaneous frequency approximations to obtain a sharper time-frequency representation (TFR). As the acquired signal consists of many components, like the meshing and rotating components of the gear and bearing, the fault component may be masked by other unrelated components. The MTEWT is used to separate the fault feature from the masking components. A variety of experimental signals of the wind turbine planetary gearbox under nonstationary conditions have been analyzed to demonstrate the effectiveness and robustness of the proposed method. Results show that the proposed method is effective in diagnosing both gear and bearing faults. PMID:29316668

The effects of a cytokine suppressive anti-inflammatory drug on the output of prostaglandin E(2) and interleukin-1 beta from human fetal membranes.

PubMed

Sullivan, M H F; Alvi, S A; Brown, N L; Elder, M G; Bennett, P R

2002-03-01

Fetal membranes are a primary source of prostaglandins and pro-inflammatory cytokines implicated in human parturition, so the inhibition of inflammatory pathways may be of benefit in pregnancies complicated by premature labour. We have therefore investigated the effects of a cytokine-suppressant anti-inflammatory drug (CSAID) on the output of prostaglandin E(2) (PGE(2)) and interleukin (IL)-1 beta from human fetal membranes in vitro. Bacterial endotoxin increased the expression of mRNA for IL-1 beta and type-2 cyclo-oxygenase (COX-2), and there were corresponding increases in the output of IL-1 beta protein and PGE(2). The CSAID decreased IL-1 beta protein, COX-2 expression and PGE(2) output, but not mRNA for IL-1 beta, indicating a post-translational effect on the production of IL-1 beta and a transcriptional affect on COX-2, with an overall reduction in PGE(2). These findings are consistent with the effects of CSAIDs in other systems, and indicate that they are of possible use in premature labour.

Suppression of transforming growth factor-beta-induced apoptosis through a phosphatidylinositol 3-kinase/Akt-dependent pathway.

PubMed

Chen, R H; Su, Y H; Chuang, R L; Chang, T Y

1998-10-15

Insulin and insulin receptor substrate 1 (IRS-1) are capable of protecting liver cells from apoptosis induced by transforming growth factor-beta1 (TGF-beta). The Ras/mitogen-activated protein kinase (MAP kinase) and the phosphatidylinositol 3-kinase (PI 3-kinase)/Akt pathways are both activated upon insulin stimulation and can protect against apoptosis under certain circumstances. We investigated which of these pathways is responsible for the protective effect of insulin on TGF-beta-induced apoptosis. An activated Ras, although elicited a strong mitogenic effect, could not protect Hep3B cells from TGF-beta-induced apoptosis. Furthermore, PD98059, a selective inhibitor of MEK, did not suppress the antiapoptotic effect of insulin. In contrast, the PI 3-kinase inhibitor, LY294002, efficiently blocked the effect of insulin. Protection against TGF-beta-induced apoptosis conferred by PI 3-kinase was further verified by stable transfection of an activated PI 3-kinase. Downstream targets of PI 3-kinase involved in this protection was further investigated. An activated Akt mimicked the antiapoptotic effect of insulin, whereas a dominant-negative Akt inhibited such effect. However, rapamycin, the p70S6 kinase inhibitor, had no effect on the protectivity of insulin against TGF-beta-induced apoptosis, suggesting that the antiapoptotic target of PI 3-kinase/Akt pathway is independent or lies upstream of the p70S6 kinase. The mechanism by which PI 3-kinase/Akt pathway interferes with the apoptotic signaling of TGF-beta was explored. Activation of PI 3-kinase did not lead to a suppression of Smad hetero-oligomerization or nuclear translocation but blocked TGF-beta-induced caspase-3-like activity. In summary, the PI 3-kinase/Akt pathway, but not the Ras/MAP kinase pathway, protects against TGF-beta-induced apoptosis by inhibiting a step downstream of Smad but upstream of caspase-3.

Early onset of puberty and early ovarian failure in CYP7B1 knockout mice.

PubMed

Omoto, Yoko; Lathe, Richard; Warner, Margaret; Gustafsson, Jan-Ake

2005-02-22

CYP7B1 is the enzyme responsible for hydroxylation and termination of the estrogenic actions of the androgen metabolite, 5alpha-androstane-3beta, 17beta-diol (3betaAdiol). 3betaAdiol is estrogenic in ERalpha or ERbeta positive cells only if they do not express CYP7B1. In this study we show that female CYP7B1(-/-) mice experience early onset of growth of the uterus and mammary glands and commence estrus cycles 2 days earlier than their wild-type littermates. Adult mammary glands and uteri appear to be under continuous estrogenic stimulation. We conclude that, by cell-specific regulation of the estrogenicity of 3betaAdiol, CYP7B1 performs two major tasks: (i) it allows 3betaAdiol to have growth inhibitory effects through ERbeta and (ii) it permits estradiol-specific activation of estrogen receptors by protection of certain cells from the estrogenic effects of 3betaAdiol. When CYP7B1 is inactivated, 3betaAdiol activates estrogen receptors indiscriminately, and the overall effect is prolonged and inappropriate exposure to estrogen.

TILTING JUPITER (A BIT) AND SATURN (A LOT) DURING PLANETARY MIGRATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vokrouhlický, David; Nesvorný, David, E-mail: vokrouhl@cesnet.cz, E-mail: davidn@boulder.swri.edu

We study the effects of planetary late migration on the gas giants’ obliquities. We consider the planetary instability models from Nesvorný and Morbidelli, in which the obliquities of Jupiter and Saturn can be excited when spin–orbit resonances occur. The most notable resonances occur when the s{sub 7} and s{sub 8} frequencies, changing as a result of planetary migration, become commensurate with the precession frequencies of Jupiter’s and Saturn’s spin vectors. We show that Jupiter may have obtained its present obliquity by crossing of the s{sub 8} resonance. This would set strict constraints on the character of migration during the earlymore » stage. Additional effects on Jupiter’s obliquity are expected during the last gasp of migration when the s{sub 7} resonance was approached. The magnitude of these effects depends on the precise value of the Jupiter’s precession constant. Saturn’s large obliquity was likely excited by capture into the s{sub 8} resonance. This probably happened during the late stage of planetary migration when the evolution of the s{sub 8} frequency was very slow, and the conditions for capture into the spin–orbit resonance with s{sub 8} were satisfied. However, whether or not Saturn is in the spin–orbit resonance with s{sub 8} at the present time is not clear because the existing observations of Saturn’s spin precession and internal structure models have significant uncertainties.« less

Inhibitory effect of transforming growth factor-. beta. (TGF-. beta. ) on insulin-like growth factor 1 (IGF-1)-induced proliferation and differentiation in primary cultures of pig preadipocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Richardson, R.L.; Hausman, G.J.; Gaskins, H.R.

1990-02-26

The influence of serum, IGF-1 and TGF-{beta} on the differentiation of preadipocytes was examined in primary cultures of porcine adipose tissue cells. In serum-supplemented or serum-free, IGF-1 (1 and 10 nM) had no effect on total cell number. However, IGF-1 (10nM) increased adipocyte number only in serum-supplemented (1% pig serum) cultures, whereas TGF-{beta} (15 pm) reduced the adipocyte number in the presence and absence of IGF-1. Replication of preadipocytes was analyzed with a ({sup 3}H) thymidine assay. Preadipocyte proliferation (cpm in adipocyte fraction) was increased by IGF-1 (10nM) only in cultures containing pig serum. TGF-{beta} had no effect on preadipocytemore » proliferation specifically, but slightly increased total ({sup 3}H) thymidine incorporation in cultures with serum. Glycerol phosphate dehydrogenase (GPDH) specific activity was decreased by adding TGF-{beta} to serum-free cultures but TGF-{beta} had little effect in serum-supplemented cultures. Cellular secretion of IGF-1 was decreased when TGF-{beta} was added to serum-free or serum-supplemented cultures. These studies indicate that TGF-{beta} does not inhibit adipocyte development in the initial growth phase, but may inhibit differentiation and/or hypertrophy at a later stage of development.« less

Electron spin resonance dating of human teeth from Toca da Santa shelter of São Raimundo Nonato, Piauí, Brazil

NASA Astrophysics Data System (ADS)

Kinoshita, A.; Figueiredo, A. M. G.; Felice, G. D.; Lage, M. C. S. M.; Guidon, N.; Baffa, O.

2008-02-01

Results of the dating of fossil human teeth excavated from a shelter in the surroundings areas of the Serra da Capivara National Park, São Raimundo Nonato, Piauí, Brazil are presented. This shelter was partially excavated to search for more data that could improve the archaeological context of the Garrincho’s limestone hill sites, where the Toca do Gordo do Garrincho shelter provided two human teeth dated by conventional C-14 in (12,170 ± 40) yBP (years before present) and calibrated age (2 Sigma, 95% probability) 15,245 14,690 yBP (Beta 136204) [E. Peyre, C. Guérin, N. Guidon, I. Coppens, CR Acad. Sci. Paris, Sciences de la terre et des planètes/ Earth & Planetary Sciences 327 (1998) 335, [1

The effect of polymorphisms of the beta(2)-adrenergic receptor on the response to regular use of albuterol in asthma.

PubMed

Israel, E; Drazen, J M; Liggett, S B; Boushey, H A; Cherniack, R M; Chinchilli, V M; Cooper, D M; Fahy, J V; Fish, J E; Ford, J G; Kraft, M; Kunselman, S; Lazarus, S C; Lemanske, R F; Martin, R J; McLean, D E; Peters, S P; Silverman, E K; Sorkness, C A; Szefler, S J; Weiss, S T; Yandava, C N

2000-07-01

Inhaled beta-adrenergic agonists are the most commonly used medications for the treatment of asthma although there is evidence that regular use may produce adverse effects in some patients. Polymorphisms of the beta(2)-adrenergic receptor (beta(2)-AR) can affect regulation of the receptor. Smaller studies examining the effects of such polymorphisms on the response to beta-agonist therapy have produced inconsistent results. We examined whether polymorphisms at codon 16 (beta(2)-AR-16) and codon 27 (beta(2)-AR-27) of the beta(2)-AR might affect the response to regular versus as-needed use of albuterol by genotyping the 190 asthmatics who had participated in a trial examining the effects of regular versus as needed albuterol use. During the 16-wk treatment period there was a small decline in morning peak expiratory flow in patients homozygous for arginine at B(2)-AR-16 (Arg/Arg) who used albuterol regularly. This effect was magnified during a 4-wk run out period, during which all patients returned to using as-needed albuterol, so that by the end of the study Arg Arg patients who had regularly used albuterol had a morning peak expiratory flow 30. 5 +/- 12.1 L/min lower (p = 0.012) than Arg/Arg patients who had used albuterol on an as needed basis. There was no decline in peak flow with regular use of albuterol in patients who were homozygous for glycine at beta(2)-AR-16. Evening peak expiratory flow also declined in the Arg/Arg patients who used albuterol regularly but not in those who used albuterol on an as-needed basis. No significant differences in outcomes between regular and as-needed treatment were associated with polymorphisms at position 27 of the beta(2)-AR. No other differences in asthma outcomes that we investigated occurred in relation to these beta(2)-AR polymorphisms. Polymorphisms of the beta(2)-AR may influence airway responses to regular inhaled beta-agonist treatment.

Grape seed procyanidin extract modulates proliferation and apoptosis of pancreatic beta-cells.

PubMed

Cedó, Lídia; Castell-Auví, Anna; Pallarès, Victor; Blay, Mayte; Ardévol, Anna; Arola, Lluís; Pinent, Montserrat

2013-05-01

Grape seed procyanidin extract (GSPE) modulates glucose homeostasis and insulinemia in several animal models. Under pathological conditions, insulin levels are dependent on pancreatic beta-cell functionality, as well as on the beta-cell mass expansion or apoptosis in the pancreas. In this study, we analysed the effects of GSPE on modulating apoptosis and proliferation in beta-cells. We tested the effects of GSPE in the INS-1E pancreatic beta-cell line, either under basal or altered conditions with high glucose, insulin or palmitate levels. GSPE enhanced the pro-apoptotic effect of high glucose and showed clear antiproliferative effects under high glucose, insulin and palmitate conditions. These antiproliferative effects are likely due to high molecular weight compounds contained in the extract. GSPE also modulated pro- and anti-apoptotic markers in the pancreas of rats fed a cafeteria diet, with the effect depending on the dose of GSPE and duration of treatment. Thus, GSPE is able to modulate apoptosis and proliferation of beta-cells under altered, but not basal, conditions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Europlanet-RI IDIS - A Data Network in Support of Planetary Research

NASA Astrophysics Data System (ADS)

Schmidt, Walter; Capria, Maria Teresa; Chanteur, Gérard

2010-05-01

The "Europlanet Research Infrastructure - Europlanet RI", supported by the European Commission's Framework Program 7, aims at integrating major parts of the distributed European Planetary Research infrastructure with as diverse components as space exploration, ground-based observations, laboratory experiments and numerical modeling teams. A central part of Europlanet RI is the "Integrated and Distributed Information Service" (IDIS), a network of data and information access facilities in Europe via which information relevant for planetary research can be easily found and retrieved. This covers the wide range from contact addresses of possible research partners, laboratories and test facilities to the access of data collected with space missions or during laboratory or simulation tests and to model software useful for their interpretation. During the following three years the capabilities of the network will be extended to allow the combination of many different data sources for comperative studies including the results of modeling calculations and simulations of instrument observations. Together with the access to complex databases for spectra of atmospheric molecules and planetary surface material IDIS will offer a versatile working environment for making the scientific exploitation of the resources put into planetary research in the past and future more effective. Many of the mentioned capabilities are already available now. List of contact web-sites: Technical node for support and management aspects: http://www.idis.europlanet-ri.eu/ Planetary Surfaces and Interiors node: http://www.idis-interiors.europlanet-ri.eu/ Planetary Plasma node: http://www.idis-plasma.europlanet-ri.eu/ Planetary Atmospheres node: http://www.idis-atmos.europlanet-ri.eu/ Small Bodies and Dust node: http://www.idis-sbdn.europlanet-ri.eu/ Planetary Dynamics and Extraterrestrial Matter node: http://www.idis-dyn.europlanet-ri.eu/

The effects of aromatic amino acid derivatives on the excitability of an identifiable giant neurone of the African giant snail (Achatina fulica Férussac).

PubMed Central

Takeuchi, H.; Tamura, H.

1980-01-01

1 The effects of derivatives of aromatic amino acids on the excitability of an identifiable giant neurone (TAN, tonically autoactive neurone) of the African giant snail (Achatina fulica Férussac) were examined. 2 The following substances had marked inhibitory effects on TAN using bath application: N-beta-phenylpropionyl-L-Tyr and N-beta-phenylpropionyl-L-Trp (critical concentration, 3 x 10(-7) M), N-beta-phenylpropionyl-L-Phe, N-cinnamoyl-DL-Trp and N-phenoxyacetyl-L-Trp (critical concentration, 10(-5) to 3 x 10(-5) M). However, N-beta-phenylpropionyl-D-Tyr and N-beta-phenylpropionyl tyramine had no effect. 3 Microdrop (150 micrometers in diameter) application of N-beta-phenylpropionyl-L-Tyr or N-beta-phenylpropionyl-l-trp containing about 100 pg resulted in marked inhibitory effects on TAN. The effect was observed in Ca2+-free, Mg2+-rich (24 mM) solution. Substitution of Cl- by acetate did not alter the response. This indicates that the two substances act directly on the TAN membrane and not via synaptic influences, and that the inhibition produced by the two substances is not due to the permeability increase of the TAN membrane to Cl-. PMID:7378654

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Yoon Pyo; Kim, Baek Gil; Department of Pathology, Yonsei University College of Medicine, Seoul

Highlights: Black-Right-Pointing-Pointer The potential of targeting ILK and integrins for highly aggressive ovarian cancer. Black-Right-Pointing-Pointer Unanticipated synergistic effect for the combination of ILK/{beta}4 integrin. Black-Right-Pointing-Pointer Combination of ILK/{beta}4 integrin effectively inhibited the PI3K/Akt/Rac1 cascade. Black-Right-Pointing-Pointer Targeting of {beta}4 integrin/ILK had potent inhibitory effects in ovarian cancer. -- Abstract: Integrins and integrin-linked kinase (ILK) are essential to cancerous invasion because they mediate physical interactions with the extracellular matrix, and regulate oncogenic signaling pathways. The purpose of our study is to determine whether deletion of {beta}1 and {beta}4 integrin and ILK, alone or in combination, has antitumoral effects in ovarian cancer. Expressionmore » of {beta}1 and {beta}4 integrin and ILK was analyzed by immunohistochemistry in 196 ovarian cancer tissue samples. We assessed the effects of depleting these molecules with shRNAs in ovarian cancer cells by Western blot, conventional RT-PCR, cell proliferation, migration, invasion, and in vitro Rac1 activity assays, and in vivo xenograft formation assays. Overexpression of {beta}4 integrin and ILK in human ovarian cancer specimens was found to correlate with tumor aggressiveness. Depletion of these targets efficiently suppresses ovarian cancer cell proliferation, migration, and invasion in vitro and xenograft tumor formation in vivo. We also demonstrated that single depletion of ILK or combination depletion of {beta}4 integrin/ILK inhibits phosphorylation of downstream signaling targets, p-Ser 473 Akt and p-Thr202/Tyr204 Erk1/2, and activation of Rac1, as well as reduce expression of MMP-2 and MMP-9 and increase expression of caspase-3 in vitro. In conclusion, targeting {beta}4 integrin combined with ILK can instigate the latent tumorigenic potential and abrogate the invasive potential in ovarian cancer.« less

Mass Wasting in Planetary Environments: Implications for Seismicity

NASA Technical Reports Server (NTRS)

Weber, Renee; Nahm, Amanda; Schmerr, Nick

2015-01-01

On Earth, mass wasting events such as rock falls and landslides are well known consequences of seismic activity. Here we investigate the regional effects of seismicity in planetary environments with the goal of determining whether such surface features on the Moon, Mars, and Mercury could be triggered by fault motion.

Physics of planetary rings

NASA Astrophysics Data System (ADS)

Gorkavyi, N.

2007-08-01

It is difficult to enumerate all the surprises presented by the planetary rings. The Saturnian rings are stratified into thousands of ringlets and the Uranian rings are compressed into narrow streams, which for some reason or other differ from circular orbits like the wheel of an old bicycle. The edge of the rings is jagged and the rings themselves are pegged down under the gravitational pressure of the satellites, bending like a ship's wake. There are spiral waves, elliptical rings, strange interlacing of narrow ringlets, and to cap it all one has observed in the Neptunian ring system three dense, bright arcs - like bunches of sausages on a transparent string. For celestial mechanics this is a spectacle as unnatural as a bear's tooth in the necklace of the English queen. In the dynamics of planetary rings the physics of collective interaction was supplemented by taking collisions between particles into account. One was led to study a kinetic equation with a rather complex collision integral - because the collisions are inelastic - which later on made it possible, both by using the Chapman-Enskog method and by using the solution of the kinetic equation for a plasma in a magnetic field, to reduce it to a closed set of (hydrodynamical) moment equations [1]. The hydrodynamical instabilities lead to the growth of short-wavelength waves and large-scale structures of the Saturnian rings [1]. We have shown that the formation of the existing dense Uranian rings is connected with the capture of positively drifting ring particles in inner Lindblad resonances which arrest this drift [1]. After the formation of dense rings at the positions of satellite resonances the collective interaction between resonant particles is amplified and the rings can leave the resonance and drift away from the planet and the parent resonance. We can expect in the C ring an appreciable positive ballistic particle drift caused by the erosion of the B ring by micrometeorites. It is therefore natural to assume that the mechanism for the formation of the narrow Saturnian and Uranian rings is the same and that the elliptical Titan, Maxwell and Huygens ringlets are direct relations of the Uranian rings. A reliable theory of the planetary rings would enable us to consider from completely different perspective the evolution of other cosmic disk systems: protosatellite disks [2], zodiacal and protoplanetary disks [3-5]. In this review we also discuss numerical models of the 3D structure and infrared emission of circumstellar dust disks, incorporating all relevant physical processes. We review the resonant structures of a dusty disk induced by the presence of planets [3-5]. It is shown that the planet, via resonances and gravitational scattering, produces an asymmetric resonant dust belt with one or more clumps intermittent with one or a few off-center cavities. These features can serve as indicators of a planet embedded in the circumstellar dust disk and, moreover, can be used to determine its major orbital parameters and even the mass of the planet. The results of our study reveal a remarkable similarity with various types of highly asymmetric circumstellar disks observed with the James Clerk Maxwell Telescope and other telescopes around Epsilon Eridani and Vega. The proposed interpretation of the clumps in those disks as being resonant patterns is testable - it predicts the asymmetric design around the star to revolve by ∼ 1 deg/yr about Vega and 0.6-0.8 deg/yr about Epsilon Eri. Our simulations indicate that Vega may have a massive planet ∼ 2 Jupiter mass at a distance ∼ 80-100 AU [3,5], and Epsilon Eri may have a less massive planet ∼ 0.2 Jovian mass as a distance of 55-60 AU [3]. Dynamical model of the origin of the warping of the Beta Pictoris disk includes the gravitational influence of a planet with a mass of about 10 masses of Earth, at a distance of 70 AU, and a small inclination (2.5 deg) of the planetary orbit to the main dust disk. The optical image from the Hubble Space Telescope (STIS, observation of team by Sara Heap, our co-author) and results of our simulation of scattered light from warped disk will be compared [4]. The direct signatures of this planet were discovered on 2002 by Keck telescope observations. References: 1. Fridman, A.M. and Gorkavyi, N.N. Physics of Planetary Rings (Celestial Mechanics of a Continuous Media). Springer-Verlag, 1999, 436 p. 2. Gorkavyi, N.N., Taidakova, T.A. The Model for Formation of Jupiter, Saturn and Neptune Satellite Systems, Astronomy Letters., 1995, v. 21 (6). pp.939-945; Discovered Saturnian and undiscovered Neptuanian retrograde satellites, BAAS, v.33, N4, 1403; The New Model of the Origin of the Moon, BAAS, 2004, 36, #2 3. Ozernoy, L.M., Gorkavyi, N.N., Mather, J.C. & Taidakova, T. 2000, Signatures of Exo-solar Planets in Dust Debris Disks, ApJ, 537:L147-L151, 2000 July 10. 4. Gorkavyi, N.N., Heap S.R., Ozernoy, L.M., Taidakova, T.A., and Mather, J.C. Indicator of Exo-Solar Planet(s) in the Circumstellar Disk Around Beta Pictoris. In:"Planetary Systems in the Universe: Observation, Formation, and Evolution". Proc. IAU Symp. No. 202, 2004, ASP Conf. Series, p.331-334. 5. Gorkavyi, N., Taidakova, T. Outermost planets of Beta Pictoris, Vega and Epsilon Eridani: goals for direct imaging. In: "Direct Imaging of Exoplanets: Science and Techniques" (C. Aime and F. Vakili, eds.). Proc. IAU Coll. No. 200, 2005, p.47-51.

Exploring the optical contrast effect in strong atomic lines for exoplanets transiting active stars

NASA Astrophysics Data System (ADS)

Cauley, Paul W.; Redfield, Seth

2017-01-01

Transmission spectroscopy is a powerful tool for detecting and characterizing planetary atmospheres. Non-photospheric features on the stellar disk, however, can contaminate the planetary signal: during transit the observed spectrum is weighted towards the features not currently being occulted by the planet. This contrast effect can mimic absorption in the planetary atmosphere for strong atomic lines such as Na I, Ca II, and the hydrogen Balmer lines. While the contrast effect is negligible for quiet stars, contributions to the transmission signal from active stellar surfaces can produce ~1% changes in the line core. It is therefore critical that these contrast signals be differentiated from true absorption features in the planetary atmosphere. Here we present our work on simulating the contrast effect for an active stellar surface. We discuss the particular case of HD 189733 b, a well-studied hot Jupiter orbiting an active K-dwarf, due to the plethora of atomic absorption signals reported in its atmosphere.Specifically, we focus on Hα to address recent suggestions that the measured in-transit signals are a result of stellar activity. In the contrast model we include center-to-limb variations and calculate limb darkening parameters as a function of wavelength across the line of interest. The model includes contributions to the spectrum from spots, faculae and plages, filaments, and the bare stellar photosphere. Stellar rotation is also included. We find that it is very difficult to reproduce the measured in-transit Hα signals for reasonable active region parameters. In addition, it is difficult to create an in-transit contrast signature that lasts for the duration of the transit unless the planet is crossing an active latitudinal belt and is always obscuring active regions. This suggests that the Hα measurements arise predominantly in the planetary atmosphere. However, the contrast effect likely contributes to these signals. Furthermore, our results could be modified if the active regions of HD 189733 b have drastically different characteristics than solar active regions. Further observations of transits across active stars will aid in disentangling the planetary signals from the stellar.

Laboratory measurements of microwave and millimeter-wave properties of planetary atmospheric constituents

NASA Technical Reports Server (NTRS)

Steffes, Paul G.

1989-01-01

Accurate data on microwave and millimeter-wave properties of potential planetary atmospheric constituents is critical for the proper interpretation of radio occultation measurements, and of radio astronomical observations of both continuum and spectral line emissions. Such data is also needed to correct for atmospheric effects on radar studies of surface reflectivity. Since the refractive and absorptive properties of atmospheric constituents often vary drastically from theoretically-predicted profiles, especially under the extreme conditions characteristic of the planetary atmosphere, laboratory measurements under simulated planetary conditions are required. This paper reviews the instrumentation and techniques used for laboratory measurement of the refractivity and absorptivity of atmospheric constituents at wavelengths longward of 1 mm, under simulated planetary conditions (temperature, pressure, and broadening gases). Techniques for measuring both gases and condensates are considered. Also reviewed are the relative accuracies of the various techniques. Laboratory measurements are reviewed which have already been made, and additional measurements which are needed for interpretation of data from Venus and the outer planets, are highlighted.

How beta diversity and the underlying causes vary with sampling scales in the Changbai mountain forests.

PubMed

Tan, Lingzhao; Fan, Chunyu; Zhang, Chunyu; von Gadow, Klaus; Fan, Xiuhua

2017-12-01

This study aims to establish a relationship between the sampling scale and tree species beta diversity temperate forests and to identify the underlying causes of beta diversity at different sampling scales. The data were obtained from three large observational study areas in the Changbai mountain region in northeastern China. All trees with a dbh ≥1 cm were stem-mapped and measured. The beta diversity was calculated for four different grain sizes, and the associated variances were partitioned into components explained by environmental and spatial variables to determine the contributions of environmental filtering and dispersal limitation to beta diversity. The results showed that both beta diversity and the causes of beta diversity were dependent on the sampling scale. Beta diversity decreased with increasing scales. The best-explained beta diversity variation was up to about 60% which was discovered in the secondary conifer and broad-leaved mixed forest (CBF) study area at the 40 × 40 m scale. The variation partitioning result indicated that environmental filtering showed greater effects at bigger grain sizes, while dispersal limitation was found to be more important at smaller grain sizes. What is more, the result showed an increasing explanatory ability of environmental effects with increasing sampling grains but no clearly trend of spatial effects. The study emphasized that the underlying causes of beta diversity variation may be quite different within the same region depending on varying sampling scales. Therefore, scale effects should be taken into account in future studies on beta diversity, which is critical in identifying different relative importance of spatial and environmental drivers on species composition variation.

PGE(2) inhibition of TGF-beta1-induced myofibroblast differentiation is Smad-independent but involves cell shape and adhesion-dependent signaling.

PubMed

Thomas, Peedikayil E; Peters-Golden, Marc; White, Eric S; Thannickal, Victor J; Moore, Bethany B

2007-08-01

Myofibroblasts are pathogenic in pulmonary fibrotic disease due to their exuberant production of matrix rich in collagen that interferes with gas exchange and the ability of these cells to contract and distort the alveolar space. Transforming growth factor-beta1 (TGF-beta1) is a well-known inducer of myofibroblast differentiation. TGF-beta1-induced transformation of fibroblasts to apoptosis-resistant myofibroblasts is adhesion-dependent and focal adhesion kinase (FAK)-mediated. Prostaglandin E(2) (PGE(2)) inhibits this differentiation via E prostanoid receptor 2 (EP2) signaling and cAMP elevation, but whether PGE(2) does so by interfering with TGF-beta1 signaling is unknown. Thus we examined the effects of PGE(2) in the presence and absence of TGF-beta1 stimulation on candidate signaling pathways in human lung fibroblasts. We now demonstrate that PGE(2) does not interfere with TGF-beta1-induced Smad phosphorylation or its translocation to the nucleus. Rather, PGE(2) has dramatic effects on cell shape and cytoskeletal architecture and disrupts the formation of appropriate focal adhesions. PGE(2) treatment diminishes TGF-beta1-induced phosphorylation of paxillin, STAT-3, and FAK and, in turn, limits activation of the protein kinase B (PKB/Akt) pathway. These alterations do not, however, result in increased apoptosis within the first 24 h of treatment. Interestingly, the effects of PGE(2) stimulation alone do not always mirror the effects of PGE(2) in the presence of TGF-beta1, indicating that the context for EP2 signaling is different in the presence of TGF-beta1. Taken together, our results demonstrate that PGE(2) has the potential to limit TGF-beta1-induced myofibroblast differentiation via adhesion-dependent, but Smad-independent, pathways.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rahman, Shaikh M., E-mail: rmizanoor@hotmail.com; Choudhury, Mahua; Janssen, Rachel C.

Highlights: Black-Right-Pointing-Pointer LXR agonist activation increases liver TG accumulation by increasing lipogenesis. Black-Right-Pointing-Pointer C/EBP{beta}{sup -/-} mouse prevents LXR activation-mediated induction of hepatic lipogenesis. Black-Right-Pointing-Pointer C/EBP{beta} deletion increases mitochondrial transport chain function. Black-Right-Pointing-Pointer Beneficial effects of LXR activation on liver cholesterol metabolism did not change. Black-Right-Pointing-Pointer C/EBP{beta} inhibition might have important therapeutic potential. -- Abstract: Drugs designed specifically to activate liver X receptors (LXRs) have beneficial effects on lowering cholesterol metabolism and inflammation but unfortunately lead to severe hepatic steatosis. The transcription factor CCAAT/enhancer binding protein beta (C/EBP{beta}) is an important regulator of liver gene expression but little is known aboutmore » its involvement in LXR-based steatosis and cholesterol metabolism. The present study investigated the role of C/EBP{beta} expression in LXR agonist (T0901317)-mediated alteration of hepatic triglyceride (TG) and lipogenesis in mice. C/EBP{beta} deletion in mice prevented LXR agonist-mediated induction of lipogenic gene expression in liver in conjunction with significant reduction of liver TG accumulation. Surprisingly, C/EBP{beta}{sup -/-} mice showed a major increase in liver mitochondrial electron chain function compared to WT mice. Furthermore, LXR activation in C/EBP{beta}{sup -/-} mice increased the expression of liver ATP-binding cassette transporter ABCG1, a gene implicated in cholesterol efflux and reducing blood levels of total and LDL-cholesterol. Together, these findings establish a central role for C/EBP{beta} in the LXR-mediated steatosis and mitochondrial function, without impairing the influence of LXR activation on lowering LDL and increasing HDL-cholesterol. Inactivation of C/EBP{beta} might therefore be an important therapeutic strategy to prevent LXR activation-mediated adverse effects on liver TG metabolism without disrupting its beneficial effects on cholesterol metabolism.« less

Evaluation of partial beta-adrenoceptor agonist activity.

PubMed

Lipworth, B J; Grove, A

1997-01-01

A partial beta-adrenoceptor (beta-AR) agonist will exhibit opposite agonist and antagonist activity depending on the prevailing degree of adrenergic tone or the presence of a beta-AR agonist with higher intrinsic activity. In vivo partial beta-AR agonist activity will be evident at rest with low endogenous adrenergic tone, as for example with chronotropicity (beta 1/beta 2), inotropicity (beta 1) or peripheral vasodilatation and finger tremor (beta 2). beta-AR blocking drugs which have partial agonist activity may exhibit a better therapeutic profile when used for hypertension because of maintained cardiac output without increased systemic vascular resistance, along with an improved lipid profile. In the presence of raised endogenous adrenergic tone such as exercise or an exogenous full agonist, beta-AR subtype antagonist activity will become evident in terms of effects on exercise induced heart rate (beta 1) and potassium (beta 2) responses. Reduction of exercise heart rate will occur to a lesser degree in the case of a beta-adrenoceptor blocker with partial beta 1-AR agonist activity compared with a beta-adrenoceptor blocker devoid of partial agonist activity. This may result in reduced therapeutic efficacy in the treatment of angina on effort when using beta-AR blocking drugs with partial beta 1-AR agonist activity. Effects on exercise hyperkalaemia are determined by the balance between beta 2-AR partial agonist activity and endogenous adrenergic activity. For predominantly beta 2-AR agonist such as salmeterol and salbutamol, potentiation of exercise hyperkalaemia occurs. For predominantly beta 2-AR antagonists such as carteolol, either potentiation or attenuation of exercise hyperkalaemia occurs at low and high doses respectively. beta 2-AR partial agonist activity may also be expressed as antagonism in the presence of an exogenous full agonist, as for example attenuation of fenoterol induced responses by salmeterol. Studies are required to investigate whether this phenomenon is relevant in the setting of acute severe asthma.

The importance of planetary rotation period for ocean heat transport.

PubMed

Cullum, J; Stevens, D; Joshi, M

2014-08-01

The climate and, hence, potential habitability of a planet crucially depends on how its atmospheric and ocean circulation transports heat from warmer to cooler regions. However, previous studies of planetary climate have concentrated on modeling the dynamics of atmospheres, while dramatically simplifying the treatment of oceans, which neglects or misrepresents the effect of the ocean in the total heat transport. Even the majority of studies with a dynamic ocean have used a simple so-called aquaplanet that has no continental barriers, which is a configuration that dramatically changes the ocean dynamics. Here, the significance of the response of poleward ocean heat transport to planetary rotation period is shown with a simple meridional barrier--the simplest representation of any continental configuration. The poleward ocean heat transport increases significantly as the planetary rotation period is increased. The peak heat transport more than doubles when the rotation period is increased by a factor of ten. There are also significant changes to ocean temperature at depth, with implications for the carbon cycle. There is strong agreement between the model results and a scale analysis of the governing equations. This result highlights the importance of both planetary rotation period and the ocean circulation when considering planetary habitability.

Dopamine transporter-dependent and -independent actions of trace amine beta-phenylethylamine.

PubMed

Sotnikova, Tatyana D; Budygin, Evgeny A; Jones, Sara R; Dykstra, Linda A; Caron, Marc G; Gainetdinov, Raul R

2004-10-01

Beta-phenylethylamine (beta-PEA) is an endogenous amine that is found in trace amounts in the brain. It is believed that the locomotor-stimulating action of beta-PEA, much like amphetamine, depends on its ability to increase extracellular dopamine (DA) concentrations owing to reversal of the direction of dopamine transporter (DAT)-mediated DA transport. beta-PEA can also bind directly to the recently identified G protein-coupled receptors, but the physiological significance of this interaction is unclear. To assess the mechanism by which beta-PEA mediates its effects, we compared the neurochemical and behavioral effects of this amine in wild type (WT), heterozygous and 'null' DAT mutant mice. In microdialysis studies, beta-PEA, administered either systemically or locally via intrastriatal infusion, produced a pronounced outflow of striatal DA in WT mice whereas no increase was detected in mice lacking the DAT (DAT-KO mice). Similarly, in fast-scan voltammetry studies beta-PEA did not alter DA release and clearance rate in striatal slices from DAT-KO mice. In behavioral studies beta-PEA produced a robust but transient increase in locomotor activity in WT and heterozygous mice. In DAT-KO mice, whose locomotor activity and stereotypy are increased in a novel environment, beta-PEA (10-100 mg/kg) exerted a potent inhibitory action. At high doses, beta-PEA induced stereotypies in WT and heterozygous mice; some manifestations of stereotypy were also observed in the DAT-KO mice. These data demonstrate that the DAT is required for the striatal DA-releasing and hyperlocomotor actions of beta-PEA. The inhibitory action on hyperactivity and certain stereotypies induced by beta-PEA in DAT-KO mice indicate that targets other than the DAT are responsible for these effects.

Increased mature interleukin-1beta (IL-1beta) secretion from THP-1 cells induced by nigericin is a result of activation of p45 IL-1beta-converting enzyme processing.

PubMed

Cheneval, D; Ramage, P; Kastelic, T; Szelestenyi, T; Niggli, H; Hemmig, R; Bachmann, M; MacKenzie, A

1998-07-10

Perregaux and Gabel (Perregaux, D., and Gabel, C. A. (1994) J. Biol. Chem. 269, 15195-15203) reported that potassium depletion of lipopolysaccharide-stimulated mouse macrophages induced by the potassium ionophore, nigericin, leads to the rapid release of mature interleukin-1beta (IL-1beta). We have now shown a similar phenomenon in lipopolysaccharide-stimulated human monocytic leukemia THP-1 cells. Rapid secretion of mature, 17-kDa IL-1beta occurred, in the presence of nigericin (4-16 microM). No effects on the release of tumor necrosis factor-alpha, IL-6, or proIL-1beta were seen. Addition of the irreversible interleukin-1beta-converting enzyme (ICE) inhibitor, Z-Val-Ala-Asp-dichlorobenzoate, or a radicicol analog, inhibited nigericin-induced mature IL-1beta release and activation of p45 ICE precursor. The radicicol analog itself did not inhibit ICE, but markedly, and very rapidly depleted intracellular levels of 31-kDa proIL-1beta. By contrast, dexamethasone, cycloheximide, and the Na+/H+ antiporter inhibitor, 5-(N-ethyl-N-isopropyl)amiloride, had no effect on nigericin-induced release of IL-1beta. We have therefore shown conclusively, for the first time, that nigericin-induced release of IL-1beta is dependent upon activation of p45 ICE processing. So far, the mechanism by which reduced intracellular potassium ion concentration triggers p45 ICE processing is not known, but further investigation in this area could lead to the discovery of novel molecular targets whereby control of IL-1beta production might be effected.

Fenoterol, a beta(2)-adrenoceptor agonist, inhibits LPS-induced membrane-bound CD14, TLR4/CD14 complex, and inflammatory cytokines production through beta-arrestin-2 in THP-1 cell line.

PubMed

Wang, Wei; Xu, Ming; Zhang, You-yi; He, Bei

2009-11-01

To investigate the molecular mechanism and signaling pathway by which fenoterol, a beta(2)-adrenergic receptor (beta(2)-AR) agonist, produces anti-inflammatory effects. THP-1, a monocytic cell line, was used to explore the mechanism of beta(2)-AR stimulation in LPS-induced secretion of inflammatory cytokines and changes of toll-like receptors (TLRs). We labeled TLR4 and CD14 using monoclonal anti-TLR4 PE-conjugated and anti-CD14 FITC-conjugated antibodies in THP-1 cells stimulated by beta(2)-AR in the presence or absence of lipopolysaccharide (LPS) and small, interfering RNA (siRNA)-mediated knockdown of beta-arrestin-2, and then analyzed their changes in distribution by flow cytometry, Western blotting and confocal analysis. LPS-induced membrane-bound CD14, TLR4/CD14 complex levels and elevation of inflammatory cytokines were all significantly reduced by pre-incubation of fenoterol (P<0.05). However, the total level of CD14 and TLR4 was not significantly changed. Interestingly, confocal microscopy revealed redistribution of CD14 and TLR4/CD14 complex under beta(2)-AR stimulation. Furthermore, siRNA-mediated knockdown of beta-arrestin-2 eliminated the anti-inflammatory effects and redistribution of CD14 and TLR4/CD14 complex stimulated by beta(2)-AR. beta(2)-AR agonist exerts its anti-inflammatory effects by down-regulating TLR signaling in THP-1 cells, potentially resulting from beta-arrestin-2 mediated redistribution of CD14 and TLR14/CD14 complex.

Current Status of a NASA High-Altitude Balloon-Based Observatory for Planetary Science

NASA Technical Reports Server (NTRS)

Varga, Denise M.; Dischner, Zach

2015-01-01

Recent studies have shown that progress can be made on over 20% of the key questions called out in the current Planetary Science Decadal Survey by a high-altitude balloon-borne observatory. Therefore, NASA has been assessing concepts for a gondola-based observatory that would achieve the greatest possible science return in a low-risk and cost-effective manner. This paper addresses results from the 2014 Balloon Observation Platform for Planetary Science (BOPPS) mission, namely successes in the design and performance of the Fine Pointing System. The paper also addresses technical challenges facing the new Gondola for High Altitude Planetary Science (GHAPS) reusable platform, including thermal control for the Optical Telescope Assembly, power generation and management, and weight-saving considerations that the team will be assessing in 2015 and beyond.

Turbulent convection in an anelastic rotating sphere: A model for the circulation on the giant planets

NASA Astrophysics Data System (ADS)

Kaspi, Yohai

This thesis studies the dynamics of a rotating compressible gas sphere, driven by internal convection, as a model for the dynamics on the giant planets. We develop a new general circulation model for the Jovian atmosphere, based on the MITgcm dynamical core augmenting the nonhydrostatic model. The grid extends deep into the planet's interior allowing the model to compute the dynamics of a whole sphere of gas rather than a spherical shell (including the strong variations in gravity and the equation of state). Different from most previous 3D convection models, this model is anelastic rather than Boussinesq and thereby incorporates the full density variation of the planet. We show that the density gradients caused by convection drive the system away from an isentropic and therefore barotropic state as previously assumed, leading to significant baroclinic shear. This shear is concentrated mainly in the upper levels and associated with baroclinic compressibility effects. The interior flow organizes in large cyclonically rotating columnar eddies parallel to the rotation axis, which drive upgradient angular momentum eddy fluxes, generating the observed equatorial superrotation. Heat fluxes align with the axis of rotation, contributing to the observed flat meridional emission. We show the transition from weak convection cases with symmetric spiraling columnar modes similar to those found in previous analytic linear theory, to more turbulent cases which exhibit similar, though less regular and solely cyclonic, convection columns which manifest on the surface in the form of waves embedded within the superrotation. We develop a mechanical understanding of this system and scaling laws by studying simpler configurations and the dependence on physical properties such as the rotation period, bottom boundary location and forcing structure. These columnar cyclonic structures propagate eastward, driven by dynamics similar to that of a Rossby wave except that the restoring planetary vorticity gradient is in the opposite direction, due to the spherical geometry in the interior. We further study these interior dynamics using a simplified barotropic annulus model, which shows that the planetary vorticity radial variation causes the eddy angular momentum flux divergence, which drives the superrotating equatorial flow. In addition we study the interaction of the interior dynamics with a stable exterior weather layer, using a quasigeostrophic two layer channel model on a beta plane, where the columnar interior is therefore represented by a negative beta effect. We find that baroclinic instability of even a weak shear can drive strong, stable multiple zonal jets. For this model we find an analytic nonlinear solution, truncated to one growing mode, that exhibits a multiple jet meridional structure, driven by the nonlinear interaction between the eddies. Finally, given the density field from our 3D convection model we derive the high order gravitational spectra of Jupiter, which is a measurable quantity for the upcoming JUNO mission to Jupiter. (Copies available exclusively from MIT Libraries, Rm. 14-0551, Cambridge, MA 02139-4307. Ph. 617-253-5668; Fax 617-253-1690.)

Regulation of interleukin-1beta and interleukin-8 production by agonists of mu and delta opiate receptors in vitro.

PubMed

Gein, S V; Gorshkova, K G; Tendryakova, S P

2009-07-01

The studies reported here showed that beta-endorphin at concentrations of 10(-7)-10(-11) M increased interleukin-1beta (IL-1beta) production in unfractionated leukocyte suspensions both in the presence of 0.1 microg/ml lipopolysaccharide (LPS) and in cultures not stimulated with LPS. Interleukin-8 (IL-8) production by leukocytes was inhibited by beta-endorphin at concentrations of 10(-7) and 10(-11) M in the presence of LPS. The stimulatory effect of beta-endorphin on IL-1beta production was not blocked by naloxone or naltrindole. Suppression of IL-8 production was blocked by naloxone and naltrindole. In the mononuclear cell and neutrophil fractions, beta-endorphin and the delta agonist DADLE increased IL-1beta synthesis in both the spontaneous and stimulated versions of the test, while beta-endorphin and the delta agonist DADLE inhibited IL-8 production in the mononuclear cell and neutrophil fractions only in LPS-stimulated cultures. The mu agonist DAGO had no effect on IL-1beta production by mononuclear cells or neutrophils, though it suppressed LPS-induced secretion of IL-8 by neutrophils.

Beta-blockers for hypertension

PubMed Central

Wiysonge, Charles S; Bradley, Hazel A; Volmink, Jimmy; Mayosi, Bongani M; Opie, Lionel H

2017-01-01

Background Beta-blockers refer to a mixed group of drugs with diverse pharmacodynamic and pharmacokinetic properties. They have shown long-term beneficial effects on mortality and cardiovascular disease (CVD) when used in people with heart failure or acute myocardial infarction. Beta-blockers were thought to have similar beneficial effects when used as first-line therapy for hypertension. However, the benefit of beta-blockers as first-line therapy for hypertension without compelling indications is controversial. This review is an update of a Cochrane Review initially published in 2007 and updated in 2012. Objectives To assess the effects of beta-blockers on morbidity and mortality endpoints in adults with hypertension. Search methods The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to June 2016: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 6), MEDLINE (from 1946), Embase (from 1974), and ClinicalTrials.gov. We checked reference lists of relevant reviews, and reference lists of studies potentially eligible for inclusion in this review, and also searched the the World Health Organization International Clinical Trials Registry Platform on 06 July 2015. Selection criteria Randomised controlled trials (RCTs) of at least one year of duration, which assessed the effects of beta-blockers compared to placebo or other drugs, as first-line therapy for hypertension, on mortality and morbidity in adults. Data collection and analysis We selected studies and extracted data in duplicate, resolving discrepancies by consensus. We expressed study results as risk ratios (RR) with 95% confidence intervals (CI) and conducted fixed-effect or random-effects meta-analyses, as appropriate. We also used GRADE to assess the certainty of the evidence. GRADE classifies the certainty of evidence as high (if we are confident that the true effect lies close to that of the estimate of effect), moderate (if the true effect is likely to be close to the estimate of effect), low (if the true effect may be substantially different from the estimate of effect), and very low (if we are very uncertain about the estimate of effect). Main results Thirteen RCTs met inclusion criteria. They compared beta-blockers to placebo (4 RCTs, 23,613 participants), diuretics (5 RCTs, 18,241 participants), calcium-channel blockers (CCBs: 4 RCTs, 44,825 participants), and renin-angiotensin system (RAS) inhibitors (3 RCTs, 10,828 participants). These RCTs were conducted between the 1970s and 2000s and most of them had a high risk of bias resulting from limitations in study design, conduct, and data analysis. There were 40,245 participants taking beta-blockers, three-quarters of them taking atenolol. We found no outcome trials involving the newer vasodilating beta-blockers (e.g. nebivolol). There was no difference in all-cause mortality between beta-blockers and placebo (RR 0.99, 95% CI 0.88 to 1.11), diuretics or RAS inhibitors, but it was higher for beta-blockers compared to CCBs (RR 1.07, 95% CI 1.00 to 1.14). The evidence on mortality was of moderate-certainty for all comparisons. Total CVD was lower for beta-blockers compared to placebo (RR 0.88, 95% CI 0.79 to 0.97; low-certainty evidence), a reflection of the decrease in stroke (RR 0.80, 95% CI 0.66 to 0.96; low-certainty evidence) since there was no difference in coronary heart disease (CHD: RR 0.93, 95% CI 0.81 to 1.07; moderate-certainty evidence). The effect of beta-blockers on CVD was worse than that of CCBs (RR 1.18, 95% CI 1.08 to 1.29; moderate-certainty evidence), but was not different from that of diuretics (moderate-certainty) or RAS inhibitors (low-certainty). In addition, there was an increase in stroke in beta-blockers compared to CCBs (RR 1.24, 95% CI 1.11 to 1.40; moderate-certainty evidence) and RAS inhibitors (RR 1.30, 95% CI 1.11 to 1.53; moderate-certainty evidence). However, there was little or no difference in CHD between beta-blockers and diuretics (low-certainty evidence), CCBs (moderate-certainty evidence) or RAS inhibitors (low-certainty evidence). In the single trial involving participants aged 65 years and older, atenolol was associated with an increased CHD incidence compared to diuretics (RR 1.63, 95% CI 1.15 to 2.32). Participants taking beta-blockers were more likely to discontinue treatment due to adverse events than participants taking RAS inhibitors (RR 1.41, 95% CI 1.29 to 1.54; moderate-certainty evidence), but there was little or no difference with placebo, diuretics or CCBs (low-certainty evidence). Authors' conclusions Most outcome RCTs on beta-blockers as initial therapy for hypertension have high risk of bias. Atenolol was the beta-blocker most used. Current evidence suggests that initiating treatment of hypertension with beta-blockers leads to modest CVD reductions and little or no effects on mortality. These beta-blocker effects are inferior to those of other antihypertensive drugs. Further research should be of high quality and should explore whether there are differences between different subtypes of beta-blockers or whether beta-blockers have differential effects on younger and older people. Beta-blockers for hypertension What is the aim of this review? The aim of this Cochrane Review was to assess whether beta-blockers decrease the number of deaths, strokes, and heart attacks associated with high blood pressure in adults. We collected and analysed all relevant studies to answer this question and found 13 relevant studies. Are beta-blockers as good as other medicines when used for treatment of adults with high blood pressure? Beta-blockers were not as good at preventing the number of deaths, strokes, and heart attacks as other classes of medicines such as diuretics, calcium-channel blockers, and renin-angiotensin system inhibitors. Most of these findings come from one type of beta-blocker called atenolol. However, beta-blockers are a diverse group of medicines with different properties, and we need more well-conducted research in this area. What was studied in the review? Millions of people with high blood pressure have strokes, heart attacks, and other diseases, and many of them die. This situation could be prevented with appropriate treatment. Researchers have tried different medicines for treating high blood pressure. What are the main results of the review? We found 13 studies from high-income countries, mainly Western Europe and North America. In the studies, the people receiving beta-blockers were compared to people who received no treatment or other medicines. The studies showed the following. Beta-blockers probably make little or no difference in the number of deaths among people on treatment for high blood pressure. This effect appears to be similar to that of diuretics and renin-angiotensin system inhibitors, but beta-blockers are probably not as good at preventing deaths from high blood pressure as calcium-channel blockers. Beta-blockers may reduce the number of strokes, an effect which appears to be similar to that of diuretics. However, beta-blockers may not be as good at preventing strokes as renin-angiotensin system inhibitors or calcium-channel blockers. Beta-blockers may make little or no difference to the number of heart attacks among people with high blood pressure. The evidence suggests that this effect may not be different from that of diuretics, renin-angiotensin system inhibitors, or calcium-channel blockers. However, among people aged 65 years and older, the evidence suggests that beta-blockers may not be as good at reducing heart attacks as diuretics. People given beta-blockers are more likely to have side effects and stop treatment than people taking renin-angiotensin system inhibitors, but there may be little or no difference in side effects between beta-blockers and diuretics or calcium-channel blockers. How up-to-date is this review? The review authors searched for studies that had been published up to June 2016. PMID:28107561

IFN-beta1b augments glucocorticoid-induced suppression of tumor necrosis factor-alpha production by increasing the number of glucocorticoid receptors on a human monocytic cell line.

PubMed

Uitdehaag, B M; Hoekstra, K; Koper, J W; Polman, C H; Dijkstra, C D

2001-03-01

We studied the effect of recombinant interferon-beta1b (IFN-beta1b) on the sensitivity to glucocorticoids (GC) and on the number of GC receptors (GCR) in the human monocytic cell line THP-1. We found that IFN-beta1b augments the suppressive effect that dexamethasone has on the stimulated production of tumor necrosis factor-alpha (TNF-alpha), most likely related to the increased number of GCR observed after exposure to IFN-beta1b. This provides a possible clue to the mechanism of action of IFN-beta in multiple sclerosis.

Dose-response effects of estrogenic mycotoxins (zearalenone, alpha- and beta-zearalenol) on motility, hyperactivation and the acrosome reaction of stallion sperm

PubMed Central

2011-01-01

Background The aim of this study was to investigate the in vitro effects of the Fusarium fungus-derived mycotoxin, zearalenone and its derivatives alpha-zearalenol and beta-zearalenol on motility parameters and the acrosome reaction of stallion sperm. Since the toxic effects of zearalenone and its derivatives are thought to result from their structural similarity to 17beta-estradiol, 17beta-estradiol was used as a positive control for 'estrogen-like' effects. Methods Stallion spermatozoa were exposed in vitro to zearalenone, alpha-zearalenol, beta-zearalenol or 17beta-estradiol at concentrations ranging from 1 pM - 0.1 mM. After 2 hours exposure, motility parameters were evaluated by computer-assisted analysis, and acrosome integrity was examined by flow cytometry after staining with fluoroscein-conjugated peanut agglutinin. Results Mycotoxins affected sperm parameters only at the highest concentration tested (0.1 mM) after 2 hours exposure. In this respect, all of the compounds reduced the average path velocity, but only alpha-zearalenol reduced percentages of motile and progressively motile sperm. Induction of motility patterns consistent with hyperactivation was stimulated according to the following rank of potency: alpha-zearalenol >17beta-estradiol > zearalenone = beta-zearalenol. The hyperactivity-associated changes observed included reductions in straight-line velocity and linearity of movement, and an increase in the amplitude of lateral head displacement, while curvilinear velocity was unchanged. In addition, whereas alpha- and beta- zearalenol increased the percentages of live acrosome-reacted sperm, zearalenone and 17beta-estradiol had no apparent effect on acrosome status. In short, alpha-zearalenol inhibited normal sperm motility, but stimulated hyperactive motility in the remaining motile cells and simultaneously induced the acrosome reaction. Beta-zearalenol induced the acrosome reaction without altering motility. Conversely, zearalenone and 17beta-estradiol did not induce the acrosome reaction but induced hyperactive motility albeit to a different extent. Conclusions Apparently, the mycotoxin zearalenone has 17beta-estradiol-like estrogenic activity that enables it to induce hyperactivated motility of equine sperm cells, whereas the zearalenol derivatives induce premature completion of the acrosome reaction and thereby adversely affect stallion sperm physiology. The alpha form of zearalenol still possessed the estrogenic ability to induce hyperactivated motility, whereas its beta stereo-isomere had lost this property. PMID:21970729

A primordial origin for misalignments between stellar spin axes and planetary orbits.

PubMed

Batygin, Konstantin

2012-11-15

The existence of gaseous giant planets whose orbits lie close to their host stars ('hot Jupiters') can largely be accounted for by planetary migration associated with viscous evolution of proto-planetary nebulae. Recently, observations of the Rossiter-McLaughlin effect during planetary transits have revealed that a considerable fraction of hot Jupiters are on orbits that are misaligned with respect to the spin axes of their host stars. This observation has cast doubt on the importance of disk-driven migration as a mechanism for producing hot Jupiters. Here I show that misaligned orbits can be a natural consequence of disk migration in binary systems whose orbital plane is uncorrelated with the spin axes of the individual stars. The gravitational torques arising from the dynamical evolution of idealized proto-planetary disks under perturbations from massive distant bodies act to misalign the orbital planes of the disks relative to the spin poles of their host stars. As a result, I suggest that in the absence of strong coupling between the angular momentum of the disk and that of the host star, or of sufficient dissipation that acts to realign the stellar spin axis and the planetary orbits, the fraction of planetary systems (including systems of 'hot Neptunes' and 'super-Earths') whose angular momentum vectors are misaligned with respect to their host stars will be commensurate with the rate of primordial stellar multiplicity.

Transforming growth factor-beta1 transcriptionally activates CD34 and prevents induced differentiation of TF-1 cells in the absence of any cell-cycle effects.

PubMed

Marone, M; Scambia, G; Bonanno, G; Rutella, S; de Ritis, D; Guidi, F; Leone, G; Pierelli, L

2002-01-01

A number of cytokines modulate self-renewal and differentiation of hematopoietic elements. Among these is transforming growth factor beta1 (TGF-beta1), which regulates cell cycle and differentiation of hematopoietic cells, but has pleiotropic activities depending on the state of responsiveness of the target cells. It has been previously shown by us and other authors that TGF-beta1 maintains human CD34(+) hematopoietic progenitors in an undifferentiated state, independently of any cell cycle effects, and that depletion of TGF-beta1 triggers differentiation accompanied by a decrease in CD34 antigen expression. In the present work, we show that exogenous TGF-beta1 upregulates the human CD34 antigen in the CD34(+) cell lines TF-1 and KG-1a, but not in the more differentiated CD34(-) cell lines HL-60 and K-562. We further studied this effect in the pluripotent erythroleukemia cell line TF-1. Here, TGF-beta1 did not effect cell growth, but induced transcriptional activation of full-length CD34 and prevented differentiation induced by differentiating agents. This effect was associated with nuclear translocation of Smad-2, activation of TAK-1, and with a dramatic decrease in p38 phosphorylation. In other systems TGF-beta1 has been shown to activate a TGF-beta-activated kinase 1 (TAK1), which in turn, activates p38. The specific inhibitor of p38 phosphorylation, SB202190, also increased CD34 RNA expression, indicating the existence of a link between p-38 inhibition by TGF-beta1 and CD34 overexpression. Our data demonstrate that TGF-beta1 transcriptionally activates CD34 and prevents differentiation of TF-1 cells by acting independently through the Smad, TAK1 and p38 pathways, and thus provide important clues for the understanding of hematopoietic development and a potential tool to modify response of hematopoietic cells to mitogens or differentiating agents.

Effect of beta2-adrenoceptor agonists and other cAMP-elevating agents on inflammatory gene expression in human ASM cells: a role for protein kinase A.

PubMed

Kaur, Manminder; Holden, Neil S; Wilson, Sylvia M; Sukkar, Maria B; Chung, Kian Fan; Barnes, Peter J; Newton, Robert; Giembycz, Mark A

2008-09-01

In diseases such as asthma, airway smooth muscle (ASM) cells play a synthetic role by secreting inflammatory mediators such as granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, or IL-8 and by expressing surface adhesion molecules, including ICAM-1. In the present study, PGE(2), forskolin, and short-acting (salbutamol) and long-acting (salmeterol and formoterol) beta(2)-adrenoceptor agonists reduced the expression of ICAM-1 and the release of GM-CSF evoked by IL-1beta in ASM cells. IL-1beta-induced IL-8 release was also repressed by PGE(2) and forskolin, whereas the beta(2)-adrenoceptor agonists were ineffective. In each case, repression of these inflammatory indexes was prevented by adenoviral overexpression of PKIalpha, a highly selective PKA inhibitor. These data indicate a PKA-dependent mechanism of repression and suggest that agents that elevate intracellular cAMP, and thereby activate PKA, may have a widespread anti-inflammatory effect in ASM cells. Since ICAM-1 and GM-CSF are highly NF-kappaB-dependent genes, we used an adenoviral-delivered NF-kappaB-dependent luciferase reporter to examine the effects of forskolin and the beta(2)-adrenoceptor agonists on NF-kappaB activation. There was no effect on luciferase activity measured in the presence of forskolin or beta(2)-adrenoceptor agonists. This finding is consistent with the observation that IL-1beta-induced expression of IL-6, a known NF-kappaB-dependent gene in ASM, was also unaffected by beta(2)-adrenoceptor agonists, forskolin, PGE(2), 8-bromo-cAMP, or rolipram. Collectively, these results indicate that repression of IL-1beta-induced ICAM-1 expression and GM-CSF release by cAMP-elevating agents, including beta(2)-adrenoceptor agonists, may not occur through a generic effect on NF-kappaB.

Beta-Alanine Supplementation Improves Throwing Velocities in Repeated Sprint Ability and 200-m Swimming Performance in Young Water Polo Players.

PubMed

Claus, Gabriel Machado; Redkva, Paulo Eduardo; Brisola, Gabriel Mota Pinheiro; Malta, Elvis Sousa; de Araujo Bonetti de Poli, Rodrigo; Miyagi, Willian Eiji; Zagatto, Alessandro Moura

2017-05-01

The purpose of this study was to investigate the effects of beta-alanine supplementation on specific tests for water polo. Fifteen young water polo players (16 ± 2 years) underwent a 200-m swimming performance, repeated-sprint ability test (RSA) with free throw (shooting), and 30-s maximal tethered eggbeater kicks. Participants were randomly allocated into two groups (placebo × beta-alanine) and supplemented with 6.4g∙day -1 of beta-alanine or a placebo for six weeks. The mean and total RSA times, the magnitude based inference analysis showed a likely beneficial effect for beta-alanine supplementation (both). The ball velocity measured in the throwing performance after each sprint in the RSA presented a very like beneficial inference in the beta-alanine group for mean (96.4%) and percentage decrement of ball velocity (92.5%, likely beneficial). Furthermore, the percentage change for mean ball velocity was different between groups (beta-alanine=+2.5% and placebo=-3.5%; p = .034). In the 30-s maximal tethered eggbeater kicks the placebo group presented decreased peak force, mean force, and fatigue index, while the beta-alanine group maintained performance in mean force (44.1%, possibly beneficial), only presenting decreases in peak force. The 200-m swimming performance showed a possibly beneficial effect (68.7%). Six weeks of beta-alanine supplementation was effective for improving ball velocity shooting in the RSA, maintaining performance in the 30-s test, and providing possibly beneficial effects in the 200-m swimming performance.

Budgeting for Exploration: the History and Political Economy of Planetary Science

NASA Astrophysics Data System (ADS)

Callahan, Jason

2013-10-01

The availability of financial resources continues to be one of the greatest limiting factors to NASA’s planetary science agenda. Historians and members of the space science community have offered many explanations for the scientific, political, and economic actions that combine to form NASA’s planetary science efforts, and this essay will use budgetary and historical analysis to examine how each of these factors have impacted the funding of U.S. exploration of the solar system. This approach will present new insights into how the shifting fortunes of the nation’s economy or the changing priorities of political leadership have affected government investment in science broadly, and space science specifically. This paper required the construction of a historical NASA budget data set displaying layered fiscal information that could be compared equivalently over time. This data set was constructed with information collected from documents located in NASA’s archives, the Library of Congress, and at the Office of Management and Budget at the White House. The essay will examine the effects of the national gross domestic product, Federal debt levels, the budgets of other Federal agencies engaged in science and engineering research, and party affiliation of leadership in Congress and the White House on the NASA budget. It will also compare historic funding levels of NASA’s astrophysics, heliophysics, and Earth science efforts to planetary science funding. By examining the history of NASA’s planetary science efforts through the lens of the budget, this essay will provide a clearer view of how effectively the planetary science community has been able to align its goals with national science priorities.

Magnetic dynamos in accreting planetary bodies

NASA Astrophysics Data System (ADS)

Golabek, G.; Labrosse, S.; Gerya, T.; Morishima, R.; Tackley, P. J.

2012-12-01

Laboratory measurements revealed ancient remanent magnetization in meteorites [1] indicating the activity of magnetic dynamos in the corresponding meteorite parent body. To study under which circumstances dynamo activity is possible, we use a new methodology to simulate the internal evolution of a planetary body during accretion and differentiation. Using the N-body code PKDGRAV [2] we simulate the accretion of planetary embryos from an initial annulus of several thousand planetesimals. The growth history of the largest resulting planetary embryo is used as an input for the thermomechanical 2D code I2ELVIS [3]. The thermomechanical model takes recent parametrizations of impact processes [4] and of the magnetic dynamo [5] into account. It was pointed out that impacts can not only deposit heat deep into the target body, which is later buried by ejecta of further impacts [6], but also that impacts expose in the crater region originally deep-seated layers, thus cooling the interior [7]. This combination of impact effects becomes even more important when we consider that planetesimals of all masses contribute to planetary accretion. This leads occasionally to collisions between bodies with large ratios between impactor and target mass. Thus, all these processes can be expected to have a profound effect on the thermal evolution during the epoch of planetary accretion and may have implications for the magnetic dynamo activity. Results show that late-formed planetesimals do not experience silicate melting and avoid thermal alteration, whereas in early-formed bodies accretion and iron core growth occur almost simultaneously and a highly variable magnetic dynamo can operate in the interior of these bodies.

Formation of spectral lines in planetary atmospheres. I - Theory for cloudy atmospheres: Application to Venus.

NASA Technical Reports Server (NTRS)

Hunt, G. E.

1972-01-01

The theory of the formation of spectral lines in a cloudy planetary atmosphere is studied in detail. It is shown that models based upon homogeneous, isotropically scattering atmospheres cannot be used to reproduce observed spectroscopic features of phase effect and the shape of spectral lines for weak and strong bands. The theory must, therefore, be developed using an inhomogeneous (gravitational) model of a planetary atmosphere, accurately incorporating all the physical processes of radiative transfer. Such a model of the lower Venus atmosphere, consistent with our present knowledge, is constructed. The results discussed in this article demonstrate the effects of the parameters that describe the atmospheric model on the spectroscopic features of spectral line profile and phase effect, at visible and near infrared wavelengths. This information enables us to develop a comprehensive theory of line formation in a Venus atmosphere.

Tolerability to beta-blocker therapy among heart failure patients in clinical practice.

PubMed

Butler, Javed; Khadim, Ghazanfar; Belue, Rhonda; Chomsky, Don; Dittus, Robert S; Griffin, Marie; Wilson, John R

2003-06-01

Although beta-blockers were well-tolerated by heart failure (HF) patients in clinical trials, tolerability of these drugs in a general population of HF patients is not well-described. We studied a total of 308 encounters with beta-blockers therapy in 268 ambulatory HF patients. Side effects and frequency and predictors of discontinuation of therapy were studied. Independent predictors of discontinuation were assessed. Weight gain (59%), fatigue (56%), dizziness (41%), and dyspnea (29%) were the most common side effects. Fifty-one patients (19%) were discontinued on therapy with any 1 particular beta-blocker. Fatigue (30%) and hypotension (28%) were the most common reasons for discontinuation. Forty (78%) of these were given a trial with a different beta-blocker. Of these, 22 (55%) attempts with a different beta-blocker were tolerated. Thus the overall absolute discontinuation rate was only 7% for patients who were given a trial with different beta-blockers or 11% for the entire study population. Independent predictors of discontinuation of therapy included advanced symptoms, nonischemic etiology, history of pulmonary disease, and higher diuretic doses. Side effects with beta-blockers in a general population of HF patients are common; however, with changes in medical management, most patients can tolerate them eventually. In case of intolerance to one kind, a trial with a different beta-blocker is indicated.

Influence of Planetary Protection Guidelines on Waste Management Operations

NASA Technical Reports Server (NTRS)

Hogan, John A.; Fisher, John W.; Levri, Julie A.; Wignarajah, Kanapathipi; Race, Margaret S.; Stabekis, Perry D.; Rummel, John D.

2005-01-01

Newly outlined missions in the Space Exploration Initiative include extended human habitation on Mars. During these missions, large amounts of waste materials will be generated in solid, liquid and gaseous form. Returning these wastes to Earth will be extremely costly, and will therefore likely remain on Mars. Untreated, these wastes are a reservoir of live/dead organisms and molecules considered to be "biomarkers" i.e., indicators of life). If released to the planetary surface, these materials can potentially confound exobiology experiments and disrupt Martian ecology indefinitely (if existent). Waste management systems must therefore be specifically designed to control release of problematic materials both during the active phase of the mission, and for any specified post-mission duration. To effectively develop waste management requirements for Mars missions, planetary protection guidelines must first be established. While previous policies for Apollo lunar missions exist, it is anticipated that the increased probability of finding evidence of life on Mars, as well as the lengthy mission durations will initially lead to more conservative planetary protection measures. To facilitate the development of overall requirements for both waste management and planetary protection for future missions, a workshop was conducted to identify how these two areas interface, and to establish a preliminary set of planetary protection guidelines that address waste management operations. This paper provides background regarding past and current planetary protection and waste management issues, and their interactions. A summary of the recommended planetary protection guidelines, anticipated ramifications and research needs for waste management system design for both forward (Mars) and backward (Earth) contamination is also provided.

The NASA Regional Planetary Image Facility (RPIF) Network: A Key Resource for Accessing and Using Planetary Spatial Data

NASA Astrophysics Data System (ADS)

Hagerty, J. J.

2017-12-01

The role of the NASA Regional Planetary Image Facility (RPIF) Network is evolving as new science-ready spatial data products continue to be created and as key historical planetary data sets are digitized. Specifically, the RPIF Network is poised to serve specialized knowledge and services in a user-friendly manner that removes most barriers to locating, accessing, and exploiting planetary spatial data, thus providing a critical data access role within a spatial data infrastructure. The goal of the Network is to provide support and training to a broad audience of planetary spatial data users. In an effort to meet the planetary science community's evolving needs, we are focusing on the following objectives: Maintain and improve the delivery of historical data accumulated over the past four decades so as not to lose critical, historical information. This is being achieved by systematically digitizing fragile materials, allowing increased access and preserving them at the same time. Help users locate, access, visualize, and exploit planetary science data. Many of the facilities have begun to establish Guest User Facilities that allow researchers to use and/or be trained on GIS equipment and other specialized tools like Socet Set/GXP photogrammetry workstations for generating digital elevation maps. Improve the connection between the Network nodes while also leveraging the unique resources of each node. To achieve this goal, each facility is developing and sharing searchable databases of their collections, including robust metadata in a standards compliant way. Communicate more effectively and regularly with the planetary science community in an effort to make potential users aware of resources and services provided by the Network, while also engaging community members in discussions about community needs. Provide a regional resource for the science community, colleges, universities, museums, media, and the public to access planetary data. Introduce new strategies for visualizing planetary data and products (e.g., 3D printing and virtual reality platforms/experiences). We anticipate that in a few years virtual reality tools will be an integral part of data analysis, providing more intuitive understanding of multiple complex data sets.

TGF-beta3 is expressed in taste buds and inhibits proliferation of primary cultured taste epithelial cells.

PubMed

Nakamura, Shin-ichi; Kawai, Takayuki; Kamakura, Takashi; Ookura, Tetsuya

2010-01-01

Transforming growth factor-betas (TGF-betas), expressed in various tissues, play important roles in embryonic development and adult tissue homeostasis through their effects on cell proliferation, cell differentiation, cell death, and cell motility. However, expression of TGF-beta signaling components and their biological effect on taste epithelia has not been elucidated. We performed expression analysis of TGF-beta signaling components in taste epithelia and found that the TGF-beta3 mRNA was specifically expressed in taste buds. Type II TGF-betas receptor (TbetaR-II) mRNA was specifically expressed in the tongue epithelia including the taste epithelia. To elucidate the biological function of TGF-beta3 in taste epithelia, we performed proliferation assay with primary cultured taste epithelial cells. In the presence of TGF-beta3, percentage of BrdU-labeled cells decreased significantly, suggesting that the TGF-beta3 inhibited the proliferation of cultured taste epithelial cells through inhibiting cell-cycle entry into S phase. By quantitative reverse transcription-polymerase chain reaction assay, we found that the TGF-beta3 resulted in an increased level of expression of p15Ink4b and p21Cip1, suggesting that the TGF-beta3 inhibited the taste epithelial cell proliferation through inhibiting G1cyclin-Cdk complexes. Taken together, these results suggested that the TGF-beta3 may regulate taste epithelial cell homeostasis through controlling cell proliferation.

Potentiating role of interleukin-1beta (IL-1beta) and IL-1beta type 1 receptors in the medial hypothalamus in defensive rage behavior in the cat.

PubMed

Hassanain, M; Bhatt, S; Zalcman, S; Siegel, A

2005-06-28

Recently, this laboratory provided evidence that interleukin-1beta (IL-1beta), an immune and brain-derived cytokine, microinjected into the medial hypothalamus, potentiates defensive rage behavior in the cat elicited from the midbrain periaqueductal gray (PAG), and that such effects are blocked by a 5-HT2 receptor antagonist. Since this finding represents the first time that a brain cytokine has been shown to affect defensive rage behavior, the present study replicated and extended these findings by documenting the specific potentiating role played by IL-1beta Type 1 receptor (IL-1RI), and the anatomical relationship between IL-1beta and 5-HT2 receptors in the medial hypothalamus. IL-1beta (10 ng) microinjected into the medial hypothalamus induced two separate phases of facilitation, one at 60 min and another at 180 min, post-injection. In turn, these effects were blocked with pretreatment of the selective IL-1 Type I receptor antagonist (IL-1ra) (10 ng), demonstrating the selectivity of the effects of IL-1beta on medial hypothalamic neurons upon PAG-elicited defensive rage behavior. The next stage of the study utilized immunohistochemical methods to demonstrate that IL-1beta and 5-HT2 receptors were present on the same neurons within regions of the medial hypothalamus where IL-1beta and the IL-1beta receptor antagonists were administered. This provided anatomical evidence suggesting a relationship between IL-1RI and 5-HT2 receptors in the medial hypothalamus that is consistent with the previous pharmacological observations in our laboratory. The overall findings show that activation of IL-1RI in the medial hypothalamus potentiates defensive rage behavior in the cat and that these effects may also be linked to the presence of 5-HT2 receptors on the same groups of neurons in this region of hypothalamus.

Does tight heart rate control improve beta-blocker efficacy? An updated analysis of the noncardiac surgical randomized trials.

PubMed

Beattie, W Scott; Wijeysundera, Duminda N; Karkouti, Keyvan; McCluskey, Stuart; Tait, Gordon

2008-04-01

Recent meta-analyses assessing the efficacy of perioperative beta-blockade trials have failed to show a reduction in postoperative morbidity and mortality. Tight control of heart rate (HR) has been suggested to improve these outcomes. Meta-analyses have not considered the influence of tight HR control on the efficacy of perioperative beta-blockade. Using previously published search strategies, we identified all randomized trials evaluating perioperative beta-blockers after noncardiac surgery. This search yielded 10 trials with 2176 patients. We used the data from these studies to correlate measures of HR control with major postoperative outcomes, primarily in-hospital myocardial infarction (MI). Odds ratio (OR) and 95% confidence intervals (CI) were calculated, and metaregression was performed correlating measures of HR control with MI. The combined results of all studies did not show a significant cardioprotective effect of beta-blockers, with considerable heterogeneity among the studies (OR = 0.76; 95% CI = 0.4-1.4; P = 0.38 heterogeneity: I(2) = 34%). However, grouping the trials on the basis of maximal HR showed that trials where the estimated maximal HR was <100 bpm were associated with cardioprotection (OR = 0.23; 95% CI = 0.08-0.65; P = 0.005) whereas trials where the estimated maximal HR was >100 bpm did not demonstrate cardioprotection (OR = 1.17; 95% CI = 0.79-1.80; P = 0.43) with no heterogeneity. Moreover, metaregression of the HR response to beta-blockade against the log OR of postoperative MI demonstrated a linear association between the effect of beta-blockade on the mean, maximal, and variation in HR and the OR of an MI (r(2) = 0.63; P < 0.001) where a larger effect of beta-blockers on HR was associated with a decreased incidence of postoperative MI. Across all studies, beta-blockade resulted in a reduction in postoperative HR (weighted mean difference: 8.6 bpm; 95% CI = -9.6 to -7.6; I(2) = 85.3%) with considerable heterogeneity. This large heterogeneity in HR response to beta-blockade was found to be related, in part, to the type of beta-blocker, specifically, metoprolol, and the concomitant use of calcium channel blockers. Calcium channel blocker use and beta-blockers other than metoprolol resulted in more effective control of HR. There was wide variability in the HR response to beta-blockade. Twenty-five percent of patients receiving beta-blockers had episodes when the HRs were more than 100 bpm, although 15% of placebo patients also had bradycardia, which would have required a dose reduction had they been administered beta-blockers. Finally, this analysis found that perioperative beta-blockade was associated with an increased incidence of bradycardia (OR = 3.49; 95% CI = 2.4-5.9) and congestive heart failure (OR = 1.68; 95% CI = 1.00-2.8). The trials that achieve the most effective control of HR are associated with a reduced incidence of postoperative MI, suggesting that effective control of HR is important for achieving cardioprotection. Second, this analysis demonstrates that administration of beta-blockers does not reliably decrease HRs in all patients, and may be associated with increased side effects. Judicious use of combination therapy with other drugs may be necessary to achieve effective postoperative control of HR.

A Theoretical and Experimental Study of Emission Spectroscopy of Planetary Surfaces

NASA Astrophysics Data System (ADS)

Henderson, Bradley Gray

1995-01-01

This thesis explores the spectral emissivity of particulate materials on planetary surfaces through theoretical modeling and supporting laboratory and field investigations. In the first part of the thesis, I develop a Monte Carlo ray tracing model to calculate the directional and spectral emissivity and the polarization state of the radiation emitted from a particulate, isothermal surface for emission angles 0^circ-90^ circ and wavelengths 7-16 mu m. The results show that roughness and scattering significantly affect the character of the emitted radiation field and should be taken into account when interpreting the physical properties of a planetary surface from IR spectrophotometry or spectropolarimetry. The remainder of the thesis focuses on understanding near-surface thermal gradients and their effects on emission spectra for different planetary environments. These gradients are formed by radiative cooling in the top few hundred microns of low conductivity particulate materials on planetary surfaces with little or no atmosphere. I model the heat transfer by conduction and radiation in the top few millimeters of a planetary regolith for scattering and non-scattering media. In conjunction with the modeling, I measure emission spectra of fine-grained quartz in an environment chamber designed to simulate the conditions on other planetary surfaces. The results show that significant thermal gradients will form in the near surface of materials on the surface of the Moon and Mercury. Their presence increases spectral contrast and creates emission maxima in the transparent regions of the spectrum. Thermal gradients are shown to be responsible for the observed wavelength shifts of the Christiansen emission peak with variations in thermal conductivity and grain size. The results are also used to analyze recent telescopic spectra of the Moon and Mercury and can explain certain features seen in those data. Thermal gradients are shown to be minor for the surface of Mars and negligible on Earth. I conclude that the spectral effects created by near-surface thermal gradients are predictable and might even provide an extra source of information about the physical nature of a planetary surface, and mid-IR emission spectroscopy should therefore prove to be useful for remote sensing of airless bodies.

Anticonvulsant properties of alpha, gamma, and alpha, gamma-substituted gamma-butyrolactones.

PubMed

Klunk, W E; Covey, D F; Ferrendelli, J A

1982-09-01

Derivatives of gamma-butyrolactone (GBL) substituted on the alpha- and/or gamma-positions were synthesized and tested for their effects on behavior in mice, on the electroencephalographs and blood pressure of paralyzed-ventilated guinea pigs, and on electrical activity of incubated hippocampal slices. Several compounds, including alpha-ethyl-alpha-methyl GBL (alpha-EMGBL), alpha, alpha-dimethyl GBL, alpha, gamma-diethyl-alpha, gamma-dimethyl GBL, and gamma-ethyl-gamma-methyl GBL, prevented seizures induced by pentylenetetrazol, beta-ethyl-beta-methyl-gamma-butyrolactone (beta-EMGBL), picrotoxin, or all three compounds in mice and guinea pigs but had no effect on seizures induced by maximal electroshock or bicuculline. Neither gamma-hydroxybutyrate (GHB) nor alpha-isopropylidine GBL had any anticonvulsant activity. The anticonvulsant alpha-substituted compounds had a potent hypotensive effect and antagonized the hypertensive effect of beta-EMGBL, alpha-EMGBL was tested in incubated hippocampal slices and was found to depress basal activity and antagonize excitation induced by beta-EMGBL. These results demonstrate that alpha-alkyl-substituted GBL and, to a lesser extent, gamma-substituted derivatives are anticonvulsant agents and that their effects are strikingly different from those of GHB or beta-alkyl-substituted GBLs, which are epileptogenic. Possibly beta- and alpha-substituted GBLs act at the same site as agonists and antagonists, respectively.

Neuroactive steroid stereospecificity of ethanol-like discriminative stimulus effects in monkeys.

PubMed

Grant, Kathleen A; Helms, Christa M; Rogers, Laura S M; Purdy, Robert H

2008-07-01

Positive modulation of GABA(A) and antagonism of N-methyl-D-aspartate receptors mediate the discriminative stimulus effects of ethanol. Endogenous neuroactive steroids produce effects similar to ethanol, suggesting that these steroids may modulate ethanol addiction. The four isomers of the functional esters at C-3 of the 3-hydroxy metabolites of 4-pregnene-3,20-dione (progesterone) [allopregnanolone (3alpha,5alpha-P), pregnanolone (3alpha,5beta-P), epiallopregnanolone (3beta,5alpha-P), and epipregnanolone (3beta,5beta-P)], a synthetic analog of steroids modified by endogenous sulfation [pregnanolone hemisuccinate (3alpha,5beta-P HS)], and a structurally similar, adrenally derived steroid [3alpha-hydroxy-5-androstan-17-one (3alpha,5alpha-A, androsterone)] were assessed for ethanol-like discriminative stimulus effects at 30 or 60 min after administration in male (n = 9) and female (n = 8) cynomolgus monkeys (Macaca fascicularis) trained to discriminate 1.0 or 2.0 g/kg ethanol (i.g.) with a 30-min pretreatment interval. The 3alpha-hydroxysteroids completely substituted for ethanol (80% of cases), whereas the 3beta-hydroxysteroids and 3alpha,5beta-P HS rarely substituted for ethanol (6% of cases). There were no sex differences. Compared with monkeys trained to discriminate 2.0 g/kg ethanol, 3alpha,5beta-P and 3alpha,5alpha-A substituted more potently in monkeys trained to discriminate 1.0 g/kg ethanol. Compared with the 5beta-reduced isomer (3alpha,5beta-P), the 5alpha isomer of pregnanolone (3alpha,5alpha-P) substituted for ethanol with 3 to 40-fold greater potency but was least efficacious in female monkeys trained to discriminate 2.0 g/kg ethanol. The data suggest that the discriminative stimulus effects of lower doses (1.0 g/kg) of ethanol are mediated to a greater extent by 3alpha,5beta-P- and 3alpha,5alpha-A-sensitive receptors compared with higher doses (2.0 g/kg). Furthermore, the discriminative stimulus effects of ethanol appear to be mediated by activity at binding sites that are particularly sensitive to 3alpha,5alpha-P.

The neuron-specific isoform of glycogen synthase kinase-3beta is required for axon growth.

PubMed

Castaño, Zafira; Gordon-Weeks, Phillip R; Kypta, Robert M

2010-04-01

Glycogen synthase kinase-3 (GSK-3) has become an important target for the treatment of mood disorders and neurodegenerative disease. It comprises three enzymes, GSK-3alpha, beta and the neuron-specific isoform, beta2. GSK-3 regulates axon growth by phosphorylating microtubule-associated proteins including Tau. A genetic polymorphism that leads to an increase in the ratio of GSK-3beta1 to GSK-3beta2 interacts with Tau haplotypes to modify disease risk in Parkinson's and Alzheimer's disease. We have examined the roles of each isoform of GSK-3 in neurons. Silencing of GSK-3beta2 inhibited retinoic acid-induced neurite outgrowth in SH-SY5Y neuroblastoma cells and axon growth in rat cortical neurons. Inhibition of neurite outgrowth was prevented by co-expression of GSK-3beta2 but not by co-expression of GSK-3alpha or GSK-3beta1. Ectopic expression GSK-3beta2 enhanced the effects of retinoic acid on neurite length and induced neurite formation in the absence of retinoic acid. GSK-3beta2 phosphorylated Tau at a subset of those sites phosphorylated by GSK-3beta1. In addition, Axin, which regulates responses to Wnt signals, associated more readily with GSK-3beta1 than with GSK-3beta2. Our results suggest that GSK-3 inhibitors that target the Axin-binding site in GSK-3 will preserve the beneficial effects of GSK-3beta2 on axon growth.

Inhibition of glycogen synthase kinase 3beta during heart failure is protective.

PubMed

Hirotani, Shinichi; Zhai, Peiyong; Tomita, Hideharu; Galeotti, Jonathan; Marquez, Juan Pablo; Gao, Shumin; Hong, Chull; Yatani, Atsuko; Avila, Jesús; Sadoshima, Junichi

2007-11-26

Glycogen synthase kinase (GSK)-3, a negative regulator of cardiac hypertrophy, is inactivated in failing hearts. To examine the histopathological and functional consequence of the persistent inhibition of GSK-3beta in the heart in vivo, we generated transgenic mice with cardiac-specific overexpression of dominant negative GSK-3beta (Tg-GSK-3beta-DN) and tetracycline-regulatable wild-type GSK-3beta. GSK-3beta-DN significantly reduced the kinase activity of endogenous GSK-3beta, inhibited phosphorylation of eukaryotic translation initiation factor 2B epsilon, and induced accumulation of beta-catenin and myeloid cell leukemia-1, confirming that GSK-3beta-DN acts as a dominant negative in vivo. Tg-GSK-3beta-DN exhibited concentric hypertrophy at baseline, accompanied by upregulation of the alpha-myosin heavy chain gene and increases in cardiac function, as evidenced by a significantly greater Emax after dobutamine infusion and percentage of contraction in isolated cardiac myocytes, indicating that inhibition of GSK-3beta induces well-compensated hypertrophy. Although transverse aortic constriction induced a similar increase in hypertrophy in both Tg-GSK-3beta-DN and nontransgenic mice, Tg-GSK-3beta-DN exhibited better left ventricular function and less fibrosis and apoptosis than nontransgenic mice. Induction of the GSK-3beta transgene in tetracycline-regulatable wild-type GSK-3beta mice induced left ventricular dysfunction and premature death, accompanied by increases in apoptosis and fibrosis. Overexpression of GSK-3beta-DN in cardiac myocytes inhibited tumor necrosis factor-alpha-induced apoptosis, and the antiapoptotic effect of GSK-3beta-DN was abrogated in the absence of myeloid cell leukemia-1. These results suggest that persistent inhibition of GSK-3beta induces compensatory hypertrophy, inhibits apoptosis and fibrosis, and increases cardiac contractility and that the antiapoptotic effect of GSK-3beta inhibition is mediated by myeloid cell leukemia-1. Thus, downregulation of GSK-3beta during heart failure could be compensatory.

Quasibiennial Periodicity of Solar and Planetary Phenomena

NASA Astrophysics Data System (ADS)

Predeanu, Irina

The quasibiennial oscillation (QBO) of various solar and geophysical parameters is anlysed, taking some planetary configurations as temporal reference points. The incidence of the QBO minima in the proximity of Sun-Mars oppositions is discussed. The increase of this effect when Mars is near the perihelion or Jupiter is conjunct to the Sun is pointed out,

Spacecraft Demand Access: Autonomy for Low-Cost Planetary Operations

NASA Technical Reports Server (NTRS)

Sweetnam, Donald

1997-01-01

In this paper we describe a new concept and prototype for dramtically reducing the cost of contact with planetary spacecraft. Known as spacecraft Demand Access, a suite of spacecraft and ground automation technologies, it enables future intelligent spacecraft to act as initiators of cost effective contact with the ground - doing it only when necessary.

Lunar and Planetary Science Conference, 9th, Houston, Tex., March 13-17, 1978, Proceedings. Volume 2 - Lunar and planetary surfaces

NASA Technical Reports Server (NTRS)

Merrill, R. B.

1978-01-01

Regolith studies are summarized with attention given to isotope and solar wind effects, core studies, and soil maturation and agglutinates. Consideration is also given to radiometric, cosmic-ray and track chronologies for meteorites and lunar samples and to lunar impact phenomena.

alpha1B-Adrenergic receptor phosphorylation and desensitization induced by transforming growth factor-beta.

PubMed Central

Romero-Avila, M Teresa; Flores-Jasso, C Fabián; García-Sáinz, J Adolfo

2002-01-01

Transforming growth factor-beta (TGF-beta) induced alpha(1B)-adrenergic receptor phosphorylation in Rat-1 fibroblasts stably expressing these adrenoceptors. This effect of TGF-beta was rapid, reaching a maximum within 30 min and decreasing thereafter, and concentration-dependent (EC(50) 0.3 pM). The phosphoinositide 3-kinase inhibitors wortmannin and LY294002, and the protein kinase C inhibitors staurosporine, Ro 318220 and bisindolylmaleimide, blocked the effect of this growth factor. alpha(1B)-Adrenergic receptor phosphorylation was associated with desensitization, as indicated by a reduction in the adrenergic-mediated production of [(3)H]inositol phosphates. Phosphorylation of alpha(1B)-adrenergic receptors by TGF-beta was also observed in Cos-1 cells transfected with the receptor. Co-transfection of the dominant-negative mutant of the regulatory subunit of phosphoinositide 3-kinase (Deltap85) inhibited the phosphorylation of alpha(1B)-adrenergic receptors induced by TGF-beta. Our results indicate that activation of TGF-beta receptors induces alpha(1B)-adrenergic receptor phosphorylation and desensitization. The data suggest that phosphoinositide 3-kinase and protein kinase C play key roles in this effect of TGF-beta. PMID:12234252

alpha1B-Adrenergic receptor phosphorylation and desensitization induced by transforming growth factor-beta.

PubMed

Romero-Avila, M Teresa; Flores-Jasso, C Fabián; García-Sáinz, J Adolfo

2002-12-01

Transforming growth factor-beta (TGF-beta) induced alpha(1B)-adrenergic receptor phosphorylation in Rat-1 fibroblasts stably expressing these adrenoceptors. This effect of TGF-beta was rapid, reaching a maximum within 30 min and decreasing thereafter, and concentration-dependent (EC(50) 0.3 pM). The phosphoinositide 3-kinase inhibitors wortmannin and LY294002, and the protein kinase C inhibitors staurosporine, Ro 318220 and bisindolylmaleimide, blocked the effect of this growth factor. alpha(1B)-Adrenergic receptor phosphorylation was associated with desensitization, as indicated by a reduction in the adrenergic-mediated production of [(3)H]inositol phosphates. Phosphorylation of alpha(1B)-adrenergic receptors by TGF-beta was also observed in Cos-1 cells transfected with the receptor. Co-transfection of the dominant-negative mutant of the regulatory subunit of phosphoinositide 3-kinase (Deltap85) inhibited the phosphorylation of alpha(1B)-adrenergic receptors induced by TGF-beta. Our results indicate that activation of TGF-beta receptors induces alpha(1B)-adrenergic receptor phosphorylation and desensitization. The data suggest that phosphoinositide 3-kinase and protein kinase C play key roles in this effect of TGF-beta.

[Therapy of heart failure with beta-blockers?].

PubMed

Osterziel, K J; Dietz, R

1997-01-01

In heart failure the chronic sympathetic stimulation alters the cardiac beta-adrenergic pathway. This alteration leads to a diminished contractile response to stimulation of the cardiac beta 1 receptor. A blockade of the beta 1 receptor partly restores the physiologic response to sympathetic stimulation at rest and during exercise. Several mechanisms resulting from the competitive blockade of the beta 1 receptor may be important. The major effect of beta-blockers seems to be triggered by a reduction of the heart rate at rest resulting in an increase of the left ventricular ejection fraction on the average by 7-8%. Patients with heart failure who are treated with a beta-blocker experience initially a slight decrease of the left ventricular function. beta-blocker therapy should therefore be initiated only in patients with stable heart failure. The starting dose of the beta-blocker has to be very small, e.g, 5 mg Metoprolol, 1.25 mg Bisoprolol or 3.125 mg Carvedilol. In a stepwise fashion the dose has to be increased to a full beta blocking effect over a period of 4-8 weeks. Despite a careful dose titration only 90% of the patients tolerate this regimen. Patients with high resting heart rates and/or dilated cardiomyopathy will have the greatest benefit. The two main reasons for withdrawal of the beta-blocker are deterioration of heart failure or symptomatic hypotension. Symptomatic improvement and a significant increase of exercise capacity appear gradually and can be measured only after more than 1 month duration of therapy. Three multicenter studies (MDC. CIBIS I, Carvedilol) evaluated the influence of beta-blockers on prognosis of heart failure. The MDC trial demonstrated a slower progression of heart failure with Metoprolol. The MDC and the CIBIS I trial could not show a significant improvement of prognosis. The larger trial with carvedilol was the first study to demonstrate a decreased mortality in patients who initially tolerate the beta-blocker therapy. One major concern in that study is the evaluation and classification of patients in the run-in phase who do not tolerate the beta-blocker. Definite studies (BEST, CIBIS II; COMET; RESOLVED; MERIT) are designed to answer these problems and to evaluate the effect of beta-blockers on mortality. Until the results of these studies are available the main goal of treatment with beta-blockers remains symptomatic improvement. Further, there is good evidence for an additional increase in life expectancy. In order to achieve optimal medical treatment and to avoid side-effects careful clinical evaluation and management of the patients is mandatory during therapy with beta-blockers.

Effects of timolol and atenolol on benign essential tremor: placebo-controlled studies based on quantitative tremor recording.

PubMed

Dietrichson, P; Espen, E

1981-08-01

Two different beta-adrenoreceptor antagonists, atenolol and timolol, were separately compared with a placebo in the suppression of essential tremor. In two-week single-blind placebo-controlled studies with cross-over, timolol (5 mg twice daily) and atenolol (100 mg once daily) produced an equal reduction in sitting heart rate and sitting blood pressure. Timolol was effective in reducing tremor while atenolol failed to reduce tremor amplitude. These results indicate that essential tremor can be reduced but not blocked, by the adrenergic blocker timolol with both beta 1 and beta 2 blocking properties; but not by the relatively selective beta 1 blocking drug atenolol. Possibly, the tremor reduction is medicated by a peripheral effect on beta 2 adrenoreceptors.

Presynaptic control of dopamine release by BETA-phenylethylamine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zharikova, A.D.; Godukhin, O.V.

The authors study the effect of extracellular ions (Ca/sup 2 +/, Na/sup 2 +/) on the beta-phenylethylamine (beta-PEA) releasing effect, dependence of this effect on the membrane potential of dopaminergic endings, and the participation of dopamine presynaptic autoreceptors in the realization of the effects of beta-PEA on dopamine (DA) release. Experi ments were carried out on noninbred male albino rats. By means of a microsyringe, (/sup 3/H)-DA hydrochloride was injected. The significance of the difference in levels of (/sup 3/H)-DA release during analogous periods of perfusion in the groups of animals compared was estimated by Student's test. These experiments inmore » vivo thus demonstrated the ability of beta-PEA to regulate DA release in different directions depending on the functional state of the dopaminergic neuron.« less

Pressure demagnetization of synthetic Al substituted hematite and its implications for planetary studies

NASA Astrophysics Data System (ADS)

Jiang, Zhaoxia; Rochette, Pierre; Liu, Qingsong; Gattacceca, Jérôme; Yu, Yongjae; Barrón, Vidal; Torrent, José

2013-11-01

Magnetic minerals can undergo high pressures during their formation and subsequent evolution, which can modify both their intrinsic magnetic properties and remanent magnetization. Aluminum-substituted hematite (Al-hematite) occurs in significant proportion in many soils and sediments, especially in temperate and warm areas. In this work we investigated the effect of high hydrostatic pressures on the magnetic remanence of two series of synthetic Al-hematites. A pressure of 1.44 GPa resulted in 50% reduction of the isothermal remanent magnetization (IRM), which was more effective than alternating field (AF) demagnetization with the largest peak field of 120 mT. In addition, repeated application of the same pressure leads to further demagnetization. Aluminum substitution may increase the resistance to the pressure effect by decreasing particle size and generating defects in magnetic lattices, which results in an increase in coercivity. Our study contributes to understanding the effects of pressure on rocks from the interior of Earth and other planets as well as shocked planetary surfaces, which is significant for future planetary studies.

Greenhouse effect in planetary atmospheres caused by molecular symmetry breaking in intermolecular interactions

NASA Astrophysics Data System (ADS)

Vigasin, A. A.; Mokhov, I. I.

2017-03-01

It is believed that the greenhouse effect is related to the parameters of absorption spectra of polyatomic molecules, usually trace gases, in planetary atmospheres. The main components of all known atmospheres of celestial bodies are symmetrical molecules that do not possess the dipole-allowed purely rotational (and in the case of diatomic molecules, vibrational-rotational) absorption spectrum. Upon increased pressure, a weak absorption appears, induced by intermolecular interaction, which can lead to a greenhouse effect. The contribution of the induced absorption in radiative forcing of a dense atmosphere may amount to a few or even tens of W/m2. In conditions typical for the atmospheres of terrestrial planets (including paleoatmospheres), the collision-induced absorption and associated greenhouse effect may lead to an increase in surface temperature above the freezing point of water. There is a correlation between the temperature of an atmosphere and the intermolecular bonding energy of gases that dominate in planetary atmospheres of the Solar System.

Effect of transforming growth factor-beta1 on decorin expression and muscle morphology during chicken embryonic and posthatch growth and development.

PubMed

Li, X; Velleman, S G

2009-02-01

During skeletal muscle development, transforming growth factor-beta1 (TGF-beta1) is a potent inhibitor of muscle cell proliferation and differentiation, as well as a regulator of extracellular matrix (ECM) production. Decorin, a member of the small leucine-rich ECM proteoglycans, binds to TGF-beta1 and modulates TGF-beta1-dependent cell growth stimulation or inhibition. The expression of decorin can be regulated by TGF-beta1 during muscle proliferation and differentiation. How TGF-beta1 affects decorin and muscle growth, however, has not been well documented in vivo. The present study investigated the effect of TGF-beta1 on decorin expression and intracellular connective tissue development during skeletal muscle growth. Exogenous TGF-beta1 significantly decreased the number of myofibers in a given area at both 1 d and 6 wk posthatch. The TGF-beta1-treated muscle had a significant decrease in decorin mRNA expression at embryonic day (ED) 10, whereas protein amounts decreased at 17 ED and 1 d posthatch compared to the control muscle. Decorin was localized in both the endomysium and perimysium in the control pectoralis major muscle. Transforming growth factor-beta1 reduced decorin in both the endomysium and perimysium from 17 ED to 6 wk posthatch. Compared to the control muscle, the perimysium space in the pectoralis major muscle was dramatically decreased by TGF-beta1 during embryonic development through posthatch growth. Because decorin regulates collagen fibrillogenesis, a major component of the ECM, the reduction of decorin by TGF-beta1 treatment may cause the irregular formation of collagen fibrils, leading to the decrease in endomysium and perimysium space. The results from the current study suggest that the effect of TGF-beta1 on decorin expression and localization was likely associated with altered development of the perimysium and the regulation of muscle fiber development.

The effects of interferon-alpha/beta in a model of rat heart transplantation

NASA Technical Reports Server (NTRS)

Slater, A. D.; Klein, J. B.; Sonnenfeld, G.; Ogden, L. L. 2nd; Gray, L. A. Jr

1992-01-01

Interferons have multiple immunologic effects. One such effect is the activation of expression of cell surface antigens. Interferon alpha/beta enhance expression of class I but not class II histocompatibility antigens. Contradictory information has been published regarding the effect of interferon-alpha/beta administration in patients with kidney transplantation. In a model of rat heart transplantation we demonstrated that administration of interferon-alpha/beta accelerated rejection in a dose-dependent fashion in the absence of maintenance cyclosporine. Animals treated with maintenance cyclosporine had evidence of increased rejection at 20 days that was resolved completely at 45 days with cyclosporine alone.

The effect of smoking cessation pharmacotherapies on pancreatic beta cell function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woynillowicz, Amanda K.; Raha, Sandeep; Nicholson, Catherine J.

The goal of our study was to evaluate whether drugs currently used for smoking cessation (i.e., nicotine replacement therapy, varenicline [a partial agonist at nicotinic acetylcholine receptors (nAChR)] and bupropion [which acts in part as a nAChR antagonist]) can affect beta cell function and determine the mechanism(s) of this effect. INS-1E cells, a rat beta cell line, were treated with nicotine, varenicline and bupropion to determine their effects on beta cell function, mitochondrial electron transport chain enzyme activity and cellular/oxidative stress. Treatment of INS-1E cells with equimolar concentrations (1 μM) of three test compounds resulted in an ablation of normalmore » glucose-stimulated insulin secretion by the cells. This disruption of normal beta cell function was associated with mitochondrial dysfunction since all three compounds tested significantly decreased the activity of mitochondrial electron transport chain enzyme activity. These results raise the possibility that the currently available smoking cessation pharmacotherapies may also have adverse effects on beta cell function and thus glycemic control in vivo. Therefore whether or not the use of nicotine replacement therapy, varenicline and bupropion can cause endocrine changes which are consistent with impaired pancreatic function warrants further investigation. -- Highlights: ► Smoking cessation drugs have the potential to disrupt beta cell function in vitro. ► The effects of nicotine, varenicline and bupropion are similar. ► The impaired beta cell function is mediated by mitochondrial dysfunction. ► If similar effects are seen in vivo, these drugs may increase the risk of diabetes.« less

Cost-effectiveness of antibiotic treatment strategies for community-acquired pneumonia: results from a cluster randomized cross-over trial.

PubMed

van Werkhoven, Cornelis H; Postma, Douwe F; Mangen, Marie-Josee J; Oosterheert, Jan Jelrik; Bonten, Marc J M

2017-01-10

To determine the cost-effectiveness of strategies of preferred antibiotic treatment with beta-lactam/macrolide combination or fluoroquinolone monotherapy compared to beta-lactam monotherapy. Costs and effects were estimated using data from a cluster-randomized cross-over trial of antibiotic treatment strategies, primarily from the reduced third payer perspective (i.e. hospital admission costs). Cost-minimization analysis (CMA) and cost-effectiveness analysis (CEA) were performed using linear mixed models. CMA results were expressed as difference in costs per patient. CEA results were expressed as incremental cost-effectiveness ratios (ICER) showing additional costs per prevented death. A total of 2,283 patients were included. Crude average costs within 90 days from the reduced third payer perspective were €4,294, €4,392, and €4,002 per patient for the beta-lactam monotherapy, beta-lactam/macrolide combination, and fluoroquinolone monotherapy strategy, respectively. CMA results were €106 (95% CI €-697 to €754) for the beta-lactam/macrolide combination strategy and €-278 (95%CI €-991 to €396) for the fluoroquinolone monotherapy strategy, both compared to the beta-lactam monotherapy strategy. The ICER was not statistically significantly different between the strategies. Other perspectives yielded similar results. There were no significant differences in cost-effectiveness of strategies of preferred antibiotic treatment of CAP on non-ICU wards with either beta-lactam monotherapy, beta-lactam/macrolide combination therapy, or fluoroquinolone monotherapy. The trial was registered with ClinicalTrials.gov, number NCT01660204 , on May 2nd, 2012.

The Effect of Planetary Albedo on Solar Orientation of Spacecraft

NASA Technical Reports Server (NTRS)

Fontana, Anthony

1967-01-01

The analytical expression for the solar orientation error caused by planetary albedo is derived. A typical solar sensor output characteristic is assumed and a computer solution to the analytical is obtained. The computer results are presented for a spacecraft in the vicinity of Earth, Venus, Mars, and the Moon. Each planetary body is assumed to be a spherical diffuse reflector with cylindrical shadows and a constant albedo. The data generated herein permit the selection of an appropriate coarse-sensor to fine-sensor switching angle for solar orientation control systems and facilitate the the interpretation of solar-referenced scientific experiment data.

The effect of TGF-beta2 on MMP-2 production and activity in highly metastatic human bladder carcinoma cell line 5637.

PubMed

Dehnavi, Ehsan; Soheili, Zahra-Soheila; Samiei, Shahram; Ataei, Zahra; Aryan, Hajar

2009-06-01

Transforming growth factor-beta (TGF-beta) superfamily regulates matrix metalloproteinases (MMP), which intrinsically regulate various cell behaviors leading to metastasis. We investigated the effect of TGF-beta(2) on MMP-2 regulation in human bladder carcinoma cell line 5637. Zymography, ELISA, and real-time polymerase chain reaction revealed that TGF-beta(2) stimulated MMP-2 production, but the transcription of its gene remained unchanged. Wortmannin could not inhibit MMP-2 secretion and activity and conversely the amount of the protein and its enzymatic activity were increased. These data suggest that TGF-beta(2) increased MMP-2 at the posttranscriptional level and this upregulation was independent of phosphatidylinositol 3-kinase signaling pathway.

Central beta-adrenergic modulation of cognitive flexibility.

PubMed

Beversdorf, David Q; White, Dawn M; Chever, Daquesha C; Hughes, John D; Bornstein, Robert A

2002-12-20

Situational stressors and anxiety impede performance on creativity tests requiring cognitive flexibility. Preliminary research revealed better performance on a task requiring cognitive flexibility, the anagram task, after propranolol (beta-adrenergic antagonist) than after ephedrine (beta-adrenergic agonist). However, propranolol and ephedrine have both peripheral and central beta-adrenergic effects. In order to determine whether noradrenergic modulation of cognitive flexibility is a centrally or peripherally mediated phenomenon, we compared the effects of propranolol (peripheral and central beta-blocker), nadolol (peripheral beta-blocker), and placebo on anagram task performance. Solution latency scores for each subject were compared across the drug conditions. Anagram solution latency scores after propranolol were significantly lower than after nadolol. This suggests a centrally mediated modulatory influence of the noradrenergic system on cognitive flexibility.

cGMP may have trophic effects on beta cell function comparable to those of cAMP, implying a role for high-dose biotin in prevention/treatment of diabetes.

PubMed

McCarty, Mark F

2006-01-01

Incretin hormones have trophic effects on beta cell function that can aid prevention and treatment of diabetes. cAMP is the primary mediator of these effects, and has been shown to potentiate glucose-stimulated insulin secretion, promote proper beta cells differentiation by increasing expression of the crucial transcription factor PDX-1, and prevent beta cell apoptosis. cGMP's role in beta cell function has received far less scrutiny, but there is emerging evidence that it may have a trophic impact on beta cell function analogous to that of cAMP. An increase in plasma glucose boosts beta cell production of cGMP, which acts as a feed-forward mediator to enhance glucose-stimulated insulin secretion. cGMP also has an anti-apoptotic effect in beta cells, and there is now indirect evidence that it promotes expression of PDX-1. Supraphysiological concentrations of biotin can directly activate guanylate cyclase, and there is limited evidence that high intakes of this vitamin can be therapeutically beneficial in diabetics and in rodent models of diabetes. Beneficial effects of cGMP on muscle insulin sensitivity and on control of hepatic glucose output may contribute to biotin's utility in diabetes. The fact that nitric oxide/cGMP exert a range of favorable effects on vascular health should further encourage exploration of biotin's preventive and therapeutic potential. If an appropriate high-dose biotin regimen could achieve a modest systemic increase in guanylate cyclase activity, without entailing unacceptable side effects or risks, such a regimen might have considerable potential for promoting vascular health and preventing or managing diabetes.

Dual beta-lactam therapy for serious Gram-negative infections: is it time to revisit?

PubMed

Rahme, Christine; Butterfield, Jill M; Nicasio, Anthony M; Lodise, Thomas P

2014-12-01

We are rapidly approaching a crisis in antibiotic resistance, particularly among Gram-negative pathogens. This, coupled with the slow development of novel antimicrobial agents, underscores the exigency of redeploying existing antimicrobial agents in innovative ways. One therapeutic approach that was heavily studied in the 1980s but abandoned over time is dual beta-lactam therapy. This article reviews the evidence for combination beta-lactam therapy. Overall, in vitro, animal and clinical data are positive and suggest that beta-lactam combinations produce a synergistic effect against Gram-negative pathogens that rivals that of beta-lactam-aminoglycoside or beta-lactam-fluoroquinolone combination therapy. Although the precise mechanism of improved activity is not completely understood, it is likely attributable to an enhanced affinity to the diverse penicillin-binding proteins found among Gram negatives. The collective data indicate that dual beta-lactam therapy should be revisited for serious Gram-negative infections, especially in light of the near availability of potent beta-lactamase inhibitors, which neutralize the effect of problematic beta-lactamases. Copyright © 2014 Elsevier Inc. All rights reserved.

Adverse CNS-effects of beta-adrenoceptor blockers.

PubMed

Gleiter, C H; Deckert, J

1996-11-01

In 1962 propranolol, the first beta adrenoceptor antagonist (beta blocker), was brought on to the market. There is now a host of different beta blockers available, and these compounds are among the most commonly prescribed groups of drugs. The efficacy of beta blockers has been proven predominantly for the treatment of cardiovascular diseases. Beta blockers are also used for certain types of CNS disorders, such as anxiety disorders, essential tremor and migraine. While low toxicity means that they have a favorable risk-benefit ratio, given the high intensity of use, it is essential to have a comprehensive knowledge of adverse events. Adverse events of beta blockers that can be related to the CNS are quite often neglected, even in textbooks of clinical pharmacology or review articles, and thus often misdiagnosed. The following article, therefore, after summarizing the use of beta blockers for CNS indications, critically reviews the literature on centrally mediated adverse events. General pharmacological features of beta blockers and their molecular basis of action will briefly be addressed to the extent that they are or may become relevant for central nervous pharmacotherapy and side-effects.

Characterization of the Rana grylio virus 3{beta}-hydroxysteroid dehydrogenase and its novel role in suppressing virus-induced cytopathic effect

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun Wei; Huang Youhua; Zhao Zhe

2006-12-08

The 3{beta}-hydroxysteroid dehydrogenase (3{beta}-HSD) isoenzymes play a key role in cellular steroid hormone synthesis. Here, a 3{beta}-HSD gene homolog was cloned from Rana grylio virus (RGV), a member of family Iridoviridae. RGV 3{beta}-HSD gene has 1068 bp, encoding a 355 aa predicted protein. Transcription analyses showed that RGV 3{beta}-HSD gene was transcribed immediate-early during infection from an initiation site 19 nucleotides upstream of the translation start site. Confocal microscopy revealed that the 3{beta}-HSD-EGFP fusion protein was exclusively colocalized with the mitochondria marker (pDsRed2-Mito) in EPC cells. Upon morphological observation and MTT assay, it was revealed that overexpression of RGV 3{beta}-HSDmore » in EPC cells could apparently suppress RGV-induced cytopathic effect (CPE). The present studies indicate that the RGV immediate-early 3{beta}-HSD gene encodes a mitochondria-localized protein, which has a novel role in suppressing virus-induced CPE. All these suggest that RGV 3{beta}-HSD might be a protein involved in host-virus interaction.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heller, René; Zuluaga, Jorge I., E-mail: rheller@physics.mcmaster.ca, E-mail: jzuluaga@fisica.udea.edu.co

With most planets and planetary candidates detected in the stellar habitable zone (HZ) being super-Earths and gas giants rather than Earth-like planets, we naturally wonder if their moons could be habitable. The first detection of such an exomoon has now become feasible, and due to observational biases it will be at least twice as massive as Mars. However, formation models predict that moons can hardly be as massive as Earth. Hence, a giant planet's magnetosphere could be the only possibility for such a moon to be shielded from cosmic and stellar high-energy radiation. Yet, the planetary radiation belt could alsomore » have detrimental effects on exomoon habitability. Here we synthesize models for the evolution of the magnetic environment of giant planets with thresholds from the runaway greenhouse (RG) effect to assess the habitability of exomoons. For modest eccentricities, we find that satellites around Neptune-sized planets in the center of the HZ around K dwarf stars will either be in an RG state and not be habitable, or they will be in wide orbits where they will not be affected by the planetary magnetosphere. Saturn-like planets have stronger fields, and Jupiter-like planets could coat close-in habitable moons soon after formation. Moons at distances between about 5 and 20 planetary radii from a giant planet can be habitable from an illumination and tidal heating point of view, but still the planetary magnetosphere would critically influence their habitability.« less

Characterizing the Physical and Thermal Properties of Planetary Regolith at Low Temperatures

NASA Technical Reports Server (NTRS)

Mantovani, James G.; Swanger, Adam; Townsend, Ivan I., III; Sibille, Laurent; Galloway, Gregory

2014-01-01

The success or failure of in-situ resource utilization for planetary surface exploration-whether for science, colonization, or commercialization-relies heavily on the design and implementation of systems that can effectively process planetary regolith and exploit its potential benefits. In most cases, this challenge necessarily includes the characterization of regolith properties at low temperatures (cryogenic). None of the nearby solar system destinations of interest, such as the moon, Mars and asteroids, possess a sufficient atmosphere to sustain the consistently "high" surface temperatures found on Earth. Therefore, they can experience permanent cryogenic temperatures or dramatic cyclical changes in surface temperature. Characterization of physical properties (e.g., specific heat, thermal and electrical conductivity) over the entire temperature profile is important when planning a mission to a planetary surface; however, the impact on mechanical properties due to the introduction of icy deposits must also be explored in order to devise effective and robust excavation technologies. The Granular Mechanics and Regolith Operations Laboratory and the Cryogenics Test Laboratory at NASA Kennedy Space Center are developing technologies and experimental methods to address these challenges and to aid in the characterization of the physical and mechanical properties of regolith at cryogenic temperatures. This paper will review the current state of knowledge concerning planetary regolith at low temperature, including that of icy regolith, and describe efforts to manipulate icy regolith through novel penetration and excavation techniques.

DOE Office of Scientific and Technical Information (OSTI.GOV)

A Kolyada; C Lee; A De Biasio

{beta}2GPI is a major antigen for autoantibodies associated with antiphospholipid syndrome (APS), an autoimmune disease characterized by thrombosis and recurrent pregnancy loss. Only the dimeric form of {beta}2GPI generated by anti-{beta}2GPI antibodies is pathologically important, in contrast to monomeric {beta}2GPI which is abundant in plasma. We created a dimeric inhibitor, A1-A1, to selectively target {beta}2GPI in {beta}2GPI/antibody complexes. To make this inhibitor, we isolated the first ligand-binding module from ApoER2 (A1) and connected two A1 modules with a flexible linker. A1-A1 interferes with two pathologically important interactions in APS, the binding of {beta}2GPI/antibody complexes with anionic phospholipids and ApoER2. Wemore » compared the efficiency of A1-A1 to monomeric A1 for inhibition of the binding of {beta}2GPI/antibody complexes to anionic phospholipids. We tested the inhibition of {beta}2GPI present in human serum, {beta}2GPI purified from human plasma and the individual domain V of {beta}2GPI. We demonstrated that when {beta}2GPI/antibody complexes are formed, A1-A1 is much more effective than A1 in inhibition of the binding of {beta}2GPI to cardiolipin, regardless of the source of {beta}2GPI. Similarly, A1-A1 strongly inhibits the binding of dimerized domain V of {beta}2GPI to cardiolipin compared to the monomeric A1 inhibitor. In the absence of anti-{beta}2GPI antibodies, both A1-A1 and A1 only weakly inhibit the binding of pathologically inactive monomeric {beta}2GPI to cardiolipin. Our results suggest that the approach of using a dimeric inhibitor to block {beta}2GPI in the pathological multivalent {beta}2GPI/antibody complexes holds significant promise. The novel inhibitor A1-A1 may be a starting point in the development of an effective therapeutic for antiphospholipid syndrome.« less

Effects of administration of beta-carotene, ascorbic acid, persimmons, and pods on antioxidative ability in UV-irradiated ODS rats.

PubMed

Hosotani, Keisuke; Yoshida, Minoru; Kitagawa, Masahiro

2005-07-01

To evaluate the effects of supplementing diets with carotenoid and ascorbic acid (AsA) on the antioxidative ability of Osteogenic Disorder-Shionogi (ODS) rats, we added synthetic beta-carotene (betaC), AsA, and powders of persimmon (Ka) and pods (Po) containing betaC and AsA to the diet and obtained the following results. The urinary 8-hydroxydeoxyguanosine (8-OHdG) concentration was low in the -betaC.AsA and +AsA groups but high in the +betaC.AsA, +Ka, and +Po groups. The thiobarbituric acid-reactive substances (TBARS) in both the liver and skin were higher in the -betaC.AsA group than in the +betaC.AsA group and were low in the +Ka and +Po groups. As antioxidant enzymes, glutathione peroxidase (GSH-Px) activity was high in the +betaC.AsA group, low in the -beta3C.AsA group in both the skin and liver, and also high in the + Ka and +Po group in the liver. Superoxide dismutase (SOD) activity was high in the -betaC.AsA group and low in the +betaC.AsA and +Ka groups in both the skin and liver. Catalase (CAT) activity in the liver was low in the -betaC.AsA, +AsA, and +betaC groups and high in the +betaC.AsA and +Po groups. These results confirmed that the administration of betaC, AsA, and persimmons and pods increases antioxidative ability in the skin and liver of ultraviolet-b(UV-B)-irradiated ODS rats.

Smad7 induces tumorigenicity by blocking TGF-beta-induced growth inhibition and apoptosis.

PubMed

Halder, Sunil K; Beauchamp, R Daniel; Datta, Pran K

2005-07-01

Smad proteins play a key role in the intracellular signaling of the transforming growth factor beta (TGF-beta) superfamily of extracellular polypeptides that initiate signaling to regulate a wide variety of biological processes. The inhibitory Smad, Smad7, has been shown to function as intracellular antagonists of TGF-beta family signaling and is upregulated in several cancers. To determine the effect of Smad7-mediated blockade of TGF-beta signaling, we have stably expressed Smad7 in a TGF-beta-sensitive, well-differentiated, and non-tumorigenic cell line, FET, that was derived from human colon adenocarcinoma. Smad7 inhibits TGF-beta-induced transcriptional responses by blocking complex formation between Smad 2/3 and Smad4. While Smad7 has no effect on TGF-beta-induced activation of p38 MAPK and ERK, it blocks the phosphorylation of Akt by TGF-beta and enhances TGF-beta-induced phosphorylation of c-Jun. FET cells expressing Smad7 show anchorage-independent growth and enhance tumorigenicity in athymic nude mice. Smad7 blocks TGF-beta-induced growth inhibition by preventing TGF-beta-induced G1 arrest. Smad7 inhibits TGF-beta-mediated downregulation of c-Myc, CDK4, and Cyclin D1, and suppresses the expression of p21(Cip1). As a result, Smad7 inhibits TGF-beta-mediated downregulation of Rb phosphorylation. Furthermore, Smad7 inhibits the apoptosis of these cells. Together, Smad7 may increase the tumorigenicity of FET cells by blocking TGF-beta-induced growth inhibition and by inhibiting apoptosis. Thus, this study provides a mechanism by which a portion of human colorectal tumors may become refractory to tumor-suppressive actions of TGF-beta that might result in increased tumorigenicity.

Why Downside Beta Is Better: An Educational Example

ERIC Educational Resources Information Center

Chong, James T.; Jennings, William P.; Phillips, G. Michael

2013-01-01

An educational example is presented that is an effective teaching illustration to help students understand the difference between traditional CAPM beta and downside (or down-market) beta and why downside beta is a superior measure for use in personal financial planning investment policy statements.

Effect of peptide aldehydes with IL-1 beta converting enzyme inhibitory properties on IL-1 alpha and IL-1 beta production in vitro.

PubMed

Németh, K; Patthy, M; Fauszt, I; Széll, E; Székely, J I; Bajusz, S

1995-12-01

Tripeptide and pentapeptide aldehydes as substrate-base inhibitors of cysteine proteases were designed in our laboratory for the inhibition of interleukin-1 beta converting enzyme (ICE), a recently described cysteine protease responsible for the processing of IL-1 beta. The biological effectivity of the peptide aldehydes was studied in THP-1 cells and human whole blood. The released and cell-associated IL-1 alpha and IL-1 beta levels were determined by ELISA from the supernatants and cell lysates, respectively. The total IL-1 like bioactivity was assayed by the D10 G4.1 cell proliferation method. The tripeptide aldehyde (Z-Val-His-Asp-H) and pentapeptide aldehyde (Eoc-Ala-Tyr-Val-Ala-Asp-H) significantly reduced IL-1 beta levels in the supernatants in relatively high concentrations (10-100 microM), but the IL-1 alpha release was unaffected by these peptides. However, a considerable decrease in the cell-associated IL-1 beta and IL-1 alpha levels was observed. N-terminal extension of the tripeptide aldehyde yielded even more potent inhibitors. Amino acid substitution at the P2 position did not cause considerable changes in the inhibitory activity. The peptide aldehydes suppressed the IL-1 beta production in a reversible manner, whereas dexamethasone, a glucocorticoid, had a prolonged inhibitory effect. The inhibitory effect of these peptides and that of dexamethasone appeared to be additive. These findings indicate that these peptide aldehydes might be used as IL-beta inhibitory agents in experimental models in which IL-1 beta is a key mediator or ICE is implicated.

Acute effect of ephedrine on 24-h energy balance

NASA Technical Reports Server (NTRS)

Shannon, J. R.; Gottesdiener, K.; Jordan, J.; Chen, K.; Flattery, S.; Larson, P. J.; Candelore, M. R.; Gertz, B.; Robertson, D.; Sun, M.

1999-01-01

Ephedrine is used to help achieve weight control. Data on its true efficacy and mechanisms in altering energy balance in human subjects are limited. We aimed to determine the acute effect of ephedrine on 24-h energy expenditure, mechanical work and urinary catecholamines in a double-blind, randomized, placebo-controlled, two-period crossover study. Ten healthy volunteers were given ephedrine (50 mg) or placebo thrice daily during each of two 24-h periods (ephedrine and placebo) in a whole-room indirect calorimeter, which accurately measures minute-by-minute energy expenditure and mechanical work. Measurements were taken of 24-h energy expenditure, mechanical work, urinary catecholamines and binding of (+/-)ephedrine in vitro to human beta1-, beta2- and beta3-adrenoreceptors. Twenty-four-hour energy expenditure was 3.6% greater (8965+/-1301 versus 8648+/-1347 kJ, P<0.05) with ephedrine than with placebo, but mechanical work was not different between the ephedrine and placebo periods. Noradrenaline excretion was lower with ephedrine (0.032+/-0.011 microg/mg creatinine) compared with placebo (0.044+/-0.012 microg/mg creatinine) (P<0.05). (+/-)Ephedrine is a relatively weak partial agonist of human beta1- and beta2-adrenoreceptors, and had no detectable activity at human beta3-adrenoreceptors. Ephedrine (50 mg thrice daily) modestly increases energy expenditure in normal human subjects. A lack of binding of ephedrine to beta3-adrenoreceptors and the observed decrease in urinary noradrenaline during ephedrine treatment suggest that the thermogenic effect of ephedrine results from direct beta1-/beta2-adrenoreceptor agonism. An indirect beta3-adrenergic effect through the release of noradrenaline seems unlikely as urinary noradrenaline decreased significantly with ephedrine.

Effects of chondroitin sulfate and interleukin-1beta on human chondrocyte cultures exposed to pressurization: a biochemical and morphological study.

PubMed

Nerucci, F; Fioravanti, A; Cicero, M R; Collodel, G; Marcolongo, R

2000-07-01

Objective This study investigated the in vitro effects of chondroitin sulfate (CS) on human articular chondrocytes cultivated in the presence or in the absence of interleukin-1beta (IL-1beta) during 10 days of culture with and without pressurization cycles. Design The effects of CS (10 and 100 microg/ml) with and without IL-1beta were assessed in the culture medium of cells exposed to pressurization cycles in the form of synusoidal waves (minimum pressure 1 Mpa, maximum pressure 5 Mpa) and a frequency of 0.25 Hz for 3 h by immunoenzymatic method on microplates for the quantitative measurement of human proteoglycans (PG). On the 4th and 10th day of culture the cells were used for morphological analysis by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Results The presence of IL-1beta determines a significant decrease in PG concentration measured in the culture medium. When the cells are cultured in the presence of IL-1beta and CS, a statistically significant restoration of PG levels is observed. Under pressurization conditions, we observed that PG concentration in the medium of cells presents a significant increase at baseline conditions, in the presence of IL-1beta+CS10 and IL-1beta+CS100, but not with IL-1beta alone. The results concerning metabolic evaluation are confirmed by the morphologic findings obtained by TEM and SEM. Conclusions These in vitro studies confirm the protective role of CS, which counteracts the IL-1beta induced effects and they confirm the importance of pressure on chondrocyte metabolism and morphology.

The beta2- and beta3-adrenoceptor-mediated relaxation induced by fenoterol in guinea pig taenia caecum.

PubMed

Akimoto, Yurie; Horinouchi, Takahiro; Tanaka, Yoshio; Koike, Katsuo

2002-10-01

Fenoterol, a beta2-adrenoceptor selective agonist, belongs to the arylethanolamine class. To understand the receptor subtypes responsible for beta-adrenoceptor-mediated relaxation of guinea pig taenia caecum, we investigated the effect of fenoterol. Fenoterol caused concentration-dependent relaxation of the guinea pig taenia caecum. Propranolol, bupranolol and butoxamine produced shifts of the concentration-response curve for fenoterol. Schild regression analyses carried out for propranolol, butoxamine and bupranolol against fenoterol gave pA2 values of 8.41, 6.33 and 8.44, respectively. However, in the presence of 3 x 10(-4) M atenolol, 10(-4) M butoxamine and 10(-6) M phentolamine to block the beta1-, beta2- and a-adrenoceptor effects, respectively, Schild regression analysis carried out for bupranolol against fenoterol gave pA2 values of 5.80. These results suggest that the relaxant response to fenoterol in the guinea pig taenia caecum is mediated by both the beta2- and the beta3-adrenoceptors.

Ways that our Solar System helps us understand the formation of other planetary systems and ways that it doesn't

NASA Technical Reports Server (NTRS)

Wetherill, G. W.

1996-01-01

Models of planetary formation can be tested by comparison of their ability to predict features of our Solar System in a consistent way, and then extrapolated to other hypothetical planetary systems by different choice of parameters. When this is done, it is found that the resulting systems are insensitive to direct effects of the mass of the star, but do strongly depend on the properties of the disk, principally its surface density. Major uncertainty results from lack of an adequate theoretical model that predicts the existence, size, and distribution of analogs of our Solar System, particularly the gas giants Jupiter and Saturn. Nevertheless, reasons can be found for expecting that planetary systems, including those containing biologically habitable planets similar to Earth, may be abundant in the Galaxy and Universe.

Ways that our Solar System helps us understand the formation of other planetary systems and ways that it doesn't.

PubMed

Wetherill, G W

1996-01-01

Models of planetary formation can be tested by comparison of their ability to predict features of our Solar System in a consistent way, and then extrapolated to other hypothetical planetary systems by different choice of parameters. When this is done, it is found that the resulting systems are insensitive to direct effects of the mass of the star, but do strongly depend on the properties of the disk, principally its surface density. Major uncertainty results from lack of an adequate theoretical model that predicts the existence, size, and distribution of analogs of our Solar System, particularly the gas giants Jupiter and Saturn. Nevertheless, reasons can be found for expecting that planetary systems, including those containing biologically habitable planets similar to Earth, may be abundant in the Galaxy and Universe.

Frost grain size metamorphism - Implications for remote sensing of planetary surfaces

NASA Technical Reports Server (NTRS)

Clark, R. N.; Fanale, F. P.; Zent, A. P.

1983-01-01

The effective grain size of a material on a planetary surface affects the strength of absorption features observed in the reflectance of a particulate surface. In the case of a planetary surface containing volatile ices, the absorption characteristics can change in connection with processes leading to a change in the grain size of the material. The present investigation is concerned with an evaluation regarding the occurrence of such processes and the implications for remote sensing applications. It is found that quantitative modeling of the kinetics of grain growth and destruction by thermal and nonthermal processes can provide a means to reconcile apparent optical paths in the volatile portions of planetary surfaces with the physical history of those surfaces. Attention is also given to conditions in the case of the Pluto/Triton system, Uranus and Saturnian satellites, and the Galilean system.

From the rat to the beta cell: a fast and effective technique of separation of Langerhans islets and direct purification of pancreatic beta cells.

PubMed

Tamagno, Gianluca; Vigolo, Simonetta; Olivieri, Massimiliano; Martini, Chiara; De Carlo, Eugenio

2014-01-01

Isolated Langerhans islets represent a useful model for the study of the endocrine pancreas. The possibility to purify pancreatic beta cells from a mixed Langerhans islet cell population may lead towards a dedicated focus on beta cell research. We describe an effective and rapid immunomagnetic technique for the direct purification of beta cells from isolated Langerhans islets of rat. After the sacrifice of the rat, the Langerhans islets were separated by ductal injection of the pancreas with collagenase, altered to a mixed Langerhans islet cell population and incubated with conditioned immunomagnetic beads targeted to the beta cell surface. The beads were previously coated with a specific antibody against the surface of the beta cell, namely K14D10. The suspension of mixed Langerhans islet cells and immunomagnetic K14D10-conditioned beads was pelleted by a magnetic particle concentrator to isolate the bead-bound cells, which were finally suspended in a culture medium. The purified cells were immunoreactive for insulin and no glucagon-positive cells were detected at immunocytochemistry. Real Time PCR confirmed the purification of the pancreatic beta cells. This immunomagnetic technique allows a rapid, effective and consistent purification of beta cells from isolated Langerhans islets in a direct manner by conditioning the immunomagnetic beads only. This technique is easy, fast and reproducible. It promises to be a reliable method for providing purified beta cells for in vitro research.

On the role of transforming growth factor-beta in the growth inhibitory effects of retinoic acid in human pancreatic cancer cells.

PubMed

Singh, Brahmchetna; Murphy, Richard F; Ding, Xian-Zhong; Roginsky, Alexandra B; Bell, Richard H; Adrian, Thomas E

2007-12-24

Retinoids are potent growth inhibitory and differentiating agents in a variety of cancer cell types. We have shown that retinoids induce growth arrest in all pancreatic cancer cell lines studied, regardless of their p53 and differentiation status. However, the mechanism of growth inhibition is not known. Since TGF-beta2 is markedly induced by retinoids in other cancers and mediates MUC4 expression in pancreatic cancer cells, we investigated the role of TGF-beta in retinoic acid-mediated growth inhibition in pancreatic cancer cells. Retinoic acid markedly inhibited proliferation of two cell lines (Capan-2 and Hs766T) in a concentration and time-dependent manner. Retinoic acid increased TGF-beta2 mRNA content and secretion of the active and latent forms of TGF-beta2 (measured by ELISA and bioassay). The concentrations of active and TGF-beta2 secreted in response to 0.1 - 10 muM retinoic acid were between 1-5 pM. TGF-beta2 concentrations within this range also inhibited proliferation. A TGF-beta neutralizing antibody blocked the growth inhibitory effects of retinoic acid in Capan-2 cells and partially inhibitory the effects in Hs766T cells. These findings indicate that TGF-beta can cause growth inhibition of pancreatic cancer cells, in a p53-independent manner. Furthermore, it demonstrates the fundamental role of TGF-beta in growth inhibition in response to retinoic acid treatment is preserved in vitro.

Effects of air pollution on thermal structure and dispersion in an urban planetary boundary layer

NASA Technical Reports Server (NTRS)

Viskanta, R.; Johnson, R. O.; Bergstrom, R. W.

1977-01-01

The short-term effects of urbanization and air pollution on the transport processes in the urban planetary boundary layer (PBL) are studied. The investigation makes use of an unsteady two-dimensional transport model which has been developed by Viskanta et al., (1976). The model predicts pollutant concentrations and temperature in the PBL. The potential effects of urbanization and air pollution on the thermal structure in the urban PBL are considered, taking into account the results of numerical simulations modeling the St. Louis, Missouri metropolitan area.

The Twenty-Fifth Lunar and Planetary Science Conference. Part 1: A-G

NASA Technical Reports Server (NTRS)

1994-01-01

Papers from the conference are presented, and the topics covered include the following: planetary geology, meteorites, planetary composition, meteoritic composition, planetary craters, lunar craters, meteorite craters, petrology, petrography, volcanology, planetary crusts, geochronology, geomorphism, mineralogy, lithology, planetary atmospheres, impact melts, volcanoes, planetary evolution, tectonics, planetary mapping, asteroids, comets, lunar soil, lunar rocks, lunar geology, metamorphism, chemical composition, meteorite craters, and planetary mantles.

Effects of Asp-179 mutations in TEMpUC19 beta-lactamase on susceptibility to beta-lactams.

PubMed Central

Vakulenko, S B; Tóth, M; Taibi, P; Mobashery, S; Lerner, S A

1995-01-01

To examine the effect of disruption of the salt bridge (between Arg-164 and Asp-179 [numbering of Ambler et al. (Biochem J. 267:269-272, 1991)]) that anchors the conserved omega-loop in class A beta-lactamases, we obtained mutant enzymes with each of the 19 other amino acid residues replacing Asp-179 in the TEM beta-lactamase encoded by pUC19 and studied the level of resistance to various beta-lactams conferred by each enzyme. All mutations of Asp-179 compromised the level of resistance to ampicillin, but most of them enhanced resistance to ceftazidime. In contrast, mutations of Asp-179 generally impaired the low levels of resistance to cefepime and aztreonam. One might expect to find clinical isolates with mutant TEM beta-lactamases with replacements of Asp-179 that express an expanded spectrum of resistance to beta-lactams including ceftazidime. PMID:7486939

Anti-aggregatory effect of cyclodextrins in the refolding process of recombinant growth hormones from Escherichia coli inclusion bodies.

PubMed

Bajorunaite, Egle; Cirkovas, Andrejus; Radzevicius, Kostas; Larsen, Kim Lambertsen; Sereikaite, Jolanta; Bumelis, Vladas-Algirdas

2009-06-01

Cyclodextrins with different ring size and ring substituents were tested for recombinant mink and porcine growth hormones aggregation suppression in the refolding process from Escherichia coli inclusion bodies. Methyl-beta-cyclodextrin and 2-hydroxypropyl-beta-cyclodextrin show a positive effect on the aggregation suppression of both proteins. The influence of different methyl-beta-cyclodextrin and 2-hydroxypropyl-beta-cyclodextrin concentrations on the renaturation yield of both growth hormones was investigated. Moreover, methyl-beta-cyclodextrin and 2-hydroxypropyl-beta-cyclodextrin suppress not only folding-related, but also temperature-related aggregates formation of both proteins. Circular dichroism experiments (monitoring of protein solution turbidity by registering high tension voltage) showed that the onset temperature of aggregation of both growth hormones increased with increasing 2-hydroxypropyl-beta-cyclodextrin concentration. In conclusion, cyclodextrins have perspectives in biotechnology of veterinary growth hormones not only for protein production, but also for its storage.

[BiOBr promoted the photocatalytic degradation of beta-cypermethrin under visible light].

PubMed

Peng, Yi-Zhu; Zhao, Xiao-Rong; Jia, Man-Ke; Zhou, Wei; Huang, Ying-Ping

2014-05-01

As a visible light photocatalyst, bismuth oxide bromide (BiOBr) was used to catalyze the degradation of beta-cypermethrin (beta-CP). The photocatalytic degradation of beta-CP was studied with gas chromatography. The effects of pH and catalyst dose on the photocatalytic degradation efficiency were discussed. The oxidization and mineralization of beta-CP were detected by chemical oxygen demand (COD) analyzer. The results showed that beta-CP could be effectively degraded under visible light irradiation using BiOBr as the catalyst. At given experimental conditions, the degradation rate of beta-CP reached 94. 68% after 10 h and the COD removal rate reached 67. 99% after 36 h. With the increase of catalyst dose and pH value, the degradation rate was improved. The photocatalytic oxidation species was determined by peroxidase method and terephthalic acid fluorescence method. These results suggested that the photocatalytic degradation process mainly referred to hydroxyl radical ( OH) mechanism.

Effect of SiO2/Al2O3 Ratio on Micro-Mesopore Formation for Pt/Beta-MCM-41 via NaOH Treatment and the Catalytic Performance in N-heptane Hydro isomerization

NASA Astrophysics Data System (ADS)

Gao, Li; Shi, Zhiyuan; Liu, Yingming; Zhao, Yuanshou; Liu, Qinghua; Xu, Chengguo; Bai, Peng; Yan, Zifeng

2018-01-01

Micro-mesoporous composite material Beta-MCM-41(BM) were hydrothermally synthesized by treating parent beta with molar SiO2/Al2O3 ratios of 12.5, 20 and 30 as precursors. The influence of SiO2/Al2O3 ratio of zeolite beta on effective micro-mesoporous composite formation was studied by investigating the crystallinity, morphology, chemical composition, acidity and textural property of Beta-MCM-41 through XRD, nitrogen adsorption, SEM, TEM, NH3-TPD, FTIR and Pyridine-FTIR. The catalytic performance was evaluated in terms of n-heptane hydro isomerization. The results demonstrated that Beta-MCM-41 supported Pt catalysts showed higher selectivity to isoheptanes than Pt/Beta. It was attributed to the superiorities of the pore structure and mesoporous accelerated the diffusion of larger molecules of isoheptanes.

The antifibrotic effects of TGF-{beta}1 siRNA on hepatic fibrosis in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lang, Qing; Liu, Qi; Xu, Ning

2011-06-10

Highlights: {yields} We constructed CCL4 induced liver fibrosis model successfully. {yields} We proofed that the TGF-{beta}1 siRNA had a definite therapy effect to CCL4 induced liver fibrosis. {yields} The therapy effect of TGF-{beta}1 siRNA had dose-dependent. -- Abstract: Background/aims: Hepatic fibrosis results from the excessive secretion of matrix proteins by hepatic stellate cells (HSCs), which proliferate during fibrotic liver injury. Transforming growth factor (TGF)-{beta}1 is the dominant stimulus for extracellular matrix (ECM) production by stellate cells. Our study was designed to investigate the antifibrotic effects of using short interference RNA (siRNA) to target TGF-{beta}1 in hepatic fibrosis and its mechanismmore » in rats exposed to a high-fat diet and carbon tetrachloride (CCL4). Methods: A total of 40 healthy, male SD (Sprague-Dawley) rats were randomly divided into five even groups containing of eight rats each: normal group, model group, TGF-{beta}1 siRNA 0.125 mg/kg treatment group, TGF-{beta}1 siRNA 0.25 mg/kg treatment group and TGF-{beta}1 siRNA negative control group (0.25 mg/kg). CCL4 and a high-fat diet were used for 8 weeks to induce hepatic fibrosis. All the rats were then sacrificed to collect liver tissue samples. A portion of the liver samples were soaked in formalin for Hematoxylin-Eosin staining, classifying the degree of liver fibrosis, and detecting the expression of type I and III collagen and TGF-{beta}1; the remaining liver samples were stored in liquid nitrogen to be used for detecting TGF-{beta}1 by Western blotting and for measuring the mRNA expression of type I and III collagen and TGF-{beta}1 by quantitative real-time polymerase chain reaction. Results: Comparing the TGF-{beta}1 siRNA 0.25 mg/kg treatment group to the model group, the TGF-{beta}1 siRNA negative control group and the TGF-{beta}1 siRNA 0.125 mg/kg treatment group showed significantly reduced levels of pathological changes, protein expression and the mRNA expression of TGF-{beta}1, type I collagen and type III collagen (P < 0.01). Conclusions: Using siRNA to target TGF-{beta}1 can inhibit the expression of TGF-{beta}1 and attenuate rat hepatic fibrosis induced by a high-fat diet and CCL4. A possible mechanism is through the down-regulation of TGF-{beta}1 expression, which could inhibit HSC activation, as well as the proliferation and collagen production of collagen reducing, so that collagen deposition in the liver is reduced.« less

The Importance of Planetary Rotation Period for Ocean Heat Transport

PubMed Central

Stevens, D.; Joshi, M.

2014-01-01

Abstract The climate and, hence, potential habitability of a planet crucially depends on how its atmospheric and ocean circulation transports heat from warmer to cooler regions. However, previous studies of planetary climate have concentrated on modeling the dynamics of atmospheres, while dramatically simplifying the treatment of oceans, which neglects or misrepresents the effect of the ocean in the total heat transport. Even the majority of studies with a dynamic ocean have used a simple so-called aquaplanet that has no continental barriers, which is a configuration that dramatically changes the ocean dynamics. Here, the significance of the response of poleward ocean heat transport to planetary rotation period is shown with a simple meridional barrier—the simplest representation of any continental configuration. The poleward ocean heat transport increases significantly as the planetary rotation period is increased. The peak heat transport more than doubles when the rotation period is increased by a factor of ten. There are also significant changes to ocean temperature at depth, with implications for the carbon cycle. There is strong agreement between the model results and a scale analysis of the governing equations. This result highlights the importance of both planetary rotation period and the ocean circulation when considering planetary habitability. Key Words: Exoplanet—Oceans—Rotation—Climate—Habitability. Astrobiology 14, 645–650. PMID:25041658

Comparative Climates of the Trappist-1 Planetary System: Results from a Simple Climate-vegetation Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alberti, Tommaso; Carbone, Vincenzo; Lepreti, Fabio

The recent discovery of the planetary system hosted by the ultracool dwarf star TRAPPIST-1 could open new paths for investigations of the planetary climates of Earth-sized exoplanets, their atmospheres, and their possible habitability. In this paper, we use a simple climate-vegetation energy-balance model to study the climate of the seven TRAPPIST-1 planets and the climate dependence on various factors: the global albedo, the fraction of vegetation that could cover their surfaces, and the different greenhouse conditions. The model allows us to investigate whether liquid water could be maintained on the planetary surfaces (i.e., by defining a “surface water zone (SWZ)”)more » in different planetary conditions, with or without the presence of a greenhouse effect. It is shown that planet TRAPPIST-1d seems to be the most stable from an Earth-like perspective, since it resides in the SWZ for a wide range of reasonable values of the model parameters. Moreover, according to the model, outer planets (f, g, and h) cannot host liquid water on their surfaces, even with Earth-like conditions, entering a snowball state. Although very simple, the model allows us to extract the main features of the TRAPPIST-1 planetary climates.« less

Research of Planetary Gear Fault Diagnosis Based on Permutation Entropy of CEEMDAN and ANFIS

PubMed Central

Kuai, Moshen; Cheng, Gang; Li, Yong

2018-01-01

For planetary gear has the characteristics of small volume, light weight and large transmission ratio, it is widely used in high speed and high power mechanical system. Poor working conditions result in frequent failures of planetary gear. A method is proposed for diagnosing faults in planetary gear based on permutation entropy of Complete Ensemble Empirical Mode Decomposition with Adaptive Noise (CEEMDAN) Adaptive Neuro-fuzzy Inference System (ANFIS) in this paper. The original signal is decomposed into 6 intrinsic mode functions (IMF) and residual components by CEEMDAN. Since the IMF contains the main characteristic information of planetary gear faults, time complexity of IMFs are reflected by permutation entropies to quantify the fault features. The permutation entropies of each IMF component are defined as the input of ANFIS, and its parameters and membership functions are adaptively adjusted according to training samples. Finally, the fuzzy inference rules are determined, and the optimal ANFIS is obtained. The overall recognition rate of the test sample used for ANFIS is 90%, and the recognition rate of gear with one missing tooth is relatively high. The recognition rates of different fault gears based on the method can also achieve better results. Therefore, the proposed method can be applied to planetary gear fault diagnosis effectively. PMID:29510569

Research of Planetary Gear Fault Diagnosis Based on Permutation Entropy of CEEMDAN and ANFIS.

PubMed

Kuai, Moshen; Cheng, Gang; Pang, Yusong; Li, Yong

2018-03-05

For planetary gear has the characteristics of small volume, light weight and large transmission ratio, it is widely used in high speed and high power mechanical system. Poor working conditions result in frequent failures of planetary gear. A method is proposed for diagnosing faults in planetary gear based on permutation entropy of Complete Ensemble Empirical Mode Decomposition with Adaptive Noise (CEEMDAN) Adaptive Neuro-fuzzy Inference System (ANFIS) in this paper. The original signal is decomposed into 6 intrinsic mode functions (IMF) and residual components by CEEMDAN. Since the IMF contains the main characteristic information of planetary gear faults, time complexity of IMFs are reflected by permutation entropies to quantify the fault features. The permutation entropies of each IMF component are defined as the input of ANFIS, and its parameters and membership functions are adaptively adjusted according to training samples. Finally, the fuzzy inference rules are determined, and the optimal ANFIS is obtained. The overall recognition rate of the test sample used for ANFIS is 90%, and the recognition rate of gear with one missing tooth is relatively high. The recognition rates of different fault gears based on the method can also achieve better results. Therefore, the proposed method can be applied to planetary gear fault diagnosis effectively.

Planetary Protection Considerations for Life Support and Habitation Systems

NASA Technical Reports Server (NTRS)

Barta, Daniel J.; Hogan, John A.

2010-01-01

Life support systems for future human missions beyond low Earth orbit may include a combination of existing hardware components and advanced technologies. Discipline areas for technology development include atmosphere revitalization, water recovery, solid waste management, crew accommodations, food production, thermal systems, environmental monitoring, fire protection and radiation protection. Life support systems will be influenced by in situ resource utilization (ISRU), crew mobility and the degree of extravehicular activity. Planetary protection represents an additional set of requirements that technology developers have generally not considered. Planetary protection guidelines will affect the kind of operations, processes, and functions that can take place during future exploration missions, including venting and discharge of liquids and solids, ejection of wastes, use of ISRU, requirements for cabin atmospheric trace contaminant concentrations, cabin leakage and restrictions on what materials, organisms, and technologies that may be brought on missions. Compliance with planetary protection requirements may drive development of new capabilities or processes (e.g. in situ sterilization, waste containment, contaminant measurement) and limit or prohibit certain kinds of operations or processes (e.g. unfiltered venting). Ultimately, there will be an effect on mission costs, including the mission trade space. Planetary protection requirements need to be considered early in technology development programs. It is expected that planetary protection will have a major impact on technology selection for future missions.

Review of Antibiotic and Non-Antibiotic Properties of Beta-lactam Molecules.

PubMed

Ochoa-Aguilar, Abraham; Ventura-Martinez, Rosa; Sotomayor-Sobrino, Marco Antonio; Gómez, Claudia; Morales-Espinoza, María del Rosario

2016-01-01

Beta-lactam molecules are a family of drugs commonly used for their antibiotic properties; however, recent research has shown that several members of this group present a large number of other effects such as neuroprotective, antioxidant, analgesic or immunomodulatory capabilities. These properties have been used in both preclinical and clinical studies in different diseases such as hypoxic neuronal damage or acute and chronic pain. The present work briefly reviews the antibiotic effect of these molecules, and will then focus specially on the non-antibiotic effects of three beta-lactam subfamilies: penicillins, cephalosporins and beta lactamase inhibitors, each of which have different molecular structure and pharmacokinetics and therefore have several potential clinical applications. A thorough search of bibliographic databases for peer-reviewed research was performed including only classic experiments or high quality reviews for the antibiotic mechanisms of beta-lactam molecules and only experimental research papers where included when the non-antibiotic properties of these molecules were searched. Only published articles from indexed journals were included. Quality of retrieved papers was assessed using standard tools. The characteristics of screened papers were described and findings of included studies were contextualized to either a mechanistic or a clinical framework. Seventy-eight papers were included in the review; the majority (56) were relative to the non-antibiotic properties of beta-lactam molecules. The non-antibiotic effects reviewed were divided accordingly to the amount of information available for each one. Twelve papers outlined the epileptogenic effects induced by beta-lactam molecules administration; these included both clinical and basic research as well as probable mechanistic explanations. Eighteen papers described a potential neuroprotective effect, mostly in basic in vitro and in vivo experiments. Analgesic properties where identified in twelve papers and basic research was described alongside with both experimental and serendipic clinical findings. Seven papers described a down-regulation effect exerted by beta-lactam molecules administration in different addiction animal models. Finally other effects such as penile erection, dopamine release facilitation and anti-neoplasic effects where described from seven papers. The findings of this review show that beta-lactam molecules may induce several effects, which may be clinically relevant in a lot of different diseases. This paper is, to our knowledge, the first comprehensive review of the non-antibiotic effects shown by beta-lactam molecules and may help increase the interest in this field, which may result in a direct translation of this effects to a clinical context.

Overview of current capabilities and research and technology developments for planetary protection

NASA Astrophysics Data System (ADS)

Frick, Andreas; Mogul, Rakesh; Stabekis, Pericles; Conley, Catharine A.; Ehrenfreund, Pascale

2014-07-01

The pace of scientific exploration of our solar system provides ever-increasing insights into potentially habitable environments, and associated concerns for their contamination by Earth organisms. Biological and organic-chemical contamination has been extensively considered by the COSPAR Panel on Planetary Protection (PPP) and has resulted in the internationally recognized regulations to which spacefaring nations adhere, and which have been in place for 40 years. The only successful Mars lander missions with system-level “sterilization” were the Viking landers in the 1970s. Since then different cleanliness requirements have been applied to spacecraft based on their destination, mission type, and scientific objectives. The Planetary Protection Subcommittee of the NASA Advisory Council has noted that a strategic Research & Technology Development (R&TD) roadmap would be very beneficial to encourage the timely availability of effective tools and methodologies to implement planetary protection requirements. New research avenues in planetary protection for ambitious future exploration missions can best be served by developing an over-arching program that integrates capability-driven developments with mission-driven implementation efforts. This paper analyzes the current status concerning microbial reduction and cleaning methods, recontamination control and bio-barriers, operational analysis methods, and addresses concepts for human exploration. Crosscutting research and support activities are discussed and a rationale for a Strategic Planetary Protection R&TD Roadmap is outlined. Such a roadmap for planetary protection provides a forum for strategic planning and will help to enable the next phases of solar system exploration.

Exploration Consequences of Particle Radiation Environments at Airless Planetary Surfaces: Lessons Learned at the Moon by LRO/CRaTER and Scaling to Other Solar System Objects

NASA Astrophysics Data System (ADS)

Spence, H. E.

2017-12-01

We examine and compare the energetic particle ionizing radiation environments at airless planetary surfaces throughout the solar system. Energetic charged particles fill interplanetary space and bathe the environments of planetary objects with a ceaseless source of sometimes powerful yet ever-present ionizing radiation. In turn, these charged particles interact with planetary bodies in various ways, depending upon the properties of the body as well as upon the nature of the charged particles themselves. The Cosmic Ray Telescope for the Effects of Radiation (CRaTER) on the Lunar Reconnaisance Orbiter (LRO), launched in 2009, continues to provide new insights into the ways by which the lunar surface is influenced by these energetic particles. In this presentation, we briefly review some of these mechanisms and how they operate at the Moon, and then compare and contrast the radiation environments at other atmospherereless planetary objects within our solar system that are potential future human exploration targets. In particular, we explore two primary sources of ionizing radiation, galactic cosmic rays (GCR) and solar energetic particles (SEP), in the environments of planetary objects that have weak or absent atmospheres and intrinsic magnetic fields. We motivate the use of simplified scaling relationships with heliocentric distance to estimate their intensity, which then serves as a basis for estimating the relative importance of various energetic particle and planetary surface physical interactions, in the context of humankind's expanding explorations beyond low-Earth orbit.

Architectures of planetary systems and implications for their formation.

PubMed

Ford, Eric B

2014-09-02

Doppler planet searches revealed that many giant planets orbit close to their host star or in highly eccentric orbits. These and subsequent observations inspired new theories of planet formation that invoke gravitation interactions in multiple planet systems to explain the excitation of orbital eccentricities and even short-period giant planets. Recently, NASA's Kepler mission has identified over 300 systems with multiple transiting planet candidates, including many potentially rocky planets. Most of these systems include multiple planets with closely spaced orbits and sizes between that of Earth and Neptune. These systems represent yet another new and unexpected class of planetary systems and provide an opportunity to test the theories developed to explain the properties of giant exoplanets. Presently, we have limited knowledge about such planetary systems, mostly about their sizes and orbital periods. With the advent of long-term, nearly continuous monitoring by Kepler, the method of transit timing variations (TTVs) has blossomed as a new technique for characterizing the gravitational effects of mutual planetary perturbations for hundreds of planets. TTVs can provide precise, but complex, constraints on planetary masses, densities, and orbits, even for planetary systems with faint host stars. In the coming years, astronomers will translate TTV observations into increasingly powerful constraints on the formation and orbital evolution of planetary systems with low-mass planets. Between TTVs, improved Doppler surveys, high-contrast imaging campaigns, and microlensing surveys, astronomers can look forward to a much better understanding of planet formation in the coming decade.

Magnetised winds and their influence in the escaping upper atmosphere of HD 209458b

NASA Astrophysics Data System (ADS)

D'Angelo, Carolina Villarreal; Esquivel, Alejandro; Schneiter, Matías; Sgró, Mario Agustín

2018-06-01

Lyman α observations during an exoplanet transit have proved to be very useful to study the interaction between the stellar wind and the planetary atmosphere. They have been extensively used to constrain planetary system parameters that are not directly observed, such as the planetary mass loss rate. In this way, Ly α observations can be a powerful tool to infer the existence of a planetary magnetic field, since it is expected that the latter will affect the escaping planetary material. To explore the effect that magnetic fields have on the Ly α absorption of HD 209458b, we run a set of 3D MHD simulations including dipolar magnetic fields for the planet and the star. We assume values for the surface magnetic field at the poles of the planet in the range of [0-5] G, and from 1 to 5 G at the poles of the star. Our models also include collisional and photo-ionisation, radiative recombination, and an approximation for the radiation pressure. Our results show that the magnetic field of the planet and the star change the shape of the Ly α absorption profile, since it controls the extent of the planetary magnetosphere and the amount of neutral material inside it. The model that best reproduces the absorption observed in HD 209458b (with canonical values for the stellar wind parameters) corresponds to a dipole planetary field of ≲ 1 gauss at the poles.

Architectures of planetary systems and implications for their formation

PubMed Central

Ford, Eric B.

2014-01-01

Doppler planet searches revealed that many giant planets orbit close to their host star or in highly eccentric orbits. These and subsequent observations inspired new theories of planet formation that invoke gravitation interactions in multiple planet systems to explain the excitation of orbital eccentricities and even short-period giant planets. Recently, NASA’s Kepler mission has identified over 300 systems with multiple transiting planet candidates, including many potentially rocky planets. Most of these systems include multiple planets with closely spaced orbits and sizes between that of Earth and Neptune. These systems represent yet another new and unexpected class of planetary systems and provide an opportunity to test the theories developed to explain the properties of giant exoplanets. Presently, we have limited knowledge about such planetary systems, mostly about their sizes and orbital periods. With the advent of long-term, nearly continuous monitoring by Kepler, the method of transit timing variations (TTVs) has blossomed as a new technique for characterizing the gravitational effects of mutual planetary perturbations for hundreds of planets. TTVs can provide precise, but complex, constraints on planetary masses, densities, and orbits, even for planetary systems with faint host stars. In the coming years, astronomers will translate TTV observations into increasingly powerful constraints on the formation and orbital evolution of planetary systems with low-mass planets. Between TTVs, improved Doppler surveys, high-contrast imaging campaigns, and microlensing surveys, astronomers can look forward to a much better understanding of planet formation in the coming decade. PMID:24778212

Twenty-Fourth Lunar and Planetary Science Conference. Part 2: G-M

NASA Technical Reports Server (NTRS)

1993-01-01

The topics covered include the following: meteorites, meteoritic composition, geochemistry, planetary geology, planetary composition, planetary craters, the Moon, Mars, Venus, asteroids, planetary atmospheres, meteorite craters, space exploration, lunar geology, planetary surfaces, lunar surface, lunar rocks, lunar soil, planetary atmospheres, lunar atmosphere, lunar exploration, space missions, geomorphology, lithology, petrology, petrography, planetary evolution, Earth surface, planetary surfaces, volcanology, volcanos, lava, magma, mineralogy, minerals, ejecta, impact damage, meteoritic damage, tectonics, etc.

Twenty-Fourth Lunar and Planetary Science Conference. Part 3: N-Z

NASA Technical Reports Server (NTRS)

1993-01-01

Papers from the conference are presented, and the topics covered include the following: planetary geology, meteorites, planetary composition, meteoritic composition, planetary craters, lunar craters, meteorite craters, petrology, petrography, volcanology, planetary crusts, geochronology, geomorphism, mineralogy, lithology, planetary atmospheres, impact melts, K-T Boundary Layer, volcanoes, planetary evolution, tectonics, planetary mapping, asteroids, comets, lunar soil, lunar rocks, lunar geology, metamorphism, chemical composition, meteorite craters, planetary mantles, and space exploration.

Beta-blockers for hypertension.

PubMed

Wiysonge, C S; Bradley, H; Mayosi, B M; Maroney, R; Mbewu, A; Opie, L H; Volmink, J

2007-01-24

Two recent systematic reviews found first-line beta-blockers to be less effective in reducing the incidence of stroke and the combined endpoint of stroke, myocardial infarction, and death compared to all other antihypertensive drugs taken together. However, beta-blockers might be better or worse than a specific class of drugs for a particular outcome measure so that comparing beta-blockers with all other classes taken together could be misleading. In addition, these systematic reviews did not assess the tolerability of beta-blockers relative to other antihypertensive medications. We thus undertook this review to re-assess the place of beta-blockade as first-line therapy for hypertension relative to each of the other major classes of antihypertensive drugs. To quantify the effectiveness and safety of beta-blockers on morbidity and mortality endpoints in adults with hypertension. We searched eligible studies up to June 2006 in the Cochrane Controlled Trials Register, Medline, Embase, and reference lists of previous reviews, and by contacting hypertension experts. We selected randomised controlled trials which assessed the effectiveness of beta-blockers compared to placebo, no therapy or other drug classes, as monotherapy or first-line therapy for hypertension, on mortality and morbidity endpoints in men and non-pregnant women aged 18 years or older. At least two authors independently applied study selection criteria, assessed study quality, and extracted data; with differences resolved by consensus. We expressed study results as relative risks (RR) with 95% confidence intervals (CI) and conducted quantitative analyses with trial participants in groups to which they were randomly allocated, regardless of which or how much treatment they actually received. In the absence of significant heterogeneity between studies (p>0.1), we performed meta-analysis using a fixed effects method. Otherwise, we used the random effects method and investigated the cause of heterogeneity by stratified analysis. In addition, we used the Higgins statistic (I(2)) to quantify the amount of between-study variability in effect attributable to true heterogeneity rather than chance. Thirteen randomised controlled trials (N=91,561 participants), which met our inclusion criteria, compared beta-blockers to placebo or no treatment (4 trials with 23,613 participants), diuretics (5 trials with 18,241 participants), calcium-channel blockers (CCBs: 4 trials with 44,825 participants), and renin-angiotensin system (RAS) inhibitors (3 trials with 10,828 participants). The risk of all-cause mortality was not different between first-line beta-blockers and placebo (RR 0.99, 95%CI 0.88 to 1.11, I(2)=0%), diuretics or RAS inhibitors, but was higher for beta-blockers compared to CCBs (RR 1.07, 95%CI 1.00 to 1.14, I(2)=2.2%; ARI=0.5%, NNH=200). The risk of total cardiovascular disease (CVD) was lower for first-line beta-blockers compared to placebo (RR 0.88, 95%CI 0.79 to 0.97, I(2)=21.4%, ARR=0.7%, NNT=140). This is primarily a reflection of the significant decrease in stroke (RR 0.80, 95%CI 0.66 to 0.96; I(2)=0%; ARR=0.5%, NNT=200); coronary heart disease (CHD) risk was not significantly different between beta-blockers and placebo. The effect of beta-blockers on CVD was significantly worse than that of CCBs (RR 1.18, 95%CI 1.08 to 1.29, I(2)=0%; ARI=1.3%, NNH=80), but was not significantly different from that of diuretics or RAS inhibitors. Increased total CVD was due to an increase in stroke compared to CCBs (RR 1.24, 95%CI 1.11 to 1.40, I(2)=0%; ARI=0.6%, NNH=180). There was also an increase in stroke with beta-blockers as compared to RAS inhibitors (RR 1.30, 95%CI 1.11 to 1.53, I(2)=29.1%; ARI=1.5%, NNH=65). CHD was not significantly different between beta-blockers and diuretics or CCBs or RAS inhibitors. In addition, patients on beta-blockers were more likely to discontinue treatment due to side effects than those on diuretics (RR 1.86, 95%CI 1.39 to 2.50, I(2)=78.2%, ARI=6.4% NNH=16) and RAS inhibitors (RR 1.41, 95%CI 1.29 to 1.54, I(2)=12.1%; ARI=5.5%, NNH=18), but there was no significant difference with CCBs. The available evidence does not support the use of beta-blockers as first-line drugs in the treatment of hypertension. This conclusion is based on the relatively weak effect of beta-blockers to reduce stroke and the absence of an effect on coronary heart disease when compared to placebo or no treatment. More importantly, it is based on the trend towards worse outcomes in comparison with calcium-channel blockers, renin-angiotensin system inhibitors, and thiazide diuretics. Most of the evidence for these conclusions comes from trials where atenolol was the beta-blocker used (75% of beta-blocker participants in this review). However, it is not known at present whether beta-blockers have differential effects on younger and elderly patients or whether there are differences between the different sub-types of beta-blockers.

Planetary science and exploration in the deep subsurface: results from the MINAR Program, Boulby Mine, UK

NASA Astrophysics Data System (ADS)

Payler, Samuel J.; Biddle, Jennifer F.; Coates, Andrew J.; Cousins, Claire R.; Cross, Rachel E.; Cullen, David C.; Downs, Michael T.; Direito, Susana O. L.; Edwards, Thomas; Gray, Amber L.; Genis, Jac; Gunn, Matthew; Hansford, Graeme M.; Harkness, Patrick; Holt, John; Josset, Jean-Luc; Li, Xuan; Lees, David S.; Lim, Darlene S. S.; McHugh, Melissa; McLuckie, David; Meehan, Emma; Paling, Sean M.; Souchon, Audrey; Yeoman, Louise; Cockell, Charles S.

2017-04-01

The subsurface exploration of other planetary bodies can be used to unravel their geological history and assess their habitability. On Mars in particular, present-day habitable conditions may be restricted to the subsurface. Using a deep subsurface mine, we carried out a program of extraterrestrial analog research - MINe Analog Research (MINAR). MINAR aims to carry out the scientific study of the deep subsurface and test instrumentation designed for planetary surface exploration by investigating deep subsurface geology, whilst establishing the potential this technology has to be transferred into the mining industry. An integrated multi-instrument suite was used to investigate samples of representative evaporite minerals from a subsurface Permian evaporite sequence, in particular to assess mineral and elemental variations which provide small-scale regions of enhanced habitability. The instruments used were the Panoramic Camera emulator, Close-Up Imager, Raman spectrometer, Small Planetary Linear Impulse Tool, Ultrasonic drill and handheld X-ray diffraction (XRD). We present science results from the analog research and show that these instruments can be used to investigate in situ the geological context and mineralogical variations of a deep subsurface environment, and thus habitability, from millimetre to metre scales. We also show that these instruments are complementary. For example, the identification of primary evaporite minerals such as NaCl and KCl, which are difficult to detect by portable Raman spectrometers, can be accomplished with XRD. By contrast, Raman is highly effective at locating and detecting mineral inclusions in primary evaporite minerals. MINAR demonstrates the effective use of a deep subsurface environment for planetary instrument development, understanding the habitability of extreme deep subsurface environments on Earth and other planetary bodies, and advancing the use of space technology in economic mining.

Effects of timolol and atenolol on benign essential tremor: placebo-controlled studies based on quantitative tremor recording.

PubMed Central

Dietrichson, P; Espen, E

1981-01-01

Two different beta-adrenoreceptor antagonists, atenolol and timolol, were separately compared with a placebo in the suppression of essential tremor. In two-week single-blind placebo-controlled studies with cross-over, timolol (5 mg twice daily) and atenolol (100 mg once daily) produced an equal reduction in sitting heart rate and sitting blood pressure. Timolol was effective in reducing tremor while atenolol failed to reduce tremor amplitude. These results indicate that essential tremor can be reduced but not blocked, by the adrenergic blocker timolol with both beta 1 and beta 2 blocking properties; but not by the relatively selective beta 1 blocking drug atenolol. Possibly, the tremor reduction is medicated by a peripheral effect on beta 2 adrenoreceptors. Images PMID:7028921

Antioxidant activity of beta-blockers: an effect mediated by scavenging reactive oxygen and nitrogen species?

PubMed

Gomes, Ana; Costa, David; Lima, José L F C; Fernandes, Eduarda

2006-07-01

The therapeutic effects of beta-blockers are normally explained by their capacity to block the beta-adrenoceptors, however, some of the beneficial cardiovascular effects shown by this group of compounds have already been associated with the antioxidant properties that some of them seem to possess. The beta-blockers atenolol, labetalol, metoprolol, pindolol, propranolol, sotalol, timolol, and carvedilol were tested for their putative scavenging activity for ROS (O(2)(-), H(2)O(2), HO(.), HOCl, and ROO(.)) and RNS ((.)NO and ONOO(-)). Some of the studied compounds are effective ROS and/or RNS scavengers, these effects being possibly useful in preventing oxidative damage verified in hypertension as well as in other cardiovascular diseases that frequently emerge in association with oxidative stress.

Clinical tolerability of generic versus brand beta blockers in heart failure with reduced left ventricular ejection fraction: a retrospective cohort from heart failure clinic.

PubMed

Chanchai, Rattanachai; Kanjanavanit, Rungsrit; Leemasawat, Krit; Amarittakomol, Anong; Topaiboon, Paleerat; Phrommintikul, Arintaya

2018-01-01

Background: Beta-blockers have been shown to decrease mortality and morbidity in heart failure with reduced ejection fraction (HFrEF) patients. However, the side effects are also dose-related, leading to the underdosing. Cost constraint may be one of the limitations of appropriate beta-blocker use; this can be improved with generic drugs. However, the effects in real life practice have not been investigated. Methods and results: This study aimed to compare the efficacy and safety of generic and brand beta-blockers in HFrEF patients. We performed a retrospective cohort analysis in HFrEF patients who received either generic or brand beta-blocker in Chiang Mai Heart Failure Clinic. The primary endpoint was the proportion of patients who received at least 50% target dose of beta-blocker between generic and brand beta-blockers. Adverse events were secondary endpoints. 217 patients (119 and 98 patients received generic and brand beta-blocker, respectively) were enrolled. There were no differences between groups regarding age, gender, etiology of heart failure, New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF), rate of receiving angiotensin converting enzyme inhibitor (ACEI), angiotensin recepter blocker (ARB), or spironolactone. Patients receiving brand beta-blockers had lower resting heart rate at baseline (74.9 and 84.2 bpm, p  = .001). Rate of achieved 50% target dose and target daily dose did not differ between groups (40.4 versus 44.5% and 48.0 versus 55.0%, p  > .05, respectively). Rate of side effects was not different between groups (32.3 versus 29.5%, p  > .05) and the most common side effect was hypotension. Conclusion: This study demonstrated that beta-blocker tolerability was comparable between brand and generic formulations. Generic or brand beta-blockers should be prescribed to HFrEF patients who have no contraindications.

Clinical tolerability of generic versus brand beta blockers in heart failure with reduced left ventricular ejection fraction: a retrospective cohort from heart failure clinic

PubMed Central

Chanchai, Rattanachai; Kanjanavanit, Rungsrit; Leemasawat, Krit; Amarittakomol, Anong; Topaiboon, Paleerat; Phrommintikul, Arintaya

2018-01-01

Abstract Background: Beta-blockers have been shown to decrease mortality and morbidity in heart failure with reduced ejection fraction (HFrEF) patients. However, the side effects are also dose-related, leading to the underdosing. Cost constraint may be one of the limitations of appropriate beta-blocker use; this can be improved with generic drugs. However, the effects in real life practice have not been investigated. Methods and results: This study aimed to compare the efficacy and safety of generic and brand beta-blockers in HFrEF patients. We performed a retrospective cohort analysis in HFrEF patients who received either generic or brand beta-blocker in Chiang Mai Heart Failure Clinic. The primary endpoint was the proportion of patients who received at least 50% target dose of beta-blocker between generic and brand beta-blockers. Adverse events were secondary endpoints. 217 patients (119 and 98 patients received generic and brand beta-blocker, respectively) were enrolled. There were no differences between groups regarding age, gender, etiology of heart failure, New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF), rate of receiving angiotensin converting enzyme inhibitor (ACEI), angiotensin recepter blocker (ARB), or spironolactone. Patients receiving brand beta-blockers had lower resting heart rate at baseline (74.9 and 84.2 bpm, p = .001). Rate of achieved 50% target dose and target daily dose did not differ between groups (40.4 versus 44.5% and 48.0 versus 55.0%, p > .05, respectively). Rate of side effects was not different between groups (32.3 versus 29.5%, p > .05) and the most common side effect was hypotension. Conclusion: This study demonstrated that beta-blocker tolerability was comparable between brand and generic formulations. Generic or brand beta-blockers should be prescribed to HFrEF patients who have no contraindications. PMID:29379674

Planetary Accretion in the Inner Solar System: Dependence on Nebula Surface Density Profile and Giant Planet Eccentricities

NASA Technical Reports Server (NTRS)

Chambers, J. E.; Cassen, P.

2002-01-01

We present 32 N-body simulations of planetary accretion in the inner Solar System, examining the effect of nebula surface density profile and initial eccentricities of Jupiter and Saturn on the compositions and orbits of the inner planets. Additional information is contained in the original extended abstract.

Numerical and Analytical Investigation of the Energy and Momentum Exchange Between the Shocked Solar Wind and Topside Ionosphere for Non-Magnetic Planets and Moons

NASA Astrophysics Data System (ADS)

Dobe, Z.; Shapiro, V. D.; Quest, K.; Szego, K.; Huba, J.

1998-11-01

Previously[1], we proposed a model of the planetary ions pick-up by the shocked solar wind flow developing in the mantle-turbulent boundary region surrounding the ionospheres of non-magnetic planets-Mars and Venus. In the present paper we are modifying this model taking into account the flow of the planetary elections immediately pick-up by E x B forces of the shocked solar wind. It is shown that flow of the cold planetary electrons drives a strong hydrodynamical instability of the electrostatic whistlers efficiently coupling planetary ions with the flow of the solar wind. The linear stage of the instability is investigated both analytically and numerically, and results are found to be in a good agreement. Nonlunear stage of the instability is investigated with the modified numerical hybrid code[2], and demonstrates both effects of acceleration and heating of the planetary ions by the solar wind. Field aligned electron acceleration is also investigated in a test particle approximation using wave power spectrum obtained in a self-consistent numerical simulation.

PROGRESS ON THE STUDY OF BETA TREATMENT OF URANIUM, DECEMBER 1, 1960-MARCH 30, 1961

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russell, R.B.

The variables affecting the beta treatment of uranium are described. Results are included on the effects of time at beta temperature, the influence of air delay before quenching, and the effects of 800 l C annealing. A description of x-ray automation equipment is presented. (N.W.R.)

Bringing Planetary Data into Learning Environments: A Community Effort

NASA Astrophysics Data System (ADS)

Shipp, S.; Higbie, M.; Lowes, L.

2005-12-01

Recognizing the need to communicate scientific findings, and the power of using real planetary data in educational settings to engage students in Earth and space science in meaningful ways, the South Central Organization of Researchers and Educators and the Solar System Exploration Education Forum, part of NASA's Science Mission Directorate's Support Network, have established the Planetary Data in Education (PDE) Initiative. The Initiative strives to: 1) Establish a collaborative community of educators, education specialists, curriculum developers, tool developers, learning technologists, scientists, and data providers to design and develop educationally appropriate products; 2) Build awareness in the broader educational and scientific community of existing programs, products, and resources; 3) Address issues hindering the effective use of planetary data in formal and informal educational settings; and 4) Encourage partnerships that leverage the community's expertise The PDE community has hosted two conferences exploring issues in using data in educational settings. The community recognizes that data are available through venues such as the Planetary Data Systems (PDS), but not in a format that the end-user in a formal or informal educational setting can digest; these data are intended for the scientific audience. Development of meaningful educational programs using planetary data requires design of appropriate learner interfaces and involvement of data providers, product developers, learning technologists, scientists, and educators. The PDE community will participate in the development of Earth Exploration Toolbooks during the DLESE Data Services Workshop and will host a workshop in the summer of 2006 to bring together small groups of educators, data providers, and learning technologists, and scientists to design and develop products that bring planetary data into educational settings. In addition, the PDE community hosts a Web site that presents elements identified as needed by the community, including examples of planetary data use in education, recommendations for program development, links to data providers, opportunities for collaboration, pertinent research, and a Web portal to access educational resources using planetary data on the DLESE Web site.

Lakshmi Planum: A distinctive highland volcanic province

NASA Astrophysics Data System (ADS)

Roberts, Kari M.; Head, James W.

Lakshmi Planum, a broad smooth plain located in western Ishtar Terra and containing two large oval depressions (Colette and Sacajawea), has been interpreted as a highland plain of volcanic origin. Lakshmi is situated 3 to 5 km above the mean planetary radius and is surrounded on all sides by bands of mountains interpreted to be of compressional tectonic origin. Four primary characteristics distinguish Lakshmi from other volcanic regions known on the planet, such as Beta Regio: (1) high altitude, (2) plateau-like nature, (3) the presence of very large, low volcanic constructs with distinctive central calderas, and (4) its compressional tectonic surroundings. Building on the previous work of Pronin, the objective is to establish the detailed nature of the volcanic deposits on Lakshmi, interpret eruption styles and conditions, sketch out an eruption history, and determine the relationship between volcanism and the tectonic environment of the region.

Lakshmi Planum: A distinctive highland volcanic province

NASA Technical Reports Server (NTRS)

Roberts, Kari M.; Head, James W.

1989-01-01

Lakshmi Planum, a broad smooth plain located in western Ishtar Terra and containing two large oval depressions (Colette and Sacajawea), has been interpreted as a highland plain of volcanic origin. Lakshmi is situated 3 to 5 km above the mean planetary radius and is surrounded on all sides by bands of mountains interpreted to be of compressional tectonic origin. Four primary characteristics distinguish Lakshmi from other volcanic regions known on the planet, such as Beta Regio: (1) high altitude, (2) plateau-like nature, (3) the presence of very large, low volcanic constructs with distinctive central calderas, and (4) its compressional tectonic surroundings. Building on the previous work of Pronin, the objective is to establish the detailed nature of the volcanic deposits on Lakshmi, interpret eruption styles and conditions, sketch out an eruption history, and determine the relationship between volcanism and the tectonic environment of the region.

Properties of ultra low frequency upstream waves at Venus and Saturn: A comparison

NASA Technical Reports Server (NTRS)

Orlowski, D. S.; Russell, C. T.; Krauss-Varban, D.; Omidi, N.

1995-01-01

The upstream regions of all planets, except Pluto, have been investigated, using in situ spacecraft measurements and a variety of analysis techniques. The detailed studies at Earth indicate that these waves are generated locally in the magnetically connected solar wind by the interaction with ions backstreaming from the shock. However, since the properties of the solar wind vary with heliocentric distance and since properties of planetary shocks depend on plasma beta, interplanetary magnetic field (IMF) spiral angle and Mach number, the amount of heating, acceleration efficiencies, etc. significantly change with heliocentric distance. In turn the waves seen at each planet propagate not in the same but different (physical) propagation modes. In this paper we compare the ULF wave observations at an outer and an inner planet. We use the results of the ratio, quantites easily derivable with sufficient accuracy at each planet. We use the full electromagnetic dispersion relation for comparison with theoretical predictions.

Design of a Day/Night Lunar Rover

NASA Astrophysics Data System (ADS)

Berkelman, Peter; Easudes, Jesse; Martin, Martin C.; Rollins, Eric; Silberman, Jack; Chen, Mei; Hancock, John; Mor, Andrew B.; Sharf, Alex; Warren, Tom; Bapna, Deepak

1995-06-01

The pair of lunar rovers discussed in this report will return video and state data to various ventures, including theme park and marketing concerns, science agencies, and educational institutions. The greatest challenge accepted by the design team was to enable operations throughout the extremely cold and dark lunar night, an unprecedented goal in planetary exploration. This is achieved through the use of the emerging technology of Alkali Metal Thermal to Electric Converters (AMTEC), provided with heat from a innovative beta-decay heat source, Krypton-85 gas. Although previous space missions have returned still images, our design will convey panoramic video from a ring of cameras around the rover. A six-wheel rocker bogie mechanism is implemented to propel the rover. The rovers will also provide the ability to safeguard their operation to allow untrained members of the general public to drive the vehicle. Additionally, scientific exploration and educational outreach will be supported with a user operable, steerable and zoomable camera.

Lightning measurements from the Pioneer Venus Orbiter

NASA Technical Reports Server (NTRS)

Scarf, F. L.; Russell, C. T.

1983-01-01

The plasma wave instrument on the Pioneer Venus Orbiter frequently detects strong and impulsive low-frequency signals when the spacecraft traverses the nightside ionosphere near periapsis. These particular noise bursts appear only when the local magnetic field is strong and steady and when the field is oriented to point down to the ionosphere thus; the signals have all characteristics of lightning whistlers. We have tried to identify lightning sources between the cloud layers and the planet itself by tracing rays along the B-field from the Orbiter down toward the surface. An extensive data set, consisting of measurements through Orbit 1185, strongly indicates a clustering of lightning sources near the Beta and Phoebe Regios, with an additional significant cluster near the Atla Regio at the eastern edge of Aphrodite Terra. These results suggest that there are localized lightning sources at or near the planetary surface.

Global scale concentrations of volcanic activity on Venus: A summary of three 23rd Lunar and Planetary Science Conference abstracts. 1: Venus volcanism: Global distribution and classification from Magellan data. 2: A major global-scale concentration of volcanic activity in the Beta-Atla-Themis region of Venus. 3: Two global concentrations of volcanism on Venus: Geologic associations and implications for global pattern of upwelling and downwelling

NASA Technical Reports Server (NTRS)

Crumpler, L. S.; Aubele, Jayne C.; Head, James W.; Guest, J.; Saunders, R. S.

1992-01-01

As part of the analysis of data from the Magellan Mission, we have compiled a global survey of the location, dimensions, and subsidiary notes of all identified volcanic features on Venus. More than 90 percent of the surface area was examined and the final catalog comprehensively identifies 1548 individual volcanic features larger than approximately 20 km in diameter. Volcanic features included are large volcanoes, intermediate volcanoes, fields of small shield volcanoes, calderas, large lava channels, and lava floods as well as unusual features first noted on Venus such as coronae, arachnoids, and novae.

Effects of beta-glucuronidase-deficient and lycopene-producing Escherichia coli strains on formation of azoxymethane-induced aberrant crypt foci in the rat colon.

PubMed

Arimochi, H; Kataoka, K; Kuwahara, T; Nakayama, H; Misawa, N; Ohnishi, Y

1999-08-27

We tried to inhibit the formation of azoxymethane-induced aberrant crypt foci (ACF) in the rat intestine by feeding a culture of a beta-glucuronidase-deficient Escherichia coli strain or a cell suspension of a lycopene-producing E. coli strain. Feeding of the former culture to F344 rats did not decrease fecal beta-glucuronidase activity or the number of ACF compared with the control beta-glucuronidase-proficient groups. However, a significant positive correlation between the fecal beta-glucuronidase activity and the ACF number was observed among groups treated with cultures of beta-glucuronidase-proficient and -deficient strains. In the group treated with lycopene-producing cells, the number of ACF was significantly lower than that in the control group. A vegetable juice containing a larger amount of lycopene than a cell suspension of the lycopene-producing E. coli also decreased the number of ACF to the same extent as a cell suspension of the lycopene-producing bacteria. These results suggest that feeding of the beta-glucuronidase-deficient E. coli is not very effective in preventing colon carcinogenesis, although activity of the fecal beta-glucuronidase is associated with AOM-induced ACF formation, and that lycopene-producing intestinal bacteria can effectively prevent colon carcinogenesis. Copyright 1999 Academic Press.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baserga, S.J.; Benz, E.J. Jr.

A number of premature translation termination mutations (nonsense mutations) have been described in the human {alpha}- and {beta}-globin genes. Studies on mRNA isolated from patients with {beta}{sup 0}-thalassemia have shown that for both the {beta}-17 and the {beta}-39 mutations less than normal levels of {beta}-globin mRNA accumulate in peripheral blood cells. (The codon at which the mutation occurs designates the name of the mutation; there are 146 codons in human {beta}-globin mRNA). In vitro studies using the cloned {beta}-39 gene have reproduced this effect in a heterologous transfection system and have suggested that the defect resides in intranuclear metabolism. Themore » authors have asked if this phenomenon of decreased mRNA accumulation is a general property of nonsense mutations and if the effect depends on the location or the type of mutation. Toward this end, they have studied the effect of five nonsense mutations and two missense mutations on the expression of human {beta}-globin mRNA in a heterologous transfection system. In all cases studied, the presence of a translation termination codon correlates with a decrease in the steady-state level of mRNA. The data suggest that the metabolism of a mammalian mRNA is affected by the presence of a mutation that affects translation.« less

Inhibitory effect of dimeric beta peptide on the recurrence and metastasis of hepatocellular carcinoma in vitro and in mice.

PubMed

Wang, Song-Mei; Zhu, Jun; Pan, Luan-Feng; Liu, Yin-Kun

2008-05-21

To block the adhesion of tumor cells to the extracellular matrix, and prevent tumor metastasis and recurrence, the dimer of the beta peptide (DLYYLMDLSYSMKGGDLYYLMDLSYSMK, beta2) was designed and synthesized and its anti-adhesion and anti-invasion effects on hepatocellular carcinoma cells were assessed. Additionally, its influence on the metastasis and recurrence of mouse hepatocellular carcinoma was measured. The anti-adhesion effect of beta2 on the highly metastatic hepatocellular carcinoma cell line HCCLM6 cells and fibronectin (FN) was assayed by the MTT assay. The inhibition of invasion of HCCLM6 cells by beta2 was observed using a Transwell (modified Boyden chamber) and matrigel. Using the hepatocellular carcinoma metastasis model and LCI-D20 nude mice, the influence of beta2 on the metastasis and recurrence of hepatocellular carcinoma after early resection was investigated. HCCLM6 cells co-incubated with 100 mumol/L, 50 micromol/L, 20 micromol/L or 10 micromol/L beta2 for 3 h showed an obvious decrease in adhesion to FN. The adhesion inhibition ratios were 11.8%, 21.7%, 29.6% and 48.7%, respectively. Additionally, HCCLM6 cells cultured with 100 mumol/L beta2 had a dramatic decrease in cell invasion. beta2 was also observed to inhibit the incisal edge recurrence and the distant metastasis of nude mice hepatocellular carcinoma after early resection (P < 0.05). The beta2 peptide can specifically block the adhesion and invasion of HCCLM6 cells, and can inhibit HCC recurrence and metastasis of LCI-D20 model posthepatectomy in vivo. Thus, beta2 should be further studied as a new anti-tumor drug.

The effect of atmospheric diabatic heating on low-frequency oscillations

NASA Astrophysics Data System (ADS)

Yen, Ming-Cheng

A diagnostic scheme is devised to illustrate a chain relationship between diabatic heating and planetary-scale divergent and rotational circulations. The scheme consists of the velocity-potential maintenance equation, which relates diabatic heating and velocity potential, and the streamfunction budget equation, which depicts the streamfunction tendency caused by the imbalance between streamfunction tendencies induced by vorticity advection and source. The proposed scheme is employed to examine the effect of tropical diabatic heating on the annual variation of subtropical jet streams. It was found that annual variations of both tropical diabatic heating and planetary-scale divergent circulation exhibit an annual in-phase seesaw oscillation between the winter and summer hemispheres. The annual variation of subtropical jet streams is caused by the adjustment of atmospheric rotational flow through planetary-scale divergent circulation in response to the annual cycle of tropical diabatic heating.

Planetary spectra for anisotropic scattering

NASA Technical Reports Server (NTRS)

Chamberlain, J. W.

1976-01-01

Some effects on planetary spectra that would be produced by departures from isotropic scattering are examined. The phase function is the simplest departure to handle analytically and the only phase function, other than the isotropic one, that can be incorporated into a Chandrasekhar first approximation. This approach has the advantage of illustrating effects resulting from anisotropies while retaining the simplicity that yields analytic solutions. The curve of growth is the sine qua non of planetary spectroscopy. The discussion emphasizes the difficulties and importance of ascertaining curves of growth as functions of observing geometry. A plea is made to observers to analyze their empirical curves of growth, whenever it seems feasible, in terms of coefficients of which are the leading terms in radiative-transfer analysis. An algebraic solution to the two sets of anisotropic H functions is developed which gives emergent intensities accurate to 0.3%.

Coupling of the quasi-biennial oscillation and the extratropical circulation in the stratosphere through planetary wave transport

NASA Technical Reports Server (NTRS)

O'Sullivan, Donal; Salby, Murry L.

1990-01-01

The effects of tropical winds on the extratropical circulation are examined using calculations of eddy transport with tropical flow that is representative of the easterly and westerly phases of the quasi-biennial oscillation (QBO). A dependence of extratropical circulation on tropical winds and the QBO is shown to originate in planetary wave transport. Also, the effects of low latitude flow on high latitude circulation and the behavior of the vortex in opposite phases of the QBO are examined.

Mycophenolate mofetil modulates adhesion receptors of the beta1 integrin family on tumor cells: impact on tumor recurrence and malignancy

PubMed Central

Engl, Tobias; Makarević, Jasmina; Relja, Borna; Natsheh, Iyad; Müller, Iris; Beecken, Wolf-Dietrich; Jonas, Dietger; Blaheta, Roman A

2005-01-01

Background Tumor development remains one of the major obstacles following organ transplantation. Immunosuppressive drugs such as cyclosporine and tacrolimus directly contribute to enhanced malignancy, whereas the influence of the novel compound mycophenolate mofetil (MMF) on tumor cell dissemination has not been explored. We therefore investigated the adhesion capacity of colon, pancreas, prostate and kidney carcinoma cell lines to endothelium, as well as their beta1 integrin expression profile before and after MMF treatment. Methods Tumor cell adhesion to endothelial cell monolayers was evaluated in the presence of 0.1 and 1 μM MMF and compared to unstimulated controls. beta1 integrin analysis included alpha1beta1 (CD49a), alpha2beta1 (CD49b), alpha3beta1 (CD49c), alpha4beta1 (CD49d), alpha5beta1 (CD49e), and alpha6beta1 (CD49f) receptors, and was carried out by reverse transcriptase-polymerase chain reaction, confocal microscopy and flow cytometry. Results Adhesion of the colon carcinoma cell line HT-29 was strongly reduced in the presence of 0.1 μM MMF. This effect was accompanied by down-regulation of alpha3beta1 and alpha6beta1 surface expression and of alpha3beta1 and alpha6beta1 coding mRNA. Adhesion of the prostate tumor cell line DU-145 was blocked dose-dependently by MMF. In contrast to MMF's effects on HT-29 cells, MMF dose-dependently up-regulated alpha1beta1, alpha2beta1, alpha3beta1, and alpha5beta1 on DU-145 tumor cell membranes. Conclusion We conclude that MMF possesses distinct anti-tumoral properties, particularly in colon and prostate carcinoma cells. Adhesion blockage of HT-29 cells was due to the loss of alpha3beta1 and alpha6beta1 surface expression, which might contribute to a reduced invasive behaviour of this tumor entity. The enhancement of integrin beta1 subtypes observed in DU-145 cells possibly causes re-differentiation towards a low-invasive phenotype. PMID:15644133

Carvedilol in the treatment of chronic heart failure: Lessons from The Carvedilol Or Metoprolol European Trial

PubMed Central

Kveiborg, Britt; Major-Petersen, Atheline; Christiansen, Buris; Torp-Pedersen, Christian

2007-01-01

Beta-blockers have been shown to improve survival in patients with chronic heart failure. The effect of different generations of beta blockers has been debated. Both metoprolol and carvedilol have demonstrated beneficial effects in placebo-controlled trials. In The Carvedilol Or Metoprolol European Trial (COMET) two beta blockers were compared in a double-blind randomized matter. This is the first direct comparison between metoprolol and carvedilol of long-term effect on survival in patients with chronic heart failure. The all-cause mortality was signif icantly reduced in the favour of carvedilol. The dose and formulation of metoprolol used in this trial has caused debate, and it has been questioned whether a similar beta1-blockade is obtained in the two intervention groups. At this time there is an unresolved debate as to whether carvedilol is a superior beta-blocker or whether differences in beta1-blockade explained the results of COMET. PMID:17583173

[Effects of Valeriana officinalis var. latifolia on expression of transforming growth factor beta 1 in hypercholesterolemic rats].

PubMed

Si, Xiao-yun; Jia, Ru-han; Huang, Cong-xin; Ding, Guo-hua; Liu, Hong-yan

2003-09-01

To evaluate the effect of Valeriana officinalis var latifolia(VOL) on expression of transforming growth factor beta 1 (TGF-beta 1) in hypercholesterolemic rats and study its possible mechanisms. Dietary-induced hypercholesterolemia was induced in male Wistar rats by given 4% cholesterol and 1% cholic acid diet for 16 weeks. Changes of serum lipid, urinary albumin, renal function and Mesangial matrix index were assessed. Moreover, immunohistochemical stain for TGF-beta 1 and type IV collagen were performed. VOL could reduce the serum levels of total cholesterol, low density lipoprotein, urinary albumin and serum creatinine. Light microscopy and immunohistochemical stain revealed that in the same time of lowing serum lipid, Mesangial matrix index was significantly reduced, accompanied by decreased expression of TGF-beta 1 and type IV collagen. VOL has the protective effect on lipid-induced nephropathy, and the inhibition of TGF-beta 1 expression might be the mechanism of VOL on renal protection.

Beta 1,3/1,6-glucan and vitamin C immunostimulate the non-specific immune response of white shrimp (Litopenaeus vannamei).

PubMed

Wu, Yu-Sheng; Liau, Shu-Yu; Huang, Cheng-Ting; Nan, Fan-Hua

2016-10-01

This study mainly evaluated the effects of orally administered beta 1,3/1,6-glucan and vitamin C on the nonspecific immune responses of white shrimp (Litopenaeus vannamei). In this study, we found that the white shrimp oral administration with 1 g/kg of beta 1,3/1,6-glucan effectively enhanced O2(-) production and phenoloxidase and superoxide dismutase activity. Shrimp were oral administration with 0.2 g/kg of vitamin C presented beneficial nonspecific immune responses and enzyme activity and also observed in the beta 1,3/1,6-glucan treatment groups. Consequently, we compared the alterations in the immune activity between the beta 1,3/1,6-glucan and vitamin C groups and the evidence illustrated that combination of beta 1,3/1,6-glucan and vitamin C presented an additive effect on inducing the nonspecific immune responses of white shrimp. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enhanced rectal absorption and reduced local irritation of the anti-inflammatory drug ethyl 4-biphenylylacetate in rats by complexation with water-soluble beta-cyclodextrin derivatives and formulation as oleaginous suppository.

PubMed

Arima, H; Kondo, T; Irie, T; Uekama, K

1992-11-01

To improve the rectal delivery of ethyl 4-biphenylylacetate (EBA), a prodrug of the anti-inflammatory drug 4-biphenylylacetic acid (BPAA), the use of highly water-soluble 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DM-beta-CyD) was investigated and compared with the use of the parent beta-cyclodextrin (beta-CyD). Among the three beta-CyDs, HP-beta-CyD was best at improving the rectal bioavailability of EBA in rats after single and multiple administrations of oleaginous suppositories (Witepsol H-5) containing the complexes. To gain insight into the enhancing effect of beta-CyDs, the absorption behaviors of EBA (observed by monitoring BPAA as an active metabolite of EBA) and beta-CyDs themselves were examined in vitro, in situ, and in vivo. The in situ recirculation study revealed that the complexed form of EBA was less absorbable from the rectal lumen in the solution state, but this disadvantageous effect of beta-CyDs was compensated in part by the inhibition of the bioconversion of EBA to BPAA. When beta-CyDs were coadministered with EBA in vivo, however, rather high amounts of HP-beta-CyD (approximately 26% of dose) and DM-beta-CyD (approximately 21% of dose), compared with beta-CyD (approximately 5% of dose), were absorbed from the rat rectum. Thus, the enhancement of rectal absorption of EBA in vivo can be explained by the facts that the hydrophilic beta-CyDs increased the release rate of EBA from the vehicle and stabilized EBA in the rectal lumen and that the drug was partly absorbed in the form of the complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of beta-adrenoceptor blocking drugs in hyperthyroidism.

PubMed

Feely, J; Peden, N

1984-05-01

There is an increasing use and variety of beta-adrenoceptor blocking agents (beta-blockers) available for the treatment of hyperthyroidism. Recent comparative studies suggest that atenolol (200mg daily), metoprolol (200mg daily); acebutolol (400mg daily), oxprenolol ( 160mg daily), nadolol ( 80mg daily) and timolol (20mg daily) produce a beneficial clinical response equal to that seen with propranolol ( 160mg daily). Most beta-blockers reduce resting heart rate by approximately 25 to 30 beats/min, although a lesser reduction is seen with those possessing intrinsic sympathomimetic activity such as oxprenolol and pindolol. While earlier studies employing large doses of intravenous propranolol concluded that beta-blockade reduced myocardial contractility, more recent non-invasive studies suggest that the predominant cardiac effect is on heart rate. In patients with cardiac failure, beta-blockers may, however, produce a profound fall in cardiac output. Nevertheless, in combination with digoxin they may be useful in controlling the atrial fibrillation of thyrocardiac disease. beta-Blockers improve nervousness and tremor (although to a lesser extent with cardioselective agents) and severe myopathy, and they also reduce the frequency of paralysis in patients with thyrotoxic periodic paralysis. There is often subjective improvement in sweating but usually no major effect on eye signs. Recent studies show a 10% reduction in oxygen consumption/basal metabolic rate with long term oral use of selective or nonselective beta-blockers. In addition, many agents (propranolol, metoprolol, nadolol and sotalol but not acebutolol, atenolol or oxprenolol) reduce circulating tri-iodothyronine (T3) concentration by between 10 and 40%, although the clinical significance of this effect (if any) is not established. beta-Blockers may also have endocrinological effects on gastrin, cyclic AMP, catecholamines and other hormone levels. Given in adequate dosage, propranolol has been shown to control thyrotoxic hypercalcaemia. Minor side effects (nausea, headaches, tiredness, etc.) are quite common but overall beta-blockers are well tolerated by the thyrotoxic patient. The major use of these drugs is in symptomatic control while awaiting definitive diagnosis or treatment. As an adjunct to antithyroid drugs or radioactive iodine, beta-blockers will produce a satisfactory clinical response in the weeks to months before these forms of therapy produce a euthyroid state. beta-Blockers are more convenient than antithyroid drugs in the control of patients receiving therapeutic radioiodine, in that continuous therapy and assessment of biochemical response is possible.(ABSTRACT TRUNCATED AT 400 WORDS)

Impact of beta-cyclodextrin and resistant starch on bile acid metabolism and fecal steroid excretion in regard to their hypolipidemic action in hamsters.

PubMed

Trautwein, E A; Forgbert, K; Rieckhoff, D; Erbersdobler, H F

1999-01-29

To examine the impact on bile acid metabolism and fecal steroid excretion as a mechanism involved in the lipid-lowering action of beta-cyclodextrin and resistant starch in comparison to cholestyramine, male golden Syrian hamsters were fed 0% (control), 8% or 12% of beta-cyclodextrin or resistant starch or 1% cholestyramine. Resistant starch, beta-cyclodextrin and cholestyramine significantly lowered plasma total cholesterol and triacylglycerol concentrations compared to control. Distinct changes in the bile acid profile of gallbladder bile were caused by resistant starch, beta-cyclodextrin and cholestyramine. While cholestyramine significantly reduced chenodeoxycholate independently of its taurine-glycine conjugation, beta-cyclodextrin and resistant starch decreased especially the percentage of taurochenodeoxycholate by -75% and -44%, respectively. As a result, the cholate:chenodeoxycholate ratio was significantly increased by 100% with beta-cyclodextrin and by 550% with cholestyramine while resistant starch revealed no effect on this ratio. beta-Cyclodextrin and resistant starch, not cholestyramine, significantly increased the glycine:taurine conjugation ratio demonstrating the predominance of glycine conjugated bile acids. Daily fecal excretion of bile acids was 4-times higher with 8% beta-cyclodextrin and 19-times with 1% cholestyramine compared to control. beta-Cyclodextrin and cholestyramine also induced a 2-fold increase in fecal neutral sterol excretion, demonstrating the sterol binding capacity of these two compounds. Resistant starch had only a modest effect on fecal bile acid excretion (80% increase) and no effect on excretion of neutral sterols, suggesting a weak interaction with intestinal steroid absorption. These data demonstrate the lipid-lowering potential of beta-cyclodextrin and resistant starch. An impaired reabsorption of circulating bile acids and intestinal cholesterol absorption leading to an increase in fecal bile acid and neutral sterol excretion is most likely the primary mechanism responsible for the lipid-lowering action of beta-cyclodextrin. In contrast, other mechanisms involving the alterations in the biliary bile acid profile or repressed hepatic lipogenesis, e.g., VLDL production, appear to be involved in the hypolipidemic effect of resistant starch.

Formulary considerations in selection of beta-blockers.

PubMed

Yedinak, K C

1993-08-01

Selection of beta-adrenergic blockers for formulary addition can be a difficult task, especially with the increasing availability of new beta-blockers, as well as the numerous differences in pharmacodynamic and pharmacokinetic properties of currently available agents. Nevertheless, appropriate evaluation of the important characteristics of beta-blockers should allow selection of the most cost-effective agents for formulary addition. Most importantly, differences in efficacy, product formulation and cost should be carefully considered when making formulary decisions. Notably, evidence from clinical trials indicates differences in efficacy among beta-blockers for post-myocardial infarction prophylaxis, situational anxiety, essential tremor, thyrotoxicosis, migraine prophylaxis and prevention of bleeding associated with oesophageal varices. For many clinical situations, it is also important to select an effective agent that is available in both an oral and intravenous formulation, especially for cardioprotection after acute myocardial infarction and for use in supraventricular arrhythmias. In addition, availability of sustained release products and generic formulations should be considered for their potential to increase compliance and decrease cost, respectively. Comparative drug costs, as well as costs associated with decreased compliance, should also be carefully evaluated. Differences in beta-receptor selectivity, duration of action and presence of intrinsic sympathomimetic activity (ISA) are also important considerations in the selection of beta-blockers for formulary consideration. Although degree of selectivity is relative, beta 1-selective agents may be less likely to induce bronchospasm in patients with chronic obstructive pulmonary disease (COPD) and may be less likely to affect glucose homeostasis in patients with diabetes mellitus. Duration of action of a beta-blocker is an important consideration for evaluation of efficacy throughout the recommended dosage interval. In addition, beta-blockers with a long duration of action can often be administered once or twice daily, potentially leading to increased compliance and thereby improved effectiveness and economic efficiency. The presence of ISA is an important consideration because certain beta-blockers with ISA may be less effective than those without ISA for certain indications. Factors considered to be less important when making formulary decisions of choice of beta-blockers include the route of elimination, lipophilicity and presence of membrane stabilising activity.

Beta-blockade after myocardial infarction: practical implications of major clinical trials.

PubMed

Rehnqvist, N; Olsson, G

1987-01-01

A survey of the literature concerning 20 years' experience of beta-blockade after myocardial infarction indicates that several positive effects are achieved and that these are neither marginal nor transient. Mortality is reduced during the first year from about 10 to 7%. This has been shown for the individual beta-blockers metoprolol, propranolol, and timolol, and also when the data on all beta-blocker trials have been pooled. The effect is further enhanced if therapy continues. Patients at high risk of mortality can be separated fairly accurately from those at low risk. Thus, prophylactic treatment with the sole purpose of reducing mortality can be individualized. Effects on reinfarction are also already present after 1 year and are enhanced during further follow-up. It has not yet been possible, however, to identify those patients in whom this end-point will not be influenced. Furthermore, during extended follow-up, the proportion of asymptomatic patients who are free of side effects increases during treatment with beta-blockade, whereas it decreases during placebo therapy, due mostly to increased numbers of patients suffering from complications such as reinfarction, angina pectoris, cerebrovascular incidents, arrhythmias, or disturbances in the peripheral circulation. Twenty percent of patients experienced improved fitness when beta-blockade treatment was withdrawn, which balances the beneficial effects. No other drugs have been shown to have comparable beneficial effects. We conclude that the practical implications of the clinical trials indicate that beta-blockade should be continued for at least 3 years after myocardial infarction in patients without severe side effects.

Particle Orbit Analysis in the Finite Beta Plasma of the Large Helical Device using Real Coordinates

NASA Astrophysics Data System (ADS)

Seki, Ryousuke; Matsumoto, Yutaka; Suzuki, Yasuhiro; Watanabe, Kiyomasa; Itagaki, Masafumi

High-energy particles in a finite beta plasma of the Large Helical Device (LHD) are numerically traced in a real coordinate system. We investigate particle orbits by changing the beta value and/or the magnetic field strength. No significant difference is found in the particle orbit classifications between the vacuum magnetic field and the finite beta plasma cases. The deviation of a banana orbit from the flux surfaces strongly depends on the beta value, although the deviation of the orbit of a passing particle is independent of the beta value. In addition, the deviation of the orbit of the passing particle, rather than that of the banana-orbit particles, depends on the magnetic field strength. We also examine the effect of re-entering particles, which repeatedly pass in and out of the last closed flux surface, in the finite beta plasma of the LHD. It is found that the number of re-entering particles in the finite beta plasma is larger than that in the vacuum magnetic field. As a result, the role of reentering particles in the finite beta plasma of the LHD is more important than that in the vacuum magnetic field, and the effect of the charge-exchange reaction on particle confinement in the finite beta plasma is large.

Design of retrovirus vectors for transfer and expression of the human. beta. -globin gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, A.D.; Bender, M.A.; Harris, E.A.S.

1988-11-01

Regulated expression of the human ..beta..-globin gene has been demonstrated in cultured murine erythroleukemia cells and in mice after retrovirus-mediated gene transfer. However, the low titer of recombinant viruses described to date results in relatively inefficient gene transfer, which limits their usefulness for animal studies and for potential gene therapy in humans for diseases involving defective ..beta..-globin genes. The authors found regions that interfered with virus production within intron 2 of the ..beta..-globin gene and on both sides of the gene. The flanking regions could be removed, but intron 2 was required for ..beta..-globin expression. Inclusion of ..beta..-globin introns necessitatesmore » an antisense orientation of the gene within the retrovirus vector. However, they found no effect of the antisense ..beta..-globin transcription on virus production. A region downstream of the ..beta..-globin gene that stimulates expression of the gene in transgenic mice was included in the viruses without detrimental effects on virus titer. Virus titers of over 10/sup 6/ CFU/ml were obtained with the final vector design, which retained the ability to direct regulated expression of human ..beta..-globin in murine erythroleukemia cells. The vector also allowed transfer and expression of the human ..beta..-globin gene in hematopoietic cells (CFU-S cells) in mice.« less

Endogenous PKI gamma limits the duration of the anti-apoptotic effects of PTH and beta-adrenergic agonists in osteoblasts.

PubMed

Chen, Xin; Song, In-Hwan; Dennis, James E; Greenfield, Edward M

2007-05-01

PKI gamma knockdown substantially extended the anti-apoptotic effects of PTH and beta-adrenergic agonists, whereas PKI gamma overexpression decreased these effects. Therefore, inhibition of PKI gamma activity may provide a useful co-therapy in combination with intermittent PTH or beta-adrenergic agonists for bone loss in conditions such as osteoporosis. PTH has both catabolic and anabolic effects on bone, which are primarily caused by cAMP/protein kinase A (PKA) signaling and regulation of gene expression. We previously showed that protein kinase inhibitor-gamma (PKI gamma) is required for efficient termination of cAMP/PKA signaling and gene expression after stimulation with PTH or beta-adrenergic agonists. Inhibition of osteoblast apoptosis is thought to be an important, but transient, mechanism partly responsible for the anabolic effects of intermittent PTH. Therefore, we hypothesized that endogenous PKI gamma also terminates the anti-apoptotic effect of PTH. PKI gamma knockdown by antisense transfection or siRNA was used to examine the ability of endogenous PKI gamma to modulate the anti-apoptotic effects of PTH and beta-adrenergic agonists in ROS 17/2.8 cells. Knockdown of PKI gamma substantially extended the anti-apoptotic effects of PTH, whether apoptosis was induced by etoposide or dexamethasone. In contrast, overexpression of PKI gamma decreased the anti-apoptotic effect of PTH pretreatment. This study is also the first demonstration that beta-adrenergic agonists mimic the anti-apoptotic effects of PTH in osteoblasts. Moreover, PKI gamma knockdown also substantially extended this anti-apoptotic effect of beta-adrenergic agonists. Taken together, these results show that endogenous PKI gamma limits the duration of the anti-apoptotic effects of cAMP/PKA signaling in osteoblasts. Because significant individual variability exists in the anabolic responses to PTH therapy in current clinical treatment of osteoporosis, inhibition of PKI gamma activity may provide a useful co-therapy in combination with intermittent PTH or beta-adrenergic agonists for bone loss in conditions such as osteoporosis. However, the potential use of such a co-therapy would depend on it not adversely affecting bone formation or other organ systems.

Twenty-Fourth Lunar and Planetary Science Conference. Part 2: G-M

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1993-01-01

The topics covered include the following: meteorites, meteoritic composition, geochemistry, planetary geology, planetary composition, planetary craters, the Moon, Mars, Venus, asteroids, planetary atmospheres, meteorite craters, space exploration, lunar geology, planetary surfaces, lunar surface, lunar rocks, lunar soil, planetary atmospheres, lunar atmosphere, lunar exploration, space missions, geomorphology, lithology, petrology, petrography, planetary evolution, Earth surface, planetary surfaces, volcanology, volcanos, lava, magma, mineralogy, minerals, ejecta, impact damage, meteoritic damage, tectonics, etc. Separate abstracts have been prepared for articles from this report.

C/EBPβ Promotes STAT3 Expression and Affects Cell Apoptosis and Proliferation in Porcine Ovarian Granulosa Cells.

PubMed

Yuan, Xiaolong; Zhou, Xiaofeng; He, Yingting; Zhong, Yuyi; Zhang, Ailing; Zhang, Zhe; Zhang, Hao; Li, Jiaqi

2018-06-13

Previous studies suggest that signal transducer and activator of transcription 3 (STAT3) and CCAAT/enhancer binding protein beta (C/EBPβ) play an essential role in ovarian granulosa cells (GCs) for mammalian follicular development. Several C/EBPβ putative binding sites were previously predicted on the STAT3 promoter in mammals. However, the molecular regulation of C/EBPβ on STAT3 and their effects on cell proliferation and apoptosis remain virtually unexplored in GCs. Using porcine GCs as a model, the 5′-deletion, luciferase report assay, mutation, chromatin immunoprecipitation, Annexin-V/PI staining and EdU assays were applied to investigate the molecular mechanism for C/EBPβ regulating the expression of STAT3 and their effects on the cell proliferation and apoptosis ability. We found that over and interfering with the expression of C/EBPβ significantly increased and decreased the messenger RNA (mRNA) and protein levels of STAT3 , respectively. The dual luciferase reporter assay showed that C/EBPβ directly bound at −1397/−1387 of STAT3 to positively regulate the mRNA and protein expressions of STAT3 . Both C/EBPβ and STAT3 were observed to inhibit cell apoptosis and promote cell proliferation. Furthermore, C/EBPβ might enhance the antiapoptotic and pro-proliferative effects of STAT3 . These results would be of great insight in further exploring the molecular mechanism of C/EBPβ and STAT3 on the function of GCs and the development of ovarian follicles in mammals.

Monocyte production of transforming growth factor beta in long-term hemodialysis: modulation by hemodialysis membranes.

PubMed

Mege, J L; Capo, C; Purgus, R; Olmer, M

1996-09-01

Cytokines are likely involved in hemodialysis-associated complications such as immunodeficiency and beta 2 microglobulin amyloidosis. Because transforming growth factors beta (TGF beta) exert immunosuppressive effects on lymphocytes, down-modulate monocyte functions, and promote fibrosis, we hypothesize that they participate in the deleterious effects of hemodialysis. We investigated the production of TGF beta 1 and TGF beta 2 by monocytes from controls and patients dialyzed with high-flux cellulose triacetate (CT) and polyacrylonitrile (PAN) membranes. The detection of both TGF beta s required an acidification step, suggesting that they are secreted as latent complexes. The spontaneous production of TGF beta 1 and TGF beta 2 was significantly higher in patients dialyzed with CT or PAN than in controls, but the oversecretion of TGF beta 1 was more sustained in CT-treated patients than in PAN-dialyzed patients. The production of interleukin-6 (IL-6) was increased in both patient groups as compared with controls. In contrast to TGF beta 1, the increase was greater in PAN-treated patients than in CT-treated patients, and the release of tumor necrosis factor alpha (TNF alpha) was increased only in PAN-treated patients. Taken together, our results show that hemodialysis is associated with the oversecretion of monocyte cytokines. Moreover, the type of dialysis membrane specifically affects the balance between the secretion of suppressive cytokines such as TGF beta and that of inflammatory cytokines such as IL-6 and TNF alpha.

Results from the GSFC fluxgate magnetometer on Pioneer 11

NASA Technical Reports Server (NTRS)

Acuna, M. H.; Ness, N. F.

1976-01-01

A high-field triaxial fluxgate magnetometer was mounted on Pioneer 11 to measure the main magnetic field of Jupiter. It is found that this planetary magnetic field is more complex than that indicated by the results of the Pioneer 10 vector helium magnetometer. At distances less than 3 Jupiter radii, the magnetic field is observed to increase more rapidly than an inverse-cubed distance law associated with any simple dipole model. Contributions from higher-order multipoles are significant, with the quadrupole and octupole being 24 and 21 percent of the dipole moment, respectively. Implications of the results for the study of trapped particles, planetary radio emission, and planetary interiors are discussed. Major conclusions are that the deviation of the main planetary magnetic field from a simple dipole leads to distortion of the L shells of the charged particles and to warping of the magnetic equator. Enhanced absorption effects associated with Amalthea and Io are predicted.

Integrating advanced visualization technology into the planetary Geoscience workflow

NASA Astrophysics Data System (ADS)

Huffman, John; Forsberg, Andrew; Loomis, Andrew; Head, James; Dickson, James; Fassett, Caleb

2011-09-01

Recent advances in computer visualization have allowed us to develop new tools for analyzing the data gathered during planetary missions, which is important, since these data sets have grown exponentially in recent years to tens of terabytes in size. As part of the Advanced Visualization in Solar System Exploration and Research (ADVISER) project, we utilize several advanced visualization techniques created specifically with planetary image data in mind. The Geoviewer application allows real-time active stereo display of images, which in aggregate have billions of pixels. The ADVISER desktop application platform allows fast three-dimensional visualization of planetary images overlain on digital terrain models. Both applications include tools for easy data ingest and real-time analysis in a programmatic manner. Incorporation of these tools into our everyday scientific workflow has proved important for scientific analysis, discussion, and publication, and enabled effective and exciting educational activities for students from high school through graduate school.

Integrated optimization of planetary rover layout and exploration routes

NASA Astrophysics Data System (ADS)

Lee, Dongoo; Ahn, Jaemyung

2018-01-01

This article introduces an optimization framework for the integrated design of a planetary surface rover and its exploration route that is applicable to the initial phase of a planetary exploration campaign composed of multiple surface missions. The scientific capability and the mobility of a rover are modelled as functions of the science weight fraction, a key parameter characterizing the rover. The proposed problem is formulated as a mixed-integer nonlinear program that maximizes the sum of profits obtained through a planetary surface exploration mission by simultaneously determining the science weight fraction of the rover, the sites to visit and their visiting sequences under resource consumption constraints imposed on each route and collectively on a mission. A solution procedure for the proposed problem composed of two loops (the outer loop and the inner loop) is developed. The results of test cases demonstrating the effectiveness of the proposed framework are presented.

Effects of beta-thujaplicin on anti-Malassezia pachydermatis remedy for canine otitis externa.

PubMed

Nakano, Yasuyuki; Wada, Makoto; Tani, Hiroyuki; Sasai, Kazumi; Baba, Eiichiroh

2005-12-01

The antifungal activity of beta-thujaplicin was evaluated against 51 Malassezia pachydermatis strains isolated from canine ear canals with or without otitis externa. For comparison, sensitivity tests were performed on M. pachydermatis isolates for nystatin, ketoconazole, and terbinafine HCl, all clinically available antifungal agents. The minimal inhibition concentrations over 50% of the tested isolates (MIC50) were 3.13 microg/ml for beta-thujaplicin and nystatin, 0.016 microg/ml for ketoconazole, and 1.56 microg/ml for terbinafine HCl. The antifungal effect for M. pachydermatis of beta-thujaplicin compared favorably with commercial antifungal agents. None of the 51 M. pachydermatis isolates showed resistance against any of the tested antibiotics investigated in this study. Ten representative isolates of M. pachydermatis were subcultured for 30 generations at concentrations close to the MIC levels of beta-thujaplicin, nystatin, ketoconazole, and terbinafine HCl, and examined to determine whether they had acquired resistance to each drug. As a result, M. pachydermatis was found to achieve resistance more easily for ketoconazole and terbinafine HCl than for beta-thujaplicin or nystatin. The MIC50 of beta-thujaplicin did not change during the course of subculture, and it is thought that the potential development of a resistant strain is low, even with continuous infusion for otitis externa therapy. beta-Thujaplicin is an inexpensive and safe treatment with anti-inflammatory and deodorant effects that can be recommended as an effective remedy for canine otitis externa.

Pressure-induced subunit dissociation and unfolding of dimeric beta-lactoglobulin.

PubMed Central

Valente-Mesquita, V L; Botelho, M M; Ferreira, S T

1998-01-01

Effects of hydrostatic pressure on dimeric beta-lactoglobulin A (beta-Lg) were investigated. Application of pressures of up to 3.5 kbar induced a significant red shift ( approximately 11 nm) and a 60% increase in intrinsic fluorescence emission of beta-Lg. These changes were very similar to those induced by guanidine hydrochloride, which caused subunit dissociation and unfolding of beta-Lg. A large hysteresis in the recovery of fluorescence parameters was observed upon decompression of beta-Lg. Pressure-induced dissociation and unfolding were not fully reversible, because of the formation of a nonnative intersubunit disulfide bond that hampered correct refolding of the dimer. Comparison between pressure dissociation/unfolding at 3 degrees C and 23 degrees C revealed a marked destabilization of beta-Lg at low temperature. The stability of beta-Lg toward pressure was significantly enhanced by 1 M NaCl, but not by glycerol (up to 20% v/v). These observations suggest that salt stabilization was not related to a general cosolvent effect, but may reflect charge screening. Interestingly, pressure-induced dissociation/unfolding was completely independent of beta-Lg concentration, in apparent violation of the law of mass action. Possible causes for this anomalous behavior are discussed. PMID:9649408

Equilibrium positions on stationary orbits and planetary principal inertia axis orientations for the Solar System

NASA Astrophysics Data System (ADS)

Romero, Pilar; Barderas, Gonzalo; Mejuto, Javier

2018-05-01

We present a qualitative analysis in a phase space to determine the longitudinal equilibrium positions on the planetary stationary orbits by applying an analytical model that considers linear gravitational perturbations. We discuss how these longitudes are related with the orientation of the planetary principal inertia axes with respect to their Prime Meridians, and then we use this determination to derive their positions with respect to the International Celestial Reference Frame. Finally, a numerical analysis of the non-linear effects of the gravitational fields on the equilibrium point locations is developed and their correlation with gravity field anomalies shown.

REVIEWS OF TOPICAL PROBLEMS: Generation of large-scale eddies and zonal winds in planetary atmospheres

NASA Astrophysics Data System (ADS)

Onishchenko, O. G.; Pokhotelov, O. A.; Astafieva, N. M.

2008-06-01

The review deals with a theoretical description of the generation of zonal winds and vortices in a turbulent barotropic atmosphere. These large-scale structures largely determine the dynamics and transport processes in planetary atmospheres. The role of nonlinear effects on the formation of mesoscale vortical structures (cyclones and anticyclones) is examined. A new mechanism for zonal wind generation in planetary atmospheres is discussed. It is based on the parametric generation of convective cells by finite-amplitude Rossby waves. Weakly turbulent spectra of Rossby waves are considered. The theoretical results are compared to the results of satellite microwave monitoring of the Earth's atmosphere.

Drug development targeting the glycogen synthase kinase-3beta (GSK-3beta)-mediated signal transduction pathway: role of GSK-3beta in myocardial protection against ischemia/reperfusion injury.

PubMed

Miura, Tetsuji; Nishihara, Masahiro; Miki, Takayuki

2009-02-01

Although reperfusion is required to salvage ischemic myocardium from necrosis, reperfusion per se induces myocardial necrosis. In this "lethal reperfusion injury", opening of the mitochondrial permeability transition pore (mPTP) upon reperfusion is crucially involved. The mPTP primarily consists of adenine nucleotide translocator (ANT) and voltage-dependent anion channel, and its opening is triggered by binding of cyclophilin-D (CyP-D) to ANT, which increases Ca(2+) sensitivity of the mPTP. Recent studies have shown that inactivation of glycogen synthase kinase-3beta (GSK-3beta) suppresses mPTP opening and protects cardiomyocytes. Multiple intracellular signals relevant to cardiomyocyte protection converge to GSK-3beta and inactivate this kinase by phosphorylation. Although the effect of GSK-3beta phosphorylation on mPTP structure and function remains unclear, suppression of ANT-CyP-D interaction by binding of phospho-GSK-3beta to ANT and reduction in GSK-3beta-mediated phosphorylation of p53 may contribute to elevation of the threshold for mPTP opening. Furthermore, a significant inverse correlation was observed between level of phospho-GSK-3beta at the time of reperfusion and the extent of myocardium infarction in heart. Together with the infarct size-limiting effect of GSK-3beta inhibitors, this finding indicates that phospho-GSK-3beta is a determinant of myocardial tolerance against reperfusion-induced necrosis. Thus, GSK-3beta appears to be a target of novel therapy for cardioprotection upon reperfusion.

Mutant HNF-1{alpha} and mutant HNF-1{beta} identified in MODY3 and MODY5 downregulate DPP-IV gene expression in Caco-2 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gu Ning; Laboratory of Neurochemistry, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto; Adachi, Tetsuya

2006-08-04

Dipeptidylpeptidase IV (DPP-IV) is a well-documented drug target for the treatment of type 2 diabetes. Hepatocyte nuclear factors (HNF)-1{alpha} and HNF-1{beta}, known as the causal genes of MODY3 and MODY5, respectively, have been reported to be involved in regulation of DPP-IV gene expression. But, it is not completely clear (i) that they play roles in regulation of DPP-IV gene expression, and (ii) whether DPP-IV gene activity is changed by mutant HNF-1{alpha} and mutant HNF-1{beta} in MODY3 and MODY5. To explore these questions, we investigated transactivation effects of wild HNF-1{alpha} and 13 mutant HNF-1{alpha}, as well as wild HNF-1{beta} and 2more » mutant HNF-1{beta}, on DPP-IV promoter luciferase gene in Caco-2 cells by means of a transient experiment. Both wild HNF-1{alpha} and wild HNF-1{beta} significantly transactivated DPP-IV promoter, but mutant HNF-1{alpha} and mutant HNF-1{beta} exhibited low transactivation activity. Moreover, to study whether mutant HNF-1{alpha} and mutant HNF-1{beta} change endogenous DPP-IV enzyme activity, we produced four stable cell lines from Caco-2 cells, in which wild HNF-1{alpha} or wild HNF-1{beta}, or else respective dominant-negative mutant HNF-1{alpha}T539fsdelC or dominant-negative mutant HNF-1{beta}R177X, was stably expressed. We found that DPP-IV gene expression and enzyme activity were significantly increased in wild HNF-1{alpha} cells and wild HNF-1{beta} cells, whereas they decreased in HNF-1{alpha}T539fsdelC cells and HNF-1{beta}R177X cells, compared with DPP-IV gene expression and enzyme activity in Caco-2 cells. These results suggest that both wild HNF-1{alpha} and wild HNF-1{beta} have a stimulatory effect on DPP-IV gene expression, but that mutant HNF-1{alpha} and mutant HNF-1{beta} attenuate the stimulatory effect.« less

Intracerebral beta-endorphin, met-enkephalin and morphine: kindling of seizures and handling-induced potentiation of epileptiform effects.

PubMed

Cain, D P; Corcoran, M E

1984-06-18

The effects of repeated infusion of small, initially subconvulsive amounts of beta-endorphin, met-enkephalin or morphine sulfate into the amygdala and hippocampus were investigated. beta-endorphin and met-enkephalin evoked epileptiform spiking when infused into the posterior amygdala or ventral hippocampus. Morphine evoked epileptiform spiking when infused into the anterior amygdala. Naloxone blocked or terminated the spiking. Repetition of the infusions led to the gradual development of bilateral generalized convulsions by beta-endorphin and met-enkephalin and to the development of tolerance to morphine. An unexpected observation was that handling, immobilization or conspecific threat potentiated the epileptiform effects of beta-endorphin and morphine in many cases. These results suggest that endogenous opiate mechanisms might play a role in convulsive seizures and that stressful stimuli can exacerbate opiate seizures.

Effect of dialyzer membranes on beta-2 microglobulin production in Thai hemodialysis patients.

PubMed

Domrongkitchaiporn, S; Chuncharunee, S; Archararit, N; Atamasirikul, K; Vanichakarn, S

1997-09-01

Responses to different types of dialyzer membranes in an Asian population may differ from those of a Caucasian population. Comparative studies on the effects of different dialyzer membranes on beta-2 microglobulin production are also limited. Therefore, we conducted this study to determine the effects of different dialyzer membranes on in vitro mononuclear cell production of beta-2 microglobulin in 9 Thai hemodialysis patients. Each patient was dialysed with 4 different types of dialyzer, including cuprophane (CUP), cellulose diacetate (CD), polysulphone (PS), and polyacrylonitrile membrane (PAN), each for a 1-month period in a randomized sequence. Mononuclear cell culture was done by taking an immediate post-dialysis blood sample at the end of the 1-month period. Beta-2 microglobulin production from cell culture was determined 24 hours later. Mononuclear cell culture and determination of beta-2 microglobulin production from the culture were also done in 10 normal controls and 10 predialysis ESRD patients. The beta-2 microglobulin productions (microgram/L) were shown as follows; Control CUP CD PS PAN [table: see text] (*p < 0.05 compared to cuprophane membrane). polysulphone and polyacrylonitrile membrane induced significantly less beta-2 microglobulin production compared to cuprophane and slightly less compared to cellulose diacetate membrane.

Beneficial effect of 17{beta}-estradiol on hyperglycemia and islet {beta}-cell functions in a streptozotocin-induced diabetic rat model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamabe, Noriko; Kang, Ki Sung; Zhu Baoting, E-mail: BTZhu@kumc.ed

2010-11-15

The modulating effect of estrogen on glucose homeostasis remains a controversial issue at present. In this study, we sought to determine the beneficial effect of 17{beta}-estradiol (E{sub 2}) on hyperglycemia and islet {beta}-cell functions in streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were injected i.p. with STZ to induce a relatively mild diabetic condition. The rats were then treated with E{sub 2} orally at 500 {mu}g/kg body weight/day for 15 days to evaluate the modulating effect on hyperglycemia, insulin secretion, and islet {beta}-cell proliferation. E{sub 2} administration for 10 days significantly lowered plasma glucose levels, increased plasma insulin levels, andmore » improved glucose tolerance by attenuating insulin response to oral glucose loading. These beneficial effects of E{sub 2} were accompanied by increases in islet number and volume, rate of islet cell proliferation, and the amount of insulin secreted. The growth-stimulatory effect of E{sub 2} on islet cells was linked to the functions of the estrogen receptor {alpha}. Notably, these protective effects of E{sub 2} on diabetic conditions were basically not observed when the STZ-treated rats had a more severe degree of islet damage and hyperglycemia. Taken together, we conclude that E{sub 2} can promote the regeneration of damaged pancreatic islets by stimulating {beta}-cell proliferation in diabetic rats, and this effect is accompanied by improvements in glucose tolerance and a decrease in plasma glucose levels. These findings suggest that oral administration of E{sub 2} may be beneficial in diabetic patients with an accelerated loss of islet {beta}-cells.« less

Comparative molecular field analysis of fenoterol derivatives: A platform towards highly selective and effective beta(2)-adrenergic receptor agonists.

PubMed

Jozwiak, Krzysztof; Woo, Anthony Yiu-Ho; Tanga, Mary J; Toll, Lawrence; Jimenez, Lucita; Kozocas, Joseph A; Plazinska, Anita; Xiao, Rui-Ping; Wainer, Irving W

2010-01-15

To use a previously developed CoMFA model to design a series of new structures of high selectivity and efficacy towards the beta(2)-adrenergic receptor. Out of 21 computationally designed structures 6 compounds were synthesized and characterized for beta(2)-AR binding affinities, subtype selectivities and functional activities. the best compound is (R,R)-4-methoxy-1-naphthylfelnoterol with K(i)beta(2)-AR=0.28microm, K(i)beta(1)-AR/K(i)beta(2)-AR=573, EC(50cAMP)=3.9nm, EC(50cardio)=16nm. The CoMFA model appears to be an effective predictor of the cardiomocyte contractility of the studied compounds which are targeted for use in congestive heart failure. Copyright 2009 Elsevier Ltd. All rights reserved.

Neurofeedback of SMR and Beta1 Frequencies: An Investigation of Learning Indices and Frequency-Specific Effects.

PubMed

Pimenta, Miguel G; van Run, Chris; de Fockert, Jan W; Gruzelier, John H

2018-05-15

Despite evidence that Sensorimotor Rhythm (SMR) and beta1 neurofeedback have distinct cognitive enhancement effects, it remains unclear whether their amplitudes can be independently enhanced. Furthermore, demands for top-down attention control, postural restraint and maintenance of cognitive set processes, all requiring low-beta frequencies, might masquerade as learning and confound interpretation. The feasibility of selectively enhancing SMR and beta1 amplitudes was investigated with the addition of a random frequency control condition that also requires the potentially confounding cognitive processes. A comprehensive approach to assessing neurofeedback learning was undertaken through the calculation of learning indices within- and across-session and pre-to-post baseline. Herein we provide the first demonstration of beta1 within-session amplitude learning that was not attributable to extraneous cognitive processes, for it was not found with random frequency training. On the other hand, within-session SMR learning might have been obscured by high interindividual variability and methodological limitations such as the type of feedback screen, the insufficient number of sessions, and the exclusion of simultaneous theta and high-beta inhibition. Interestingly, SMR and beta1 amplitude increased across sessions in the three groups suggesting unspecific effects of neurofeedback in the low beta frequency band. Moreover, there was no clear evidence of frequency specificity associated with either SMR or beta1 training. Some methodological limitations may underpin the divergent results with previous studies. Copyright © 2017 IBRO. All rights reserved.

GSK-3beta inhibition enhances sorafenib-induced apoptosis in melanoma cell lines.

PubMed

Panka, David J; Cho, Daniel C; Atkins, Michael B; Mier, James W

2008-01-11

Glycogen synthase kinase-3beta (GSK-3beta) can participate in the induction of apoptosis or, alternatively, provide a survival signal that minimizes cellular injury. We previously demonstrated that the multikinase inhibitor sorafenib induces apoptosis in melanoma cell lines. In this report, we show that sorafenib activates GSK-3beta in multiple subcellular compartments and that this activation undermines the lethality of the drug. Pharmacologic inhibition and/or down-modulation of the kinase enhances sorafenib-induced apoptosis as determined by propidium iodide staining and by assessing the mitochondrial release of apoptosis-inducing factor and Smac/DIABLO. Conversely, the forced expression of a constitutively active form of the enzyme (GSK-3beta(S9A)) protects the cells from the apoptotic effects of the drug. This protective effect is associated with a marked increase in basal levels of Bcl-2, Bcl-x(L), and survivin and a diminution in the degree to which these anti-apoptotic proteins are down-modulated by sorafenib exposure. Sorafenib down-modulates the pro-apoptotic Bcl-2 family member Noxa in cells with high constitutive GSK-3beta activity. Pharmacologic inhibition of GSK-3beta prevents the disappearance of Noxa induced by sorafenib and enhances the down-modulation of Mcl-1. Down-modulation of Noxa largely eliminates the enhancing effect of GSK-3 inhibition on sorafenib-induced apoptosis. These data provide a strong rationale for the use of GSK-3beta inhibitors as adjuncts to sorafenib treatment and suggest that preservation of Noxa may contribute to their efficacy.

Test Before You Fly - High Fidelity Planetary Environment Simulation

NASA Technical Reports Server (NTRS)

Craven, Paul; Ramachandran, Narayanan; Vaughn, Jason; Schneider, Todd; Nehls, Mary

2012-01-01

The lunar surface environment will present many challenges to the survivability of systems developed for long duration lunar habitation and exploration of the lunar, or any other planetary, surface. Obstacles will include issues pertaining especially to the radiation environment (solar plasma and electromagnetic radiation) and lunar regolith dust. The Planetary Environments Chamber is one piece of the MSFC capability in Space Environmental Effects Test and Analysis. Comprised of many unique test systems, MSFC has the most complete set of SEE test capabilities in one location allowing examination of combined space environmental effects without transporting already degraded, potentially fragile samples over long distances between tests. With this system, the individual and combined effects of the lunar radiation and regolith environment on materials, sub-systems, and small systems developed for the lunar return can be investigated. This combined environments facility represents a unique capability to NASA, in which tests can be tailored to any one aspect of the lunar environment (radiation, temperature, vacuum, regolith) or to several of them combined in a single test.

La Terra: esperimenti a scuola

NASA Astrophysics Data System (ADS)

Roselli, Alessandra; D'Amico, Angelalucia; Pisegna, Daniela; Palma, Francesco; di Nardo, Giustino; Cofini, Marika; Cerasani, Paolo; Cerratti, Valentina

2006-02-01

Easy but effective methods used in past centuries allow rediscovery and good knowledge of the planet Earth. The latitude station and planetary radius were measured with Eratosthenes method. The gravity acceleration obtained from pendulum period was used to calculate the terrestrial mass and the density of internal planetary layers. Finally, the estimate of atmosphere density and geometrical thickness complete the view of the planet's properties.

Beta-blockers in the management of hypertension: focus on nebivolol.

PubMed

Wojciechowski, David; Papademetriou, Vasilios

2008-04-01

Hypertension is a major cardiovascular risk factor but most patients remain asymptomatic for many years. Successful therapy not only needs to be effective, it also needs to be well tolerated. beta-blockers are well established as effective antihypertensive agents. However, one major drawback to the currently available beta-blockers, particularly the noncardioselective beta-blockers, is their side-effect profile, including sexual dysfunction, fatigue, depression and metabolic abnormalities such as impaired glucose tolerance and lipid abnormalities. Nebivolol (Bystolic), a novel, highly cardioselective, third-generation beta-blocker that recently received approval by the US FDA for the treatment of hypertension in the USA, is effective in treating blood pressure and has a favorable side-effect profile. Studies conducted in Europe, where nebivolol has been available for some time for the treatment of hypertension, have shown that nebivolol achieves blood pressure reductions comparable to other beta-blockers but with fewer side effects. Additionally, nebivolol has demonstrated similar efficacy in blood pressure reduction when compared with calcium channel blockers and inhibitors of the renin-angiotensin system. When combined with hydrochlorothiazide there was an additive antihypertensive effect. Lastly, nebivolol exhibits a vasodilatory property that is related to its effect on nitric oxide, an intrinsic vasodilator produced in the vascular endothelium. Nebivolol enhances nitric oxide bioavailability. Studies have also demonstrated nebivolol's ability to function as an antioxidant and decrease markers of oxidative stress. These effects are believed to ultimately produce a modulation of the endothelial dysfunction typically seen in hypertension.

Effects of fixture rotation on coating uniformity for high-performance optical filter fabrication

NASA Astrophysics Data System (ADS)

Rubin, Binyamin; George, Jason; Singhal, Riju

2018-04-01

Coating uniformity is critical in fabricating high-performance optical filters by various vacuum deposition methods. Simple and planetary rotation systems with shadow masks are used to achieve the required uniformity [J. B. Oliver and D. Talbot, Appl. Optics 45, 13, 3097 (2006); O. Lyngnes, K. Kraus, A. Ode and T. Erguder, in `Method for Designing Coating Thickness Uniformity Shadow Masks for Deposition Systems with a Planetary Fixture', 2014 Technical Conference Proceedings, Optical Coatings, August 13, 2014, DOI: 10.14332/svc14.proc.1817.]. In this work, we discuss the effect of rotation pattern and speed on thickness uniformity in an ion beam sputter deposition system. Numerical modeling is used to determine statistical distribution of random thickness errors in coating layers. The relationship between thickness tolerance and production yield are simulated theoretically and demonstrated experimentally. Production yields for different optical filters produced in an ion beam deposition system with planetary rotation are presented. Single-wavelength and broadband optical monitoring systems were used for endpoint monitoring during filter deposition. Limitations of thickness tolerances that can be achieved in systems with planetary rotation are shown. Paths for improving production yield in an ion beam deposition system are described.

Upregulation of adipose 11-beta-hydroxysteroid dehydrogenase type 1 expression in ovariectomized rats is due to obesity rather than lack of estrogen.

PubMed

Paulsen, Søren K; Nielsen, Maria P; Richelsen, Bjørn; Bruun, Jens M; Flyvbjerg, Allan; Pedersen, Steen B

2008-04-01

Increased tissue activity of cortisol induced by the activation of inert cortisone to active cortisol through 11-beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) may play a role in the metabolic syndrome. We recently found that 11beta-HSD1 in subcutaneous adipose tissue (AT) was lower in lean women compared with lean men. Estrogen suppresses hepatic and renal 11beta-HSD1 in rats; hence we investigated the in vitro effect of estrogen on human and rat AT, and the in vivo effects on rat AT 11beta-HSD1 expression. Wistar rats were divided into four groups of eight animals. One group was sham-operated (controls) and others were ovariectomized (OVX). One OVX group was left untreated (OVX-E), another (OVX+E) received estrogen treatment, and one received a hypo-caloric diet (OVX-E+D), matching the weight gain of the control group. AT from women undergoing liposuction or surgery and from killed male and female rats were incubated with estrogen alone or in the presence of IL-1beta. Gene expressions were determined by real-time reverse transcriptase PCR. Ovariectomy resulted in a 280% increase in adipose 11beta-HSD1 expression P < 0.05). 11beta-HSD1 expression in the (OVX+E)-group was significantly reduced compared with the nonsubstituted group (P < 0.05). 11beta-HSD1 expression in the (OVX-E+D)-group was reduced significantly (P < 0.05) when compared with the level of the estrogen-substituted group. No significant differences between the control group, the (OVX+E)-group, and the (OVX-E+D)-group were found. In the in vitro studies, no direct effect of estrogen on adipose 11beta-HSD1 was found. The upregulation of 11beta-HSD1 in ovariectomized rats was most likely due to changes in body composition rather than lack of estrogen.

Simultaneous intake of beta-glucan and plant stanol esters affects lipid metabolism in slightly hypercholesterolemic subjects.

PubMed

Theuwissen, Elke; Mensink, Ronald P

2007-03-01

Intake of food products rich in water-soluble fiber beta-glucan and products enriched with plant stanol esters lower serum cholesterol. Combining 2 functional food ingredients into one food product may achieve additional reductions of serum cholesterol. Our objective was to investigate the effects of a simultaneous intake of beta-glucan plus plant stanol esters on lipid metabolism in mildly hypercholesterolemic volunteers. In a randomized, controlled, 3-period crossover study, 40 mildly hypercholesterolemic men and women received muesli in random order twice a day for 4 wk, which provided, in total, 5 g control fiber from wheat (control muesli), 5 g oat beta-glucan (beta-glucan muesli), or 5 g oat beta-glucan plus 1.5 g plant stanols (combination muesli). beta-Glucan muesli decreased serum LDL cholesterol by 5.0% compared with control muesli (P = 0.013). Combination muesli reduced LDL cholesterol by 9.6% compared with control muesli (P < 0.001), and by 4.4% compared with beta-glucan muesli (P = 0.036). Serum HDL cholesterol and triacylglycerol concentrations did not differ after the 3 treatments. Compared with control muesli, beta-glucan muesli increased bile acid synthesis (P = 0.043) and decreased cholesterol absorption (P = 0.011). Addition of plant stanols did not influence bile acid synthesis but decreased cholesterol absorption (P < 0.001) and raised cholesterol synthesis (P = 0.016) compared with control muesli, and the plant stanols decreased cholesterol absorption compared with beta-glucan muesli (P = 0.004). The combination muesli decreased serum concentrations of sitostanol compared with control muesli (P = 0.010). Plasma concentrations of lipid-soluble antioxidants did not differ after the 3 treatments. beta-Glucan muesli effectively lowered serum LDL cholesterol concentrations. The addition of plant stanol esters to beta-glucan-enriched muesli further lowered serum LDL cholesterol, although effects were slightly less than predicted.

Effects of beta-escin and saponin on the transverse-tubular system and sarcoplasmic reticulum membranes of rat and toad skeletal muscle.

PubMed

Launikonis, B S; Stephenson, D G

1999-05-01

Mechanically skinned skeletal muscle fibres from rat and toad were exposed to the permeabilizing agents beta-escin and saponin. The effects of these agents on the sealed transverse tubular system (t-system) and sarcoplasmic reticulum (SR) were examined by looking at changes in the magnitude of the force responses to t-system depolarization, the time course of the fluorescence of fura-2 trapped in the sealed t-system, and changes in the magnitude of caffeine-induced contractures following SR loading with Ca2+ under defined conditions. In the presence of 2 microg ml-1 beta-escin and saponin, the response to t-system depolarization was not completely abolished, decreasing to a plateau, and a large proportion of fura-2 remained in the sealed t-system. At 10 microg ml-1, both agents abolished the ability of both rat and toad preparations to respond to t-system depolarization after 3 min of exposure, but a significant amount of fura-2 remained in sealed t-tubules even after exposure to 100 microg ml-1 beta-escin and saponin for 10 min. beta-Escin took longer than saponin to reduce the t-system depolarizations and fura-2 content of the sealed t-system to a similar level. The ability of the SR to load Ca2+ was reduced to a lower level after treatment with beta-escin than saponin. This direct effect on the SR occurred at much lower concentrations for rat (2 microg ml-1 beta-escin and 10 microg ml-1 saponin) than toad (10 microg ml-1 beta-escin and 150 microg ml-1 saponin). The reverse order in sensitivities to beta-escin and saponin of t-system and SR membranes indicates that the mechanisms of action of beta-escin and saponin are different in the two types of membrane. In conclusion, this study shows that: (1) beta-escin has a milder action on the surface membrane than saponin; (2) beta-escin is a more potent modifier of SR function; (3) simple permeabilization of membranes is not sufficient to explain the effects of beta-escin and saponin on muscle membranes; and (4) the t-system network within muscle fibres is not a homogeneous compartment.

Fermentable metabolite of Zymomonas mobilis controls collagen reduction in photoaging skin by improving TGF-beta/Smad signaling suppression.

PubMed

Tanaka, Hiroshi; Yamaba, Hiroyuki; Kosugi, Nobuhiko; Mizutani, Hiroshi; Nakata, Satoru

2008-04-01

Solar ultraviolet (UV) irradiation causes damages on human skin and premature skin aging (photoaging). UV-induced reduction of type I collagen in dermis is widely considered primarily induction of wrinkled appearance of photoaging skin. Type I procollagen synthesis is reduced under UV irradiation by blocking transforming growth factor-beta (TGF-beta)/Smad signaling; more specifically, it is down-regulation of TGF-beta type II receptor (T beta RII). Therefore, preventing UV-induced loss of T beta RII results decreased type I collagen reduction in photoaging skin. Zymomonas mobilis is an alcohol fermentable, gram-negative facultative anaerobic bacterium whose effect on skin tissue is scarcely studied. We investigated the protective effects of fermentable metabolite of Z. mobilis (FM of Z. mobilis) against reduction of type I procollagen synthesis of UV-induced down-regulation of T beta RII in human dermal fibroblasts FM of Z. mobilis was obtained from lyophilization of bacterium culture supernatant. The levels of T beta RII and type I procollagen mRNA in human dermal fibroblasts were measured by quantitative real-time RT-PCR, and T beta RII protein levels were assayed by western blotting. T beta RII, type I procollagen, and type I collagen proteins in human dermal fibroblasts or hairless mouse skin were detected by immunostaining. FM of Z. mobilis inhibited down regulation of T beta RII mRNA, and protein levels in UVB irradiated human dermal fibroblasts consequently recover reduced type I procollagen synthesis. These results indicate UVB irradiation inhibits type I procollagen synthesis by suppression of TGF-beta/Smad signaling pathway, and FM of Z. mobilis has inhibitory effect on UVB-induced reduction of type I procollagen synthesis. While short period UVB irradiation decreased both T beta RII and type I procollagen protein levels in hairless mouse skin, topical application of FM of Z. mobilis prevented this decrease. Wrinkle formation in hairless mouse skin surface was accelerated by continuous 5 month UVB irradiation along with a reduction of type I collagen in the dermis, but this change was prevented by topical application of FM of Z. mobilis. From this experimental data, it is suggested that FM of Z. mobilis is effective for suppression of wrinkle formation in photoaging skin by inhibition of type I procollagen synthesis reduction.

[Effects of penetration enhancers on curcumin transdermal drug delivery].

PubMed

Gao, Zhen-Shen; Wang, Lan; Zhang, Mei

2012-01-01

To study the effects of penetration enhancers and their combinations on the curcumine transdermal drug delivery (CUR-TDDS). The penetration rate of curcumin through rat skin in vitro was measured using Valia-Chien diffusion cells, and orthogonal design method was set up for experimental design. The optimum penetration enhancers were: 3% hydroxypropyl beta cyclodextrins (HP-beta-CD), 9% borneol and 3% peppermint oil. The HP-beta-CD has the most potent enhancing effect.

How disturbing are side effects of beta blockers.

PubMed

Besterman, E M

1983-07-01

Drug side effects are notoriously difficult to evaluate accurately. In this particular context there are further problems arising from the exclusion of many patients in some of the few published series of populations exposed to beta-blocking drugs. In some of these same series, placebo side effects appear to affect almost as many patients as the active drug. However, detailed breakdown of these side effects show significant differences in the actual complaints made by patients of each group. Apart from the well known major complications of beta-blocking drugs, the lesser but still disturbing ones to mention include generalized fatigue, muscle weakness, cold extremities, nightmares and impotence. A change of beta-blocking preparation or else lowering the dosage often ameliorates these problems.

Effect of geometrical configuration of radioactive sources on radiation intensity in beta-voltaic nuclear battery system: A preliminary result

DOE Office of Scientific and Technical Information (OSTI.GOV)

Basar, Khairul, E-mail: khbasar@fi.itb.ac.id; Riupassa, Robi D., E-mail: khbasar@fi.itb.ac.id; Bachtiar, Reza, E-mail: khbasar@fi.itb.ac.id

2014-01-01

It is known that one main problem in the application of beta-voltaic nuclear battery system is its low efficiency. The efficiency of the beta-voltaic nuclear battery system mainly depends on three aspects: source of radioactive radiation, interface between materials in the system and process of converting electron-hole pair to electric current in the semiconductor material. In this work, we show the effect of geometrical configuration of radioactive sources on radiation intensity of beta-voltaic nuclear battery system.

Avenues for Scientist Involvement in Planetary Science Education and Public Outreach

NASA Astrophysics Data System (ADS)

Shipp, S. S.; Buxner, S.; Cobabe-Ammann, E. A.; Dalton, H.; Bleacher, L.; Scalice, D.

2012-12-01

The Planetary Science Education and Public Outreach (E/PO) Forum is charged by NASA's Science Mission Directorate (SMD) with engaging, extending, and supporting the community of E/PO professionals and scientists involved in planetary science education activities in order to help them more effectively and efficiently share NASA science with all learners. A number of resources and opportunities for involvement are available for planetary scientists involved in - or interested in being involved in - E/PO. The Forum provides opportunities for community members to stay informed, communicate, collaborate, leverage existing programs and partnerships, and become more skilled education practitioners. Interested planetary scientists can receive newsletters, participate in monthly calls, interact through an online community workspace, and attend annual E/PO community meetings and meetings of opportunity at science and education conferences. The Forum also provides professional development opportunities on a myriad of topics, from common pre-conceptions in planetary science to program evaluation, to delivering effective workshops. Thematic approaches, such as the Year of the Solar System (http://solarsystem.nasa.gov/yss), are coordinated by the Forum; through these efforts resources are presented topically, in a manner that can be easily ported into diverse learning environments. Information about the needs of audiences with which scientists interact - higher education, K-12 education, informal education, and public - currently is being researched by SMD's Audience-Based Working Groups. Their findings and recommendations will be made available to inform the activities and products of E/PO providers so they are able to better serve these audiences. Also in production is a "one-stop-shop" of SMD E/PO products and resources that can be used in conjunction with E/PO activities. Further supporting higher-education efforts, the Forum coordinates a network of planetary science faculty, bringing them together at science conferences to share resources and experiences and to discuss pertinent education research. An online higher education clearinghouse, (EarthSpace - http://www.lpi.usra.edu/earthspace), has been developed to provide faculty with news and funding information, the latest education research and resources for teaching undergraduates, and undergraduate course materials, including lectures, labs, and homework. The presentation will explore the Planetary Science E/PO Forum pathways and tools available to support scientists involved in - or interested in being involved in - E/PO.

Measuring the accelerating effect of the planetary-scale waves on Venus observed with UVI/AKATSUKI and ground-based telescopes

NASA Astrophysics Data System (ADS)

Imai, M.; Kouyama, T.; Takahashi, Y.; Watanabe, S.; Yamazaki, A.; Yamada, M.; Nakamura, M.; Satoh, T.; Imamura, T.; Nakaoka, T.; Kawabata, M.; Yamanaka, M.; Kawabata, K. S.

2017-12-01

Venus has a global cloud layer, and the atmosphere rotates with the speed over 100 m/s. The scattering of solar radiance and absorber in clouds cause the strong dark and bright contrast in 365 nm unknown absorption bands. The Japanese Venus orbiter AKATSUKI and the onboard instrument UVI capture 100 km mesoscale cloud features over the entire visible dayside area. In contrast, planetary-scale features are observed when the orbiter is at the moderate distance from Venus and when the Sun-Venus-orbiter phase angle is smaller than 45 deg. Cloud top wind velocity was measured with the mesoscale cloud tracking technique, however, observations of the propagation velocity and its variation of the planetary-scale feature are not well conducted because of the limitation of the observable area. The purpose of the study is measuring the effect of wind acceleration by planetary-scale waves. Each cloud motion can be represented as the wind and phase velocity of the planetary-scale waves, respectively. We conducted simultaneous observations of the zonal motion of both mesoscale and planetary-scale feature using UVI/AKATSUKI and ground-based Pirka and Kanata telescopes in Japan. Our previous ground-based observation revealed the periodicity change of planetary-scale waves with a time scale of a couple of months. For the initial analysis of UVI images, we used the time-consecutive images taken in the orbit #32. During this orbit (from Nov. 13 to 20, 2016), 7 images were obtained with 2 hr time-interval in a day whose spatial resolution ranged from 10-35 km. To investigate the typical mesoscale cloud motion, the Gaussian-filters with sigma = 3 deg. were used to smooth geometrically mapped images with 0.25 deg. resolution. Then the amount of zonal shift for each 5 deg. latitudinal bands between the pairs of two time-consecutive images were estimated by searching the 2D cross-correlation maximum. The final wind velocity (or rotation period) for mesoscale features were determined with a small error about +/- 0.1-day period in equatorial region (Figure 2). The same method will be applied for planetary-scale features captured by UVI, and ground-based observations compensate the discontinuity in UVI data. At the presentation, the variability in winds and wave propagation velocity with the time scale of a couple of months will be shown.

TGF-beta1 release from biodegradable polymer microparticles: its effects on marrow stromal osteoblast function

NASA Technical Reports Server (NTRS)

Lu, L.; Yaszemski, M. J.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

2001-01-01

BACKGROUND: Controlled release of transforming growth factor-beta1 (TGF-beta1) to a bone defect may be beneficial for the induction of a bone regeneration cascade. The objectives of this work were to assess the feasibility of using biodegradable polymer microparticles as carriers for controlled TGF-beta1 delivery and the effects of released TGF-beta1 on the proliferation and differentiation of marrow stromal cells in vitro. METHODS: Recombinant human TGF-beta1 was incorporated into microparticles of blends of poly(DL-lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG). Fluorescein isothiocynate-labeled bovine serum albumin (FITC-BSA) was co-encapsulated as a porogen. The effects of PEG content (0, 1, or 5% by weight [wt%]) and buffer pH (3, 5, or 7.4) on the protein release kinetics and the degradation of PLGA were determined in vitro for as long as 28 days. Rat marrow stromal cells were seeded on a biodegradable poly(propylene fumarate) (PPF) substrate. The dose response and biological activity of released TGF-beta1 was determined after 3 days in culture. The effects of TGF-beta1 released from PLGA/PEG microparticles on marrow stromal cell proliferation and osteoblastic differentiation were assessed during a 21-day period. RESULTS: TGF-beta1 was encapsulated along with FITC-BSA into PLGA/PEG blend microparticles and released in a multiphasic fashion including an initial burst for as long as 28 days in vitro. Increasing the initial PEG content resulted in a decreased cumulative mass of released proteins. Aggregation of FITC-BSA occurred at lower buffer pH, which led to decreased release rates of both proteins. The degradation of PLGA was increased at higher PEG content and significantly accelerated at acidic pH conditions. Rat marrow stromal cells cultured on PPF substrates showed a dose response to TGF-beta1 released from the microparticles similar to that of added TGF-beta1, indicating that the activity of TGF-beta1 was retained during microparticle fabrication and after growth factor release. At an optimal TGF-beta1 dosage of 1.0 ng/ml after 3 days, the released TGF-beta1 enhanced the proliferation and osteoblastic differentiation of marrow stromal cells over 21 days of culture, with increased total cell number, alkaline phosphatase activity, and osteocalcin production. CONCLUSIONS: PLGA/PEG blend microparticles can serve as delivery vehicles for controlled release of TGF-beta1, and the released growth factor enhances marrow stromal cell proliferation and osteoblastic differentiation in vitro. CLINICAL RELEVANCE: Controlled release of TGF-beta1 from PLGA/PEG microparticles is representative of emerging tissue engineering technologies that may modulate cellular responses to encourage bone regeneration at a skeletal defect site.

Rationale and design of a trial evaluating the effects of losartan vs. nebivolol vs. the association of both on the progression of aortic root dilation in Marfan syndrome with FBN1 gene mutations.

PubMed

Gambarin, Fabiana I; Favalli, Valentina; Serio, Alessandra; Regazzi, Mario; Pasotti, Michele; Klersy, Catherine; Dore, Roberto; Mannarino, Savina; Viganò, Mario; Odero, Attilio; Amato, Simona; Tavazzi, Luigi; Arbustini, Eloisa

2009-04-01

The major clinical problem of Marfan syndrome (MFS) is the aortic root aneurysm, with risk of dissection when the root diameter approximates 5 cm. In MFS, a key molecule, transforming growth factor-beta (TGF-beta), normally bound to the extracellular matrix, is free and activated. In an experimental setting, TGF-beta blockade prevents the aortic root structural damage and dilatation. The angiotensin receptor 1 blockers (sartanics) exert an anti-TGF-beta effect; trials are now ongoing for evaluating the effect of losartan compared with atenolol in MFS. beta-Adrenergic blockers are the drugs most commonly used in MFS. The third-generation beta-adrenergic blocker nebivolol retains the beta-adrenergic blocker effects on heart rate and further exerts antistiffness effects, typically increased in MFS. The open-label phase III study will include 291 patients with MFS and proven FBN1 gene mutations, with aortic root dilation (z-score > or =2.5). The patients will be randomized to nebivolol, losartan and the combination of the two drugs. The primary end point is the comparative evaluation of the effects of losartan, nebivolol and the association of both on the progression of aortic root growth rate. Secondary end points include the pharmacokinetics of the two drugs, comparative evaluation of serum levels of total and active TGF-beta, quantitative assessment of the expression of the mutated gene (FBN1, both 5' and 3'), pharmacogenetic bases of drug responsiveness. The quality of life evaluation in the three groups will be assessed. Statistical evaluation includes an interim analysis at month 24 and conclusive analyses at month 48. The present study will add information about pharmacological therapy in MFS, supporting the new application of angiotensin receptor 1 blockers and finding beta-adrenergic blockers that may give more specific effects. Moreover, the study will further deepen understanding of the pathogenetic mechanisms that are active in Marfan syndrome through the pharmacogenomic and transcriptomic mechanisms that may explain MFS phenotype variability.

Clinical experience with trimegestone as a new progestin in HRT.

PubMed

Grubb, Gary; Spielmann, Daniele; Pickar, James; Constantine, Ginger

2003-11-01

Trimegestone (TMG) is a novel, 19-norpregnane progestin, which demonstrates endometrial selectivity with a reduced progestin-related side effect profile when compared to several other currently marketed progestins. TMG has been studied in combination with 17beta-estradiol (17beta-E2) and conjugated equine estrogens (CEE). TMG-containing HRT agents were effective in relieving vasomotor symptoms and providing protection from endometrial hyperplasia with < or =1% hyperplasia. In clinical trials with sequential regimens, TMG provided predictable withdrawal bleeding associated with a low incidence of irregular and prolonged bleeding. Clinical studies of continuous combined regimens of estrogen/TMG combinations demonstrated high levels of amenorrhea. Both 17beta-E2 and CEE/TMG combinations have shown improved bone mineral density and quality-of-life assessments. Both continuous combined and sequential regimens of 17beta-E2/TMG and CEE/TMG have a favorable clinical profile. TMG provides an important new option for the treatment of postmenopausal symptoms and the prevention of osteoporosis.

NOMINAL VALUES FOR SELECTED SOLAR AND PLANETARY QUANTITIES: IAU 2015 RESOLUTION B3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prša, Andrej; Harmanec, Petr; Torres, Guillermo

In this brief communication we provide the rationale for and the outcome of the International Astronomical Union (IAU) resolution vote at the XXIXth General Assembly in Honolulu, Hawaii, in 2015, on recommended nominal conversion constants for selected solar and planetary properties. The problem addressed by the resolution is a lack of established conversion constants between solar and planetary values and SI units: a missing standard has caused a proliferation of solar values (e.g., solar radius, solar irradiance, solar luminosity, solar effective temperature, and solar mass parameter) in the literature, with cited solar values typically based on best estimates at the timemore » of paper writing. As precision of observations increases, a set of consistent values becomes increasingly important. To address this, an IAU Working Group on Nominal Units for Stellar and Planetary Astronomy formed in 2011, uniting experts from the solar, stellar, planetary, exoplanetary, and fundamental astronomy, as well as from general standards fields to converge on optimal values for nominal conversion constants. The effort resulted in the IAU 2015 Resolution B3, passed at the IAU General Assembly by a large majority. The resolution recommends the use of nominal solar and planetary values, which are by definition exact and are expressed in SI units. These nominal values should be understood as conversion factors only, not as the true solar/planetary properties or current best estimates. Authors and journal editors are urged to join in using the standard values set forth by this resolution in future work and publications to help minimize further confusion.« less

Nominal Values for Selected Solar and Planetary Quantities: IAU 2015 Resolution B3

NASA Astrophysics Data System (ADS)

Prša, Andrej; Harmanec, Petr; Torres, Guillermo; Mamajek, Eric; Asplund, Martin; Capitaine, Nicole; Christensen-Dalsgaard, Jørgen; Depagne, Éric; Haberreiter, Margit; Hekker, Saskia; Hilton, James; Kopp, Greg; Kostov, Veselin; Kurtz, Donald W.; Laskar, Jacques; Mason, Brian D.; Milone, Eugene F.; Montgomery, Michele; Richards, Mercedes; Schmutz, Werner; Schou, Jesper; Stewart, Susan G.

2016-08-01

In this brief communication we provide the rationale for and the outcome of the International Astronomical Union (IAU) resolution vote at the XXIXth General Assembly in Honolulu, Hawaii, in 2015, on recommended nominal conversion constants for selected solar and planetary properties. The problem addressed by the resolution is a lack of established conversion constants between solar and planetary values and SI units: a missing standard has caused a proliferation of solar values (e.g., solar radius, solar irradiance, solar luminosity, solar effective temperature, and solar mass parameter) in the literature, with cited solar values typically based on best estimates at the time of paper writing. As precision of observations increases, a set of consistent values becomes increasingly important. To address this, an IAU Working Group on Nominal Units for Stellar and Planetary Astronomy formed in 2011, uniting experts from the solar, stellar, planetary, exoplanetary, and fundamental astronomy, as well as from general standards fields to converge on optimal values for nominal conversion constants. The effort resulted in the IAU 2015 Resolution B3, passed at the IAU General Assembly by a large majority. The resolution recommends the use of nominal solar and planetary values, which are by definition exact and are expressed in SI units. These nominal values should be understood as conversion factors only, not as the true solar/planetary properties or current best estimates. Authors and journal editors are urged to join in using the standard values set forth by this resolution in future work and publications to help minimize further confusion.

Combined use of calcium-channel and beta-adrenergic blockers for the treatment of chronic stable angina. Rationale, efficacy, and adverse effects.

PubMed

Strauss, W E; Parisi, A F

1988-10-01

During the past decade, the therapy for stable angina pectoris has greatly expanded with the introduction of the calcium-channel blockers. Initially studied as monotherapy, these agents have been regularly used in combination with other antianginal medications, most notably the beta-adrenergic blockers. Although there are pharmacologic rationales for combining these agents, in daily practice, the major impetus for combination therapy is continuing angina during monotherapy. At least one well-conducted double-blind study was done to confirm that diltiazem, verapamil, and nifedipine each can markedly improve both subjective and objective measures of efficacy when used in combination with a beta-blocker. However, individual patient responses are of chief importance. Many persons do better with monotherapy than with combination treatment. The offsetting hemodynamic effects of nifedipine and a beta-blocker generally work well together; however, minor side effects are not infrequent. In the patient with underlying conduction system disease, this combination is clearly preferable. Diltiazem with a beta-blocker is usually well-tolerated, with a low incidence of adverse effects, similar to the experience with diltiazem monotherapy. Verapamil in conjunction with a beta-blocker warrants the greatest concern; approximately 10% to 15% of patients will have significant bradycardia, heart block, hypotension, or congestive failure. When these agents are used concurrently, reduced dosages, especially of the beta-blocker, will likely result in a lower incidence of adverse effects with maintained efficacy.

Inhibition of GSK-3beta ameliorates hepatic ischemia-reperfusion injury through GSK-3beta/beta-catenin signaling pathway in mice.

PubMed

Xia, Yong-Xiang; Lu, Ling; Wu, Zheng-Shan; Pu, Li-Yong; Sun, Bei-Cheng; Wang, Xue-Hao

2012-06-01

Glycogen synthase kinase (GSK)-3beta/beta-catenin signaling regulates ischemia-reperfusion (I/R)-induced apoptosis and proliferation, and inhibition of GSK-3beta has beneficial effects on I/R injury in the heart and the central nervous system. However, the role of this signaling in hepatic I/R injury remains unclear. The present study aimed to investigate the effects and mechanism of GSK-3beta/beta-catenin signaling in hepatic I/R injury. Male C57BL/6 mice (weighing 22-25 g) were pretreated with either SB216763, an inhibitor of GSK-3beta, or vehicle. These mice were subjected to partial hepatic I/R. Blood was collected for test of alanine aminotransferase (ALT), and liver specimen for assays of phosphorylation at the Ser9 residue of GSK-3beta, GSK-3beta activity, axin 2 and the anti-apoptotic factors Bcl-2 and survivin, as well as the proliferative factors cyclin D1 and proliferating cell nuclear antigen, and apoptotic index (TUNEL). Real-time PCR, Western blotting and immunohistochemical staining were used. SB216763 increased phospho-GSK-3beta levels and suppressed GSK-3beta activity (1880+/-229 vs 3280+/-272 cpm, P<0.01). ALT peaked at 6 hours after reperfusion. Compared with control, SB216763 decreased ALT after 6 hours of reperfusion (4451+/-424 vs 7868+/-845 IU/L, P<0.01), and alleviated hepatocyte necrosis and vacuolization. GSK-3beta inhibition led to the accumulation of beta-catenin in the cytosol (0.40+/-0.05 vs 1.31+/-0.11, P<0.05) and nucleus (0.62+/-0.14 vs 1.73+/-0.12, P<0.05), beta-catenin further upregulated the expression of axin 2. Upregulation of GSK-3beta/beta-catenin signaling increased Bcl-2, survivin and cyclin D1. Serological and histological analyses showed that SB216763 alleviated hepatic I/R-induced injury by reducing apoptosis (1.4+/-0.2% vs 3.6+/-0.4%, P<0.05) and enhanced liver proliferation (56+/-8% vs 19+/-4%, P<0.05). Inhibition of GSK-3beta ameliorates hepatic I/R injury through the GSK-3beta/beta-catenin signaling pathway.

Inhibitory effect of OPC-15161, a component of fungus Thielavia minor, on proliferation and extracellular matrix production of rat cultured hepatic stellate cells.

PubMed

Sugawara, H; Ueno, T; Torimura, T; Inuzuka, S; Tanikawa, K

1998-03-01

A component of fungus Thielavia minor, OPC-15161, has been shown to inhibit the proliferation and extracellular matrix production of extracellular matrix-producing mesangial cells in the kidney in vivo. In this study, we examined the effects of OPC-15161 on the proliferation and extracellular matrix production of rat cultured hepatic stellate cells (HSCs). To determine the effect of OPC-15161 on proliferation of HSCs, the cell number and the uptake of [3H]thymidine were investigated in the presence and absence of interleukin-1beta (IL-1beta). IL-1beta significantly increased the uptake of [3H]thymidine in the HSCs, and the addition of OPC-15161 inhibited the uptake in a dose-dependent manner. The cell number of HSCs was also increased by IL-1beta, which was inhibited by OPC-15161. Production of extracellular matrix by OPC-15161 was studied by the production of [3H]-hydroxyproline in the presence and absence of transforming growth factor-beta1 (TGF-beta1). TGF-beta1 significantly increased the production of [3H]-hydroxyproline in the cells, whereas the addition of OPC-15161 inhibited this effect dose dependently. We also investigated the effects of OPC-15161 on Ca2+ mobilization and measured D-myo-inositol 1,4,5-triphosphate (IP3) in the HSCs. IL-1beta induced the increase of intracellular Ca2+ and IP3 concentrations in the HSCs, which were decreased by OPC-15161. Based on these results, we conclude that OPC-1 5161 inhibited the proliferation and production of hydroxyproline in cultured rat HSCs, and thus, it may have a role in prevention of liver fibrosis in vivo.

78 FR 68050 - Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-13

... Joshua, Inc., Alpha Joshua (Prime), Inc., Beta Willow (Prime), Inc., Beta Willow, Inc., Beta Joshua, Inc...: KCP&L Rate Schedule 137 Filing to be effective 1/1/ 2014. Filed Date: 11/1/13. Accession Number...

Troglitazone stimulates {beta}-arrestin-dependent cardiomyocyte contractility via the angiotensin II type 1{sub A} receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tilley, Douglas G., E-mail: douglas.tilley@jefferson.edu; Center for Translational Medicine, Thomas Jefferson University; Nguyen, Anny D.

2010-06-11

Peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) agonists are commonly used to treat cardiovascular diseases, and are reported to have several effects on cardiovascular function that may be due to PPAR{gamma}-independent signaling events. Select angiotensin receptor blockers (ARBs) interact with and modulate PPAR{gamma} activity, thus we hypothesized that a PPAR{gamma} agonist may exert physiologic effects via the angiotensin II type 1{sub A} receptor (AT1{sub A}R). In AT1{sub A}R-overexpressing HEK 293 cells, both angiotensin II (Ang II) and the PPAR{gamma} agonist troglitazone (Trog) enhanced AT1{sub A}R internalization and recruitment of endogenous {beta}-arrestin1/2 ({beta}arr1/2) to the AT1{sub A}R. A fluorescence assay to measure diacylglycerolmore » (DAG) accumulation showed that although Ang II induced AT1{sub A}R-G{sub q} protein-mediated DAG accumulation, Trog had no impact on DAG generation. Trog-mediated recruitment of {beta}arr1/2 was selective to AT1{sub A}R as the response was prevented by an ARB- and Trog-mediated {beta}arr1/2 recruitment to {beta}1-adrenergic receptor ({beta}1AR) was not observed. In isolated mouse cardiomyocytes, Trog increased both % and rate of cell shortening to a similar extent as Ang II, effects which were blocked with an ARB. Additionally, these effects were found to be {beta}arr2-dependent, as cardiomyocytes isolated from {beta}arr2-KO mice showed blunted contractile responses to Trog. These findings show for the first time that the PPAR{gamma} agonist Trog acts at the AT1{sub A}R to simultaneously block G{sub q} protein activation and induce the recruitment of {beta}arr1/2, which leads to an increase in cardiomyocyte contractility.« less

Lunar and Planetary Science XXXV: Undergraduate Education and Research Programs, Facilities, and Information Access

NASA Technical Reports Server (NTRS)

2004-01-01

The titles in this section include: 1) GRIDVIEW: Recent Improvements in Research and Education Software for Exploring Mars Topography; 2) Software and Hardware Upgrades for the University of North Dakota Asteroid and Comet Internet Telescope (ACIT); 3) Web-based Program for Calculating Effects of an Earth Impact; 4) On-Line Education, Web- and Virtual-Classes in an Urban University: A Preliminary Overview; 5) Modelling Planetary Material's Structures: From Quasicrystalline Microstructure to Crystallographic Materials by Use of Mathematica; 6) How We Used NASA Lunar Set in Planetary and Material Science Studies: Textural and Cooling Sequences in Sections of Lava Column from a Thin and a Thick Lava-Flow, from the Moon and Mars with Terrestrial Analogue and Chondrule Textural Comparisons; 7) Classroom Teaching of Space Technology and Simulations by the Husar Rover Model; 8) New Experiments (In Meteorology, Aerosols, Soil Moisture and Ice) on the New Hunveyor Educational Planetary Landers of Universities and Colleges in Hungary; 9) Teaching Planetary GIS by Constructing Its Model for the Test Terrain of the Hunveyor and Husar; 10) Undergraduate Students: An Untapped Resource for Planetary Researchers; 11) Analog Sites in Field Work of Petrology: Rock Assembly Delivered to a Plain by Floods on Earth and Mars; 12) RELAB (Reflectance Experiment Laboratory): A NASA Multiuser Spectroscopy Facility; 13) Full Text Searching and Customization in the NASA ADS Abstract Service.

Planetary system formation: Effects of planet-disk tidal interaction

NASA Astrophysics Data System (ADS)

Bryden, Geoffrey

The standard theory of planet formation begins with the coagulation of solid planetesimals (Safronov 1969, Wetherill & Stewart 1989) followed by the accretion of disk gas once the solid core reaches a critical mass >~10M⊕ (Perri & Cameron 1974, Mizuno 1980, Bodenheimer & Pollack 1986). The classic picture of planet formation, in which each planet's position in the nebula remain fixed, is challenged by the observed distribution of extra-solar planets (e.g. Mayor & Queloz 1995, Butler et al. 1999). The majority of these planets are on short-period orbits ( P<~10 days) very close to their central stars ( ap<~0.1 AU), suggesting that orbital migration plays an important role in the formation of planetary systems. The intent of this thesis is to explore the inclusion of protoplanetary tidal forces into the classical theory of planetary system formation. Protoplanetary interaction with the surrounding gaseous nebulae directly determines giant planets' semi-major axes, masses, gas/solid ratio, and relative spacing. In essence, the process of gap formation determines the primary observational characteristics of both individual planets and their composite systems. Detailed simulations of gap formation produce a range of planetary masses consistent with the observed distribution. Fully self-interacting models of planetary system formation can be used to create a wide variety of planetary systems, ranging from the solar system to Upsilon Andromeda (Butler et al. 1999).

Beta-cell function, incretin effect, and incretin hormones in obese youth along the span of glucose tolerance from normal to prediabetes to Type 2 diabetes

USDA-ARS?s Scientific Manuscript database

Using the hyperglycemic and euglycemic clamp, we demonstrated impaired Beta-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled Beta-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. Bet...

Fenoterol inhibits superoxide anion generation by human polymorphonuclear leukocytes via beta-adrenoceptor-dependent and -independent mechanisms.

PubMed

Mirza, Zafar Nazir; Kato, Masahiko; Kimura, Hirokazu; Tachibana, Atsushi; Fujiu, Toru; Suzuki, Masato; Mochizuki, Hiroyuki; Tokuyama, Kenichi; Morikawa, Akihiro

2002-05-01

Beta2-adrenoceptor agonists, used widely as bronchodilator in treating bronchial asthma, may have anti-inflammatory activity. We examined whether various widely prescribed beta2-adrenoceptor agonists differ in anti-inflammatory mechanisms. We investigated effects of these drugs on superoxide anion generation by stimulated human polymorphonuclear leukocytes in vitro using chemiluminescence. At high concentrations, fenoterol significantly inhibited both N-formylmethionyl-leucyl-phenylalanine- and phorbol myristate acetate-induced superoxide generation by neutrophils. In contrast, salbutamol or procaterol partially inhibited generation with the former stimulus but not the latter. Inhibition by salbutamol or procaterol was completely reversed by either propranolol, a nonselective beta-adrenoceptor antagonist, or ICI-118551, a beta2-adrenoceptor-selective antagonist. In contrast, the effect of fenoterol at concentrations exceeding 10(-6) M against superoxide generation with the former stimulus was only partially reversed by antagonists, and the effect of high concentrations of fenoterol against generation with the latter stimulus was not reversed. No drugs scavenged superoxide at the highest concentration used (10(-5) M). Fenoterol at high concentrations has an inhibitory effect on superoxide generation that includes a component not mediated via beta2-adrenoceptors. Direct inhibition at or downstream from protein kinase C may be involved.

Alendronate augments interleukin-1{beta} release from macrophages infected with periodontal pathogenic bacteria through activation of caspase-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deng Xue; Tamai, Riyoko; Endo, Yasuo

2009-02-15

Nitrogen-containing bisphosphonates (NBPs) are anti-bone-resorptive drugs with inflammatory side effects that include osteomyelitis and osteonecrosis of the jaw. Oral bacteria have been considered to be a trigger for these NBP-associated jaw bone diseases. The present study examined the effects of alendronate (a typical NBP) and clodronate (a non-NBP) on the production of proinflammatory cytokines by macrophages infected with Porphyromonas gingivalis and Tannerella forsythia, which are important pathogens of periodontal diseases. Pretreatment with alendronate augmented IL-1{beta}, but not TNF{alpha}, production by macrophages infected with P. gingivalis or T. forsythia. This augmentation of IL-1{beta} production was inhibited by clodronate. Furthermore, caspase-1, amore » promoter of IL-1{beta} production, was activated by treatment with alendronate, and caspase-1 inhibitor reduced the production of IL-1{beta} induced by alendronate and P. gingivalis. These results suggest that NBPs augment periodontal pathogenic bacteria-induced IL-1{beta} release via caspase-1 activation, and this phenomenon may contribute to the development of NBP-associated inflammatory side effects including jaw osteomyelitis. Co-treatment with clodronate may prevent and/or reduce these inflammatory effects induced by NBPs.« less

The tremorolytic action of beta-adrenoceptor blockers in essential, physiological and isoprenaline-induced tremor is mediated by beta-adrenoceptors located in a deep peripheral compartment.

PubMed

Abila, B; Wilson, J F; Marshall, R W; Richens, A

1985-10-01

The effects of intravenous propranolol 100 micrograms kg-1, sotalol 500 micrograms kg-1, timolol 7.8 micrograms kg-1, atenolol 125 micrograms kg-1 and placebo on essential, physiological and isoprenaline-induced tremor were studied. These beta-adrenoceptor blocker doses produced equal reduction of standing-induced tachycardia in essential tremor patients. Atenolol produced significantly less reduction of essential and isoprenaline-induced tremor than the non-selective drugs, confirming the importance of beta 2-adrenoceptor blockade in these effects. Propranolol and sotalol produced equal maximal inhibition of isoprenaline-induced tremor but propranolol was significantly more effective in reducing essential tremor. The rate of development of the tremorolytic effect was similar in essential, physiological and isoprenaline-induced tremors but all tremor responses developed significantly more slowly than the heart rate responses. It is proposed that these results indicate that the tremorolytic activity of beta-adrenoceptor blockers in essential, physiological and isoprenaline-induced tremor is exerted via the same beta 2-adrenoceptors located in a deep peripheral compartment which is thought to be in the muscle spindles.

The tremorolytic action of beta-adrenoceptor blockers in essential, physiological and isoprenaline-induced tremor is mediated by beta-adrenoceptors located in a deep peripheral compartment.

PubMed Central

Abila, B; Wilson, J F; Marshall, R W; Richens, A

1985-01-01

The effects of intravenous propranolol 100 micrograms kg-1, sotalol 500 micrograms kg-1, timolol 7.8 micrograms kg-1, atenolol 125 micrograms kg-1 and placebo on essential, physiological and isoprenaline-induced tremor were studied. These beta-adrenoceptor blocker doses produced equal reduction of standing-induced tachycardia in essential tremor patients. Atenolol produced significantly less reduction of essential and isoprenaline-induced tremor than the non-selective drugs, confirming the importance of beta 2-adrenoceptor blockade in these effects. Propranolol and sotalol produced equal maximal inhibition of isoprenaline-induced tremor but propranolol was significantly more effective in reducing essential tremor. The rate of development of the tremorolytic effect was similar in essential, physiological and isoprenaline-induced tremors but all tremor responses developed significantly more slowly than the heart rate responses. It is proposed that these results indicate that the tremorolytic activity of beta-adrenoceptor blockers in essential, physiological and isoprenaline-induced tremor is exerted via the same beta 2-adrenoceptors located in a deep peripheral compartment which is thought to be in the muscle spindles. PMID:2866785

Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on beta-amyloid-induced toxicity in PC12 cells.

PubMed

Iuvone, Teresa; Esposito, Giuseppe; Esposito, Ramona; Santamaria, Rita; Di Rosa, Massimo; Izzo, Angelo A

2004-04-01

Abstract Alzheimer's disease is widely held to be associated with oxidative stress due, in part, to the membrane action of beta-amyloid peptide aggregates. Here, we studied the effect of cannabidiol, a major non-psychoactive component of the marijuana plant (Cannabis sativa) on beta-amyloid peptide-induced toxicity in cultured rat pheocromocytoma PC12 cells. Following exposure of cells to beta-amyloid peptide (1 micro g/mL), a marked reduction in cell survival was observed. This effect was associated with increased reactive oxygen species (ROS) production and lipid peroxidation, as well as caspase 3 (a key enzyme in the apoptosis cell-signalling cascade) appearance, DNA fragmentation and increased intracellular calcium. Treatment of the cells with cannabidiol (10(-7)-10(-4)m) prior to beta-amyloid peptide exposure significantly elevated cell survival while it decreased ROS production, lipid peroxidation, caspase 3 levels, DNA fragmentation and intracellular calcium. Our results indicate that cannabidiol exerts a combination of neuroprotective, anti-oxidative and anti-apoptotic effects against beta-amyloid peptide toxicity, and that inhibition of caspase 3 appearance from its inactive precursor, pro-caspase 3, by cannabidiol is involved in the signalling pathway for this neuroprotection.

Evaluation of pharmacological induction of fatty acid beta-oxidation in X-linked adrenoleukodystrophy.

PubMed

McGuinness, M C; Zhang, H P; Smith, K D

2001-01-01

X-linked adrenoleukodystrophy (X-ALD) is an inherited neurometabolic disorder associated with elevated levels of saturated unbranched very-long-chain fatty acids (VLCFA; C > 22:0) in plasma and tissues, and reduced VLCFA beta-oxidation in fibroblasts, white blood cells, and amniocytes from X-ALD patients. The X-ALD gene (ABCD1) at Xq28 encodes the adrenoleukodystrophy protein (ALDP) that is related to the peroxisomal ATP-binding cassette (ABCD) transmembrane half-transporter proteins. The function of ALDP is unknown and its role in VLCFA accumulation unresolved. Previously, our laboratory has shown that sodium 4-phenylbutyrate (4PBA) treatment of X-ALD fibroblasts results in increased peroxisomal VLCFA beta-oxidation activity and increased expression of the X-ALD-related protein, ALDRP, encoded by the ABCD2 gene. In this study, the effect of various pharmacological agents on VLCFA beta-oxidation in ALD mouse fibroblasts is tested. 4PBA, styrylacetate and benzyloxyacetate (structurally related to 4PBA), and trichostatin A (functionally related to 4PBA) increase both VLCFA (peroxisomal) and long-chain fatty acid [LCFA (peroxisomal and mitochondrial)] beta-oxidation. Isobutyrate, zaprinast, hydroxyurea, and 5-azacytidine had no effect on VLCFA or LCFA beta-oxidation. Lovastatin had no effect on fatty acid beta-oxidation under normal tissue culture conditions but did result in an increase in both VLCFA and LCFA beta-oxidation when ALD mouse fibroblasts were cultured in the absence of cholesterol. The effect of trichostatin A on peroxisomal VLCFA beta-oxidation is shown to be independent of an increase in ALDRP expression, suggesting that correction of the biochemical abnormality in X-ALD is not dependent on pharmacological induction of a redundant gene (ABCD2). These studies contribute to a better understanding of the role of ALDP in VLCFA accumulation and may lead to the development of more effective pharmacological therapies. Copyright 2001 Academic Press.

Changes in immune and metabolic gut response in broilers fed beta-mannanase in beta-mannan containing diets

USDA-ARS?s Scientific Manuscript database

Beta-mannans, found in soy-based broiler feed, are known to cause physiological effects that are hypothesized to be related to gut inflammation. Previous studies have shown that the incorporation of beta-mannanase in the diet or as a supplement results in improvements to certain performance paramet...

TGF-.beta. antagonists as mitigators of radiation-induced tissue damage

DOEpatents

Barcellos-Hoff, Mary H.

1997-01-01

A method for treating tissue damage caused by radiation is described by use of a TGF-.beta. antagonist, such as an anti-TGF-.beta. antibody or a TGF-.beta. latency associated protein. It is administered not more than a week after exposure, and is particularly useful in mitigating the side effects of breast cancer therapy.

TGF-{beta} antagonists as mitigators of radiation-induced tissue damage

DOEpatents

Barcellos-Hoff, M.H.

1997-04-01

A method for treating tissue damage caused by radiation is described by use of a TGF-{beta} antagonist, such as an anti-TGF-{beta} antibody or a TGF-{beta} latency associated protein. It is administered not more than a week after exposure, and is particularly useful in mitigating the side effects of breast cancer therapy.

Beta 2-microglobulin kinetics in maintenance hemodialysis: a comparison of conventional and high-flux dialyzers and the effects of dialyzer reuse.

PubMed

DiRaimondo, C R; Pollak, V E

1989-05-01

beta 2-Microglobulin (beta 2M) forms synovial and bony amyloid deposits in long-term hemodialysis patients. To define the kinetics of beta 2M during hemodialysis and the effects of dialyzer reprocessing, we measured serum beta 2M, plasma C3a, and neutrophil counts immediately predialysis; 15, 90, and 180 minutes after beginning dialysis; and 15 minutes postdialysis in ten chronic hemodialysis patients. The studies were performed during first and third uses of cuprammonium rayon and polysulfone dialyzers processed by rinsing with water, then bleach, in an automated system (Seratronics DRS 4) and then packed in 1.5% formaldehyde. Mean serum beta 2M (corrected for ultrafiltration) decreased by 16.6% +/- 18.1% with new cuprammonium dialyzers and 57.1% +/- 12.8% with new polysulfone dialyzers. Dialyzer reprocessing had no significant effect on this decline. Predialysis serum beta 2M decreased by 30.4% +/- 15.5% 1 month after switching from cuprammonium to polysulfone dialyzers; these levels remained stable after 3 months of dialysis with polysulfone. Complement activation and neutropenia during dialysis were significantly more marked with cuprammonium, but were not affected by reprocessing of either dialyzer. In vitro adsorption of 124I-beta 2M to polysulfone fibers was greater than to cuprammonium; adsorption was not influenced by dialyzer reprocessing.

Interferon-beta1a reduces plasma CD31+ endothelial microparticles (CD31+EMP) in multiple sclerosis.

PubMed

Sheremata, William A; Jy, Wenche; Delgado, Sylvia; Minagar, Alireza; McLarty, Jerry; Ahn, Yeon

2006-09-04

A correlation between plasma CD31+ endothelial microparticles (CD31+EMP) levels and clinical, as well as brain MRI activity, in multiple sclerosis (MS) patients has been previously reported. However, the effect(s) of treatment with interferon-beta1a (IFN-beta1a) on plasma levels of CD31+EMP has not been assessed. In a prospective study, we measured plasma CD31+EMP levels in 30 patients with relapsing-remitting MS. Using flow cytometry, in a blinded study, we measured plasma CD31+EMP in 30 consecutive patients with relapsing-remitting MS (RRMS) prior to and 4, 12, 24 and 52 weeks after initiation of intramuscular therapy with interferon-beta1a (IFN-beta1a), 30 micrograms weekly. At each visit, clinical examination was performed and expanded disability status scale (EDSS) scores were assessed. Plasma levels of CD31+EMP were significantly reduced from 24 through 52 weeks following initiation of treatment with IFN-beta1a. Our data suggest that serial measurement of plasma CD31+EMP levels may be used as a surrogate marker of response to therapy with INF-beta1a. In addition, the decline in plasma levels of CD31+EMP further supports the concept that IFN-beta1a exerts stabilizing effect on the cerebral endothelial cells in pathogenesis of MS.

The adrenergic receptor subtypes present in frog (Rana esculenta) skin.

PubMed

Bellantuono, Vito; Cassano, Giuseppe; Lippe, Claudio

2008-08-01

Frog skin transports ions and water under hormonal control. In spite of the fundamental role played by adrenergic stimulation in maintaining the water balance of the organism, the receptor subtype(s) present in the skin have not been identified yet. We measured the increase in short-circuit current (ISC, an estimate of ion transport) induced by cirazoline, clonidine, xamoterol, formoterol, or BRL 37344, in order to verify the presence of alpha1, alpha2, beta1, beta2, or beta3 receptor subtypes, respectively. Only after treatment with formoterol, BRL 37344 and, to a lesser extent, cirazoline was measured a significant increase in ISC (57%, 33.2%, and 4.7%, respectively). The formoterol and BRL 37344 concentrations producing half-maximal effect (EC50) were 1.12 and 70.1 nM, respectively. Moreover, the formoterol effect was inhibited by treatment with ICI 118551 (antagonist of beta2 receptors) while SR 59230A (antagonist of beta3 receptors) had no effect; opposite findings were obtained when the BRL 37344 stimulation was investigated. Finally, by measuring the transepithelial fluxes of 22Na+ and 36Cl-, we demonstrated that Na+ absorption is increased by activation of beta2 and beta3 and is cAMP-sensitive, whereas the Cl- secretion is only increased by activation of beta2 receptors and is cAMP- and calmodulin-sensitive.

Mechanistic studies of cancer cell mitochondria- and NQO1-mediated redox activation of beta-lapachone, a potentially novel anticancer agent

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Jason Z.; Ke, Yuebin; Misra, Hara P.

Beta-lapachone (beta-Lp) derived from the Lapacho tree is a potentially novel anticancer agent currently under clinical trials. Previous studies suggested that redox activation of beta-Lp catalyzed by NAD(P)H:quinone oxidoreductase 1 (NQO1) accounted for its killing of cancer cells. However, the exact mechanisms of this effect remain largely unknown. Using chemiluminescence and electron paramagnetic resonance (EPR) spin-trapping techniques, this study for the first time demonstrated the real-time formation of ROS in the redox activation of beta-lapachone from cancer cells mediated by mitochondria and NQO1 in melanoma B16–F10 and hepatocellular carcinoma HepG2 cancer cells. ES936, a highly selective NQO1 inhibitor, and rotenone,more » a selective inhibitor of mitochondrial electron transport chain (METC) complex I were found to significantly block beta-Lp meditated redox activation in B16–F10 cells. In HepG2 cells ES936 inhibited beta-Lp-mediated oxygen radical formation by ∼ 80% while rotenone exerted no significant effect. These results revealed the differential contribution of METC and NQO1 to beta-lapachone-induced ROS formation and cancer cell killing. In melanoma B16–F10 cells that do not express high NQO1 activity, both NOQ1 and METC play a critical role in beta-Lp redox activation. In contrast, in hepatocellular carcinoma HepG2 cells expressing extremely high NQO1 activity, redox activation of beta-Lp is primarily mediated by NQO1 (METC plays a minor role). These findings will contribute to our understanding of how cancer cells are selectively killed by beta-lapachone and increase our ability to devise strategies to enhance the anticancer efficacy of this potentially novel drug while minimizing its possible adverse effects on normal cells. - Highlights: • Both isolated mitochondria and purified NQO1 are able to generate ROS by beta-Lp. • The differential roles of mitochondria and NQO1 in mediating redox activation of beta-Lp • In cancer cells with low NQO1 expression, mitochondria play a critical role in beta-Lp redox activation. • In cancer cells with high NQO1 activity, redox activation of beta-Lp is primarily mediated by NQO1.« less

Activated type I TGFbeta receptor (Alk5) kinase confers enhancedsurvival to mammary epithelial cells and accelerates mammary tumorprogression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muraoka-Cook, Rebecca S.; Shin, Incheol; Yi, Jae Youn

2005-01-02

The transforming growth factor-betas (TGF{beta}s) are members of a large superfamily of pleiotropic cytokines that also includes the activins and the bone morphogenetic proteins (BMPs). Members of the TGF{beta} family regulate complex physiological processes such cell proliferation, differentiation, adhesion, cell-cell and cell-matrix interactions, motility, and cell death, among others (Massague, 1998). Dysregulation of TGF{beta} signaling contributes to several pathological processes including cancer, fibrosis, and auto-immune disorders (Massague et al., 2000). The TGF{beta}s elicit their biological effects by binding to type II and type I transmembrane receptor serine-threonine kinases (T{beta}RII and T{beta}RI) which, in turn, phosphorylated Smad 2 and Smad 3.more » Phosphorylated Smad 2/3 associate with Smad 4 and, as a heteromeric complex, translocate to the nucleus where they regulate gene transcription. The inhibitory Smad7 down regulates TGF{beta} signaling by binding to activated T{beta}RI and interfering with its ability to phosphorylate Smad 2/3 (Derynck and Zhang, 2003; Shi and Massague, 2003). Signaling is also regulated by Smad proteolysis. TGF{beta} receptor-mediated activation results in multi-ubiquitination of Smad 2 in the nucleus and subsequent degradation of Smad 2 by the proteasome (Lo and Massague, 1999). Activation of TGF{beta} receptors also induces mobilization of a Smad 7-Smurf complex from the nucleus to the cytoplasm; this complex recognizes the activated receptors and mediates their ubiquitination and internalization via caveolin-rich vesicles, leading to termination of TGF{beta} signaling (Di Guglielmo et al., 2003). Other signal transducers/pathways have been implicated in TGF{beta} actions. These include the extracellular signal-regulated kinase (Erk), c-Jun N-terminal kinase (Jnk), p38 mitogen-activated protein kinase (MAPK), protein phosphatase PP2A, phosphatidylinositol-3 kinase (PI3K), and the family of Rho GTPases [reviewed in (Derynck and Zhang, 2003)]. Although signaling by Smads has been shown to be causally associated with the anti-proliferative effect of TGF{beta} (Datto et al., 1999; Liu et al., 1997), the role of non-Smad effectors on mediating the cellular effects of TGF{beta} is less well characterized.« less

Pharmacological Beta-Adrenergic Receptor Activation Attenuates Neutrophil Recruitment by a Mechanism Dependent on Nicotinic Receptor and the Spleen.

PubMed

Silva, Rangel L; Castanheira, Fernanda V; Figueiredo, Jozi G; Bassi, Gabriel S; Ferreira, Sérgio H; Cunha, Fernando Q; Cunha, Thiago M; Kanashiro, Alexandre

2016-08-01

The aim of this study was to identify the effect of beta-adrenergic receptor activation on neutrophil migration in experimental peritonitis elucidating the neuroimmune components involved such as nicotinic receptors and the spleen. Mice pre-treated with mecamylamine (nicotinic antagonist) and propranolol (beta-adrenergic antagonist) or splenectomized animals were treated with isoproterenol (beta-adrenergic agonist) prior to intraperitoneal injection of carrageenan. After 4 h, the infiltrating neutrophils and the local cytokine/chemokine levels were evaluated in the peritoneal lavage. The effect of isoproterenol on neutrophil chemotaxis was investigated in a Boyden chamber. Isoproterenol inhibited neutrophil trafficking, reducing the cytokine/chemokine release and neutrophil chemotaxis. Surprisingly, the isoproterenol effect on neutrophil migration was totally reverted by splenectomy and mecamylamine pre-treatment. In contrast, the inhibitory effect of nicotine on neutrophil migration was abrogated only by splenectomy but not by propranolol pre-treatment. Collectively, our data show that beta-adrenergic receptor activation regulates the acute neutrophil recruitment via splenic nicotinic receptor.

Protection from sunburn with beta-Carotene--a meta-analysis.

PubMed

Köpcke, Wolfgang; Krutmann, Jean

2008-01-01

Nutritional protection against skin damage from sunlight is increasingly advocated to the general public, but its effectiveness is controversial. In this meta-analysis, we have systematically reviewed the existing literature on human supplementation studies on dietary protection against sunburn by beta-carotene. A review of literature until June 2007 was performed in PubMed, ISI Web of Science and EBM Cochrane library and identified a total of seven studies which evaluated the effectiveness of beta-carotene in protection against sunburn. Data were abstracted from these studies by means of a standardized data collection protocol. The subsequent meta-analysis showed that (1) beta-carotene supplementation protects against sunburn and (2) the study duration had a significant influence on the effected size. Regression plot analysis revealed that protection required a minimum of 10 weeks of supplementation with a mean increase of the protective effect of 0.5 standard deviations with every additional month of supplementation. Thus, dietary supplementation of humans with beta-carotene provides protection against sunburn in a time-dependent manner.

Solar wind pickup of ionized Venus exosphere atoms

NASA Technical Reports Server (NTRS)

Curtis, S. A.

1981-01-01

Previous calculations of electrostatic and electromagnetic growth rates for plasma instabilities have neglected the thermal spread of the distribution function of the planetary ions. We consider the effects of finite temperatures for exospheric ions borne in the solar wind. Specifically, growth rates are calculated for electromagnetic instabilities in the low-frequency case for Alfven waves and the intermediate frequency case for whistlers. Also, electrostatic growth rates are calculated for the intermediate frequency regime. From these growth rates, estimates are derived for the pickup times of the planetary ions. The electromagnetic instabilities are shown to produce the most rapid pickup. In the situation where the angle between the local Venus magnetic field and the plasma flow direction is small, the pickup times for both electromagnetic and electrostatic instabilities become very long. A possible consequence of this effect is to produce regions of enhanced planetary ion density in favorable Venus magnetic field-solar wind flow geometries.

New Antennas and Methods for the Low Frequency Stellar and Planetary Radio Astronomy

NASA Astrophysics Data System (ADS)

Konovalenko, A. A.; Falkovich, I. S.; Rucker, H. O.; Lecacheux, A.; Zarka, Ph.; Koliadin, V. L.; Zakharenko, V. V.; Stanislavsky, A. A.; Melnik, V. N.; Litvinenko, G. V.; Gridin, A. A.; Bubnov, I. N.; Kalinichenko, N. N.; Reznik, A. P.; Sidorchuk, M. A.; Stepkin, S. V.; Mukha, D. V.; Nikolajenko, V. S.; Karlsson, R.; Thide, B.

According to the special Program of the National Academy of Sciences of Ukraine, creation of the new giant Ukrainian radio telescope (GURT) was started a few years ago on the UTR-2 radio telescope observatory. The main goal is to reach maximum band at the lowest frequencies (10-70 MHz), effective area (step-by-step up to 100,000 sq.m), and high interference immunity for resolving many astrophysical tasks when the sensitivity is less limited by the confusion effects. These tasks include stellar radio astronomy (the Sun, solar wind, flare stars, pulsars, transients) and planetary one (Jupiter, planetary lightnings, Earth ionosphere, the Moon, exoplanets). This array should be complementary to the LOFAR, E-LOFAR systems. The first stages of the GURT (6 x 25 cross dipole active elements) and broad-band digital registration of the impulsive and sporadic events were tested in comparison with the existing largest decameter array UTR-2.

Planetary Habitability

NASA Technical Reports Server (NTRS)

Kasting, James F.

1997-01-01

This grant was entitled 'Planetary Habitability' and the work performed under it related to elucidating the conditions that lead to habitable, i.e. Earth-like, planets. Below are listed publications for the past two and a half years that came out of this work. The main thrusts of the research involved: (1) showing under what conditions atmospheric O2 and O3 can be considered as evidence for life on a planet's surface; (2) determining whether CH4 may have played a role in warming early Mars; (3) studying the effect of varying UV levels on Earth-like planets around different types of stars to see whether this would pose a threat to habitability; and (4) studying the effect of chaotic obliquity variations on planetary climates and determining whether planets that experienced such variations might still be habitable. Several of these topics involve ongoing research that has been carried out under a new grant number, but which continues to be funded by NASA's Exobiology program.

Laboratory Impact Experiments

NASA Astrophysics Data System (ADS)

Horanyi, M.; Munsat, T.

2017-12-01

The experimental and theoretical programs at the SSERVI Institute for Modeling Plasmas, Atmospheres, and Cosmic Dust (IMPACT) address the effects of hypervelocity dust impacts and the nature of the space environment of granular surfaces interacting with solar wind plasma and ultraviolet radiation. These are recognized as fundamental planetary processes due their role in shaping the surfaces of airless planetary objects, their plasma environments, maintaining dust haloes, and sustaining surface bound exospheres. Dust impacts are critically important for all airless bodies considered for possible human missions in the next decade: the Moon, Near Earth Asteroids (NEAs), Phobos, and Deimos, with direct relevance to crew and mission safety and our ability to explore these objects. This talk will describe our newly developed laboratory capabilities to assess the effects of hypervelocity dust impacts on: 1) the gardening and redistribution of dust particles; and 2) the generation of ionized and neutral gasses on the surfaces of airless planetary bodies.

Does selective beta-1 blockade provide bone marrow protection after trauma/hemorrhagic shock?

PubMed

Pasupuleti, Latha V; Cook, Kristin M; Sifri, Ziad C; Kotamarti, Srinath; Calderon, Gabriel M; Alzate, Walter D; Livingston, David H; Mohr, Alicia M

2012-09-01

Previously, nonselective beta-blockade (BB) with propranolol demonstrated protection of the bone marrow (BM) after trauma and hemorrhagic shock (HS). Because selective beta-1 blockers are used commonly for their cardiac protection, the aim of this study was to more clearly define the role of specific beta adrenergic receptors in BM protection after trauma and HS. Male Sprague-Dawley rats underwent unilateral lung contusion (LC) followed by HS for 45 minutes. After resuscitation, animals were injected with a selective beta-blocker, atenolol (B1B), butoxamine (B2B), or SR59230A (B3B). Animals were killed at 3 hours or 7 days. Heart rate and blood pressure were measured throughout the study period. BM cellularity, growth of hematopoietic progenitor cells (HPCs) in BM, and hemoglobin levels (Hb) were assessed. Treatment with a B2B or B3B after LCHS restored both BM cellularity and BM HPC colony growth at 3 hours and 7 days. In contrast, treatment with a B1B had no effect on BM cellularity or HPC growth but did decrease heart effectively rate throughout the study. Treatment with a B3B after LCHS increased Hb as compared with LCHS alone. After trauma and HS, protection of BM for 7 days was seen with use of either a selective beta-2 or beta-3 blocker. Use of a selective beta-1 blocker was ineffective in protecting the BM despite a physiologic decrease in heart rate. Therefore, the protection of BM is via the beta-2 and beta-3 receptors and it is not via a direct cardiovascular effect. Published by Mosby, Inc.

Beta-blockers for the treatment of problematic hemangiomas

PubMed Central

Sharma, Vishal K; Fraulin, Frankie OG; Dumestre, Danielle O; Walker, Lori; Harrop, A Robertson

2013-01-01

OBJECTIVE: To examine treatment indications, efficacy and side effects of oral beta-blockers for the treatment of problematic hemangiomas. METHODS: A retrospective review of patients with hemangiomas presenting to the Alberta Children’s Hospital Vascular Birthmark Clinic (Calgary, Alberta) between 2009 and 2011 was conducted. The subset of patients treated with oral beta-blockers was further characterized, investigating indication for treatment, response to treatment, time to resolution of indication, duration of treatment, occurrence of rebound growth and side effects of therapy. RESULTS: Between 2009 and 2011, 311 new patients with hemangiomas were seen, of whom 105 were treated with oral beta-blockers. Forty-five patients completed beta-blocker treatment while the remainder continue to receive therapy. Indications for treatment were either functional concerns (68.6%) or disfigurement (31.4%). Functional concerns included ulceration (29.5%), periocular location with potential for visual interference (28.6%), airway interference (4.8%), PHACES syndrome (3.8%), auditory interference (0.95%) and visceral location with congestive heart failure (0.95%). The median age at beta-blocker initiation was 3.3 months; median duration of therapy was 10.6 months; and median maximal treatment dose was 1.5 mg/kg/day for propranolol and 1.6 mg/kg/day for atenolol. Ninety-nine patients (94.3%) responded to therapy with size reduction, colour changes, softened texture and/or healing of ulceration. Rebound growth requiring an additional course of therapy was observed in 23 patients. Side effects from beta-blockers included cool extremities (26.7%), irritability (17.1%), lower gastrointestinal upset (14.3%), emesis (11.4%), hypotension (10.5%), poor feeding (7.6%), lethargy (4.8%), bronchospasm (0.95%) and rash (0.95%). Side effects did not result in complete discontinuation of beta-blocker treatment in any case; however, they prompted a switch to a different beta-blocker preparation in some cases. Resolution of the primary indication, requiring a median time of three months, occurred in 87 individuals (82.9%). CONCLUSIONS: Treatment of infantile hemangiomas with oral beta-blocker therapy is highly effective and well tolerated, with more than 94% of patients demonstrating a response to treatment and 90% showing resolution of the primary functional indication for treatment. PMID:24431932

Proteomic profiling of bone marrow mesenchymal stem cells upon TGF-beta stimulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Daojing; Park, Jennifer S.; Chu, Julia S.F.

Bone marrow mesenchymal stem cells (MSCs) can differentiate into different types of cells, and have tremendous potential for cell therapy and tissue engineering. Transforming growth factor {beta}1 (TGF-{beta}) plays an important role in cell differentiation and vascular remodeling. We showed that TGF-{beta} induced cell morphology change and an increase in actin fibers in MSCs. To determine the global effects of TGF-{beta} on MSCs, we employed a proteomic strategy to analyze the effect of TGF-{beta} on the human MSC proteome. By using two-dimensional gel electrophoresis and electrospray ionization coupled to Quadrupole/time-of-flight tandem mass spectrometers, we have generated a proteome reference mapmore » of MSCs, and identified {approx}30 proteins with an increase or decrease in expression or phosphorylation in response to TGF-{beta}. The proteins regulated by TGF-{beta} included cytoskeletal proteins, matrix synthesis proteins, membrane proteins, metabolic enzymes, etc. TGF-{beta} increased the expression of smooth muscle (SM) {alpha}-actin and decreased the expression of gelsolin. Over-expression of gelsolin inhibited TGF-{beta}-induced assembly of SM {alpha}-actin; on the other hand, knocking down gelsolin expression enhanced the assembly of {alpha}-actin and actin filaments without significantly affecting {alpha}-actin expression. These results suggest that TGF-{beta} coordinates the increase of {alpha}-actin and the decrease of gelsolin to promote MSC differentiation. This study demonstrates that proteomic tools are valuable in studying stem cell differentiation and elucidating the underlying molecular mechanisms.« less

Correlation between cortical beta power and gait speed is suppressed in a parkinsonian model, but restored by therapeutic deep brain stimulation.

PubMed

Polar, Christian A; Gupta, Rahul; Lehmkuhle, Mark J; Dorval, Alan D

2018-05-30

The motor cortex and subthalamic nucleus (STN) of patients with Parkinson's disease (PD) exhibit abnormally high levels of electrophysiological oscillations in the ~12-35 Hz beta-frequency range. Recent studies have shown that beta is partly carried forward to regulate future motor states in the healthy condition, suggesting that steady state beta power is lower when a sequence of movements occurs in a short period of time, such as during fast gait. However, whether this relationship between beta power and motor states persists upon parkinsonian onset or in response to effective therapy is unclear. Using a 6-hydroxy dopamine (6-OHDA) rat model of PD and a custom-built behavioral and neurophysiological recording system, we aimed to elucidate a better understanding of the mechanisms underlying cortical beta power and PD symptoms. In addition to elevated levels of beta oscillations, we show that parkinsonian onset was accompanied by a decoupling of movement intensity - quantified as gait speed - from cortical beta power. Although subthalamic deep brain stimulation (DBS) reduced general levels of beta oscillations in the cortex of all PD animals, the brain's capacity to regulate steady state levels of beta power as a function of movement intensity was only restored in animals with therapeutic DBS. We propose that, in addition to lowering general levels of cortical beta power, restoring the brain's ability to maintain this inverse relationship is critical for effective symptom suppression. Copyright © 2017. Published by Elsevier Inc.

Lack of TXNIP protects against mitochondria-mediated apoptosis but not against fatty acid-induced ER stress-mediated beta-cell death.

PubMed

Chen, Junqin; Fontes, Ghislaine; Saxena, Geetu; Poitout, Vincent; Shalev, Anath

2010-02-01

We have previously shown that lack of thioredoxin-interacting protein (TXNIP) protects against diabetes and glucotoxicity-induced beta-cell apoptosis. Because the role of TXNIP in lipotoxicity is unknown, the goal of the present study was to determine whether TXNIP expression is regulated by fatty acids and whether TXNIP deficiency also protects beta-cells against lipoapoptosis. RESARCH DESIGN AND METHODS: To determine the effects of fatty acids on beta-cell TXNIP expression, INS-1 cells and isolated islets were incubated with/without palmitate and rats underwent cyclic infusions of glucose and/or Intralipid prior to islet isolation and analysis by quantitative real-time RT-PCR and immunoblotting. Using primary wild-type and TXNIP-deficient islets, we then assessed the effects of palmitate on apoptosis (transferase-mediated dUTP nick-end labeling [TUNEL]), mitochondrial death pathway (cytochrome c release), and endoplasmic reticulum (ER) stress (binding protein [BiP], C/EBP homologous protein [CHOP]). Effects of TXNIP deficiency were also tested in the context of staurosporine (mitochondrial damage) or thapsigargin (ER stress). Glucose elicited a dramatic increase in islet TXNIP expression both in vitro and in vivo, whereas fatty acids had no such effect and, when combined with glucose, even abolished the glucose effect. We also found that TXNIP deficiency does not effectively protect against palmitate or thapsigargin-induced beta-cell apoptosis, but specifically prevents staurosporine- or glucose-induced toxicity. Our results demonstrate that unlike glucose, fatty acids do not induce beta-cell expression of proapoptotic TXNIP. They further reveal that TXNIP deficiency specifically inhibits the mitochondrial death pathway underlying beta-cell glucotoxicity, whereas it has very few protective effects against ER stress-mediated lipoapoptosis.

Artesunate protects pancreatic beta cells against cytokine-induced damage via SIRT1 inhibiting NF-κB activation.

PubMed

Yu, L; Chen, J F; Shuai, X; Xu, Y; Ding, Y; Zhang, J; Yang, W; Liang, X; Su, D; Yan, C

2016-01-01

Artesunate (ART) has been known as the most effective and safe reagents to treat malaria for many years. In this study, we explored whether ART could protect pancreatic beta-cell against cytokine-induced damage. The production of nitrite (NO) was detected with the Griess Assay Kit. SIRT1 and inducible nitric oxide synthase (iNOS) expression were determined with Western blot. The transcriptional activity of NF-κB was evaluated by luciferase reporter assay. The expression of Sirt1 was silenced by RNA interference. Glucose-stimulated insulin secretion (GSIS) and potassium-stimulated insulin secretion (KSIS) assays were performed to measure the effect of ART on pancreatic beta-cells' function. The effect of ART on beta-cells apoptosis was evaluated by using Hochest/PI staining and TUNEL assay. ART enhanced GSIS (KSIS) and reduced apoptosis of pancreatic beta-cells induced by IL-1β. Further study showed that ART inhibited IL-1β-induced increase of NF-κB activity, iNOS expression, and NO production. Moreover, ART up-regulated SIRT1 expression in INS-1 cells and islets exposed to IL-1β. Inhibition of SIRT1 expression could partially abolished the inhibitory effect of ART on NF-κB activity in IL-1β-treated beta-cells. More importantly, the protective effect of ART on cytokine-induced damage was reversed by silencing SIRT1 expression. ART can elicit a protective effect on beta-cells exposed to IL-1β by stimulating SIRT1 expression, which resulted in the decrease of NF-κB activity, iNOS expression, and NO production. Hence, ART might be an effective drug for diabetes.

Right ventricular beneficial effects of beta adrenergic receptor kinase inhibitor (betaARKct) gene transfer in a rat model of severe pressure overload.

PubMed

Molina, Ezequiel J; Gupta, Dipin; Palma, Jon; Gaughan, John P; Macha, Mahender

2009-06-01

Heart failure is associated with abnormalities in betaAR cascade regulation, calcium cycling, expression of inflammatory mediators and apoptosis. Adenoviral mediated gene transfer of betaARKct has beneficial indirect effects on these pathologic processes upon the left ventricular myocardium. The concomitant biochemical changes that occur in the right ventricle have not been well characterized. Sprague-Dawley rats underwent aortic banding and were followed by echocardiography. After a decrease in fractional shortening of 25% from baseline, intracoronary injection of adenoviral-betaARKct (n=14) or adenoviral-beta-galactosidase (control, n=13) was performed. Rats were randomly euthanized on post-operative day 7, 14 or 21. Protein analysis including RV myocardial levels of betaARKct, betaARK1, SERCA(2a), inflammatory tissue mediators (IL-1, IL-6 and TNF-alpha), apoptotic markers (bax and bak), and MAP kinases (jnk, p38 and erk) was performed. ANOVA was employed for group comparison. Adenoviral-betaARKct treated animals showed increased expression of betaARKct and decreased levels of betaARK1 compared with controls. This treatment group also demonstrated normalization of SERCA(2a) expression and decreased levels of the inflammatory markers IL-1, IL-6 and TNF-alpha. The pro-apoptotic markers bax and bak were similarly improved. Ventricular levels of the MAP kinase jnk were increased. Differences were most significant 7 days after gene transfer, but the majority of these changes persisted at 21 days. These results suggest that attenuation of the pathologic mechanisms of beta adrenergic receptor desensitization, SERCA(2a) expression, inflammation and apoptosis, not only occur in the left ventricle but also in the right ventricular myocardium after intracoronary gene transfer of betaARKct during heart failure.

[Vasodilative effects of indole alkaloids obtained from domestic plants, Uncaria rhynchophylla Miq. and Amsonia elliptica Roem. et Schult].

PubMed

Ozaki, Y

1990-02-01

Vasodilative effects of hirsutine (HS) and hirsuteine (HST) which were isolated from the domestic plant Uncaria rhynchophylla Miq. and beta-yohimbine (beta-Y) which was isolated from the domestic plant Amsonia elliptica Roem. et Schult. were carried out. In the hind-limb artery of anesthetized dogs, intra-arterial administration of HS, HST and beta-Y caused a vasodilatation. The vasodilative potency of HS was somewhat stronger than that of HST, and the potency of both alkaloids was approximately equal to that of papaverine. The vasodilative effect of beta-Y was similar to that of yohimbine, which is considered to be derived from its alpha-adrenoceptor blocking effect, and the potency of both alkaloids was approximately the same, while the effect of beta-Y was stronger than that of papaverine. In the coronary artery, HS showed a vasodilatation and its potency was weaker than that of papaverine. Also, HS showed the same effect in the cerebral artery, and the potency of HS was approximately the same as that of papaverine. These results suggest that the mode of the vasodilative effect induced by HS may partly differ from that of papaverine.

Combination monoamine oxidase inhibitor and beta-blocker treatment of migraine, with anxiety and depression.

PubMed

Merikangas, K R; Merikangas, J R

1995-11-01

This paper presents the results of a study comparing the effectiveness of a beta-adrenergic blocking agent, atenolol, a monoamine oxidase inhibitor (MAO-I), phenelzine, and the combination in treatment of 61 adults with migraine headache. The goals of the study are (1) to investigate the safety of concomitant treatment of migraine with beta-blockers and phenelzine, (2) to assess whether orthostatic hypertension and other side effects would be relieved, and (3) to compare the results of this open trial of phenelzine to those of a previous study using similar methods. Phenelzine was associated with a large decrease in the frequency and severity of migraine attacks. Anxiety and depression were also reduced by phenelzine both alone, and in combination with a beta-blocker. The results show that the combination of MAO-I's and beta-blockers can be administered safely, and can lead to the reduction in the side effects with either drug alone.

Interleukin 1 beta inhibits synaptic strength and long-term potentiation in the rat CA1 hippocampus.

PubMed

Bellinger, F P; Madamba, S; Siggins, G R

1993-11-19

Cytokines such as interleukin-1 beta (IL-1 beta) are released in the nervous system following inflammation or infection. Recently, IL-1 beta was shown to enhance synaptic inhibitory mechanisms. We therefore investigated the effect of IL-1 beta superfusion on long-term potentiation (LTP), the cellular model of memory and learning, evoked in the CA1 region by tetanic stimulation of the stratum radiatum in the rat hippocampal slice. IL-1 beta (150 pM-1.5 nM) superfused 10 min before tetanic stimulation significantly reduced LTP of the slope of the population excitatory postsynaptic potential (pEPSP) and the population spike (PS) amplitude in CA1 in a concentration-dependent manner. IL-1 beta (1.5 nM) applied for 10 min 1 h before tetanus significantly inhibited LTP of the PS amplitude and pEPSP slope and reduced pEPSP and PS values before tetanus as well, although the PS returned to control values before tetanus. Heat-inactivated IL-1 beta had no effect on pre-tetanus pEPSP or PS values or the induction of LTP. These data demonstrate that IL-1 beta modulates synaptic potentials and reduces LTP. These findings have important implications for the role of IL-1 beta in neuronal disorders following infection, perhaps best exemplified by HIV-1-associated dementia.

Density-dependent induction of apoptosis by transforming growth factor-beta 1 in a human ovarian carcinoma cell line.

PubMed

Mathieu, C; Jozan, S; Mazars, P; Côme, M G; Moisand, A; Valette, A

1995-01-01

Transforming growth factor-beta 1 inhibited proliferation of a human ovarian carcinoma cell line (NIH-OVCAR-3). The inhibition of NIH-OVCAR-3 cell proliferation was accompanied by a decrease in clonogenic potential, evidenced by the reduced ability of TGF-beta 1-treated NIH-OVCAR-3 cells to form colonies on a plastic substratum. This rapid decrease of clonogenic potential, which was detected 6 h after addition of TGF-beta 1 was dose-dependent (IC50 = 4 pM). Fluorescence microscopy of DAPI-stained cells supported by electron-microscopic examination showed that TGF-beta 1 induced chromatin condensation and nuclear fragmentation. In addition, oligonucleosomal-sized fragments were detected in the TGF-beta 1-treated cells. These features indicated that TGF-beta 1 induced NIH-OVCAR-3 cell death by an apoptosis-like mechanism. This TGF-beta 1 apoptotic effect was subject to modulation by cell density. It was observed that an increase in cell density (up to 20 x 10(3) cells/cm2) protected NIH-OVCAR-3 cells against apoptosis induced by TGF-beta 1. Conditioned medium from high-density cultures of NIH-OVCAR-3 cells did not inhibit apoptosis induced by TGF-beta 1 on NIH-OVCAR-3 cells cultured at low density, suggesting that the protective effect of cell density was not related to the cell secretion of a soluble survival factor.

Autoradiographic localization of beta-adrenoceptors in asthmatic human lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spina, D.; Rigby, P.J.; Paterson, J.W.

1989-11-01

The autoradiographic distribution and density of beta-adrenoceptors in human non-diseased and asthmatic bronchi were investigated using (125I)iodocyanopindolol (I-CYP). Analysis of the effects of the beta-adrenoceptor antagonists on I-CYP binding demonstrated that betaxolol (20 nM, beta 1-selective) had no significant effect on specific grain density in either nonasthmatic or asthmatic human bronchus, whereas ICI-118551 (20 nM, beta 2-selective) inhibited I-CYP binding by 85 +/- 9% and 89 +/- 3%, respectively. Thus, homogeneous populations of beta 2-adrenoceptors existed in bronchi from both sources. Large populations of beta-adrenoceptors were localized to the bronchial epithelium, submucosal glands, and airway smooth muscle. Asthmatic bronchial tissuemore » featured epithelial damage with exfoliated cells associated with luminal mucus plugs. A thickened basement membrane and airway smooth muscle hyperplasia were also evident. High levels of specific I-CYP binding were also detected over asthmatic bronchial smooth muscle, as assessed by autoradiography and quantitation of specific grain densities. Isoproterenol and fenoterol were 10- and 13-fold less potent, respectively, in bronchi from asthmatic lung than in those from nonasthmatic lung. However, this attenuated responsiveness to beta-adrenoceptor agonists was not caused by reduced beta-adrenoceptor density in asthmatic airways. A defect may exist in the coupling between beta-adrenoceptors and postreceptor mechanisms in severely asthmatic lung.« less

Soybean beta-conglycinin peptone suppresses food intake and gastric emptying by increasing plasma cholecystokinin levels in rats.

PubMed

Nishi, Takashi; Hara, Hiroshi; Tomita, Fusao

2003-02-01

Cholecystokinin (CCK) is an important physiologic mediator that regulates satiety and gastric emptying. We demonstrated previously that soybean peptone acts directly on rat small intestinal mucosal cells to stimulate CCK release. In the present study, we examined the effects of beta-conglycinin, a major component of soy protein, and its peptone on food intake and gastric emptying after an intraduodenal infusion of beta-conglycinin peptone in relation to CCK release and interaction with the mucosal cell membrane. Intraduodenal infusion of beta-conglycinin peptone inhibited food intake in a dose-dependent manner, but that of whole soy peptone or camostat did not. The suppression of food intake by beta-conglycinin peptone was abolished by an intravenous injection of devazepide, a selective peripheral CCK receptor antagonist. The beta-conglycinin peptone infusion strongly suppressed gastric emptying with marked increases in portal CCK levels. We also observed that the beta-conglycinin peptone dose dependently and more potently stimulated CCK release from isolated dispersed mucosal cells of the rat jejunum than did beta-conglycinin itself. This stimulation corresponded to the binding activity of the peptide or protein to solubilized components of the rat jejunum membrane as evaluated by surface plasmon biosensor. These results indicate that beta-conglycinin peptone suppresses food intake, and this effect may be due to beta-conglycinin peptone in the lumen stimulating endogenous CCK release with direct acceptance to the intestinal cells.

Interleukin-1 beta induced synthesis of protein kinase C-delta and protein kinase C-epsilon in EL4 thymoma cells: possible involvement of phosphatidylinositol 3-kinase.

PubMed

Varley, C L; Royds, J A; Brown, B L; Dobson, P R

2001-01-01

We present evidence here that the proinflammatory cytokine, interleukin-1 beta (IL-1 beta) stimulates a significant increase in protein kinase C (PKC)-epsilon and PKC-delta protein levels and increases PKC-epsilon, but not PKC-delta, transcripts in EL4 thymoma cells. Incubation of EL4 cells with IL-1 beta induced protein synthesis of PKC-epsilon (6-fold increase) by 7 h and had a biphasic effect on PKC-delta levels with peaks at 4 h (2-fold increase) and 24 h (4-fold increase). At the level of mRNA, PKC-epsilon, but not PKC-delta levels, were induced after incubation of EL4 cells with IL-1 beta. The signalling mechanisms utilized by IL-1 beta to induce the synthesis of these PKC isoforms were investigated. Two phosphatidylinositol (PI) 3-kinase-specific inhibitors, wortmannin and LY294002, inhibited IL-1 beta-induced synthesis of PKC-epsilon. However, the PI 3-kinase inhibitors had little effect on the IL-1 beta-induced synthesis of PKC-delta in these cells. Our results indicate that IL-1 beta induced both PKC-delta and PKC-epsilon expression over different time periods. Furthermore, our evidence suggests that IL-1 beta induction of PKC-epsilon, but not PKC-delta, may occur via the PI 3-kinase pathway. Copyright 2001 S. Karger AG, Basel

Neurotensin protects pancreatic beta cells from apoptosis.

PubMed

Coppola, Thierry; Béraud-Dufour, Sophie; Antoine, Aurélie; Vincent, Jean-Pierre; Mazella, Jean

2008-01-01

The survival of pancreatic beta cells depends on the balance between external cytotoxic and protective molecular systems. The neuropeptide neurotensin (NT) has been shown to regulate certain functions of the endocrine pancreas including insulin and glucagon release. However, the mechanism of action of NT as well as the identification of receptors involved in the pancreatic functions of the peptide remained to be studied. We demonstrate here that NT is an efficient protective agent of pancreatic beta cells against cytotoxic agents. Both beta-TC3 and INS-1E cell lines and the mouse pancreatic islet cells express the three known NT receptors. The incubation of beta cells with NT protects cells from apoptosis induced either by staurosporine or by IL-1beta. In beta-TC3 cells, NT activates both MAP and PI-3 kinases pathways and strongly reduces the staurosporine or the Il-1beta-induced caspase-3 activity by a mechanism involving Akt activation. The NTSR2 agonist levocabastine displays the same protective effect than NT whereas the NTSR1 antagonist is unable to block the effect of NT suggesting the predominant involvement of the NTSR2 in the action of NT on beta cells. These results clearly indicate for the first time that NT is able to protect endocrine beta cells from external cytotoxic agents, a role well correlated with its release in the circulation after a meal.

The Therapeutic Effect of the Antitumor Drug 11beta and Related Molecules on Polycystic Kidney Disease

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-15-1-0364 TITLE: The Therapeutic Effect of the Antitumor Drug 11beta and Related Molecules on Polycystic Kidney Disease...SUBTITLE The Therapeutic Effect of the Antitumor Drug 11beta and Related Molecules on Polycystic Kidney Disease 5a. CONTRACT NUMBER 5b. GRANT NUMBER...synthetic multifunctional compounds as therapeutics for polycystic kidney disease (PKD). In collaboration with the Essigmann lab at MIT, we have

PROGRESS ON THE STUDY OF BETA TREATMENT OF URANIUM, APRIL 1, 1961 TO JULY 31, 1961

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russell, R.B.; Wolff, A.K.

Progress on the work on the effect of variables affecting the beta treatment of uranium is described. Included are results on the effect of beta time and temperature on the as-quenched grain size, the influence of air delay before quenching, and the growth index of metal isothermally transformed at different temperatures. The relative effects of both size and cooling medium on the radial growth index are summarized. (auth)

Effects of physiological versus pharmacological beta-carotene supplementation on cell proliferation and histopathological changes in the lungs of cigarette smoke-exposed ferrets.

PubMed

Liu, C; Wang, X D; Bronson, R T; Smith, D E; Krinsky, N I; Russell, R M

2000-12-01

There remains a remarkable discordance between the results of observational epidemiological studies and intervention trials using beta-carotene as a potential chemopreventive agent. One question that needs to be examined is whether the adverse outcomes of human beta-carotene trials are related to the large doses of beta-carotene that were administered. In the present study, ferrets were given a physiological (low) dose or a pharmacological (high) dose of beta-carotene supplementation (0.43 mg versus 2.4 mg/kg body wt/day, which is equivalent to 6 mg versus 30 mg/day in humans) and exposed to cigarette smoke for 6 months. We investigated the effects of these doses of beta-carotene on retinoid concentrations, expression of retinoic acid receptors (RARs), activator protein 1 (AP-1; c-Jun and c-Fos), cyclin D1, proliferating cellular nuclear antigen (PCNA), and histopathological changes in the lungs of both normal and cigarette smoke-exposed ferrets. Thirty-six male ferrets were treated in six groups-control, smoke-exposed (SM), low-dose beta-carotene (LBC), high-dose beta-carotene (HBC), low-dose beta-carotene plus smoke exposure (LBC+SM) or high-dose beta-carotene plus smoke exposure (HBC+SM)-for 6 months. Retinoic acid concentration and RAR beta gene expression, but not expression of RAR alpha and RAR gamma, was reduced in the lung tissue of HBC+SM, HBC, SM and LBC+SM ferrets, but not in that of LBC ferrets, as compared with the control group. Expression of AP-1 and PCNA was greater in HBC+SM, HBC, SM and LBC+SM ferrets, but not in the LBC ferrets, as compared with the control group. Increased amounts of cyclin D1 and keratinized squamous metaplasia were observed in the lung tissue of HBC+SM, HBC and SM groups but not in that of the LBC+SM, LBC or control groups. These data suggest that, in contrast with a pharmacological dose of beta-carotene, a physiological dose of beta-carotene in smoke-exposed ferrets has no potentially detrimental effects and may afford weak protection against lung damage induced by cigarette smoke.

Steroids from the leaves of Chinese Melia azedarach and their cytotoxic effects on human cancer cell lines.

PubMed

Wu, Shi-Biao; Ji, Yan-Ping; Zhu, Jing-Jing; Zhao, Yun; Xia, Gang; Hu, Ying-He; Hu, Jin-Feng

2009-09-01

Three new (1-3) and several known (4-6) steroids were isolated from the leaves of Chinese Melia azedarach. The structures of the new compounds were elucidated by means of spectroscopic methods including 2D NMR techniques and mass spectrometry to be (20S)-5,24(28)-ergostadiene-3beta,7alpha,16beta,20-tetrol (1), (20S)-5-ergostene-3beta,7alpha,16beta,20-tetrol (2), and 2alpha,3beta-dihydro-5-pregnen-16-one (3). The cytotoxicities of the isolated compounds against three human cancer cell lines (A549, H460, U251) were evaluated; only compounds 1, 2, and (20S)-5-stigmastene-3beta,7alpha,20-triol (4) were found to show significant cyctotoxic effects with IC(50)s from 12.0 to 30.1 microg/mL.

Effect of interleukin-1beta on the behavior of rats during mild stress in the open-field test.

PubMed

Pertsov, S S; Koplik, E V; Simbirtsev, A S; Kalinichenko, L S

2009-11-01

We studied the effect of interleukin-1beta on the behavior of rats with different individual typological characteristics during mild stress in the open-field test. Intraperitoneal injection of interleukin-1beta (5 microg/kg, 108 U/mg) was followed by a decrease in orientation and exploratory activity of passive and, particularly, of active animals in the open field. As differentiated from rats receiving physiological saline, the initial differences in behavioral characteristics of active and passive animals were not revealed in the repeated test after injection of interleukin-1beta. We conclude that interleukin-1beta abolishes the behavioral differences between active and passive specimens in the open field. These data suggest that administration of interleukin-1beta to rats leads to reorganization of the mechanisms for emotional evaluation of adverse emotiogenic factors under conditions of mild stress in the open-field test.

The Promiscuity of [beta]-Strand Pairing Allows for Rational Design of [beta]-Sheet Face Inversion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Makabe, Koki; Koide, Shohei

2009-06-17

Recent studies suggest the dominant role of main-chain H-bond formation in specifying {beta}-sheet topology. Its essentially sequence-independent nature implies a large degree of freedom in designing {beta}-sheet-based nanomaterials. Here we show rational design of {beta}-sheet face inversions by incremental deletions of {beta}-strands from the single-layer {beta}-sheet of Borrelia outer surface protein A. We show that a {beta}-sheet structure can be maintained when a large number of native contacts are removed and that one can design large-scale conformational transitions of a {beta}-sheet such as face inversion by exploiting the promiscuity of strand-strand interactions. High-resolution X-ray crystal structures confirmed the success ofmore » the design and supported the importance of main-chain H-bonds in determining {beta}-sheet topology. This work suggests a simple but effective strategy for designing and controlling nanomaterials based on {beta}-rich peptide self-assemblies.« less

Ferulic acid destabilizes preformed {beta}-amyloid fibrils in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ono, Kenjiro; Hirohata, Mie; Yamada, Masahito

2005-10-21

Inhibition of the formation of {beta}-amyloid fibrils (fA{beta}), as well as the destabilization of preformed fA{beta} in the CNS, would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We reported previously that curcumin (Cur) inhibits fA{beta} formation from A{beta} and destabilizes preformed fA{beta} in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of ferulic acid (FA) on the formation, extension, and destabilization of fA{beta} at pH 7.5 at 37 deg C in vitro. We next compared the anti-amyloidogenic activities of FA with Cur, rifampicin, and tetracycline. Ferulic acid dose-dependentlymore » inhibited fA{beta} formation from amyloid {beta}-peptide, as well as their extension. Moreover, it destabilized preformed fA{beta}s. The overall activity of the molecules examined was in the order of: Cur > FA > rifampicin = tetracycline. FA could be a key molecule for the development of therapeutics for AD.« less

Modulating drug loading and release profile of beta-cyclodextrin polymers by means of cross-linked degree.

PubMed

Wang, Qi-fang; Li, San-ming; Zhang, Yu-yang; Zhang, Hong

2011-02-01

The purpose of the present study is to use beta-cyclodextrin polymers (beta-CDP) with different cross-linked degree (CLD) to form inclusion complexes with ibuprofen and examine the effects of structural and compositional factors of beta-CDP on its drug loading and release behaviors. A series of beta-CDP with different CLD were synthesized and characterized by Fourier Transform Infrared Spectroscopy (FT-IR) and 13C NMR spectrum. The beta-CDP was systemically characterized for the relation between the CLD of beta-CDP and the drug loading and release as well. The results of FT-IR and 13C NMR showed that similar peak-shaped vibration of beta-CDP and beta-CD implies that the polymer keeps the original characteristic structure of beta-CD. The CLD of the beta-CDP played a critical role in the drug loading and release, increasing the CLD resulted in reduction of drug loading, but increase in drug release.

Regulation of GM-CSF-induced dendritic cell development by TGF-beta1 and co-developing macrophages.

PubMed

Yamaguchi, Y

1998-01-01

Using a culture system of bone marrow progenitor cells with GM-CSF and TGF-beta1, a study was performed to analyze the effect of TGF-beta1 on the development of dendritic cells (DC) and to elucidate the regulatory role of macrophages co-developing with dendritic cells. The results demonstrate that DC generated in the presence of TGF-beta1 were immature with respect to the expression of CD86, nonspecific esterase activity and cell shape. Such inhibitory effects of TGF-beta1 were dependent on FcR+ macrophages, which were depleted by panning. TGF-beta1 did not appear to inhibit the commitment of progenitor cells to the DC lineage. In addition, TGF-beta1 also acted directly on the intermediate stage of DC to prevent their over-maturation, which results in a preferential decrease in MHC class II, but not in CD86, in the presence of TNF-alpha. FcR+ suppressive macrophages were also shown to facilitate DC maturation when stimulated via FcR-mediated signals even in the presence of TGF-beta1. These results indicate that TGF-beta1 indirectly and directly regulate the development of DC and that co-developing macrophages have a regulatory role in DC maturation.

Role of beta1-adrenoceptor in the basolateral amygdala of rats with anxiety-like behavior.

PubMed

Fu, Ailing; Li, Xiaorong; Zhao, Baoquan

2008-05-23

There are evidence suggesting that the function of adrenergic receptor is affected in the amygdala of animals with anxiety-like behavior. However, beta-adrenoceptor (beta-AR) subtypes, consisting of three subtypes, exert different effects on anxiety regulation. In order to determine the function of the beta1-AR subtype in anxiety-like behavior, we investigated the change of beta1-AR expression by immunostaining in the basolateral amygdala (BLA) of rats treated by conditional fear training. The results indicated that the level of beta1-AR was significantly increased in the BLA of fear-conditioned animals as compared that of controls. In animal behavioral tests, animals treated with selective beta1-AR antagonist metoprolol before conditional fear training exhibited a significant attenuation of anxiety-like behavior characterized by increased percentage of time spent and percentage of entries in the open arms, and increased number of head-dips in the elevated plus-maze (EPM) test compared with the animals treated with only saline. Furthermore, the rats pretreated with metoprolol in the conditional fear training significantly decreased the freezing behavior in the test compared with the controls. The results suggested that the beta1-AR played an important role in anxiety-like behavior, and inhibition of the beta1-AR in the BLA could produce anxiolytic effect.

Loss of c-myc repression coincides with ovarian cancer resistance to transforming growth factor beta growth arrest independent of transforming growth factor beta/Smad signaling.

PubMed

Baldwin, Rae Lynn; Tran, Hang; Karlan, Beth Y

2003-03-15

Many epithelial carcinomas, including ovarian, are refractory to the antiproliferative effects of transforming growth factor (TGF) beta. In some cancers, TGF-beta resistance has been linked to TGF-beta receptor II (TbetaR-II) and Smad4 mutations; however, in ovarian cancer, the mechanism of resistance remains unclear. Primary ovarian epithelial cell cultures were used as a model system to determine the mechanisms of TGF-beta resistance. To simulate in vivo responses to TGF-beta, primary cultures derived from normal human ovarian surface epithelium (HOSE) and from ovarian carcinomas (CSOC) were grown on collagen I gel, the predominant matrix molecule in the ovarian tumor milieu. When treated with 5 ng/ml TGF-beta for 72 h, HOSE (n = 11) proliferation was inhibited by 20 +/- 21% on average. In contrast, CSOC (n = 10) proliferation was stimulated 5 +/- 10% in response to TGF-beta (a statistically significant difference in response when compared with HOSE; P = 0.001). To dissect the TGF-beta/Smad signaling pathway we used a quantitative RNase protection assay (RPA) for measuring mRNA levels of TGF-beta pathway components in 20 HOSE and 20 CSOC cultures. Basal mRNA levels of TGF-beta receptors I and II, downstream signaling components Smad2, 3, 4, 6, 7, and the transcriptional corepressors Ski and SnoN did not show a statistically significant difference between HOSE and CSOC, and cannot explain their differential susceptibility to TGF-beta-induced cell cycle arrest. To assess functional differences of the TGF-beta pathway in TGF-beta-sensitive HOSE and TGF-beta-resistant CSOC, we measured Smad2/4 and 3/4 complex induction after TGF-beta treatment. HOSE and CSOC showed equivalent Smad2/4 and 3/4 complex induction after TGF-beta exposure for 0, 0.5, 2, and 4 h. It has been proposed that SnoN and Ski are corepressors of the TGF-beta/Smad pathway and undergo TGF-beta-induced degradation followed by reinduction of SnoN mRNA. However, our data show equivalent SnoN degradation in HOSE and CSOC, and equivalent SnoN mRNA induction after TGF-beta treatment. Surprising, TGF-beta-induced Ski degradation was not observed in HOSE or CSOC, suggesting that Ski may not function as a TGF-beta/Smad corepressor in ovarian epithelial cells. These data implied that the TGF-beta/Smad pathway remains functional in CSOC, although CSOC cells are resistant to antimitogenic TGF-beta effects. CSOC resistance to TGF-beta coincided with the loss of c-myc down-regulation. These data suggest that TGF-beta/Smad signaling is blocked downstream of Smad complex formation or that an alternate signaling pathway other than TGF-beta/Smad may transmit TGF-beta-induced cell cycle arrest in the ovarian epithelium.

Effect of beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors and antioxidant vitamins on free radical lipid oxidation in rat liver.

PubMed

Lankin, V Z; Ivanova, M V; Konovalova, G G; Tikhaze, A K; Kaminnyi, A I; Kukharchuk, V V

2007-04-01

We studied the effects of two inhibitors of beta-hydroxy-beta-methylglutaryl coenzyme A reductase, simvastatin and lovastatin, on the lag phase of ascorbate-dependent lipid oxidation in rat liver. Oxidizability of liver biological membranes significantly increased in intact animals and rats with induced hypercholesterolemia after peroral administration of these statins. The lag phase of ascorbate-dependent lipid oxidation in liver biomembranes decreased by 2.1 times in hypercholesterolemic rats. In animals of the lovastatin group this parameter decreased by 4.4 times compared to the control. In intact rats receiving simvastatin, the lag phase of oxidation in biomembranes from the liver decreased practically by 2 times. At the same time, in animals receiving simvastatin in combination with antioxidant vitamins (vitamins E and C, provitamin A) and selenium, the period of induction of oxidation increased by 3.3 times. Our results indicate that beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors produce a prooxidant effect on the liver, which can be prevented by administration of antioxidant agents.

Antiproliferative properties of toremifene on AIDS-related Kaposi's sarcoma cells.

PubMed

Hong, Angela; Leigh, Bryan R

2002-12-01

Kaposi's sarcoma (KS) is the most common neoplastic apoptosis manifestation of acquired immunodeficiency syndrome. Toremifene is known to upregulate transforming growth factor beta-1 (TGF-beta1), which is a growth-inhibitory factor for KS. We investigated the in vitro effect of toremifene on KS cells. MTT assay was used to measure the growth of four KS cell lines and a human umbilical vein endothelial (HUVE) cell line after incubation with toremifene. Reverse transcription polymerase chain reaction and ELISA were used to measure the level of TGF-beta1. The IC(50) for the KS cells ranged from 2.2 to 3.2 microM, and 80% of the growth inhibition occurred within 24 h. Toremifene enhanced TGF-beta1 mRNA expression, and the level of TGF-beta1 increased from 103 to 473 pg/ml after 48 h of incubation. Toremifene had no effect on the growth of HUVE cells. Toremifene has a specific antiproliferative effect on KS cells. The stimulation of TGF-beta1 production may play a role in the antiproliferative process. Copyright 2002 S. Karger AG, Basel

Characterization and inhibition of beta-adrenergic receptor kinase in intact myocytes.

PubMed

Laugwitz, K L; Kronsbein, K; Schmitt, M; Hoffmann, K; Seyfarth, M; Schömig, A; Ungerer, M

1997-08-01

beta-Adrenergic receptor kinase (beta ARK) phosphorylates and thereby inactivates agonist-occupied beta-adrenergic receptors (beta AR). beta ARK is thought to play an important role in the regulation of cardiac function. Therefore, we studied beta ARK activation and its inhibition in intact smooth muscle cells and in cardiomyoblasts. beta AR agonist-stimulated translocation of beta ARK was monitored by immunofluorescence labelling with specific antibodies and confocal laser scanning microscopy in DDT-MF 2 hamster smooth muscle cells and in H9c2 rat cardiomyoblasts. In unstimulated cells. beta ARK was mainly located in the cytosol. After beta AR agonist stimulation, the beta ARK signal was partially translocated to the membranes. Liposomal gene transfer of the COOH-terminus of beta ARK ('beta ARKmini') as a beta ARK inhibitor led to functional expression of this protein in both cell lines with high efficiency. Western blots with beta ARK antibodies showed a gene concentration-dependent immunoreactivity of the 'beta ARKmini' protein. 'beta ARKmini'-transfected myocytes demonstrated reduced membrane targeting of the beta ARK immuno-fluorescence signal. Additionally, the effect of 'beta ARKmini' on beta AR-induced desensitization of myocytic cAMP accumulation was investigated. In control cells, desensitization with isoproterenol led to a subsequent reduction of beta AR-induced cAMP accumulation. In 'beta ARKmini'-transfected myocytes, this beta AR-induced desensitization was significantly diminished, whereas normal beta AR-induced cAMP accumulation was unaffected. A gene concentration of 2 micrograms 'beta ARKmini' DNA/100,000 cardiomyoblasts, and of 0.7 microgram 'beta ARKmini' DNA/100,000 DDT-MF2 smooth muscle cells led to approximately 5.9- and approximately 5.6-fold overexpressions of 'beta ARKmini' vs. native beta ARK, respectively. These gene doses proved sufficient to attenuate beta-adrenergic desensitization significantly. (1) beta ARK translocation was evidenced in DDT-MF2 smooth muscle cells and in cardiomyoblasts by confocal laser scanning microscopy. (2) Feasibility of 'beta ARKmini' gene transfer to myocytes was demonstrated, and necessary gene doses for beta ARK inhibition were titered. (3) Overexpression of 'beta ARKmini' functionally interacted with endogenous beta-adrenergic signal transduction, leading to sustained cAMP accumulation after prolonged beta-adrenergic stimulation.

Radiative effects of ozone waves on the Northern Hemisphere polar vortex and its modulation by the QBO

NASA Astrophysics Data System (ADS)

Silverman, Vered; Harnik, Nili; Matthes, Katja; Lubis, Sandro W.; Wahl, Sebastian

2018-05-01

The radiative effects induced by the zonally asymmetric part of the ozone field have been shown to significantly change the temperature of the NH winter polar cap, and correspondingly the strength of the polar vortex. In this paper, we aim to understand the physical processes behind these effects using the National Center for Atmospheric Research (NCAR)'s Whole Atmosphere Community Climate Model, run with 1960s ozone-depleting substances and greenhouse gases. We find a mid-winter polar vortex influence only when considering the quasi-biennial oscillation (QBO) phases separately, since ozone waves affect the vortex in an opposite manner. Specifically, the emergence of a midlatitude QBO signal is delayed by 1-2 months when radiative ozone-wave effects are removed. The influence of ozone waves on the winter polar vortex, via their modulation of shortwave heating, is not obvious, given that shortwave heating is largest during fall, when planetary stratospheric waves are weakest. Using a novel diagnostic of wave 1 temperature amplitude tendencies and a synoptic analysis of upward planetary wave pulses, we are able to show the chain of events that lead from a direct radiative effect on weak early fall upward-propagating planetary waves to a winter polar vortex modulation. We show that an important stage of this amplification is the modulation of individual wave life cycles, which accumulate during fall and early winter, before being amplified by wave-mean flow feedbacks. We find that the evolution of these early winter upward planetary wave pulses and their induced stratospheric zonal mean flow deceleration is qualitatively different between QBO phases, providing a new mechanistic view of the extratropical QBO signal. We further show how these differences result in opposite radiative ozone-wave effects between east and west QBOs.

Adverse reactions and interactions with beta-adrenoceptor blocking drugs.

PubMed

Lewis, R V; McDevitt, D G

1986-01-01

beta-Blocking drugs are widely used throughout the world and serious adverse reactions are relatively uncommon. Most of those which do occur are pharmacologically predictable and may be avoided by ensuring that patients who are to be given beta-blockers do not have a predisposition to the development of bronchospasm, cardiac failure or peripheral ischaemia. In some situations, the use of a beta 1-selective blocking drug may reduce the risk of a severe adverse reaction, but there is little evidence that other ancillary properties such as partial agonist activity are of relevance in this context. Long term experience with many of the beta-blockers in current use suggests that unpredictable major adverse reactions such as the practolol oculomucocutaneous syndrome are unlikely to be repeated, although some of these drugs may be associated with immunological disturbances and some have been implicated in the development of retroperitoneal fibrosis. beta-Blocking drugs appear to be associated with a number of subjective side effects including muscle fatigue, peripheral coldness and some neurological symptoms. These side effects are highly subjective and are therefore difficult to quantify and it is not known whether they are of major importance in terms of their effect upon patients' overall well-being. It cannot be assumed that simply because such side effects can be elicited that they do, in fact, matter. However, because beta-blockers are often prescribed for patients who have no symptoms and for whom the benefits of therapy are generally small, such side effects would be of considerable importance if they had an overall effect upon quality of life. There are theoretical reasons to suppose that the incidence and severity of such side effects may be related to the ancillary properties of the individual drugs, but there is little evidence that parameters such as beta 1-selectivity, or partial agonist activity are clinically important determinants of the severity of these side effects. Lipophilicity, however, may be associated with an increased incidence of neurological symptoms. beta-Blocking drugs may cause a variety of metabolic disturbances including an increase in serum VLDL-cholesterol concentrations. However, long term studies have not shown that such disturbances are associated with an increased risk of cardiovascular disease, indicating that such metabolic changes may not be of major importance in practice. beta-Blocking drugs may be involved in a number of interactions with other drugs, but few of these have been shown to be of clinical significance.(ABSTRACT TRUNCATED AT 400 WORDS)

Planetary quarantine

NASA Technical Reports Server (NTRS)

1977-01-01

Those areas of future missions which will be impacted by planetary quarantine (PQ) constraints were identified. The specific objectives for this reporting period were (1) to perform an analysis of the effects of PQ on an outer planet atmospheric probe, and (2) to prepare a quantitative illustration of spacecraft microbial reduction resulting from exposure to space environments. The Jupiter Orbiter Probe mission was used as a model for both of these efforts.

The effect of latent heat release on synoptic-to-planetary wave interactions and its implication for satellite observations: Theoretical modeling

NASA Technical Reports Server (NTRS)

Branscome, Lee E.; Bleck, Rainer; Obrien, Enda

1990-01-01

The project objectives are to develop process models to investigate the interaction of planetary and synoptic-scale waves including the effects of latent heat release (precipitation), nonlinear dynamics, physical and boundary-layer processes, and large-scale topography; to determine the importance of latent heat release for temporal variability and time-mean behavior of planetary and synoptic-scale waves; to compare the model results with available observations of planetary and synoptic wave variability; and to assess the implications of the results for monitoring precipitation in oceanic-storm tracks by satellite observing systems. Researchers have utilized two different models for this project: a two-level quasi-geostrophic model to study intraseasonal variability, anomalous circulations and the seasonal cycle, and a 10-level, multi-wave primitive equation model to validate the two-level Q-G model and examine effects of convection, surface processes, and spherical geometry. It explicitly resolves several planetary and synoptic waves and includes specific humidity (as a predicted variable), moist convection, and large-scale precipitation. In the past year researchers have concentrated on experiments with the multi-level primitive equation model. The dynamical part of that model is similar to the spectral model used by the National Meteorological Center for medium-range forecasts. The model includes parameterizations of large-scale condensation and moist convection. To test the validity of results regarding the influence of convective precipitation, researchers can use either one of two different convective schemes in the model, a Kuo convective scheme or a modified Arakawa-Schubert scheme which includes downdrafts. By choosing one or the other scheme, they can evaluate the impact of the convective parameterization on the circulation. In the past year researchers performed a variety of initial-value experiments with the primitive-equation model. Using initial conditions typical of climatological winter conditions, they examined the behavior of synoptic and planetary waves growing in moist and dry environments. Surface conditions were representative of a zonally averaged ocean. They found that moist convection associated with baroclinic wave development was confined to the subtropics.

Obtaining and Using Planetary Spatial Data into the Future: The Role of the Mapping and Planetary Spatial Infrastructure Team (MAPSIT)

NASA Technical Reports Server (NTRS)

Radebaugh, J.; Thomson, B. J.; Archinal, B.; Hagerty, J.; Gaddis, L.; Lawrence, S. J.; Sutton, S.

2017-01-01

Planetary spatial data, which include any remote sensing data or derived products with sufficient positional information such that they can be projected onto a planetary body, continue to rapidly increase in volume and complexity. These data are the hard-earned fruits of decades of planetary exploration, and are the end result of mission planning and execution. Maintaining these data using accessible formats and standards for all scientists has been necessary for the success of past, present, and future planetary missions. The Mapping and Planetary Spatial Infrastructure Team (MAPSIT) is a group of planetary community members tasked by NASA Headquarters to work with the planetary science community to identify and prioritize their planetary spatial data needs to help determine the best pathways for new data acquisition, usable product derivation, and tools/capability development that supports NASA's planetary science missions.

Inactivation properties of voltage-gated K+ channels altered by presence of beta-subunit.

PubMed

Rettig, J; Heinemann, S H; Wunder, F; Lorra, C; Parcej, D N; Dolly, J O; Pongs, O

1994-05-26

Structural and functional diversity of voltage-gated Kv1-type potassium channels in rat brain is enhanced by the association of two different types of subunits, the membrane-bound, poreforming alpha-subunits and a peripheral beta-subunit. We have cloned a beta-subunit (Kv beta 1) that is specifically expressed in the rat nervous system. Association of Kv beta 1 with alpha-subunits confers rapid A-type inactivation on non-inactivating Kv1 channels (delayed rectifiers) in expression systems in vitro. This effect is mediated by an inactivating ball domain in the Kv beta 1 amino terminus.

A hospital perspective on the cost-effectiveness of beta-blockade for prophylaxis of atrial fibrillation after cardiothoracic surgery.

PubMed

Gillespie, Effie L; White, C Michael; Kluger, Jeffrey; Sahni, Jasmine; Gallagher, Robert; Coleman, Craig I

2005-12-01

Prophylactic beta-blockade is the recommended strategy for suppressing atrial fibrillation after cardiothoracic surgery (CTS). However, beta-blockade's impact on the hospital length of stay (LOS) and other economic end points has not been adequately assessed. The present evaluation sought to determine whether beta-blocker use after CTS is a cost-effective strategy for the prevention of postoperative atrial fibrillation (POAF). This was a piggyback cost-effectiveness analysis of a prospective cohort evaluation comprising 1660 patients undergoing CTS at an urban academic hospital from October 1999 to October 2003. Patients receiving beta-blocker prophylaxis were matched 1:1 with control patients not receiving prophylaxis based on age >70 years, valvular surgery, history of atrial fibrillation, male sex, and use of preoperative digoxin or beta-blockers. The incidence of POAF, total hospital costs, and LOS were compared in each group. Nonparametric bootstrapping analysis was performed to examine the study results as part of a quadrant analysis and to calculate CIs for the incremental cost-effectiveness ratio. LOS and total costs were also compared in patients with and without POAF, regardless of beta-blocker use. Use of prophylactic beta-blockade was associated with a 17.3 % reduction in the incidence of POAF (P = 0.02) and a 2.2-day reduction in LOS (P = 0.001) compared with nonuse. It also was associated with a 25.7% reduction in total hospital costs compared with nonuse (mean [SD], $30,978 [$33,108] vs $41,700 [$67,369], respectively; P < 0.001), possibly due to a 27.6% reduction in room and board costs ($11,144 [$15,398] vs $14,920 [$22,132]; P < 0.001). In the bootstrapping analysis, 99.0% of the time prophylactic beta-blockade fell into quadrant IV, which indicated superior effectiveness and lower total costs. Regardless of beta-blocker use, patients who developed POAF had a significantly longer LOS compared with those who did not develop POAF (14.7 [19.1] days vs 10.1 [11.1] days, respectively; P < 0.001) and higher total costs ($47,240 [$85,941] vs $32,516 [$34,644]; P < 0.001). At the institution studied, beta-blocker prophylaxis against POAF after CTS was associated with significantly reduced total costs compared with nonuse of beta-blocker prophylaxis. Patients who developed POAF had significantly increased LOS and total costs compared with those who did not develop POAE An adequately powered prospective, randomized, placebo-controlled trial is necessary to confirm the results of this evaluation.

Betaxolol, a selective beta(1)-adrenergic receptor antagonist, diminishes anxiety-like behavior during early withdrawal from chronic cocaine administration in rats.

PubMed

Rudoy, C A; Van Bockstaele, E J

2007-06-30

Anxiety has been indicated as one of the main symptoms of the cocaine withdrawal syndrome in human addicts and severe anxiety during withdrawal may potentially contribute to relapse. As alterations in noradrenergic transmission in limbic areas underlie withdrawal symptomatology for many drugs of abuse, the present study sought to determine the effect of cocaine withdrawal on beta-adrenergic receptor (beta(1) and beta(2)) expression in the amygdala. Male Sprague Dawley rats were administered intraperitoneal (i.p.) injections of cocaine (20 mg/kg) once daily for 14 days. Two days following the last cocaine injection, amygdala brain regions were micro-dissected and processed for Western blot analysis. Results showed that beta(1)-adrenergic receptor, but not beta(2)-adrenergic receptor expression was significantly increased in amygdala extracts of cocaine-withdrawn animals as compared to controls. This finding motivated further studies aimed at determining whether treatment with betaxolol, a highly selective beta(1)-adrenergic receptor antagonist, could ameliorate cocaine withdrawal-induced anxiety. In these studies, betaxolol (5 mg/kg via i.p. injection) was administered at 24 and then 44 h following the final chronic cocaine administration. Anxiety-like behavior was evaluated using the elevated plus maze test approximately 2 h following the last betaxolol injection. Following behavioral testing, betaxolol effects on beta(1)-adrenergic receptor protein expression were examined by Western blotting in amygdala extracts from rats undergoing cocaine withdrawal. Animals treated with betaxolol during cocaine withdrawal exhibited a significant attenuation of anxiety-like behavior characterized by increased time spent in the open arms and increased entries into the open arms compared to animals treated with only saline during cocaine withdrawal. In contrast, betaxolol did not produce anxiolytic-like effects in control animals treated chronically with saline. Furthermore, treatment with betaxolol during early cocaine withdrawal significantly decreased beta(1)-adrenergic receptor protein expression in the amygdala to levels comparable to those of control animals. The present findings suggest that the anxiolytic-like effect of betaxolol on cocaine-induced anxiety may be related to its effect on amygdalar beta(1)-adrenergic receptors that are up-regulated during early phases of drug withdrawal. These data support the efficacy of betaxolol as a potential effective pharmacotherapy in treating cocaine withdrawal-induced anxiety during early phases of abstinence.

Effect of transforming growth factor-beta1 on embryonic and posthatch muscle growth and development in normal and low score normal chicken.

PubMed

Li, X; Velleman, S G

2009-02-01

During skeletal muscle development, transforming growth factor-beta1 (TGF-beta1) is a potent inhibitor of muscle cell proliferation and differentiation. The TGF-beta1 signal is carried by Smad proteins into the cell nucleus, inhibiting the expression of key myogenic regulatory factors including MyoD and myogenin. However, the molecular mechanism by which TGF-beta1 inhibits muscle cell proliferation and differentiation has not been well documented in vivo. The present study investigated the effect of TGF-beta1 on in vivo skeletal muscle growth and development. A chicken line, Low Score Normal (LSN) with reduced muscling and upregulated TGF-beta1 expression, was used and compared to a normal chicken line. The injection of TGF-beta1 at embryonic day (ED) 3 significantly reduced the pectoralis major (p. major) muscle weight in the normal birds at 1 wk posthatch, whereas no significant difference was observed in the LSN birds. The difference between normal and LSN birds in response to TGF-beta1 is likely due to different levels of endogenous TGF-beta1 where the LSN birds have increased TGF-beta1 expression in their p. major muscle at both 17 ED and 6 wk posthatch. Smad3 expression was reduced by TGF-beta1 from 10 ED to 1 wk posthatch in normal p. major muscle. Unlike Smad3, Smad7 expression was not significantly affected by TGF-beta1 until posthatch in both normal and LSN p. major muscle. Expression of MyoD was reduced 35% by TGF-beta1 during embryonic development in normal p. major muscle, whereas LSN p. major muscle showed a delayed decrease at 1 d posthatch in MyoD expression in response to the TGF-beta1 treatment. Myogenin expression was reduced 29% by TGF-beta1 after hatch in normal p. major muscle. In LSN p. major muscle, TGF-beta1 treatment significantly decreased myogenin expression by 43% at 1 d posthatch and 32% at 1 wk posthatch. These data suggested that TGF-beta1 reduced p. major muscle growth by inhibiting MyoD and myogenin expression during both embryonic and posthatch development. Furthermore, TGF-beta1 also reduced the expression of the cell adhesion receptor beta1 integrin subunit during embryonic and posthatch muscle growth in normal and LSN chickens. Therefore, the reduction of beta1 integrin in response to TGF-beta1 is also associated with decreased posthatch muscle growth. The results from this study indicate that TGF-beta1 inhibits skeletal muscle growth by regulating MyoD and myogenin expression. These data also suggest that a beta1 integrin-mediated alternative pathway is likely involved in the TGF-beta1-induced reduction of muscle growth.

Analysis of hydrophobic interactions of antagonists with the beta2-adrenergic receptor.

PubMed

Novoseletsky, V N; Pyrkov, T V; Efremov, R G

2010-01-01

The adrenergic receptors mediate a wide variety of physiological responses, including vasodilatation and vasoconstriction, heart rate modulation, and others. Beta-adrenergic antagonists ('beta-blockers') thus constitute a widely used class of drugs in cardiovascular medicine as well as in management of anxiety, migraine, and glaucoma. The importance of the hydrophobic effect has been evidenced for a wide range of beta-blocker properties. To better understand the role of the hydrophobic effect in recognition of beta-blockers by their receptor, we carried out a molecular docking study combined with an original approach to estimate receptor-ligand hydrophobic interactions. The proposed method is based on automatic detection of molecular fragments in ligands and the analysis of their interactions with receptors separately. A series of beta-blockers, based on phenylethanolamines and phenoxypropanolamines, were docked to the beta2-adrenoceptor binding site in the crystal structure. Hydrophobic complementarity between the ligand and the receptor was calculated using the PLATINUM web-server (http://model.nmr.ru/platinum). Based on the analysis of the hydrophobic match for molecular fragments of beta-blockers, we have developed a new scoring function which efficiently predicts dissociation constant (pKd) with strong correlations (r(2) approximately 0.8) with experimental data.

Effects of cigarette smoke exposure on nicotinic acetylcholine receptor subunits {alpha}7 and {beta}2 in the sudden infant death syndrome (SIDS) brainstem

DOE Office of Scientific and Technical Information (OSTI.GOV)

Machaalani, Rita, E-mail: rita.machaalani@sydney.edu.au; Bosch Institute, The University of Sydney, NSW 2006; The Children's Hospital at Westmead, NSW 2145

It is postulated that nicotine, as the main neurotoxic constituent of cigarette smoke, influences SIDS risk through effects on nicotinic acetylcholine receptors (nAChRs) in brainstem nuclei that control respiration and arousal. This study compared {alpha}7 and {beta}2 nAChR subunit expression in eight nuclei of the caudal and rostral medulla and seven nuclei of the pons between SIDS (n = 46) and non-SIDS infants (n = 14). Evaluation for associations with known SIDS risk factors included comparison according to whether infants had a history of exposure to cigarette smoke in the home, and stratification for sleep position and gender. Compared tomore » non-SIDS infants, SIDS infants had significantly decreased {alpha}7 in the caudal nucleus of the solitary tract (cNTS), gracile and cuneate nuclei, with decreased {beta}2 in the cNTS and increased {beta}2 in the facial. When considering only the SIDS cohort: 1-cigarette smoke exposure was associated with increased {alpha}7 in the vestibular nucleus and increased {beta}2 in the rostral dorsal motor nucleus of the vagus, rNTS and Cuneate, 2-there was a gender interaction for {alpha}7 in the gracile and cuneate, and {beta}2 in the cNTS and rostral arcuate nucleus, and 3-there was no effect of sleep position on {alpha}7, but prone sleep was associated with decreased {beta}2 in three nuclei of the pons. In conclusion, SIDS infants demonstrate differences in expression of {alpha}7 and {beta}2 nAChRs within brainstem nuclei that control respiration and arousal, which is independent on prior history of cigarette smoke exposure, especially for the NTS, with additional differences for smoke exposure ({beta}2), gender ({alpha}7 and {beta}2) and sleep position ({beta}2) evident. -- Highlights: Black-Right-Pointing-Pointer The 'normal' response to smoke exposure is decreased {alpha}7 and {beta}2 in certain nuclei. Black-Right-Pointing-Pointer SIDS infants have decreased {alpha}7 in cNTS, Grac and Cun. Black-Right-Pointing-Pointer SIDS infants have decreased {beta}2 in cNTS and increased {beta}2 in facial. Black-Right-Pointing-Pointer The NTS is more sensitive to both {alpha}7 and {beta}2 regulation in SIDS. Black-Right-Pointing-Pointer Smoke exposure amongst SIDS induces a different response; increased {alpha}7 and {beta}2.« less

TGF-beta1 secretion of ROS-17/2.8 cultures on NiTi implant material.

PubMed

Kapanen, Anita; Kinnunen, Anne; Ryhänen, Jorma; Tuukkanen, Juha

2002-08-01

The biocompatibility of an orthopedic implant depends on the effect of the implant on bone-forming cells, osteoblasts. Changes in osteoblastic proliferation, maturation and differentiation are important events in ossification that enable monitoring the effect of the implant. Transforming growth factor-beta (TGF-beta) is known to suppress osteoblast proliferation and, on the other hand, to induce the maturation and differentiation of osteoblasts. Moreover, osteoblasts produce TGF-beta, which is embedded in the bone matrix and activated by bone-resorbing osteoclasts. TGF-beta inhibits osteoclastic activity. Here, we show for the first time the effect of nickel titanium shape memory metal (NiTi) on osteoblastic cytokine expression. In this study, we measured the levels of TGF-beta with enzyme-linked immunosorbent assay (ELISA) from a ROS-17/2.8 osteosarcoma cell line cultured on different metal alloy discs. ELISA results were proportioned to total DNA content of the samples. We compared NiTi, to stainless steel (Stst), pure titanium (Ti) and pure nickel (Ni). The TGF-beta1/DNA value in the NiTi group (0.0007 +/- 0.0003) was comparable with those seen in the Stst (0.0008 +/- 0.0001) and Ti (0.0007 +/- 0.0001) groups. The concentration in the Ni group was lower (0.0006 +/- 0.0003), though not statistically significantly so. In addition, the effect of surface roughness on TGF-beta1 production was studied. We compared three different grades of roughness in three differently hot-rolled alloys: NiTi. hot-rolled at 950 degrees C. Ti alloy hot-rolled at 850 degrees C (TiI) and the same Ti alloy hot-rolled at 1,050 degrees C (TiII). We found that increasing roughness of the NiTi surface increased the TGF-beta1 concentration. On the other hand, all roughness groups of TiII showed low levels of TGF-beta1. while a rough TiI surface induced similar TGF-beta1, expression as rough NiTi. Further, these same measurements made with interleukine 6 (IL-6) were found to be under the detection limit in these cultures. We conclude that a rough NiTi surface promotes TGF-beta1 expression in ROS-17/2.8 cells.

Human ovarian cancer xenografts in nude mice: chemotherapy trials with paclitaxel, cisplatin, vinorelbine and titanocene dichloride.

PubMed

Villena-Heinsen, C; Friedrich, M; Ertan, A K; Farnhammer, C; Schmidt, W

1998-07-01

The new cytostatics titanocene dichloride and vinorelbine were compared to cisplatin and paclitaxel using a human ovarian cancer xenografts model. Biopsy material from a native human ovarian carcinoma was expanded and transplanted into 96 nude mice. The animals were divided into six treatment groups: cisplatin 3 x 4 mg/kg, paclitaxel 5 x 26 mg/kg, vinorelbine 1 x 20 mg/kg, titanocene dichloride 3 x 30 mg/kg, titanocene dichloride 3 x 40 mg/kg and a control group treated with 0.9% saline. Each experiment was repeated with eight mice in each treatment group. Treatment groups were evaluated in terms of average daily increase in tumor volume and average daily body weight increase of nude mice based on slopes of least-square regressions performed on individual animals. The slope factors alpha and beta of the body weight (alpha) and tumor volume changes (beta) within each group during the course of an experiment were calculated. Both a statistically significant decrease (p<0.05) in the body weight of the experimental animals (cisplatin: alpha = -0.5163, vinorelbine: alpha = -0.6598, paclitaxel: alpha = -0.6746, titanocene dichloride 3 x 30 mg/kg: alpha = -0.6259, titanocene dichloride 3 x 40 mg/kg: alpha = -0.7758) and a significant reduction (p<0.05) of the increase in tumor volume (cisplatin: beta = 12.049, vinorelbine: beta = 0.504, paclitaxel: beta = -1.636, titanocene dichloride 3 x 30 mg/kg: beta = 6.212, titanocene dichloride 3 x 40 mg/kg: beta= -0.685) was shown in all treated groups compared to the control group (alpha = -0.1398; beta = 23.056). No significant weight changes were observed between the individually treated groups. A statistically significant reduction of the tumor growth occured under paclitaxel (beta = -1.636), vinorelbine (beta = 0.504) and titanocene dichloride medication 3 x 40 mg/kg (beta = -0.685), as compared to the group treated with cisplatin (beta = 12.049). We found titanocene dichloride to be as effective as paclitaxel and more effective than cisplatin. Vinorelbine seems to be a very effective antineoplastic agent exhibiting a significant higher cytostatic effect than cisplatin. Both titanocene dichloride and vinorelbine provide new therapeutic options in women with ovarian carcinoma not responding to standard chemotherapy.

Synthesis, Characterization, In Vitro Evaluation, and Preclinical Profiling of beta-Cyclodextrin Polyrotaxane Families for Use As Potential Niemann-Pick Type C Therapeutics

NASA Astrophysics Data System (ADS)

Collins, Christopher J.

Niemann-Pick Disease Type C (NPC) is a rare, autosomal recessive genetic disorder featuring a loss of proteins responsible for unesterified cholesterol (UC) trafficking through the late endosomes/lysosomes (LE/LY) of every cell of the body. Disruption of this pathway leads to abnormal accumulation and storage of UC and other lipids. A broad range of visceral and neurological symptoms result from this accumulation exhibiting a variable age of onset and a disease progression that is ultimately fatal. The disease has an incidence of approximately 1 in 120,000 live births and has no known effective treatment. beta-Cyclodextrin (beta-CD) are natural small molecules macrocycles composed of glucose units with a hydrophobic inner cavity and hydrophilic outer rims. beta-CD derivatives have recently been shown to be effective therapeutics for NPC in cellular and animal models. In the mouse model of the disease, beta-CD therapy increases overall lifetime by as much as 50% and slows the progression of neurodegeneration. The progress has led to the initiation of a National Institutes of Health phase I clinical trial. A main drawback of beta-CD administration is the poor pharmacokinetic profile characterized by rapid renal clearance of the drug through the urine. Libraries of beta-CD derivative carrying high molecular weight polyrotaxane (PR) systems have been designed to prevent glomerular filtration of the injected beta-CD dose. An initial family of unmodified beta-CD PRs was synthesized, characterized, and their therapeutic efficacy was tested in NPC fibroblasts. This was followed by screening of PRs consisting of mixed beta-CD derivative threading featuring charged sulfobutylether beta-CD. Finally, we sought to define PR structure-property effects on in vivo pharmacokinetics, biodistribution, toxicity, immunogenicity, and protein hard corona composition. This was accomplished using a family of gadolinium carrying PRs composed of triblock Pluronic co-polymers of varying molecular weights and hydrophilic/lipophilic ratios. The effect of varying threaded beta-CD derivative surface chemistry on PR mediated hemolysis and hard protein corona was also studied. Knowing if structure-property relationships exist in the in vivo performances of PR materials will help with building pre-clinical profile, selecting candidate materials for a given application, and understanding therapeutic outcomes.

Ellagic acid promotes A{beta}42 fibrillization and inhibits A{beta}42-induced neurotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feng, Ying; Tsinghua University School of Medicine, Haidian District, Beijing 100084; Yang, Shi-gao

Smaller, soluble oligomers of {beta}-amyloid (A{beta}) play a critical role in the pathogenesis of Alzheimer's disease (AD). Selective inhibition of A{beta} oligomer formation provides an optimum target for AD therapy. Some polyphenols have potent anti-amyloidogenic activities and protect against A{beta} neurotoxicity. Here, we tested the effects of ellagic acid (EA), a polyphenolic compound, on A{beta}42 aggregation and neurotoxicity in vitro. EA promoted A{beta} fibril formation and significant oligomer loss, contrary to previous results that polyphenols inhibited A{beta} aggregation. The results of transmission electron microscopy (TEM) and Western blot displayed more fibrils in A{beta}42 samples co-incubated with EA in earlier phasesmore » of aggregation. Consistent with the hypothesis that plaque formation may represent a protective mechanism in which the body sequesters toxic A{beta} aggregates to render them harmless, our MTT results showed that EA could significantly reduce A{beta}42-induced neurotoxicity toward SH-SY5Y cells. Taken together, our results suggest that EA, an active ingredient in many fruits and nuts, may have therapeutic potential in AD.« less

The Twenty-Fifth Lunar and Planetary Science Conference. Part 2: H-O

NASA Technical Reports Server (NTRS)

1994-01-01

Various papers on lunar and planetary science are presented, covering such topics as: planetary geology, lunar geology, meteorites, shock loads, cometary collisions, planetary mapping, planetary atmospheres, chondrites, chondrules, planetary surfaces, impact craters, lava flow, achondrites, geochemistry, stratigraphy, micrometeorites, tectonics, mineralogy, petrology, geomorphology, and volcanology.

Twenty-Second Lunar and Planetary Science Conference

NASA Technical Reports Server (NTRS)

1991-01-01

The papers in this collection were written for general presentation, avoiding jargon and unnecessarily complex terms. Some of the topics covered include: planetary evolution, planetary satellites, planetary composition, planetary surfaces, planetary geology, volcanology, meteorite impacts and composition, and cosmic dust. Particular emphasis is placed on Mars and the Moon.

Logistic regression of family data from retrospective study designs.

PubMed

Whittemore, Alice S; Halpern, Jerry

2003-11-01

We wish to study the effects of genetic and environmental factors on disease risk, using data from families ascertained because they contain multiple cases of the disease. To do so, we must account for the way participants were ascertained, and for within-family correlations in both disease occurrences and covariates. We model the joint probability distribution of the covariates of ascertained family members, given family disease occurrence and pedigree structure. We describe two such covariate models: the random effects model and the marginal model. Both models assume a logistic form for the distribution of one person's covariates that involves a vector beta of regression parameters. The components of beta in the two models have different interpretations, and they differ in magnitude when the covariates are correlated within families. We describe ascertainment assumptions needed to estimate consistently the parameters beta(RE) in the random effects model and the parameters beta(M) in the marginal model. Under the ascertainment assumptions for the random effects model, we show that conditional logistic regression (CLR) of matched family data gives a consistent estimate beta(RE) for beta(RE) and a consistent estimate for the covariance matrix of beta(RE). Under the ascertainment assumptions for the marginal model, we show that unconditional logistic regression (ULR) gives a consistent estimate for beta(M), and we give a consistent estimator for its covariance matrix. The random effects/CLR approach is simple to use and to interpret, but it can use data only from families containing both affected and unaffected members. The marginal/ULR approach uses data from all individuals, but its variance estimates require special computations. A C program to compute these variance estimates is available at http://www.stanford.edu/dept/HRP/epidemiology. We illustrate these pros and cons by application to data on the effects of parity on ovarian cancer risk in mother/daughter pairs, and use simulations to study the performance of the estimates. Copyright 2003 Wiley-Liss, Inc.

Concurrent ganirelix and follitropin beta therapy is an effective and safe regimen for ovulation induction in women with polycystic ovary syndrome.

PubMed

Elkind-Hirsch, Karen E; Webster, Bobby W; Brown, Crystal P; Vernon, Michael W

2003-03-01

To evaluate controlled ovarian stimulation cycles using the GnRH antagonist ganirelix in combination with the recombinant FSH, follitropin-beta, in women with polycystic ovary syndrome (PCOS). Prospective, nonrandomized clinical study. Hospital-based infertility practice. Twenty women with PCOS planning to undergo ovarian stimulation. Fasting glucose and insulin levels were used to calculate insulin resistance ratios (FG/I). After pretreatment with oral contraceptives, serum LH levels were determined, and 250 microg ganirelix was administered on cycle day 2. Upon suppression of LH, concurrent ganirelix and follitropin-beta therapy (morning ganirelix and evening follitropin-beta) was started and continued until the day of hCG. Days of stimulation, dose of follitropin-beta, pregnancy, and ongoing pregnancy were compared based on FG/I ratios. One dose of ganirelix effectively suppressed LH levels in all patients. All patients ovulated as documented by a rise in progesterone. Significant differences were observed between the insulin-resistant and non-insulin-resistant groups for both days of stimulation and dose of follitropin-beta. The overall clinical pregnancy rate was 44.4%, with an ongoing pregnancy rate of 27.8%. In this preliminary study, we demonstrate the effectiveness of a concurrent ganirelix and follitropin-beta therapy for ovarian stimulation in women with PCOS.

beta. -adrenergic relaxation of smooth muscle: differences between cells and tissues

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scheid, C.R.

1987-09-01

The present studies were carried out in an attempt to resolve the controversy about the Na/sup +/ dependence of ..beta..-adrenergic relaxation in smooth muscle. Previous studies on isolated smooth muscle cells from the toad stomach had suggested that at least some of the actions of ..beta..-adrenergic agents, including a stimulatory effect on /sup 45/Ca efflux, were dependent on the presence of a normal transmembrane Na/sup +/ gradient. Studies by other investigators using tissues derived from mammalian sources had suggested that the relaxing effect of ..beta..-adrenergic agents was Na/sup +/ independent. Uncertainty remained as to whether these discrepancies reflected differences betweenmore » cells and tissues or differences between species. Thus, in the present studies, the authors utilized both tissues and cells from the same source, the stomach muscle of the toad Bufo marinus, and assessed the Na/sup +/ dependence of ..beta..-adrenergic relaxation. They found that elimination of a normal Na/sup +/ gradient abolished ..beta..-adrenergic relaxation of isolated cells. In tissues, however, similar manipulations had no effect on relaxation. The reasons for this discrepancy are unclear but do not appear to be attributable to changes in smooth muscle function following enzymatic dispersion. Thus the controversy concerning the mechanisms of ..beta..-adrenergic relaxation may reflect inherent differences between tissues and cells.« less

Effects of the beta-blocker propranolol on cued and contextual fear conditioning in humans.

PubMed

Grillon, Christian; Cordova, Jeremy; Morgan, Charles Andrew; Charney, Dennis S; Davis, Michael

2004-09-01

Beta-adrenergic receptors are involved in the consolidation of emotional memories. Yet, a number of studies using Pavlovian cued fear conditioning have been unable to demonstrate an effect of beta-adrenergic blockade on acquisition or retention of fear conditioning. Evidence for the involvement of beta-adrenergic receptors in emotional memories comes mostly from studies using fear inhibitory avoidance in rodents. It is possible that fear inhibitory avoidance is more akin to contextual conditioning than to cued fear conditioning, suggesting that context conditioning may be disrupted by beta-adrenergic blockade. This study investigated the effects of the beta-adrenergic blocker propranolol on cued and contextual fear conditioning in humans. Subjects were given either placebo (n=15) or 40 mg propranolol (n=15) prior to differential cued conditioning. A week later, they were tested for retention of context and cued fear conditioning using physiological (startle reflex and electrodermal activity) and subjective measures of emotional arousal. The results were consistent with the hypothesis. The skin conductance level (SCL) and the subjective measure of arousal suggested reduced emotional arousal upon returning to the conditioning context in the propranolol group, compared to the placebo group. The acquisition and retention of cued fear conditioning were not affected by propranolol. These results suggest that beta-adrenergic receptors are involved in contextual fear conditioning.

Propranolol blocks the stimulatory effects of naloxone on ventilation and oxygen consumption in hamsters.

PubMed

Schlenker, E H; Eikanger, J

1997-06-01

The purposes of these studies were: 1) to determine the effects of various doses of propranolol, a nonspecific beta-adrenergic antagonist, on ventilation, oxygen consumption, and body temperature in hamsters, and 2) to test the hypothesis that in hamsters the stimulatory effects of naloxone, an opioid receptor antagonist, on ventilation and oxygen consumption occur, at least in part, through the release of catecholamines that act via beta-adrenergic receptors. Propranolol, a non-specific beta adrenergic receptor antagonist, at a 20 mg/kg depressed body temperature, oxygen consumption, tidal volume, and ventilation relative to saline. The lower dose of 10 mg/kg had only transitory effects on tidal volume at 60 min and ventilation at 30 min post-injection-Naloxone (1 mg/kg) relative to saline stimulated ventilation and oxygen consumption. These effects were blocked by propranolol pretreatment. The results of these experiments demonstrate that in the hamster, 1) body temperature, oxygen consumption, and ventilation appear to be modulated by beta-adrenergic receptors, and 2) the stimulatory effects of naloxone on oxygen consumption and ventilation may occur through the interaction of endogenous opioids and beta-adrenergic receptor systems.

Neurotoxic effects of ecstasy on the thalamus.

PubMed

de Win, Maartje M L; Jager, Gerry; Booij, Jan; Reneman, Liesbeth; Schilt, Thelma; Lavini, Cristina; Olabarriaga, Sílvia D; Ramsey, Nick F; Heeten, Gerard J den; van den Brink, Wim

2008-10-01

Neurotoxic effects of ecstasy have been reported, although it remains unclear whether effects can be attributed to ecstasy, other recreational drugs or a combination of these. To assess specific/independent neurotoxic effects of heavy ecstasy use and contributions of amphetamine, cocaine and cannabis as part of The Netherlands XTC Toxicity (NeXT) study. Effects of ecstasy and other substances were assessed with (1)H-magnetic resonance spectroscopy, diffusion tensor imaging, perfusion weighted imaging and [(123)I]2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane ([(123)I]beta-CIT) single photon emission computed tomography (serotonin transporters) in a sample (n=71) with broad variation in drug use, using multiple regression analyses. Ecstasy showed specific effects in the thalamus with decreased [(123)I]beta-CIT binding, suggesting serotonergic axonal damage; decreased fractional anisotropy, suggesting axonal loss; and increased cerebral blood volume probably caused by serotonin depletion. Ecstasy had no effect on brain metabolites and apparent diffusion coefficients. Converging evidence was found for a specific toxic effect of ecstasy on serotonergic axons in the thalamus.

Planetary Atmosphere and Surfaces Chamber (PASC): A Platform to Address Various Challenges in Astrobiology

NASA Astrophysics Data System (ADS)

Mateo-Marti, Eva

2014-08-01

The study of planetary environments of astrobiological interest has become a major challenge. Because of the obvious technical and economical limitations on in situ planetary exploration, laboratory simulations are one of the most feasible research options to make advances both in planetary science and in developing a consistent description of the origin of life. With this objective in mind, we applied vacuum technology to the design of versatile vacuum chambers devoted to the simulation of planetary atmospheres' conditions. These vacuum chambers are able to simulate atmospheres and surface temperatures representative of the majority of planetary objects, and they are especially appropriate for studying the physical, chemical and biological changes induced in a particular sample by in situ irradiation or physical parameters in a controlled environment. Vacuum chambers are a promising potential tool in several scientific and technological fields, such as engineering, chemistry, geology and biology. They also offer the possibility of discriminating between the effects of individual physical parameters and selected combinations thereof. The implementation of our vacuum chambers in combination with analytical techniques was specifically developed to make feasible the in situ physico-chemical characterization of samples. Many wide-ranging applications in astrobiology are detailed herein to provide an understanding of the potential and flexibility of these experimental systems. Instruments and engineering technology for space applications could take advantage of our environment-simulation chambers for sensor calibration. Our systems also provide the opportunity to gain a greater understanding of the chemical reactivity of molecules on surfaces under different environments, thereby leading to a greater understanding of interface processes in prebiotic chemical reactions and facilitating studies of UV photostability and photochemistry on surfaces. Furthermore, the stability and presence of certain minerals on planetary surfaces and the potential habitability of microorganisms under various planetary environmental conditions can be studied using our apparatus. Therefore, these simulation chambers can address multiple different challenging and multidisciplinary astrobiological studies.

GLP-1 mediates antiapoptotic effect by phosphorylating Bad through a beta-arrestin 1-mediated ERK1/2 activation in pancreatic beta-cells.

PubMed

Quoyer, Julie; Longuet, Christine; Broca, Christophe; Linck, Nathalie; Costes, Safia; Varin, Elodie; Bockaert, Joël; Bertrand, Gyslaine; Dalle, Stéphane

2010-01-15

Strategies based on activating GLP-1 receptor (GLP-1R) are intensively developed for the treatment of type 2 diabetes. The exhaustive knowledge of the signaling pathways linked to activated GLP-1R within the beta-cells is of major importance. In beta-cells, GLP-1 activates the ERK1/2 cascade by diverse pathways dependent on either Galpha(s)/cAMP/cAMP-dependent protein kinase (PKA) or beta-arrestin 1, a scaffold protein. Using pharmacological inhibitors, beta-arrestin 1 small interfering RNA, and islets isolated from beta-arrestin 1 knock-out mice, we demonstrate that GLP-1 stimulates ERK1/2 by two temporally distinct pathways. The PKA-dependent pathway mediates rapid and transient ERK1/2 phosphorylation that leads to nuclear translocation of the activated kinases. In contrast, the beta-arrestin 1-dependent pathway produces a late ERK1/2 activity that is restricted to the beta-cell cytoplasm. We further observe that GLP-1 phosphorylates the cytoplasmic proapoptotic protein Bad at Ser-112 but not at Ser-155. We find that the beta-arrestin 1-dependent ERK1/2 activation engaged by GLP-1 mediates the Ser-112 phosphorylation of Bad, through p90RSK activation, allowing the association of Bad with the scaffold protein 14-3-3, leading to its inactivation. beta-Arrestin 1 is further found to mediate the antiapoptotic effect of GLP-1 in beta-cells through the ERK1/2-p90RSK-phosphorylation of Bad. This new regulatory mechanism engaged by activated GLP-1R involving a beta-arrestin 1-dependent spatiotemporal regulation of the ERK1/2-p90RSK activity is now suspected to participate in the protection of beta-cells against apoptosis. Such signaling mechanism may serve as a prototype to generate new therapeutic GLP-1R ligands.

Conversion of human choriogonadotropin into a follitropin by protein engineering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campbell, R.K.; Dean-Emig, D.M.; Moyle, W.R.

1991-02-01

Human reproduction is dependent upon the action of follicle-stimulating hormone (hFSH), luteinizing hormone (hLH), and chorionic gonadotropin (hCG). While the {alpha} subunits of these heterodimeric proteins can be interchanged without effect on receptor-binding specificity, their {beta} subunits differ and direct hormone binding to either LH/CG or FSH receptors. Previous studies employing chemical modifications of the hormones, monoclonal antibodies, or synthetic peptides have implicated hCG {beta}-subunit residues between Cys-38 and Cys-57 and corresponding regions of hLH{beta} and hFSH{beta} in receptor recognition and activation. Since the {beta} subunits of hCG or hLH and hFSH exhibit very little sequence similarity in this region,more » the authors postulated that these residues might contribute to hormone specificity. To test this hypothesis the authors constructed chimeric hCG/hFSH {beta} subunits, coexpressed them with the human {alpha} subunit, and examined their ability to interact with LH and FSH receptors and hormone-specific monoclonal antibodies. Surprisingly, substitution of hFSH{beta} residues 33-52 for hCG{beta} residues 39-58 had no effect on receptor binding or stimulation. However, substitution of hFSH{beta} residues 88-108 in place of the carboxyl terminus of hCG{beta} (residues 94-145) resulted in a hormone analog identical to hFSH in its ability to bind and stimulate FSH receptors. The altered binding specificity displayed by this analog is not attributable solely to the replacement of hCG{beta} residues 108-145 or substitution of residues in the determinant loop located between hCD{beta} residues 93 and 100.« less

Downregulation of miR-133 and miR-590 contributes to nicotine-induced atrial remodelling in canines.

PubMed

Shan, Hongli; Zhang, Yong; Lu, Yanjie; Zhang, Ying; Pan, Zhenwei; Cai, Benzhi; Wang, Ning; Li, Xuelian; Feng, Tieming; Hong, Yuan; Yang, Baofeng

2009-08-01

The present study was designed to decipher molecular mechanisms underlying nicotine's promoting atrial fibrillation (AF) by inducing atrial structural remodelling. The canine model of AF was successfully established by nicotine administration and rapid pacing. The atrial fibroblasts isolated from healthy dogs were treated with nicotine. The role of microRNAs (miRNAs) on the expression and regulation of transforming growth factor-beta1 (TGF-beta1), TGF-beta receptor type II (TGF-betaRII), and collagen production was evaluated in vivo and in vitro. Administration of nicotine for 30 days increased AF vulnerability by approximately eight- to 15-fold in dogs. Nicotine stimulated remarkable collagen production and atrial fibrosis both in vitro in cultured canine atrial fibroblasts and in vivo in atrial tissues. Nicotine produced significant upregulation of expression of TGF-beta1 and TGF-betaRII at the protein level, and a 60-70% decrease in the levels of miRNAs miR-133 and miR-590. This downregulation of miR-133 and miR-590 partly accounts for the upregulation of TGF-beta1 and TGF-betaRII, because our data established TGF-beta1 and TGF-betaRII as targets for miR-133 and miR-590 repression. Transfection of miR-133 or miR-590 into cultured atrial fibroblasts decreased TGF-beta1 and TGF-betaRII levels and collagen content. These effects were abolished by the antisense oligonucleotides against miR-133 or miR-590. The effects of nicotine were prevented by an alpha7 nicotinic acetylcholine receptor antagonist. We conclude that the profibrotic response to nicotine in canine atrium is critically dependent upon downregulation of miR-133 and miR-590.

Beta-lactamase induction and cell wall metabolism in Gram-negative bacteria

PubMed Central

Zeng, Ximin; Lin, Jun

2013-01-01

Production of beta-lactamases, the enzymes that degrade beta-lactam antibiotics, is the most widespread and threatening mechanism of antibiotic resistance. In the past, extensive research has focused on the structure, function, and ecology of beta-lactamases while limited efforts were placed on the regulatory mechanisms of beta-lactamases. Recently, increasing evidence demonstrate a direct link between beta-lactamase induction and cell wall metabolism in Gram-negative bacteria. Specifically, expression of beta-lactamase could be induced by the liberated murein fragments, such as muropeptides. This article summarizes current knowledge on cell wall metabolism, beta-lactam antibiotics, and beta-lactamases. In particular, we comprehensively reviewed recent studies on the beta-lactamase induction by muropeptides via two major molecular mechanisms (the AmpG–AmpR–AmpC pathway and BlrAB-like two-component regulatory system) in Gram-negative bacteria. The signaling pathways for beta-lactamase induction offer a broad array of promising targets for the discovery of new antibacterial drugs used for combination therapies. Therefore, to develop effective mitigation strategies against the widespread beta-lactam resistance, examination of the molecular basis of beta-lactamase induction by cell wall fragment is highly warranted. PMID:23734147

DOE Office of Scientific and Technical Information (OSTI.GOV)

Popp, R.A.; Popp, D.M.; Johnson, F.M.

Mice homozygous for a spontaneous mutation, in which the ..beta..-major globin gene is deleted, have clinical symptoms of ..beta..-thalassemia. These mice have a hypocellular, hypochromic, microcytic anemia that becomes more severe with increasing age. The defective red cell morphology, decreased osmotic fragility of erythrocytes and shortened red cell life span found in ..beta..-thalassemic mice are similar to those observed in human ..beta..-thalassemia. Synthesis of ..beta..-globin is depressed but not as much as might be expected because the expression of the..beta..-minor globin gene is enhanced to encode two to three times more globin than in normal mice. Splenomegaly, an enlarged poolmore » of stem cells for erythropoiesis, and iron overloading occur in older mice. The fact that these mice remain moderately healthy makes them a very suitable animal model in which to develop and test alternative techniques of gene therapy that could be successfully applied to the treatment of human thalassemia. Homozygous ..beta..-thalassemic mice have large deposits of iron in their tissues, which might make these mice also useful for in vivo tests of the effectiveness and possible long-term side effects for newly developed iron chelators.« less

Homogeneous spectroscopic parameters for bright planet host stars from the northern hemisphere . The impact on stellar and planetary mass

NASA Astrophysics Data System (ADS)

Sousa, S. G.; Santos, N. C.; Mortier, A.; Tsantaki, M.; Adibekyan, V.; Delgado Mena, E.; Israelian, G.; Rojas-Ayala, B.; Neves, V.

2015-04-01

Aims: In this work we derive new precise and homogeneous parameters for 37 stars with planets. For this purpose, we analyze high resolution spectra obtained by the NARVAL spectrograph for a sample composed of bright planet host stars in the northern hemisphere. The new parameters are included in the SWEET-Cat online catalogue. Methods: To ensure that the catalogue is homogeneous, we use our standard spectroscopic analysis procedure, ARES+MOOG, to derive effective temperatures, surface gravities, and metallicities. These spectroscopic stellar parameters are then used as input to compute the stellar mass and radius, which are fundamental for the derivation of the planetary mass and radius. Results: We show that the spectroscopic parameters, masses, and radii are generally in good agreement with the values available in online databases of exoplanets. There are some exceptions, especially for the evolved stars. These are analyzed in detail focusing on the effect of the stellar mass on the derived planetary mass. Conclusions: We conclude that the stellar mass estimations for giant stars should be managed with extreme caution when using them to compute the planetary masses. We report examples within this sample where the differences in planetary mass can be as high as 100% in the most extreme cases. Based on observations obtained at the Telescope Bernard Lyot (USR5026) operated by the Observatoire Midi-Pyrénées and the Institut National des Science de l'Univers of the Centre National de la Recherche Scientifique of France (Run ID L131N11 - OPTICON_2013A_027).

Beta-lactam antibiotics modulate T-cell functions and gene expression via covalent binding to cellular albumin.

PubMed

Mor, Felix; Cohen, Irun R

2013-02-19

Recent work has suggested that beta-lactam antibiotics might directly affect eukaryotic cellular functions. Here, we studied the effects of commonly used beta-lactam antibiotics on rodent and human T cells in vitro and in vivo on T-cell-mediated experimental autoimmune diseases. We now report that experimental autoimmune encephalomyelitis and adjuvant arthritis were significantly more severe in rats treated with cefuroxime and other beta-lactams. T cells appeared to mediate the effect: an anti-myelin basic protein T-cell line treated with cefuroxime or penicillin was more encephalitogenic in adoptive transfer experiments. The beta-lactam ampicillin, in contrast to cefuroxime and penicillin, did not enhance encephalomyelitis, but did inhibit the autoimmune diabetes developing spontaneously in nonobese diabetic mice. Gene expression analysis of human peripheral blood T cells showed that numerous genes associated with T helper 2 (Th2) and T regulatory (Treg) differentiation were down-regulated in T cells stimulated in the presence of cefuroxime; these genes were up-regulated in the presence of ampicillin. The T-cell protein that covalently bound beta-lactam antibiotics was found to be albumin. Human and rodent T cells expressed albumin mRNA and protein, and penicillin-modified albumin was taken up by rat T cells, leading to enhanced encephalitogenicity. Thus, beta-lactam antibiotics in wide clinical use have marked effects on T-cell behavior; beta-lactam antibiotics can function as immunomodulators, apparently through covalent binding to albumin.

Effect of HMB/Arg/Gln on the prevention of radiation dermatitis in head and neck cancer patients treated with concurrent chemoradiotherapy.

PubMed

Imai, Takayuki; Matsuura, Kazuto; Asada, Yukinori; Sagai, Shun; Katagiri, Katsunori; Ishida, Eiichi; Saito, Daisuke; Sadayasu, Rei; Wada, Hitoshi; Saijo, Shigeru

2014-05-01

This prospective randomized Phase II study was designed to evaluate the preventive effect of an oral nutrition supplement composed of beta-hydroxy-beta-methylbutyrate, arginine and glutamine (beta-hydroxy-beta-methylbutyrate/arginine/glutamine) on radiation dermatitis in head and neck cancer patients. Forty patients with histologically proven head and neck cancer, treated with concurrent chemoradiotherapy involving cisplatin were recruited. They were randomly assigned to the beta-hydroxy-beta-methylbutyrate/arginine/glutamine supplement treatment group (Group A) or the control group that received no supplement (Group B). The primary endpoint of this study was the percentage of patients developing ≥Grade 3 dermatitis. The secondary endpoints were the percentage of patients developing ≥Grade 2 dermatitis, and the duration of each grade of dermatitis relative to the observation period. The incidence of ≥Grade 3 dermatitis did not differ between the two groups. However, as secondary endpoints of this study, the incidence of ≥Grade 2 dermatitis was lower in Group A than B (62.6 vs. 94.4%; P < 0.05), and the duration of ≥Grade 1 dermatitis was shorter in Group A than B (44.8 vs. 56.7%; P < 0.01), as was the duration of ≥Grade 2 dermatitis (16.5 vs. 26.5%; P < 0.05). Our study indicated that beta-hydroxy-beta-methylbutyrate/arginine/glutamine supplementation was potentially effective in the prevention of radiation dermatitis in head and neck cancer patients.

Role of glycogen synthase kinase 3 beta (GSK3beta) in mediating the cytotoxic effects of the histone deacetylase inhibitor trichostatin A (TSA) in MCF-7 breast cancer cells.

PubMed

Alao, John P; Stavropoulou, Alexandra V; Lam, Eric W-F; Coombes, R Charles

2006-10-03

Histone deacetylase inhibitors (HDACIs) have been shown to induce apoptotic and autophagic cell death in vitro and in vivo. The molecular mechanisms that underlie these cytotoxic effects are not yet clearly understood. Recently, HDACIs were shown to induce Akt dephosphorylation by disrupting HDAC-protein phosphatase 1 (PP1) complexes. This disruption results in the increased association of PP1 with Akt, resulting in the dephosphorylation and consequent inactivation of the kinase. Akt enhances cellular survival through the phosphorylation-dependent inhibition of several pro-apoptotic proteins. Akt is an important negative regulator of GSK3beta, a kinase that has been shown to regulate apoptosis in response to various stimuli. In the present study, we investigated the role of GSK3beta in mediating the cytotoxic effects in MCF-7 breast cancer cells treated with trichostatin A (TSA), a prototype HDACI. We show that TSA induces Akt dephosphorylation in a PP1-dependent manner, resulting in activation of GSK3beta in MCF-7 cells. Similarly, knockdown of HDAC1 and-2 by small interfering RNA (siRNA) resulted in the dephosphorylation of Akt and GSK3beta. Selective inhibition of GSK3beta attenuated TSA induced cytotoxicity and resulted in enhanced proliferation following drug removal. Our findings identify GSK3beta as an important mediator of TSA-induced cytotoxicity in MCF-7 breast cancer cells.

Protoplanetary disk formation and evolution models: DM Tau and GM Aur

NASA Astrophysics Data System (ADS)

Hueso, R.; Guillot, T.

2002-09-01

We study the formation and evolution of protoplanetary disks using an axisymmetric turbulent disk model. We compare model results with observational parameters derived for the DM Tau and GM Aur systems. These are relatively old T Tauri stars with large and massive protoplanetary disks. Early disk formation is studied in the standard scenario of slowly rotating isothermal collapsing spheres and is strongly dependent on the initial angular momentum and the collapse accretion rate. The viscous evolution of the disk is integrated in time using the classical Alpha prescription of turbulence. We follow the temporal evolution of the disks until their characteristics fit the observed characteristics of DM Tau and GM Aur. We therefore obtain the set of model parameters that are able to explain the present state of these disks. We also study the disk evolution under the Beta parameterization of turbulence, recently proposed for sheared flows on protoplanetary disks. Both parameterizations allow explaining the present state of both DM Tau and GM Aur. We infer a value of Alpha between 5x10-3 to 0.02 for DM Tau and one order of magnitude smaller for GM Aur. Values of the Beta parameter are in accordance with theoretical predictions of Beta around 2x10-5 but with a larger dispersion on other model parameters, which make us favor the Alpha parameterization of turbulence. Implications for planetary system development in these systems are presented. In particular, GM Aur is a massive and slowly evolving disk where conditions are very favorable for planetesimal growth. The large value of present disk mass and the relatively small observed accretion rate of this system may also be indicative of the presence of an inner gas giant planet. Acknowledgements: This work has been supported by Programme Nationale de Planetologie. R. Hueso acknowledges a post-doctoral fellowship from Gobierno Vasco.

High fat programming of beta cell compensation, exhaustion, death and dysfunction.

PubMed

Cerf, Marlon E

2015-03-01

Programming refers to events during critical developmental windows that shape progeny health outcomes. Fetal programming refers to the effects of intrauterine (in utero) events. Lactational programming refers to the effects of events during suckling (weaning). Developmental programming refers to the effects of events during both fetal and lactational life. Postnatal programming refers to the effects of events either from birth (lactational life) to adolescence or from weaning (end of lactation) to adolescence. Islets are most plastic during the early life course; hence programming during fetal and lactational life is most potent. High fat (HF) programming is the maintenance on a HF diet (HFD) during critical developmental life stages that alters progeny metabolism and physiology. HF programming induces variable diabetogenic phenotypes dependent on the timing and duration of the dietary insult. Maternal obesity reinforces HF programming effects in progeny. HF programming, through acute hyperglycemia, initiates beta cell compensation. However, HF programming eventually leads to chronic hyperglycemia that triggers beta cell exhaustion, death and dysfunction. In HF programming, beta cell dysfunction often co-presents with insulin resistance. Balanced, healthy nutrition during developmental windows is critical for preserving beta cell structure and function. Thus early positive nutritional interventions that coincide with the development of beta cells may reduce the overwhelming burden of diabetes and metabolic disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Monitoring total endotoxin and (1 --> 3)-beta-D-glucan at the air exhaust of concentrated animal feeding operations.

PubMed

Yang, Xufei; Wang, Xinlei; Zhang, Yuanhui; Lee, Jongmin; Su, Jingwei; Gates, Richard S

2013-10-01

Mitigation of bioaerosol emissions from concentrated animal feeding operations (CAFOs) demands knowledge of bioaerosol concentrations feeding into an end-of-pipe air treatment process. The aim of this preliminary study was to measure total endotoxin and (1 --> 3)-beta-glucan concentrations at the air exhaust of 18 commercial CAFOs and to examine their variability with animal operation type (swine farrowing, swine gestation, swine weaning, swine finishing, manure belt laying hen, and tom turkey) and season (cold, mild, and hot). The measured airborne concentrations of total endotoxin ranged from 98 to 23,157 endotoxin units (EU)/m3, and the airborne concentrations of total (1 --> 3)-beta-D-glucan ranged from 2.4 to 537.9 ng/m3. Animal operation type in this study had a significant effect on airborne concentrations of total endotoxin and (1 --> 3)-beta-D-glucan but no significant effect on their concentrations in total suspended particulate (TSP). Both endotoxin and (1 --> 3)-beta-D-glucan attained their highest airborne concentrations in visited tom turkey buildings. Comparatively, season had no significant effect on airborne concentrations of total endotoxin or (1 --> 3)-beta-D-glucan. Endotoxin and (1 --> 3)-beta-glucan concentrations in TSP dust appeared to increase as the weather became warmer, and this seasonal effect was significant in swine buildings. Elevated indoor temperatures in the hot season were considered to facilitate the growth and propagation of bacteria and fungi, thus leading to higher biocomponent concentrations in TSP.

Collisional stripping of planetary crusts

NASA Astrophysics Data System (ADS)

Carter, Philip J.; Leinhardt, Zoë M.; Elliott, Tim; Stewart, Sarah T.; Walter, Michael J.

2018-02-01

Geochemical studies of planetary accretion and evolution have invoked various degrees of collisional erosion to explain differences in bulk composition between planets and chondrites. Here we undertake a full, dynamical evaluation of 'crustal stripping' during accretion and its key geochemical consequences. Crusts are expected to contain a significant fraction of planetary budgets of incompatible elements, which include the major heat producing nuclides. We present smoothed particle hydrodynamics simulations of collisions between differentiated rocky planetesimals and planetary embryos. We find that the crust is preferentially lost relative to the mantle during impacts, and we have developed a scaling law based on these simulations that approximates the mass of crust that remains in the largest remnant. Using this scaling law and a recent set of N-body simulations of terrestrial planet formation, we have estimated the maximum effect of crustal stripping on incompatible element abundances during the accretion of planetary embryos. We find that on average approximately one third of the initial crust is stripped from embryos as they accrete, which leads to a reduction of ∼20% in the budgets of the heat producing elements if the stripped crust does not reaccrete. Erosion of crusts can lead to non-chondritic ratios of incompatible elements, but the magnitude of this effect depends sensitively on the details of the crust-forming melting process on the planetesimals. The Lu/Hf system is fractionated for a wide range of crustal formation scenarios. Using eucrites (the products of planetesimal silicate melting, thought to represent the crust of Vesta) as a guide to the Lu/Hf of planetesimal crust partially lost during accretion, we predict the Earth could evolve to a superchondritic 176Hf/177Hf (3-5 parts per ten thousand) at present day. Such values are in keeping with compositional estimates of the bulk Earth. Stripping of planetary crusts during accretion can lead to detectable changes in bulk composition of lithophile elements, but the fractionation is relatively subtle, and sensitive to the efficiency of reaccretion.

Double beta decays of {sup 106}Cd

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suhonen, Jouni

2011-12-16

The two-neutrino (2{nu}2{beta}) and neutrinoless (0{nu}2{beta}) double beta decays of {sup 106}Cd are studied for the transitions to the ground state 0{sub gs}{sup +} and 0{sup +} and 2{sup +} excited states in {sup 106}Pd by using realistic many-body wave functions calculated in the framework of the quasiparticle random-phase approximation. Effective, G-matrix-derived nuclear forces are used in realistic single-particle model spaces. All the possible channels, {beta}{sup +}{beta}{sup +}, {beta}{sup +}EC, and ECEC, are discussed for both the 2{nu}2{beta} and 0{nu}2{beta} decays. The associated half-lives are computed and particular attention is devoted to the study of the detectability of the resonantmore » neutrinoless double electron capture (R0{nu}ECEC) process in {sup 106}Cd. The calculations of the present article constitute the thus far most complete and up-to-date investigation of the double-beta-decay properties of {sup 106}Cd.« less

Ultrasound-mediated interferon {beta} gene transfection inhibits growth of malignant melanoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamaguchi, Kazuki; Department of Anatomy, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka City 814-0180; Feril, Loreto B., E-mail: ferilism@yahoo.com

2011-07-22

Highlights: {yields} Successful ultrasound-mediated transfection of melanoma (C32) cells with IFN-{beta} genes both in vitro and in vivo. {yields} Ultrasound-mediated IFN-{beta} transfection inhibited proliferation of melanoma cells in vitro. {yields} Ultrasound-mediated IFN-{beta} transfection inhibited melanoma tumor growth in vivo. -- Abstract: We investigated the effects of ultrasound-mediated transfection (sonotransfection) of interferon {beta} (IFN-{beta}) gene on melanoma (C32) both in vitro and in vivo. C32 cells were sonotransfected with IFN-{beta} in vitro. Subcutaneous C32 tumors in mice were sonicated weekly immediately after intra-tumor injection with IFN-{beta} genes mixed with microbubbles. Successful sonotransfection with IFN-{beta} gene in vitro was confirmed by ELISA,more » which resulted in C32 growth inhibition. In vivo, the growth ratio of tumors transfected with IFN-{beta} gene was significantly lower than the other experimental groups. These results may lead to a new method of treatment against melanoma and other hard-to-treat cancers.« less

Effect of polymorphic variants of GH, Pit-1, and beta-LG genes on milk production of Holstein cows.

PubMed

Heidari, M; Azari, M A; Hasani, S; Khanahmadi, A; Zerehdaran, S

2012-04-01

Effect of polymorphic variants of growth hormone (GH), beta-lactoglobulin (beta-LG), and Pit-1 genes on milk yield was analyzed in a Holstein herd. Genotypes of the cows for these genes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Allele frequencies were 0.884 and 0.116 for L and V variants of GH, 0.170 and 0.830 for A and B variants of Pit-1, and 0.529 and 0.471 for A and B variants of beta-LG, respectively. GLM procedure of SAS software was used to test the effects of these genes on milk yield. Results indicated significant effects of these genes on milk yield (P < 0.05). Cows with LL genotype of GH produced more milk than cows with LVgenotype (P < 0.05). Also, for Pit-1 gene, animals with AB genotype produced more milk than BB genotype (P < 0.05). In the case of beta-LG gene, milk yield of animals with AA genotype was more than BB genotype (P < 0.01). Therefore, it might be concluded that homozygote genotypes of GH (LL) and beta-LG (AA) were superior compared to heterozygote genotypes, whereas, the heterozygote genotype of Pit-1 gene (AB) was desirable.

Physico-chemical and Biological Evaluation of Flavonols: Fisetin, Quercetin and Kaempferol Alone and Incorporated in beta Cyclodextrins.

PubMed

Corina, Danciu; Bojin, Florina; Ambrus, Rita; Muntean, Delia; Soica, Codruta; Paunescu, Virgil; Cristea, Mirabela; Pinzaru, Iulia; Dehelean, Cristina

2017-01-01

Fisetin,quercetin and kaempferol are among the important representatives of flavonols, biological active phytocomounds, with low water solubility. To evaluate the antimicrobial effect, respectively the antiproliferative and pro apoptotic activity on the B164A5 murine melanoma cell line of pure flavonols and their beta cyclodextrins complexes. Incorporation of fisetin, quercetin and kaempferol in beta cyclodextrins was proved by scanning electron microscopy (SEM), differencial scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). Pure compounds and their complexes were tested for antiproliferative (MTT) and pro-apoptotic activity (Annexin V-PI) on the B164A5 murine melanoma cell line and for the antimicrobial properties (Disk Diffusion Method) on the selected strains. The phytocompounds presented in a different manner in vitro chemopreventive activity against B164A5 murine melanoma cell line and weak antimicrobial effect. The three flavonols: fisetin, quercetin and kaempferol were successfully incorporated in beta-cyclodextrin (BCD) and hydroxylpropyl-beta-cyclodextrin (HPBCD). Incorporation in beta cyclodextrins had a mix effect on the biological activity conducing to decrease, increase or consistent effect compared to pure phytocompound, depending on the screened process and on the chosen combination. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Hydrogen sulfide protects cardiomyocytes from hypoxia/reoxygenation-induced apoptosis by preventing GSK-3beta-dependent opening of mPTP.

PubMed

Yao, Ling-Ling; Huang, Xiao-Wei; Wang, Yong-Gang; Cao, Yin-Xiang; Zhang, Cai-Cai; Zhu, Yi-Chun

2010-05-01

Hydrogen sulfide (H(2)S) is an endogenously generated gaseous transmitter, which has recently been suggested to regulate cardiovascular functions. The present study aims to clarify the mechanisms underlying the cardioprotective effects of H(2)S. Signaling elements were examined in cardiomyocytes cultured under hypoxia/reoxygenation conditions and in a rat model of ischemia-reperfusion. In cultured cardiomyocytes, sodium hydrosulfide (NaHS; 10, 30, and 50 mumol/l) showed concentration-dependent inhibitory effects on cardiomyocyte apoptosis induced by hypoxia/reoxygenation. These effects were associated with an increase in phosphorylation of glycogen synthase kinase-3beta (GSK-3beta) (Ser9) and a decrease in Bax translocation, caspase-3 activation, and mitochondrial permeability transition pore (mPTP) opening. Transfection of a phosphorylation-resistant mutant of GSK-3beta at Ser9 attenuated the effects of NaHS in reducing cardiomyocyte apoptosis, Bax translocation, caspase-3 activation, and mPTP opening. In a rat model of ischemia-reperfusion, NaHS administration reduced myocardial infarct size and increased the phosphorylation of GSK-3beta (Ser9) at a dose of 30 mumol/kg. In conclusion, the H(2)S donor prevents cardiomyocyte apoptosis by inducing phosphorylation of GSK-3beta (Ser9) and subsequent inhibition of mPTP opening.

Planetary influence in the gap of a protoplanetary disk: structure formation and an application to V1247 Ori

NASA Astrophysics Data System (ADS)

Alvarez-Meraz, R.; Nagel, E.; Rendon, F.; Barragan, O.

2017-10-01

We present a set of hydrodynamical models of a planetary system embedded in a protoplanetary disk in order to extract the number of dust structures formed in the disk, their masses and sizes, within optical depth ranges τ≤0.5, 0.5<τ<2 and τ≥2. The study of the structures shows: (1) an increase in the number of planets implies an increase in the creation rate of massive structures; (2) a lower planetary mass accretion corresponds to slower time effects for optically thin structures; (3) an increase in the number of planets allows a faster evolution of the structures in the Hill radius for the different optical depth ranges of the inner planets. An ad-hoc simulation was run using the available information of the stellar system V1247 Ori, leading to a model of a planetary system which explains the SED and is consistent with interferometric observations of structures.

From Dust to Planets: Connecting the Dots

NASA Astrophysics Data System (ADS)

Weidenschilling, Stuart

The principal objective is to construct a self-consistent model linking two key early stages of planetary origins: formation of planetesimals by collisional growth of aggregate bodies from grains in the solar nebula, and accretion of those planetesimals into planetary embryos. We will simulate these processes by using a series of numerical codes to model (i) particle settling and coagulation, using the latest and most comprehensive experimental data on collisional outcomes, (ii) detailed vertical structure of a particle layer in the nebular midplane subject to shear-generated turbulence, and possible streaming instability due to transverse particle motions, and (iii) accretion of planetary embryos from planetesimals that have grown large enough to decouple from the gas and experience Keplerian motion dominated by gravitational forces. The proposed work will clarify conditions necessary for planetesimal formation and the effects of turbulence on this process, and will bridge the gap between the dynamical regimes controlled by forces of gas drag and gravity. It will also determine how initial sizes of planetesimals affect the timescales and outcomes of planetary accretion.

Saturn's Magnetic Field from the Cassini Grand Finale orbits

NASA Astrophysics Data System (ADS)

Dougherty, M. K.; Cao, H.; Khurana, K. K.; Hunt, G. J.; Provan, G.; Kellock, S.; Burton, M. E.; Burk, T. A.

2017-12-01

The fundamental aims of the Cassini magnetometer investigation during the Cassini Grand Finale orbits were determination of Saturn's internal planetary magnetic field and the rotation rate of the deep interior. The unique geometry of the orbits provided an unprecedented opportunity to measure the intrinsic magnetic field at close distances never before encountered. The surprising close alignment of Saturn's magnetic axis with its spin axis, known about since the days of Pioneer 11, has been a focus of the team's analysis since Cassini Saturn Orbit Insertion. However, the varying northern and southern magnetospheric planetary period oscillations, which fill the magnetosphere, has been a factor in masking the field signals from the interior. Here we describe an overview of the magnetometer results from the Grand Finale orbits, including confirmation of the extreme axisymmetric nature of the planetary magnetic field, implications for knowledge of the rotation rate and the behaviour of external magnetic fields (arising from the ring current, field aligned currents both at high and low latitudes and the modulating effect of the planetary period oscillations).

Lunar Science Conference, 8th, Houston, Tex., March 14-18, 1977, Proceedings. Volume 1 - The moon and the inner solar system. Volume 2 - Petrogenetic studies of mare and highland rocks. Volume 3 - Planetary and lunar surfaces

NASA Technical Reports Server (NTRS)

Merril, R. B.

1977-01-01

Solar system processes are considered along with the origin and evolution of the moon, planetary geophysics, lunar basins and crustal layering, lunar magnetism, the lunar surface as a planetary probe, remote observations of lunar and planetary surfaces, earth-based measurements, integrated studies, physical properties of lunar materials, and asteroids, meteorites, and the early solar system. Attention is also given to studies of mare basalts, the kinetics of basalt crystallization, topical studies of mare basalts, highland rocks, experimental studies of highland rocks, geochemical studies of highland rocks, studies of materials of KREEP composition, a consortium study of lunar breccia 73215, topical studies on highland rocks, Venus, and regional studies of the moon. Studies of surface processes, are reported, taking into account cratering mechanics and fresh crater morphology, crater statistics and surface dating, effects of exposure and gardening, and the chemistry of surfaces.

Experimental study of turbulent flow heat transfer and pressure drop in plate heat exchanger with chevron plates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muley, A.; Manglik, R.M.

1999-02-01

Experimental heat transfer and isothermal pressure drop data for single-phase water flows in a plate heat exchanger (PHE) with chevron plates are presented. In a single-pass U-type counterflow PHE, three different chevron plate arrangements are considered: two symmetric plate arrangements with {beta} = 30 deg/30 deg and 60 deg/60 deg, and one mixed-plate arrangement with {beta} = 30 deg/60 deg. For water (2 < Pr < 6) flow rates in the 600 < Re < 10{sup 4} regime, data for Nu and f are presented. The results show significant effects of both the chevron angle {beta} and surface area enlargementmore » factor {phi}. As {beta} increases, and compared to a flat-plate pack, up to two to five times higher Nu are obtained; the concomitant f, however, are 13 to 44 times higher. Increasing {phi} also has a similar, though smaller effect. Based on experimental data for Re {ge} 1000 and 30 deg {le} {beta} {le} 60 deg, predictive correlations of the form Nu = C{sub 1}({beta}) D{sub 1}({phi}) Re{sup p1({beta})} Pr{sup 1/3} ({mu}/{mu}{sub w}){sup 0.14} and f = C{sub 2}({beta}) D{sub 2}({phi}) Re{sup p2({beta})} are devised. Finally, at constant pumping power, and depending upon Re, {beta}, and {phi}, the heat transfer is found to be enhanced by up to 2.8 times that in an equivalent flat-plate channel.« less

All-trans beta-carotene enhances mitogenic responses and ornithine decarboxylase activity of BALB/c 3T3 fibroblast cells induced by tumor promoter and fetal bovine serum but suppresses mutagen-dependent umu C gene expression in Salmonella typhimurium (TA 1535/pSK 1002).

PubMed

Okai, Y; Higashi-Okai, K; Yano, Y; Otani, S

1996-01-19

Although previous epidemiological studies have indicated that beta-carotene is an important agent for the chemical prevention against carcinogenesis, a recent prospective study has strikingly suggested that supplementation with beta-carotene significantly increased the incidence of some types of cancer (The alpha-Tocopherol and beta-Carotene Cancer Prevention Study Group, New Engl. J. Med., 330 (1994) 1031-1035). To analyze the discrepancy of this problem, the authors analyze the effects of beta-carotene on biochemical and biological events associated with carcinogenesis by in vitro experiments. (1) All-trans beta-carotene enhanced the proliferation and DNA synthesis of BALB/c 3T3 cells induced by a tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and fetal bovine serum, although beta-carotene itself did not show mitogenic activity. (2) All-trans beta-carotene caused a remarkable stimulation for the early induction of ornithine decarboxylase (ODC) activity after the stimulation of TPA and fetal bovine serum. (3) All-trans beta-carotene exhibited significant antimutagenic activity which suppresses umu C gene expression in Salmonella typhimurium (TA 1535/pSK 1002) induced by a typical mutagen, 2-aminoanthracene (2-AA). These experimental results suggest that all-trans beta-carotene might cause beneficial and harmful effects on different phases of carcinogenesis.

Ultraviolet observations of close-binary and pulsating nuclei of planetary nebulae; Winds and shells around low-mass supergiants; The close-binary nucleus of the planetary nebula HFG-1; A search for binary nuclei of planetary nebulae; UV monitoring of irregularly variable planetary nuclei; and The pulsating nucleus of the planetary nebula Lo 4

NASA Technical Reports Server (NTRS)

Bond, Howard E.

1992-01-01

A brief summary of the research highlights is presented. The topics covered include the following: binary nuclei of planetary nebulae; other variable planetary nuclei; low-mass supergiants; and other IUE-related research.

Beta-blockers influence the short-term and long-term prognostic information of natriuretic peptides and catecholamines in chronic heart failure independent from specific agents.

PubMed

Frankenstein, Lutz; Nelles, Manfred; Slavutsky, Maxim; Schellberg, Dieter; Doesch, Andreas; Katus, Hugo; Remppis, Andrew; Zugck, Christian

2007-10-01

In chronic heart failure (CHF), the physiologic effects of natriuretic peptides and catecholamines are interdependent. Furthermore, reports state an agent-dependent effect of individual beta-blockers on biomarkers. Data on the short-term and long-term predictive power comparing these biomarkers as well as accounting for the influence of beta-blocker treatment both on the marker or the resultant prognostic information are scarce. We included 513 consecutive patients with systolic CHF, measured atrial natriuretic peptide (ANP), N-terminal prohormone brain natriuretic peptide (NTproBNP), noradrenaline, and adrenaline, and monitored them for 90 +/- 25 months. Death or the combination of death and cardiac transplantation at 1 year, 5 years, and overall follow-up were considered end points. Compared with patients not taking beta-blockers, patients taking beta-blockers had significantly lower levels of catecholamines but not natriuretic peptides. Only for adrenaline was the amount of this effect related to the specific beta-blocker chosen. Receiver operating characteristic curves demonstrated superior prognostic accuracy for NTproBNP both at the 1- and 5-year follow-up compared with ANP, noradrenaline, and adrenaline. In multivariate analysis including established risk markers (New York Heart Association functional class, left ventricular ejection fraction, peak oxygen uptake, and 6-minute walk test), of all neurohumoral parameters, only NTproBNP remained an independent predictor for both end points. Long-term beta-blocker therapy is associated with decreased levels of plasma catecholamines but not natriuretic peptides. This effect is independent from the actual beta-blocker chosen for natriuretic peptides and noradrenaline. In multivariate analysis, both for short-term and long-term prediction of mortality or the combined end point of death and cardiac transplantation, only NTproBNP remained independent from established clinical risk markers.

Coupling between Mercury and its nightside magnetosphere: Cross-tail current sheet asymmetry and substorm current wedge formation

NASA Astrophysics Data System (ADS)

Poh, Gangkai; Slavin, James A.; Jia, Xianzhe; Raines, Jim M.; Imber, Suzanne M.; Sun, Wei-Jie; Gershman, Daniel J.; DiBraccio, Gina A.; Genestreti, Kevin J.; Smith, Andy W.

2017-08-01

We analyzed MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) magnetic field and plasma measurements taken during 319 crossings of Mercury's cross-tail current sheet. We found that the measured BZ in the current sheet is higher on the dawnside than the duskside by a factor of ≈3 and the asymmetry decreases with downtail distance. This result is consistent with expectations based upon MHD stress balance. The magnetic fields threading the more stretched current sheet in the duskside have a higher plasma beta than those on the dawnside, where they are less stretched. This asymmetric behavior is confirmed by mean current sheet thickness being greatest on the dawnside. We propose that heavy planetary ion (e.g., Na+) enhancements in the duskside current sheet provides the most likely explanation for the dawn-dusk current sheet asymmetries. We also report the direct measurement of Mercury's substorm current wedge (SCW) formation and estimate the total current due to pileup of magnetic flux to be ≈11 kA. The conductance at the foot of the field lines required to close the SCW current is found to be ≈1.2 S, which is similar to earlier results derived from modeling of Mercury's Region 1 field-aligned currents. Hence, Mercury's regolith is sufficiently conductive for the current to flow radially then across the surface of Mercury's highly conductive iron core. Mercury appears to be closely coupled to its nightside magnetosphere by mass loading of upward flowing heavy planetary ions and electrodynamically by field-aligned currents that transfer momentum and energy to the nightside auroral oval crust and interior. Heavy planetary ion enhancements in Mercury's duskside current sheet provide explanation for cross-tail asymmetries found in this study. The total current due to the pileup of magnetic flux and conductance required to close the SCW current is found to be ≈11 kA and 1.2 S. Mercury is coupled to magnetotail by mass loading of heavy ions and field-aligned currents driven by reconnection-related fast plasma flow.

Apparent relationship between solar-sector boundaries and 300-mb vorticity: Possible explanation in terms of upward propagation of planetary-scale waves

NASA Technical Reports Server (NTRS)

Deland, R. J.

1974-01-01

The selection process for sector structure boundary crossings used in vorticity correlation studies is examined and the possible influence of ascending planetary scale waves is assessed. It is proposed that some of the observed correlations between geomagnetic and meteorological variations may be due to meteorological effects on the geometric variables, rather than due to common solar origin.

Planetary Gearbox Fault Diagnosis Using a Single Piezoelectric Strain Sensor

DTIC Science & Technology

2014-12-23

However, the fault detection of planetary gearbox is very complicate since the c omplex nature of dynamic rolling structure of p lanetary gearbox...vibration transfer paths due to the unique dynamic structure of rotating planet gears. Therefore, it is difficult to diagnose PGB faults via vibration...al. 2014). To overcome the above mentioned challenges in developing effective PGB fau lt diagnosis capability , a research investigation on

Studies of planetary upper atmospheres through occultations

NASA Technical Reports Server (NTRS)

Elliot, J. L.

1982-01-01

The structure, composition, dynamics and energy balance of planetary upper atmospheres through interpretation of steller occultation data from Uranus is discussed. The wave-optical problem of modelling strong scintillation for arbitrary turbulent atmospheres is studied, as well as influence of turbulence. It was concluded that quasi-global features of atmospheric structure are accurately determined by numerical inversion. Horizontally inhomogeneous structures are filtered out and have little effect on temperature profiles.

Massive collisions in debris disks: possible application to the beta Pic disc

NASA Astrophysics Data System (ADS)

Kral, Q.; Thébault, P.; Augereau, J.-C.; Boccaletti, A.; Charnoz, S.

2014-09-01

The new LIDT-DD code has been used to study massive collisions in debris discs. This new hybrid model is a fully self-consistent code coupling dynamics and collisions to study debris discs (Kral et al. 2013). It models the full complexity of debris discs' physics such as high velocity collisions, radiation-pressure affected orbits, wide range of grains' dynamical behaviour, etc. LIDT-DD can be used on many possible applications. Our first test case concerns the violent breakup of a massive planetesimal such as the ones happening during the late stages of planetary formation or with the biggest bodies in debris belts. We investigate the duration, magnitude and spatial structure of the signature left by such a violent event, as well as its observational detectability. We find that the breakup of a Ceres-sized body creates an asymmetric dust disc that is homogenized, by the coupled action of collisions and dynamics. The luminosity excess in the breakup's aftermath should be detectable by mid-IR photometry, from a 30 pc distance. As for the asymmetric structures, we derive synthetic images for the SPHERE/VLT and MIRI/JWST instruments, showing that they should be clearly visible and resolved from a 10 pc distance. We explain the observational signature of such impacts and give scaling laws to extrapolate our results to different configurations. These first results confirm that our code can be used to study the massive collision scenario to explain some asymmetries in the Beta-Pic disc.

Microwave Processing of Planetary Surfaces for the Extraction of Volatiles

NASA Technical Reports Server (NTRS)

Ethridge, Edwin C.; Kaukler, William

2011-01-01

In-Situ Resource Utilization will be necessary for sustained exploration of space. Volatiles are present in planetary soils, but water by far has the most potential for effective utilization. The presence of water at the lunar poles, Mars, and possibly on Phobos opens the possibility of producing LOX for propellant. Water is also a useful radiation shielding material , and valuable to replenish expendables (water and oxygen) required for habitation in space. Because of the strong function of water vapor pressure with temperature, heating soil effectively liberates water vapor by sublimation. Microwave energy will penetrate soil and heat from within much more efficiently than heating from the surface with radiant heat. This is especially true under vacuum conditions since the heat transfer rate is very low. The depth of microwave penetration is a strong function of the microwave frequency and to a lesser extent on soil dielectric properties. Methods for complex electric permittivity and magnetic permeability measurement are being developed and used for measurements of lunar soil simulants. A new method for delivery of microwaves deep into a planetary surface is being prototyped with laboratory experiments and modeled with COMSOL MultiPhysics. We are planning to set up a planetary testbed in a large vacuum chamber in the coming year. Recent results are discussed.

Nonlinear dynamics of planetary gears using analytical and finite element models

NASA Astrophysics Data System (ADS)

Ambarisha, Vijaya Kumar; Parker, Robert G.

2007-05-01

Vibration-induced gear noise and dynamic loads remain key concerns in many transmission applications that use planetary gears. Tooth separations at large vibrations introduce nonlinearity in geared systems. The present work examines the complex, nonlinear dynamic behavior of spur planetary gears using two models: (i) a lumped-parameter model, and (ii) a finite element model. The two-dimensional (2D) lumped-parameter model represents the gears as lumped inertias, the gear meshes as nonlinear springs with tooth contact loss and periodically varying stiffness due to changing tooth contact conditions, and the supports as linear springs. The 2D finite element model is developed from a unique finite element-contact analysis solver specialized for gear dynamics. Mesh stiffness variation excitation, corner contact, and gear tooth contact loss are all intrinsically considered in the finite element analysis. The dynamics of planetary gears show a rich spectrum of nonlinear phenomena. Nonlinear jumps, chaotic motions, and period-doubling bifurcations occur when the mesh frequency or any of its higher harmonics are near a natural frequency of the system. Responses from the dynamic analysis using analytical and finite element models are successfully compared qualitatively and quantitatively. These comparisons validate the effectiveness of the lumped-parameter model to simulate the dynamics of planetary gears. Mesh phasing rules to suppress rotational and translational vibrations in planetary gears are valid even when nonlinearity from tooth contact loss occurs. These mesh phasing rules, however, are not valid in the chaotic and period-doubling regions.

Study of long term structural and functional changes in medically controlled glaucoma

PubMed Central

Pandey, Achyut N; Sujata, S

2014-01-01

AIM Prospectively analyze the long term structural and functional changes in patients of primary open angle glaucoma (POAG) receiving medical therapy (beta blockers and non beta blockers). In this study an attempt has been made to evaluate whether medical reduction of IOP prevents or delays the progression of glaucomatous visual field loss and/or optic nerve damage in patients with open angle glaucoma. METHODS Study conducted over a period of 27 months, at a tertiary eye care hospital including both eyes of 40 patients with POAG. Group 1 (20 patients, 40 eyes) received beta-blockers, and Group 2 (20 patients, 40 eyes) received non-beta-blockers. Each patient underwent intraocular pressure measurement, best corrected visual acuity, slit-lamp, fundus examination, gonioscopy, central corneal thickness, visual field assessment by Humphrey automated perimetry and retinal nerve fibre layer thickness by Stratus optical coherence tomography at baseline and at two subsequent visits. The average time interval between each visit was 10-11 months. The statistical analysis was done using one-way analysis of variance (ANOVA). Post-hoc test, using tukey' method were adopted. Probablity (P) value of 0.05 or less was considered to be statistically significant. RESULTS A total of 80 eyes of 40 patients of POAG were enrolled, 24 males, 16 females, age group 50-80 years. In both beta and non beta blocker group, reduction (improvement) in mean IOP from initial levels to the levels achieved at the 2nd and 3rd visits was statistically significant. One way ANOVA (df=2), fisher f value=11.64, P=0.000, one way ANOVA (df=3), fisher f value=35.61, P=0.000. Both mean deviation (MD) and pattern standard deviation (PSD) in both beta and non beta blockers at different visits were not statistically significant. Retinal nerve fibre layer thickness (RNFL) -only mean inferior retinal nerve fibre layer, the difference between the mean value in beta and non beta blocker groupwere statistically significant. [unpaired t test value (df=78) =2.27, P=0.03]. Side effects with beta blocker were conjunctival hyperemia (10%), burning (5%), and conjunctival hyperemia (5%) in non beta blockers. CONCLUSION Non-beta-blockers are as effective as beta-blockers in bringing about a significant lowering of intraocular pressure to the normal range, and in preventing progressive damage to the visual fields and retinal nerve fibre layer. The absence of systemic side effects and superior IOP lowering efficacy has made non beta-blockers attractive for first line therapy for the treatment of glaucoma worldwide. PMID:24634878

Study of long term structural and functional changes in medically controlled glaucoma.

PubMed

Pandey, Achyut N; Sujata, S

2014-01-01

Prospectively analyze the long term structural and functional changes in patients of primary open angle glaucoma (POAG) receiving medical therapy (beta blockers and non beta blockers). In this study an attempt has been made to evaluate whether medical reduction of IOP prevents or delays the progression of glaucomatous visual field loss and/or optic nerve damage in patients with open angle glaucoma. Study conducted over a period of 27 months, at a tertiary eye care hospital including both eyes of 40 patients with POAG. Group 1 (20 patients, 40 eyes) received beta-blockers, and Group 2 (20 patients, 40 eyes) received non-beta-blockers. Each patient underwent intraocular pressure measurement, best corrected visual acuity, slit-lamp, fundus examination, gonioscopy, central corneal thickness, visual field assessment by Humphrey automated perimetry and retinal nerve fibre layer thickness by Stratus optical coherence tomography at baseline and at two subsequent visits. The average time interval between each visit was 10-11 months. The statistical analysis was done using one-way analysis of variance (ANOVA). Post-hoc test, using tukey' method were adopted. Probablity (P) value of 0.05 or less was considered to be statistically significant. A total of 80 eyes of 40 patients of POAG were enrolled, 24 males, 16 females, age group 50-80 years. In both beta and non beta blocker group, reduction (improvement) in mean IOP from initial levels to the levels achieved at the 2nd and 3rd visits was statistically significant. One way ANOVA (df=2), fisher f value=11.64, P=0.000, one way ANOVA (df=3), fisher f value=35.61, P=0.000. Both mean deviation (MD) and pattern standard deviation (PSD) in both beta and non beta blockers at different visits were not statistically significant. Retinal nerve fibre layer thickness (RNFL) -only mean inferior retinal nerve fibre layer, the difference between the mean value in beta and non beta blocker groupwere statistically significant. [unpaired t test value (df=78) =2.27, P=0.03]. Side effects with beta blocker were conjunctival hyperemia (10%), burning (5%), and conjunctival hyperemia (5%) in non beta blockers. Non-beta-blockers are as effective as beta-blockers in bringing about a significant lowering of intraocular pressure to the normal range, and in preventing progressive damage to the visual fields and retinal nerve fibre layer. The absence of systemic side effects and superior IOP lowering efficacy has made non beta-blockers attractive for first line therapy for the treatment of glaucoma worldwide.

Quantifying the effects of diuretics and β-adrenoceptor blockers on glycaemic control in diabetes mellitus - a systematic review and meta-analysis.

PubMed

Hirst, Jennifer A; Farmer, Andrew J; Feakins, Benjamin G; Aronson, Jeffrey K; Stevens, Richard J

2015-05-01

Although there are reports that β-adrenoceptor antagonists (beta-blockers) and diuretics can affect glycaemic control in people with diabetes mellitus, there is no clear information on how blood glucose concentrations may change and by how much. We report results from a systematic review to quantify the effects of these antihypertensive drugs on glycaemic control in adults with established diabetes. We systematically reviewed the literature to identify randomized controlled trials in which glycaemic control was studied in adults with diabetes taking either beta-blockers or diuretics. We combined data on HbA1c and fasting blood glucose using fixed effects meta-analysis. From 3864 papers retrieved, we found 10 studies of beta-blockers and 12 studies of diuretics to include in the meta-analysis. One study included both comparisons, totalling 21 included reports. Beta-blockers increased fasting blood glucose concentrations by 0.64 mmol l(-1) (95% CI 0.24, 1.03) and diuretics by 0.77 mmol l(-1) (95% CI 0.14, 1.39) compared with placebo. Effect sizes were largest in trials of non-selective beta-blockers (1.33, 95% CI 0.72, 1.95) and thiazide diuretics (1.69, 95% CI 0.60, 2.69). Beta-blockers increased HbA1c concentrations by 0.75% (95% CI 0.30, 1.20) and diuretics by 0.24% (95% CI -0.17, 0.65) compared with placebo. There was no significant difference in the number of hypoglycaemic events between beta-blockers and placebo in three trials. Randomized trials suggest that thiazide diuretics and non-selective beta-blockers increase fasting blood glucose and HbA1c concentrations in patients with diabetes by moderate amounts. These data will inform prescribing and monitoring of beta-blockers and diuretics in patients with diabetes. © 2014 The British Pharmacological Society.

Quantifying the effects of diuretics and β-adrenoceptor blockers on glycaemic control in diabetes mellitus – a systematic review and meta-analysis

PubMed Central

Hirst, Jennifer A; Farmer, Andrew J; Feakins, Benjamin G; Aronson, Jeffrey K; Stevens, Richard J

2015-01-01

Aims Although there are reports that β-adrenoceptor antagonists (beta-blockers) and diuretics can affect glycaemic control in people with diabetes mellitus, there is no clear information on how blood glucose concentrations may change and by how much. We report results from a systematic review to quantify the effects of these antihypertensive drugs on glycaemic control in adults with established diabetes. Methods We systematically reviewed the literature to identify randomized controlled trials in which glycaemic control was studied in adults with diabetes taking either beta-blockers or diuretics. We combined data on HbA1c and fasting blood glucose using fixed effects meta-analysis. Results From 3864 papers retrieved, we found 10 studies of beta-blockers and 12 studies of diuretics to include in the meta-analysis. One study included both comparisons, totalling 21 included reports. Beta-blockers increased fasting blood glucose concentrations by 0.64 mmol l−1 (95% CI 0.24, 1.03) and diuretics by 0.77 mmol l−1 (95% CI 0.14, 1.39) compared with placebo. Effect sizes were largest in trials of non-selective beta-blockers (1.33, 95% CI 0.72, 1.95) and thiazide diuretics (1.69, 95% CI 0.60, 2.69). Beta-blockers increased HbA1c concentrations by 0.75% (95% CI 0.30, 1.20) and diuretics by 0.24% (95% CI −0.17, 0.65) compared with placebo. There was no significant difference in the number of hypoglycaemic events between beta-blockers and placebo in three trials. Conclusions Randomized trials suggest that thiazide diuretics and non-selective beta-blockers increase fasting blood glucose and HbA1c concentrations in patients with diabetes by moderate amounts. These data will inform prescribing and monitoring of beta-blockers and diuretics in patients with diabetes. PMID:25377481

ON THE EFFECT OF GIANT PLANETS ON THE SCATTERING OF PARENT BODIES OF IRON METEORITE FROM THE TERRESTRIAL PLANET REGION INTO THE ASTEROID BELT: A CONCEPT STUDY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haghighipour, Nader; Scott, Edward R. D., E-mail: nader@ifa.hawaii.edu

2012-04-20

In their model for the origin of the parent bodies of iron meteorites, Bottke et al. proposed differentiated planetesimals, formed in 1-2 AU during the first 1.5 Myr, as the parent bodies, and suggested that these objects and their fragments were scattered into the asteroid belt as a result of interactions with planetary embryos. Although viable, this model does not include the effect of a giant planet that might have existed or been growing in the outer regions. We present the results of a concept study where we have examined the effect of a planetary body in the orbit ofmore » Jupiter on the early scattering of planetesimals from the terrestrial region into the asteroid belt. We integrated the orbits of a large battery of planetesimals in a disk of planetary embryos and studied their evolutions for different values of the mass of the planet. Results indicate that when the mass of the planet is smaller than 10 M{sub Circled-Plus }, its effects on the interactions among planetesimals and planetary embryos are negligible. However, when the planet mass is between 10 and 50 M{sub Circled-Plus }, simulations point to a transitional regime with {approx}50 M{sub Circled-Plus} being the value for which the perturbing effect of the planet can no longer be ignored. Simulations also show that further increase of the mass of the planet strongly reduces the efficiency of the scattering of planetesimals from the terrestrial planet region into the asteroid belt. We present the results of our simulations and discuss their possible implications for the time of giant planet formation.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelson, D.R.; Palmer, K.J.; Johnson, A.M.

The effects of prolonged oral administration of the antidepressants paroxetine and amitriptyline on rat brain cortical {beta}{sub 1}- and {beta}{sub 2}-adrenoceptor numbers and affinities were investigated using ({sup 3}H)-CGP 12177. Although amitriptyline, 27 mg/kg, caused a significant 20% reduction in the number of {beta}{sub 1}-adrenoceptors, paroxetine, at does up to 8.9 mg/kg p.o., did not influence binding of ({sup 3}H)-CGP 12177 to cortical {beta}{sub 1}- or {beta}{sub 2}-adrenoceptors. This study with paroxetine provides further evidence that the down-regulation of central {beta}{sub 1}-adrenoceptors in rat brain after repeated administration is not a property of all antidepressant drugs.

The effect of pH and triethanolamine on sulfisoxazole complexation with hydroxypropyl-beta-cyclodextrin.

PubMed

Gladys, Granero; Claudia, Garnero; Marcela, Longhi

2003-11-01

A novel complexation of sulfisoxazole with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was studied. Two systems were used: binary complexes prepared with HP-beta-CD and multicomponent system (HP-beta-CD and the basic compound triethanolamine (TEA)). Inclusion complex formation in aqueous solutions and in solid state were investigated by the solubility method, thermal analysis (differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)), Fourier-transform infrared spectroscopy (FT-IR) and dissolution studies. The solid complexes of sulfisoxazole were prepared by freeze-drying the homogeneous concentrated aqueous solutions in molar ratios of sulfisoxazole:HP-beta-CD 1:1 and 1:2, and sulfisoxazole:TEA:HP-beta-CD 1:1:2. FT-IR and thermal analysis showed differences among sulfisoxazole:HP-beta-CD and sulfisoxazole:TEA:HP-beta-CD and their corresponding physical mixtures and individual components. The HP-beta-CD solubilization of sulfisoxazole could be improved by ionization of the drug molecule through pH adjustments. However, larger improvements of the HP-beta-CD solubilization are obtained when multicomponent systems are used, allowing to reduce the amount of CD necessary to prepare the target formulation.

The pleiotropic roles of transforming growth factor beta inhomeostasis and carcinogenesis of endocrine organs.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fleisch, Markus C.; Maxwell, Christopher A.; Barcellos-Hoff,Mary-Helen

2006-01-13

Transforming growth factor beta (TGF-beta) is a ubiquitous cytokine that plays a critical role in numerous pathways regulating cellular and tissue homeostasis. TGF-beta is regulated by hormones and is a primary mediator of hormone response in uterus, prostate and mammary gland. This review will address the role of TGF-beta in regulating hormone dependent proliferation and morphogenesis. The subversion of TGF-beta regulation during the processes of carcinogenesis, with particular emphasis on its effects on genetic stability and epithelial to mesenchymal transition (EMT), will also be examined. An understanding of the multiple and complex mechanisms of TGF-beta regulation of epithelial function, andmore » the ultimate loss of TGF-beta function during carcinogenesis, will be critical in the design of novel therapeutic interventions for endocrine-related cancers.« less

{alpha}-Lipoic acid exhibits anti-amyloidogenicity for {beta}-amyloid fibrils in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ono, Kenjiro; Hirohata, Mie; Yamada, Masahito

2006-03-24

Inhibition of the formation of {beta}-amyloid fibrils (fA{beta}), as well as the destabilization of preformed fA{beta} in the CNS would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of {alpha}-lipoic acid (LA) and the metabolic product of LA, dihydrolipoic acid (DHLA), on the formation, extension, and destabilization of fA{beta} at pH 7.5 at 37 {sup o}C in vitro. LA and DHLA dose-dependently inhibited fA{beta} formation from amyloid {beta}-protein, as well as their extension. Moreover, they destabilized preformed fA{beta}s. LA and DHLA couldmore » be key molecules for the development of therapeutics for AD.« less

Determining Beta Sheet Crystallinity in Fibrous Proteins by Thermal Analysis and Infrared Spectroscopy

NASA Astrophysics Data System (ADS)

Hu, Xiao; Kaplan, David; Cebe, Peggy

2007-03-01

We report a study of self-assembled beta pleated sheets in Bombyx mori silk fibroin films using thermal analysis and infrared spectroscopy. Crystallization of beta pleated sheets was effected either by heating the films above the glass transition temperature (Tg) and holding isothermally, or by exposure to methanol. The fractions of secondary structural components including random coils, alpha helices, beta pleated sheets, turns, and side chains, were evaluated using Fourier self-deconvolution (FSD) of the infrared absorbance spectra. As crystalline beta sheets form, the heat capacity increment from the TMDSC trace at Tg is systematically decreased and is linearly well correlated with beta sheet content determined from FSD. This analysis of beta sheet content can serve as an alternative to X-ray methods and may have wide applicability to other crystalline beta sheet forming proteins.

A soluble and active form of Wnt-3a protein is involved in myogenic differentiation after cholesterol depletion.

PubMed

Portilho, Débora M; Martins, Eliane R; Costa, Manoel L; Mermelstein, Cláudia S

2007-12-22

Cholesterol is one of the major lipids of plasma membranes. Recently, we have shown that cholesterol depletion by methyl-beta-cyclodextrin (M beta CD) induces the activation of the Wnt/beta-catenin pathway and enhances myogenic differentiation. Here, we show that M beta CD-conditioned media accelerates myogenesis in a similar way as M beta CD does, suggesting that the effects induced by M beta CD could be caused by soluble factors present in the culture medium. Soluble Wnt-3 protein is significantly enhanced in M beta CD-conditioned medium. Wnt-3a-enriched media induces myogenesis as much as M beta CD does, whereas Wnt-5a-enriched media inhibits. We suggest that Wnt-3a is involved in the myogenic induction observed after cholesterol depletion.

Influence of food acidulants and antioxidant spices on the bioaccessibility of beta-carotene from selected vegetables.

PubMed

Veda, Supriya; Platel, Kalpana; Srinivasan, Krishnapura

2008-09-24

Four common food acidulants--amchur, lime, tamarind, and kokum--and two antioxidant spices--turmeric and onion--were examined for their influence on the bioaccessibility of beta-carotene from two fleshy and two leafy vegetables. Amchur and lime generally enhanced the bioaccessibility of beta-carotene from these test vegetables in many instances. Such an improved bioaccessibility was evident in both raw and heat-processed vegetables. The effect of lime juice was generally more pronounced than that of amchur. Turmeric significantly enhanced the bioaccessibility of beta-carotene from all of the vegetables tested, especially when heat-processed. Onion enhanced the bioaccessibility of beta-carotene from pressure-cooked carrot and amaranth leaf and from open-pan-boiled pumpkin and fenugreek leaf. Lime juice and the antioxidant spices turmeric and onion minimized the loss of beta-carotene during heat processing of the vegetables. In the case of antioxidant spices, improved bioaccessibility of beta-carotene from heat-processed vegetables is attributable to their role in minimizing the loss of this provitamin. Lime juice, which enhanced the bioaccessibility of this provitamin from both raw and heat-processed vegetables, probably exerted this effect by some other mechanism in addition to minimizing the loss of beta-carotene. Thus, the presence of food acidulants (lime juice/amchur) and antioxidant spices (turmeric/onion) proved to be advantageous in the context of deriving maximum beta-carotene from the vegetable sources.

Functional analysis of multiple carotenogenic genes from Lycium barbarum and Gentiana lutea L. for their effects on beta-carotene production in transgenic tobacco.

PubMed

Ji, Jing; Wang, Gang; Wang, Jiehua; Wang, Ping

2009-02-01

Carotenoids are red, yellow and orange pigments, which are widely distributed in nature and are especially abundant in yellow-orange fruits and vegetables and dark green leafy vegetables. Carotenoids are essential for photosynthesis and photoprotection in plant life and also have different beneficial effects in humans and animals (van den Berg et al. 2000). For example, beta-carotene plays an essential role as the main dietary source of vitamin A. To obtain further insight into beta-carotene biosynthesis in two important economic plant species, Lycium barbarum and Gentiana lutea L., and to investigate and prioritize potential genetic engineering targets in the pathway, the effects of five carotenogenic genes from these two species, encoding proteins including geranylgeranyl diphosphate synthase, phytoene synthase and delta-carotene desaturase gene, lycopene beta-cyclase, lycopene epsilon-cyclase were functionally analyzed in transgenic tobacco (Nicotiana tabacum) plants. All transgenic tobacco plants constitutively expressing these genes showed enhanced beta-carotene contents in their leaves and flowers to different extents. The addictive effects of co-ordinate expression of double transgenes have also been investigated.

Regulation of adhesion and growth of fibrosarcoma cells by NF-kappa B RelA involves transforming growth factor beta.

PubMed Central

Perez, J R; Higgins-Sochaski, K A; Maltese, J Y; Narayanan, R

1994-01-01

The NF-kappa B transcription factor is a pleiotropic activator that participates in the induction of a wide variety of cellular genes. Antisense oligomer inhibition of the RelA subunit of NF-kappa B results in a block of cellular adhesion and inhibition of tumor cell growth. Investigation of the molecular basis for these effects showed that in vitro inhibition of the growth of transformed fibroblasts by relA antisense oligonucleotides can be reversed by the parental-cell-conditioned medium. Cytokine profile analysis of these cells treated with relA antisense oligonucleotides revealed inhibition of transforming growth factor beta 1 (TGF-beta 1 to the transformed fibroblasts reversed the inhibitory effects of relA antisense oligomers on soft agar colony formation and cell adhesion to the substratum. Direct inhibition of TGF-beta 1 expression by antisense phosphorothioates to TGF-beta 1 mimicked the in vitro effects of blocking cell adhesion that are elicited by antisense relA oligomers. These results may explain the in vitro effects of relA antisense oligomers on fibrosarcoma cell growth and adhesion. Images PMID:8035811

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu Jiawei; Division of Molecular Medicine, Harbor-UCLA Medical Center, David Geffen School of Medicine, University of California Los Angeles, Torrance, CA 90502; Lu Zhenyu

The corneal endothelial cells form a boundary layer between anterior chamber and cornea. This single cell layer is important to maintain cornea transparency by eliciting net fluid transport into the anterior chamber. Injuries of the corneal endothelial layer in humans lead to corneal swelling and translucence. This hindrance is thought to be due to limited proliferative capacity of the endothelial layer. Fibroblast growth factor 2 (FGF-2) and transforming growth factor-beta 2 (TGF-{beta}2) are both found in aqueous humor, and these two cytokines promote and inhibit cell growth, respectively. The intracellular signaling mechanisms by which TGF-{beta}2 suppresses the mitogenic response tomore » FGF-2, however, remain unclear. We have addressed this question by investigating potential crosstalk between FGF-2-induced and TGF-{beta}2-regulated intracellular signaling events in cultured bovine corneal endothelial (BCE) cells. We found that TGF-{beta}2 and FGF-2 oppositely affect BCE cell proliferation and TGF-{beta}2 can override the stimulating effects of FGF-2 by increasing COX-2 expression in these cells. Consistent with these findings, overexpression of COX-2 significantly reduced FGF-2-induced cell proliferation whereas a COX-2 specific inhibitor NS398 reversed the effect of TGF-{beta}2 on FGF-2-induced cell proliferation. The COX-2 product prostaglandin E2 (PGE-2) blocks FGF-2-induced cell proliferation. Whereas FGF-2 stimulates cell proliferation by activating the AKT pathway, TGF-{beta}2 and PGE-2 both inhibit this pathway. In accordance with the effect of PGE-2, cAMP also inhibits FGF-2-induced AKT activation. These findings suggest that the mitogenic response to FGF-2 in vivo in the corneal endothelial layer may be inhibited by TGF-{beta}2-induced suppression of the PI3-kinase/AKT signaling pathway.« less

Effect of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function.

PubMed

Takasu, Toshiyuki; Ukai, Masashi; Sato, Shuichi; Matsui, Tetsuo; Nagase, Itsuro; Maruyama, Tatsuya; Sasamata, Masao; Miyata, Keiji; Uchida, Hisashi; Yamaguchi, Osamu

2007-05-01

We evaluated the pharmacological characteristics of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]-ethyl} acetanilide (YM178). YM178 increased cyclic AMP accumulation in Chinese hamster ovary (CHO) cells expressing human beta3-adrenoceptor (AR). The half-maximal effective concentration (EC50) value was 22.4 nM. EC50 values of YM178 for human beta1- and beta2-ARs were 10,000 nM or more, respectively. The ratio of intrinsic activities of YM178 versus maximal response induced by isoproterenol (nonselective beta-AR agonist) was 0.8 for human beta3-ARs, 0.1 for human beta1-ARs, and 0.1 for human beta2-ARs. The relaxant effects of YM178 were evaluated in rats and humans bladder strips precontracted with carbachol (CCh) and compared with those of isoproterenol and 4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (CGP-12177A) (beta3-AR agonist). EC50 values of YM178 and isoproterenol in rat bladder strips precontracted with 10(-6) M CCh were 5.1 and 1.4 microM, respectively, whereas those in human bladder strips precontracted with 10(-7) M CCh were 0.78 and 0.28 microM, respectively. In in vivo study, YM178 at a dose of 3 mg/kg i.v. decreased the frequency of rhythmic bladder contraction induced by intravesical filling with saline without suppressing its amplitude in anesthetized rats. These findings suggest the suitability of YM178 as a therapeutic drug for the treatment of symptoms of overactive bladder such as urinary frequency, urgency, and urge incontinence.